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    Clinical Trial Results:
    A randomized, double-blind, placebo-controlled multicenter study of secukinumab 150 mg in patients with active nonradiographic axial spondyloarthritis to evaluate the safety, tolerability and efficacy up to 2 years, followed by an optional phase of either 150 mg or 300 mg randomized dose escalation for up to another 2 years

    Summary
    EudraCT number
    		 2015-001106-33
    Trial protocol
    		 DE   GB   AT   ES   NL   HU   PT   NO   SE   BE   BG   FR   CZ   IT  
    Global end of trial date
    11 Mar 2021

    Results information
    Results version number
    		 v2(current)
    This version publication date
    09 Jun 2022
    First version publication date
    13 Dec 2021
    Other versions
    		 v1
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    CAIN457H2315
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02696031
    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
    01 Jul 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    11 Mar 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective was to demonstrate that secukinumab 150 mg s.c. (without load) at Week 52 was superior to placebo in TNF-alpha inhibitor naïve (TNFi-naïve) patients with active nr-axSpA based on the proportion of patients achieving an ASAS40 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
    29 Apr 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 27
    Country: Number of subjects enrolled
    Austria: 3
    Country: Number of subjects enrolled
    Belgium: 10
    Country: Number of subjects enrolled
    Bulgaria: 7
    Country: Number of subjects enrolled
    Czechia: 71
    Country: Number of subjects enrolled
    France: 19
    Country: Number of subjects enrolled
    Germany: 52
    Country: Number of subjects enrolled
    United Kingdom: 24
    Country: Number of subjects enrolled
    Hungary: 21
    Country: Number of subjects enrolled
    Israel: 11
    Country: Number of subjects enrolled
    Italy: 14
    Country: Number of subjects enrolled
    Japan: 13
    Country: Number of subjects enrolled
    Korea, Republic of: 2
    Country: Number of subjects enrolled
    Mexico: 6
    Country: Number of subjects enrolled
    Netherlands: 9
    Country: Number of subjects enrolled
    Norway: 8
    Country: Number of subjects enrolled
    Poland: 65
    Country: Number of subjects enrolled
    Portugal: 14
    Country: Number of subjects enrolled
    Russian Federation: 54
    Country: Number of subjects enrolled
    Spain: 72
    Country: Number of subjects enrolled
    Sweden: 7
    Country: Number of subjects enrolled
    Switzerland: 8
    Country: Number of subjects enrolled
    Turkey: 2
    Country: Number of subjects enrolled
    United States: 36
    Worldwide total number of subjects
    555
    EEA total number of subjects
    372
    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)
    546
    From 65 to 84 years
    9
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 A total of 1583 patients were screened for this study, of which 555 patients (35.1%) were randomized. Overall, 1028 patients (64.9%) discontinued prior to screening phase completion, most due to screen failure (1000 patients, 63.2%).

    Pre-assignment
    Screening details
    		 555 participants were planned and also analyzed.

    Period 1
    Period 1 title
    Up to Week 104
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor
    Blinding implementation details
    This was a blinded placebo controlled study up to week 52. All patients received secukinumab 150 mg as open-label treatment from Week 52 up to Week 100, unless they had discontinued study treatment.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Secukinumab, Load, Core Phase
    Arm description
    		 AIN457 150 mg s.c. load, Core Phase
    Arm type
    		 Experimental

    Investigational medicinal product name
    secukinumab
    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 Load

    Arm title
    		 Secukinumab, No Load, Core Phase
    Arm description
    		 AIN457 150 mg s.c. no load, Core Phase
    Arm type
    		 Experimental

    Investigational medicinal product name
    secukinumab
    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 No Load

    Arm title
    		 Placebo, Core Phase
    Arm description
    		 Placebo s.c., Core Phase
    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 (1 mL)

    Number of subjects in period 1
    		Secukinumab, Load, Core Phase Secukinumab, No Load, Core Phase Placebo, Core Phase
    Started
    185
    184
    186
    Completed
    146
    143
    149
    Not completed
    39
    41
    37
         Physician decision
    1
    2
    3
         Consent withdrawn by subject
    15
    10
    16
         Pt completed wk 52 and then withdrew
    -
    1
    -
         Adverse event, non-fatal
    7
    11
    5
         Pregnancy
    -
    2
    1
         Lost to follow-up
    2
    3
    1
         Lack of efficacy
    13
    12
    11
         Protocol deviation
    1
    -
    -
    Period 2
    Period 2 title
    Extension phase from wk 104 to wk 208
    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
    At Week 104, all patients who finished the core phase according to the protocol were asked to continue in an optional, exploratory extension phase. Patients who achieved ASAS20 response at Week 104 (Core Phase Responders) were randomized to the treatment groups, which were blinded.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 AIN457 150 mg Extension phase
    Arm description
    		 AIN457 150 mg Core Phase Responders who were rerandomized at week 104 to the 150 mg in the Extension phase (from Week 104 to week 208).
    Arm type
    		 Experimental

    Investigational medicinal product name
    secukinumab
    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

    Arm title
    		 AIN457 300 mg Extension phase
    Arm description
    		 AIN457 150 mg Core Phase Responders who were rerandomized at week 104 to the 300 mg in the Extension phase (from Week 104 to week 208).
    Arm type
    		 Experimental

    Investigational medicinal product name
    secukinumab
    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 300 mg

    Arm title
    		 AIN457 300 mg Open Label Extension phase
    Arm description
    		 AIN457 150 mg Open Label Core Phase Non-Responders who were assigned at week 104 to the 300 mg Open Label in the Extension phase (from Week 104 to week 208).
    Arm type
    		 Experimental

    Investigational medicinal product name
    secukinumab
    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 300 mg

