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

March 18, 2026 updated by: Vertex Pharmaceuticals Incorporated

A Phase 3b Study to Evaluate Efficacy and Safety of a Single Dose of Autologous CRISPR Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (CTX001) in Subjects With Transfusion-Dependent β-Thalassemia or Severe Sickle Cell Disease

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
26

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Germany
      • Düsseldorf, Germany
        • Recruiting
        • University Hospital Dusseldorf - Department of Pediatric Oncology, Hematology and Clinical Immunology
  • Italy
      • Rome, Italy
        • Recruiting
        • IRCSS Ospedale Pediatrico Bambino Gesu - Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica
  • Saudi Arabia
      • Al Mathar Ash Shamali, Saudi Arabia
        • Recruiting
        • King Faisal Specialist Hospital & Research Centre - Riyadh - Hematology
  • United States
    • New York
      • New York, New York, United States, 10032
        • Recruiting
        • New York Presbyterian Hospital - Morgan Stanley Children's Hospital
    • North Carolina
      • Charlotte, North Carolina, United States, 28203
        • Recruiting
        • Levine Children's Hospital - Hematology
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • TriStar Medical Group Children's Specialists - Pediatric Oncology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

12 years to 35 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  • 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

Key Exclusion Criteria:

  • 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

Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Biological: CTX001
Administered by intravenous (IV) infusion following myeloablative conditioning with busulfan
Other Names:
  • Exagamglogene autotemcel
  • Exa-cel

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Fetal Hemoglobin (HbF) Concentration Over Time
Time Frame: Up to 12 Months After CTX001 Infusion
Up to 12 Months After CTX001 Infusion
Total Hemoglobin (Hb) Concentration Over Time
Time Frame: Up to 12 Months After CTX001 Infusion
Up to 12 Months After CTX001 Infusion

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
TDT and SCD: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: From Signing of Informed Consent up to 12 Months After CTX001 Infusion
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)
Time Frame: Within 42 Days After CTX001 Infusion
Within 42 Days After CTX001 Infusion
TDT and SCD: Time to Engraftment
Time Frame: Up to 12 Months After CTX001 Infusion
Up to 12 Months After CTX001 Infusion
TDT and SCD: Incidence of Transplant-Related Mortality (TRM) Within 100 Days After CTX001 Infusion
Time Frame: Within 100 Days After CTX001 Infusion
Within 100 Days After CTX001 Infusion
TDT and SCD: Incidence of TRM Within 12 Months After CTX001 Infusion
Time Frame: Within 12 Months After CTX001 Infusion
Within 12 Months After CTX001 Infusion
TDT and SCD: Incidence of All-cause Mortality
Time Frame: From Signing of Informed Consent up to 12 Months After CTX001 Infusion
From Signing of Informed Consent up to 12 Months After CTX001 Infusion
TDT and SCD: Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time
Time Frame: Up to 12 Months After CTX001 Infusion
Up to 12 Months After CTX001 Infusion
TDT and SCD: Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time
Time Frame: Up to 12 Months After CTX001 Infusion
Up to 12 Months After CTX001 Infusion
TDT: Duration Transfusion Free in Participants
Time Frame: Up to 12 Months After CTX001 Infusion
Up to 12 Months After CTX001 Infusion
TDT and SCD: Relative Reduction in Annualized Volume of RBC Transfusions
Time Frame: From Day 60 up to 12 Months After CTX001 Infusion
From Day 60 up to 12 Months After CTX001 Infusion
SCD: Relative Reduction in Annualized Rate of Severe Vaso-Occlusive Crises (VOCs)
Time Frame: From Baseline up to 12 Months After CTX001 Infusion
From Baseline up to 12 Months After CTX001 Infusion
SCD: Relative Reduction in Annualized Rate of Inpatient Hospitalizations for Severe VOCs
Time Frame: From Baseline up to 12 Months After CTX001 Infusion
From Baseline up to 12 Months After CTX001 Infusion
SCD: Relative Reduction in Annualized Duration of Hospitalization for Severe VOCs
Time Frame: From Baseline up to 12 Months After CTX001 Infusion
From Baseline up to 12 Months After CTX001 Infusion
SCD: Relative Reduction in Haptoglobin
Time Frame: From Baseline up to 12 Months After CTX001 Infusion
From Baseline up to 12 Months After CTX001 Infusion
SCD: Relative Reduction in Lactate dehydrogenase
Time Frame: From Baseline up to 12 Months After CTX001 Infusion
From Baseline up to 12 Months After CTX001 Infusion
SCD: Relative Reduction in Total Bilirubin
Time Frame: From Baseline up to 12 Months After CTX001 Infusion
From Baseline up to 12 Months After CTX001 Infusion
SCD: Relative Reduction in Indirect Bilirubin
Time Frame: From Baseline up to 12 Months After CTX001 Infusion
From Baseline up to 12 Months After CTX001 Infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Vertex Pharmaceuticals Incorporated

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
CRISPR Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 2, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 9, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 9, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 26, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 26, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 28, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 23, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 18, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • VX21-CTX001-161
  • 2024-514641-12-00 (Other Identifier: EU CT number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

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/

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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