A Study Evaluating the Safety and Efficacy of EDIT-301 in Participants With Severe Sickle Cell Disease (RUBY)
Primary Purpose
Sickle Cell Disease, Hemoglobinopathies
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
EDIT-301
Sponsored by
About this trial
This is an interventional treatment trial for Sickle Cell Disease focused on measuring Anemia, Anemia, Sickle Cell, Anemia, Hemolytic, Congenital, Anemia, Hemolytic, Genetic Diseases, Inborn, Cell Disorders, Sickle, HbS Disease, Sickling Disorder Due to Hemoglobin S, Hematologic Diseases
Eligibility Criteria
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
Sites / Locations
- UCSF Benioff Children's HospitalRecruiting
- Children's Hospital ColoradoRecruiting
- Smilow Cancer HospitalRecruiting
- Johns Hopkins All Children's HospitalRecruiting
- Children's Healthcare of AtlantaRecruiting
- Ann & Robert H. Lurie Children's Hospital of ChicagoRecruiting
- University of Mississippi Medical CenterRecruiting
- Columbia University Medical Center - Department of PediatricsRecruiting
- Columbia University Medical CenterRecruiting
- The University of North Carolina at Chapel HillRecruiting
- Atrium HealthRecruiting
- University Hospitals Rainbow Babies & Children's HospitalRecruiting
- Cleveland ClinicRecruiting
- Nationwide Children's HospitalRecruiting
- The James Cancer HospitalRecruiting
- Children's Hospital of PhiladelphiaRecruiting
- Medical University of South CarolinaRecruiting
- Tristar Medical Group Children's Specialists/Sarah Cannon Center for Blood CancersRecruiting
- Texas Oncology - Baylor Charles A. Sammons Cancer CenterRecruiting
- Cook Children'sRecruiting
- Ottawa Hospital Research InstituteRecruiting
- Princess Margaret Cancer CentreRecruiting
- Centre Hospitalier Universitaire Sainte-JustineRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
EDIT-301
Arm Description
EDIT-301 (autologous gene edited (CD)34+ hematopoietic stem cells) will be administered as a one-time intravenous infusion.
Outcomes
Primary Outcome Measures
Proportion of subjects achieving complete resolution of severe vaso-occlusive events (VOEs)
Secondary Outcome Measures
Complete resolution of severe VOE
Change from baseline in annualized rate of severe VOE by at least 90%
Change from baseline in annualized rate of severe VOE by at least 75%
Change from baseline in annualized rate of severe VOE by at least 50%
Difference (pre-treatment vs. post-treatment) in annualized rates of severe VOEs
Change from baseline in annualized rate of hospitalization for severe VOE
Proportion of subjects with sustained HbF ≥ 20% (HbF/Hb) compared with pre-conditioning Baseline
Proportion of subjects with mean HbF ≥ 30% (HbF/Hb) compared with pre-conditioning Baseline
Proportion of subjects with mean total Hb ≥ 10 g/dL compared with Baseline
Proportion of subjects with mean total Hb increase from baseline ≥ 2 g/dL
Difference (pre-treatment versus post-treatment) in annualized number of units of pRBC transfused for SCD-related indications
Change from baseline in HbF concentration (g/dL)
Change from baseline in total Hb concentration (g/dL)
Change from baseline in markers of hemolysis (reticulocyte count, indirect bilirubin, lactate dehydrogenase, haptoglobin)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04853576
Brief Title
A Study Evaluating the Safety and Efficacy of EDIT-301 in Participants With Severe Sickle Cell Disease (RUBY)
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 4, 2021 (Actual)
Primary Completion Date
August 2025 (Anticipated)
Study Completion Date
August 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Editas Medicine, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy, safety and tolerability of treatment with EDIT-301 in adult 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 subjects with severe SCD, from 18 to 50 years of age, inclusive.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease, Hemoglobinopathies
Keywords
Anemia, Anemia, Sickle Cell, Anemia, Hemolytic, Congenital, Anemia, Hemolytic, Genetic Diseases, Inborn, Cell Disorders, Sickle, HbS Disease, Sickling Disorder Due to Hemoglobin S, Hematologic Diseases
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
EDIT-301
Arm Type
Experimental
Arm Description
EDIT-301 (autologous gene edited (CD)34+ hematopoietic stem cells) will be administered as a one-time intravenous infusion.
Intervention Type
Genetic
Intervention Name(s)
EDIT-301
Intervention Description
Administered by IV infusion after myeloablative conditioning with busulfan.
Primary Outcome Measure Information:
Title
Proportion of subjects achieving complete resolution of severe vaso-occlusive events (VOEs)
Time Frame
up to 2 years post EDIT-301 infusion
Secondary Outcome Measure Information:
Title
Complete resolution of severe VOE
Time Frame
up to 2 years post EDIT-301 infusion
Title
Change from baseline in annualized rate of severe VOE by at least 90%
Time Frame
up to 2 years post EDIT-301 infusion
Title
Change from baseline in annualized rate of severe VOE by at least 75%
Time Frame
up to 2 years post EDIT-301 infusion
Title
Change from baseline in annualized rate of severe VOE by at least 50%
Time Frame
up to 2 years post EDIT-301 infusion
Title
Difference (pre-treatment vs. post-treatment) in annualized rates of severe VOEs
Time Frame
up to 2 years post EDIT-301 infusion
Title
Change from baseline in annualized rate of hospitalization for severe VOE
Time Frame
up to 2 years post EDIT-301 infusion
Title
Proportion of subjects with sustained HbF ≥ 20% (HbF/Hb) compared with pre-conditioning Baseline
Time Frame
up to 2 years post EDIT-301 infusion
Title
Proportion of subjects with mean HbF ≥ 30% (HbF/Hb) compared with pre-conditioning Baseline
Time Frame
up to 2 years post EDIT-301 infusion
Title
Proportion of subjects with mean total Hb ≥ 10 g/dL compared with Baseline
Time Frame
up to 2 years post EDIT-301 infusion
Title
Proportion of subjects with mean total Hb increase from baseline ≥ 2 g/dL
Time Frame
up to 2 years post EDIT-301 infusion
Title
Difference (pre-treatment versus post-treatment) in annualized number of units of pRBC transfused for SCD-related indications
Time Frame
up to 2 years post EDIT-301 infusion
Title
Change from baseline in HbF concentration (g/dL)
Time Frame
up to 2 years post EDIT-301 infusion
Title
Change from baseline in total Hb concentration (g/dL)
Time Frame
up to 2 years post EDIT-301 infusion
Title
Change from baseline in markers of hemolysis (reticulocyte count, indirect bilirubin, lactate dehydrogenase, haptoglobin)
Time Frame
up to 2 years post EDIT-301 infusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Editas Medicine's Clinical Trial Team
Phone
617-401-9007
Email
Patients@editasmed.com
Facility Information:
Facility Name
UCSF Benioff Children's Hospital
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Individual Site Status
Recruiting
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Name
Smilow Cancer Hospital
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06511
Country
United States
Individual Site Status
Recruiting
Facility Name
Johns Hopkins All Children's Hospital
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33701
Country
United States
Individual Site Status
Recruiting
Facility Name
Children's Healthcare of Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Individual Site Status
Recruiting
Facility Name
Ann & Robert H. Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Mississippi Medical Center
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Individual Site Status
Recruiting
Facility Name
Columbia University Medical Center - Department of Pediatrics
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Individual Site Status
Recruiting
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Individual Site Status
Recruiting
Facility Name
The University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Individual Site Status
Recruiting
Facility Name
Atrium Health
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Individual Site Status
Recruiting
Facility Name
University Hospitals Rainbow Babies & Children's Hospital
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Individual Site Status
Recruiting
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Recruiting
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Individual Site Status
Recruiting
Facility Name
The James Cancer Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Individual Site Status
Recruiting
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Individual Site Status
Recruiting
Facility Name
Tristar Medical Group Children's Specialists/Sarah Cannon Center for Blood Cancers
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Recruiting
Facility Name
Texas Oncology - Baylor Charles A. Sammons Cancer Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Individual Site Status
Recruiting
Facility Name
Cook Children's
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Individual Site Status
Recruiting
Facility Name
Ottawa Hospital Research Institute
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Individual Site Status
Recruiting
Facility Name
Princess Margaret Cancer Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Universitaire Sainte-Justine
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H3T 1C5
Country
Canada
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
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A Study Evaluating the Safety and Efficacy of EDIT-301 in Participants With Severe Sickle Cell Disease (RUBY)
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