Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44338   clinical trials with a EudraCT protocol, of which   7368   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Effisayil™ 2: Multi-center, randomized, parallel group, double blind, placebo controlled, Phase IIb dose-finding study to evaluate efficacy and safety of BI 655130 (Spesolimab) compared to placebo in preventing generalized pustular psoriasis (GPP) flares in patients with history of GPP

    Summary
    EudraCT number
    		 2018-003081-14
    Trial protocol
    		 DE   BE   ES   NL   GR   FR   CZ   PL   BG   IT   HR  
    Global end of trial date
    23 Nov 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    07 Jun 2023
    First version publication date
    07 Jun 2023
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    1368-0027
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04399837
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Boehringer Ingelheim
    Sponsor organisation address
    Binger Strasse 173, Ingelheim am Rhein, Germany, 55216
    Public contact
    Boehringer Ingelheim, Call Center, Boehringer Ingelheim, 001 18002430127, clintriage.rdg@boehringer-ingelheim.com
    Scientific contact
    Boehringer Ingelheim, Call Center, Boehringer Ingelheim, 001 18002430127, clintriage.rdg@boehringer-ingelheim.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-002475-PIP02-19
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    13 Jan 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    23 Nov 2022
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Nov 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the trial was to demonstrate a non-flat dose response curve and evaluate the dose-response relationship for 3 subcutaneous (s.c.) dosing regimens of spesolimab (with each regimen consisting of a single loading dose and a separate maintenance s.c. dosing regimen) versus placebo, on the primary endpoint, the time to the first GPP flare onset up to Week 48. The secondary objective was to demonstrate superiority versus placebo for each of spesolimab high dose (300 milligram (mg) every 4 weeks (q4w)) and spesolimab medium dose (300 mg q12w) on the primary endpoint, the time to the first generalized pustular psoriasis (GPP) flare onset up to Week 48, as well as the key secondary endpoint, the occurrence of at least one GPP flare up to Week 48. Another objective was to evaluate safety and tolerability of multiple s.c. doses of spesolimab in patients with history of GPP.
    Protection of trial subjects
    Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study. All subjects were free to withdraw from the clinical trial at any time for any reason given. Close monitoring of all subjects was adhered to throughout the trial conduct. Rescue medication was allowed for all subjects as required.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    08 Jun 2020
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Efficacy, Safety
    Long term follow-up duration
    		 5 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 3
    Country: Number of subjects enrolled
    Belgium: 2
    Country: Number of subjects enrolled
    Chile: 4
    Country: Number of subjects enrolled
    China: 24
    Country: Number of subjects enrolled
    France: 3
    Country: Number of subjects enrolled
    Germany: 10
    Country: Number of subjects enrolled
    Greece: 1
    Country: Number of subjects enrolled
    Italy: 1
    Country: Number of subjects enrolled
    Japan: 6
    Country: Number of subjects enrolled
    Korea, Republic of: 3
    Country: Number of subjects enrolled
    Malaysia: 25
    Country: Number of subjects enrolled
    Mexico: 2
    Country: Number of subjects enrolled
    Netherlands: 1
    Country: Number of subjects enrolled
    Philippines: 9
    Country: Number of subjects enrolled
    Russian Federation: 15
    Country: Number of subjects enrolled
    South Africa: 1
    Country: Number of subjects enrolled
    Spain: 3
    Country: Number of subjects enrolled
    Taiwan: 5
    Country: Number of subjects enrolled
    Thailand: 12
    Country: Number of subjects enrolled
    Tunisia: 8
    Country: Number of subjects enrolled
    Turkey: 8
    Country: Number of subjects enrolled
    United States: 2
    Country: Number of subjects enrolled
    Viet Nam: 9
    Worldwide total number of subjects
    157
    EEA total number of subjects
    21
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    10
    Adults (18-64 years)
    136
    From 65 to 84 years
    11
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 This was a 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.

    Pre-assignment
    Screening details
    		 Subjects attended a specialist site which ensured that they (the subjects) met all inclusion and none of the exclusion criteria. 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).

