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    Clinical Trial Results:
    Randomized, double-blind, placebo-controlled, study of spesolimab in patients with moderate to severe hidradenitis suppurativa

    Summary
    EudraCT number
    		 2020-003672-40
    Trial protocol
    		 FR   HU   CZ   BE   NL   DE   GR   IT   ES  
    Global end of trial date
    21 Apr 2022

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

    Trial information

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    Trial identification
    Sponsor protocol code
    1368-0052
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04762277
    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)
    No
    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?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    01 Jun 2022
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    19 Jan 2022
    Global end of trial reached?
    Yes
    Global end of trial date
    21 Apr 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to estimate the effect of spesolimab compared to placebo for the mean percent change from baseline in total abscess and inflammatory nodule (AN) count at Week 12 in patients with moderate to severe hidradenitis suppurativa (HS). Secondary objectives of this trial were the evaluation of efficacy of spesolimab on secondary endpoints versus placebo.
    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
    03 May 2021
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 28 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 8
    Country: Number of subjects enrolled
    Belgium: 2
    Country: Number of subjects enrolled
    Canada: 3
    Country: Number of subjects enrolled
    Czechia: 2
    Country: Number of subjects enrolled
    France: 7
    Country: Number of subjects enrolled
    Germany: 10
    Country: Number of subjects enrolled
    Italy: 5
    Country: Number of subjects enrolled
    Netherlands: 4
    Country: Number of subjects enrolled
    Norway: 3
    Country: Number of subjects enrolled
    Poland: 7
    Country: Number of subjects enrolled
    Spain: 1
    Country: Number of subjects enrolled
    United States: 11
    Worldwide total number of subjects
    63
    EEA total number of subjects
    41
    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)
    0
    Adults (18-64 years)
    63
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This was an international, phase IIa multi-center, double-blind, placebo-controlled trial assessing the efficacy and safety of spesolimab in patients with moderate to severe Hidradenitis suppurativa (HS).

    Pre-assignment
    Screening details
    		 All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

    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
    		 Subject, Investigator, Monitor, Carer, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Patients received placebo administered intravenously (i.v.) at Weeks 0, 1, and 2, and subcutaneously injection at Weeks 4, 6, 8, and 10.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo matching to spesolimab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Patients received placebo administered subcutaneously at Weeks 4, 6, 8, and 10.

    Investigational medicinal product name
    Placebo matching to spesolimab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Patients received placebo administered intravenously (i.v.) at Weeks 0, 1, and 2.

    Arm title
    		 Spesolimab
    Arm description
    		 Patients received 1200 mg of spesolimab administered intravenously (i.v.) at Weeks 0, 1, and 2, and subcutaneously injection at Weeks 4, 6, 8, and 10.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Spesolimab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Patients received 1200 mg of spesolimab administered subcutaneously injection at Weeks 4, 6, 8, and 10.

    Investigational medicinal product name
    Spesolimab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Patients received 1200 mg of spesolimab administered intravenously (i.v.) at Weeks 0, 1, and 2.

    Number of subjects in period 1 [1]
    		Placebo Spesolimab
    Started
    17
    35
    Completed
    16
    32
    Not completed
    1
    3
         Consent withdrawn by subject
    -
    2
         Adverse event, non-fatal
    1
    -
         Protocol deviation
    -
    1
    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 63 patients which were screened only 52 were randomized to receive "placebo" or "spesolimab".

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Patients received placebo administered intravenously (i.v.) at Weeks 0, 1, and 2, and subcutaneously injection at Weeks 4, 6, 8, and 10.

    Reporting group title
    Spesolimab
    Reporting group description
    		 Patients received 1200 mg of spesolimab administered intravenously (i.v.) at Weeks 0, 1, and 2, and subcutaneously injection at Weeks 4, 6, 8, and 10.

