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    Clinical Trial Results:
    A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Efficacy of AMG 181 in Subjects With Moderate to Severe Crohn’s Disease

    Summary
    EudraCT number
    		 2012-000529-31
    Trial protocol
    		 BE   GB   CZ   DK   DE   AT   HU   NL  
    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
    20110232
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01696396
    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
    To evaluate the efficacy of abrilumab (AMG 181) as measured by the proportion of subjects achieving Crohn’s Disease Activity Index (CDAI) remission (CDAI < 150) at week 8.
    Protection of trial subjects
    This study was conducted in accordance with International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) 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 (IP). The IECs and IRBs also reviewed and approved other written subject information, any proposed advertising material, and all subsequent Protocol Amendments and changes to the ICF. 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
    04 Dec 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: 34
    Country: Number of subjects enrolled
    United States: 35
    Country: Number of subjects enrolled
    Austria: 7
    Country: Number of subjects enrolled
    Belgium: 35
    Country: Number of subjects enrolled
    Czech Republic: 26
    Country: Number of subjects enrolled
    Denmark: 7
    Country: Number of subjects enrolled
    France: 30
    Country: Number of subjects enrolled
    Germany: 8
    Country: Number of subjects enrolled
    Hungary: 23
    Country: Number of subjects enrolled
    Netherlands: 28
    Country: Number of subjects enrolled
    Switzerland: 6
    Country: Number of subjects enrolled
    United Kingdom: 15
    Worldwide total number of subjects
    254
    EEA total number of subjects
    179
    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)
    253
    From 65 to 84 years
    1
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 This study was conducted at 84 centers in Canada, European Union, and the United States. Participants were enrolled from 04 December 2012 to 30 September 2014. 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 2:1:2:1 ratio to 1 of 4 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

    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 to abrilumab 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 (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 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 21 mg Q4W/Abrilumab 210 mg Q3M Abrilumab 70 mg Q4W/Abrilumab 210 mg Q3M Abrilumab 210 mg/Abrilumab 210 mg Q3M
    Started
    100
    27
    85
    42
    Received Study Drug
    98
    26
    84
    41
    Entered Open-label Period
    84
    21
    75
    37
    Completed
    69
    20
    59
    28
    Not completed
    31
    7
    26
    14
         Adverse event, serious fatal
    -
    -
    1
    -
         Consent withdrawn by subject
    19
    5
    19
    11
         Decision by Sponsor
    3
    1
    2
    2
         Lost to follow-up
    9
    1
    4
    1

    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 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 (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 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 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
    		 100 27 85 42 254
    Age, Customized
    Units: Subjects
        18 – 64 years
    		 99 27 85 42 253
        ≥ 65 years
    		 1 0 0 0 1
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 36.2 ( 11.2 ) 38.9 ( 14.2 ) 35.6 ( 11.8 ) 36.5 ( 9.4 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 58 12 51 23 144
        Male
    		 42 15 34 19 110
    Race/Ethnicity, Customized
    Units: Subjects
        Asian
    		 0 0 0 1 1
        Black or African American
    		 2 0 0 1 3
        White
    		 97 26 82 40 245
        Other
    		 1 1 3 0 5
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 0 1 0 1 2
        Not Hispanic or Latino
    		 100 26 85 41 252
        Unknown or Not Reported
    		 0 0 0 0 0
    Any Prior Anti-Tumor Necrosis Factor (TNF) Use
    Units: Subjects
        Yes
    		 80 21 67 33 201
        No
    		 20 6 18 9 53
    Enrollment Prior to Protocol Amendment 3
    Units: Subjects
        Yes
    		 44 0 29 16 89
        No
    		 56 27 56 26 165
    Duration of Crohn’s Diease
    Units: years
        arithmetic mean (standard deviation)
    		 11.07 ( 8.33 ) 12.58 ( 9.55 ) 10.69 ( 7.75 ) 11.31 ( 7.54 ) -
    Crohn’s Disease Activity Index (CDAI) Score
    The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with a higher score indicating more-severe disease activity. Patients with scores of > 450 are considered to have very severe disease.
    Units: units on a scale
        arithmetic mean (standard deviation)
    		 303.8 ( 63.2 ) 310.0 ( 83.5 ) 314.0 ( 60.4 ) 319.3 ( 67.5 ) -

    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 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 (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 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 Crohn’s Disease Activity Index (CDAI) score < 150. The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with higher scores indicating more-severe disease activity. 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- vs post-Protocol Amendment 3) and baseline CDAI Score (adjusted remission rate). The full analysis set includes all randomized participants who received at least 1 dose of study drug. Both unadjusted and adjusted 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 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
    98
    26
    84
    41
    Units: percentage of participants
    number (not applicable)
        Unadjusted remission rate
    13.3
    23.1
    14.3
    19.5
        Adjusted remission rate
    12.8
    23.1
    14.4
    21.9
    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 CDAI score and stratification factors (prior vs no prior TNF antagonist use and enrollment pre- vs post-protocol amendment).
    Comparison groups
    Abrilumab 70 mg Q4W/Abrilumab 210 mg Q3M v Placebo/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    182
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 = 0.76 [2]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.15
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.54
         upper limit
    		 2.44
    Notes
    [1] - The study was powered for formal statistical testing of the abrilumab 70 mg group. The primary and key secondary endpoints were tested under a sequential framework of statistical hypotheses, each with 2-sided significance level of 0.10 for the treatment effect of abrilumab 70 mg compared with placebo.
    [2] - Adjusted for baseline CDAI 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 CDAI 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
    182
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in Adjusted Remission Rates
    Point estimate
    1.6
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -7.9
         upper limit
    		 8.9
    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 CDAI 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
    139
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 = 0.22 [4]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.91
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.8
         upper limit
    		 4.57
    Notes
    [3] - Analysis was not part of the formal testing
    [4] - Adjusted for baseline CDAI 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 CDAI 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
    139
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [5]
    Method
    Parameter type
    		 Difference in Adjusted Remission Rates
    Point estimate
    9.1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -4.6
         upper limit
    		 19.4
    Notes
    [5] - 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 estimated from a logistic regression model adjusted for baseline CDAI 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
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [6]
    P-value
    		 = 0.25 [7]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.05
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.74
         upper limit
    		 5.73
    Notes
    [6] - Analysis was not part of the formal testing
    [7] - Adjusted for baseline CDAI 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 CDAI 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
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [8]
    Method
    Parameter type
    		 Difference in Adjusted Remission Rates
    Point estimate
    10.3
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -6.8
         upper limit
    		 22.6
    Notes
    [8] - Analysis was not part of the formal testing

