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    Clinical Trial Results:
    A randomized, double-blind, multicenter study assessing short (16 weeks) and long-term efficacy (up to 1 year), safety, and tolerability of 2 subcutaneous secukinumab dose regimens in adult patients with moderate to severe hidradenitis suppurativa (SUNRISE)

    Summary
    EudraCT number
    		 2018-002062-39
    Trial protocol
    		 GB   FR   DE   SK   CZ   BE   DK   LT   GR   NL   ES   HU   PL   BG   HR   IT  
    Global end of trial date
    19 Jul 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    04 Aug 2023
    First version publication date
    04 Aug 2023
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CAIN457M2302
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03713632
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    Novartis Campus, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, novartis.email@novartis.com
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, novartis.email@novartis.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
    19 Jul 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Jul 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 demonstrate the efficacy of secukinumab compared to placebo with respect to Hidradenitis Suppurativa Clinical Response (HiSCR) after 16 weeks of treatment.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    25 Feb 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 14
    Country: Number of subjects enrolled
    Belgium: 7
    Country: Number of subjects enrolled
    Bulgaria: 10
    Country: Number of subjects enrolled
    Canada: 14
    Country: Number of subjects enrolled
    Colombia: 10
    Country: Number of subjects enrolled
    Croatia: 2
    Country: Number of subjects enrolled
    Czechia: 7
    Country: Number of subjects enrolled
    Denmark: 10
    Country: Number of subjects enrolled
    France: 71
    Country: Number of subjects enrolled
    Germany: 68
    Country: Number of subjects enrolled
    Greece: 13
    Country: Number of subjects enrolled
    Guatemala: 11
    Country: Number of subjects enrolled
    Hungary: 11
    Country: Number of subjects enrolled
    India: 6
    Country: Number of subjects enrolled
    Italy: 14
    Country: Number of subjects enrolled
    Israel: 9
    Country: Number of subjects enrolled
    Lebanon: 4
    Country: Number of subjects enrolled
    Lithuania: 10
    Country: Number of subjects enrolled
    Malaysia: 15
    Country: Number of subjects enrolled
    Netherlands: 5
    Country: Number of subjects enrolled
    Philippines: 3
    Country: Number of subjects enrolled
    Poland: 22
    Country: Number of subjects enrolled
    Russian Federation: 15
    Country: Number of subjects enrolled
    Singapore: 9
    Country: Number of subjects enrolled
    Slovakia: 8
    Country: Number of subjects enrolled
    South Africa: 21
    Country: Number of subjects enrolled
    Spain: 27
    Country: Number of subjects enrolled
    Switzerland: 7
    Country: Number of subjects enrolled
    Turkey: 14
    Country: Number of subjects enrolled
    United Kingdom: 20
    Country: Number of subjects enrolled
    United States: 81
    Country: Number of subjects enrolled
    Viet Nam: 5
    Worldwide total number of subjects
    543
    EEA total number of subjects
    285
    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)
    536
    From 65 to 84 years
    7
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Participants enrolled in 132 study sites worldwide.

    Period 1
    Period 1 title
    Treatment Period 1 (until week 16)
    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
    		 AIN457 Q2W
    Arm description
    		 Secukinumab 300mg every 2 weeks (Treatment Period 1 and 2)
    Arm type
    		 Experimental

    Investigational medicinal product name
    secukinumab
    Investigational medicinal product code
    AIN457
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Secukinumab 300mgevery 2 weeks

    Arm title
    		 AIN457 Q4W
    Arm description
    		 Secukinumab 300mg every 4 weeks (Treatment Period 1 and 2)
    Arm type
    		 Experimental

    Investigational medicinal product name
    secukinumab
    Investigational medicinal product code
    AIN457
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Secukinumab 300mgevery 4 weeks

    Arm title
    		 Placebo
    Arm description
    		 Placebo group to secukinumab 300mg (Treatment Period 1)
    Arm type
    		 Placebo

    Investigational medicinal product name
    placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    placebo

    Number of subjects in period 1
    		AIN457 Q2W AIN457 Q4W Placebo
    Started
    180
    180
    183
    Full Analysis Set
    180
    180
    183
    Completed
    170
    169
    167
    Not completed
    10
    11
    16
         Consent withdrawn by subject
    6
    6
    8
         Adverse event, non-fatal
    1
    4
    4
         Technical problems
    1
    -
    1
         Pregnancy
    -
    -
    1
         Lost to follow-up
    1
    1
    1
         Lack of efficacy
    1
    -
    1
    Period 2
    Period 2 title
    Treatment Period 2 (after week 16)
    Is this the baseline period?
    		 No
    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
    		 AIN457 Q2W
    Arm description
    		 Secukinumab 300mg every 2 weeks (Treatment Period 1 and 2)
    Arm type
    		 Experimental

    Investigational medicinal product name
    secukinumab
    Investigational medicinal product code
    AIN457
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Secukinumab 300mg every 2 weeks

    Arm title
    		 AIN457 Q4W
    Arm description
    		 Secukinumab 300mg every 4 weeks (Treatment Period 1 and 2)
    Arm type
    		 Experimental

    Investigational medicinal product name
    secukinumab
    Investigational medicinal product code
    AIN457
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Secukinumab 300mg every 4 weeks

