Back to resultsAnti-vasculaR Endothelial Growth Factor plUs Anti-angiopoietin 2 in Fixed comBination therapY: Evaluation for the Treatment of Diabetic Macular Edema (RUBY)
Primary Purpose
Diabetic Macular Edema
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
REGN910-3
Intravitreal Aflibercept Injection (IAI)
Sponsored by
About this trial
This is an interventional treatment trial for Diabetic Macular Edema
Eligibility Criteria
Key Inclusion Criteria:
- Men or women ≥18 years of age with type 1 or type 2 diabetes mellitus who have clinically significant DME with central involvement in the study eye
- BCVA ETDRS letter score of 73 to 24 (Snellen equivalent of 20/40 to 20/320) in the study eye
- Willing and able to comply with clinic visits and study-related procedures
- Provide signed informed consent
Key Exclusion Criteria:
- Evidence of macular edema due to any cause other than diabetes mellitus in either eye
- IVT anti-VEGF in the study eye within 12 weeks of the screening visit
- Panretinal laser photocoagulation or macular laser photocoagulation in the study eye within 3 months of screening
Note: Other inclusion/ exclusion criteria apply
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm Type
Experimental
Experimental
Active Comparator
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
REGN910-3 (3 mg: 2 mg)
REGN910-3 (6 mg:2 mg)
Aflibercept 2 mg
REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q8
REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q12
Aflibercept 2 mg Q4 to Aflibercept 2 mg Q8
Aflibercept 2 mg Q4 to Aflibercept 2 mg Q12
Aflibercept 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8
Arm Description
Participants were administered intravitreal injection of REGN910-3 (3 milligram (mg):2 mg) every 4 weeks (Q4) on Day 1, Week 4, and Week 8 for 3 initial doses followed by every Week 8 (Q8) dosing beginning at Week 16 up to Week 32.
Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to week 12.
Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12.
Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) at Week 16 and Q8 through Week 32.
Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) at Week 20 and Q12 through Week 32.
Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI at Week16 and Q8 through Week 32.
Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI at Week 20 and Q12 through Week 32.
Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) at week 16 and Q8 through week 32.
Outcomes
Primary Outcome Measures
Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 12
Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at 4 meters. Best Corrected Visual Acuity (BCVA) score was measured using an eye chart and was reported as the number of letters read correctly at a testing distance of 4 meters using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. Change from baseline calculated by subtracting baseline value from observed post-baseline value at Week 12.
Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 36
Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at 4 meters. BCVA score was measured using an eye chart and was reported as the number of letters read correctly at a testing distance of 4 meters using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. Change from baseline calculated by subtracting baseline value from observed post-baseline value at Week 36.
Secondary Outcome Measures
Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) at Week 12
Central Sub-field Retinal Thickness (CST) was assessed using Spectral Domain Optical Coherence Tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. SD-OCT was performed in the study eye after pupil dilation. A negative change from baseline indicated improvement. Change from baseline calculated by subtracting baseline value from LOCF post-baseline value at Week 12.
Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) at Week 36
CST was assessed using spectral domain optical coherence tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. SD-OCT was performed in the study eye after pupil dilation. A negative change from baseline indicated improvement. Change from baseline calculated by subtracting baseline value from LOCF post-baseline value at Week 36.
Percentage of Participants With a ≥ 2-step Improvement at Week 12 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline
The Diabetic Retinopathy Disease Severity Scale (DRSS) was used to describe overall retinopathy severity. It measured the 5 levels of diabetic retinopathy ranging from absence of retinopathy to severe retinopathy (none, mild, moderate, severe, and proliferative).
Percentage of Participants With a ≥ 2-step Improvement at Week 36 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline
The Diabetic Retinopathy Disease Severity Scale (DRSS) was used to describe overall retinopathy severity. It measured the 5 levels of diabetic retinopathy ranging from absence of retinopathy to severe retinopathy (none, mild, moderate, severe, and proliferative).
Full Information
NCT ID
NCT02712008
First Posted
March 14, 2016
Last Updated
October 1, 2018
Sponsor
Regeneron Pharmaceuticals
Collaborators
Bayer
1. Study Identification
Unique Protocol Identification Number
NCT02712008
Brief Title
Anti-vasculaR Endothelial Growth Factor plUs Anti-angiopoietin 2 in Fixed comBination therapY: Evaluation for the Treatment of Diabetic Macular Edema
Acronym
RUBY
Official Title
A Randomized, Double-Masked, Active-Controlled, Phase 2 Study of the Efficacy, Safety, and Tolerability of Repeated Doses of Intravitreal REGN910-3 in Patients With Diabetic Macular Edema
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
March 2, 2016 (undefined)
Primary Completion Date
July 10, 2017 (Actual)
Study Completion Date
July 10, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Regeneron Pharmaceuticals
Collaborators
Bayer
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary objective of the study was to compare the efficacy of intravitreal (IVT)-administered REGN910-3 compared to intravitreal aflibercept injection (IAI) in improving best corrected visual acuity (BCVA) in participants with diabetic macular edema (DME).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Macular Edema
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
302 (Actual)
8. Arms, Groups, and Interventions
Arm Title
REGN910-3 (3 mg: 2 mg)
Arm Type
Experimental
Arm Description
Participants were administered intravitreal injection of REGN910-3 (3 milligram (mg):2 mg) every 4 weeks (Q4) on Day 1, Week 4, and Week 8 for 3 initial doses followed by every Week 8 (Q8) dosing beginning at Week 16 up to Week 32.
Arm Title
REGN910-3 (6 mg:2 mg)
Arm Type
Experimental
Arm Description
Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to week 12.
Arm Title
Aflibercept 2 mg
Arm Type
Active Comparator
Arm Description
Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12.
Arm Title
REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q8
Arm Type
Experimental
Arm Description
Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At Week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) at Week 16 and Q8 through Week 32.
Arm Title
REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q12
Arm Type
Experimental
Arm Description
Participants were administered intravitreal injection of REGN910-3 (6 mg:2 mg) Q4 on Day 1, Week 4 and Week 8 for 3 initial doses. At week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) at Week 20 and Q12 through Week 32.
Arm Title
Aflibercept 2 mg Q4 to Aflibercept 2 mg Q8
Arm Type
Experimental
Arm Description
Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI at Week16 and Q8 through Week 32.
Arm Title
Aflibercept 2 mg Q4 to Aflibercept 2 mg Q12
Arm Type
Experimental
Arm Description
Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At Week 12, participants were re-randomized to receive IAI at Week 20 and Q12 through Week 32.
Arm Title
Aflibercept 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8
Arm Type
Experimental
Arm Description
Participants were administered intravitreal injection of Aflibercept (IAI) 2 mg Q4 on Day 1, Week 4 and Week 8 for 3 initial doses up to Week 12. At week 12, participants were re-randomized to receive REGN910-3 (6 mg:2 mg) at week 16 and Q8 through week 32.
Intervention Type
Drug
Intervention Name(s)
REGN910-3
Intervention Description
Co-formulation for intravitreal (IVT) injection consisting of REGN910 (nesvacumab) and REGN3 (aflibercept)
Intervention Type
Drug
Intervention Name(s)
Intravitreal Aflibercept Injection (IAI)
Other Intervention Name(s)
EYLEA® (aflibercept) Injection, BAY86-5321
Primary Outcome Measure Information:
Title
Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 12
Description
Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at 4 meters. Best Corrected Visual Acuity (BCVA) score was measured using an eye chart and was reported as the number of letters read correctly at a testing distance of 4 meters using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. Change from baseline calculated by subtracting baseline value from observed post-baseline value at Week 12.
Time Frame
Baseline, Week 12
Title
Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 36
Description
Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at 4 meters. BCVA score was measured using an eye chart and was reported as the number of letters read correctly at a testing distance of 4 meters using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. Change from baseline calculated by subtracting baseline value from observed post-baseline value at Week 36.
Time Frame
Baseline, Week 36
Secondary Outcome Measure Information:
Title
Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) at Week 12
Description
Central Sub-field Retinal Thickness (CST) was assessed using Spectral Domain Optical Coherence Tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. SD-OCT was performed in the study eye after pupil dilation. A negative change from baseline indicated improvement. Change from baseline calculated by subtracting baseline value from LOCF post-baseline value at Week 12.
Time Frame
Baseline, Week 12
Title
Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) at Week 36
Description
CST was assessed using spectral domain optical coherence tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. SD-OCT was performed in the study eye after pupil dilation. A negative change from baseline indicated improvement. Change from baseline calculated by subtracting baseline value from LOCF post-baseline value at Week 36.
Time Frame
Baseline, Week 36
Title
Percentage of Participants With a ≥ 2-step Improvement at Week 12 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline
Description
The Diabetic Retinopathy Disease Severity Scale (DRSS) was used to describe overall retinopathy severity. It measured the 5 levels of diabetic retinopathy ranging from absence of retinopathy to severe retinopathy (none, mild, moderate, severe, and proliferative).
Time Frame
Baseline, Week 12
Title
Percentage of Participants With a ≥ 2-step Improvement at Week 36 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline
Description
The Diabetic Retinopathy Disease Severity Scale (DRSS) was used to describe overall retinopathy severity. It measured the 5 levels of diabetic retinopathy ranging from absence of retinopathy to severe retinopathy (none, mild, moderate, severe, and proliferative).
Time Frame
Baseline, Week 36
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Men or women ≥18 years of age with type 1 or type 2 diabetes mellitus who have clinically significant DME with central involvement in the study eye
BCVA ETDRS letter score of 73 to 24 (Snellen equivalent of 20/40 to 20/320) in the study eye
Willing and able to comply with clinic visits and study-related procedures
Provide signed informed consent
Key Exclusion Criteria:
Evidence of macular edema due to any cause other than diabetes mellitus in either eye
IVT anti-VEGF in the study eye within 12 weeks of the screening visit
Panretinal laser photocoagulation or macular laser photocoagulation in the study eye within 3 months of screening
Note: Other inclusion/ exclusion criteria apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trial Management
Organizational Affiliation
Regeneron Pharmaceuticals
Official's Role
Study Director
Facility Information:
City
Mesa
State/Province
Arizona
Country
United States
City
Tucson
State/Province
Arizona
Country
United States
City
Arcadia
State/Province
California
Country
United States
City
Beverly Hills
State/Province
California
Country
United States
City
Mountain View
State/Province
California
Country
United States
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Oceanside
State/Province
California
Country
United States
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Palm Desert
State/Province
California
Country
United States
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Colorado Springs
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Colorado
Country
United States
City
New London
State/Province
Connecticut
Country
United States
City
Lakeland
State/Province
Florida
Country
United States
City
Tampa
State/Province
Florida
Country
United States
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Winter Haven
State/Province
Florida
Country
United States
City
Augusta
State/Province
Georgia
Country
United States
City
Decatur
State/Province
Georgia
Country
United States
City
'Aiea
State/Province
Hawaii
Country
United States
City
Chicago
State/Province
Illinois
Country
United States
City
New Albany
State/Province
Indiana
Country
United States
City
Shawnee Mission
State/Province
Kansas
Country
United States
City
Lexington
State/Province
Kentucky
Country
United States
City
Portland
State/Province
Maine
Country
United States
City
Baltimore
State/Province
Maryland
Country
United States
City
Rockville
State/Province
Maryland
Country
United States
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Boston
State/Province
Massachusetts
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United States
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Grand Rapids
State/Province
Michigan
Country
United States
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Jackson
State/Province
Michigan
Country
United States
City
Minneapolis
State/Province
Minnesota
Country
United States
City
Florissant
State/Province
Missouri
Country
United States
City
Las Vegas
State/Province
Nevada
Country
United States
City
Bloomfield
State/Province
New Jersey
Country
United States
City
Edison
State/Province
New Jersey
Country
United States
City
Teaneck
State/Province
New Jersey
Country
United States
City
Albany
State/Province
New York
Country
United States
City
Rochester
State/Province
New York
Country
United States
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Asheville
State/Province
North Carolina
Country
United States
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Charlotte
State/Province
North Carolina
Country
United States
City
Kingston
State/Province
Pennsylvania
Country
United States
City
Florence
State/Province
South Carolina
Country
United States
City
West Columbia
State/Province
South Carolina
Country
United States
City
Rapid City
State/Province
South Dakota
Country
United States
City
Germantown
State/Province
Tennessee
Country
United States
City
Nashville
State/Province
Tennessee
Country
United States
City
Abilene
State/Province
Texas
Country
United States
City
Austin
State/Province
Texas
Country
United States
City
Dallas
State/Province
Texas
Country
United States
City
Fort Worth
State/Province
Texas
Country
United States
City
Harlingen
State/Province
Texas
Country
United States
City
Houston
State/Province
Texas
Country
United States
City
San Antonio
State/Province
Texas
Country
United States
City
The Woodlands
State/Province
Texas
Country
United States
City
Willow Park
State/Province
Texas
Country
United States
City
Bellevue
State/Province
Washington
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Anti-vasculaR Endothelial Growth Factor plUs Anti-angiopoietin 2 in Fixed comBination therapY: Evaluation for the Treatment of Diabetic Macular Edema
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