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Investigator, Monitor, Subject, Carer, Data analyst, Assessor
    Blinding implementation details
    To maintain the treatment blind during the trial, all patients received the blinded treatments every 4 weeks.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm 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 tretament 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).
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo to match Solution for Injection (BI 655130)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    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 tretament 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).

    Investigational medicinal product name
    Spesolimab
    Investigational medicinal product code
    BI 655130
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    The patients who experienced a flare were administered 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).

    Investigational medicinal product name
    Spesolimab
    Investigational medicinal product code
    BI 655130
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    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.

    Arm title
    		 Spesolimab SC low dose
    Arm description
    		 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). 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 R1/D1 of flare or at R1/D1 and at 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).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Spesolimab
    Investigational medicinal product code
    BI 655130
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    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). The patients who experienced a flare during the 48 week randomised treatment period and received IV spesolimab were administered 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).

    Investigational medicinal product name
    Spesolimab
    Investigational medicinal product code
    BI 655130
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    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 R1/D1 of flare or at R1/D1 and at R3/D8.

    Arm title
    		 Spesolimab SC medium dose
    Arm description
    		 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). 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).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Spesolimab
    Investigational medicinal product code
    BI 655130
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    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.

    Investigational medicinal product name
    Spesolimab
    Investigational medicinal product code
    BI 655130
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    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). The patients who experienced a flare during the 48 week randomised treatment period and received IV spesolimab were administered 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).

    Arm title
    		 Spesolimab SC high dose
    Arm description
    		 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).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Spesolimab
    Investigational medicinal product code
    BI 655130
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    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 and received IV spesolimab were administered 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).

    Investigational medicinal product name
    Spesolimab
    Investigational medicinal product code
    BI 655130
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    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.

    Number of subjects in period 1 [1]
    		Placebo Spesolimab SC low dose Spesolimab SC medium dose Spesolimab SC high dose
    Started
    31
    31
    31
    30
    Completed
    30
    27
    28
    26
    Not completed
    1
    4
    3
    4
         Consent withdrawn by subject
    1
    2
    1
    1
         Other than listed
    -
    2
    2
    3
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Out of 157 enrolled patients only 123 were randomized.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting 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 tretament 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).

    Reporting group title
    Spesolimab SC low dose
    Reporting group description
    		 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). 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 R1/D1 of flare or at R1/D1 and at 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).

    Reporting group title
    Spesolimab SC medium dose
    Reporting group description
    		 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). 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).

    Reporting group title
    Spesolimab SC high dose
    Reporting group description
    		 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).

