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    Clinical Trial Results:
    A randomized, partially-blinded, active-controlled multicenter study of secukinumab to demonstrate reduction of radiographic progression versus GP2017 (adalimumab biosimilar) at 104 weeks and to assess the long term safety, tolerability and efficacy up to 2 years in patients with active ankylosing spondylitis

    Summary
    EudraCT number
    2017-000679-10
    Trial protocol
    GB   DE   ES   FR   CZ   SK   FI   DK   NL   PT   PL   GR   RO  
    Global end of trial date
    29 Nov 2021

    Results information
    Results version number
    v1(current)
    This version publication date
    15 Dec 2022
    First version publication date
    15 Dec 2022
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CAIN457K2340
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03259074
    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
    29 Nov 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Nov 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Demonstrate the proportion of subjects on secukinumab (150 mg s.c. or 300 mg s.c.) with no radiographic progression as measured by mSASSS at Week 104 is superior to subjects on GP2017 (adalimumab biosimilar 40 mg s.c.).
    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
    30 Nov 2017
    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
    Argentina: 1
    Country: Number of subjects enrolled
    Australia: 9
    Country: Number of subjects enrolled
    Belgium: 3
    Country: Number of subjects enrolled
    Canada: 9
    Country: Number of subjects enrolled
    Chile: 40
    Country: Number of subjects enrolled
    Colombia: 7
    Country: Number of subjects enrolled
    Czechia: 71
    Country: Number of subjects enrolled
    Denmark: 7
    Country: Number of subjects enrolled
    Finland: 2
    Country: Number of subjects enrolled
    France: 17
    Country: Number of subjects enrolled
    Germany: 72
    Country: Number of subjects enrolled
    Greece: 6
    Country: Number of subjects enrolled
    Israel: 11
    Country: Number of subjects enrolled
    Japan: 15
    Country: Number of subjects enrolled
    Korea, Democratic People's Republic of: 47
    Country: Number of subjects enrolled
    Mexico: 19
    Country: Number of subjects enrolled
    Monaco: 4
    Country: Number of subjects enrolled
    Netherlands: 8
    Country: Number of subjects enrolled
    Peru: 35
    Country: Number of subjects enrolled
    Philippines: 20
    Country: Number of subjects enrolled
    Poland: 80
    Country: Number of subjects enrolled
    Portugal: 18
    Country: Number of subjects enrolled
    Romania: 8
    Country: Number of subjects enrolled
    Russian Federation: 126
    Country: Number of subjects enrolled
    Slovakia: 19
    Country: Number of subjects enrolled
    Spain: 62
    Country: Number of subjects enrolled
    Taiwan: 42
    Country: Number of subjects enrolled
    Turkey: 17
    Country: Number of subjects enrolled
    United Kingdom: 52
    Country: Number of subjects enrolled
    United States: 32
    Worldwide total number of subjects
    859
    EEA total number of subjects
    373
    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)
    814
    From 65 to 84 years
    45
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    A total of 859 subjects were randomized to treatment at 171 sites in 30 countries in Europe, North America, South America, and Asia

    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, Data analyst, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    AIN457 150 mg/placebo
    Arm description
    AIN457 150 mg and a matching placebo was administered subcutaneously via pre-filled syringes at Baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks until Week 104
    Arm type
    Experimental

    Investigational medicinal product name
    secukinumab
    Investigational medicinal product code
    AIN457
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled pen
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    150 mg and matching placebo

    Arm title
    AIN457 300 mg
    Arm description
    AIN457 300 mg (2 x 150 mg) was administered subcutaneously via pre-filled syringes at Baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks until Week 104
    Arm type
    Experimental

    Investigational medicinal product name
    secukinumab
    Investigational medicinal product code
    AIN457
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled pen
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    300 mg

    Arm title
    GP2017 40mg
    Arm description
    GP2017 (adalimumab biosimilar) 40 mg was administered subcutaneously via pre-filled syringes at Baseline followed by dosing every 2 weeks until Week 104
    Arm type
    Active comparator

    Investigational medicinal product name
    adalimumab biosimilar
    Investigational medicinal product code
    GP2017
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled pen
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    40 mg