    Reporting group values
    		 Placebo Spesolimab Total
    Number of subjects
    		 17 35 52
    Age categorical
    Safety Analysis Set (SAF): This patient set included all patients who were randomized and received at least one dose of study drug.
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 17 35 52
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Age Continuous
    Safety Analysis Set (SAF): This patient set included all patients who were randomized and received at least one dose of study drug.
    Units: years
        arithmetic mean (standard deviation)
    		 34.1 ( 11.0 ) 35.7 ( 11.3 ) -
    Sex: Female, Male
    Safety Analysis Set (SAF): This patient set included all patients who were randomized and received at least one dose of study drug.
    Units: Participants
        Female
    		 10 21 31
        Male
    		 7 14 21
    Race (NIH/OMB)
    Safety Analysis Set (SAF): This patient set included all patients who were randomized and received at least one dose of study drug.
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0
        Asian
    		 2 4 6
        Native Hawaiian or Other Pacific Islander
    		 0 1 1
        Black or African American
    		 2 2 4
        White
    		 12 23 35
        More than one race
    		 0 0 0
        Unknown or Not Reported
    		 1 5 6
    Ethnicity (NIH/OMB)
    Safety Analysis Set (SAF): This patient set included all patients who were randomized and received at least one dose of study drug.
    Units: Subjects
        Hispanic or Latino
    		 1 1 2
        Not Hispanic or Latino
    		 15 29 44
        Unknown or Not Reported
    		 1 5 6
    Total number of abscesses and inflammatory nodules
    Total number of abscesses and inflammatory nodules at baseline.
    Units: abscesses and inflammatory nodules
        arithmetic mean (standard deviation)
    		 18.9 ( 15.7 ) 11.6 ( 9.3 ) -

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Patients received placebo administered intravenously (i.v.) at Weeks 0, 1, and 2, and subcutaneously injection at Weeks 4, 6, 8, and 10.

    Reporting group title
    Spesolimab
    Reporting group description
    		 Patients received 1200 mg of spesolimab administered intravenously (i.v.) at Weeks 0, 1, and 2, and subcutaneously injection at Weeks 4, 6, 8, and 10.

    Subject analysis set title
    Placebo
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Patients received placebo administered intravenously (i.v.) at Weeks 0, 1, and 2, and subcutaneously injection at Weeks 4, 6, 8, and 10.

    Subject analysis set title
    Spesolimab
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Patients received 1200 mg of spesolimab administered intravenously (i.v.) at Weeks 0, 1, and 2, and subcutaneously injection at Weeks 4, 6, 8, and 10.

    Primary: Percent change from baseline in total abscess and inflammatory nodule count at Week 12

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    End point title
    		 Percent change from baseline in total abscess and inflammatory nodule count at Week 12
    End point description
    Percent change from baseline in total abscess and inflammatory nodule count at Week 12= [(Total Abscess at Week 12 + Total Inflammatory Nodule at Week 12) - (Total Abscess at baseline + Total Inflammatory Nodule at baseline)] *100/ (Total Abscess at baseline + Total Inflammatory Nodule at baseline). Percent change from baseline in total abscess and inflammatory nodule count at Week 12 was modelled using mixed effects model for repeated measures (MMRM) accounting for the following sources of variation: fixed, categorical effects of treatment at each visit, the effect of stratum (stratification according to tumor necrosis factor inhibitor (TNFi)-naive population vs. TNFi-failure population) and the fixed continuous effects of baseline at each visit (Weeks 1, 2, 4, 6, 8, 10, and 12). The Least Squares Mean (Standard Error) at Week 12 is reported.
    End point type
    Primary
    End point timeframe
    Baseline (Week 0) and at Weeks 1, 2, 4, 6, 8, 10, and 12 after first drug administration.
    End point values
    		 Placebo Spesolimab
    Number of subjects analysed
    14 [1]
    30 [2]
    Units: percent change
        least squares mean (standard error)
    -34.7 ( 11.1 )
    -38.8 ( 7.5 )
    Notes
    [1] - Safety Analysis Set (SAF)
    [2] - Safety Analysis Set (SAF)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    MMRM accounting for the following sources of variation: fixed, categorical effects of treatment at each visit, the effect of stratum (stratification according to TNFi-naive population vs. TNFi-failure population) and the fixed continuous effects of baseline at each visit. The unstructured covariance structure was used to model the within patient measurements. To estimate denominator degrees of freedom the Kenward-Roger approximation was used.
    Comparison groups
    Placebo v Spesolimab
    Number of subjects included in analysis
    44
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -4.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -31.7
         upper limit
    		 23.4

