Clinical trial NCT05951205: Evaluation of Efficacy and Safety of a Single Dose of Exa-cel in Participants With Severe Sickle Cell Disease, βS/βC Genotype
Official title: A Phase 3 Study to Evaluate Efficacy and Safety of a Single Dose of Exa-cel in Subjects With Severe Sickle Cell Disease, βS/βC Genotype
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Sickle Cell Disease
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2023-07-18
Enrollment: 12
Sex: ALL
Minimum age (years): 12
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility 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.

Primary outcomes:
measure: Proportion of Participants with an Average Fetal Hemoglobin (HbF) Greater Than or Equal To (>=) 20 percent (%) on or After 6 Months
timeFrame: From 60 Days after Last Red Blood Cell (RBC) transfusion up to 24 Months after exa-cel infusion
Secondary outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From Signing of Informed Consent up to 24 Months After exa-cel Infusion
measure: 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)
timeFrame: Within 42 Days After exa-cel Infusion
measure: Time to Neutrophil Engraftment
timeFrame: Up to 24 months After exa-cel Infusion
measure: Time to Platelet Engraftment
timeFrame: Up to 24 months After exa-cel Infusion
measure: Incidence of Transplant-Related Mortality (TRM)
timeFrame: Up to 100 Days After exa-cel Infusion
measure: Incidence of Transplant-Related Mortality (TRM)
timeFrame: Within 12 Months After exa-cel Infusion
measure: Incidence of All-cause Mortality
timeFrame: From Signing of Informed Consent up to 24 Months After exa-cel Infusion
measure: Proportion of Participants With No Severe Vaso-Occlusive Crises (VOCs) for At least 12 Months (VF12)
timeFrame: From 60 Days after Last RBC transfusion up to 24 Months After exa-cel Infusion
measure: Proportion of Participants Free from Inpatient Hospitalization For Severe VOCs Sustained for At least 12 Months (HF12)
timeFrame: From 60 Days after Last RBC transfusion up to 24 Months After exa-cel Infusion
measure: Relative Reduction in Annualized Rate of Severe VOCs
timeFrame: From Baseline up to 24 Months After exa-cel Infusion
measure: Duration of Severe VOC Free in Participants who Have Achieved VF12
timeFrame: From 60 Days after Last RBC transfusion up to 24 Months After exa-cel Infusion
measure: Relative Reduction in Rate of Inpatient Hospitalizations for Severe VOCs
timeFrame: From Baseline up to 24 Months After exa-cel Infusion
measure: Relative Reduction in Annualized Duration of Hospitalization for Severe VOCs
timeFrame: From Baseline up to 24 Months After exa-cel Infusion
measure: Proportion of Participants With Sustained HbF >= 20 % for At least 3, 6, or 12 months
timeFrame: From 60 Days after Last RBC transfusion up to 24 Months After exa-cel Infusion
measure: Relative Reduction in Annualized Volume of RBC Transfusions
timeFrame: From Baseline Up To 24 Months After exa-cel Infusion
measure: HbF Concentration Over Time
timeFrame: Up To 24 Months After exa-cel Infusion
measure: Total Hemoglobin (Hb) Concentration Over Time
timeFrame: Up To 24 Months After exa-cel Infusion
measure: Change In Reticulocyte Count Over Time
timeFrame: From Baseline Up To 24 Months After exa-cel Infusion
measure: Change in Indirect Bilirubin Over Time
timeFrame: From Baseline Up To 24 Months After exa-cel Infusion
measure: Change in Haptoglobin Over Time
timeFrame: From Baseline Up To 24 Months After exa-cel Infusion
measure: Change in Lactate dehydrogenase (LDH) Over Time
timeFrame: From Baseline Up To 24 Months After exa-cel Infusion
measure: Time to First Detectable Haptoglobin
timeFrame: Up to 24 Months After exa-cel Infusion
measure: Time to First Normalized LDH
timeFrame: Up to 24 Months After exa-cel Infusion
measure: Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time
timeFrame: Up To 24 Months After exa-cel Infusion
measure: Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time
timeFrame: Up To 24 Months After exa-cel Infusion
measure: Change in Pain Scale (11-point numerical rating scale (NRS)) Assessment Over Time In Adults (>=18 Years)
timeFrame: From Baseline Up To 24 Months After exa-cel Infusion
measure: Change in Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Over Time In Adults (>=18 Years)
timeFrame: From Baseline Up To 24 Months After exa-cel Infusion
measure: Change in Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me)
timeFrame: From Baseline Up To 24 Months After exa-cel Infusion
measure: Change in Pain Scale (11-point NRS) Assessment Over Time In Adolescents (12 to <18 years of age)
timeFrame: From Baseline Up To 24 Months After exa-cel Infusion
measure: Change in Pediatric Quality of Life Inventory (PedsQL; self-report and parent proxy versions) Generic Core In Adolescents (12 to <18 years of age)
timeFrame: From Baseline Up To 24 Months After exa-cel Infusion
measure: Change in PedsQL SCD module (self-report and parent proxy versions) In Adolescents (12 to <18 years of age)
timeFrame: From Baseline Up To 24 Months After exa-cel Infusion
Other outcomes:
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