[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"sickle-cell-disease\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:sickle-cell-disease":36},{"pageToken":4,"total":5,"offset":6,"count":7,"results":8},null,160,0,25,[9,50,81,95,126,153,178,197,221,245,271,291,327,352,374,394,414,434,454,481,503,536,557,585,610],{"id":10,"slug":11,"hasResults":12,"nctId":13,"briefTitle":14,"officialTitle":15,"acronym":4,"eligibilityCriteria":16,"healthyVolunteers":12,"sex":17,"minAge":4,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":4,"briefSummary":22,"conditions":23,"keywords":4,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":38,"lastUpdatePostDateStruct":39,"startDateStruct":42,"completionDateStruct":44,"leadSponsor":46,"locationsCount":49},"100054158","athn-transcends-a-natural-history-study-of-non-neoplastic-hematologic-disorders-100054158",false,"NCT04398628","ATHN Transcends: A Natural History Study of Non-Neoplastic Hematologic Disorders","ATHN Transcends: A Natural History Cohort Study of the Safety, Effectiveness, and Practice of Treatment in People With Non-Neoplastic Hematologic Disorders","Participants who meet the following inclusion criteria and none of the exclusion criteria are eligible for enrollment in one of the open disease-specific arms.\n\nInclusion Criteria:\n\n1. Any age\n2. Having a congenital or acquired blood disorder; or\n3. Having a bleeding phenotype as indicated by an age adjusted abnormal ISTH Bleeding Assessment Tool score with an unknown diagnosis; or\n4. Connective tissue disorder with bleeding tendency as indicated by an age adjusted abnormal ISTH Bleeding Assessment Tool score.\n5. Eligible for a currently active disease-specific arm.\n6. Concurrent enrollment in the ATHNdataset or current ATHNdataset participant.\n\nExclusion Criteria:\n\n1\\. Does not qualify for inclusion in a currently activedisease-specific arm; participants may be eligible to enroll as future cohorts and arms are activated; 2. Unable to give informed consent or assent 3. Unwilling to perform study procedures\n\nCohort Participant Selection\n\nEach participant is to be enrolled in the cohort for which they qualify as defined below.\n\nHemophilia Cohort\n\nInclusion Criteria:\n\nParticipants who meet any of the following inclusion criteria are eligible for enrollment into this cohort:\n\n1. Factor VIII or factor IX activity \\\u003C50%, without another explanation for low clotting factor other than congenital hemophilia or being a known carrier for congenital hemophilia; OR\n2. Carrier for congenital hemophilia with a factor VIII \\>=50% or factor IX activity \\>=50% with or without a bleeding phenotype as indicated by an ISTH Bleeding Assessment Tool score of ≥4 for adult males, ≥6 for adult females, or ≥3 for children younger than 18 years OR\n3. Known congenital hemophilia that have a factor level \\>50% after receiving vector, OR 4. Acquired hemophilia.\n\nExclusion Criteria:\n\nNone\n\nVon Willebrand Disease Cohort\n\nInclusion Criteria:\n\nParticipants who meet the following inclusion criteria are eligible for enrollment into this cohort:\n\n1\\. Meeting the definition of VWD or low VWF per most recent international guidelines\n\nExclusion Criteria:\n\nNone\n\nCongenital Platelet Disorders Cohort\n\nInclusion Criteria:\n\nParticipants who meet the following inclusion criteria are eligible for enrollment into this cohort:\n\n1. Abnormalities of platelet function a. Glanzmann thrombasthenia (GPIIb or GPIIIa) b. Bernard-Soulier syndrome (GPIbalpha, GPIbbeta, or GPIX)\n2. Abnormalities of platelet granules\n3. Abnormalities of platelet signal transduction\n4. Abnormalities of platelet secretion\n5. Collagen Receptor Defect\n6. ADP Receptor Defect\n7. Thromboxane Receptor Defect\n8. Giant Platelet Disorder\n9. Abnormalities in platelet aggregation testing due to another or unknown cause (not drug related)\n\nExclusion Criteria:\n\n1\\. Platelet disorders secondary to medications or other substances\n\nRare Disorders Cohort\n\nInclusion Criteria:\n\nParticipants who meet the following inclusion criteria are eligible for enrollment into this cohort:\n\n1\\. Have an established Rare Coagulation Disorder (RCD) diagnosis of one of the following:\n\n1. PAI-1 deficiency\n2. Factor I, II, V, VII, X, XI, XIII deficiencies\n3. Combined FV and FVIII deficiency\n4. Plasminogen deficiency\n5. Decreased tissue plasminogen activator\n6. Afibrinogenemia\u002Fhypofibrinogenemia\u002Fdysfibrinogenemia\n7. Thrombotic Thrombocytopenia Purpura or Congenital Hemolytic Uremic Syndrome\n8. Wiskott-Aldrich\n9. Methylenetetrahydrofolate Reductase Deficiency\n\nExclusion Criteria:\n\nNone\n\nBleeding NOS Cohort\n\nInclusion Criteria:\n\nParticipants who meet the following inclusion criteria are eligible for enrollment into this cohort:\n\n1. Have a bleeding phenotype as indicated by an ISTH Bleeding Assessment Tool score of ≥4 for adult males, ≥6 for adult females, or ≥3 for children younger than 18 years with an unknown diagnosis, OR\n2. Connective tissue disorder with bleeding tendency as indicated by an ISTH Bleeding Assessment Tool score of ≥4 for adult males, ≥6 for adult females, or ≥3 for children younger than 18 years.\n\nExclusion Criteria:\n\nNone\n\nThrombosis\u002FThrombophilia Cohort\n\nInclusion Criteria\n\nParticipants who meet the following inclusion criteria are eligible for enrollment into this cohort:\n\n1\\. Have a prior history of arterial or venous thrombosis. 2. Participants with a known congenital or acquired thrombophilia with or without thrombosis.\n\na. Common congenital thrombophilias: i. Protein C deficiency ii. Protein S deficiency iii. Antithrombin deficiency iv. Factor V Leiden v. Prothrombin gene mutation b. Rare genetic factors i. Hyperhomocysteinemia c. Indeterminate genetic factors i. Elevated factor VIII ii. Elevated factor IX iii. Elevated factor XI iv. Elevated lipoprotein (a) d. Acquired thrombophilias i. Lupus anticoagulant ii. Anti-cardiolipin antibodies\u002FBeta2 glycoprotein antibodies iii. Antiphospholipid syndrome\n\nExclusion Criteria Acquired thrombophilia secondary to medications (birth control pills or hormone replacement therapy), overweight or obesity, smoking, cancer, pregnancy, surgery, injury, prolonged inactivity\u002Fbedrest, heart failure, inflammatory bowel disease, or kidney disease\n\nNon-Neoplastic Hematologic Conditions Cohort\n\nInclusion Criteria\n\nParticipants who meet the following inclusion criteria are eligible for enrollment into this cohort:\n\n1\\. Having any congenital or acquired non-neoplastic hematologic disorder not included in any other cohort\n\nExclusion Criteria None\n\nArm\u002FModule Participant Selection\n\nPreviously Untreated Patients Arm\n\nInclusion Criteria:\n\n1. Diagnosis of congenital hemophilia A (FVIII \\\u003C40%) or hemophilia B (FIX \\\u003C40% or below lower limit for age)\n2. Age \\\u003C18 years at time of enrollment\n3. Parent or authorized guardian or legally authorized representative (LAR) can provide informed consent\n4. Care established at one of the ATHN Transcends participating HTCs\n5. Clotting Factor Concentrate (CFC) exposure, fresh frozen plasma (FFP), cryoprecipitate, and single donor platelets \\\u003C3 exposure days (ED)\n\nExclusion Criteria\n\n1. Concomitant diagnosis with another bleeding disorder\n2. History of a confirmed, positive inhibitor\n\nINHIBIT Module\n\nInclusion Criteria:\n\n1\\. Diagnosis of severe factor VIII deficiency with baseline factor VIII level \\\u003C1% 2. Initiating or plan to initiate prophylaxis with emicizumab or factor replacement 3. Factor concentrate exposure, Fresh Frozen Plasma (FFP), cryoprecipitate, and single donor platelets ≤3 EDs 4. ≤5 years of age\n\nExclusion Criteria\n\n1. Concomitant diagnosis with bleeding disorder other than hemophilia A\n2. Immune disorder\n3. Previous history or presence of factor VIII inhibitor. A confirmed, positive inhibitor is defined as two consecutive positive inhibitor titers (≥ 0.6 BU) that result in changes in treatment recommendations.\n\nEfanesoctocog alfa (ALTUVIIIO®) Module\n\nInclusion criteria:\n\n1. Ability of the potential participant's legally authorized representative (e.g., their parent or legal guardian) to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential health information in accordance with national and local participant privacy regulation.\n2. People with severe HA with a baseline FVIII activity of less than 1%. (While inclusion for participation in ATHN Transcends lists \\\u003C5% FVIII activity, this proposed module will limit enrollment to people with FVIII activity levels of \\\u003C1%.) Other severities may be included per ATHN Transcends PI approval.\n3. \\\u003C18 years of age.\n4. No history of a confirmed, positive FVIII inhibitor.\n5. Sex assigned at birth of male, female, or intersex.\n6. Participants should have no more than three (3) exposure days of blood products (fresh frozen plasma, cryoprecipitate, or platelets), no more than three (3) doses of any FVIII concentrate other than efanesoctocog alfa, and up to three (3) doses of efanesoctocog alfa prior to enrollment.\n7. Site PI confirmed all inclusion criteria has been met.\n\nExclusion criteria:\n\n1. Not meeting all the inclusion criteria; confirmed by site PI.\n2. Any exposure to blood products or FVIII replacement products except as described in the inclusion criteria.\n3. History of positive inhibitor testing.\n4. History of hypersensitivity reactions associated with efanesoctocog alfa administration.\n5. Other coagulation disorder(s) in addition to Hemophilia A.\n6. Any concurrent clinically significant major disease such as cancer that, in the opinion of the investigator, would make the participant unsuitable for enrollment.\n7. Concurrent systemic treatment with chemotherapy and\u002For other immunosuppressant medications. Use of corticosteroids for the treatment of asthma or management of acute allergic or otherwise life-threatening episodes is allowed except for systemic corticosteroid treatment given to children daily or on an alternate day schedule at \\> 2 mg\u002Fkg\u002Fday of prednisone or its equivalent or \\> 20 mg\u002Fday if the duration is longer than 14 days.\n8. Enrollment in a concurrent clinical interventional drug study.\n9. Intake of an Investigational Medicinal Product within three (3) months prior to inclusion in this study.\n10. Inability to comply with study requirements.\n11. Other, unspecified reasons that, in the investigator's opinion, make the participant unsuitable for enrollment.\n\nHemophilia Natural History Arm\n\nInclusion Criteria\n\n1. Congenital or acquired hemophilia A or B of any severity with or without inhibitors receiving a current therapy, a non-factor product, or for whom use of a non-factor product is a possibility, OR\n2. Females of any age, with confirmed congenital hemophilia A or B carrier status with genetic mutational analysis and any factor level.\n\nExclusion Criteria\n\n1. Presence of any known bleeding disorder other than congenital hemophilia A or B\n2. Presence of concurrent hemophilia and a second hemostatic defect (low von Willebrand Factor (vWF) without vWD diagnosis is not excluded)\n3. Unable or unwilling to comply with the study arm protocol.\n\nNonacog beta pegol (Rebinyn®) Module\n\nInclusion Criteria:\n\n1. Has provided signed written consent for the nonacog beta pegol (Rebinyn®)Module before any study-related activities.\n2. Male participants, at any age with hemophilia B, naïve or minimally exposed (up to 3 EDs) to nonacog beta pegol treatment at time of study enrollment. Additional doses may be allowable per ATHN Transcends PI approval.\n3. Decision to initiate continuous prophylaxis treatment with commercially available nonacog beta pegol has been made by the participant(s)\u002FLegally Authorized Representative(s) (LAR(s)) and the treating physician before and independently from the decision to include the participant in this study.\n\nExclusion Criteria:\n\n1. Previous participation in this study. Participation is defined as having given informed consent in this study.\n2. Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation, including a diagnosis or suspicion of attention deficit hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) per the discretion of the Principal Investigator.\n3. Known or suspected hypersensitivity to nonacog beta pegol or related products.\n4. Clinical suspicion or presence of FIX inhibitor at time of inclusion.\n5. Inability or unwillingness to undergo neurological assessment\u002Fstructured developmental history.\n\nEmicizumab (Hemlibra®) Module\n\nInclusion Criteria:\n\n1. Participant currently treated with emicizumab (Hemlibra®)\n2. Currently enrolled in the Hemophilia Natural History Arm of ATHN Transcends\n\nExclusion Criteria:\n\n1\\. Unable or unwilling to comply with the protocol\n\nDistress Module\n\nInclusion Criteria:\n\n1. Congenital hemophilia A or B of any severity with or without inhibitors receiving a current therapy, a non-factor product, or for whom use of a non-factor product is a possibility\n2. Age 18 years of age or older\n3. English speaking\n\nExclusion Criteria:\n\n1. Presence of any known bleeding disorder other than congenital hemophilia A or B;\n2. Presence of concurrent hemophilia and a second hemostatic defect (low von Willebrand Factor (vWF) without vWD diagnosis is not excluded); and\n3. Unable or unwilling to comply with the study arm protocol\n\nHemophilia Gene Therapy Outcomes Arm\n\nInclusion Criteria\n\n1. Hemophilia A or B of any severity with or without inhibitors having received or will receive a hemophilia gene transfer product in the next 6 months.\n2. Age 18 years and older.\n3. Able to give informed consent.\n\nExclusion Criteria None\n\nEtranacogene dezaparvovec (HEMGENIX®) Module\n\nInclusion Criteria:\n\nEtranacogene dezaparvovec (HEMGENIX®) Cohort\n\n1. Age 18 years of age or older\n2. Treatment with commercial etranacogene dezaparvovec (HEMGENIX®)\n3. Have provided signed written informed consent within 3 months before or within 6 months after etranacogene dezaparvovec (HEMGENIX®) treatment, or within 6 months of when the study is initiated at the treating site.\n\nFIX Prophylaxis Cohort\n\n1. Age 18 years of age or older\n2. Treatment with FIX prophylaxis therapy\n3. Has provided signed written consent at any time for ATHN Transcends Study\n\nExclusion Criteria, both cohorts:\n\n1\\. Have been treated with etranacogene dezaparvovec in a clinical trial prior to commercial availability. These patients are still eligible for enrollment in the Gene Therapy Outcomes Arm, and their data may be collected for separate analysis.