Efficacy and Safety of VEGF Trap Eye in Diabetic Macular Edema (DME) With Central Involvement

Study Overview
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Brief Summary
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To determine the efficacy of intravitreally (IVT) administered VEGF Trap-Eye on the best-corrected visual acuity (BCVA) assessed by the early treatment diabetic retinopathy study (ETDRS) chart in subjects with diabetic macular edema (DME) with central involvement.

Official Title
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A Randomized, Double Masked, Active Controlled, Phase III Study of the Efficacy and Safety of Repeated Doses of Intravitreal VEGF Trap Eye in Subjects With Diabetic Macular Edema

Conditions
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Macular Edema

Intervention / Treatment
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* Biological: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)
* Biological: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)
* Procedure: Macular Laser Photocoagulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults ≥ 18 years with type 1 or 2 diabetes mellitus Subjects with diabetic macular edema (DME) secondary to diabetes mellitus involving the center of the macula in the study eye Decrease in vision determined to be primarily the result of DME in the study eye Best-corrected visual acuity (BCVA) early treatment diabetic retinopathy study (ETDRS) letter score of 73 to 24 (20/40 to 20/320) in the study eye Exclusion Criteria: Laser photocoagulation (panretinal or macular) in the study eye within 90 days of Day 1 More than 2 previous macular laser treatments in the study eye Previous use of intraocular or periocular corticosteroids in the study eye within 120 days of Day 1 Previous treatment with antiangiogenic drugs in either eye (pegaptanib sodium, bevacizumab, ranibizumab etc.) within 90 days of Day 1 Active proliferative diabetic retinopathy (PDR) in the study eye Uncontrolled diabetes mellitus, as defined by HbA1c >12% 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 |
| --- | --- |
| Experimental: Intravitreal Aflibercept Injection 2Q4<br>Participants received 2 mg Intravitreal aflibercept injection (IAI) (Eylea, VEGF [vascular endothelial growth factor] Trap-Eye, BAY86-5321) every 4 weeks (2Q4) over 48 weeks. | Biological: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)<br>* Participants received 2mg Intravitreal aflibercept injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321) every 4 weeks (2Q4).<br>|
| Experimental: Intravitreal Aflibercept Injection 2Q8<br>Participants received 2 mg Intravitreal aflibercept injection (IAI) (Eylea, VEGF Trap-Eye, BAY86-5321) every 4 weeks until Week 16 and every 8 weeks (2Q8) thereafter, over 48 weeks. | Biological: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)<br>* Participants received 2mg Intravitreal aflibercept injection (IAI) (EYLEA, VEGF Trap-Eye, BAY86-5321) every 4 weeks for 5 visits followed by injections every 8 weeks (2Q8).<br>|
| Active Comparator: Macular Laser Photocoagulation<br>Participants received laser treatment at baseline and as needed at visits at which laser retreatment criteria were met, but no more frequently than every 12 weeks over 48 weeks. | Procedure: Macular Laser Photocoagulation<br>* Participants received laser treatment at baseline and as needed at visits at which laser retreatment criteria were met, but no more frequently than every 12 weeks.<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, which is a widely accepted international standard for macular laser photocoagulation treatment. A higher score represents better functioning. LOCF censored measurements after additional treatment. | Baseline up to 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 | Visual function of the study eye was assessed using the ETDRS protocol. A higher score represents better functioning. | Baseline up to 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 | Visual function of the study eye was assessed using the ETDRS protocol. A higher score represents better functioning. | Baseline up to week 52 | 
| Percentage of Participants With a Greater Than Equal (>=) Two-step Improvement From Baseline in the ETDRS Diabetic Retinopathy Severity Score (DRSS) as Assessed by Fundus Photography (FP) at Week 52 - LOCF | ETDRS DRSS: None (level 10); Mild to moderate nonproliferative diabetic retinopathy (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 up to week 52 | 
| Change From Baseline in Central Retinal Thickness (CRT) at Week 52 as Assessed on Optical Coherence Tomography (OCT) - LOCF | CRT 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. | Baseline up to 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 up to 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 up to week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetic Macular Edema, DME, VEGF Trap-Eye, best-corrected visual acuity (BCVA)