Managing Neovascular (Known as Wet) Age-related Macular Degeneration Over 2 Years Using Different Treatment Schedules of 2 mg Intravitreal Aflibercept Injected in the Eye

Study Overview
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Brief Summary
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This study aims to evaluate the optimal use, efficacy, and safety of a Treat-and-Extend regimen with aflibercept in subjects with nAMD.

Detailed Description
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The T&E dosing regimen for nAMD has emerged as a preferred regimen for many treating physicians aiming at maximizing outcomes by proactively treating the subject at each visit and by extending the treatment interval (if extension criteria are met), thus limiting visits, monitoring, and injections. To this day, there is limited evidence available addressing the question of what are useful intervals for treating and monitoring, how do they differ among subjects, and how are retreatment criteria applied to achieve long-term desirable outcomes in real-life practice. This study is designed to evaluate the optimal use, efficacy, and safety of the T&E regimen with intravitreal aflibercept in subjects with nAMD.

Official Title
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Managing Neovascular Age-related Macular Degeneration (nAMD) Over 2 Years With a Treat and Extend (T&E) Regimen of 2 mg Intravitreal Aflibercept - a Randomized, Open-label, Active-controlled, Parallel-group Phase IV/IIIb Study (ARIES)

Conditions
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Macular Degeneration

Intervention / Treatment
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* Drug: Eylea (Intravitreal Aflibercept, VEGF Trap-Eye, BAY86-5321)
* Drug: Eylea (Intravitreal Aflibercept, VEGF Trap-Eye, BAY86-5321)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women ≥ 50 years of age. Active primary subfoveal CNV lesions secondary to nAMD, including juxtafoveal lesions that affect the fovea as evidenced by FA in the study eye. Patients with polypoidal choroidal vasculopathy or retinal angiomatous proliferation are eligible to participate in the study, and their condition should be captured in the eCRF. ETDRS BCVA of 73 to 25 letters (20/40 to 20/320 Snellen equivalent) in the study eye. The area of CNV must occupy at least 50% of the total lesion. Exclusion Criteria: Any prior ocular (in the study eye) or systemic treatment or surgery for nAMD, except dietary supplements or vitamins. Any prior or concomitant therapy with another investigational agent to treat nAMD in the study eye. Prior treatment with anti-VEGF agents as follows: Prior treatment with anti-VEGF therapy in the study eye is not allowed Prior treatment with anti-VEGF therapy in the fellow eye with an investigational agent (not approved, e.g. bevacizumab) within the last 3 months before the first dose in the study. Such treatment will also not be allowed during the study. Prior treatment with an approved anti-VEGF therapy in the fellow eye is allowed. Prior systemic anti-VEGF therapy, investigational or approved, within the last 3 months before the first dose in the study, and such treatment will not be allowed during the study. Total lesion size >12 disc areas (30.5 mm2, including blood, scars and neovascularization) as assessed by FA in the study eye. Subretinal hemorrhages that are either 50% or more of the total lesion area, or if the blood is under the fovea and is 1 or more disc areas in size in the study eye. (If the blood is under the fovea, then the fovea must be surrounded by 270 degrees by visible CNV). Scar or fibrosis making up >50% of the total lesion in the study eye. Scar, fibrosis, or atrophy involving the center of the fovea in the study eye. Presence of retinal pigment epithelial tears or rips involving the macula in the study eye.

Ages Eligible for Study
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Minimum Age: 50 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early-start T&E / Arm 1<br>Early-start T&E arm: test group, early treatment individualization | Drug: Eylea (Intravitreal Aflibercept, VEGF Trap-Eye, BAY86-5321)<br>* 3 monthly doses followed by individualized treatment intervals of between 8 to16 weeks based on protocol-defined anatomical criteria<br>|
| Active Comparator: Late-start T&E / Arm 2<br>Late-start T&E arm; per label, control group, treatment individualization after Year 1 | Drug: Eylea (Intravitreal Aflibercept, VEGF Trap-Eye, BAY86-5321)<br>* 3 monthly doses followed by five 8-weekly doses (5 x 2Q8), then by individualized treatment intervals of between 8 to 16 weeks based on protocol-defined anatomical criteria<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in BCVA as Measured by the ETDRS Letter Score | BCVA (best corrected visual acuity) was measured by the ETDRS (Early Treatment Diabetic Retinopathy Study) letter score of 73 to 25 (= Acuity of 20/40 to 20/320) in the study eye at 4 meters; a higher score represents better functioning. | From Week 16 to Week 104 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Maintaining Vision (<3 Lines Loss) at Week 104 Compared With Baseline | Participants maintained 3 lines (15 letters) vision loss in BCVA (Best-corrected visual acuity) as measured by the ETDRS (Early Treatment Diabetic Retinopathy Study) letter. | at Week 104 | 
| Change in BCVA From Baseline to Week 52, Baseline to Week 104, and Week 16 to Week 52 | BCVA (best corrected visual acuity) was measured by the ETDRS (Early Treatment Diabetic Retinopathy Study) letter score of 73 to 25 (= Acuity of 20/40 to 20/320) in the study eye at 4 meters; a higher score represents better functioning. | from baseline to Week 52, baseline to Week 104, and Week 16 to Week 52 | 
| Percentage of Participants Maintaining Vision (<3 Lines Loss) at Week 52 Compared With Baseline | Participants maintained 3 lines (15 letters) vision loss in BCVA (Best-corrected visual acuity) as measured by the ETDRS (Early Treatment Diabetic Retinopathy Study) letter. | At week 52 | 
| Percentage of Participants Gained 3-line at Week 52 and Week 104 Compared With Baseline | Participants gained 3 lines (15 letters) in BCVA (Best-corrected visual acuity) as measured by the ETDRS (Early Treatment Diabetic Retinopathy Study) letter. | At Week 52 and Week 104 | 
| Change in Central Retinal Thickness (CRT) | CRT were evaluated using spectral domain Optical coherence tomograph (OCT). | From baseline to Week 52, baseline to Week 104, Week 16 to Week 52, and Week 16 to Week 104 | 
| Number of Study Drug Injections From Baseline to Week 52 and Baseline to Week 104 |  | At Week 52 and Week 104 | 
| Duration of Last Treatment Interval |  | Early-Start T&E: from week 16 up to Week 104 or early termination; Late-Start T&E: From end of Year 1 up to Week 104 or early termination | 
| Percentage of Participants Requiring Retreatment at 8 Weeks, 10 Weeks, 12 Weeks, 14 Weeks, and 16 Weeks as the Last Treatment Interval |  | at 8 weeks, 10 weeks, 12 weeks, 14 weeks, and 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neovascular age-related macular degeneration, nAMD)