[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100538150":3},{"organization":4,"armGroups":7,"interventions":14,"overallOfficials":21,"centralContacts":26,"locations":30,"responsibleParty":32,"collaborators":34,"id":37,"slug":38,"hasResults":39,"nctId":40,"briefTitle":41,"officialTitle":42,"acronym":30,"eligibilityCriteria":43,"healthyVolunteers":39,"sex":44,"minAge":45,"maxAge":46,"enrollmentInfo":47,"targetDuration":30,"studyType":50,"phases":51,"briefSummary":53,"conditions":54,"keywords":30,"overallStatus":56,"whyStopped":30,"lastUpdateSubmitDate":57,"lastUpdatePostDateStruct":58,"startDateStruct":61,"completionDateStruct":63,"leadSponsor":65,"locationsCount":30},{"fullName":5,"class":6},"Bioray Laboratories","INDUSTRY",[8],{"label":9,"type":10,"description":11,"interventionNames":12},"BRL-101","EXPERIMENTAL","BRL-101 (autologous CD34+ hHSPCs modified with CRISPR-Cas9 at the BCL11A gene. Subjects will receive a single infusion of BRL-101.",[13],"Drug: BRL-101 autologous hematopoietic stem and progenitor cells injection",[15],{"type":16,"name":17,"description":18,"armGroupLabels":19,"otherNames":20},"DRUG","BRL-101 autologous hematopoietic stem and progenitor cells injection","CD34 + autologous hematopoietic stem and progenitor cells edited at the BCL11A gene.",[9],[9],[22],{"name":23,"affiliation":24,"role":25},"Jun shi, PhD","Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College","STUDY_CHAIR",[27],{"name":23,"role":28,"phone":29,"phoneExt":30,"email":31},"CONTACT","13752253515",null,"shijun@ihcams.ac.cn",{"type":33,"investigatorFullName":30,"investigatorTitle":30,"investigatorAffiliation":30,"oldNameTitle":30,"oldOrganization":30},"SPONSOR",[35],{"name":24,"class":36},"UNKNOWN","100538150","clinical-study-on-the-safety-and-efficacy-of-brl-101-in-the-treatment-of-sickle-cell-disease-100538150",false,"NCT06287086","Clinical Study on the Safety and Efficacy of BRL-101 in the Treatment of Sickle Cell Disease","Clinical Study on the Safety and Efficacy of a Single Intravenous Dose of CRISPR\u002FCas9-Edited Autologous CD34+ Hematopoietic Stem\u002FProgenitor Cells (BRL-101) in the Treatment of Sickle Cell Disease","Inclusion Criteria:\n\nSubjects must meet all the following inclusion criteria to be eligible for enrolment into the study:\n\n1. Subject (or their legally authorized representative or guardian) will sign and date an informed consent form (ICF) and, where applicable, an assent form.\n2. Subjects 3 to 35 years of age, inclusive, on the date of informed consent.\n3. Clinically confirmed severe SCD, genotypes include: βS\u002FβS, βS\u002Fβ + or βS\u002Fβ0. Severe SCD is defined as having at least 2 VOC events per year during the 2 years prior to screening and requiring appropriate supportive care, including a pain management program, HU therapy (if indicated).\n4. Karnofsky performance status of ≥80% for subjects ≥16 years of age. Lansky performance status of ≥80% for subjects \\\u003C16 years of age (see Appendix 1 and 2).\n5. Eligible for autologous stem cell transplant as per investigator's judgment.\n6. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, contraceptive guidelines, and other study procedures.\n7. Willing to participate in an additional long-term follow-up study after completion of this study (Study 2022-LTF-BRL-101).\n8. Subjects of childbearing potential must use effective contraception for at least 6 months after BRL-101 infusion during the study.\n\nExclusion Criteria\n\nSubjects meeting any of the following criteria are not eligible for enrolment in the study:\n\n1. Known contraindications, intolerance, or hypersensitivity to hematopoietic stem cell mobilizers, busulfan injection, or dimethyl sulfoxide (DMSO) or study drug-related components.\n2. Eligible for allogeneic hematopoietic stem cell transplantation and have found HLA-identical donors.\n3. Prior allo-HSCT, gene therapy or gene editing therapy.\n4. Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator.\n5. HbF level \\>15.0%, irrespective of concomitant treatment with HbF inducing treatments such as HU.\n6. Treatment with regular RBC transfusions that, in the opinion of the investigator, cannot be interrupted after engraftment.\n7. More than 10 unplanned hospitalizations or emergency department visits related to SCD in the 1 year before screening and the investigator considered this to be a significant chronic pain rather than an acute pain crisis.\n8. A history of clinically significant transcranial Doppler (TCD) test abnormalities or test abnormalities in the opinion of the investigator.\n9. History of untreated Moyamoya disease or presence of Moyamoya disease at Screening that in the opinion of the investigator puts the subjects at the risk of bleeding.\n10. the subject has participated in other clinical studies and used drugs within 3 months before screening.\n11. White blood cell count \\\u003C 3 × 109\u002FL and\u002For platelet count \\\u003C 100 × 109\u002FL not due to hypersplenism as judged by the investigator.\n12. INR \\> 1.5×ULN, APTT \\> 1.5×ULN.\n13. Creatinine \\> 1.5 × ULN or endogenous creatinine clearance \\\u003C 60 ml\u002Fmin (calculated according to the Cockcroft-Gault formula, see Appendix 3).\n14. ALT or AST\\> 3×ULN, or direct bilirubin value \\> 2.5×ULN.\n15. Severe iron overload with serum ferritin ≥ 5000 ng\u002Fml, liver iron \\> 15 mg Fe\u002Fg dry weight (or liver MRIT2\\* \\\u003C 1.4 ms or \\> 588 Hz), or heart MRI-T2\\* \\\u003C 10 ms.\n16. LVEF \\\u003C 50%.\n17. DLco \\\u003C 50% predicted (corrected haemoglobin or\u002Fand alveolar volume) or forced vital capacity (FVC) (measured\u002Fpredicted) \\\u003C 60% (For children for whom DLco could not be determined), or abnormal blood gas analysis (for younger children with undetectable ventilatory function only).\n18. Hepatitis B virus surface antigen (HBsAg) positive or HBV-DNA positive; hepatitis C virus (HCV) antibody positive; human immunodeficiency virus (HIV) antibody positive; syphilis (TP) -specific antibody positive; Epstein-Barr virus EBV-DNA positive; cytomegalovirus CMV-DNA positive.\n19. History of a significant bleeding disorder.\n20. History or family history of malignancy or myeloproliferative disorder.\n21. Any prior or current cardiovascular system diseases, such as congestive heart failure, arrhythmia, myocardial disease, valvular heart disease or pulmonary hypertension; cirrhosis, liver fibrosis or active hepatitis; central nervous system diseases or mental illness.\n22. Presence of immune dysfunction or endocrine disorders, such as insulin-dependent diabetes mellitus, hyperthyroidism, or insufficiency.\n23. Pregnant or breastfeeding females.\n24. Any condition that, in the opinion of the investigator, would make participation in this clinical study inappropriate.","ALL","3 Years","35 Years",{"count":48,"type":49},1,"ESTIMATED","INTERVENTIONAL",[52],"NA","This is a single center, non-randomized, open label, single-dose study in subjects with Sickle Cell Disease (SCD). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) (BRL-101)",[55],"Sickle Cell Disease","NOT_YET_RECRUITING","2024-05-30",{"date":59,"type":60},"2024-06-03","ACTUAL",{"date":62,"type":49},"2024-06-14",{"date":64,"type":49},"2026-06-10",{"name":5,"class":6}]