\n\nCongenital Platelet Disorders Arm\n\nInclusion Criteria\n\n1. Platelet adhesion defect\n\n   1. Bernard Soulier syndrome (Defective GPIb-IX-V receptor, impaired adhesion to vWF)\n   2. Velocardio-facial syndrome\u002FDiGeorge syndrome (Defective GPIb-IX-V receptor)\n   3. Platelet type vWD (Defective GPIb-IX-V, gain of function interaction between vWF-GP1bα)\n2. Platelet aggregation defect\n\n   1. Glanzmann thrombasthenia (Defective integrin αIIbβ3 (GPIIb\u002FIIIa)\n   2. Platelet aggregation defect, NOS\n3. Agonist receptor defects\n\n   1. Epinephrine\n   2. ADP\n   3. Collagen\n   4. Thromboxane A2\n4. Platelet signaling defects\n\n   1. Cyclooxygenase deficiency (PTGS1 mutation)\n   2. Phospholipase A2 deficiency\n   3. Thromboxane synthase deficiency (TBXAS1 mutation)\n   4. G protein activation defect (GNAS mutation)\n   5. Scott syndrome (defect in phosphatidyl serine translocation)\n5. Platelet Granule disorders\n\n   1. Dense granule storage pool disorder\n\n      * Hermansky Pudlak syndrome\n      * Chediak Higashi syndrome\n      * Griscelli syndrome\n   2. Alpha granule storage pool disorder\n\n      * Grey platelet syndrome\n      * Arthrogryposis-Renal Dysfunction-Cholestasis (ARC) syndrome\n      * Quebec platelet disorder\n      * Paris-Trousseau syndrome\n   3. Combined alpha delta granule deficiency\n6. Platelet cytoskeletal structure defects\n\n   1. Wiskott Aldrich syndrome\n   2. MYH9 associated disorders (myosin heavy chain)\n\n      * May Hegglin syndrome\n      * Fechtner syndrome\n      * Sebastian syndrome\n      * Epstein syndrome\n   3. Other mutations\n\n      * FLNA mutations (Filamin)\n      * DIAPH1 (Actin and microtubules)\n      * ACTN1 (alpha actinin)\n      * TPM4 (tropomyosin)\n      * TUBB1 (beta tubulin)\n7. Other Congenital thrombocytopenias\n\n   1. Familial platelet disorders and predisposition to AML (RUNX1)\n   2. X linked thrombocytopenia with dyserythropoiesis (GATA1)\n   3. Congenital amegakaryocytic thrombocytopenia (MPL)\n\nExclusion Criteria\n\n1. Diagnosis of von Willebrand Disease (Meeting the definition of vWD or low vWF per most recent international guidelines)\n2. Diagnosis of Hemophilia A or Hemophilia B (Factor VIII or IX ≤ 40%)\n\nGlanzmann Thrombasthenia (GT) Module\n\nInclusion Criteria\n\n1. Participant has signed the informed consent\u002Fassent form\n2. Participant has flow cytometry or aggregometry or genetics confirmed GT\n3. Participant is willing to perform study procedures, including daily bleed tracking for 3 months and further if requested\n4. Participants are 2 years or older at time of consent\n\nExclusion Criteria None","ALL",{"count":19,"type":20},3000,"ESTIMATED","OBSERVATIONAL","In parallel with the growth of ATHN's clinical studies, the number of new therapies for all blood disorders is increasing significantly. Some of the recently FDA-approved therapies for congenital and acquired hematologic conditions have not yet demonstrated long-term safety and effectiveness beyond the pivotal trials that led to their approval. In addition, results from well controlled, pivotal studies often cannot be replicated once a therapy has been approved for general use.2,3,4,5\n\nIn 2019 alone, the FDA has issued approvals for 24 new therapies for congenital and acquired hematologic conditions.6 In addition, almost 10,000 new studies for hematologic diseases are currently registered on www.clinicaltrials.gov.7\n\nWith this increase in potential new therapies possible, it is imperative that clinicians and clinical researchers in the field of non-neoplastic hematology have a uniform, secure, unbiased, and enduring method to collect long-term safety and efficacy data. As emphasized in a recently published review, accurate, uniform and quality national data collection is critical in clinical research, particularly for longitudinal cohort studies covering a lifetime of biologic risk.8",[24,25,26,27,28,29,30,31,32,33,34,35,36],"Hematologic Disorder","Bleeding Disorder","Connective Tissue Disorder","Hemophilia","Thrombosis","Von Willebrand Diseases","Thrombophilia","Rare Bleeding Disorder","Platelet Disorder","Factor IX Deficiency","Factor VIII Deficiency","Thalassemia","Sickle Cell Disease","RECRUITING","2026-07-10",{"date":40,"type":41},"2026-07-13","ACTUAL",{"date":43,"type":41},"2020-09-30",{"date":45,"type":20},"2035-12",{"name":47,"class":48},"American Thrombosis and Hemostasis Network","NETWORK",71,{"id":51,"slug":52,"hasResults":12,"nctId":53,"briefTitle":54,"officialTitle":55,"acronym":4,"eligibilityCriteria":56,"healthyVolunteers":12,"sex":17,"minAge":57,"maxAge":58,"enrollmentInfo":59,"targetDuration":4,"studyType":61,"phases":62,"briefSummary":65,"conditions":66,"keywords":68,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":38,"lastUpdatePostDateStruct":72,"startDateStruct":73,"completionDateStruct":75,"leadSponsor":77,"locationsCount":80},"100053445","phase-1-partial-stem-cell-transplant-for-sickle-cell-disease-from-matched-donors-100053445","NCT07599176","Partial Stem Cell Transplant for Sickle Cell Disease From Matched Donors","Matched Related Donor Non-myeloablative Hematopoietic Cell Transplantation With Alemtuzumab, 400 cGy TBI, and Abatacept for Sickle Cell Disease and Beta-Thalassemia","* INCLUSION CRITERIA\n\nRECIPIENT:\n\nParticipants must fulfill one disease category (1 or 2) and 3\n\n1. Patients with sickle cell disease at high risk for disease related morbidity or mortality, defined by having an end-organ damage (A, B, C, D, OR E) or complication(s) not ameliorated by sickle cell-specific therapies (F):\n\n   A. Stroke defined as a clinically significant neurologic event that is accompanied by an infarct on cerebral MRI ORb\n\n   B. Abnormal trans-cranial Doppler examination (\\>=200 cm\u002Fs); OR\n\n   C. Silent cerebral infarct defined as an infarct-like lesion based on an MRI signal abnormality at least 3 mm in one dimension and visible in two planes on FLAIR or T2- weighted images (or similar image with 3D imaging) and documented neurological examination performed by a neurologist demonstrating the participant has a normal neurologic examination, or an abnormality on examination that could not be explained by the location of the brain lesion(s); OR\n\n   D. Sickle cell related renal insufficiency defined by a creatinine level \\>=1.5 times the upper limit of normal and kidney biopsy consistent with sickle cell nephropathy OR nephrotic syndrome OR creatinine clearance \\\u003C60mL\u002Fmin\u002F1.73m2 for patients \\\u003C16 years of age or \\\u003C50mL\u002Fmin for patients \\>16 years of age OR requiring peritoneal or hemodialysis; OR\n\n   Age (Years): \\\u003C= 5 \u002F Upper limit of normal serum creatinine (mg\u002Fdl): 0.8\n\n   Age (Years): 5 \\\u003C age \\\u003C= 10 \u002F Upper limit of normal serum creatinine (mg\u002Fdl): 1.0\n\n   Age (Years): 10 \\\u003C age \\\u003C= 15 \u002F Upper limit of normal serum creatinine (mg\u002Fdl): 1.2\n\n   Age (Years): \\> 15 \u002F Upper limit of normal serum creatinine (mg\u002Fdl): 1.3\n\n   E. Tricuspid regurgitant jet velocity (TRV) of \\>=2.5 m\u002Fs in patients at least 3 weeks after a vaso-occlusive crisis; OR\n\n   F. Recurrent severe priapism defined as at least two episodes of an erection lasting \\>=4 hours requiring medical intervention (e.g. aspiration, injection of vasoconstrictor, prior penile surgery.); OR\n\n   G. Sickle hepatopathy defined as EITHER ferritin \\>1000mcg\u002FL OR direct bilirubin \\>0.4 mg\u002FdL at baseline; OR\n\n   H. Vaso-occlusive crises: more than 1 hospital admission per year while on a therapeutic dose of sickle cell treatment \u002Fmedication; OR\n\n   I. Acute chest syndrome (ACS): any ACS while on sickle cell treatment \u002Fmedication\n2. Patients with beta-thalassemia who have grade 2 or 3 iron overload, determined by the presence of 2 or more of the following:\n\n   * Portal fibrosis by liver biopsy\n   * Inadequate chelation history (defined as failure to maintain adequate compliance with chelation with deferoxamine initiated within 18 months of the first transfusion and administered at least 5 days each week)\n   * Hepatomegaly of greater than 2 cm below the costochondral margin or by other imaging scans\n3. Non disease specific\n\n   * Ages \\>=4 years and less than 65 years old\n   * Fully matched human leukocyte antigen (HLA) donors at A, B, C, and DR loci (8 of 8 or 10 of 10)\n   * Ability to comprehend and willing to sign an informed consent, assent obtained from minors when applicable. Negative serum or urine beta-HCG, when applicable\n   * Agree to use birth control throughout the study and 3 months after abatacept or sirolimus administration.\n\n     * Female subjects must agree to use a medically acceptable method of birth control such as oral contraceptive, intrauterine device, barrier and spermicide, or implant\u002Finjection from start of screening until immunosuppression is stopped.\n     * Male subjects must agree to use effective contraception (including condoms) from start of screening until immunosuppression is stopped.\n\nDONOR:\n\n* Fully matched human leukocyte antigen (HLA) donors at A, B, C, and DR loci (8 of 8 or 10 of 10) are intended for this study.\n* Donors age 4 or older and \\>=15 kg (or weight deemed acceptable by IR for line placement, DTM for apheresis, and pediatric consult service) eligible to donate hematopoietic stem cells, are eligible for this study.\n* Donors will be evaluated in accordance with existing Standard NIH Policies and Procedures for determination of eligibility and suitability for clinical donation. Donors will sign on a separate protocol, 20-H-0099 NHLBI standard of care protocol for the mobilization and collection of HSCs. Note that participation in this study is offered to all eligible donors, but is not required for a donor to make a stem cell donation, so it is possible that not all donors will enroll onto this study.\n\nEXCLUSION CRITERIA\n\nRECIPIENT:\n\n* Karnofsky or Lanksy performance status of \\\u003C40\n* Diffusing capacity of carbon monoxide \\\u003C35% predicted: DLCO corrected for hemoglobin or KCO (corrected for lung volume). This criterion may be omitted in young children (e.g. near age 5) or other individuals who may have difficulty understanding or complying with instructions of testing.\n* Baseline oxygen saturation of \\\u003C85% or PaO2 \\\u003C70\n* Left ventricular ejection fraction: \\\u003C35% estimated by ECHO\n* Transaminases \\>5x upper limit of normal for age\n* Evidence of uncontrolled bacterial, viral, or fungal infections (currently taking medication and progression of clinical symptoms) within one month prior to starting the conditioning regimen\n* Major anticipated illness or organ failure incompatible with survival from HCT\n* Pregnant or breastfeeding\n\nDONOR:\n\n* Pregnant or breastfeeding\n* Cognitively impaired subjects","4 Years","65 Years",{"count":60,"type":20},90,"INTERVENTIONAL",[63,64],"PHASE1","PHASE2","This is a non-ablative (partial) stem cell transplant for patients with severe sickle cell disease or beta-thalassemia requiring red cell transfusions. The intensity of the transplant is slightly increased from our previous transplant regimens. The goal is to aim for higher percentage of donor cells to stably remain in the recipients long term.",[36,67],"Beta-thalassemia",[36,69,70,71],"Beta-Thalassemia","Stem Cell Transplant","Chimerism",{"date":40,"type":41},{"date":74,"type":41},"2026-07-08",{"date":76,"type":20},"2035-06-30",{"name":78,"class":79},"National Heart, Lung, and Blood Institute (NHLBI)","NIH",1,{"id":82,"slug":4,"hasResults":12,"nctId":53,"briefTitle":54,"officialTitle":55,"acronym":4,"eligibilityCriteria":83,"healthyVolunteers":12,"sex":17,"minAge":57,"maxAge":58,"enrollmentInfo":84,"targetDuration":4,"studyType":61,"phases":85,"briefSummary":65,"conditions":86,"keywords":87,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":88,"lastUpdatePostDateStruct":89,"startDateStruct":91,"completionDateStruct":93,"leadSponsor":94,"locationsCount":80},"100641763","* INCLUSION CRITERIA\n\nRECIPIENT:\n\nParticipants must fulfill one disease category (1 or 2) and 3\n\n1. Patients with sickle cell disease at high risk for disease related morbidity or mortality, defined by having an end-organ damage (A, B, C, D, OR E) or complication(s) not ameliorated by sickle cell-specific therapies (F):\n\n   A. Stroke defined as a clinically significant neurologic event that is accompanied by an infarct on cerebral MRI ORb\n\n   B. Abnormal trans-cranial Doppler examination (\\>=200 cm\u002Fs); OR\n\n   C. Silent cerebral infarct defined as an infarct-like lesion based on an MRI signal abnormality at least 3 mm in one dimension and visible in two planes on FLAIR or T2- weighted images (or similar image with 3D imaging) and documented neurological examination performed by a neurologist demonstrating the participant has a normal neurologic examination, or an abnormality on examination that could not be explained by the location of the brain lesion(s); OR\n\n   D. Sickle cell related renal insufficiency defined by a creatinine level \\>=1.5 times the upper limit of normal and kidney biopsy consistent with sickle cell nephropathy OR nephrotic syndrome OR creatinine clearance \\\u003C60mL\u002Fmin\u002F1.73m2 for patients \\\u003C16 years of age or \\\u003C50mL\u002Fmin for patients \\>16 years of age OR requiring peritoneal or hemodialysis; OR\n\n   Age (Years): \\\u003C= 5 \u002F Upper limit of normal serum creatinine (mg\u002Fdl): 0.8\n\n   Age (Years): 5 \\\u003C age \\\u003C= 10 \u002F Upper limit of normal serum creatinine (mg\u002Fdl): 1.0\n\n   Age (Years): 10 \\\u003C age \\\u003C= 15 \u002F Upper limit of normal serum creatinine (mg\u002Fdl): 1.2\n\n   Age (Years): \\> 15 \u002F Upper limit of normal serum creatinine (mg\u002Fdl): 1.3\n\n   E. Tricuspid regurgitant jet velocity (TRV) of \\>=2.5 m\u002Fs in patients at least 3 weeks after a vaso-occlusive crisis; OR\n\n   F. Recurrent severe priapism defined as at least two episodes of an erection lasting \\>=4 hours requiring medical intervention (e.g. aspiration, injection of vasoconstrictor, prior penile surgery.); OR\n\n   G. Sickle hepatopathy defined as EITHER ferritin \\>1000mcg\u002FL OR direct bilirubin \\>0.4 mg\u002FdL at baseline; OR\n\n   H. Vaso-occlusive crises: more than 1 hospital admission per year while on a therapeutic dose of sickle cell treatment \u002Fmedication; OR\n\n   I. Acute chest syndrome (ACS): any ACS while on sickle cell treatment \u002Fmedication\n2. Patients with beta-thalassemia who have grade 2 or 3 iron overload, determined by the presence of 2 or more of the following:\n\n   * Portal fibrosis by liver biopsy\n   * Inadequate chelation history (defined as failure to maintain adequate compliance with chelation with deferoxamine initiated within 18 months of the first transfusion and administered at least 5 days each week)\n   * Hepatomegaly of greater than 2 cm below the costochondral margin or by other imaging scans\n3. Non disease specific\n\n   * Ages \\>=4 years and less than 65 years old\n   * Fully matched human leukocyte antigen (HLA) donors at A, B, C, and DR loci (8 of 8 or 10 of 10\n   * Ability to comprehend and willing to sign an informed consent, assent obtained from minors when applicable. Negative serum or urine beta-HCG, when applicable\n   * Agree to use birth control throughout the study and 3 months after abatacept or sirolimus administration.\n\n     * Female subjects must agree to use a medically acceptable method of birth control such as oral contraceptive, intrauterine device, barrier and spermicide, or implant\u002Finjection from start of screening until immunosuppression is stopped.\n     * Male subjects must agree to use effective contraception (including condoms) from start of screening until immunosuppression is stopped.\n\nDONOR:\n\n* Fully matched human leukocyte antigen (HLA) donors at A, B, C, and DR loci (8 of 8 or 10 of 10) are intended for this study.\n* Donors age 4 or older and \\>=15 kg (or weight deemed acceptable by IR for line placement, DTM for apheresis, and pediatric consult service) eligible to donate hematopoietic stem cells, are eligible for this study.\n* Donors will be evaluated in accordance with existing Standard NIH Policies and Procedures for determination of eligibility and suitability for clinical donation. Donors will sign on a separate protocol, 20-H-0099 NHLBI standard of care protocol for the mobilization and collection of HSCs. Note that participation in this study is offered to all eligible donors, but is not required for a donor to make a stem cell donation, so it is possible that not all donors will enroll onto this study.\n\nEXCLUSION CRITERIA\n\nRECIPIENT:\n\n* Karnofsky or Lanksy performance status of \\\u003C40\n* Diffusion capacity of carbon monoxide (DLCO) \\\u003C35% predicted (corrected for hemoglobin and alveolar volume). This criterion may be omitted in young children (e.g. near age 5) or other individuals who may have difficulty understanding or complying with instructions of testing.\n* Baseline oxygen saturation of \\\u003C85% or PaO2 \\\u003C70\n* Left ventricular ejection fraction: \\\u003C35% estimated by ECHO\n* Transaminases \\>5x upper limit of normal for age\n* Evidence of uncontrolled bacterial, viral, or fungal infections (currently taking medication and progression of clinical symptoms) within one month prior to starting the conditioning regimen\n* Major anticipated illness or organ failure incompatible with survival from HCT\n* Pregnant or breastfeeding\n\nDONOR:\n\n* Pregnant or breastfeeding\n* Cognitively impaired subjects",{"count":60,"type":20},[63,64],[36,67],[36,69,70,71],"2026-07-01",{"date":90,"type":41},"2026-07-02",{"date":92,"type":20},"2026-07-07",{"date":76,"type":20},{"name":78,"class":79},{"id":96,"slug":97,"hasResults":12,"nctId":98,"briefTitle":99,"officialTitle":100,"acronym":101,"eligibilityCriteria":102,"healthyVolunteers":12,"sex":17,"minAge":103,"maxAge":104,"enrollmentInfo":105,"targetDuration":4,"studyType":61,"phases":107,"briefSummary":108,"conditions":109,"keywords":110,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":116,"lastUpdatePostDateStruct":117,"startDateStruct":118,"completionDateStruct":120,"leadSponsor":122,"locationsCount":125},"100425430","phase-1-gene-correction-in-autologous-cd34-hematopoietic-stem-cells-hbs-to-hba-to-treat-severe-sickle-cell-disease-100425430","NCT04819841","Gene Correction in Autologous CD34+ Hematopoietic Stem Cells (HbS to HbA) to Treat Severe Sickle Cell Disease","A Phase I\u002FII Study of Nula-cel in Autologous CD34+ Hematopoietic Stem Cells to Convert HbS to HbA for Treating Severe Sickle Cell Disease","Restore","Inclusion Criteria:\n\n* ≥12 to ≤ 40 years\n* Severe disease, as defined by having experienced at least one of the following SCD-related events despite appropriate supportive care measures:\n* recurrent severe VOC (≥ 4 episodes in the preceding 2 years)\n* ACS (≥ 2 episodes in the prior 2 years with at least one episode in the past year)\n* Lansky\u002FKarnofsky performance status of ≥ 80\n\nExclusion Criteria:\n\n* Available 10\u002F10 HLA-matched sibling donor\n* Prior HSCT or gene therapy\n* Prior or current malignancy or myeloproliferative or a significant coagulation or immunodeficiency disorder\n* Clinically significant and active bacterial, viral, fungal or parasitic infection\n* Pregnancy or breastfeeding in a postpartum female\n* Presence of a chromosomal abnormality\u002Fmutation that may put the participant at an increased risk for MDS or AML per investigator's judgment","12 Years","50 Years",{"count":106,"type":20},15,[63,64],"This study is a first-in-human, single-arm, open-label Phase I\u002FII study of nula-cel in approximately 15 participants, diagnosed with severe Sickle Cell Disease. The primary objective is to evaluate safety of the treatment in this patient population, as well as preliminary efficacy and pharmacodynamic data.",[36],[111,112,113,114,115],"sickle cell disease","sickle cell anemia","gene correction","gene therapy","CRISPR","2026-06-30",{"date":90,"type":41},{"date":119,"type":41},"2021-11-15",{"date":121,"type":20},"2028-12-31",{"name":123,"class":124},"Kamau Therapeutics","INDUSTRY",6,{"id":127,"slug":128,"hasResults":12,"nctId":129,"briefTitle":130,"officialTitle":130,"acronym":4,"eligibilityCriteria":131,"healthyVolunteers":12,"sex":17,"minAge":132,"maxAge":133,"enrollmentInfo":134,"targetDuration":4,"studyType":61,"phases":135,"briefSummary":137,"conditions":138,"keywords":139,"overallStatus":143,"whyStopped":4,"lastUpdateSubmitDate":144,"lastUpdatePostDateStruct":145,"startDateStruct":146,"completionDateStruct":148,"leadSponsor":150,"locationsCount":80},"100636189","assessing-molecular-mechanisms-and-effects-of-music-therapy-in-youth-with-sickle-cell-disease-using-single-cell-rna-sequencing-100636189","NCT07562451","Assessing Molecular Mechanisms and Effects of Music Therapy in Youth With Sickle Cell Disease Using Single-cell RNA-sequencing","Inclusion Criteria:\n\n* Diagnosed with SCD\n* English fluency (for survey completion)\n* Have access to a personal electronic device (e.g., phone, tablet) with access to the internet\n* Meet the criteria for chronic pain defined by the International Association for the Study of Pain (IASP). IASP defines chronic pain as pain that is both:\n\n  1. Persistent or recurrent for ≥ 3 months\n  2. is associated with significant emotional distress or functional disability.30\n\nExclusion Criteria:\n\n* Major hearing deficiency or medical condition in which listening to music may be contraindicated (e.g., reflex epilepsy).","8 Years","18 Years",{"count":7,"type":20},[136],"NA","The goal of this clinical trial is to evaluate whether a 4-week music therapy (MT) intervention can reduce chronic pain and improve psychosocial outcomes in youth with sickle cell disease (SCD).\n\nThe main questions it aims to answer are:\n\n* Does MT reduce pain intensity, frequency of pain episodes, and improve health-related quality of life (HRQoL)?\n* Does MT alter immune cell composition and gene expression in inflammatory pathways, as measured by single-cell RNA sequencing (scRNA-seq)?\n\nResearchers will compare participants randomized to music therapy versus a control condition to see if MT produces superior improvements in pain and psychosocial outcomes, and distinct molecular changes.",[36],[140,141,142],"Music therapy","Pain control","Sickle cell disease","NOT_YET_RECRUITING","2026-06-29",{"date":88,"type":41},{"date":147,"type":20},"2026-07",{"date":149,"type":20},"2028-04",{"name":151,"class":152},"Emory University","OTHER",{"id":154,"slug":155,"hasResults":12,"nctId":156,"briefTitle":157,"officialTitle":158,"acronym":4,"eligibilityCriteria":159,"healthyVolunteers":160,"sex":17,"minAge":103,"maxAge":161,"enrollmentInfo":162,"targetDuration":4,"studyType":61,"phases":164,"briefSummary":165,"conditions":166,"keywords":167,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":144,"lastUpdatePostDateStruct":171,"startDateStruct":172,"completionDateStruct":174,"leadSponsor":176,"locationsCount":125},"100558096","phase-1-a-phase-iii-study-of-itu512-in-healthy-participants-and-patients-with-sickle-cell-disease-100558096","NCT06546670","A Phase I\u002FII Study of ITU512 in Healthy Participants and Patients With Sickle Cell Disease","A Phase I\u002FII Clinical Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of ITU512 in Healthy Participants and Patients With Sickle Cell Disease","Key Inclusion Criteria:\n\nPart 1 (Healthy participants)\n\n* Healthy male participants and female participants of non-childbearing potential between 18-55 years of age\n* In good health as determined by the investigator's assessment of medical history, physical examination, vital signs, ECG, and laboratory tests\n* Participants must weigh at least 50 kg at screening and first baseline (admission) and must have a body mass index (BMI) within the range of 18.0-32.0 kg\u002Fm2 inclusive.\n\nPart 2 (Sickle Cell Disease)\n\n\\- Male and female participants with a diagnosis of sickle cell disease\n\nKey Exclusion Criteria:\n\nPart 1 (Healthy participants)\n\n* QTcF ≥ 450 msec (as a mean value of triplicates)\n* History of arrhythmias\n* History of significant illness which has not resolved within two (2) weeks prior to initial dosing\n* Women of child-bearing potential (WOCBP)\n\nPart 2 (Sickle Cell Disease)\n\n* Current use of hydroxyurea\u002Fhydroxycarbamide (HU\u002FHC)\n* QTcF ≥ 450 msec (as a mean value of triplicates)\n* History of arrhythmias\n\nOther protocol-defined inclusion\u002Fexclusion criteria may apply.",true,"55 Years",{"count":163,"type":20},161,[63,64],"The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary food effect of ITU512 as well as the fetal hemoglobin (HbF)-inducing capacity of ITU512. This will be the first evaluation of the potential therapeutic effect of ITU512 in healthy participants and patients with sickle cell disease (SCD).",[36],[168,169,170,142],"ITU512","Low molecular weight","Small molecule",{"date":116,"type":41},{"date":173,"type":41},"2024-08-15",{"date":175,"type":20},"2030-02-19",{"name":177,"class":124},"Novartis Pharmaceuticals",{"id":179,"slug":180,"hasResults":12,"nctId":181,"briefTitle":182,"officialTitle":182,"acronym":4,"eligibilityCriteria":183,"healthyVolunteers":12,"sex":17,"minAge":103,"maxAge":184,"enrollmentInfo":185,"targetDuration":4,"studyType":21,"phases":4,"briefSummary":187,"conditions":188,"keywords":4,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":189,"lastUpdatePostDateStruct":190,"startDateStruct":191,"completionDateStruct":193,"leadSponsor":195,"locationsCount":80},"100552761","peripheral-arterial-tonometry-and-neurocognition-in-sickle-cell-disease-100552761","NCT06477289","Peripheral Arterial Tonometry and Neurocognition in Sickle Cell Disease","Inclusion Criteria:\n\n* Diagnosed with sickle cell disease of any genotype\n* Participant in the Sickle Cell Clinical Research and Intervention Program\n* Between 12-25 years of age at the time of enrollment\n* English is the primary language\n* Access to an electronic device with WiFi\n\nExclusion Criteria:\n\n* History of an intellectual disability\n* History of a traumatic brain injury or seizure disorder\n* History of a stroke\n* Undergoing potential curative treatment for SCD (stem cell transplant or gene therapy)\n* Currently prescribed an intervention for a sleep disorder\n* Inability or unwillingness of research participant or legal guardian\u002Frepresentative to give written informed consent.","25 Years",{"count":186,"type":20},65,"This study will examine sleep disordered breathing and sleep quality in participants (ages 12-25) diagnosed with sickle cell disease of any genotype. We will utilize remote peripheral arterial tonometry (PAT) and questionnaires to evaluate difficulties with sleep. PAT assessments will occur remotely in the homes of participants.\n\nNeurocognitive, behavioral, and neuroimaging evaluations will occur on the same day as a routine clinic visit.\n\nPrimary Objective:\n\nEvaluate the relationship between nocturnal oxyhemoglobin saturation (SpO2) and neurocognitive functioning (working memory and verbal comprehension) in individuals (ages 12-25) diagnosed with sickle cell disease controlling for age, genotype, and social vulnerability.\n\nSecondary Objective:\n\nAssess differences in white matter integrity, silent cerebral infarcts, neuroinflammation, and functional connectivity among individuals (ages 12-25) diagnosed with sickle cell disease with and without sleep disordered breathing after controlling for age.\n\nAssess differences in self- and caregiver-reported mood and pain severity among individuals (ages 12-25) diagnosed with sickle cell disease with and without sleep disordered breathing after controlling for age.\n\nExploratory Objectives:\n\nExplore the relationship between nocturnal oxyhemoglobin saturation (SpO2) and neurocognitive functioning (attention, processing speed, verbal memory, visual memory, motor dexterity) in individuals (ages 12-25) diagnosed with sickle cell disease controlling for age, genotype, and social vulnerability.\n\nAssess the feasibility of an optical imaging tool (Speckle Contrast Optical Spectroscopy - Open-Motion 3.0) to measure cerebral blood flow and blood volume in patients diagnosed with sickle cell disease (ages 12-25).\n\nAssess the concordance between measurement of cerebral blood flow and volume using speckle contrast optical spectroscopy and arterial spin labeling brain MRI.",[36],"2026-06-25",{"date":144,"type":41},{"date":192,"type":41},"2024-09-16",{"date":194,"type":20},"2028-06",{"name":196,"class":152},"St. Jude Children's Research Hospital",{"id":198,"slug":199,"hasResults":12,"nctId":200,"briefTitle":201,"officialTitle":202,"acronym":203,"eligibilityCriteria":204,"healthyVolunteers":12,"sex":17,"minAge":133,"maxAge":205,"enrollmentInfo":206,"targetDuration":4,"studyType":61,"phases":207,"briefSummary":208,"conditions":209,"keywords":210,"overallStatus":143,"whyStopped":4,"lastUpdateSubmitDate":213,"lastUpdatePostDateStruct":214,"startDateStruct":215,"completionDateStruct":217,"leadSponsor":219,"locationsCount":80},"100644758","virtual-reality-for-scd-voc-100644758","NCT07674277","Virtual Reality for SCD VOC","Randomized EvaLuation of ImmErsive Virtual Experiences in Sickle Cell Disease (RELIEVE-SCD)","RELIEVE-SCD","Inclusion Criteria:\n\n* Adult (age ≥ 18 years) patients\n* History of sickle cell disease\n* Treatment plan by clinical care team includes the use of intravenous opioids to -treat acute pain.