Effisayil™ 1: A Study to Test Spesolimab (BI 655130) in Patients With a Flare-up of a Skin Disease Called Generalized Pustular Psoriasis

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03782792
• Collaborator: (none)
• Enrollment: 53
• Locations: 37
• Arms: 2
• Actual Duration (Months): 23.2
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To evaluate efficacy, safety, and tolerability of spesolimab (BI 655130) compared to placebo in patients with Generalized Pustular Psoriasis (GPP) presenting with an acute flare of moderate to severe intensity.

Condition or Disease	Intervention/Treatment	Phase
Generalized Pustular Psoriasis	Drug: Spesolimab; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 53 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Effisayil™ 1:Multi-center, Double-blind, Randomised, Placebo-controlled, Phase II Study to Evaluate Efficacy, Safety and Tolerability of a Single Intravenous Dose of Spesolimab (BI 655130) in Patients With Generalized Pustular Psoriasis (GPP) Presenting With an Acute Flare of Moderate to Severe Intensity
• Actual Study Start Date: Jan 31, 2019
• Actual Primary Completion Date: Sep 23, 2020
• Actual Study Completion Date: Jan 5, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Spesolimab	Drug: Spesolimab; Solution for infusion; Other Names: BI 655130
Experimental: Placebo	Drug: Placebo; Solution for infusion

Outcome Measures

Primary Outcome Measures

1. Proportion of Patients With a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) Pustulation Subscore of 0 Indicating no Visible Pustules at Week 1 [At Week 1.]

   The Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) relies on clinical assessment of the Generalized Pustular Psoriasis (GPP) patient's skin presentation. The investigator (or qualified site personnel) scored the erythema, pustules, and scaling of all GPP lesions from 0 to 4. The GPPGA pustulation subscore ranges from 0 to 4 where: 0 = clear; = almost clear; = mild: = moderate; = severe. A lower GPPGA pustulation subscore indicates a better outcome. A GPPGA pustulation subscore of 0 means no visible pustules. The proportion of patients who achieved a GPPGA pustulation subscore of 0 at Week 1 is reported.

Secondary Outcome Measures

1. Key Secondary: Proportion of Patients With a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) Score of 0 or 1 at Week 1 [At Week 1.]

   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. A lower GPPGA score indicates a better outcome, with 0 being clear and 1 being almost clear. The proportion of patients with a GPPGA score of 0 or 1 at Week 1 is reported.

2. Proportion of Patients With a Psoriasis Area and Severity Index for Generalized Pustular Psoriasis (GPPASI) 75 at Week 4 [At Week 4.]

   Generalized Pustular Psoriasis Area and Severity Index (GPPASI) provides a numeric scoring for a patient's overall Generalized Pustular Psoriasis (GPP) disease state, ranging from 0 to 72. It is a linear combination of percent of surface area of skin affected by erythema, pustules, and scaling and the severity of erythema, pustules, and scaling (desquamation) over 4 body regions (head, trunk, upper limbs and lower limbs). A higher score indicates a worse disease state, while a score of 0 indicates no disease. GPPASI 75 is based on the percent reduction from baseline, generally summarized as a dichotomous outcome based on achieving over an 75% reduction. Proportion of patients with GPPASI 75 at Week 4 is reported.

3. Change From Baseline in Pain Visual Analog Scale (VAS) Score at Week 4 [Baseline and at Week 4.]

   The pain Visual Analogue Scale (VAS) is a participant-administered single-item scale designed to measure skin pain intensity from generalized pustular psoriasis (GPP) using a 100 millimeter (mm) horizontal VAS. Overall severity of participant's skin pain from GPP is indicated by placing a single mark on the horizontal 100 mm scale from 0 mm (no pain) to 100 mm (pain as bad as one can imagine). Change from baseline was calculated by subtracting the VAS score at baseline from the VAS score at Week 4. A negative change indicates an improvement from baseline. Death, any use of escape medication, OL Spesolimab at Day 8, or rescue medication with Spesolimab after Day 8, prior to observing the endpoint was considered to reflect a failure to achieve the endpoint outcome, i.e. non-response (NR). NR is not a missing value but the worst possible outcome of the endpoint. For example, if the achieved data is (NR, NR, NR, NR, NR, NR, 2, 3, 3, 3, 5) then Q1 is NR, median is NR and Q3 is 3.

4. Change From Baseline in Psoriasis Symptom Scale (PSS) Score at Week 4 [Baseline and at Week 4.]

   PSS is a 4-item patient-reported outcome instrument that assesses the severity of psoriasis symptoms in moderate to severe psoriasis patients. The symptoms included are: pain, redness, itching, and burning. The symptom severity was assessed using a 5 point scale ranging from 0 to 4 where 0=none, 1=mild, 2=moderate, 3=severe, 4=very severe. The symptom scores are added to an unweighted total score (range: 0 to 16). A lower PSS score indicates a better outcome. Change from baseline =PSS score at Week 4 - PSS score at baseline. Death, any use of escape medication, OL Spesolimab at Day 8, or rescue medication with Spesolimab after Day 8, prior to observing the endpoint was considered to reflect a failure to achieve the endpoint outcome, i.e. non-response (NR). NR is not a missing value but the worst possible outcome of the endpoint. For example, if the achieved data is (NR, NR, NR, NR, NR, NR, 2, 3, 3, 3, 5) then Q1 is NR, median is NR and Q3 is 3.

5. Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Score at Week 4 [Baseline and at Week 4.]

   The FACIT-Fatigue is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Each items is scored from 0 to 4. Score range is 0 (extreme fatigue)-52 (no fatigue). Change from baseline=FACIT Fatigue score at Week 4- FACIT-Fatigue score at baseline. Death, any use of escape medication, OL Spesolimab at Day 8, or rescue medication with Spesolimab after Day 8, prior to observing the endpoint was considered to reflect a failure to achieve the endpoint outcome, i.e. non-response (NR). NR is not a missing value but the worst possible outcome of the endpoint. For example, if the achieved data is s (NR, NR, NR, NR, NR, NR, 2, 3, 3, 3, 5) then Q1 is NR, median is NR and Q3 is 3.

6. Proportion of Patients With a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) Score of 0 or 1 at Week 4 [At Week 4.]

   GPPGA relied on clinical assessment of the Generalized Pustular Psoriasis (GPP) patient's skin presentation. The GPPGA total score is 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 scores 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. A lower GPPGA score indicates a better outcome, with 0 being clear and 1 being almost clear. The proportion of participants with a GPPGA score of 0 or 1 at Week 4 is reported.

7. Proportion of Patients With a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) Pustulation Sub-score of 0 Indicating no Visible Pustules at Week 4 [At Week 4.]

   The Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) relies on clinical assessment of the Generalized Pustular Psoriasis (GPP) patient's skin presentation. The investigator (or qualified site personnel) scores the erythema, pustules, and scaling of all GPP lesions from 0 to 4. The GPPGA pustulation subscore ranges from 0 to 4 where: 0 = clear; = almost clear; = mild: = moderate; = severe. A lower GPPGA pustulation subscore indicates a better outcome. The proportion of patients who achieved a GPPGA pustulation subscore of 0 at Week 1 is reported.

8. Proportion of Patients With a Generalized Pustular Psoriasis Area and Severity Index (GPPASI) 50 at Week 4 [At Week 4.]

   Generalized Pustular Psoriasis Area and Severity Index (GPPASI) provides a numeric scoring for a patient's overall Generalized Pustular Psoriasis (GPP) disease state, ranging from 0 to 72. It is a linear combination of percent of surface area of skin affected by erythema, pustules, and scaling and the severity of erythema, pustules, and scaling (desquamation) over 4 body regions (head, trunk, upper limbs and lower limbs). A higher score indicates a worse disease state, while a score of 0 indicates no disease. GPPASI 50 is based on the percent reduction from baseline, generally summarized as a dichotomous outcome based on achieving over an 50 % reduction. Proportion of patients with GPPASI 50 at Week 4 is reported.

