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Evaluation of Safety and Efficacy of CTX001 in Pediatric Participants With Severe Sickle Cell Disease (SCD)

Primary Purpose

Sickle Cell Disease, Hydroxyurea Failure, Hydroxyurea Intolerance

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 Sickle Cell Disease

Eligibility Criteria

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

Key Inclusion Criteria:

  • Diagnosis of severe SCD as defined by:

    • Documented SCD genotypes
    • History of at least two severe VOCs events per year for the previous two years prior to enrollment
  • Hydroxyurea therapy failure or intolerance at any point in the past
  • Eligible for autologous stem cell transplant as per investigators judgment

Key Exclusion Criteria:

  • A willing and healthy 10/10 human leukocyte antigen (HLA)-matched related donor
  • Prior hematopoietic stem cell transplant (HSCT).
  • Clinically significant and active bacterial, viral, fungal, or parasitic infection

Other protocol defined Inclusion/Exclusion criteria may apply.

Sites / Locations

  • Atrium Health Levine Children's HospitalRecruiting
  • Children's Hospital of Philadelphia
  • St. Jude Children's Research Hospital
  • The Children's Hospital at TriStar Centennial Medical Center/ Sarah Cannon Center for Blood Cancers
  • University Hospital Duesseldorf - Department of Pediatric Oncology, Hematology and Clinical ImmunologyRecruiting
  • Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica Ospedale Pediatrico Bambino Gesu - IRCCSRecruiting
  • 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 do not Have any Severe Vaso-occlusive Crises (VOCs) for at Least 12 Consecutive Months (VF12)

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 Free from Inpatient Hospitalization for Severe VOCs 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 Annualized Rate of Inpatient Hospitalizations for Severe VOCs
Relative Reduction in Annualized Duration of Hospitalization for Severe VOCs
Proportion of Participants With Sustained Fetal Hemoglobin (HbF) ≥20 Percent (%) for at Least 3 Months
Proportion of Participants With Sustained HbF ≥20% for at Least 6 Months
Proportion of Participants With Sustained HbF ≥20% for at Least 12 Months
Proportion of Participants With Sustained HbF ≥30% for at Least 3 Months
Proportion of Participants With Sustained HbF ≥30% for at Least 6 Months
Proportion of Participants With Sustained HbF ≥30% for at Least 12 Months
Time for Participants to Reach HbF ≥20%
Time for Participants to Reach HbF ≥30%
Relative Reduction from Baseline in Annualized Volume of RBC Transfusions
HbF Concentrations Over Time
Hemoglobin (Hb) Concentrations Over Time
Change in Reticulocyte Count Over Time
Change in Indirect Bilirubin Over Time
Change in Haptoglobin Over Time
Time to First Detectable Haptoglobin
Change in Lactate Dehydrogenase (LDH) Over Time
Time to First Normalized LDH (Defined as Within Normal Limits per Local Laboratory)
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

Full Information

First Posted
April 7, 2022
Last Updated
August 28, 2023
Sponsor
Vertex Pharmaceuticals Incorporated
Collaborators
CRISPR Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT05329649
Brief Title
Evaluation of Safety and Efficacy of CTX001 in Pediatric Participants With Severe Sickle Cell Disease (SCD)
Official Title
A Phase 3 Study to Evaluate the Safety and Efficacy of a Single Dose of CTX001 in Pediatric Subjects With Severe Sickle Cell Disease
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 2, 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 severe SCD and hydroxyurea (HU) failure or intolerance. 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
Sickle Cell Disease, Hydroxyurea Failure, Hydroxyurea Intolerance, Hemoglobinopathies, Hematological Diseases

