Randomized, Double‑Masked, Multicenter Phase 2/3 Trial of Intravitreal MK‑8748 versus Aflibercept in Neovascular Age‑Related Macular Degeneration

The primary objective is to demonstrate that intravitreal EYE201/MK-8748 is non‑inferior to aflibercept with respect to the mean change in best‑corrected visual acuity (BCVA), measured in ETDRS letters, from baseline to Year 1 in participants with neovascular age‑related macular degeneration, thereby assessing its potential to maintain visual function comparable to the current standard of care.

In total, 830 individuals were enrolled, comprising both female and male subjects. Eligibility required a diagnosis of Neovascular age-related macular degeneration (NVAMD) confirmed within 21 days before the first dose, with treatment‑naïve choroidal neovascularization (including subfoveal, juxtafoveal, extrafoveal lesions, retinal angiomatous proliferations, or polypoidal choroidal vascularization) in at least one eye and a documented vision loss attributable to NVAMD. Participants were selected from the age categories denoted by codes 3 and 4, reflecting the trial’s predefined age range. General health status was not otherwise restricted, and no specific lifestyle requirements such as diet or physical activity were stipulated in the inclusion criteria.

The study is a randomized, double-masked, multicenter, 3‑arm, integrated Phase 2/3 trial evaluating intravitreal MK‑8748 versus 2 mg aflibercept in participants with neovascular age‑related macular degeneration (NVAMD). After an initial screening visit to confirm treatment‑naïve choroidal neovascularization and other eligibility criteria, eligible subjects are randomized and receive the first intravitreal injection at the baseline visit. Subsequent study visits occur at predefined intervals (e.g., monthly for the first three months, then quarterly) to assess safety, administer additional injections, and record efficacy outcomes, culminating in an end‑of‑study visit at 12 months. The primary efficacy endpoint is the mean change in Best‑Corrected Visual Acuity (BCVA) measured in ETDRS letters from baseline to Year 1. Participant involvement therefore spans approximately one year from randomization to the final assessment. Early termination may occur if a participant experiences a serious adverse event, fails to meet continued eligibility, withdraws consent, or violates critical protocol requirements.

The investigational product, designated EYE201/MK-8748, is supplied as a solution for intravitreal injection. Each dose contains 0 mg of the active substance mk-8748 and is prepared in a sterile solution intended for injection into the vitreous cavity. Administration is performed by qualified personnel using the recommended aseptic technique.

The comparator arm utilizes aflibercept, provided in the pharmaceutical form PHF00231MIG for intravitreal use. The administered dose is 2 mg per injection. The product is supplied as a sterile solution for injection into the eye.

All study treatments are delivered by intravitreal injection according to the predefined dosing schedule outlined in the protocol. Participants receive the assigned injection at the scheduled visit intervals, and adherence to the dosing schedule is documented by the study staff. Injection dates, lot numbers, and administered volumes are recorded in the case report form to facilitate compliance monitoring.

Efficacy will be evaluated using the primary endpoint of mean change in Best‑Corrected Visual Acuity (ETDRS letters) from baseline to Year 1. Visual acuity will be measured with a standardized Early Treatment of Diabetic Retinopathy Study (ETDRS) chart at the screening visit (baseline) and at the Year 1 assessment.

The primary analysis will compare the mean change in ETDRS letters between the investigational intravitreal MK‑8748 arm and the aflibercept comparator arm to determine non‑inferiority. Statistical methods appropriate for comparing mean changes between groups will be applied.