A Study Evaluating the Safety and Efficacy of EDIT-301 in Participants With Severe Sickle Cell Disease (RUBY)

Sickle Cell Disease Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04853576
• Other study ID #: EM-SCD-301-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 4, 2021
• Est. completion date: August 2025

Study information

• Verified date: January 2024
• Source: Editas Medicine, Inc.
• Contact: Editas Medicine's 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 efficacy, safety and tolerability of treatment with EDIT-301 in adult and adolescent participants with severe sickle cell disease (SCD).

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 and adolescent subjects with severe SCD, from 12 to 50 years of age, inclusive.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: August 2025
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 50 Years

Eligibility

Key Inclusion Criteria:

Diagnosis of severe sickle cell disease as defined by:

• Documented SCD genotype (ßS/ßS, ßS/ß0, ßS/ß+, or others) and

• History of at least two severe vaso-occlusive events per year requiring medical attention despite hydroxyurea or other supportive care measures in the two year-period prior to provision of informed consent or assent, as applicable

Karnofsky (for subjects >16 years of age) or Lansky (for subjects = 16 years of age) Performance Status = 80%

Normal transcranial doppler velocity in subjects 16 years of age or younger

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

Other protocol defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Hemoglobinopathies
• Sickle Cell Disease

Intervention

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

Locations

Country	Name	City	State
Canada	Centre Hospitalier Universitaire Sainte-Justine	Montréal	Quebec
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
United States	Children's Healthcare of Atlanta	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Atrium Health	Charlotte	North Carolina
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	University Hospitals Rainbow Babies & Children's Hospital	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	The James Cancer Hospital	Columbus	Ohio
United States	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Cook Children's	Fort Worth	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Tristar Medical Group Children's Specialists/Sarah Cannon Center for Blood Cancers	Nashville	Tennessee
United States	Smilow Cancer Hospital	New Haven	Connecticut
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	UCSF Benioff Children's Hospital	Oakland	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida

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 subjects achieving complete resolution of severe vaso-occlusive events (VOEs)		up to 2 years post EDIT-301 infusion
Secondary	Proportion of subjects achieving complete resolution of VOEs		up to 2 years post EDIT-301 infusion
Secondary	Proportion of subjects with 90% reduction in annualized rate of severe VOE compared to pre-treatment period		up to 2 years post EDIT-301 infusion
Secondary	Proportion of subjects with 75% reduction in annualized rate of severe VOE compared to pre-treatment period		up to 2 years post EDIT-301 infusion
Secondary	Proportion of subjects with 50% reduction in annualized rate of severe VOE compared to pre-treatment period		up to 2 years post EDIT-301 infusion
Secondary	Difference (pre-treatment vs. post-treatment) in annualized rates of severe VOEs		up to 2 years post EDIT-301 infusion
Secondary	Difference (pre-treatment vs. post-treatment) in annualized rate of hospitalization for severe VOEs		up to 2 years post EDIT-301 infusion
Secondary	Proportion of subjects with sustained HbF = 20% (HbF/Hb) compared with baseline		up to 2 years post EDIT-301 infusion
Secondary	Proportion of subjects with mean HbF = 30% (HbF/Hb) compared with baseline		up to 2 years post EDIT-301 infusion
Secondary	Proportion of subjects with mean total Hb = 10 g/dL compared with baseline		up to 2 years post EDIT-301 infusion
Secondary	Proportion of subjects with mean total Hb increase from baseline of = 2 g/dL		up to 2 years post EDIT-301 infusion
Secondary	Difference (pre-treatment versus post-treatment) in annualized number of units of pRBC transfused for SCD-related indications		up to 2 years post EDIT-301 infusion
Secondary	Change from baseline in HbF concentration (g/dL)		up to 2 years post EDIT-301 infusion
Secondary	Change from baseline in total Hb concentration (g/dL)		up to 2 years post EDIT-301 infusion
Secondary	Change from baseline in markers of hemolysis (absolute reticulocyte count, indirect bilirubin, lactate dehydrogenase, haptoglobin)		up to 2 years post EDIT-301 infusion
Secondary	Time to neutrophil engraftment (the first day in which 3 consecutive absolute neutrophil count (ANC) = 0.5 x 109/L laboratory values obtained on different days)		up to 24 months after EDIT-301 infusion
Secondary	Time to platelet engraftment (the first day in which 3 consecutive platelets = 50 x 109/L laboratory values obtained for at least 7 days following the last platelet transfusion and 10 days following any administration of thrombopoietin (TPO) mimetics)		up to 24 months after EDIT-301 infusion
Secondary	Frequency and severity of adverse events (AEs)		up to 24 months post EDIT-301 infusion