    Reporting group values
    		 Placebo Spesolimab SC low dose Spesolimab SC medium dose Spesolimab SC high dose Total
    Number of subjects
    		 31 31 31 30 123
    Age categorical
    Randomized Set: This patient set includes all randomized patients.
    Units: Subjects
        In utero
    		 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0
        Adolescents (12-17 years)
    		 2 2 2 2 8
        Adults (18-64 years)
    		 28 27 27 25 107
        From 65-84 years
    		 1 2 2 3 8
        85 years and over
    		 0 0 0 0 0
    Age Continuous
    Randomized Set: This patient set includes all randomized patients.
    Units: years
        arithmetic mean (standard deviation)
    		 39.5 ( 14.0 ) 38.9 ( 16.5 ) 42.9 ( 16.7 ) 40.2 ( 16.4 ) -
    Sex: Female, Male
    Randomized Set: This patient set includes all randomized patients.
    Units: Participants
        Female
    		 18 20 20 18 76
        Male
    		 13 11 11 12 47
    Race (NIH/OMB)
    Randomized Set: This patient set includes all randomized patients.
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0
        Asian
    		 17 20 21 21 79
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0
        Black or African American
    		 0 0 0 0 0
        White
    		 14 11 10 9 44
        More than one race
    		 0 0 0 0 0
        Unknown or Not Reported
    		 0 0 0 0 0
    Ethnicity (NIH/OMB)
    Randomized Set: This patient set includes all randomized patients.
    Units: Subjects
        Hispanic or Latino
    		 3 3 0 1 7
        Not Hispanic or Latino
    		 28 28 31 29 116
        Unknown or Not Reported
    		 0 0 0 0 0
    Number of patients in the categories 0 or 1 of GPPGA score
    Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) relied on the clinical assessment of GPP patient’s skin presentation. The total score is calculated by taking the mean of the three subscores: 1) erythema; 2) pustules and 3) scaling/crusting which were assessed using a scale score 0 to 4 (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe). The final GPPGA score: 0 , if scores for all three subscores are 0, 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. Number of patients in the categories 0 or 1 of GPPGA score is reported.
    Units: Subjects
        GPPGA score = 0
    		 4 2 8 3 17
        GPPGA score = 1
    		 27 29 23 27 106
    Number of patients in the categories 0 or 1 of GPPGA pustules subscore
    The Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustules subscore relied on clinical assessment of the Generalized Pustular Psoriasis (GPP) pustules presentation. The investigator (or qualified site personnel) scored the pustules of all GPP lesions from 0 to 4 where: 0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe. Number of patients in the categories 0 or 1 of GPPGA pustules subscore is reported. Randomized Set.
    Units: Subjects
        GPPGA pustules subscore=0
    		 21 23 24 20 88
        GPPGA pustules subscore=1
    		 10 8 7 10 35
    Concomitant use of systemic GPP medication at randomization
    Number of patients in each category of concomitant use of systemic GPP medication at randomization (-28 days to randomization). The reported categories of concomitant use of systemic GPP medication at randomization are: Yes; No. Randomized Set: This patient set includes all randomized patients.
    Units: Subjects
        Systemic GPP medication at randomization=No
    		 9 6 8 8 31
        Systemic GPP medication at randomization=Yes
    		 22 25 23 22 92
    Psoriasis Symptom Scale (PSS) total score at baseline
    The PSS is a 4-item patient-reported outcome (PRO) instrument that was developed to assess the severity of 4 psoriasis symptoms in patients with moderate to severe psoriasis. The symptoms included are: pain, redness, itching, and burning. Current symptom severity is assessed using a 5-point scale ranging from 0 (none) to 4 (very severe). The symptom scores are added to an unweighted total score (range: 0 (no symptoms) to 16 (severe symptoms). Randomized Set.
    Units: score on a scale
        arithmetic mean (standard deviation)
    		 3.6 ( 2.9 ) 4.1 ( 3.8 ) 3.9 ( 2.9 ) 5.3 ( 3.8 ) -
    DLQI total score at baseline
    The Dermatology Quality of Life Index (DLQI) is a patient-administered, ten-question, quality of life questionnaire that covers six domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships and treatment. Response categories range from 0 (not relevant) to 3 (very much). Question 7 is a “yes”/ “no” question where “yes” is scored as 3. Total score is obtained by summing the scores of each question resulting in a range of 0 (no effect on patient's life) to 30 (extremely large effect on patient’s life). Randomized Set.
    Units: score on a scale
        arithmetic mean (standard deviation)
    		 7.2 ( 5.6 ) 7.6 ( 6.7 ) 6.6 ( 5.6 ) 11.1 ( 6.9 ) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting 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 tretament 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).

    Reporting group title
    Spesolimab SC low dose
    Reporting group description
    		 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). 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 R1/D1 of flare or at R1/D1 and at 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).

    Reporting group title
    Spesolimab SC medium dose
    Reporting group description
    		 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). 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).

    Reporting group title
    Spesolimab SC high dose
    Reporting group description
    		 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).

    Subject analysis set title
    Spesolimab IV SD
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    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.

    Subject analysis set title
    Spesolimab IV DD
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    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.

    Subject analysis set title
    Spesolimab OL SC
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    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).

    Subject analysis set title
    Spesolimab SC low dose (safety)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    This arm includes all the patients randomized to the arm “Spesolimab SC low dose” plus one patient who was randomized to “Placebo” arm but received active spesolimab dose.