    Number of subjects in period 1
    AIN457 150 mg/placebo AIN457 300 mg GP2017 40mg
    Started
    287
    286
    286
    Completed
    254
    237
    243
    Not completed
    33
    49
    43
         Adverse event, serious fatal
    1
    1
    3
         Physician decision
    4
    12
    10
         Adverse event, non-fatal
    9
    12
    8
         Protocol Deviation
    1
    1
    3
         Progressive Disease
    1
    -
    -
         Pregnancy
    1
    1
    -
         Subject/Guardian Decision
    13
    16
    14
         Lost to follow-up
    2
    4
    3
         New Therapy For Study Indication
    1
    2
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    AIN457 150 mg/placebo
    Reporting group description
    AIN457 150 mg and a matching placebo was administered subcutaneously via pre-filled syringes at Baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks until Week 104

    Reporting group title
    AIN457 300 mg
    Reporting group description
    AIN457 300 mg (2 x 150 mg) was administered subcutaneously via pre-filled syringes at Baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks until Week 104

    Reporting group title
    GP2017 40mg
    Reporting group description
    GP2017 (adalimumab biosimilar) 40 mg was administered subcutaneously via pre-filled syringes at Baseline followed by dosing every 2 weeks until Week 104

    Reporting group values
    AIN457 150 mg/placebo AIN457 300 mg GP2017 40mg Total
    Number of subjects
    287 286 286 859
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    277 269 268 814
        From 65-84 years
    10 17 18 45
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    42.1 ± 11.99 42.2 ± 12.47 41.9 ± 12.68 -
    Sex: Female, Male
    Units:
        Female
    57 63 65 185
        Male
    230 223 221 674
    Race/Ethnicity, Customized
    Units: Subjects
        White
    225 227 228 680
        Black or African American
    1 2 0 3
        Asian
    40 39 50 129
        American Indian or Alaska Native
    19 15 7 41
        Other
    1 0 0 1
        Multiple
    1 3 1 5
    Modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) scores
    The modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) evaluates the outside corners of the vertebral spine for erosions, sclerosis, squaring, bony growths and spinal bridging. The mSASSS assesses the participant's spinal vertebrae for structural changes and scores each vertebrae from 0 (normal vertebrae) to 3 (bony growth that bridges one vertebrae to the neighboring vertebrae). A total of 24 vertebral corners are scored for a possible maximum grade of 72.
    Units: mSASSS scores
        arithmetic mean (standard deviation)
    17.602 ± 21.3286 16.527 ± 20.8153 15.695 ± 19.4955 -

    End points

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    End points reporting groups
    Reporting group title
    AIN457 150 mg/placebo
    Reporting group description
    AIN457 150 mg and a matching placebo was administered subcutaneously via pre-filled syringes at Baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks until Week 104

    Reporting group title
    AIN457 300 mg
    Reporting group description
    AIN457 300 mg (2 x 150 mg) was administered subcutaneously via pre-filled syringes at Baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks until Week 104

    Reporting group title
    GP2017 40mg
    Reporting group description
    GP2017 (adalimumab biosimilar) 40 mg was administered subcutaneously via pre-filled syringes at Baseline followed by dosing every 2 weeks until Week 104

    Primary: Percentage of participants with no radiographic progression (estimate + 95% CI) at Week 104 (Multiple imputation) (Full analysis set)

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    End point title
    Percentage of participants with no radiographic progression (estimate + 95% CI) at Week 104 (Multiple imputation) (Full analysis set)
    End point description
    Radiographic progression was based on scores from the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The mSASSS is the sum of scores assessing the vertebral corners of the lumbar and cervical spine as 0 (normal), 1 (erosion, sclerosis, or squaring), 2 (syndesmophyte), or 3 (bridging syndesmophyte) with a total range from 0-72. No radiographic progression was defined as the change from baseline in mSASSS score <= 0.5.
    End point type
    Primary
    End point timeframe
    Baseline and at Week 104
    End point values
    AIN457 150 mg/placebo AIN457 300 mg GP2017 40mg
    Number of subjects analysed
    287
    286
    286
    Units: Percentage of participants
        number (not applicable)
    66.1
    66.9
    65.6
    Statistical analysis title
    AIN157 150 vs GP2017 at Week 104
    Comparison groups
    AIN457 150 mg/placebo v GP2017 40mg
    Number of subjects included in analysis
    573
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.7164 [1]
    Method
    Regression, Logistic
    Parameter type
    Marginal difference
    Point estimate
    1.51
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.63
         upper limit
    9.64
    Notes
    [1] - Logistic regression model with treatment as a factor and baseline mSASSS score as a covariate using marginal standardization method.
    Statistical analysis title
    AIN157 300 vs GP2017 at Week 104
    Comparison groups
    AIN457 300 mg v GP2017 40mg
    Number of subjects included in analysis
    572
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.6925
    Method
    Regression, Logistic
    Parameter type
    Marginal difference
    Point estimate
    1.67
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.61
         upper limit
    9.95

