Evaluation of Efficacy and Safety of a Single Dose of Exa-cel in Participants With Severe Sickle Cell Disease, βS/βC Genotype
Study Details
Study Description
Brief Summary
The purpose of the study is to evaluate the efficacy and safety of CTX001 (exa-cel) in adolescent and adult participants with severe sickle cell disease (SCD), βS/βC genotype (HbSC).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Exa-cel Participants will receive a single infusion of exa-cel (autologous CD34+ hHSPCs modified with CRISPR-Cas9 at the erythroid lineage-specific enhancer of the BCL11A gene) through a central venous catheter. |
Biological: Exa-cel
Administered by intravenous (IV) infusion following myeloablative conditioning with busulfan.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Proportion of Participants with an Average Fetal Hemoglobin (HbF) Greater Than or Equal To (>=) 20 percent (%) on or After 6 Months [From 60 Days after Last Red Blood Cell (RBC) transfusion up to 24 Months after exa-cel 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 exa-cel Infusion]
- Proportion of Participants With Neutrophil Engraftment (First day of 3 Consecutive Measurements of Absolute Neutrophil Count (ANC) >=500 per Microliter [mcgL] on 3 Different Days) [Within 42 Days After exa-cel Infusion]
- Time to Neutrophil Engraftment [Up to 24 months After exa-cel Infusion]
- Time to Platelet Engraftment [Up to 24 months After exa-cel Infusion]
- Incidence of Transplant-Related Mortality (TRM) [Up to 100 Days After exa-cel Infusion]
- Incidence of Transplant-Related Mortality (TRM) [Within 12 Months After exa-cel Infusion]
- Incidence of All-cause Mortality [From Signing of Informed Consent up to 24 Months After exa-cel Infusion]
- Proportion of Participants With No Severe Vaso-Occlusive Crises (VOCs) for At least 12 Months (VF12) [From 60 Days after Last RBC transfusion up to 24 Months After exa-cel Infusion]
- Proportion of Participants Free from Inpatient Hospitalization For Severe VOCs Sustained for At least 12 Months (HF12) [From 60 Days after Last RBC transfusion up to 24 Months After exa-cel Infusion]
- Relative Reduction in Annualized Rate of Severe VOCs [From Baseline up to 24 Months After exa-cel Infusion]
- Duration of Severe VOC Free in Participants who Have Achieved VF12 [From 60 Days after Last RBC transfusion up to 24 Months After exa-cel Infusion]
- Relative Reduction in Rate of Inpatient Hospitalizations for Severe VOCs [From Baseline up to 24 Months After exa-cel Infusion]
- Relative Reduction in Annualized Duration of Hospitalization for Severe VOCs [From Baseline up to 24 Months After exa-cel Infusion]
- Proportion of Participants With Sustained HbF >= 20 % for At least 3, 6, or 12 months [From 60 Days after Last RBC transfusion up to 24 Months After exa-cel Infusion]
- Relative Reduction in Annualized Volume of RBC Transfusions [From Baseline Up To 24 Months After exa-cel Infusion]
- HbF Concentration Over Time [Up To 24 Months After exa-cel Infusion]
- Total Hemoglobin (Hb) Concentration Over Time [Up To 24 Months After exa-cel Infusion]
- Change In Reticulocyte Count Over Time [From Baseline Up To 24 Months After exa-cel Infusion]
- Change in Indirect Bilirubin Over Time [From Baseline Up To 24 Months After exa-cel Infusion]
- Change in Haptoglobin Over Time [From Baseline Up To 24 Months After exa-cel Infusion]
- Change in Lactate dehydrogenase (LDH) Over Time [From Baseline Up To 24 Months After exa-cel Infusion]
- Time to First Detectable Haptoglobin [Up to 24 Months After exa-cel Infusion]
- Time to First Normalized LDH [Up to 24 Months After exa-cel Infusion]
- Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time [Up To 24 Months After exa-cel Infusion]
- Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time [Up To 24 Months After exa-cel Infusion]
- Change in Pain Scale (11-point numerical rating scale (NRS)) Assessment Over Time In Adults (>=18 Years) [From Baseline Up To 24 Months After exa-cel Infusion]
- Change in Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Over Time In Adults (>=18 Years) [From Baseline Up To 24 Months After exa-cel Infusion]
- Change in Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me) [From Baseline Up To 24 Months After exa-cel Infusion]
- Change in Pain Scale (11-point NRS) Assessment Over Time In Adolescents (12 to <18 years of age) [From Baseline Up To 24 Months After exa-cel Infusion]
- Change in Pediatric Quality of Life Inventory (PedsQL; self-report and parent proxy versions) Generic Core In Adolescents (12 to <18 years of age) [From Baseline Up To 24 Months After exa-cel Infusion]
- Change in PedsQL SCD module (self-report and parent proxy versions) In Adolescents (12 to <18 years of age) [From Baseline Up To 24 Months After exa-cel Infusion]
Eligibility Criteria
Criteria
Key Inclusion Criteria:
-
Participants with documented βS/βC (HbSC) genotype
-
Participants must be 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
-
Participants with prior hematopoietic stem cell transplant (HSCT)
-
Treatment with regular RBC transfusions that, in the opinion of the investigator, cannot be interrupted after engraftment.
Other protocol defined Inclusion/Exclusion criteria may apply.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Vertex Pharmaceuticals Incorporated
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- VX21-CTX001-171
- 2023-503247-34-00
- 2021-006375-41