    Subject analysis set title
    Placebo (safety)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    This arm includes all the patients who were randomized to the arm “Placebo" and were administered placebo matching solution for injection of Spesolimab.

    Primary: Time to first Generalized Pustular Psoriasis (GPP) flare

    		 Close Top of page
    End point title
    		 Time to first Generalized Pustular Psoriasis (GPP) flare
    End point description
    A GPP flare was defined as increase in GPP 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 SoC for GPP worsening, was considered to represent a GPP flare onset. GPPGA relied on clinical assessment of the 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 subscores are 0, - 1, if 0 < mean < 1.5, - 2, if 1.5 ≤ mean < 2.5, - 3, if 2.5 ≤ mean < 3.5, - 4, if mean ≥ 3.5. Randomized Set (EM−PM): This patient set includes all randomized patients.EM:primary estimand for randomised maintenance period. PM: primary method for censoring.
    End point type
    Primary
    End point timeframe
    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.
    End point values
    		 Placebo Spesolimab SC low dose Spesolimab SC medium dose Spesolimab SC high dose
    Number of subjects analysed
    31 [1]
    31 [2]
    31 [3]
    30 [4]
    Units: weeks
        median (confidence interval 95%)
    37.3 (4.0 to 999999)
    999999 (-999999 to 999999)
    999999 (-999999 to 999999)
    999999 (-999999 to 999999)
    Notes
    [1] - Randomized Set (EM−PM). 999999= NA=Insufficient number of participants with events.
    [2] - Randomized Set (EM−PM). -999999 and 999999= NA=Insufficient number of participants with events.
    [3] - Randomized Set (EM−PM). -999999 and 999999= NA=Insufficient number of participants with events.
    [4] - Randomized Set (EM−PM). -999999 and 999999= NA=Insufficient number of participants with events.
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    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).
    Comparison groups
    Placebo v Spesolimab SC low dose v Spesolimab SC medium dose v Spesolimab SC high dose
    Number of subjects included in analysis
    123
    Analysis specification
    Pre-specified
    Analysis type
    		 other [5]
    P-value
    		 = 0.002
    Method
    		 MCP-Mod linear model fit
    Parameter type
    		 Multiple contrast test
    Point estimate
    3.041
    Confidence interval
         level
    		 0%
         sides
    2-sided
         lower limit
    		 -999999
         upper limit
    		 999999
    Notes
    [5] - 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. Model assumption: Dose effect is linear with the increase of dose. -999999 and 999999= Not applicable=No confidence interval applicable for this analysis.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    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).
    Comparison groups
    Placebo v Spesolimab SC low dose v Spesolimab SC medium dose v Spesolimab SC high dose
    Number of subjects included in analysis
    123
    Analysis specification
    Pre-specified
    Analysis type
    		 other [6]
    P-value
    		 = 0.002
    Method
    		 MCP-Mod Emax2 model fit
    Parameter type
    		 Multiple contrast test
    Point estimate
    3.033
    Confidence interval
         level
    		 0%
         sides
    2-sided
         lower limit
    		 -999999
         upper limit
    		 999999
    Notes
    [6] - 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. Model assumption: 95% of the maximum effect is achieved at low dose. -999999 and 999999= Not applicable=No confidence interval for this analysis
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    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).
    Comparison groups
    Placebo v Spesolimab SC low dose v Spesolimab SC medium dose v Spesolimab SC high dose
    Number of subjects included in analysis
    123
    Analysis specification
    Pre-specified
    Analysis type
    		 other [7]
    P-value
    		 = 0.002
    Method
    		 MCP-Mod Emax1 model fit
    Parameter type
    		 Multiple contrast test
    Point estimate
    3.088
    Confidence interval
         level
    		 0%
         sides
    2-sided
         lower limit
    		 -999999
         upper limit
    		 999999
    Notes
    [7] - 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. Model assumption: 70% of the maximum effect is achieved at low dose. -999999 and 999999= Not applicable=No confidence interval for this analysis
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    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).
    Comparison groups
    Placebo v Spesolimab SC low dose v Spesolimab SC medium dose v Spesolimab SC high dose
    Number of subjects included in analysis
    123
    Analysis specification
    Pre-specified
    Analysis type
    		 other [8]
    P-value
    		 = 0.003
    Method
    		 MCP-Mod exponential model fit
    Parameter type
    		 Multiple contrast test
    Point estimate
    2.977
    Confidence interval
         level
    		 0%
         sides
    2-sided
         lower limit
    		 -999999
         upper limit
    		 999999
    Notes
    [8] - 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. Model assumption: 35% of the maximum effect is achieved at medium dose. -999999 and 999999= Not applicable=No confidence interval for this analysis
    Statistical analysis title
    		 Statistical Analysis 5
    Statistical analysis description
    Hazard ratio and its 95% CI (confidence interval) are from Cox regression model stratified by use of systemic GPP medication at randomisation.
    Comparison groups
    Placebo v Spesolimab SC medium dose
    Number of subjects included in analysis
    62
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [9]
    P-value
    		 = 0.0269 [10]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.468
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.206
         upper limit
    		 1.064
    Notes
    [9] - Null hypothesis: Effect of spesolimab 300 mg every 12 weeks on prolonging the time to the first GPP flare up to week 48 ≤ Placebo.
    [10] - 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.
    Statistical analysis title
    		 Statistical Analysis 6
    Statistical analysis description
    Hazard ratio and its 95% CI (confidence interval) are from Cox regression model stratified by use of systemic GPP medication at randomisation.
    Comparison groups
    Placebo v Spesolimab SC high dose
    Number of subjects included in analysis
    61
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [11]
    P-value
    		 = 0.0005 [12]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.157
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.046
         upper limit
    		 0.541
    Notes
    [11] - Null hypothesis: Effect of spesolimab 300 mg every 4 weeks on prolonging the time to the first GPP flare up to week 48 ≤ Placebo.
    [12] - 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.

