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

Phase 3

Recruiting

• Conditions: Hydroxyurea Intolerance; Sickle Cell Disease; Hydroxyurea Failure; Hemoglobinopathies; Hematological Diseases
• Interventions: Biological: CTX001

• Registration Number: NCT05329649
• Lead Sponsor: Vertex Pharmaceuticals Incorporated

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-04-07
• Study First Submitted QC: 2022-04-07
• Study First Posted: 2022-04-15
• Study Start: 2022-05-02
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-16
• Last Update Posted: 2024-10-17
• Primary Completion: 2026-05
• Study Completion: 2026-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 15

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CTX001	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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 HbF ≥20% for at Least 12 Months	Up to 24 Months After CTX001 Infusion
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	From Signing of Informed Consent 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
Hemoglobin (Hb) Concentrations Over Time	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 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 HbF ≥20% for at Least 6 Months	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 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
Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time	Up to 24 Months After CTX001 Infusion
Time to Engraftment	Up to 24 Months After CTX001 Infusion
Incidence of All-cause Mortality	From Signing of Informed Consent up to 24 Months After CTX001 Infusion
Relative Reduction in Annualized Rate of Severe VOCs	From Baseline 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
Time for Participants to Reach HbF ≥20%	Up to 24 Months After CTX001 Infusion
Proportion of Participants with Detectable Haptoglobin Over Time	Up to 24 Months After CTX001 Infusion
Incidence of TRM Within 12 Months After CTX001 Infusion	Within 12 Months After Infusion
Relative Reduction in Annualized Duration of Hospitalization for Severe VOCs	From Baseline 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
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
Change in Reticulocyte Count 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
Proportion of Participants with Normalized LDH Over Time	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
Change in Indirect Bilirubin 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

Trial Locations

Locations (7)

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Atrium Health Levine Children's Hospital; 🇺🇸 Charlotte, North Carolina, United States

St. Jude Children's Research Hospital; 🇺🇸 Memphis, Tennessee, United States

The Children's Hospital at TriStar Centennial Medical Center/ Sarah Cannon Center for Blood Cancers; 🇺🇸 Nashville, Tennessee, United States

University Hospital Duesseldorf - Department of Pediatric Oncology, Hematology and Clinical Immunology; 🇩🇪 Dusseldorf, Germany

Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica Ospedale Pediatrico Bambino Gesu - IRCCS; 🇮🇹 Rome, Italy

St Mary's Hospital; 🇬🇧 London, United Kingdom