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

NCT05356195 | Active Not Recruiting Phase 3 FDA Drug

• 2 other identifiers: VX21-CTX001-1412021-002172-39
• Study Type: interventional
• Target: 16
• Locations: 5 countries
• Sites: 6

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).

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants who Achieve Transfusion Independence for at Least 12 Consecutive Months (TI12)

  Up to 24 Months After CTX001 Infusion

Secondary Outcomes (13)

• 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

• 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

• Change in Fetal Hemoglobin Concentration Over Time

  From Baseline (Pre-transfusion) up to 24 Months After CTX001 Infusion

Study Arms (1)

CTX001

EXPERIMENTAL

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

Interventions

CTX001 BIOLOGICAL

Administered by intravenous infusion following myeloablative conditioning with busulfan.

Also known as: Exagamglogene autotemcel, Exa-cel

CTX001

Eligibility Criteria

• Age: 2 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead
• CRISPR Therapeutics: collaborator

Study Sites (6)

TriStar Medical Group Children's Specialists - Pediatric Oncology

Nashville, Tennessee, 37203, United States

Location

Hospital for Sick Children - Hematology

Toronto, Canada

Location

University Hospital Dusseldorf - Department of Pediatric Oncology, Hematology and Clinical Immunology

Düsseldorf, Germany

Location

IRCSS Ospedale Pediatrico Bambino Gesu - Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica

Rome, Italy

Location

Great Ormond Street Hospital for Children

London, United Kingdom

Location

St.Mary's Hospital - Children's Clinical Research Facility

London, United Kingdom

Location

MeSH Terms

Conditions

beta-Thalassemia; Thalassemia; Genetic Diseases, Inborn; Hematologic Diseases; Hemoglobinopathies

Interventions

exagamglogene autotemcel

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2022
• First Posted: May 2, 2022
• Study Start: May 3, 2022
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026
• Last Updated: March 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (1); IT (1); GB (2); DE (1)