9. Percent Change in Generalized Pustular Psoriasis Area and Severity Index (GPPASI) From Baseline at Week 4 [Baseline and at Week 4.]

   GPPASI provides a numeric scoring for a patient's overall Generalized Pustular Psoriasis (GPP) disease state, ranging from 0 (no disease) to 72 (worse disease state). It is a linear combination of percent of surface area of skin affected by erythema, pustules, and scaling and the severity of erythema, pustules, and scaling (desquamation) over 4 body regions (head, trunk, upper limbs and lower limbs). %GPPASI change from baseline=(GPPASI at Week 4-GPPASI at baseline) *100/(GPPASI at baseline). Death, any use of escape medication, OL Spesolimab at Day 8, or rescue medication with Spesolimab after Day 8, prior to observing the endpoint was considered to reflect a failure to achieve the endpoint outcome, i.e. non-response (NR).NR is not a missing value but the worst possible outcome of the endpoint. For example, if the achieved data is (NR, NR, NR, NR, NR, NR, 2, 3, 3, 3, 5) then Q1 is NR, median is NR and Q3 is 3. Planned statistical analysis were not performed due to lack of valid data.

10. Proportion of Patients With a Generalized Pustular Psoriasis Area and Severity Index (GPPASI) 50 at Week 1 [At Week 1.]

    Generalized Pustular Psoriasis Area and Severity Index (GPPASI) provides a numeric scoring for a patient's overall Generalized Pustular Psoriasis (GPP) disease state, ranging from 0 to 72. It is a linear combination of percent of surface area of skin affected by erythema, pustules, and scaling and the severity of erythema, pustules, and scaling (desquamation) over 4 body regions (head, trunk, upper limbs and lower limbs). A higher score indicates a worse disease state, while a score of 0 indicates no disease. GPPASI 50 is based on the percent reduction from baseline, generally summarized as a dichotomous outcome based on achieving over an 50 % reduction. Proportion of patients with GPPASI 50 at Week 1 is reported.

11. Percent Change in Generalized Pustular Psoriasis Area and Severity Index (GPPASI) From Baseline at Week 1 [At Week 1.]

    Generalized Pustular Psoriasis Area and Severity Index (GPPASI) provides a numeric scoring for a patient's overall Generalized Pustular Psoriasis (GPP) disease state, ranging from 0 to 72. It is a linear combination of percent of surface area of skin affected by erythema, pustules, and scaling and the severity of erythema, pustules, and scaling (desquamation) over 4 body regions (head, trunk, upper limbs and lower limbs). A higher score indicates a worse disease state, while a score of 0 indicates no disease. The percent change from baseline at Week 1 is calculated as: % GPPASI change from baseline = (GPPASI at Week 1 - GPPASI at baseline) *100/GPPASI at baseline. If % GPPASI change from baseline is positive, it means the disease is becoming worse.

12. Occurrence of Treatment Emergent Adverse Events (TEAEs) up to Week 1 [From start of treatment until Day 7, up to 7 days.]

    TEAEs were all Adverse Events (AEs) occurring between start of treatment and Day 8 (Day 8 excluded). AEs that started before first drug intake and deteriorated under treatment were also considered as 'treatment-emergent'. The exposure-adjusted incidence rate was calculated as: Incidence rate [1/100 patients-years] = 100 × number of patients with AE / Total AE specific time at risk [patient-years] where: Time at risk [patient-years] = (date of onset of TEAE - study drug start date + 1) /365.25

13. Number of Patients With Treatment Emergent Adverse Events (TEAEs) up to Week 1 [From start of treatment until Day 7, up to 7 days.]

    TEAEs were all Adverse Events (AEs) occurring between start of treatment and Day 8 (Day 8 excluded). AEs that started before first drug intake and deteriorated under treatment were also considered as 'treatment-emergent'.

14. Occurrence of Treatment Emergent Adverse Events (TEAEs) Within the Treatment Phase [From start of treatment until end of the residual effect period (REP) but censored at any use of open label spesolimab, up to 16 weeks.]

    TEAEs were all Adverse Events (AEs) occurring between start of treatment and end of the residual effect period (REP) (16 weeks). AEs that started before first drug intake and deteriorated under treatment were also considered as 'treatment-emergent'. The exposure-adjusted incidence rate was calculated as: Incidence rate [1/100 patients-years] = 100 × number of patients with AE / Total AE specific time at risk [patient-years] where Time at risk where: Time at risk [patient-years] = (date of onset of TEAE - study drug start date + 1) /365.25 If, for a patient, the selected TEAE did not occur then the time at risk was censored at min Date of death For patients who did not roll over into the Open Label Extension (OLE) study: last contact date Visit14/15 For patients who rolled over into the OLE study: the 1st dose in the OLE study Drug stop date + 112 days Date of Day 8 if OL spesolimab was given Date of rescue medication if spesolimab was given.

15. Number of Patients With Treatment Emergent Adverse Events (TEAEs) Within the Treatment Phase [From start of treatment until end of the residual effect period (REP) but censored at any use of open label spesolimab, up to 16 weeks.]

    TEAEs were all Adverse Events (AEs) occurring between start of treatment and end of the residual effect period (REP) (16 weeks). AEs that started before first drug intake and deteriorated under treatment were also considered as 'treatment-emergent'.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with GPPGA of 0 or 1 and a known and documented history of GPP per European Rare And Severe Psoriasis Expert Network (ERASPEN) criteria regardless of IL36RN mutation status, with previous evidence of fever, and/or asthenia, and/or myalgia, and/or elevated C-reactive protein, and/or leucocytosis with peripheral blood neutrophilia (above ULN) OR

-- Patients with an acute flare of moderate to severe intensity meeting the (ERASPEN) criteria of GPP with a known and documented history of GPP (per ERASPEN criteria) regardless of IL36RN mutation status, with previous evidence of fever, and/or asthenia, and/or myalgia, and/or elevated C-reactive protein, and/or leucocytosis with peripheral blood neutrophilia (above ULN)

• Male or female patients, aged 18 to 75 years at screening.

• Signed and dated written informed consent prior to admission to the study in accordance with ICH GCP and local legislation prior to start of any screening procedures.

• Women of childbearing potential 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. Note: A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. Tubal ligation is not a method of permanent sterilization. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause

• Further inclusion criteria apply

Exclusion Criteria:

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

• Patients with primary erythrodermic psoriasis vulgaris.

• Patients with primary plaque psoriasis vulgaris without presence of pustules or with pustules that are restricted to psoriatic plaques.

• Drug-triggered Acute Generalized Exanthematous Pustulosis (AGEP).

• Immediate life-threatening flare of GPP or requiring intensive care treatment, according to the investigator's judgement. Life-threatening complications mainly include, but are not limited to, cardiovascular/cytokine driven shock, pulmonary distress syndrome, or renal failure.

