A Study to Test Whether BI 655130 (Spesolimab) Prevents Flare-ups in Patients With Generalized Pustular Psoriasis

Effisayil™ 2: Multi-center, Randomized, Parallel Group, Double Blind, Placebo Controlled, Phase IIb Dose-finding Study to Evaluate Efficacy and Safety of BI 655130 (Spesolimab) Compared to Placebo in Preventing Generalized Pustular Psoriasis (GPP) Flares in Patients With History of GPP.

This is a study in adolescents and adults with Generalized Pustular Psoriasis (GPP). People between 12 and 75 years old can take part in the study. The study is open to people who had GPP flare-ups in the past but whose skin is clear or almost clear when they join the study. The purpose of the study is to test 3 different doses of a medicine called spesolimab and to see whether it helps to prevent GPP flare-ups.

Participants are put into 4 groups by chance. Three groups get different doses of spesolimab. The fourth group gets a placebo. Placebo looks like spesolimab but does not contain any medicine.

Spesolimab and placebo are given as an injection under the skin. Participants are in the study for about 1 year and 4 months. During this time, they visit the study site about 15 times. For the first 11 months, participants get spesolimab or placebo injections every month. At the study visits, the doctors check participants' skin for signs of a new GPP flare-up. The doctors also check the general health of the participants.

If a participant has a GPP flare-up during the study, more visits may be necessary. In case of a flare-up, participants get a dose of spesolimab as an infusion into a vein.

Inclusion Criteria:

• Patients with a known and documented history of GPP per ERASPEN criteria (see Section 3.3.1) regardless of IL36RN mutation status, with at least 2 presentations of moderate to severe GPP flares with fresh pustulation (new appearance or worsening) in the past.
• Patients with a GPPGA score of 0 or 1 at screening and randomization.
• Patients who are not on concomitant GPP treatment at time of randomization (V2) must have had at least two presentations of moderate to severe GPP flare in the past year, at least one of which had evidence of either fever and/or elevated CRP and/or elevated WBC, and/or asthenia and/or myalgia.
• Patients who are not on concomitant GPP treatment at time of randomization (V2) but who were on concomitant GPP treatment until shortly before randomization (V2) (≤ 12 weeks before randomization), these patients must have a history of flaring while on concomitant treatment for GPP or in case of dose reduction or discontinuation of their concomitant medication.
• Patients who are on concomitant treatment regimen with retinoids and/or methotrexate and/or cyclosporine must stop at the day of randomization (V2). These patients must have a history of flaring while on concomitant treatment for GPP or in case of dose reduction or discontinuation of these concomitant medications.
• Male or female patients, aged 12 to 75 years at screening. For all patients, a minimum weight of 40 kg is required.
• Signed and dated written informed consent and assent in accordance with ICH-GCP and local legislation prior to admission in the trial.
• Women of childbearing potential (WOCBP)1 must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the CTP as well as in the patient, parent(s) (or patient's legal guardian) information.

Exclusion Criteria:

1. Patients with SAPHO (Synovitis-acne-pustulosis-hyperostosis-osteitis) syndrome.

2. Patients with primary erythrodermic psoriasis vulgaris.

3. Severe, progressive, or uncontrolled hepatic disease, defined as >3-fold Upper Limit of Normal (ULN) elevation in Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) or alkaline phosphatase, or >2-fold ULN elevation in total bilirubin.

4. Treatment with:

   1. Any restricted medication as specified in the CTP, or any drug considered likely to interfere with the safe conduct of the study, as assessed by the investigator.
   2. Any prior exposure to BI 655130 or another IL36R inhibitor biologic.

5. Increased risk of infectious complications (e.g. recent pyogenic infection, any congenital or acquired immunodeficiency (e.g. HIV), past organ or stem cell transplantation), as assessed by the investigator.

6. Relevant chronic or acute infections including active tuberculosis, human immunodeficiency virus (HIV) infection or viral hepatitis at the time of randomization. A patient can be re-screened if the patient was treated and is cured from the acute infection.

7. Active or Latent Tuberculosis (TB):

   • Patients with active tuberculosis should be excluded
   • Patients with a positive QuantiFERON® (or if applicable, T-Spot®) TB test during screening are excluded, unless the patient had previous diagnosis of active or latent TB and has completed appropriate treatment per the discretion of the local investigator within the last 3 years and at the latest at the time of screening (i.e. 2 to 4 weeks before study drug administration); patients may be re-screened once to meet this criterion)
   • Patients with suspected false positive or indeterminate QuantiFERON® (or if applicable, T-Spot®) TB result may be re-tested once
   • If QuantiFERON® (or if applicable, T-Spot®) TB testing is not available or provides indeterminate results after repeat testing, a tuberculin skin test (TST) can be performed: A TST reaction of ≥10mm (≥5mm if receiving ≥15mg/d prednisone or its equivalent) is considered positive.

8. History of allergy/hypersensitivity to the systemically administered trial medication agent or its excipients.

Further exclusion criteria apply.