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

Phase 1

Recruiting

• Conditions: Hemoglobinopathies; Transfusion Dependent Beta Thalassemia; Thalassemia Intermedia; Thalassemia Major
• Interventions: Genetic: EDIT-301

• 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

Study Timeline

• Study Start: 2022-04-29
• Study First Submitted: 2022-06-27
• Study First Submitted QC: 2022-07-01
• Study First Posted: 2022-07-06
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-26
• Last Update Posted: 2024-01-29
• Primary Completion: 2025-09
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: 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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

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)

Princess Margaret Cancer Centre-University Health Network; 🇨🇦 Toronto, Ontario, Canada

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

University of California San Francisco; 🇺🇸 Oakland, California, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

Columbia University Medical Center - Department of Pediatrics; 🇺🇸 New York, New York, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Tristar Medical Group Children's Specialists/Sarah Cannon Center for Blood Cancers; 🇺🇸 Nashville, Tennessee, United States

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States