    Arm title
    		 Placebo - Re-randomized to AIN457 Q2W
    Arm description
    		 Placebo group, re-randomized to secukinumab 300mg Q2W at week 16 (Treatment Period 2)
    Arm type
    		 Experimental

    Investigational medicinal product name
    secukinumab
    Investigational medicinal product code
    AIN457
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Secukinumab 300mg every 2 weeks

    Arm title
    		 Placebo - Re-randomized to AIN457 Q4W
    Arm description
    		 Placebo group, re-randomized to secukinumab 300mg Q4W at week 16 (Treatment Period 2)
    Arm type
    		 Experimental

    Investigational medicinal product name
    secukinumab
    Investigational medicinal product code
    AIN457
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Secukinumab 300mg every 4 weeks

    Number of subjects in period 2
    		AIN457 Q2W AIN457 Q4W Placebo - Re-randomized to AIN457 Q2W Placebo - Re-randomized to AIN457 Q4W
    Started
    170
    169
    81
    86
    Completed
    149
    133
    68
    69
    Not completed
    21
    36
    13
    17
         Adverse event, serious fatal
    -
    1
    -
    -
         Consent withdrawn by subject
    9
    18
    9
    12
         Physician decision
    1
    2
    -
    2
         Adverse event, non-fatal
    6
    3
    2
    1
         Technical problems
    1
    -
    -
    -
         Pregnancy
    -
    1
    -
    -
         Lost to follow-up
    1
    8
    1
    -
         Lack of efficacy
    3
    3
    1
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    AIN457 Q2W
    Reporting group description
    		 Secukinumab 300mg every 2 weeks (Treatment Period 1 and 2)

    Reporting group title
    AIN457 Q4W
    Reporting group description
    		 Secukinumab 300mg every 4 weeks (Treatment Period 1 and 2)

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo group to secukinumab 300mg (Treatment Period 1)

    Reporting group values
    		 AIN457 Q2W AIN457 Q4W Placebo Total
    Number of subjects
    		 180 180 183 543
    Age Categorical
    Units: Participants
        <=18 years
    		 0 0 0 0
        Between 18 and 65 years
    		 177 178 181 536
        >=65 years
    		 3 2 2 7
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 37.3 ( 11.48 ) 35.5 ( 11.41 ) 36.2 ( 11.25 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 98 103 105 306
        Male
    		 82 77 78 237
    Race/Ethnicity, Customized
    Units: Subjects
        White
    		 133 139 143 415
        Black or African American
    		 18 19 12 49
        Asian
    		 16 16 19 51
        Native Hawaiian or Other Pacific Islander
    		 1 0 0 1
        American Indian or Alaska native
    		 7 5 8 20
        Multiple
    		 4 1 1 6
        Not Reported
    		 1 0 0 1

    End points

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    End points reporting groups
    Reporting group title
    AIN457 Q2W
    Reporting group description
    		 Secukinumab 300mg every 2 weeks (Treatment Period 1 and 2)

    Reporting group title
    AIN457 Q4W
    Reporting group description
    		 Secukinumab 300mg every 4 weeks (Treatment Period 1 and 2)

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo group to secukinumab 300mg (Treatment Period 1)
    Reporting group title
    AIN457 Q2W
    Reporting group description
    		 Secukinumab 300mg every 2 weeks (Treatment Period 1 and 2)

    Reporting group title
    AIN457 Q4W
    Reporting group description
    		 Secukinumab 300mg every 4 weeks (Treatment Period 1 and 2)

    Reporting group title
    Placebo - Re-randomized to AIN457 Q2W
    Reporting group description
    		 Placebo group, re-randomized to secukinumab 300mg Q2W at week 16 (Treatment Period 2)

    Reporting group title
    Placebo - Re-randomized to AIN457 Q4W
    Reporting group description
    		 Placebo group, re-randomized to secukinumab 300mg Q4W at week 16 (Treatment Period 2)

    Primary: Percentage of participants with Hidradenitis Suppurativa Clinical Response (HiSCR50)

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    End point title
    		 Percentage of participants with Hidradenitis Suppurativa Clinical Response (HiSCR50)
    End point description
    HiSCR50 at Week 16 is defined as at least a 50% decrease in Abscess and inflammatory Nodule (AN) count compared to baseline with no increase in the number of abscesses and/or in the number of draining fistulas from baseline to Week 16. The baseline is defined as the last assessment (including unscheduled visits) obtained before/on the day of the first administration of the study treatment, or on the randomization date if there had been no drug administration. This endpoint was analyzed by logistic regression.
    End point type
    Primary
    End point timeframe
    16 weeks
    End point values
    		 AIN457 Q2W AIN457 Q4W Placebo
    Number of subjects analysed
    180
    180
    183
    Units: Percentage of Participants
        number (not applicable)
    42.3
    46.1
    31.2
    Statistical analysis title
    		 logistic regression
    Comparison groups
    AIN457 Q2W v Placebo
    Number of subjects included in analysis
    363
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0149 [1]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.64
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.05
         upper limit
    		 2.55
    Notes
    [1] - one-sided p-value
    Statistical analysis title
    		 logistic regression
    Comparison groups
    AIN457 Q4W v Placebo
    Number of subjects included in analysis
    363
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0022 [2]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.22
         upper limit
    		 2.96
    Notes
    [2] - one-sided p-value

