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    Clinical Trial Results:
    A randomized, double-blind, placebo-controlled, multicenter study of secukinumab to demonstrate the efficacy at 16 weeks and to assess the long term safety, tolerability and efficacy up to 2 years in patients with active ankylosing spondylitis

    Summary
    EudraCT number
    		 2010-024529-18
    Trial protocol
    		 GB   DE   BE   BG   IT  
    Global end of trial date
    18 Dec 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    09 Jul 2016
    First version publication date
    09 Jul 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CAIN457F2305
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01358175
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    CH-4002, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharmaceuticals, 41 613241111,
    Scientific contact
    Clinical Disclosure Office, Novartis Pharmaceuticals, 41 613241111,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    18 Dec 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Dec 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective was to demonstrate that the efficacy of at least one dose of secukinumab at Week 16 is superior to placebo in patients with active AS based on the proportion of patients achieving an ASAS 20 (Assessment of Spondyloarthritis International Society) 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
    19 Oct 2011
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Peru: 37
    Country: Number of subjects enrolled
    Russian Federation: 70
    Country: Number of subjects enrolled
    Taiwan: 57
    Country: Number of subjects enrolled
    Turkey: 4
    Country: Number of subjects enrolled
    United States: 23
    Country: Number of subjects enrolled
    United Kingdom: 23
    Country: Number of subjects enrolled
    Belgium: 19
    Country: Number of subjects enrolled
    Bulgaria: 28
    Country: Number of subjects enrolled
    Canada: 5
    Country: Number of subjects enrolled
    France: 13
    Country: Number of subjects enrolled
    Germany: 28
    Country: Number of subjects enrolled
    Italy: 12
    Country: Number of subjects enrolled
    Mexico: 40
    Country: Number of subjects enrolled
    Netherlands: 12
    Worldwide total number of subjects
    371
    EEA total number of subjects
    135
    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)
    354
    From 65 to 84 years
    17
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A screening (SCR) period running 4 weeks before randomization was used to assess eligibility, followed by a treatment period of 2 years.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer, Assessor
    Blinding implementation details
    monitor/sponsor up to week 52

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Secukinumab 10 mg/kg i.v. / 75 mg s.c.
    Arm description
    		 Three i.v. infusions: at Baseline and Weeks 2 and 4, followed by one S.C. injection every four weeks until the end of the study.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Secukinumab
    Investigational medicinal product code
    AIN457
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Secukinumab (75 mg)

    Arm title
    		 Secukinumab 10 mg/kg i.v. / 150 mg s.c.
    Arm description
    		 Three i.v. infusions: at Baseline and Weeks 2 and 4, followed by one S.C. injection every four weeks until the end of the study.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Secukinumab
    Investigational medicinal product code
    AIN457
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Secukinumab (150 mg)

    Arm title
    		 Placebo
    Arm description
    		 Placebo iv at Baseline, Week 2 and Week 4, and then Placebo S.C. at Week 8 and Week 12
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Placebo

    Number of subjects in period 1
    		Secukinumab 10 mg/kg i.v. / 75 mg s.c. Secukinumab 10 mg/kg i.v. / 150 mg s.c. Placebo
    Started
    124
    125
    122
    Completed
    103
    97
    90
    Not completed
    21
    28
    32
         Adverse event, serious fatal
    1
    -
    1
         Consent withdrawn by subject
    9
    5
    10
         Physician decision
    1
    -
    -
         Adverse event, non-fatal
    6
    11
    11
         Pregnancy
    -
    1
    -
         Non Compliance with Study Treatment
    -
    1
    1
         Lost to follow-up
    1
    1
    3
         Technical issues
    -
    1
    -
         Lack of efficacy
    3
    8
    6

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Secukinumab 10 mg/kg i.v. / 75 mg s.c.
    Reporting group description
    		 Three i.v. infusions: at Baseline and Weeks 2 and 4, followed by one S.C. injection every four weeks until the end of the study.

    Reporting group title
    Secukinumab 10 mg/kg i.v. / 150 mg s.c.
    Reporting group description
    		 Three i.v. infusions: at Baseline and Weeks 2 and 4, followed by one S.C. injection every four weeks until the end of the study.