\n* Receiving treatment from the Stoler Infusion center\n\nExclusion Criteria:\n\n* Prior enrollment in this study\n* Presenting with a chief complaint suggestive of a complicated crisis (such as concern for acute chest syndrome, splenic sequestration, hepatic sequestration, pulmonary embolism) as determined by the clinical care provider\n* Not being treated with intravenous opioids for the vaso-occlusive crisis\n* Patients who lack the capacity to provide informed consent\n* Medical history of seizures or known intolerance to virtual reality devices\n* In the opinion of the investigator and based on chart review and direct questioning of the patient, there are preexisting disabilities like vision and hearing defects that preclude the use of a head mounted virtual reality device.\n* Known to be pregnant\n* Incarcerated at the time of evaluation\n* Over the age of 89 years old","89 Years",{"count":7,"type":20},[136],"This pilot study will evaluate the feasibility, tolerability, and preliminary analgesic effect of headset-based virtual reality interventions for adults with sickle cell disease experiencing vaso-occlusive crisis treated in an infusion center. Participants will be enrolled during routine outpatient sickle cell clinic visits and may receive study interventions during future qualifying infusion center visits for vaso-occlusive pain. Using a randomized, two-period crossover design, each participant will be assigned to receive two of three headset-based conditions across separate visits: sham 2D headset control, passive immersive 3D virtual reality, or active immersive interactive 3D virtual reality. The primary outcome is pain burden during the first 60 minutes after intervention start, measured as area under the curve of 0-10 numeric rating scale pain scores. Secondary outcomes include feasibility of intervention delivery, headset tolerability, pain at 120 minutes, opioid use, and participant-reported immersion and acceptability.",[36],[211,36,212],"virtual reality (VR)","vaso-occlusive crisis","2026-06-23",{"date":144,"type":41},{"date":216,"type":20},"2026-08-01",{"date":218,"type":20},"2027-12",{"name":220,"class":152},"University of Maryland, Baltimore",{"id":222,"slug":223,"hasResults":12,"nctId":224,"briefTitle":225,"officialTitle":226,"acronym":227,"eligibilityCriteria":228,"healthyVolunteers":12,"sex":17,"minAge":229,"maxAge":58,"enrollmentInfo":230,"targetDuration":4,"studyType":61,"phases":232,"briefSummary":234,"conditions":235,"keywords":4,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":236,"lastUpdatePostDateStruct":237,"startDateStruct":238,"completionDateStruct":240,"leadSponsor":242,"locationsCount":244},"100591087","phase-3-the-efficacy-and-safety-of-rilzabrutinib-in-participants-aged-10-to-65-years-with-sickle-cell-disease-100591087","NCT06975865","The Efficacy and Safety of Rilzabrutinib in Participants Aged 10 to 65 Years With Sickle-cell Disease","A 52-week, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Flexible-adaptive, Group Sequential Study to Evaluate the Efficacy and Safety of Rilzabrutinib in Participants Aged 10 to 65 Years With Sickle-cell Disease","LIBRA","Inclusion Criteria:\n\n* Participants who have been diagnosed with SCD.\n* Participants who have had between ≥2 and ≤10 episodes of documented clinical VOC within 12 months of the screening events.\n* Participants who are either not on hydroxyurea and\u002For L-glutamine at the Screening Visit and does not plan to receive them during the course of the study or has received HU and\u002For L-glutamine for a minimum of 6 months. Participants on hydroxyurea and\u002For L-glutamine must have been on a stable weight-based dose level (mg\u002Fkg) for at least 3 months prior to the Screening Visit, with the intent to continue at the same weight-based dose level for the duration of the study, except for safety reasons.\n* Participants with Eastern Cooperative Oncology Group (ECOG) performance status grade 2 or lower.\n* Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.\n* For participants ≥10 to \\\u003C18 years of age: the parent(s)\u002Flegal guardian(s) must provide written informed consent prior to any study-related procedures being performed.\n\nExclusion Criteria:\n\n* Participants are excluded from the study if any of the following criteria apply: Participants with medical history of lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for the past 3 years.\n* Clinically relevant cardiac abnormality, in the opinion of the Investigator or electrocardiogram (ECG) findings.\n* Participants with history of stroke, or history of abnormal transcranial doppler.\n* Participants with uncontrolled or active HBV infection and\u002For HCV infection including those receiving antiviral therapy at the time of screening.\n* HIV infection.\n* A history of active or latent tuberculosis (TB)\n* Positive COVID-19 molecular test.\n* Participant is taking or has received crizanlizumab (ADAKVEO®) within 90 days and\u002For voxelotor (OXBRYTA®) within 30 days prior to the Screening visit.\n\nThe above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.","10 Years",{"count":231,"type":20},192,[233],"PHASE3","This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, flexible-adaptive, group-sequential study (Part A), followed by an open-label LTE period (Part B) to investigate the efficacy, and safety of rilzabrutinib in participants with sickle-cell disease (SCD).\n\nStudy details include:\n\n* Study duration: a 52-week double-blind period (Part A), followed by an open-label LTE period (Part B). Double-blind period has two parts, 50% (adult only) until the interim analysis (a proof-concept part analogous to a phase 2b study), and 50% (adult and children) after the interim analysis. Only the participants who complete double-blind treatment period (Part A) are eligible to continue to the LTE period. The duration of the LTE period (Part B) will be from the first-participant-in (FPI)-LTE (Part B) until the last participant who enters the LTE has completed 52 weeks.\n* Treatment duration: 52-week double-blind period (Part A); LTE period (Part B) from the (FPI until the last participant who enters the LTE has completed 52 weeks.\n* Visit frequency: Week visits based on the Schedule of Assessments.",[36],"2026-06-22",{"date":213,"type":41},{"date":239,"type":41},"2025-08-12",{"date":241,"type":20},"2028-12-29",{"name":243,"class":124},"Sanofi",53,{"id":246,"slug":247,"hasResults":12,"nctId":248,"briefTitle":249,"officialTitle":250,"acronym":251,"eligibilityCriteria":252,"healthyVolunteers":12,"sex":17,"minAge":253,"maxAge":4,"enrollmentInfo":254,"targetDuration":4,"studyType":61,"phases":256,"briefSummary":257,"conditions":258,"keywords":260,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":236,"lastUpdatePostDateStruct":263,"startDateStruct":265,"completionDateStruct":267,"leadSponsor":269,"locationsCount":80},"100578974","phase-3-efficacy-and-safety-of-tocilizumab-for-acute-chest-syndrome-treatment-in-patients-with-sickle-cell-disease-100578974","NCT06818266","Efficacy and Safety of Tocilizumab for Acute Chest Syndrome Treatment in Patients With Sickle Cell Disease","Efficacy and Safety of Tocilizumab for Acute Chest Syndrome Treatment in Pediatric and Adult Patients With Sickle Cell Disease","TOCIACS","Inclusion Criteria:\n\n1. SCD patient of all genotypes (SS, SC, S\u002Fβ0 and S\u002Fβ+ or other major SCD syndrome)\n2. Age ≥ 2 years old\n3. Hospitalized for ACS, defined by the WHO as the association of fever and\u002For acute respiratory symptoms with a new pulmonary infiltrate on chest imaging, (X-ray, lung ultrasound, or CT scan)\n4. Requiring supplemental oxygen ≥ 2 L\u002Fmin for SpO2 ≥ 95% or non-invasive respiratory support (high flow nasal oxygen or continuous positive airway pressure or bilevel non-invasive ventilation) or invasive mechanical ventilation or ECMO, for less than 48 hours\n5. Negative pregnancy test for girls or women of childbearing age\n6. Freely given, informed and written consent of patient or legal representatives\n7. Affiliation to the social security (or health insurance)\n8. Effective contraception up to 3 months after the administration of treatment (tocilizumab or placebo)\n\nExclusion Criteria:\n\n1. Impossibility to perform tocilizumab\u002Fplacebo injection within the first 48 hours of supplemental oxygen ≥2L\u002Fmin for SpO2≥95% and\u002For respiratory support (as defined in inclusion criteria n°4). If exchange transfusion is indicated at inclusion, it has to be performed before the injection of tocilizumab\u002Fplacebo.\n2. Known hypersensitivity to tocilizumab or its excipients\n3. Known active current severe bacterial, viral, fungal, mycobacterial, or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, hepatitis B and C, and herpes zoster)\n4. Immunization with a live\u002Fattenuated vaccine within the last 4 weeks\n5. Immunomodulatory therapy, anti-rejection therapy, cell depleting therapies and investigational agents within the last 3 months\n6. History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies\n7. History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower gastrointestinal disease such as Crohn's disease, ulcerative colitis, or other symptomatic lower gastrointestinal conditions that might predispose a patient to perforations\n8. Evidence of malignant disease or malignancies diagnosed within the last 3 years\n9. Pregnancy or breastfeeding\n10. Imminent and inevitable progression towards death in the opinion of the investigator\n11. Absolute neutrophil count \\\u003C 1.0 G\u002FL or platelets \\\u003C 50 G\u002FL\n12. ALT or AST \\> 5-fold the upper limit of normal\n13. Glomerular Filtration rate (GFR) \\\u003C 60 mL\u002Fmin\u002F1,73 m²\n14. Current enrolment in another interventional research concerning a medicinal product for human use","2 Years",{"count":255,"type":20},130,[233],"The purpose of this study is to determine whether a single infusion of tocilizumab is effective in reducing the time to successful weaning from both supplemental oxygen and any respiratory support, in pediatric and adult patients with sickle cell disease (SCD) during acute chest syndrome (ACS).",[36,259],"Acute Chest Syndrome",[142,261,262],"Acute chest syndrome","Tocilizumab",{"date":264,"type":41},"2026-06-24",{"date":266,"type":41},"2025-08-27",{"date":268,"type":20},"2027-07",{"name":270,"class":152},"Assistance Publique - Hôpitaux de Paris",{"id":272,"slug":273,"hasResults":12,"nctId":274,"briefTitle":275,"officialTitle":276,"acronym":4,"eligibilityCriteria":277,"healthyVolunteers":12,"sex":17,"minAge":103,"maxAge":4,"enrollmentInfo":278,"targetDuration":4,"studyType":61,"phases":280,"briefSummary":281,"conditions":282,"keywords":4,"overallStatus":143,"whyStopped":4,"lastUpdateSubmitDate":283,"lastUpdatePostDateStruct":284,"startDateStruct":285,"completionDateStruct":287,"leadSponsor":289,"locationsCount":4},"100641605","phase-3-a-study-to-investigate-the-effect-of-mitapivat-on-transfusion-burden-in-subjects-with-sickle-cell-disease-scd-100641605","NCT07656415","A Study to Investigate the Effect of Mitapivat on Transfusion Burden in Subjects With Sickle Cell Disease (SCD)","A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Evaluate the Effect of Mitapivat on Transfusion Burden in Subjects With Sickle Cell Disease","Inclusion Criteria:\n\n* Age ≥12 years.\n* Documented diagnosis of SCD (hemoglobin SS (HbSS), combined heterozygosity for hemoglobins S and C (HbSC), sickle cell hemoglobin (HbS)\u002Fβ0-thalassemia, HbS\u002Fβ+-thalassemia, or other sickle cell syndrome variants).\n* No more than 10 SCPCs in the 12 months before providing informed assent\u002Fconsent.\n* At least 1 transfusion of packed RBCs in the 12 months before informed assent\u002Fconsent.\n* Hb ≥5.5 and ≤10.5 g\u002FdL. Hb concentration must be based on an average of at least 2 Hb concentration measurements (separated by ≥7 days) collected during the Screening Period.\n* Additional signs or symptoms of hemolysis, as evidenced by any laboratory assessment during the Screening Period with\n\n  * Hb \\\u003C8 g\u002FdL, or\n  * Absolute reticulocyte count \\> upper limit of normal (ULN), or\n  * Indirect bilirubin \\>ULN, or\n  * LDH \\>ULN\n* If taking hydroxyurea, the hydroxyurea dose must be stable for at least 90 days prior to randomization. Discontinuation of hydroxyurea requires a 90-day washout prior to informed assent\u002Fconsent.\n* Women of childbearing potential (WOCBP) and pediatric female subjects who have attained menarche must be abstinent of sexual activities that may induce pregnancy as part of their usual lifestyle or agree to use a highly effective method of contraception from the time of providing informed assent\u002Fconsent, throughout the study, and for 28 days after the last dose of study drug; if the highly effective method of contraception is hormonal contraception, then an acceptable barrier method must also be used.\n* Written informed assent\u002Fconsent (for subjects under 18 years of age, or prior to the age at which a subject is considered legally an adult per local regulations, parental permission and child assent will be obtained) must be obtained before any study-related procedures are conducted and subjects must be willing to comply with all study procedures for the duration of the study.\n\nExclusion Criteria:\n\n* Pregnant, breastfeeding, or parturient.\n* Receiving regularly scheduled RBC transfusion therapy (also termed chronic, prophylactic, or preventative transfusion); episodic transfusion in response to worsened anemia or vaso-occlusive crisis (VOC) is permitted. Additionally, a subject who requires episodic transfusion(s) may not have received a transfusion(s) within 60 days before providing informed assent\u002Fconsent or during the Screening Period.\n* Hospitalized for an SCPC and\u002For other vaso-occlusive event within 14 days prior to providing informed assent\u002Fconsent or during the Screening Period. A hospitalization is defined as an in-patient admission to a hospital that may or may not be preceded by an emergency room or outpatient clinic visit. A visit to an emergency room that does not result in an in-patient admission does not meet the definition of hospitalization.\n* Currently receiving treatment with a disease-modifying therapy for SCD (eg, voxelotor, crizanlizumab, L-glutamine), with the exception of hydroxyurea. The last dose of voxelotor, crizanlizumab, and L-glutamine must have been administered at least 90 days before randomization.\n* History of any malignancy except for nonmelanomatous skin cancer in situ, cervical carcinoma in situ, or breast carcinoma in situ. Subjects must not have active disease or received anticancer treatment ≤5 years before providing informed assent\u002Fconsent.\n* History of active and uncontrolled cardiac or pulmonary disease within 6 months before randomization, including but not limited to:\n\n  * New York Heart Association Class III or IV heart failure or clinically significant dysrhythmia.\n  * Myocardial infarction or unstable angina pectoris; hemorrhagic, embolic, or thrombotic stroke; deep venous thrombosis; or pulmonary or arterial embolism.\n  * Heart rate-corrected QT interval using Fridericia's method of ≥470 milliseconds for female subjects and ≥450 milliseconds for male subjects, except for right or left bundle branch block.\n  * Severe pulmonary fibrosis as defined by severe hypoxia, evidence of right-sided heart failure, and radiographic pulmonary fibrosis \\>50%.\n  * Severe pulmonary hypertension as defined by severe symptoms associated with hypoxia, right heart failure, and oxygen indicated.\n* Hepatobiliary disorders including but not limited to:\n\n  * Liver disease with histopathological evidence or clinical diagnosis of cirrhosis or severe fibrosis.\n  * Clinically symptomatic cholelithiasis or cholecystitis (subjects with prior cholecystectomy are eligible).\n  * History of drug-induced cholestatic hepatitis.\n  * Aspartate aminotransferase (AST) \\>2.5× ULN (unless due to hemolysis and\u002For hepatic iron deposition) and alanine aminotransferase (ALT) \\>2.5× ULN (unless due to hepatic iron deposition).\n* Renal dysfunction as defined by an estimated glomerular filtration rate \\\u003C30 milliliters per minute (mL\u002Fmin)\u002F1.73-meter square (m\\^2) by the Chronic Kidney Disease Epidemiology Collaboration creatinine equation.\n* Active uncontrolled infection requiring systemic antimicrobial therapy.\n* Positive test for hepatitis C virus (HCV) antibody (Ab) with evidence of active HCV infection, or positive test for hepatitis B surface antigen (HBsAg).\n* Positive test for human immunodeficiency virus (HIV)-1 antibody or HIV-2 antibody.\n* History of major surgery (including splenectomy) ≤16 weeks before providing informed assent\u002Fconsent and\u002For planning on undergoing a major surgical procedure during the study.\n* Current enrollment or past participation (within 90 days before randomization or a time frame equivalent to 5 half-lives of the investigational study drug, whichever is longer) in any other clinical study involving an investigational study drug or device.\n* Past enrollment in a clinical study involving mitapivat.\n* Prior exposure to gene therapy or prior bone marrow or stem cell transplantation.\n* Currently receiving treatment with hematopoietic stimulating agents; the last dose must have been administered at least 90 days before randomization.\n* Receiving products that are strong inhibitors of Cytochrome3A4\u002F5 (CYP3A4\u002F5) that have not been stopped for ≥5 days or a time frame equivalent to 5 half-lives (whichever is longer), or strong inducers of Cytochrome3A4 (CYP3A4) that have not been stopped for ≥28 days or a time frame equivalent to 5 half-lives (whichever is longer), prior to randomization.\n* Receiving anabolic steroids that have not been stopped for at least 4 weeks before randomization. Testosterone replacement therapy to treat hypogonadism is allowed; the testosterone dose and preparation must be stable for ≥10 weeks before randomization.\n* Known allergy to mitapivat or tablet excipients (microcrystalline cellulose, croscarmellose sodium, sodium stearyl fumarate, mannitol, magnesium stearate, and the Opadry Blue II film-coat \\[hypromellose, titanium dioxide, lactose monohydrate, triacetin, and FD\\&C Blue #2\\]).\n* Any medical, hematological, psychological, or behavioral condition(s), including alcohol use disorder, or prior or current therapy that, in the opinion of the Investigator, may confer an unacceptable risk to participating in the study and\u002For could confound the interpretation of the study data. Also excluded are:\n\n  * Subjects unable to receive RBC transfusions (eg, due to presence of allo-antibodies, lack of blood availability).\n  * Subjects deprived of liberty by court or administrative decision (eg, persons accommodated in an institution by order of an authority or court).\n  * Subjects undergoing psychiatric care without their consent.\n  * Subjects admitted to a health or social establishment for purposes other than research.\n  * Adult Subjects subject to a legal protection measure (guardian, curatorship, legal protection).\n  * Subjects unable to express their consent.\n* Receiving herbal or dietary supplements that have not been stable in dose and preparation for ≥8 weeks prior to randomization.",{"count":279,"type":20},159,[233],"The primary objective of this study is to determine the effect of mitapivat versus placebo on the need for transfusions in subjects with SCD.",[36],"2026-06-19",{"date":213,"type":41},{"date":286,"type":20},"2026-08",{"date":288,"type":20},"2030-08",{"name":290,"class":124},"Agios Pharmaceuticals, Inc.",{"id":292,"slug":293,"hasResults":12,"nctId":294,"briefTitle":295,"officialTitle":296,"acronym":297,"eligibilityCriteria":298,"healthyVolunteers":12,"sex":17,"minAge":103,"maxAge":299,"enrollmentInfo":300,"targetDuration":4,"studyType":61,"phases":302,"briefSummary":303,"conditions":304,"keywords":305,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":319,"lastUpdatePostDateStruct":320,"startDateStruct":321,"completionDateStruct":323,"leadSponsor":325,"locationsCount":326},"100549825","phase-3-a-study-to-investigate-the-efficacy-and-safety-of-crizanlizumab-5-mgkg-compared-with-placebo-in-adolescent-and-adult-sickle-cell-disease-patients-who-experience-frequent-vaso-occlusive-crises-sparkle-100549825","NCT06439082","A Study to Investigate the Efficacy and Safety of Crizanlizumab (5 mg\u002Fkg) Compared With Placebo in Adolescent and Adult Sickle Cell Disease Patients Who Experience Frequent Vaso-Occlusive Crises (SPARKLE)","A Phase III, Multicenter, Randomized, Placebo Controlled, Double-blind Study to Assess Efficacy and Safety of Crizanlizumab (5 mg\u002Fkg) Versus Placebo, With or Without Hydroxyurea\u002FHydroxycarbamide Therapy, in Adolescent and Adult Sickle Cell Disease Patients With Frequent Vaso-Occlusive Crises","SPARKLE","Key Inclusion Criteria:\n\n1. Participants must be aged 12 years and older on the day of signing informed consent. Adolescents include participants aged 12 to \\\u003C18 years old and adults include participants aged 18 years and older.\n2. Confirmed diagnosis of SCD by Hb electrophoresis or high-performance liquid chromatography (HPLC) (performed locally or by central laboratory if not available locally). All SCD genotypes are eligible.\n3. Experienced 4 to 12 VOCs (refer to Section 8.3.1 for study definition of VOC) that are HCP-managed (including VOCs leading to management at a health care facility or those managed via remote consultation) within the 12 months prior to the screening visit. Baseline VOCs are determined by medical history and are required to be documented at source.\n4. If the participant is on HU\u002FHC, they must be taking it for at least 6 months and at stable dose for at least 3 months prior to the Screening visit and plan to continue taking it at the same dose and schedule until at least the participant has reached 52 weeks of the planned study treatment. Participants who have initiated HU\u002FHC 6-12 months prior to the screening visit must have evidence of insufficient control of acute pain despite initiation. These participants must have a cumulative of 4-12 VOCs in the 12 months prior to the screening period, with at least 2 during the last 6 months while on HU\u002FHC. If receiving erythropoietin stimulating agent, the participant must have been receiving the drug for at least 6 months prior to screening visit and plan to continue taking the drug at the same dose and schedule until the participant has reached 52 weeks of the planned study treatment.\n\nParticipants who have not been receiving HU\u002FHC, and\u002For erythropoietin stimulating agent must not have received it for at least 6 months prior to screening visit.\n\nKey Exclusion Criteria:\n\n1. Fewer than 4 or more than 12 VOCs that are HCP-managed (including VOCs leading to management at a health care facility or those managed via remote consultation) within the 12 months prior to screening visit as determined by medical history and documented at source.\n2. History of stem cell transplant and\u002For gene therapy.\n3. Received blood products within 30 days prior to Week 1 Day 1 dosing.\n4. Any documented history of a clinical stroke or intracranial hemorrhage, or an uninvestigated neurologic finding within the past 12 months before screening visit. Silent infarct only present on imaging is not excluded.\n5. Participating in a chronic transfusion program (pre-planned series of transfusions for prophylactic purposes) and\u002For planning to undergo an exchange transfusion during the duration of the study; episodic transfusion in response to worsened anemia or VOC is permitted.\n6. Contraindication or hypersensitivity to any drug or metabolites from similar class as study drug or to any excipients of the study drug formulation. History of severe hypersensitivity reaction to other monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction.","100 Years",{"count":301,"type":20},315,[233],"A phase III, multi-center, randomized, placebo-controlled, double-blind study to assess efficacy and safety of crizanlizumab (5 mg\u002Fkg) versus placebo, with or without hydroxyurea\u002Fhydroxycarbamide therapy, in adolescent and adult Sickle Cell Disease patients with frequent vaso-occlusive crises.",[36],[36,306,307,308,309,310,311,312,313,314,315,316,317,318],"SCD","SEG101","Crizanlizumab","Hydroxyurea\u002F Hydroxycarbamide Therapy","Vaso-Occlusive Crises","Sickle Cell Anemia","blood disorders","hemoglobin","red blood cells","sickle-like shape","mutation in hemoglobin gene","sickle-cell trait","sickle-cell crisis","2026-06-18",{"date":236,"type":41},{"date":322,"type":41},"2024-10-24",{"date":324,"type":20},"2030-04-19",{"name":177,"class":124},32,{"id":328,"slug":329,"hasResults":12,"nctId":330,"briefTitle":331,"officialTitle":331,"acronym":4,"eligibilityCriteria":332,"healthyVolunteers":160,"sex":17,"minAge":133,"maxAge":333,"enrollmentInfo":334,"targetDuration":4,"studyType":21,"phases":4,"briefSummary":336,"conditions":337,"keywords":341,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":344,"lastUpdatePostDateStruct":345,"startDateStruct":346,"completionDateStruct":348,"leadSponsor":350,"locationsCount":80},"100357727","collection-of-human-biospecimens-for-basic-and-clinical-research-into-globin-variants-100357727","NCT03937817","Collection of Human Biospecimens for Basic and Clinical Research Into Globin Variants","* PARTICIPANT INCLUSION CRITERIA:\n\n  1. Aged 18-70 years.\n  2. Able to provide informed consent.\n  3. Willing to allow biological samples to be stored for future research.\n  4. Willing to provide one or more of the following tissues: saliva, urine, blood, blood waste products, adipose tissue, bronchial brushing, and\u002For BAL samples.\n  5. Willing to allow genetic testing on collected biological samples.\n\n     PARTICIPANT EXCLUSION CRITERIA:\n* Exclusion Criteria for All Participants\n\nThe following exclusion criteria apply to all participants who will provide any of the following samples in-person at the NIH CC: saliva, urine, blood, blood waste products, adipose tissue, bronchial brushing, and\u002For BAL samples:\n\n1. Pregnancy.\n2. Positive testing for hepatitis B virus, hepatitis C virus, or HIV (as determined by serum screening tests or relevant viral quantitative studies.)\n3. Any condition that requires active medical intervention or monitoring to avert serious danger to the individual s health or wellbeing.\n4. Any condition that, in the opinion of the PI, contraindicates participation in this study.\n\n   * Additional Exclusion Criteria for Individuals Giving Blood for Research\n\n1\\. Hemoglobin \\\u003C 10 g\u002FdL for healthy female volunteers, \\\u003C 12 g\u002FdL for healthy male volunteers, or \\\u003C 6 g\u002FdL for participants with sickle cell disease or other chronic anemias.\n\n-Additional Exclusion Criteria for Adipose Tissue Biopsy\n\nIndividuals meeting any of the following criteria will be excluded from undergoing adipose tissue biopsy. If the participant no longer meets any of these criteria at a later time, then they will be allowed to undergo this procedure.\n\n1. Currently taking anticoagulation medication.\n2. Platelets \\\u003C 100,000\u002FmicroL.\n3. History of keloid formation (or irregular fibrous tissue formed at the site of a scar or injury).\n4. History of adverse reactions to lidocaine or other local anesthetics.\n5. Any condition that, in the opinion of the PI, contraindicates this procedure.\n\nUse of aspirin (or acetylsalicylic acid) and nonsteroidal anti-inflammatory drugs (NSAIDs) are permitted.\n\n-Additional Exclusion Criteria for Bronchoscopy\n\nIndividuals meeting any of the following criteria will be excluded from undergoing bronchoscopy. If the participant no longer meets any of these criteria at a later time, then they will be allowed to undergo this procedure.\n\n1. Prothrombin time (PT) \\> 1 second above the upper limit of normal (ULN) or international normalized ratio \\> 1.3.\n2. Partial thromboplastin time (PTT) \\> 1 second above ULN.\n3. Platelets \\\u003C 150,000\u002FmicroL.\n4. Currently taking anticoagulation medication.\n5. Use of aspirin within 2 weeks of the bronchoscopy or NSAIDs within 2 days of the bronchoscopy.\n6. Diagnosis of a pulmonary disorder (eg, asthma, chronic bronchitis, cystic fibrosis, or bronchiectasis).\n7. Respiratory tract infection within the last 4 weeks.\n8. History of adverse reactions to systemic and\u002For local anesthetics that will be used for this procedure.\n9. History of cigarette smoking within the past 3 months.\n10. History of chronic opioid use.\n11. History of drug or alcohol abuse.\n12. Post-bronchodilator forced expiratory volume in 1 second (FEV1) \\\u003C 40% of predicted or pre-bronchodilator FEV1 \\\u003C 35% of predicted.\n13. Active bronchospasm on physical examination.\n14. History of lidocaine allergy.\n15. Any condition that, in the opinion of the PI, contraindicates this procedure.\n\nCo-enrollment guidelines: Participants may be co-enrolled in other studies. However, the PI must be notified of co-enrollment.","70 Years",{"count":335,"type":20},300,"Background:\n\nBlood disorders like sickle cell disease and malaria affect many people around the world. Researchers want to learn more about blood disorders. To do this, they need to collect biological samples from people with blood disorders. They also need to collect samples from healthy people.\n\nObjective:\n\nTo collect samples to use for research on blood disorders.\n\nEligibility:\n\nPeople ages 18-70 who have blood disorders. Healthy volunteers without blood disorders are also needed.\n\nDesign:\n\nParticipants will be screened with a medical history, physical exam, and blood and urine tests.\n\nParticipants will give one or more samples. They will give them over 5 years. They can choose not to give any of the samples:\n\nSaliva: Participants will spit into a tube. They may also have the inside of their mouth swabbed.\n\nUrine: Participants will urinate into a cup.\n\nBlood and blood waste products: Blood will be taken through a needle in the participant s arm.\n\nFat samples: An area on the participant s belly or buttock will be numbed. A small cut will be made into the skin and a small piece of fat removed.\n\nMucus and cells from the lungs: The participant will be sedated. A flexible tube will be inserted through the nose or mouth into the lung airways. These participants will also have a physical exam, chest x-ray, and heart tests after the procedure.\n\n...",[338,36,339,340],"Alpha and Beta Thalassemia","Malaria","Human Physiology",[342,339,36,338,343],"Assay Development","Natural History","2026-06-17",{"date":319,"type":41},{"date":347,"type":41},"2019-09-25",{"date":349,"type":20},"2029-03-31",{"name":351,"class":79},"National Institute of Allergy and Infectious Diseases (NIAID)",{"id":353,"slug":354,"hasResults":12,"nctId":355,"briefTitle":356,"officialTitle":357,"acronym":358,"eligibilityCriteria":359,"healthyVolunteers":12,"sex":17,"minAge":103,"maxAge":4,"enrollmentInfo":360,"targetDuration":4,"studyType":61,"phases":362,"briefSummary":363,"conditions":364,"keywords":4,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":365,"lastUpdatePostDateStruct":366,"startDateStruct":367,"completionDateStruct":369,"leadSponsor":371,"locationsCount":373},"100563138","phase-3-a-study-to-evaluate-how-well-etavopivat-works-in-people-with-sickle-cell-disease-100563138","NCT06612268","A Study to Evaluate How Well Etavopivat Works in People With Sickle Cell Disease","A Global Phase 3, Randomised, Double-blind and Placebo-controlled Study Evaluating the Efficacy and Safety of Etavopivat in Adolescents and Adults With Sickle Cell Disease","Hibiscus 2","Inclusion Criteria:\n\n* Male or female.\n* Age 12 years or above at the time of signing the informed consent.\n* Confirmed diagnosis of sickle cell disease: Documentation of sickle cell disease (SCD) genotype (HbSS, HbSβ0-thalassemia or other sickle cell syndrome variants) based on prior history of laboratory testing or screening test results from central laboratory. Molecular genotyping is not required. SCD genotype may be determined from the results of haemoglobin (Hb) electrophoresis, high-performance liquid chromatography (HPLC) or similar testing. Note that Hb electrophoresis is performed by the central laboratory at screening.\n* Have 1-15 episodes of documented vaso occlusive crises (VOC) within the 12 months prior to screening. Documentation must exist in the participant's medical record prior to randomisation. Events based solely on participant recall without supporting documentation should not be counted towards eligibility.\n* Hb greater than or equal to (≥) 5.0 and less than or equal to (≤) 10.0 g\u002FdL (greater than or equal to (≥) 50 and less than or equal to (≤) 100 g\u002FL) at screening.\n\nExclusion Criteria:\n\n* More than 15 VOCs within the past 12 months prior to screening documented in the participant's medical record. Events based solely on participant recall without supporting documentation should not be counted towards eligibility.\n* Use of voxelotor or similar agent within 28 days prior to starting study treatment or anticipated need for this agent during the study.\n* Use of a selectin antagonist (e.g., crizanlizumab, monoclonal antibody or small molecule) within 28 days or 5 half-lives (whichever is longer) prior to starting study treatment or anticipated need for such agents during the study.\n* Receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) or greater than or equal to 6 transfusion events in the previous 12 months (i.e., an average of 1 transfusion event every 60 days).\n* Participants who have received an RBC transfusion for any reason within 60 days of the screening period or 60 days of the randomisation day are only eligible if HbA (adult haemoglobin) less than 10% by Hb electrophoresis is documented prior to starting study treatment.\n* Receiving or use of concomitant medications that are strong inducers of CYP3A4 (cytochrome p450 3a4) within 2 weeks of starting study treatment or anticipated need for such agents during the study.\n* Use of erythropoietin or other haematopoietic growth factor treatment within 28 days of starting study treatment or anticipated need for such agents during the study.\n* Receipt of prior cellular-based therapy (e.g., haematopoietic cell transplant, gene modification therapy).\n* Hepatic dysfunction characterized by:\n\n  * Alanine aminotransferase (ALT) greater than 4.0 × upper limit of normal (ULN) or\n  * Direct bilirubin greater than 3.0 × ULN.\n* Participants who are not taking or are unable to take antimalarial prophylaxis at the time of consent and during the study if they live in areas of endemic malaria where prophylaxis is recommended.\n* Severe renal dysfunction (estimated glomerular filtration rate \\[eGFR\\] at screening, calculated by the central laboratory greater than 30 mL\u002Fmin\u002F1.73 m\\^ 2) or on chronic dialysis.\n* Travelled distance on standardized 6MWT below 100m at screening.",{"count":361,"type":20},408,[233],"This study is conducted to confirm whether etavopivat works well at reducing the number of Vaso-occlusive crisis VOCs (sickle cell pain crises) caused by obstructions in blood vessels in adults and adolescents living with sickle cell disease. The study will also evaluate how well etavopivat can reduce the damage to different organs, improve your exercise tolerance and reduce fatigue in people with sickle cell disease.The participants will either get etavopivat or placebo. Which treatment the participants will get is decided by chance. Etavopivat is a new medicine and is currently being tested in other studies in addition to this one. The study will last for about 2 years.",[36],"2026-06-16",{"date":344,"type":41},{"date":368,"type":41},"2025-02-17",{"date":370,"type":20},"2029-03-12",{"name":372,"class":124},"Novo Nordisk A\u002FS",174,{"id":375,"slug":376,"hasResults":12,"nctId":377,"briefTitle":378,"officialTitle":378,"acronym":379,"eligibilityCriteria":380,"healthyVolunteers":12,"sex":17,"minAge":4,"maxAge":4,"enrollmentInfo":381,"targetDuration":4,"studyType":21,"phases":4,"briefSummary":383,"conditions":384,"keywords":385,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":365,"lastUpdatePostDateStruct":387,"startDateStruct":388,"completionDateStruct":390,"leadSponsor":392,"locationsCount":80},"100369718","hydroxyurea-exposure-limiting-pregnancy-and-follow-up-lactation-100369718","NCT04093986","Hydroxyurea Exposure Limiting Pregnancy and Follow-Up Lactation","HELPFUL","Inclusion Criteria:\n\n* Medical records or data available from previous clinical care prior to June 20, 2019 of pregnant females with SCD, including women who miscarried, had a still birth, or completed labor at any gestational stage, with any hydroxyurea exposure during either pregnancy and\u002For while breastfeeding.\n* Medical records or data available from previous clinical care prior to June 20, 2019 about pregnancy and breastfeeding outcomes, both for babies with hydroxyurea exposure and other babies by these same women.\n\nExclusion Criteria:\n\n* Unavailable medical records or lack of information about hydroxyurea exposure.",{"count":382,"type":20},200,"The purpose of this research study is to document and understand the effects of hydroxyurea exposure for women with SCD and their babies, during both gestation and lactation.",[36,311],[386],"Hydroxyurea",{"date":319,"type":41},{"date":389,"type":41},"2019-12-22",{"date":391,"type":20},"2030-12-31",{"name":393,"class":152},"Children's Hospital Medical Center, Cincinnati",{"id":395,"slug":396,"hasResults":12,"nctId":397,"briefTitle":398,"officialTitle":398,"acronym":399,"eligibilityCriteria":400,"healthyVolunteers":12,"sex":17,"minAge":132,"maxAge":401,"enrollmentInfo":402,"targetDuration":4,"studyType":61,"phases":404,"briefSummary":405,"conditions":406,"keywords":407,"overallStatus":143,"whyStopped":4,"lastUpdateSubmitDate":408,"lastUpdatePostDateStruct":409,"startDateStruct":410,"completionDateStruct":411,"leadSponsor":413,"locationsCount":4},"100577383","transcranial-photobiomodulation-treatment-in-patients-with-sickle-cell-disease-100577383","NCT06797583","Transcranial Photobiomodulation Treatment in Patients With Sickle Cell Disease","PHOTOSCAN","Inclusion Criteria:\n\n* Patient diagnosed with sickle cell disease of any genotype\n* Enrolled in the Sickle Cell Clinical Research and Intervention Program (SCCRIP)\n* Between the ages of 8 to 17 years\n* Primary language is English\n* Participant and Parent\u002FLegal Guardian is willing to participate and provide consent\u002Fassent according to institutional guidelines\n\nExclusion Criteria:\n\n* History of an abnormal transcranial doppler screening\n* History of a documented silent cerebral infarct\n* History of documented central nervous system injury, including a traumatic brain injury, Moya Moya disease, or overt stroke\n* Participant received transfusion treatment within the past three months.","17 Years",{"count":403,"type":20},60,[136],"Participants are being asked to take part in this clinical trial, a type of research study, because investigators want to learn more about oxygen usage in the brain. Patients diagnosed with sickle cell disease are at risk for difficulties with thinking and academic skills. The brain requires a consistent supply of oxygen for normal function, but this supply is reduced among patients with sickle cell disease. The development of new treatments to improve cerebrovascular functioning is needed to limit these difficulties. Transcranial photobiomodulation (i.e., light stimulation to the brain) has the potential to improve cerebrovascular and neurocognitive functioning among patients with sickle cell disease.Participants will be selected randomly (like the flip of a coin) to receive either active light therapy or placebo (no active light treatment).\n\nPrimary Objectives\n\n* Measure the participation rate in a study of transcranial photobiomodulation to improve cognitive functioning in a sample of children with sickle cell disease (ages 8- 17 years).\n* Assess self- and caregiver-reported ratings of feasibility and acceptability.\n* Evaluate the frequency and nature of side effects associated with transcranial photobiomodulation.\n\nSecondary Objectives\n\n* To assess the change in cognitive performance associated with transcranial photobiomodulation compared to a sham control condition.\n* To measure changes in cerebrovascular oxygenation (oxygenated and deoxygenated hemoglobin) following transcranial photobiomodulation compared to a sham control condition.",[36],[36],"2026-06-15",{"date":344,"type":41},{"date":286,"type":20},{"date":412,"type":20},"2029-12",{"name":196,"class":152},{"id":415,"slug":416,"hasResults":12,"nctId":417,"briefTitle":418,"officialTitle":419,"acronym":4,"eligibilityCriteria":420,"healthyVolunteers":12,"sex":17,"minAge":4,"maxAge":421,"enrollmentInfo":422,"targetDuration":424,"studyType":21,"phases":4,"briefSummary":425,"conditions":426,"keywords":4,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":408,"lastUpdatePostDateStruct":427,"startDateStruct":428,"completionDateStruct":430,"leadSponsor":432,"locationsCount":433},"100539288","uganda-sickle-surveillance-study-us-3-100539288","NCT06301893","Uganda Sickle Surveillance Study (US-3)","Prevalence and Mapping of Sickle Cell Trait and Disease in Uganda","Inclusion Criteria:\n\n* Up to 1,000,000 samples may be collected during 2015 - 2030 following primary analysis based on surveillance findings.\n\nExclusion Criteria:\n\n* Repeat samples on the same individuals during the study period will be excluded.","12 Months",{"count":423,"type":20},1000000,"6 Years","It is estimated that over 250,000 babies are born with sickle cell disease (SCD) annually in sub-Saharan Africa, and only 10% - 50% of them survive beyond five years of age. Data describing the magnitude of the sickle cell problem are lacking in most African countries. The available data on prevalence were mainly from older studies and small numbers of hospitalized patients. In Uganda, approximately 25,000 children are born with SCD but 70-80% die before their 5th birthday. Lehmann and Raper found 'sicklaemia' prevalence of 0.8% and 45% in the Sebei and Bambaa ethnic groups, respectively. A recent study found a SCT and SCD prevalence of 3% - 19% and 0% - 3%, respectively but this study addressed only 5 of Uganda's 111 districts and used a small convenience sample of children aged 6 - 60 months. The objective of this study is to determine the prevalence and map out the burden of SCT and SCD in Uganda.",[36],{"date":365,"type":41},{"date":429,"type":41},"2013-09-07",{"date":431,"type":20},"2032-12-31",{"name":393,"class":152},4,{"id":435,"slug":436,"hasResults":12,"nctId":437,"briefTitle":438,"officialTitle":438,"acronym":439,"eligibilityCriteria":440,"healthyVolunteers":12,"sex":17,"minAge":441,"maxAge":4,"enrollmentInfo":442,"targetDuration":4,"studyType":61,"phases":444,"briefSummary":445,"conditions":446,"keywords":4,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":408,"lastUpdatePostDateStruct":447,"startDateStruct":448,"completionDateStruct":450,"leadSponsor":452,"locationsCount":80},"100468755","empowering-adolescents-and-young-adults-with-sickle-cell-disease-as-partners-in-treatment-decision-making-empower-aya-100468755","NCT05383911","Empowering Adolescents and Young Adults With Sickle Cell Disease as Partners in Treatment Decision Making (EMPOWER-AYA)","EMPOWER-AYA","Inclusion Criteria:\n\n* Patients diagnosed with SCD ages 15-25 years receiving treatment at Nemours and their caregivers will be included. Patients must be deemed candidates for initiation of one or more disease-modifying therapies by their SCD healthcare provider.