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Evaluation of Efficacy and Safety of a Single Dose of CTX001 in Participants With Transfusion-Dependent β-Thalassemia and Severe Sickle Cell Disease

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ClinicalTrials.gov Identifier: NCT05477563
Recruitment Status : Recruiting
First Posted : July 28, 2022
Last Update Posted : May 19, 2023
Sponsor:
Collaborator:
CRISPR Therapeutics
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

Study Description
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Brief Summary:
This is a single-dose, open-label study in participants with transfusion-dependent β-thalassemia (TDT) or severe sickle cell disease (SCD). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) using CTX001.

Condition or disease Intervention/treatment Phase
Beta-Thalassemia Thalassemia Hematologic Diseases Genetic Diseases, Inborn Hemoglobinopathies Sickle Cell Anemia Sickle Cell Disease Biological: CTX001 Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3b Study to Evaluate Efficacy and Safety of a Single Dose of Autologous CRISPR Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (CTX001) in Subjects With Transfusion-Dependent β-Thalassemia or Severe Sickle Cell Disease
Actual Study Start Date : August 2, 2022
Estimated Primary Completion Date : February 2025
Estimated Study Completion Date : February 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: CTX001
CTX001 (autologous CD34+ hHSPCs modified with CRISPR-Cas9 at the erythroid lineage-specific enhancer of the BCL11A gene). Participants will receive a single infusion of CTX001 through a central venous catheter.
 Biological: CTX001
Administered by intravenous (IV) infusion following myeloablative conditioning with busulfan.
Other Names:
  • Exagamglogene autotemcel
  • Exa-cel


Outcome Measures
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Primary Outcome Measures :
  1. Fetal Hemoglobin (HbF) Concentration Over Time [ Time Frame: Up to 12 Months After CTX001 Infusion ]
  2. Total Hemoglobin (Hb) Concentration Over Time [ Time Frame: Up to 12 Months After CTX001 Infusion ]

Secondary Outcome Measures :
  1. TDT and SCD: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From Signing of Informed Consent up to 12 Months After CTX001 Infusion ]
  2. TDT and SCD: 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 ]
  3. TDT and SCD: Time to Engraftment [ Time Frame: Up to 12 Months After CTX001 Infusion ]
  4. TDT and SCD: Incidence of Transplant-Related Mortality (TRM) Within 100 Days After CTX001 Infusion [ Time Frame: Within 100 Days After CTX001 Infusion ]
  5. TDT and SCD: Incidence of TRM Within 12 Months After CTX001 Infusion [ Time Frame: Within 12 Months After CTX001 Infusion ]
  6. TDT and SCD: Incidence of All-cause Mortality [ Time Frame: From Signing of Informed Consent up to 12 Months After CTX001 Infusion ]
  7. TDT and SCD: Relative Reduction in Annualized Volume of RBC Transfusions [ Time Frame: From Day 60 up to 12 Months After CTX001 Infusion ]
  8. TDT and SCD: Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time [ Time Frame: Up to 12 Months After CTX001 Infusion ]
  9. TDT and SCD: Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time [ Time Frame: Up to 12 Months After CTX001 Infusion ]
  10. TDT: Duration Transfusion Free in Participants [ Time Frame: Up to 12 Months After CTX001 Infusion ]
  11. SCD: Relative Reduction in Annualized Rate of Severe Vaso-Occlusive Crises (VOCs) [ Time Frame: From Baseline up to 12 Months After CTX001 Infusion ]
  12. SCD: Relative Reduction in Annualized Rate of Inpatient Hospitalizations for Severe VOCs [ Time Frame: From Baseline up to 12 Months After CTX001 Infusion ]
  13. SCD: Relative Reduction in Annualized Duration of Hospitalization for Severe VOCs [ Time Frame: From Baseline up to 12 Months After CTX001 Infusion ]
  14. SCD: Relative Reduction in Haptoglobin [ Time Frame: From Baseline up to 12 Months After CTX001 Infusion ]
  15. SCD: Relative Reduction in Lactate dehydrogenase [ Time Frame: From Baseline up to 12 Months After CTX001 Infusion ]
  16. SCD: Relative Reduction in Total Bilirubin [ Time Frame: From Baseline up to 12 Months After CTX001 Infusion ]
  17. SCD: Relative Reduction in Indirect Bilirubin [ Time Frame: From Baseline up to 12 Months After CTX001 Infusion ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years to 35 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Participants with TDT and SCD:

    • Eligible for autologous stem cell transplant as per investigator's judgment.

  • Participants with TDT:

    • Diagnosis of TDT as defined by:

      • Documented homozygous β-thalassemia 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 milliliter (mL)/kilograms (kg)/year or 10 units/year of packed red blood cells (RBC) transfusions in the prior 2 years before signing the consent or the last rescreening for patients going through re-screening

  • Participants with SCD:

    • 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

Key Exclusion Criteria:

  • Participants with TDT and SCD:

    • 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)
    • Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator

  • Participants with TDT:

    • Participants with associated α-thalassemia and >1 alpha deletion, or alpha multiplications
    • Participants with sickle cell β-thalassemia variant

  • Participants with SCD:

    • History of untreated moyamoya syndrome or presence of moyamoya syndrome at screening

Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05477563


Contacts
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Contact: Medical Information 617-341-6777 medicalinfo@vrtx.com

Locations
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United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
United States, North Carolina
Atrium Health Levine Children's Hospital Recruiting
Charlotte, North Carolina, United States, 28203
United States, Tennessee
SCRI at the Children's Hospital at TriStar Centennial Recruiting
Nashville, Tennessee, United States, 37203
Italy
Ospedale Pediatrico Bambino Gesù, IRCCS Recruiting
Rome, Italy
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
CRISPR Therapeutics
More Information
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Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT05477563    
Other Study ID Numbers: VX21-CTX001-161
2021-006390-37 ( EudraCT Number )
First Posted: July 28, 2022    Key Record Dates
Last Update Posted: May 19, 2023
Last Verified: February 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Thalassemia
Hematologic Diseases
beta-Thalassemia
Hemoglobinopathies
 Genetic Diseases, Inborn
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia