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

• ClinicalTrials.gov Identifier: NCT04399837
• Recruitment Status: Completed
• First Posted: May 22, 2020
• Results First Posted: December 14, 2023
• Last Update Posted: December 14, 2023
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Generalized Pustular Psoriasis
• Interventions: Drug: Spesolimab; Drug: Placebo
• Enrollment: 123

Participant Flow

Recruitment Details

This was a randomized multicenter, parallel group, double-blind, placebo-controlled Phase IIb trial comprising of 3 active doses compared to placebo in adolescents from 12 years to less than 18 years of age and adult patients with history of Generalized Pustular Psoriasis (GPP) and presenting (at screening and at randomization) with a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) score of 0 or 1 (clear or almost clear).

Pre-assignment Details

Subjects were screened for eligibility prior to participation and attended a specialist site which ensured that they (the subjects) met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated. The randomization was stratified accounting for use of systemic GPP medications at randomization (yes vs. no), and the blocking factors, region (Japan vs. non-Japan) and population (adults vs. adolescents).

Arm/Group Title	Placebo	Spesolimab SC Low Dose	Spesolimab SC Medium Dose	Spesolimab SC High Dose
Arm/Group Description	Patients were subcutaneously (SC) injected on Day 1 of Week 1 a loading dose of solution for injection of placebo matching solution for injection of spesolimab followed by a maintenance treatment which consisted of a subcutaneous injection of solution for injection of placebo matching solution for injection of spesolimab every 4 weeks (i.e. on Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40 and 44). The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 of flare (R1/D1) or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).	Patients received on Day 1 of Week 1 a loading dose which consisted of two subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300mg) and two subcutaneous injections of placebo matching solution for injection of spesolimab. The loading dose was followed by a maintenance treatment which consisted of one SC injection of 150 mg of solution for injection of spesolimab and one SC injection of placebo matching solution for injection of spesolimab every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).	Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered subcutaneously every 12 weeks or every 4 weeks (intensified maintenance therapy).	Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 4 weeks (i.e. at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44). The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
Period Title: Overall Study
Started	31	31	31	30
Completed [1]	30	27	28	26
Not Completed	1	4	3	4
Reason Not Completed
Other than listed	0	2	2	3
Withdrawal by Subject	1	2	1	1
[1] Completed trial

Baseline Characteristics

Arm/Group Title		Placebo	Spesolimab SC Low Dose	Spesolimab SC Medium Dose	Spesolimab SC High Dose	Total
Arm/Group Description		Patients were subcutaneously (SC) injected on Day 1 of Week 1 a loading dose of solution for injection of placebo matching solution for injection of spesolimab followed by a maintenance treatment which consisted of a subcutaneous injection of solution for injection of placebo matching solution for injection of spesolimab every 4 weeks (i.e. on Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40 and 44). The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 of flare (R1/D1) or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).	Patients received on Day 1 of Week 1 a loading dose which consisted of two subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300mg) and two subcutaneous injections of placebo matching solution for injection of spesolimab. The loading dose was followed by a maintenance treatment which consisted of one SC injection of 150 mg of solution for injection of spesolimab and one SC injection of placebo matching solution for injection of spesolimab every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).	Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered subcutaneously every 12 weeks or every 4 weeks (intensified maintenance therapy).	Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 4 weeks (i.e. at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44). The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).	Total of all reporting groups
Overall Number of Baseline Participants		31	31	31	30	123
Baseline Analysis Population Description		Randomized Set: This patient set includes all randomized patients.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	31 participants	31 participants	31 participants	30 participants	123 participants
		39.5 (14.0)	38.9 (16.5)	42.9 (16.7)	40.2 (16.4)	40.4 (15.8)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	31 participants	31 participants	31 participants	30 participants	123 participants
	Female	18 58.1%	20 64.5%	20 64.5%	18 60.0%	76 61.8%
	Male	13 41.9%	11 35.5%	11 35.5%	12 40.0%	47 38.2%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	31 participants	31 participants	31 participants	30 participants	123 participants
	Hispanic or Latino	3 9.7%	3 9.7%	0 0.0%	1 3.3%	7 5.7%
	Not Hispanic or Latino	28 90.3%	28 90.3%	31 100.0%	29 96.7%	116 94.3%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	31 participants	31 participants	31 participants	30 participants	123 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	17 54.8%	20 64.5%	21 67.7%	21 70.0%	79 64.2%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	White	14 45.2%	11 35.5%	10 32.3%	9 30.0%	44 35.8%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Number of patients in the categories 0 or 1 of GPPGA score [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	31 participants	31 participants	31 participants	30 participants	123 participants
	0	4 12.9%	2 6.5%	8 25.8%	3 10.0%	17 13.8%
	1	27 87.1%	29 93.5%	23 74.2%	27 90.0%	106 86.2%
		[1] Measure Description: Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) relied on the clinical assessment of GPP patient's skin presentation. The total score is calculated by taking the mean of the three subscores: 1) erythema; 2) pustules and 3) scaling/crusting which were assessed using a scale score 0 to 4 (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe). The final GPPGA score: 0 , if scores for all three subscores are 0,; if 0 < mean < 1.5;; if 1.5 ≤ mean < 2.5;; if 2.5 ≤ mean < 3.5;; if mean ≥ 3.5. Number of patients in the categories 0 or 1 of GPPGA score is reported.
Number of patients in the categories 0 or 1 of GPPGA pustules subscore [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	31 participants	31 participants	31 participants	30 participants	123 participants
	0	21 67.7%	23 74.2%	24 77.4%	20 66.7%	88 71.5%
	1	10 32.3%	8 25.8%	7 22.6%	10 33.3%	35 28.5%
		[1] Measure Description: The Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustules subscore relied on clinical assessment of the Generalized Pustular Psoriasis (GPP) pustules presentation. The investigator (or qualified site personnel) scored the pustules of all GPP lesions from 0 to 4 where: 0 = clear; = almost clear;; = mild;; = moderate;; = severe. Number of patients in the categories 0 or 1 of GPPGA pustules subscore is reported.
Concomitant use of systemic GPP medication at randomization [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	31 participants	31 participants	31 participants	30 participants	123 participants
	No	9 29.0%	6 19.4%	8 25.8%	8 26.7%	31 25.2%
	Yes	22 71.0%	25 80.6%	23 74.2%	22 73.3%	92 74.8%
		[1] Measure Description: Number of patients in each category of concomitant use of systemic GPP medication at randomization (-28 days to randomization). The reported categories of concomitant use of systemic GPP medication at randomization are: Yes; No.
Psoriasis Symptom Scale (PSS) total score at baseline [1] [2]; Mean (Standard Deviation); Unit of measure: Score on a scale
	Number Analyzed	31 participants	31 participants	31 participants	30 participants	123 participants
		3.6 (2.9)	4.1 (3.8)	3.9 (2.9)	5.3 (3.8)	4.2 (3.4)
		[1] Measure Description: The PSS is a 4-item patient-reported outcome (PRO) instrument that was developed to assess the severity of 4 psoriasis symptoms in patients with moderate to severe psoriasis. The symptoms included are: pain, redness, itching, and burning. Current symptom severity is assessed using a 5-point scale ranging from 0 (none) to 4 (very severe). The symptom scores are added to an unweighted total score (range: 0 (no symptoms) to 16 (severe symptoms).; [2] Measure Analysis Population Description: Randomized Set: This patient set includes all randomized patients.
DLQI total score at baseline [1] [2]; Mean (Standard Deviation); Unit of measure: Score on a scale
	Number Analyzed	31 participants	30 participants	31 participants	29 participants	121 participants
		7.2 (5.6)	7.6 (6.7)	6.6 (5.6)	11.1 (6.9)	8.1 (6.4)
		[1] Measure Description: The Dermatology Quality of Life Index (DLQI) is a patient-administered, ten-question, quality of life questionnaire that covers six domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships and treatment. Response categories range from 0 (not relevant) to 3 (very much). Question 7 is a "yes"/ "no" question where "yes" is scored as 3. Total score is obtained by summing the scores of each question resulting in a range of 0 (no effect on patient's life) to 30 (extremely large effect on patient's life).; [2] Measure Analysis Population Description: This patient set includes all randomized patients. Adolescents aged below 16 years were optional to the questionnaire, therefore two adolescent whose age was below 16 years were not asked to fill this questionnaire.

