Evaluation of Intravitreal OPT-302 and Ranibizumab Versus Ranibizumab Monotherapy in Neovascular Age-related Macular Degeneration

The primary objective of this study is to evaluate the **efficacy** of intravitreal 2.0 mg OPT-302 when administered in combination with intravitreal 0.5 mg ranibizumab in participants with neovascular age-related macular degeneration (nAMD). This is clinically relevant as nAMD is a leading cause of vision loss, and improving treatment efficacy could significantly impact patient outcomes.

Secondary objectives include determining the effects of adding intravitreal 2.0 mg OPT-302 to intravitreal 0.5 mg ranibizumab from baseline to week 52 in terms of efficacy, specifically focusing on changes in Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) letter score. This assessment is crucial for understanding the potential benefits of the combination therapy on visual acuity, a key measure of treatment success in nAMD.

The clinical trial involves a total of **688 participants** diagnosed with **neovascular age-related macular degeneration (wet AMD)**. The study population includes both male and female subjects who are at least 50 years of age. Participants were selected based on specific criteria, including the presence of an active subfoveal or juxtafoveal choroidal neovascularization (CNV) lesion with foveal involvement secondary to AMD in the study eye, and an Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) score between 60 and 25 letters in the study eye. The trial population encompasses a vulnerable group, indicating careful consideration of ethical standards in participant selection. Lifestyle factors such as diet, physical activity, and habits were not specified by the sponsor.

The clinical trial is designed as a **randomized**, double-masked, controlled study to evaluate the efficacy and safety of intravitreal OPT-302 in combination with **ranibizumab** compared to ranibizumab alone in participants with neovascular age-related macular degeneration (nAMD). The trial aims to determine the efficacy of intravitreal 2.0 mg OPT-302 when administered alongside intravitreal 0.5 mg ranibizumab. The primary endpoint is the mean change from baseline to Week 52 in ETDRS BCVA letters, with secondary endpoints including the proportion of participants gaining 15 or more ETDRS BCVA letters and changes in CNV area by fluorescein angiography.

The trial is expected to last until May 31, 2026, with participant recruitment having commenced on September 27, 2021. Participants will be involved in the study for a maximum treatment period of 96 weeks. The study includes several key visits: an initial screening visit to assess eligibility based on criteria such as age (at least 50 years), presence of active subfoveal CNV lesions, and an ETDRS BCVA score between 60 and 25 letters. Follow-up visits will occur regularly to monitor the efficacy and safety of the treatment, with assessments including visual acuity tests and imaging studies. The end-of-study visit will evaluate the overall outcomes and any long-term effects of the treatment.

Participants may be withdrawn from the study early if they experience adverse effects that compromise their safety or if they fail to adhere to the study protocol. The trial is not categorized as low intervention and is classified as a Phase III trial, focusing on a common condition, neovascular age-related macular degeneration, which is not considered a rare disease. The study employs a rigorous methodology to ensure the reliability and validity of the results, contributing valuable data to the understanding and treatment of nAMD.

The clinical trial involves the administration of **OPT-302**, a solution for injection, which is a biological product of biotechnological origin. The active substance in OPT-302 is **vascular endothelial growth factor receptor 3 extracellular domains 1-3 fused to an IgG1 Fc fragment**. This experimental medication is administered via **intravitreal use**. The maximum daily dose is 2 mg, with a total maximum dose of 48 mg over a treatment period of up to 96 weeks. The pharmaceutical form is a solution for injection, and the product is not a paediatric formulation. Compliance with the dosing schedule is monitored throughout the trial.

In addition to OPT-302, the trial includes the administration of **Lucentis**, which contains the active substance **ranibizumab**. Lucentis is provided as a 10 mg/ml solution for injection in a pre-filled syringe. It is also a biological product of biotechnological origin. The administration route is **intravitreal use**, with a maximum daily dose of 0.5 mg and a total maximum dose of 12 mg over a 96-week treatment period. Lucentis is used as a comparator treatment in the study, and participant compliance with the dosing regimen is carefully monitored.

The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the mean change from baseline to Week 52 in Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letters. This endpoint will provide a quantitative measure of visual acuity improvement in participants with neovascular age-related macular degeneration (nAMD) receiving intravitreal OPT-302 in combination with **ranibizumab** compared to those receiving ranibizumab alone.

Secondary endpoints include the proportion of participants gaining 15 or more ETDRS BCVA letters from baseline to Week 52, the proportion gaining 10 or more ETDRS BCVA letters, and the change in choroidal neovascularization (CNV) area as assessed by fluorescein angiography (FA) from baseline to Week 52. Additionally, the absence of both subretinal fluid (SRF) and intraretinal (IR) cysts by spectral domain optical coherence tomography (SD-OCT) at Week 52 will be evaluated. These endpoints will provide further insights into the efficacy of the treatment regimen in improving visual outcomes and anatomical changes in the retina.