    Secondary: Percentage of Participants with Remission at Week 12

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    End point title
    		 Percentage of Participants with Remission at Week 12
    End point description
    Remission was defined as a CDAI score < 150. The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with higher scores indicating more-severe disease activity. 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- vs post-Protocol Amendment 3) and baseline CDAI Score (adjusted remission 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
    Week 12
    End point values
    		 Placebo/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
    98
    26
    84
    41
    Units: percentage of participants
    number (not applicable)
        Unadjusted remission rate
    18.1
    33.3
    25.3
    27.0
        Adjusted remission rate
    20.1
    43.8
    31.0
    34.8
    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 CDAI 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
    182
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.16 [9]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.78
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 3.53
    Notes
    [9] - Adjusted for baseline CDAI 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 CDAI 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
    182
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in Adjusted Remission Rates
    Point estimate
    10.9
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -1.8
         upper limit
    		 21
    Statistical analysis title
    		 Comparison of Abriumab vs Placebo
    Statistical analysis description
    Comparisons between treatment groups were made using remission rates estimated from a logistic regression model adjusted for baseline CDAI 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
    139
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [10]
    P-value
    		 = 0.13 [11]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.12
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.93
         upper limit
    		 4.84
    Notes
    [10] - Analysis was not part of the formal testing
    [11] - Adjusted for baseline CDAI 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 CDAI 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
    139
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [12]
    Method
    Parameter type
    		 Difference in Adjusted Remission Rates
    Point estimate
    14.7
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -2.1
         upper limit
    		 27.5
    Notes
    [12] - 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 estimated from a logistic regression model adjusted for baseline CDAI 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
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [13]
    P-value
    		 = 0.056 [14]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.17
         upper limit
    		 8.2
    Notes
    [13] - Analysis was not part of the formal testing
    [14] - Adjusted for baseline CDAI 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 CDAI 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
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [15]
    Method
    Parameter type
    		 Difference in Adjusted Remission Rates
    Point estimate
    23.7
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 2.8
         upper limit
    		 39.2
    Notes
    [15] - Analysis was not part of the formal testing

    Secondary: Percentage of Participants with Response at Week 12

    		 Close Top of page
    End point title
    		 Percentage of Participants with Response at Week 12
    End point description
    Response was defined as either remission (CDAI score < 150) or a decrease from baseline in CDAI score of ≥ 100 points. The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with higher scores indicating more-severe disease activity. 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 CDAI score (adjusted response rate). The full analysis set was used in the analysis; both unadjusted and adjusted response rates were calculated using non-responder imputation.
    End point type
    Secondary
    End point timeframe
    Baseline and week 12
    End point values
    		 Placebo/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
    98
    26
    84
    41
    Units: percentage of participants
    number (not applicable)
        Unadjusted response rate
    27.7
    41.7
    45.3
    43.2
        Adjusted response rate
    35.3
    50.4
    55.1
    50.9
    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 CDAI 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
    182
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.021 [16]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.25
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.27
         upper limit
    		 4.01
    Notes
    [16] - Adjusted for baseline CDAI score and stratification factors.
    Statistical analysis title
    		 Difference in Response Rates
    Statistical analysis description
    The difference in response rates, estimated from a logistic regression model adjusted for baseline CDAI 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
    182
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in Adjusted Response Rates
    Point estimate
    19.8
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 5.8
         upper limit
    		 31.3
    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 CDAI 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
    139
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [17]
    P-value
    		 = 0.14 [18]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.9
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.94
         upper limit
    		 3.87
    Notes
    [17] - Analysis was not part of the formal testing
    [18] - Adjusted for baseline CDAI score and stratification factors.
    Statistical analysis title
    		 Difference in Response Rates
    Statistical analysis description
    The difference in response rates, estimated from a logistic regression model adjusted for baseline CDAI 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
    139
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [19]
    Method
    Parameter type
    		 Difference in Adjusted Response Rates
    Point estimate
    15.7
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -2.3
         upper limit
    		 29.7
    Notes
    [19] - 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 estimated from a logistic regression model adjusted for baseline CDAI 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
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [20]
    P-value
    		 = 0.23 [21]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.87
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.79
         upper limit
    		 4.39
    Notes
    [20] - Analysis was not part of the formal testing
    [21] - Adjusted for baseline CDAI score and stratification factors.
    Statistical analysis title
    		 Difference in Response Rates
    Statistical analysis description
    The difference in response rates, estimated from a logistic regression model adjusted for baseline CDAI 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
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [22]
    Method
    Parameter type
    		 Difference in Adjusted Response Rates
    Point estimate
    15.1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -6.4
         upper limit
    		 31.3
    Notes
    [22] - 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 as either remission (CDAI score < 150) or a decrease from baseline in CDAI score of ≥ 100 points. The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with higher scores indicating more-severe disease activity. 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 CDAI score (adjusted response rate). The full analysis set was used in the analysis; 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 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
    98
    26
    84
    41
    Units: percentage of participants
    number (not applicable)
        Unadjusted response rate
    26.4
    33.3
    42.9
    30.6
        Adjusted response rate
    30.6
    33.8
    46.6
    32.6
    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 CDAI 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
    182
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.047 [23]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.98
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.13
         upper limit
    		 3.47
    Notes
    [23] - Adjusted for baseline CDAI score and stratification factors.
    Statistical analysis title
    		 Difference in Response Rates
    Statistical analysis description
    The difference in response rates, estimated from a logistic regression model adjusted for baseline CDAI 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
    182
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in Adjusted Response Rates
    Point estimate
    16
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 2.4
         upper limit
    		 27.1
    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 CDAI 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
    139
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [24]
    P-value
    		 = 0.84 [25]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.09
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.52
         upper limit
    		 2.29
    Notes
    [24] - Analysis was not part of the formal testing
    [25] - Adjusted for baseline CDAI score and stratification factors.
    Statistical analysis title
    		 Difference in Response Rates
    Statistical analysis description
    The difference in response rates, estimated from a logistic regression model adjusted for baseline CDAI 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
    139
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [26]
    Method
    Parameter type
    		 Difference in Adjusted Response Rates
    Point estimate
    1.9
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -15.2
         upper limit
    		 15.2
    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 response rates estimated from a logistic regression model adjusted for baseline CDAI 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
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [27]
    P-value
    		 = 0.78 [28]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.15
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.49
         upper limit
    		 2.72
    Notes
    [27] - Analysis was not part of the formal testing
    [28] - Adjusted for baseline CDAI score and stratification factors.
    Statistical analysis title
    		 Difference in Response Rates
    Statistical analysis description
    The difference in response rates, estimated from a logistic regression model adjusted for baseline CDAI 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
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [29]
    Method
    Parameter type
    		 Difference in Adjusted Response Rates
    Point estimate
    3.1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -17.4
         upper limit
    		 18.3
    Notes
    [29] - Analysis was not part of the formal testing

    Secondary: Percentage of Participants with Sustained Remission at Both Week 12 and Week 24

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    End point title
    		 Percentage of Participants with Sustained Remission at Both Week 12 and Week 24
    End point description
    Remission was defined as a CDAI score < 150. Sustained remission was defined as achieving remission at both week 12 and week 24. CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, general well-being, presence or absence of extra-intestinal manifestations or fistula, use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600 with higher scores indicating more-severe disease activity. 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 CDAI score (adjusted remission rate). The full analysis set was used for the analysis; both unadjusted and adjusted sustained remission rates were calculated using non-responder imputation.
    End point type
    Secondary
    End point timeframe
    Week 12 and week 24
    End point values
    		 Placebo/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
    98
    26
    84
    41
    Units: percentage of participants
    number (not applicable)
        Unadjusted remission rate
    8.2
    19.2
    11.9
    17.1
        Adjusted remission rate
    9.0
    25.0
    14.0
    21.7
    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 CDAI 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
    182
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.34 [30]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.65
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.69
         upper limit
    		 3.91
    Notes
    [30] - Adjusted for baseline CDAI score and stratification factors.
    Statistical analysis title
    		 Difference is Sustained Remission Rates
    Statistical analysis description
    The difference in sustained remission rates, estimated from a logistic regression model adjusted for baseline CDAI 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
    182
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in Adjusted Remission Rates
    Point estimate
    5
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -3.9
         upper limit
    		 11.7
    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 CDAI 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
    139
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [31]
    P-value
    		 = 0.078 [32]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.82
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.07
         upper limit
    		 7.41
    Notes
    [31] - Analysis was not part of the formal testing
    [32] - Adjusted for baseline CDAI score and stratification factors.
    Statistical analysis title
    		 Difference is Sustained Remission Rates
    Statistical analysis description
    The difference in sustained remission rates, estimated from a logistic regression model adjusted for baseline CDAI 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
    139
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [33]
    Method
    Parameter type
    		 Difference in Adjusted Remission Rates
    Point estimate
    12.8
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.6
         upper limit
    		 22.6
    Notes
    [33] - 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 estimated from a logistic regression model adjusted for baseline CDAI 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
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [34]
    P-value
    		 = 0.083 [35]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.37
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.07
         upper limit
    		 10.66
    Notes
    [34] - Analysis was not part of the formal testing
    [35] - Adjusted for baseline CDAI score and stratification factors.
    Statistical analysis title
    		 Difference is Sustained Remission Rates
    Statistical analysis description
    The difference in sustained remission rates, estimated from a logistic regression model adjusted for baseline CDAI 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
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [36]
    Method
    Parameter type
    		 Difference in Adjusted Remission Rates
    Point estimate
    16
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -1.2
         upper limit
    		 28.3
    Notes
    [36] - Analysis was not part of the formal testing

