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

Phase 2
Completed
Conditions
Diabetic Macular Edema
Interventions
Drug: Intravitreal Aflibercept Injection (IAI)
Registration Number
NCT02712008
Lead Sponsor
Regeneron Pharmaceuticals
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).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
302
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q12REGN910-3Participants 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.
REGN910-3 (3 mg: 2 mg)REGN910-3Participants 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.
Aflibercept 2 mgIntravitreal Aflibercept Injection (IAI)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.
Aflibercept 2 mg Q4 to Aflibercept 2 mg Q8Intravitreal Aflibercept Injection (IAI)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.
Aflibercept 2 mg Q4 to Aflibercept 2 mg Q12Intravitreal Aflibercept Injection (IAI)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.
Aflibercept 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8REGN910-3Participants 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.
Aflibercept 2 mg Q4 to REGN910-3 (6 mg:2 mg) Q8Intravitreal Aflibercept Injection (IAI)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.
REGN910-3 (6 mg:2 mg) Q4 to REGN910-3 (6 mg:2 mg) Q8REGN910-3Participants 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.
REGN910-3 (6 mg:2 mg)REGN910-3Participants 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.
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Best Corrected Visual Acuity (BCVA) Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 12Baseline, 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 36Baseline, 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
NameTimeMethod
Change From Baseline in Central Sub-field Retinal Thickness (CST) Measured by Spectral Domain Optical Coherence Tomography (SD-OCT) at Week 12Baseline, 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 36Baseline, 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 BaselineBaseline, 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 BaselineBaseline, 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).

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