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

A Phase 3b Study to Evaluate Efficacy and Safety of a Single Dose of Autologous CRISPR Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (CTX001) in Subjects With Transfusion-Dependent β-Thalassemia or Severe Sickle Cell Disease

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Estimated): 26
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Medical Information; Phone Number: 6173416777; Email: medicalinfo@vrtx.com

Study Locations

• Germany
  • Düsseldorf, Germany
    • Recruiting
    • University Hospital Dusseldorf - Department of Pediatric Oncology, Hematology and Clinical Immunology
• Italy
  • Rome, Italy
    • Recruiting
    • IRCSS Ospedale Pediatrico Bambino Gesu - Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica
• Saudi Arabia
  • Al Mathar Ash Shamali, Saudi Arabia
    • Recruiting
    • King Faisal Specialist Hospital & Research Centre - Riyadh - Hematology
• United States
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • New York Presbyterian Hospital - Morgan Stanley Children's Hospital
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Recruiting
      • Levine Children's Hospital - Hematology
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • TriStar Medical Group Children's Specialists - Pediatric Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 35 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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.

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 a single infusion of CTX001 through a central venous catheter.	Biological: CTX001; Administered by intravenous (IV) infusion following myeloablative conditioning with busulfan; Other Names: Exagamglogene autotemcel; Exa-cel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Fetal Hemoglobin (HbF) Concentration Over Time	Up to 12 Months After CTX001 Infusion
Total Hemoglobin (Hb) Concentration Over Time	Up to 12 Months After CTX001 Infusion

Secondary Outcome Measures

Outcome Measure	Time Frame
TDT and SCD: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	From Signing of Informed Consent up to 12 Months After CTX001 Infusion
TDT and SCD: 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
TDT and SCD: Time to Engraftment	Up to 12 Months After CTX001 Infusion
TDT and SCD: Incidence of Transplant-Related Mortality (TRM) Within 100 Days After CTX001 Infusion	Within 100 Days After CTX001 Infusion
TDT and SCD: Incidence of TRM Within 12 Months After CTX001 Infusion	Within 12 Months After CTX001 Infusion
TDT and SCD: Incidence of All-cause Mortality	From Signing of Informed Consent up to 12 Months After CTX001 Infusion
TDT and SCD: Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time	Up to 12 Months After CTX001 Infusion
TDT and SCD: Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time	Up to 12 Months After CTX001 Infusion
TDT: Duration Transfusion Free in Participants	Up to 12 Months After CTX001 Infusion
TDT and SCD: Relative Reduction in Annualized Volume of RBC Transfusions	From Day 60 up to 12 Months After CTX001 Infusion
SCD: Relative Reduction in Annualized Rate of Severe Vaso-Occlusive Crises (VOCs)	From Baseline up to 12 Months After CTX001 Infusion
SCD: Relative Reduction in Annualized Rate of Inpatient Hospitalizations for Severe VOCs	From Baseline up to 12 Months After CTX001 Infusion
SCD: Relative Reduction in Annualized Duration of Hospitalization for Severe VOCs	From Baseline up to 12 Months After CTX001 Infusion
SCD: Relative Reduction in Haptoglobin	From Baseline up to 12 Months After CTX001 Infusion
SCD: Relative Reduction in Lactate dehydrogenase	From Baseline up to 12 Months After CTX001 Infusion
SCD: Relative Reduction in Total Bilirubin	From Baseline up to 12 Months After CTX001 Infusion
SCD: Relative Reduction in Indirect Bilirubin	From Baseline up to 12 Months After CTX001 Infusion

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated
• Collaborators: CRISPR Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2022
• Primary Completion (Estimated): June 9, 2027
• Study Completion (Estimated): June 9, 2027

Study Registration Dates

• First Submitted: July 26, 2022
• First Submitted That Met QC Criteria: July 26, 2022
• First Posted (Actual): July 28, 2022

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 18, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Genetic Diseases, Inborn; Anemia, Sickle Cell; Thalassemia; beta-Thalassemia; Hematologic Diseases; Hemoglobinopathies; exagamglogene autotemcel
• Other Study ID Numbers: VX21-CTX001-161; 2024-514641-12-00 (Other Identifier: EU CT 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/our-science/clinical-trials-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