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

    		 Close Top of page
    End point title
    		 Percentage of Participants with Sustained Remission at Both Week 8 and Week 24
    End point description
    Remission was defined as a CDAI score < 150. Sustained remission was defined as achieving remission at both week 8 and week 24. CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, general well-being, presence or absence of extra-intestinal manifestations or fistula, use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600 with higher scores indicating more-severe disease activity. 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 CDAI score (adjusted remission rate). The full analysis set was used for the analysis; both unadjusted and adjusted sustained 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 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
    98
    26
    84
    41
    Units: percentage of participants
    number (not applicable)
        Unadjusted remission rate
    7.1
    15.4
    9.5
    12.2
        Adjusted remission rate
    5.9
    14.3
    8.7
    12.7
    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 CDAI 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
    182
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.47 [37]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.52
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.59
         upper limit
    		 3.93
    Notes
    [37] - Adjusted for baseline CDAI score and stratification factors.
    Statistical analysis title
    		 Difference is Sustained Remission Rates
    Statistical analysis description
    The difference in sustained remission rates, estimated from a logistic regression model adjusted for baseline CDAI 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
    182
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in Adjusted Remission Rates
    Point estimate
    2.8
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -4.7
         upper limit
    		 8.1
    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 CDAI 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
    139
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [38]
    P-value
    		 = 0.21 [39]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.32
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.77
         upper limit
    		 6.98
    Notes
    [38] - Analysis was not part of the formal testing
    [39] - Adjusted for baseline CDAI score and stratification factors.
    Statistical analysis title
    		 Difference is Sustained Remission Rates
    Statistical analysis description
    The difference in sustained remission rates, estimated from a logistic regression model adjusted for baseline CDAI 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
    139
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [40]
    Method
    Parameter type
    		 Difference in Adjusted Remission Rates
    Point estimate
    6.8
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -4.3
         upper limit
    		 14.5
    Notes
    [40] - 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 estimated from a logistic regression model adjusted for baseline CDAI 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
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [41]
    P-value
    		 = 0.21 [42]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.66
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 9.45
    Notes
    [41] - Analysis was not part of the formal testing
    [42] - Adjusted for baseline CDAI score and stratification factors.
    Statistical analysis title
    		 Difference is Sustained Remission Rates
    Statistical analysis description
    The difference in sustained remission rates, estimated from a logistic regression model adjusted for baseline CDAI 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
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [43]
    Method
    Parameter type
    		 Difference in Adjusted Remission Rates
    Point estimate
    8.4
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -6
         upper limit
    		 17.9
    Notes
    [43] - Analysis was not part of the formal testing

    Secondary: Change from Baseline in CDAI Score at Week 12

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    End point title
    		 Change from Baseline in CDAI Score at Week 12
    End point description
    The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with a higher score indicating more-severe disease activity. The full analysis set was used in the analysis; missing data were handled using the inverse probability weighting (IPW) method.
    End point type
    Secondary
    End point timeframe
    Baseline and week 12
    End point values
    		 Placebo/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
    98
    26
    84
    41
    Units: units on a scale
        least squares mean (standard error)
    -55.32 ( 11.41 )
    -92.16 ( 21.85 )
    -97.41 ( 12.92 )
    -96.11 ( 22.78 )
    Statistical analysis title
    		 Comparison of Abrilumab vs Placebo
    Statistical analysis description
    Comparisons between treatment arms was conducted using an inverse probability weighting (IPW) generalized estimating equations (GEE) model adjusted for prior anti-TNF use, pre-versus post-protocol amendment 3 and baseline CDAI score.
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 70 mg Q4W/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    182
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.006
    Method
    		 IPW GEE Model
    Parameter type
    		 LS Mean Treatment Difference
    Point estimate
    -42.09
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -67.3
         upper limit
    		 -16.9
    Statistical analysis title
    		 Comparison of Abrilumab vs Placebo
    Statistical analysis description
    Comparisons between treatment arms was conducted using an inverse probability weighting (IPW) generalized estimating equations (GEE) model adjusted for prior anti-TNF use, pre-versus post-protocol amendment 3 and baseline CDAI score.
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 210 mg/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [44]
    P-value
    		 = 0.095
    Method
    		 IPW GEE Model
    Parameter type
    		 LS Mean Treatment Difference
    Point estimate
    -40.79
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -81.5
         upper limit
    		 -0.5
    Notes
    [44] - Analysis was not part of the formal testing
    Statistical analysis title
    		 Comparison of Abrilumab vs Placebo
    Statistical analysis description
    Comparisons between treatment arms was conducted using an inverse probability weighting (IPW) generalized estimating equations (GEE) model adjusted for prior anti-TNF use, pre-versus post-protocol amendment 3 and baseline CDAI score.
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 21 mg Q4W/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [45]
    P-value
    		 = 0.11
    Method
    		 IPW GEE Model
    Parameter type
    		 LS Mean Treatment Difference
    Point estimate
    -36.84
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -74.3
         upper limit
    		 0.7
    Notes
    [45] - Analysis was not part of the formal testing

