EDIT-301 for Autologous Hematopoietic Stem Cell Transplant (HSCT) in Participants With Transfusion-Dependent Beta Thalassemia (TDT)
Phase 1
Active, not recruiting
- Conditions
- HemoglobinopathiesTransfusion Dependent Beta ThalassemiaThalassemia IntermediaThalassemia Major
- Registration Number
- NCT05444894
- Lead Sponsor
- Editas Medicine, Inc.
- Brief Summary
The purpose of this study is to evaluate the safety, tolerability, and efficacy of treatment with EDIT-301 in adult participants with Transfusion Dependent beta Thalassemia
- Detailed Description
This is a Phase 1/2 single-arm, open-label, multicenter study evaluating the safety, tolerability, and efficacy of a single unit dose of EDIT-301 for autologous hematopoietic stem cell transplant in adult participants with TDT, age 18 to 35 years, inclusive
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 9
Inclusion Criteria
Diagnosis of Transfusion Dependent B-Thalassemia as defined by:
- Documented homozygous β-thalassemia or compound heterozygous β-thalassemia including β-thalassemia/hemoglobin E (HbE) based on historical data in medical records, and
- History of at least 100 mL/kg/year or 10 U/year of packed red blood cell (RBC) transfusions in the 2 years prior to signing informed consent
- Clinically stable and eligible to undergo autologous HSCT
- Karnofsky Performance Status ≥ 70
Key
Exclusion Criteria
- Available 10/10 human leukocyte antigen (HLA)-matched related donor
- Prior HSCT or contraindications to autologous HSCT
- Participants with associated a history of α-thalassemia and > 1 alpha chain deletion, or alpha multiplications as documented in medical records
- Participants with a history of other inherited hemoglobinopathy or thalassemic mutation (Hb S, C, D or other) as documented in medical records
- Prior receipt of gene therapy
- Inadequate bone marrow function, as defined by white blood cell count of < 3 x 10^9/L or a platelet count < 100 x 10^9/L (without hypersplenism), per investigator judgement
- Inadequate organ function
- Advanced liver disease
- Any prior or current malignancy, or immunodeficiency disorder,
- Immediate family member with a known or suspected Familial Cancer Syndrome
- Clinically significant and active bacterial, viral, fungal, or parasitic infection
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method Proportion of participants achieving engraftment defined as neutrophil engraftment (defined as demonstrating absolute neutrophil count (ANC) ≥ 0.5 x 10^9/L post EDIT-301 infusion for 3 consecutive measurements obtained on different days) EDIT-301 infusion (Day 0) to 42 days post EDIT-301 infusion Frequency and severity of adverse events (AEs) (incidence of AEs and Grade 3 or higher serious adverse events, using National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v.5.0) Screening through up to 24 months post EDIT-301 infusion
- Secondary Outcome Measures
Name Time Method Change in the fetal hemoglobin (HbF) concentration compared to baseline overtime Baseline through up to 24 months post EDIT-301 infusion Proportion of participants with hemoglobin concentration ≥ 9 g/dL EDIT-301 infusion (Day 0) through 3, 6, 12 months up to 24 months post EDIT-301 infusion Proportion of alleles per participant with intended genetic modification present in bone marrow cells over time EDIT-301 infusion (Day 0) through up to 24 months post EDIT-301 infusion Incidence of all-cause mortality Screening through up to 24 months post EDIT-301 infusion Proportion of alleles per participant with intended genetic modification present in peripheral blood over time EDIT-301 infusion (Day 0) through up to 24 months post EDIT-301 infusion Change in the total hemoglobin concentration compared to baseline overtime Baseline through up to 24 months post EDIT-301 infusion Change in parameters of iron overload compared to baseline over time Baseline through up to 24 months post EDIT-301 infusion Kinetics of HSPC engraftment EDIT-301 infusion (Day 0) to first day of 3 consecutive measurements of platelets ≥ 50 x 10^9/L for at least 1 week following the last platelet transfusion and 10 days following thrombopoietin mimetics use up to 24 months post EDIT-301 infusion. Time to platelet engraftment
Proportion of participants achieving the sustained transfusion reduction (TR) for at least 6 months and at least 12 months from 3 months post-EDIT-301 infusion 3 months post EDIT-301 infusion through up to 24 months post EDIT-301 infusion Proportion of participants achieving the sustained transfusion independence (TI) for at least 6 months and, at least 12 months from 3 months post EDIT-301 infusion 3 months through up to 24 months post EDIT-301 infusion Proportion of participants receiving iron chelation therapy over time EDIT-301 infusion (Day 0) through up to 24 months post EDIT-301 infusion Incidence of transplant related mortality EDIT-301 infusion (Day 0) through Day 100 post EDIT-301 infusion and from EDIT-301 infusion (Day 0) through 12 months post EDIT-301 infusion
Trial Locations
- Locations (8)
University of California San Francisco
🇺🇸Oakland, California, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Columbia University Medical Center - Department of Pediatrics
🇺🇸New York, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Tristar Medical Group Children's Specialists/Sarah Cannon Center for Blood Cancers
🇺🇸Nashville, Tennessee, United States
Princess Margaret Cancer Centre-University Health Network
🇨🇦Toronto, Ontario, Canada
University of California San Francisco🇺🇸Oakland, California, United States