\n* Nemours SCD healthcare providers will also be included.\n* English language fluency is a requirement for all participants.\n\nExclusion Criteria:\n\n* Patients\u002F caregivers who previously participated in usability testing of the intervention will be excluded.\n* Patients will also be excluded if they have history of seizures, if their medical status or cognitive functioning preclude completion of interviews, or if no legal guardian is available to provide consent (for patients \\\u003C 18 years).\n* Providers still completing training will be excluded.","15 Years",{"count":443,"type":20},68,[136],"This study will evaluate the acceptability, feasibility, and preliminary efficacy of a shared decision making intervention for adolescents and young adults (AYAs) with sickle cell disease (SCD). 60 AYAs with SCD ages 15-25 and their caregivers and 8 SCD providers will participate in the pilot pragmatic trial. AYAs, caregivers, and providers will be recruited from Nemours Children's Hospital, Delaware (NCH-DE), Nemours Children's Hospital in Orlando, FL (NCH-ORL), and Nemours Children's Health at Wolfson Children's Hospital in Jacksonville, FL (NCH-JAX). NCH-DE participants (n=30) will receive the SDM intervention including a virtual reality patient health education component, whereas NCH-ORL and NCH-JAX participants (n=30) will receive the SDM intervention with standard patient education materials (print, video). SCD providers will be trained to use the toolkit components and will introduce decision aids during an outpatient clinic visit for AYAs who are candidates for one or more disease-modifying therapies.",[36],{"date":365,"type":41},{"date":449,"type":41},"2024-11-26",{"date":451,"type":20},"2027-06-30",{"name":453,"class":152},"Nemours Children's Clinic",{"id":455,"slug":456,"hasResults":12,"nctId":457,"briefTitle":458,"officialTitle":459,"acronym":460,"eligibilityCriteria":461,"healthyVolunteers":12,"sex":17,"minAge":133,"maxAge":4,"enrollmentInfo":462,"targetDuration":4,"studyType":61,"phases":464,"briefSummary":466,"conditions":467,"keywords":468,"overallStatus":143,"whyStopped":4,"lastUpdateSubmitDate":473,"lastUpdatePostDateStruct":474,"startDateStruct":475,"completionDateStruct":477,"leadSponsor":479,"locationsCount":80},"100642743","early-phase-1-feasibilty-and-acceptability-of-amani-100642743","NCT07648043","Feasibilty and Acceptability of Amani","Feasibilty and Acceptability of Amani, a Virtual Reality Application for Adults With Sickle Cell Disease","Amani","Inclusion Criteria:\n\n* Adults (≥ 18 years) who are diagnosed with sickle cell disease\n* Primarily followed at the Massachusetts General Hospital (MGH) Sickle Cell Disease Center\n* Have ability to comprehend and speak English given Amani is currently only available in English.\n\nExclusion Criteria:\n\n* Have severe psychiatric (psychotic disorder, bipoloar disorder) or cognitive impairment which the treating hematologist believes would preclude ability to participate in the clinical trial",{"count":463,"type":20},40,[465],"EARLY_PHASE1","Adults with sickle cell disease (SCD) experience severe pain, emotional distress, and social isolation that diminish their quality of life. This project will test Amani, a novel virtual reality supportive care intervention designed to improve coping skills and strengthen peer support. If feasible and acceptable, Amani offers an accessible digital supportive care intervention to improve psychological well-being and quality of life among individuals living with SCD and potentially other chronic illnesses.",[36],[111,469,470,471,472],"virtual reality","non-pharmacologic analgesia","social support","coping","2026-06-09",{"date":408,"type":41},{"date":476,"type":20},"2027-01-01",{"date":478,"type":20},"2028-04-30",{"name":480,"class":152},"Massachusetts General Hospital",{"id":482,"slug":483,"hasResults":12,"nctId":484,"briefTitle":485,"officialTitle":486,"acronym":487,"eligibilityCriteria":488,"healthyVolunteers":12,"sex":17,"minAge":253,"maxAge":4,"enrollmentInfo":489,"targetDuration":4,"studyType":61,"phases":491,"briefSummary":492,"conditions":493,"keywords":4,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":494,"lastUpdatePostDateStruct":495,"startDateStruct":497,"completionDateStruct":499,"leadSponsor":501,"locationsCount":502},"100562904","phase-3-a-research-study-looking-at-long-term-treatment-with-etavopivat-in-people-with-sickle-cell-disease-or-thalassaemia-100562904","NCT06609226","A Research Study Looking at Long-term Treatment With Etavopivat in People With Sickle Cell Disease or Thalassaemia","An Open-label, Multi-centre, Rollover Study to Characterise Long-term Safety and Efficacy of Etavopivat in Adults, Adolescents and Children Who Have Sickle Cell Disease or Thalassaemia and Have Completed a Treatment Period in an Etavopivat Study","FLORAL","Inclusion Criteria:\n\n* Participant must have ongoing participation in an etavopivat parent study for treatment of sickle cell disease (SCD) or thalassaemia and have completed at least a treatment period of the parent study.\n* Participant must have derived clinical benefit from treatment with etavopivat, as determined by the investigator.\n* Any participant with dose reduction or temporary discontinuation will need to be successfully rechallenged to the full dose of etavopivat before transferring.\n* Participants on hydroxyurea (HU), crizanlizumab or l-glutamine oral powder (Endari®) treatment at the time of consent may be eligible if they have been on a stable dose in the parent study as defined at the investigator's discretion. Necessary adjustments related to weight or age are accepted. Participants with temporary dose reductions or pauses due to medical reasons may still be considered to have a stable dose, as determined by the investigator, who will assess the impact of these adjustments based on clinical context and the participant's overall health status.\n\nExclusion Criteria:\n\n* Any disorder, except for conditions associated with SCD or thalassaemia, which in the investigator's opinion might jeopardise participant's safety or compliance with the protocol.\n* Participant withdrew or had permanent treatment discontinuation from an etavopivat clinical study.\n* Participants on permanent dose reduction (greater than \\[\\>\\] 28 days or more) or ongoing temporary treatment discontinuation.\n* Use of any of the following within the timeframes prior to the transfer visit as stated:\n* Use of haemoglobin S (HbS) polymerisation inhibitors within participation of the parent study or anticipated need for this agent during this study.\n* Use of an experimental selectin antagonist (e.g., monoclonal antibody or small molecule) within the parent study or anticipated need for such agents during this study.\n* Use of erythropoietin or other haematopoietic growth factor treatment for more than 4 consecutive weeks during the parent study or anticipated need of such agents for a maintenance treatment during this study.\n* Receiving or use of concomitant medications that are strong inducers of cytochrome P450 (CYP) 3A4 within 2 weeks of the transfer visit or anticipated need for such agents during the study.\n* Current participation in a study that is not a designated parent study, or planned participation in any other clinical study, for the duration of FLORAL.",{"count":490,"type":20},480,[233],"Etavopivat is a new medicine under development for treating blood disorders like sickle cell disease and thalassaemia. Sickle cell disease and thalassaemia are inherited blood disorders that affect haemoglobin. Haemoglobin is the protein that carries oxygen through the body. This study is looking into how safe treatment with etavopivat is and how well it works over a long period of time. The study will last for up to 264 weeks, but it will end earlier if etavopivat is approved in the participant's country.",[36,35],"2026-06-08",{"date":496,"type":41},"2026-06-10",{"date":498,"type":41},"2025-01-10",{"date":500,"type":20},"2030-12-30",{"name":372,"class":124},105,{"id":504,"slug":505,"hasResults":12,"nctId":506,"briefTitle":507,"officialTitle":507,"acronym":4,"eligibilityCriteria":508,"healthyVolunteers":12,"sex":17,"minAge":4,"maxAge":4,"enrollmentInfo":509,"targetDuration":229,"studyType":21,"phases":4,"briefSummary":511,"conditions":512,"keywords":525,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":529,"lastUpdatePostDateStruct":530,"startDateStruct":531,"completionDateStruct":533,"leadSponsor":535,"locationsCount":80},"100264360","investigation-of-the-genetics-of-hematologic-diseases-100264360","NCT02720679","Investigation of the Genetics of Hematologic Diseases","Inclusion Criteria:\n\n* An individual (proband) receiving therapy or expert consultation regarding a non-malignant hematologic disorder, MDS or MPN.\n* A biologically-related individual to the identified proband to include: first, second or third degree relatives.\n\nExclusion Criteria:\n\n* None",{"count":510,"type":20},1716,"The purpose of this study is to collect and store samples and health information for current and future research to learn more about the causes and treatment of blood diseases. This is not a therapeutic or diagnostic protocol for clinical purposes. Blood, bone marrow, hair follicles, nail clippings, urine, saliva and buccal swabs, left over tissue, as well as health information will be used to study and learn about blood diseases by using genetic and\u002For genomic research. In general, genetic research studies specific genes of an individual; genomic research studies the complete genetic makeup of an individual.\n\nIt is not known why many people have blood diseases, because not all genes causing these diseases have been found. It is also not known why some people with the same disease are sicker than others, but this may be related to their genes. By studying the genomes in individuals with blood diseases and their family members, the investigators hope to learn more about how diseases develop and respond to treatment which may provide new and better ways to diagnose and treat blood diseases.\n\nPrimary Objective:\n\n* Establish a repository of DNA and cryopreserved blood cells with linked clinical information from individuals with non-malignant blood diseases and biologically-related family members, in conjunction with the existing St. Jude biorepository, to conduct genomic and functional studies to facilitate secondary objectives.\n\nSecondary Objectives:\n\n* Utilize next generation genomic sequencing technologies to Identify novel genetic alternations that associate with disease status in individuals with unexplained non-malignant blood diseases.\n* Use genomic approaches to identify modifier genes in individuals with defined monogenic non-malignant blood diseases.\n* Use genomic approaches to identify genetic variants associated with treatment outcomes and toxicities for individuals with non-malignant blood disease.\n* Use single cell genomics, transcriptomics, proteomics and metabolomics to investigate biomarkers for disease progression, sickle cell disease (SCD) pain events and the long-term cellular and molecular effects of hydroxyurea therapy.\n* Using longitudinal assessment of clinical and genetic, study the long-term outcomes and evolving genetic changes in non-malignant blood diseases.\n\nExploratory Objectives\n\n* Determine whether analysis of select patient-derived bone marrow hematopoietic progenitor\u002Fstem (HSPC) cells or induced pluripotent stem (iPS) cells can recapitulate genotype-phenotype relationships and provide insight into disease mechanisms.\n* Determine whether analysis of circulating mature blood cells and their progenitors from selected patients with suspected or proven genetic hematological disorders can recapitulate genotype-phenotype relationships and provide insight into disease mechanisms.",[513,514,515,516,517,36,518,519,520,521,522,523,524],"Bone Marrow Failure Syndromes","Erythrocyte Disorder","Leukocyte Disorder","Hemostasis","Blood Coagulation Disorder","Dyskeratosis Congenita","Diamond-Blackfan Anemia","Congenital Thrombocytopenia","Severe Congenital Neutropenia","Fanconi Anemia","Myelodysplastic Syndromes","Myeloproliferative Diseases",[526,527,528],"Genetics","Whole genome sequencing","Pediatrics and hematology","2026-06-05",{"date":473,"type":41},{"date":532,"type":41},"2016-06-17",{"date":534,"type":20},"2050-07",{"name":196,"class":152},{"id":537,"slug":538,"hasResults":12,"nctId":539,"briefTitle":540,"officialTitle":541,"acronym":4,"eligibilityCriteria":542,"healthyVolunteers":160,"sex":17,"minAge":133,"maxAge":299,"enrollmentInfo":543,"targetDuration":4,"studyType":21,"phases":4,"briefSummary":545,"conditions":546,"keywords":548,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":529,"lastUpdatePostDateStruct":552,"startDateStruct":553,"completionDateStruct":4,"leadSponsor":555,"locationsCount":80},"100098389","blood-sampling-for-research-related-to-sickle-cell-disease-100098389","NCT00542230","Blood Sampling for Research Related to Sickle Cell Disease","High Sensitivity Screening of Compound Libraries to Discover a Drug for the Treatment of Sickle Cell Disease","* INCLUSION CRITERIA:\n* Patients with sickle cell trait\n* Patients with known hemoglobinopathies involving one or two genes for sickle hemoglobin\n* Healthy volunteers for control experiments\n* Age range: adults greater than or equal to 18 years of age\n\nEXCLUSION CRITERIA:\n\n* Subjects who are unable to comprehend the investigational nature of the laboratory research are ineligible to enroll in this protocol.\n* As a safety precaution in handling the blood samples, patients with HIV, Hepatitis B or Hepatitis C will be excluded from the study. HIV, Hepatitis B or Hepatitits C testing will not be done under this study. Participants must be co-enrolled under another NIH protocol where the screening evaluation has been performed.",{"count":544,"type":20},250,"This study will collect representative blood samples from healthy children and adults and from children and adults who have unique red blood cell features that are related to sickle cell disease. Sickle cell disease is a blood disease that limits the ability of red blood cells to carry oxygen throughout the body. The purpose of the study is to collect a variety of blood samples that may then be used to investigate advances and potential new drug treatments for sickle cell disease.