    Secondary: Key secondary endpoint: The occurrence of at least one Generalized Pustular Psoriasis (GPP) flare up to Week 48

    		 Close Top of page
    End point title
    		 Key secondary endpoint: The occurrence of at least one Generalized Pustular Psoriasis (GPP) flare up to Week 48
    End point 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 GPP 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. 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 of three subscores are 0, 1, if 0 < mean < 1.5; 2, if 1.5 ≤ mean < 2.5; 3, if 2.5 ≤ mean < 3.5; 4, if mean ≥ 3.5. Randomized Set (EM−MI): This patient set includes all randomized patients. MI: multiple imputation method.
    End point type
    Secondary
    End point timeframe
    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.
    End point values
    		 Placebo Spesolimab SC low dose Spesolimab SC medium dose Spesolimab SC high dose
    Number of subjects analysed
    31 [13]
    31 [14]
    31 [15]
    30 [16]
    Units: proportion of patients
        number (confidence interval 95%)
    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)
    Notes
    [13] - Randomized Set (EM−MI).
    [14] - Randomized Set (EM−MI).
    [15] - Randomized Set (EM−MI).
    [16] - Randomized Set (EM−MI).
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference=Spesolimab high dose-Placebo.
    Comparison groups
    Placebo v Spesolimab SC high dose
    Number of subjects included in analysis
    61
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [17]
    P-value
    		 = 0.0013 [18]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -0.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.621
         upper limit
    		 -0.159
    Notes
    [17] - 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.
    [18] - 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

    Secondary: Time to first worsening of Dermatology Quality of Life Index (DLQI) up to Week 48

