Overview

This is a single-dose, open-label study in participants with transfusion-dependent β-thalassemia (TDT) or severe 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) using CTX001.

Eligibility

Key Inclusion Criteria:

• Participants with TDT and SCD:
  • Eligible for autologous stem cell transplant as per investigator's judgment.
• Participants with TDT:
  • Diagnosis of TDT as defined by:
    • Documented homozygous β-thalassemia or compound heterozygous β-thalassemia including β-thalassemia/hemoglobin E (HbE). Participants 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 milliliter (mL)/kilograms (kg)/year or 10 units/year of packed red blood cells (RBC) transfusions in the prior 2 years before signing the consent or the last rescreening for patients going through re-screening
• Participants with SCD:
  • Diagnosis of severe SCD as defined by:
    • Documented SCD genotypes
    • History of at least two severe VOCs events per year for the previous two years prior to enrollment

Key Exclusion Criteria:

• Participants with TDT and SCD:
  • A willing and healthy 10/10 human leukocyte antigen (HLA)-matched related donor is available per investigator's judgement
  • Prior hematopoietic stem cell transplant (HSCT)
  • Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator
• Participants with TDT:
  • Participants with associated α-thalassemia and >1 alpha deletion, or alpha multiplications
  • Participants with sickle cell β-thalassemia variant
• Participants with SCD:
  • History of untreated moyamoya syndrome or presence of moyamoya syndrome at screening

Other protocol defined Inclusion/Exclusion criteria may apply.