Evaluation of Safety and Efficacy of CTX001 in Pediatric Participants With Transfusion-Dependent β-Thalassemia (TDT)
Study Details
Study Description
Brief 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).
| 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 single infusion of CTX001 through central venous catheter. |
Biological: CTX001
Administered by intravenous infusion following myeloablative conditioning with busulfan.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Proportion of Participants who Achieve Transfusion Independence for at Least 12 Consecutive Months (TI12) [Up to 24 Months After CTX001 Infusion]
Secondary Outcome Measures
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [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) [Within 42 Days After CTX001 Infusion]
- Time to Engraftment [Up to 24 Months After CTX001 Infusion]
- Incidence of Transplant-related Mortality (TRM) Within 100 Days After CTX001 Infusion [Within 100 Days After CTX001 Infusion]
- Incidence of TRM Within 12 Months After CTX001 Infusion [Within 12 Months After Infusion]
- Incidence of All-cause Mortality [From Signing of Informed Consent up to 24 Months After CTX001 Infusion]
- Proportion of Participants who Achieve Transfusion Independence for at Least 6 Consecutive Months (TI6) [Up to 24 Months After CTX001 Infusion]
- 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]
- Relative Change in Annualized Volume of RBC Transfusions [From Baseline up to 24 Months After CTX001 Infusion]
- Transfusion Free Duration for Participants who Achieve TI12 [Up to 24 Months After CTX001 Infusion]
- Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time [Up to 24 Months After CTX001 Infusion]
- Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time [Up to 24 Months After CTX001 Infusion]
- Change in Fetal Hemoglobin Concentration Over Time [From Baseline (Pre-transfusion) up to 24 Months After CTX001 Infusion]
- Change in Total Hemoglobin Concentration Over Time [From Baseline (Pre-transfusion) up to 24 Months After CTX001 Infusion]
- Change in Proportion of Circulating Erythrocytes Expressing Fetal Hemoglobin (F-cells) Over Time [From Baseline (Pre-transfusion) up to 24 Months After CTX001 Infusion]
Eligibility Criteria
Criteria
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)
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | SCRI at the Children's Hospital at TriStar Centennial | Nashville | Tennessee | United States | 37203 |
Sponsors and Collaborators
- Vertex Pharmaceuticals Incorporated
- CRISPR Therapeutics
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- VX21-CTX001-141
- 2021-002172-39