EDIT-301 for Autologous HSCT in Subjects With Severe Sickle Cell Disease

Sponsor

Editas Medicine, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04853576

Collaborator

(none)

Enrollment

Locations

Arm

50.9

Anticipated Duration (Months)

2.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy, safety and tolerability of treatment with EDIT-301 in adult subjects with severe sickle cell disease (SCD).

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease Hemoglobinopathies	Genetic: EDIT-301	Phase 1/Phase 2

Detailed Description

This is a Phase 1/2 single-arm, open-label, multicenter study evaluating the safety and efficacy of a single unit dose of EDIT-301 for autologous hematopoietic stem cell transplant (HSCT) in subjects with severe SCD. Planned study subjects will be comprised of male and female adult subjects with severe SCD, from 18 to 50 years of age, inclusive.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1/2 Study to Evaluate the Safety and Efficacy of a Single Dose of Autologous Clustered Regularly Interspaced Short Palindromic Repeats Gene-edited CD34+ Human Hematopoietic Stem and Progenitor Cells (EDIT-301) in Subjects With Severe Sickle Cell Disease

Actual Study Start Date :

May 4, 2021

Anticipated Primary Completion Date :

Aug 1, 2025

Anticipated Study Completion Date :

Aug 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 IV 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 IV infusion after myeloablative conditioning with busulfan.

Outcome Measures

Primary Outcome Measures

Difference (pre-treatment versus post-treatment) in the rates of severe vaso-occlusive events (VOEs) requiring medical attention. [up to 2 years post EDIT-301 infusion]

Secondary Outcome Measures

Proportion of subjects with mean HbF > 20% (HbF/Hb) compared with pre-conditioning Baseline [up to 2 years post EDIT-301 infusion]
Proportion of subjects with mean Hb ≥ 10 g/dL starting ≥ 60 days after last packed red blood cell (pRBC) transfusion compared with preconditioning Baseline [up to 2 years post EDIT-301 infusion]
Annualized number of units of pRBC transfused for SCD-related indications [up to 2 years post EDIT-301 infusion]
Change from baseline in annualized rate of hospitalization for severe VOE [up to 2 years post EDIT-301 infusion]
Change from baseline in annualized rate of severe VOE by at least 75% [up to 2 years post EDIT-301 infusion]
Change from baseline in annualized rate of severe VOE by at least 90% [up to 2 years post EDIT-301 infusion]
Complete resolution of severe VOE [up to 2 years post EDIT-301 infusion]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Diagnosis of severe sickle cell disease as defined by:

Documented severe SCD genotype (βS/βS, βS/β0, or βS/β+)
History of at least two severe vaso-occlusive crisis events per year requiring medical attention despite hydroxyurea or other supportive care measures in the two year-period prior to provision of informed consent

Karnofsky Performance Status ≥ 80

Key Exclusion Criteria:

Available 10/10 HLA-matched related donor
Prior HSCT or contraindications to autologous HSCT
Any contraindications to the use of plerixafor during the mobilization of hematopoietic stem cells (HSCs) and any contraindications to the use of busulfan and any other medicinal products required during the myeloablative conditioning, including hypersensitivity to the active substances or to any of the excipients
Unable to receive red blood cell (RBC) transfusion for any reason
Unable or unwilling to comply with standard of care changes in background medical treatment in preparation of, during, or following HSCT, including and not limited to discontinuation of hydroxyurea, voxelotor, crizanlizumab, or L-glutamine
Any history of severe cerebral vasculopathy
Inadequate end 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF Benioff Children's Hospital	Oakland	California	United States	94609
2	Children's Hospital Colorado	Aurora	Colorado	United States	80045
3	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
4	Columbia University Medical Center - Department of Pediatrics	New York	New York	United States	10032
5	Columbia University Medical Center	New York	New York	United States	10032
6	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
7	Cleveland Clinic	Cleveland	Ohio	United States	44195
8	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
9	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
10	Medical University of South Carolina	Charleston	South Carolina	United States	29425
11	Tristar Medical Group Children's Specialists/Sarah Cannon Center for Blood Cancers	Nashville	Tennessee	United States	37203
12	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas	United States	75246
13	Ottawa Hospital Research Institute	Ottawa	Ontario	Canada	K1H 8L6
14	Centre Hospitalier Universitaire Sainte-Justine	Montréal	Quebec	Canada	H3T 1C5