Evaluation of Handling and Ocular Safety of Aflibercept Pre-Filled Syringe in Chorioretinal Vascular Diseases: A Single-Arm, Open-Label, Multicenter Study

The primary objective of this clinical study is to demonstrate the **appropriate and safe handling** of the AVT06 pre-filled syringe (PFS) in subjects with **chorioretinal vascular disease**, which includes conditions such as neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), myopic choroidal neovascularization (CNV), retinal vein occlusion (RVO), and diabetic retinopathy (DR). Additionally, the study aims to evaluate the **ocular safety** of AVT06 when administered using the PFS. These objectives are clinically relevant as they address the safety and usability of a treatment delivery method for serious ocular conditions, potentially impacting patient outcomes and treatment adherence.

The clinical trial involves a total of **12 participants** diagnosed with various forms of **chorioretinal vascular disease**, including neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), myopic choroidal neovascularization (CNV), retinal vein occlusion (RVO), and diabetic retinopathy (DR). The study population comprises both male and female subjects aged 18 years and older. Participants were selected based on their diagnosis and eligibility for aflibercept treatment in the study eye, as determined by the Principal Investigator. The trial does not include a vulnerable population. Participants are required to comply with specific contraception guidelines during and after the treatment period. The selection criteria ensure that subjects are either treatment-naïve or already receiving aflibercept or its marketed biosimilar, and they must be willing and able to adhere to all study procedures. The trial does not specify any particular lifestyle considerations such as diet or physical activity.

The clinical trial is designed as a **single-arm, open-label, multicenter study** to evaluate the handling and safety of AVT06 pre-filled syringe (PFS) in subjects with **chorioretinal vascular disease**, including neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), myopic choroidal neovascularization (CNV), retinal vein occlusion (RVO), and diabetic retinopathy (DR). The trial aims to demonstrate the appropriate and safe handling of AVT06 PFS and to evaluate ocular safety when administered intravitreally. The study is expected to commence on November 16, 2023, and conclude by February 11, 2025, with a maximum treatment period of 54 weeks.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥18 years), diagnosis of the specified conditions, and ability to comply with study procedures. The study eye will be selected by the Principal Investigator. Following the screening, participants will receive AVT06 injections, with the primary endpoint being the proportion of successful injections on Day 1 and the incidence of ocular treatment-emergent adverse events (TEAEs) from baseline to Week 4. The study will include follow-up visits to monitor safety and efficacy, culminating in an end-of-study visit to assess overall outcomes.

Participant involvement is expected to last up to 54 weeks, with conditions for early termination including non-compliance with study procedures or the occurrence of significant adverse events. The trial does not include a control group, and all participants will receive the investigational product. The study is not classified as a low-intervention trial and is categorized as a phase 3 study. The trial will adhere to ethical guidelines, requiring informed consent from all participants or their legal representatives before any study-specific procedures are conducted.

The clinical trial involves the administration of **Aflibercept**, a solution for injection provided in a pre-filled syringe. This experimental medication is identified by the sponsor product code AVT06 and is manufactured by Alvotech Swiss AG. Aflibercept is classified under the ATC code L01XX44 and is derived from a protein of other origin. The pharmaceutical form is specifically designed for **intravitreal use**, which involves the injection of the solution directly into the eye. The maximum daily dose of Aflibercept is 2 mg, with a total maximum dose of 26 mg over the course of the treatment period. The treatment period is set to a maximum of 54 weeks. The study aims to evaluate the handling and ocular safety of the AVT06 pre-filled syringe in subjects with chorioretinal vascular disease.

In this clinical trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the administration of Aflibercept to assess its safety and handling. The trial is designed as a single-arm, open-label, multicenter study, which means all participants receive the experimental treatment, and both the researchers and participants are aware of the treatment being administered. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol and to accurately assess the safety and efficacy of the treatment.

Efficacy in this clinical trial will be assessed using primary endpoints that focus on the administration and safety of the investigational product, AVT06, a pre-filled syringe containing **Aflibercept**. The primary endpoints include the proportion of AVT06 injections successfully administered with the pre-filled syringe on Day 1 and the incidence of ocular treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), and serious adverse events (SAEs) associated with the study eye from Baseline to Week 4. These endpoints are designed to evaluate both the handling and ocular safety of the product in subjects with chorioretinal vascular disease.