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    Clinical Trial Results:
    A randomized, double-blind, placebo-controlled Phase III multicenter study of subcutaneous secukinumab in prefilled syringes to demonstrate the efficacy at 16 weeks and to assess the long-term efficacy, safety and tolerability up to 5 years in patients with active Ankylosing Spondylitis

    Summary
    EudraCT number
    		 2012-000046-35
    Trial protocol
    		 GB   CZ   IT   NL   AT   FI   DE   ES  
    Global end of trial date
    18 Sep 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    31 Aug 2019
    First version publication date
    31 Aug 2019
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CAIN457F2310
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01649375
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    CH-4002, Basel, Switzerland,
    Public contact
    Study Director, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.com
    Scientific contact
    Study Director, 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
    18 Sep 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Sep 2018
    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 that the efficacy of secukinumab 75 mg sc or 150 mg sc at Week 16 was superior to placebo in patients with active AS based on the proportion of patients achieving an ASAS20 (Assessment of SpondyloArthritis International Society criteria) response.
    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
    18 Oct 2012
    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
    Spain: 12
    Country: Number of subjects enrolled
    Switzerland: 6
    Country: Number of subjects enrolled
    United Kingdom: 22
    Country: Number of subjects enrolled
    United States: 21
    Country: Number of subjects enrolled
    Austria: 9
    Country: Number of subjects enrolled
    Canada: 12
    Country: Number of subjects enrolled
    Czech Republic: 51
    Country: Number of subjects enrolled
    Finland: 17
    Country: Number of subjects enrolled
    Germany: 7
    Country: Number of subjects enrolled
    Italy: 12
    Country: Number of subjects enrolled
    Netherlands: 6
    Country: Number of subjects enrolled
    Russian Federation: 37
    Country: Number of subjects enrolled
    Singapore: 7
    Worldwide total number of subjects
    219
    EEA total number of subjects
    136
    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)
    212
    From 65 to 84 years
    5
    85 years and over
    2

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Two hundred fifty-three subjects were screened and 219 were randomized

    Period 1
    Period 1 title
    Up to Week 16
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Secukinumab 75 mg
    Arm description
    		 Secukinumab 75 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Secukinumab 75 mg
    Investigational medicinal product code
    AIN457
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Secukinumab 75 mg once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4

    Arm title
    		 Secukinumab 150 mg
    Arm description
    		 Secukinumab 150 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    Secukinumab 150 mg
    Investigational medicinal product code
    AIN457
    Other name
    Pharmaceutical forms
    Solution for infusion in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Secukinumab 150 mg once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4

    Arm title
    		 Placebo
    Arm description
    		 Placebo subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks up to week 16
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks up to week 16

    Number of subjects in period 1
    		Secukinumab 75 mg Secukinumab 150 mg Placebo
    Started
    73
    72
    74
    Completed
    68
    66
    66
    Not completed
    5
    6
    8
         Adverse event, serious fatal
    1
    -
    -
         Consent withdrawn by subject
    2
    1
    2
         Physician decision
    -
    -
    1
         Adverse event, non-fatal
    2
    5
    4
         Lack of efficacy
    -
    -
    1
    Period 2
    Period 2 title
    Week 16 up to Week 260
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor
    Blinding implementation details
    Trial continued to be blinded up to week 52 and then was unblinded for the remainder of the trial

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Secukinumab 75 mg
    Arm description
    		 Secukinumab 75 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Secukinumab 75 mg
    Investigational medicinal product code
    AIN457
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Secukinumab 75 mg once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4

    Arm title
    		 Secukinumab 150 mg
    Arm description
    		 Secukinumab 150 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    Secukinumab 150 mg
    Investigational medicinal product code
    AIN457
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Secukinumab 150 mg once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every four weeks starting at Week 4

    Arm title
    		 Placebo - secukinumab 75 mg
    Arm description
    		 Placebo patients re-randomized to secukinumab 75 mg subcutaneous injection every 4 weeks starting from week 16.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Secukinumab 75 mg
    Investigational medicinal product code
    AIN457
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Patients re-randomized to secukinumab 75 mg subcutaneous injection every 4 weeks starting from week 16

    Arm title
    		 Placebo - secukinumab 150 mg
    Arm description
    		 Placebo patients re-randomized to secukinumab 150 mg subcutaneous injection every 4 weeks starting from week 16.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Secukinumab 75 mg
    Investigational medicinal product code
    AIN457
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Patients re-randomized to secukinumab 75 mg subcutaneous injection every 4 weeks starting from week 16