    Secondary: Change from Baseline in mSASSS (estimate + 95% CI) at Week 104 (Multiple imputation) (Full analysis set)

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    End point title
    Change from Baseline in mSASSS (estimate + 95% CI) at Week 104 (Multiple imputation) (Full analysis set)
    End point description
    Radiographic changes in the spine were based on the change in score of the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) from baseline to Week 104. The mSASSS is the sum of scores assessing the vertebral corners of the lumbar and cervical spine as 0 (normal), 1 (erosion, sclerosis, or squaring), 2 (syndesmophyte), or 3 (bridging syndesmophyte) with a total range from 0-72.
    End point type
    Secondary
    End point timeframe
    Baseline and at Week 104
    End point values
    AIN457 150 mg/placebo AIN457 300 mg GP2017 40mg
    Number of subjects analysed
    287
    286
    286
    Units: mSASSS scores
        least squares mean (standard error)
    0.54 ± 0.175
    0.55 ± 0.180
    0.72 ± 0.177
    Statistical analysis title
    AIN157 150 vs GP2017 at Week 104
    Comparison groups
    AIN457 150 mg/placebo v GP2017 40mg
    Number of subjects included in analysis
    573
    Analysis specification
    Pre-specified
    Analysis type
    [2]
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.18
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.646
         upper limit
    0.293
    Notes
    [2] - Due to the pre-defined hierarchical testing strategy, p values beyond the failed primary endpoint were not presented.
    Statistical analysis title
    AIN157 300 vs GP2017 at Week 104
    Comparison groups
    AIN457 300 mg v GP2017 40mg
    Number of subjects included in analysis
    572
    Analysis specification
    Pre-specified
    Analysis type
    [3]
    Method
    Parameter type
    LS mean difference
    Point estimate
    -0.16
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.639
         upper limit
    0.315
    Notes
    [3] - Due to the pre-defined hierarchical testing strategy, p values beyond the failed primary endpoint were not presented.

    Secondary: Percentage of participants without new syndesmophytes by mSASSS (estimate + 95% CI) between baseline and Week 104 (Multiple imputation) (Syndesmophyte subset)

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    End point title
    Percentage of participants without new syndesmophytes by mSASSS (estimate + 95% CI) between baseline and Week 104 (Multiple imputation) (Syndesmophyte subset)
    End point description
    Syndesmophytes are bony growths that develop on corner of the vertebrae of the spine which are indicators of AS. A participant was considered to have a syndesmophyte if at least one reader assessed vertebral corner as >= 2 at on the mSASSS scale at baseline. Only participants with a syndesmophyte at baseline were evaluated at Week 104 for new syndesmophytes. A new syndesmophyte was a syndesmophyte present at Week 104 which was not present at baseline. Absence of new syndesmophyte was defined as having individual vertebral score < 2 on the mSASSS scale for all interpretable locations that had no syndesmophyte at baseline. Missing responses for subjects without new syndesmophyte at Week 104 were imputed by multiple imputation (MCMC).
    End point type
    Secondary
    End point timeframe
    Baseline and at Week 104
    End point values
    AIN457 150 mg/placebo AIN457 300 mg GP2017 40mg
    Number of subjects analysed
    211
    204
    212
    Units: Percentage of participants
        number (not applicable)
    56.9
    53.8
    53.3
    Statistical analysis title
    150 mg vs 300 mg AIN457 at Week 104
    Comparison groups
    AIN457 150 mg/placebo v AIN457 300 mg
    Number of subjects included in analysis
    415
    Analysis specification
    Pre-specified
    Analysis type
    [4]
    Method
    Parameter type
    Marginal difference
    Point estimate
    4.32
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.62
         upper limit
    14.27
    Notes
    [4] - Due to the pre-defined hierarchical testing strategy, p values beyond the failed primary endpoint were not presented.
    Statistical analysis title
    AIN457 300 mg vs GP2017 40 mg at Week 104
    Comparison groups
    AIN457 300 mg v GP2017 40mg
    Number of subjects included in analysis
    416
    Analysis specification
    Pre-specified
    Analysis type
    [5]
    Method
    Parameter type
    Marginal difference
    Point estimate
    1.09
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -9.13
         upper limit
    11.31
    Notes
    [5] - Due to the pre-defined hierarchical testing strategy, p values beyond the failed primary endpoint were not presented.