    Secondary: Change from Baseline in CDAI Score at Week 8

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    End point title
    		 Change from Baseline in CDAI Score at Week 8
    End point description
    The CDAI is a weighted, composite index of 8 disease variables (stool frequency, severity of abdominal pain, degree of general well-being, presence or absence of extra-intestinal manifestations or fistula, use or non-use of antidiarrheal agents, presence or absence of an abdominal mass, hematocrit, and body weight). Scores range from approximately 0 to 600, with a higher score indicating more-severe disease activity. The full analysis set was used for the analysis; missing data were handled using the inverse probability weighting (IPW) method.
    End point type
    Secondary
    End point timeframe
    Baseline and week 8
    End point values
    		 Placebo/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
    98
    26
    84
    41
    Units: units on a scale
        least squares mean (standard error)
    -64.05 ( 9.62 )
    -80.42 ( 20.86 )
    -91.52 ( 11.78 )
    -87.64 ( 19.89 )
    Statistical analysis title
    		 Comparison of Abrilumab vs Placebo
    Statistical analysis description
    Comparisons between treatment arms was conducted using an inverse probability weighting (IPW) generalized estimating equations (GEE) model adjusted for prior anti-TNF use, pre-versus post-protocol amendment 3 and baseline CDAI score.
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 70 mg Q4W/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    182
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.045
    Method
    		 IPW GEE Model
    Parameter type
    		 LS Mean Treatment Difference
    Point estimate
    -27.47
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -50
         upper limit
    		 -4.9
    Statistical analysis title
    		 Comparison of Abrilumab vs Placebo
    Statistical analysis description
    Comparisons between treatment arms was conducted using an inverse probability weighting (IPW) generalized estimating equations (GEE) model adjusted for prior anti-TNF use, pre-versus post-protocol amendment 3 and baseline CDAI score.
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 21 mg Q4W/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [46]
    P-value
    		 = 0.45
    Method
    		 IPW GEE Model
    Parameter type
    		 LS Mean Treatment Difference
    Point estimate
    -16.37
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -51.8
         upper limit
    		 19.1
    Notes
    [46] - Analysis was not part of the formal testing
    Statistical analysis title
    		 Comparison of Abrilumab vs Placebo
    Statistical analysis description
    Comparisons between treatment arms was conducted using an inverse probability weighting (IPW) generalized estimating equations (GEE) model adjusted for prior anti-TNF use, pre-versus post-protocol amendment 3 and baseline CDAI score.
    Comparison groups
    Placebo/Abrilumab 210 mg Q3M v Abrilumab 210 mg/Abrilumab 210 mg Q3M
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [47]
    P-value
    		 = 0.27
    Method
    		 IPW GEE Model
    Parameter type
    		 LS Mean Treatment Difference
    Point estimate
    -23.59
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -58.7
         upper limit
    		 11.5
    Notes
    [47] - 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.
    Adverse event reporting additional description
    One participant randomized to the 21 mg abrilumab treatment group received 70 mg abrilumab in error and is counted in that group for safety analyses in both treatment periods.
    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 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 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 21 mg Q4W DB Period: Abrilumab 70 mg Q4W DB Period: Abrilumab 210 mg OL Period: Placebo/Abrilumab 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 / 98 (14.29%)
    7 / 25 (28.00%)
    13 / 85 (15.29%)
    6 / 41 (14.63%)
    24 / 84 (28.57%)
    3 / 20 (15.00%)
    19 / 76 (25.00%)
    12 / 37 (32.43%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    1
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Chronic myeloid leukaemia
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    1 / 76 (1.32%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Surgical and medical procedures
    Cholecystectomy
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    1 / 76 (1.32%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    Ileocolectomy
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    1 / 84 (1.19%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Scoliosis surgery
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    1 / 84 (1.19%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    General disorders and administration site conditions
    Adverse drug reaction
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    1 / 37 (2.70%)
         occurrences causally related to treatment / all
    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
    Chills
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    1 / 76 (1.32%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Influenza like illness
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    1 / 76 (1.32%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    1 / 84 (1.19%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Pyrexia
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Social circumstances
    Aborted pregnancy
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    1 / 85 (1.18%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Reproductive system and breast disorders
    Cervical dysplasia
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    1 / 76 (1.32%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Respiratory, thoracic and mediastinal disorders
    Pleuritic pain
         subjects affected / exposed
    0 / 98 (0.00%)
    1 / 25 (4.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Injury, poisoning and procedural complications
    Anastomotic leak
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    1 / 37 (2.70%)
         occurrences causally related to treatment / all
    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
    Clavicle fracture
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Intestinal anastomosis complication
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    1 / 84 (1.19%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    1 / 76 (1.32%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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 / 1
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    1 / 76 (1.32%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    1 / 1
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    1 / 84 (1.19%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Myocardial ischaemia
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    1 / 76 (1.32%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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 / 1
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Transient ischaemic attack
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    1 / 37 (2.70%)
         occurrences causally related to treatment / all
    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
