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    Clinical Trial Results:
    A Randomized, Double Blind, Multiple Dose Placebo Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of AMG 181 in Subjects with Moderate to Severe Ulcerative Colitis

    Summary
    EudraCT number
    		 2011-005251-13
    Trial protocol
    		 GR   DE   DK   GB   CZ   BE   HU   NL   AT   IT   PL   EE   LV  
    Global end of trial date
    10 Apr 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    24 Apr 2019
    First version publication date
    24 Apr 2019
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    20110166
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01694485
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Amgen Inc.
    Sponsor organisation address
    One Amgen Center Drive, Thousand Oaks, CA, United States, 91320
    Public contact
    IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com
    Scientific contact
    IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.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
    10 Apr 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    10 Apr 2018
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of this study is to evaluate the effect of abrilumab on induction of remission in adults with moderate to severe ulcerative colitis after 8 weeks of treatment as assessed by a total Mayo Score ≤ 2 points, with no individual subscore > 1 point.
    Protection of trial subjects
    This study was conducted in accordance with International Council for Harmonisation (ICH) Good Clinical Practice (GCP) and other applicable countries regulations/guidelines. The Independent Ethics Committees (IECs) or Institutional Review Boards (IRBs) involved at each center in this study reviewed and approved the study Protocol and the Informed Consent Form (ICF) before recruitment of subjects into the study and shipment of investigational product. Subjects provided their written informed consent at will, after adequate explanation of the aims, methods, anticipated benefits, and potential hazards of the study and before any protocol-specific screening procedures were conducted or any investigational product was administered.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    16 Nov 2012
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 24 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 25
    Country: Number of subjects enrolled
    United States: 17
    Country: Number of subjects enrolled
    Australia: 18
    Country: Number of subjects enrolled
    Austria: 2
    Country: Number of subjects enrolled
    Belgium: 28
    Country: Number of subjects enrolled
    Czech Republic: 16
    Country: Number of subjects enrolled
    Denmark: 14
    Country: Number of subjects enrolled
    Estonia: 4
    Country: Number of subjects enrolled
    France: 32
    Country: Number of subjects enrolled
    Germany: 9
    Country: Number of subjects enrolled
    Greece: 2
    Country: Number of subjects enrolled
    Hungary: 37
    Country: Number of subjects enrolled
    Italy: 19
    Country: Number of subjects enrolled
    Latvia: 5
    Country: Number of subjects enrolled
    Netherlands: 11
    Country: Number of subjects enrolled
    Norway: 1
    Country: Number of subjects enrolled
    Poland: 12
    Country: Number of subjects enrolled
    Russian Federation: 32
    Country: Number of subjects enrolled
    Switzerland: 41
    Country: Number of subjects enrolled
    United Kingdom: 34
    Worldwide total number of subjects
    359
    EEA total number of subjects
    226
    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
    5
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Participants were enrolled at 92 centers located in North America, Europe, and Australia from 16 November 2012 to 11 May 2015. The study consisted of a 24-week double-blind treatment period, a 108-week open-label treatment period, and a safety follow-up period.

    Pre-assignment
    Screening details
    		 Participants were to be randomly assigned in a 2:1:2:2:2 ratio to 1 of 5 treatment groups. Due to a misalignment error, some participants were erroneously assigned to incorrect treatment resulting in a final randomization ratio different from that originally stipulated in the protocol.

    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, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo/Abrilumab 210 mg Q3M
    Arm description
    		 Participants randomized to receive placebo by subcutaneous injection on day 1, week 2, week 4, and every 4 weeks thereafter until week 24. During the open-label period, participants received abrilumab 210 mg once every 3 months (Q3M) for 108 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo matching to abrilumab administered by subcutaneous injection

    Arm title
    		 Abrilumab 7 mg Q4W/Abrilumab 210 mg Q3M
    Arm description
    		 Participants randomized to receive 7 mg abrilumab by subcutaneous injection on day 1, week 2, week 4, and every 4 weeks (Q4W) thereafter until week 24. During the open-label period, participants received abrilumab 210 mg once every 3 months for 108 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Abrilumab
    Investigational medicinal product code
    AMG 181
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered by subcutaneous injection.

    Arm title
    		 Abrilumab 21 mg Q4W/Abrilumab 210 mg Q3M
    Arm description
    		 Participants randomized to receive 21 mg abrilumab by subcutaneous injection on day 1, week 2, week 4, and every 4 weeks thereafter until week 24. During the open-label period, participants received abrilumab 210 mg once every 3 months for 108 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Abrilumab
    Investigational medicinal product code
    AMG 181
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered by subcutaneous injection.

    Arm title
    		 Abrilumab 70 mg Q4W/Abrilumab 210 mg Q3M
    Arm description
    		 Participants randomized to receive 70 mg abrilumab by subcutaneous injection on day 1, week 2, week 4, and every 4 weeks thereafter until week 24. During the open-label period, participants received abrilumab 210 mg once every 3 months for 108 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Abrilumab
    Investigational medicinal product code
    AMG 181
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered by subcutaneous injection.

    Arm title
    		 Abrilumab 210 mg/Abrilumab 210 mg Q3M
    Arm description
    		 Participants randomized to receive a single dose of 210 mg abrilumab by subcutaneous injection on day 1, followed by placebo at week 2, week 4, and every 4 weeks thereafter until week 24. During the open-label period, participants received abrilumab 210 mg once every 3 months for 108 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Abrilumab
    Investigational medicinal product code
    AMG 181
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered by subcutaneous injection.

    Number of subjects in period 1
    		Placebo/Abrilumab 210 mg Q3M Abrilumab 7 mg Q4W/Abrilumab 210 mg Q3M Abrilumab 21 mg Q4W/Abrilumab 210 mg Q3M Abrilumab 70 mg Q4W/Abrilumab 210 mg Q3M Abrilumab 210 mg/Abrilumab 210 mg Q3M
    Started
    117
    22
    40
    100
    80
    Received Treatment
    116
    21
    40
    98
    79
    Completed Week 8 Assessment
    106
    18
    38
    94
    76
    Entered Open-label Period
    100
    19
    36
    88
    68
    Completed
    84
    15
    27
    62
    55
    Not completed
    33
    7
    13
    38
    25
         Adverse event, serious fatal
    1
    -
    -
    1
    -
         Consent withdrawn by subject
    20
    6
    7
    25
    18
         Sponsor Decision
    3
    -
    -
    2
    -
         Lost to follow-up
    9
    1
    6
    10
    7

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo/Abrilumab 210 mg Q3M
    Reporting group description
    		 Participants randomized to receive placebo by subcutaneous injection on day 1, week 2, week 4, and every 4 weeks thereafter until week 24. During the open-label period, participants received abrilumab 210 mg once every 3 months (Q3M) for 108 weeks.

    Reporting group title
    Abrilumab 7 mg Q4W/Abrilumab 210 mg Q3M
    Reporting group description
    		 Participants randomized to receive 7 mg abrilumab by subcutaneous injection on day 1, week 2, week 4, and every 4 weeks (Q4W) thereafter until week 24. During the open-label period, participants received abrilumab 210 mg once every 3 months for 108 weeks.

