Evaluation of Aflibercept for Neovascular Glaucoma Prevention in Patients with Large Choroid Melanoma Undergoing Proton Therapy

The primary objective of this study is to **compare** the rate of neovascular glaucoma five years after proton therapy in patients with large choroid melanoma. This comparison is between a group of patients treated preventively with intravitreal anti-VEGF injections and a second group receiving a placebo injection. Neovascular glaucoma is a significant complication that can arise following treatment for choroid melanoma, and its prevention is crucial for preserving vision and quality of life in affected patients. The study evaluates the efficacy of **aflibercept**, an anti-VEGF agent, in reducing the incidence of this condition, thereby potentially offering a preventive strategy for patients undergoing proton therapy for large choroid melanoma.

The clinical trial involves participants diagnosed with **choroid melanoma** characterized by a thickness of 7 mm or more and/or a basal diameter exceeding 15 mm, all of whom have been treated with proton therapy. The study population includes both male and female subjects aged 18 years and older. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants were selected based on specific inclusion criteria, including the presence of large choroid melanoma and prior treatment with proton therapy. No additional lifestyle considerations such as diet, physical activity, or habits have been specified for this trial.

The clinical trial is designed to evaluate the efficacy of **aflibercept** in preventing neovascular glaucoma in patients with large choroid melanoma treated by proton therapy. This study is a randomized, double-blind, controlled trial, comparing the rate of neovascular glaucoma five years post-proton therapy between two groups: one receiving preventive intravitreal injections of anti-VEGF and the other receiving a placebo injection. The trial is expected to span from June 2017 to June 2025, with participant involvement lasting up to 23 months.

Participants will undergo a series of study visits, beginning with an inclusion visit to confirm eligibility based on criteria such as age (≥18 years) and specific tumor characteristics (choroid melanoma more than 7 mm thick and/or over 15 mm in basal diameter). Follow-up visits will be scheduled to monitor the occurrence of neovascular glaucoma, assessed through clinical diagnosis at the slit lamp. The end-of-study visit will conclude the participant's involvement, evaluating the primary endpoint of glaucoma occurrence.

Participants may be withdrawn from the study if they experience adverse effects or if they no longer meet the inclusion criteria. The trial's primary endpoint is the occurrence of neovascular glaucoma following radiation-induced proton therapy. No secondary endpoints are specified. The study aims to provide valuable insights into the preventive potential of anti-VEGF therapy in this patient population.

The clinical trial involves the use of **Eylea**, a pharmaceutical product containing the active substance **aflibercept**. Eylea is formulated as a **solution for injection** in a pre-filled syringe, with a concentration of 40 mg/mL. The medication is administered via **intravitreal injection**, a route specifically chosen for its efficacy in delivering the drug directly to the eye. The maximum total dose allowed during the trial is 20 mg, and the treatment period is capped at 23 weeks. The product is manufactured by Bayer AG and is not a pediatric formulation. Aflibercept, the active ingredient, is a protein-based substance, classified under the ATC code S01LA05.

In addition to the experimental treatment, the study includes a comparator group receiving a **placebo**. This group will undergo a false injection procedure, designed to mimic the administration of the active drug without delivering any therapeutic agent. This approach is intended to provide a control for evaluating the efficacy of aflibercept in preventing neovascular glaucoma in patients with large choroid melanoma treated with proton therapy. Compliance with the dosing schedule and administration procedures will be closely monitored to ensure the integrity of the trial data.

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint, which is the occurrence of **neovascular glaucoma** following radiation-induced proton therapy. This will be determined through clinical diagnosis, specifically by examination at the slit lamp. The trial aims to compare the rate of neovascular glaucoma five years after proton therapy in patients with large choroid melanoma. Participants will be divided into two groups: one receiving preventive intravitreal anti-VEGF injections and the other receiving a placebo injection. The efficacy assessment will focus on the difference in neovascular glaucoma rates between these two groups. The trial is designed to provide a comprehensive evaluation of the preventive efficacy of anti-VEGF treatment in this patient population.