Evaluation of Safety and Efficacy of CTX001 in Pediatric Participants With Transfusion-Dependent β-Thalassemia (TDT)

Hematologic Diseases Clinical Trial

Official title:

A Phase 3 Study to Evaluate the Safety and Efficacy of a Single Dose of CTX001 in Pediatric Subjects With Transfusion-Dependent β-Thalassemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05356195
• Other study ID #: VX21-CTX001-141
• Secondary ID: 2021-002172-39
• Status: Recruiting
• Phase: Phase 3
• Start date: May 3, 2022
• Est. completion date: May 2026

Study information

• Verified date: April 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 TDT. 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 TDT as defined by:
• Documented homozygous or compound heterozygous ß-thalassemia including ß-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 mL/kilograms (kg)/year of packed RBC transfusions in the prior 24 months before signing of consent (or the last rescreening for patients going through repeat screening) or, for participants initiating transfusion therapy <24 months before signing of consent, requirement for packed RBC transfusion at least every 3 to 4 weeks for =6 months
• Eligible for autologous stem cell transplant as per investigator's judgment.

Key Exclusion Criteria:

• 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)
• Participants with associated a-thalassemia and >1 alpha deletion, or alpha multiplications
• Participants with sickle cell ß-thalassemia variant
• Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Beta-Thalassemia
• Genetic Diseases, Inborn
• Hematologic Diseases
• Hemoglobinopathies
• Thalassemia

Intervention

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

Locations

Country	Name	City	State
Canada	The Hospital for Sick Children	Toronto
Germany	Universitätsklinikum Düsseldorf Hospital Duesseldorf	Düsseldorf
Italy	Ospedale Pediatrico Bambino Gesù, IRCCS	Rome
United Kingdom	Great Ormond Street Hospital for Children NHS Foundation Trust	London
United Kingdom	St Mary's Hospital	London
United States	SCRI at the Children's Hospital at TriStar Centennial	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated	CRISPR Therapeutics

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Participants who Achieve Transfusion Independence for at Least 12 Consecutive Months (TI12)		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	Proportion of Participants who Achieve Transfusion Independence for at Least 6 Consecutive Months (TI6)		Up to 24 Months After CTX001 Infusion
Secondary	Proportion of Participants Achieving at Least 95 Percent (%), 90%, 85%, 75% and 50% Reduction in Annualized Transfusions		From Baseline up to 24 Months After CTX001 Infusion
Secondary	Relative Reduction in Annualized Volume of RBC Transfusions		From Baseline up to 24 Months After CTX001 Infusion
Secondary	Transfusion Free Duration for Participants who Achieve TI12		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	Change in Fetal Hemoglobin Concentration Over Time		From Baseline (Pre-transfusion) up to 24 Months After CTX001 Infusion
Secondary	Change in Total Hemoglobin Concentration Over Time		From Baseline (Pre-transfusion) up to 24 Months After CTX001 Infusion