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Randomized Set (EM-PM): This patient set includes all randomized patients. EM: Primary estimand for randomised maintenance period, where any use of rescue medication with intravenous spesolimab, or investigator-prescribed SoC for GPP worsening is considered as GPP flare. PM: Primary method for censoring, which is made at the earliest date of End of Study (EoS), Day 351 if no intercurrent event.

Arm/Group Title	Placebo	Spesolimab SC Low Dose	Spesolimab SC Medium Dose	Spesolimab SC High Dose
Arm/Group Description:	Patients were subcutaneously (SC) injected on Day 1 of Week 1 a loading dose of solution for injection of placebo matching solution for injection of spesolimab followed by a maintenance treatment which consisted of a subcutaneous injection of solution for injection of placebo matching solution for injection of spesolimab every 4 weeks (i.e. on Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40 and 44). The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 of flare (R1/D1) or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).	Patients received on Day 1 of Week 1 a loading dose which consisted of two subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300mg) and two subcutaneous injections of placebo matching solution for injection of spesolimab. The loading dose was followed by a maintenance treatment which consisted of one SC injection of 150 mg of solution for injection of spesolimab and one SC injection of placebo matching solution for injection of spesolimab every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).	Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered subcutaneously every 12 weeks or every 4 weeks (intensified maintenance therapy).	Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 4 weeks (i.e. at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44). The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
Overall Number of Participants Analyzed	31	31	31	30
Median (95% Confidence Interval); Unit of Measure: weeks
	37.3 [1]; (4.0 to NA)	NA [1]; (NA to NA)	NA [1]; (NA to NA)	NA [1]; (NA to NA)

[1]

