Study of Intravitreal Aflibercept Injection (IAI; EYLEA®; BAY86-5321) in Patients With Diabetic Macular Edema

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy of Intravitreal Aflibercept Injection (IAI; EYLEA®; BAY86-5321) on the best corrected visual acuity (BCVA) assessed by the early treatment diabetic retinopathy study (ETDRS) chart in patients with diabetic macular edema (DME) with central involvement.

Official Title
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A Double-Masked, Randomized, Active-Controlled, Phase 3 Study of the Efficacy and Safety of Intravitreal Administration of VEGF Trap-Eye in Patients With Diabetic Macular Edema

Conditions
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Diabetic Macular Edema

Intervention / Treatment
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* Drug: Intravitreal Aflibercept Injection (IAI; EYLEA®; BAY86-5321)
* Procedure: Macular Laser Photocoagulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The following is an abbreviated list of inclusion criteria: Adults ≥ 18 years with type 1 or 2 diabetes mellitus Decrease in vision determined to be primarily the result of DME in the study eye BCVA ETDRS letter score of 73 to 24 (20/40 to 20/320) in the study eye Exclusion Criteria: The following is an abbreviated list of exclusion criteria: Laser photocoagulation (panretinal or macular) in the study eye within 90 days of day 1 Previous use of intraocular or periocular corticosteroids in the study eye within 120 days of day 1 Previous treatment with anti-angiogenic drugs in the study eye (pegaptanib sodium, bevacizumab, ranibizumab, etc.) within 90 days of day 1 Active proliferative diabetic retinopathy (PDR) in the study eye Uncontrolled diabetes mellitus Only 1 functional eye even if that eye is otherwise eligible for the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Macular Laser Photocoagulation Treatment (Control)<br>Participants received macular laser treatment at baseline and as-needed at visits at which laser re-treatment criteria were met, but no more frequently than every 12 weeks. | Procedure: Macular Laser Photocoagulation<br>* Laser therapy<br>|
| Experimental: Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q4<br>Participants received 2mg Intravitreal aflibercept injection (IAI) every 4 weeks. | Drug: Intravitreal Aflibercept Injection (IAI; EYLEA®; BAY86-5321)<br> <br> |
| Experimental: Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2Q8<br>Participants received 2mg Intravitreal aflibercept injection (IAI) every 4 weeks for 5 visits followed by injections every 8 weeks. | Drug: Intravitreal Aflibercept Injection (IAI; EYLEA®; BAY86-5321)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Best Corrected Visual Acuity (BCVA) as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Week 52 - Last Observation Carried Forward (LOCF) | Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score of 73 to 24 (= Acuity of 20/40 to 20/320) in the study eye were included; a higher score represents better functioning. | Baseline and Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Gained at Least 10 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 52 - LOCF |  | Baseline and Week 52 | 
| Percentage of Participants Who Gained at Least 15 Letters in BCVA as Measured by ETDRS Letter Score Compared With Baseline at Week 52 - LOCF |  | Baseline and Week 52 | 
| Percentage of Participants With a ≥2-step Improvement From Baseline in the ETDRS DRSS (Diabetic Retinopathy Severity Score) as Assessed by FP (Fundus Photography) at Week 52 - LOCF | Baseline ETDRS DRSS: None (level 10); Mild to moderate nonproliferative DR (levels 14, 15, 20, 35, and 43); Moderately severe/severe nonproliferative DR (levels 47 and 53); Mild/moderate/high-risk/advanced proliferative DR (levels 61, 65, 71,75, 81, and 85) | Baseline and Week 52 | 
| Change From Baseline in Central Retinal Thickness (CRT) at Week 52 as Assessed on Optical Coherence Tomography (OCT) - LOCF |  | Baseline and Week 52 | 
| Change From Baseline in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Near Activities Subscale at Week 52 - LOCF | The NEI VFQ-25 total score ranges from 0-100 with a score of 0 being the worst outcome and 100 being the best outcome. The NEI VFQ questionnaire is organized as a collection of subscales that are all scored from 0-100. Near activities are defined as reading ordinary print in newspapers, performing work or hobbies requiring near vision, or finding something on a crowded shelf. | Baseline and Week 52 | 
| Change From Baseline in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Distance Activities Subscale at Week 52 - LOCF | The NEI VFQ-25 total score ranges from 0-100 with a score of 0 being the worst outcome and 100 being the best outcome. The NEI VFQ questionnaire is organized as a collection of subscales that are all scored from 0-100. Distance activities are defined as reading street signs or names on stores, and going down stairs, steps, or curbs. | Baseline and Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetic Macular Edema, Diabetic Retinopathy