    		 Close Top of page
    End point title
    		 Time to first worsening of Dermatology Quality of Life Index (DLQI) up to Week 48
    End point 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). Randomized Set (EM−PM): This patient set includes all randomized patients. EM:primary estimand for randomised maintenance period. PM: primary method for censoring.
    End point type
    Secondary
    End point timeframe
    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.
    End point values
    		 Placebo Spesolimab SC low dose Spesolimab SC medium dose Spesolimab SC high dose
    Number of subjects analysed
    31 [19]
    31 [20]
    31 [21]
    30 [22]
    Units: weeks
        median (confidence interval 95%)
    16.0 (4.0 to 999999)
    35.8 (8.1 to 999999)
    49.3 (8.7 to 49.3)
    999999 (-999999 to 999999)
    Notes
    [19] - Randomized Set (EM−PM). 999999= NA=Insufficient number of participants with events.
    [20] - Randomized Set (EM−PM). 999999= NA=Insufficient number of participants with events.
    [21] - Randomized Set (EM−PM). 999999= NA=Insufficient number of participants with events.
    [22] - Randomized Set (EM−PM). -999999 and 999999= NA=Insufficient number of participants with events.
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    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 spesolimab high dose vs. Placebo
    Comparison groups
    Placebo v Spesolimab SC high dose
    Number of subjects included in analysis
    61
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [23]
    P-value
    		 = 0.001 [24]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.259
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.109
         upper limit
    		 0.62
    Notes
    [23] - 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.
    [24] - One sided p−value was computed from the log−rank test stratified by use of systemic GPP medication at randomisation.

    Secondary: Time to first worsening of Psoriasis Symptom Scale (PSS) up to Week 48

    		 Close Top of page
    End point title
    		 Time to first worsening of Psoriasis Symptom Scale (PSS) up to Week 48
    End point 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)). Randomized Set (EM−PM): This patient set includes all randomized patients. EM:primary estimand for randomised maintenance period. PM: primary method for censoring.
    End point type
    Secondary
    End point timeframe
    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.
    End point values
    		 Placebo Spesolimab SC low dose Spesolimab SC medium dose Spesolimab SC high dose
    Number of subjects analysed
    31 [25]
    31 [26]
    31 [27]
    30 [28]
    Units: weeks
        median (confidence interval 95%)
    16.0 (4.0 to 999999)
    999999 (8.1 to 999999)
    999999 (8.7 to 999999)
    999999 (12.0 to 999999)
    Notes
    [25] - Randomized Set (EM−PM). 999999= NA=Insufficient number of participants with events.
    [26] - Randomized Set (EM−PM). 999999= NA=Insufficient number of participants with events.
    [27] - Randomized Set (EM−PM). 999999= NA=Insufficient number of participants with events.
    [28] - Randomized Set (EM−PM). 999999= NA=Insufficient number of participants with events.
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Hazard ratio and its 95% CI (confidence interval) are from Cox regression model stratified by use of systemic GPP medication at randomisation. spesolimab high dose vs. Placebo
    Comparison groups
    Placebo v Spesolimab SC high dose
    Number of subjects included in analysis
    61
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [29]
    P-value
    		 = 0.0134 [30]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.424
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.197
         upper limit
    		 0.914
    Notes
    [29] - 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.
    [30] - 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

    Secondary: Sustained remission

    		 Close Top of page
    End point title
    		 Sustained remission
    End point 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 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 of three subscores are 0, - 1, if 0 < mean < 1.5, - 2, if 1.5 ≤ mean < 2.5, - 3, if 2.5 ≤ mean < 3.5, - 4, if mean ≥ 3.5. Randomized Set (EM−MI): This patient set includes all randomized patients. MI: multiple imputation method.
    End point type
    Secondary
    End point timeframe
    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.
    End point values
    		 Placebo Spesolimab SC low dose Spesolimab SC medium dose Spesolimab SC high dose
    Number of subjects analysed
    31 [31]
    31 [32]
    31 [33]
    30 [34]
    Units: proportion of patients
        number (confidence interval 95%)
    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)
    Notes
    [31] - Randomized Set (EM−MI).
    [32] - Randomized Set (EM−MI).
    [33] - Randomized Set (EM−MI).
    [34] - Randomized Set (EM−MI).
    No statistical analyses for this end point

    Secondary: The occurrence of treatment emergent adverse events (TEAEs)

