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

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified February 2026 by Vertex Pharmaceuticals Incorporated
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 25, 2022
First Posted
July 27, 2022
Last Update Posted
March 22, 2026
Last Verified
February 2026

ClinicalTrials.gov processed this data on March 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Beta-ThalassemiaThalassemiaHematologic DiseasesGenetic Diseases, InbornHemoglobinopathiesSickle Cell DiseaseSickle Cell Anemia
Biological: CTX001

Study Design

Study TypeInterventional
Actual 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 1, 2022
Actual Primary Completion Date1yr 2w from now
Actual Study Completion Date1yr 2w from now

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

Eligibility Criteria

Ages Eligible for Study(Child, Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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

Sponsors and CollaboratorsVertex Pharmaceuticals Incorporated
Locations
New York Presbyterian Hospital - Morgan Stanley Children's Hospital | New York New York, United States, 10032Levine Children's Hospital - Hematology | Charlotte North Carolina, United States, 28203TriStar Medical Group Children's Specialists - Pediatric Oncology | Nashville Tennessee, United States, 37203University Hospital Dusseldorf - Department of Pediatric Oncology, Hematology and Clinical Immunology | Düsseldorf , Germany, IRCSS Ospedale Pediatrico Bambino Gesu - Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica | Rome , Italy, King Faisal Specialist Hospital & Research Centre - Riyadh - Hematology | Al Mathar Ash Shamali , Saudi Arabia,