[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"leadSponsorName\":\"Fondazione Telethon\",\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:":69},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,2,0,[8,40],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":29,"lastUpdatePostDateStruct":30,"startDateStruct":33,"completionDateStruct":35,"leadSponsor":37,"locationsCount":5},"100645364","phase-2-gene-modified-stem-cell-therapy-for-subjects-with-transfusion-dependent-beta-thalassemia-100645364",false,"NCT07680803","Gene-Modified Stem Cell Therapy for Subjects With Transfusion-dependent Beta-thalassemia","A Single Arm, Open Label, Multicenter, Single-dose, Phase 2b Clinical Study Evaluating Efficacy and Safety of Gene Therapy Using Autologous CD34+ Hematopoietic Stem Cells Transduced With the GLOBE Lentiviral Vector Using an Improved Transduction Protocol in Subjects With Transfusion-dependent Beta-thalassemia","Inclusion Criteria:\n\n1. Must be willing to adhere to the protocol as evidenced by written informed consent for adults or parental informed consent and subject assent for adolescents and children.\n2. Male and female adults\u002Fadolescents\u002Fchildren diagnosed with transfusion-dependent β-thalassemia (homozygous or compound heterozygous). At least 2 out of the 9 patients must have B0\u002FB0 or B0\u002FB0-like genotype. In case the genetic diagnosis available at screening wasn't performed in a certified laboratory (check under PI's or delegated investigator's responsibility), the genetic diagnosis will be repeated at clinical sites during the screening phase.\n3. Documented history of at least 100 ml\u002Fkg\u002Fyear or 10 U\u002Fyear of packed red blood cell transfusions in each of the 2 years prior to signing informed consent.\n4. Age ≥ 18 years and ≤ 35 years for Group 1, Age ≥ 3 years and ≤ 35 years for Group 2.\n5. Karnofsky Index or Lansky ≥ 80%.\n6. Adequate cardiac, renal, hepatic and pulmonary functions resulting in eligibility to undergo autologous HSCT as evidenced by:\n\n   1. Left ventricular ejection fraction (LVEF) greater than 45% by echo and normal ECG or presence of abnormalities not significant for cardiac disease. Absence of severe pulmonary hypertension.\n   2. Diffusing capacity of the lung for carbon monoxide (DLCO) \\> 50% and forced expiratory volume in 1 sec (FEV1) and forced expiratory vital capacity (FVC) \\> 60% predicted (if non cooperative: pulse oximetry \\> 95 % in room air).\n   3. Serum creatinine \\\u003C 2 x upper limit of normal and estimated GFR \\> 60 ml\u002Fmin\u002F1.73m2, calculated using the CKD-EPI formula (Levey 2009) for adults and the modified Schwartz formula (Schwartz 2009) for pediatric patients.\n   4. Absent-mild-moderate liver iron overload on T2\\*MRI (i.e. LIC \\\u003C 15 mg Fe\u002Fgr dry weight assessed at screening. T2\\*MRI at screening can be avoided if performed less than 6 months before enrolment at treatment centers).\n   5. Absent-mild-moderate cardiac iron overload T2\\*MRI (i.e. \\> 20 msec assessed at screening. T2\\*MRI at screening can be avoided if performed less than 6 months before enrolment at treatment centers).\n   6. Absence of severe liver fibrosis or cirrhosis on Shear Wave (less than 6 months before enrolment) or of other advanced liver disorder.\n7. For all patients in reproductive age, agreement to use highly effective and adequate method of contraception for at least 12 months following DP administration (including both females of childbearing potential and males with partners of childbearing potential).\n8. Good adherence to transfusion and chelation programme, as indirect evidence of good adherence to treatment and follow-up evaluations for the current trial.\n9. Availability of an adequate and well documented transfusion history (at least previous 24 months) or availability to follow a regular transfusion regimen according to guidelines and provide a detailed transfusion record of the 24 months prior to the DP administration.\n\nExclusion Criteria:\n\n1. Use of other investigational agents within 4 weeks prior to study enrolment (within 6 weeks if use of long-acting agents).\n2. Severe, active viral, bacterial or fungal infection at eligibility evaluation.\n3. Current or prior malignant neoplasia (except local skin cancer or cervical intraepithelial neoplasia) or exceptional family history of familial cancer syndromes.\n4. Current or prior immunodeficiency disorder.\n5. History of uncontrolled seizures.\n6. Aspartate transaminase (AST), alanine transaminase (ALT) \\>3 × the upper limit of normal (ULN), or direct bilirubin value \\>2.5 × ULN.