EDIT-301 for Autologous Hematopoietic Stem Cell Transplant (HSCT) in Participants With Transfusion-Dependent Beta Thalassemia (TDT)

Sponsor

Editas Medicine, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05444894

Collaborator

(none)

Enrollment

Location

Arm

43.1

Anticipated Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Transfusion Dependent Beta Thalassemia Hemoglobinopathies Thalassemia Major Thalassemia Intermedia	Genetic: EDIT-301	Phase 1/Phase 2

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

6 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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)

Actual Study Start Date :

Apr 29, 2022

Anticipated Primary Completion Date :

Sep 1, 2025

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: EDIT-301 EDIT-301 (autologous gene edited (CD)34+ hematopoietic stem cells) will be administered as a one-time intravenous infusion.	Genetic: EDIT-301 Administered by intravenous infusion after myeloablative conditioning with busulfan.

Arm

Intervention/Treatment

Experimental: EDIT-301

EDIT-301 (autologous gene edited (CD)34+ hematopoietic stem cells) will be administered as a one-time intravenous infusion.

Genetic: EDIT-301

Administered by intravenous infusion after myeloablative conditioning with busulfan.

Outcome Measures

Primary Outcome Measures

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

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
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
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 fetal hemoglobin (HbF) concentration compared to baseline overtime [Baseline 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]
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 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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 35 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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