Phase 3 Randomized, Double-Masked, Placebo-Controlled Trial of Brepocitinib Tosilate in Adults with Active Non-Infectious Intermediate, Posterior, and Panuveitis

The primary objective of this Phase 3 randomized, double-masked, placebo-controlled study is to evaluate the **efficacy** of brepocitinib in adults with active, non-infectious intermediate uveitis, posterior uveitis, and panuveitis. This is clinically relevant as these forms of uveitis can lead to significant visual impairment and are challenging to manage with existing therapies. The study aims to determine whether brepocitinib can provide a therapeutic benefit in reducing inflammation and preserving vision in affected individuals.

Secondary objectives include further evaluation of the efficacy of brepocitinib in participants with non-infectious intermediate uveitis, posterior uveitis, and panuveitis. This will help to better understand the potential of brepocitinib as a treatment option for these conditions, providing additional insights into its therapeutic profile and impact on disease progression.

The clinical trial involves a total of **45 participants** diagnosed with **active non-infectious uveitis**, specifically intermediate uveitis, posterior uveitis, or panuveitis. The study population comprises adult subjects aged between **18 to 75 years**, including both male and female participants. All participants are required to have active uveitic disease in at least one eye and must weigh more than 40 kg with a body mass index of 40 kg/m² or less. The trial does not include a vulnerable population. Participants were selected based on their diagnosis and health status, ensuring they meet the specified inclusion criteria. Lifestyle factors such as diet and physical activity were not specified as part of the selection criteria.

The clinical trial is designed to evaluate the efficacy and safety of **brepocitinib** in adults with active non-infectious uveitis, specifically intermediate uveitis, posterior uveitis, and panuveitis. This is a Phase 3, randomized, double-masked, placebo-controlled study. The trial will involve the administration of brepocitinib tablets, with a placebo group for comparison. The study is expected to commence recruitment in February 2025 and conclude by February 2028, with a total duration of approximately three years.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (18-75 years), diagnosis of non-infectious uveitis, active uveitic disease in at least one eye, and a body weight over 40 kg with a body mass index of 40 kg/m² or less. Following successful screening, participants will be randomized to receive either brepocitinib or a placebo. The primary endpoint is the time to treatment failure from Week 6 to Week 48, with secondary endpoints including changes in visual acuity and central subfield thickness from baseline to Weeks 24 and 48.

Study visits will include regular follow-up assessments to monitor efficacy and safety, with specific evaluations at key intervals such as Weeks 6, 24, and 48. The end-of-study visit will occur at the conclusion of the treatment period, or earlier if a participant meets criteria for treatment failure or experiences adverse events necessitating withdrawal. The expected length of participant involvement is up to 96 weeks, with conditions for early termination including significant adverse reactions or non-compliance with study protocols.

The clinical trial involves the administration of several treatments, including the experimental medication **brepocitinib**. Brepocitinib is provided in tablet form and is chemically known as brepocitinib tosilate. The maximum daily dose is 45 mg, with a total maximum dose of 30,240 mg over a treatment period of 96 weeks. The route of administration is oral, and the medication is produced by Priovant Therapeutics, Inc. Participant compliance with the dosing schedule will be monitored throughout the trial.

In addition to brepocitinib, the trial includes the use of **Prednison** tablets as auxiliary treatments. Prednison is available in three different dosages: 5 mg, 10 mg, and 20 mg, all manufactured by Galenpharma GmbH. These tablets are also administered orally, with a maximum daily dose of 60 mg and a total maximum dose of 40,320 mg over the same 96-week period. Prednison is classified under glucocorticoids and is used to support the primary treatment.

A placebo tablet is also utilized in the study to match the 45 mg brepocitinib tablet. The placebo is designed to mimic the appearance of the brepocitinib tablet to maintain the double-masked nature of the trial. The placebo does not contain any active substances and serves as a control to evaluate the efficacy of the experimental treatment.

The efficacy of oral **brepocitinib** in adults with active, non-infectious intermediate uveitis, posterior uveitis, and panuveitis will be assessed through a series of primary and secondary endpoints. The primary endpoint is the time to treatment failure, measured from Period 1 Week 6 up to Period 1 Week 48. Secondary endpoints include the proportion of participants meeting treatment failure criteria from Period 1 Week 6 to Period 1 Week 24, changes in the logarithm of the minimum angle of resolution (logMAR) best corrected visual acuity (BCVA) in each eye from the best state achieved at or prior to Period 1 Week 6 up to Period 1 Week 24 and Week 48, and changes in central subfield thickness from the best state achieved in each eye at or prior to Period 1 Week 6 up to Period 1 Week 24 and Week 48.

These efficacy parameters will be collected and analyzed at specified timepoints throughout the trial duration. The assessments will utilize validated scales and measurements to ensure accuracy and reliability. The trial is designed as a Phase 3 randomized, double-masked, placebo-controlled study, with the primary objective of evaluating the efficacy of **brepocitinib** in the specified patient population. The study is expected to conclude by February 2028, with recruitment starting in February 2025.