\n7. Baseline prothrombin time (International Normalized Ratio; INR) \\>1.5 × ULN.\n8. Other clinical conditions judged non compatible with the procedure and\u002For the treatment.\n9. Positivity for HIV (serology or RNA), and\u002For HbsAg and\u002For HBV DNA and\u002For HCV RNA (patients who have completed antiviral treatment for HCV may only be enrolled if they have achieved a sustained virologic response, defined as undetectable HCV RNA at least 12 weeks after completion of therapy) and\u002For evidence of active infection of Treponema Pallidum or Mycoplasma species.\n10. Positive history of significant previous thrombotic events. In case of a positive thrombophilic screening, patient's inclusion will be evaluated according to national guidelines.\n11. Active alcohol or substance abuse within 6 months of the study.\n12. Pregnancy or lactation.\n13. Previous allogeneic hematopoietic stem cell transplantation.\n14. Previous gene therapy treatment (gene addition or gene editing).\n15. For patients until the age of 14 years only: availability of an HLA-matched family donor.\n16. Patients with associated α-thalassemia and \\>1 alpha deletion, or alpha multiplications.\n17. Any other condition that would not allow the potential subject to complete follow-up examinations during the course of the study and, in the opinion of the investigator, makes the potential subject unsuitable for the study.","ALL","3 Years","35 Years",{"count":20,"type":21},9,"ESTIMATED","INTERVENTIONAL",[24],"PHASE2","This is a prospective, dual-centre, single dose, Phase IIb, single arm, open label study. The proposed clinical trial involves a single infusion of autologous HSPCs genetically modified with the GLOBE lentiviral vector, using an improved transduction protocol in 9 patients affected by transfusion dependent Beta-Thalassemia.\n\nFour study phases are foreseen:\n\n1. Screening phase, during which the conditions required by the clinical protocol for patients' inclusion\u002Fexclusion will be assessed after the signature of the informed consents\u002Fassents. Patients will be recruited from the two participating sites: IRCCS Ospedale San Raffaele (OSR), Department of Pediatric Immunohematology and adult Hematology (OSR Stem Cells Programme) (Milan) and IRCCS Ospedale Pediatrico Bambino Gesù (OPBG), Department of Haematology, Oncology and Gene and Cell Therapy (Rome).\n2. Baseline phase, carried from the end of the screening phase to the day before the start of the conditioning regimen.\n3. Treatment phase, from the first day of conditioning regimen until DP administration.\n4. Follow-up phase: from DP administration until 2 years follow-up.",[27],"Transfusion-dependent Beta-Thalassemia","NOT_YET_RECRUITING","2026-07-01",{"date":31,"type":32},"2026-07-02","ACTUAL",{"date":34,"type":21},"2026-07",{"date":36,"type":21},"2030-10",{"name":38,"class":39},"Fondazione Telethon","OTHER",{"id":41,"slug":42,"hasResults":11,"nctId":43,"briefTitle":44,"officialTitle":45,"acronym":46,"eligibilityCriteria":47,"healthyVolunteers":11,"sex":16,"minAge":48,"maxAge":49,"enrollmentInfo":50,"targetDuration":4,"studyType":22,"phases":52,"briefSummary":54,"conditions":55,"keywords":57,"overallStatus":59,"whyStopped":4,"lastUpdateSubmitDate":60,"lastUpdatePostDateStruct":61,"startDateStruct":63,"completionDateStruct":65,"leadSponsor":67,"locationsCount":68},"100644236","phase-1-gene-modified-stem-cell-therapy-for-children-with-autosomal-recessive-osteopetrosis-aro-100644236","NCT07665021","Gene-Modified Stem Cell Therapy for Children With Autosomal Recessive Osteopetrosis (ARO)","A Phase I\u002FII Open Label Study to Assess Safety, Feasibility and Efficacy of ex Vivo Expanded, Autologous Haematopoietic Stem and Progenitor Cell Populations That Contain CD34+ Cells Transduced With a Lentiviral Vector Encoding the TCIRG1 cDNA in Children With Autosomal Recessive Osteopetrosis Caused by Mutations in the TCIRG1 Gene.","ARO","Inclusion Criteria:\n\n1. Diagnosis of autosomal recessive osteopetrosis caused by mutations in the TCIRG1 gene, defined by one of the following:\n\n   1. Clinical features of osteopetrosis and documented pathogenic\u002Flikely pathogenic biallelic variants (homozygosity or compound heterozygosity, whereby at least 1 allele must contain a known pathogenic mutation) in the TCIRG1 gene causing malignant infantile osteopetrosis.\n   2. If a patient presents with clinical features suggestive of severe osteopetrosis (i.e. generalized osteosclerosis, club-shaped long bones, skull base sclerosis, recurrent fractures and osteomyelitis, cranial nerve entrapment leading to visual and\u002For hearing loss, bone marrow insufficiency) and at least one pathogenic\u002Flikely pathogenic mutation of the TCIRG1 gene, the patient is eligible following discussion with an expert in this pathology.