Pharmacokinetic Evaluation of Systemic Exposure to High-Dose Aflibercept in Bilateral Intravitreal Administration for DME and nAMD Patients

The primary objective of this study is to evaluate the **systemic pharmacokinetics** following bilateral administration of 8 mg aflibercept in adults diagnosed with **diabetic macular edema** (DME) or **neovascular age-related macular degeneration** (nAMD). This is clinically relevant as understanding the systemic exposure of aflibercept can inform safety profiles and optimize dosing regimens for these conditions, potentially improving therapeutic outcomes and minimizing systemic side effects. No secondary objectives are specified for this study.

The clinical trial involves participants diagnosed with **neovascular age-related macular degeneration (nAMD)** or **diabetic macular edema (DME)**. The study population includes both male and female subjects aged 18 years and older, with no upper age limit specified. Participants are required to have active disease in both eyes, necessitating intravitreal anti-VEGF treatment, as determined by the investigator. The trial includes individuals with type 1 or type 2 diabetes mellitus and DME with central involvement, or those diagnosed with nAMD with active subfoveal choroidal neovascularization. Best corrected visual acuity must fall within a specific range, and participants must not be pregnant or breastfeeding, with requirements for effective contraception for those of childbearing potential. The sponsor has not provided the total number of participants. The trial population was selected based on specific ophthalmic and systemic health criteria, and it includes a vulnerable population. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed as an **open-label**, non-randomized, multi-center, phase 4 pharmacokinetic study. The primary objective is to evaluate the systemic pharmacokinetics after bilateral administration of 8 mg of **aflibercept** in adults diagnosed with either **neovascular age-related macular degeneration (nAMD)** or **diabetic macular edema (DME)**. The trial is expected to commence recruitment on September 1, 2024, and conclude by February 27, 2026. Participants will be involved in the study for a maximum treatment period of 48 weeks.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as age, diagnosis, and visual acuity. The inclusion criteria require participants to be adults (≥18 years) with active disease in both eyes, necessitating intravitreal anti-VEGF treatment. Women of childbearing potential and men with partners of childbearing potential must agree to use effective contraception during the study and for four months after the last dose. The primary endpoint is the maximum observed concentration (Cmax) of free aflibercept.

Following the screening visit, participants will receive bilateral intravitreal injections of aflibercept. Subsequent follow-up visits will be scheduled to monitor systemic exposure and assess any adverse effects. The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted. Conditions that may lead to early termination from the study include non-compliance with the study protocol, withdrawal of consent, or any adverse event that, in the investigator's opinion, warrants discontinuation for the participant's safety.

The clinical trial involves the administration of **Eylea**, a pharmaceutical product containing the active substance **aflibercept**. Eylea is formulated as a **solution for injection** with a concentration of 114.3 mg/ml. The medication is administered via **intravitreal use**, which involves injecting the solution directly into the eye. The trial protocol specifies a high dose of 8 mg of aflibercept to be administered bilaterally, meaning into both eyes, to participants diagnosed with diabetic macular edema or neovascular age-related macular degeneration. The maximum daily dose is set at 16 mg, with a total maximum dose of 96 mg over the course of the treatment period, which spans up to 48 weeks. The product is supplied with a BD Blunt Fill Needle (18 gauge filter needle) for the extraction of the injection solution from the vial into the injection syringe. It is important to note that the filter needle is not intended for injection.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on evaluating the systemic pharmacokinetics of aflibercept following its bilateral administration. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol. The trial is designed to assess the systemic exposure of aflibercept, a protein-based therapeutic agent, following its administration in the specified patient population. The study is conducted under the sponsorship of Bayer AG, with modifications to the investigational medicinal product compared to its marketing authorization, specifically regarding labeling and secondary packaging.

Efficacy in this clinical trial will be assessed primarily through the measurement of the **maximum observed concentration (Cmax)** of free aflibercept. This parameter will be used to evaluate the systemic pharmacokinetics following bilateral intravitreal administration of high-dose aflibercept in adults with diabetic macular edema or neovascular age-related macular degeneration. The trial is designed as an open-label, non-randomized, multi-center, phase 4 pharmacokinetic study. The collection and analysis of the efficacy parameter will be conducted in accordance with the study protocol, ensuring accurate and reliable data to assess the systemic exposure of aflibercept. The trial will involve the administration of aflibercept solution for injection, with the use of a filter needle for extraction from the vial into the injection syringe, although the filter needle is not intended for injection. The study is expected to conclude by February 2026, with recruitment starting in September 2024.