    Number of subjects in period 2 [1]
    		AIN457 150 mg Extension phase AIN457 300 mg Extension phase AIN457 300 mg Open Label Extension phase
    Started
    147
    147
    78
    Completed
    137
    132
    72
    Not completed
    10
    15
    6
         Consent withdrawn by subject
    6
    8
    2
         Physician decision
    1
    1
    -
         Adverse event, non-fatal
    1
    4
    1
         Non-compliance with study treatment
    1
    -
    -
         Lost to follow-up
    -
    1
    -
         Lack of efficacy
    1
    1
    3
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: The counts are verified as correct; the treatment arms changed from the core phase to the extension phase.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Secukinumab, Load, Core Phase
    Reporting group description
    		 AIN457 150 mg s.c. load, Core Phase

    Reporting group title
    Secukinumab, No Load, Core Phase
    Reporting group description
    		 AIN457 150 mg s.c. no load, Core Phase

    Reporting group title
    Placebo, Core Phase
    Reporting group description
    		 Placebo s.c., Core Phase

    Reporting group values
    		 Secukinumab, Load, Core Phase Secukinumab, No Load, Core Phase Placebo, Core Phase Total
    Number of subjects
    		 185 184 186 555
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0
        Adults (18-64 years)
    		 183 180 183 546
        From 65-84 years
    		 2 4 3 9
        85 years and over
    		 0 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 39.1 ± 11.45 39.8 ± 11.68 39.3 ± 11.47 -
    Sex: Female, Male
    Units: Participants
        Female
    		 105 100 95 300
        Male
    		 80 84 91 255
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 9 8 7 24
        Not Hispanic or Latino
    		 165 162 161 488
        Unknown or Not Reported
    		 11 14 18 43
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaska Native
    		 0 2 0 2
        Asian
    		 4 8 11 23
        Black or African American
    		 0 2 1 3
        White
    		 176 165 167 508
        Other
    		 5 7 7 19

    End points

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    End points reporting groups
    Reporting group title
    Secukinumab, Load, Core Phase
    Reporting group description
    		 AIN457 150 mg s.c. load, Core Phase

    Reporting group title
    Secukinumab, No Load, Core Phase
    Reporting group description
    		 AIN457 150 mg s.c. no load, Core Phase

    Reporting group title
    Placebo, Core Phase
    Reporting group description
    		 Placebo s.c., Core Phase
    Reporting group title
    AIN457 150 mg Extension phase
    Reporting group description
    		 AIN457 150 mg Core Phase Responders who were rerandomized at week 104 to the 150 mg in the Extension phase (from Week 104 to week 208).

    Reporting group title
    AIN457 300 mg Extension phase
    Reporting group description
    		 AIN457 150 mg Core Phase Responders who were rerandomized at week 104 to the 300 mg in the Extension phase (from Week 104 to week 208).

    Reporting group title
    AIN457 300 mg Open Label Extension phase
    Reporting group description
    		 AIN457 150 mg Open Label Core Phase Non-Responders who were assigned at week 104 to the 300 mg Open Label in the Extension phase (from Week 104 to week 208).

    Primary: The proportion of TNF naive participants who achieved an Assessment of Spondylo Arthritis International Society (ASAS) 40 response at week 16

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    End point title
    		 The proportion of TNF naive participants who achieved an Assessment of Spondylo Arthritis International Society (ASAS) 40 response at week 16
    End point description
    Assessment of SpondyloArthritis International Society criteria (ASAS) consist of 6 domains (4 main and 2 additional assessment domains): 1. Patient’s global assessment measured on a visual analog scale (VAS); 2. Patient’s assessment of back pain, measured on a VAS; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions as measured by VAS; 4. Inflammation represented by mean duration and severity of morning stiffness, on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) as measured by VAS; 5. Spinal mobility represented by the Bath Ankylosing Spondylitis Metrology Index (BASMI) lateral spinal flexion assessment; 6. C-reactive protein (acute phase reactant). ASAS40 response is defined as 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. A higher score on the VAS signifies higher severity.
    End point type
    Primary
    End point timeframe
    Week 16
    End point values
    		 Secukinumab, Load, Core Phase Secukinumab, No Load, Core Phase Placebo, Core Phase
    Number of subjects analysed
    164
    166
    171
    Units: Participants
    68
    70
    50
    Statistical analysis title
    		 Secukinumab Load v Placebo
    Statistical analysis description
    week 16
    Comparison groups
    Secukinumab, Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    335
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0197 [1]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.09
         upper limit
    		 2.7
    Notes
    [1] - unadjusted p-value
    Statistical analysis title
    		 Secukinumab No Load v Placebo
    Statistical analysis description
    week 16
    Comparison groups
    Secukinumab, No Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    337
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0146 [2]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.12
         upper limit
    		 2.76
    Notes
    [2] - unadjusted p-value

    Primary: The proportion of TNF naive participants who achieved an Assessment of SpondyloArthritis International Society (ASAS) 40 response at week 52

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    End point title
    		 The proportion of TNF naive participants who achieved an Assessment of SpondyloArthritis International Society (ASAS) 40 response at week 52
    End point description
    Assessment of SpondyloArthritis International Society criteria (ASAS) consist of 6 domains (4 main and 2 additional assessment domains): 1. Patient’s global assessment measured on a visual analog scale (VAS); 2. Patient’s assessment of back pain, measured on a VAS; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions as measured by VAS; 4. Inflammation represented by mean duration and severity of morning stiffness, on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) as measured by VAS; 5. Spinal mobility represented by the Bath Ankylosing Spondylitis Metrology Index (BASMI) lateral spinal flexion assessment; 6. C-reactive protein (acute phase reactant). ASAS40 response is defined as 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. A higher score on the VAS signifies higher severity.
    End point type
    Primary
    End point timeframe
    Week 52
    End point values
    		 Secukinumab, Load, Core Phase Secukinumab, No Load, Core Phase Placebo, Core Phase
    Number of subjects analysed
    164
    166
    171
    Units: Participants
    58
    66
    34
    Statistical analysis title
    		 Secukinumab No Load v Placebo
    Statistical analysis description
    week 52
    Comparison groups
    Secukinumab, No Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    337
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001 [3]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.64
         upper limit
    		 4.36
    Notes
    [3] - unadjusted p-value
    Statistical analysis title
    		 Secukinumab Load v Placebo
    Statistical analysis description
    week 52
    Comparison groups
    Secukinumab, Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    335
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0017 [4]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.35
         upper limit
    		 3.63
    Notes
    [4] - unadjusted p-value

