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

Sickle Cell Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05329649
• Other study ID #: VX21-CTX001-151
• Secondary ID: 2021-002173-26
• Status: Recruiting
• Phase: Phase 3
• Start date: May 2, 2022
• Est. completion date: May 2026

Study information

• Verified date: February 2024
• Source: Vertex Pharmaceuticals Incorporated
• Contact: Medical Information
• Phone: 617-341-6777
• Email: medicalinfo[@]vrtx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: May 2026
• Est. primary completion date: May 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 11 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Hematologic Diseases
• Hematological Diseases
• Hemoglobinopathies
• Sickle Cell Disease

Intervention

Biological:
• CTX001
Administered by intravenous infusion following myeloablative conditioning with busulfan.

Locations

Country	Name	City	State
Germany	University Hospital Duesseldorf - Department of Pediatric Oncology, Hematology and Clinical Immunology	Dusseldorf
Italy	Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica Ospedale Pediatrico Bambino Gesu - IRCCS	Rome
United Kingdom	St Mary's Hospital	London
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	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated	CRISPR Therapeutics

Countries where clinical trial is conducted

United States,  Germany,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Proportion of Participants Free from Inpatient Hospitalization for Severe VOCs for at Least 12 Months (HF12)		Up to 24 Months After CTX001 Infusion
Secondary	Relative Reduction in Annualized Rate of Severe VOCs		From Baseline up to 24 Months After CTX001 Infusion
Secondary	Duration of Severe VOC Free in Participants who Have Achieved VF12		Up to 24 Months After CTX001 Infusion
Secondary	Relative Reduction in Annualized Rate of Inpatient Hospitalizations for Severe VOCs		From Baseline up to 24 Months After CTX001 Infusion
Secondary	Proportion of Participants With Sustained Fetal Hemoglobin (HbF) =20 Percent (%) for at Least 3 Months		Up to 24 Months After CTX001 Infusion
Secondary	Proportion of Participants With Sustained HbF =20% for at Least 6 Months		Up to 24 Months After CTX001 Infusion
Secondary	Proportion of Participants With Sustained HbF =20% for at Least 12 Months		Up to 24 Months After CTX001 Infusion
Secondary	Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time		Up to 24 Months After CTX001 Infusion
Secondary	Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time		Up to 24 Months After CTX001 Infusion
Secondary	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)		From Signing of Informed Consent up to 24 Months After CTX001 Infusion
Secondary	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
Secondary	Time to Engraftment		Up to 24 Months After CTX001 Infusion
Secondary	Incidence of Transplant-related Mortality (TRM) Within 100 Days After CTX001 Infusion		Within 100 Days After CTX001 infusion
Secondary	Incidence of TRM Within 12 Months After CTX001 Infusion		Within 12 Months After Infusion
Secondary	Incidence of All-cause Mortality		From Signing of Informed Consent up to 24 Months After CTX001 Infusion
Secondary	Relative Reduction in Annualized Duration of Hospitalization for Severe VOCs		From Baseline up to 24 Months After CTX001 Infusion
Secondary	Proportion of Participants With Sustained HbF =30% for at Least 3 Months		Up to 24 Months After CTX001 Infusion
Secondary	Proportion of Participants With Sustained HbF =30% for at Least 6 Months		Up to 24 Months After CTX001 Infusion
Secondary	Proportion of Participants With Sustained HbF =30% for at Least 12 Months		Up to 24 Months After CTX001 Infusion
Secondary	Time for Participants to Reach HbF =20%		Up to 24 Months After CTX001 Infusion
Secondary	Time for Participants to Reach HbF =30%		Up to 24 Months After CTX001 Infusion
Secondary	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
Secondary	HbF Concentrations Over Time		Up to 24 Months After CTX001 Infusion
Secondary	Hemoglobin (Hb) Concentrations Over Time		Up to 24 Months After CTX001 Infusion
Secondary	Change in Reticulocyte Count Over Time		From Baseline up to 24 Months After CTX001 Infusion
Secondary	Change in Indirect Bilirubin Over Time		From Baseline up to 24 Months After CTX001 Infusion
Secondary	Change in Haptoglobin Over Time		From Baseline up to 24 Months After CTX001 Infusion
Secondary	Proportion of Participants with Detectable Haptoglobin Over Time		Up to 24 Months After CTX001 Infusion
Secondary	Change in Lactate Dehydrogenase (LDH) Over Time		From Baseline (Pre-infusion) up to 24 Months After CTX001 Infusion
Secondary	Proportion of Participants with Normalized LDH Over Time		Up to 24 Months After CTX001 Infusion