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo iv at Baseline, Week 2 and Week 4, and then Placebo S.C. at Week 8 and Week 12

    Reporting group values
    		 Secukinumab 10 mg/kg i.v. / 75 mg s.c. Secukinumab 10 mg/kg i.v. / 150 mg s.c. Placebo Total
    Number of subjects
    		 124 125 122 371
    Age Categorical
    Units: participants
        <=18 years
    		 0 0 0 0
        Between 18 and 65 years
    		 117 122 115 354
        >=65 years
    		 7 3 7 17
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 42.3 ± 13.24 40.1 ± 11.61 43.1 ± 12.44 -
    Gender, Male/Female
    Units: participants
        Female
    		 36 41 37 114
        Male
    		 88 84 85 257

    End points

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    End points reporting groups
    Reporting group title
    Secukinumab 10 mg/kg i.v. / 75 mg s.c.
    Reporting group description
    		 Three i.v. infusions: at Baseline and Weeks 2 and 4, followed by one S.C. injection every four weeks until the end of the study.

    Reporting group title
    Secukinumab 10 mg/kg i.v. / 150 mg s.c.
    Reporting group description
    		 Three i.v. infusions: at Baseline and Weeks 2 and 4, followed by one S.C. injection every four weeks until the end of the study.

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo iv at Baseline, Week 2 and Week 4, and then Placebo S.C. at Week 8 and Week 12

    Primary: Assessment of responders for the SpondyloArthritis International Society / ASAS 20 response

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    End point title
    		 Assessment of responders for the SpondyloArthritis International Society / ASAS 20 response
    End point description
    ASAS 20 response is a validated composite assessment, reflecting the proportion of treated patients who achieve within a defined timeframe at least 20% improvement in score in at least 3 of a conventional set of 4 clinical domains relevent to AS and no worsening in the fourth domain. ASAS 20 is used to assess the efficacy of at least one dose of secukinumab against placebo.
    End point type
    Primary
    End point timeframe
    16 weeks
    End point values
    		 Secukinumab 10 mg/kg i.v. / 75 mg s.c. Secukinumab 10 mg/kg i.v. / 150 mg s.c. Placebo
    Number of subjects analysed
    124
    125
    122
    Units: % responders
        number (not applicable)
    59.7
    60.8
    28.7
    Statistical analysis title
    		 Assessment of Responders
    Comparison groups
    Secukinumab 10 mg/kg i.v. / 75 mg s.c. v Placebo
    Number of subjects included in analysis
    246
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.2
         upper limit
    		 6.42
    Statistical analysis title
    		 Assessment of Responders
    Comparison groups
    Secukinumab 10 mg/kg i.v. / 150 mg s.c. v Placebo
    Number of subjects included in analysis
    247
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.28
         upper limit
    		 6.65

    Secondary: Assessment of responders for the SpondyloArthritis International Society ASAS 40 response

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    End point title
    		 Assessment of responders for the SpondyloArthritis International Society ASAS 40 response
    End point description
    ASAS 40 response is a validated composite assessment, reflecting the proportion of treated patients who achieve within a defined timeframe at least 40% improvement in score in at least 3 of a conventional set of 4 clinical domains relevent to AS and no worsening in the fourth domain. ASAS 40 is used to assess the efficacy of at least one dose of secukinumab against placebo.
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    		 Secukinumab 10 mg/kg i.v. / 75 mg s.c. Secukinumab 10 mg/kg i.v. / 150 mg s.c. Placebo
    Number of subjects analysed
    124
    125
    122
    Units: % responders
        number (not applicable)
    33.1
    41.6
    13.1
    No statistical analyses for this end point

    Secondary: Change from baseline in Serum hsCRP

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    End point title
    		 Change from baseline in Serum hsCRP
    End point description
    The change from baseline in hsCRP is expressed as a ratio of post-baseline to baseline values. With the ratio normalized to 1.0 at baseline, ratios less than 1.0 represent decreased post-baseline values, whereas ratios greater than 1.0 represent increased post-baseline values.
    End point type
    Secondary
    End point timeframe
    Week 16
    End point values
    		 Secukinumab 10 mg/kg i.v. / 75 mg s.c. Secukinumab 10 mg/kg i.v. / 150 mg s.c. Placebo
    Number of subjects analysed
    124
    125
    122
    Units: ratio
        least squares mean (standard error)
    0.45 ± 1.092
    0.4 ± 1.09
    0.97 ± 1.095
    No statistical analyses for this end point

    Secondary: Assessment of responders for the SpondyloArthritis International Society ASAS 5/6 response

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    End point title
    		 Assessment of responders for the SpondyloArthritis International Society ASAS 5/6 response
    End point description
    ASAS 5/6 response is a validated composite assessment, reflecting the proportion of treated patients who achieve within a defined timeframe at least 20% improvement in score in at least 5 of a conventional set of 6 clinical domains relevent to AS and no worsening in the remaining domain. In this study, ASAS 5/6 is used to assess the efficacy of at least one dose of secukinumab against placebo.
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    		 Secukinumab 10 mg/kg i.v. / 75 mg s.c. Secukinumab 10 mg/kg i.v. / 150 mg s.c. Placebo
    Number of subjects analysed
    124
    125
    122
    Units: % change from baseline
        number (not applicable)
    45.2
    48.8
    13.1
    No statistical analyses for this end point

