A Safety and Efficacy Study Evaluating CTX001 in Participants With Transfusion-Dependent β-Thalassemia

Vertex Pharmaceuticals

Status and phase: Completed; Phase 3; Phase 2

Conditions: Thalassemia; Beta-Thalassemia; Hemoglobinopathies; Genetic Diseases, Inborn; Hematologic Diseases

Treatments: Biological: CTX001

Study type: Interventional

Funder types: Industry

Identifiers

NCT03655678

2024-516894-57-00 (Other Identifier)

CTX001-111

Details and patient eligibility

About

This is a single-arm, open-label, multi-site, single-dose Phase 1/2/3 study in participans 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.

Enrollment: 59 patients

Sex: All

Ages: 12 to 35 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Diagnosis of transfusion-dependent β-thalassemia (TDT) as defined by

  1. 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
  2. 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
• Participants with associated α-thalassemia and >1 alpha deletion or alpha multiplications
• Participants 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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59 participants in 1 patient group

CTX001

Experimental group

Description:

CTX001 (autologous CD34+ hHSPCs modified with CRISPR-Cas9 at the erythroid lineage-specific enhancer of the BCL11A gene). Participants will receive a single infusion of CTX001 through a central venous catheter.

Treatment:

Biological: CTX001