Long-term Safety Evaluation of GT005 in Geographic Atrophy Secondary to Age-related Macular Degeneration Post Antecedent Gyroscope Study

The primary objective of the ORACLE study is to evaluate the long-term **safety** of **GT005** in participants with **geographic atrophy** secondary to **age-related macular degeneration** (AMD) who have been treated in a previous Gyroscope-sponsored study. The study aims to assess the incidence and severity of ocular and systemic adverse events over a period of up to 5 years post-treatment. This evaluation is clinically relevant as it provides critical data on the sustained safety profile of GT005, which is essential for understanding its long-term impact on patients with this progressive retinal condition.

The clinical trial involves a total of **133 participants** who have previously been treated with GT005 in antecedent studies GT005-01 (FOCUS), GT005-02 (EXPLORE), and GT005-03 (HORIZON). The study population includes both **male and female** subjects, with an age range that encompasses adults and the elderly. Participants are individuals with **geographic atrophy (GA)** secondary to age-related macular degeneration (AMD). The trial does not include a vulnerable population. Selection criteria required participants to have received GT005 in a prior study and to be willing to provide written informed consent, attend study visits, and complete study assessments. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The sponsor has not provided additional information regarding the general health status of the participants.

The clinical trial is designed to evaluate the long-term safety of **GT005** in participants with **geographic atrophy** secondary to **age-related macular degeneration** who have previously received treatment in antecedent studies. This is a phase 2 trial, which is not classified as low intervention. The trial employs a **randomized**, **double-blind**, and **controlled** design to ensure the reliability and validity of the results. The primary endpoint is to assess the incidence and severity of ocular and systemic adverse events over a period of up to five years post-treatment. The trial is expected to conclude by March 2029, with recruitment having commenced in July 2022.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as prior treatment with GT005 in specific antecedent studies and the ability to provide informed consent. Follow-up visits will be scheduled periodically to monitor the participants' health status and collect data on any adverse events. The end-of-study visit will mark the completion of the trial for each participant, where final assessments will be conducted. The expected duration of participant involvement is up to five years, contingent upon the absence of any conditions that may necessitate early termination, such as significant adverse events or withdrawal of consent.

The clinical trial involves the administration of an **experimental medication** identified as PPY988A, which is a **suspension for injection**. The active substance in this formulation is GT005, a structurally diverse substance developed by Gyroscope Therapeutics Ltd. The pharmaceutical form of PPY988A is specifically designed for **subretinal use**, which involves the delivery of the medication directly into the subretinal space. This route of administration is intended to target the affected area in participants with geographic atrophy secondary to age-related macular degeneration. The study aims to evaluate the long-term safety of GT005, with a focus on monitoring the incidence and severity of ocular and systemic adverse events over a period of up to five years post-treatment.

In this trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The study is designed to solely assess the safety profile of the GT005 treatment. Participant compliance with the dosing schedule is monitored throughout the study duration to ensure accurate assessment of the treatment's safety. The trial does not involve any pediatric formulations, and the product is not classified as an orphan drug. The study is conducted under the sponsorship of Gyroscope Therapeutics Ltd, with a focus on participants who have previously been treated in a Gyroscope-sponsored antecedent study.

The efficacy of the investigational product **GT005** will be assessed in a clinical trial involving participants with geographic atrophy secondary to age-related macular degeneration. The primary endpoint for evaluating efficacy is the incidence and severity of ocular and systemic adverse events. This endpoint will be measured over a long-term follow-up period of up to 5 years post-treatment. The study will focus on participants who have previously received **GT005** in an antecedent study. Data collection will involve monitoring and recording adverse events to determine the safety profile of **GT005**. The trial is categorized as a phase 2 study, and the evaluation of efficacy will be conducted in accordance with the study's objectives to ensure comprehensive safety assessment.