Evaluation of Efficacy and Safety of a Single Dose of CTX001 in Participants With Transfusion-Dependent β-Thalassemia and Severe Sickle Cell Disease

NCT05477563 | Recruiting Phase 3 FDA Drug

• 2 other identifiers: VX21-CTX001-1612024-514641-12-00
• Study Type: interventional
• Target: 26
• Locations: 4 countries
• Sites: 6

Brief Summary

This is a single-dose, open-label study in participants with transfusion-dependent β-thalassemia (TDT) or 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

Thalassemia; Hematologic Diseases; Genetic Diseases, Inborn; Hemoglobinopathies; Sickle Cell Disease; Sickle Cell Anemia; Beta-Thalassemia

Outcome Measures

Primary Outcomes (2)

• Fetal Hemoglobin (HbF) Concentration Over Time

  Up to 12 Months After CTX001 Infusion

• Total Hemoglobin (Hb) Concentration Over Time

  Up to 12 Months After CTX001 Infusion

Secondary Outcomes (17)

• TDT and SCD: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  From Signing of Informed Consent up to 12 Months After CTX001 Infusion

• TDT and SCD: Proportion of Participants With Engraftment (First day of 3 Consecutive Measurements of Absolute Neutrophil Count (ANC) >=500 per Microliter [mcgL] on 3 Different Days)

  Within 42 Days After CTX001 Infusion

• TDT and SCD: Time to Engraftment

  Up to 12 Months After CTX001 Infusion

• TDT and SCD: Incidence of Transplant-Related Mortality (TRM) Within 100 Days After CTX001 Infusion

  Within 100 Days After CTX001 Infusion

• TDT and SCD: Incidence of TRM Within 12 Months After CTX001 Infusion

  Within 12 Months 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). Participants will receive a single infusion of CTX001 through a central venous catheter.

Biological: CTX001

Interventions

CTX001 BIOLOGICAL

Administered by intravenous (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:

• Participants with TDT and SCD:
• Eligible for autologous stem cell transplant as per investigator's judgment.
• Participants with TDT:
• Diagnosis of 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 milliliter (mL)/kilograms (kg)/year or 10 units/year of packed red blood cells (RBC) transfusions in the prior 2 years before signing the consent or the last rescreening for patients going through re-screening
• Participants with SCD:
• Diagnosis of severe SCD as defined by:
• Documented SCD genotypes
• History of at least two severe VOCs events per year for the previous two years prior to enrollment

You may not qualify if:

• Participants with TDT and SCD:
• A willing and healthy 10/10 human leukocyte antigen (HLA)-matched related donor is available per investigator's judgement
• Prior hematopoietic stem cell transplant (HSCT)
• Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator
• Participants with TDT:
• Participants with associated α-thalassemia and \>1 alpha deletion, or alpha multiplications
• Participants with sickle cell β-thalassemia variant
• Participants with SCD:
• History of untreated moyamoya syndrome or presence of moyamoya syndrome at screening

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead

Study Sites (6)

New York Presbyterian Hospital - Morgan Stanley Children's Hospital

New York, New York, 10032, United States

RECRUITING

Levine Children's Hospital - Hematology

Charlotte, North Carolina, 28203, United States

RECRUITING

TriStar Medical Group Children's Specialists - Pediatric Oncology

Nashville, Tennessee, 37203, United States

RECRUITING

University Hospital Dusseldorf - Department of Pediatric Oncology, Hematology and Clinical Immunology

Düsseldorf, Germany

RECRUITING

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

Rome, Italy

RECRUITING

King Faisal Specialist Hospital & Research Centre - Riyadh - Hematology

Al Mathar Ash Shamali, Saudi Arabia

RECRUITING

MeSH Terms

Conditions

beta-Thalassemia; Thalassemia; Hematologic Diseases; Genetic Diseases, Inborn; Hemoglobinopathies; Anemia, Sickle Cell

Interventions

exagamglogene autotemcel

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Medical Information

CONTACT

6173416777; medicalinfo@vrtx.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2022
• First Posted: July 28, 2022
• Study Start: August 2, 2022
• Primary Completion (Estimated): June 9, 2027
• Study Completion (Estimated): June 9, 2027
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); US (3); DE (1); SA (1)