Phase 3 Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Remibrutinib in Adults with Moderate to Severe Hidradenitis Suppurativa

The primary objective of this Phase 3 study is to demonstrate the **efficacy** of remibrutinib compared to placebo in achieving HiSCR50 response after 16 weeks of treatment in adult patients with moderate to severe **hidradenitis suppurativa**. This is clinically relevant as achieving HiSCR50 indicates a significant reduction in inflammatory nodules and abscesses, which are key symptoms of the disease, thereby improving patient outcomes.

Secondary objectives include:

• Demonstrating the efficacy of remibrutinib compared to placebo after 16 weeks 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 for **Hidradenitis Suppurativa (HS)** involves a total of 282 participants. 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 moderate to severe HS, characterized by 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 and lifestyle considerations such as diet and physical activity are not specified. The selection criteria required participants to have a clinical history and physical examination confirming HS for at least six months prior to the baseline visit. The sponsor has not provided additional information regarding specific lifestyle factors or other health conditions of the participants.

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 diagnosis of hidradenitis suppurativa for at least six months prior to the baseline visit and present with moderate to severe symptoms.

Following the screening, participants will be randomized to receive either remibrutinib or placebo, with the treatment administered orally in the form of film-coated tablets. The trial will involve multiple follow-up visits to monitor the participants' response to treatment, assess safety, and record 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 compared to baseline. Secondary endpoints include AN50, percentage change in IHS4, and HiSCR75, among others, all evaluated at Week 16.

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 in June 2025 and conclude by January 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 study aims to provide comprehensive data on the potential benefits and risks associated with remibrutinib in treating moderate to severe hidradenitis suppurativa.

The clinical trial involves the administration of **Remibrutinib**, a low molecular weight compound that covalently binds and inhibits Bruton’s tyrosine kinase. This investigational drug is provided in the form of a film-coated tablet, identified by the sponsor product code LOU064. The administration route is oral, with a maximum daily dose of 00 mg, and the treatment period extends up to 68 weeks. The trial aims to assess the efficacy, safety, and tolerability of two doses of Remibrutinib in adult patients with moderate to severe hidradenitis suppurativa.

A placebo matching the Remibrutinib film-coated tablet is also utilized in the study. This placebo is designed to mimic the appearance and administration route of the active treatment, ensuring the double-blind nature of the trial. The placebo is administered orally, with no active pharmaceutical ingredients, and serves as a control to evaluate the true efficacy of Remibrutinib.

Additionally, the trial includes the use of **Triamcinolone Acetonide** and **Salicylic Acid** as auxiliary treatments. These substances are administered via intralesional use, providing injectable anti-inflammatory effects by influencing multiple signal transduction pathways. The pharmaceutical form is identified as PHF00024MIG, and the treatment period is consistent with the main investigational product, extending up to 68 weeks.

Systemic antibiotics, including **Clindamycin Hydrochloride**, are also part of the auxiliary treatments. Clindamycin is administered orally, with the pharmaceutical form identified as PHF00006MIG. The use of systemic antibiotics is intended to manage any potential bacterial infections associated with hidradenitis suppurativa, complementing the primary investigational treatment.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol. The study design incorporates rigorous measures to maintain the integrity of the double-blind, placebo-controlled methodology, thereby providing reliable data on the efficacy and safety of Remibrutinib in the target patient population.

The efficacy of the clinical trial will be assessed by evaluating the primary and secondary endpoints related to the treatment of moderate to severe **hidradenitis suppurativa**. The primary endpoint is the achievement of HiSCR50 at Week 16, which 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, percentage change from baseline in IHS4 at Week 16, and the achievement of HiSCR75 and HiSCR90 at Week 16. Additional secondary endpoints involve the assessment 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, and the achievement of NRS30 at Week 16 among participants with baseline NRS ≥ 3. The occurrence of treatment-emergent adverse events and serious adverse events during the study will also be monitored.