    Reporting group title
    Abrilumab 21 mg Q4W/Abrilumab 210 mg Q3M
    Reporting group description
    		 Participants randomized to receive 21 mg abrilumab by subcutaneous injection on day 1, week 2, week 4, and every 4 weeks thereafter until week 24. During the open-label period, participants received abrilumab 210 mg once every 3 months for 108 weeks.

    Reporting group title
    Abrilumab 70 mg Q4W/Abrilumab 210 mg Q3M
    Reporting group description
    		 Participants randomized to receive 70 mg abrilumab by subcutaneous injection on day 1, week 2, week 4, and every 4 weeks thereafter until week 24. During the open-label period, participants received abrilumab 210 mg once every 3 months for 108 weeks.

    Reporting group title
    Abrilumab 210 mg/Abrilumab 210 mg Q3M
    Reporting group description
    		 Participants randomized to receive a single dose of 210 mg abrilumab by subcutaneous injection on day 1, followed by placebo at week 2, week 4, and every 4 weeks thereafter until week 24. During the open-label period, participants received abrilumab 210 mg once every 3 months for 108 weeks.

    Reporting group values
    		 Placebo/Abrilumab 210 mg Q3M Abrilumab 7 mg Q4W/Abrilumab 210 mg Q3M Abrilumab 21 mg Q4W/Abrilumab 210 mg Q3M Abrilumab 70 mg Q4W/Abrilumab 210 mg Q3M Abrilumab 210 mg/Abrilumab 210 mg Q3M Total
    Number of subjects
    		 117 22 40 100 80 359
    Age, Customized
    Units: Subjects
        18 – 64 years
    		 113 22 40 99 80 354
        ≥ 65 years
    		 4 0 0 1 0 5
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 41.0 ( 13.3 ) 42.0 ( 12.4 ) 38.3 ( 11.6 ) 39.3 ( 12.2 ) 39.8 ( 12.0 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 36 8 12 32 32 120
        Male
    		 81 14 28 68 48 239
    Race/Ethnicity, Customized
    Units: Subjects
        Asian
    		 5 2 1 7 1 16
        White
    		 109 20 39 89 78 335
        Other
    		 3 0 0 4 1 8
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 4 0 2 0 3 9
        Not Hispanic or Latino
    		 113 22 38 100 77 350
        Unknown or Not Reported
    		 0 0 0 0 0 0
    Any Prior Anti-Tumor Necrosis Factor (TNF) Use
    Units: Subjects
        Yes
    		 69 6 10 56 39 180
        No
    		 48 16 30 44 41 179
    Enrollment Prior to Protocol Amendment 3
    Units: Subjects
        Yes
    		 76 0 0 58 38 172
        No
    		 41 22 40 42 42 187
    Duration of Ulcerative Colitis
    Units: years
        arithmetic mean (standard deviation)
    		 7.83 ( 5.58 ) 9.07 ( 6.57 ) 7.05 ( 5.39 ) 9.39 ( 7.25 ) 9.44 ( 7.88 ) -
    Total Mayo Score
    Units: years
        arithmetic mean (standard deviation)
    		 8.9 ( 1.5 ) 8.1 ( 1.4 ) 8.6 ( 1.7 ) 9.0 ( 1.5 ) 9.1 ( 1.4 ) -

    End points

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    End points reporting groups
    Reporting group title
    Placebo/Abrilumab 210 mg Q3M
    Reporting group description
    		 Participants randomized to receive placebo by subcutaneous injection on day 1, week 2, week 4, and every 4 weeks thereafter until week 24. During the open-label period, participants received abrilumab 210 mg once every 3 months (Q3M) for 108 weeks.

    Reporting group title
    Abrilumab 7 mg Q4W/Abrilumab 210 mg Q3M
    Reporting group description
    		 Participants randomized to receive 7 mg abrilumab by subcutaneous injection on day 1, week 2, week 4, and every 4 weeks (Q4W) thereafter until week 24. During the open-label period, participants received abrilumab 210 mg once every 3 months for 108 weeks.

    Reporting group title
    Abrilumab 21 mg Q4W/Abrilumab 210 mg Q3M
    Reporting group description
    		 Participants randomized to receive 21 mg abrilumab by subcutaneous injection on day 1, week 2, week 4, and every 4 weeks thereafter until week 24. During the open-label period, participants received abrilumab 210 mg once every 3 months for 108 weeks.

    Reporting group title
    Abrilumab 70 mg Q4W/Abrilumab 210 mg Q3M
    Reporting group description
    		 Participants randomized to receive 70 mg abrilumab by subcutaneous injection on day 1, week 2, week 4, and every 4 weeks thereafter until week 24. During the open-label period, participants received abrilumab 210 mg once every 3 months for 108 weeks.

    Reporting group title
    Abrilumab 210 mg/Abrilumab 210 mg Q3M
    Reporting group description
    		 Participants randomized to receive a single dose of 210 mg abrilumab by subcutaneous injection on day 1, followed by placebo at week 2, week 4, and every 4 weeks thereafter until week 24. During the open-label period, participants received abrilumab 210 mg once every 3 months for 108 weeks.

