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

Sickle Cell Disease Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05951205
• Other study ID #: VX21-CTX001-171
• Secondary ID: 2023-503247-34-0
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: April 2024
• Est. completion date: December 2029

Study information

• Verified date: July 2023
• Source: Vertex Pharmaceuticals Incorporated
• Contact: Medical Information
• Phone: 617-341-6777
• Email: medicalinfo[@]vrtx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 12
• Est. completion date: December 2029
• Est. primary completion date: December 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 35 Years

Eligibility

Key Inclusion Criteria:

• Participants with documented ßS/ßC (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.

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Biological:
• Exa-cel
Administered by intravenous (IV) infusion following myeloablative conditioning with busulfan.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Time to Neutrophil Engraftment		Up to 24 months After exa-cel Infusion
Secondary	Time to Platelet Engraftment		Up to 24 months After exa-cel Infusion
Secondary	Incidence of Transplant-Related Mortality (TRM)		Up to 100 Days After exa-cel Infusion
Secondary	Incidence of Transplant-Related Mortality (TRM)		Within 12 Months After exa-cel Infusion
Secondary	Incidence of All-cause Mortality		From Signing of Informed Consent up to 24 Months After exa-cel Infusion
Secondary	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
Secondary	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
Secondary	Relative Reduction in Annualized Rate of Severe VOCs		From Baseline up to 24 Months After exa-cel Infusion
Secondary	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
Secondary	Relative Reduction in Rate of Inpatient Hospitalizations for Severe VOCs		From Baseline up to 24 Months After exa-cel Infusion
Secondary	Relative Reduction in Annualized Duration of Hospitalization for Severe VOCs		From Baseline up to 24 Months After exa-cel Infusion
Secondary	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
Secondary	Relative Reduction in Annualized Volume of RBC Transfusions		From Baseline Up To 24 Months After exa-cel Infusion
Secondary	HbF Concentration Over Time		Up To 24 Months After exa-cel Infusion
Secondary	Total Hemoglobin (Hb) Concentration Over Time		Up To 24 Months After exa-cel Infusion
Secondary	Change In Reticulocyte Count Over Time		From Baseline Up To 24 Months After exa-cel Infusion
Secondary	Change in Indirect Bilirubin Over Time		From Baseline Up To 24 Months After exa-cel Infusion
Secondary	Change in Haptoglobin Over Time		From Baseline Up To 24 Months After exa-cel Infusion
Secondary	Change in Lactate dehydrogenase (LDH) Over Time		From Baseline Up To 24 Months After exa-cel Infusion
Secondary	Time to First Detectable Haptoglobin		Up to 24 Months After exa-cel Infusion
Secondary	Time to First Normalized LDH		Up to 24 Months After exa-cel Infusion
Secondary	Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time		Up To 24 Months After exa-cel Infusion
Secondary	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
Secondary	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
Secondary	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
Secondary	Change in Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me)		From Baseline Up To 24 Months After exa-cel Infusion
Secondary	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
Secondary	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
Secondary	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