    Number of subjects in period 2
    		Secukinumab 75 mg Secukinumab 150 mg Placebo - secukinumab 75 mg Placebo - secukinumab 150 mg
    Started
    68
    66
    32
    34
    Completed
    48
    53
    20
    29
    Not completed
    20
    13
    12
    5
         Adverse event, serious fatal
    1
    1
    -
    -
         Consent withdrawn by subject
    7
    2
    3
    1
         Physician decision
    -
    2
    -
    -
         Adverse event, non-fatal
    5
    2
    3
    2
         Non-compliance
    -
    1
    1
    -
         Technical issues
    -
    1
    1
    -
         Lack of efficacy
    7
    4
    4
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Secukinumab 75 mg
    Reporting group description
    		 Secukinumab 75 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks.

    Reporting group title
    Secukinumab 150 mg
    Reporting group description
    		 Secukinumab 150 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks up to week 16

    Reporting group values
    		 Secukinumab 75 mg Secukinumab 150 mg Placebo Total
    Number of subjects
    		 73 72 74 219
    Age, Customized
    Units: Subjects
        < 65
    		 70 70 72 212
        >= 65 to 74
    		 2 2 1 5
        >= 75
    		 1 0 1 2
    Sex: Female, Male
    Units: Subjects
        Female
    		 22 26 18 66
        Male
    		 51 46 56 153
    Race/Ethnicity, Customized
    Units: Subjects
        White
    		 70 69 70 209
        Asian
    		 3 2 4 9
        American Indian or Alaska Native
    		 0 1 0 1

    End points

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    End points reporting groups
    Reporting group title
    Secukinumab 75 mg
    Reporting group description
    		 Secukinumab 75 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks.

    Reporting group title
    Secukinumab 150 mg
    Reporting group description
    		 Secukinumab 150 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks up to week 16
    Reporting group title
    Secukinumab 75 mg
    Reporting group description
    		 Secukinumab 75 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks.

    Reporting group title
    Secukinumab 150 mg
    Reporting group description
    		 Secukinumab 150 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks

    Reporting group title
    Placebo - secukinumab 75 mg
    Reporting group description
    		 Placebo patients re-randomized to secukinumab 75 mg subcutaneous injection every 4 weeks starting from week 16.

    Reporting group title
    Placebo - secukinumab 150 mg
    Reporting group description
    		 Placebo patients re-randomized to secukinumab 150 mg subcutaneous injection every 4 weeks starting from week 16.

    Primary: Percentage of participants achieving ASAS 20 (SpondyloArthritis International Society criteria) response at week 16

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    End point title
    		 Percentage of participants achieving ASAS 20 (SpondyloArthritis International Society criteria) response at week 16
    End point description
    ASAS 20 response is a validated composite assessment, reflecting the proportion of treated patients who achieve within a defined timeframe an improvement of 20% and ≥1 unit on a scale of 10 in at least three of the four ASAS main domains and no worsening of ≥20% and ≥1 unit in the remaining domain. ASAS 20 is used to assess the efficacy of at least one dose of secukinumab against placebo.
    End point type
    Primary
    End point timeframe
    Baseline up to 16 weeks
    End point values
    		 Secukinumab 75 mg Secukinumab 150 mg Placebo
    Number of subjects analysed
    73
    72
    74
    Units: percentage of participants
        number (not applicable)
    41.1
    61.1
    28.4
    Statistical analysis title
    		 75 mg vs placebo
    Comparison groups
    Secukinumab 75 mg v Placebo
    Number of subjects included in analysis
    147
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0967
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 3.67
    Statistical analysis title
    		 150 mg vs placebo
    Comparison groups
    Secukinumab 150 mg v Placebo
    Number of subjects included in analysis
    146
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    4.38
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.14
         upper limit
    		 8.96

    Secondary: Percentage of participants achieving ASAS 40 (SpondyloArthritis International Society criteria) response at week 16

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    End point title
    		 Percentage of participants achieving ASAS 40 (SpondyloArthritis International Society criteria) response at week 16
    End point description
    ASAS 40 response is a validated composite assessment, reflecting the proportion of treated patients who achieve within a defined timeframe an improvement of ≥40% and ≥2 units on a scale of 10 in at least three of the four ASAS main domains and no worsening at all in the remaining domain. ASAS 40 is used to assess the efficacy of at least one dose of secukinumab against placebo.
    End point type
    Secondary
    End point timeframe
    Baseline up to 16 weeks
    End point values
    		 Secukinumab 75 mg Secukinumab 150 mg Placebo
    Number of subjects analysed
    73
    72
    74
    Units: percentage of participants
        number (not applicable)
    26.0
    36.1
    10.8
    Statistical analysis title
    		 75 mg vs placebo
    Comparison groups
    Secukinumab 75 mg v Placebo
    Number of subjects included in analysis
    147
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0194
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.19
         upper limit
    		 7.48
    Statistical analysis title
    		 150 mg vs placebo
    Comparison groups
    Secukinumab 150 mg v Placebo
    Number of subjects included in analysis
    146
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0004
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    5.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.06
         upper limit
    		 12.44

    Secondary: Change from baseline at week 16 in serum hsCRP

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    End point title
    		 Change from baseline at week 16 in serum hsCRP
    End point description
    The change from baseline in hsCRP is expressed as a ratio of post-baseline to baseline values. With the ratio normalized to 1.0 at baseline, ratios less than 1.0 represent decreased post-baseline values, whereas ratios greater than 1.0 represent increased post-baseline values. Blood levels of C-reactive protein (CRP), an acute phase reactant, are indicative of inflammation and of its severity, and can be used to monitor treatment response. A high sensitvity CRP (hsCRP) test is implemented in this study to assess the efficacy of at least one dose of secukinumab versus placebo in reducing AS elicited systemic inflammation over time.
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    		 Secukinumab 75 mg Secukinumab 150 mg Placebo
    Number of subjects analysed
    73
    72
    74
    Units: mg/L
        least squares mean (standard error)
    0.61 ( 1.103 )
    0.55 ( 1.104 )
    1.13 ( 1.105 )
    Statistical analysis title
    		 75 mg vs placebo
    Comparison groups
    Secukinumab 75 mg v Placebo
    Number of subjects included in analysis
    147
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.54
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.41
         upper limit
    		 0.71
    Statistical analysis title
    		 150 mg vs placebo
    Comparison groups
    Secukinumab 150 mg v Placebo
    Number of subjects included in analysis
    146
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.37
         upper limit
    		 0.64

    Secondary: Percentage of participants achieving ASAS 5/6 (SpondyloArthritis International Society criteria) response at week 16

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    End point title
    		 Percentage of participants achieving ASAS 5/6 (SpondyloArthritis International Society criteria) response at week 16
    End point description
    ASAS 5/6 response is a validated composite assessment, reflecting the proportion of treated patients who achieve within a defined timeframe at least 20% improvement in score in at least 5 of a conventional set of 6 clinical domains relevant to AS. In this study, ASAS 5/6 is used to assess the efficacy of at least one dose of secukinumab against placebo.
    End point type
    Secondary
    End point timeframe
    Baseline up to 16 weeks
    End point values
    		 Secukinumab 75 mg Secukinumab 150 mg Placebo
    Number of subjects analysed
    73
    72
    74
    Units: percentage of participants
        number (not applicable)
    34.2
    43.1
    8.1
    Statistical analysis title
    		 75 mg vs placebo
    Comparison groups
    Secukinumab 75 mg v Placebo
    Number of subjects included in analysis
    147
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0003
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    6.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.31
         upper limit
    		 16.26
    Statistical analysis title
    		 75 mg vs placebo
    Comparison groups
    Secukinumab 150 mg v Placebo
    Number of subjects included in analysis
    146
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    9.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.47
         upper limit
    		 24.12

    Secondary: Change from baseline at week 16 for total Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)

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    End point title
    		 Change from baseline at week 16 for total Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
    End point description
    BASDAI is a validated assessment tool using 0 through 10 scales (0 indicating "no problem" and 10 indicating " worst problem"), to characterize six clinical domains pertaining to five major symptoms of AS perceived by the patients. Computed composite scores of 4 or greater indicate suboptimal disease control. In this study, the BASDAI is used to assess the efficacy of at least one dose of secukinumab verus placebo.
    End point type
    Secondary
    End point timeframe
    Baseline up to 16 weeks
    End point values
    		 Secukinumab 75 mg Secukinumab 150 mg Placebo
    Number of subjects analysed
    73
    72
    74
    Units: scores on a scale
        least squares mean (standard error)
    -1.92 ( 0.249 )
    -2.19 ( 0.248 )
    -0.85 ( 0.252 )
    Statistical analysis title
    		 75 mg vs placebo
    Comparison groups
    Secukinumab 75 mg v Placebo
    Number of subjects included in analysis
    147
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -1.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.77
         upper limit
    		 -0.37
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.353
    Statistical analysis title
    		 150 mg vs placebo
    Comparison groups
    Secukinumab 150 mg v Placebo
    Number of subjects included in analysis
    146
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0002
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -1.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.04
         upper limit
    		 -0.65
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.353

    Secondary: Change from baseline at week 16 in Physical Function Component Summary (PCS) of the Medical Outcomes Study Questionnaire Short-form Health Survey (SF-36)

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    End point title
    		 Change from baseline at week 16 in Physical Function Component Summary (PCS) of the Medical Outcomes Study Questionnaire Short-form Health Survey (SF-36)
    End point description
    SF-36 is a 36 item questionnaire which measures Quality of Life across eight domains, which are both phyically and emotionally based. Two overall summary scores, the Phyical Component Summary (PCS) and Mental Component Summary (MCS) can be computed. In this study, SF-36 PCS is used to assess improvement from baseline of at least one dose of secukinumab versus placebo.
    End point type
    Secondary
    End point timeframe
    Baseline up to 16 weeks
    End point values
    		 Secukinumab 75 mg Secukinumab 150 mg Placebo
    Number of subjects analysed
    73
    72
    74
    Units: scores on a scale
        least squares mean (standard error)
    4.77 ( 0.798 )
    6.06 ( 0.784 )
    1.92 ( 0.786 )
    Statistical analysis title
    		 75 mg vs placebo
    Comparison groups
    Secukinumab 75 mg v Placebo
    Number of subjects included in analysis
    147
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.011
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    2.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.66
         upper limit
    		 5.03
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.108
    Statistical analysis title
    		 150 mg vs placebo
    Comparison groups
    Secukinumab 150 mg v Placebo
    Number of subjects included in analysis
    146
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0002
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    4.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.96
         upper limit
    		 6.32
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.105

    Secondary: Change from baseline at week 16 in ASQoL

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    End point title
    		 Change from baseline at week 16 in ASQoL
    End point description
    ASQoL is an 18 item questionnaire that assesses disease-specific quality of life (QoL), consisting of statements that are relevant to the physical and mental conditions for a participant with AS: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each statement is answered by the participant as a 'Yes' (scored as 1) or 'No' (scored as 0). All item scores are summed to give a total score. Total score can range from 0 (good QoL) to 18 (poor QoL). In this study, ASQoL is used to assess improvement from baseline of at least one dose of secukinumab versus placebo.
    End point type
    Secondary
    End point timeframe
    Baseline up to 16 weeks
    End point values
    		 Secukinumab 75 mg Secukinumab 150 mg Placebo
    Number of subjects analysed
    73
    72
    74
    Units: scores on a scale
        least squares mean (standard error)
    -3.33 ( 0.537 )
    -4.00 ( 0.528 )
    -1.37 ( 0.530 )
    Statistical analysis title
    		 75 mg vs placebo
    Comparison groups
    Secukinumab 75 mg v Placebo
    Number of subjects included in analysis
    147
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0096
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -1.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.43
         upper limit
    		 -0.48
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.748
    Statistical analysis title
    		 150 mg vs placebo
    Comparison groups
    Secukinumab 150 mg v Placebo
    Number of subjects included in analysis
    146
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0005
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -2.63
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.09
         upper limit
    		 -1.16
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.743

    Secondary: Percentage of participants achieving ASAS partial remission at week 16

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    End point title
    		 Percentage of participants achieving ASAS partial remission at week 16
    End point description
    ASAS partial remission is a composite assessment, reflecting the proportion of treated patients who achieve within a defined time frame a value not above 2 units in each of the 4 ASAS domains on a scale of 10. In this study ASAS partial remission is used to assess the efficacy of at least one dose of secukinumab versus placebo.
    End point type
    Secondary
    End point timeframe
    Baseline up to 16 weeks
    End point values
    		 Secukinumab 75 mg Secukinumab 150 mg Placebo
    Number of subjects analysed
    73
    72
    74
    Units: percentage of participants
        number (not applicable)
    15.1
    13.9
    4.1
    Statistical analysis title
    		 75 mg vs placebo
    Comparison groups
    Secukinumab 75 mg v Placebo
    Number of subjects included in analysis
    147
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0325
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    4.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.13
         upper limit
    		 16.21
    Statistical analysis title
    		 150 mg vs placebo
    Comparison groups
    Secukinumab 150 mg v Placebo
    Number of subjects included in analysis
    146
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0471
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.02
         upper limit
    		 15.01

