Hematological Diseases, Hemoglobinopathies, Hydroxyurea Failure, Hydroxyurea Intolerance, Sickle Cell Disease
Conditions
Brief summary
This is a single-dose, open-label study in pediatric participants with severe SCD and hydroxyurea (HU) failure or intolerance. 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 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 * Hydroxyurea (HU) failure unless HU intolerant * Eligible for autologous stem cell transplant as per investigators judgment Key
Exclusion criteria
* A willing and healthy 10/10 human leukocyte antigen (HLA)-matched related donor * Prior hematopoietic stem cell transplant (HSCT). * Clinically significant and active bacterial, viral, fungal, or parasitic infection Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of Participants who do not Have any Severe Vaso-occlusive Crises (VOCs) for at Least 12 Consecutive Months (VF12) | Up to 24 Months After CTX001 Infusion |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of Participants Free from Inpatient Hospitalization for Severe VOCs for at Least 12 Months (HF12) | Up to 24 Months After CTX001 Infusion |
| Relative Reduction in Annualized Rate of Severe VOCs | From Baseline up to 24 Months After CTX001 Infusion |
| Duration of Severe VOC Free in Participants who Have Achieved VF12 | Up to 24 Months After CTX001 Infusion |
| Relative Reduction in Annualized Rate of Inpatient Hospitalizations for Severe VOCs | From Baseline up to 24 Months After CTX001 Infusion |
| Proportion of Participants With Sustained Fetal Hemoglobin (HbF) ≥20 Percent (%) for at Least 3 Months | Up to 24 Months After CTX001 Infusion |
| Proportion of Participants With Sustained HbF ≥20% for at Least 6 Months | Up to 24 Months After CTX001 Infusion |
| Proportion of Participants With Sustained HbF ≥20% for at Least 12 Months | 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 |
| 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 Duration of Hospitalization for Severe VOCs | From Baseline up to 24 Months After CTX001 Infusion |
| Proportion of Participants With Sustained HbF ≥30% for at Least 3 Months | Up to 24 Months After CTX001 Infusion |
| Proportion of Participants With Sustained HbF ≥30% for at Least 6 Months | Up to 24 Months After CTX001 Infusion |
| Proportion of Participants With Sustained HbF ≥30% for at Least 12 Months | Up to 24 Months After CTX001 Infusion |
| Time for Participants to Reach HbF ≥20% | Up to 24 Months After CTX001 Infusion |
| Time for Participants to Reach HbF ≥30% | Up to 24 Months After CTX001 Infusion |
| Relative Reduction from Baseline in Annualized Volume and Episodes of RBC Transfusions for SCD-related indications starting after Month 12 post-CTX001 infusion | Up to 24 Months After CTX001 Infusion |
| HbF Concentrations Over Time | Up to 24 Months After CTX001 Infusion |
| Hemoglobin (Hb) Concentrations Over Time | Up to 24 Months After CTX001 Infusion |
| Change in Reticulocyte Count Over Time | From Baseline up to 24 Months After CTX001 Infusion |
| Change in Indirect Bilirubin Over Time | From Baseline up to 24 Months After CTX001 Infusion |
| Change in Haptoglobin Over Time | From Baseline up to 24 Months After CTX001 Infusion |
| Proportion of Participants with Detectable Haptoglobin Over Time | Up to 24 Months After CTX001 Infusion |
| Change in Lactate Dehydrogenase (LDH) Over Time | From Baseline (Pre-infusion) up to 24 Months After CTX001 Infusion |
| Proportion of Participants with Normalized LDH Over Time | Up to 24 Months After CTX001 Infusion |
Countries
Germany, Italy, United Kingdom, United States
Outcome results
None listed