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

NCT05329649 | Active Not Recruiting Phase 3 FDA Drug

• 2 other identifiers: VX21-CTX001-1512021-002173-26
• Study Type: interventional
• Target: 13
• Locations: 4 countries
• Sites: 7

Brief Summary

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).

Conditions

Hemoglobinopathies; Hematological Diseases; Sickle Cell Disease; Hydroxyurea Failure; Hydroxyurea Intolerance

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (30)

• Proportion of Participants Free from Inpatient Hospitalization for Severe VOCs for at Least 12 Months (HF12)

  Up to 24 Months After CTX001 Infusion

• Relative Reduction in Annualized Rate of Severe VOCs

  From Baseline 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

• Relative Reduction in Annualized Rate of Inpatient Hospitalizations for Severe VOCs

  From Baseline 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

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 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead
• CRISPR Therapeutics: collaborator

Study Sites (7)

Levine Children's Hospital - Hematology

Charlotte, North Carolina, 28203, United States

Location

The Children's Hospital of Philadelphia - Hematology

Philadelphia, Pennsylvania, 19104, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

TriStar Medical Group Children's Specialists - Pediatric Oncology

Nashville, Tennessee, 37203, United States

Location

University Hospital Duesseldorf - 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

St.Mary's Hospital - Haematology Dept

London, United Kingdom

Location

MeSH Terms

Conditions

Anemia, Sickle Cell; Hemoglobinopathies; Hematologic Diseases

Interventions

exagamglogene autotemcel

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemic and Lymphatic Diseases; Genetic Diseases, Inborn; 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: April 15, 2022
• Study Start: May 2, 2022
• Primary Completion: May 31, 2026
• Study Completion: May 31, 2026
• Last Updated: March 9, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); IT (1); DE (1); US (4)