Evaluation of Efficacy and Safety of a Single Dose of CTX001 in Participants With Transfusion-Dependent β-Thalassemia and Severe Sickle Cell Disease
Phase 3
Recruiting
- Conditions
- Beta-ThalassemiaGenetic Diseases, InbornThalassemiaHematologic DiseasesHemoglobinopathiesSickle Cell AnemiaSickle Cell Disease
- Interventions
- Biological: CTX001
- Registration Number
- NCT05477563
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 26
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.
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 a single infusion of CTX001 through a central venous catheter. CTX001 CTX001 CTX001 (autologous CD34+ hHSPCs modified with CRISPR-Cas9 at the erythroid lineage-specific enhancer of the BCL11A gene). Participants will receive a single infusion of CTX001 through a central venous catheter.
- Primary Outcome Measures
Name Time Method Fetal Hemoglobin (HbF) Concentration Over Time Up to 12 Months After CTX001 Infusion Total Hemoglobin (Hb) Concentration Over Time Up to 12 Months After CTX001 Infusion
- Secondary Outcome Measures
Name Time Method 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) Within 42 Days After CTX001 Infusion TDT and SCD: Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time Up to 12 Months After CTX001 Infusion TDT and SCD: Time to Engraftment Up to 12 Months After CTX001 Infusion TDT and SCD: Relative Reduction in Annualized Volume of RBC Transfusions From Day 60 up to 12 Months After CTX001 Infusion TDT: Duration Transfusion Free in Participants Up to 12 Months After CTX001 Infusion SCD: Relative Reduction in Annualized Rate of Inpatient Hospitalizations for Severe VOCs From Baseline up to 12 Months After CTX001 Infusion SCD: Relative Reduction in Haptoglobin From Baseline up to 12 Months After CTX001 Infusion SCD: Relative Reduction in Total Bilirubin From Baseline up to 12 Months After CTX001 Infusion SCD: Relative Reduction in Indirect Bilirubin From Baseline up to 12 Months After CTX001 Infusion TDT and SCD: Incidence of Transplant-Related Mortality (TRM) Within 100 Days After CTX001 Infusion Within 100 Days After CTX001 Infusion TDT and SCD: Incidence of All-cause Mortality From Signing of Informed Consent up to 12 Months After CTX001 Infusion SCD: Relative Reduction in Annualized Rate of Severe Vaso-Occlusive Crises (VOCs) From Baseline up to 12 Months After CTX001 Infusion SCD: Relative Reduction in Lactate dehydrogenase From Baseline up to 12 Months After CTX001 Infusion TDT and SCD: Incidence of TRM Within 12 Months After CTX001 Infusion Within 12 Months After CTX001 Infusion TDT and SCD: Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time Up to 12 Months After CTX001 Infusion SCD: Relative Reduction in Annualized Duration of Hospitalization for Severe VOCs From Baseline up to 12 Months After CTX001 Infusion TDT and SCD: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) From Signing of Informed Consent up to 12 Months After CTX001 Infusion
Trial Locations
- Locations (6)
TriStar Medical Group Children's Specialist
🇺🇸Nashville, Tennessee, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Atrium Health Levine Children's Hospital
🇺🇸Charlotte, North Carolina, United States
Universitätsklinikum Düsseldorf Hospital Duesseldorf
🇩🇪Dusseldorf, Germany
Ospedale Pediatrico Bambino Gesù, IRCCS
🇮🇹Rome, Italy
King Faisal Specialist Hospital and Research Centre
🇸🇦Al Mathar Ash Shamali, Saudi Arabia