Insufficient number of participants with events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Spesolimab SC Low Dose, Spesolimab SC Medium Dose, Spesolimab SC High Dose
	Comments	A flat vs. non-flat dose-response relationship across the 3 doses of spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 4 different plausible dose-response patterns (linear, Emax 1, Emax 2 and exponential) while protecting the overall probability of type I error (one-sided alpha of 0.05).
	Type of Statistical Test	Other
	Comments	The generalized MCP-Mod procedure for time to event endpoints is based on the log hazard ratio of the active doses vs. placebo obtained via a Cox regression model on the time to first GPP flare.
Statistical Test of Hypothesis	P-Value	0.002
	Comments	[Not Specified]
	Method	MCP-Mod linear model fit
	Comments	Model assumption: Dose effect is linear with the increase of dose.
Method of Estimation	Estimation Parameter	Multiple contrast test
	Estimated Value	3.041
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Spesolimab SC Low Dose, Spesolimab SC Medium Dose, Spesolimab SC High Dose
	Comments	A flat vs. non-flat dose-response relationship across the 3 doses of spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 4 different plausible dose-response patterns (linear, Emax 1, Emax 2 and exponential) while protecting the overall probability of type I error (one-sided alpha of 0.05).
	Type of Statistical Test	Other
	Comments	The generalized MCP-Mod procedure for time to event endpoints is based on the log hazard ratio of the active doses vs. placebo obtained via a Cox regression model on the time to first GPP flare.
Statistical Test of Hypothesis	P-Value	0.002
	Comments	[Not Specified]
	Method	MCP-Mod Emax2 model fit
	Comments	Model assumption: 95% of the maximum effect is achieved at low dose.
Method of Estimation	Estimation Parameter	Multiple contrast test
	Estimated Value	3.033
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Spesolimab SC Low Dose, Spesolimab SC Medium Dose, Spesolimab SC High Dose
	Comments	A flat vs. non-flat dose-response relationship across the 3 doses of spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 4 different plausible dose-response patterns (linear, Emax 1, Emax 2 and exponential) while protecting the overall probability of type I error (one-sided alpha of 0.05).
	Type of Statistical Test	Other
	Comments	The generalized MCP-Mod procedure for time to event endpoints is based on the log hazard ratio of the active doses vs. placebo obtained via a Cox regression model on the time to first GPP flare.
Statistical Test of Hypothesis	P-Value	0.002
	Comments	[Not Specified]
	Method	MCP-Mod Emax1 model fit
	Comments	Model assumption: 70% of the maximum effect is achieved at low dose.
Method of Estimation	Estimation Parameter	Multiple contrast test
	Estimated Value	3.088
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Spesolimab SC Low Dose, Spesolimab SC Medium Dose, Spesolimab SC High Dose
	Comments	A flat vs. non-flat dose-response relationship across the 3 doses of spesolimab and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 4 different plausible dose-response patterns (linear, Emax 1, Emax 2 and exponential) while protecting the overall probability of type I error (one-sided alpha of 0.05).
	Type of Statistical Test	Other
	Comments	The generalized MCP-Mod procedure for time to event endpoints is based on the log hazard ratio of the active doses vs. placebo obtained via a Cox regression model on the time to first GPP flare.
Statistical Test of Hypothesis	P-Value	0.003
	Comments	[Not Specified]
	Method	MCP-Mod exponential model fit
	Comments	Model assumption: 35% of the maximum effect is achieved at medium dose.
Method of Estimation	Estimation Parameter	Multiple contrast test
	Estimated Value	2.977
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Spesolimab SC Medium Dose
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	Null hypothesis: Effect of spesolimab 300 mg every 12 weeks on prolonging the time to the first GPP flare up to week 48 ≤ Placebo.
Statistical Test of Hypothesis	P-Value	0.0269
	Comments	One-sided p-value was computed from the log-rank test stratified by use of systemic GPP medication at randomisation. Threshold for statistical significance: one-sided p-value ≤ 0.01875.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.468
	Confidence Interval	(2-Sided) 95%; 0.206 to 1.064
	Estimation Comments	Hazard ratio and its 95% Confidence Interval are from Cox regression model stratified by use of systemic GPP medication at randomisation.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Spesolimab SC High Dose
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	Null hypothesis: Effect of spesolimab 300 mg every 4 weeks on prolonging the time to the first GPP flare up to week 48 ≤ Placebo.
Statistical Test of Hypothesis	P-Value	0.0005
	Comments	One-sided p-value is computed from the log-rank test stratified by use of systemic GPP medication at randomisation. Threshold for statistical significance: One-sided p-value ≤0.0125.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.157
	Confidence Interval	(2-Sided) 95%; 0.046 to 0.541
	Estimation Comments	Hazard ratio and its 95% CI (confidence interval) are from Cox regression model stratified by use of systemic GPP medication at randomisation.

2. Secondary Outcome

Title	Key Secondary Endpoint: The Occurrence of at Least One Generalized Pustular Psoriasis (GPP) Flare up to Week 48
Description	Proportion of patients with at least one GPP flare up to Week 48 is reported. Proportions were rounded up to three decimal places. A GPP flare was defined as increase in Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) score by ≥ 2 from baseline and the pustular component of GPPGA ≥ 2. Any use of rescue medication, or investigator-prescribed SoC for GPP worsening, prior to week 48 was considered to represent the onset of a GPP flare. Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) relied on the clinical assessment of GPP patient's skin presentation. The total score is calculated by taking the mean of the three subscores: 1) erythema; 2) pustules and 3) scaling/crusting which were assessed using a scale score 0 to 4 (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe). The final GPPGA score: 0 , if scores for all three subscores are 0,; if 0 < mean < 1.5;; if 1.5 ≤ mean < 2.5;; if 2.5 ≤ mean < 3.5;; if mean ≥ 3.5.
Time Frame	GPPGA was regularly assessed at baseline (Week 1) and up to Week 48 (at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48). Patients could come to site for flare confirmation anytime as unscheduled visit. Visit window was ±7 days.

Outcome Measure Data

Analysis Population Description

Randomized Set (EM-MI): This patient set includes all randomized patients. EM:primary estimand for randomised maintenance period, where any use of rescue medication with intravenous spesolimab, or investigator - prescribed SoC for GPP worsening is considered as GPP flare. MI: multiple imputation method using sequential logistic regression method.

Arm/Group Title	Placebo	Spesolimab SC Low Dose	Spesolimab SC Medium Dose	Spesolimab SC High Dose
Arm/Group Description:	Patients were subcutaneously (SC) injected on Day 1 of Week 1 a loading dose of solution for injection of placebo matching solution for injection of spesolimab followed by a maintenance treatment which consisted of a subcutaneous injection of solution for injection of placebo matching solution for injection of spesolimab every 4 weeks (i.e. on Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40 and 44). The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 of flare (R1/D1) or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).	Patients received on Day 1 of Week 1 a loading dose which consisted of two subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300mg) and two subcutaneous injections of placebo matching solution for injection of spesolimab. The loading dose was followed by a maintenance treatment which consisted of one SC injection of 150 mg of solution for injection of spesolimab and one SC injection of placebo matching solution for injection of spesolimab every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).	Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered subcutaneously every 12 weeks or every 4 weeks (intensified maintenance therapy).	Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 4 weeks (i.e. at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44). The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
Overall Number of Participants Analyzed	31	31	31	30
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: proportion of patients
	0.516; (0.348 to 0.680)	0.226; (0.114 to 0.398)	0.297; (0.181 to 0.445)	0.127; (0.050 to 0.289)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Spesolimab SC High Dose
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	Null hypothesis: The proportion of patients who do not experience a GPP flare up to week 48 on BI 655130 300 mg every 4 weeks ≤ Placebo.
Statistical Test of Hypothesis	P-Value	0.0013
	Comments	One-sided p-value was computed from the Cochran-Mantel-Haenszel test stratified by use of systemic GPP medication at randomisation. one-sided alpha= 0.00625
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.390
	Confidence Interval	(2-Sided) 95%; -0.621 to -0.159
	Estimation Comments	Risk difference=Spesolimab high dose-Placebo.

3. Secondary Outcome

Title	Time to First Worsening of Psoriasis Symptom Scale (PSS) up to Week 48
Description	Worsening of Psoriasis Symptom Scale (PSS) was defined as a 4-point increase in total score from baseline. Intake of rescue medication, or investigator-prescribed SoC for GPP worsening, was considered as onset of a worsening. The PSS is a 4-item patient-reported outcome (PRO) instrument that was developed to assess the severity of 4 psoriasis symptoms in patients with moderate to severe psoriasis. The symptoms included are: pain, redness, itching, and burning. Current symptom severity is assessed using a 5-point scale ranging from 0 (none) to 4 (very severe). The symptom scores are added to an unweighted total score (range: 0 (no symptoms) to 16 (severe symptoms)).
Time Frame	PSS assessments were performed at: Baseline (Week 1) and up to Week 48 (at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48). Visit window was ±7 days.

Outcome Measure Data

Analysis Population Description

Randomized Set (EM-PM): This patient set includes all randomized patients. EM:primary estimand for randomised maintenance period, where any use of rescue medication with intravenous spesolimab, or investigator-prescribed SoC for GPP worsening is considered as GPP flare. PM: primary method for censoring, which is made at the earliest date of End of Study (EoS), Day 351 if no intercurrent event.

Arm/Group Title	Placebo	Spesolimab SC Low Dose	Spesolimab SC Medium Dose	Spesolimab SC High Dose
Arm/Group Description:	Patients were subcutaneously (SC) injected on Day 1 of Week 1 a loading dose of solution for injection of placebo matching solution for injection of spesolimab followed by a maintenance treatment which consisted of a subcutaneous injection of solution for injection of placebo matching solution for injection of spesolimab every 4 weeks (i.e. on Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40 and 44). The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 of flare (R1/D1) or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).	Patients received on Day 1 of Week 1 a loading dose which consisted of two subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300mg) and two subcutaneous injections of placebo matching solution for injection of spesolimab. The loading dose was followed by a maintenance treatment which consisted of one SC injection of 150 mg of solution for injection of spesolimab and one SC injection of placebo matching solution for injection of spesolimab every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).	Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered subcutaneously every 12 weeks or every 4 weeks (intensified maintenance therapy).	Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 4 weeks (i.e. at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44). The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
Overall Number of Participants Analyzed	31	31	31	30
Median (95% Confidence Interval); Unit of Measure: weeks
	16.0 [1]; (4.0 to NA)	NA [1]; (8.1 to NA)	NA [1]; (8.7 to NA)	NA [1]; (12.0 to NA)

[1]

Insufficient number of participants with events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Spesolimab SC High Dose
	Comments	Hazard ratio and its 95% CI (confidence interval) are from Cox regression model stratified by use of systemic GPP medication at randomisation.
	Type of Statistical Test	Superiority
	Comments	Null hypothesis: Effect of BI 655130 300 mg every 4 weeks on prolonging the time to first worsening of PSS up to week 48 ≤ Placebo.
Statistical Test of Hypothesis	P-Value	0.0134
	Comments	One-sided p-value was computed from the log-rank test stratified by use of systemic GPP medication at randomisation. one-sided alpha= 0.00625
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.424
	Confidence Interval	(2-Sided) 95%; 0.197 to 0.914
	Estimation Comments	spesolimab high dose vs. Placebo

4. Secondary Outcome

Title	Time to First Worsening of Dermatology Quality of Life Index (DLQI) up to Week 48
Description	Worsening of DLQI up to week 48 was defined as a 4-point increase in total score from baseline. Intake of rescue medication, or investigator-prescribed SoC for GPP worsening, was considered as onset of a worsening. The DLQI is a patient-administered, ten-question, quality of life questionnaire that covers six domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships and treatment. Response categories include "not relevant" (score of 0), "not at all" (score of 0), "a little" (score of 1), "a lot" (score of 2) and "very much" (score of 3). Question 7 is a "yes"/ "no" question where "yes" is scored as 3. DLQI total score is calculated by summing the scores of each question resulting in a range of 0 (no effect on patient's life) to 30 (extremely large effect on patient's life).
Time Frame	DLQI assessments were performed at: Baseline (Week 1) and up to Week 48 (at Week 4, 8, 12, 24, 36 and 48). Visit window was ±7 days. Time window for Week 48 was from Week 46 to Week 50.

Outcome Measure Data

Analysis Population Description

Randomized Set (EM-PM): This patient set includes all randomized patients. EM:primary estimand for randomised maintenance period, where any use of rescue medication with intravenous spesolimab, or investigator-prescribed SoC for GPP worsening is considered as GPP flare. PM: primary method for censoring, which is made at the earliest date of End of Study (EoS), Day 351 if no intercurrent event.

Arm/Group Title	Placebo	Spesolimab SC Low Dose	Spesolimab SC Medium Dose	Spesolimab SC High Dose
Arm/Group Description:	Patients were subcutaneously (SC) injected on Day 1 of Week 1 a loading dose of solution for injection of placebo matching solution for injection of spesolimab followed by a maintenance treatment which consisted of a subcutaneous injection of solution for injection of placebo matching solution for injection of spesolimab every 4 weeks (i.e. on Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40 and 44). The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 of flare (R1/D1) or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).	Patients received on Day 1 of Week 1 a loading dose which consisted of two subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300mg) and two subcutaneous injections of placebo matching solution for injection of spesolimab. The loading dose was followed by a maintenance treatment which consisted of one SC injection of 150 mg of solution for injection of spesolimab and one SC injection of placebo matching solution for injection of spesolimab every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).	Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered subcutaneously every 12 weeks or every 4 weeks (intensified maintenance therapy).	Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 4 weeks (i.e. at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44). The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
Overall Number of Participants Analyzed	31	31	31	30
Median (95% Confidence Interval); Unit of Measure: weeks
	16.0 [1]; (4.0 to NA)	35.8 [1]; (8.1 to NA)	49.3; (8.7 to 49.3)	NA [1]; (NA to NA)

[1]

Insufficient number of participants with events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Spesolimab SC High Dose
	Comments	Hazard ratio and its 95% CI (confidence interval) are from Cox regression model stratified by use of systemic GPP medication at randomisation. one-sided alpha= 0.00625
	Type of Statistical Test	Superiority
	Comments	Null hypothesis: Effect of BI 655130 300 mg every 4 weeks on prolonging the time to the first worsening of DLQI up to week 48 ≤ Placebo.
Statistical Test of Hypothesis	P-Value	0.0010
	Comments	One sided p-value was computed from the log-rank test stratified by use of systemic GPP medication at randomisation.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.259
	Confidence Interval	(2-Sided) 95%; 0.109 to 0.620
	Estimation Comments	spesolimab high dose vs. Placebo