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    1 / 41 (2.44%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Gastrointestinal disorders
    Abdominal hernia
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    1 / 37 (2.70%)
         occurrences causally related to treatment / all
    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
    Abdominal pain
         subjects affected / exposed
    0 / 98 (0.00%)
    1 / 25 (4.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    1 / 76 (1.32%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain lower
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    1 / 84 (1.19%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Anal fistula
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    1 / 85 (1.18%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    1 / 76 (1.32%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    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
    Chronic gastritis
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    1 / 84 (1.19%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Constipation
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    1 / 41 (2.44%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Crohn's disease
         subjects affected / exposed
    9 / 98 (9.18%)
    4 / 25 (16.00%)
    3 / 85 (3.53%)
    2 / 41 (4.88%)
    9 / 84 (10.71%)
    2 / 20 (10.00%)
    8 / 76 (10.53%)
    6 / 37 (16.22%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 4
    1 / 3
    0 / 2
    1 / 13
    1 / 2
    2 / 8
    2 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    1 / 84 (1.19%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Enterocolonic fistula
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    1 / 76 (1.32%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Ileal stenosis
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    2 / 84 (2.38%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    1 / 37 (2.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    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
    Ileus
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    1 / 85 (1.18%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    1 / 76 (1.32%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    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
    Intestinal obstruction
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    1 / 85 (1.18%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Large intestine perforation
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    1 / 84 (1.19%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Small intestinal obstruction
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 25 (0.00%)
    3 / 85 (3.53%)
    1 / 41 (2.44%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    1 / 76 (1.32%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    0 / 1
    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
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    1 / 76 (1.32%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Biliary colic
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    1 / 84 (1.19%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Drug-induced liver injury
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    1 / 84 (1.19%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Hepatic function abnormal
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Renal and urinary disorders
    Nephritis
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    1 / 41 (2.44%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Nephrolithiasis
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    1 / 84 (1.19%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Infections and infestations
    Abdominal abscess
         subjects affected / exposed
    0 / 98 (0.00%)
    1 / 25 (4.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    1 / 84 (1.19%)
    0 / 20 (0.00%)
    1 / 76 (1.32%)
    1 / 37 (2.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal wall abscess
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 25 (0.00%)
    1 / 85 (1.18%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    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
    Abscess intestinal
         subjects affected / exposed
    0 / 98 (0.00%)
    1 / 25 (4.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Anal abscess
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    1 / 85 (1.18%)
    0 / 41 (0.00%)
    1 / 84 (1.19%)
    0 / 20 (0.00%)
    3 / 76 (3.95%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    3 / 4
    0 / 0
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis perforated
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    1 / 76 (1.32%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Clostridium difficile colitis
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Clostridium difficile infection
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    1 / 84 (1.19%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    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
    Erysipelas
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    1 / 84 (1.19%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Escherichia sepsis
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Escherichia urinary tract infection
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    1 / 76 (1.32%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    External ear cellulitis
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    1 / 76 (1.32%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Gastroenteritis
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    1 / 84 (1.19%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Gastroenteritis viral
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    1 / 85 (1.18%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Influenza
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    1 / 84 (1.19%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Intrauterine infection
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    1 / 37 (2.70%)
         occurrences causally related to treatment / all
    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
    Necrotising fasciitis
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    1 / 37 (2.70%)
         occurrences causally related to treatment / all
    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
    Pelvic abscess
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    1 / 76 (1.32%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Perineal abscess
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    1 / 85 (1.18%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Pneumonia parainfluenzae viral
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    1 / 85 (1.18%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Postoperative wound infection
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    1 / 85 (1.18%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Psoas abscess
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Retroperitoneal abscess
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    1 / 37 (2.70%)
         occurrences causally related to treatment / all
    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
    Septic shock
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    1 / 37 (2.70%)
         occurrences causally related to treatment / all
