Evaluation of Safety and Efficacy of CTX001 in Pediatric Participants With Severe Sickle Cell Disease (SCD)

A Phase 3 Study to Evaluate the Safety and Efficacy of a Single Dose of CTX001 in Pediatric Subjects With Severe Sickle Cell Disease

This is a single-dose, open-label study in pediatric participants with severe SCD and hydroxyurea (HU) failure or intolerance. 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: Active, not recruiting
• Conditions: Sickle Cell Disease; Hemoglobinopathies; Hematological Diseases; Hydroxyurea Failure; Hydroxyurea Intolerance
• Intervention / Treatment: Biological: CTX001

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Düsseldorf, Germany
    • University Hospital Duesseldorf - Department of Pediatric Oncology, Hematology and Clinical Immunology
• Italy
  • Rome, Italy
    • IRCSS Ospedale Pediatrico Bambino Gesu - Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica
• United Kingdom
  • London, United Kingdom
    • St.Mary's Hospital - Haematology Dept
• United States
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Levine Children's Hospital - Hematology
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia - Hematology
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital
    • Nashville, Tennessee, United States, 37203
      • TriStar Medical Group Children's Specialists - Pediatric Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 11 years (Child)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• 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
• Hydroxyurea (HU) failure unless HU intolerant
• Eligible for autologous stem cell transplant as per investigators judgment

Key Exclusion Criteria:

• A willing and healthy 10/10 human leukocyte antigen (HLA)-matched related donor
• Prior hematopoietic stem cell transplant (HSCT).
• Clinically significant and active bacterial, viral, fungal, or parasitic infection

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 do not Have any Severe Vaso-occlusive Crises (VOCs) for at Least 12 Consecutive Months (VF12)	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 Transplant-related Mortality (TRM) Within 100 Days After CTX001 Infusion	Within 100 Days 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 Participants Free from Inpatient Hospitalization for Severe VOCs for at Least 12 Months (HF12)	Up to 24 Months After CTX001 Infusion
Duration of Severe VOC Free in Participants who Have Achieved VF12	Up to 24 Months After CTX001 Infusion
Proportion of Participants With Sustained Fetal Hemoglobin (HbF) ≥20 Percent (%) for at Least 3 Months	Up to 24 Months After CTX001 Infusion
Proportion of Participants With Sustained HbF ≥20% for at Least 6 Months	Up to 24 Months After CTX001 Infusion
Proportion of Participants With Sustained HbF ≥20% for at Least 12 Months	Up to 24 Months After CTX001 Infusion
Proportion of Participants With Sustained HbF ≥30% for at Least 3 Months	Up to 24 Months After CTX001 Infusion
Proportion of Participants With Sustained HbF ≥30% for at Least 6 Months	Up to 24 Months After CTX001 Infusion
Proportion of Participants With Sustained HbF ≥30% for at Least 12 Months	Up to 24 Months After CTX001 Infusion
Time for Participants to Reach HbF ≥20%	Up to 24 Months After CTX001 Infusion
Time for Participants to Reach HbF ≥30%	Up to 24 Months After CTX001 Infusion
HbF Concentrations Over Time	Up to 24 Months After CTX001 Infusion
Hemoglobin (Hb) Concentrations Over Time	Up to 24 Months After CTX001 Infusion
Change in Reticulocyte Count Over Time	From Baseline up to 24 Months After CTX001 Infusion
Change in Indirect Bilirubin Over Time	From Baseline up to 24 Months After CTX001 Infusion
Change in Haptoglobin Over Time	From Baseline up to 24 Months After CTX001 Infusion
Change in Lactate Dehydrogenase (LDH) Over Time	From Baseline (Pre-infusion) 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
Relative Reduction in Annualized Rate of Severe VOCs	From Baseline up to 24 Months After CTX001 Infusion
Relative Reduction in Annualized Rate of Inpatient Hospitalizations for Severe VOCs	From Baseline up to 24 Months After CTX001 Infusion
Relative Reduction in Annualized Duration of Hospitalization for Severe VOCs	From Baseline up to 24 Months After CTX001 Infusion
Relative Reduction from Baseline in Annualized Volume and Episodes of RBC Transfusions for SCD-related indications starting after Month 12 post-CTX001 infusion	Up to 24 Months After CTX001 Infusion
Proportion of Participants with Detectable Haptoglobin Over Time	Up to 24 Months After CTX001 Infusion
Proportion of Participants with Normalized LDH Over Time	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 2, 2022
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026

Study Registration Dates

• First Submitted: April 7, 2022
• First Submitted That Met QC Criteria: April 7, 2022
• First Posted (Actual): April 15, 2022

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 5, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell; Hematologic Diseases; Hemoglobinopathies; exagamglogene autotemcel
• Other Study ID Numbers: VX21-CTX001-151; 2021-002173-26 (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