A Safety and Efficacy Study Evaluating CTX001 in Subjects With Severe Sickle Cell Disease

NCT03745287 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: CTX001-121
• Study Type: interventional
• Target: 63
• Locations: 7 countries
• Sites: 17

Brief Summary

This is a single-arm, open-label, multi-site, single-dose Phase 1/2/3 study in subjects with severe sickle cell disease (SCD). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (hHSPCs) using CTX001.

Conditions

Sickle Cell Disease; Hematological Diseases; Hemoglobinopathies

Outcome Measures

Primary Outcomes (7)

• Proportion of subjects who have not experienced any severe vaso-occlusive crisis (VOC) for at least 12 consecutive months (VF12)

  From 60 days after last RBC transfusion up to 2 years after CTX001 infusion

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

  Within 42 days after CTX001 infusion

• Time to engraftment

  From CTX001 infusion up to 2 years after CTX001 infusion

• Frequency and severity of collected adverse events (AEs)

  From screening to 2 years after CTX001 infusion

• Incidence of transplant-related mortality (TRM) within 100 days after CTX001 infusion

  Within 100 days after CTX001 infusion

• Incidence of TRM within 1 year after CTX001 infusion

  Within 1 year after CTX001 infusion

• All-cause mortality

  2 years after mobilization

Secondary Outcomes (26)

• Proportion of subjects free from inpatient hospitalization for severe VOCs sustained for at least 12 months (HF12)

  From 60 days after last RBC transfusion up to 2 years after CTX001 infusion

• Proportion of subjects who have not experienced any severe VOC for at least 9 consecutive months (VF9) any time after CTX001 infusion

  From 60 days after last RBC transfusion up to 2 years after CTX001 infusion

• Proportion of subjects with 90 percent (%), 80%, 75% or 50% reduction in annualized rate of severe VOCs

  From 60 days after last RBC transfusion up to 2 years after CTX001 infusion

• Relative change from baseline in annualized rate of severe VOCs

  From 60 days after last RBC transfusion up to 2 years after CTX001 infusion

• Duration of severe VOC free in subjects who have achieved VF12

  From 60 days after last RBC transfusion up to 2 years after CTX001 infusion

Study Arms (1)

CTX001

EXPERIMENTAL

CTX001 (autologous CD34+ hHSPCs modified with CRISPR-Cas9 at the erythroid lineage-specific enhancer of the BCL11A gene). Subjects 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 severe sickle cell disease as defined by:
• Documented severe sickle cell disease genotype
• History of at least two severe vaso-occlusive crisis events per year for the previous two years prior to enrollment
• Eligible for autologous stem cell transplant as per investigators judgment

You may not qualify if:

• An available 10/10 human leukocyte antigen (HLA)-matched related donor
• Prior hematopoietic stem cell transplant (HSCT)
• Clinically significant and active bacterial, viral, fungal, or parasitic infection

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead
• CRISPR Therapeutics: collaborator

Study Sites (17)

Lucile Packard Children's Hospital of Stanford University

Palo Alto, California, 94304, United States

Location

Ann & Robert Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

University of Illinois at Chicago Hospitals and Health Systems

Chicago, Illinois, 60612, United States

Location

Columbia University Medical Center (21+ years)

New York, New York, 10032, United States

Location

Columbia University Medical Center (≤21 years)

New York, New York, 10032, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

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

Nashville, Tennessee, 37203, United States

Location

Methodist Children's Hospital/Texas Transplant Institute

San Antonio, Texas, 78229, United States

Location

Hopital Universitaire des Enfants Reine Fabiola (HUDERF)

Brussels, Belgium

Location

The Hospital for Sick Children

Toronto, Canada

Location

Hopital Necker Enfants Malades

Paris, France

Location

University Hospital Duesseldorf

Düsseldorf, Germany

Location

Regensburg University Hospital, Clinic and Polyclinic for Paediatric and Adolescent Medicine, Paediatric Haemotology, Oncology and Stem Cell Transplantation

Regensburg, Germany

Location

Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica Ospedale Pediatrico Bambino Gesu - IRCCS

