A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Oral Brepocitinib in Adults with Dermatomyositis

The primary objective of this study is to evaluate the efficacy of **brepocitinib** for the treatment of **dermatomyositis** based on the Total Improvement Score (TIS) after 52 weeks of administration once daily (QD), in comparison to placebo. This objective is clinically relevant as it aims to determine the potential of brepocitinib to improve overall disease activity in patients with dermatomyositis, a condition characterized by muscle weakness and skin rash, which can significantly impact quality of life.

Secondary objectives include:

• Evaluating the efficacy of brepocitinib based on the TIS responder rate after 52 weeks, compared to placebo.
• Assessing the efficacy based on the Health Assessment Questionnaire Disability Index (HAQ-DI) after 52 weeks, compared to placebo.
• Evaluating the efficacy based on the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) Activity Score after 52 weeks, compared to placebo.
• In participants taking oral corticosteroids at baseline, evaluating the change in oral corticosteroid dose.

These secondary objectives are important for understanding the broader impact of brepocitinib on functional ability, skin disease severity, and potential steroid-sparing effects in patients with dermatomyositis.

The clinical trial involves a total of **109 participants** diagnosed with **dermatomyositis**, a condition characterized by inflammation of the skin and muscles. The study population includes both male and female subjects, aged between 18 and 75 years. Participants were selected based on their diagnosis according to the 2017 EULAR/ACR Classification Criteria for Idiopathic Inflammatory Myopathies, with active muscle and skin disease at screening and baseline. The trial includes individuals who are currently or have previously been treated with corticosteroids, hydroxychloroquine, and/or one non-steroid immunosuppressant. Participants' weight ranges from over 40 kg to under 130 kg, with a body mass index (BMI) of less than 40 kg/m². The study population is not limited by gender, and both male and female subjects are included. The trial also considers vulnerable populations, ensuring a comprehensive evaluation of the treatment's efficacy across diverse demographic groups.

The clinical trial is a **Phase 3**, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of **Brepocitinib** in adults diagnosed with **dermatomyositis**. The trial aims to assess the efficacy of Brepocitinib based on the Total Improvement Score (TIS) after 52 weeks of administration, compared to a placebo. Participants will be randomly assigned to receive either Brepocitinib or a placebo, with the study drug administered orally in tablet form. The trial is expected to last until December 31, 2025, with recruitment having commenced on November 1, 2022.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis, and current or past therapy. The inclusion criteria specify that participants must be between 18 and 75 years of age, have active muscle and skin disease, and meet specific weight and body mass index requirements. Following the screening, participants will attend regular follow-up visits to monitor their response to the treatment and any adverse effects. The primary endpoint is the TIS at Week 52, while secondary endpoints include the proportion of responders achieving a TIS of at least 40 points, changes in the HAQ Disability Index score, and changes in the CDASI Activity Score.

The expected length of participant involvement is approximately 52 weeks, with conditions for early termination including significant adverse events or withdrawal of consent. The study will conclude with an end-of-study visit to assess the final outcomes and gather data for analysis. The trial is not classified as low intervention, and the investigational product, Brepocitinib, is a potent tyrosine kinase TYK2/JAK1 inhibitor, highly selective over other human kinases. Participants will be closely monitored throughout the trial to ensure safety and adherence to the study protocol.

The clinical trial involves the administration of **Brepocitinib**, a potent tyrosine kinase TYK2/JAK1 inhibitor, which is highly selective over other human kinases. The experimental medication is provided in the form of a **tablet** and is intended for **oral use**. The active substance in Brepocitinib is **brepocitinib tosilate**, a chemical compound. The maximum daily dose of Brepocitinib is 30 mg, with a total maximum dose of 3120 mg over a treatment period of 114 days. The medication is administered once daily (QD) to evaluate its efficacy in treating dermatomyositis.

In addition to the experimental medication, the study includes a **placebo** group to serve as a comparator. The placebo is designed to match the Brepocitinib 25 mg and 5 mg tablets in appearance but does not contain any active substance. The placebo is administered under the same conditions as the active treatment to maintain the double-blind nature of the study. The use of a placebo allows for the assessment of Brepocitinib's efficacy by comparing outcomes between the active treatment and placebo groups.

The efficacy of Brepocitinib in the treatment of **dermatomyositis** will be assessed in a Phase 3, randomized, double-blind, placebo-controlled clinical trial. The primary endpoint for evaluating efficacy is the Total Improvement Score (TIS) at Week 52. TIS is a composite endpoint based on the 6 Disease Activity Core Set Measure (CSM) scores, ranging from 0 to 100, as per the 2016 EULAR/ACR Myositis Response Criteria. Secondary endpoints include the proportion of responders achieving a TIS of ≥ 40 points, indicating moderate improvement at Week 52, change from baseline in the HAQ Disability Index score at Week 52, change from baseline in the CDASI Activity Score at Week 52, and among participants taking oral corticosteroids at baseline, the average daily prednisone-equivalent dose from Week 36 to Week 52 minus baseline.