    Secondary: Percent change from baseline in draining fistula count at Week 12

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    End point title
    		 Percent change from baseline in draining fistula count at Week 12
    End point description
    Percent change from baseline in draining fistula at Week 12 was calculated as: [(total draining fistula at Week 12) - (total draining fistula at baseline)] * 100 %/ (total draining fistula at baseline). Percent change from baseline in draining fistula count at Week 12 was modelled using mixed effects model for repeated measures (MMRM) accounting for the following sources of variation: fixed, categorical effects of treatment at each visit, the effect of stratum (stratification according to tumor necrosis factor inhibitor (TNFi)-naive population vs. TNFi-failure population) and the fixed continuous effects of baseline at each visit (Weeks 1, 2, 4, 6, 8, 10, and 12). The Least Squares Mean (Standard Error) at Week 12 is reported.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 0) and at Weeks 1, 2, 4, 6, 8, 10, and 12 after first drug administration.
    End point values
    		 Placebo Spesolimab
    Number of subjects analysed
    13 [3]
    24 [4]
    Units: percent change
        least squares mean (standard deviation)
    56.6 ( 23.0 )
    -40.1 ( 16.8 )
    Notes
    [3] - Safety Analysis Set (SAF)
    [4] - Safety Analysis Set (SAF)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    MMRM accounting for the following sources of variation: fixed, categorical effects of treatment at each visit, the effect of stratum (stratification according to TNFi-naive population vs. TNFi-failure population) and the fixed continuous effects of baseline at each visit. The unstructured covariance structure was used to model the within patient measurements. To estimate denominator degrees of freedom the Kenward-Roger approximation was used.
    Comparison groups
    Placebo v Spesolimab
    Number of subjects included in analysis
    37
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -96.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -154.5
         upper limit
    		 -38.8

    Secondary: Achievement of Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 12

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    End point title
    		 Achievement of Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 12
    End point description
    HiSCR is defined as at least a 50% reduction in the total abscess and inflammatory nodule (AN) count with no increase in abscess count and no increase in draining fistula count relative to baseline. Proportion of patients with achievement of Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 12 is reported. Proportion of patients with achievement of HiSCR at Week 12 was calculated as: number of patients with achievement of HiSCR at Week 12/number of patients analyzed. Proportions were rounded up to three decimal places.
    End point type
    Secondary
    End point timeframe
    At baseline (Week 0) and at Week 12.
    End point values
    		 Placebo Spesolimab
    Number of subjects analysed
    17 [5]
    35 [6]
    Units: proportion of patients
        number (not applicable)
    0.176
    0.314
    Notes
    [5] - Safety Analysis Set (SAF)
    [6] - Safety Analysis Set (SAF)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The difference in the proportion of patients with a response between Spesolimab and placebo was analysed using a logistic regression model. The model included treatment and stratification factor (tumor necrosis factor inhibitor (TNFi)-naive population versus TNFi-failure population) as two categorical variables.
    Comparison groups
    Placebo v Spesolimab
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    0.138
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.129
         upper limit
    		 0.339

    Secondary: Absolute change from baseline in International Hidradenitis Suppurativa Severity Score System (IHS4) value at Week 12

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    End point title
    		 Absolute change from baseline in International Hidradenitis Suppurativa Severity Score System (IHS4) value at Week 12
    End point description
    The IHS4 assesses the hidradenitis suppurativa (HS) severity and the resulting IHS4 score is arrived at by= number of nodules * 1 + number of abscesses * 2 + number of draining fistula * 4. A total score of 3 or less signifies mild, 4-10 signifies moderate and 11 or higher signifies severe disease. Absolute change from baseline in IHS4 value at Week 12 was modelled using mixed effects model for repeated measures (MMRM) accounting for the following sources of variation: fixed, categorical effects of treatment at each visit, the effect of stratum (stratification according to tumor necrosis factor inhibitor (TNFi)-naive population vs. TNFi-failure population) and the fixed continuous effects of baseline at each visit (Weeks 1, 2, 4, 6, 8, 10, and 12). The Least Squares Mean (Standard Error) at Week 12 is reported.
    End point type
    Secondary
    End point timeframe
    At baseline (Week 0) and at Weeks 1, 2, 4, 6, 8, 10, and 12 after first drug administration.
    End point values
    		 Placebo Spesolimab
    Number of subjects analysed
    14 [7]
    30 [8]
    Units: units on a scale
        least squares mean (standard error)
    4.9 ( 4.7 )
    -9.0 ( 3.2 )
    Notes
    [7] - Safety Analysis Set (SAF)
    [8] - Safety Analysis Set (SAF)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    MMRM accounting for the following sources of variation: fixed, categorical effects of treatment at each visit, the effect of stratum (stratification according to TNFi-naive population vs. TNFi-failure population) and the fixed continuous effects of baseline at each visit. The unstructured covariance structure was used to model the within patient measurements. To estimate denominator degrees of freedom the Kenward-Roger approximation was used.
    Comparison groups
    Placebo v Spesolimab
    Number of subjects included in analysis
    44
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -13.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -25.6
         upper limit
    		 -2.3

