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Beta-ThalassemiaPhase 2/3NCT03655678

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

A Phase 2/3 study testing CTX001 in people with Beta-Thalassemia and Thalassemia, run by Vertex Pharmaceuticals Incorporated at 14 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 12 to 35 years
What is being tested?
CTX001
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
59 participants
Where
14 sitesin 5 countries
Study dates
14 Sep 2018to 13 Nov 2025
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 to 35 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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

Who cannot join

  • 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.

Trial locations and contacts

14 sites in 5 countries.

14 sites in 5 countries

United States6 sites

  • Ann & Robert Lurie Children's Hospital of Chicago

    Chicago, Illinois, 60611

  • The Children's Hospital at TriStar Centennial Medical Center/ Sarah Cannon Center for Blood Cancers

    Nashville, Tennessee, 37203

  • Columbia University Medical Center (21+ years)

    New York, New York, 10032

  • Columbia University Medical Center

    New York, New York, 10032

  • Lucile Packard Children's Hospital

    Palo Alto, California, 94304

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

Other trials in United States

Germany3 sites

  • Universitätsklinikum Düsseldorf Hospital Duesseldorf

    Düsseldorf

  • Regensburg University Hospital, Clinic and Polyclinic for Paediatric and Adolescent Medicine

    Regensburg

  • University Hospital Tübingen

    Tübingen

Other trials in Germany

Canada2 sites

  • The Hospital for Sick Children

    Toronto

  • British Columbia Children's Hospital

    Vancouver

Other trials in Canada

United Kingdom2 sites

  • Imperial College Healthcare NHS Trust, Hammersmith Hospital

    London

  • University College London Hospitals NHS Foundation Trust

    London

Other trials in United Kingdom

Italy1 site

  • Ospedale Pediatrico Bambino Gesù, IRCCS

    Rome

Other trials in Italy

About this study

Official 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

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.

Being tested
CTX001
Keywords
CRISPR-Cas9, Beta-Thalassemia, Hemoglobinopathies
Medical subject headings
beta-Thalassemia, Thalassemia, Genetic Diseases, Inborn, Hematologic Diseases, Hemoglobinopathies

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CTX001Biological

    Also called Exagamglogene autotemcel, Exa-cel

    Administered by IV infusion following myeloablative conditioning with busulfan

Study groups in NCT03655678
Study groupRoleWhat they receive
CTX001ExperimentalCTX001 (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.
Receives: Biological: CTX001

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 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)

    Measured: Within 42 days after CTX001 infusion

  3. Time to neutrophil and platelet engraftment

    Measured: Days post-infusion to engraftment

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

    Measured: Signing of informed consent through Month 24 visit

  5. Incidence of transplant-related mortality (TRM)

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

  6. All-cause mortality

    Measured: Signing of informed consent through Month 24 visit

Secondary outcomes (14)

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

    Measured: 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

    Measured: 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

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

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

    Measured: 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

    Measured: 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

    Measured: Day 1 CTX001 infusion through Month 24 visit

  7. Change in fetal hemoglobin concentration over time

    Measured: Baseline (pre-transfusion) through Month 24 visit

  8. Change in total hemoglobin concentration over time

    Measured: 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)

    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."

    Measured: Screening visit through Month 24 visit

  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.

    Measured: Screening visit through Month 24 visit

  11. Change in patient reported outcome (PRO) over time assessed using EQ-5D-Youth (EQ-5D-Y)

    Measured: Screening visit through Month 24 visit

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

    Measured: Screening visit through Month 24 visit

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

    Measured: Screening visit through Month 24 visit

  14. Proportion of participants receiving iron chelation therapy

    Measured: 1 month post-CTX001 infusion through Month 24 visit

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2018
  2. Study start14 Sep 2018
  3. Primary completion13 Nov 2025
  4. Study completion13 Nov 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
59 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03655678
Sponsor's protocol ID
CTX001-111
Other IDs
2024-516894-57-00
Status last verified
Dec 2025
First submitted
29 Aug 2018
Last updated
17 Dec 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/our-science/clinical-trials-data-sharing/

Publications

  • Sheth S, Corbacioglu S, de la Fuente J, Algeri M, Rupprecht J, Kuo KHM, Shah AJ, Lang P, Merkeley H, Carpenter B, Mapara MY, Liem RI, Grupp S, Chopra Y, Li AM, Kwiatkowski JL, Kirby-Allen M, Cappellini MD, Kattamis A, Zairis S, Liu T, Hobbs W, Frangoul H, Locatelli F, Meisel R; CLIMB THAL-111 and CLIMB-131 Study Groups. Correction of Ineffective Erythropoiesis and Normalization of Iron Homeostasis After Exagamglogene Autotemcel in Transfusion-Dependent beta-Thalassemia. Am J Hematol. 2026 Aug;101(8):1969-1979. doi: 10.1002/ajh.70382. Epub 2026 Jun 7.

    PubMed 42252696

  • Fuente J, Frangoul H, Lang P, Wall D, Meisel R, Corbacioglu S, Li AM, Shah AJ, Carpenter B, Kwiatkowski JL, Mapara MY, Liem RI, Rupprecht J, Kuo KHM, Merkeley H, Algeri M, Smith W, Kohli P, Li N, Rubin J, Zhang S, Hobbs W, Locatelli F. Improvements in health-related quality of life in patients with transfusion-dependent beta-thalassemia after exagamglogene autotemcel. Blood Adv. 2025 Dec 23;9(24):6502-6510. doi: 10.1182/bloodadvances.2025016702.

    PubMed 40862696

  • Locatelli F, Lang P, Wall D, Meisel R, Corbacioglu S, Li AM, de la Fuente J, Shah AJ, Carpenter B, Kwiatkowski JL, Mapara M, Liem RI, Cappellini MD, Algeri M, Kattamis A, Sheth S, Grupp S, Handgretinger R, Kohli P, Shi D, Ross L, Bobruff Y, Simard C, Zhang L, Morrow PK, Hobbs WE, Frangoul H; CLIMB THAL-111 Study Group. Exagamglogene Autotemcel for Transfusion-Dependent beta-Thalassemia. N Engl J Med. 2024 May 9;390(18):1663-1676. doi: 10.1056/NEJMoa2309673. Epub 2024 Apr 24.

    PubMed 38657265

  • Brusson M, Miccio A. Genome editing approaches to beta-hemoglobinopathies. Prog Mol Biol Transl Sci. 2021;182:153-183. doi: 10.1016/bs.pmbts.2021.01.025. Epub 2021 Mar 1.

    PubMed 34175041

  • Frangoul H, Altshuler D, Cappellini MD, Chen YS, Domm J, Eustace BK, Foell J, de la Fuente J, Grupp S, Handgretinger R, Ho TW, Kattamis A, Kernytsky A, Lekstrom-Himes J, Li AM, Locatelli F, Mapara MY, de Montalembert M, Rondelli D, Sharma A, Sheth S, Soni S, Steinberg MH, Wall D, Yen A, Corbacioglu S. CRISPR-Cas9 Gene Editing for Sickle Cell Disease and beta-Thalassemia. N Engl J Med. 2021 Jan 21;384(3):252-260. doi: 10.1056/NEJMoa2031054. Epub 2020 Dec 5.

    PubMed 33283989

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing CTX001 in people with Beta-Thalassemia and Thalassemia, run by Vertex Pharmaceuticals Incorporated at 14 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States, Germany, Canada, United Kingdom, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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]). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03655678, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2025.

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