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

ClinicalTrials.gov processed this data on May 14, 2024. Link to the current ClinicalTrials.gov record.

Recruitment Status

RECRUITING (See Contacts and Locations)
Verified March 2024 by Vertex Pharmaceuticals Incorporated, CRISPR Therapeutics

Sponsor

Vertex Pharmaceuticals Incorporated

Information Provided by (Responsible Party)

Vertex Pharmaceuticals Incorporated

Clinicaltrials.gov Identifier

NCT05477563
Other Study ID Numbers: VX21-CTX001-161
First Submitted: July 26, 2022
First Posted: July 28, 2022
Last Update Posted: May 16, 2024
Last Verified: March 2024
History of Changes

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Study Description

Not Provided
Condition or Disease Intervention/Treatment
  • Beta-Thalassemia
  • Thalassemia
  • Hematologic Diseases
  • Genetic Diseases, Inborn
  • Hemoglobinopathies
  • Sickle Cell Anemia
  • Sickle Cell Disease
  • Biological: CTX001

Study Design

Study TypeInterventional
Anticipated Enrollment26 participants
Design AllocationN/A
Interventional ModelSingle Group Assignment
MaskingNone (Open Label)
Primary PurposeTreatment
Official TitleA 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
Study Start DateAugust 2, 2022
Anticipated Primary Completion DateFebruary 2025
Anticipated Study Completion DateFebruary 2025

Groups and Cohorts

Group/ CohortIntervention/ Treatment
  • 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.

Outcome Measures

Primary Outcome Measures

  1. Fetal Hemoglobin (HbF) Concentration Over Time [Up to 12 Months After CTX001 Infusion]
  2. Total Hemoglobin (Hb) Concentration Over Time [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) [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) [Within 42 Days After CTX001 Infusion]
  3. TDT and SCD: Time to Engraftment [Up to 12 Months After CTX001 Infusion]
  4. TDT and SCD: Incidence of Transplant-Related Mortality (TRM) Within 100 Days After CTX001 Infusion [Within 100 Days After CTX001 Infusion]
  5. TDT and SCD: Incidence of TRM Within 12 Months After CTX001 Infusion [Within 12 Months After CTX001 Infusion]
  6. TDT and SCD: Incidence of All-cause Mortality [From Signing of Informed Consent up to 12 Months After CTX001 Infusion]
  7. TDT and SCD: Relative Reduction in Annualized Volume of RBC Transfusions [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 [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 [Up to 12 Months After CTX001 Infusion]
  10. TDT: Duration Transfusion Free in Participants [Up to 12 Months After CTX001 Infusion]
  11. SCD: Relative Reduction in Annualized Rate of Severe Vaso-Occlusive Crises (VOCs) [From Baseline up to 12 Months After CTX001 Infusion]
  12. SCD: Relative Reduction in Annualized Rate of Inpatient Hospitalizations for Severe VOCs [From Baseline up to 12 Months After CTX001 Infusion]
  13. SCD: Relative Reduction in Annualized Duration of Hospitalization for Severe VOCs [From Baseline up to 12 Months After CTX001 Infusion]
  14. SCD: Relative Reduction in Haptoglobin [From Baseline up to 12 Months After CTX001 Infusion]
  15. SCD: Relative Reduction in Lactate dehydrogenase [From Baseline up to 12 Months After CTX001 Infusion]
  16. SCD: Relative Reduction in Total Bilirubin [From Baseline up to 12 Months After CTX001 Infusion]
  17. SCD: Relative Reduction in Indirect Bilirubin [From Baseline up to 12 Months After CTX001 Infusion]

Eligibility Criteria

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

Sponsors and Collaborators Vertex Pharmaceuticals Incorporated, CRISPR Therapeutics
CRISPR Therapeutics
Locations
  • Columbia University Medical Center | New York, New York, United States, 10032
  • Atrium Health Levine Children's Hospital | Charlotte, North Carolina, United States, 28203
  • SCRI at the Children's Hospital at TriStar Centennial | Nashville, Tennessee, United States, 37203
  • Universitätsklinikum Düsseldorf Hospital Duesseldorf | Duesseldorf, Germany,
  • Ospedale Pediatrico Bambino Gesù, IRCCS | Rome, Italy,
  • King Faisal Specialist Hospital and Research Centre | Al Mathar Ash Shamali, Saudi Arabia,

More Information

Additional Relevant MeSH Terms

  • Anemia, Sickle Cell
  • Thalassemia
  • beta-Thalassemia
  • Hematologic Diseases
  • Hemoglobinopathies
  • Genetic Diseases, Inborn
  • Anemia, Hemolytic, Congenital
  • Anemia, Hemolytic
  • Anemia