Rome, Italy

Location

Imperial College Healthcare NHS Trust, Hammersmith Hospital

London, United Kingdom

Location

Royal London and St Bartholomew's Hospital, Pathology and Pharmacy Building

London, United Kingdom

Location

Related Publications (9)

• Sharma A, Locatelli F, Bhatia M, Molinari L, Mapara MY, Liem RI, Dedeken L, Wall D, Eckrich MJ, Kuo KHM, Smith W, Imren S, Kohli P, Li N, Liu T, Rubin J, Hobbs W, Grupp SA, Frangoul H. Improvements in health-related quality of life in patients with severe sickle cell disease after exagamglogene autotemcel. Blood Adv. 2025 Dec 23;9(24):6481-6490. doi: 10.1182/bloodadvances.2025016701.

  PMID: 40857358 DERIVED

• Ligon JA, Cupit-Link MC, Yu C, Levine J, Foley T, Rotz S, Sharma A, Gomez-Lobo V, Shah NN. Pediatric Cancer Immunotherapy and Potential for Impact on Fertility: A Need for Evidence-Based Guidance. Transplant Cell Ther. 2024 Aug;30(8):737-749. doi: 10.1016/j.jtct.2024.06.006. Epub 2024 Jun 10.

  PMID: 38866240 DERIVED

• Frangoul H, Locatelli F, Sharma A, Bhatia M, Mapara M, Molinari L, Wall D, Liem RI, Telfer P, Shah AJ, Cavazzana M, Corbacioglu S, Rondelli D, Meisel R, Dedeken L, Lobitz S, de Montalembert M, Steinberg MH, Walters MC, Eckrich MJ, Imren S, Bower L, Simard C, Zhou W, Xuan F, Morrow PK, Hobbs WE, Grupp SA; CLIMB SCD-121 Study Group. Exagamglogene Autotemcel for Severe Sickle Cell Disease. N Engl J Med. 2024 May 9;390(18):1649-1662. doi: 10.1056/NEJMoa2309676. Epub 2024 Apr 24.

  PMID: 38661449 DERIVED

• Sharma A, Young A, Carroll Y, Darji H, Li Y, Mandrell BN, Nelson MN, Owens CL, Irvine M, Caples M, Jerkins LP, Unguru Y, Hankins JS, Johnson LM. Gene therapy in sickle cell disease: Attitudes and informational needs of patients and caregivers. Pediatr Blood Cancer. 2023 Jun;70(6):e30319. doi: 10.1002/pbc.30319. Epub 2023 Mar 28.

  PMID: 36975201 DERIVED

• Persaud Y, Mandrell BN, Sharma A, Carroll Y, Irvine M, Olufadi Y, Kang G, Hijano DR, Rai P, Hankins JS, Johnson LM. Attitudes toward COVID-19 vaccine among pediatric patients with sickle cell disease and their caregivers. Pediatr Blood Cancer. 2023 May;70(5):e30274. doi: 10.1002/pbc.30274. Epub 2023 Mar 1.

  PMID: 36860093 DERIVED

• Bhoopalan SV, Yen JS, Levine RM, Sharma A. Editing human hematopoietic stem cells: advances and challenges. Cytotherapy. 2023 Mar;25(3):261-269. doi: 10.1016/j.jcyt.2022.08.003. Epub 2022 Sep 17.

  PMID: 36123234 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

• Modarai SR, Kanda S, Bloh K, Opdenaker LM, Kmiec EB. Precise and error-prone CRISPR-directed gene editing activity in human CD34+ cells varies widely among patient samples. Gene Ther. 2021 Feb;28(1-2):105-113. doi: 10.1038/s41434-020-00192-z. Epub 2020 Sep 1.

  PMID: 32873924 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell; Hematologic Diseases; Hemoglobinopathies

Interventions

exagamglogene autotemcel

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemic and Lymphatic Diseases; Genetic Diseases, Inborn; 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: November 9, 2018
• First Posted: November 19, 2018
• Study Start: November 27, 2018
• Primary Completion: July 7, 2025
• Study Completion: July 7, 2025
• Last Updated: August 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); FR (1); DE (2); CA (1); US (9); GB (2); BE (1)