5. Secondary Outcome

Title	Sustained Remission
Description	Proportion of patients with sustained remission at all visits up to Week 48. Proportions were rounded up to three decimal places. Remission was defined as a patient with a GPPGA score of 0 or 1 (clear or almost clear) at all visits up to week 48, without intake of rescue medication, or investigator-prescribed SoC for GPP worsening. GPPGA relied on clinical assessment of the Generalized Pustular Psoriasis (GPP) patient's skin presentation. The GPPGA total score was calculated by taking the mean of the erythema subscore, pustules subscore and scaling/crusting subscore. The severity of each subscore was assessed using a 5 point scale score ranging from 0 to 4 (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe). The final GPPGA score is assigned as follows: 0 , if scores for all three subscores are 0,; 1, if 0 < mean < 1.5,; 2, if 1.5 ≤ mean < 2.5,; 3, if 2.5 ≤ mean < 3.5,; 4, if mean ≥ 3.5.
Time Frame	GPPGA was regularly assessed at baseline (Week 1) and up to Week 48 (at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48). Patients could come to site for flare confirmation anytime as unscheduled visit. Visit window was ±7 days.

Outcome Measure Data

Analysis Population Description

Randomized Set (EM-MI): This patient set includes all randomized patients. EM:primary estimand for randomised maintenance period, where any use of rescue medication with intravenous spesolimab, or investigator-prescribed SoC for GPP worsening is considered as GPP flare. MI: multiple imputation method using sequential logistic regression method.

Arm/Group Title	Placebo	Spesolimab SC Low Dose	Spesolimab SC Medium Dose	Spesolimab SC High Dose
Arm/Group Description:	Patients were subcutaneously (SC) injected on Day 1 of Week 1 a loading dose of solution for injection of placebo matching solution for injection of spesolimab followed by a maintenance treatment which consisted of a subcutaneous injection of solution for injection of placebo matching solution for injection of spesolimab every 4 weeks (i.e. on Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40 and 44). The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 of flare (R1/D1) or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).	Patients received on Day 1 of Week 1 a loading dose which consisted of two subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300mg) and two subcutaneous injections of placebo matching solution for injection of spesolimab. The loading dose was followed by a maintenance treatment which consisted of one SC injection of 150 mg of solution for injection of spesolimab and one SC injection of placebo matching solution for injection of spesolimab every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).	Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered subcutaneously every 12 weeks or every 4 weeks (intensified maintenance therapy).	Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 4 weeks (i.e. at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44). The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
Overall Number of Participants Analyzed	31	31	31	30
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: proportion of patients
	0.290; (0.161 to 0.466)	0.516; (0.348 to 0.680)	0.452; (0.292 to 0.622)	0.633; (0.471 to 0.770)

6. Secondary Outcome

Title	The Occurrence of Treatment Emergent Adverse Events (TEAEs)
Description	Percentage of patients with treatment emergent adverse events (TEAEs) is reported. Percentages were rounded up to one decimal places. Time Frame: Placebo, Spesolimab (Speso) SC low, medium, high: From randomized study treatment start until the first use of rescue medication with IV spesolimab or until last dose + 16 weeks, up to 62 weeks. Speso IV SD and Speso IV DD: From first use of rescue medication with IV spesolimab until OL maintenance spesolimab SC or until last dose of spesolimab IV + 16 weeks, up to 17 weeks. Speso OL SC: From the first dose of OL spesolimab SC treatment until last dose + 16 weeks, up to 62 weeks.
Time Frame	Up to 62 weeks (for detailed timeframe see description).

Outcome Measure Data

Analysis Population Description

Arms "Placebo, Speso SC Low, medium, high":Safety Set (SAF)-This patient set included all patients who were randomized and received at least one dose of study drug. One patient who was randomized to placebo arm but received active spesolimab dose is reported under the arm "Spesolimab SC low" instead of "Placebo".

Arms "Speso IV SD, Speso IV SD": Safety Analysis set for flare rescue treatment period (SAF-FT).

Arm "Speso OL SC": Safety Analysis set for OL maintenance treatment period (SAF-MT).

Arm/Group Title	Placebo	Spesolimab SC Low Dose	Spesolimab SC Medium Dose	Spesolimab SC High Dose	Spesolimab IV SD	Spesolimab IV DD	Spesolimab OL SC
Arm/Group Description:	Patients were subcutaneously (SC) injected on Day 1 of Week 1 a loading dose of solution for injection of placebo matching solution for injection of spesolimab followed by a maintenance treatment which consisted of a subcutaneous injection of solution for injection of placebo matching solution for injection of spesolimab every 4 weeks (i.e. on Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40 and 44). The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 of flare (R1/D1) or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).	Patients received on Day 1 of Week 1 a loading dose which consisted of two subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300mg) and two subcutaneous injections of placebo matching solution for injection of spesolimab. The loading dose was followed by a maintenance treatment which consisted of one SC injection of 150 mg of solution for injection of spesolimab and one SC injection of placebo matching solution for injection of spesolimab every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).	Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered subcutaneously every 12 weeks or every 4 weeks (intensified maintenance therapy).	Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 4 weeks (i.e. at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44). The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).	This arm includes the patients who were randomized at study start in the arms "Placebo" or "Spesolimab SC low dose" or "Spesolimab SC medium dose" or "Spesolimab SC high dose" who took a single dose (SD) of rescue treatment of 900 milligram (mg) of spesolimab administered intravenously (IV) at Day 1 of flare (R1/D1) because of a GPP flare during the 48-week treatment randomised period.	This arm includes the patients who were randomized at study start in the arms "Placebo" or "Spesolimab SC low dose" or "Spesolimab SC medium dose" or "Spesolimab SC high dose" who took two doses (DD) of rescue treatment of spesolimab each 900 milligram (mg) of spesolimab administered intravenously (IV) at Day 1 and at Day 8 of flare (R1/D1 and R3/D8) because of a GPP flare during the 48-week treatment randomised period.	This arm includes the patients who were randomized at study start in the arms "Placebo" or "Spesolimab SC low dose" or "Spesolimab SC medium dose" or "Spesolimab SC high dose" who experienced a flare during the 48-week randomised treatment period and were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at either Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare and then followed by maintenance treatment which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
Overall Number of Participants Analyzed	30	32	31	30	22	10	20
Measure Type: Number; Unit of Measure: percentage of patients
	86.7	90.6	93.5	86.7	68.2	60.0	75.0

