Evaluation of Safety and Efficacy of CTX001 in Pediatric Participants With Severe Sickle Cell Disease (SCD)
Study Details
Study Description
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).
| 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 do not Have any Severe Vaso-occlusive Crises (VOCs) for at Least 12 Consecutive Months (VF12) [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 Free from Inpatient Hospitalization for Severe VOCs for at Least 12 Months (HF12) [Up to 24 Months After CTX001 Infusion]
- Relative Change 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 Change in Annualized Rate of Inpatient Hospitalizations for Severe VOCs [From Baseline up to 24 Months After CTX001 Infusion]
- Relative Change in Annualized Duration of Hospitalization 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 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]
- Change in Number of Units of RBC Transfused for SCD-related Indications Over Time [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 Proportion of Circulating Erythrocytes Expressing Fetal Hemoglobin (F-cells) Over Time [From Baseline 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]
- Time to First Detectable Haptoglobin [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]
- Time to First Normalized LDH (Defined as Within Normal Limits per Local Laboratory) [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]
Eligibility Criteria
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 therapy failure or intolerance at any point in the past
-
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/Exclusion criteria may apply.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Children's Hospital at TriStar Centennial Medical Center/ Sarah Cannon Center for Blood Cancers | 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-CTX001-151
- 2021-002173-26