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 do not Have any Severe Vaso-occlusive Crises (VOCs) for at Least 12 Consecutive Months (VF12)
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 Free from Inpatient Hospitalization for Severe VOCs for at Least 12 Months (HF12)
Time Frame
Up to 24 Months After CTX001 Infusion
Title
Relative Reduction in Annualized Rate of Severe VOCs
Time Frame
From Baseline up to 24 Months After CTX001 Infusion
Title
Duration of Severe VOC Free in Participants who Have Achieved VF12
Time Frame
Up to 24 Months After CTX001 Infusion
Title
Relative Reduction in Annualized Rate of Inpatient Hospitalizations for Severe VOCs
Time Frame
From Baseline up to 24 Months After CTX001 Infusion
Title
Relative Reduction in Annualized Duration of Hospitalization for Severe VOCs
Time Frame
From Baseline up to 24 Months After CTX001 Infusion
Title
Proportion of Participants With Sustained Fetal Hemoglobin (HbF) ≥20 Percent (%) for at Least 3 Months
Time Frame
Up to 24 Months After CTX001 Infusion
Title
Proportion of Participants With Sustained HbF ≥20% for at Least 6 Months
Time Frame
Up to 24 Months After CTX001 Infusion
Title
Proportion of Participants With Sustained HbF ≥20% for at Least 12 Months
Time Frame
Up to 24 Months After CTX001 Infusion
Title
Proportion of Participants With Sustained HbF ≥30% for at Least 3 Months
Time Frame
Up to 24 Months After CTX001 Infusion
Title
Proportion of Participants With Sustained HbF ≥30% for at Least 6 Months
Time Frame
Up to 24 Months After CTX001 Infusion
Title
Proportion of Participants With Sustained HbF ≥30% for at Least 12 Months
Time Frame
Up to 24 Months After CTX001 Infusion
Title
Time for Participants to Reach HbF ≥20%
Time Frame
Up to 24 Months After CTX001 Infusion
Title
Time for Participants to Reach HbF ≥30%
Time Frame
Up to 24 Months After CTX001 Infusion
Title
Relative Reduction from Baseline in Annualized Volume of RBC Transfusions
Time Frame
Up to 24 Months After CTX001 Infusion
Title
HbF Concentrations Over Time
Time Frame
Up to 24 Months After CTX001 Infusion
Title
Hemoglobin (Hb) Concentrations Over Time
Time Frame
Up to 24 Months After CTX001 Infusion
Title
Change in Reticulocyte Count Over Time
Time Frame
From Baseline up to 24 Months After CTX001 Infusion
Title
Change in Indirect Bilirubin Over Time
Time Frame
From Baseline up to 24 Months After CTX001 Infusion
Title
Change in Haptoglobin Over Time
Time Frame
From Baseline up to 24 Months After CTX001 Infusion
Title
Time to First Detectable Haptoglobin
Time Frame
Up to 24 Months After CTX001 Infusion
Title
Change in Lactate Dehydrogenase (LDH) Over Time
Time Frame
From Baseline (Pre-infusion) up to 24 Months After CTX001 Infusion
Title
Time to First Normalized LDH (Defined as Within Normal Limits per Local Laboratory)
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

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 severe SCD as defined by: Documented SCD genotypes History of at least two severe VOCs events per year for the previous two years prior to enrollment Hydroxyurea (HU) failure unless HU intolerant Eligible for autologous stem cell transplant as per investigators judgment Key Exclusion Criteria: A willing and healthy 10/10 human leukocyte antigen (HLA)-matched related donor Prior hematopoietic stem cell transplant (HSCT). Clinically significant and active bacterial, viral, fungal, or parasitic infection 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
Atrium Health Levine Children's Hospital
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Individual Site Status
Recruiting
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
St. Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
The Children's Hospital at TriStar Centennial Medical Center/ Sarah Cannon Center for Blood Cancers
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
University Hospital Duesseldorf - Department of Pediatric Oncology, Hematology and Clinical Immunology
City
Dusseldorf
Country
Germany
Individual Site Status
Recruiting
Facility Name
Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica Ospedale Pediatrico Bambino Gesu - IRCCS
City
Rome
Country
Italy
Individual Site Status
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 Severe Sickle Cell Disease (SCD)

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