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

Primary Purpose

Sickle Cell Disease

Status

Not yet recruiting

Phase

Phase 3

Locations

Study Type

Interventional

Intervention

Exa-cel

About this trial

This is an interventional treatment trial for Sickle Cell Disease

Eligibility Criteria

12 Years - 35 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Exa-cel

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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 to Neutrophil Engraftment

Time to Platelet Engraftment

Incidence of Transplant-Related Mortality (TRM)

Incidence of All-cause Mortality

Proportion of Participants With No Severe Vaso-Occlusive Crises (VOCs) for At least 12 Months (VF12)

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

Relative Reduction in Annualized Rate of Severe VOCs

Duration of Severe VOC Free in Participants who Have Achieved VF12

Relative Reduction in Rate of Inpatient Hospitalizations for Severe VOCs

Relative Reduction in Annualized Duration of Hospitalization for Severe VOCs

Proportion of Participants With Sustained HbF >= 20 % for At least 3, 6, or 12 months

Relative Reduction in Annualized Volume of RBC Transfusions

HbF Concentration Over Time

Total Hemoglobin (Hb) Concentration Over Time

Change In Reticulocyte Count Over Time

Change in Indirect Bilirubin Over Time

Change in Haptoglobin Over Time

Change in Lactate dehydrogenase (LDH) Over Time

Time to First Detectable Haptoglobin

Time to First Normalized LDH

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

Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time

Change in Pain Scale (11-point numerical rating scale (NRS)) Assessment Over Time In Adults (>=18 Years)

Change in Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Over Time In Adults (>=18 Years)

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

Change in Pain Scale (11-point NRS) Assessment Over Time In Adolescents (12 to <18 years of age)

Change in Pediatric Quality of Life Inventory (PedsQL; self-report and parent proxy versions) Generic Core In Adolescents (12 to <18 years of age)

Change in PedsQL SCD module (self-report and parent proxy versions) In Adolescents (12 to <18 years of age)

Full Information

NCT ID

NCT05951205

First Posted

June 23, 2023

Last Updated

July 14, 2023

Sponsor

Vertex Pharmaceuticals Incorporated

1. Study Identification

Unique Protocol Identification Number

NCT05951205

Brief Title

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

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

January 2024 (Anticipated)

Primary Completion Date

December 2029 (Anticipated)

Study Completion Date

December 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Vertex Pharmaceuticals Incorporated

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sickle Cell Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Exa-cel

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Exa-cel

Other Intervention Name(s)

Exagamglogene autotemcel, CTX001

Intervention Description

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

Primary Outcome Measure Information:

Title

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 Outcome Measure Information:

Title

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

Title

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

Title

Time to Neutrophil Engraftment

Time Frame

Up to 24 months After exa-cel Infusion

Title

Time to Platelet Engraftment

Time Frame

Up to 24 months After exa-cel Infusion

Title

Incidence of Transplant-Related Mortality (TRM)

Time Frame

Up to 100 Days After exa-cel Infusion

Title

Incidence of Transplant-Related Mortality (TRM)

Time Frame

Within 12 Months After exa-cel Infusion

Title

Incidence of All-cause Mortality

Time Frame

From Signing of Informed Consent up to 24 Months After exa-cel Infusion

Title

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

Title

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

Title

Relative Reduction in Annualized Rate of Severe VOCs

Time Frame

From Baseline up to 24 Months After exa-cel Infusion

Title

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

Title

Relative Reduction in Rate of Inpatient Hospitalizations for Severe VOCs

Time Frame

From Baseline up to 24 Months After exa-cel Infusion

Title

Relative Reduction in Annualized Duration of Hospitalization for Severe VOCs

Time Frame

From Baseline up to 24 Months After exa-cel Infusion

Title

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

Title

Relative Reduction in Annualized Volume of RBC Transfusions

Time Frame

From Baseline Up To 24 Months After exa-cel Infusion

Title

HbF Concentration Over Time

Time Frame

Up To 24 Months After exa-cel Infusion

Title

Total Hemoglobin (Hb) Concentration Over Time

Time Frame

Up To 24 Months After exa-cel Infusion

Title

Change In Reticulocyte Count Over Time

Time Frame

From Baseline Up To 24 Months After exa-cel Infusion

Title

Change in Indirect Bilirubin Over Time

Time Frame

From Baseline Up To 24 Months After exa-cel Infusion

Title

Change in Haptoglobin Over Time

Time Frame

From Baseline Up To 24 Months After exa-cel Infusion

Title

Change in Lactate dehydrogenase (LDH) Over Time

Time Frame

From Baseline Up To 24 Months After exa-cel Infusion

Title

Time to First Detectable Haptoglobin

Time Frame

Up to 24 Months After exa-cel Infusion

Title

Time to First Normalized LDH

Time Frame

Up to 24 Months After exa-cel Infusion

Title

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

Time Frame

Up To 24 Months After exa-cel Infusion

Title

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

Title

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

Title

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

Title

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

Time Frame

From Baseline Up To 24 Months After exa-cel Infusion

Title

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

Title

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

Title

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Maximum Age & Unit of Time

35 Years

Accepts Healthy Volunteers

Eligibility Criteria

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Medical Information

Phone

617-341-6777

medicalinfo@vrtx.com

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent-research/clinical-trial-data-sharing

Learn more about this trial

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

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