Evaluation of Spesolimab Efficacy and Safety in Adult Patients with Ulcerative Pyoderma Gangrenosum: A Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this clinical trial is to evaluate the **superiority** of spesolimab over placebo in achieving complete closure of the target ulcer in patients with **pyoderma gangrenosum**. This is measured by a 100% reduction in the pyoderma gangrenosum area (PGAR-100) at any time up to Week 26. The clinical relevance of this objective lies in its potential to provide a more effective treatment option for patients suffering from this debilitating skin condition, which currently lacks sufficient therapeutic interventions.

Secondary objectives aim to demonstrate the superiority of spesolimab against placebo for the key secondary endpoints. These objectives are crucial for further understanding the broader efficacy and safety profile of spesolimab, thereby supporting its potential use as a systemic therapy for pyoderma gangrenosum.

The clinical trial involves a total of **59 participants** diagnosed with **pyoderma gangrenosum**, a rare and painful skin condition. The study population includes both male and female adults aged 18 years and older, as per the local legislation for age of consent. Participants were selected based on a confirmed diagnosis of ulcerative pyoderma gangrenosum, requiring systemic therapy, with at least one measurable ulcer. The trial does not include a vulnerable population. Participants' general health status is not specified, but they must have a target ulcer diagnosed within the last six months, or longer if active and progressing. Lifestyle considerations such as diet, physical activity, or habits are not detailed in the available data. Key inclusion criteria include the ability to provide informed consent and, for women of childbearing potential, the use of highly effective birth control methods. The selection process ensures that participants meet specific clinical criteria to evaluate the efficacy of spesolimab compared to placebo in achieving complete closure of the target ulcer.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled**, parallel-group study to evaluate the safety and efficacy of **spesolimab** in adult patients with **pyoderma gangrenosum** requiring systemic therapy. The trial aims to demonstrate the superiority of spesolimab over placebo by assessing the complete closure of the target ulcer, defined as 100% pyoderma gangrenosum area reduction (PGAR-100), at any time up to Week 26. The trial is expected to commence recruitment on January 17, 2025, and conclude by June 15, 2027, with a maximum treatment period of 52 weeks.

Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on criteria such as age, diagnosis, and ulcer characteristics. The inclusion criteria require participants to be adults aged 18 years or older, with a confirmed diagnosis of ulcerative pyoderma gangrenosum and at least one measurable ulcer. The screening visit will also ensure that the target ulcer has been diagnosed within the last six months, unless it is active and progressing. Women of childbearing potential must adhere to effective birth control methods throughout the study.

Following the screening, participants will be randomized to receive either spesolimab or a placebo, administered as a **solution for infusion** via **intravenous use**. The trial includes multiple follow-up visits to monitor the participants' response to treatment, with primary and secondary endpoints assessed at various intervals. The primary endpoint is the achievement of PGAR-100 of the target ulcer, confirmed at a subsequent visit at least two weeks later. Secondary endpoints include the reduction in pain scores and the time to recurrence of ulcers among those achieving complete response by Week 26.

The expected duration of participant involvement is up to 52 weeks, with conditions for early termination including withdrawal of consent, adverse events, or non-compliance with the study protocol. The trial is conducted in accordance with International Council on Harmonisation-Good Clinical Practice (ICH-GCP) guidelines, ensuring ethical and scientific integrity throughout the study process.

The clinical trial involves the administration of **spesolimab**, an experimental medication, to evaluate its safety and efficacy in adult patients with ulcerative **pyoderma gangrenosum**. Spesolimab, identified by the sponsor product code BI 655130, is provided in the pharmaceutical form of a **solution for infusion**. The active substance, spesolimab, is a protein of other origin, developed by Boehringer Ingelheim International. The medication is administered via the **intravenous route**. The dosing schedule is designed to ensure participant safety and compliance, with a maximum treatment period of 52 weeks. The specific dosage and frequency of administration are determined based on the trial protocol, with careful monitoring of participant compliance throughout the study.

In addition to spesolimab, a **placebo** is used as a comparator treatment in this double-blind, placebo-controlled trial. The placebo is designed to match the spesolimab solution for infusion in appearance but does not contain any active substance. The use of a placebo allows for the assessment of spesolimab's efficacy by comparing outcomes between the treatment and control groups. The placebo is administered following the same route and schedule as the experimental medication to maintain the study's blinding and integrity.

The efficacy of spesolimab in the treatment of **ulcerative pyoderma gangrenosum** will be assessed through a multi-centre, randomised, placebo-controlled, double-blind, parallel-group clinical trial. The primary endpoint for evaluating efficacy is the achievement of complete closure, defined as 100% pyoderma gangrenosum area reduction (PGAR-100), of the target ulcer at any time up to Week 26, confirmed at the next consecutive visit at least two weeks later. Secondary endpoints include the achievement of PGAR-100 of the target ulcer specifically at Week 26, PGAR-100 of any measurable ulcer (≥5 cm² at baseline) at any time up to Week 26, and PGAR-100 of all measurable ulcers at any time up to Week 26, each confirmed at the next consecutive visit. Additionally, a reduction of ≥3 points in the Numeric Rating Scale (NRS) Pain score from baseline at Week 4 will be evaluated, as well as the time to recurrence among participants who achieved complete response at Week 26, monitored up to Week 52.