- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05477563
Evaluation of Efficacy and Safety of a Single Dose of CTX001 in Participants With Transfusion-Dependent β-Thalassemia and Severe Sickle Cell Disease
March 14, 2024 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
Recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Estimated)
26
Phase
- 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
- Name: Medical Information
- Phone Number: 617-341-6777
- Email: medicalinfo@vrtx.com
Study Locations
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Duesseldorf, Germany
- Recruiting
- Universitätsklinikum Düsseldorf Hospital Duesseldorf
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Rome, Italy
- Active, not recruiting
- Ospedale Pediatrico Bambino Gesù, IRCCS
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New York
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New York, New York, United States, 10032
- Recruiting
- Columbia University Medical Center
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North Carolina
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Charlotte, North Carolina, United States, 28203
- Recruiting
- Atrium Health Levine Children's Hospital
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Tennessee
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Nashville, Tennessee, United States, 37203
- Recruiting
- SCRI at the Children's Hospital at TriStar Centennial
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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
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 |
Intervention / Treatment |
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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.
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Administered by intravenous (IV) infusion following myeloablative conditioning with busulfan.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Fetal Hemoglobin (HbF) Concentration Over Time
Time Frame: Up to 12 Months After CTX001 Infusion
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Up to 12 Months After CTX001 Infusion
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Total Hemoglobin (Hb) Concentration Over Time
Time Frame: Up to 12 Months After CTX001 Infusion
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Up to 12 Months After CTX001 Infusion
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Secondary Outcome Measures
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
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From Signing of Informed Consent up to 12 Months After CTX001 Infusion
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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
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Within 42 Days After CTX001 Infusion
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TDT and SCD: Time to Engraftment
Time Frame: Up to 12 Months After CTX001 Infusion
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Up to 12 Months After CTX001 Infusion
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TDT and SCD: Incidence of Transplant-Related Mortality (TRM) Within 100 Days After CTX001 Infusion
Time Frame: Within 100 Days After CTX001 Infusion
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Within 100 Days After CTX001 Infusion
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TDT and SCD: Incidence of TRM Within 12 Months After CTX001 Infusion
Time Frame: Within 12 Months After CTX001 Infusion
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Within 12 Months After CTX001 Infusion
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TDT and SCD: Incidence of All-cause Mortality
Time Frame: From Signing of Informed Consent up to 12 Months After CTX001 Infusion
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From Signing of Informed Consent up to 12 Months After CTX001 Infusion
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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
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Up to 12 Months After CTX001 Infusion
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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
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Up to 12 Months After CTX001 Infusion
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TDT: Duration Transfusion Free in Participants
Time Frame: Up to 12 Months After CTX001 Infusion
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Up to 12 Months After CTX001 Infusion
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TDT and SCD: Relative Reduction in Annualized Volume of RBC Transfusions
Time Frame: From Day 60 up to 12 Months After CTX001 Infusion
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From Day 60 up to 12 Months After CTX001 Infusion
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SCD: Relative Reduction in Annualized Rate of Severe Vaso-Occlusive Crises (VOCs)
Time Frame: From Baseline up to 12 Months After CTX001 Infusion
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From Baseline up to 12 Months After CTX001 Infusion
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SCD: Relative Reduction in Annualized Rate of Inpatient Hospitalizations for Severe VOCs
Time Frame: From Baseline up to 12 Months After CTX001 Infusion
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From Baseline up to 12 Months After CTX001 Infusion
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SCD: Relative Reduction in Annualized Duration of Hospitalization for Severe VOCs
Time Frame: From Baseline up to 12 Months After CTX001 Infusion
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From Baseline up to 12 Months After CTX001 Infusion
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SCD: Relative Reduction in Haptoglobin
Time Frame: From Baseline up to 12 Months After CTX001 Infusion
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From Baseline up to 12 Months After CTX001 Infusion
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SCD: Relative Reduction in Lactate dehydrogenase
Time Frame: From Baseline up to 12 Months After CTX001 Infusion
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From Baseline up to 12 Months After CTX001 Infusion
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SCD: Relative Reduction in Total Bilirubin
Time Frame: From Baseline up to 12 Months After CTX001 Infusion
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From Baseline up to 12 Months After CTX001 Infusion
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SCD: Relative Reduction in Indirect Bilirubin
Time Frame: From Baseline up to 12 Months After CTX001 Infusion
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From Baseline up to 12 Months After CTX001 Infusion
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
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)
August 2, 2022
Primary Completion (Estimated)
February 1, 2025
Study Completion (Estimated)
February 1, 2025
Study Registration Dates
First Submitted
July 26, 2022
First Submitted That Met QC Criteria
July 26, 2022
First Posted (Actual)
July 28, 2022
Study Record Updates
Last Update Posted (Actual)
March 15, 2024
Last Update Submitted That Met QC Criteria
March 14, 2024
Last Verified
March 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- VX21-CTX001-161
- 2021-006390-37 (EudraCT 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/independent-research/clinical-trial-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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Clinical Trials on CTX001
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Vertex Pharmaceuticals IncorporatedCRISPR TherapeuticsEnrolling by invitationHematologic Diseases | Genetic Diseases, Inborn | Sickle Cell Disease | Hemoglobinopathies | Sickle Cell Anemia | Thalassemia | Beta-ThalassemiaUnited States, Canada, Italy, United Kingdom, Germany
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Vertex Pharmaceuticals IncorporatedCRISPR TherapeuticsActive, not recruitingHematologic Diseases | Genetic Diseases, Inborn | Hemoglobinopathies | Thalassemia | Beta-ThalassemiaUnited States, United Kingdom, Germany, Canada, Italy
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Vertex Pharmaceuticals IncorporatedCRISPR TherapeuticsRecruitingSickle Cell Disease | Hemoglobinopathies | Hematological Diseases | Hydroxyurea Failure | Hydroxyurea IntoleranceUnited States, Italy, United Kingdom, Germany
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Vertex Pharmaceuticals IncorporatedCRISPR TherapeuticsActive, not recruitingSickle Cell Disease | Hemoglobinopathies | Hematological DiseasesUnited States, Belgium, Canada, France, Germany, Italy, United Kingdom
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Vertex Pharmaceuticals IncorporatedNot yet recruiting
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Vertex Pharmaceuticals IncorporatedCRISPR TherapeuticsRecruitingHematologic Diseases | Genetic Diseases, Inborn | Hemoglobinopathies | Thalassemia | Beta-ThalassemiaUnited States, Germany, Italy, United Kingdom, Canada