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

Phase 2

Completed

• Conditions: Diabetic Macular Edema
• Interventions: Drug: Intravitreal Aflibercept Injection; Procedure: Laser Photocoagulation

• Registration Number: NCT00789477
• Lead Sponsor: Regeneron Pharmaceuticals

Brief Summary

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

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

Study Timeline

• Study First Submitted: 2008-11-07
• Study First Submitted QC: 2008-11-07
• Study First Posted: 2008-11-11
• Study Start: 2008-12
• Primary Completion: 2009-12
• Study Completion: 2010-09
• Disposition First Submitted: 2011-04-19
• Disposition First Submitted QC: 2011-05-02
• Disposition First Posted: 2011-05-05
• Status Verified: 2014-08
• Results First Submitted: 2014-08-28
• Results First Submitted QC: 2014-08-28
• Last Update Submitted: 2014-08-28
• Results First Posted: 2014-09-09
• Last Update Posted: 2014-09-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 221

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intravitreal Aflibercept Injection 2PRN	Intravitreal Aflibercept Injection	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
Intravitreal Aflibercept Injection .5Q4	Intravitreal Aflibercept Injection	Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) .5 mg every 4 weeks
Intravitreal Aflibercept Injection 2Q8	Intravitreal Aflibercept Injection	Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2mg every 4 weeks for 3 visits followed by every 8 weeks
Intravitreal Aflibercept Injection 2Q4	Intravitreal Aflibercept Injection	Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321) 2 mg every 4 weeks
Laser Photocoagulation	Laser Photocoagulation	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.

Primary Outcome Measures

Name	Time	Method
Change in BCVA From Baseline to Week 24 - Last Observation Carried Forward (LOCF)	At week 24	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).

Secondary Outcome Measures

Name	Time	Method
Participants With Gains in ETDRS Letter Score of at Least 15 Letters - LOCF	At week 24 and week 52	Missing values were imputed with post-baseline values during on-treatment period by using last observation carried forward (LOCF).
Change From Baseline in Central Retinal Thickness (CRT) as Assessed by Optical Coherence Tomography (OCT) - LOCF	At week 24 and week 52	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).
Number of Focal Laser Treatments	Week 1 to week 48
Change in BCVA From Baseline to Week 52 - LOCF	At week 52	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).