Phase 3 Open-Label Extension Study on the Safety of Intravitreal Avacincaptad Pegol in Geographic Atrophy Patients Post-GATHER2 Completion

The primary objective of this open-label extension Phase 3 trial is to evaluate the long-term **safety** of monthly intravitreal administration of **avacincaptad pegol**, a complement C5 inhibitor, in patients with **geographic atrophy** who have previously completed the Phase 3 Study ISEE2008 (GATHER2). This assessment is crucial for understanding the extended safety profile of avacincaptad pegol, which is administered as a solution for injection, and its potential implications for ongoing treatment strategies in managing geographic atrophy.

The clinical trial involves a total of **154 participants** who have been diagnosed with **geographic atrophy**. The study population includes both male and female subjects aged 50 years or older. Participants were selected based on their completion of Study ISEE2008 (GATHER2) through the Month 24 visit on study treatment, regardless of whether they received avacincaptad pegol or Sham previously. The trial population is characterized by individuals who are capable of returning for all trial visits over the 18-month duration. Participants must provide new written informed consent to partake in this open-label extension trial. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, indicating that special considerations may be necessary for the ethical conduct of the study.

The clinical trial is designed to evaluate the long-term safety of **avacincaptad pegol** administered intravitreally in patients with **geographic atrophy** who have previously completed the Phase 3 Study ISEE2008 (GATHER2). This trial is structured as an open-label extension, allowing for the continued assessment of safety over an 18-month period. The trial employs a randomized, controlled design, ensuring that participants are allocated to receive either the investigational product or a control under blinded conditions. The trial is expected to conclude by April 10, 2025.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age and previous completion of the GATHER2 study. Following the screening, participants will attend regular follow-up visits to monitor safety endpoints, including adverse events, and secondary endpoints such as immunogenicity and pharmacokinetics. The trial will culminate in an end-of-study visit, where final assessments will be conducted.

The expected duration of participant involvement is approximately 18 months, during which they must be able to attend all scheduled visits. Conditions that may lead to early termination from the study include the inability to comply with the study protocol or the occurrence of significant adverse events that compromise participant safety. The trial is conducted under rigorous scientific and ethical standards to ensure the integrity of the data and the safety of the participants.

The clinical trial involves the administration of **Avacincaptad pegol**, a **solution for injection** formulated for **intravitreal use**. The active substance, avacincaptad pegol, is of nucleic acid origin and is developed by Astellas Pharma Global Development, Inc. The medication is administered at a dosage of 2 mg per injection, with a maximum total dose of 34 mg over a treatment period of 17 months. The administration frequency is monthly, and the trial aims to assess the long-term safety of this treatment in patients with geographic atrophy who have completed the previous phase 3 study, ISEE2008 (GATHER2). Participant compliance is monitored through regular follow-ups and assessments.

In addition to the experimental treatment, **Fluorescein sodium** is used as an auxiliary substance in the trial. This compound, also a **solution for injection**, is of chemical origin and is commonly known as fluorescein disodium. It is administered at a maximum daily dose of 500 mg, although the total dose over the treatment period is not specified. The use of fluorescein sodium is intended to support the primary treatment and provide additional data on the safety and efficacy of the experimental medication. The administration of fluorescein sodium follows standard protocols for its use in clinical settings.

The efficacy of the clinical trial involving **avacincaptad pegol** will be assessed through specific endpoints. The primary endpoint focuses on the occurrence of adverse events (AEs), which will be systematically recorded and analyzed throughout the trial duration. Secondary endpoints include the evaluation of immunogenicity and pharmacokinetics, providing additional insights into the drug's efficacy and safety profile. These parameters will be measured using appropriate laboratory tests and validated scales at predetermined intervals, ensuring comprehensive data collection and analysis. The trial is designed to assess the long-term safety of monthly intravitreal administration of **avacincaptad pegol** in patients with geographic atrophy (GA) who have completed the previous Phase 3 study, ISEE2008 (GATHER2). The trial will continue until the estimated end date of April 10, 2025, with data collection occurring at various timepoints to ensure robust efficacy assessment.