Adverse Events

Time Frame	Placebo, Spesolimab (Speso) SC low, medium, high: From randomized study treatment start until the first use of rescue medication with IV spesolimab or until last dose + 16 weeks, up to 62 weeks. Speso IV SD and Speso IV DD: From first use of rescue medication with IV spesolimab until OL maintenance spesolimab SC or until last IV dose + 16 weeks, up to 17 weeks. Speso OL SC: From the first dose of OL spesolimab SC treatment until last dose + 16 weeks, up to 62 weeks.
Adverse Event Reporting Description	Arms "Placebo, Speso SC Low, medium, high":Safety Set (SAF)-This patient set included all patients who were randomized and received at least one dose of study drug. One patient who was randomized to placebo arm but received active spesolimab dose is reported under the arm "Spesolimab SC low" instead of "Placebo". Arms "Speso IV SD, Speso IV SD": SAF-FT- Safety Analysis set for flare rescue treatment period. Arm "Speso OL SC": SAF-MT- Safety Analysis set for OL maintenance treatment period.
Arm/Group Title	Placebo	Spesolimab SC Low Dose	Spesolimab SC Medium Dose	Spesolimab SC High Dose	Spesolimab IV SD	Spesolimab IV DD	Spesolimab OL SC
Arm/Group Description	Patients were subcutaneously (SC) injected on Day 1 of Week 1 a loading dose of solution for injection of placebo matching solution for injection of spesolimab followed by a maintenance treatment which consisted of a subcutaneous injection of solution for injection of placebo matching solution for injection of spesolimab every 4 weeks (i.e. on Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40 and 44). The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 of flare (R1/D1) or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).	Patients received on Day 1 of Week 1 a loading dose which consisted of two subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300mg) and two subcutaneous injections of placebo matching solution for injection of spesolimab. The loading dose was followed by a maintenance treatment which consisted of one SC injection of 150 mg of solution for injection of spesolimab and one SC injection of placebo matching solution for injection of spesolimab every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).	Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 12 weeks (i.e. at Week 12, 24 and 36). To maintain the treatment blind during the trial the patients in this arm received two SC injections of placebo matching solution for injection of spesolimab at Week 4, 8, 16, 20, 28, 32, 40 and 44. The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered subcutaneously every 12 weeks or every 4 weeks (intensified maintenance therapy).	Patients received on Day 1 of Week 1 a loading dose which consisted of four subcutaneous (SC) injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab= 600 mg). The loading dose was followed by a maintenance treatment which consisted of two SC injections of 150 mg of solution for injection of spesolimab (total dose of spesolimab=300 mg) every 4 weeks (i.e. at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44). The patients who experienced a flare during the 48 week randomised treatment period were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare followed by OL maintenance treatment if time allowed which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).	This arm includes the patients who were randomized at study start in the arms "Placebo" or "Spesolimab SC low dose" or "Spesolimab SC medium dose" or "Spesolimab SC high dose" who took a single dose (SD) of rescue treatment of 900 milligram (mg) of spesolimab administered intravenously (IV) at Day 1 of flare (R1/D1) because of a GPP flare during the 48 week treatment randomised period.	This arm includes the patients who were randomized at study start in the arms "Placebo" or "Spesolimab SC low dose" or "Spesolimab SC medium dose" or "Spesolimab SC high dose" who took two doses (DD) of rescue treatment of spesolimab each 900 milligram (mg) of spesolimab administered intravenously (IV) at Day 1 and at Day 8 of flare (R1/D1 and R3/D8) because of a GPP flare during the 48 week treatment randomised period.	This arm includes the patients who were randomized at study start in the arms "Placebo" or "Spesolimab SC low dose" or "Spesolimab SC medium dose" or "Spesolimab SC high dose" who experienced a flare during the 48 week randomised treatment period and were administered intravenously (IV) in an open label (OL) fashion with 900 milligram (mg) of solution for infusion of spesolimab at either Day 1 (R1/D1) of flare or at Day 1 (R1/D1) and at Day 8 (R3/D8) of flare and then followed by maintenance treatment which consisted of 300 mg of spesolimab administered SC every 12 weeks or every 4 weeks (intensified maintenance therapy).
All-Cause Mortality
	Placebo	Spesolimab SC Low Dose	Spesolimab SC Medium Dose	Spesolimab SC High Dose	Spesolimab IV SD	Spesolimab IV DD	Spesolimab OL SC
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/30 (0.00%)	0/32 (0.00%)	0/31 (0.00%)	0/30 (0.00%)	0/22 (0.00%)	0/10 (0.00%)	0/20 (0.00%)
Serious Adverse Events
	Placebo	Spesolimab SC Low Dose	Spesolimab SC Medium Dose	Spesolimab SC High Dose	Spesolimab IV SD	Spesolimab IV DD	Spesolimab OL SC
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/30 (3.33%)	5/32 (15.63%)	1/31 (3.23%)	3/30 (10.00%)	1/22 (4.55%)	4/10 (40.00%)	1/20 (5.00%)
Cardiac disorders
Palpitations † 1	0/30 (0.00%)	1/32 (3.13%)	0/31 (0.00%)	0/30 (0.00%)	0/22 (0.00%)	0/10 (0.00%)	0/20 (0.00%)
General disorders
Oedema † 1	0/30 (0.00%)	0/32 (0.00%)	0/31 (0.00%)	0/30 (0.00%)	0/22 (0.00%)	1/10 (10.00%)	0/20 (0.00%)
Hepatobiliary disorders
Cholelithiasis † 1	0/30 (0.00%)	0/32 (0.00%)	0/31 (0.00%)	1/30 (3.33%)	0/22 (0.00%)	0/10 (0.00%)	0/20 (0.00%)
Infections and infestations
Cellulitis † 1	0/30 (0.00%)	0/32 (0.00%)	0/31 (0.00%)	0/30 (0.00%)	0/22 (0.00%)	1/10 (10.00%)	0/20 (0.00%)
Encephalitis viral † 1	0/30 (0.00%)	1/32 (3.13%)	0/31 (0.00%)	0/30 (0.00%)	0/22 (0.00%)	0/10 (0.00%)	0/20 (0.00%)
Pneumonia † 1	0/30 (0.00%)	1/32 (3.13%)	0/31 (0.00%)	0/30 (0.00%)	0/22 (0.00%)	1/10 (10.00%)	0/20 (0.00%)
Septic shock † 1	0/30 (0.00%)	0/32 (0.00%)	0/31 (0.00%)	0/30 (0.00%)	0/22 (0.00%)	1/10 (10.00%)	0/20 (0.00%)
Skin bacterial infection † 1	0/30 (0.00%)	0/32 (0.00%)	1/31 (3.23%)	0/30 (0.00%)	0/22 (0.00%)	0/10 (0.00%)	0/20 (0.00%)
Urinary tract infection † 1	0/30 (0.00%)	0/32 (0.00%)	0/31 (0.00%)	0/30 (0.00%)	1/22 (4.55%)	0/10 (0.00%)	0/20 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma † 1	0/30 (0.00%)	0/32 (0.00%)	0/31 (0.00%)	0/30 (0.00%)	0/22 (0.00%)	0/10 (0.00%)	1/20 (5.00%)
Breast cancer † 1	0/30 (0.00%)	0/32 (0.00%)	0/31 (0.00%)	1/30 (3.33%)	0/22 (0.00%)	0/10 (0.00%)	0/20 (0.00%)
Nervous system disorders
Cerebral ischaemia † 1	0/30 (0.00%)	0/32 (0.00%)	0/31 (0.00%)	0/30 (0.00%)	0/22 (0.00%)	1/10 (10.00%)	0/20 (0.00%)
Hypertensive encephalopathy † 1	0/30 (0.00%)	1/32 (3.13%)	0/31 (0.00%)	0/30 (0.00%)	0/22 (0.00%)	0/10 (0.00%)	0/20 (0.00%)
Multiple sclerosis † 1	1/30 (3.33%)	0/32 (0.00%)	0/31 (0.00%)	0/30 (0.00%)	0/22 (0.00%)	0/10 (0.00%)	0/20 (0.00%)
Skin and subcutaneous tissue disorders
Angioedema † 1	0/30 (0.00%)	1/32 (3.13%)	0/31 (0.00%)	0/30 (0.00%)	0/22 (0.00%)	0/10 (0.00%)	0/20 (0.00%)
Drug eruption † 1	0/30 (0.00%)	1/32 (3.13%)	0/31 (0.00%)	0/30 (0.00%)	0/22 (0.00%)	0/10 (0.00%)	0/20 (0.00%)
Pustular psoriasis † 1	0/30 (0.00%)	1/32 (3.13%)	1/31 (3.23%)	1/30 (3.33%)	0/22 (0.00%)	1/10 (10.00%)	0/20 (0.00%)
1 Term from vocabulary, MedDRA 25.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo	Spesolimab SC Low Dose	Spesolimab SC Medium Dose	Spesolimab SC High Dose	Spesolimab IV SD	Spesolimab IV DD	Spesolimab OL SC
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	24/30 (80.00%)	25/32 (78.13%)	23/31 (74.19%)	20/30 (66.67%)	12/22 (54.55%)	3/10 (30.00%)	14/20 (70.00%)
Gastrointestinal disorders
Constipation † 1	0/30 (0.00%)	0/32 (0.00%)	0/31 (0.00%)	0/30 (0.00%)	0/22 (0.00%)	1/10 (10.00%)	0/20 (0.00%)
Nausea † 1	2/30 (6.67%)	2/32 (6.25%)	0/31 (0.00%)	0/30 (0.00%)	1/22 (4.55%)	0/10 (0.00%)	0/20 (0.00%)
Odynophagia † 1	0/30 (0.00%)	0/32 (0.00%)	0/31 (0.00%)	0/30 (0.00%)	0/22 (0.00%)	1/10 (10.00%)	0/20 (0.00%)
Vomiting † 1	2/30 (6.67%)	0/32 (0.00%)	0/31 (0.00%)	0/30 (0.00%)	0/22 (0.00%)	0/10 (0.00%)	0/20 (0.00%)
General disorders
Asthenia † 1	0/30 (0.00%)	0/32 (0.00%)	0/31 (0.00%)	0/30 (0.00%)	0/22 (0.00%)	1/10 (10.00%)	1/20 (5.00%)
