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

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

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 Overview

• Status: Withdrawn
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Biological: Exa-cel

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: Exagamglogene autotemcel; CTX001

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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 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

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Study record dates

Study Major Dates

• Study Start (Estimated): July 31, 2027
• Primary Completion (Estimated): December 31, 2033
• Study Completion (Estimated): December 31, 2033

Study Registration Dates

• First Submitted: June 23, 2023
• First Submitted That Met QC Criteria: July 14, 2023
• First Posted (Actual): July 18, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell; exagamglogene autotemcel
• Other Study ID Numbers: VX21-CTX001-171; 2023-503247-34-00 (Other Identifier: EU CT number); 2021-006375-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/our-science/clinical-trials-data-sharing/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No