    Secondary: Absolute change from baseline in Hidradenitis Suppurativa Area and Severity Index (HASI) score at Week 12

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    End point title
    		 Absolute change from baseline in Hidradenitis Suppurativa Area and Severity Index (HASI) score at Week 12
    End point description
    HASI includes four domains to assess the severity of HS disease activity, which are erythema, induration, open ulcer and draining fistula and scored on a Likert scale 0 (none) to 3 (severe/extensive) for each predetermined body region. For body surface area (BSA) assessment, the number of palms (one palm indicates 1% of the patient’s BSA) involved for each body region (head, right axilla, left axilla, anterior chest, back, anterior bathing trunk, posterior bathing trunk, other) is assessed and converted to a percentage of that region. An area score was assigned to each region using the approach (0 = none, 1 = 1–9%, 2 = 10–29%, 3 = 30–49%, 4 = 50–69%, 5 = 70–89%, 6 = 90– 100%). Scores for the four domains of HS are summed and adjusted for the area affected, and the score of each area are summed to calculate the total HASI score, which ranges from 0 (no disease) to 72 (severe disease). The Least Squares Mean (Standard Error (SE)) derive from MMRM.
    End point type
    Secondary
    End point timeframe
    MMRM included measurements at baseline (Week 0) and at Weeks 1, 2, 4, 6, 8, 10, and 12 after first drug administration. MMRM estimates of absolute change from baseline in HASI score at Week 12 is reported in the table below..
    End point values
    		 Placebo Spesolimab
    Number of subjects analysed
    14 [9]
    30 [10]
    Units: units on a scale
        least squares mean (standard error)
    -3.8 ( 6.9 )
    -23.6 ( 4.7 )
    Notes
    [9] - Safety Analysis Set (SAF)
    [10] - Safety Analysis Set (SAF)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    MMRM accounting for the following sources of variation: fixed, categorical effects of treatment at each visit, the effect of stratum (stratification according to TNFi-naive population vs. TNFi-failure population) and the fixed continuous effects of baseline at each visit. The unstructured covariance structure was used to model the within patient measurements. To estimate denominator degrees of freedom the Kenward-Roger approximation was used.
    Comparison groups
    Placebo v Spesolimab
    Number of subjects included in analysis
    44
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -19.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -36.9
         upper limit
    		 -2.7

    Secondary: Achievement of Hidradenitis Suppurativa Physician Global Assessment (HS-PGA) score of 0 or 1 at Week 12

