Effisayil® REP: An open-label, multicenter, single-arm, post-marketing trial (in select countries) to evaluate efficacy and safety and the impact of immunogenicity on efficacy, safety, and pharmacokinetics of spesolimab i.v. in treatment of patients with Generalized Pustular Psoriasis (GPP) presenting with a recurrent flare following their initial GPP flare treatment with spesolimab i.v.

The primary objective of this study is to evaluate the **response** to recurrent flare treatment with spesolimab administered intravenously in patients with **Generalized Pustular Psoriasis** (GPP) who have previously received treatment for an initial flare with the same medication. This objective is clinically relevant as it aims to assess the efficacy of spesolimab in managing subsequent flares, which is crucial for improving long-term disease management and patient outcomes in GPP.

The clinical trial involves a total of **33 participants** diagnosed with **Generalized Pustular Psoriasis** (GPP). The study population includes both male and female subjects aged 18 years and older, as per local legislation for age of consent. Participants were selected based on a documented history of GPP, with a focus on those experiencing frequent flares. The trial includes individuals who are not on concomitant GPP treatment at the time of screening, as well as those who must discontinue such treatment upon initial administration of the trial drug. The study population is characterized by a history of GPP flares, and participants are required to provide signed informed consent in accordance with ICH GCP guidelines. Women of childbearing potential are required to use highly effective birth control methods. The trial does not exclude vulnerable populations, ensuring a comprehensive evaluation of the treatment's efficacy across a diverse group of individuals.

The clinical trial is designed to evaluate the efficacy and safety of **spesolimab**, administered intravenously, in treating recurrent flares in patients with **Generalized Pustular Psoriasis** (GPP) following their initial flare treatment with the same medication. This trial is an open-label, multicenter, single-arm study, which means that all participants will receive the investigational product, and both the researchers and participants will be aware of the treatment being administered. The trial is expected to run until April 2027, with recruitment starting in November 2023.

Participants will undergo a series of study visits, beginning with a screening visit to determine eligibility based on specific inclusion criteria, such as a documented history of GPP and a GPPGA pustulation subscore of 0 or 1. Eligible participants will then proceed to the initial administration of the trial drug. Follow-up visits will be conducted to monitor the participants' response to treatment, with the primary endpoint being the achievement of a GPPGA pustulation subscore of 0, indicating no visible pustules at Week 1. Secondary endpoints include achieving a pustulation subscore of 0 or 1 with a ≥2-point reduction from baseline at Week 1.

The expected length of participant involvement in the trial is contingent upon the treatment period, which is capped at a maximum of 1 week. Participants may be withdrawn from the study early if they do not meet the ongoing eligibility criteria, experience adverse effects that necessitate discontinuation, or choose to withdraw consent. The trial aims to confirm the efficacy and safety of spesolimab in treating recurrent GPP flares, with the ultimate goal of converting the conditional marketing authorization into a full marketing authorization.

The clinical trial involves the administration of **spesolimab**, an experimental medication, which is a **solution for infusion**. The pharmaceutical form of spesolimab is specifically designed for intravenous administration. The dosage regimen for this trial includes a maximum daily dose of 900 mg, with a total maximum dose of 1800 mg over the course of the treatment period. The treatment period is limited to a maximum of one day. Spesolimab is of biological origin, classified as a protein of other origin, and is not formulated for pediatric use. The administration of spesolimab is intended to evaluate its efficacy and safety in patients with Generalized Pustular Psoriasis (GPP) experiencing a recurrent flare following initial treatment with the same medication.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The trial is structured as an open-label, single-arm study, focusing solely on the administration of spesolimab. Participant compliance with the dosing schedule is monitored through standard clinical trial procedures to ensure adherence to the protocol. The trial aims to assess the impact of immunogenicity on the efficacy, safety, and pharmacokinetics of spesolimab in the specified patient population.

Efficacy in this clinical trial will be assessed by evaluating the response to treatment with spesolimab intravenous (i.v.) in patients with **Generalized Pustular Psoriasis (GPP)** experiencing recurrent flares. The primary endpoint for efficacy is the achievement of a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0, indicating no visible pustules, at Week 1. Secondary endpoints include achieving a GPPGA pustulation subscore of 0 or 1, with a reduction of at least 2 points from baseline at Week 1. The baseline is defined as the last measurement prior to the first dose of re-treatment with spesolimab i.v.