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

• Further exclusion criteria apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	University of Miami	Miami	Florida	United States	33125
3	University of South Florida	Tampa	Florida	United States	33612
4	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
5	The First Hospital of Dalian Medical University	Dalian		China	116011
6	2nd Affiliated Hosp Zhejiang University College of Medical	Hangzhou		China	310009
7	Shanghai Skin Disease Hospital	Shanghai		China	200000
8	Huashan Hospital, Fudan University	Shanghai		China	200040
9	Tianjin Medical University General Hospital	Tianjin		China	30052
10	HOP Saint-André	Bordeaux		France	33000
11	HOP Saint-Louis	Paris		France	75010
12	HOP Robert Debré	Reims		France	51092
13	Charité - Universitätsmedizin Berlin	Berlin		Germany	10117
14	Universitätsklinikum Bonn AöR	Bonn		Germany	53127
15	Universitätsklinikum Essen AöR	Essen		Germany	45147
16	Klinikum der Universität München - Campus Innenstadt	München		Germany	80337
17	Nagoya City University Hospital	Aichi, Nagoya		Japan	467-8602
18	Fukuoka University Hospital	Fukuoka, Fukuoka		Japan	814-0180
19	Asahikawa Medical University Hospital	Hokkaido, Asahikawa		Japan	078-8510
20	Tohoku University Hospital	Miyagi, Sendai		Japan	980-8574
21	Tokyo Medical University Hachioji Medical Center	Tokyo, Hachioji		Japan	193-0998
22	Tokyo Medical University Hospital	Tokyo, Shinjuku-ku		Japan	160-0023
23	Severance Hospital	Seoul		Korea, Republic of	03722
24	Hospital Sultanah Aminah	Johor Bahru		Malaysia	80100
25	Hospital Sultan Ismail	Johor Bahru		Malaysia	81100
26	Hospital Kuala Lumpur	Kuala Lumpur		Malaysia	50586
27	Hospital Pakar Sultanah Fatimah	Muar		Malaysia	84000
28	Hospital Raja Permaisuri Bainun	Negeri Perak/Ipoh		Malaysia	30450
29	Hospital Pulau Pinang	Pulau Pinang		Malaysia	10990
30	Hospital Selayang	Selangor		Malaysia	68100
31	National University Hospital	Singapore		Singapore	119074
32	University Hospital of Lausanne	Lausanne		Switzerland	1011
33	National Taiwan University Hospital	Taipei		Taiwan	10016
34	Ramathibodi Hospital	Ratchatewi, Bangkok		Thailand	10400
35	Farhat Hached Hospital	Sousse		Tunisia	4000
36	Hedi Chaker Hospital, Department of Dermatology	Tunisia		Tunisia	1053
37	La Rabta Hospital	Tunis		Tunisia	1007

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jun 26, 2020
• Statistical Analysis Plan - Dec 22, 2020

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT03782792
• Other Study ID Numbers: 1368-0013; 2017-004231-37
• First Posted: Dec 20, 2018
• Last Update Posted: Mar 9, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Psoriasis

Study Results

Participant Flow

Recruitment Details	This was a randomized, placebo-controlled, double-blind, parallel-group, single-dose trial with 2 treatment groups (spesolimab and placebo) to evaluate efficacy, tolerability, and safety of spesolimab (BI 655130) compared with placebo in patients with Generalized Pustular Psoriasis (GPP) presenting with an acute flare of moderate to severe intensity.
Pre-assignment Detail	All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly 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.

Arm/Group Title	Placebo	Spesolimab 900 mg i.v SD
Arm/Group Description	Patients received intravenously (i.v.) solution for infusion containing 900 milligram (mg) of placebo to spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.	Patients received intravenously (i.v.) a single dose (SD) of solution for infusion containing 900 milligram (mg) of spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.
Period Title: Overall Study
STARTED	18	35
Received Open Label Treatment With Spesolimab at Wk1/D8	15	12
Received Rescue Treatment With Spesolimab After Wk1	2	4
COMPLETED	17	32
NOT COMPLETED	1	3

Baseline Characteristics

Arm/Group Title	Placebo	Spesolimab 900 mg i.v SD	Total
Arm/Group Description	Patients received intravenously (i.v.) solution for infusion containing 900 milligram (mg) of placebo to spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.	Patients received intravenously (i.v.) a single dose (SD) of solution for infusion containing 900 milligram (mg) of spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.	Total of all reporting groups
Overall Participants	18	35	53
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	42.6 (8.4)	43.2 (12.1)	43.0 (10.9)
Sex: Female, Male (Count of Participants)
Female	15 83.3%	21 60%	36 67.9%
Male	3 16.7%	14 40%	17 32.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	18 100%	35 100%	53 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	13 72.2%	16 45.7%	29 54.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	5 27.8%	19 54.3%	24 45.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients With a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) Pustulation Subscore of 0 Indicating no Visible Pustules at Week 1
Description	The Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) relies on clinical assessment of the Generalized Pustular Psoriasis (GPP) patient's skin presentation. The investigator (or qualified site personnel) scored the erythema, pustules, and scaling of all GPP lesions from 0 to 4. The GPPGA pustulation subscore ranges from 0 to 4 where: 0 = clear; = almost clear; = mild: = moderate; = severe. A lower GPPGA pustulation subscore indicates a better outcome. A GPPGA pustulation subscore of 0 means no visible pustules. The proportion of patients who achieved a GPPGA pustulation subscore of 0 at Week 1 is reported.
Time Frame	At Week 1.

Outcome Measure Data

Analysis Population Description

Randomized Set (RS) (via estimand EN-NRI): This patient set included all randomized patients. EN = Any assessments after death, or any use of escape medication due to disease worsening (defined as worsening of clinical status or GPP skin and/or systemic symptoms as defined by the investigator) prior to Week 1 were considered to represent a non-response. NRI = Non-response imputation for any missing data.

Arm/Group Title	Placebo	Spesolimab 900 mg i.v SD
Arm/Group Description	Patients received intravenously (i.v.) solution for infusion containing 900 milligram (mg) of placebo to spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.	Patients received intravenously (i.v.) a single dose (SD) of solution for infusion containing 900 milligram (mg) of spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.
Measure Participants	18	35
Number (95% Confidence Interval) [Proportion of participants]	0.056 0.3%	0.543 1.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Spesolimab 900 mg i.v SD
	Comments	The Suissa-Shuster Z-pooled test was implemented to test the treatment effect on the primary endpoint on the RS (estimand EN) at a 1-sided, alpha level of 0.025. Confidence intervals (95%) around the risk difference were produced using the Chan and Zhang method.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments	One-sided P Value.
	Method	Suissa-Shuster Z-pooled test
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.487
	Confidence Interval	(2-Sided) 95%; 0.215 to 0.672
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference=Response rate of spesolimab - response rate of placebo.

2. Secondary Outcome

Title	Key Secondary: Proportion of Patients With a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) Score of 0 or 1 at Week 1
Description	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. A lower GPPGA score indicates a better outcome, with 0 being clear and 1 being almost clear. The proportion of patients with a GPPGA score of 0 or 1 at Week 1 is reported.
Time Frame	At Week 1.

Outcome Measure Data

Analysis Population Description

Randomized Set (RS) (via estimand EN-NRI): This patient set included all randomized patients. EN =Any assessments after death, or any use of escape medication due to disease worsening (defined as worsening of clinical status or GPP skin and/or systemic symptoms as defined by the investigator) prior to Week 1 were considered to represent a non-response. NRI = Non-response imputation for any missing data.

Arm/Group Title	Placebo	Spesolimab 900 mg i.v SD
Arm/Group Description	Patients received intravenously (i.v.) solution for infusion containing 900 milligram (mg) of placebo to spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.	Patients received intravenously (i.v.) a single dose (SD) of solution for infusion containing 900 milligram (mg) of spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.
Measure Participants	18	35
Number (95% Confidence Interval) [Proportion of participants]	0.111 0.6%	0.429 1.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Spesolimab 900 mg i.v SD
	Comments	The Suissa-Shuster Z-pooled test was implemented to test the treatment effect on the RS (estimand EN) at a 1-sided, alpha level of 0.025. Confidence intervals (95%) around the risk difference were produced using the Chan and Zhang method.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0118
	Comments	One-sided P Value.
	Method	Suissa-Shuster Z-pooled test
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.317
	Confidence Interval	(2-Sided) 95%; 0.022 to 0.527
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference=Response rate of spesolimab - response rate of placebo.

3. Secondary Outcome

Title	Proportion of Patients With a Psoriasis Area and Severity Index for Generalized Pustular Psoriasis (GPPASI) 75 at Week 4
Description	Generalized Pustular Psoriasis Area and Severity Index (GPPASI) provides a numeric scoring for a patient's overall Generalized Pustular Psoriasis (GPP) disease state, ranging from 0 to 72. It is a linear combination of percent of surface area of skin affected by erythema, pustules, and scaling and the severity of erythema, pustules, and scaling (desquamation) over 4 body regions (head, trunk, upper limbs and lower limbs). A higher score indicates a worse disease state, while a score of 0 indicates no disease. GPPASI 75 is based on the percent reduction from baseline, generally summarized as a dichotomous outcome based on achieving over an 75% reduction. Proportion of patients with GPPASI 75 at Week 4 is reported.
Time Frame	At Week 4.

Outcome Measure Data

Analysis Population Description

Randomized Set (RS) (via estimand EN-NRI): This patient set included all randomized patients. EN = Any assessments after death, or any use of escape medication before or after Day 8, open-label spesolimab at Day 8, or rescue medication with spesolimab after Day 8 were considered to represent a non-response. NRI = Non-response imputation for any missing data.

Arm/Group Title	Placebo	Spesolimab 900 mg i.v SD
Arm/Group Description	Patients received intravenously (i.v.) solution for infusion containing 900 milligram (mg) of placebo to spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.	Patients received intravenously (i.v.) a single dose (SD) of solution for infusion containing 900 milligram (mg) of spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.
Measure Participants	18	35
Number (95% Confidence Interval) [Proportion of participants]	0.111 0.6%	0.457 1.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Spesolimab 900 mg i.v SD
	Comments	The Suissa-Shuster Z-pooled test was implemented to test the treatment effect on the RS (estimand EN) at a 1-sided, alpha level of 0.025. Confidence intervals (95%) around the risk difference were produced using the Chan and Zhang method.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0081
	Comments	One-sided P Value.
	Method	Suissa-Shuster Z-pooled test
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.346
	Confidence Interval	(2-Sided) 95%; 0.058 to 0.554
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference=Response rate of spesolimab - response rate of placebo.

4. Secondary Outcome

Title	Change From Baseline in Pain Visual Analog Scale (VAS) Score at Week 4
Description	The pain Visual Analogue Scale (VAS) is a participant-administered single-item scale designed to measure skin pain intensity from generalized pustular psoriasis (GPP) using a 100 millimeter (mm) horizontal VAS. Overall severity of participant's skin pain from GPP is indicated by placing a single mark on the horizontal 100 mm scale from 0 mm (no pain) to 100 mm (pain as bad as one can imagine). Change from baseline was calculated by subtracting the VAS score at baseline from the VAS score at Week 4. A negative change indicates an improvement from baseline. Death, any use of escape medication, OL Spesolimab at Day 8, or rescue medication with Spesolimab after Day 8, prior to observing the endpoint was considered to reflect a failure to achieve the endpoint outcome, i.e. non-response (NR). NR is not a missing value but the worst possible outcome of the endpoint. For example, if the achieved data is (NR, NR, NR, NR, NR, NR, 2, 3, 3, 3, 5) then Q1 is NR, median is NR and Q3 is 3.
Time Frame	Baseline and at Week 4.

Outcome Measure Data

Analysis Population Description

Randomized Set (RS) (via estimand EN-LOCF): This patient set included all randomized patients. EN = Death or any use of escape medication before or after Day 8, open-label spesolimab at Day 8, or rescue medication with spesolimab after Day 8 were considered to represent a non-response and assigned with the worst possible outcomes in rank analysis. LOCF = last observation carried forward imputation for any missing data.

Arm/Group Title	Placebo	Spesolimab 900 mg i.v SD
Arm/Group Description	Patients received intravenously (i.v.) solution for infusion containing 900 milligram (mg) of placebo to spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.	Patients received intravenously (i.v.) a single dose (SD) of solution for infusion containing 900 milligram (mg) of spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.
Measure Participants	18	35
Median (Inter-Quartile Range) [Units on a scale]	NA	-22.45

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Spesolimab 900 mg i.v SD
	Comments	The effect of spesolimab was evaluated by a Wilcoxon rank test using the RS. Any assessments after death, the use of escape medication (before or after Day 8), open label spesolimab on Day 8, or rescue medication with spesolimab after Day 8 were assigned worst ranks for the testing. Missing data at Week 4 were imputed and handled via assessment of ranks.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0012
	Comments	One-sided P Value.
	Method	Wilcoxon (Mann-Whitney)
	Comments
Other Statistical Analysis		The difference between treatments, based on the RS, using a modified Hodges-Lehmann (HL) estimate of the median difference and 95% Confidence Intervals could not be calculated due to lack of valid data.

5. Secondary Outcome

Title	Change From Baseline in Psoriasis Symptom Scale (PSS) Score at Week 4
Description	PSS is a 4-item patient-reported outcome instrument that assesses the severity of psoriasis symptoms in moderate to severe psoriasis patients. The symptoms included are: pain, redness, itching, and burning. The symptom severity was assessed using a 5 point scale ranging from 0 to 4 where 0=none, 1=mild, 2=moderate, 3=severe, 4=very severe. The symptom scores are added to an unweighted total score (range: 0 to 16). A lower PSS score indicates a better outcome. Change from baseline =PSS score at Week 4 - PSS score at baseline. Death, any use of escape medication, OL Spesolimab at Day 8, or rescue medication with Spesolimab after Day 8, prior to observing the endpoint was considered to reflect a failure to achieve the endpoint outcome, i.e. non-response (NR). NR is not a missing value but the worst possible outcome of the endpoint. For example, if the achieved data is (NR, NR, NR, NR, NR, NR, 2, 3, 3, 3, 5) then Q1 is NR, median is NR and Q3 is 3.
Time Frame	Baseline and at Week 4.

Outcome Measure Data

Analysis Population Description

Randomized Set (RS) (via estimand EN-LOCF): This patient set included all randomized patients. EN = Any assessments after death, or any use of escape medication before or after Day 8, open-label spesolimab at Day 8, or rescue medication with spesolimab after Day 8 were considered to represent a non-response and assigned with the worst possible outcomes in rank analysis. LOCF = last observation carried forward imputation for any missing data.

Arm/Group Title	Placebo	Spesolimab 900 mg i.v SD
Arm/Group Description	Patients received intravenously (i.v.) solution for infusion containing 900 milligram (mg) of placebo to spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.	Patients received intravenously (i.v.) a single dose (SD) of solution for infusion containing 900 milligram (mg) of spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.
Measure Participants	18	35
Median (Inter-Quartile Range) [Units on a scale]	NA	-2.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Spesolimab 900 mg i.v SD
	Comments	The effect of spesolimab was evaluated by a Wilcoxon rank test using the RS. Any assessments after death, the use of escape medication (before or after Day 8), open label spesolimab on Day 8, or rescue medication with spesolimab after Day 8 were assigned worst ranks for the testing. Missing data at Week 4 were imputed and handled via assessment of ranks.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0044
	Comments	One-sided P Value.
	Method	Wilcoxon (Mann-Whitney)
	Comments
Other Statistical Analysis		The difference between treatments, based on the RS, using a modified Hodges-Lehmann (HL) estimate of the median difference and 95% Confidence Intervals could not be calculated due to lack of valid data.

6. Secondary Outcome

Title	Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Score at Week 4
Description	The FACIT-Fatigue is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Each items is scored from 0 to 4. Score range is 0 (extreme fatigue)-52 (no fatigue). Change from baseline=FACIT Fatigue score at Week 4- FACIT-Fatigue score at baseline. Death, any use of escape medication, OL Spesolimab at Day 8, or rescue medication with Spesolimab after Day 8, prior to observing the endpoint was considered to reflect a failure to achieve the endpoint outcome, i.e. non-response (NR). NR is not a missing value but the worst possible outcome of the endpoint. For example, if the achieved data is s (NR, NR, NR, NR, NR, NR, 2, 3, 3, 3, 5) then Q1 is NR, median is NR and Q3 is 3.
Time Frame	Baseline and at Week 4.

Outcome Measure Data

Analysis Population Description

Randomized Set (RS) (via estimand EN-LOCF): This patient set included all randomized patients. EN = Any assessments after death, or any use of escape medication before or after Day 8, open-label spesolimab at Day 8, or rescue medication with spesolimab after Day 8 were considered to represent a non-response and assigned with the worst possible outcomes in rank analysis. LOCF = last observation carried forward imputation for any missing data.

Arm/Group Title	Placebo	Spesolimab 900 mg i.v SD
Arm/Group Description	Patients received intravenously (i.v.) solution for infusion containing 900 milligram (mg) of placebo to spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.	Patients received intravenously (i.v.) a single dose (SD) of solution for infusion containing 900 milligram (mg) of spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.
Measure Participants	18	35
Median (Inter-Quartile Range) [Units on a scale]	NA	3.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Spesolimab 900 mg i.v SD
	Comments	The effect of spesolimab was evaluated by a Wilcoxon rank test using the RS. Any assessments after death, the use of escape medication (before or after Day 8), open label spesolimab on Day 8, or rescue medication with spesolimab after Day 8 were assigned worst ranks for the testing. Missing data at Week 4 were imputed and handled via assessment of ranks.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0012
	Comments	One-sided P Value.
	Method	Wilcoxon (Mann-Whitney)
	Comments
Other Statistical Analysis		The difference between treatments, based on the RS, using a modified Hodges-Lehmann (HL) estimate of the median difference and 95% Confidence Intervals could not be calculated due to lack of valid data.

7. Secondary Outcome

Title	Proportion of Patients With a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) Score of 0 or 1 at Week 4
Description	GPPGA relied on clinical assessment of the Generalized Pustular Psoriasis (GPP) patient's skin presentation. The GPPGA total score is 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 scores 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. A lower GPPGA score indicates a better outcome, with 0 being clear and 1 being almost clear. The proportion of participants with a GPPGA score of 0 or 1 at Week 4 is reported.
Time Frame	At Week 4.

Outcome Measure Data

Analysis Population Description

Randomized Set (RS) (via estimand EN-NRI): This patient set included all randomized patients. EN = Any assessments after death, or the use of escape medication (before or after Day 8), or open-label spesolimab at Day 8, or rescue medication with spesolimab after Day 8, was considered a failure to achieve the endpoint outcome (i.e. non-response). NRI = Non-response imputation for any missing data.

Arm/Group Title	Placebo	Spesolimab 900 mg i.v SD
Arm/Group Description	Patients received intravenously (i.v.) solution for infusion containing 900 milligram (mg) of placebo to spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.	Patients received intravenously (i.v.) a single dose (SD) of solution for infusion containing 900 milligram (mg) of spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.
Measure Participants	18	35
Number (95% Confidence Interval) [Proportion of participants]	0.111 0.6%	0.486 1.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Spesolimab 900 mg i.v SD
	Comments	Confidence intervals (95%) around the risk difference were produced using the Chan and Zhang method.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.375
	Confidence Interval	(2-Sided) 95%; 0.058 to 0.581
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference=Response rate of spesolimab - response rate of placebo.

8. Secondary Outcome

Title	Proportion of Patients With a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) Pustulation Sub-score of 0 Indicating no Visible Pustules at Week 4
Description	The Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) relies on clinical assessment of the Generalized Pustular Psoriasis (GPP) patient's skin presentation. The investigator (or qualified site personnel) scores the erythema, pustules, and scaling of all GPP lesions from 0 to 4. The GPPGA pustulation subscore ranges from 0 to 4 where: 0 = clear; = almost clear; = mild: = moderate; = severe. A lower GPPGA pustulation subscore indicates a better outcome. The proportion of patients who achieved a GPPGA pustulation subscore of 0 at Week 1 is reported.
Time Frame	At Week 4.

Outcome Measure Data

Analysis Population Description

Randomized Set (RS) (via estimand EN-NRI): This patient set included all randomized patients. EN = Any assessments after death, or the use of escape medication (before or after Day 8), or open-label spesolimab at Day 8, or rescue medication with spesolimab after Day 8, was considered a failure to achieve the endpoint outcome (i.e. non-response). NRI = Non-response imputation for any missing data.

Arm/Group Title	Placebo	Spesolimab 900 mg i.v SD
Arm/Group Description	Patients received intravenously (i.v.) solution for infusion containing 900 milligram (mg) of placebo to spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.	Patients received intravenously (i.v.) a single dose (SD) of solution for infusion containing 900 milligram (mg) of spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.
Measure Participants	18	35
Number (95% Confidence Interval) [Proportion of participants]	0.111 0.6%	0.514 1.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Spesolimab 900 mg i.v SD
	Comments	Confidence intervals (95%) around the risk difference were produced using the Chan and Zhang method.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.403
	Confidence Interval	(2-Sided) 95%; 0.096 to 0.607
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference=Response rate of spesolimab - response rate of placebo.

9. Secondary Outcome

Title	Proportion of Patients With a Generalized Pustular Psoriasis Area and Severity Index (GPPASI) 50 at Week 4
Description	Generalized Pustular Psoriasis Area and Severity Index (GPPASI) provides a numeric scoring for a patient's overall Generalized Pustular Psoriasis (GPP) disease state, ranging from 0 to 72. It is a linear combination of percent of surface area of skin affected by erythema, pustules, and scaling and the severity of erythema, pustules, and scaling (desquamation) over 4 body regions (head, trunk, upper limbs and lower limbs). A higher score indicates a worse disease state, while a score of 0 indicates no disease. GPPASI 50 is based on the percent reduction from baseline, generally summarized as a dichotomous outcome based on achieving over an 50 % reduction. Proportion of patients with GPPASI 50 at Week 4 is reported.
Time Frame	At Week 4.

Outcome Measure Data

Analysis Population Description

Randomized Set (RS) (via estimand EN-NRI): This patient set included all randomized patients. EN = Any assessments after death, or the use of escape medication (before or after Day 8), or open-label spesolimab at Day 8, or rescue medication with spesolimab after Day 8, was considered a failure to achieve the endpoint outcome (i.e. non-response). NRI = Non-response imputation for any missing data.

Arm/Group Title	Placebo	Spesolimab 900 mg i.v SD
Arm/Group Description	Patients received intravenously (i.v.) solution for infusion containing 900 milligram (mg) of placebo to spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.	Patients received intravenously (i.v.) a single dose (SD) of solution for infusion containing 900 milligram (mg) of spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.
Measure Participants	18	35
Number (95% Confidence Interval) [Proportion of participants]	0.111 0.6%	0.543 1.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Spesolimab 900 mg i.v SD
	Comments	Confidence intervals (95%) around the risk difference were produced using the Chan and Zhang method.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.432
	Confidence Interval	(2-Sided) 95%; 0.096 to 0.636
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference=Response rate of spesolimab - response rate of placebo.

