Evaluation of Safety and Efficacy of CTX001 in Pediatric Participants With Transfusion-Dependent β-Thalassemia (TDT)

Phase 3

Recruiting

• Conditions: Thalassemia; Genetic Diseases, Inborn; Beta-Thalassemia; Hematologic Diseases; Hemoglobinopathies
• Interventions: Biological: CTX001

• Registration Number: NCT05356195
• Lead Sponsor: Vertex Pharmaceuticals Incorporated

Brief Summary

This is a single-dose, open-label study in pediatric participants with TDT. The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) (CTX001).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-04-07
• Study First Submitted QC: 2022-04-29
• Study First Posted: 2022-05-02
• Study Start: 2022-05-03
• Status Verified: 2024-06
• Last Update Submitted: 2024-10-16
• Last Update Posted: 2024-10-17
• Primary Completion: 2026-05
• Study Completion: 2026-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

• Diagnosis of TDT as defined by:

  • Documented homozygous 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 mL/kilograms (kg)/year of packed RBC transfusions in the prior 24 months before signing of consent (or the last rescreening for patients going through repeat screening) or, for participants initiating transfusion therapy <24 months before signing of consent, requirement for packed RBC transfusion at least every 3 to 4 weeks for ≥6 months

• Eligible for autologous stem cell transplant as per investigator's judgment.

Key

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Exclusion Criteria

• 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)
• Participants with associated α-thalassemia and >1 alpha deletion, or alpha multiplications
• Participants with sickle cell β-thalassemia variant
• Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator

Other protocol defined Inclusion/Exclusion criteria may apply.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Proportion of Participants who Achieve Transfusion Independence for at Least 12 Consecutive Months (TI12)	Up to 24 Months After CTX001 Infusion

Secondary Outcome Measures

Name	Time	Method
Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time	Up to 24 Months After CTX001 Infusion
Change in Fetal Hemoglobin Concentration Over Time	From Baseline (Pre-transfusion) up to 24 Months After CTX001 Infusion
Proportion of Participants With Engraftment (First day of 3 Consecutive Measurements of Absolute Neutrophil Count [ANC] ≥500 per Microliter [mcgL] on 3 Different Days)	Within 42 Days After CTX001 Infusion
Incidence of Transplant-related Mortality (TRM) Within 100 Days After CTX001 Infusion	Within 100 Days After CTX001 Infusion
Proportion of Participants who Achieve Transfusion Independence for at Least 6 Consecutive Months (TI6)	Up to 24 Months After CTX001 Infusion
Proportion of Participants Achieving at Least 95 Percent (%), 90%, 85%, 75% and 50% Reduction in Annualized Transfusions	From Baseline up to 24 Months After CTX001 Infusion
Change in Total Hemoglobin Concentration Over Time	From Baseline (Pre-transfusion) up to 24 Months After CTX001 Infusion
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	From Signing of Informed Consent up to 24 Months After CTX001 Infusion
Time to Engraftment	Up to 24 Months After CTX001 Infusion
Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time	Up to 24 Months After CTX001 Infusion
Incidence of All-cause Mortality	From Signing of Informed Consent up to 24 Months After CTX001 Infusion
Incidence of TRM Within 12 Months After CTX001 Infusion	Within 12 Months After Infusion
Transfusion Free Duration for Participants who Achieve TI12	Up to 24 Months After CTX001 Infusion
Relative Reduction in Annualized Volume and Episodes of RBC Transfusions starting Month 10 After CTX001 infusion	From Baseline up to 24 Months After CTX001 Infusion

Trial Locations

Locations (6)

SCRI at the Children's Hospital at TriStar Centennial; 🇺🇸 Nashville, Tennessee, United States

The Hospital for Sick Children; 🇨🇦 Toronto, Canada

Universitätsklinikum Düsseldorf Hospital Duesseldorf; 🇩🇪 Düsseldorf, Germany

Ospedale Pediatrico Bambino Gesù, IRCCS; 🇮🇹 Rome, Italy

Great Ormond Street Hospital for Children NHS Foundation Trust; 🇬🇧 London, United Kingdom

St Mary's Hospital; 🇬🇧 London, United Kingdom