    		 Close Top of page
    End point title
    		 The occurrence of treatment emergent adverse events (TEAEs) [35]
    End point 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. 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. Arms "Speso IV SD, Speso IV DD": SAF-FT- Safety Analysis set for flare rescue treatment period. Arm "Speso OL SC": SAF-MT- Safety Analysis set for OL maintenance treatment period.
    End point type
    Secondary
    End point timeframe
    Up to 62 weeks (for detailed timeframe see description).
    Notes
    [35] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The baseline period arm "Spesolimab SC low dose" is reported as a Subject Analysis Set, because it includes also on patient from the Placebo arm. The patients from the placebo arm was randomized to “Placebo” arm but received active spesolimab dose, therefore is reported under the arm "Spesolimab SC low dose".
    End point values
    		 Spesolimab SC medium dose Spesolimab SC high dose Spesolimab IV SD Spesolimab IV DD Spesolimab OL SC Spesolimab SC low dose (safety) Placebo (safety)
    Number of subjects analysed
    31
    30
    22
    10
    20
    32
    30
    Units: percentage of patients
        number (not applicable)
    93.5
    86.7
    68.2
    60.0
    75.0
    90.6
    86.7
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Up to 62 weeks (for detailed timeframe please see the description of the endpoint "The occurrence of treatment emergent adverse events (TEAEs)").
    Adverse event reporting additional description
    Placebo, Speso SC Low, medium, high":Safety Set (SAF). One patient who was randomized to placebo arm but received active spesolimab dose is reported under the arm "Spesolimab SC low". "Speso IV SD and DD": SAF-FT- Safety Analysis set for flare rescue treatment period. "Speso OL SC": SAF-MT- Safety Analysis set for OL maintenance treatment period.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting 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 tretament 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).

    Reporting group title
    Speso SC low dose
    Reporting group description
    		 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). 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 R1/D1 of flare or at R1/D1 and at 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).

    Reporting group title
    Speso SC medium dose
    Reporting group description
    		 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). 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).

    Reporting group title
    Speso SC high dose
    Reporting group description
    		 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).

    Reporting group title
    Speso IV SD
    Reporting group description
    		 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.

    Reporting group title
    Speso IV DD
    Reporting group description
    		 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.

    Reporting group title
    Speso OL SC
    Reporting group description
    		 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).

