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

A Phase 3 Study to Evaluate the Safety and Efficacy of a Single Dose of CTX001 in Pediatric Subjects With Transfusion-Dependent β-Thalassemia

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).

Study Overview

• Status: Recruiting
• Conditions: Hematologic Diseases; Genetic Diseases, Inborn; Hemoglobinopathies; Thalassemia; Beta-Thalassemia
• Intervention / Treatment: Biological: CTX001

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Medical Information; Phone Number: 617-341-6777; Email: medicalinfo@vrtx.com

Study Locations

• Canada
  • Toronto, Canada
    • Active, not recruiting
    • The Hospital for Sick Children
• Germany
  • Düsseldorf, Germany
    • Recruiting
    • Universitätsklinikum Düsseldorf Hospital Duesseldorf
• Italy
  • Rome, Italy
    • Active, not recruiting
    • Ospedale Pediatrico Bambino Gesù, IRCCS
• United Kingdom
  • London, United Kingdom
    • Recruiting
    • St Mary's Hospital
  • London, United Kingdom
    • Active, not recruiting
    • Great Ormond Street Hospital For Children NHS Foundation Trust
• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Active, not recruiting
      • SCRI at the Children's Hospital at TriStar Centennial

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 months to 9 years (Child)
• Accepts Healthy Volunteers: No

Description

Key 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 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: CTX001; Administered by intravenous infusion following myeloablative conditioning with busulfan.; Other Names: Exagamglogene autotemcel; Exa-cel

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	From Signing of Informed Consent 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
Time to Engraftment	Up to 24 Months After CTX001 Infusion
Incidence of TRM Within 12 Months After CTX001 Infusion	Within 12 Months After Infusion
Incidence of All-cause Mortality	From Signing of Informed Consent 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
Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time	Up to 24 Months 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
Transfusion Free Duration for Participants who Achieve TI12	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
Change in Total Hemoglobin Concentration Over Time	From Baseline (Pre-transfusion) up to 24 Months After CTX001 Infusion
Relative Reduction in Annualized Volume of RBC Transfusions	From Baseline up to 24 Months After CTX001 Infusion

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated
• Collaborators: CRISPR Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2022
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: April 7, 2022
• First Submitted That Met QC Criteria: April 29, 2022
• First Posted (Actual): May 2, 2022

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hematologic Diseases; Thalassemia; beta-Thalassemia; Genetic Diseases, Inborn; Hemoglobinopathies
• Other Study ID Numbers: VX21-CTX001-141; 2021-002172-39 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent-research/clinical-trial-data-sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No