10. Secondary Outcome

Title	Percent Change in Generalized Pustular Psoriasis Area and Severity Index (GPPASI) From Baseline at Week 4
Description	GPPASI provides a numeric scoring for a patient's overall Generalized Pustular Psoriasis (GPP) disease state, ranging from 0 (no disease) to 72 (worse disease state). It is a linear combination of percent of surface area of skin affected by erythema, pustules, and scaling and the severity of erythema, pustules, and scaling (desquamation) over 4 body regions (head, trunk, upper limbs and lower limbs). %GPPASI change from baseline=(GPPASI at Week 4-GPPASI at baseline) *100/(GPPASI at baseline). Death, any use of escape medication, OL Spesolimab at Day 8, or rescue medication with Spesolimab after Day 8, prior to observing the endpoint was considered to reflect a failure to achieve the endpoint outcome, i.e. non-response (NR).NR is not a missing value but the worst possible outcome of the endpoint. For example, if the achieved data is (NR, NR, NR, NR, NR, NR, 2, 3, 3, 3, 5) then Q1 is NR, median is NR and Q3 is 3. Planned statistical analysis were not performed due to lack of valid data.
Time Frame	Baseline and at Week 4.

Outcome Measure Data

Analysis Population Description

Randomized Set (RS) (via estimand EN-LOCF): This patient set included all randomized patients. EN = Any assessments after death, or any use of escape medication before or after Day 8, open-label spesolimab at Day 8, or rescue medication with spesolimab after Day 8 were considered to represent a non-response and assigned with the worst possible outcomes in rank analysis. LOCF = last observation carried forward imputation for any missing data.

Arm/Group Title	Placebo	Spesolimab 900 mg i.v SD
Arm/Group Description	Patients received intravenously (i.v.) solution for infusion containing 900 milligram (mg) of placebo to spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.	Patients received intravenously (i.v.) a single dose (SD) of solution for infusion containing 900 milligram (mg) of spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.
Measure Participants	18	35
Median (Inter-Quartile Range) [Percentage change]	NA	-60.50

11. Secondary Outcome

Title	Proportion of Patients With a Generalized Pustular Psoriasis Area and Severity Index (GPPASI) 50 at Week 1
Description	Generalized Pustular Psoriasis Area and Severity Index (GPPASI) provides a numeric scoring for a patient's overall Generalized Pustular Psoriasis (GPP) disease state, ranging from 0 to 72. It is a linear combination of percent of surface area of skin affected by erythema, pustules, and scaling and the severity of erythema, pustules, and scaling (desquamation) over 4 body regions (head, trunk, upper limbs and lower limbs). A higher score indicates a worse disease state, while a score of 0 indicates no disease. GPPASI 50 is based on the percent reduction from baseline, generally summarized as a dichotomous outcome based on achieving over an 50 % reduction. Proportion of patients with GPPASI 50 at Week 1 is reported.
Time Frame	At Week 1.

Outcome Measure Data

Analysis Population Description

Randomized Set (RS) (via estimand EN-NRI): This patient set included all randomized patients. EN = Any assessments after death, or the use of escape medication (before or after Day 8), or open-label spesolimab at Day 8, or rescue medication with spesolimab after Day 8, was considered a failure to achieve the endpoint outcome (i.e. non-response). NRI = Non-response imputation for any missing data.

Arm/Group Title	Placebo	Spesolimab 900 mg i.v SD
Arm/Group Description	Patients received intravenously (i.v.) solution for infusion containing 900 milligram (mg) of placebo to spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.	Patients received intravenously (i.v.) a single dose (SD) of solution for infusion containing 900 milligram (mg) of spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.
Measure Participants	18	35
Number (95% Confidence Interval) [Proportion of participants]	0.278 1.5%	0.429 1.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Spesolimab 900 mg i.v SD
	Comments	Confidence intervals (95%) around the risk difference were produced using the Chan and Zhang method.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.151
	Confidence Interval	(2-Sided) 95%; -0.138 to 0.401
	Parameter Dispersion	Type: Value:
	Estimation Comments	Risk difference=Response rate of spesolimab - response rate of placebo.

12. Secondary Outcome

Title	Percent Change in Generalized Pustular Psoriasis Area and Severity Index (GPPASI) From Baseline at Week 1
Description	Generalized Pustular Psoriasis Area and Severity Index (GPPASI) provides a numeric scoring for a patient's overall Generalized Pustular Psoriasis (GPP) disease state, ranging from 0 to 72. It is a linear combination of percent of surface area of skin affected by erythema, pustules, and scaling and the severity of erythema, pustules, and scaling (desquamation) over 4 body regions (head, trunk, upper limbs and lower limbs). A higher score indicates a worse disease state, while a score of 0 indicates no disease. The percent change from baseline at Week 1 is calculated as: % GPPASI change from baseline = (GPPASI at Week 1 - GPPASI at baseline) *100/GPPASI at baseline. If % GPPASI change from baseline is positive, it means the disease is becoming worse.
Time Frame	At Week 1.

Outcome Measure Data

Analysis Population Description

Randomized Set (RS) (via estimand EN-LOCF): This patient set included all randomized patients. EN = Any assessments after death, or any use of escape medication before or after Day 8, open-label spesolimab at Day 8, or rescue medication with spesolimab after Day 8 were considered to represent a non-response and assigned with the worst possible outcomes in rank analysis. LOCF = last observation carried forward imputation for any missing data.

Arm/Group Title	Placebo	Spesolimab 900 mg i.v SD
Arm/Group Description	Patients received intravenously (i.v.) solution for infusion containing 900 milligram (mg) of placebo to spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.	Patients received intravenously (i.v.) a single dose (SD) of solution for infusion containing 900 milligram (mg) of spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.
Measure Participants	18	35
Median (Inter-Quartile Range) [Percentage change]	1.02	-42.80

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Spesolimab 900 mg i.v SD
	Comments	Any assessments after death, the use of escape medication (before or after Day 8), open label spesolimab on Day 8, or rescue medication with spesolimab after Day 8 and assigned with the worst possible outcomes in rank analysis. Missing data at Week 4 were imputed and handled via assessment of ranks.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-16.88
	Confidence Interval	(2-Sided) 95%; -67.32 to 12.76
	Parameter Dispersion	Type: Value:
	Estimation Comments	Median difference was calculated by modified Hodges-Lehmann method.

13. Secondary Outcome

Title	Occurrence of Treatment Emergent Adverse Events (TEAEs) up to Week 1
Description	TEAEs were all Adverse Events (AEs) occurring between start of treatment and Day 8 (Day 8 excluded). AEs that started before first drug intake and deteriorated under treatment were also considered as 'treatment-emergent'. The exposure-adjusted incidence rate was calculated as: Incidence rate [1/100 patients-years] = 100 × number of patients with AE / Total AE specific time at risk [patient-years] where: Time at risk [patient-years] = (date of onset of TEAE - study drug start date + 1) /365.25
Time Frame	From start of treatment until Day 7, up to 7 days.

Outcome Measure Data

Analysis Population Description

Safety Analysis set (SAF): This patient set included all patients who were randomized and received at least one dose of study drug on Day 1. Patients were analyzed according to the actual treatment received.

Arm/Group Title	Placebo	Spesolimab 900 mg i.v SD
Arm/Group Description	Patients received intravenously (i.v.) solution for infusion containing 900 milligram (mg) of placebo to spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.	Patients received intravenously (i.v.) a single dose (SD) of solution for infusion containing 900 milligram (mg) of spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.
Measure Participants	18	35
Number [events per 100 patient-years at risk]	6445.6	8650.7

14. Secondary Outcome

Title	Number of Patients With Treatment Emergent Adverse Events (TEAEs) up to Week 1
Description	TEAEs were all Adverse Events (AEs) occurring between start of treatment and Day 8 (Day 8 excluded). AEs that started before first drug intake and deteriorated under treatment were also considered as 'treatment-emergent'.
Time Frame	From start of treatment until Day 7, up to 7 days.

Outcome Measure Data

Analysis Population Description

Safety Analysis set (SAF): This patient set included all patients who were randomized and received at least one dose of study drug on Day 1. Patients were analyzed according to the actual treatment received.