    Secondary: Change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index / BASDAI

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    End point title
    		 Change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index / BASDAI
    End point description
    BASDAI is a validated assessment tool using 0 through 10 scales (0 indicating "no problem" and 10 indicating " worst problem"), to characterize six clinical domains pertaining to five major symptoms of AS perceived by the patients. Computed composite scores of 4 or greater indicate suboptimal disease control. In this study, the BASDAI is used to assess the efficacy of at least one dose of secukinumab verus placebo.
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    		 Secukinumab 10 mg/kg i.v. / 75 mg s.c. Secukinumab 10 mg/kg i.v. / 150 mg s.c. Placebo
    Number of subjects analysed
    124
    125
    122
    Units: units on scale
        number (not applicable)
    -2.34
    -2.32
    -0.59
    No statistical analyses for this end point

    Secondary: Change from baseline in Physical function component of the short-form health survey / SF-36 PCS

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    End point title
    		 Change from baseline in Physical function component of the short-form health survey / SF-36 PCS
    End point description
    SF-36 is a 36 item questionnaire which measures Quality of Life across eight domains, which are both phyically and emotionally based. Two overall summary scores, the Phyical Component Summary (PCS) and Mental Component Summary (MCS) can be computed. In this study, SF-36 PCS is used to assess improvement from baseline of at least one dose of secukinumab versus placebo.
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    		 Secukinumab 10 mg/kg i.v. / 75 mg s.c. Secukinumab 10 mg/kg i.v. / 150 mg s.c. Placebo
    Number of subjects analysed
    124
    125
    122
    Units: units on a scale
        number (not applicable)
    5.64
    5.57
    0.96
    No statistical analyses for this end point

    Secondary: Change from Baseline in Ankylosing Spondylitis Quality of Life questionnaire / ASQoL

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    End point title
    		 Change from Baseline in Ankylosing Spondylitis Quality of Life questionnaire / ASQoL
    End point description
    ASQoL is an 18 item questionnaire that assesses disease-specific quality of life (QoL), consisting of statements that are relevant to the physical and mental conditions for a participant with AS: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each statement is answered by the participant as a 'Yes' (scored as 1) or 'No' (scored as 0). All item scores are summed to give a total score. Total score can range from 0 (good QoL) to 18 (poor QoL). In this study, ASQoL is used to assess improvement from baseline of at least one dose of secukinumab versus placebo.
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    		 Secukinumab 10 mg/kg i.v. / 75 mg s.c. Secukinumab 10 mg/kg i.v. / 150 mg s.c. Placebo
    Number of subjects analysed
    124
    125
    122
    Units: units on a scale
        number (not applicable)
    -3.61
    -3.58
    -1.04
    No statistical analyses for this end point

    Secondary: Assessment of responders for ASAS partial remission

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    End point title
    		 Assessment of responders for ASAS partial remission
    End point description
    ASAS partial remission is a composite assessment, reflecting the proportion of treated patients who achieve within a defined time frame a value not above 2 units in each of the 4 ASAS domains on a scale of 10. In this study ASAS partial remission is used to assess the efficacy of at least one dose of secukinumab versus placebo.
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    		 Secukinumab 10 mg/kg i.v. / 75 mg s.c. Secukinumab 10 mg/kg i.v. / 150 mg s.c. Placebo
    Number of subjects analysed
    124
    125
    122
    Units: % responders
        number (not applicable)
    16.1
    15.2
    3.3
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit
    Adverse event reporting additional description
    Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.0
    Reporting groups
    Reporting group title
    AIN457 75 mg
    Reporting group description
    		 AIN457 75 mg

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

    Reporting group title
    Any AIN457
    Reporting group description
    		 Any AIN457

