Evaluation of Efficacy and Safety of a Single Dose of Exa-cel in Participants With Severe Sickle Cell Disease, βS/βC Genotype
Phase 3
Not yet recruiting
- Conditions
- Sickle Cell Disease
- Interventions
- Biological: Exa-cel
- Registration Number
- NCT05951205
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 12
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Exa-cel 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.
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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 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 Time to Neutrophil Engraftment 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 Change in Haptoglobin Over Time From Baseline 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 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 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 Incidence of All-cause Mortality From Signing of Informed Consent 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 Total Hemoglobin (Hb) Concentration Over Time 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 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 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 Incidence of Transplant-Related Mortality (TRM) Within 12 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 Relative Reduction in Rate of Inpatient Hospitalizations for Severe VOCs From Baseline up to 24 Months After exa-cel Infusion HbF Concentration Over Time 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 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 Time to Platelet Engraftment Up to 24 months After exa-cel Infusion Change In Reticulocyte Count 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 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 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