    Primary: Percentage of Participants with Remission at Week 8

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    End point title
    		 Percentage of Participants with Remission at Week 8
    End point description
    Remission was defined as a total Mayo Score ≤ 2 points, with no individual subscore > 1 point. The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician’s global assessment), each graded semi-quantitatively on a score of 0 to 3 where 0 represents normal and higher score represents more severe disease status. The total Mayo Score is the sum of the four item scores, ranging from 0 to 12 points. Higher scores represent more severe disease. The remission rate was calculated based on observed data (unadjusted remission rate) and also after applying a logistic regression model including the factors of treatment group, stratification factors (prior anti-TNF use and pre- versus post-Protocol Amendment 3) and baseline total Mayo Score (adjusted remission rate). The full analysis set includes randomized participants who received at least 1 dose of study drug. Remission rates were calculated using non-responder imputation.
    End point type
    Primary
    End point timeframe
    Week 8
    End point values
    		 Placebo/Abrilumab 210 mg Q3M Abrilumab 7 mg Q4W/Abrilumab 210 mg Q3M Abrilumab 21 mg Q4W/Abrilumab 210 mg Q3M Abrilumab 70 mg Q4W/Abrilumab 210 mg Q3M Abrilumab 210 mg/Abrilumab 210 mg Q3M
    Number of subjects analysed
    116
    21
    40
    98
    79
    Units: percentage of participants
    number (not applicable)
        Unadjusted remission rate
    4.3
    0.0
    2.5
    13.3
    12.7
        Adjusted remission rate
    4.4
    1.6
    2.9
    13.5
    13.4
    Statistical analysis title
    		 Comparison of Abrilumab vs Placebo
    Statistical analysis description
    Comparisons between treatment groups were made using remission rates estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 70 mg Q4W/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    214
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 = 0.021 [2]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.35
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.41
         upper limit
    		 7.95
    Notes
    [1] - The study was powered for formal statistical testing of the abrilumab 70 mg and 210 mg groups. To account for multiplicity of statistical testing, primary and key secondary end points for the 2 highest doses of abrilumab (70 and 210 mg) were tested at the end of the 8-week induction period under a sequential framework at a 2-sided significance level of 0.10 using the Bonferroni-based chain procedure.
    [2] - Adjusted for baseline total Mayo Score and stratification factors.
    Statistical analysis title
    		 Difference in Remission Rates
    Statistical analysis description
    The difference in remission rates, estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 70 mg Q4W/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    214
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in Adjusted Remission Rates
    Point estimate
    9
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.6
         upper limit
    		 14.6
    Statistical analysis title
    		 Comparison of Abrilumab vs Placebo
    Statistical analysis description
    Comparisons between treatment groups were made using remission rates from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 210 mg/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 = 0.03 [4]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.33
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.34
         upper limit
    		 8.26
    Notes
    [3] - The study was powered for formal statistical testing of the abrilumab 70 mg and 210 mg groups. To account for multiplicity of statistical testing, primary and key secondary end points for the 2 highest doses of abrilumab (70 and 210 mg) were tested at the end of the 8-week induction period under a sequential framework at a 2-sided significance level of 0.10 using the Bonferroni-based chain procedure.
    [4] - Adjusted for baseline total Mayo Score and stratification factors
    Statistical analysis title
    		 Difference in Remission Rates
    Statistical analysis description
    The difference in remission rates, estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 210 mg/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in Adjusted Remission Rates
    Point estimate
    8.9
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.8
         upper limit
    		 14.9
    Statistical analysis title
    		 Comparison of Abrilumab vs Placebo
    Statistical analysis description
    Comparisons between treatment groups were made using remission rates from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 21 mg Q4W/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [5]
    P-value
    		 = 0.64 [6]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.64
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.13
         upper limit
    		 3.17
    Notes
    [5] - Comparisons of abrilumab 21 mg with placebo were not included in the hypothesis testing procedure and were not adjusted for multiplicity.
    [6] - Adjusted for baseline total Mayo Score and stratification factors
    Statistical analysis title
    		 Difference in Remission Rates
    Statistical analysis description
    The difference in remission rates estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 21 mg Q4W/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [7]
    Method
    Parameter type
    		 Difference in Adjusted Remission Rates
    Point estimate
    -1.6
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -5.2
         upper limit
    		 5.5
    Notes
    [7] - Analysis was not part of the formal testing.
    Statistical analysis title
    		 Comparison of Abrilumab vs Placebo
    Statistical analysis description
    Comparisons between treatment groups were made using remission rates from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 7 mg Q4W/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    137
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [8]
    P-value
    		 = 0.49 [9]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.34
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.03
         upper limit
    		 4.33
    Notes
    [8] - Comparisons of abrilumab 7 mg with placebo were not included in the hypothesis testing procedure and were not adjusted for multiplicity.
    [9] - Adjusted for baseline total Mayo Score and stratification factors
    Statistical analysis title
    		 Difference in Remission Rates
    Statistical analysis description
    The difference in remission rates estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 7 mg Q4W/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    137
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [10]
    Method
    Parameter type
    		 Difference in Adjusted Remission Rates
    Point estimate
    -2.9
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -5.5
         upper limit
    		 5.4
    Notes
    [10] - Analysis was not part of the formal testing.

    Secondary: Percentage of Participants with Response at Week 8

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    End point title
    		 Percentage of Participants with Response at Week 8
    End point description
    Response was defined by a decrease from baseline in the total Mayo Score of ≥ 3 points and ≥ 30%, with an accompanying decrease in the rectal bleeding subscore ≥ 1 point or an absolute rectal bleeding subscore = 0 or 1. The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician’s global assessment); the total Mayo score ranges from 0 to 12 points, with higher scores representing more severe disease. The response rate was calculated based on observed data (unadjusted response rate) and also after applying a logistic regression model including the factors of treatment group, stratification factors (prior anti-TNF use and pre- versus post-Protocol Amendment 3) and baseline total Mayo Score (adjusted response rate). The full analysis set includes all randomized participants who received at least 1 dose of study drug. Both unadjusted and adjusted response rates were calculated using non-responder imputation.
    End point type
    Secondary
    End point timeframe
    Baseline and week 8
    End point values
    		 Placebo/Abrilumab 210 mg Q3M Abrilumab 7 mg Q4W/Abrilumab 210 mg Q3M Abrilumab 21 mg Q4W/Abrilumab 210 mg Q3M Abrilumab 70 mg Q4W/Abrilumab 210 mg Q3M Abrilumab 210 mg/Abrilumab 210 mg Q3M
    Number of subjects analysed
    116
    21
    40
    98
    79
    Units: percentage of participants
    number (not applicable)
        Unadjusted response rate
    25.9
    14.3
    50.0
    49.0
    46.8
        Adjusted response rate
    26.0
    12.3
    47.2
    49.4
    47.4
    Statistical analysis title
    		 Comparison of Abrilumab vs Placebo
    Statistical analysis description
    Comparisons between treatment groups were made using response rates estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 70 mg Q4W/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    214
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [11]
    P-value
    		 < 0.001 [12]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.78
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.71
         upper limit
    		 4.52
    Notes
    [11] - If both comparisons of the primary endpoint reached statistical significance at 0.10, results from the 2 key secondary endpoints (response and mucosal healing at week 8) were to be sequentially (70 mg vs placebo then 210 mg vs placebo) tested at significance level of 0.05 independently of each other, according to the Bonferroni-based chain procedure.
    [12] - Adjusted for baseline total Mayo Score and stratification factors.
    Statistical analysis title
    		 Difference in Response Rates
    Statistical analysis description
    The difference in adjusted response rates, estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 70 mg Q4W/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    214
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in Adjusted Response Rates
    Point estimate
    23.4
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 11.8
         upper limit
    		 33.2
    Statistical analysis title
    		 Comparison on Abrilumab vs Placebo
    Statistical analysis description
    Comparisons between treatment groups were made using response rates from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 210 mg/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [13]
    P-value
    		 = 0.003 [14]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.57
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.53
         upper limit
    		 4.31
    Notes
    [13] - If both comparisons of the primary endpoint reached statistical significance at 0.10, results from the 2 key secondary endpoints (response and mucosal healing at week 8) were to be sequentially (70 mg vs placebo then 210 mg vs placebo) tested at significance level of 0.05 independently of each other, according to the Bonferroni-based chain procedure.
    [14] - Adjusted for baseline total Mayo Score and stratification factors.
    Statistical analysis title
    		 Difference in Response rates
    Statistical analysis description
    The difference in adjusted response rates, estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 210 mg/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in Adjusted Response Rates
    Point estimate
    21.4
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 9
         upper limit
    		 31.8
    Statistical analysis title
    		 Comparison of Abrilumab vs Placebo
    Statistical analysis description
    Comparisons between treatment groups were made using response rates from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 21 mg Q4W/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [15]
    P-value
    		 = 0.024 [16]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.54
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.29
         upper limit
    		 5.02
    Notes
    [15] - Comparisons of abrilumab 21 mg with placebo were not included in the hypothesis testing procedure and were not adjusted for multiplicity.
    [16] - Adjusted for baseline total Mayo Score and stratification factors.
    Statistical analysis title
    		 Difference in Response rates
    Statistical analysis description
    The difference in adjusted response rates, estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 21 mg Q4W/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [17]
    Method
    Parameter type
    		 Difference in Adjusted Response Rates
    Point estimate
    21.2
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 4.9
         upper limit
    		 34.1
    Notes
    [17] - Analysis was not part of the formal testing.
    Statistical analysis title
    		 Comparison of Abrilumab vs Placebo
    Statistical analysis description
    Comparisons between treatment groups were made using response rates from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 7 mg Q4W/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    137
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [18]
    P-value
    		 = 0.18 [19]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.4
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.13
         upper limit
    		 1.22
    Notes
    [18] - Comparisons of abrilumab 7 mg with placebo were not included in the hypothesis testing procedure and were not adjusted for multiplicity.
    [19] - Adjusted for baseline total Mayo Score and stratification factors.
    Statistical analysis title
    		 Difference in Response Rates
    Statistical analysis description
    The difference in adjusted response rates, estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 7 mg Q4W/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    137
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [20]
    Method
    Parameter type
    		 Difference in Adjusted Response Rates
    Point estimate
    -13.7
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -24.4
         upper limit
    		 2.7
    Notes
    [20] - Analysis was not part of the formal testing.

