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

Phase 3RecruitingNCT05356195

Vertex Pharmaceuticals Incorporated15 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Beta-Thalassemia Thalassemia Genetic Diseases, Inborn Hematologic Diseases Hemoglobinopathies

Interventions

Eligibility

Sex: ALLMin age: 2 YearsMax age: 11 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Diagnosis of TDT as defined by: * Documented homozygous or compound heterozygous β-thalassemia including β-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 α-thalassemia and \>1 alpha deletion, or alpha multiplications * Participants with sickle cell β-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.

Locations (6)

TriStar Medical Group Children's Specialists - Pediatric Oncology

Nashville, Tennessee, United States

RECRUITING

Hospital for Sick Children - Hematology

Toronto, Canada

RECRUITING

University Hospital Dusseldorf - Department of Pediatric Oncology, Hematology and Clinical Immunology

Düsseldorf, Germany

RECRUITING

IRCSS Ospedale Pediatrico Bambino Gesu - Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica

Rome, Italy

RECRUITING

Great Ormond Street Hospital for Children

London, United Kingdom

RECRUITING

St.Mary's Hospital - Children's Clinical Research Facility

London, United Kingdom

RECRUITING

Outcomes

Primary Outcomes

Proportion of Participants who Achieve Transfusion Independence for at Least 12 Consecutive Months (TI12)

Time frame: Up to 24 Months After CTX001 Infusion

Secondary Outcomes

Proportion of Participants Achieving at Least 95 Percent (%), 90%, 85%, 75% and 50% Reduction in Annualized Transfusions

Time frame: From Baseline up to 24 Months After CTX001 Infusion

Transfusion Free Duration for Participants who Achieve TI12

Time frame: Up to 24 Months After CTX001 Infusion

Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time

Time frame: Up to 24 Months After CTX001 Infusion

Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time

Time frame: Up to 24 Months After CTX001 Infusion

Change in Fetal Hemoglobin Concentration Over Time

Time frame: From Baseline (Pre-transfusion) up to 24 Months After CTX001 Infusion

Change in Total Hemoglobin Concentration Over Time

Time frame: From Baseline (Pre-transfusion) up to 24 Months After CTX001 Infusion

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time frame: 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)

Time frame: Within 42 Days After CTX001 Infusion

Time to Engraftment

Time frame: Up to 24 Months After CTX001 Infusion

Incidence of Transplant-related Mortality (TRM) Within 100 Days After CTX001 Infusion

Time frame: Within 100 Days After CTX001 Infusion

Incidence of TRM Within 12 Months After CTX001 Infusion

Time frame: Within 12 Months After Infusion

Incidence of All-cause Mortality

Time frame: From Signing of Informed Consent up to 24 Months After CTX001 Infusion

Relative Reduction in Annualized Volume and Episodes of RBC Transfusions starting Month 10 After CTX001 infusion

Time frame: From Baseline up to 24 Months After CTX001 Infusion

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

Overview

Conditions

Interventions

Eligibility

Locations (6)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts