Sickle Cell Disease
Conditions
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).
Interventions
BIOLOGICALExa-cel
Administered by intravenous (IV) infusion following myeloablative conditioning with busulfan.
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 35 Years
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 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 |
Outcome results
None listed