Efficacy and Safety of Two Different Aflibercept Regimens in Subjects With Neovascular Age-related Macular Degeneration (nAMD)

Study Overview
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Brief Summary
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To compare the efficacy of 2 mg aflibercept administered by two different intravitreal (IVT) treatment regimens to subjects with neovascular age-related macular degeneration (nAMD)

Detailed Description
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330 Patients who have completed at least one year of treatment with aflibercept will be randomized to two different aflibercept regimens and followed for 76 weeks.

Official Title
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An Open-label, Randomized, Active-controlled, Parallel-group, Phase-3b Study of the Efficacy, Safety, and Tolerability of 2 mg Aflibercept Administered by Intravitreal Injections Using Two Different Treatment Regimens to Subjects With Neovascular Age-related Macular Degeneration (nAMD).

Conditions
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Macular Degeneration

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The following criteria must have been met at the initial start of aflibercept treatment (i.e. start of aflibercept treatment at least 1 year before this study): Subject had primary subfoveal choroidal neovascularization (CNV) lesions secondary to nAMD, including juxtafoveal lesions that affect the fovea, as evidenced by fluorescein angiography/photography (FA/FP) of the study eye within 3 weeks before the initiation of aflibercept treatment. The area of CNV occupied at least 50% of the total lesion within 3 weeks before the initiation of aflibercept treatment. Documented best-corrected visual acuity (BCVA) was 20/40 to 20/320 (letter score of 73 to 25) in the study eye at the initiation of treatment. Men and women >= 51 years of age The subject's history of aflibercept treatment meets ALL of the following: Treatment in the study eye was initiated with three monthly (-1 week/+2 weeks) doses of 2 mg aflibercept and improvements of visual and anatomic outcomes were observed Following the above initiation phase, the intervals between treatments were between 6 weeks and 12 weeks Exclusion Criteria: - Any prior or concomitant therapy with an investigational or approved agent to treat neovascular AMD in the study eye other than aflibercept. Total lesion size > 12 disc areas (30.5 mm2, including blood, scars and neovascularization) as assessed by fluorescein angiography (FA) in the study eye Subretinal hemorrhage that was: 50% or more of the total lesion area, or if the blood was under the fovea, and the blood under the fovea was 1 or more disc areas in size in the study eye. Scar or fibrosis making up more than 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. Causes of CNV other than AMD in the study eye.

Ages Eligible for Study
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Minimum Age: 51 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: Aflibercept extended dosing<br>Aflibercept was administered 2mg per injection intravitreal (IVT) in the study eye in Aflibercept extended dosing. Flexible dosing interval is ≥ 8 weeks (no upper limit) based on visual and anatomic outcomes as judged by the investigator. When/if visual and anatomical outcomes indicated that the disease had re-activated, the treatment interval reverted to the last treatment interval in which the disease was inactive (ie, no signs of exudation were observed). | Drug: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)<br>* A dose of 2 mg aflibercept injected intravitreally<br>|
| Active Comparator: Aflibercept 2Q8 (2 mg aflibercept administered every 8 weeks)<br>Aflibercept was administered 2mg per injection IVT in the study eye in Aflibercept 2Q8. Fixed dosing interval is 8 weeks (±3 days), modification of the treatment interval was not allowed. | Drug: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)<br>* A dose of 2 mg aflibercept injected intravitreally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) Letter Score for the Study Eye | Visual function was assessed with the procedure from the ETDRS adapted for the Age Related Eye Disease Study using charts with 70 letters at a starting distance of 4 meters. Charts are organized in 14 lines of decreasing size with 5 letters each. Participants reading up to 19 letters at 4 meters were tested at 1 meter to read the first 6 lines. The score equals the sum of letters read at 1 meter and 4 meters. If more than 19 letters are read at 4 meters the score equals the number of letters read plus 30. The score range is 0 to 100, and a higher score represents better visual function. | From baseline to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Maintaining Vision in the Study Eye | A participant was classified as maintaining vision if the participant had lost fewer than 15 letters in the ETDRS letter score compared to baseline. | At week 52 | 
| Percentage of Participants Who Gained From Baseline 5 or More Letters in the Study Eye |  | At week 52 | 
| Mean Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye | Retinal characteristic was evaluated using Optical coherence tomography (OCT). | From baseline to week 52 | 
| Mean Change From Baseline in Choroidal Neovascularization (CNV) Area in the Study Eye | Choroidal neovascularization measured by optical coherence tomography (OCT). | From baseline to week 52 | 
| Percentage of Participants Who Lost From Baseline 30 or More Letters in the Study Eye |  | At week 52 | 
| Mean Change From Baseline in Total Score for National Eye Institute 25-Item Visual Function (NEI VFQ-25) Questionnaire | National Eye Institute 25-Item Visual Function Questionnaire (NEI VFQ-25) total score ranges from 0 to 100, where 100 represents the best possible score and 0 represents the worst. | From baseline to week 52 | 
| Number of Participants With Treatment-emergent Adverse Events (TEAE) |  | Started after the first application of aflibercept in the study and less than or equal to 30 days after the last dose of study drug over approximately 1.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Age-related macular degeneration (AMD), Eylea treatment, Treat and Extend, Intravitreal