Chest discomfort † 1	0/30 (0.00%)	0/32 (0.00%)	0/31 (0.00%)	0/30 (0.00%)	0/22 (0.00%)	1/10 (10.00%)	0/20 (0.00%)
Injection site erythema † 1	1/30 (3.33%)	4/32 (12.50%)	4/31 (12.90%)	5/30 (16.67%)	0/22 (0.00%)	0/10 (0.00%)	2/20 (10.00%)
Injection site induration † 1	0/30 (0.00%)	1/32 (3.13%)	0/31 (0.00%)	1/30 (3.33%)	0/22 (0.00%)	0/10 (0.00%)	2/20 (10.00%)
Injection site pain † 1	2/30 (6.67%)	1/32 (3.13%)	1/31 (3.23%)	2/30 (6.67%)	0/22 (0.00%)	0/10 (0.00%)	2/20 (10.00%)
Injection site swelling † 1	0/30 (0.00%)	0/32 (0.00%)	2/31 (6.45%)	1/30 (3.33%)	0/22 (0.00%)	0/10 (0.00%)	1/20 (5.00%)
Pyrexia † 1	1/30 (3.33%)	3/32 (9.38%)	2/31 (6.45%)	2/30 (6.67%)	2/22 (9.09%)	0/10 (0.00%)	0/20 (0.00%)
Infections and infestations
COVID-19 † 1	1/30 (3.33%)	2/32 (6.25%)	1/31 (3.23%)	3/30 (10.00%)	0/22 (0.00%)	0/10 (0.00%)	2/20 (10.00%)
Folliculitis † 1	0/30 (0.00%)	2/32 (6.25%)	0/31 (0.00%)	1/30 (3.33%)	1/22 (4.55%)	0/10 (0.00%)	2/20 (10.00%)
Influenza † 1	0/30 (0.00%)	2/32 (6.25%)	0/31 (0.00%)	1/30 (3.33%)	0/22 (0.00%)	0/10 (0.00%)	0/20 (0.00%)
Nasopharyngitis † 1	2/30 (6.67%)	1/32 (3.13%)	3/31 (9.68%)	0/30 (0.00%)	0/22 (0.00%)	0/10 (0.00%)	1/20 (5.00%)
Upper respiratory tract infection † 1	4/30 (13.33%)	3/32 (9.38%)	6/31 (19.35%)	0/30 (0.00%)	1/22 (4.55%)	1/10 (10.00%)	4/20 (20.00%)
Urinary tract infection † 1	0/30 (0.00%)	1/32 (3.13%)	0/31 (0.00%)	4/30 (13.33%)	2/22 (9.09%)	1/10 (10.00%)	3/20 (15.00%)
Investigations
Blood creatine phosphokinase increased † 1	2/30 (6.67%)	4/32 (12.50%)	1/31 (3.23%)	0/30 (0.00%)	0/22 (0.00%)	0/10 (0.00%)	0/20 (0.00%)
Blood trypsin increased † 1	1/30 (3.33%)	2/32 (6.25%)	0/31 (0.00%)	0/30 (0.00%)	1/22 (4.55%)	0/10 (0.00%)	0/20 (0.00%)
Protein urine present † 1	2/30 (6.67%)	1/32 (3.13%)	0/31 (0.00%)	0/30 (0.00%)	0/22 (0.00%)	0/10 (0.00%)	0/20 (0.00%)
Tryptase increased † 1	0/30 (0.00%)	3/32 (9.38%)	0/31 (0.00%)	0/30 (0.00%)	0/22 (0.00%)	0/10 (0.00%)	0/20 (0.00%)
Metabolism and nutrition disorders
Hyperlipidaemia † 1	0/30 (0.00%)	0/32 (0.00%)	0/31 (0.00%)	0/30 (0.00%)	0/22 (0.00%)	1/10 (10.00%)	0/20 (0.00%)
Hypertriglyceridaemia † 1	1/30 (3.33%)	2/32 (6.25%)	0/31 (0.00%)	0/30 (0.00%)	0/22 (0.00%)	0/10 (0.00%)	0/20 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/30 (3.33%)	4/32 (12.50%)	1/31 (3.23%)	3/30 (10.00%)	2/22 (9.09%)	0/10 (0.00%)	0/20 (0.00%)
Joint swelling † 1	0/30 (0.00%)	2/32 (6.25%)	0/31 (0.00%)	0/30 (0.00%)	0/22 (0.00%)	0/10 (0.00%)	0/20 (0.00%)
Nervous system disorders
Dizziness † 1	0/30 (0.00%)	0/32 (0.00%)	0/31 (0.00%)	1/30 (3.33%)	0/22 (0.00%)	1/10 (10.00%)	0/20 (0.00%)
Headache † 1	1/30 (3.33%)	1/32 (3.13%)	1/31 (3.23%)	2/30 (6.67%)	2/22 (9.09%)	0/10 (0.00%)	2/20 (10.00%)
Psychiatric disorders
Anxiety † 1	2/30 (6.67%)	1/32 (3.13%)	0/31 (0.00%)	0/30 (0.00%)	0/22 (0.00%)	0/10 (0.00%)	0/20 (0.00%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain † 1	1/30 (3.33%)	0/32 (0.00%)	1/31 (3.23%)	0/30 (0.00%)	0/22 (0.00%)	1/10 (10.00%)	0/20 (0.00%)
Skin and subcutaneous tissue disorders
Dermatitis contact † 1	0/30 (0.00%)	1/32 (3.13%)	2/31 (6.45%)	0/30 (0.00%)	0/22 (0.00%)	0/10 (0.00%)	0/20 (0.00%)
Erythema † 1	0/30 (0.00%)	1/32 (3.13%)	0/31 (0.00%)	1/30 (3.33%)	2/22 (9.09%)	0/10 (0.00%)	0/20 (0.00%)
Pruritus † 1	0/30 (0.00%)	1/32 (3.13%)	1/31 (3.23%)	2/30 (6.67%)	1/22 (4.55%)	0/10 (0.00%)	0/20 (0.00%)
Psoriasis † 1	3/30 (10.00%)	4/32 (12.50%)	5/31 (16.13%)	4/30 (13.33%)	1/22 (4.55%)	1/10 (10.00%)	0/20 (0.00%)
Pustular psoriasis † 1	16/30 (53.33%)	9/32 (28.13%)	9/31 (29.03%)	2/30 (6.67%)	5/22 (22.73%)	0/10 (0.00%)	4/20 (20.00%)
Seborrhoeic dermatitis † 1	1/30 (3.33%)	2/32 (6.25%)	1/31 (3.23%)	0/30 (0.00%)	0/22 (0.00%)	0/10 (0.00%)	0/20 (0.00%)
Urticaria † 1	2/30 (6.67%)	1/32 (3.13%)	1/31 (3.23%)	0/30 (0.00%)	0/22 (0.00%)	0/10 (0.00%)	1/20 (5.00%)
1 Term from vocabulary, MedDRA 25.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim
• Phone: 1-800-243-0127
• EMail: clintriage.rdg@boehringer-ingelheim.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT04399837
• Other Study ID Numbers: 1368-0027; 2018-003081-14 ( EudraCT Number )
• First Submitted: May 20, 2020
• First Posted: May 22, 2020
• Results First Submitted: November 21, 2023
• Results First Posted: December 14, 2023
• Last Update Posted: December 14, 2023