Efficacy and Safety of Intravitreal ANX007 in Geographic Atrophy Secondary to Age-Related Macular Degeneration: A Phase 3 Randomized Controlled Trial

The primary objective of this study is to evaluate the **efficacy** of intravitreal (IVT) injections of ANX007 on visual function and visual acuity in patients with **geographic atrophy** secondary to age-related macular degeneration. This is clinically relevant as it aims to address the progressive vision loss associated with this condition, potentially offering a therapeutic option to preserve visual function.

Secondary objectives include:

• Evaluating the efficacy of IVT injections of ANX007 on additional measures of visual function and visual acuity.
• Comparing the geographic atrophy (GA) lesion growth rate from IVT injections of ANX007 with sham control.
• Comparing the change in [CCI] with IVT injections of ANX007 with sham control.
• Assessing the safety and tolerability of IVT injections of ANX007.
• Assessing patient-reported outcomes.

The clinical trial involves a total of **517 participants** diagnosed with **geographic atrophy secondary to Age-Related Macular Degeneration**. The study population includes both male and female subjects, aged 50 years and older, who are capable of providing informed consent and willing to participate in a 24-month study with monthly visits. Participants were selected based on specific inclusion criteria, including a diagnosis confirmed by an independent Central Reading Center and a baseline best-corrected visual acuity (BCVA) within a specified range. The trial does not exclude vulnerable populations, and participants may have fellow eyes treated with approved anti-complement drugs under certain conditions. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria. The study aims to evaluate the efficacy of intravitreal injections of ANX007 on visual function and visual acuity.

The clinical trial is designed as a **randomized**, double-masked, parallel-group, sham-controlled study to evaluate the efficacy, safety, and tolerability of **ANX007** administered via intravitreal injection in patients with **geographic atrophy** secondary to age-related macular degeneration. The trial is structured to include two arms, with participants randomly assigned to receive either the active treatment or a sham procedure. The study is planned to span a total duration of 24 months, with monthly visits required for participants.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility is assessed based on specific criteria, including age, diagnosis of geographic atrophy, and visual acuity requirements. Following successful screening, participants will undergo baseline assessments before commencing the treatment phase. Monthly follow-up visits are scheduled to monitor the primary endpoint, which is the proportion of patients experiencing a best corrected visual acuity (BCVA) loss of 15 letters or more from baseline, as assessed by the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Secondary endpoints include the incidence and severity of treatment-emergent adverse events (TEAEs) through the 12th and 24th months.

The expected length of participant involvement is 24 months, with conditions for early termination including significant adverse events or non-compliance with study protocols. The end-of-study visit will involve final assessments to evaluate the long-term effects of the treatment. Participants must be at least 50 years old, capable of providing informed consent, and willing to comply with the study requirements. The trial is not categorized as low intervention and is conducted under the auspices of Annexon, Inc., with the investigational product being a protein-based formulation. The study is anticipated to start recruitment in March 2025 and conclude by February 2028.

The clinical trial involves the administration of **ANX007**, an investigational medication developed by Annexon, Inc. ANX007 is formulated as an **injection** and is administered via the **intravitreal route**. The active substance in ANX007 is a protein of other origin, specifically designed for the treatment of **geographic atrophy** secondary to age-related macular degeneration. The trial aims to evaluate the efficacy, safety, and tolerability of ANX007 in improving visual function and visual acuity. The maximum treatment period for ANX007 is 24 months, with the dosing schedule and specific dosage amounts to be determined based on the study protocol. Participant compliance with the dosing regimen will be monitored throughout the trial to ensure adherence to the treatment plan.

In addition to the experimental treatment, the study includes a **sham-controlled** arm to serve as a comparator. The sham procedure involves a simulated injection process without the administration of the active drug, allowing for the assessment of the treatment's efficacy against a placebo effect. This control is essential for maintaining the double-masked design of the trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments. The inclusion of a sham control helps to provide a robust evaluation of ANX007's therapeutic potential in the target patient population.

The efficacy of ANX007 in patients with **Geographic Atrophy (GA)** secondary to Age-Related Macular Degeneration (AMD) will be assessed through a Phase 3, multicenter, randomized, parallel-group, double-masked, sham-controlled study. The primary endpoint for evaluating efficacy is the proportion of patients experiencing a best corrected visual acuity (BCVA) loss of 15 letters or more from baseline, as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at any two consecutive visits. This primary endpoint will be assessed at a timepoint based on the accumulation of the target event rate, occurring no earlier than Month 12 and no later than Month 18.

Secondary endpoints include the incidence and severity of ocular and systemic treatment-emergent adverse events (TEAEs) through Month 12 and Month 24. The study will involve intravitreal injections of ANX007, with efficacy assessments focusing on visual function and visual acuity. The trial is designed to ensure rigorous evaluation of the treatment's impact on visual outcomes in the specified patient population.