A Study to Test Whether BI 655130 (Spesolimab) Prevents F... | NCT04399837 | Trialant
NCT04399837
Sponsor
Boehringer Ingelheim
Status
Completed
Last Update Posted
Oct 20, 2025Actual
Enrollment
123Actual
Phase
Phase 2
Conditions
Generalized Pustular Psoriasis
Interventions
Spesolimab
Placebo
Countries
United States
Argentina
Belgium
Chile
China
France
Germany
Greece
Italy
Japan
Malaysia
Mexico
Netherlands
Philippines
Russia
South Africa
South Korea
Spain
Taiwan
Thailand
Tunisia
Turkey (Türkiye)
Vietnam
Protocol Section
Identification Module
NCT ID
NCT04399837
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
1368-0027
Secondary IDs
ID
Type
Description
Link
2018-003081-14
EudraCT Number
Brief Title
A Study to Test Whether BI 655130 (Spesolimab) Prevents Flare-ups in Patients With Generalized Pustular Psoriasis
Official Title
Effisayilâ„¢ 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.
Acronym
Not provided
Organization
Boehringer IngelheimINDUSTRY
Status Module
Record Verification Date
Oct 2025
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jun 4, 2020Actual
Primary Completion Date
Nov 23, 2022Actual
Completion Date
Nov 23, 2022Actual
First Submitted Date
May 20, 2020
First Submission Date that Met QC Criteria
May 20, 2020
First Posted Date
May 22, 2020Actual
Results Waived
Not provided
Results First Submitted Date
Nov 21, 2023
Results First Submitted that Met QC Criteria
Nov 21, 2023
Results First Posted Date
Dec 14, 2023Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Oct 9, 2025
Last Update Posted Date
Oct 20, 2025Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Boehringer IngelheimINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
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.
Detailed Description
Not provided
Conditions Module
Conditions
Generalized Pustular Psoriasis
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
123Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Spesolimab SC low dose
Experimental
Drug: Spesolimab
Spesolimab SC medium dose
Experimental
Drug: Spesolimab
Spesolimab SC high dose
Experimental
Drug: Spesolimab
Placebo
Placebo Comparator
Drug: Placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Spesolimab
Drug
Solution for injection
Spesolimab SC high dose
Spesolimab SC low dose
Spesolimab SC medium dose
Outcomes Module
Primary Outcomes
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 Outcomes
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.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
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:
Patients with SAPHO (Synovitis-acne-pustulosis-hyperostosis-osteitis) syndrome.
Patients with primary erythrodermic psoriasis vulgaris.
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.
Treatment with:
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.
Any prior exposure to BI 655130 or another IL36R inhibitor biologic.
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.
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.
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.
History of allergy/hypersensitivity to the systemically administered trial medication agent or its excipients.
Gordon KB, Augustin M, Barker J, Tada Y, Lebwohl MG, Tang M, Hofmann P, Thoma C, Gottlieb AB. Effect of spesolimab on sustained disease control in patients with generalized pustular psoriasis: Post hoc analysis of the EFFISAYIL 2 study. J Am Acad Dermatol. 2025 Jun;92(6):1235-1242. doi: 10.1016/j.jaad.2025.01.089. Epub 2025 Mar 7.
Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization).
Subjects were screened for eligibility prior to participation and attended a specialist site which ensured that they (the subjects) met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
The randomization was stratified accounting for use of systemic GPP medications at randomization (yes vs. no), and the blocking factors, region (Japan vs. non-Japan) and population (adults vs. adolescents).
Recruitment Details
This was a randomized multicenter, parallel group, double-blind, placebo-controlled Phase IIb trial comprising of 3 active doses compared to placebo in adolescents from 12 years to less than 18 years of age and adult patients with history of Generalized Pustular Psoriasis (GPP) and presenting (at screening and at randomization) with a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) score of 0 or 1 (clear or almost clear).
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Placebo
Patients were subcutaneously (SC) injected on Day 1 of Week 1 a loading dose of solution for injection of placebo matching solution for injection of spesolimab followed by a maintenance treatment which consisted of a subcutaneous injection of solution for injection of placebo matching solution for injection of spesolimab every 4 weeks (i.e. on Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40 and 44).
The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 of flare (R1/D1) or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
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).
St Louis
Missouri
63108
United States
Buenos Aires Skin S.A.
CABA
C1055AA0
Argentina
Hospital Italiano de Buenos Aires
CABA
C1056AB
Argentina
Brussels - UNIV Saint-Luc
Brussels
1200
Belgium
ClÃnica Dermacross S.A.
