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

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Sickle Cell Disease; Hemoglobinopathies
• Intervention / Treatment: Genetic: EDIT-301

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

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital Research Institute
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
  • Quebec
    • Montréal, Quebec, Canada, H3T 1C5
      • Centre Hospitalier Universitaire Sainte-Justine
• United States
  • California
    • Oakland, California, United States, 94609
      • UCSF Benioff Children's Hospital
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Smilow Cancer Hospital
  • Florida
    • Saint Petersburg, Florida, United States, 33701
      • Johns Hopkins All Children's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10032
      • Columbia University Medical Center - Department of Pediatrics
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • The University of North Carolina at Chapel Hill
    • Charlotte, North Carolina, United States, 28204
      • Atrium Health
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Rainbow Babies & Children's Hospital
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
    • Columbus, Ohio, United States, 43210
      • The James Cancer Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tristar Medical Group Children's Specialists/Sarah Cannon Center for Blood Cancers
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology - Baylor Charles A. Sammons Cancer Center
    • Fort Worth, Texas, United States, 76104
      • Cook Children's

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

Diagnosis of severe sickle cell disease as defined by:

• Documented SCD genotype (βS/βS, βS/β0, βS/β+, 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

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 IV 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 subjects achieving complete resolution of severe vaso-occlusive events (VOEs)	from Month 6 through Month 18 post EDIT-301 infusion

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in HbF concentration (g/dL)	up to 2 years post EDIT-301 infusion
Change from baseline in total Hb concentration (g/dL)	up to 2 years post EDIT-301 infusion
Change from baseline in markers of hemolysis (absolute reticulocyte count, indirect bilirubin, lactate dehydrogenase, haptoglobin)	up to 2 years post EDIT-301 infusion
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
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
Frequency and severity of adverse events (AEs)	up to 24 months post EDIT-301 infusion
Proportion of subjects achieving complete resolution of VOEs	from Month 6 through Month 18 post EDIT-301 infusion
Proportion of subjects with 90% reduction in annualized rate of severe VOE compared to pre-treatment period	starting from 6 months up to 2 years post EDIT-301 infusion
Proportion of subjects with 75% reduction in annualized rate of severe VOE compared to pre-treatment period	starting from 6 months up to 2 years post EDIT-301 infusion
Proportion of subjects with 50% reduction in annualized rate of severe VOE compared to pre-treatment period	starting from 6 months up to 2 years post EDIT-301 infusion
Difference (pre-treatment vs. post-treatment) in annualized rates of severe VOEs	starting from 6 months up to 2 years post EDIT-301 infusion
Difference (pre-treatment vs. post-treatment) in annualized rate of hospitalization for severe VOEs	starting from 6 months up to 2 years post EDIT-301 infusion
Proportion of subjects with sustained HbF ≥ 20% (HbF/Hb) compared with baseline	starting from 6 months up to 2 years post EDIT-301 infusion
Proportion of subjects with mean HbF ≥ 30% (HbF/Hb) compared with baseline	starting from 6 months up to 2 years post EDIT-301 infusion
Proportion of subjects with mean total Hb ≥ 10 g/dL compared with baseline	starting from 6 months up to 2 years post EDIT-301 infusion
Proportion of subjects with mean total Hb increase from baseline of ≥ 2 g/dL	starting from 6 months up to 2 years post EDIT-301 infusion
Difference (pre-treatment versus post-treatment) in annualized number of units of pRBC transfused for SCD-related indications	starting from 6 months up to 2 years post EDIT-301 infusion

Collaborators and Investigators

• Sponsor: Editas Medicine, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2021
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: April 16, 2021
• First Submitted That Met QC Criteria: April 16, 2021
• First Posted (Actual): April 21, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 29, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Anemia; Hematologic Diseases; Genetic Diseases, Inborn; Anemia, Sickle Cell; HbS Disease; Sickling Disorder Due to Hemoglobin S; Anemia, Hemolytic; Anemia, Hemolytic, Congenital; Cell Disorders, Sickle
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Anemia, Sickle Cell; Hemoglobinopathies
• Other Study ID Numbers: EM-SCD-301-001

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