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.

Study Overview

• Status: Completed
• Conditions: Generalized Pustular Psoriasis
• Intervention / Treatment: Drug: Spesolimab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 123
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Caba, Argentina, C1055AA0
    • Buenos Aires Skin S.A.
  • Caba, Argentina, C1056AB
    • Hospital Italiano de Buenos Aires
• Belgium
  • Bruxelles, Belgium, 1200
    • Brussels - UNIV Saint-Luc
• Chile
  • Vitacura, Chile, 7640881
    • Clinica Dermacross S.A.
• China
  • Guangzhou, China, 510288
    • Sun yet-sen Memorial Hospital, Sun yet-sen Univesity
  • Hangzhou, China, 310009
    • The Second Affiliated Hospital Zhejiang University School of Medicine
  • Shanghai, China, 200000
    • Shanghai skin disease hospital
  • Shanghai, China, 200040
    • Huashan Hospital, Fudan University
  • Shenyang, China, 110001
    • The First Hospital of China Medical University
  • Tianjin, China, 300120
    • Tianjin Academy Of Traditional Chinese Medicine Affiliated Hospital
  • Xi'an, China, 710004
    • Second Affiliated Hospital of Xi'an JiaoTong University
• France
  • Nice, France, 06200
    • HOP l'Archet
  • Paris, France, 75010
    • HOP Saint-Louis
• Germany
  • Bad Bentheim, Germany, 48455
    • Fachklinik Bad Bentheim
  • Bonn, Germany, 53127
    • Universitätsklinikum Bonn AöR
  • Frankfurt am Main, Germany, 60596
    • Universitatsklinikum Frankfurt
  • München, Germany, 80337
    • Klinikum der Universität München - Campus Innenstadt
  • Münster, Germany, 48149
    • Universitatsklinikum Munster
  • Oldenburg, Germany, 26133
    • Klinikum Oldenburg AöR
  • Würzburg, Germany, 97080
    • Universitätsklinikum Würzburg AÖR
• Greece
  • Thessaloniki, Greece, 54643
    • General Hospital of Thessaloniki "Ippokrateio"
• Italy
  • Rozzano (MI), Italy, 20089
    • Istituto Clinico Humanitas
• Japan
  • Aichi, Nagoya, Japan, 467-8602
    • Nagoya City University Hospital
  • Fukuoka, Kitakyushu, Japan, 800-0296
    • Kyushu Rosai Hospital
  • Ibaraki, Inashiki-gun, Japan, 300-0395
    • Tokyo Medical University Ibaraki Medical Center
  • Saitama, Iruma-gun, Japan, 350-0495
    • Saitama Medical University Hospital
  • Tokyo, Hachioji, Japan, 193-0998
    • Tokyo Medical University Hachioji Medical Center
  • Tokyo, Shinjuku-ku, Japan, 160-0023
    • Tokyo Medical University Hospital
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Pusan National Univ. Hosp
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital
• Malaysia
  • Ipoh, Malaysia, 30450
    • Hospital Raja Permaisuri Bainun
  • Johor Bahru, Malaysia, 80100
    • Hospital Sultanah Aminah
  • Johor Bahru, Malaysia, 81100
    • Hospital Sultan Ismail
  • Kota Kinabalu, Malaysia, 88586
    • Queen Elizabeth Hospital
  • Kuala Lumpur, Malaysia, 50586
    • Hospital Kuala Lumpur
  • Kuching, Sarawak, Malaysia, 93586
    • Sarawak General Hospital
  • Muar, Malaysia, 84000
    • Hospital Pakar Sultanah Fatimah
  • Pulau Pinang, Malaysia, 10990
    • Hospital Pulau Pinang
• Mexico
  • Guadalajara, Mexico, 44610
    • Centro de Investigación de Enfermedades Autoinmunes S.C.
  • Monterrey, Mexico, 64460
    • Hospital Universitario Dr Jose Eleuterio Gonzalez
• Netherlands
  • Rotterdam, Netherlands, 3015 GD
    • Erasmus Medisch Centrum
• Philippines
  • Davao City, Philippines, 8000
    • Southern Philippines Medical Center
  • Iloilo City, Iloilo, Philippines, 5000
    • Iloilo Doctors Hospital
  • Makati City, Philippines, 1229
    • Center for Skin Research, Testing and Product Development
• Russian Federation
  • Chelyabinsk, Russian Federation, 454048
    • SBHI Chelyabinsk Reg.Clin.Derma.Dispen.
  • Kazan, Russian Federation, 420111
    • LLC "Medical Center Azbuka Zdorovia"
  • Kirov, Russian Federation, 610035
    • FSBEI HE "Kirov State Medical University"
  • Saint-Petersburg, Russian Federation, 197022
    • 1stPavlov St.Med.Univ.St.-Petersburg Res.Inst.
  • Saratov, Russian Federation, 410028
    • Saratov State Med.Univ.n.a.Razumovskogo
  • St. Petersburg, Russian Federation, 190123
    • LLC Skin Disease Clinic of Pier Volkenstein, St. Petersburg
  • St. Petersburg, Russian Federation, 194156
    • LLC "Avrora Medfort"
• South Africa
  • Cape Town, South Africa, 7405
    • Arthritis Clinical Research Trials
• Spain
  • Esplugues Del Llobregat, Spain, 08950
    • Hospital Sant Joan de Déu
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
• Taiwan
  • Linkou, Taiwan, 333
    • Chang Gung Medical Foundation (CGMF) - Linkou Bran
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