    Secondary: Percentage change from baseline in AN count

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    End point title
    		 Percentage change from baseline in AN count
    End point description
    Percent change from baseline in abscesses and inflammatory nodules (AN) count. This endpoint was analyzed by analysis of covariance.
    End point type
    Secondary
    End point timeframe
    Baseline, 16 weeks
    End point values
    		 AIN457 Q2W AIN457 Q4W Placebo
    Number of subjects analysed
    180
    180
    183
    Units: Percentage change from baseline
        least squares mean (standard error)
    -39.3 ( 4.43 )
    -45.5 ( 4.08 )
    -22.4 ( 4.84 )
    Statistical analysis title
    		 ANCOVA
    Comparison groups
    AIN457 Q4W v Placebo
    Number of subjects included in analysis
    363
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0001 [3]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -22.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -35.24
         upper limit
    		 -10.63
    Notes
    [3] - one-side p-value
    Statistical analysis title
    		 ANCOVA
    Comparison groups
    AIN457 Q2W v Placebo
    Number of subjects included in analysis
    363
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0051 [4]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    -16.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -28.79
         upper limit
    		 -3.88
    Notes
    [4] - one-side p-value

    Secondary: Percentage of participants with Hidradenitis Suppurativa (HS) flares

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    End point title
    		 Percentage of participants with Hidradenitis Suppurativa (HS) flares
    End point description
    Percentage of participants who experience at least one flare over 16 weeks. A flare is defined as at least a 25% increase in abscesses and inflammatory nodules (AN) count with a minimum increase of 2 AN relative to baseline. This endpoint was analyzed by logistic regression.
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    		 AIN457 Q2W AIN457 Q4W Placebo
    Number of subjects analysed
    180
    180
    183
    Units: Percentage of Participants
        number (not applicable)
    20.1
    15.6
    27.0
    Statistical analysis title
    		 logistic regression
    Comparison groups
    AIN457 Q4W v Placebo
    Number of subjects included in analysis
    363
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0049 [5]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.29
         upper limit
    		 0.84
    Notes
    [5] - one-sided p-value
    Statistical analysis title
    		 logistic regression
    Comparison groups
    AIN457 Q2W v Placebo
    Number of subjects included in analysis
    363
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0732 [6]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.41
         upper limit
    		 1.14
    Notes
    [6] - one-sided p-value

    Secondary: Percentage of participants achieving NRS30

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    End point title
    		 Percentage of participants achieving NRS30
    End point description
    Patients achieving Numerical Rating Scale score of 30 (NRS30) at week 16, defined as at least a 30% reduction and at least one unit reduction from baseline in the Patient's Global assessment of Skin Pain (where range 0 [no skin pain] to 10 [worst skin pain]). This endpoint was analyzed by logistic regression. The protocol defines this outcome measure to be tested using combined data with CAIN457M2301 (NCT03713619). As this record is supposed to contain only results from CAIN457M2302, descriptive data based only on CAIN457M2302 are presented.
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    		 AIN457 Q2W AIN457 Q4W Placebo
    Number of subjects analysed
    135
    129
    132
    Units: Percentage of participants
        number (not applicable)
    38.6
    34.7
    22.4
    Statistical analysis title
    		 logistic regression
    Comparison groups
    AIN457 Q4W v Placebo
    Number of subjects included in analysis
    261
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0206 [7]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.03
         upper limit
    		 3.37
    Notes
    [7] - one-sided p-value
    Statistical analysis title
    		 logistic regression
    Comparison groups
    AIN457 Q2W v Placebo
    Number of subjects included in analysis
    267
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0026 [8]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.28
         upper limit
    		 4.09
    Notes
    [8] - one-sided p-value

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events (AEs) were reported from first dose of study treatment, up to approximately 52 weeks for AIN457 (up to 60 weeks for subjects who did not move to the extension study) and up to 16 weeks for placebo.
    Adverse event reporting additional description
    AEs are any sign or symptom that occurs during the conduct of the trial and safety follow-up
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    AIN457 Q2W
    Reporting group description
    		 Subjects who were randomized to AIN457 (secukinumab) 300mg Q2W dose regimen at the study entry. Adverse events were assessed up to Week 60

    Reporting group title
    Any AIN457
    Reporting group description
    		 Subjects who received at least 1 dose of secukinumab

    Reporting group title
    Any AIN457 Q2W
    Reporting group description
    		 Subjects who received at least 1 dose of secukinumab 300 mg Q2W dose (including subjects who switched from placebo to secukinumab Q2W at Week 16). Adverse events were assessed up to Week 60

    Reporting group title
    Any AIN457 Q4W
    Reporting group description
    		 Subjects who received at least 1 dose of secukinumab 300 mg Q4W dose (including subjects who switched from placebo to secukinumab Q4W at Week 16). Adverse events were assessed up to Week 60

    Reporting group title
    AIN457 Q4W
    Reporting group description
    		 Subjects who were randomized to AIN457 (secukinumab) 300mg Q4W dose regimen at the study entry. Adverse events were assessed up to Week 60

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects who were randomized to matching placebo at the study entry. Adverse events were assessed up to Week 16

    Serious adverse events
    		 AIN457 Q2W Any AIN457 Any AIN457 Q2W Any AIN457 Q4W AIN457 Q4W Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    19 / 180 (10.56%)
    45 / 527 (8.54%)
    22 / 261 (8.43%)
    23 / 266 (8.65%)
    15 / 180 (8.33%)
    5 / 183 (2.73%)
         number of deaths (all causes)
    0
    2
    0
    2
    1
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 527 (0.19%)
    0 / 261 (0.00%)
    1 / 266 (0.38%)
    1 / 180 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 527 (0.19%)
    1 / 261 (0.38%)
    0 / 266 (0.00%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    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
    Vascular disorders
    Hypotension
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 527 (0.19%)
    1 / 261 (0.38%)
    0 / 266 (0.00%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    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
    General disorders and administration site conditions
    Unevaluable event
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 527 (0.19%)
    1 / 261 (0.38%)
    0 / 266 (0.00%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    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
    Systemic inflammatory response syndrome
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 527 (0.19%)
    1 / 261 (0.38%)
    0 / 266 (0.00%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    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
    Pyrexia
         subjects affected / exposed
    2 / 180 (1.11%)
    2 / 527 (0.38%)
    2 / 261 (0.77%)
    0 / 266 (0.00%)
    0 / 180 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Amyloidosis
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 527 (0.19%)
    0 / 261 (0.00%)
    1 / 266 (0.38%)
    1 / 180 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Scrotal inflammation
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 527 (0.19%)
    0 / 261 (0.00%)
    1 / 266 (0.38%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 180 (0.00%)
    0 / 527 (0.00%)
    0 / 261 (0.00%)
    0 / 266 (0.00%)
    0 / 180 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    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
    Psychiatric disorders
    Obsessive-compulsive disorder
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 527 (0.19%)
    1 / 261 (0.38%)
    0 / 266 (0.00%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    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
    Depression
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 527 (0.19%)
    1 / 261 (0.38%)
    0 / 266 (0.00%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    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
    Confusional state
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 527 (0.19%)
    0 / 261 (0.00%)
    1 / 266 (0.38%)
    1 / 180 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fibula fracture
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 527 (0.19%)
    0 / 261 (0.00%)
    1 / 266 (0.38%)
    1 / 180 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 527 (0.19%)
    0 / 261 (0.00%)
    1 / 266 (0.38%)
    1 / 180 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intentional overdose
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 527 (0.19%)
    0 / 261 (0.00%)
    1 / 266 (0.38%)
    1 / 180 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 527 (0.19%)
    0 / 261 (0.00%)
    1 / 266 (0.38%)
    1 / 180 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    1 / 180 (0.56%)
    2 / 527 (0.38%)
    1 / 261 (0.38%)
    1 / 266 (0.38%)
    1 / 180 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skull fracture
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 527 (0.19%)
    0 / 261 (0.00%)
    1 / 266 (0.38%)
    1 / 180 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Arrhythmia
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 527 (0.19%)
    1 / 261 (0.38%)
    0 / 266 (0.00%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    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
    Myocardial infarction
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 527 (0.19%)
    0 / 261 (0.00%)
    1 / 266 (0.38%)
    1 / 180 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    Nervous system disorders
    Sciatica
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 527 (0.19%)
    1 / 261 (0.38%)
    0 / 266 (0.00%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    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
    Gastrointestinal disorders
    Inflammatory bowel disease
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 527 (0.19%)
    0 / 261 (0.00%)
    1 / 266 (0.38%)
    1 / 180 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis ulcerative
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 527 (0.19%)
    1 / 261 (0.38%)
    0 / 266 (0.00%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    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
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 527 (0.19%)
    0 / 261 (0.00%)
    1 / 266 (0.38%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 527 (0.19%)
    1 / 261 (0.38%)
    0 / 266 (0.00%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    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
    Cholecystitis
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 527 (0.19%)
    1 / 261 (0.38%)
    0 / 266 (0.00%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    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
    Cholelithiasis
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 527 (0.19%)
    1 / 261 (0.38%)
    0 / 266 (0.00%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    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
    Skin and subcutaneous tissue disorders
    Hidradenitis
         subjects affected / exposed
    4 / 180 (2.22%)
    5 / 527 (0.95%)
    5 / 261 (1.92%)
    0 / 266 (0.00%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
    0 / 5
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 180 (1.11%)
    2 / 527 (0.38%)
    2 / 261 (0.77%)
    0 / 266 (0.00%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Glomerular vascular disorder
         subjects affected / exposed
    0 / 180 (0.00%)
    0 / 527 (0.00%)
    0 / 261 (0.00%)
    0 / 266 (0.00%)
    0 / 180 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    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
    Nephrolithiasis
         subjects affected / exposed
    1 / 180 (0.56%)
    2 / 527 (0.38%)
    1 / 261 (0.38%)
    1 / 266 (0.38%)
    1 / 180 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pelvi-ureteric obstruction
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 527 (0.19%)
    1 / 261 (0.38%)
    0 / 266 (0.00%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    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
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 180 (0.00%)
    2 / 527 (0.38%)
    0 / 261 (0.00%)
    2 / 266 (0.75%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 527 (0.19%)
    1 / 261 (0.38%)
    0 / 266 (0.00%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    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
    Muscle spasms
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 527 (0.19%)
    1 / 261 (0.38%)
    0 / 266 (0.00%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    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
    Infections and infestations
    Abscess
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 527 (0.19%)
    1 / 261 (0.38%)
    0 / 266 (0.00%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    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
    Abscess limb
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 527 (0.19%)
    0 / 261 (0.00%)
    1 / 266 (0.38%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    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
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 180 (0.00%)
    0 / 527 (0.00%)
    0 / 261 (0.00%)
    0 / 266 (0.00%)
    0 / 180 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    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
    Cellulitis
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 527 (0.19%)
    0 / 261 (0.00%)
    1 / 266 (0.38%)
    1 / 180 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 527 (0.19%)
    0 / 261 (0.00%)
    1 / 266 (0.38%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    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
    Colonic abscess
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 527 (0.19%)
    0 / 261 (0.00%)
    1 / 266 (0.38%)
    1 / 180 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis infectious
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 527 (0.19%)
    0 / 261 (0.00%)
    1 / 266 (0.38%)
    1 / 180 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dermatitis infected
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 527 (0.19%)
    0 / 261 (0.00%)
    1 / 266 (0.38%)
    1 / 180 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injection site abscess
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 527 (0.19%)
    1 / 261 (0.38%)
    0 / 266 (0.00%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    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
    Scrotal infection
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 527 (0.19%)
    0 / 261 (0.00%)
    1 / 266 (0.38%)
    1 / 180 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 527 (0.19%)
    1 / 261 (0.38%)
    0 / 266 (0.00%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    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
    Otitis externa
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 527 (0.19%)
    0 / 261 (0.00%)
    1 / 266 (0.38%)
    1 / 180 (0.56%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Localised infection
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 527 (0.19%)
    1 / 261 (0.38%)
    0 / 266 (0.00%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    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
    Soft tissue infection
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 527 (0.19%)
    0 / 261 (0.00%)
    1 / 266 (0.38%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 527 (0.19%)
    1 / 261 (0.38%)
    0 / 266 (0.00%)
    0 / 180 (0.00%)
    1 / 183 (0.55%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sweat gland infection
         subjects affected / exposed
    1 / 180 (0.56%)
    2 / 527 (0.38%)
    1 / 261 (0.38%)
    1 / 266 (0.38%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
    1 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 527 (0.19%)
    0 / 261 (0.00%)
    1 / 266 (0.38%)
    0 / 180 (0.00%)
    0 / 183 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    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
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 AIN457 Q2W Any AIN457 Any AIN457 Q2W Any AIN457 Q4W AIN457 Q4W Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    123 / 180 (68.33%)
    348 / 527 (66.03%)
    174 / 261 (66.67%)
    174 / 266 (65.41%)
    125 / 180 (69.44%)
    84 / 183 (45.90%)
    Investigations
    Lipase increased
         subjects affected / exposed
    3 / 180 (1.67%)
    12 / 527 (2.28%)
    5 / 261 (1.92%)
    7 / 266 (2.63%)
    7 / 180 (3.89%)
    1 / 183 (0.55%)
         occurrences all number
    5
    15
    7
    8
    8
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    5 / 180 (2.78%)
    6 / 527 (1.14%)
    5 / 261 (1.92%)
    1 / 266 (0.38%)
    1 / 180 (0.56%)
    0 / 183 (0.00%)
         occurrences all number
    5
    6
    5
    1
    1
    0
    SARS-CoV-2 test positive
         subjects affected / exposed
    3 / 180 (1.67%)
    9 / 527 (1.71%)
    5 / 261 (1.92%)
    4 / 266 (1.50%)
    4 / 180 (2.22%)
    3 / 183 (1.64%)
         occurrences all number
    3
    9
    5
    4
    4
    3
    Weight decreased
         subjects affected / exposed
    0 / 180 (0.00%)
    4 / 527 (0.76%)
    0 / 261 (0.00%)
    4 / 266 (1.50%)
    4 / 180 (2.22%)
    0 / 183 (0.00%)
         occurrences all number
    0
    4
    0
    4
    4
    0
    Injury, poisoning and procedural complications
    Ligament sprain
         subjects affected / exposed
    1 / 180 (0.56%)
    6 / 527 (1.14%)
    1 / 261 (0.38%)
    5 / 266 (1.88%)
    4 / 180 (2.22%)
    0 / 183 (0.00%)
         occurrences all number
    1
    6
    1
    5
    4
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    11 / 180 (6.11%)
    21 / 527 (3.98%)
    14 / 261 (5.36%)
    7 / 266 (2.63%)
    6 / 180 (3.33%)
    2 / 183 (1.09%)
         occurrences all number
    11
    23
    16
    7
    6
    2
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    4 / 180 (2.22%)
    13 / 527 (2.47%)
    6 / 261 (2.30%)
    7 / 266 (2.63%)
    7 / 180 (3.89%)
    3 / 183 (1.64%)
         occurrences all number
    4
    16
    6
    10
    10
    3
    Headache
         subjects affected / exposed
    31 / 180 (17.22%)
    75 / 527 (14.23%)
    39 / 261 (14.94%)
    36 / 266 (13.53%)
    27 / 180 (15.00%)
    16 / 183 (8.74%)
         occurrences all number
    59
    121
    72
    49
    39
    23
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    7 / 180 (3.89%)
    21 / 527 (3.98%)
    9 / 261 (3.45%)
    12 / 266 (4.51%)
    8 / 180 (4.44%)
    3 / 183 (1.64%)
         occurrences all number
    12
    28
    15
    13
    9
    4
    Influenza like illness
         subjects affected / exposed
    1 / 180 (0.56%)
    6 / 527 (1.14%)
    1 / 261 (0.38%)
    5 / 266 (1.88%)
    5 / 180 (2.78%)
    0 / 183 (0.00%)
         occurrences all number
    1
    9
    1
    8
    8
    0
    Fatigue
         subjects affected / exposed
    4 / 180 (2.22%)
    14 / 527 (2.66%)
    7 / 261 (2.68%)
    7 / 266 (2.63%)
    6 / 180 (3.33%)
    2 / 183 (1.09%)
         occurrences all number
    4
    20
    8
    12
    11
    2
    Gastrointestinal disorders
    Gastrooesophageal reflux disease
         subjects affected / exposed
    4 / 180 (2.22%)
    13 / 527 (2.47%)
    7 / 261 (2.68%)
    6 / 266 (2.26%)
    4 / 180 (2.22%)
    1 / 183 (0.55%)
         occurrences all number
    4
    13
    7
    6
    4
    1
    Abdominal pain
         subjects affected / exposed
    4 / 180 (2.22%)
    15 / 527 (2.85%)
    5 / 261 (1.92%)
    10 / 266 (3.76%)
    7 / 180 (3.89%)
    2 / 183 (1.09%)
         occurrences all number
    4
    15
    5
    10
    7
    2
    Abdominal pain upper
         subjects affected / exposed
    3 / 180 (1.67%)
    14 / 527 (2.66%)
    4 / 261 (1.53%)
    10 / 266 (3.76%)
    9 / 180 (5.00%)
    1 / 183 (0.55%)
         occurrences all number
    3
    15
    4
    11
    9
    1
    Constipation
         subjects affected / exposed
    4 / 180 (2.22%)
    5 / 527 (0.95%)
    4 / 261 (1.53%)
    1 / 266 (0.38%)
    1 / 180 (0.56%)
    2 / 183 (1.09%)
         occurrences all number
    4
    5
    4
    1
    1
    2
    Dental caries
         subjects affected / exposed
    4 / 180 (2.22%)
    5 / 527 (0.95%)
    4 / 261 (1.53%)
    1 / 266 (0.38%)
    1 / 180 (0.56%)
    0 / 183 (0.00%)
         occurrences all number
    4
    5
    4
    1
    1
    0
    Diarrhoea
         subjects affected / exposed
    13 / 180 (7.22%)
    38 / 527 (7.21%)
    19 / 261 (7.28%)
    19 / 266 (7.14%)
    14 / 180 (7.78%)
    13 / 183 (7.10%)
         occurrences all number
    16
    48
    22
    26
    21
    16
    Toothache
         subjects affected / exposed
    6 / 180 (3.33%)
    12 / 527 (2.28%)
    7 / 261 (2.68%)
    5 / 266 (1.88%)
    5 / 180 (2.78%)
    0 / 183 (0.00%)
         occurrences all number
    8
    16
    10
    6
    6
    0
    Nausea
         subjects affected / exposed
    6 / 180 (3.33%)
    19 / 527 (3.61%)
    12 / 261 (4.60%)
    7 / 266 (2.63%)
    5 / 180 (2.78%)
    4 / 183 (2.19%)
         occurrences all number
    7
    21
    13
    8
    6
    5
    Haemorrhoids
         subjects affected / exposed
    1 / 180 (0.56%)
    6 / 527 (1.14%)
    1 / 261 (0.38%)
    5 / 266 (1.88%)
    5 / 180 (2.78%)
    0 / 183 (0.00%)
         occurrences all number
    1
    6
    1
    5
    5
    0
    Vomiting
         subjects affected / exposed
    2 / 180 (1.11%)
    7 / 527 (1.33%)
    6 / 261 (2.30%)
    1 / 266 (0.38%)
    1 / 180 (0.56%)
    1 / 183 (0.55%)
         occurrences all number
    2
    9
    7
    2
    2
    1
    Reproductive system and breast disorders
    Dysmenorrhoea
         subjects affected / exposed
    2 / 180 (1.11%)
    8 / 527 (1.52%)
    3 / 261 (1.15%)
    5 / 266 (1.88%)
    5 / 180 (2.78%)
    0 / 183 (0.00%)
         occurrences all number
    2
    20
    3
    17
    17
    0
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    8 / 180 (4.44%)
    17 / 527 (3.23%)
    8 / 261 (3.07%)
    9 / 266 (3.38%)
    8 / 180 (4.44%)
    1 / 183 (0.55%)
         occurrences all number
    8
    18
    8
    10
    9
    1
    Cough
         subjects affected / exposed
    5 / 180 (2.78%)
    15 / 527 (2.85%)
    6 / 261 (2.30%)
    9 / 266 (3.38%)
    7 / 180 (3.89%)
    3 / 183 (1.64%)
         occurrences all number
    5
    15
    6
    9
    7
    3
    Skin and subcutaneous tissue disorders
    Dermatitis
         subjects affected / exposed
    3 / 180 (1.67%)
    8 / 527 (1.52%)
    4 / 261 (1.53%)
    4 / 266 (1.50%)
    4 / 180 (2.22%)
    1 / 183 (0.55%)
         occurrences all number
    4
    9
    5
    4
    4
    1
    Eczema
         subjects affected / exposed
    10 / 180 (5.56%)
    18 / 527 (3.42%)
    11 / 261 (4.21%)
    7 / 266 (2.63%)
    6 / 180 (3.33%)
    1 / 183 (0.55%)
         occurrences all number
    11
    19
    12
    7
    6
    1
    Hidradenitis
         subjects affected / exposed
    21 / 180 (11.67%)
    57 / 527 (10.82%)
    26 / 261 (9.96%)
    31 / 266 (11.65%)
    23 / 180 (12.78%)
    14 / 183 (7.65%)
         occurrences all number
    40
    91
    47
    44
    35
    18
    Intertrigo
         subjects affected / exposed
    4 / 180 (2.22%)
    14 / 527 (2.66%)
    6 / 261 (2.30%)
    8 / 266 (3.01%)
    5 / 180 (2.78%)
    0 / 183 (0.00%)
         occurrences all number
    4
    15
    6
    9
    5
    0
    Pruritus
         subjects affected / exposed
    8 / 180 (4.44%)
    16 / 527 (3.04%)
    11 / 261 (4.21%)
    5 / 266 (1.88%)
    3 / 180 (1.67%)
    5 / 183 (2.73%)
         occurrences all number
    11
    21
    15
    6
    4
    5
    Psoriasis
         subjects affected / exposed
    6 / 180 (3.33%)
    12 / 527 (2.28%)
    6 / 261 (2.30%)
    6 / 266 (2.26%)
    4 / 180 (2.22%)
    0 / 183 (0.00%)
         occurrences all number
    6
    12
    6
    6
    4
    0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    6 / 180 (3.33%)
    11 / 527 (2.09%)
    6 / 261 (2.30%)
    5 / 266 (1.88%)
    5 / 180 (2.78%)
    4 / 183 (2.19%)
         occurrences all number
    6
    11
    6
    5
    5
    4
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    7 / 180 (3.89%)
    20 / 527 (3.80%)
    11 / 261 (4.21%)
    9 / 266 (3.38%)
    4 / 180 (2.22%)
    5 / 183 (2.73%)
         occurrences all number
    7
    23
    12
    11
    6
    5
    Back pain
         subjects affected / exposed
    4 / 180 (2.22%)
    21 / 527 (3.98%)
    7 / 261 (2.68%)
    14 / 266 (5.26%)
    12 / 180 (6.67%)
    4 / 183 (2.19%)
         occurrences all number
    4
    25
    7
    18
    16
    4
    Myalgia
         subjects affected / exposed
    3 / 180 (1.67%)
    10 / 527 (1.90%)
    4 / 261 (1.53%)
    6 / 266 (2.26%)
    4 / 180 (2.22%)
    3 / 183 (1.64%)
         occurrences all number
    3
    13
    4
    9
    7
    3
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    5 / 180 (2.78%)
    12 / 527 (2.28%)
    5 / 261 (1.92%)
    7 / 266 (2.63%)
    5 / 180 (2.78%)
    2 / 183 (1.09%)
         occurrences all number
    5
    12
    5
    7
    5
    2
    COVID-19
         subjects affected / exposed
    10 / 180 (5.56%)
    27 / 527 (5.12%)
    13 / 261 (4.98%)
    14 / 266 (5.26%)
    7 / 180 (3.89%)
    3 / 183 (1.64%)
         occurrences all number
    10
    27
    13
    14
    7
    9
    Conjunctivitis
         subjects affected / exposed
    4 / 180 (2.22%)
    11 / 527 (2.09%)
    4 / 261 (1.53%)
    7 / 266 (2.63%)
    6 / 180 (3.33%)
    0 / 183 (0.00%)
         occurrences all number
    4
    12
    4
    8
    7
    0
    Ear infection
         subjects affected / exposed
    4 / 180 (2.22%)
    6 / 527 (1.14%)
    5 / 261 (1.92%)
    1 / 266 (0.38%)
    1 / 180 (0.56%)
    0 / 183 (0.00%)
         occurrences all number
    5
    7
    6
    1
    1
    0
    Folliculitis
         subjects affected / exposed
    9 / 180 (5.00%)
    13 / 527 (2.47%)
    9 / 261 (3.45%)
    4 / 266 (1.50%)
    2 / 180 (1.11%)
    3 / 183 (1.64%)
         occurrences all number
    10
    14
    10
    4
    2
    3
    Influenza
         subjects affected / exposed
    5 / 180 (2.78%)
    8 / 527 (1.52%)
    7 / 261 (2.68%)
    1 / 266 (0.38%)
    1 / 180 (0.56%)
    0 / 183 (0.00%)
         occurrences all number
    5
    8
    7
    1
    1
    0
    Sinusitis
         subjects affected / exposed
    3 / 180 (1.67%)
    10 / 527 (1.90%)
    7 / 261 (2.68%)
    3 / 266 (1.13%)
    3 / 180 (1.67%)
    3 / 183 (1.64%)
         occurrences all number
    3
    11
    7
    4
    4
    3
    Rhinitis
         subjects affected / exposed
    4 / 180 (2.22%)
    13 / 527 (2.47%)
    6 / 261 (2.30%)
    7 / 266 (2.63%)
    4 / 180 (2.22%)
    1 / 183 (0.55%)
         occurrences all number
    4
    13
    6
    7
    4
    1
    Pharyngitis
         subjects affected / exposed
    3 / 180 (1.67%)
    13 / 527 (2.47%)
    4 / 261 (1.53%)
    9 / 266 (3.38%)
    6 / 180 (3.33%)
    3 / 183 (1.64%)
         occurrences all number
    5
    16
    6
    10
    7
    3
    Oral candidiasis
         subjects affected / exposed
    5 / 180 (2.78%)
    8 / 527 (1.52%)
    5 / 261 (1.92%)
    3 / 266 (1.13%)
    1 / 180 (0.56%)
    0 / 183 (0.00%)
         occurrences all number
    6
    12
    6
    6
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    21 / 180 (11.67%)
    53 / 527 (10.06%)
    28 / 261 (10.73%)
    25 / 266 (9.40%)
    18 / 180 (10.00%)
    16 / 183 (8.74%)
         occurrences all number
    28
    65
    35
    30
    22
    19
    Skin candida
         subjects affected / exposed
    6 / 180 (3.33%)
    12 / 527 (2.28%)
    8 / 261 (3.07%)
    4 / 266 (1.50%)
    4 / 180 (2.22%)
    1 / 183 (0.55%)
         occurrences all number
    7
    16
    10
    6
    6
    1
    Urinary tract infection
         subjects affected / exposed
    7 / 180 (3.89%)
    20 / 527 (3.80%)
    8 / 261 (3.07%)
    12 / 266 (4.51%)
    7 / 180 (3.89%)
    5 / 183 (2.73%)
         occurrences all number
    10
    24
    11
    13
    7
    5
    Upper respiratory tract infection
         subjects affected / exposed
    13 / 180 (7.22%)
    27 / 527 (5.12%)
    16 / 261 (6.13%)
    11 / 266 (4.14%)
    8 / 180 (4.44%)
    7 / 183 (3.83%)
         occurrences all number
    17
    33
    20
    13
    9
    8
    Tonsillitis
         subjects affected / exposed
    2 / 180 (1.11%)
    9 / 527 (1.71%)
    4 / 261 (1.53%)
    5 / 266 (1.88%)
    4 / 180 (2.22%)
    0 / 183 (0.00%)
         occurrences all number
    2
    9
    4
    5
    4
    0
    Sweat gland infection
         subjects affected / exposed
    3 / 180 (1.67%)
    11 / 527 (2.09%)
    9 / 261 (3.45%)
    2 / 266 (0.75%)
    2 / 180 (1.11%)
    3 / 183 (1.64%)
         occurrences all number
    4
    15
    12
    3
    3
    3

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    17 Jun 2020
    The rationale for the amendment reflects the guidance released from several Health Authorities (FDA, EMA, Medical and Healthcare Products Regulatory Agency) to introduce a level of flexibility in drug dispensation, protocol assessments and visit schedule if a major health care event requires it (i.e., COVID-19 pandemic. While adherence to protocol procedure and GCPs remains mandatory, Novartis has edited the wording in some sections of the protocol to allow the subjects in the trial to continue treatment while being monitored for safety in these situations. These changes were introduced to reduce the risk of exposure for subjects and study staff, and potentially the risk for transmission of infectious diseases (e.g., COVID-19). In addition, a ‘special scenario’ was added to the study design to ensure a careful, onsite assessment of lesions at Week 52, by allowing for the possibility to perform up to 3 unscheduled visits in case lockdowns or mobility restriction would impede the subject or the site to perform the visit on site. In case of a global health crisis impeding the subjects (or the sites) to attend (or perform) Week 52 study visit on site, the subjects in the study were allowed to receive additional study treatment up to 12 weeks after Week 50, or until they could return to the study site to perform the Week 52 assessment (whichever occurs first). This additional, optional phase permitted the subjects to be assessed for eligibility to roll over to the 4-year long-term extension study. During this period, the subjects were continuously monitored for safety. Lastly, the Amendment 01 allowed for an increase in the number of randomized subjects up to 15% to account for the disruptive impact of the COVID-19 pandemic.
    08 Jan 2021
    The purpose of this amendment was to update the statistical analysis section including adjusting the split of the overall alpha level allocating 80% to testing the high dose secukinumab regimen (300 mg Q2W) versus placebo, based on the recent findings from Study CAIN457A2324 demonstrating an improved benefit of the secukinumab 300 mg Q2W when used in subjects with psoriasis over 90 kg. These data were not available at the time of the initial release of the protocol. In addition, following the FDA feedback this amendment introduced the value of the individual lesion count assessed at the randomization visit only to be used as ‘baseline’ in the statistical analyses, instead of the weighted average across the 2 screening visits and the baseline (randomization) visit. Moreover, a secondary endpoint evaluating only the AN count was added. Analyzing AN count on the original, continuous scale, enabled a more sensitive and granular approach to summarizing the clinical effect of treatment (Revuz 2009, Kimball et al 2018). Lastly, the exploratory objective section has been updated to include a specific analysis to evaluate the benefit of secukinumab in the bio-naive population and in the subjects with body weight above and below 90 kg, and to explore treatment effect with regard to inflammatory markers (CRP and ESR).

    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
    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.

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