    Secondary: Change from Baseline in MRI Berlin SI joint edema score (estimate + 95% CI) ANCOVA up to Week 104 (Observed data) (MRI subset)

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    End point title
    Change from Baseline in MRI Berlin SI joint edema score (estimate + 95% CI) ANCOVA up to Week 104 (Observed data) (MRI subset)
    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. Higher scores indicate more inflammation.
    End point type
    Secondary
    End point timeframe
    Baseline and at Week 104
    End point values
    AIN457 150 mg/placebo AIN457 300 mg GP2017 40mg
    Number of subjects analysed
    137
    137
    144
    Units: Berlin SI joint edema scores
        least squares mean (standard error)
    -1.527 ± 0.1057
    -1.378 ± 0.1097
    -1.710 ± 0.1087
    Statistical analysis title
    AIN457 150 vs GP2017 at Week 104
    Statistical analysis description
    Week 104 - 150 mg
    Comparison groups
    AIN457 150 mg/placebo v GP2017 40mg
    Number of subjects included in analysis
    281
    Analysis specification
    Pre-specified
    Analysis type
    [6]
    Method
    Parameter type
    LS Means
    Point estimate
    0.183
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.12
         upper limit
    0.48
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1517
    Notes
    [6] - Due to the pre-defined hierarchical testing strategy, p values beyond the failed primary endpoint were not presented.
    Statistical analysis title
    AIN457 300 mg vs GP2017 40 mg at Week 104
    Statistical analysis description
    Week 104 - 300 mg
    Comparison groups
    AIN457 300 mg v GP2017 40mg
    Number of subjects included in analysis
    281
    Analysis specification
    Pre-specified
    Analysis type
    [7]
    Method
    Parameter type
    LS Means
    Point estimate
    0.332
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.03
         upper limit
    0.64
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1545
    Notes
    [7] - Due to the pre-defined hierarchical testing strategy, p values beyond the failed primary endpoint were not presented.

    Secondary: Change from Baseline in Berlin modification of ASspiMRI-a edema score (estimate + 95% CI) up to Week 104 (MRI subset)

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    End point title
    Change from Baseline in Berlin modification of ASspiMRI-a edema score (estimate + 95% CI) up to Week 104 (MRI subset)
    End point description
    Magnetic Resonance Images (MRI) of the spine were assessed for the presence and severity of bone marrow edema in the spinal vertebrae according to the Berlin modification of the ASspiMRI-a edema score with a maximum score of 69. Higher scores indicate more inflammation.
    End point type
    Secondary
    End point timeframe
    Baseline and at Week 104
    End point values
    AIN457 150 mg/placebo AIN457 300 mg GP2017 40mg
    Number of subjects analysed
    137
    137
    144
    Units: Berlin mod. of ASspiMRI-a edema scores
        least squares mean (standard error)
    -1.224 ± 0.2306
    -1.683 ± 0.2373
    -2.101 ± 0.2378
    Statistical analysis title
    AIN457 150 mg vs GP2017 at Week 104
    Statistical analysis description
    Week 104 - 150 mg
    Comparison groups
    AIN457 150 mg/placebo v GP2017 40mg
    Number of subjects included in analysis
    281
    Analysis specification
    Pre-specified
    Analysis type
    [8]
    Method
    Parameter type
    LS Means
    Point estimate
    0.877
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.22
         upper limit
    1.53
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.3316
    Notes
    [8] - Due to the pre-defined hierarchical testing strategy, p values beyond the failed primary endpoint were not presented.
    Statistical analysis title
    AIN457 300 mg vs GP2017 40 mg at Week 104
    Statistical analysis description
    Week 104 - 300 mg
    Comparison groups
    AIN457 300 mg v GP2017 40mg
    Number of subjects included in analysis
    281
    Analysis specification
    Pre-specified
    Analysis type
    [9]
    Method
    Parameter type
    LS Means
    Point estimate
    0.419
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.24
         upper limit
    1.08
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.3357
    Notes
    [9] - Due to the pre-defined hierarchical testing strategy, p values beyond the failed primary endpoint were not presented.