• Thailand
  • Bangkok, Thailand, 10330
    • King Chulalongkorn Memorial Hospital
  • Bangkok, Thailand, 10400
    • Institute of Dermatology
  • Ratchatewi, Bangkok, Thailand, 10400
    • Ramathibodi Hospital
• Tunisia
  • Sfax, Tunisia, 1053
    • Hedi Chaker Hospital, Department of Dermatology
  • Sousse, Tunisia, 4000
    • Farhat Hached Hospital
  • Tunis, Tunisia, 1007
    • La Rabta Hospital
  • Tunis, Tunisia, 1008
    • Charles Nicolle Hospital
  • Tunis, Tunisia, 1008
    • Habib Thameur Hospital
• Turkey
  • Bursa, Turkey, 16059
    • Uludag University Medicine Faculty Departmant of Dermatology
  • Istanbul, Turkey, 34093
    • Bezmi Alem Valide Sultan Vakif Gureba Egitim ve Arastirma Hastanesi
  • Istanbul, Turkey, 34098
    • Istanbul Universitesi Cerrahpasa Tip Fakultesi
  • Istanbul, Turkey, 34460
    • Marmara Universitesi Tip Fakultesi
• United States
  • Michigan
    • Auburn Hills, Michigan, United States, 48326
      • Oakland Hills Dermatology
  • Missouri
    • Saint Louis, Missouri, United States, 63108
      • Washington University School of Medicine
• Vietnam
  • Ha Noi, Vietnam, 10000
    • National Hospital of Dermatology and Venereology
  • Ho Chi Minh, Vietnam, 70000
    • HCMC Hospital of Dermato-Venereology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Solution for injection
Experimental: Spesolimab SC low dose	Drug: Spesolimab; Solution for injection
Experimental: Spesolimab SC medium dose	Drug: Spesolimab; Solution for injection
Experimental: Spesolimab SC high dose	Drug: Spesolimab; Solution for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Generalized Pustular Psoriasis (GPP) Flare	A GPP flare was defined as increase in Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) score by ≥ 2 from baseline and the pustular component of GPPGA ≥ 2) up to week 48. Use of rescue medication, or investigator-prescribed Standard of Care (SoC) for GPP worsening, was considered to represent a GPP flare onset. GPPGA relied on clinical assessment of the Generalized Pustular Psoriasis (GPP) patient's skin presentation. The GPPGA total score was calculated by taking the mean of the erythema subscore, pustules subscore and scaling/crusting subscore. The severity of each subscore was assessed using a 5 point scale score ranging from 0 to 4 (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe). The final GPPGA score is assigned as follows: 0 , if scores for all three subscores are 0,; 1, if 0 < mean < 1.5,; 2, if 1.5 ≤ mean < 2.5,; 3, if 2.5 ≤ mean < 3.5,; 4, if mean ≥ 3.5.	GPPGA was regularly assessed at baseline (Week 1) and up to Week 48 (at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48). Patients could come to site for flare confirmation anytime as unscheduled visit. Visit window was ±7 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Key Secondary Endpoint: The Occurrence of at Least One Generalized Pustular Psoriasis (GPP) Flare up to Week 48	Proportion of patients with at least one GPP flare up to Week 48 is reported. Proportions were rounded up to three decimal places. A GPP flare was defined as increase in Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) score by ≥ 2 from baseline and the pustular component of GPPGA ≥ 2. Any use of rescue medication, or investigator-prescribed SoC for GPP worsening, prior to week 48 was considered to represent the onset of a GPP flare. Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) relied on the clinical assessment of GPP patient's skin presentation. The total score is calculated by taking the mean of the three subscores: 1) erythema; 2) pustules and 3) scaling/crusting which were assessed using a scale score 0 to 4 (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe). The final GPPGA score: 0 , if scores for all three subscores are 0,; if 0 < mean < 1.5;; if 1.5 ≤ mean < 2.5;; if 2.5 ≤ mean < 3.5;; if mean ≥ 3.5.	GPPGA was regularly assessed at baseline (Week 1) and up to Week 48 (at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48). Patients could come to site for flare confirmation anytime as unscheduled visit. Visit window was ±7 days.
Time to First Worsening of Psoriasis Symptom Scale (PSS) up to Week 48	Worsening of Psoriasis Symptom Scale (PSS) was defined as a 4-point increase in total score from baseline. Intake of rescue medication, or investigator-prescribed SoC for GPP worsening, was considered as onset of a worsening. The PSS is a 4-item patient-reported outcome (PRO) instrument that was developed to assess the severity of 4 psoriasis symptoms in patients with moderate to severe psoriasis. The symptoms included are: pain, redness, itching, and burning. Current symptom severity is assessed using a 5-point scale ranging from 0 (none) to 4 (very severe). The symptom scores are added to an unweighted total score (range: 0 (no symptoms) to 16 (severe symptoms)).	PSS assessments were performed at: Baseline (Week 1) and up to Week 48 (at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48). Visit window was ±7 days.
Time to First Worsening of Dermatology Quality of Life Index (DLQI) up to Week 48	Worsening of DLQI up to week 48 was defined as a 4-point increase in total score from baseline. Intake of rescue medication, or investigator-prescribed SoC for GPP worsening, was considered as onset of a worsening. The DLQI is a patient-administered, ten-question, quality of life questionnaire that covers six domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships and treatment. Response categories include "not relevant" (score of 0), "not at all" (score of 0), "a little" (score of 1), "a lot" (score of 2) and "very much" (score of 3). Question 7 is a "yes"/ "no" question where "yes" is scored as 3. DLQI total score is calculated by summing the scores of each question resulting in a range of 0 (no effect on patient's life) to 30 (extremely large effect on patient's life).	DLQI assessments were performed at: Baseline (Week 1) and up to Week 48 (at Week 4, 8, 12, 24, 36 and 48). Visit window was ±7 days. Time window for Week 48 was from Week 46 to Week 50.
Sustained Remission	Proportion of patients with sustained remission at all visits up to Week 48. Proportions were rounded up to three decimal places. Remission was defined as a patient with a GPPGA score of 0 or 1 (clear or almost clear) at all visits up to week 48, without intake of rescue medication, or investigator-prescribed SoC for GPP worsening. GPPGA relied on clinical assessment of the Generalized Pustular Psoriasis (GPP) patient's skin presentation. The GPPGA total score was calculated by taking the mean of the erythema subscore, pustules subscore and scaling/crusting subscore. The severity of each subscore was assessed using a 5 point scale score ranging from 0 to 4 (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe). The final GPPGA score is assigned as follows: 0 , if scores for all three subscores are 0,; 1, if 0 < mean < 1.5,; 2, if 1.5 ≤ mean < 2.5,; 3, if 2.5 ≤ mean < 3.5,; 4, if mean ≥ 3.5.	GPPGA was regularly assessed at baseline (Week 1) and up to Week 48 (at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48). Patients could come to site for flare confirmation anytime as unscheduled visit. Visit window was ±7 days.
The Occurrence of Treatment Emergent Adverse Events (TEAEs)	Percentage of patients with treatment emergent adverse events (TEAEs) is reported. Percentages were rounded up to one decimal places. Time Frame: Placebo, Spesolimab (Speso) SC low, medium, high: From randomized study treatment start until the first use of rescue medication with IV spesolimab or until last dose + 16 weeks, up to 62 weeks. Speso IV SD and Speso IV DD: From first use of rescue medication with IV spesolimab until OL maintenance spesolimab SC or until last dose of spesolimab IV + 16 weeks, up to 17 weeks. Speso OL SC: From the first dose of OL spesolimab SC treatment until last dose + 16 weeks, up to 62 weeks.	Up to 62 weeks (for detailed timeframe see description).

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• Morita A, Choon SE, Bachelez H, Anadkat MJ, Marrakchi S, Zheng M, Tsai TF, Turki H, Hua H, Rajeswari S, Thoma C, Burden AD. Design of Effisayil 2: A Randomized, Double-Blind, Placebo-Controlled Study of Spesolimab in Preventing Flares in Patients with Generalized Pustular Psoriasis. Dermatol Ther (Heidelb). 2023 Jan;13(1):347-359. doi: 10.1007/s13555-022-00835-6. Epub 2022 Nov 5.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2020
• Primary Completion (Actual): November 23, 2022
• Study Completion (Actual): November 23, 2022

Study Registration Dates

• First Submitted: May 20, 2020
• First Submitted That Met QC Criteria: May 20, 2020
• First Posted (Actual): May 22, 2020

Study Record Updates

• Last Update Posted (Estimated): December 14, 2023
• Last Update Submitted That Met QC Criteria: November 21, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: 1368-0027; 2018-003081-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".

Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

The data shared are the raw clinical study data sets.

• IPD Sharing Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• IPD Sharing Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No