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Evaluation of Safety and Efficacy of CTX001 in Pediatric Participants With Transfusion-Dependent β-Thalassemia (TDT)

Primary Purpose

Beta-Thalassemia, Thalassemia, Genetic Diseases, Inborn

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
CTX001
Sponsored by
Vertex Pharmaceuticals Incorporated
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Beta-Thalassemia

Eligibility Criteria

2 Years - 11 Years (Child)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

  • Diagnosis of TDT as defined by:

    • Documented homozygous or compound heterozygous β-thalassemia including β-thalassemia/hemoglobin E (HbE). Participants can be enrolled based on historical data, but a confirmation of the genotype using the study central laboratory will be required before busulfan conditioning
    • History of at least 100 mL/kilograms (kg)/year of packed RBC transfusions in the prior 24 months before signing of consent (or the last rescreening for patients going through repeat screening) or, for participants initiating transfusion therapy <24 months before signing of consent, requirement for packed RBC transfusion at least every 3 to 4 weeks for ≥6 months
  • 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
  • Prior hematopoietic stem cell transplant (HSCT)
  • Participants with associated α-thalassemia and >1 alpha deletion, or alpha multiplications
  • Participants with sickle cell β-thalassemia variant
  • Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator

Other protocol defined Inclusion/Exclusion criteria may apply.

Sites / Locations

  • SCRI at the Children's Hospital at TriStar Centennial
  • The Hospital for Sick Children
  • Universitätsklinikum Düsseldorf Hospital DuesseldorfRecruiting
  • Ospedale Pediatrico Bambino Gesù, IRCCS
  • Great Ormond Street Hospital for Children NHS Foundation Trust
  • St Mary's HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CTX001

Arm Description

CTX001 (autologous CD34+ hHSPCs modified with CRISPR-Cas9 at the erythroid lineage-specific enhancer of the BCL11A gene). Participants will receive single infusion of CTX001 through central venous catheter.

Outcomes

Primary Outcome Measures

Proportion of Participants who Achieve Transfusion Independence for at Least 12 Consecutive Months (TI12)

Secondary Outcome Measures

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Proportion of Participants With Engraftment (First day of 3 Consecutive Measurements of Absolute Neutrophil Count [ANC] ≥500 per Microliter [mcgL] on 3 Different Days)
Time to Engraftment
Incidence of Transplant-related Mortality (TRM) Within 100 Days After CTX001 Infusion
Incidence of TRM Within 12 Months After CTX001 Infusion
Incidence of All-cause Mortality
Proportion of Participants who Achieve Transfusion Independence for at Least 6 Consecutive Months (TI6)
Proportion of Participants Achieving at Least 95 Percent (%), 90%, 85%, 75% and 50% Reduction in Annualized Transfusions
Relative Reduction in Annualized Volume of RBC Transfusions
Transfusion Free Duration for Participants who Achieve TI12
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 Fetal Hemoglobin Concentration Over Time
Change in Total Hemoglobin Concentration Over Time

Full Information

First Posted
April 7, 2022
Last Updated
August 2, 2023
Sponsor
Vertex Pharmaceuticals Incorporated
Collaborators
CRISPR Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT05356195
Brief Title
Evaluation of Safety and Efficacy of CTX001 in Pediatric Participants With Transfusion-Dependent β-Thalassemia (TDT)
Official Title
A Phase 3 Study to Evaluate the Safety and Efficacy of a Single Dose of CTX001 in Pediatric Subjects With Transfusion-Dependent β-Thalassemia
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 3, 2022 (Actual)
Primary Completion Date
May 2026 (Anticipated)
Study Completion Date
May 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vertex Pharmaceuticals Incorporated
Collaborators
CRISPR Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This is a single-dose, open-label study in pediatric participants with TDT. The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) (CTX001).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Beta-Thalassemia, Thalassemia, Genetic Diseases, Inborn, Hematologic Diseases, Hemoglobinopathies

