Evaluation of Faricimab Efficacy and Safety in Neovascular Age-Related Macular Degeneration: A Phase IIIb/IV Multicenter, Randomized, Open-Label Study

The primary objective of this study is to evaluate the **efficacy** of intravitreal (IVT) injections of faricimab in patients with **neovascular age-related macular degeneration**. This is assessed by measuring the change from baseline in best corrected visual acuity (BCVA) averaged over Weeks 44, 48, and 52, following the regimen in each of the treatment arms. This objective is clinically relevant as it directly addresses the potential of faricimab to improve visual outcomes in patients, which is a critical aspect of managing this progressive eye condition.

Secondary objectives include: - Evaluating the efficacy of IVT injections of faricimab on additional BCVA outcomes in the study eye. - Assessing the efficacy of IVT injections of faricimab on anatomic outcomes using optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) in the study eye. - Determining the durability of IVT injections of faricimab in the study eye. - Evaluating the ocular and non-ocular safety and tolerability of IVT injections of faricimab.

The clinical trial involves a total of **185 participants** diagnosed with **Neovascular Age-Related Macular Degeneration**. The study population includes both male and female subjects, aged **50 years and older**, who are overtly healthy as determined by a comprehensive medical evaluation, including medical history and physical examination. Participants were selected based on specific ocular criteria, such as active treatment-naïve macular neovascularization secondary to age-related macular degeneration, confirmed by the presence of intraretinal or subretinal fluid affecting the central subfield on OCT. The trial population is required to have a best corrected visual acuity (BCVA) of 83 to 24 letters, inclusive, using the early treatment diabetic retinopathy study protocol. Additionally, participants must have sufficiently clear ocular media and adequate pupillary dilation to allow for the acquisition of high-quality retinal images. The study includes a vulnerable population, and participants have agreed to adhere to specified contraception requirements. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **randomized**, open-label, two-arm study to evaluate the efficacy, safety, and durability of **faricimab** administered up to every 24 weeks in patients with **neovascular age-related macular degeneration**. The trial will involve intravitreal injections of faricimab, with the primary objective being the change from baseline in best corrected visual acuity (BCVA) averaged over Weeks 44, 48, and 52. The study is expected to commence recruitment in July 2025 and conclude by January 2028, with a maximum treatment period of 96 weeks for participants.

Participants will undergo a sequence of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥50 years), health status, and specific ocular conditions. The inclusion criteria require active treatment-naïve macular neovascularization secondary to age-related macular degeneration, confirmed by the presence of intraretinal or subretinal fluid affecting the central subfield on optical coherence tomography (OCT). The BCVA must be between 83 to 24 letters, inclusive, using the early treatment diabetic retinopathy study (ETDRS) protocol.

Following the screening, participants will be randomized into one of the two treatment arms. Regular follow-up visits will be scheduled to monitor the change in BCVA and central subfield thickness (CST) over time, as well as to assess the incidence and severity of ocular and non-ocular adverse events. The study will also evaluate the proportion of participants on various treatment intervals at Weeks 52 and 100. The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted.

Participant involvement is expected to last up to 96 weeks, with conditions for early termination including withdrawal of consent, adverse events, or any other medical reasons deemed necessary by the investigator. The trial aims to provide comprehensive data on the long-term effectiveness and safety of faricimab in treating neovascular age-related macular degeneration.

The clinical trial involves the administration of **Vabysmo**, a **120 mg/mL solution for injection**. The active substance in Vabysmo is **faricimab**, a bispecific antibody targeting both vascular endothelial growth factor A (VEGF-A) and angiopoietin 2 (Ang-2). The pharmaceutical form of Vabysmo is a solution for injection, specifically designed for **intravitreal use**. The dosing regimen allows for administration up to every 24 weeks, with a maximum daily dose of 6 mg and a total dose not exceeding 0.15 g over the treatment period. The maximum treatment duration is 96 weeks. The solution is provided in secondary packaging specifically for clinical trial use.

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 efficacy, safety, and durability of faricimab in patients with **neovascular age-related macular degeneration**. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol. The trial is conducted in an open-label, randomized, two-arm format, allowing for a comprehensive assessment of the treatment's impact on best corrected visual acuity (BCVA) over specified intervals.

The efficacy of the clinical trial will be assessed by evaluating the change from baseline in **best corrected visual acuity (BCVA)**. This primary endpoint will be measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart at a starting distance of 4 meters. The primary efficacy assessment will focus on the average change in BCVA over Weeks 44, 48, and 52. Secondary endpoints include the change from baseline in BCVA averaged over Weeks 92, 96, and 100, as well as the change in central subfield thickness (CST) over similar timeframes. Additional secondary endpoints will assess the proportion of participants on various treatment intervals (Q4W, Q8W, Q12W, Q16W, Q20W, and Q24W) at Weeks 52 and 100, and the incidence and severity of both ocular and non-ocular adverse events. These efficacy parameters will be collected and analyzed at specified timepoints throughout the trial to determine the impact of intravitreal injections of faricimab on patients with neovascular age-related macular degeneration.