Safety, Tolerability, and Efficacy of Aflibercept in Patients With Neovascular Age-Related Macular Degeneration

Study Overview
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Brief Summary
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The primary objectives of the study are to determine the safety of high-dose aflibercept (hereafter referred to as HD) and to determine if HD provides greater intraocular pharmacodynamic (PD) effect and/or longer duration of action compared to intravitreal aflibercept injection (hereafter referred to as IAI).

Official Title
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A Randomized, Single-Masked, Active-Controlled Phase 2 Study of the Safety, Tolerability, and Efficacy of Repeated Doses of High-Dose Aflibercept in Patients With Neovascular Age-Related Macular Degeneration

Conditions
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Neovascular (Wet) Age-Related Macular Degeneration

Intervention / Treatment
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* Drug: aflibercept
* Drug: High-dose aflibercept


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Men or women ≥50 years of age with active subfoveal choroidal neovascularization (CNV) secondary to nAMD Best Corrected Visual Acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score of 78 to 24 (Snellen equivalent of 20/32 to 20/320) in the study eye Key Exclusion Criteria: Evidence of CNV due to any cause other than nAMD in either eye Evidence of diabetic macular edema (DME) or diabetic retinopathy (defined as more than 1 microaneurysm) in either eye in diabetic patients Prior use of IVT anti-VEGF agents (aflibercept, ranibizumab, bevacizumab, brolucizumab, pegaptanib sodium) in the study eye Prior IVT investigational agents in either eye (eg, anti-ang-2/anti-VEGF bispecific monoclonal antibodies, gene therapy) Previous use of intraocular or periocular corticosteroids within 120 days of screening or treatment with an IVT steroid implant at any time in the study eye History of vitreoretinal surgery (including scleral buckling) in the study eye Any other intraocular surgery within 12 weeks (84 days) before the screening visit History of corneal transplant or corneal dystrophy in study eye NOTE: Other protocol defined inclusion/exclusion criteria apply.

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: intravitreal aflibercept injection (IAI)<br>Treatment-naïve patients with neovascular wet age-related macular degeneration (nAMD) randomized in a 1:1 ratio | Drug: aflibercept<br>* Intravitreally (IVT) administered as a liquid formulation in a vial<br>* Other names: BAY86-5321;|
| Experimental: High-dose aflibercept (HD)<br>Treatment-naïve patients with nAMD randomized in a 1:1 ratio | Drug: High-dose aflibercept<br>* Intravitreally (IVT) administered as a liquid formulation in a vial<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) |  | Up to Week 44 | 
| Number of Participants With at Least One Serious TEAE |  | Up to Week 44 | 
| Number of Participants Without Retinal Fluid in the Center Subfield of Study Eye | Center subfield=the circular area in 1 millimeter (mm) diameter centered around the center point of the fovea. Without fluid defined as absence of intraretinal fluid (IRF) and/or subretinal fluid (SRF) in the center subfield. Presence of retinal fluid was assessed by spectral domain optical coherence tomography (SD-OCT) | At Week 16 |