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

NCT ID: NCT03655678

Last Updated: 2025-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

59 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-09-14

Study Completion Date

2025-11-13

Brief Summary

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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.

Detailed Description

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Conditions

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Beta-Thalassemia Thalassemia Genetic Diseases, Inborn Hematologic Diseases Hemoglobinopathies

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

CTX001

Intervention Type BIOLOGICAL

Administered by IV infusion following myeloablative conditioning with busulfan

Interventions

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CTX001

Administered by IV infusion following myeloablative conditioning with busulfan

Intervention Type BIOLOGICAL

Other Intervention Names

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Exagamglogene autotemcel Exa-cel

Eligibility Criteria

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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

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
Minimum Eligible Age

12 Years

Maximum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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CRISPR Therapeutics

INDUSTRY

Sponsor Role collaborator

Vertex Pharmaceuticals Incorporated

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Lucile Packard Children's Hospital

Palo Alto, California, United States

Site Status

Ann & Robert Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Site Status

Columbia University Medical Center (21+ years)

New York, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

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

Nashville, Tennessee, United States

Site Status

The Hospital for Sick Children

Toronto, , Canada

Site Status

British Columbia Children's Hospital

Vancouver, , Canada

Site Status

Universitätsklinikum Düsseldorf Hospital Duesseldorf

Düsseldorf, , Germany

Site Status

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

Regensburg, , Germany

Site Status

University Hospital Tübingen

Tübingen, , Germany

Site Status

Ospedale Pediatrico Bambino Gesù, IRCCS

Rome, , Italy

Site Status

Imperial College Healthcare NHS Trust, Hammersmith Hospital

London, , United Kingdom

Site Status

University College London Hospitals NHS Foundation Trust

London, , United Kingdom

Site Status

Countries

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United States Canada Germany Italy United Kingdom

References

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de la 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 WE, Locatelli F. Improvements in Health-Related Quality of Life in Patients with Transfusion-Dependent beta-Thalassemia After Exagamglogene Autotemcel. Blood Adv. 2025 Aug 19:bloodadvances.2025016702. doi: 10.1182/bloodadvances.2025016702. Online ahead of print.

Reference Type DERIVED
PMID: 40862696 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38657265 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34175041 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33283989 (View on PubMed)

Other Identifiers

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CTX001-111

Identifier Type: -

Identifier Source: org_study_id

2024-516894-57-00

Identifier Type: OTHER

Identifier Source: secondary_id