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

NCT03655678 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: CTX001-1112024-516894-57-00
• Study Type: interventional
• Target: 59
• Locations: 5 countries
• Sites: 14

Brief 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.

Conditions

Beta-Thalassemia; Thalassemia; Genetic Diseases, Inborn; Hematologic Diseases; Hemoglobinopathies

Keywords

CRISPR-Cas9; Beta-Thalassemia; Hemoglobinopathies

Outcome Measures

Primary Outcomes (6)

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

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

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

  Within 42 days after CTX001 infusion

• Time to neutrophil and platelet engraftment

  Days post-infusion to engraftment

• Frequency and severity of collected adverse events (AEs)

  Signing of informed consent through Month 24 visit

• Incidence of transplant-related mortality (TRM)

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

• All-cause mortality

  Signing of informed consent through Month 24 visit

Secondary Outcomes (14)

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

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

• 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

  From Month 10 up to 24 months post-CTX001 infusion

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

  From Month 10 up to 24 months post-CTX001 infusion

• Duration of transfusion free in participants who have achieved TI12

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

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

  Day 1 CTX001 infusion through Month 24 visit

Study Arms (1)

CTX001

EXPERIMENTAL

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

Interventions

CTX001 BIOLOGICAL

Administered by IV infusion following myeloablative conditioning with busulfan

Also known as: Exagamglogene autotemcel, Exa-cel

CTX001

Eligibility Criteria

• Age: 12 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead
• CRISPR Therapeutics: collaborator

Study Sites (14)

Lucile Packard Children's Hospital

Palo Alto, California, 94304, United States

Location

Ann & Robert Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Columbia University Medical Center (21+ years)

New York, New York, 10032, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

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

Nashville, Tennessee, 37203, United States

Location

The Hospital for Sick Children

Toronto, Canada

Location

British Columbia Children's Hospital

Vancouver, Canada

Location

Universitätsklinikum Düsseldorf Hospital Duesseldorf

Düsseldorf, Germany

Location

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

Regensburg, Germany

Location

University Hospital Tübingen

Tübingen, Germany

Location

Ospedale Pediatrico Bambino Gesù, IRCCS

Rome, Italy

Location

Imperial College Healthcare NHS Trust, Hammersmith Hospital

London, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 40862696 DERIVED

• 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.

  PMID: 38657265 DERIVED

• 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.

  PMID: 34175041 DERIVED

• 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.

  PMID: 33283989 DERIVED

MeSH Terms

Conditions

beta-Thalassemia; Thalassemia; Genetic Diseases, Inborn; Hematologic Diseases; Hemoglobinopathies

Interventions

exagamglogene autotemcel

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2018
• First Posted: August 31, 2018
• Study Start: September 14, 2018
• Primary Completion: November 13, 2025
• Study Completion: November 13, 2025
• Last Updated: December 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); DE (3); US (6); GB (2); CA (2)