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CTX001
Arm Type
Experimental
Arm Description
CTX001 (autologous CD34+ hHSPCs modified with CRISPR-Cas9 at the erythroid lineage-specific enhancer of the BCL11A gene). Participants will receive single infusion of CTX001 through central venous catheter.
Intervention Type
Biological
Intervention Name(s)
CTX001
Other Intervention Name(s)
Exagamglogene autotemcel, Exa-cel
Intervention Description
Administered by intravenous infusion following myeloablative conditioning with busulfan.
Primary Outcome Measure Information:
Title
Proportion of Participants who Achieve Transfusion Independence for at Least 12 Consecutive Months (TI12)
Time Frame
Up to 24 Months After CTX001 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 CTX001 Infusion
Title
Proportion of Participants With 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 CTX001 Infusion
Title
Time to Engraftment
Time Frame
Up to 24 Months After CTX001 Infusion
Title
Incidence of Transplant-related Mortality (TRM) Within 100 Days After CTX001 Infusion
Time Frame
Within 100 Days After CTX001 Infusion
Title
Incidence of TRM Within 12 Months After CTX001 Infusion
Time Frame
Within 12 Months After Infusion
Title
Incidence of All-cause Mortality
Time Frame
From Signing of Informed Consent up to 24 Months After CTX001 Infusion
Title
Proportion of Participants who Achieve Transfusion Independence for at Least 6 Consecutive Months (TI6)
Time Frame
Up to 24 Months After CTX001 Infusion
Title
Proportion of Participants Achieving at Least 95 Percent (%), 90%, 85%, 75% and 50% Reduction in Annualized Transfusions
Time Frame
From Baseline up to 24 Months After CTX001 Infusion
Title
Relative Reduction in Annualized Volume of RBC Transfusions
Time Frame
From Baseline up to 24 Months After CTX001 Infusion
Title
Transfusion Free Duration for Participants who Achieve TI12
Time Frame
Up to 24 Months After CTX001 Infusion
Title
Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time
Time Frame
Up to 24 Months After CTX001 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 CTX001 Infusion
Title
Change in Fetal Hemoglobin Concentration Over Time
Time Frame
From Baseline (Pre-transfusion) up to 24 Months After CTX001 Infusion
Title
Change in Total Hemoglobin Concentration Over Time
Time Frame
From Baseline (Pre-transfusion) up to 24 Months After CTX001 Infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
11 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Diagnosis of TDT as defined by: Documented homozygous or compound heterozygous β-thalassemia including β-thalassemia/hemoglobin E (HbE). Participants can be enrolled based on historical data, but a confirmation of the genotype using the study central laboratory will be required before busulfan conditioning History of at least 100 mL/kilograms (kg)/year of packed RBC transfusions in the prior 24 months before signing of consent (or the last rescreening for patients going through repeat screening) or, for participants initiating transfusion therapy <24 months before signing of consent, requirement for packed RBC transfusion at least every 3 to 4 weeks for ≥6 months 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 Prior hematopoietic stem cell transplant (HSCT) Participants with associated α-thalassemia and >1 alpha deletion, or alpha multiplications Participants with sickle cell β-thalassemia variant Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator Other protocol defined Inclusion/Exclusion criteria may apply.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Medical Information
Phone
617-341-6777
Email
medicalinfo@vrtx.com
Facility Information:
Facility Name
SCRI at the Children's Hospital at TriStar Centennial
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
The Hospital for Sick Children
City
Toronto
Country
Canada
Individual Site Status
Active, not recruiting
Facility Name
Universitätsklinikum Düsseldorf Hospital Duesseldorf
City
Düsseldorf
Country
Germany
Individual Site Status
Recruiting
Facility Name
Ospedale Pediatrico Bambino Gesù, IRCCS
City
Rome
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
Great Ormond Street Hospital for Children NHS Foundation Trust
City
London
Country
United Kingdom
Individual Site Status
Active, not recruiting
Facility Name
St Mary's Hospital
City
London
Country
United Kingdom
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No
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 Safety and Efficacy of CTX001 in Pediatric Participants With Transfusion-Dependent β-Thalassemia (TDT)

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