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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05356195
Recruitment Status : Recruiting
First Posted : May 2, 2022
Last Update Posted : June 1, 2022
Sponsor:
Collaborator:
CRISPR Therapeutics
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

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).

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

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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 3 Study to Evaluate the Safety and Efficacy of a Single Dose of CTX001 in Pediatric Subjects With Transfusion-Dependent β-Thalassemia
Actual Study Start Date : May 3, 2022
Estimated Primary Completion Date : May 2026
Estimated Study Completion Date : May 2026


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 single infusion of CTX001 through central venous catheter.
Biological: CTX001
Administered by intravenous infusion following myeloablative conditioning with busulfan.
Other Names:
  • Exagamglogene autotemcel
  • Exa-cel




Primary Outcome Measures :
  1. 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 Measures :
  1. 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 ]
  2. 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. Time to Engraftment [ Time Frame: Up to 24 Months After CTX001 Infusion ]
  4. Incidence of Transplant-related Mortality (TRM) Within 100 Days After CTX001 Infusion [ Time Frame: Within 100 Days After CTX001 Infusion ]
  5. Incidence of TRM Within 12 Months After CTX001 Infusion [ Time Frame: Within 12 Months After Infusion ]
  6. Incidence of All-cause Mortality [ Time Frame: From Signing of Informed Consent up to 24 Months After CTX001 Infusion ]
  7. Proportion of Participants who Achieve Transfusion Independence for at Least 6 Consecutive Months (TI6) [ Time Frame: Up to 24 Months After CTX001 Infusion ]
  8. 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 ]
  9. Relative Change in Annualized Volume of RBC Transfusions [ Time Frame: From Baseline up to 24 Months After CTX001 Infusion ]
  10. Transfusion Free Duration for Participants who Achieve TI12 [ Time Frame: Up to 24 Months After CTX001 Infusion ]
  11. Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time [ Time Frame: Up to 24 Months After CTX001 Infusion ]
  12. 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 ]
  13. Change in Fetal Hemoglobin Concentration Over Time [ Time Frame: From Baseline (Pre-transfusion) up to 24 Months After CTX001 Infusion ]
  14. Change in Total Hemoglobin Concentration Over Time [ Time Frame: From Baseline (Pre-transfusion) up to 24 Months After CTX001 Infusion ]
  15. Change in Proportion of Circulating Erythrocytes Expressing Fetal Hemoglobin (F-cells) Over Time [ Time Frame: From Baseline (Pre-transfusion) up to 24 Months After CTX001 Infusion ]


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Ages Eligible for Study:   2 Years to 11 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


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): NCT05356195


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

Locations
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United States, Tennessee
SCRI at the Children's Hospital at TriStar Centennial Recruiting
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
CRISPR Therapeutics
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Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT05356195    
Other Study ID Numbers: VX21-CTX001-141
2021-002172-39 ( EudraCT Number )
First Posted: May 2, 2022    Key Record Dates
Last Update Posted: June 1, 2022
Last Verified: April 2022
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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Thalassemia
Hematologic Diseases
beta-Thalassemia
Hemoglobinopathies
Genetic Diseases, Inborn
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia