A Phase 2b, Randomized, Double-masked, Multicenter, Dose-ranging, Sham-controlled Clinical Trial to Evaluate Intravitreal JNJ-81201887 (AAVCAGsCD59) Compared to Sham Procedure for the Treatment of Geographic Atrophy (GA) Secondary to Age-related Macular Degeneration (AMD)

The primary objective of this Phase 2b, randomized, double-masked, multicenter, dose-ranging, sham-controlled clinical trial is to evaluate the **change in geographic atrophy (GA) lesion growth** in eyes treated with JNJ-81201887 compared to a sham control. This is clinically relevant as GA is a progressive and irreversible condition associated with age-related macular degeneration (AMD), leading to significant visual impairment. By assessing the efficacy of JNJ-81201887, a potential therapeutic intervention, the study aims to address an unmet need in slowing or halting the progression of GA, thereby preserving vision and improving quality of life for affected individuals.

The clinical trial involves a total of **167 participants** diagnosed with **Geographic Atrophy** secondary to Age-related Macular Degeneration (AMD). The study population includes both male and female subjects aged **60 years or older**. Participants were selected based on specific criteria, including the presence of non-subfoveal GA with measurable lesion areas ranging from 2.5 mm² to 17.5 mm². The trial population encompasses individuals from a vulnerable population, indicating additional ethical considerations in the study design. Participants' general health status is not specified, but the inclusion criteria necessitate a negative pregnancy test for women of childbearing potential. Lifestyle factors such as diet, physical activity, or habits are not detailed in the available data. The selection process ensures that participants are capable of understanding the study's purpose and procedures, as evidenced by the requirement to sign an informed consent form.

The clinical trial is a **randomized**, double-masked, multicenter, dose-ranging, sham-controlled study designed to evaluate the efficacy of intravitreal JNJ-81201887 compared to a sham procedure for the treatment of **geographic atrophy** secondary to age-related macular degeneration. The primary objective is to assess the change in GA lesion growth in eyes treated with JNJ-81201887 compared to the sham control. The trial is expected to commence recruitment in May 2023 and conclude by July 2025, with an estimated duration of participant involvement spanning approximately two years.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (60 years or older) and specific characteristics of GA lesions. The study will include multiple follow-up visits to monitor the progression of the condition and the effects of the treatment. The end-of-study visit will conclude the participant's involvement, during which final assessments will be conducted to evaluate the primary endpoint, which is the change in the square root of the GA lesion area measured on fundus autofluorescence.

The trial will involve the administration of JNJ-81201887 via **intravitreal use** and will include a placebo group receiving a sham procedure. The study is designed to ensure that neither the participants nor the investigators are aware of the treatment assignments, maintaining the double-masked nature of the trial. Participants may be withdrawn from the study early if they experience adverse effects or if they no longer meet the inclusion criteria. The trial will adhere to rigorous scientific and ethical standards to ensure the validity and reliability of the results.

The clinical trial involves the administration of several treatments, including experimental and non-experimental medications. The experimental medication **JNJ-81201887** is a **solution for injection** containing the active substance **adeno-associated virus serotype 2 encoding soluble CD59**. This gene therapy product is administered via **intravitreal use**. The dosing schedule allows for a maximum treatment period of one day, with no specified daily or total dose amount, as it is a single administration. The product is developed by Janssen-Cilag International N.V. and is not a paediatric formulation.

Another experimental treatment in the trial is **Prednison acis**, available in **tablet** form with two dosage strengths: **5 mg** and **20 mg**. The active substance is **prednisone**, a chemical compound, and the tablets are administered **orally**. The maximum daily and total dose for both strengths is **40 mg**, with a treatment period extending up to 20 days. The tablets are manufactured by ACIS Arzneimittel GmbH and have undergone over-encapsulation for the trial.

The trial also includes a **placebo** designed to match the **Prednisone 20 mg and 5 mg** tablets. The placebo is used to maintain the double-masked nature of the study, ensuring that neither the participants nor the investigators know who receives the active treatment or the placebo. The placebo does not contain any active substance and is not associated with a specific pharmaceutical form or route of administration.

Additionally, the trial utilizes **Kenacort-A 40**, a **suspension for injection** containing **triamcinolone acetonide** as the active substance. This chemical compound is administered via **ocular use**. The maximum daily and total dose is **40 mg**, with a treatment period limited to one day. The product is manufactured by Bristol-Myers Squibb B.V. and is not a paediatric formulation.

Participant compliance with the dosing schedule and administration routes is monitored throughout the trial to ensure adherence to the protocol. The trial aims to evaluate the efficacy of JNJ-81201887 in reducing the growth of geographic atrophy lesions in patients with age-related macular degeneration, compared to a sham procedure.

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint, which is the change in the square root of the **geographic atrophy (GA)** lesion area in the study eye. This measurement will be conducted using fundus autofluorescence (FAF) imaging. The trial aims to compare the efficacy of intravitreal JNJ-81201887 (AAVCAGsCD59) against a sham procedure for the treatment of GA secondary to age-related macular degeneration (AMD). The primary endpoint will be measured at specified intervals throughout the study to monitor changes in the GA lesion area. The trial is designed as a Phase 2b, randomized, double-masked, multicenter, dose-ranging, sham-controlled study, ensuring rigorous assessment of the treatment's efficacy. The study will follow a structured schedule for collecting and analyzing the efficacy data, although specific timepoints for these assessments are not detailed in the provided information.