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

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)

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

Study Overview

• Status: Recruiting
• Conditions: Hemoglobinopathies; Thalassemia Major; Thalassemia Intermedia; Transfusion Dependent Beta Thalassemia
• Intervention / Treatment: Genetic: EDIT-301

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 Type: Interventional
• Enrollment (Estimated): 9
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Editas Medicine Clinical Trial Team; Phone Number: 617-401-9007; Email: Patients@editasmed.com

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • Princess Margaret Cancer Centre-University Health Network
• United States
  • California
    • Oakland, California, United States, 94609
      • Recruiting
      • University of California San Francisco
  • Minnesota
    • Minneapolis, Minnesota, United States, 55410
      • Recruiting
      • University of Minnesota
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center - Department of Pediatrics
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tristar Medical Group Children's Specialists/Sarah Cannon Center for Blood Cancers

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.; Other Names: renizgamglogene autogedtemcel; reni-cel

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kinetics of HSPC engraftment	Time to neutrophil 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
Kinetics of HSPC engraftment	Time to platelet 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.
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

Collaborators and Investigators

• Sponsor: Editas Medicine, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2022
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: June 27, 2022
• First Submitted That Met QC Criteria: July 1, 2022
• First Posted (Actual): July 6, 2022

Study Record Updates

• Last Update Posted (Actual): January 29, 2024
• Last Update Submitted That Met QC Criteria: January 26, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Beta-Thalassemia; Hemoglobinopathies; CRISPR-Cas 12a; Autologous CD34+
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Thalassemia; beta-Thalassemia; Hemoglobinopathies
• Other Study ID Numbers: EM-301-BThal-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No