    Secondary: Percentage of responders for Assessment of SpondyloArthritis International Society 20 (ASAS20)

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    End point title
    Percentage of responders for Assessment of SpondyloArthritis International Society 20 (ASAS20) [10]
    End point description
    Assessment of SpondyloArthritis International Society criteria (ASAS) consist of 4 domains measured on visual analog scales (VAS): 1. Patient's global assessment; 2. Patient's assessment of back pain; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions; 4. Inflammation represented by mean duration and severity of morning stiffness, on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). 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 104
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The comparison was between 2 doses of AIN457 only.
    End point values
    AIN457 150 mg/placebo AIN457 300 mg
    Number of subjects analysed
    287
    286
    Units: Percentage participants with ASAS20
        number (confidence interval 95%)
    83.1 (77.8 to 87.4)
    82.9 (77.3 to 87.4)
    Statistical analysis title
    AIN457 150 mg vs AIN457 300 mg at Week 104
    Comparison groups
    AIN457 150 mg/placebo v AIN457 300 mg
    Number of subjects included in analysis
    573
    Analysis specification
    Pre-specified
    Analysis type
    [11]
    Method
    Parameter type
    Marginal difference
    Point estimate
    1.54
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.1
         upper limit
    8.18
    Notes
    [11] - Due to the pre-defined hierarchical testing strategy, p values beyond the failed primary endpoint were not presented.

    Secondary: Percentage of responders for Assessment of SpondyloArthritis International Society 40 (ASAS 40)

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    End point title
    Percentage of responders for Assessment of SpondyloArthritis International Society 40 (ASAS 40) [12]
    End point description
    Assessment of SpondyloArthritis International Society criteria (ASAS) consist of 4 domains measured on visual analog scales (VAS): 1. Patient's global assessment; 2. Patient's assessment of back pain; 3. Function represented by Bath Ankylosing Spondylitis Functional Index (BASFI) average of 10 questions; 4. Inflammation represented by mean duration and severity of morning stiffness, on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). 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 104
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The comparison was between 2 doses of AIN457 only.
    End point values
    AIN457 150 mg/placebo AIN457 300 mg
    Number of subjects analysed
    287
    286
    Units: Percentage participants with ASAS40
        number (confidence interval 95%)
    69.9 (63.7 to 75.4)
    73.5 (67.3 to 78.9)
    Statistical analysis title
    AIN457 150 mg vs AIN457 300 mg at Week 104
    Comparison groups
    AIN457 150 mg/placebo v AIN457 300 mg
    Number of subjects included in analysis
    573
    Analysis specification
    Pre-specified
    Analysis type
    [13]
    Method
    Parameter type
    Marginal difference
    Point estimate
    -2.34
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -10.18
         upper limit
    5.51
    Notes
    [13] - Due to the pre-defined hierarchical testing strategy, p values beyond the failed primary endpoint were not presented.

    Secondary: Percentage of responders for Assessment of SpondyloArthritis International Society with a partial remission response (Full analysis set)

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    End point title
    Percentage of responders for Assessment of SpondyloArthritis International Society with a partial remission response (Full analysis set) [14]
    End point description
    The ASAS partial remission response criteria consisted of the following assessment domains measured on visual analogue scales (VAS): 1. Patient’s global assessment; 2. Patient's assessment of back pain; 3. Function represented by BASFI average of 10 questions regarding ability to perform specific tasks; 4. Inflammation represented by mean duration and severity of morning stiffness, on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The ASAS partial remission criteria was defined as a value not above 2 units in each of the four domains on a scale of 10.
    End point type
    Secondary
    End point timeframe
    Week 104
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The comparison was between 2 doses of AIN457 only.
    End point values
    AIN457 150 mg/placebo AIN457 300 mg
    Number of subjects analysed
    287
    286
    Units: Percentage participants
        number (confidence interval 95%)
    31.5 (25.9 to 37.7)
    30.2 (24.5 to 36.6)
    Statistical analysis title
    AIN457 150 mg vs AIN457 300 mg at Week 104
    Comparison groups
    AIN457 150 mg/placebo v AIN457 300 mg
    Number of subjects included in analysis
    573
    Analysis specification
    Pre-specified
    Analysis type
    [15]
    Method
    Marginal difference
    Parameter type
    Marginal difference
    Point estimate
    2.18
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.34
         upper limit
    9.69
    Notes
    [15] - Due to the pre-defined hierarchical testing strategy, p values beyond the failed primary endpoint were not presented.

