A Safety and Efficacy Study Evaluating CTX001 in Subjects With Transfusion-Dependent β-Thalassemia
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|ClinicalTrials.gov Identifier: NCT03655678|
Recruitment Status : Active, not recruiting
First Posted : August 31, 2018
Last Update Posted : December 1, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Beta-Thalassemia Thalassemia Genetic Diseases, Inborn Hematologic Diseases Hemoglobinopathies||Biological: CTX001||Phase 2 Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||45 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||September 14, 2018|
|Estimated Primary Completion Date :||August 2024|
|Estimated Study Completion Date :||August 2024|
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.
Administered by IV infusion following myeloablative conditioning with busulfan
- 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] ]
- 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 ]
- Time to neutrophil and platelet engraftment [ Time Frame: Days post-infusion to engraftment ]
- Frequency and severity of collected adverse events (AEs) [ Time Frame: Signing of informed consent through Month 24 visit ]
- Incidence of transplant-related mortality (TRM) [ Time Frame: Baseline (pre-transfusion) to 100 days and 1 year post-CTX001 infusion ]
- All-cause mortality [ Time Frame: Signing of informed consent through Month 24 visit ]
- 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 ]
- 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 ]
- Relative change from baseline in transfusions 60 days after CTX001 infusion [ Time Frame: From Day 60 up to 24 months post-CTX001 infusion ]
- 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 ]
- Proportion of alleles with intended genetic modification in peripheral blood leukocytes over time [ Time Frame: Day 1 CTX001 infusion through Month 24 visit ]
- 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 ]
- Change in fetal hemoglobin concentration over time [ Time Frame: Baseline (pre-transfusion) through Month 24 visit ]
- Change in total hemoglobin concentration over time [ Time Frame: Baseline (pre-transfusion) through Month 24 visit ]
- 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 ]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."
- 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 ]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.
- Change in patient reported outcome (PRO) over time assessed using EQ-5D-Youth (EQ-5D-Y) [ Time Frame: Screening visit through Month 24 visit ]
- Change in PRO over time assessed using pediatric quality of life inventory (PedsQL) [ Time Frame: Screening visit through Month 24 visit ]
- 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 ]
- Proportion of subjects receiving iron chelation therapy [ Time Frame: 1 month post-CTX001 infusion through Month 24 visit ]
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|Ages Eligible for Study:||12 Years to 35 Years (Child, Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03655678
|United States, California|
|Stanford, California, United States, 94305|
|United States, Illinois|
|Ann & Robert Lurie Children's Hospital of Chicago|
|Chicago, Illinois, United States, 60611|
|United States, New York|
|Manhattan, New York, United States, 10027|
|United States, Tennessee|
|The Children's Hospital at TriStar Centennial Medical Center/ Sarah Cannon Center for Blood Cancers|
|Nashville, Tennessee, United States, 37203|
|Hospital for Sick Children|
|BC Children's Hospital|
|University Hospital Duesseldorf|
|University Hospital Regensburg|
|University Hospital Tübingen|
|Imperial College Healthcare|
|London, United Kingdom|
|University College London Hospitals NHS Foundation Trust|
|London, United Kingdom|
|Responsible Party:||Vertex Pharmaceuticals Incorporated|
|Other Study ID Numbers:||
|First Posted:||August 31, 2018 Key Record Dates|
|Last Update Posted:||December 1, 2022|
|Last Verified:||November 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|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|
Genetic Diseases, Inborn
Anemia, Hemolytic, Congenital