Evaluation of Efficacy and Safety of a Single Dose of CTX001 in Participants With Transfusion-Dependent β-Thalassemia and Severe Sickle Cell Disease

Phase 3RecruitingNCT05477563

Vertex Pharmaceuticals Incorporated26 enrolled

Overview

This is a single-dose, open-label study in participants with transfusion-dependent β-thalassemia (TDT) or severe sickle cell disease (SCD). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) using CTX001.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Beta-Thalassemia Thalassemia Hematologic Diseases Genetic Diseases, Inborn Hemoglobinopathies Sickle Cell Disease

Eligibility

Sex: ALLMin age: 12 YearsMax age: 35 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Participants with TDT and SCD: * Eligible for autologous stem cell transplant as per investigator's judgment. * Participants with TDT: * Diagnosis of TDT as defined by: * Documented homozygous β-thalassemia 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 milliliter (mL)/kilograms (kg)/year or 10 units/year of packed red blood cells (RBC) transfusions in the prior 2 years before signing the consent or the last rescreening for patients going through re-screening * Participants with SCD: * 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 Key Exclusion Criteria: * Participants with TDT and SCD: * 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) * Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator * Participants with TDT: * Participants with associated α-thalassemia and \>1 alpha deletion, or alpha multiplications * Participants with sickle cell β-thalassemia variant * Participants with SCD: * History of untreated moyamoya syndrome or presence of moyamoya syndrome at screening Other protocol defined Inclusion/Exclusion criteria may apply.

Locations (6)

New York Presbyterian Hospital - Morgan Stanley Children's Hospital

New York, New York, United States

RECRUITING

Levine Children's Hospital - Hematology

Charlotte, North Carolina, United States

RECRUITING

TriStar Medical Group Children's Specialists - Pediatric Oncology

Nashville, Tennessee, United States

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

King Faisal Specialist Hospital & Research Centre - Riyadh - Hematology

Al Mathar Ash Shamali, Saudi Arabia

RECRUITING

Outcomes

Primary Outcomes

Fetal Hemoglobin (HbF) Concentration Over Time

Time frame: Up to 12 Months After CTX001 Infusion

Total Hemoglobin (Hb) Concentration Over Time

Time frame: Up to 12 Months After CTX001 Infusion

Secondary Outcomes

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

Time frame: From Signing of Informed Consent up to 12 Months After CTX001 Infusion

TDT and SCD: 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

TDT and SCD: Time to Engraftment

Time frame: Up to 12 Months After CTX001 Infusion

TDT and SCD: Incidence of Transplant-Related Mortality (TRM) Within 100 Days After CTX001 Infusion

Time frame: Within 100 Days After CTX001 Infusion

TDT and SCD: Incidence of TRM Within 12 Months After CTX001 Infusion

Time frame: Within 12 Months After CTX001 Infusion

TDT and SCD: Incidence of All-cause Mortality

Time frame: From Signing of Informed Consent up to 12 Months After CTX001 Infusion

TDT and SCD: Relative Reduction in Annualized Volume of RBC Transfusions

Time frame: From Day 60 up to 12 Months After CTX001 Infusion

TDT and SCD: Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time

Time frame: Up to 12 Months After CTX001 Infusion

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

Time frame: Up to 12 Months After CTX001 Infusion

TDT: Duration Transfusion Free in Participants

Time frame: Up to 12 Months After CTX001 Infusion

SCD: Relative Reduction in Annualized Rate of Severe Vaso-Occlusive Crises (VOCs)