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    End point title
    		 Achievement of Hidradenitis Suppurativa Physician Global Assessment (HS-PGA) score of 0 or 1 at Week 12
    End point description
    HS-PGA documents the physician’s assessment of the patient’s HS at a given timepoint. The HS-PGA score ranges from 0 to 5, where: 0=clear - no abscesses, draining fistula, inflammatory nodules or noninflammatory nodules); 1=minimal - no abscesses, draining fistula or inflammatory nodules and the presence of noninflammatory nodules); 2=mild - no abscesses or draining fistula and 1-4 inflammatory nodules, or 1 abscess or draining tunnel and no inflammatory nodules); 3=moderate - no abscesses or draining fistula and ≥5 inflammatory nodules, or 1 abscess or draining fistula and ≥1 inflammatory nodule, or 2-5 abscesses or draining fistula and <10 inflammatory nodules); 4=severe - 2-5 abscesses or draining fistula and ≥10 inflammatory nodules); 5=very severe - >5 abscesses or draining fistula). Proportion of patients with achievement of HS-PGA score of 0 or 1 at Week 12 was calculated as: number of patients with achievement of HS-PGA score of 0 or 1 at Week 12/number of patients analyzed.
    End point type
    Secondary
    End point timeframe
    At Week 12.
    End point values
    		 Placebo Spesolimab
    Number of subjects analysed
    17 [11]
    35 [12]
    Units: proportion of patients
        number (not applicable)
    0.000
    0.057
    Notes
    [11] - Safety Analysis Set (SAF)
    [12] - Safety Analysis Set (SAF)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The difference in the proportion of patients with a response between Spesolimab and placebo was analysed using a logistic regression model. The model included treatment and stratification factor (tumor necrosis factor inhibitor (TNFi)-naive population versus TNFi-failure population) as two categorical variables.
    Comparison groups
    Placebo v Spesolimab
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    0.057
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.132
         upper limit
    		 0.186

    Secondary: Achievement of at least 30% reduction from baseline in Numerical Rating Scale (NRS30) in Patient’s Global Assessment of HS Pain at Week 12

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    End point title
    		 Achievement of at least 30% reduction from baseline in Numerical Rating Scale (NRS30) in Patient’s Global Assessment of HS Pain at Week 12
    End point description
    The HS Pain Numerical Rating Scale (NRS) is an endpoint for the assessment of HS-related pain severity. Recall period is 24 hours and response is given by an 11-point scale ranging from 0 (no pain) to 10 (worst possible pain). For the analysis of pain, weekly average of daily assessment was calculated for each visit based on values prior to the visit. Missing daily values within a week were ignored if there are at least 4 reported values. Proportion of patients with achievement of at least 30% reduction from baseline in NRS30 in Patient’s Global Assessment of HS Pain at Week 12. Proportion of patients with achievement of at least 30% reduction from baseline in NRS30 in Patient’s Global Assessment of HS Pain at Week 12 was calculated as: number of patients with achievement of at least 30% reduction from baseline in NRS30 in Patient’s Global Assessment of HS Pain at Week 12/number of patients analyzed. Proportions were rounded up to three decimal places.
    End point type
    Secondary
    End point timeframe
    At baseline (Week 0) and at Week 12.
    End point values
    		 Placebo Spesolimab
    Number of subjects analysed
    17 [13]
    35 [14]
    Units: proportion of patients
        number (not applicable)
    0.059
    0.229
    Notes
    [13] - Safety Analysis Set (SAF)
    [14] - Safety Analysis Set (SAF)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The difference in the proportion of patients with a response between Spesolimab and placebo was analysed using a logistic regression model. The model included treatment and stratification factor (tumor necrosis factor inhibitor (TNFi)-naive population versus TNFi-failure population) as two categorical variables.
    Comparison groups
    Placebo v Spesolimab
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    0.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.067
         upper limit
    		 0.338

    Secondary: Occurrence of complete elimination of draining fistulas at Week 12

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    End point title
    		 Occurrence of complete elimination of draining fistulas at Week 12
    End point description
    Proportion of patients with occurrence of complete elimination of draining fistulas at Week 12 is reported. Proportion of patients with occurrence of complete elimination of draining fistulas at Week 12 was calculated as: number of patients with occurrence of complete elimination of draining fistulas at Week 12/number of patients analyzed. Proportions were rounded up to three decimal places.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 0) and at Week 12.
    End point values
    		 Placebo Spesolimab
    Number of subjects analysed
    15 [15]
    28 [16]
    Units: proportion of patients
        number (not applicable)
    0.067
    0.250
    Notes
    [15] - Safety Analysis Set (SAF)
    [16] - Safety Analysis Set (SAF)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The difference in the proportion of patients with a response between Spesolimab and placebo was analysed using a logistic regression model. The model included treatment and stratification factor (tumor necrosis factor inhibitor (TNFi)-naive population versus TNFi-failure population) as two categorical variables.
    Comparison groups
    Placebo v Spesolimab
    Number of subjects included in analysis
    43
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    0.183
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.079
         upper limit
    		 0.375