    Serious adverse events
    		 Placebo Speso SC low dose Speso SC medium dose Speso SC high dose Speso IV SD Speso IV DD Speso OL SC
    Total subjects affected by serious adverse events
         subjects affected / exposed
    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%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    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%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    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%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    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%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Multiple sclerosis
         subjects affected / exposed
    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%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive encephalopathy
         subjects affected / exposed
    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%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    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%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Oedema
         subjects affected / exposed
    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%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    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%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    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%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug eruption
         subjects affected / exposed
    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%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pustular psoriasis
         subjects affected / exposed
    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%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    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%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Encephalitis viral
         subjects affected / exposed
    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%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    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%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    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%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin bacterial infection
         subjects affected / exposed
    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%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    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%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo Speso SC low dose Speso SC medium dose Speso SC high dose Speso IV SD Speso IV DD Speso OL SC
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    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%)
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    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%)
         occurrences all number
    3
    5
    1
    0
    0
    0
    0
    Tryptase increased
         subjects affected / exposed
    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%)
         occurrences all number
    0
    5
    0
    0
    0
    0
    0
    Protein urine present
         subjects affected / exposed
    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%)
         occurrences all number
    2
    1
    0
    0
    0
    0
    0
    Blood trypsin increased
         subjects affected / exposed
    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%)
         occurrences all number
    1
    6
    0
    0
    1
    0
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    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%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    Headache
         subjects affected / exposed
    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%)
         occurrences all number
    1
    1
    1
    2
    2
    0
    2
    General disorders and administration site conditions
    Injection site pain
         subjects affected / exposed
    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%)
         occurrences all number
    2
    1
    2
    2
    0
    0
    4
    Injection site swelling
         subjects affected / exposed
    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%)
         occurrences all number
    0
    0
    2
    1
    0
    0
    1
    Pyrexia
         subjects affected / exposed
    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%)
         occurrences all number
    1
    3
    2
    2
    2
    0
    0
    Injection site induration
         subjects affected / exposed
    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%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    2
    Chest discomfort
         subjects affected / exposed
    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%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Asthenia
         subjects affected / exposed
    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%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    Injection site erythema
         subjects affected / exposed
    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%)
         occurrences all number
    1
    16
    6
    17
    0
    0
    6
    Gastrointestinal disorders
    Odynophagia
         subjects affected / exposed
    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%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Vomiting
         subjects affected / exposed
    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%)
         occurrences all number
    3
    0
    0
    0
    0
    0
    0
    Constipation
         subjects affected / exposed
    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%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Nausea
         subjects affected / exposed
    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%)
         occurrences all number
    3
    2
    0
    0
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    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%)
         occurrences all number
    1
    0
    1
    0
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Dermatitis contact
         subjects affected / exposed
    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%)
         occurrences all number
    0
    1
    2
    0
    0
    0
    0
    Erythema
         subjects affected / exposed
    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%)
         occurrences all number
    0
    1
    0
    1
    2
    0
    0
    Pruritus
         subjects affected / exposed
    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%)
         occurrences all number
    0
    1
    1
    2
    1
    0
    0
    Psoriasis
         subjects affected / exposed
    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%)
         occurrences all number
    3
    4
    6
    5
    1
    1
    0
    Pustular psoriasis
         subjects affected / exposed
    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%)
         occurrences all number
    16
    9
    10
    2
    6
    0
    6
    Seborrhoeic dermatitis
         subjects affected / exposed
    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%)
         occurrences all number
    1
    2
    2
    0
    0
    0
    0
    Urticaria
         subjects affected / exposed
    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%)
         occurrences all number
    4
    1
    1
    0
    0
    0
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    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%)
         occurrences all number
    2
    1
    0
    0
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    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%)
         occurrences all number
    1
    4
    2
    5
    3
    0
    0
    Joint swelling
         subjects affected / exposed
    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%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    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%)
         occurrences all number
    1
    2
    1
    3
    0
    0
    2
    Folliculitis
         subjects affected / exposed
    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%)
         occurrences all number
    0
    4
    0
    1
    1
    0
    2
    Influenza
         subjects affected / exposed
    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%)
         occurrences all number
    0
    2
    0
    1
    0
    0
    0
    Urinary tract infection
         subjects affected / exposed
    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%)
         occurrences all number
    0
    1
    0
    6
    2
    1
    3
    Upper respiratory tract infection
         subjects affected / exposed
    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%)
         occurrences all number
    5
    5
    8
    0
    1
    1
    6
    Nasopharyngitis
         subjects affected / exposed
    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%)
         occurrences all number
    2
    1
    4
    0
    0
    0
    1
    Metabolism and nutrition disorders
    Hypertriglyceridaemia
         subjects affected / exposed
    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%)
         occurrences all number
    1
    2
    0
    0
    0
    0
    0
    Hyperlipidaemia
         subjects affected / exposed
    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%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    29 Jul 2020
    Global Amendment No. 1: Changes to Section 7, no longer monitoring the event rate, since it is expected that sufficient events would be observed in the target population. Changes to Section 7.4, changes to randomization to make sure adolescents were included in each treatment arm.
    19 Apr 2021
    Global Amendment No. 2: Changes to Section 7.2.2, to align with Pediatric Investigational Plan (PIP). Changes to Section 7.2.3, descriptive analysis of adults vs pediatric patients to align with PIP. Changes to Section 4.1.4 to permit home administration of treatment drug, if necessary, due to COVID-19.
    28 Jul 2022
    Global Amendment No. 3: Changes to Section 5.2.6.1.4, to include peripheral neuropathy as an adverse event of special interest. Changes to Section 4.2.2.2, to allow the investigator to determine if a patient should continue rescue therapy.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Tue May 27 23:05:58 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA