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

Phase 1

Active, not recruiting

• Conditions: Hemoglobinopathies; Sickle Cell Disease
• Interventions: Genetic: EDIT-301

• Registration Number: NCT04853576
• Lead Sponsor: Editas Medicine, Inc.

Brief 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).

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 Timeline

• Study First Submitted: 2021-04-16
• Study First Submitted QC: 2021-04-16
• Study First Posted: 2021-04-21
• Study Start: 2021-05-04
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-04
• Last Update Posted: 2024-10-08
• Primary Completion: 2025-08
• Study Completion: 2025-08

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 45

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
EDIT-301	EDIT-301	EDIT-301 (autologous gene edited (CD)34+ hematopoietic stem cells) will be administered as a one-time intravenous infusion.

Primary Outcome Measures

Name	Time	Method
Proportion of subjects achieving complete resolution of severe vaso-occlusive events (VOEs)	up to 2 years post EDIT-301 infusion

Secondary Outcome Measures

Name	Time	Method
Proportion of subjects with mean total Hb increase from baseline of ≥ 2 g/dL	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	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
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
Difference (pre-treatment vs. post-treatment) in annualized rates of severe VOEs	up to 2 years post EDIT-301 infusion
Difference (pre-treatment vs. post-treatment) in annualized rate of hospitalization for severe VOEs	up to 2 years post EDIT-301 infusion
Proportion of subjects with sustained HbF ≥ 20% (HbF/Hb) compared with baseline	up to 2 years post EDIT-301 infusion
Proportion of subjects with mean HbF ≥ 30% (HbF/Hb) compared with baseline	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 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
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
Proportion of subjects with mean total Hb ≥ 10 g/dL compared with baseline	up to 2 years post 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	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	up to 2 years post EDIT-301 infusion
Change from baseline in HbF concentration (g/dL)	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

Trial Locations

Locations (24)

UCSF Benioff Children's Hospital; 🇺🇸 Oakland, California, United States

Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States

Smilow Cancer Hospital; 🇺🇸 New Haven, Connecticut, United States

Johns Hopkins All Children's Hospital; 🇺🇸 Saint Petersburg, Florida, United States

Children's Healthcare of Atlanta; 🇺🇸 Atlanta, Georgia, United States

Ann & Robert H. Lurie Children's Hospital of Chicago; 🇺🇸 Chicago, Illinois, United States

University of Mississippi Medical Center; 🇺🇸 Jackson, Mississippi, United States

Hackensack University Medical Center; 🇺🇸 Hackensack, New Jersey, United States

Columbia University Medical Center - Department of Pediatrics; 🇺🇸 New York, New York, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

The University of North Carolina at Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States

Atrium Health; 🇺🇸 Charlotte, North Carolina, United States

University Hospitals Rainbow Babies & Children's Hospital; 🇺🇸 Cleveland, Ohio, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Nationwide Children's Hospital; 🇺🇸 Columbus, Ohio, United States

The James Cancer Hospital; 🇺🇸 Columbus, Ohio, United States

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

Tristar Medical Group Children's Specialists/Sarah Cannon Center for Blood Cancers; 🇺🇸 Nashville, Tennessee, United States

Texas Oncology - Baylor Charles A. Sammons Cancer Center; 🇺🇸 Dallas, Texas, United States

Cook Children's; 🇺🇸 Fort Worth, Texas, United States

Ottawa Hospital Research Institute; 🇨🇦 Ottawa, Ontario, Canada

Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada

Centre Hospitalier Universitaire Sainte-Justine; 🇨🇦 Montréal, Quebec, Canada