Hemoglobinopathies, Thalassemia Intermedia, Thalassemia Major, Transfusion Dependent Beta Thalassemia
Conditions
Keywords
Beta-Thalassemia, Hemoglobinopathies, CRISPR-Cas 12a, Autologous CD34+
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
Interventions
GENETICEDIT-301
Administered by intravenous infusion after myeloablative conditioning with busulfan.
Sponsors
Editas Medicine, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
Key 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 | — |
| 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 | — |
| Change in the total hemoglobin concentration compared to baseline overtime | Baseline through up to 24 months post EDIT-301 infusion | — |
| Change in the fetal hemoglobin (HbF) concentration compared to baseline overtime | Baseline through 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 | 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 | — |
| Change in parameters of iron overload compared to baseline over time | Baseline 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 | — |
| 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 | — |
| Kinetics of HSPC engraftment | 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 | Time to neutrophil engraftment |
Countries
Canada, United States
Outcome results
None listed