Evaluation of Efficacy and Safety of a Single Dose of CTX001 in Participants With Transfusion-Dependent β-Thalassemia and Severe Sickle Cell Disease

Vertex Pharmaceuticals

Status and phase: Enrolling; Phase 3

Conditions: Thalassemia; Beta-Thalassemia; Hemoglobinopathies; Genetic Diseases, Inborn; Sickle Cell Anemia; Sickle Cell Disease; Hematologic Diseases

Treatments: Biological: CTX001

Study type: Interventional

Funder types: Industry

Identifiers

NCT05477563

EU CT number (Other Identifier)

VX21-CTX001-161

Details and patient eligibility

About

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.

Enrollment: 26 estimated patients

Sex: All

Ages: 12 to 35 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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26 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