Evaluation of Efficacy and Safety of a Single Dose of Exa-cel in Participants With Severe Sickle Cell Disease, βS/ βC Genotype

Vertex Pharmaceuticals Incorporated

Overview

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).

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Conditions

Sickle Cell Disease

Interventions

Exa-celBIOLOGICAL

Administered by intravenous (IV) infusion following myeloablative conditioning with busulfan.

Eligibility

Sex: ALLMin age: 12 YearsMax age: 35 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Proportion of Participants with an Average Fetal Hemoglobin (HbF) Greater Than or Equal To (>=) 20 percent (%) on or After 6 Months

Time frame: From 60 Days after Last Red Blood Cell (RBC) transfusion up to 24 Months after exa-cel infusion

Secondary Outcomes

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time frame: 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)

Time frame: Within 42 Days After exa-cel Infusion

Time to Neutrophil Engraftment

Time frame: Up to 24 months After exa-cel Infusion

Time to Platelet Engraftment

Time frame: Up to 24 months After exa-cel Infusion

Incidence of Transplant-Related Mortality (TRM)

Time frame: Up to 100 Days After exa-cel Infusion

Incidence of Transplant-Related Mortality (TRM)

Time frame: Within 12 Months After exa-cel Infusion

Incidence of All-cause Mortality

Time frame: 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)

Time frame: From 60 Days after Last RBC transfusion up to 24 Months After exa-cel Infusion

Data from ClinicalTrials.gov

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Proportion of Participants Free from Inpatient Hospitalization For Severe VOCs Sustained for At least 12 Months (HF12)

Time frame: From 60 Days after Last RBC transfusion up to 24 Months After exa-cel Infusion

Relative Reduction in Annualized Rate of Severe VOCs

Time frame: From Baseline up to 24 Months After exa-cel Infusion

Duration of Severe VOC Free in Participants who Have Achieved VF12

Time frame: 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

Time frame: From Baseline up to 24 Months After exa-cel Infusion

Relative Reduction in Annualized Duration of Hospitalization for Severe VOCs

Time frame: 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

Time frame: From 60 Days after Last RBC transfusion up to 24 Months After exa-cel Infusion

Relative Reduction in Annualized Volume of RBC Transfusions

Time frame: From Baseline Up To 24 Months After exa-cel Infusion

HbF Concentration Over Time

Time frame: Up To 24 Months After exa-cel Infusion

Total Hemoglobin (Hb) Concentration Over Time

Time frame: Up To 24 Months After exa-cel Infusion

Change In Reticulocyte Count Over Time

Time frame: From Baseline Up To 24 Months After exa-cel Infusion

Change in Indirect Bilirubin Over Time

Time frame: From Baseline Up To 24 Months After exa-cel Infusion

Change in Haptoglobin Over Time

Time frame: From Baseline Up To 24 Months After exa-cel Infusion

Change in Lactate dehydrogenase (LDH) Over Time

Time frame: From Baseline Up To 24 Months After exa-cel Infusion

Time to First Detectable Haptoglobin

Time frame: Up to 24 Months After exa-cel Infusion

Time to First Normalized LDH

Time frame: Up to 24 Months After exa-cel Infusion

Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time

Time frame: 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

Time frame: 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)

Time frame: 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)

Time frame: From Baseline Up To 24 Months After exa-cel Infusion

Change in Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: From Baseline Up To 24 Months After exa-cel Infusion