- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03655678
A Safety and Efficacy Study Evaluating CTX001 in Subjects With Transfusion-Dependent β-Thalassemia
December 21, 2023 updated by: Vertex Pharmaceuticals Incorporated
A Phase 1/2/3 Study of the Safety and Efficacy of a Single Dose of Autologous CRISPR-Cas9 Modified CD34+ Human Hematopoietic Stem and Progenitor Cells (hHSPCs) in Subjects With Transfusion-Dependent β-Thalassemia
This is a single-arm, open-label, multi-site, single-dose Phase 1/2/3 study in subjects 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.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Estimated)
45
Phase
- Phase 2
- 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 Locations
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Toronto, Canada
- Hospital for Sick Children
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Vancouver, Canada
- BC Children's Hospital
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Düsseldorf, Germany
- University Hospital Duesseldorf
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Regensburg, Germany
- University Hospital Regensburg
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Tuebingen, Germany
- University Hospital Tübingen
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Rome, Italy
- Bambino Gesu
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London, United Kingdom
- University College London Hospitals NHS Foundation Trust
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London, United Kingdom
- Imperial College Healthcare
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California
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Stanford, California, United States, 94305
- Stanford University
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Illinois
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Chicago, Illinois, United States, 60611
- Ann & Robert Lurie Children's Hospital of Chicago
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New York
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Manhattan, New York, United States, 10027
- Columbia University
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- Children's Hospital of Philadelphia
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Tennessee
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Nashville, Tennessee, United States, 37203
- The Children's Hospital at TriStar Centennial Medical Center/ Sarah Cannon Center for Blood Cancers
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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
10 years to 33 years (Child, Adult)
Accepts Healthy Volunteers
No
Description
Key Inclusion Criteria:
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). Subjects 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.
Key Exclusion Criteria:
- A willing and healthy 10/10 Human Leukocyte Antigen (HLA)-matched related donor is available per investigator's judgement.
- Prior allo-HSCT.
- Subjects with associated α-thalassemia and >1 alpha deletion or alpha multiplications.
- Subjects 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.
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).
Subjects will receive a single infusion of CTX001 through a central venous catheter.
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Administered by 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 |
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Proportion of subjects achieving transfusion independence for at least 12 consecutive months (TI12)
Time Frame: From 60 days after last RBC transfusion up to 24 months post-CTX001 infusion]
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From 60 days after last RBC transfusion up to 24 months post-CTX001 infusion]
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Proportion of subjects with engraftment (first day of 3 consecutive measurements of absolute neutrophil count [ANC] ≥500/µL on three different days)
Time Frame: Within 42 days after CTX001 infusion
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Within 42 days after CTX001 infusion
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Time to neutrophil and platelet engraftment
Time Frame: Days post-infusion to engraftment
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Days post-infusion to engraftment
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Frequency and severity of collected adverse events (AEs)
Time Frame: Signing of informed consent through Month 24 visit
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Signing of informed consent through Month 24 visit
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Incidence of transplant-related mortality (TRM)
Time Frame: Baseline (pre-transfusion) to 100 days and 1 year post-CTX001 infusion
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Baseline (pre-transfusion) to 100 days and 1 year post-CTX001 infusion
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All-cause mortality
Time Frame: Signing of informed consent through Month 24 visit
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Signing of informed consent through Month 24 visit
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Proportion of subjects achieving transfusion independence for at least 6 consecutive months (TI6)
Time Frame: From 60 days after last RBC transfusion up to 24 months post-CTX001 infusion
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From 60 days after last RBC transfusion up to 24 months post-CTX001 infusion
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Proportion of subjects achieving at least 95 percent (%), 90%, 85%, 75%, and 50% reduction from baseline in annualized transfusions 60 days after CTX001 infusion
Time Frame: From Day 60 up to 24 months post-CTX001 infusion
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From Day 60 up to 24 months post-CTX001 infusion
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Relative change from baseline in transfusions 60 days after CTX001 infusion
Time Frame: From Day 60 up to 24 months post-CTX001 infusion
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From Day 60 up to 24 months post-CTX001 infusion
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Duration of transfusion free in subjects who have achieved TI12
Time Frame: From 60 days after last RBC transfusion up to 24 months post-CTX001 infusion
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From 60 days after last RBC transfusion up to 24 months post-CTX001 infusion
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Proportion of alleles with intended genetic modification in peripheral blood leukocytes over time
Time Frame: Day 1 CTX001 infusion through Month 24 visit
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Day 1 CTX001 infusion through Month 24 visit
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Proportion of alleles with intended genetic modification present in CD34+ cells of bone marrow over time
Time Frame: Day 1 CTX001 infusion through Month 24 visit
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Day 1 CTX001 infusion through Month 24 visit
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Change in fetal hemoglobin concentration over time
Time Frame: Baseline (pre-transfusion) through Month 24 visit
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Baseline (pre-transfusion) through Month 24 visit
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Change in total hemoglobin concentration over time
Time Frame: Baseline (pre-transfusion) through Month 24 visit
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Baseline (pre-transfusion) through Month 24 visit
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Change in health-related quality of life (HRQoL) from baseline over time using EuroQol Questionnaire (5 dimensions - 5 levels of severity - EQ-5D-5L)
Time Frame: Screening visit through Month 24 visit
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The EQ-5D-5L Questionnaire consists of the EQ-5D descriptive system and the EQ visual analogue scale (VAS).
