Randomised, double-blind, placebo-controlled, Phase IIb/Phase III study to evaluate the efficacy and safety of spesolimab in patients with moderate to severe hidradenitis suppurativa. Lunsayil 1.

The primary objective of this randomized, double-blind, placebo-controlled Phase IIb/Phase III study is to evaluate the **efficacy** and **safety** of spesolimab in patients with moderate to severe **hidradenitis suppurativa**. The study is divided into two parts: the dose-finding Phase IIb (Part 1), which aims to determine the optimal dose of spesolimab for further development in Phase III, and the confirmatory Phase III (Part 2), which is designed to assess the therapeutic efficacy and safety profile of spesolimab in the target patient population. This study is clinically relevant as it seeks to address the unmet medical need for effective treatment options in patients suffering from this chronic and debilitating skin condition.

The clinical trial involves a total of **104 participants** diagnosed with **hidradenitis suppurativa**, a chronic skin condition. The study population includes both male and female subjects, with an age range that encompasses adults of full age of consent. Participants were selected based on specific criteria, including having moderate to severe hidradenitis suppurativa with lesions in at least two distinct anatomic areas. The trial includes individuals who are either biologic naive or have been exposed to TNF inhibitors for hidradenitis suppurativa, with all participants having prior exposure to antibiotics for the condition. The study does not specify particular lifestyle considerations such as diet or physical activity. The trial population includes a vulnerable population, indicating careful consideration of ethical standards in participant selection.

The clinical trial is a **randomized**, **double-blind**, **placebo-controlled** study designed to evaluate the efficacy and safety of **spesolimab** in patients with moderate to severe **hidradenitis suppurativa**. The trial is structured in two parts: a dose-finding Phase IIb and a confirmatory Phase III. The primary objective is to determine the optimal dose and assess the efficacy and safety of spesolimab. The trial is expected to run from May 2023 to September 2028, with participant involvement lasting up to 48 weeks, depending on the treatment group assignment.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, disease severity, and previous treatment history. Following randomization, participants will receive either spesolimab or placebo, administered as a **solution for infusion** or **solution for injection in pre-filled syringe**. The study includes regular follow-up visits to monitor safety, efficacy, and any adverse events. The primary endpoint is the percent change from baseline in the dT count, with additional secondary endpoints evaluated throughout the study.

The end-of-study visit will occur after the final treatment period, where comprehensive assessments will be conducted to evaluate the long-term effects of the treatment. Participants may be withdrawn from the study early if they experience significant adverse effects, fail to comply with study procedures, or if the investigator deems it necessary for their safety. The trial is conducted in accordance with ICH-GCP guidelines and local legislation, ensuring the ethical treatment of all participants.

The clinical trial involves the administration of **spesolimab**, a biologic agent, in two pharmaceutical forms. The first form is a **solution for infusion**, with a maximum daily dose of 1800 mg and a total maximum dose of 7200 mg over a treatment period of up to 4 weeks. The infusion is administered intravenously, and the product is identified by the sponsor product code BI 655130. The active substance, spesolimab, is a protein of biological origin, specifically a humanized monoclonal antibody targeting IL1RL2. The manufacturer, Boehringer Ingelheim International, ensures the product's compliance with regulatory standards.

The second form of spesolimab is a **solution for injection in a pre-filled syringe**, with a maximum daily dose of 1200 mg and a total maximum dose of 30000 mg over a treatment period of up to 48 weeks. This form is administered subcutaneously. The product is also identified by the sponsor product code BI 655130 and shares the same active substance characteristics as the infusion form. The pre-filled syringe format is designed to facilitate ease of administration and ensure accurate dosing.

In addition to the experimental treatments, the study includes a **placebo** control group. The placebo is provided in two forms: a solution for injection and a solution for infusion, both designed to match the respective spesolimab formulations. The placebo is used to maintain the double-blind nature of the trial, ensuring unbiased assessment of spesolimab's efficacy and safety. The placebo does not contain any active substance and is administered following the same schedule and route as the corresponding spesolimab form.

Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol. This includes regular assessments and documentation of administration times and doses. The trial is structured to evaluate the optimal dosing regimen and confirm the therapeutic potential of spesolimab in patients with moderate to severe hidradenitis suppurativa.

The efficacy of spesolimab in patients with moderate to severe **hidradenitis suppurativa** will be assessed in a randomized, double-blind, placebo-controlled Phase IIb/Phase III clinical trial. The primary endpoint for evaluating efficacy is the percent change from baseline in the dT count. This endpoint will be measured at specified timepoints throughout the trial to determine the therapeutic effect of spesolimab compared to placebo. The trial is structured in two parts: a dose-finding Phase IIb to identify the optimal dose, followed by a confirmatory Phase III to further assess efficacy and safety. The trial will involve patients who are either biologic naive or have been exposed to TNFi for hidradenitis suppurativa, with all participants having a history of antibiotic treatment for the condition. The study aims to provide comprehensive data on the efficacy of spesolimab, contributing to its potential development as a treatment option for this patient population.