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Timeframe for AE
    Adverse event reporting additional description
    AE additional description
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    Any AIN457 75 mg
    Reporting group description
    		 Any AIN457 75 mg

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo

    Reporting group title
    Any AIN457 150 mg
    Reporting group description
    		 Any AIN457 150 mg

    Serious adverse events
    		 Any AIN457 75 mg Placebo Any AIN457 150 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    25 / 105 (23.81%)
    4 / 74 (5.41%)
    31 / 155 (20.00%)
         number of deaths (all causes)
    2
    0
    1
         number of deaths resulting from adverse events
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Glioblastoma
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intraductal proliferative breast lesion
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Paraganglion neoplasm
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Superficial spreading melanoma stage unspecified
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 74 (1.35%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Haematoma
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombophlebitis superficial
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Drug ineffective
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Sarcoidosis
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Vaginal haemorrhage
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Nasal septum deviation
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory arrest
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Sleep apnoea syndrome
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 74 (1.35%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Concussion
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 74 (1.35%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Multiple injuries
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal cord injury cervical
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Splenic rupture
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    2 / 105 (1.90%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Nervous system disorders
    Carpal tunnel syndrome
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    2 / 155 (1.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    2 / 155 (1.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Quadriparesis
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Quadriplegia
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Iron deficiency anaemia
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Iridocyclitis
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Iritis
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal hernia
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anal fissure
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis ischaemic
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis microscopic
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis ulcerative
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Crohn's disease
         subjects affected / exposed
    2 / 105 (1.90%)
    0 / 74 (0.00%)
    2 / 155 (1.29%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Incarcerated hiatus hernia
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Nephrotic syndrome
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stress urinary incontinence
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Ankylosing spondylitis
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 74 (1.35%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Costochondritis
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Foot deformity
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 74 (1.35%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Anal abscess
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arthritis bacterial
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Febrile infection
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gallbladder abscess
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis salmonella
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 74 (0.00%)
    1 / 155 (0.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Groin abscess
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Meningitis viral
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 105 (1.90%)
    0 / 74 (0.00%)
    2 / 155 (1.29%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Postoperative wound infection
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 74 (0.00%)
    0 / 155 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Any AIN457 75 mg Placebo Any AIN457 150 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    76 / 105 (72.38%)
    26 / 74 (35.14%)
    99 / 155 (63.87%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    9 / 105 (8.57%)
    0 / 74 (0.00%)
    15 / 155 (9.68%)
         occurrences all number
    10
    0
    15
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    2 / 105 (1.90%)
    4 / 74 (5.41%)
    3 / 155 (1.94%)
         occurrences all number
    2
    6
    3
    Headache
         subjects affected / exposed
    9 / 105 (8.57%)
    6 / 74 (8.11%)
    15 / 155 (9.68%)
         occurrences all number
    10
    6
    26
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    4 / 105 (3.81%)
    5 / 74 (6.76%)
    5 / 155 (3.23%)
         occurrences all number
    4
    5
    9
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    9 / 105 (8.57%)
    1 / 74 (1.35%)
    17 / 155 (10.97%)
         occurrences all number
    13
    1
    18
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    5 / 105 (4.76%)
    1 / 74 (1.35%)
    11 / 155 (7.10%)
         occurrences all number
    6
    1
    12
    Oropharyngeal pain
         subjects affected / exposed
    4 / 105 (3.81%)
    2 / 74 (2.70%)
    8 / 155 (5.16%)
         occurrences all number
    5
    2
    9
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    6 / 105 (5.71%)
    1 / 74 (1.35%)
    4 / 155 (2.58%)
         occurrences all number
    6
    1
    4
    Musculoskeletal and connective tissue disorders
    Ankylosing spondylitis
         subjects affected / exposed
    6 / 105 (5.71%)
    1 / 74 (1.35%)
    6 / 155 (3.87%)
         occurrences all number
    6
    1
    9
    Arthralgia
         subjects affected / exposed
    8 / 105 (7.62%)
    2 / 74 (2.70%)
    10 / 155 (6.45%)
         occurrences all number
    14
    2
    12
    Back pain
         subjects affected / exposed
    7 / 105 (6.67%)
    2 / 74 (2.70%)
    13 / 155 (8.39%)
         occurrences all number
    8
    2
    13
    Bursitis
         subjects affected / exposed
    6 / 105 (5.71%)
    0 / 74 (0.00%)
    4 / 155 (2.58%)
         occurrences all number
    6
    0
    7
    Musculoskeletal pain
         subjects affected / exposed
    7 / 105 (6.67%)
    0 / 74 (0.00%)
    8 / 155 (5.16%)
         occurrences all number
    7
    0
    11
    Osteoarthritis
         subjects affected / exposed
    6 / 105 (5.71%)
    1 / 74 (1.35%)
    4 / 155 (2.58%)
         occurrences all number
    6
    1
    5
    Pain in extremity
         subjects affected / exposed
    2 / 105 (1.90%)
    1 / 74 (1.35%)
    11 / 155 (7.10%)
         occurrences all number
    2
    1
    13
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    15 / 105 (14.29%)
    1 / 74 (1.35%)
    14 / 155 (9.03%)
         occurrences all number
    23
    1
    15
    Gastroenteritis
         subjects affected / exposed
    6 / 105 (5.71%)
    1 / 74 (1.35%)
    13 / 155 (8.39%)
         occurrences all number
    8
    1
    17
    Influenza
         subjects affected / exposed
    13 / 105 (12.38%)
    0 / 74 (0.00%)
    14 / 155 (9.03%)
         occurrences all number
    15
    0
    16
    Nasopharyngitis
         subjects affected / exposed
    30 / 105 (28.57%)
    3 / 74 (4.05%)
    35 / 155 (22.58%)
         occurrences all number
    71
    3
    73
    Oral herpes
         subjects affected / exposed
    6 / 105 (5.71%)
    0 / 74 (0.00%)
    8 / 155 (5.16%)
         occurrences all number
    16
    0
    32
    Pharyngitis
         subjects affected / exposed
    6 / 105 (5.71%)
    0 / 74 (0.00%)
    3 / 155 (1.94%)
         occurrences all number
    7
    0
    3
    Rhinitis
         subjects affected / exposed
    6 / 105 (5.71%)
    1 / 74 (1.35%)
    5 / 155 (3.23%)
         occurrences all number
    7
    1
    5
    Sinusitis
         subjects affected / exposed
    5 / 105 (4.76%)
    1 / 74 (1.35%)
    8 / 155 (5.16%)
         occurrences all number
    6
    1
    11
    Upper respiratory tract infection
         subjects affected / exposed
    13 / 105 (12.38%)
    2 / 74 (2.70%)
    16 / 155 (10.32%)
         occurrences all number
    38
    2
    32
    Urinary tract infection
         subjects affected / exposed
    5 / 105 (4.76%)
    2 / 74 (2.70%)
    9 / 155 (5.81%)
         occurrences all number
    6
    2
    13
    Metabolism and nutrition disorders
    Hyperlipidaemia
         subjects affected / exposed
    5 / 105 (4.76%)
    1 / 74 (1.35%)
    8 / 155 (5.16%)
         occurrences all number
    5
    1
    8

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    22 Nov 2013
    -To expand the statistical hierarchy (primary plus ranked secondary variables) to include more endpoints which were relevant to determining the overall therapeutic value of a therapy for Ankylosing Spondylitis. These endpoints included but were not limited to ASQoL, BASDAI and SF-36. -Analysis was changed to include all patients in the FAS, rather than focusing only on the subset of patients who were TNFα-inhibitor naïve, as the FAS would be more representative of the general population of AS patients. - Align the primary and secondary assessments with the ASAS Handbook (Sieper et al 2009) -Limit blinded study duration to reduce patient burden in administering a second syringe containing placebo to maintain blind . As the primary endpoint analysis (PEA) was conducted after all patients completed Week 16, there was no longer a need for the sponsor to be blinded past this analysis. -The conduct of the interim analysis was revised. However, sites and patients remained blinded until all patients reached Week 52 to reduce bias when assessing the effect of the secukinumab doses over 52 weeks.
    18 Sep 2015
    -The study medication for patients on the 75 mg sc treatment arm could have been be escalated from 75 mg sc to 150 mg sc every 4 weeks for patients whose overall therapeutic response is not fully achieved with the current dose of 75 mg sc and may improve with a higher dose, as judged by the investigator. The escalation of the study medication may be determined at any site visit. - DMC discontinued after week 52. - To align with these specifications in local prescribing information, protocol exclusion criterion #12 was changed to: Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unwilling to use effective contraception during the entire study or longer if required by locally approved prescribing information. - Protocol exclusion criterion #16 was updated for greater clarity to “If the total bilirubin concentration is increased above 2 x ULN, total bilirubin should be differentiated into the direct and indirect reacting bilirubin.”

    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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