A Safety and Efficacy Study Evaluating CTX001 in Participants With Transfusion-Dependent β-Thalassemia

Recruitment Status
COMPLETED
(See Contacts and Locations)Verified November 2025 by Vertex Pharmaceuticals Incorporated
Sponsor
Vertex Pharmaceuticals Incorporated
Information Provided by (Responsible Party)
Vertex Pharmaceuticals Incorporated
Clinicaltrials.gov Identifier
NCT03655678
Other Study ID Numbers:
CTX001-111
First Submitted
August 28, 2018
First Posted
August 30, 2018
Last Update Posted
December 16, 2025
Last Verified
November 2025

ClinicalTrials.gov processed this data on December 2025. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Beta-ThalassemiaThalassemiaGenetic Diseases, InbornHematologic DiseasesHemoglobinopathies
Biological: CTX001

Study Design

Study TypeInterventional
Actual Enrollment59 participants
Design AllocationN/A
Interventional ModelSingle Group Assignment
MaskingNone (Open Label)
Primary PurposeTreatment
Official TitleA Phase 1/2/3 Study of the Safety and Efficacy of a Single Dose of Autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (hHSPCs) in Subjects With Transfusion-Dependent β-Thalassemia
Study Start DateSeptember 13, 2018
Actual Primary Completion DateNovember 12, 2025
Actual Study Completion DateNovember 12, 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 IV infusion following myeloablative conditioning with busulfan

Outcome Measures

Primary Outcome Measures
  1. Proportion of participants achieving transfusion independence for at least 12 consecutive months (TI12)
  2. Proportion of participants with engraftment (first day of 3 consecutive measurements of absolute neutrophil count [ANC] ≥500/µL on three different days)
  3. Time to neutrophil and platelet engraftment
  4. Frequency and severity of collected adverse events (AEs)
  5. Incidence of transplant-related mortality (TRM)
  6. All-cause mortality
Secondary Outcome Measures
  1. Proportion of participants achieving transfusion independence for at least 6 consecutive months (TI6)
  2. Proportion of participants achieving at least 95 percent (%), 90%, 85%, 75%, and 50% reduction from baseline in annualized volume of RBC transfusions after Month 10 after CTX001 infusion
  3. Relative reduction from baseline in annualized volume of RBC transfusions after Month 10 after CTX001 infusion
  4. Duration of transfusion free in participants who have achieved TI12
  5. Proportion of alleles with intended genetic modification in peripheral blood leukocytes over time
  6. Proportion of alleles with intended genetic modification present in CD34+ cells of bone marrow over time
  7. Change in fetal hemoglobin concentration over time
  8. Change in total hemoglobin concentration over time
  9. Change in health-related quality of life (HRQoL) from baseline over time using EuroQol Questionnaire (5 dimensions - 5 levels of severity - EQ-5D-5L)
    The EQ-5D-5L Questionnaire consists of the EQ-5D descriptive system and the EQ visual analogue scale (VAS). The EQ-5D comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression, and 5 levels: no problems to extreme problems. The subject marks the most appropriate statement in each dimension, resulting in a 1-digit number for that dimension. The digits can be combined in a 5-digit number describing the subject's health state. The EQ VAS records the subject's self-rated health on a 100-point VAS, endpoints labelled "the best health you can imagine" and "the worst health you can imagine."
  10. Change in health-related quality of life (HRQoL) from baseline over time using the Functional assessment of cancer therapy-bone marrow transplant questionnaire (FACT-BMT)
    The FACT-BMT Questionnaire includes physical, social, family, emotional, and functional well-being, and treatment specific concerns of bone marrow transplantation. Each statement has a 5-point Likert-type response scale ranging from 0=not at all to 4=very much. The subject marks one number per line as it applies to the past 7 days. Questionnaires are scored; the higher the score, the better the QOL.
  11. Change in patient reported outcome (PRO) over time assessed using EQ-5D-Youth (EQ-5D-Y)
  12. Change in PRO over time assessed using pediatric quality of life inventory (PedsQL)
  13. Changes in liver iron concentration (LIC) and cardiac iron content (CIC) and ferritin parameters of iron overload
  14. Proportion of participants receiving iron chelation therapy

Eligibility Criteria

Ages Eligible for Study(Child, Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
Diagnosis of transfusion-dependent β-thalassemia (TDT) as defined by 1. 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 2. History of at least 100 mL/kg/year or ≥10 units/year of packed RBC transfusions in the prior 2 years before signing the consent or the last rescreening for patients going through re-screening
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 allo-HSCT
Participants with associated α-thalassemia and \>1 alpha deletion or alpha multiplications
Participants with sickle cell beta thalassemia variant
Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator
White blood cell (WBC) count \<3 × 10\^9/L or platelet count \<50 × 10\^9/L not related to hypersplenism Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Sponsors and CollaboratorsVertex Pharmaceuticals Incorporated
Locations
Lucile Packard Children's Hospital | Palo Alto California, United States, 94304Ann & Robert Lurie Children's Hospital of Chicago | Chicago Illinois, United States, 60611Columbia University Medical Center (21+ years) | New York New York, United States, 10032Columbia University Medical Center | New York New York, United States, 10032Children's Hospital of Philadelphia | Philadelphia Pennsylvania, United States, 19104The Children's Hospital at TriStar Centennial Medical Center/ Sarah Cannon Center for Blood Cancers | Nashville Tennessee, United States, 37203The Hospital for Sick Children | Toronto , Canada, British Columbia Children's Hospital | Vancouver , Canada, Universitätsklinikum Düsseldorf Hospital Duesseldorf | Düsseldorf , Germany, Regensburg University Hospital, Clinic and Polyclinic for Paediatric and Adolescent Medicine | Regensburg , Germany, University Hospital Tübingen | Tübingen , Germany, Ospedale Pediatrico Bambino Gesù, IRCCS | Rome , Italy, Imperial College Healthcare NHS Trust, Hammersmith Hospital | London , United Kingdom, University College London Hospitals NHS Foundation Trust | London , United Kingdom,