Evaluation of Tinlarebant Efficacy and Safety in Adolescents with Stargardt Disease: A Phase 3 Randomized, Double-Masked, Placebo-Controlled Trial

The primary objective of this Phase 3, multicenter, randomized, double-masked, placebo-controlled study is to assess the **efficacy** of Tinlarebant in slowing the rate of growth of atrophic lesions in adolescent subjects with Stargardt Disease (STGD1). This is clinically relevant as it aims to address the progression of retinal degeneration, which is a hallmark of STGD1, potentially preserving vision in affected individuals.

Secondary objectives include: - Assessing the efficacy of Tinlarebant based on changes in the area of decreased autofluorescence, best-corrected visual acuity (BCVA), and photoreceptor morphology. - Evaluating the pharmacodynamics of Tinlarebant in adolescent STGD1 subjects. - Assessing systemic and ocular safety and tolerability of Tinlarebant. These objectives are crucial for understanding the broader impact of Tinlarebant on visual function and safety in this patient population.

The clinical trial involves a total of **96 participants** diagnosed with **Stargardt Disease**. The study population comprises both male and female subjects aged between **12 to 20 years**. Participants were selected based on their clinical diagnosis of Stargardt Disease, with at least one mutation identified in the ABCA4 gene. The trial includes individuals with an aggregate atrophic lesion size within 3 disc areas (7.62 mm²) in the study eye, and a best-corrected visual acuity (BCVA) of 20/200 or better. The trial population is characterized by a vulnerable group, given the age range and specific health condition. Participants' general health status is not specified beyond the inclusion criteria related to their ocular condition. Lifestyle considerations such as diet, physical activity, or habits are not detailed in the available data. The selection process ensures that participants and their guardians provide informed consent as per ethical guidelines.

This clinical trial is a **Phase 3**, multicenter, randomized, double-masked, placebo-controlled study designed to evaluate the safety and efficacy of **Tinlarebant** in the treatment of **Stargardt Disease** in adolescent subjects. The trial aims to assess the efficacy of Tinlarebant in slowing the rate of growth of atrophic lesions in subjects with Stargardt Disease, specifically those with an aggregate definitely decreased autofluorescence (DDAF) lesion size of ≤1.90 mm² at baseline. The study will also evaluate the overall efficacy in the adolescent population. The trial is expected to last approximately 28 months, with an estimated recruitment start date of May 30, 2022, and an estimated end date of September 19, 2025.

Participants will be randomly assigned to receive either Tinlarebant or a matching placebo, administered orally in tablet form. The study will include several key visits: an initial screening visit to determine eligibility, regular follow-up visits to monitor safety and efficacy, and an end-of-study visit to assess the final outcomes. The primary efficacy endpoint is the difference in the size of the aggregate area of atrophy at Month 25 compared to baseline, within the subgroup of subjects with a baseline lesion size of ≤1.90 mm². Secondary endpoints include the difference in the size of the total area of decreased autofluorescence at Month 25 compared to baseline.

Participants are expected to be involved in the study for the entire duration unless specific conditions necessitate early termination. These conditions may include adverse events, withdrawal of consent, or any other reason deemed appropriate by the investigator. The study is designed to ensure rigorous scientific evaluation while maintaining the safety and well-being of the participants throughout the trial period.

The clinical trial involves the administration of **Tinlarebant**, an experimental medication, to evaluate its safety and efficacy in the treatment of Stargardt Disease in adolescent subjects. The investigational product, known as LBS-008, is formulated as a **tablet** and contains the active substance **Tinlarebant**. The medication is administered orally, with a maximum daily dose of 5 mg. The treatment period extends up to 24 months. The formulation is specifically designed for pediatric use, and the trial aims to assess the efficacy of Tinlarebant in slowing the rate of growth of atrophic lesions in subjects with Stargardt Disease.

In addition to the experimental treatment, the study includes a **placebo** group to serve as a comparator. The placebo is designed to match the appearance of the Tinlarebant 5 mg tablets, ensuring the double-masked nature of the trial. The placebo is administered orally, following the same dosing schedule as the active treatment group. This allows for a controlled comparison to evaluate the true efficacy of Tinlarebant in the study population.

The efficacy of Tinlarebant in the treatment of **Stargardt Disease** will be assessed through a Phase 3, multicenter, randomized, double-masked, placebo-controlled study. The primary efficacy endpoints include the difference in the size of the aggregate area of atrophy, specifically the definitely decreased autofluorescence (DDAF), at Month 25 compared to Baseline. This will be evaluated within a subgroup of subjects with a baseline DDAF lesion size of ≤1.90 mm², as well as in the overall population, contingent upon demonstrating treatment efficacy in the specified subgroup. The assessment will be conducted using fundus autofluorescence (FAF) photography.

Secondary efficacy endpoints will include the difference in the total area of decreased autofluorescence (DAF), which is the sum of DDAF and questionably decreased autofluorescence (QDAF), at Month 25 compared to Baseline. These measurements will also be obtained through FAF photography. The study will involve adolescent subjects with clinically diagnosed Stargardt Disease, and the efficacy assessments will be conducted at specified timepoints, with the primary endpoint evaluated at Month 25.