Phase 3 Evaluation of Remibrutinib Efficacy and Safety in Adults with Moderate to Severe Hidradenitis Suppurativa

The primary objective of this study is to demonstrate the **efficacy** of remibrutinib compared to placebo in achieving a HiSCR50 response after 16 weeks of treatment in patients with moderate to severe **hidradenitis suppurativa**. This is clinically relevant as achieving a HiSCR50 response indicates a significant reduction in inflammatory lesions, which is a critical measure of treatment success in this chronic and painful skin condition.

Secondary objectives include:

• Demonstrating the efficacy of remibrutinib compared to placebo after 16 weeks of treatment with respect to the proportion of participants with AN50 response, percentage change from baseline in IHS4, proportion of participants with HiSCR75, HiSCR90, and HiSCR50 response at Week 8, proportion of participants experiencing HS flares, and clinical response in HS-related skin pain (NRS 30) at worst.
• Demonstrating the safety and tolerability of remibrutinib.

The clinical trial involves a total of **282 participants** diagnosed with **Hidradenitis Suppurativa (HS)**. The study population includes both male and female subjects who are 18 years of age or older. Participants were selected based on a confirmed diagnosis of HS, characterized by moderate to severe symptoms, including at least five abscesses and/or inflammatory nodules affecting at least two distinct anatomical areas. The trial does not include a vulnerable population. Participants' general health status is not specified beyond the inclusion criteria related to HS. Lifestyle considerations such as diet, physical activity, or habits are not detailed in the available data. The selection criteria ensure that participants have a clinical history and physical examination confirming HS for at least six months prior to the baseline visit.

The clinical trial is a **randomized, double-blind, double-dummy, placebo-controlled, multicenter, Phase 3 study** designed to assess the efficacy, safety, and tolerability of two doses of **remibrutinib** over a 68-week treatment period in adult patients with moderate to severe **hidradenitis suppurativa**. The primary objective is to demonstrate the efficacy of remibrutinib compared to placebo with respect to HiSCR50 after 16 weeks of treatment. The trial will include a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis, and severity of the condition. Participants must have a clinical history and physical examination confirming hidradenitis suppurativa for at least six months prior to the baseline visit.

Following the screening, participants will be randomized to receive either remibrutinib or placebo. The trial will include multiple follow-up visits to monitor the participants' response to treatment and any adverse events. The primary endpoint is the achievement of HiSCR50 at Week 16, defined as at least a 50% decrease in abscess and inflammatory nodule count with no increase in the number of abscesses and draining tunnels/fistulae compared to baseline. Secondary endpoints include the achievement of AN50, HiSCR75, and HiSCR90 at Week 16, as well as the occurrence of treatment-emergent adverse events.

The expected length of participant involvement is up to 68 weeks, with conditions for early termination including withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The trial is estimated to start recruitment on June 5, 2025, and is expected to conclude by November 24, 2028. Participants will be closely monitored throughout the study to ensure adherence to the protocol and to evaluate the long-term effects of the treatment.

The clinical trial involves the administration of several treatments, including **remibrutinib**, **clindamycin hydrochloride**, and a combination of **triamcinolone acetonide** and **salicylic acid**. The primary experimental medication, remibrutinib, is provided in the form of a film-coated tablet. It is a low molecular weight compound that covalently binds and inhibits Bruton’s tyrosine kinase. The administration route is oral, and the treatment period extends up to 68 weeks. The dosage is specified in milligrams, although the exact daily and total dose amounts are not provided. Participant compliance is monitored throughout the study to ensure adherence to the dosing schedule.

Clindamycin hydrochloride is used as an auxiliary treatment in the trial. It is administered orally in a pharmaceutical form denoted as PHF00006MIG. Clindamycin is a systemic antibiotic, and its role in the trial is supportive, complementing the primary treatment. The maximum treatment period is also 68 weeks, with compliance monitoring in place to ensure proper administration.

The trial also includes the use of triamcinolone acetonide combined with salicylic acid, administered via intralesional use. This combination is intended to provide injectable anti-inflammatory effects by influencing multiple signal transduction pathways. The pharmaceutical form is identified as PHF00024MIG, and the treatment duration is consistent with the other medications at 68 weeks. Compliance monitoring is similarly applied to this treatment to maintain the integrity of the trial results.

Additionally, a placebo is utilized in the study, specifically designed to match the remibrutinib film-coated tablet. The placebo serves as a control to assess the efficacy of remibrutinib. It is administered orally, and the treatment period aligns with the other study medications. Compliance with placebo administration is monitored to ensure the validity of the trial outcomes.

The efficacy of the investigational product, **remibrutinib**, will be assessed in a randomized, double-blind, double-dummy, placebo-controlled, multicenter Phase 3 clinical trial. The primary endpoint for evaluating efficacy is the achievement of HiSCR50 at Week 16. HiSCR50 is defined as at least a 50% decrease in Abscess and Inflammatory Nodule (AN) count with no increase in the number of abscesses and in the number of draining tunnels/fistulae compared to baseline.

Secondary endpoints include the achievement of AN50 at Week 16, which is defined as at least a 50% decrease in AN count compared to baseline, and the percentage change from baseline in IHS4 at Week 16. Additional secondary endpoints are the achievement of HiSCR75 and HiSCR90 at Week 16, defined as at least a 75% and 90% decrease in AN count, respectively, with no increase in the number of abscesses and draining tunnels/fistulae compared to baseline. The occurrence of flaring up to Week 16, defined as at least a 25% increase in AN count with a minimum increase of 2 AN relative to baseline, will also be assessed. Furthermore, the achievement of HiSCR50 at Week 8 and NRS30 at Week 16, among participants with baseline NRS ≥ 3, will be evaluated. NRS30 is defined as at least a 30% reduction and at least a 2-unit reduction from baseline in Patient's Global Assessment of Skin Pain - at worst over the past 7 days.

The efficacy parameters will be measured and collected at specified timepoints, including Week 8 and Week 16, using validated scales and patient-reported outcomes. The analysis will focus on comparing the efficacy of remibrutinib to placebo in achieving these endpoints, thereby demonstrating its potential benefit in treating moderate to severe hidradenitis suppurativa over a 68-week treatment period.