Evaluation of Faricimab Loading Doses in Treatment-Naive Patients with Neovascular Age-Related Macular Degeneration

The primary objective of this study is to evaluate the efficacy of two initial **faricimab** loading doses in achieving a non-active state in patients with treatment-naive neovascular age-related macular degeneration (AMD). This is clinically relevant as achieving a non-active disease state can potentially halt the progression of vision loss associated with neovascular AMD, thereby improving patient outcomes.

Secondary objectives include identifying characteristics that predict disease activity and assessing the impact of two initial loading doses of faricimab on the timing of disease activity recurrence and functional development. These secondary aims are crucial for understanding the broader implications of faricimab treatment and optimizing therapeutic strategies for neovascular AMD.

The clinical trial involves participants diagnosed with **neovascular age-related macular degeneration** (nAMD). The study population includes both male and female subjects aged 50 years and older. Participants are required to be treatment-naïve for nAMD in the study eye, with the condition confirmed through fluorescein and/or indocyanine green angiography. The trial does not include a vulnerable population. The **Best Corrected Visual Acuity** (BCVA) of participants should range between 78 and 24 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at the start of the study. The sponsor has not provided information regarding the total number of participants. The selection of the study eye is based on the lower BCVA if both eyes are eligible. Participants' general health status and lifestyle considerations such as diet and physical activity are not specified. The sponsor has not disclosed additional details about the trial population selection process.

The clinical trial is designed to evaluate the efficacy of two initial **faricimab** loading doses in patients with treatment-naïve neovascular age-related macular degeneration (nAMD). This study is a randomized, double-blind, controlled trial with an estimated duration extending until June 2025. Participants will be involved in the study for a maximum treatment period of 20 weeks. The trial aims to determine the proportion of patients without disease activity at week 8, with secondary endpoints including changes in best corrected visual acuity (BCVA) and central subfield thickness from baseline to weeks 4 and 8.

Participants must be at least 50 years old and have a confirmed diagnosis of nAMD in the study eye, with specific criteria for choroidal neovascularization lesion size and BCVA. The study eye will be selected based on the lower BCVA if both eyes are eligible. The trial will commence with a screening visit to confirm eligibility, followed by the administration of the initial faricimab loading doses. Follow-up visits will occur at regular intervals to monitor disease activity and assess treatment efficacy through various measurements, including optical coherence tomography (OCT) and angiography.

The end-of-study visit will conclude the participant's involvement, with data collected to evaluate the primary and secondary endpoints. Participants may be withdrawn from the study if they experience adverse events or if they no longer meet the inclusion criteria. The trial is categorized as a low-intervention, Phase IV study, ensuring a focus on safety and efficacy in a real-world setting. The study's design and procedures are structured to provide comprehensive data on the treatment's impact on nAMD, contributing valuable insights into the management of this condition.

The clinical trial involves the administration of **Vabysmo**, a pharmaceutical product containing the active substance **faricimab**. Vabysmo is formulated as a **solution for injection** with a concentration of 120 mg/mL. The medication is administered via **intravitreal use**, which involves injecting the solution directly into the eye. The dosing regimen for this trial includes two initial loading doses, with a maximum daily dose of 6 mg and a total maximum dose of 18 mg over a treatment period of up to 20 weeks. The primary objective of the study is to evaluate the efficacy of these loading doses in achieving a non-active state of neovascular age-related macular degeneration (AMD).

Faricimab is a bispecific antibody targeting both vascular endothelial growth factor A (VEGF-A) and angiopoietin 2 (Ang-2). It is classified under the ATC code S01LA09 and is produced by Roche Registration GmbH. The substance is derived from a protein origin and is not designated as an orphan drug. The trial does not involve any pediatric formulations, and no additional non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the study protocol. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the treatment regimen.

Efficacy in the clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is the proportion of patients without **disease activity** at week 8. Secondary endpoints include the proportion of patients with varying treatment intervals (4, 6, 8, 10, 12, 14, or 16 weeks) between the second and third faricimab injections, changes in best corrected visual acuity (BCVA) from baseline to weeks 4 and 8, and changes in central subfield thickness from baseline to weeks 4 and 8. Additionally, characteristics and measurements obtained through optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), angiography, and BCVA assessments will be evaluated to predict active or non-active disease.