    Secondary: Percentage of Participants with Mucosal Healing at Week 8

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    End point title
    		 Percentage of Participants with Mucosal Healing at Week 8
    End point description
    Mucosal healing was defined using the rectosigmoidoscopy subscore of Mayo assessment as absolute subscore for rectosigmoidoscopy of 0 or 1. Flexible rectosigmoidoscopy was performed as part of the Mayo assessment, graded semi-quantitatively on a scale of 0 to 3 where 0 represents normal and higher score represents more severe disease status. The healing rate (percentage of participants with mucosal healing) was calculated based on observed data (unadjusted healing rate) and also after applying a logistic regression model including the factors of treatment group, stratification factors (prior anti-TNF use and pre- versus post-Protocol Amendment 3) and baseline rectosigmoidoscopy score (adjusted healing rate). The full analysis set includes all randomized participants who received at least 1 dose of study drug. Both unadjusted and adjusted healing rates were calculated using non-responder imputation.
    End point type
    Secondary
    End point timeframe
    Baseline and week 8
    End point values
    		 Placebo/Abrilumab 210 mg Q3M Abrilumab 7 mg Q4W/Abrilumab 210 mg Q3M Abrilumab 21 mg Q4W/Abrilumab 210 mg Q3M Abrilumab 70 mg Q4W/Abrilumab 210 mg Q3M Abrilumab 210 mg/Abrilumab 210 mg Q3M
    Number of subjects analysed
    116
    21
    40
    98
    79
    Units: percentage of participants
    number (not applicable)
        Unadjusted healing rate
    21.6
    14.3
    15.0
    32.7
    29.1
        Adjusted healing rate
    16.8
    12.2
    13.9
    32.2
    29.8
    Statistical analysis title
    		 Comparison of Abrilumab vs Placebo
    Statistical analysis description
    Comparisons between treatment groups were made using healing rates estimated from a logistic regression model adjusted for baseline rectosigmoidoscopy score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 70 mg Q4W/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    214
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [21]
    P-value
    		 = 0.011 [22]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.34
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.35
         upper limit
    		 4.07
    Notes
    [21] - If both comparisons of the primary endpoint reached statistical significance at 0.10, results from the 2 key secondary endpoints (response and mucosal healing at week 8) were to be sequentially (70 mg vs placebo then 210 mg vs placebo) tested at significance level of 0.05 independently of each other, according to the Bonferroni-based chain procedure.
    [22] - Adjusted for baseline rectosigmoidoscopy score and stratification factors.
    Statistical analysis title
    		 Difference in Mucosal Healing Rates
    Statistical analysis description
    The difference in adjusted healing rates, estimated from a logistic regression model adjusted for baseline rectosigmoidoscopy score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 70 mg Q4W/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    214
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in Adjusted Healing Rates
    Point estimate
    15.3
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 4.8
         upper limit
    		 24
    Statistical analysis title
    		 Comparison of Abrilumab vs Placebo
    Statistical analysis description
    Comparisons between treatment groups were made using healing rates from a logistic regression model adjusted for baseline rectosigmoidoscopy score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 210 mg/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [23]
    P-value
    		 = 0.041 [24]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.15
         upper limit
    		 3.82
    Notes
    [23] - If both comparisons of the primary endpoint reached statistical significance at 0.10, results from the 2 key secondary endpoints (response and mucosal healing at week 8) were to be sequentially (70 mg vs placebo then 210 mg vs placebo) tested at significance level of 0.05 independently of each other, according to the Bonferroni-based chain procedure.
    [24] - Adjusted for baseline rectosigmoidoscopy score and stratification factors.
    Statistical analysis title
    		 Difference in Mucosal Healing Rates
    Statistical analysis description
    The difference in adjusted healing rates, estimated from a logistic regression model adjusted for baseline rectosigmoidoscopy score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 210 mg/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in Adjusted Healing Rates
    Point estimate
    13
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.7
         upper limit
    		 22.1
    Statistical analysis title
    		 Comparison of Abrilumab vs Placebo
    Statistical analysis description
    Comparisons between treatment groups were made using healing rates from a logistic regression model adjusted for baseline rectosigmoidoscopy score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 21 mg Q4W/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [25]
    P-value
    		 = 0.68
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.8
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.32
         upper limit
    		 1.97
    Notes
    [25] - Comparisons of abrilumab 21 mg with placebo were not included in the hypothesis testing procedure and were not adjusted for multiplicity.
    Statistical analysis title
    		 Difference in Mucosal Healing Rates
    Statistical analysis description
    The difference in adjusted healing rates, estimated from a logistic regression model adjusted for baseline rectosigmoidoscopy score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 21 mg Q4W/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [26]
    Method
    Parameter type
    		 Difference in Adjusted Healing Rates
    Point estimate
    -3
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -11.9
         upper limit
    		 9.4
    Notes
    [26] - Analysis was not part of the formal testing.
    Statistical analysis title
    		 Comparison of Abrilumab vs Placebo
    Statistical analysis description
    Comparisons between treatment groups were made using healing rates from a logistic regression model adjusted for baseline rectosigmoidoscopy score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 7 mg Q4W/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    137
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [27]
    P-value
    		 = 0.6 [28]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.69
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.21
         upper limit
    		 2.22
    Notes
    [27] - Comparisons of abrilumab 7 mg with placebo were not included in the hypothesis testing procedure and were not adjusted for multiplicity.
    [28] - Adjusted for baseline rectosigmoidoscopy score and stratification factors.
    Statistical analysis title
    		 Difference in Mucosal Healing Rates
    Statistical analysis description
    The difference in adjusted healing rates, estimated from a logistic regression model adjusted for baseline rectosigmoidoscopy score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 7 mg Q4W/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    137
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [29]
    Method
    Parameter type
    		 Difference in Adjusted Healing Rates
    Point estimate
    -4.6
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -14.9
         upper limit
    		 11.3
    Notes
    [29] - Analysis was not part of the formal testing.

