Title
A Safety and Efficacy Study Evaluating CTX001 in Subjects With Transfusion-Dependent β-Thalassemia
A Phase 1/2/3 Study of the Safety and Efficacy of a Single Dose of Autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (hHSPCs) in Subjects With Transfusion-Dependent β-Thalassemia
Phase
Phase 1/Phase 2Lead Sponsor
CRISPR TherapeuticsStudy Type
InterventionalStatus
Active, not recruitingIndication/Condition
Thalassemia Beta-Thalassemia Genetic Diseases, Inborn Hematologic Diseases HemoglobinopathiesIntervention/Treatment
CTX001Study Participants
45This is a single-arm, open-label, multi-site, single-dose Phase 1/2/3 study in subjects with transfusion-dependent β-thalassemia (TDT). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (hHSPCs) using CTX001.
Administered by IV infusion following myeloablative conditioning with busulfan
CTX001 (autologous CD34+ hHSPCs modified with CRISPR-Cas9 at the erythroid lineage-specific enhancer of the BCL11A gene). Subjects will receive a single infusion of CTX001 through a central venous catheter.
Key Inclusion Criteria: Diagnosis of transfusion-dependent β-thalassemia (TDT) as defined by: Documented homozygous β-thalassemia or compound heterozygous β-thalassemia including β-thalassemia/hemoglobin E (HbE). Subjects can be enrolled based on historical data, but a confirmation of the genotype using the study central laboratory will be required before busulfan conditioning. History of at least 100 mL/kg/year or ≥10 units/year of packed RBC transfusions in the prior 2 years before signing the consent or the last rescreening for patients going through re-screening. Eligible for autologous stem cell transplant as per investigator's judgment. Key Exclusion Criteria: A willing and healthy 10/10 Human Leukocyte Antigen (HLA)-matched related donor is available per investigator's judgement. Prior allo-HSCT. Subjects with associated α-thalassemia and >1 alpha deletion or alpha multiplications. Subjects with sickle cell beta thalassemia variant. Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator. White blood cell (WBC) count <3 × 10^9/L or platelet count <50 × 10^9/L not related to hypersplenism. Other protocol defined Inclusion/Exclusion criteria may apply.
