Beta-Thalassemia, Genetic Diseases, Inborn, Hematologic Diseases, Hemoglobinopathies, Thalassemia
Conditions
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).
Interventions
BIOLOGICALCTX001
Administered by intravenous infusion following myeloablative conditioning with busulfan.
Sponsors
Vertex Pharmaceuticals Incorporated
CRISPR Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 11 Years
Healthy volunteers
No
Inclusion 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) * 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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of Participants who Achieve Transfusion Independence for at Least 12 Consecutive Months (TI12) | Up to 24 Months After CTX001 Infusion |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 |
| Relative Reduction in Annualized Volume and Episodes of RBC Transfusions starting Month 10 After CTX001 infusion | From Baseline up to 24 Months After CTX001 Infusion |
Countries
Canada, Germany, Italy, United Kingdom, United States
Outcome results
None listed