DME And VEGF Trap-Eye [Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321)] INvestigation of Clinical Impact

Study Overview
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Brief Summary
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This is a Phase 2, doubled-masked, randomized study of the efficacy and safety of Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) in subjects with diabetic macular edema (DME). Approximately 200 subjects will be randomized in the US, Canada, Australia and EU.

Detailed Description
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Qualified subjects will be randomized to one of 5 treatment arms. The active (treatment) phase of the study will be 52 weeks, with a 6 month safety follow-up

Official Title
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A Double-Masked, Randomized, Controlled Study of the Safety, Tolerability and Biological Effect of Repeated Intravitreal Administration of VEGF Trap-Eye in Patients With Diabetic Macular Edema (DME)

Conditions
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Diabetic Macular Edema

Intervention / Treatment
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* Procedure: Laser Photocoagulation
* Drug: Intravitreal Aflibercept Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with clinically significant DME with central involvement Adults 18 years or older with type 1 or 2 diabetes mellitus with diabetic macular edema ETDRS BCVA: 20/40 to 20/320 (letter score of 73 to 24) in the study eye Exclusion Criteria: History of vitreoretinal surgery in the study eye Panretinal laser photocoagulation or macular laser photocoagulation in the study eye within 3 months of screening Previous use of intraocular or periocular corticosteroids in the study eye within 3 months of screening Previous treatment with anti-angiogenic drugs in either eye (pegaptanib sodium, anecortave acetate, bevacizumab, ranibizumab, etc) within 3 months of screening Uncontrolled diabetes mellitus Uncontrolled hypertension defined as systolic > 180mmHg or > 160 mmHg on 2 consecutive measurements or diastolic > 100 mmHg on optimal medical regimen Ocular disorders in the study eye, other than DME, that may confound interpretation of study results

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravitreal Aflibercept Injection .5Q4<br>Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) .5 mg every 4 weeks | Drug: Intravitreal Aflibercept Injection<br> <br> * Other names: IAI; EYLEA®; BAY86-5321; VEGF Trap-Eye;|
| Experimental: Intravitreal Aflibercept Injection 2Q4<br>Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2 mg every 4 weeks | Drug: Intravitreal Aflibercept Injection<br> <br> * Other names: IAI; EYLEA®; BAY86-5321; VEGF Trap-Eye;|
| Experimental: Intravitreal Aflibercept Injection 2Q8<br>Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2mg every 4 weeks for 3 visits followed by every 8 weeks | Drug: Intravitreal Aflibercept Injection<br> <br> * Other names: IAI; EYLEA®; BAY86-5321; VEGF Trap-Eye;|
| Experimental: Intravitreal Aflibercept Injection 2PRN<br>Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2mg every 4 weeks for 3 visits followed by PRN (as-needed) dosing according to the re-treatment criteria | Drug: Intravitreal Aflibercept Injection<br> <br> * Other names: IAI; EYLEA®; BAY86-5321; VEGF Trap-Eye;|
| Active Comparator: Laser Photocoagulation<br>Focal laser at week 1, and one week after visits at which the participant met laser re-treatment criteria to the end of the study (week 52) starting at week 16; laser re- treatment was permitted no more than once every 16 weeks. | Procedure: Laser Photocoagulation<br>* laser every 16 weeks as needed<br>* Other names: macular laser therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in BCVA From Baseline to Week 24 - Last Observation Carried Forward (LOCF) | Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at 4 meters. Measurements were taken at every study visit. Missing values were imputed with post-baseline values during on-treatment period by using last observation carried forward (LOCF). | At week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in BCVA From Baseline to Week 52 - LOCF | Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at 4 meters. Missing values were imputed with post-baseline values during on-treatment period by using last observation carried forward (LOCF). | At week 52 | 
| Participants With Gains in ETDRS Letter Score of at Least 15 Letters - LOCF | Missing values were imputed with post-baseline values during on-treatment period by using last observation carried forward (LOCF). | At week 24 and week 52 | 
| Change From Baseline in Central Retinal Thickness (CRT) as Assessed by Optical Coherence Tomography (OCT) - LOCF | Retinal thickness was evaluated using OCT at every visit except week 1. Missing values were imputed with post-baseline values during on-treatment period by using last observation carried forward (LOCF). | At week 24 and week 52 | 
| Number of Focal Laser Treatments |  | Week 1 to week 48 |