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo

    Serious adverse events
    		 AIN457 75 mg AIN457 150 mg Any AIN457 Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    24 / 179 (13.41%)
    22 / 181 (12.15%)
    46 / 360 (12.78%)
    5 / 122 (4.10%)
         number of deaths (all causes)
    1
    0
    1
    1
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    B-cell lymphoma
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Bladder transitional cell carcinoma
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 181 (0.55%)
    1 / 360 (0.28%)
    0 / 122 (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
    Breast cancer
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 181 (0.55%)
    1 / 360 (0.28%)
    0 / 122 (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
    Lymphoma
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 181 (0.00%)
    0 / 360 (0.00%)
    1 / 122 (0.82%)
         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
    Vascular disorders
    Peripheral venous disease
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Varicose vein
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 181 (0.55%)
    1 / 360 (0.28%)
    0 / 122 (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
    Pregnancy, puerperium and perinatal conditions
    Abortion incomplete
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 181 (0.55%)
    1 / 360 (0.28%)
    0 / 122 (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
    General disorders and administration site conditions
    Adverse drug reaction
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 181 (0.00%)
    0 / 360 (0.00%)
    1 / 122 (0.82%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Application site pain
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Chest discomfort
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Pyrexia
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    Asthma
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Dyspnoea
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Pulmonary fibrosis
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 179 (0.56%)
    1 / 181 (0.55%)
    2 / 360 (0.56%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    Psychiatric disorders
    Completed suicide
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 181 (0.00%)
    0 / 360 (0.00%)
    1 / 122 (0.82%)
         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 / 1
    Depression
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 181 (0.00%)
    0 / 360 (0.00%)
    1 / 122 (0.82%)
         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 / 1
    Injury, poisoning and procedural complications
    Cartilage injury
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Cervical vertebral fracture
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Craniocerebral injury
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Dislocation of vertebra
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 181 (0.55%)
    1 / 360 (0.28%)
    0 / 122 (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
    Laceration
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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 limb fracture
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 181 (0.55%)
    1 / 360 (0.28%)
    0 / 122 (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
    Postoperative thrombosis
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 181 (0.55%)
    1 / 360 (0.28%)
    0 / 122 (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
    Rib fracture
         subjects affected / exposed
    0 / 179 (0.00%)
    2 / 181 (1.10%)
    2 / 360 (0.56%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 181 (0.55%)
    1 / 360 (0.28%)
    0 / 122 (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
    Thoracic vertebral fracture
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Tibia fracture
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 181 (0.55%)
    1 / 360 (0.28%)
    0 / 122 (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
    Upper limb fracture
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Myocardial infarction
         subjects affected / exposed
    2 / 179 (1.12%)
    2 / 181 (1.10%)
    4 / 360 (1.11%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Brain oedema
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 181 (0.55%)
    1 / 360 (0.28%)
    0 / 122 (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
    Generalised tonic-clonic seizure
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 181 (0.55%)
    1 / 360 (0.28%)
    0 / 122 (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
    Hemiparesis
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 181 (0.55%)
    1 / 360 (0.28%)
    0 / 122 (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
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 181 (0.55%)
    1 / 360 (0.28%)
    0 / 122 (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
    Subarachnoid haemorrhage
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Trigeminal neuralgia
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Vocal cord paresis
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 181 (0.00%)
    0 / 360 (0.00%)
    1 / 122 (0.82%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Abdominal lymphadenopathy
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Anaemia
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 181 (0.00%)
    0 / 360 (0.00%)
    1 / 122 (0.82%)
