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Completed

NCT Number: NCT03655678

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

This is a single-arm, open-label, multi-site, single-dose Phase 1/2/3 study in participans with transfusion-dependent β-thalassemia (TDT). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (hHSPCs) using CTX001.

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Key information

Conditions

Beta-Thalassemia Anemia Anemia, Hemolytic Anemia, Hemolytic, Congenital Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemoglobinopathies Thalassemia

Age range

12 year–35 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

The Hospital for Sick Children, Toronto, Canada

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • Diagnosis of transfusion-dependent β-thalassemia (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 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.

Treatment and study plan

CTX001

Biological

Administered by IV infusion following myeloablative conditioning with busulfan

Other names: Exagamglogene autotemcel, Exa-cel

Primary outcomes

  1. Proportion of participants achieving transfusion independence for at least 12 consecutive months (TI12)

    Time frame: From 60 days after last RBC transfusion up to 24 months post-CTX001 infusion]

  2. Proportion of participants with engraftment (first day of 3 consecutive measurements of absolute neutrophil count [ANC] ≥500/µL on three different days)

    Time frame: Within 42 days after CTX001 infusion

  3. Time to neutrophil and platelet engraftment

    Time frame: Days post-infusion to engraftment

  4. Frequency and severity of collected adverse events (AEs)

    Time frame: Signing of informed consent through Month 24 visit

  5. Incidence of transplant-related mortality (TRM)

    Time frame: Baseline (pre-transfusion) to 100 days and 1 year post-CTX001 infusion

  6. All-cause mortality

    Time frame: Signing of informed consent through Month 24 visit

Secondary outcomes

  1. Proportion of participants achieving transfusion independence for at least 6 consecutive months (TI6)

    Time frame: From 60 days after last RBC transfusion up to 24 months post-CTX001 infusion

  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

    Time frame: From Month 10 up to 24 months post-CTX001 infusion

  3. Relative reduction from baseline in annualized volume of RBC transfusions after Month 10 after CTX001 infusion

    Time frame: From Month 10 up to 24 months post-CTX001 infusion

  4. Duration of transfusion free in participants who have achieved TI12

    Time frame: From 60 days after last RBC transfusion up to 24 months post-CTX001 infusion

  5. Proportion of alleles with intended genetic modification in peripheral blood leukocytes over time

    Time frame: Day 1 CTX001 infusion through Month 24 visit

  6. Proportion of alleles with intended genetic modification present in CD34+ cells of bone marrow over time

    Time frame: Day 1 CTX001 infusion through Month 24 visit

  7. Change in fetal hemoglobin concentration over time

    Time frame: Baseline (pre-transfusion) through Month 24 visit

  8. Change in total hemoglobin concentration over time

    Time frame: Baseline (pre-transfusion) through Month 24 visit

  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)

    Time frame: Screening visit through Month 24 visit

    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)

    Time frame: Screening visit through Month 24 visit

    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)

    Time frame: Screening visit through Month 24 visit

  12. Change in PRO over time assessed using pediatric quality of life inventory (PedsQL)

    Time frame: Screening visit through Month 24 visit

  13. Changes in liver iron concentration (LIC) and cardiac iron content (CIC) and ferritin parameters of iron overload

    Time frame: Screening visit through Month 24 visit

  14. Proportion of participants receiving iron chelation therapy

    Time frame: 1 month post-CTX001 infusion through Month 24 visit

Sponsors and collaborators

Lead sponsor

Vertex Pharmaceuticals Incorporated

Industry

Collaborators

  • CRISPR Therapeutics

Registry information

Official study title

A 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

Important dates

Study start
2018
Primary completion
2025
Study completion
2025
First posted
Aug 31, 2018
Registry last updated
Dec 17, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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