\n\nVolunteers must be at least 18 years of old. Samples will be taken both from healthy volunteers and from volunteers who have unique red blood cell features that are related to sickle cell disease. Candidates will be screened with a medical history.\n\nDuring the study, participants will undergo a one- to two-hour outpatient procedure at the National Institutes of Health Clinical Center. Once researchers have explained the study and obtained the participant s consent, participants will donate 8 cc (approximately 2 teaspoons) of blood.\n\nBecause repeat testing helps researchers validate study findings, participants who have the unique red blood cell features mentioned above may also be asked if they are willing to return and donate another 2 cc to 8 cc of blood for additional studies. The amount of blood drawn will not exceed 50 ml with any eight-week period for adults or 7 cc within any six-week period for children.",[547,36,311],"Sickle Cell Trait",[549,550,547,551,36,343],"Erythrocytes","Drug Screen","Sickle Hemoglobin",{"date":494,"type":41},{"date":554,"type":41},"2007-11-07",{"name":556,"class":79},"National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)",{"id":558,"slug":559,"hasResults":12,"nctId":560,"briefTitle":561,"officialTitle":562,"acronym":4,"eligibilityCriteria":563,"healthyVolunteers":12,"sex":17,"minAge":564,"maxAge":299,"enrollmentInfo":565,"targetDuration":4,"studyType":61,"phases":566,"briefSummary":568,"conditions":569,"keywords":570,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":577,"lastUpdatePostDateStruct":578,"startDateStruct":579,"completionDateStruct":581,"leadSponsor":583,"locationsCount":584},"100412996","phase-4-rollover-study-for-patients-with-sickle-cell-disease-who-have-completed-a-prior-novartis-sponsored-crizanlizumab-study-100412996","NCT04657822","Rollover Study for Patients With Sickle Cell Disease Who Have Completed a Prior Novartis-Sponsored Crizanlizumab Study","An Open-label, Multi-center, Phase IV, Rollover Study for Patients With Sickle Cell Disease Who Have Completed a Prior Novartis-Sponsored Crizanlizumab Study","Inclusion Criteria:\n\n1. Written informed consent\u002Fassent, according to local guidelines, signed by the adult patients. In the population under 18 years, it will be signed by the patient and\u002For by the parents or legal guardian prior to enrolling in the rollover study and receiving study medication\n2. SCD patient currently enrolled in a Novartis-sponsored study receiving crizanlizumab and has fulfilled all the requirements in the parent study. Patient is currently benefiting from the treatment with crizanlizumab as determined by the investigator and has completed the treatment schedule as planned in the parent study\n3. Patient has demonstrated compliance to the planned visit schedule in the parent study, and in the opinion of the investigator has shown willingness and ability to comply with future visit schedules\n\nExclusion Criteria:\n\n1. Patient had permanently discontinued from crizanlizumab study treatment in the parent study before the parent study completion\n2. Ongoing\u002Funresolved treatment-related Grade 3 or higher AEs, and\u002For any ongoing AE requiring dose interruption. Patients meeting all other eligibility criteria may be enrolled once toxicities have resolved unless those toxicities were grade 4\n3. Concurrent participation in any other investigational clinical trial other than the parent study or plan to participate in any other investigational clinical trial\n4. Pregnant or nursing women\n5. Women of childbearing potential who are unwilling to be on highly effective contraceptives during dosing and until 15 weeks after stopping treatment with crizanlizumab\n6. SCD patients who do not meet parent study protocol criteria to continue with crizanlizumab","6 Months",{"count":255,"type":20},[567],"PHASE4","This is a multi-center multi-national rollover study to allow continued access to crizanlizumab for patients with sickle cell disease (SCD) who are on crizanlizumab treatment in a Novartis-sponsored study (parent study) and are benefiting from the treatment as judged by the investigator.",[36],[306,571,572,307,142,573,574,575,576],"Vaso-occlusive Crisis","crizanlizumab","Sickle cell disorder","VOC","P-selectin","Sickle cell anemia","2026-06-04",{"date":494,"type":41},{"date":580,"type":41},"2021-06-10",{"date":582,"type":20},"2031-06-10",{"name":177,"class":124},31,{"id":586,"slug":587,"hasResults":12,"nctId":588,"briefTitle":589,"officialTitle":589,"acronym":4,"eligibilityCriteria":590,"healthyVolunteers":160,"sex":591,"minAge":229,"maxAge":133,"enrollmentInfo":592,"targetDuration":4,"studyType":21,"phases":4,"briefSummary":594,"conditions":595,"keywords":596,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":603,"lastUpdatePostDateStruct":604,"startDateStruct":605,"completionDateStruct":607,"leadSponsor":609,"locationsCount":80},"100623098","functional-ovarian-reserve-in-sickle-cell-disease-100623098","NCT07392216","Functional Ovarian Reserve in Sickle Cell Disease","Inclusion Criteria:\n\n* Sickle cell disease of any genotype or a healthy sibling, relative, household member, or other females of similar race\u002Fethnicity of a patient with sickle cell disease\n* Age at enrollment ≥ 10 years and \\\u003C 19 years\n* Females\n\nExclusion Criteria:\n\n* History of hematopoietic stem cell transplantation or gene therapy prior to enrollment or preparing for hematopoietic stem cell transplantation or gene therapy prior to enrollment\n* Inability or unwillingness of research participant or legal guardian\u002Frepresentative to give written informed consent\n* Pregnancy","FEMALE",{"count":593,"type":20},440,"This study aims to look at AMH levels in female children with SCD as they go through puberty to see if they are at the same level as other children without SCD at the same age and\u002For pubertal stage and will also look at how treatment exposures and pain crises affect the AMH levels in children with SCD.\n\nPrimary Objective:\n\n* To evaluate whether AMH levels are lower in pre-teens and adolescent females with SCD when compared with healthy female controls (siblings, relatives, non-relatives of similar race\u002Fethnicity) at the same age and pubertal stage.\n\nSecondary Objectives:\n\n* To evaluate whether AMH has a similar trajectory in female pre-teens and adolescents with SCD when compared with the general population and controls.\n* To describe pubertal timing, menstrual history, and markers of functional ovarian reserve (FOR), as well as prevalence of premature ovarian insufficiency (POI) as determined by medical history and laboratory markers in pre-teens and adolescents with SCD in comparison with their female controls.\n* To correlate AMH levels with FSH and estradiol levels, normal pubertal timing, and menstrual history in children and adolescents with SCD.\n* To correlate the severity of SCD (number of vaso-occlusive events) with pubertal timing, presence of normal vs abnormal menstruation, and laboratory markers of FOR, in pre-teens and adolescents with SCD.\n* To correlate the use of SCD modifying treatment modalities with pubertal timing, menstrual pattern, and laboratory markers of FOR in pre-teens and adolescents with SCD.",[36],[597,36,598,599,600,601,602],"Ovary Function","Children","Female","Puberty","Anti-Mullerian Hormone (AMH)","Healthy Controls","2026-06-03",{"date":577,"type":41},{"date":606,"type":41},"2026-06-02",{"date":608,"type":20},"2034-02",{"name":196,"class":152},{"id":611,"slug":612,"hasResults":12,"nctId":613,"briefTitle":614,"officialTitle":615,"acronym":4,"eligibilityCriteria":616,"healthyVolunteers":12,"sex":17,"minAge":133,"maxAge":4,"enrollmentInfo":617,"targetDuration":4,"studyType":61,"phases":619,"briefSummary":620,"conditions":621,"keywords":4,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":603,"lastUpdatePostDateStruct":622,"startDateStruct":623,"completionDateStruct":625,"leadSponsor":627,"locationsCount":629},"100607393","phase-1-a-phase-1b-open-label-study-of-disc-3405-in-participants-with-sickle-cell-disease-scd-100607393","NCT07187973","A Phase 1b, Open-Label Study of DISC-3405 in Participants With Sickle Cell Disease (SCD)","A Phase 1b Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DISC-3405 in Participants With Sickle Cell Disease","Inclusion Criteria:\n\n1. Aged 18 years or older at the time of signing the informed consent form (ICF).\n2. Male or female study participants with SCD HbSC or HbSS.\n3. Participants who have been diagnosed with any of the following SCD-related complications: between 1-10 episodes of VOC in the past 12 months, any history of sickle cell related retinopathy, silent cerebral infarct, avascular necrosis, sensorineural hearing loss; or at least 1 episode of priapism, hepatic sequestration, splenic sequestration, or splenic infarct within the last 12 months as assessed locally.\n4. Hgb ≥7.0 g\u002FdL during Screening. The first 2 participants must have an Hgb ≥9 g\u002FdL.\n5. Normal alpha globin gene screen.\n6. Absolute reticulocyte count or % reticulocyte count \\>1.5 × upper limit of normal (ULN) during Screening.\n7. TSAT ≥15% at Screening.\n8. Ferritin ≥50 ng\u002FmL for HbSC or ≥100 ng\u002FmL for HbSS (ferritin must be \\\u003C1000 ng\u002FmL at Screening).\n9. For participants taking hydroxyurea, L-glutamine, or crizanlizumab, stable dose for at least 2 months prior to Screening and with no anticipated need for dose adjustments during the study.\n10. If male, not vasectomized for at least 6 months, with female sexual partner(s) of childbearing potential, agrees he and partner will use double methods of the following highly effective methods of birth control (described below) from the first dose of randomized study drug until 120 days after the last administration of study drug and must not donate sperm during their study participation:\n\n    1. Stable hormonal contraceptive (≥3 months; female partner) in conjunction with a barrier method (eg, condom \\[male or female\\] or diaphragm).\n    2. Intrauterine device, in place for at least 3 months (female partner) in conjunction with a barrier method (eg, condom \\[male or female\\] or diaphragm).\n    3. Surgically sterile by hysterectomy, bilateral oophorectomy, or bilateral tubal ligation (female partner) in conjunction with a barrier method (eg, condom \\[male or female\\] or diaphragm).\n11. If female, then EITHER postmenopausal, defined as at least 12 months natural, spontaneous amenorrhea, 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) \\>40 mIU\u002FmL at Screening, or at least 6 weeks following surgical menopause (bilateral oophorectomy with or without hysterectomy); surgically sterile, OR agree to use 1 of the following highly effective methods of birth control on Day 1 (or earlier) and for at least 120 days after the last administration of study drug:\n\n    1. Stable hormonal contraceptive (≥3 months) in conjunction with a barrier method (eg, condom \\[male or female\\] or diaphragm).\n    2. Intrauterine device, in place for at least 3 months in conjunction with a barrier method (eg, condom \\[male or female\\] or diaphragm).\n    3. Tubal ligation or single male partner with vasectomy in conjunction with a barrier method (eg, condom \\[male or female\\] or diaphragm).\n12. Negative pregnancy test (females of childbearing potential) prior to dosing.\n13. Able to understand the study aims, procedures, and requirements, and provide written informed consent.\n14. Able to comply with all study procedures.\n\nExclusion Criteria:\n\n1. Participants who are receiving regularly scheduled blood (RBC) transfusion therapy or phlebotomy or have received RBC transfusion or phlebotomy within 60 days of Screening.\n2. Hospitalized for VOC or other sickle cell related complication within 14 days of Screening.\n3. Participants with clinically significant bacterial, fungal, parasitic, or viral infection.\n4. Active HIV, hepatitis B, or C. A positive hepatitis or HIV result should be discussed between the Investigator and Sponsor prior to enrollment.\n5. Significant renal dysfunction, evidenced by estimated glomerular filtration rate of \\\u003C60 mL\u002Fmin\u002F1.73 m2 at the Screening visit, as assessed locally.\n6. Hepatic dysfunction characterized by alanine aminotransferase (ALT) \\>2.5 × ULN.\n7. Any episode of ACS in the last 6 months.\n8. Prior or planned hematopoietic stem cell transplant or gene therapy.\n9. History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to Screening.\n10. History of invasive malignancies within the last 5 years, except localized cured prostate cancer and cervical cancer, or other malignancies deemed acceptable by the Sponsor.\n11. Major surgery within 8 weeks before Screening or incomplete recovery from any previous surgery.\n12. A history or known allergic reaction to any IP excipients or history of anaphylaxis to any food or drug.\n13. History of alcohol dependence or excessive alcohol consumption, as assessed by the Investigator.\n14. Other medical or psychiatric condition or laboratory finding not specifically noted above that, in the judgment of the Investigator or Sponsor, would put the participant at an unacceptable risk or otherwise preclude the participant from participating in the study.\n15. Condition or concomitant medication that would confound the ability to interpret clinical, clinical laboratory, including a major psychiatric condition that has had an exacerbation or required hospitalization in the last 6 months.\n16. If female, pregnant or breastfeeding.\n17. Participation in any other clinical protocol or investigational study that involves administration of experimental therapy and\u002For therapeutic devices within 30 days of Screening.\n18. Participants with a history of transient ischemic attack or stroke may be considered in consultation with Sponsor.",{"count":618,"type":20},24,[63],"This is an open-label, multicenter, within-participant dose-escalation study examining up to 3 dose levels of DISC-3405 and will assess the safety, tolerability, PK, and PD of DISC 3405 in participants with sickle cell disease.",[36],{"date":577,"type":41},{"date":624,"type":41},"2026-01-06",{"date":626,"type":20},"2027-10",{"name":628,"class":124},"Disc Medicine, Inc",7]