The EQ-5D comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression, and 5 levels: no problems to extreme problems.
The subject marks the most appropriate statement in each dimension, resulting in a 1-digit number for that dimension.
The digits can be combined in a 5-digit number describing the subject's health state.
The EQ VAS records the subject's self-rated health on a 100-point VAS, endpoints labelled "the best health you can imagine" and "the worst health you can imagine."
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Screening visit through Month 24 visit
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Change in health-related quality of life (HRQoL) from baseline over time using the Functional assessment of cancer therapy-bone marrow transplant questionnaire (FACT-BMT)
Time Frame: Screening visit through Month 24 visit
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The FACT-BMT Questionnaire includes physical, social, family, emotional, and functional well-being, and treatment specific concerns of bone marrow transplantation.
Each statement has a 5-point Likert-type response scale ranging from 0=not at all to 4=very much.
The subject marks one number per line as it applies to the past 7 days.
Questionnaires are scored; the higher the score, the better the QOL.
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Screening visit through Month 24 visit
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Change in patient reported outcome (PRO) over time assessed using EQ-5D-Youth (EQ-5D-Y)
Time Frame: Screening visit through Month 24 visit
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Screening visit through Month 24 visit
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Change in PRO over time assessed using pediatric quality of life inventory (PedsQL)
Time Frame: Screening visit through Month 24 visit
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Screening visit through Month 24 visit
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Changes in liver iron concentration (LIC) and cardiac iron content (CIC) and ferritin parameters of iron overload
Time Frame: Screening visit through Month 24 visit
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Screening visit through Month 24 visit
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Proportion of subjects receiving iron chelation therapy
Time Frame: 1 month post-CTX001 infusion through Month 24 visit
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1 month post-CTX001 infusion through Month 24 visit
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
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)
September 14, 2018
Primary Completion (Estimated)
August 1, 2024
Study Completion (Estimated)
August 1, 2024
Study Registration Dates
First Submitted
August 29, 2018
First Submitted That Met QC Criteria
August 30, 2018
First Posted (Actual)
August 31, 2018
Study Record Updates
Last Update Posted (Actual)
December 22, 2023
Last Update Submitted That Met QC Criteria
December 21, 2023
Last Verified
November 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CTX001-111
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
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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Vertex Pharmaceuticals IncorporatedNot yet recruiting
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Vertex Pharmaceuticals IncorporatedCRISPR TherapeuticsRecruitingHematologic Diseases | Genetic Diseases, Inborn | Sickle Cell Disease | Hemoglobinopathies | Sickle Cell Anemia | Thalassemia | Beta-ThalassemiaUnited States, Italy, Germany
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Vertex Pharmaceuticals IncorporatedCRISPR TherapeuticsRecruitingHematologic Diseases | Genetic Diseases, Inborn | Hemoglobinopathies | Thalassemia | Beta-ThalassemiaUnited States, Germany, Italy, United Kingdom, Canada
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ElsanRecruiting