Arm/Group Title	Placebo	Spesolimab 900 mg i.v SD
Arm/Group Description	Patients received intravenously (i.v.) solution for infusion containing 900 milligram (mg) of placebo to spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.	Patients received intravenously (i.v.) a single dose (SD) of solution for infusion containing 900 milligram (mg) of spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.
Measure Participants	18	35
Count of Participants [Participants]	12 66.7%	27 77.1%

15. Secondary Outcome

Title	Occurrence of Treatment Emergent Adverse Events (TEAEs) Within the Treatment Phase
Description	TEAEs were all Adverse Events (AEs) occurring between start of treatment and end of the residual effect period (REP) (16 weeks). AEs that started before first drug intake and deteriorated under treatment were also considered as 'treatment-emergent'. The exposure-adjusted incidence rate was calculated as: Incidence rate [1/100 patients-years] = 100 × number of patients with AE / Total AE specific time at risk [patient-years] where Time at risk where: Time at risk [patient-years] = (date of onset of TEAE - study drug start date + 1) /365.25 If, for a patient, the selected TEAE did not occur then the time at risk was censored at min Date of death For patients who did not roll over into the Open Label Extension (OLE) study: last contact date Visit14/15 For patients who rolled over into the OLE study: the 1st dose in the OLE study Drug stop date + 112 days Date of Day 8 if OL spesolimab was given Date of rescue medication if spesolimab was given.
Time Frame	From start of treatment until end of the residual effect period (REP) but censored at any use of open label spesolimab, up to 16 weeks.

Outcome Measure Data

Analysis Population Description

Safety Analysis set (SAF): This patient set included all patients who were randomized and received at least one dose of study drug on Day 1. Patients were analyzed according to the actual treatment received.

Arm/Group Title	Placebo	Spesolimab 900 mg i.v SD
Arm/Group Description	Patients received intravenously (i.v.) solution for infusion containing 900 milligram (mg) of placebo to spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.	Patients received intravenously (i.v.) a single dose (SD) of solution for infusion containing 900 milligram (mg) of spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.
Measure Participants	18	35
Number [events per 100 patient-years at risk]	3083.3	2391.0

16. Secondary Outcome

Title	Number of Patients With Treatment Emergent Adverse Events (TEAEs) Within the Treatment Phase
Description	TEAEs were all Adverse Events (AEs) occurring between start of treatment and end of the residual effect period (REP) (16 weeks). AEs that started before first drug intake and deteriorated under treatment were also considered as 'treatment-emergent'.
Time Frame	From start of treatment until end of the residual effect period (REP) but censored at any use of open label spesolimab, up to 16 weeks.

Outcome Measure Data

Analysis Population Description

Safety Analysis set (SAF): This patient set included all patients who were randomized and received at least one dose of study drug on Day 1. Patients were analyzed according to the actual treatment received.

Arm/Group Title	Placebo	Spesolimab 900 mg i.v SD
Arm/Group Description	Patients received intravenously (i.v.) solution for infusion containing 900 milligram (mg) of placebo to spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.	Patients received intravenously (i.v.) a single dose (SD) of solution for infusion containing 900 milligram (mg) of spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.
Measure Participants	18	35
Count of Participants [Participants]	13 72.2%	29 82.9%