Vitacura
7640881
Chile
Sun yet-sen Memorial Hospital, Sun yet-sen Univesity
Guangzhou
510288
China
The Second Affiliated Hospital Zhejiang University School of Medicine
Hangzhou
310009
China
Shanghai Skin Disease Hospital
Shanghai
200000
China
Huashan Hospital, Fudan University
Shanghai
200040
China
The First Hospital of China Medical University
Shenyang
110001
China
Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital
Tianjin
300120
China
Second Affiliated Hospital of Xi'an JiaoTong University
Xi'an
710004
China
HOP l'Archet
Nice
06200
France
HOP Saint-Louis
Paris
75010
France
Fachklinik Bad Bentheim
Bad Bentheim
48455
Germany
Universitätsklinikum Bonn AöR
Bonn
53127
Germany
Universitätsklinikum Frankfurt
Frankfurt am Main
60596
Germany
Klinikum der Universität München - Campus Innenstadt
München
80337
Germany
Universitätsklinikum Münster
Münster
48149
Germany
Klinikum Oldenburg AöR
Oldenburg
26133
Germany
Universitätsklinikum Würzburg AÖR
Würzburg
97080
Germany
General Hospital of Thessaloniki "Ippokrateio"
Thessaloniki
54643
Greece
Istituto Clinico Humanitas
Rozzano (MI)
20089
Italy
Nagoya City University Hospital
Aichi, Nagoya
467-8602
Japan
Kyushu Rosai Hospital
Fukuoka, Kitakyushu
800-0296
Japan
Tokyo Medical University Ibaraki Medical Center
Ibaraki, Inashiki-gun
300-0395
Japan
Saitama Medical University Hospital
Saitama, Iruma-gun
350-0495
Japan
Tokyo Medical University Hachioji Medical Center
Tokyo, Hachioji
193-0998
Japan
Tokyo Medical University Hospital
Tokyo, Shinjuku-ku
160-0023
Japan
Hospital Raja Permaisuri Bainun
Ipoh
30450
Malaysia
Hospital Sultanah Aminah
Johor Bahru
80100
Malaysia
Hospital Sultan Ismail
Johor Bahru
81100
Malaysia
Queen Elizabeth Hospital
Kota Kinabalu
88586
Malaysia
Hospital Kuala Lumpur
Kuala Lumpur
50586
Malaysia
Sarawak General Hospital
Kuching, Sarawak
93586
Malaysia
Hospital Pakar Sultanah Fatimah
Muar town
84000
Malaysia
Hospital Pulau Pinang
Pulau Pinang
10990
Malaysia
Centro de Investigación de Enfermedades Autoinmunes S.C.
Guadalajara
44610
Mexico
Hospital Universitario Dr Jose Eleuterio Gonzalez
Monterrey
64460
Mexico
Erasmus Medisch Centrum
Rotterdam
3015 GD
Netherlands
Southern Philippines Medical Center
Davao City
8000
Philippines
Iloilo Doctors Hospital
Iloilo City, Iloilo
5000
Philippines
Center for Skin Research, Testing and Product Development
Makati City
1229
Philippines
SBHI Chelyabinsk Reg.Clin.Derma.Dispen.
Chelyabinsk
454048
Russia
LLC "Medical Center Azbuka Zdorovia"
Kazan'
420111
Russia
FSBEI HE "Kirov State Medical University"
Kirov
610035
Russia
LLC Skin Disease Clinic of Pier Volkenstein, St. Petersburg
Chang Gung Medical Foundation (CGMF) - Linkou Bran
Linkou District
333
Taiwan
National Taiwan University Hospital
Taipei
10002
Taiwan
King Chulalongkorn Memorial Hospital
Bangkok
10330
Thailand
Institute of Dermatology
Bangkok
10400
Thailand
Ramathibodi Hospital
Ratchatewi, Bangkok
10400
Thailand
Hedi Chaker Hospital, Department of Dermatology
Sfax
1053
Tunisia
Farhat Hached Hospital
Sousse
4000
Tunisia
La Rabta Hospital
Tunis
1007
Tunisia
Charles Nicolle Hospital
Tunis
1008
Tunisia
Habib Thameur Hospital
Tunis
1008
Tunisia
Uludag University Medicine Faculty Departmant of Dermatology
Bursa
16059
Turkey (Türkiye)
Bezmi Alem Valide Sultan Vakif Gureba Egitim ve Arastirma Hastanesi
Istanbul
34093
Turkey (Türkiye)
Istanbul Universitesi Cerrahpasa Tip Fakultesi
Istanbul
34098
Turkey (Türkiye)
Marmara Universitesi Tip Fakultesi
Istanbul
34460
Turkey (Türkiye)
National Hospital of Dermatology and Venereology
HÃ Ná»™i
10000
Vietnam
HCMC Hospital of Dermato-Venereology
Ho Chi Minh City
70000
Vietnam
Derived
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.
FG001
Spesolimab SC Low Dose
Patients received on Day 1 of Week 1 a loading dose which consisted of two subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300mg) and two subcutaneous injections of placebo matching solution for injection of spesolimab. The loading dose was followed by a maintenance treatment which consisted of one SC injection of 150 mg of solution for injection of spesolimab and one SC injection of placebo matching solution for injection of spesolimab every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
FG002
Spesolimab SC Medium Dose
Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered subcutaneously every 12 weeks or every 4 weeks (intensified maintenance therapy).
FG003
Spesolimab SC High Dose
Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 4 weeks (i.e. at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44). The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
FG00031 subjects
FG00131 subjects
FG00231 subjects
FG00330 subjects
COMPLETED
Completed trial
FG00030 subjects
FG00127 subjects
FG00228 subjects
FG00326 subjects
NOT COMPLETED
FG0001 subjects
FG0014 subjects
FG0023 subjects
FG0034 subjects
Type
Comment
Reasons
Other than listed
FG0000 subjects
FG0012 subjects
FG0022 subjects
FG0033 subjects
Withdrawal by Subject
FG0001 subjects
FG0012 subjects
FG0021 subjects
FG0031 subjects
Randomized Set: This patient set includes all randomized patients.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Placebo
Patients were subcutaneously (SC) injected on Day 1 of Week 1 a loading dose of solution for injection of placebo matching solution for injection of spesolimab followed by a maintenance treatment which consisted of a subcutaneous injection of solution for injection of placebo matching solution for injection of spesolimab every 4 weeks (i.e. on Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40 and 44).
The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 of flare (R1/D1) or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
BG001
Spesolimab SC Low Dose
Patients received on Day 1 of Week 1 a loading dose which consisted of two subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300mg) and two subcutaneous injections of placebo matching solution for injection of spesolimab. The loading dose was followed by a maintenance treatment which consisted of one SC injection of 150 mg of solution for injection of spesolimab and one SC injection of placebo matching solution for injection of spesolimab every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
BG002
Spesolimab SC Medium Dose
Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered subcutaneously every 12 weeks or every 4 weeks (intensified maintenance therapy).
BG003
Spesolimab SC High Dose
Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 4 weeks (i.e. at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44). The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
BG004
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00031
BG00131
BG00231
BG00330
BG004123
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
ParticipantsBG00031
ParticipantsBG00131
ParticipantsBG00231
ParticipantsBG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00031
ParticipantsBG00131
ParticipantsBG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00031
ParticipantsBG00131
ParticipantsBG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00031
ParticipantsBG00131
ParticipantsBG002
Number of patients in the categories 0 or 1 of GPPGA score
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. Number of patients in the categories 0 or 1 of GPPGA score is reported.
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00031
ParticipantsBG001
Number of patients in the categories 0 or 1 of GPPGA pustules subscore
The Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustules subscore relied on clinical assessment of the Generalized Pustular Psoriasis (GPP) pustules presentation. The investigator (or qualified site personnel) scored the pustules of all GPP lesions from 0 to 4 where:
0 = clear;
= almost clear;
= mild;
= moderate;
= severe. Number of patients in the categories 0 or 1 of GPPGA pustules subscore is reported.
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00031
ParticipantsBG00131
Concomitant use of systemic GPP medication at randomization
Number of patients in each category of concomitant use of systemic GPP medication at randomization (-28 days to randomization). The reported categories of concomitant use of systemic GPP medication at randomization are:
Yes; No.
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG00031
ParticipantsBG00131
ParticipantsBG002
Psoriasis Symptom Scale (PSS) total score at baseline
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).
Randomized Set: This patient set includes all randomized patients.
Mean
Standard Deviation
score on a scale
Title
Denominators
Categories
ParticipantsBG00031
ParticipantsBG001
DLQI total score at baseline
The Dermatology Quality of Life Index (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 range from 0 (not relevant) to 3 (very much). Question 7 is a "yes"/ "no" question where "yes" is scored as 3. Total score is obtained 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).
This patient set includes all randomized patients. Adolescents aged below 16 years were optional to the questionnaire, therefore two adolescent whose age was below 16 years were not asked to fill this questionnaire.
Mean
Standard Deviation
score on a scale
Title
Denominators
Categories
ParticipantsBG00031
ParticipantsBG001
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
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.
Randomized Set (EM-PM): This patient set includes all randomized patients. EM: Primary estimand for randomised maintenance period, where any use of rescue medication with intravenous spesolimab, or investigator-prescribed SoC for GPP worsening is considered as GPP flare. PM: Primary method for censoring, which is made at the earliest date of End of Study (EoS), Day 351 if no intercurrent event.
Posted
Median
95% Confidence Interval
weeks
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.
ID
Title
Description
OG000
Placebo
Patients were subcutaneously (SC) injected on Day 1 of Week 1 a loading dose of solution for injection of placebo matching solution for injection of spesolimab followed by a maintenance treatment which consisted of a subcutaneous injection of solution for injection of placebo matching solution for injection of spesolimab every 4 weeks (i.e. on Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40 and 44).
The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 of flare (R1/D1) or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
OG001
Spesolimab SC Low Dose
Patients received on Day 1 of Week 1 a loading dose which consisted of two subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300mg) and two subcutaneous injections of placebo matching solution for injection of spesolimab. The loading dose was followed by a maintenance treatment which consisted of one SC injection of 150 mg of solution for injection of spesolimab and one SC injection of placebo matching solution for injection of spesolimab every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
OG002
Spesolimab SC Medium Dose
Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered subcutaneously every 12 weeks or every 4 weeks (intensified maintenance therapy).