    Secondary: Percentage of participants with Assessment of SpondyloArthritis International Society for inactive disease response (Observed data) (Full analysis set)

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    End point title
    Percentage of participants with Assessment of SpondyloArthritis International Society for inactive disease response (Observed data) (Full analysis set) [16]
    End point description
    The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a composite index to assess disease activity in AS. Parameters used for the ASDAS include spinal pain (BASDAI question 2), the patient’s global assessment of disease activity, peripheral pain/swelling (BASDAI question 3), duration of morning stiffness (BASDAI question 6) and C-reactive protein (CRP) in mg/L (Sieper 2009, Lukas 2009). Disease activity states are inactive disease, moderate disease activity, high disease activity, and very high disease activity. The 3 values selected to separate these states were < 1.3 between inactive disease and moderate disease activity, < 2.1 between moderate disease activity and high disease activity, and > 3.5 between high disease activity and very high disease activity. Selected cutoffs for improvement scores were a change ≥ 1.1 unit for “minimal clinically important improvement” and a change ≥ 2.0 units for “major improvement” (Machado 2011).
    End point type
    Secondary
    End point timeframe
    Week 104
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The comparison was between 2 doses of AIN457 only.
    End point values
    AIN457 150 mg/placebo AIN457 300 mg
    Number of subjects analysed
    287
    286
    Units: Percentage of participants
        number (confidence interval 95%)
    31.1 (25.5 to 37.4)
    31.7 (25.7 to 38.3)
    Statistical analysis title
    AIN457 150 mg vs AIN457 300 mg at Week 104
    Comparison groups
    AIN457 150 mg/placebo v AIN457 300 mg
    Number of subjects included in analysis
    573
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Marginal difference
    Point estimate
    0.33
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.08
         upper limit
    7.74

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were reported from first dose of study treatment until end of study treatment plus 84 days up to a maximum of 900 days for AIN457 and 939 days for GP2017.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    AIN457 150 mg/placebo
    Reporting group description
    AIN457 150 mg and a matching placebo was administered subcutaneously via pre-filled syringes at Baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks until Week 104

    Reporting group title
    GP2017 40 mg
    Reporting group description
    GP2017 (adalimumab biosimilar) 40 mg was administered subcutaneously via pre-filled syringes at Baseline followed by dosing every 2 weeks until Week 104

    Reporting group title
    AIN457 300 mg
    Reporting group description
    AIN457 300 mg (2 x 150 mg) was administered subcutaneously via pre-filled syringes at Baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks until Week 104

    Serious adverse events
    AIN457 150 mg/placebo GP2017 40 mg AIN457 300 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    40 / 286 (13.99%)
    32 / 285 (11.23%)
    29 / 285 (10.18%)
         number of deaths (all causes)
    1
    3
    1
         number of deaths resulting from adverse events
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    1 / 286 (0.35%)
    0 / 285 (0.00%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bladder neoplasm
         subjects affected / exposed
    1 / 286 (0.35%)
    0 / 285 (0.00%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chloroma
         subjects affected / exposed
    1 / 286 (0.35%)
    0 / 285 (0.00%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Ovarian cancer
         subjects affected / exposed
    0 / 286 (0.00%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Papillary thyroid cancer
         subjects affected / exposed
    1 / 286 (0.35%)
    0 / 285 (0.00%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Iliac artery occlusion
         subjects affected / exposed
    0 / 286 (0.00%)
    0 / 285 (0.00%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Iliac artery stenosis
         subjects affected / exposed
    0 / 286 (0.00%)
    0 / 285 (0.00%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Phlebitis
         subjects affected / exposed
    0 / 286 (0.00%)
    0 / 285 (0.00%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombosis
         subjects affected / exposed
    0 / 286 (0.00%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion
         subjects affected / exposed
    1 / 286 (0.35%)
    0 / 285 (0.00%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    0 / 286 (0.00%)
    0 / 285 (0.00%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Drug intolerance
         subjects affected / exposed
    1 / 286 (0.35%)
    0 / 285 (0.00%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Medical device pain
         subjects affected / exposed
    1 / 286 (0.35%)
    0 / 285 (0.00%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 286 (0.00%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    0 / 286 (0.00%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Immune system disorders
    Immunosuppression
         subjects affected / exposed
    0 / 286 (0.00%)
    0 / 285 (0.00%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Endometrial hyperplasia
         subjects affected / exposed
    0 / 286 (0.00%)
    0 / 285 (0.00%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ovarian cyst
         subjects affected / exposed
    1 / 286 (0.35%)
    0 / 285 (0.00%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 286 (0.00%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 286 (0.35%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax spontaneous
         subjects affected / exposed
    0 / 286 (0.00%)
    0 / 285 (0.00%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression suicidal
         subjects affected / exposed
    1 / 286 (0.35%)
    0 / 285 (0.00%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    1 / 286 (0.35%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Product issues
    Device dislocation
         subjects affected / exposed
    0 / 286 (0.00%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device issue
         subjects affected / exposed
    0 / 286 (0.00%)
    0 / 285 (0.00%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Exposure during pregnancy
         subjects affected / exposed
    0 / 286 (0.00%)
    0 / 285 (0.00%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 286 (0.35%)
    0 / 285 (0.00%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 286 (0.00%)
    1 / 285 (0.35%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Joint injury
         subjects affected / exposed
    1 / 286 (0.35%)
    0 / 285 (0.00%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 286 (0.00%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    1 / 286 (0.35%)
    0 / 285 (0.00%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    0 / 286 (0.00%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    1 / 286 (0.35%)
    0 / 285 (0.00%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 286 (0.35%)
    0 / 285 (0.00%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Facial paresis
         subjects affected / exposed
    1 / 286 (0.35%)
    0 / 285 (0.00%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Brain hypoxia
         subjects affected / exposed
    0 / 286 (0.00%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Guillain-Barre syndrome
         subjects affected / exposed
    0 / 286 (0.00%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lacunar stroke
         subjects affected / exposed
    1 / 286 (0.35%)
    0 / 285 (0.00%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Parkinson's disease
         subjects affected / exposed
    0 / 286 (0.00%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    1 / 286 (0.35%)
    0 / 285 (0.00%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Iridocyclitis
         subjects affected / exposed
    2 / 286 (0.70%)
    0 / 285 (0.00%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    0 / 286 (0.00%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Retinal vein occlusion
         subjects affected / exposed
    0 / 286 (0.00%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Chronic gastrointestinal bleeding
         subjects affected / exposed
    0 / 286 (0.00%)
    0 / 285 (0.00%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    3 / 286 (1.05%)
    0 / 285 (0.00%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis ulcerative
         subjects affected / exposed
    1 / 286 (0.35%)
    0 / 285 (0.00%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Crohn's disease
         subjects affected / exposed
    2 / 286 (0.70%)
    0 / 285 (0.00%)
    3 / 285 (1.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 286 (0.35%)
    0 / 285 (0.00%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    0 / 286 (0.00%)
    0 / 285 (0.00%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis eosinophilic
         subjects affected / exposed
    0 / 286 (0.00%)
    0 / 285 (0.00%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorder
         subjects affected / exposed
    0 / 286 (0.00%)
    0 / 285 (0.00%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 286 (0.00%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    0 / 286 (0.00%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    0 / 286 (0.00%)
    0 / 285 (0.00%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ileal ulcer
         subjects affected / exposed
    0 / 286 (0.00%)
    0 / 285 (0.00%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 286 (0.35%)
    2 / 285 (0.70%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    0 / 286 (0.00%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholangitis
         subjects affected / exposed
    0 / 286 (0.00%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    1 / 286 (0.35%)
    0 / 285 (0.00%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 286 (0.00%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholestasis
         subjects affected / exposed
    1 / 286 (0.35%)
    0 / 285 (0.00%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Eczema
         subjects affected / exposed
    0 / 286 (0.00%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Purpura
         subjects affected / exposed
    1 / 286 (0.35%)
    0 / 285 (0.00%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 286 (0.00%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    1 / 286 (0.35%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Micturition disorder
         subjects affected / exposed
    0 / 286 (0.00%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    0 / 286 (0.00%)
    0 / 285 (0.00%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    1 / 286 (0.35%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 286 (0.00%)
    0 / 285 (0.00%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Synovial cyst
         subjects affected / exposed
    0 / 286 (0.00%)
    0 / 285 (0.00%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    3 / 286 (1.05%)
    1 / 285 (0.35%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    0 / 286 (0.00%)
    0 / 285 (0.00%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abscess intestinal
         subjects affected / exposed
    0 / 286 (0.00%)
    0 / 285 (0.00%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anal abscess
         subjects affected / exposed
    1 / 286 (0.35%)
    0 / 285 (0.00%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 286 (0.35%)
    1 / 285 (0.35%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    1 / 286 (0.35%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    1 / 286 (0.35%)
    0 / 285 (0.00%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 286 (0.35%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 286 (0.00%)
    0 / 285 (0.00%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Epididymitis
         subjects affected / exposed
    1 / 286 (0.35%)
    0 / 285 (0.00%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    1 / 286 (0.35%)
    0 / 285 (0.00%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myelitis
         subjects affected / exposed
    0 / 286 (0.00%)
    0 / 285 (0.00%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oral herpes
         subjects affected / exposed
    1 / 286 (0.35%)
    0 / 285 (0.00%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 286 (0.00%)
    2 / 285 (0.70%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary tuberculosis
         subjects affected / exposed
    0 / 286 (0.00%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 286 (0.00%)
    0 / 285 (0.00%)
    2 / 285 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 286 (0.00%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 286 (0.00%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Suspected COVID-19
         subjects affected / exposed
    0 / 286 (0.00%)
    1 / 285 (0.35%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 286 (0.00%)
    2 / 285 (0.70%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 286 (0.00%)
    0 / 285 (0.00%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 286 (0.35%)
    0 / 285 (0.00%)
    0 / 285 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Type 1 diabetes mellitus
         subjects affected / exposed
    0 / 286 (0.00%)
    0 / 285 (0.00%)
    1 / 285 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    AIN457 150 mg/placebo GP2017 40 mg AIN457 300 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    106 / 286 (37.06%)
    99 / 285 (34.74%)
    107 / 285 (37.54%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    11 / 286 (3.85%)
    15 / 285 (5.26%)
    11 / 285 (3.86%)
         occurrences all number
    12
    16
    12
    Nervous system disorders
    Headache
         subjects affected / exposed
    16 / 286 (5.59%)
    17 / 285 (5.96%)
    17 / 285 (5.96%)
         occurrences all number
    17
    25
    22
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    20 / 286 (6.99%)
    11 / 285 (3.86%)
    22 / 285 (7.72%)
         occurrences all number
    25
    12
    27
    Musculoskeletal and connective tissue disorders
    Ankylosing spondylitis
         subjects affected / exposed
    11 / 286 (3.85%)
    12 / 285 (4.21%)
    17 / 285 (5.96%)
         occurrences all number
    12
    13
    23
    Arthralgia
         subjects affected / exposed
    16 / 286 (5.59%)
    12 / 285 (4.21%)
    13 / 285 (4.56%)
         occurrences all number
    21
    14
    16
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    17 / 286 (5.94%)
    18 / 285 (6.32%)
    25 / 285 (8.77%)
         occurrences all number
    22
    22
    32
    Nasopharyngitis
         subjects affected / exposed
    47 / 286 (16.43%)
    44 / 285 (15.44%)
    40 / 285 (14.04%)
         occurrences all number
    61
    54
    55

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Aug 2019
    1. Testing was revised from a pooled secukinumab dose group versus GP2017 in the primary objective to compare the individual secukinumab doses versus GP2017. Thus, the primary objective was changed as follows: “To demonstrate the proportion of subjects on secukinumab (combined 150 mg s.c. and or 300 mg s.c.) with no radiographic progression as measured by mSASSS at Week 104 is superior to subjects on GP2017 (adalimumab biosimilar 40 mg s.c.).” The statistical testing was altered to align with this change. 2. The Withdrawal of Consent (WoC) language was revised according to the European Economic Area (EEA) General Data Protection Regulation (GDPR) required guidelines.
    04 Feb 2021
    The blinding strategy was aligned between subjects, investigators, site personnel and the Sponsor. The designated Sponsor personnel became unblinded to treatment group (GP2017 or secukinumab) but dose of secukinumab (150 mg or 300 mg) remained blinded.

    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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