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

Hemoglobinopathies Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05444894
• Other study ID #: EM-301-BThal-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 29, 2022
• Est. completion date: December 2025

Study information

• Verified date: January 2024
• Source: Editas Medicine, Inc.
• Contact: Editas Medicine Clinical Trial Team
• Phone: 617-401-9007
• Email: Patients[@]editasmed.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 9
• Est. completion date: December 2025
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 35 Years

Eligibility

Key Inclusion Criteria:

Diagnosis of Transfusion Dependent B-Thalassemia as defined by:

• Documented homozygous ß-thalassemia or compound heterozygous ß-thalassemia including ß-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 a-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

Related Conditions & MeSH terms

• beta-Thalassemia
• Hemoglobinopathies
• Thalassemia
• Thalassemia Intermedia
• Thalassemia Major

Intervention

Genetic:
• EDIT-301
Administered by intravenous infusion after myeloablative conditioning with busulfan.

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre-University Health Network	Toronto	Ontario
United States	Cleveland Clinic	Cleveland	Ohio
United States	University of Minnesota	Minneapolis	Minnesota
United States	Tristar Medical Group Children's Specialists/Sarah Cannon Center for Blood Cancers	Nashville	Tennessee
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	University of California San Francisco	Oakland	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Editas Medicine, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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.
Secondary	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
Secondary	Incidence of all-cause mortality		Screening through up to 24 months post EDIT-301 infusion
Secondary	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
Secondary	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
Secondary	Change in the fetal hemoglobin (HbF) concentration compared to baseline overtime		Baseline through up to 24 months post EDIT-301 infusion
Secondary	Change in the total hemoglobin concentration compared to baseline overtime		Baseline through up to 24 months post EDIT-301 infusion
Secondary	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
Secondary	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
Secondary	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
Secondary	Change in parameters of iron overload compared to baseline over time		Baseline through up to 24 months post EDIT-301 infusion
Secondary	Proportion of participants receiving iron chelation therapy over time		EDIT-301 infusion (Day 0) through up to 24 months post EDIT-301 infusion