A Multicenter Study to Evaluate the Safety, Tolerability, and Efficacy of a Single Dose of Autologous Clustered Regularly Interspaced Short Palindromic Repeats Gene-edited Cluster of Differentiation 34 (CD34+) Human Hematopoietic Stem and Progenitor Cells (HSPC) (EDIT-301) in Transfusion-Dependent Beta Thalassemia (TDT)

Editas Medicine, Inc.8 sites in 2 countries9 target enrollmentApril 29, 2022

ConditionsTransfusion Dependent Beta Thalassemia Hemoglobinopathies Thalassemia Major Thalassemia Intermedia

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Transfusion Dependent Beta Thalassemia
Sponsor: Editas Medicine, Inc.
Enrollment: 9
Locations: 8
Primary Endpoint: 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)
Status: Active, not recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

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

Registry

clinicaltrials.gov

Start Date

April 29, 2022

End Date

December 2025

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Editas Medicine, Inc.

Responsible Party

Sponsor

Eligibility Criteria

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

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

Outcomes

Primary Outcomes

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

Secondary Outcomes

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.)
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)