    Secondary: The proportion of participants who achieved an Assessment of SpondyloArthritis International Society (ASAS) 40 response

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    End point title
    		 The proportion of participants who achieved an Assessment of SpondyloArthritis International Society (ASAS) 40 response
    End point description
    Assessment of SpondyloArthritis International Society criteria (ASAS) consist of 6 domains (4 main and 2 additional assessment domains): 1. Patient’s global assessment measured on a visual analog scale (VAS); 2. Patient’s assessment of back pain, measured on a VAS; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions as measured by VAS; 4. Inflammation represented by mean duration and severity of morning stiffness, on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) as measured by VAS; 5. Spinal mobility represented by the Bath Ankylosing Spondylitis Metrology Index (BASMI) lateral spinal flexion assessment; 6. C-reactive protein (acute phase reactant). ASAS40 response is defined as 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. A higher score on the VAS signifies higher severity.
    End point type
    Secondary
    End point timeframe
    Week 16 and week 52
    End point values
    		 Secukinumab, Load, Core Phase Secukinumab, No Load, Core Phase Placebo, Core Phase
    Number of subjects analysed
    185
    184
    186
    Units: Participants
        week 16
    74
    75
    52
        week 52
    62
    70
    36
    Statistical analysis title
    		 Secukinumab Load v Placebo
    Statistical analysis description
    week 16
    Comparison groups
    Secukinumab, Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    371
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0108 [5]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.14
         upper limit
    		 2.74
    Notes
    [5] - unadjusted p-value
    Statistical analysis title
    		 Secukinumab No Load v Placebo
    Statistical analysis description
    week 16
    Comparison groups
    Secukinumab, No Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    370
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0087 [6]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.16
         upper limit
    		 2.78
    Notes
    [6] - unadjusted p-value
    Statistical analysis title
    		 Secukinumab Load v Placebo
    Comparison groups
    Secukinumab, Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    371
    Analysis specification
    Pre-specified
    Analysis type
    		 [7]
    P-value
    		 = 0.0016 [8]
    Method
    		 Regression, Linear
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.34
         upper limit
    		 3.49
    Notes
    [7] - week 52
    [8] - unadjusted p-value
    Statistical analysis title
    		 Secukinumab No Load v Placebo
    Comparison groups
    Secukinumab, No Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    370
    Analysis specification
    Pre-specified
    Analysis type
    		 [9]
    P-value
    		 < 0.0001 [10]
    Method
    		 Regression, Linear
    Parameter type
    		 Median difference (net)
    Point estimate
    2.61
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.62
         upper limit
    		 4.19
    Notes
    [9] - week 52
    [10] - unadjusted p-value

    Secondary: The proportion of participants who achieved an Assessment of SpondyloArthritis International Society (ASAS) 20 response

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    End point title
    		 The proportion of participants who achieved an Assessment of SpondyloArthritis International Society (ASAS) 20 response
    End point description
    Assessment of SpondyloArthritis International Society criteria (ASAS) consist of 6 domains (4 main and 2 additional assessment domains): 1. Patient’s global assessment measured on a visual analog scale (VAS); 2. Patient’s assessment of back pain, measured on a VAS; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions as measured by VAS; 4. Inflammation represented by mean duration and severity of morning stiffness, on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) as measured by VAS; 5. Spinal mobility represented by the Bath Ankylosing Spondylitis Metrology Index (BASMI) lateral spinal flexion assessment; 6. C-reactive protein (acute phase reactant). ASAS 20 response is defined as an improvement of ≥20% and ≥1 unit on a scale of 10 in at least three of the four main domains and no worsening of ≥20% and ≥1 unit on a scale of 10 in the remaining domain. A higher score on the VAS signifies higher severity.
    End point type
    Secondary
    End point timeframe
    Week 16
    End point values
    		 Secukinumab, Load, Core Phase Secukinumab, No Load, Core Phase Placebo, Core Phase
    Number of subjects analysed
    185
    184
    186
    Units: Participants
    105
    107
    85
    Statistical analysis title
    		 Secukinumab Load v Placebo
    Statistical analysis description
    week 16
    Comparison groups
    Secukinumab, Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    371
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.026 [11]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.06
         upper limit
    		 2.43
    Notes
    [11] - unadjusted p-value
    Statistical analysis title
    		 Secukinumab No Load v Placebo
    Statistical analysis description
    week 16
    Comparison groups
    Secukinumab, No Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    370
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0149 [12]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.11
         upper limit
    		 2.54
    Notes
    [12] - unadjusted p-value

    Secondary: The proportion of participants who achieved an Assessment of SpondyloArthritis International Society (ASAS) 5/6 response

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    End point title
    		 The proportion of participants who achieved an Assessment of SpondyloArthritis International Society (ASAS) 5/6 response
    End point description
    Assessment of SpondyloArthritis International Society criteria (ASAS) consist of 6 domains (4 main and 2 additional assessment domains): 1. Patient’s global assessment measured on a visual analog scale (VAS); 2. Patient’s assessment of back pain, measured on a VAS; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions as measured by VAS; 4. Inflammation represented by mean duration and severity of morning stiffness, on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) as measured by VAS; 5. Spinal mobility represented by the Bath Ankylosing Spondylitis Metrology Index (BASMI) lateral spinal flexion assessment; 6. C-reactive protein (acute phase reactant). The ASAS 5/6 improvement criteria is an improvement of ≥20% in at least five of all six domains. A higher score on the VAS signifies higher severity.
    End point type
    Secondary
    End point timeframe
    Week 16
    End point values
    		 Secukinumab, Load, Core Phase Secukinumab, No Load, Core Phase Placebo, Core Phase
    Number of subjects analysed
    185
    184
    186
    Units: Participants
    74
    66
    44
    Statistical analysis title
    		 Secukinumab Load v Placebo
    Statistical analysis description
    week 16
    Comparison groups
    Secukinumab, Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    371
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0005 [13]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.43
         upper limit
    		 3.58
    Notes
    [13] - unadjusted p-value
    Statistical analysis title
    		 Secukinumab No Load v Placebo
    Statistical analysis description
    week 16
    Comparison groups
    Secukinumab, No Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    370
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0094 [14]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.16
         upper limit
    		 2.94
    Notes
    [14] - unadjusted p-value

    Secondary: The proportion of participants who achieved an Assessment of SpondyloArthritis International Society Partial Remission (ASAS PR)

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    End point title
    		 The proportion of participants who achieved an Assessment of SpondyloArthritis International Society Partial Remission (ASAS PR)
    End point description
    Assessment of SpondyloArthritis International Society criteria (ASAS) consist of 6 domains (4 main and 2 additional assessment domains): 1. Patient’s global assessment measured on a visual analog scale (VAS); 2. Patient’s assessment of back pain, measured on a VAS; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions as measured by VAS; 4. Inflammation represented by mean duration and severity of morning stiffness, on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) as measured by VAS; 5. Spinal mobility represented by the Bath Ankylosing Spondylitis Metrology Index (BASMI) lateral spinal flexion assessment; 6. C-reactive protein (acute phase reactant). The ASAS partial remission criteria are defined as a value not above 2 units in each of the four main domains on a scale of 10. A higher score on the VAS signifies higher severity.
    End point type
    Secondary
    End point timeframe
    Week 16
    End point values
    		 Secukinumab, Load, Core Phase Secukinumab, No Load, Core Phase Placebo, Core Phase
    Number of subjects analysed
    185
    184
    186
    Units: Participants
    40
    39
    13
    Statistical analysis title
    		 Secukinumab Load v Placebo
    Statistical analysis description
    week 16
    Comparison groups
    Secukinumab, Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    371
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001 [15]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.95
         upper limit
    		 7.39
    Notes
    [15] - unadjusted p-value
    Statistical analysis title
    		 Secukinumab No Load v Placebo
    Statistical analysis description
    week 16
    Comparison groups
    Secukinumab, No Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    370
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0001 [16]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.64
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.87
         upper limit
    		 7.1
    Notes
    [16] - unadjusted p-value

    Secondary: Change in Bath Ankylosing Spondylitis Functional Index (BASFI)

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    End point title
    		 Change in Bath Ankylosing Spondylitis Functional Index (BASFI)
    End point description
    The Bath Ankylosing Spondylitis Functional Index (BASFI) is a set of 10 questions designed to determine the degree of functional limitation in those subjects with AS. The ten questions were chosen with a major input from subjects with AS. The first 8 questions consider activities related to functional anatomy. The final 2 questions assess the subjects’ ability to cope with everyday life. A 100 mm visual analog scale (VAS) is used to answer the questions. The mean of the ten questions gives the BASFI score – a value between 0 and 10. (0 being no problem and 10 being the worst problem, captured as a continuous visual analog scale (VAS)). A higher score on the VAS signifies higher severity.
    End point type
    Secondary
    End point timeframe
    Week 16
    End point values
    		 Secukinumab, Load, Core Phase Secukinumab, No Load, Core Phase Placebo, Core Phase
    Number of subjects analysed
    181
    177
    177
    Units: Index
        least squares mean (standard error)
    -1.75 ± 0.202
    -1.64 ± 0.204
    -1.01 ± 0.206
    Statistical analysis title
    		 Secukinumab Load v Placebo
    Statistical analysis description
    week 16
    Comparison groups
    Secukinumab, Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    358
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0041 [17]
    Method
    		 MMRM
    Parameter type
    		 LS Mean
    Point estimate
    -0.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.26
         upper limit
    		 -0.24
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.259
    Notes
    [17] - unadjusted p-value
    Statistical analysis title
    		 Secukinumab No Load v Placebo
    Statistical analysis description
    week 16
    Comparison groups
    Secukinumab, No Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    354
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0143 [18]
    Method
    		 MMRM
    Parameter type
    		 LS Mean
    Point estimate
    -0.64
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.15
         upper limit
    		 -0.13
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.259
    Notes
    [18] - unadjusted p-value

    Secondary: The proportion of patients to achieve a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 response

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    End point title
    		 The proportion of patients to achieve a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 response
    End point description
    The BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) consists of a 0 through 10 scale (0 being no problem and 10 being the worst problem, captured as a continuous VAS), which is used to answer 6 questions pertaining to the 5 major symptoms of AS. The BASDAI 50 is defined as an improvement of at least 50% in the BASDAI compared to baseline. A higher score on the VAS signifies higher severity.
    End point type
    Secondary
    End point timeframe
    Week 16 and 52
    End point values
    		 Secukinumab, Load, Core Phase Secukinumab, No Load, Core Phase Placebo, Core Phase
    Number of subjects analysed
    185
    184
    186
    Units: Participants
        week 16
    69
    69
    39
        week 52
    57
    65
    37
    Statistical analysis title
    		 Secukinumab Load v Placebo
    Statistical analysis description
    week 16
    Comparison groups
    Secukinumab, Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    371
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0001 [19]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.58
         upper limit
    		 4.07
    Notes
    [19] - unadjusted p-value
    Statistical analysis title
    		 Secukinumab No Load v Placebo
    Statistical analysis description
    week 16
    Comparison groups
    Secukinumab, No Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    370
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0002 [20]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.51
         upper limit
    		 3.89
    Notes
    [20] - unadjusted p-value
    Statistical analysis title
    		 Secukinumab Load v Placebo
    Statistical analysis description
    week 52
    Comparison groups
    Secukinumab, Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    371
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0056 [21]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.22
         upper limit
    		 3.24
    Notes
    [21] - unadjusted p-value
    Statistical analysis title
    		 Secukinumab No Load v Placebo
    Statistical analysis description
    week 52
    Comparison groups
    Secukinumab, No Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    370
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0005 [22]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.45
         upper limit
    		 3.78
    Notes
    [22] - unadjusted p-value

    Secondary: Change in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)

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    End point title
    		 Change in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
    End point description
    The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is a validated assessment tool using 1 through 10 scales (1 indicating "no problem" and 10 indicating " worst problem"), to characterize six clinical domains (fatigue, spinal pain, joint pain/selling, localized tenderness, morning stiffness duration, morning stiffness severity) pertaining to five major symptoms of Ankylosing Spondylitis (AS). The computed final BASDAI score is a value between 0 and 10 with a higher score indicating worse disease. A higher score on the VAS signifies higher severity.
    End point type
    Secondary
    End point timeframe
    Week 16
    End point values
    		 Secukinumab, Load, Core Phase Secukinumab, No Load, Core Phase Placebo, Core Phase
    Number of subjects analysed
    181
    177
    177
    Units: scores on a scale
        least squares mean (standard error)
    -2.35 ± 0.201
    -2.43 ± 0.203
    -1.46 ± 0.205
    Statistical analysis title
    		 Secukinumab Load v Placebo
    Statistical analysis description
    week 16
    Comparison groups
    Secukinumab, Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    358
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0006 [23]
    Method
    		 mixed model repeated measures (MMRM)
    Parameter type
    		 LS Mean of treatment difference
    Point estimate
    -0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.39
         upper limit
    		 -0.38
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.256
    Notes
    [23] - unadjusted p-value
    Statistical analysis title
    		 Secukinumab No Load v Placebo
    Statistical analysis description
    week 16
    Comparison groups
    Secukinumab, No Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    354
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0002 [24]
    Method
    		 mixed model repeated measures (MMRM)
    Parameter type
    		 LS Mean of Treatment Difference
    Point estimate
    -0.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.47
         upper limit
    		 -0.47
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.255
    Notes
    [24] - unadjusted p-value

    Secondary: Change in Ankylosing Spondylitis Quality of Life (ASQoL) scores at week 16

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    End point title
    		 Change in Ankylosing Spondylitis Quality of Life (ASQoL) scores at week 16
    End point description
    The Ankylosing Spondylitis Quality of Life scores (ASQoL) is a self-administered questionnaire designed to assess health-related quality of life in adult patients with Ankylosing Spondylitis. The ASQoL contains 18 items with a dichotomous yes/no response option. A single point is assigned for each "yes" response and no points for each "no" response resulting in overall scores that range from 0 (least severity) to 18 (highest severity). As such, lower score indicate better quality of life. Items include an assessment of mobility/energy, self-care and mood/emotion. The recall period is "at the moment," and the measure requires approximately 6 minutes to complete.
    End point type
    Secondary
    End point timeframe
    Week 16
    End point values
    		 Secukinumab, Load, Core Phase Secukinumab, No Load, Core Phase Placebo, Core Phase
    Number of subjects analysed
    181
    176
    177
    Units: Scores on a scale
        least squares mean (standard error)
    -3.45 ± 0.408
    -3.62 ± 0.414
    -1.84 ± 0.421
    Statistical analysis title
    		 Secukinumab Load v Placebo
    Statistical analysis description
    week 16
    Comparison groups
    Secukinumab, Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    358
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0008 [25]
    Method
    		 MMRM
    Parameter type
    		 LS Mean
    Point estimate
    -1.61
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.54
         upper limit
    		 -0.67
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.478
    Notes
    [25] - unadjusted p-value
    Statistical analysis title
    		 Secukinumab No Load v Placebo
    Statistical analysis description
    week 16
    Comparison groups
    Secukinumab, No Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    353
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0002 [26]
    Method
    		 MMRM
    Parameter type
    		 LS Mean
    Point estimate
    -1.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.72
         upper limit
    		 -0.84
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.479
    Notes
    [26] - unadjusted p-value

    Secondary: Change in Ankylosing Spondylitis Quality of Life (ASQoL) scores at week 52

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    End point title
    		 Change in Ankylosing Spondylitis Quality of Life (ASQoL) scores at week 52
    End point description
    The Ankylosing Spondylitis Quality of Life scores (ASQoL) is a self-administered questionnaire designed to assess health-related quality of life in adult patients with Ankylosing Spondylitis. The ASQoL contains 18 items with a dichotomous yes/no response option. A single point is assigned for each "yes" response and no points for each "no" response resulting in overall scores that range from 0 (least severity) to 18 (highest severity). As such, lower score indicate better quality of life. Items include an assessment of mobility/energy, self-care and mood/emotion. The recall period is "at the moment," and the measure requires approximately 6 minutes to complete. Summary statistics are presented for participants (n) without intercurrent events.
    End point type
    Secondary
    End point timeframe
    Week 52
    End point values
    		 Secukinumab, Load, Core Phase Secukinumab, No Load, Core Phase Placebo, Core Phase
    Number of subjects analysed
    83
    88
    54
    Units: Scores on a scale
        arithmetic mean (standard deviation)
    -7.1 ± 4.77
    -7.6 ± 5.38
    -6.4 ± 4.64
    Statistical analysis title
    		 Secukinumab Load v Placebo
    Comparison groups
    Secukinumab, Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    137
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0012 [27]
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [27] - Unadjusted p-value. The endpoint was analyzed by composite estimand strategy. Extreme unfavorable value is assigned for patients with treatment escape or missing data.
    Statistical analysis title
    		 Secukinumab No Load v Placebo
    Comparison groups
    Secukinumab, No Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    142
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001 [28]
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [28] - Unadjusted p-value. The endpoint was analyzed by composite estimand strategy. Extreme unfavorable value is assigned for patients with treatment escape or missing data.

    Secondary: The proportion of patients who achieved an Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-Reactive Protein (CRP) inactive disease

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    End point title
    		 The proportion of patients who achieved an Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-Reactive Protein (CRP) inactive disease
    End point description
    Ankylosing Spondylitis Disease Activity Score (ASDAS) - C-reactive protein (CRP) inactive disease criteria are defined as a value below 1.3. Higher score indicates worse symptoms. The formula is: ASDAS-CRP = 0.121 x total back pain + 0.110 x patient global + 0.073 x peripheral pain/swelling + 0.058 x duration of morning stiffness + 0.579 x ln(hsCRP +1)
    End point type
    Secondary
    End point timeframe
    Week 52
    End point values
    		 Secukinumab, Load, Core Phase Secukinumab, No Load, Core Phase Placebo, Core Phase
    Number of subjects analysed
    185
    184
    186
    Units: Participants
    29
    44
    19
    Statistical analysis title
    		 Secukinumab Load v Placebo
    Statistical analysis description
    week 52
    Comparison groups
    Secukinumab, Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    371
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0577 [29]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.98
         upper limit
    		 3.45
    Notes
    [29] - unadjusted p-value
    Statistical analysis title
    		 Secukinumab No Load v Placebo
    Statistical analysis description
    week 52
    Comparison groups
    Secukinumab, No Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    370
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0003 [30]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.65
         upper limit
    		 5.41
    Notes
    [30] - unadjusted p-value

    Secondary: Change in high sensitivity C-reactive protein

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    End point title
    		 Change in high sensitivity C-reactive protein
    End point description
    High sensitivity C-reactive protein is measured as a marker of inflammation from blood samples during the study.
    End point type
    Secondary
    End point timeframe
    Week 16
    End point values
    		 Secukinumab, Load, Core Phase Secukinumab, No Load, Core Phase Placebo, Core Phase
    Number of subjects analysed
    180
    176
    175
    Units: ratio
        least squares mean (standard error)
    0.64 ± 1.078
    0.64 ± 1.079
    0.91 ± 1.080
    Statistical analysis title
    		 Secukinumab Load v Placebo
    Statistical analysis description
    week 16
    Comparison groups
    Secukinumab, Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    355
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0002 [31]
    Method
    		 MMRM
    Parameter type
    		 Relative Treatment Effect
    Point estimate
    0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.58
         upper limit
    		 0.84
    Notes
    [31] - unadjusted p-value
    Statistical analysis title
    		 Secukinumab No Load v Placebo
    Statistical analysis description
    week 16
    Comparison groups
    Secukinumab, No Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    351
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0002 [32]
    Method
    		 MMRM
    Parameter type
    		 Relative Treatment Effect
    Point estimate
    0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.58
         upper limit
    		 0.84
    Notes
    [32] - unadjusted p-value

    Secondary: Change in Short Form-36 Physical Component Summary (SF-36 PCS)

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    End point title
    		 Change in Short Form-36 Physical Component Summary (SF-36 PCS)
    End point description
    The Short Form-36 Physical Component Summary (SF-36 PCS) is an instrument to measure health-related quality of life among healthy patients and patients with acute and chronic conditions. It consists of eight subscales (domains) that can be scored individually: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role- Emotional, and Mental Health. Two overall summary scores, the Physical Component Summary (PCS) and the Mental Component Summary (MCS) also can be computed. The eight domains are based on a scale from 0-100 while PCS and MCS are norm-based scores with a mean of 50 and a standard deviation of 10. Higher scores indicate a higher level of functioning. A positive change from baseline score indicates an improvement.
    End point type
    Secondary
    End point timeframe
    Week 16
    End point values
    		 Secukinumab, Load, Core Phase Secukinumab, No Load, Core Phase Placebo, Core Phase
    Number of subjects analysed
    182
    176
    178
    Units: Scores on a Scale
        least squares mean (standard error)
    5.71 ± 0.683
    5.57 ± 0.694
    2.93 ± 0.705
    Statistical analysis title
    		 Secukinumab Load v Placebo
    Statistical analysis description
    week 16
    Comparison groups
    Secukinumab, Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    360
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0006 [33]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean of Treatment Difference
    Point estimate
    2.77
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.2
         upper limit
    		 4.34
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.799
    Notes
    [33] - unadjusted p-value
    Statistical analysis title
    		 Secukinumab No Load v Placebo
    Statistical analysis description
    week 16
    Comparison groups
    Secukinumab, No Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    354
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0011 [34]
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean of Treatment Difference
    Point estimate
    2.64
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.06
         upper limit
    		 4.22
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.803
    Notes
    [34] - unadjusted p-value

    Secondary: Change in Sacroiliac Joint Edema - week 16

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    End point title
    		 Change in Sacroiliac Joint Edema - week 16
    End point description
    Magnetic Resonance Images (MRI) of the Sacroiliac Joint (SIJ) were assessed for the presence and severity of SIJ bone marrow edema according to the Berlin Active Inflammatory Lesions Scoring with a maximum score of 24.
    End point type
    Secondary
    End point timeframe
    Week 16
    End point values
    		 Secukinumab, Load, Core Phase Secukinumab, No Load, Core Phase Placebo, Core Phase
    Number of subjects analysed
    180
    177
    174
    Units: Scores on a Scale
        arithmetic mean (standard error)
    -1.68 ± 0.24
    -1.03 ± 0.18
    -0.39 ± 0.15
    Statistical analysis title
    		 Secukinumab Load v Placebo
    Statistical analysis description
    week 16
    Comparison groups
    Secukinumab, Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    354
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001 [35]
    Method
    		 ANCOVA
    Parameter type
    		 ANCOVA
    Confidence interval
    Notes
    [35] - unadjusted p-value
    Statistical analysis title
    		 Secukinumab No Load v Placebo
    Statistical analysis description
    week 16
    Comparison groups
    Secukinumab, No Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    351
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001 [36]
    Method
    		 ANCOVA
    Parameter type
    		 ANCOVA
    Confidence interval
    Notes
    [36] - unadjusted p-value

    Secondary: Change in Sacroiliac Joint Edema - week 52

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    End point title
    		 Change in Sacroiliac Joint Edema - week 52
    End point description
    Magnetic Resonance Images (MRI) of the Sacroiliac Joint (SIJ) were assessed for the presence and severity of SIJ bone marrow edema according to the Berlin Active Inflammatory Lesions Scoring with a maximum score of 24.
    End point type
    Secondary
    End point timeframe
    Week 52
    End point values
    		 Secukinumab, Load, Core Phase Secukinumab, No Load, Core Phase Placebo, Core Phase
    Number of subjects analysed
    81
    87
    53
    Units: Scores on a scale
        arithmetic mean (standard deviation)
    -2.9 ± 4.54
    -1.9 ± 3.40
    -0.1 ± 1.97
    Statistical analysis title
    		 Secukinumab Load v Placebo
    Comparison groups
    Secukinumab, Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    134
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001 [37]
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [37] - Unadjusted p-value. The endpoint was analyzed by composite estimand strategy. Extreme unfavorable value is assigned for patients with treatment escape or missing data.
    Statistical analysis title
    		 Secukinumab No Load v Placebo
    Comparison groups
    Secukinumab, No Load, Core Phase v Placebo, Core Phase
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001 [38]
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [38] - Unadjusted p-value. The endpoint was analyzed by composite estimand strategy. Extreme unfavorable value is assigned for patients with treatment escape or missing data.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events are reported from first dose of study treatment until end of study treatment plus 12 wks post-treatment, up to a maximum timeframe of 1520 days (approx. 4.2 years).
    Adverse event reporting additional description
    Safety results summarize long term data for all patients for the entire period of their study participation, which, for the majority of pts, combines the core phase and the extension phase (not all pts participated in the extension). The table is presented by dose group, AIN457 150 mg and AIN457 300 mg and placebo.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    Any AIN457 150 mg, in Core Phase and Extension Phase
    Reporting group description
    		 Includes patients originally randomized to AIN457 150 mg (Load and No Load) at baseline and placebo patients switched to AIN457 150 mg before or at W52 (AEs occuring after the switch) who either were re-randomized (Core Phase Responders) to AIN457 150 mg at W104 or did not participate in the Extension Phase.

    Reporting group title
    Any AIN457 300 mg in Extension Phase
    Reporting group description
    		 Includes patients re-randomized (Core Phase Responders) or re-assigned (Core Phase Non-Responders) to AIN457 300 mg at W104 (Extension Phase) and patients re-randomized (Core Phase Responders) to AIN457 150 mg at W104 who up-titrated to AIN457 300 mg (only AEs occurring after up-titration).

    Reporting group title
    Any AIN457, In Core Phase and Extension Phase
    Reporting group description
    		 Includes patients randomized or switched (AEs occuring after the switch) to AIN457 150 mg (Load and No Load) who either were re-randomized (Core Phase Responders) to AIN457 150 mg or AIN457 300 mg at W104 or did not participate in the Extension Phase.

    Reporting group title
    Placebo, Core Phase
    Reporting group description
    		 Includes patients originally randomized to Placebo (AEs until the time of a switch to AIN457 150 mg)

    Serious adverse events
    		 Any AIN457 150 mg, in Core Phase and Extension Phase Any AIN457 300 mg in Extension Phase Any AIN457, In Core Phase and Extension Phase Placebo, Core Phase
    Total subjects affected by serious adverse events
         subjects affected / exposed
    48 / 543 (8.84%)
    11 / 254 (4.33%)
    58 / 543 (10.68%)
    8 / 186 (4.30%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acrochordon
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fibroadenoma of breast
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    0 / 543 (0.00%)
    1 / 254 (0.39%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal adenocarcinoma
         subjects affected / exposed
    0 / 543 (0.00%)
    1 / 254 (0.39%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Arteriosclerosis
         subjects affected / exposed
    0 / 543 (0.00%)
    0 / 254 (0.00%)
    0 / 543 (0.00%)
    1 / 186 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic aneurysm
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 543 (0.00%)
    0 / 254 (0.00%)
    0 / 543 (0.00%)
    1 / 186 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Bartholin's cyst
         subjects affected / exposed
    0 / 543 (0.00%)
    0 / 254 (0.00%)
    0 / 543 (0.00%)
    1 / 186 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervix enlargement
         subjects affected / exposed
    0 / 543 (0.00%)
    0 / 254 (0.00%)
    0 / 543 (0.00%)
    1 / 186 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endometrial disorder
         subjects affected / exposed
    0 / 543 (0.00%)
    0 / 254 (0.00%)
    0 / 543 (0.00%)
    1 / 186 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian cyst
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vaginal prolapse
         subjects affected / exposed
    0 / 543 (0.00%)
    0 / 254 (0.00%)
    0 / 543 (0.00%)
    1 / 186 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Varicocele
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pneumomediastinum
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nasal septum deviation
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Substance-induced mood disorder
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Arthroscopy
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Brain contusion
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clavicle fracture
         subjects affected / exposed
    0 / 543 (0.00%)
    0 / 254 (0.00%)
    0 / 543 (0.00%)
    1 / 186 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin laceration
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendon injury
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    1 / 543 (0.18%)
    1 / 254 (0.39%)
    2 / 543 (0.37%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    0 / 543 (0.00%)
    0 / 254 (0.00%)
    0 / 543 (0.00%)
    1 / 186 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 543 (0.00%)
    0 / 254 (0.00%)
    0 / 543 (0.00%)
    1 / 186 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic valve incompetence
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Myelopathy
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal claudication
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Iridocyclitis
         subjects affected / exposed
    1 / 543 (0.18%)
    1 / 254 (0.39%)
    2 / 543 (0.37%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Appendiceal mucocoele
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis ulcerative
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Crohn's disease
         subjects affected / exposed
    2 / 543 (0.37%)
    1 / 254 (0.39%)
    3 / 543 (0.55%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 1
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 543 (0.00%)
    1 / 254 (0.39%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal fistula
         subjects affected / exposed
    0 / 543 (0.00%)
    1 / 254 (0.39%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatitis acute
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Biliary colic
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug-induced liver injury
         subjects affected / exposed
    0 / 543 (0.00%)
    1 / 254 (0.39%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Skin disorder
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    IgA nephropathy
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Calculus urinary
         subjects affected / exposed
    0 / 543 (0.00%)
    1 / 254 (0.39%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 543 (0.00%)
    0 / 254 (0.00%)
    0 / 543 (0.00%)
    1 / 186 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    3 / 543 (0.55%)
    0 / 254 (0.00%)
    3 / 543 (0.55%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Back disorder
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    1 / 186 (0.54%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc disorder
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Synovitis
         subjects affected / exposed
    1 / 543 (0.18%)
    1 / 254 (0.39%)
    2 / 543 (0.37%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Anal abscess
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eczema infected
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epiglottitis
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 543 (0.18%)
    1 / 254 (0.39%)
    2 / 543 (0.37%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    3 / 543 (0.55%)
    0 / 254 (0.00%)
    3 / 543 (0.55%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vaccination site cellulitis
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral tracheitis
         subjects affected / exposed
    0 / 543 (0.00%)
    0 / 254 (0.00%)
    0 / 543 (0.00%)
    1 / 186 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atypical pneumonia
         subjects affected / exposed
    0 / 543 (0.00%)
    1 / 254 (0.39%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonsillar abscess
         subjects affected / exposed
    0 / 543 (0.00%)
    1 / 254 (0.39%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis streptococcal
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 543 (0.00%)
    1 / 254 (0.39%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    1 / 543 (0.18%)
    0 / 254 (0.00%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Electrolyte imbalance
         subjects affected / exposed
    0 / 543 (0.00%)
    1 / 254 (0.39%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 543 (0.00%)
    1 / 254 (0.39%)
    1 / 543 (0.18%)
    0 / 186 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Any AIN457 150 mg, in Core Phase and Extension Phase Any AIN457 300 mg in Extension Phase Any AIN457, In Core Phase and Extension Phase Placebo, Core Phase
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    320 / 543 (58.93%)
    74 / 254 (29.13%)
    335 / 543 (61.69%)
    67 / 186 (36.02%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    29 / 543 (5.34%)
    5 / 254 (1.97%)
    34 / 543 (6.26%)
    3 / 186 (1.61%)
         occurrences all number
    31
    5
    36
    4
    Nervous system disorders
    Headache
         subjects affected / exposed
    61 / 543 (11.23%)
    7 / 254 (2.76%)
    65 / 543 (11.97%)
    9 / 186 (4.84%)
         occurrences all number
    76
    11
    87
    11
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    55 / 543 (10.13%)
    6 / 254 (2.36%)
    61 / 543 (11.23%)
    10 / 186 (5.38%)
         occurrences all number
    71
    6
    77
    11
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    43 / 543 (7.92%)
    6 / 254 (2.36%)
    48 / 543 (8.84%)
    9 / 186 (4.84%)
         occurrences all number
    57
    6
    63
    10
    Back pain
         subjects affected / exposed
    36 / 543 (6.63%)
    3 / 254 (1.18%)
    38 / 543 (7.00%)
    3 / 186 (1.61%)
         occurrences all number
    42
    3
    45
    4
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    23 / 543 (4.24%)
    6 / 254 (2.36%)
    28 / 543 (5.16%)
    2 / 186 (1.08%)
         occurrences all number
    27
    6
    33
    2
    Nasopharyngitis
         subjects affected / exposed
    137 / 543 (25.23%)
    33 / 254 (12.99%)
    146 / 543 (26.89%)
    32 / 186 (17.20%)
         occurrences all number
    239
    42
    281
    48
    Sinusitis
         subjects affected / exposed
    30 / 543 (5.52%)
    5 / 254 (1.97%)
    34 / 543 (6.26%)
    3 / 186 (1.61%)
         occurrences all number
    39
    5
    44
    3
    Upper respiratory tract infection
         subjects affected / exposed
    65 / 543 (11.97%)
    16 / 254 (6.30%)
    77 / 543 (14.18%)
    13 / 186 (6.99%)
         occurrences all number
    109
    18
    127
    13
    Urinary tract infection
         subjects affected / exposed
    38 / 543 (7.00%)
    9 / 254 (3.54%)
    42 / 543 (7.73%)
    4 / 186 (2.15%)
         occurrences all number
    49
    14
    63
    4
    Pharyngitis
         subjects affected / exposed
    27 / 543 (4.97%)
    5 / 254 (1.97%)
    31 / 543 (5.71%)
    1 / 186 (0.54%)
         occurrences all number
    32
    5
    37
    1

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    28 Nov 2016
    The powering of the study was re-evaluated, triggering a changed order in the testing hierarchy as well as adjustments of the population for the primary endpoint to TNFi-naïve patients only. After feedback from the FDA, changes were made to Analysis Plan B to focus on the no-load dosing regimen. The test for HLA-B27 was moved from the baseline visit to Screening Visit 2 to facilitate the screening process for the sites. The maximally allowed proportion of TNF-IR patients was changed from 30% to 20%. Historic MRIs were accepted, if taken within 3 months of baseline and in alignment of the imaging criteria to facilitate the re-screening process for patients and sites. The wording in the SAE reporting section was updated to be aligned with current and future SAE reporting processes. A decision was taken to replace the eSource system and collect the data for the study in OC/RDC in all countries.
    11 Jul 2018
    Addition of an extension phase to the current core protocol. The order of the secondary endpoints of the Analysis Plan B in the hierarchy was updated to elevate several Load regimen endpoints to reflect their clinical relevance. Addition of group-sequential testing for the Week 24 interim analysis of the Week 52 time points (Analysis Plan B). The wording for the Withdrawal of Consent section was updated to align with the European Economic Area (EEA) General Data Protection Regulation (GDPR) requirements.

    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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