    Secondary: Occurrence of at least one flare at Week 12

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    End point title
    		 Occurrence of at least one flare at Week 12
    End point description
    Proportion of patients with occurrence of at least one flare at Week 12. Flare was defined as at least 25 % increase in abscess and inflammatory nodule count with a minimum increase of 2 relative to baseline. Proportion of patients with occurrence of at least one flare at Week 12 was calculated as: number of patients with occurrence of at least one flare at Week 12/number of patients analyzed. Proportions were rounded up to three decimal places.
    End point type
    Secondary
    End point timeframe
    At Week 12.
    End point values
    		 Placebo Spesolimab
    Number of subjects analysed
    17 [17]
    35 [18]
    Units: proportion of patients
        number (not applicable)
    0.176
    0.086
    Notes
    [17] - Safety Analysis Set (SAF)
    [18] - Safety Analysis Set (SAF)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The difference in the proportion of patients with a response between Spesolimab and placebo was analysed using a logistic regression model. The model included treatment and stratification factor (tumor necrosis factor inhibitor (TNFi)-naive population versus TNFi-failure population) as two categorical variables.
    Comparison groups
    Placebo v Spesolimab
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    -0.091
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.331
         upper limit
    		 0.089

    Secondary: Absolute change from baseline in hidradenitis Suppurativa Quality of Life (HiS-QoL) total score at Week 12

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    End point title
    		 Absolute change from baseline in hidradenitis Suppurativa Quality of Life (HiS-QoL) total score at Week 12
    End point description
    HiS-QoL is a patient-administered, 17-item instrument to measure HS-specific quality of life in clinical trials with a 7-day recall period. The 17-item HiS-QoL included four symptom items, eight activity-adaptation items and five psychosocial items. The item scores are summed to create a total ranging from 0 to 68, with higher scores indicating more severe impact on health-related quality of life. Absolute change from baseline in HiS-QoL total score at Week 12 was modelled using MMRM accounting for the following sources of variation: fixed, categorical effects of treatment at each visit, the effect of stratum (stratification according to tumor necrosis factor inhibitor (TNFi)-naive population vs. TNFi-failure population) and the fixed continuous effects of baseline at each visit (Weeks 1, 4, 8, and 12).
    End point type
    Secondary
    End point timeframe
    At baseline (Week 0) and at Weeks 1, 4, 8, and 12 after first drug administration.
    End point values
    		 Placebo Spesolimab
    Number of subjects analysed
    14 [19]
    25 [20]
    Units: units on a scale
        least squares mean (standard error)
    -4.5 ( 3.2 )
    -5.8 ( 2.4 )
    Notes
    [19] - Safety Analysis Set (SAF)
    [20] - Safety Analysis Set (SAF)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    MMRM accounting for the following sources of variation: fixed, categorical effects of treatment at each visit, the effect of stratum (stratification according to TNFi-naive population vs. TNFi-failure population) and the fixed continuous effects of baseline at each visit. The unstructured covariance structure was used to model the within patient measurements. To estimate denominator degrees of freedom the Kenward-Roger approximation was used.
    Comparison groups
    Placebo v Spesolimab
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.5
         upper limit
    		 6.9

    Secondary: Absolute change from baseline in Dermatology Life Quality Index (DLQI) score at Week 12

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    End point title
    		 Absolute change from baseline in Dermatology Life Quality Index (DLQI) score at Week 12
    End point description
    The DLQI is a patient-administered, ten-question, quality of life questionnaire that covers six domains: 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). DLQI total score is calculated by summing the scores of each question resulting in a range of 0 to 30 with higher scores indicating greater health-related quality of life impairment. Absolute change from baseline in DLQI score at Week 12 was modelled using MMRM accounting for the following sources of variation: fixed, categorical effects of treatment at each visit, the effect of stratum (stratification according to tumor necrosis factor inhibitor (TNFi)-naive population vs. TNFi-failure population) and the fixed continuous effects of baseline at each visit (Weeks 1, 4, 8, and 12).
    End point type
    Secondary
    End point timeframe
    At baseline (Week 0) and at Weeks 1, 4, 8, and 12 after first drug administration.
    End point values
    		 Placebo Spesolimab
    Number of subjects analysed
    14 [21]
    30 [22]
    Units: units on a scale
        least squares mean (standard error)
    -2.8 ( 1.8 )
    -2.8 ( 1.2 )
    Notes
    [21] - Safety Analysis Set (SAF)
    [22] - Safety Analysis Set (SAF)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    MMRM accounting for the following sources of variation: fixed, categorical effects of treatment at each visit, the effect of stratum (stratification according to TNFi-naive population vs. TNFi-failure population) and the fixed continuous effects of baseline at each visit. The unstructured covariance structure was used to model the within patient measurements. To estimate denominator degrees of freedom the Kenward-Roger approximation was used.
    Comparison groups
    Placebo v Spesolimab
    Number of subjects included in analysis
    44
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.4
         upper limit
    		 4.3

    Secondary: The occurrence of Treatment Emergent Adverse Events

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    End point title
    		 The occurrence of Treatment Emergent Adverse Events
    End point description
    Percentage of patients with occurrence of Treatment Emergent Adverse Events (TEAEs) is reported. Percentage of patients with occurrence of Treatment Emergent Adverse Events (TEAEs) was calculated as: number of patients with occurrence of TEAEs / number of patients analyzed. Percentages were rounded to one decimal place. Safety Analysis Set (SAF): This patient set included all patients who were randomized and received at least one dose of study drug. One patient randomised to receive placebo took spesolimab during the study, therefore was considered in spesolimab arm instead for safety reporting.
    End point type
    Secondary
    End point timeframe
    Up to 12 weeks for patients who did roll-over to the open-label extension (OLE) trial (trial number 1368-0067 (EudraCT number: 2020-005587-55) and up to 28 weeks who did not roll-over to the OLE trial.
    End point values
    		 Placebo Spesolimab
    Number of subjects analysed
    16
    36
    Units: percentage of patients
        number (not applicable)
    87.5
    77.8
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 12 weeks for patients who did roll-over to the open-label extension (OLE) trial (trial number 1368-0067 (EudraCT number: 2020-005587-55) and up to 28 weeks who did not roll-over to the OLE trial.
    Adverse event reporting additional description
    Safety Analysis Set (SAF): This patient set included all patients who were randomized and received at least one dose of study drug. One patient randomised to receive placebo took spesolimab during the study, therefore was considered in spesolimab arm instead for safety reporting.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Spesolimab
    Reporting group description
    		 Patients received 1200 mg of spesolimab administered intravenously (i.v.) at Weeks 0, 1, and 2, and subcutaneously injection at Weeks 4, 6, 8, and 10.

    Reporting group title
    Placebo
    Reporting group description
    		 Patients received placebo administered intravenously (i.v.) at Weeks 0, 1, and 2, and subcutaneously injection at Weeks 4, 6, 8, and 10.

