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

Overview

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).

Full Title of Study: “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

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: July 10, 2017

Interventions

  • Drug: REGN910-3
    • Co-formulation for intravitreal (IVT) injection consisting of REGN910 (nesvacumab) and REGN3 (aflibercept)
  • Drug: Intravitreal Aflibercept Injection (IAI)

Arms, Groups and Cohorts

  • Experimental: REGN910-3 (3 mg: 2 mg)
    • 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.
  • Experimental: REGN910-3 (6 mg:2 mg)
    • 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.
  • Active Comparator: Aflibercept 2 mg
    • 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.
  • Experimental: REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q8
    • 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.
  • Experimental: REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q12
    • 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.
  • Experimental: Aflibercept 2 mg Q4 to Aflibercept 2 mg Q8
    • 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.
  • Experimental: Aflibercept 2 mg Q4 to Aflibercept 2 mg Q12
    • 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.
  • Experimental: Aflibercept 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8
    • 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.

Clinical Trial Outcome Measures

Primary Measures

  • Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 12
    • Time Frame: Baseline, 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
    • Time Frame: Baseline, 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 Measures

  • Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) at Week 12
    • Time Frame: Baseline, 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
    • Time Frame: Baseline, 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
    • Time Frame: Baseline, Week 12
    • 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
    • Time Frame: Baseline, Week 36
    • 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).

Participating in This Clinical Trial

Key Inclusion Criteria:

1. 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 2. BCVA ETDRS letter score of 73 to 24 (Snellen equivalent of 20/40 to 20/320) in the study eye 3. Willing and able to comply with clinic visits and study-related procedures 4. Provide signed informed consent Key Exclusion Criteria:

1. Evidence of macular edema due to any cause other than diabetes mellitus in either eye 2. IVT anti-VEGF in the study eye within 12 weeks of the screening visit 3. Panretinal laser photocoagulation or macular laser photocoagulation in the study eye within 3 months of screening Note: Other inclusion/ exclusion criteria apply

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Regeneron Pharmaceuticals
  • Collaborator
    • Bayer
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Clinical Trial Management, Study Director, Regeneron Pharmaceuticals

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.