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
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
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
Administered by intravenous infusion after myeloablative conditioning with busulfan.
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
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)
Time frame: 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)
Time frame: Screening through up to 24 months post EDIT-301 infusion
Kinetics of HSPC engraftment
Time to neutrophil engraftment
Time frame: EDIT-301 infusion (Day 0) to first day in which 3 consecutive measurements obtained on different days demonstrate ANC ≥ 0.5 x 10^9/L up to 24 months post EDIT-301 infusion
Kinetics of HSPC engraftment
Time to platelet engraftment
Time frame: 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.
Incidence of transplant related mortality
Time frame: 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
Incidence of all-cause mortality
Time frame: 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
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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
Time frame: EDIT-301 infusion (Day 0) through up to 24 months post EDIT-301 infusion
Proportion of alleles per participant with intended genetic modification present in bone marrow cells over time
Time frame: EDIT-301 infusion (Day 0) through up to 24 months post EDIT-301 infusion
Change in the fetal hemoglobin (HbF) concentration compared to baseline overtime
Time frame: Baseline through up to 24 months post EDIT-301 infusion
Change in the total hemoglobin concentration compared to baseline overtime
Time frame: Baseline through up to 24 months post EDIT-301 infusion
Proportion of participants with hemoglobin concentration ≥ 9 g/dL
Time frame: EDIT-301 infusion (Day 0) through 3, 6, 12 months up to 24 months post EDIT-301 infusion
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
Time frame: 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
Time frame: 3 months through up to 24 months post EDIT-301 infusion
Change in parameters of iron overload compared to baseline over time
Time frame: Baseline through up to 24 months post EDIT-301 infusion
Proportion of participants receiving iron chelation therapy over time
Time frame: EDIT-301 infusion (Day 0) through up to 24 months post EDIT-301 infusion