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

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ClinicalTrials.gov Identifier: NCT05329649
Recruitment Status : Recruiting
First Posted : April 15, 2022
Last Update Posted : January 25, 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 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).

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Hydroxyurea Failure Hydroxyurea Intolerance Hemoglobinopathies Hematological Diseases 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 3 Study to Evaluate the Safety and Efficacy of a Single Dose of CTX001 in Pediatric Subjects With Severe Sickle Cell Disease
Actual Study Start Date : May 2, 2022
Estimated Primary Completion Date : May 2026
Estimated Study Completion Date : May 2026

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 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


Outcome Measures
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Primary Outcome Measures :
  1. 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 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 Free from Inpatient Hospitalization for Severe VOCs for at Least 12 Months (HF12) [ Time Frame: Up to 24 Months After CTX001 Infusion ]
  8. Relative Change in Annualized Rate of Severe VOCs [ Time Frame: From Baseline up to 24 Months After CTX001 Infusion ]
  9. Duration of Severe VOC Free in Participants who Have Achieved VF12 [ Time Frame: Up to 24 Months After CTX001 Infusion ]
  10. Relative Change in Annualized Rate of Inpatient Hospitalizations for Severe VOCs [ Time Frame: From Baseline up to 24 Months After CTX001 Infusion ]
  11. Relative Change in Annualized Duration of Hospitalization for Severe VOCs [ Time Frame: From Baseline up to 24 Months After CTX001 Infusion ]
  12. Proportion of Participants With Sustained Fetal Hemoglobin (HbF) ≥20 Percent (%) for at Least 3 Months [ Time Frame: Up to 24 Months After CTX001 Infusion ]
  13. Proportion of Participants With Sustained HbF ≥20% for at Least 6 Months [ Time Frame: Up to 24 Months After CTX001 Infusion ]
  14. Proportion of Participants With Sustained HbF ≥20% for at Least 12 Months [ Time Frame: Up to 24 Months After CTX001 Infusion ]
  15. Proportion of Participants With Sustained HbF ≥30% for at Least 3 Months [ Time Frame: Up to 24 Months After CTX001 Infusion ]
  16. Proportion of Participants With Sustained HbF ≥30% for at Least 6 Months [ Time Frame: Up to 24 Months After CTX001 Infusion ]
  17. Proportion of Participants With Sustained HbF ≥30% for at Least 12 Months [ Time Frame: Up to 24 Months After CTX001 Infusion ]
  18. Time for Participants to Reach HbF ≥20% [ Time Frame: Up to 24 Months After CTX001 Infusion ]
  19. Time for Participants to Reach HbF ≥30% [ Time Frame: Up to 24 Months After CTX001 Infusion ]
  20. Change in Number of Units of RBC Transfused for SCD-related Indications Over Time [ Time Frame: Up to 24 Months After CTX001 Infusion ]
  21. HbF Concentrations Over Time [ Time Frame: Up to 24 Months After CTX001 Infusion ]
  22. Hemoglobin (Hb) Concentrations Over Time [ Time Frame: Up to 24 Months After CTX001 Infusion ]
  23. Change in Proportion of Circulating Erythrocytes Expressing Fetal Hemoglobin (F-cells) Over Time [ Time Frame: From Baseline up to 24 Months After CTX001 Infusion ]
  24. Change in Reticulocyte Count Over Time [ Time Frame: From Baseline up to 24 Months After CTX001 Infusion ]
  25. Change in Indirect Bilirubin Over Time [ Time Frame: From Baseline up to 24 Months After CTX001 Infusion ]
  26. Change in Haptoglobin Over Time [ Time Frame: From Baseline up to 24 Months After CTX001 Infusion ]
  27. Time to First Detectable Haptoglobin [ Time Frame: Up to 24 Months After CTX001 Infusion ]
  28. Change in Lactate Dehydrogenase (LDH) Over Time [ Time Frame: From Baseline (Pre-infusion) up to 24 Months After CTX001 Infusion ]
  29. Time to First Normalized LDH (Defined as Within Normal Limits per Local Laboratory) [ Time Frame: Up to 24 Months After CTX001 Infusion ]
  30. Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time [ Time Frame: Up to 24 Months After CTX001 Infusion ]
  31. 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 ]

Eligibility Criteria
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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 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.

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): NCT05329649


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

Locations
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United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
The Children's Hospital at TriStar Centennial Medical Center/ Sarah Cannon Center for Blood Cancers Active, not recruiting
Nashville, Tennessee, United States, 37203
Italy
Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica Ospedale Pediatrico Bambino Gesu - 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: NCT05329649    
Other Study ID Numbers: VX21-CTX001-151
2021-002173-26 ( EudraCT Number )
First Posted: April 15, 2022    Key Record Dates
Last Update Posted: January 25, 2023
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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Anemia, Sickle Cell
Hemoglobinopathies
Hematologic Diseases
Anemia, Hemolytic, Congenital
 Anemia, Hemolytic
Anemia
Genetic Diseases, Inborn