Units
Counts
Participants
OG00031
OG00131
OG00231
OG003
Title
Denominators
Categories
Title
Measurements
OG00037.3(4.0 to NA)Insufficient number of participants with events.
OG001NA(NA to NA)Insufficient number of participants with events.
OG002NA
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
OG002
OG003
A flat vs. non-flat dose-response relationship across the 3 doses of spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 4 different plausible dose-response patterns (linear, Emax 1, Emax 2 and exponential) while protecting the overall probability of type I error (one-sided alpha of 0.05).
MCP-Mod linear model fit
Model assumption: Dose effect is linear with the increase of dose.
0.002
Multiple contrast test
3.041
Other
Secondary
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.
Randomized Set (EM-MI): This patient set includes all randomized patients. EM:primary estimand for randomised maintenance period, where any use of rescue medication with intravenous spesolimab, or investigator - prescribed SoC for GPP worsening is considered as GPP flare. MI: multiple imputation method using sequential logistic regression method.
Posted
Number
95% Confidence Interval
proportion of patients
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.
ID
Title
Description
OG000
Placebo
Secondary
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)).
Randomized Set (EM-PM): This patient set includes all randomized patients. EM:primary estimand for randomised maintenance period, where any use of rescue medication with intravenous spesolimab, or investigator-prescribed SoC for GPP worsening is considered as GPP flare. PM: primary method for censoring, which is made at the earliest date of End of Study (EoS), Day 351 if no intercurrent event.
Posted
Median
95% Confidence Interval
weeks
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.
ID
Title
Description
OG000
Placebo
Patients were subcutaneously (SC) injected on Day 1 of Week 1 a loading dose of solution for injection of placebo matching solution for injection of spesolimab followed by a maintenance treatment which consisted of a subcutaneous injection of solution for injection of placebo matching solution for injection of spesolimab every 4 weeks (i.e. on Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40 and 44).
The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 of flare (R1/D1) or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
Secondary
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).
Randomized Set (EM-PM): This patient set includes all randomized patients. EM:primary estimand for randomised maintenance period, where any use of rescue medication with intravenous spesolimab, or investigator-prescribed SoC for GPP worsening is considered as GPP flare. PM: primary method for censoring, which is made at the earliest date of End of Study (EoS), Day 351 if no intercurrent event.
Posted
Median
95% Confidence Interval
weeks
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.
ID
Title
Description
OG000
Placebo
Patients were subcutaneously (SC) injected on Day 1 of Week 1 a loading dose of solution for injection of placebo matching solution for injection of spesolimab followed by a maintenance treatment which consisted of a subcutaneous injection of solution for injection of placebo matching solution for injection of spesolimab every 4 weeks (i.e. on Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40 and 44).
The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 of flare (R1/D1) or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
Secondary
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.
Randomized Set (EM-MI): This patient set includes all randomized patients. EM:primary estimand for randomised maintenance period, where any use of rescue medication with intravenous spesolimab, or investigator-prescribed SoC for GPP worsening is considered as GPP flare. MI: multiple imputation method using sequential logistic regression method.
Posted
Number
95% Confidence Interval
proportion of patients
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.
ID
Title
Description
OG000
Placebo
Patients were subcutaneously (SC) injected on Day 1 of Week 1 a loading dose of solution for injection of placebo matching solution for injection of spesolimab followed by a maintenance treatment which consisted of a subcutaneous injection of solution for injection of placebo matching solution for injection of spesolimab every 4 weeks (i.e. on Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40 and 44).
The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 of flare (R1/D1) or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
Secondary
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.
Arms "Placebo, Speso SC Low, medium, high":Safety Set (SAF)-This patient set included all patients who were randomized and received at least one dose of study drug. One patient who was randomized to placebo arm but received active spesolimab dose is reported under the arm "Spesolimab SC low" instead of "Placebo".
Arms "Speso IV SD, Speso IV SD": Safety Analysis set for flare rescue treatment period (SAF-FT).
Arm "Speso OL SC": Safety Analysis set for OL maintenance treatment period (SAF-MT).
Posted
Number
percentage of patients
Up to 62 weeks (for detailed timeframe see description).
ID
Title
Description
OG000
Placebo
Patients were subcutaneously (SC) injected on Day 1 of Week 1 a loading dose of solution for injection of placebo matching solution for injection of spesolimab followed by a maintenance treatment which consisted of a subcutaneous injection of solution for injection of placebo matching solution for injection of spesolimab every 4 weeks (i.e. on Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40 and 44).
The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 of flare (R1/D1) or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
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 IV dose + 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.
Description
Arms "Placebo, Speso SC Low, medium, high":Safety Set (SAF)-This patient set included all patients who were randomized and received at least one dose of study drug. One patient who was randomized to placebo arm but received active spesolimab dose is reported under the arm "Spesolimab SC low" instead of "Placebo".
Arms "Speso IV SD, Speso IV SD": SAF-FT- Safety Analysis set for flare rescue treatment period.
Arm "Speso OL SC": SAF-MT- Safety Analysis set for OL maintenance treatment period.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Placebo
Patients were subcutaneously (SC) injected on Day 1 of Week 1 a loading dose of solution for injection of placebo matching solution for injection of spesolimab followed by a maintenance treatment which consisted of a subcutaneous injection of solution for injection of placebo matching solution for injection of spesolimab every 4 weeks (i.e. on Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40 and 44).
The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 of flare (R1/D1) or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
0
30
1
30
24
30
EG001
Spesolimab SC Low Dose
Patients received on Day 1 of Week 1 a loading dose which consisted of two subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300mg) and two subcutaneous injections of placebo matching solution for injection of spesolimab. The loading dose was followed by a maintenance treatment which consisted of one SC injection of 150 mg of solution for injection of spesolimab and one SC injection of placebo matching solution for injection of spesolimab every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
0
32
5
32
25
32
EG002
Spesolimab SC Medium Dose
Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered subcutaneously every 12 weeks or every 4 weeks (intensified maintenance therapy).
0
31
1
31
23
31
EG003
Spesolimab SC High Dose
Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 4 weeks (i.e. at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44). The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
0
30
3
30
20
30
EG004
Spesolimab IV SD
This arm includes the patients who were randomized at study start in the arms "Placebo" or "Spesolimab SC low dose" or "Spesolimab SC medium dose" or "Spesolimab SC high dose" who took a single dose (SD) of rescue treatment of 900 milligram (mg) of spesolimab administered intravenously (IV) at Day 1 of flare (R1/D1) because of a GPP flare during the 48 week treatment randomised period.
0
22
1
22
12
22
EG005
Spesolimab IV DD
This arm includes the patients who were randomized at study start in the arms "Placebo" or "Spesolimab SC low dose" or "Spesolimab SC medium dose" or "Spesolimab SC high dose" who took two doses (DD) of rescue treatment of spesolimab each 900 milligram (mg) of spesolimab administered intravenously (IV) at Day 1 and at Day 8 of flare (R1/D1 and R3/D8) because of a GPP flare during the 48 week treatment randomised period.
0
10
4
10
3
10
EG006
Spesolimab OL SC
This arm includes the patients who were randomized at study start in the arms "Placebo" or "Spesolimab SC low dose" or "Spesolimab SC medium dose" or "Spesolimab SC high dose" who experienced a flare during the 48 week randomised treatment period and were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at either Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare and then followed by maintenance treatment which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
0
20
1
20
14
20
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Palpitations
Cardiac disorders
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0011 affected32 at risk
EG0020 affected31 at risk
EG0030 affected30 at risk
EG0040 affected22 at risk
EG0050 affected10 at risk
EG0060 affected20 at risk
Oedema
General disorders
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0010 affected32 at risk
EG0020 affected31 at risk
EG003
Cholelithiasis
Hepatobiliary disorders
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0010 affected32 at risk
EG0020 affected31 at risk
EG003
Cellulitis
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0010 affected32 at risk
EG0020 affected31 at risk
EG003
Encephalitis viral
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0011 affected32 at risk
EG0020 affected31 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0011 affected32 at risk
EG0020 affected31 at risk
EG003
Septic shock
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0010 affected32 at risk
EG0020 affected31 at risk
EG003
Skin bacterial infection
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0010 affected32 at risk
EG0021 affected31 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0010 affected32 at risk
EG0020 affected31 at risk
EG003
Basal cell carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0010 affected32 at risk
EG0020 affected31 at risk
EG003
Breast cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0010 affected32 at risk
EG0020 affected31 at risk
EG003
Cerebral ischaemia
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0010 affected32 at risk
EG0020 affected31 at risk
EG003
Hypertensive encephalopathy
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0011 affected32 at risk
EG0020 affected31 at risk
EG003
Multiple sclerosis
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0001 affected30 at risk
EG0010 affected32 at risk
EG0020 affected31 at risk
EG003
Angioedema
Skin and subcutaneous tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0011 affected32 at risk
EG0020 affected31 at risk
EG003
Drug eruption
Skin and subcutaneous tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0011 affected32 at risk
EG0020 affected31 at risk
EG003
Pustular psoriasis
Skin and subcutaneous tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0011 affected32 at risk
EG0021 affected31 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Constipation
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0010 affected32 at risk
EG0020 affected31 at risk
EG0030 affected30 at risk
EG0040 affected22 at risk
EG0051 affected10 at risk
EG0060 affected20 at risk
Nausea
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0002 affected30 at risk
EG0012 affected32 at risk
EG0020 affected31 at risk
EG003
Odynophagia
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0010 affected32 at risk
EG0020 affected31 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 25.1
Systematic Assessment
EG0002 affected30 at risk
EG0010 affected32 at risk
EG0020 affected31 at risk
EG003
Asthenia
General disorders
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0010 affected32 at risk
EG0020 affected31 at risk
EG003
Chest discomfort
General disorders
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0010 affected32 at risk
EG0020 affected31 at risk
EG003
Injection site erythema
General disorders
MedDRA 25.1
Systematic Assessment
EG0001 affected30 at risk
EG0014 affected32 at risk
EG0024 affected31 at risk
EG003
Injection site induration
General disorders
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0011 affected32 at risk
EG0020 affected31 at risk
EG003
Injection site pain
General disorders
MedDRA 25.1
Systematic Assessment
EG0002 affected30 at risk
EG0011 affected32 at risk
EG0021 affected31 at risk
EG003
Injection site swelling
General disorders
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0010 affected32 at risk
EG0022 affected31 at risk
EG003
Pyrexia
General disorders
MedDRA 25.1
Systematic Assessment
EG0001 affected30 at risk
EG0013 affected32 at risk
EG0022 affected31 at risk
EG003
COVID-19
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0001 affected30 at risk
EG0012 affected32 at risk
EG0021 affected31 at risk
EG003
Folliculitis
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0012 affected32 at risk
EG0020 affected31 at risk
EG003
Influenza
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0012 affected32 at risk
EG0020 affected31 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0002 affected30 at risk
EG0011 affected32 at risk
EG0023 affected31 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0004 affected30 at risk
EG0013 affected32 at risk
EG0026 affected31 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0011 affected32 at risk
EG0020 affected31 at risk
EG003
Blood creatine phosphokinase increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0002 affected30 at risk
EG0014 affected32 at risk
EG0021 affected31 at risk
EG003
Blood trypsin increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0001 affected30 at risk
EG0012 affected32 at risk
EG0020 affected31 at risk
EG003
Protein urine present
Investigations
MedDRA 25.1
Systematic Assessment
EG0002 affected30 at risk
EG0011 affected32 at risk
EG0020 affected31 at risk
EG003
Tryptase increased
Investigations
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0013 affected32 at risk
EG0020 affected31 at risk
EG003
Hyperlipidaemia
Metabolism and nutrition disorders
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0010 affected32 at risk
EG0020 affected31 at risk
EG003
Hypertriglyceridaemia
Metabolism and nutrition disorders
MedDRA 25.1
Systematic Assessment
EG0001 affected30 at risk
EG0012 affected32 at risk
EG0020 affected31 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 25.1
Systematic Assessment
EG0001 affected30 at risk
EG0014 affected32 at risk
EG0021 affected31 at risk
EG003
Joint swelling
Musculoskeletal and connective tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0012 affected32 at risk
EG0020 affected31 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0010 affected32 at risk
EG0020 affected31 at risk
EG003
Headache
Nervous system disorders
MedDRA 25.1
Systematic Assessment
EG0001 affected30 at risk
EG0011 affected32 at risk
EG0021 affected31 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA 25.1
Systematic Assessment
EG0002 affected30 at risk
EG0011 affected32 at risk
EG0020 affected31 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA 25.1
Systematic Assessment
EG0001 affected30 at risk
EG0010 affected32 at risk
EG0021 affected31 at risk
EG003
Dermatitis contact
Skin and subcutaneous tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0011 affected32 at risk
EG0022 affected31 at risk
EG003
Erythema
Skin and subcutaneous tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0011 affected32 at risk
EG0020 affected31 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA 25.1
Systematic Assessment
EG0000 affected30 at risk
EG0011 affected32 at risk
EG0021 affected31 at risk
EG003
Psoriasis
Skin and subcutaneous tissue disorders
MedDRA 25.1
Systematic Assessment
EG0003 affected30 at risk
EG0014 affected32 at risk
EG0025 affected31 at risk
EG003
Pustular psoriasis
Skin and subcutaneous tissue disorders
MedDRA 25.1
Systematic Assessment
EG00016 affected30 at risk
EG0019 affected32 at risk
EG0029 affected31 at risk
EG003
Seborrhoeic dermatitis
Skin and subcutaneous tissue disorders
MedDRA 25.1
Systematic Assessment
EG0001 affected30 at risk
EG0012 affected32 at risk
EG0021 affected31 at risk
EG003
Urticaria
Skin and subcutaneous tissue disorders
MedDRA 25.1
Systematic Assessment
EG0002 affected30 at risk
EG0011 affected32 at risk
EG0021 affected31 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 4 weeks (i.e. at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44). The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
30
(NA to NA)
Insufficient number of participants with events.
OG003NA(NA to NA)Insufficient number of participants with events.
The generalized MCP-Mod procedure for time to event endpoints is based on the log hazard ratio of the active doses vs. placebo obtained via a Cox regression model on the time to first GPP flare.
OG000
OG001
OG002
OG003
A flat vs. non-flat dose-response relationship across the 3 doses of spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 4 different plausible dose-response patterns (linear, Emax 1, Emax 2 and exponential) while protecting the overall probability of type I error (one-sided alpha of 0.05).
MCP-Mod Emax2 model fit
Model assumption: 95% of the maximum effect is achieved at low dose.
0.002
Multiple contrast test
3.033
Other
The generalized MCP-Mod procedure for time to event endpoints is based on the log hazard ratio of the active doses vs. placebo obtained via a Cox regression model on the time to first GPP flare.
OG000
OG001
OG002
OG003
A flat vs. non-flat dose-response relationship across the 3 doses of spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 4 different plausible dose-response patterns (linear, Emax 1, Emax 2 and exponential) while protecting the overall probability of type I error (one-sided alpha of 0.05).
MCP-Mod Emax1 model fit
Model assumption: 70% of the maximum effect is achieved at low dose.
0.002
Multiple contrast test
3.088
Other
The generalized MCP-Mod procedure for time to event endpoints is based on the log hazard ratio of the active doses vs. placebo obtained via a Cox regression model on the time to first GPP flare.
OG000
OG001
OG002
OG003
A flat vs. non-flat dose-response relationship across the 3 doses of spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 4 different plausible dose-response patterns (linear, Emax 1, Emax 2 and exponential) while protecting the overall probability of type I error (one-sided alpha of 0.05).
MCP-Mod exponential model fit
Model assumption: 35% of the maximum effect is achieved at medium dose.
0.003
Multiple contrast test
2.977
Other
The generalized MCP-Mod procedure for time to event endpoints is based on the log hazard ratio of the active doses vs. placebo obtained via a Cox regression model on the time to first GPP flare.
OG000
OG002
Log Rank
0.0269
One-sided p-value was computed from the log-rank test stratified by use of systemic GPP medication at randomisation.
Threshold for statistical significance: one-sided p-value ≤ 0.01875.
Hazard Ratio (HR)
0.468
2-Sided
95
0.206
1.064
Hazard ratio and its 95% Confidence Interval are from Cox regression model stratified by use of systemic GPP medication at randomisation.
Superiority
Null hypothesis: Effect of spesolimab 300 mg every 12 weeks on prolonging the time to the first GPP flare up to week 48 ≤ Placebo.
OG000
OG003
Log Rank
0.0005
One-sided p-value is computed from the log-rank test stratified by use of systemic GPP medication at randomisation.
Threshold for statistical significance: One-sided p-value ≤0.0125.
Hazard Ratio (HR)
0.157
2-Sided
95
0.046
0.541
Hazard ratio and its 95% CI (confidence interval) are from Cox regression model stratified by use of systemic GPP medication at randomisation.
Superiority
Null hypothesis: Effect of spesolimab 300 mg every 4 weeks on prolonging the time to the first GPP flare up to week 48 ≤ Placebo.
Patients were subcutaneously (SC) injected on Day 1 of Week 1 a loading dose of solution for injection of placebo matching solution for injection of spesolimab followed by a maintenance treatment which consisted of a subcutaneous injection of solution for injection of placebo matching solution for injection of spesolimab every 4 weeks (i.e. on Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40 and 44).
The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 of flare (R1/D1) or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
OG001
Spesolimab SC Low Dose
Patients received on Day 1 of Week 1 a loading dose which consisted of two subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300mg) and two subcutaneous injections of placebo matching solution for injection of spesolimab. The loading dose was followed by a maintenance treatment which consisted of one SC injection of 150 mg of solution for injection of spesolimab and one SC injection of placebo matching solution for injection of spesolimab every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
OG002
Spesolimab SC Medium Dose
Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered subcutaneously every 12 weeks or every 4 weeks (intensified maintenance therapy).
OG003
Spesolimab SC High Dose
Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 4 weeks (i.e. at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44). The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
Units
Counts
Participants
OG00031
OG00131
OG00231
OG00330
Title
Denominators
Categories
Title
Measurements
OG0000.516(0.348 to 0.680)
OG0010.226(0.114 to 0.398)
OG0020.297(0.181 to 0.445)
OG0030.127(0.050 to 0.289)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Cochran-Mantel-Haenszel
0.0013
One-sided p-value was computed from the Cochran-Mantel-Haenszel test stratified by use of systemic GPP medication at randomisation.
one-sided alpha= 0.00625
Risk Difference (RD)
-0.390
2-Sided
95
-0.621
-0.159
Risk difference=Spesolimab high dose-Placebo.
Superiority
Null hypothesis: The proportion of patients who do not experience a GPP flare up to week 48 on BI 655130 300 mg every 4 weeks ≤ Placebo.
OG001
Spesolimab SC Low Dose
Patients received on Day 1 of Week 1 a loading dose which consisted of two subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300mg) and two subcutaneous injections of placebo matching solution for injection of spesolimab. The loading dose was followed by a maintenance treatment which consisted of one SC injection of 150 mg of solution for injection of spesolimab and one SC injection of placebo matching solution for injection of spesolimab every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
OG002
Spesolimab SC Medium Dose
Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered subcutaneously every 12 weeks or every 4 weeks (intensified maintenance therapy).
OG003
Spesolimab SC High Dose
Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 4 weeks (i.e. at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44). The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
Units
Counts
Participants
OG00031
OG00131
OG00231
OG00330
Title
Denominators
Categories
Title
Measurements
OG00016.0(4.0 to NA)Insufficient number of participants with events.
OG001NA(8.1 to NA)Insufficient number of participants with events.
OG002NA(8.7 to NA)Insufficient number of participants with events.
OG003NA(12.0 to NA)Insufficient number of participants with events.
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Hazard ratio and its 95% CI (confidence interval) are from Cox regression model stratified by use of systemic GPP medication at randomisation.
Log Rank
0.0134
One-sided p-value was computed from the log-rank test stratified by use of systemic GPP medication at randomisation.
one-sided alpha= 0.00625
Hazard Ratio (HR)
0.424
2-Sided
95
0.197
0.914
spesolimab high dose vs. Placebo
Superiority
Null hypothesis: Effect of BI 655130 300 mg every 4 weeks on prolonging the time to first worsening of PSS up to week 48 ≤ Placebo.
OG001
Spesolimab SC Low Dose
Patients received on Day 1 of Week 1 a loading dose which consisted of two subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300mg) and two subcutaneous injections of placebo matching solution for injection of spesolimab. The loading dose was followed by a maintenance treatment which consisted of one SC injection of 150 mg of solution for injection of spesolimab and one SC injection of placebo matching solution for injection of spesolimab every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
OG002
Spesolimab SC Medium Dose
Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered subcutaneously every 12 weeks or every 4 weeks (intensified maintenance therapy).
OG003
Spesolimab SC High Dose
Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 4 weeks (i.e. at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44). The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
Units
Counts
Participants
OG00031
OG00131
OG00231
OG00330
Title
Denominators
Categories
Title
Measurements
OG00016.0(4.0 to NA)Insufficient number of participants with events.
OG00135.8(8.1 to NA)Insufficient number of participants with events.
OG00249.3(8.7 to 49.3)
OG003NA(NA to NA)Insufficient number of participants with events.
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Hazard ratio and its 95% CI (confidence interval) are from Cox regression model stratified by use of systemic GPP medication at randomisation.
one-sided alpha= 0.00625
Log Rank
0.0010
One sided p-value was computed from the log-rank test stratified by use of systemic GPP medication at randomisation.
Hazard Ratio (HR)
0.259
2-Sided
95
0.109
0.620
spesolimab high dose vs. Placebo
Superiority
Null hypothesis: Effect of BI 655130 300 mg every 4 weeks on prolonging the time to the first worsening of DLQI up to week 48 ≤ Placebo.
OG001
Spesolimab SC Low Dose
Patients received on Day 1 of Week 1 a loading dose which consisted of two subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300mg) and two subcutaneous injections of placebo matching solution for injection of spesolimab. The loading dose was followed by a maintenance treatment which consisted of one SC injection of 150 mg of solution for injection of spesolimab and one SC injection of placebo matching solution for injection of spesolimab every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
OG002
Spesolimab SC Medium Dose
Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered subcutaneously every 12 weeks or every 4 weeks (intensified maintenance therapy).
OG003
Spesolimab SC High Dose
Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 4 weeks (i.e. at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44). The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
Units
Counts
Participants
OG00031
OG00131
OG00231
OG00330
Title
Denominators
Categories
Title
Measurements
OG0000.290(0.161 to 0.466)
OG0010.516(0.348 to 0.680)
OG0020.452(0.292 to 0.622)
OG0030.633(0.471 to 0.770)
OG001
Spesolimab SC Low Dose
Patients received on Day 1 of Week 1 a loading dose which consisted of two subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300mg) and two subcutaneous injections of placebo matching solution for injection of spesolimab. The loading dose was followed by a maintenance treatment which consisted of one SC injection of 150 mg of solution for injection of spesolimab and one SC injection of placebo matching solution for injection of spesolimab every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
OG002
Spesolimab SC Medium Dose
Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered subcutaneously every 12 weeks or every 4 weeks (intensified maintenance therapy).
OG003
Spesolimab SC High Dose
Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 4 weeks (i.e. at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44). The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
OG004
Spesolimab IV SD
This arm includes the patients who were randomized at study start in the arms "Placebo" or "Spesolimab SC low dose" or "Spesolimab SC medium dose" or "Spesolimab SC high dose" who took a single dose (SD) of rescue treatment of 900 milligram (mg) of spesolimab administered intravenously (IV) at Day 1 of flare (R1/D1) because of a GPP flare during the 48-week treatment randomised period.
OG005
Spesolimab IV DD
This arm includes the patients who were randomized at study start in the arms "Placebo" or "Spesolimab SC low dose" or "Spesolimab SC medium dose" or "Spesolimab SC high dose" who took two doses (DD) of rescue treatment of spesolimab each 900 milligram (mg) of spesolimab administered intravenously (IV) at Day 1 and at Day 8 of flare (R1/D1 and R3/D8) because of a GPP flare during the 48-week treatment randomised period.
OG006
Spesolimab OL SC
This arm includes the patients who were randomized at study start in the arms "Placebo" or "Spesolimab SC low dose" or "Spesolimab SC medium dose" or "Spesolimab SC high dose" who experienced a flare during the 48-week randomised treatment period and were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at either Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare and then followed by maintenance treatment which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).