\n2. Patient's parents\u002Flegal guardians' capacity to understand the study goals, the study requirements (i.e., attending study visits, completing questionnaires, taking study medications), potential risks associated with joining a study, and willingness to provide verbal and written informed consent.\n3. Age: ≥ 28 days and ≤ 2 years old.\n4. Body weight: ≥ 4 kg.\n5. Adequate cardiac, pulmonary, renal and hepatic function as evidenced by:\n\n   1. Left ventricular ejection fraction (LVEF) ≥45% by echo and normal electrocardiogram (ECG) or presence of abnormalities not significant for cardiac disease. Absence of clinically significant heart valve disease.\n   2. Pulse oximetry ≥90% in room air and no evidence for parenchymal lung disease on chest X-ray or CT scan.\n   3. serum creatinine \\\u003C1.5x upper limit normal in the absence of any form of renal replacement therapy.\n   4. Alanine aminotransferase (ALT) and\u002For aspartate aminotransferase (AST) ≤2.5 x and total bilirubin ≤1.5x upper limit of normal (ULN). Normal coagulation tests (INR \\\u003C1.5).\n\nExclusion Criteria:\n\n1. Availability of a medically appropriate, logistically feasible, fully HLA-matched (10\u002F10) sibling or unrelated donor. The chances of finding a suitable, fully matched unrelated donor should be estimated through a preliminary donor bank search by an experienced transplant team. If the patient is judged unlikely to be treated with a fully matched allogeneic HSCT within 6 weeks from activating search procedures, he\u002Fshe can be considered eligible for this gene therapy study.\n\n   This criterion will not be applied to patients whose country of origin does not offer an allogeneic HSCT as a treatment option.\n2. History of uncontrolled seizures or severe psychiatric symptoms.\n3. Clinically relevant active viral, bacterial or fungal infection.\n4. Positivity for HIV (serology or RNA), and\u002For HbsAg and\u002For HBV DNA and\u002For HCV RNA and\u002For active infection for Treponema Pallidum or Mycoplasma.\n5. Known hypersensitivity to the drugs required for conditioning chemotherapy, or any excipients used in these products.\n6. Use of other investigational agents within 4 weeks prior to study enrolment (within 6 weeks if long-acting agents).\n7. Previous allogeneic HSCT or gene therapy with a different product.\n8. Patients affected by neoplasia, a familial predisposition to hematologic malignancies or any hematologic\u002Fcytogenetic alterations that may suggest a high risk of developing hematologic malignancies.\n9. Patients with end-organ damage or any other severe condition which, in the judgment of the investigator, would make the patient inappropriate for either HSPC collection or autologous transplant.","28 Days","2 Years",{"count":51,"type":21},8,[53,24],"PHASE1","This is a non-randomized, one-arm, open label, single-center, phase I\u002FII, prospective study, to assess safety, feasibility and efficacy of FT024 in 8 children (Age: ≥ 28 days and ≤ 2 years old, Body weight: ≥ 4 kg) affected by ARO-1.\n\nOnce written informed consent has been obtained, and subsequently screening procedures have been completed, harvesting of HSPCs will occur. FT024 manufacturing will occur within a designated GMP manufacturing facility. Following FT024 release, patients will be admitted to the clinical center for the receipt of a reduced toxicity conditioning regimen based on Treosulfan and Thiotepa and then, the infusion of the FT024. Thereafter, regular follow-up of patients will occur for up to 2 years (+720 days).\n\nIn case of partial hematological recovery, additional FT024 boost will be administered without conditioning within + 180 days post first FT024 infusion. At the +720-day visit, patients will be invited to participate in a long-term follow-up study, which will last for an additional 13 years.\n\nPatient recruitment is expected to take 3 years. The study will last approximately 5 years and 6 months, from the first visit of the first patient to the final visit of the last patient. Each patient will take part in the study for about 30 months, from screening to last follow up visit.",[56],"Osteopetrosis",[58],"autosomal recessive osteopetrosis caused by the mutations in TCRG1 gene","RECRUITING","2026-06-18",{"date":62,"type":32},"2026-06-24",{"date":64,"type":21},"2026-06-20",{"date":66,"type":21},"2031-06-30",{"name":38,"class":39},1,""]