Adverse Events

Time Frame	Placebo and Spesolimab 900 mg i.v. SD arms: From the start of infusion of randomized medication at Day 1 (D1) of Week 1 (Wk1) until the end of its REP (16 weeks) but were censored at any use of open-label (OL) spesolimab. OL Spesolimab: From the start of OL spesolimab at Wk1/D8 until the end of its REP (16 weeks) but were censored at any use of rescue medication with spesolimab. Rescue Spesolimab: From the start of rescue medication with spesolimab until the end of its REP (16 weeks).
Adverse Event Reporting Description	Safety Analysis set (SAF): This patient set included all patients who were randomized and received at least one dose of study drug on Day 1.
Arm/Group Title	Placebo		Spesolimab 900 mg i.v. SD		Open Label (OL) D8 Spesolimab 900 mg i.v.		Rescue Spesolimab 900 mg i.v.
Arm/Group Description	Patients received intravenously (i.v.) solution for infusion containing 900 milligram (mg) of placebo to spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patients worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.		Patients received intravenously (i.v.) a single dose of solution for infusion containing 900 milligram (mg) of spesolimab on Day 1 (D1) of Week 1 (Wk1). Based on the subsequent treatment response, participants were then to be followed up for 12 to 28 weeks. If the severity and progression of the disease worsened within the first week the investigator could treat the patient with a Standard of Care (SoC) treatment of his/her choice (escape medication). If the disease condition was stable, it was recommended to wait until the primary endpoint visit (Wk1/D8) before prescribing an escape medication (SoC) since there was an option to administer open label (OL) spesolimab instead at this time. If escape medication was administered within the first week, the patient was not eligible to receive treatment with a single OL i.v. dose of 900 mg spesolimab on D8. If the condition of the patient worsened after Wk1/D8 patients were eligible to receive rescue treatment with open label spesolimab (only one single rescue i.v. dose of 900 mg spesolimab) after Wk1 to Wk 12.		This arm included patients who in addition to the randomized treatment (either intravenously (i.v.) placebo solution to spesolimab at Day 1 or 900 milligram (mg) i.v. spesolimab at Day 1) received also Open Label Treatment with 900 mg I.V spesolimab at Week 1 (Wk1)/Day 8 (D8).		This arm included patients who in addition to the randomized treatment (either intravenously (i.v.) placebo solution to spesolimab at Day 1 or 900 milligram (mg) i.v spesolimab at Day 1) also one single rescue i.v. dose of 900 mg spesolimab between Week 1(Wk 1) to Week 12 (Wk 12).
All Cause Mortality
	Placebo		Spesolimab 900 mg i.v. SD		Open Label (OL) D8 Spesolimab 900 mg i.v.		Rescue Spesolimab 900 mg i.v.
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/35 (0%)		0/27 (0%)		0/6 (0%)
Serious Adverse Events
	Placebo		Spesolimab 900 mg i.v. SD		Open Label (OL) D8 Spesolimab 900 mg i.v.		Rescue Spesolimab 900 mg i.v.
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/18 (16.7%)		6/35 (17.1%)		6/27 (22.2%)		2/6 (33.3%)
Hepatobiliary disorders
Drug-induced liver injury	0/18 (0%)		1/35 (2.9%)		0/27 (0%)		0/6 (0%)
Infections and infestations
Influenza	0/18 (0%)		0/35 (0%)		1/27 (3.7%)		0/6 (0%)
Urinary tract infection	0/18 (0%)		1/35 (2.9%)		0/27 (0%)		0/6 (0%)
Musculoskeletal and connective tissue disorders
Arthritis	0/18 (0%)		1/35 (2.9%)		0/27 (0%)		0/6 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin	0/18 (0%)		0/35 (0%)		1/27 (3.7%)		0/6 (0%)
Skin and subcutaneous tissue disorders
Drug reaction with eosinophilia and systemic symptoms	0/18 (0%)		2/35 (5.7%)		0/27 (0%)		0/6 (0%)
Psoriasis	0/18 (0%)		0/35 (0%)		1/27 (3.7%)		0/6 (0%)
Pustular psoriasis	3/18 (16.7%)		4/35 (11.4%)		3/27 (11.1%)		2/6 (33.3%)
Other (Not Including Serious) Adverse Events
	Placebo		Spesolimab 900 mg i.v. SD		Open Label (OL) D8 Spesolimab 900 mg i.v.		Rescue Spesolimab 900 mg i.v.
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/18 (72.2%)		23/35 (65.7%)		14/27 (51.9%)		4/6 (66.7%)
Blood and lymphatic system disorders
Anaemia	1/18 (5.6%)		2/35 (5.7%)		0/27 (0%)		0/6 (0%)
Erythropenia	1/18 (5.6%)		0/35 (0%)		0/27 (0%)		0/6 (0%)
Cardiac disorders
Palpitations	1/18 (5.6%)		0/35 (0%)		0/27 (0%)		0/6 (0%)
Gastrointestinal disorders
Abdominal pain	0/18 (0%)		0/35 (0%)		0/27 (0%)		1/6 (16.7%)
Abdominal pain upper	0/18 (0%)		1/35 (2.9%)		0/27 (0%)		1/6 (16.7%)
Diarrhoea	0/18 (0%)		1/35 (2.9%)		3/27 (11.1%)		1/6 (16.7%)
Nausea	0/18 (0%)		3/35 (8.6%)		0/27 (0%)		1/6 (16.7%)
Vomiting	1/18 (5.6%)		2/35 (5.7%)		1/27 (3.7%)		2/6 (33.3%)
General disorders
Asthenia	1/18 (5.6%)		1/35 (2.9%)		1/27 (3.7%)		0/6 (0%)
Fatigue	0/18 (0%)		2/35 (5.7%)		0/27 (0%)		0/6 (0%)
Inflammation	1/18 (5.6%)		0/35 (0%)		0/27 (0%)		0/6 (0%)
Oedema peripheral	1/18 (5.6%)		2/35 (5.7%)		0/27 (0%)		0/6 (0%)
Pyrexia	4/18 (22.2%)		2/35 (5.7%)		2/27 (7.4%)		2/6 (33.3%)
Hepatobiliary disorders
Hepatic function abnormal	1/18 (5.6%)		0/35 (0%)		0/27 (0%)		0/6 (0%)
Infections and infestations
Otitis externa	0/18 (0%)		0/35 (0%)		2/27 (7.4%)		0/6 (0%)
Pustule	0/18 (0%)		1/35 (2.9%)		0/27 (0%)		1/6 (16.7%)
Streptococcal infection	1/18 (5.6%)		0/35 (0%)		0/27 (0%)		0/6 (0%)
Urinary tract infection	0/18 (0%)		1/35 (2.9%)		1/27 (3.7%)		1/6 (16.7%)
Injury, poisoning and procedural complications
Tendon injury	1/18 (5.6%)		0/35 (0%)		0/27 (0%)		0/6 (0%)
Investigations
Alanine aminotransferase increased	2/18 (11.1%)		1/35 (2.9%)		0/27 (0%)		0/6 (0%)
Aspartate aminotransferase increased	1/18 (5.6%)		1/35 (2.9%)		0/27 (0%)		0/6 (0%)
Blood lactate dehydrogenase increased	1/18 (5.6%)		0/35 (0%)		0/27 (0%)		0/6 (0%)
C-reactive protein increased	0/18 (0%)		2/35 (5.7%)		0/27 (0%)		0/6 (0%)
Eosinophil count increased	1/18 (5.6%)		0/35 (0%)		0/27 (0%)		0/6 (0%)
Eosinophil percentage increased	1/18 (5.6%)		0/35 (0%)		0/27 (0%)		0/6 (0%)
Haematocrit decreased	1/18 (5.6%)		0/35 (0%)		0/27 (0%)		0/6 (0%)
Haemoglobin decreased	1/18 (5.6%)		0/35 (0%)		0/27 (0%)		0/6 (0%)
High density lipoprotein decreased	1/18 (5.6%)		0/35 (0%)		0/27 (0%)		0/6 (0%)
High density lipoprotein increased	1/18 (5.6%)		0/35 (0%)		0/27 (0%)		0/6 (0%)
Platelet count increased	1/18 (5.6%)		1/35 (2.9%)		0/27 (0%)		0/6 (0%)
Protein total decreased	1/18 (5.6%)		0/35 (0%)		0/27 (0%)		0/6 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/18 (5.6%)		0/35 (0%)		0/27 (0%)		0/6 (0%)
Hyperuricaemia	1/18 (5.6%)		0/35 (0%)		0/27 (0%)		0/6 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/18 (5.6%)		2/35 (5.7%)		1/27 (3.7%)		0/6 (0%)
Bone pain	0/18 (0%)		0/35 (0%)		0/27 (0%)		1/6 (16.7%)
Joint effusion	1/18 (5.6%)		0/35 (0%)		0/27 (0%)		0/6 (0%)
Joint swelling	1/18 (5.6%)		0/35 (0%)		0/27 (0%)		0/6 (0%)
Myalgia	1/18 (5.6%)		2/35 (5.7%)		1/27 (3.7%)		1/6 (16.7%)
Oligoarthritis	0/18 (0%)		0/35 (0%)		0/27 (0%)		1/6 (16.7%)
Osteoarthritis	1/18 (5.6%)		0/35 (0%)		0/27 (0%)		0/6 (0%)
Pain in extremity	1/18 (5.6%)		2/35 (5.7%)		2/27 (7.4%)		1/6 (16.7%)
Tendonitis	1/18 (5.6%)		1/35 (2.9%)		0/27 (0%)		0/6 (0%)
Nervous system disorders
Dizziness	2/18 (11.1%)		0/35 (0%)		0/27 (0%)		0/6 (0%)
Headache	1/18 (5.6%)		4/35 (11.4%)		1/27 (3.7%)		0/6 (0%)
Paraesthesia	1/18 (5.6%)		0/35 (0%)		0/27 (0%)		0/6 (0%)
Syncope	0/18 (0%)		0/35 (0%)		0/27 (0%)		1/6 (16.7%)
Psychiatric disorders
Anxiety	1/18 (5.6%)		0/35 (0%)		0/27 (0%)		0/6 (0%)
Insomnia	1/18 (5.6%)		0/35 (0%)		0/27 (0%)		0/6 (0%)
Reproductive system and breast disorders
Dysmenorrhoea	0/18 (0%)		0/35 (0%)		0/27 (0%)		1/6 (16.7%)
Hypomenorrhoea	0/18 (0%)		0/35 (0%)		0/27 (0%)		1/6 (16.7%)
Respiratory, thoracic and mediastinal disorders
Cough	1/18 (5.6%)		0/35 (0%)		1/27 (3.7%)		0/6 (0%)
Skin and subcutaneous tissue disorders
Alopecia	1/18 (5.6%)		0/35 (0%)		0/27 (0%)		0/6 (0%)
Dermatitis allergic	1/18 (5.6%)		0/35 (0%)		0/27 (0%)		0/6 (0%)
Erythema	0/18 (0%)		0/35 (0%)		2/27 (7.4%)		0/6 (0%)
Pain of skin	1/18 (5.6%)		0/35 (0%)		0/27 (0%)		0/6 (0%)
Pruritus	0/18 (0%)		1/35 (2.9%)		2/27 (7.4%)		0/6 (0%)
Psoriasis	0/18 (0%)		2/35 (5.7%)		1/27 (3.7%)		0/6 (0%)
Pustular psoriasis	4/18 (22.2%)		17/35 (48.6%)		5/27 (18.5%)		2/6 (33.3%)
Skin erosion	0/18 (0%)		0/35 (0%)		0/27 (0%)		1/6 (16.7%)
Urticaria	1/18 (5.6%)		1/35 (2.9%)		0/27 (0%)		1/6 (16.7%)
Vascular disorders
Haemorrhage	0/18 (0%)		0/35 (0%)		0/27 (0%)		1/6 (16.7%)
Hypotension	1/18 (5.6%)		0/35 (0%)		0/27 (0%)		0/6 (0%)

Limitations/Caveats

Due to the trial design, a large proportion of patients had received escape medication or non-randomized spesolimab by Week 4, based on worsening, insufficient response, or non-response. This should be taken into account for the interpretation of the results at Week 4. A large proportion of patients in both arms had been treated as non-responders at Week 4, and the true efficacy outcomes for the randomized treatment at this time-point were never observed for the analysis.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.