    Serious adverse events
    		 Spesolimab Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 16 (6.25%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Psychiatric disorders
    Suicidal behaviour
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 16 (6.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Spesolimab Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    26 / 36 (72.22%)
    14 / 16 (87.50%)
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    2
    Injection site erythema
         subjects affected / exposed
    4 / 36 (11.11%)
    0 / 16 (0.00%)
         occurrences all number
    7
    0
    Fatigue
         subjects affected / exposed
    4 / 36 (11.11%)
    0 / 16 (0.00%)
         occurrences all number
    5
    0
    Injection site pain
         subjects affected / exposed
    3 / 36 (8.33%)
    1 / 16 (6.25%)
         occurrences all number
    4
    1
    Injection site papule
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Pain
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Injection site nodule
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Reproductive system and breast disorders
    Menstrual disorder
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Intermenstrual bleeding
         subjects affected / exposed
    1 / 36 (2.78%)
    1 / 16 (6.25%)
         occurrences all number
    1
    1
    Breast discomfort
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Productive cough
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Dyspnoea
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Cough
         subjects affected / exposed
    1 / 36 (2.78%)
    1 / 16 (6.25%)
         occurrences all number
    1
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    2 / 36 (5.56%)
    1 / 16 (6.25%)
         occurrences all number
    2
    1
    Investigations
    Platelet count increased
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Bacterial test positive
         subjects affected / exposed
    1 / 36 (2.78%)
    1 / 16 (6.25%)
         occurrences all number
    1
    1
    Injury, poisoning and procedural complications
    Head injury
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Animal bite
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Arrhythmia
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Nervous system disorders
    Disturbance in attention
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Headache
         subjects affected / exposed
    4 / 36 (11.11%)
    3 / 16 (18.75%)
         occurrences all number
    7
    5
    Dizziness
         subjects affected / exposed
    1 / 36 (2.78%)
    1 / 16 (6.25%)
         occurrences all number
    1
    1
    Sciatica
         subjects affected / exposed
    2 / 36 (5.56%)
    0 / 16 (0.00%)
         occurrences all number
    2
    0
    Tremor
         subjects affected / exposed
    1 / 36 (2.78%)
    1 / 16 (6.25%)
         occurrences all number
    1
    1
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Eye disorders
    Keratitis
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Angular cheilitis
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Diarrhoea
         subjects affected / exposed
    2 / 36 (5.56%)
    0 / 16 (0.00%)
         occurrences all number
    2
    0
    Nausea
         subjects affected / exposed
    4 / 36 (11.11%)
    0 / 16 (0.00%)
         occurrences all number
    5
    0
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    2 / 36 (5.56%)
    1 / 16 (6.25%)
         occurrences all number
    3
    2
    Intertrigo
         subjects affected / exposed
    1 / 36 (2.78%)
    1 / 16 (6.25%)
         occurrences all number
    1
    1
    Hidradenitis
         subjects affected / exposed
    1 / 36 (2.78%)
    2 / 16 (12.50%)
         occurrences all number
    1
    3
    Acne
         subjects affected / exposed
    2 / 36 (5.56%)
    0 / 16 (0.00%)
         occurrences all number
    2
    0
    Hand dermatitis
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    1 / 36 (2.78%)
    1 / 16 (6.25%)
         occurrences all number
    1
    1
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    1 / 36 (2.78%)
    1 / 16 (6.25%)
         occurrences all number
    1
    1
    Back pain
         subjects affected / exposed
    2 / 36 (5.56%)
    1 / 16 (6.25%)
         occurrences all number
    2
    1
    Infections and infestations
    COVID-19
         subjects affected / exposed
    1 / 36 (2.78%)
    1 / 16 (6.25%)
         occurrences all number
    1
    1
    Nasopharyngitis
         subjects affected / exposed
    3 / 36 (8.33%)
    3 / 16 (18.75%)
         occurrences all number
    3
    3
    Folliculitis
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    3
    Urinary tract infection
         subjects affected / exposed
    2 / 36 (5.56%)
    0 / 16 (0.00%)
         occurrences all number
    2
    0
    Pilonidal cyst
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Rhinitis
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Tonsillitis
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 36 (5.56%)
    0 / 16 (0.00%)
         occurrences all number
    3
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    01 Jul 2021
    The wording for HS severity was updated. For Visit 2, the flexibility of timing in some assessments and collection of safety lab samples were increased. Based on Health Authority recommendation, the wording of some secondary efficacy endpoints was rephrased, and treatment-emergent adverse events (TEAEs)-related secondary safety endpoint was added. The wording of some further efficacy endpoints was rephrased. The acceptable equivalent scoring to international hidradenitis suppurativa severity score system (IHS4) scoring in inclusion criteria #3 was clarified. Exclusion criteria #2 regarding the use of systemic non-biologic immunomodulatory and immunosuppressive agents was added. The wording in Exclusion criteria #2 was updated and, the restricted lesion of topical corticosteroids was clarified. The wording in exclusion criteria #3 was updated. Exclusion criteria #4 regarding prior exposure to Interleukin 36 receptor (IL-36R) inhibitors was added. Based on Health Authority recommendation, exclusion criteria #14 regarding hepatic disease was updated. Some scenarios for discontinuation of trial treatment were added. Based on Health Authority recommendation, some examples of reason for temporary interruption of trial treatment were added. Signals of suicidal ideation and suicidal behavior were clarified, and the actions of the concerned patients were updated. Based on Health Authority recommendation, the description regarding handling the trial treatment on a patient treated with rescue treatment was deleted. Restriction of immunosuppressive biologics was clarified for handling rescue treatment. For the adverse event of special interest (AESI) “hepatic injury”, the alternative utilizable samples was added to the definition. The flexibility of study visit procedures within the corresponding visit window was clarified.

    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
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    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
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