Anti-vasculaR Endothelial Growth Factor plUs Anti-angiopoietin 2 in Fixed comBination therapY: Evaluation for the Treatment of Diabetic Macular Edema

NCT02712008 | Completed Phase 2 Results DMC

• 1 other identifier: R910-3-DME-1518
• Study Type: interventional
• Target: 302
• Locations: 1 country
• Sites: 51

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).

Conditions

Diabetic Macular Edema

Outcome Measures

Primary Outcomes (2)

• 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.

  Baseline, 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.

  Baseline, Week 36

Secondary Outcomes (4)

• Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) at Week 12

  Baseline, Week 12

• Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) at Week 36

  Baseline, Week 36

• Percentage of Participants With a ≥ 2-step Improvement at Week 12 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline

  Baseline, Week 12

• Percentage of Participants With a ≥ 2-step Improvement at Week 36 in Diabetic Retinopathy Severity Scale (DRSS) From Baseline

  Baseline, Week 36

Study Arms (8)

REGN910-3 (3 mg: 2 mg)

EXPERIMENTAL

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.

Drug: REGN910-3

REGN910-3 (6 mg:2 mg)

EXPERIMENTAL

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.

Drug: REGN910-3

Aflibercept 2 mg

ACTIVE COMPARATOR

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.

Drug: Intravitreal Aflibercept Injection (IAI)

REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q8

EXPERIMENTAL

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.

Drug: REGN910-3

REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q12

EXPERIMENTAL

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.

Drug: REGN910-3

Aflibercept 2 mg Q4 to Aflibercept 2 mg Q8

EXPERIMENTAL

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.

Drug: Intravitreal Aflibercept Injection (IAI)

Aflibercept 2 mg Q4 to Aflibercept 2 mg Q12

EXPERIMENTAL

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.

Drug: Intravitreal Aflibercept Injection (IAI)

Aflibercept 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8

EXPERIMENTAL

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.

Drug: REGN910-3; Drug: Intravitreal Aflibercept Injection (IAI)

Interventions

REGN910-3 DRUG

Co-formulation for intravitreal (IVT) injection consisting of REGN910 (nesvacumab) and REGN3 (aflibercept)

Aflibercept 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8; REGN910-3 (3 mg: 2 mg); REGN910-3 (6 mg:2 mg); REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q12; REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q8

Intravitreal Aflibercept Injection (IAI) DRUG

Also known as: EYLEA® (aflibercept) Injection, BAY86-5321

Aflibercept 2 mg; Aflibercept 2 mg Q4 to Aflibercept 2 mg Q12; Aflibercept 2 mg Q4 to Aflibercept 2 mg Q8; Aflibercept 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead
• Bayer: collaborator

Study Sites (51)

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Mesa, Arizona, United States

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Tucson, Arizona, United States

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Arcadia, California, United States

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Beverly Hills, California, United States

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Mountain View, California, United States

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Oceanside, California, United States

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Palm Desert, California, United States

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Colorado Springs, Colorado, United States

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New London, Connecticut, United States

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Lakeland, Florida, United States

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Tampa, Florida, United States

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Winter Haven, Florida, United States

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Augusta, Georgia, United States

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Decatur, Georgia, United States

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‘Aiea, Hawaii, United States

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Chicago, Illinois, United States

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New Albany, Indiana, United States

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Shawnee Mission, Kansas, United States

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Lexington, Kentucky, United States

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Portland, Maine, United States

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Baltimore, Maryland, United States

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Rockville, Maryland, United States

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Boston, Massachusetts, United States

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Grand Rapids, Michigan, United States

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Jackson, Michigan, United States

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Minneapolis, Minnesota, United States

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Florissant, Missouri, United States

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Las Vegas, Nevada, United States

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Bloomfield, New Jersey, United States

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Edison, New Jersey, United States

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Teaneck, New Jersey, United States

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Albany, New York, United States

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Rochester, New York, United States

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Asheville, North Carolina, United States

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Charlotte, North Carolina, United States

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Kingston, Pennsylvania, United States

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Florence, South Carolina, United States

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West Columbia, South Carolina, United States

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Rapid City, South Dakota, United States

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Germantown, Tennessee, United States

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Nashville, Tennessee, United States

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Abilene, Texas, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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Fort Worth, Texas, United States

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Harlingen, Texas, United States

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Houston, Texas, United States

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San Antonio, Texas, United States

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The Woodlands, Texas, United States

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Willow Park, Texas, United States

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Bellevue, Washington, United States

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MeSH Terms

Interventions

aflibercept; Injections

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Results Point of Contact

• Title: Clinical Trial Management
• Organization: Regeneron Pharmaceuticals, Inc.

clinicaltrials@regeneron.com

844-734-6643

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2016
• First Posted: March 17, 2016
• Study Start: March 2, 2016
• Primary Completion: July 10, 2017
• Study Completion: July 10, 2017
• Last Updated: October 3, 2018
• Results First Posted: October 3, 2018

Record last verified: 2018-10

Locations

US (51)