    Secondary: Percentage of Participants with Sustained Remission at Week 8 and Week 24

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    End point title
    		 Percentage of Participants with Sustained Remission at Week 8 and Week 24
    End point description
    Remission was defined as a total Mayo Score ≤ 2 points, with no individual subscore > 1 point. Sustained remission was defined as achieving the criteria for remission at both week 8 and week 24. The Mayo Score is a composite index of four items (stool frequency, rectal bleeding, rectosigmoidoscopy findings, and physician’s global assessment); the total Mayo Score ranges from 0 to 12 points with higher scores representing more severe disease. The remission rate was calculated based on observed data (unadjusted remission rate) and also after applying a logistic regression model including the factors of treatment group, stratification factors (prior anti-TNF use and pre- versus post-Protocol Amendment 3) and baseline total Mayo Score (adjusted remission rate). The full analysis set includes all randomized participants who received at least 1 dose of study drug. Both non-adjusted and adjusted remission rates were calculated using non-responder imputation.
    End point type
    Secondary
    End point timeframe
    Week 8 and week 24
    End point values
    		 Placebo/Abrilumab 210 mg Q3M Abrilumab 7 mg Q4W/Abrilumab 210 mg Q3M Abrilumab 21 mg Q4W/Abrilumab 210 mg Q3M Abrilumab 70 mg Q4W/Abrilumab 210 mg Q3M Abrilumab 210 mg/Abrilumab 210 mg Q3M
    Number of subjects analysed
    116
    21
    40
    98
    79
    Units: percentage of participants
    number (not applicable)
        Unadjusted remission rate
    2.6
    0.0
    2.5
    8.2
    3.8
        Adjusted remission rate
    3.3
    1.6
    2.8
    9.1
    4.3
    Statistical analysis title
    		 Comparison of Abrilumab vs Placebo
    Statistical analysis description
    Comparisons between treatment groups were made using sustained remission rates estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 70 mg Q4W/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    214
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.09 [30]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.94
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.03
         upper limit
    		 8.36
    Notes
    [30] - Adjusted for baseline total Mayo Score and stratification factors.
    Statistical analysis title
    		 Difference in Sustained Remission Rates
    Statistical analysis description
    The difference in adjusted sustained remission rates, estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 70 mg Q4W/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    214
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in Adjusted Remission Rates
    Point estimate
    5.8
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.6
         upper limit
    		 10.4
    Statistical analysis title
    		 Comparison of Abrilumab vs Placebo
    Statistical analysis description
    Comparisons between treatment groups were made using sustained remission rates from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 210 mg/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.72 [31]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.32
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.38
         upper limit
    		 4.56
    Notes
    [31] - Adjusted for baseline total Mayo Score and stratification factors.
    Statistical analysis title
    		 Difference in Sustained Remission Rates
    Statistical analysis description
    The difference in adjusted sustained remission rates, estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 210 mg/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in Adjusted Remission Rates
    Point estimate
    1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -4.7
         upper limit
    		 4.6
    Statistical analysis title
    		 Comparison of Abrilumab vs Placebo
    Statistical analysis description
    Comparisons between treatment groups were made using sustained remission rates from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 21 mg Q4W/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [32]
    P-value
    		 = 0.86 [33]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.83
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.16
         upper limit
    		 4.41
    Notes
    [32] - Analysis was not part of the formal testing.
    [33] - Adjusted for baseline total Mayo Score and stratification factors.
    Statistical analysis title
    		 Difference in Sustained Remission Rates
    Statistical analysis description
    The difference in adjusted sustained remission rates estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 21 mg Q4W/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [34]
    Method
    Parameter type
    		 Difference in Adjusted Remission Rates
    Point estimate
    -0.5
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -3.9
         upper limit
    		 6.2
    Notes
    [34] - Analysis was not part of the formal testing.
    Statistical analysis title
    		 Comparison of Abrilumab vs Placebo
    Statistical analysis description
    Comparisons between treatment groups were made using sustained remission rates from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 7 mg Q4W/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    137
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [35]
    P-value
    		 = 0.64 [36]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.49
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.04
         upper limit
    		 6.31
    Notes
    [35] - Analysis was not part of the formal testing.
    [36] - Adjusted for baseline total Mayo Score and stratification factors.
    Statistical analysis title
    		 Difference in Sustained Remission Rates
    Statistical analysis description
    The difference in adjusted sustained remission rates estimated from a logistic regression model adjusted for baseline total Mayo Score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 7 mg Q4W/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    137
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [37]
    Method
    Parameter type
    		 Difference in Adjusted Remission Rates
    Point estimate
    -1.7
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -4.2
         upper limit
    		 6.4
    Notes
    [37] - Analysis was not part of the formal testing.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    24 weeks in the double-blind period and 108 weeks in the open-label period
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    DB Period: Placebo
    Reporting group description
    		 Participants received placebo by subcutaneous injection on day 1, week 2, week 4, and every 4 weeks thereafter until week 24 during the double-blind (DB) treatment period.

    Reporting group title
    DB Period: Abrilumab 7 mg Q4W
    Reporting group description
    		 Participants received 7 mg abrilumab by subcutaneous injection on day 1, week 2, week 4, and every 4 weeks (Q4W) thereafter until week 24 during the double-blind treatment period.

    Reporting group title
    DB Period: Abrilumab 21 mg Q4W
    Reporting group description
    		 Participants received 21 mg abrilumab by subcutaneous injection on day 1, week 2, week 4, and every 4 weeks thereafter until week 24 during the double-blind treatment period.

    Reporting group title
    DB Period: Abrilumab 70 mg Q4W
    Reporting group description
    		 Participants received 70 mg abrilumab by subcutaneous injection on day 1, week 2, week 4, and every 4 weeks thereafter until week 24 during the double-blind treatment period.

    Reporting group title
    DB Period: Abrilumab 210 mg
    Reporting group description
    		 Participants received a single dose of 210 mg abrilumab by subcutaneous injection on day 1, followed by placebo at week 2, week 4, and every 4 weeks thereafter until week 24 during the double-blind treatment period.

    Reporting group title
    OL Period: Placebo/Abrilumab 210 mg Q3M
    Reporting group description
    		 Participants who received placebo during the double-blind treatment period received abrilumab 210 mg once every 3 months (Q3M) for 108 weeks during the open-label (OL) treatment period.

    Reporting group title
    OL Period: Abrilumab 7 mg Q4W/210 mg Q3M
    Reporting group description
    		 Participants who received 7 mg abrilumab Q4W in the DB treatment period received abrilumab 210 mg once every 3 months for 108 weeks during the open-label period.

    Reporting group title
    OL Period: Abrilumab 21 mg Q4W/210 mg Q3M
    Reporting group description
    		 During the open-label period, participants who received 21 mg abrilumab Q4W during the DB treatment period received abrilumab 210 mg once every 3 months for 108 weeks.

    Reporting group title
    OL Period: Abrilumab 70 mg Q4W/210 mg Q3M
    Reporting group description
    		 Participants who received 70 mg abrilumab Q4W during the DB treatment period received abrilumab 210 mg once every 3 months for 108 weeks during the open-label period.

    Reporting group title
    OL Period: Abrilumab 210 mg/210 mg Q3M
    Reporting group description
    		 Participants who received 210 mg abrilumab during the DB treatment period received abrilumab 210 mg once every 3 months for 108 weeks during the open-label period.

    Serious adverse events
    		 DB Period: Placebo DB Period: Abrilumab 7 mg Q4W DB Period: Abrilumab 21 mg Q4W DB Period: Abrilumab 70 mg Q4W DB Period: Abrilumab 210 mg OL Period: Placebo/Abrilumab 210 mg Q3M OL Period: Abrilumab 7 mg Q4W/210 mg Q3M OL Period: Abrilumab 21 mg Q4W/210 mg Q3M OL Period: Abrilumab 70 mg Q4W/210 mg Q3M OL Period: Abrilumab 210 mg/210 mg Q3M
    Total subjects affected by serious adverse events
         subjects affected / exposed
    14 / 116 (12.07%)
    1 / 20 (5.00%)
    3 / 40 (7.50%)
    5 / 99 (5.05%)
    7 / 79 (8.86%)
    13 / 100 (13.00%)
    3 / 18 (16.67%)
    4 / 36 (11.11%)
    14 / 89 (15.73%)
    6 / 68 (8.82%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Epstein-Barr virus associated lymphoma
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    1 / 100 (1.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sarcoidosis
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    1 / 100 (1.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pharyngeal haemorrhage
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    1 / 89 (1.12%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    1 / 79 (1.27%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    1 / 79 (1.27%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    1 / 79 (1.27%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Norovirus test positive
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    1 / 18 (5.56%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Post lumbar puncture syndrome
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Heart valve incompetence
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    1 / 89 (1.12%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Migraine
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    1 / 100 (1.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    2 / 100 (2.00%)
    0 / 18 (0.00%)
    1 / 36 (2.78%)
    0 / 89 (0.00%)
    1 / 68 (1.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemolytic anaemia
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    1 / 99 (1.01%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    1 / 100 (1.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 116 (1.72%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    1 / 68 (1.47%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    1 / 100 (1.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis ulcerative
         subjects affected / exposed
    5 / 116 (4.31%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    4 / 99 (4.04%)
    2 / 79 (2.53%)
    6 / 100 (6.00%)
    0 / 18 (0.00%)
    2 / 36 (5.56%)
    4 / 89 (4.49%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
    0 / 1
    0 / 4
    0 / 2
    1 / 7
    0 / 0
    0 / 2
    1 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    1 / 89 (1.12%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal dysplasia
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    1 / 36 (2.78%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestinal obstruction
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Megacolon
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Proctalgia
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    1 / 89 (1.12%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Pemphigoid
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    1 / 68 (1.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Nephrolithiasis
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    1 / 100 (1.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Ankylosing spondylitis
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    1 / 89 (1.12%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthralgia
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    1 / 68 (1.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    1 / 100 (1.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal abscess
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    1 / 89 (1.12%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal abscess
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    1 / 18 (5.56%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal infection
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    1 / 89 (1.12%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cytomegalovirus infection
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    1 / 68 (1.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    1 / 79 (1.27%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    1 / 79 (1.27%)
    0 / 100 (0.00%)
    1 / 18 (5.56%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis bacterial
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    1 / 36 (2.78%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal infection
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    1 / 89 (1.12%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Perineal abscess
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    1 / 79 (1.27%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis streptococcal
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    1 / 89 (1.12%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    1 / 99 (1.01%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    1 / 68 (1.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary tuberculosis
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    1 / 89 (1.12%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 20 (5.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    1 / 89 (1.12%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    1 / 79 (1.27%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 DB Period: Placebo DB Period: Abrilumab 7 mg Q4W DB Period: Abrilumab 21 mg Q4W DB Period: Abrilumab 70 mg Q4W DB Period: Abrilumab 210 mg OL Period: Placebo/Abrilumab 210 mg Q3M OL Period: Abrilumab 7 mg Q4W/210 mg Q3M OL Period: Abrilumab 21 mg Q4W/210 mg Q3M OL Period: Abrilumab 70 mg Q4W/210 mg Q3M OL Period: Abrilumab 210 mg/210 mg Q3M
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    47 / 116 (40.52%)
    9 / 20 (45.00%)
    16 / 40 (40.00%)
    55 / 99 (55.56%)
    35 / 79 (44.30%)
    55 / 100 (55.00%)
    10 / 18 (55.56%)
    19 / 36 (52.78%)
    53 / 89 (59.55%)
    26 / 68 (38.24%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lipoma
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    1 / 18 (5.56%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    5 / 99 (5.05%)
    0 / 79 (0.00%)
    1 / 100 (1.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    1 / 68 (1.47%)
         occurrences all number
    1
    0
    0
    5
    0
    1
    0
    0
    0
    1
    Pregnancy, puerperium and perinatal conditions
    Pregnancy
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    1 / 18 (5.56%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    3 / 116 (2.59%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    3 / 99 (3.03%)
    1 / 79 (1.27%)
    1 / 100 (1.00%)
    1 / 18 (5.56%)
    0 / 36 (0.00%)
    4 / 89 (4.49%)
    1 / 68 (1.47%)
         occurrences all number
    3
    0
    1
    4
    1
    1
    1
    0
    5
    1
    Fatigue
         subjects affected / exposed
    3 / 116 (2.59%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    8 / 99 (8.08%)
    3 / 79 (3.80%)
    1 / 100 (1.00%)
    0 / 18 (0.00%)
    1 / 36 (2.78%)
    1 / 89 (1.12%)
    1 / 68 (1.47%)
         occurrences all number
    3
    0
    1
    8
    3
    1
    0
    1
    1
    1
    Hyperthermia
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    1 / 79 (1.27%)
    0 / 100 (0.00%)
    1 / 18 (5.56%)
    0 / 36 (0.00%)
    1 / 89 (1.12%)
    0 / 68 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    3
    0
    1
    0
    Influenza like illness
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    2 / 99 (2.02%)
    1 / 79 (1.27%)
    2 / 100 (2.00%)
    1 / 18 (5.56%)
    0 / 36 (0.00%)
    4 / 89 (4.49%)
    0 / 68 (0.00%)
         occurrences all number
    1
    0
    1
    2
    1
    6
    1
    0
    5
    0
    Localised oedema
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    1 / 18 (5.56%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Immune system disorders
    Allergy to arthropod bite
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    1 / 100 (1.00%)
    1 / 18 (5.56%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    3
    1
    0
    0
    0
    Food allergy
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 20 (5.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 116 (1.72%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    5 / 99 (5.05%)
    2 / 79 (2.53%)
    2 / 100 (2.00%)
    0 / 18 (0.00%)
    1 / 36 (2.78%)
    4 / 89 (4.49%)
    1 / 68 (1.47%)
         occurrences all number
    2
    0
    0
    5
    2
    2
    0
    1
    4
    1
    Dyspnoea
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    0 / 99 (0.00%)
    2 / 79 (2.53%)
    0 / 100 (0.00%)
    1 / 18 (5.56%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences all number
    0
    0
    1
    0
    2
    0
    1
    0
    0
    0
    Investigations
    Blood phosphorus decreased
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    1 / 99 (1.01%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    1 / 18 (5.56%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    1
    0
    0
    0
    Weight decreased
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    1 / 18 (5.56%)
    0 / 36 (0.00%)
    3 / 89 (3.37%)
    1 / 68 (1.47%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    1
    0
    3
    1
    Injury, poisoning and procedural complications
    Limb injury
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    1 / 18 (5.56%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Congenital, familial and genetic disorders
    Phimosis
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 20 (5.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Nervous system disorders
    Carpal tunnel syndrome
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    1 / 18 (5.56%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    Headache
         subjects affected / exposed
    7 / 116 (6.03%)
    1 / 20 (5.00%)
    2 / 40 (5.00%)
    11 / 99 (11.11%)
    8 / 79 (10.13%)
    3 / 100 (3.00%)
    2 / 18 (11.11%)
    1 / 36 (2.78%)
    5 / 89 (5.62%)
    4 / 68 (5.88%)
         occurrences all number
    8
    1
    5
    14
    11
    4
    2
    1
    5
    4
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 116 (0.86%)
    1 / 20 (5.00%)
    2 / 40 (5.00%)
    2 / 99 (2.02%)
    2 / 79 (2.53%)
    4 / 100 (4.00%)
    1 / 18 (5.56%)
    3 / 36 (8.33%)
    6 / 89 (6.74%)
    2 / 68 (2.94%)
         occurrences all number
    1
    1
    2
    2
    2
    5
    1
    5
    7
    2
    Lymphadenopathy
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 20 (5.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    1 / 68 (1.47%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    1
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 20 (5.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    1 / 89 (1.12%)
    0 / 68 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    1
    0
    Eye disorders
    Eye swelling
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    1 / 18 (5.56%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    3 / 116 (2.59%)
    1 / 20 (5.00%)
    3 / 40 (7.50%)
    1 / 99 (1.01%)
    1 / 79 (1.27%)
    8 / 100 (8.00%)
    1 / 18 (5.56%)
    3 / 36 (8.33%)
    6 / 89 (6.74%)
    0 / 68 (0.00%)
         occurrences all number
    3
    1
    3
    2
    2
    8
    1
    3
    6
    0
    Abdominal pain lower
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    1 / 99 (1.01%)
    0 / 79 (0.00%)
    1 / 100 (1.00%)
    1 / 18 (5.56%)
    0 / 36 (0.00%)
    1 / 89 (1.12%)
    0 / 68 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    0
    1
    0
    Aphthous ulcer
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 20 (5.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    1 / 89 (1.12%)
    0 / 68 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    1
    0
    Colitis ulcerative
         subjects affected / exposed
    4 / 116 (3.45%)
    0 / 20 (0.00%)
    2 / 40 (5.00%)
    7 / 99 (7.07%)
    6 / 79 (7.59%)
    17 / 100 (17.00%)
    4 / 18 (22.22%)
    11 / 36 (30.56%)
    22 / 89 (24.72%)
    8 / 68 (11.76%)
         occurrences all number
    4
    0
    2
    8
    7
    18
    4
    15
    24
    9
    Diarrhoea
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 20 (0.00%)
    3 / 40 (7.50%)
    3 / 99 (3.03%)
    5 / 79 (6.33%)
    2 / 100 (2.00%)
    0 / 18 (0.00%)
    2 / 36 (5.56%)
    5 / 89 (5.62%)
    1 / 68 (1.47%)
         occurrences all number
    1
    0
    4
    3
    5
    2
    0
    4
    6
    1
    Frequent bowel movements
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    1 / 18 (5.56%)
    1 / 36 (2.78%)
    0 / 89 (0.00%)
    1 / 68 (1.47%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    1
    0
    1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    2 / 40 (5.00%)
    2 / 99 (2.02%)
    1 / 79 (1.27%)
    2 / 100 (2.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences all number
    0
    0
    2
    2
    1
    2
    0
    0
    0
    0
    Haematochezia
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    1 / 99 (1.01%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    1 / 18 (5.56%)
    1 / 36 (2.78%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences all number
    1
    0
    1
    1
    0
    0
    1
    3
    0
    0
    Nausea
         subjects affected / exposed
    4 / 116 (3.45%)
    0 / 20 (0.00%)
    2 / 40 (5.00%)
    4 / 99 (4.04%)
    5 / 79 (6.33%)
    2 / 100 (2.00%)
    1 / 18 (5.56%)
    1 / 36 (2.78%)
    5 / 89 (5.62%)
    1 / 68 (1.47%)
         occurrences all number
    5
    0
    2
    4
    5
    2
    1
    2
    5
    1
    Vomiting
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    3 / 99 (3.03%)
    2 / 79 (2.53%)
    4 / 100 (4.00%)
    1 / 18 (5.56%)
    2 / 36 (5.56%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences all number
    1
    0
    1
    3
    2
    5
    1
    2
    0
    0
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    1 / 116 (0.86%)
    1 / 20 (5.00%)
    0 / 40 (0.00%)
    2 / 99 (2.02%)
    0 / 79 (0.00%)
    2 / 100 (2.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences all number
    1
    1
    0
    2
    0
    3
    0
    0
    0
    0
    Pruritus
         subjects affected / exposed
    2 / 116 (1.72%)
    1 / 20 (5.00%)
    0 / 40 (0.00%)
    1 / 99 (1.01%)
    3 / 79 (3.80%)
    3 / 100 (3.00%)
    1 / 18 (5.56%)
    0 / 36 (0.00%)
    1 / 89 (1.12%)
    2 / 68 (2.94%)
         occurrences all number
    2
    1
    0
    1
    3
    3
    1
    0
    1
    3
    Pruritus generalised
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    1 / 18 (5.56%)
    0 / 36 (0.00%)
    1 / 89 (1.12%)
    0 / 68 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    1
    0
    Rash
         subjects affected / exposed
    3 / 116 (2.59%)
    1 / 20 (5.00%)
    0 / 40 (0.00%)
    4 / 99 (4.04%)
    1 / 79 (1.27%)
    5 / 100 (5.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    1 / 89 (1.12%)
    0 / 68 (0.00%)
         occurrences all number
    3
    1
    0
    4
    1
    6
    0
    0
    2
    0
    Skin ulcer
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    1 / 18 (5.56%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Swelling face
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    1 / 18 (5.56%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Urticaria
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 20 (5.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    1 / 100 (1.00%)
    0 / 18 (0.00%)
    1 / 36 (2.78%)
    1 / 89 (1.12%)
    0 / 68 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    1
    1
    0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    1 / 18 (5.56%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Proteinuria
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    1 / 18 (5.56%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    5 / 116 (4.31%)
    0 / 20 (0.00%)
    4 / 40 (10.00%)
    11 / 99 (11.11%)
    6 / 79 (7.59%)
    11 / 100 (11.00%)
    2 / 18 (11.11%)
    3 / 36 (8.33%)
    9 / 89 (10.11%)
    1 / 68 (1.47%)
         occurrences all number
    6
    0
    4
    18
    6
    11
    2
    3
    11
    1
    Back pain
         subjects affected / exposed
    4 / 116 (3.45%)
    1 / 20 (5.00%)
    0 / 40 (0.00%)
    2 / 99 (2.02%)
    1 / 79 (1.27%)
    5 / 100 (5.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    8 / 89 (8.99%)
    0 / 68 (0.00%)
         occurrences all number
    4
    1
    0
    2
    1
    6
    0
    0
    8
    0
    Joint swelling
         subjects affected / exposed
    1 / 116 (0.86%)
    1 / 20 (5.00%)
    1 / 40 (2.50%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    1 / 100 (1.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    1 / 68 (1.47%)
         occurrences all number
    1
    1
    1
    0
    0
    1
    0
    0
    0
    1
    Rheumatic disorder
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    1 / 18 (5.56%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    Infections and infestations
    Candida infection
         subjects affected / exposed
    0 / 116 (0.00%)
    2 / 20 (10.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    1 / 100 (1.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    1
    0
    0
    0
    0
    Conjunctivitis
         subjects affected / exposed
    1 / 116 (0.86%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    1 / 100 (1.00%)
    1 / 18 (5.56%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    1 / 68 (1.47%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    1
    0
    0
    1
    Gastroenteritis
         subjects affected / exposed
    2 / 116 (1.72%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    4 / 99 (4.04%)
    0 / 79 (0.00%)
    2 / 100 (2.00%)
    0 / 18 (0.00%)
    3 / 36 (8.33%)
    3 / 89 (3.37%)
    1 / 68 (1.47%)
         occurrences all number
    2
    0
    0
    5
    0
    2
    0
    4
    3
    2
    Influenza
         subjects affected / exposed
    4 / 116 (3.45%)
    2 / 20 (10.00%)
    0 / 40 (0.00%)
    2 / 99 (2.02%)
    0 / 79 (0.00%)
    3 / 100 (3.00%)
    1 / 18 (5.56%)
    1 / 36 (2.78%)
    2 / 89 (2.25%)
    0 / 68 (0.00%)
         occurrences all number
    4
    2
    0
    2
    0
    4
    1
    1
    4
    0
    Nasopharyngitis
         subjects affected / exposed
    7 / 116 (6.03%)
    0 / 20 (0.00%)
    6 / 40 (15.00%)
    9 / 99 (9.09%)
    8 / 79 (10.13%)
    9 / 100 (9.00%)
    0 / 18 (0.00%)
    1 / 36 (2.78%)
    5 / 89 (5.62%)
    6 / 68 (8.82%)
         occurrences all number
    7
    0
    6
    10
    9
    13
    0
    1
    10
    10
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 116 (1.72%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    4 / 99 (4.04%)
    1 / 79 (1.27%)
    5 / 100 (5.00%)
    0 / 18 (0.00%)
    2 / 36 (5.56%)
    5 / 89 (5.62%)
    0 / 68 (0.00%)
         occurrences all number
    3
    0
    0
    5
    1
    5
    0
    2
    6
    0
    Urinary tract infection
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    0 / 40 (0.00%)
    3 / 99 (3.03%)
    0 / 79 (0.00%)
    1 / 100 (1.00%)
    1 / 18 (5.56%)
    0 / 36 (0.00%)
    1 / 89 (1.12%)
    1 / 68 (1.47%)
         occurrences all number
    0
    0
    0
    3
    0
    1
    1
    0
    1
    1
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 116 (0.00%)
    0 / 20 (0.00%)
    1 / 40 (2.50%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    1 / 18 (5.56%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    0
    0
    0
    Weight gain poor
         subjects affected / exposed
    0 / 116 (0.00%)
    1 / 20 (5.00%)
    0 / 40 (0.00%)
    0 / 99 (0.00%)
    0 / 79 (0.00%)
    0 / 100 (0.00%)
    0 / 18 (0.00%)
    0 / 36 (0.00%)
    0 / 89 (0.00%)
    0 / 68 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    01 Jun 2012
    Amendment 1 introduced changes that incorporated feedback received from regulatory authorities in Europe and the US. Briefly: - The subject population at study entry was limited to subjects who had an inadequate response to, or intolerance to, immunomodulators or anti-TNF agents. - Methods of birth control were added. - The safety follow-up period was extended from 12 months to 24 months. - Immunomodulators were to be withdrawn in all subjects at week 8. - Recommendations for withdrawal of open-label AMG 181 during the open-label period were added. - The use of concomitant medications during the study was clarified. - Hepatotoxicity rules on stopping of and rechallenge with investigational product were added. - In compliance with a requirement contained in the then-current version of the European Union Clinical Trial Directive, the safety reporting language in Protocol Section 9.2.2 (“Reporting Procedures for Serious Adverse Events”) was updated. The reporting timeline for the investigator to report serious adverse events to Amgen upon knowledge of the event was changed to within 24 hours. Language that limited the types of serious adverse events the investigator was to report to Amgen after the end of study was deleted. - In the statistical considerations section, the statistical method proposed for the primary analysis was changed to an IPW GEE model. The lists of covariates and subgroup analyses were updated. - Other minor changes included corrections of typographical errors and small edits to clarify intent.
    11 Feb 2013
    Amendment 2 introduced the following changes: - The protocol was amended to ensure that the study was adequately sized to evaluate the primary endpoint of the study in light of results from a phase 3 study of vedolizumab in subjects with Ulcerative Colitis (Feagan et al, 2012). The assumptions for sample size were updated accordingly with the type I error rate adjusted to a 2-sided alpha level of 0.10 that resulted in a 14% increase in the study sample size. The enrollment of subjects with any prior exposure to anti-TNF agents was limited to approximately 50% in order to assess the efficacy of AMG 181 in both anti-TNF agent naïve and anti-TNF agent exposed subjects. - Minor updates were made to Section 2 (Background and Rationale). - Minor clarifications and corrections were made to eligibility criteria. - Clarifications and corrections were made to Section 7 (Study Procedures). - Reasons for removal of subjects from the study were updated in Section 8 (Removal and Replacement of Subjects) and Section 9 (Safety Data Collection, Recording, and Reporting). - Updates to Section 9 (Safety Data Collection, Recording, and Reporting) were made to ensure that adverse event reporting and reports of lactation followed the sponsor’s standard procedures. - Typographic and formatting errors were corrected throughout the Protocol.
    25 Sep 2013
    Amendment 3 introduced the following changes: • A systematic misalignment between the IP packaging and the IPIM occurred such that subjects enrolled prior to Protocol Amendment 3 were randomly assigned to treatment groups at ratios different from those stipulated in the Protocol. A higher proportion of subjects received placebo and some subjects received a dose higher than they were randomly assigned. All subjects were expected to have received a dose level defined by the Protocol. No increased safety risks were identified for any subjects. Changes to Statistical Considerations were made as summarized below: - Neither the randomization nor study blind was compromised and the intent-to-treat principle was maintained. The full analysis consisted of all randomized subjects who had received at least 1 dose of IP. Subjects enrolled under Amendment 3 were to be analyzed according to their IVRS randomized treatment group. Subjects enrolled prior to Amendment 3 were to be analyzed according to the randomly assigned yet erroneous treatment as the result of the systemic misalignment. - Due to the unintended difference in the randomization ratio and the disproportion of subjects in treatment arms prior to Amendment 3, a linear trend test was no longer appropriate. The primary and key secondary endpoints were to be tested under a sequential framework for the 2 highest doses of AMG 181. The total sample size of 360 with the unintended final randomization allocation had approximately 87% and 84% power to detect differences between the AMG 181 70 mg and 210 mg groups vs placebo using a 0.10 2-sided test. - The AMG 181 70 mg group vs the placebo group was to be tested prior to AMG 181 210 mg group vs placebo group analyses. • Clarifications to Study Design were done. • Inclusion Criteria were updated such that at non-US sites, subjects who demonstrated an inadequate response to, loss of response to, or intolerance to corticosteroids were to be allowed in the study.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    12 Jul 2013
    Routine PK analyses by the unblended clinical pharmacology group reported a systematic inconsistency in expected exposures for the 7 mg and 21 mg dose cohorts. The study was immediately paused for investigation, which showed a consistent discrepancy between the IP instruction manual (IPIM) description of vial positions and the actual vial positions in the IP package. Once the discrepancy was corrected and affected patients completed their double-blind treatment period, the study resumed enrollment and randomization per protocol.
    06 Dec 2013

    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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