         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
    Pancytopenia
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Ear and labyrinth disorders
    Sudden hearing loss
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Vertigo
         subjects affected / exposed
    0 / 179 (0.00%)
    0 / 181 (0.00%)
    0 / 360 (0.00%)
    1 / 122 (0.82%)
         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
    Eye disorders
    Cataract
         subjects affected / exposed
    1 / 179 (0.56%)
    1 / 181 (0.55%)
    2 / 360 (0.56%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uveitis
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 181 (0.55%)
    1 / 360 (0.28%)
    0 / 122 (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
    Gastrointestinal disorders
    Colitis
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Diarrhoea
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Epigastric discomfort
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Gastritis
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 181 (0.55%)
    1 / 360 (0.28%)
    0 / 122 (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
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 181 (0.55%)
    1 / 360 (0.28%)
    0 / 122 (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
    Hiatus hernia
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Lumbar hernia
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Pancreatitis
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 181 (0.55%)
    1 / 360 (0.28%)
    0 / 122 (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
    Pancreatitis acute
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 181 (0.55%)
    1 / 360 (0.28%)
    0 / 122 (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
    Small intestinal obstruction
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 181 (0.55%)
    1 / 360 (0.28%)
    0 / 122 (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
    Cholelithiasis
         subjects affected / exposed
    2 / 179 (1.12%)
    0 / 181 (0.00%)
    2 / 360 (0.56%)
    0 / 122 (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
    Hepatitis toxic
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 181 (0.55%)
    1 / 360 (0.28%)
    0 / 122 (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
    Hepatosplenomegaly
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Renal and urinary disorders
    Renal colic
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 181 (0.55%)
    1 / 360 (0.28%)
    0 / 122 (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
    Endocrine disorders
    Hyperparathyroidism
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Musculoskeletal and connective tissue disorders
    Ankylosing spondylitis
         subjects affected / exposed
    0 / 179 (0.00%)
    3 / 181 (1.66%)
    3 / 360 (0.83%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 181 (0.55%)
    1 / 360 (0.28%)
    0 / 122 (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
    Rotator cuff syndrome
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Helicobacter gastritis
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (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
    Pneumonia
         subjects affected / exposed
    1 / 179 (0.56%)
    0 / 181 (0.00%)
    1 / 360 (0.28%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 179 (0.00%)
    1 / 181 (0.55%)
    1 / 360 (0.28%)
    0 / 122 (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
    Tonsillitis
         subjects affected / exposed
    0 / 179 (0.00%)
    2 / 181 (1.10%)
    2 / 360 (0.56%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 AIN457 75 mg AIN457 150 mg Any AIN457 Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    125 / 179 (69.83%)
    142 / 181 (78.45%)
    267 / 360 (74.17%)
    56 / 122 (45.90%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    8 / 179 (4.47%)
    6 / 181 (3.31%)
    14 / 360 (3.89%)
    0 / 122 (0.00%)
         occurrences all number
    9
    6
    15
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    6 / 179 (3.35%)
    5 / 181 (2.76%)
    11 / 360 (3.06%)
    2 / 122 (1.64%)
         occurrences all number
    7
    6
    13
    2
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 179 (0.00%)
    4 / 181 (2.21%)
    4 / 360 (1.11%)
    0 / 122 (0.00%)
         occurrences all number
    0
    6
    6
    0
    Pyrexia
         subjects affected / exposed
    0 / 179 (0.00%)
    5 / 181 (2.76%)
    5 / 360 (1.39%)
    2 / 122 (1.64%)
         occurrences all number
    0
    8
    8
    2
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    9 / 179 (5.03%)
    10 / 181 (5.52%)
    19 / 360 (5.28%)
    2 / 122 (1.64%)
         occurrences all number
    11
    13
    24
    2
    Dyspnoea
         subjects affected / exposed
    4 / 179 (2.23%)
    1 / 181 (0.55%)
    5 / 360 (1.39%)
    1 / 122 (0.82%)
         occurrences all number
    4
    4
    8
    1
    Nasal congestion
         subjects affected / exposed
    4 / 179 (2.23%)
    2 / 181 (1.10%)
    6 / 360 (1.67%)
    1 / 122 (0.82%)
         occurrences all number
    4
    2
    6
    1
    Rhinorrhoea
         subjects affected / exposed
    4 / 179 (2.23%)
    3 / 181 (1.66%)
    7 / 360 (1.94%)
    0 / 122 (0.00%)
         occurrences all number
    4
    3
    7
    0
    Oropharyngeal pain
         subjects affected / exposed
    13 / 179 (7.26%)
    16 / 181 (8.84%)
    29 / 360 (8.06%)
    6 / 122 (4.92%)
         occurrences all number
    23
    23
    46
    6
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    5 / 179 (2.79%)
    0 / 181 (0.00%)
    5 / 360 (1.39%)
    0 / 122 (0.00%)
         occurrences all number
    5
    0
    5
    0
    Insomnia
         subjects affected / exposed
    4 / 179 (2.23%)
    6 / 181 (3.31%)
    10 / 360 (2.78%)
    2 / 122 (1.64%)
         occurrences all number
    7
    7
    14
    2
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    3 / 179 (1.68%)
    6 / 181 (3.31%)
    9 / 360 (2.50%)
    1 / 122 (0.82%)
         occurrences all number
    3
    6
    9
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 179 (0.56%)
    4 / 181 (2.21%)
    5 / 360 (1.39%)
    1 / 122 (0.82%)
         occurrences all number
    1
    4
    5
    1
    Low density lipoprotein increased
         subjects affected / exposed
    1 / 179 (0.56%)
    5 / 181 (2.76%)
    6 / 360 (1.67%)
    1 / 122 (0.82%)
         occurrences all number
    1
    6
    7
    1
    Osteoprotegerin decreased
         subjects affected / exposed
    2 / 179 (1.12%)
    6 / 181 (3.31%)
    8 / 360 (2.22%)
    2 / 122 (1.64%)
         occurrences all number
    2
    6
    8
    2
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    5 / 179 (2.79%)
    4 / 181 (2.21%)
    9 / 360 (2.50%)
    0 / 122 (0.00%)
         occurrences all number
    5
    4
    9
    0
    Laceration
         subjects affected / exposed
    4 / 179 (2.23%)
    1 / 181 (0.55%)
    5 / 360 (1.39%)
    1 / 122 (0.82%)
         occurrences all number
    6
    2
    8
    1
    Wound
         subjects affected / exposed
    4 / 179 (2.23%)
    6 / 181 (3.31%)
    10 / 360 (2.78%)
    0 / 122 (0.00%)
         occurrences all number
    4
    7
    11
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    6 / 179 (3.35%)
    8 / 181 (4.42%)
    14 / 360 (3.89%)
    4 / 122 (3.28%)
         occurrences all number
    8
    8
    16
    4
    Headache
         subjects affected / exposed
    20 / 179 (11.17%)
    22 / 181 (12.15%)
    42 / 360 (11.67%)
    7 / 122 (5.74%)
         occurrences all number
    25
    40
    65
    12
    Paraesthesia
         subjects affected / exposed
    3 / 179 (1.68%)
    7 / 181 (3.87%)
    10 / 360 (2.78%)
    0 / 122 (0.00%)
         occurrences all number
    4
    7
    11
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    4 / 179 (2.23%)
    4 / 181 (2.21%)
    8 / 360 (2.22%)
    0 / 122 (0.00%)
         occurrences all number
    4
    6
    10
    0
    Leukopenia
         subjects affected / exposed
    12 / 179 (6.70%)
    8 / 181 (4.42%)
    20 / 360 (5.56%)
    1 / 122 (0.82%)
         occurrences all number
    15
    10
    25
    1
    Lymphadenopathy
         subjects affected / exposed
    6 / 179 (3.35%)
    3 / 181 (1.66%)
    9 / 360 (2.50%)
    0 / 122 (0.00%)
         occurrences all number
    6
    4
    10
    0
    Neutropenia
         subjects affected / exposed
    5 / 179 (2.79%)
    3 / 181 (1.66%)
    8 / 360 (2.22%)
    0 / 122 (0.00%)
         occurrences all number
    6
    3
    9
    0
    Eye disorders
    Uveitis
         subjects affected / exposed
    4 / 179 (2.23%)
    7 / 181 (3.87%)
    11 / 360 (3.06%)
    2 / 122 (1.64%)
         occurrences all number
    4
    8
    12
    2
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    3 / 179 (1.68%)
    9 / 181 (4.97%)
    12 / 360 (3.33%)
    0 / 122 (0.00%)
         occurrences all number
    3
    9
    12
    0
    Abdominal pain upper
         subjects affected / exposed
    9 / 179 (5.03%)
    8 / 181 (4.42%)
    17 / 360 (4.72%)
    0 / 122 (0.00%)
         occurrences all number
    9
    8
    17
    0
    Constipation
         subjects affected / exposed
    4 / 179 (2.23%)
    4 / 181 (2.21%)
    8 / 360 (2.22%)
    2 / 122 (1.64%)
         occurrences all number
    5
    5
    10
    2
    Diarrhoea
         subjects affected / exposed
    22 / 179 (12.29%)
    25 / 181 (13.81%)
    47 / 360 (13.06%)
    7 / 122 (5.74%)
         occurrences all number
    29
    34
    63
    7
    Crohn's disease
         subjects affected / exposed
    4 / 179 (2.23%)
    1 / 181 (0.55%)
    5 / 360 (1.39%)
    0 / 122 (0.00%)
         occurrences all number
    6
    1
    7
    0
    Mouth ulceration
         subjects affected / exposed
    9 / 179 (5.03%)
    7 / 181 (3.87%)
    16 / 360 (4.44%)
    3 / 122 (2.46%)
         occurrences all number
    14
    11
    25
    4
    Nausea
         subjects affected / exposed
    9 / 179 (5.03%)
    10 / 181 (5.52%)
    19 / 360 (5.28%)
    2 / 122 (1.64%)
         occurrences all number
    11
    12
    23
    2
    Tongue ulceration
         subjects affected / exposed
    1 / 179 (0.56%)
    4 / 181 (2.21%)
    5 / 360 (1.39%)
    0 / 122 (0.00%)
         occurrences all number
    1
    6
    7
    0
    Skin and subcutaneous tissue disorders
    Dermatitis
         subjects affected / exposed
    0 / 179 (0.00%)
    6 / 181 (3.31%)
    6 / 360 (1.67%)
    0 / 122 (0.00%)
         occurrences all number
    0
    7
    7
    0
    Pruritus
         subjects affected / exposed
    3 / 179 (1.68%)
    7 / 181 (3.87%)
    10 / 360 (2.78%)
    1 / 122 (0.82%)
         occurrences all number
    3
    8
    11
    1
    Rash
         subjects affected / exposed
    2 / 179 (1.12%)
    7 / 181 (3.87%)
    9 / 360 (2.50%)
    0 / 122 (0.00%)
         occurrences all number
    2
    7
    9
    0
    Urticaria
         subjects affected / exposed
    1 / 179 (0.56%)
    4 / 181 (2.21%)
    5 / 360 (1.39%)
    0 / 122 (0.00%)
         occurrences all number
    1
    4
    5
    0
    Musculoskeletal and connective tissue disorders
    Ankylosing spondylitis
         subjects affected / exposed
    4 / 179 (2.23%)
    7 / 181 (3.87%)
    11 / 360 (3.06%)
    4 / 122 (3.28%)
         occurrences all number
    4
    9
    13
    5
    Arthralgia
         subjects affected / exposed
    11 / 179 (6.15%)
    13 / 181 (7.18%)
    24 / 360 (6.67%)
    4 / 122 (3.28%)
         occurrences all number
    18
    15
    33
    5
    Back pain
         subjects affected / exposed
    7 / 179 (3.91%)
    12 / 181 (6.63%)
    19 / 360 (5.28%)
    0 / 122 (0.00%)
         occurrences all number
    8
    13
    21
    0
    Muscle contracture
         subjects affected / exposed
    1 / 179 (0.56%)
    4 / 181 (2.21%)
    5 / 360 (1.39%)
    0 / 122 (0.00%)
         occurrences all number
    3
    4
    7
    0
    Muscle spasms
         subjects affected / exposed
    3 / 179 (1.68%)
    4 / 181 (2.21%)
    7 / 360 (1.94%)
    0 / 122 (0.00%)
         occurrences all number
    3
    4
    7
    0
    Musculoskeletal pain
         subjects affected / exposed
    4 / 179 (2.23%)
    3 / 181 (1.66%)
    7 / 360 (1.94%)
    0 / 122 (0.00%)
         occurrences all number
    4
    4
    8
    0
    Neck pain
         subjects affected / exposed
    5 / 179 (2.79%)
    3 / 181 (1.66%)
    8 / 360 (2.22%)
    0 / 122 (0.00%)
         occurrences all number
    5
    3
    8
    0
    Osteoporosis
         subjects affected / exposed
    2 / 179 (1.12%)
    6 / 181 (3.31%)
    8 / 360 (2.22%)
    1 / 122 (0.82%)
         occurrences all number
    2
    6
    8
    1
    Rotator cuff syndrome
         subjects affected / exposed
    4 / 179 (2.23%)
    1 / 181 (0.55%)
    5 / 360 (1.39%)
    0 / 122 (0.00%)
         occurrences all number
    5
    1
    6
    0
    Pain in extremity
         subjects affected / exposed
    6 / 179 (3.35%)
    5 / 181 (2.76%)
    11 / 360 (3.06%)
    2 / 122 (1.64%)
         occurrences all number
    9
    5
    14
    2
    Tendonitis
         subjects affected / exposed
    5 / 179 (2.79%)
    3 / 181 (1.66%)
    8 / 360 (2.22%)
    2 / 122 (1.64%)
         occurrences all number
    6
    3
    9
    2
    Infections and infestations
    Acute tonsillitis
         subjects affected / exposed
    5 / 179 (2.79%)
    3 / 181 (1.66%)
    8 / 360 (2.22%)
    0 / 122 (0.00%)
         occurrences all number
    5
    3
    8
    0
    Gastroenteritis
         subjects affected / exposed
    7 / 179 (3.91%)
    7 / 181 (3.87%)
    14 / 360 (3.89%)
    1 / 122 (0.82%)
         occurrences all number
    8
    7
    15
    1
    Bronchitis
         subjects affected / exposed
    2 / 179 (1.12%)
    10 / 181 (5.52%)
    12 / 360 (3.33%)
    2 / 122 (1.64%)
         occurrences all number
    2
    10
    12
    2
    Infection parasitic
         subjects affected / exposed
    4 / 179 (2.23%)
    1 / 181 (0.55%)
    5 / 360 (1.39%)
    0 / 122 (0.00%)
         occurrences all number
    4
    1
    5
    0
    Influenza
         subjects affected / exposed
    13 / 179 (7.26%)
    17 / 181 (9.39%)
    30 / 360 (8.33%)
    2 / 122 (1.64%)
         occurrences all number
    17
    22
    39
    2
    Nasopharyngitis
         subjects affected / exposed
    35 / 179 (19.55%)
    44 / 181 (24.31%)
    79 / 360 (21.94%)
    9 / 122 (7.38%)
         occurrences all number
    59
    77
    136
    9
    Pharyngitis
         subjects affected / exposed
    12 / 179 (6.70%)
    21 / 181 (11.60%)
    33 / 360 (9.17%)
    1 / 122 (0.82%)
         occurrences all number
    16
    25
    41
    1
    Oral herpes
         subjects affected / exposed
    2 / 179 (1.12%)
    8 / 181 (4.42%)
    10 / 360 (2.78%)
    0 / 122 (0.00%)
         occurrences all number
    3
    13
    16
    0
    Rhinitis
         subjects affected / exposed
    5 / 179 (2.79%)
    12 / 181 (6.63%)
    17 / 360 (4.72%)
    0 / 122 (0.00%)
         occurrences all number
    7
    16
    23
    0
    Sinusitis
         subjects affected / exposed
    4 / 179 (2.23%)
    7 / 181 (3.87%)
    11 / 360 (3.06%)
    3 / 122 (2.46%)
         occurrences all number
    4
    8
    12
    3
    Tonsillitis
         subjects affected / exposed
    0 / 179 (0.00%)
    5 / 181 (2.76%)
    5 / 360 (1.39%)
    0 / 122 (0.00%)
         occurrences all number
    0
    6
    6
    0
    Upper respiratory tract infection
         subjects affected / exposed
    21 / 179 (11.73%)
    17 / 181 (9.39%)
    38 / 360 (10.56%)
    2 / 122 (1.64%)
         occurrences all number
    35
    24
    59
    2
    Urinary tract infection
         subjects affected / exposed
    3 / 179 (1.68%)
    9 / 181 (4.97%)
    12 / 360 (3.33%)
    0 / 122 (0.00%)
         occurrences all number
    4
    13
    17
    0
    Metabolism and nutrition disorders
    Dyslipidaemia
         subjects affected / exposed
    16 / 179 (8.94%)
    14 / 181 (7.73%)
    30 / 360 (8.33%)
    6 / 122 (4.92%)
         occurrences all number
    16
    14
    30
    6
    Hypercholesterolaemia
         subjects affected / exposed
    3 / 179 (1.68%)
    5 / 181 (2.76%)
    8 / 360 (2.22%)
    2 / 122 (1.64%)
         occurrences all number
    3
    7
    10
    2
    Hyperglycaemia
         subjects affected / exposed
    0 / 179 (0.00%)
    4 / 181 (2.21%)
    4 / 360 (1.11%)
    1 / 122 (0.82%)
         occurrences all number
    0
    6
    6
    1
    Hyperlipidaemia
         subjects affected / exposed
    3 / 179 (1.68%)
    2 / 181 (1.10%)
    5 / 360 (1.39%)
    3 / 122 (2.46%)
         occurrences all number
    3
    2
    5
    3

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    04 Aug 2011
    This protocol amendment is issued to clarify discrepancies in the protocol. However, none of the changes has an impact on the conduct of the trial or the patient’s treatment. A discrepancy between the population and the inclusion criteria was clarified. Wording on the subject number for re-screened subject was removed. Subject will be tracked using a unique subject identifier, that will be applied within the database but not visible for the investigator and therefore the sentence was misleading. A serum biomarker sample log was added in the appendix.
    10 Dec 2012
    This protocol amendment is issued to update sections of the data analysis plan, specifically to update how missing values are handled. The guidance language for study treatment interruptions and discontinuation has been clarified. The notable laboratory values and guidance for subject observation post study treatment administration have been aligned with the wording used in all current secukinumab arthritis studies. None of the changes made are due to safety concerns and none of the changes have impact on the conduct of the trial or alter in any way the treatment of study subjects.
    22 Nov 2013
    This protocol amendment is primarily issued for the following reasons: To expand the statistical hierarchy (primary plus ranked secondary variables) to include more endpoints which are relevant to determining the overall therapeutic value of a therapy for Ankylosing Spondylitis. These endpoints include but are not limited to ASQoL, BASDAI and SF-36. In addition, the analysis was changed to include all patients in the FAS, rather than focusing only on the subset of patients who are TNFα inhibitor naïve, as the FAS would be more representative of the general population of AS patients.To align the primary and secondary assessments with the ASAS Handbook (Sieper 2009) As the primary endpoint is at Week 16, there is no longer a need for the sponsor to be blinded past this endpoint. The conduct of the interim analysis was revised. However, sites and patients will remain blinded until all patients reach Week 52 to ensure an unbiased assessment of the secukinumab doses. None of the changes made are due to safety concerns and none of the changes have an impact on the conduct of the trial or alter in any way the treatment of study subjects.

    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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