Evaluation of Efficacy and Safety of Intravitreal EYE103 Versus Ranibizumab in Diabetic Macular Edema: A Randomized, Double-Masked, Multi-Center Study

The primary objective of this study is to demonstrate the **non-inferiority** of EYE103 (0.5 mg or 0.8 mg) compared to anti-VEGF 0.5 mg, specifically **ranibizumab**, in participants with **Diabetic Macular Edema**. This will be assessed by measuring the mean change in best-corrected visual acuity (BCVA) from baseline to Week 52, utilizing the standardized ETDRS (Early Treatment of Diabetic Retinopathy Study) chart. The clinical relevance of this objective lies in potentially providing an alternative treatment option that is as effective as the current standard therapy, which could enhance patient outcomes and expand therapeutic choices for managing this condition.

The clinical trial involves a total of **570 participants** diagnosed with **Diabetic Macular Edema**. The study population includes both male and female subjects aged 18 years and older. Participants were selected based on their ability to understand the study procedures and provide informed consent. The trial does not include a vulnerable population. Key lifestyle considerations such as diet and physical activity are not specified. Participants are required to adhere to specific contraceptive measures if they are of childbearing potential. The general health status of the participants is not detailed, but they must meet the inclusion criteria related to age and gender. The trial aims to assess the non-inferiority of EYE103 compared to anti-VEGF in terms of visual acuity improvement over a 52-week period.

The clinical trial is designed as a **randomized**, double-masked, multi-center, three-arm pivotal Phase II/III study. The primary objective is to evaluate the efficacy and safety of intravitreal EYE103 compared with intravitreal **ranibizumab** (0.5 mg) in participants with **diabetic macular edema**. The trial aims to demonstrate the non-inferiority of EYE103 to anti-VEGF 0.5 mg, as measured by the mean change in best-corrected visual acuity (BCVA) using the standardized ETDRS chart from Day 1 to Year 1, with the primary endpoint being the average of Weeks 48 and 52.

The trial is expected to commence recruitment on September 1, 2024, and conclude by August 31, 2027. Participants will be involved in the study for a duration of up to 52 weeks. The study includes several key visits: an initial screening visit to assess eligibility based on inclusion criteria such as age and consent, followed by regular follow-up visits to monitor treatment effects and safety. The end-of-study visit will occur at the conclusion of the 52-week period to assess the final outcomes.

Participants will be randomly assigned to one of three treatment arms, receiving either EYE103, ranibizumab, or a comparator. The study will maintain a double-masked design to ensure unbiased results. The inclusion criteria require participants to be at least 18 years old, with specific conditions for females of childbearing potential and males regarding contraception. Participants may be terminated early from the study if they experience adverse effects or fail to comply with study protocols.

The clinical trial involves the evaluation of three treatments for **diabetic macular edema**. The first treatment is **Lucentis** (ranibizumab), a **solution for injection** with a concentration of 10 mg/ml. It is administered via **intravitreal use**. The maximum daily dose is 0.5 mg, with a total maximum dose of 12 mg over a treatment period of up to 24 months. Lucentis is produced by Novartis Europharm Limited and is not a pediatric formulation. The role of Lucentis in the trial is as a comparator to the experimental treatment.

The second treatment is **Fluorescein Alcon® 10% Injektionslösung**, which contains the active substance **fluorescein sodium**. This is also a **solution for injection** and is used as a contrast agent. The maximum daily dose is 500 mg, with a total maximum dose of 3 g over a treatment period of up to 6 months. This product is manufactured by Alcon Deutschland GmbH and serves an auxiliary role in the trial.

The experimental treatment in this trial is **EYE103**, a **solution for injection** containing the active substance of the same name. It is administered via **intravitreal use**. The maximum daily dose is 0.8 mg, with a total maximum dose of 19.2 mg over a treatment period of up to 24 months. EYE103 is produced by Eyebiotech Limited and is not a pediatric formulation. The primary objective of the study is to demonstrate the non-inferiority of EYE103 compared to Lucentis, as measured by the change in best-corrected visual acuity (BCVA) over a 52-week period.

Efficacy in this clinical trial will be assessed by evaluating the **mean change in best-corrected visual acuity (BCVA)** using the standardized ETDRS (Early Treatment of Diabetic Retinopathy Study) chart. The primary endpoint is defined as the mean change in ETDRS BCVA from Baseline (Day 1) to Year 1, which is the average of Weeks 48 and 52. This assessment aims to demonstrate the non-inferiority of EYE103 (0.5 mg or 0.8 mg) compared to anti-VEGF 0.5 mg in participants with diabetic macular edema.