Evaluation of Efficacy and Safety of a Single Dose of CTX001 in Participants With Transfusion-Dependent β-Thalassemia and Severe Sickle Cell Disease
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Biological: CTX001
Administered by intravenous (IV) infusion following myeloablative conditioning with busulfan.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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]
- 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: Time to Engraftment [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 TRM Within 12 Months After CTX001 Infusion [Within 12 Months After CTX001 Infusion]
- TDT and SCD: Incidence of All-cause Mortality [From Signing of Informed Consent up to 12 Months After CTX001 Infusion]
- TDT and SCD: Relative Change in Annualized Volume of Transfusions [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 [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 [Up to 12 Months After CTX001 Infusion]
- TDT: Duration Transfusion Free in Participants [Up to 12 Months After CTX001 Infusion]
- SCD: Relative Change in Annualized Rate of Severe Vaso-Occlusive Crises (VOCs) [From Baseline up to 12 Months After CTX001 Infusion]
- SCD: Relative Change in Rate of Inpatient Hospitalizations for Severe VOCs [From Baseline up to 12 Months After CTX001 Infusion]
- SCD: Relative Change in Annualized Duration of Hospitalization for Severe VOCs [From Baseline up to 12 Months After CTX001 Infusion]
- SCD: Relative Change in Haptoglobin [From Baseline up to 12 Months After CTX001 Infusion]
- SCD: Relative Change in Lactate dehydrogenase [From Baseline up to 12 Months After CTX001 Infusion]
- SCD: Relative Change in Total Bilirubin [From Baseline up to 12 Months After CTX001 Infusion]
- SCD: Relative Change in Indirect Bilirubin [From Baseline up to 12 Months After CTX001 Infusion]
Eligibility Criteria
Criteria
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
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Participants with SCD:
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Diagnosis of severe SCD as defined by:
-
Documented SCD genotypes
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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)
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Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator
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Participants with TDT:
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Participants with associated α-thalassemia and >1 alpha deletion, or alpha multiplications
-
Participants with sickle cell β-thalassemia variant
-
Participants with SCD:
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History of untreated moyamoya syndrome or presence of moyamoya syndrome at screening
Other protocol defined Inclusion/Exclusion criteria may apply.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Vertex Pharmaceuticals Incorporated
- CRISPR Therapeutics
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- VX21-CTX001-161
- 2021-006390-37