    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
    Tubo-ovarian abscess
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    1 / 76 (1.32%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Urinary tract infection
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    0 / 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
    Vulval abscess
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    1 / 85 (1.18%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    1 / 76 (1.32%)
    0 / 37 (0.00%)
         occurrences causally related to treatment / all
    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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 DB Period: Placebo 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 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
    61 / 98 (62.24%)
    14 / 25 (56.00%)
    48 / 85 (56.47%)
    27 / 41 (65.85%)
    61 / 84 (72.62%)
    16 / 20 (80.00%)
    55 / 76 (72.37%)
    28 / 37 (75.68%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 98 (2.04%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    1 / 41 (2.44%)
    1 / 84 (1.19%)
    0 / 20 (0.00%)
    1 / 76 (1.32%)
    2 / 37 (5.41%)
         occurrences all number
    2
    0
    0
    1
    1
    0
    1
    2
    Surgical and medical procedures
    Female sterilisation
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    2 / 98 (2.04%)
    1 / 25 (4.00%)
    1 / 85 (1.18%)
    1 / 41 (2.44%)
    5 / 84 (5.95%)
    0 / 20 (0.00%)
    1 / 76 (1.32%)
    2 / 37 (5.41%)
         occurrences all number
    2
    1
    1
    1
    5
    0
    1
    2
    Fatigue
         subjects affected / exposed
    4 / 98 (4.08%)
    1 / 25 (4.00%)
    2 / 85 (2.35%)
    3 / 41 (7.32%)
    3 / 84 (3.57%)
    0 / 20 (0.00%)
    1 / 76 (1.32%)
    0 / 37 (0.00%)
         occurrences all number
    5
    1
    2
    4
    3
    0
    1
    0
    Influenza like illness
         subjects affected / exposed
    4 / 98 (4.08%)
    3 / 25 (12.00%)
    4 / 85 (4.71%)
    0 / 41 (0.00%)
    5 / 84 (5.95%)
    1 / 20 (5.00%)
    7 / 76 (9.21%)
    3 / 37 (8.11%)
         occurrences all number
    4
    3
    6
    0
    5
    2
    9
    4
    Malaise
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    1 / 85 (1.18%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    2 / 76 (2.63%)
    0 / 37 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    2
    0
    Oedema peripheral
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 25 (0.00%)
    1 / 85 (1.18%)
    3 / 41 (7.32%)
    1 / 84 (1.19%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    1 / 37 (2.70%)
         occurrences all number
    1
    0
    1
    3
    1
    1
    0
    1
    Pain
         subjects affected / exposed
    2 / 98 (2.04%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    1
    0
    0
    Pyrexia
         subjects affected / exposed
    2 / 98 (2.04%)
    2 / 25 (8.00%)
    4 / 85 (4.71%)
    2 / 41 (4.88%)
    4 / 84 (4.76%)
    3 / 20 (15.00%)
    2 / 76 (2.63%)
    5 / 37 (13.51%)
         occurrences all number
    3
    2
    4
    2
    5
    3
    4
    8
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    1 / 41 (2.44%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 25 (0.00%)
    1 / 85 (1.18%)
    1 / 41 (2.44%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    1
    0
    1
    1
    0
    1
    0
    0
    Hiccups
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    3 / 98 (3.06%)
    0 / 25 (0.00%)
    4 / 85 (4.71%)
    2 / 41 (4.88%)
    4 / 84 (4.76%)
    1 / 20 (5.00%)
    1 / 76 (1.32%)
    3 / 37 (8.11%)
         occurrences all number
    3
    0
    4
    2
    5
    1
    1
    3
    Pneumothorax
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    2 / 98 (2.04%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    1 / 41 (2.44%)
    1 / 84 (1.19%)
    2 / 20 (10.00%)
    2 / 76 (2.63%)
    3 / 37 (8.11%)
         occurrences all number
    2
    0
    0
    1
    1
    2
    2
    3
    Insomnia
         subjects affected / exposed
    3 / 98 (3.06%)
    1 / 25 (4.00%)
    1 / 85 (1.18%)
    0 / 41 (0.00%)
    3 / 84 (3.57%)
    0 / 20 (0.00%)
    5 / 76 (6.58%)
    2 / 37 (5.41%)
         occurrences all number
    3
    1
    1
    0
    3
    0
    5
    3
    Restlessness
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    0
    Investigations
    Blood iron decreased
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    3
    0
    0
    Blood urea increased
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Clostridium test positive
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    1 / 84 (1.19%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    7 / 98 (7.14%)
    1 / 25 (4.00%)
    4 / 85 (4.71%)
    2 / 41 (4.88%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    2 / 76 (2.63%)
    1 / 37 (2.70%)
         occurrences all number
    10
    1
    6
    2
    0
    0
    2
    1
    Headache
         subjects affected / exposed
    11 / 98 (11.22%)
    4 / 25 (16.00%)
    12 / 85 (14.12%)
    8 / 41 (19.51%)
    7 / 84 (8.33%)
    3 / 20 (15.00%)
    2 / 76 (2.63%)
    3 / 37 (8.11%)
         occurrences all number
    12
    6
    15
    10
    10
    4
    3
    3
    Memory impairment
         subjects affected / exposed
    2 / 98 (2.04%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    1 / 84 (1.19%)
    1 / 20 (5.00%)
    1 / 76 (1.32%)
    0 / 37 (0.00%)
         occurrences all number
    2
    0
    0
    0
    1
    1
    1
    0
    Nervous system disorder
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Paraesthesia
         subjects affected / exposed
    2 / 98 (2.04%)
    2 / 25 (8.00%)
    7 / 85 (8.24%)
    2 / 41 (4.88%)
    4 / 84 (4.76%)
    0 / 20 (0.00%)
    1 / 76 (1.32%)
    2 / 37 (5.41%)
         occurrences all number
    2
    2
    9
    2
    4
    0
    2
    2
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    3 / 84 (3.57%)
    2 / 20 (10.00%)
    3 / 76 (3.95%)
    1 / 37 (2.70%)
         occurrences all number
    1
    0
    0
    0
    4
    2
    3
    1
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    1 / 41 (2.44%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 25 (0.00%)
    1 / 85 (1.18%)
    3 / 41 (7.32%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    1 / 76 (1.32%)
    2 / 37 (5.41%)
         occurrences all number
    1
    0
    1
    3
    0
    0
    1
    2
    Abdominal pain
         subjects affected / exposed
    9 / 98 (9.18%)
    1 / 25 (4.00%)
    8 / 85 (9.41%)
    1 / 41 (2.44%)
    9 / 84 (10.71%)
    2 / 20 (10.00%)
    10 / 76 (13.16%)
    2 / 37 (5.41%)
         occurrences all number
    10
    1
    8
    2
    10
    2
    10
    2
    Anal fistula
         subjects affected / exposed
    0 / 98 (0.00%)
    1 / 25 (4.00%)
    1 / 85 (1.18%)
    0 / 41 (0.00%)
    3 / 84 (3.57%)
    0 / 20 (0.00%)
    1 / 76 (1.32%)
    2 / 37 (5.41%)
         occurrences all number
    0
    1
    1
    0
    3
    0
    1
    2
    Constipation
         subjects affected / exposed
    2 / 98 (2.04%)
    1 / 25 (4.00%)
    1 / 85 (1.18%)
    2 / 41 (4.88%)
    2 / 84 (2.38%)
    1 / 20 (5.00%)
    2 / 76 (2.63%)
    1 / 37 (2.70%)
         occurrences all number
    2
    1
    5
    3
    5
    1
    3
    1
    Crohn's disease
         subjects affected / exposed
    8 / 98 (8.16%)
    1 / 25 (4.00%)
    2 / 85 (2.35%)
    2 / 41 (4.88%)
    14 / 84 (16.67%)
    1 / 20 (5.00%)
    12 / 76 (15.79%)
    3 / 37 (8.11%)
         occurrences all number
    8
    1
    2
    2
    15
    1
    15
    4
    Diarrhoea
         subjects affected / exposed
    2 / 98 (2.04%)
    0 / 25 (0.00%)
    4 / 85 (4.71%)
    2 / 41 (4.88%)
    5 / 84 (5.95%)
    0 / 20 (0.00%)
    5 / 76 (6.58%)
    2 / 37 (5.41%)
         occurrences all number
    2
    0
    4
    2
    5
    0
    6
    2
    Gastrointestinal fistula
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Nausea
         subjects affected / exposed
    8 / 98 (8.16%)
    1 / 25 (4.00%)
    2 / 85 (2.35%)
    3 / 41 (7.32%)
    7 / 84 (8.33%)
    2 / 20 (10.00%)
    5 / 76 (6.58%)
    4 / 37 (10.81%)
         occurrences all number
    8
    1
    2
    3
    8
    4
    5
    5
    Oral discomfort
         subjects affected / exposed
    0 / 98 (0.00%)
    1 / 25 (4.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    0
    0
    Proctalgia
         subjects affected / exposed
    2 / 98 (2.04%)
    1 / 25 (4.00%)
    1 / 85 (1.18%)
    1 / 41 (2.44%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    1 / 37 (2.70%)
         occurrences all number
    2
    2
    1
    2
    0
    2
    0
    1
    Toothache
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    1 / 41 (2.44%)
    1 / 84 (1.19%)
    2 / 20 (10.00%)
    0 / 76 (0.00%)
    2 / 37 (5.41%)
         occurrences all number
    1
    0
    0
    1
    2
    2
    0
    2
    Vomiting
         subjects affected / exposed
    3 / 98 (3.06%)
    0 / 25 (0.00%)
    3 / 85 (3.53%)
    3 / 41 (7.32%)
    5 / 84 (5.95%)
    2 / 20 (10.00%)
    2 / 76 (2.63%)
    2 / 37 (5.41%)
         occurrences all number
    3
    0
    3
    3
    6
    2
    3
    2
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    2 / 98 (2.04%)
    2 / 25 (8.00%)
    0 / 85 (0.00%)
    1 / 41 (2.44%)
    1 / 84 (1.19%)
    0 / 20 (0.00%)
    1 / 76 (1.32%)
    1 / 37 (2.70%)
         occurrences all number
    2
    2
    0
    2
    1
    0
    1
    1
    Hyperhidrosis
         subjects affected / exposed
    1 / 98 (1.02%)
    1 / 25 (4.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    1 / 84 (1.19%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    1
    1
    0
    0
    1
    1
    0
    0
    Pruritus
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    1 / 41 (2.44%)
    2 / 84 (2.38%)
    1 / 20 (5.00%)
    2 / 76 (2.63%)
    0 / 37 (0.00%)
         occurrences all number
    1
    0
    0
    1
    2
    1
    2
    0
    Rash
         subjects affected / exposed
    2 / 98 (2.04%)
    1 / 25 (4.00%)
    0 / 85 (0.00%)
    1 / 41 (2.44%)
    6 / 84 (7.14%)
    0 / 20 (0.00%)
    2 / 76 (2.63%)
    4 / 37 (10.81%)
         occurrences all number
    2
    1
    0
    1
    7
    0
    2
    4
    Rash maculo-papular
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    1 / 37 (2.70%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    1
    Skin ulcer
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    1
    0
    0
    Urinary incontinence
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    10 / 98 (10.20%)
    1 / 25 (4.00%)
    8 / 85 (9.41%)
    3 / 41 (7.32%)
    5 / 84 (5.95%)
    2 / 20 (10.00%)
    7 / 76 (9.21%)
    5 / 37 (13.51%)
         occurrences all number
    12
    1
    10
    5
    8
    2
    8
    5
    Arthritis
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 25 (0.00%)
    1 / 85 (1.18%)
    0 / 41 (0.00%)
    2 / 84 (2.38%)
    1 / 20 (5.00%)
    1 / 76 (1.32%)
    0 / 37 (0.00%)
         occurrences all number
    1
    0
    1
    0
    2
    1
    1
    0
    Back pain
         subjects affected / exposed
    4 / 98 (4.08%)
    0 / 25 (0.00%)
    1 / 85 (1.18%)
    0 / 41 (0.00%)
    1 / 84 (1.19%)
    1 / 20 (5.00%)
    3 / 76 (3.95%)
    1 / 37 (2.70%)
         occurrences all number
    4
    0
    1
    0
    1
    2
    3
    1
    Muscle spasms
         subjects affected / exposed
    1 / 98 (1.02%)
    2 / 25 (8.00%)
    0 / 85 (0.00%)
    2 / 41 (4.88%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    1 / 37 (2.70%)
         occurrences all number
    1
    2
    0
    2
    0
    1
    0
    1
    Myalgia
         subjects affected / exposed
    2 / 98 (2.04%)
    2 / 25 (8.00%)
    1 / 85 (1.18%)
    3 / 41 (7.32%)
    2 / 84 (2.38%)
    2 / 20 (10.00%)
    2 / 76 (2.63%)
    2 / 37 (5.41%)
         occurrences all number
    2
    2
    1
    3
    2
    4
    2
    2
    Infections and infestations
    Anal abscess
         subjects affected / exposed
    1 / 98 (1.02%)
    1 / 25 (4.00%)
    2 / 85 (2.35%)
    0 / 41 (0.00%)
    1 / 84 (1.19%)
    0 / 20 (0.00%)
    4 / 76 (5.26%)
    0 / 37 (0.00%)
         occurrences all number
    1
    1
    4
    0
    3
    0
    4
    0
    Bronchitis
         subjects affected / exposed
    2 / 98 (2.04%)
    1 / 25 (4.00%)
    3 / 85 (3.53%)
    2 / 41 (4.88%)
    4 / 84 (4.76%)
    1 / 20 (5.00%)
    2 / 76 (2.63%)
    0 / 37 (0.00%)
         occurrences all number
    2
    1
    3
    2
    5
    1
    2
    0
    Cellulitis
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    1 / 84 (1.19%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    2
    0
    0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    1 / 85 (1.18%)
    0 / 41 (0.00%)
    2 / 84 (2.38%)
    1 / 20 (5.00%)
    1 / 76 (1.32%)
    1 / 37 (2.70%)
         occurrences all number
    0
    0
    1
    0
    3
    1
    1
    1
    Conjunctivitis
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    1 / 84 (1.19%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    1
    0
    0
    Fungal infection
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Gastroenteritis
         subjects affected / exposed
    6 / 98 (6.12%)
    0 / 25 (0.00%)
    3 / 85 (3.53%)
    1 / 41 (2.44%)
    2 / 84 (2.38%)
    0 / 20 (0.00%)
    7 / 76 (9.21%)
    2 / 37 (5.41%)
         occurrences all number
    6
    0
    3
    1
    2
    0
    8
    2
    Gastroenteritis viral
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    1 / 85 (1.18%)
    0 / 41 (0.00%)
    1 / 84 (1.19%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    1
    0
    0
    Herpes zoster
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    1 / 84 (1.19%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    Influenza
         subjects affected / exposed
    1 / 98 (1.02%)
    1 / 25 (4.00%)
    1 / 85 (1.18%)
    3 / 41 (7.32%)
    4 / 84 (4.76%)
    1 / 20 (5.00%)
    10 / 76 (13.16%)
    6 / 37 (16.22%)
         occurrences all number
    1
    1
    1
    3
    4
    2
    13
    7
    Nasopharyngitis
         subjects affected / exposed
    11 / 98 (11.22%)
    2 / 25 (8.00%)
    7 / 85 (8.24%)
    3 / 41 (7.32%)
    12 / 84 (14.29%)
    2 / 20 (10.00%)
    14 / 76 (18.42%)
    6 / 37 (16.22%)
         occurrences all number
    12
    2
    8
    4
    22
    3
    25
    7
    Psoas abscess
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Sinusitis
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    1 / 85 (1.18%)
    2 / 41 (4.88%)
    1 / 84 (1.19%)
    2 / 20 (10.00%)
    3 / 76 (3.95%)
    2 / 37 (5.41%)
         occurrences all number
    0
    0
    1
    3
    6
    2
    3
    2
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    7 / 85 (8.24%)
    1 / 41 (2.44%)
    6 / 84 (7.14%)
    0 / 20 (0.00%)
    2 / 76 (2.63%)
    3 / 37 (8.11%)
         occurrences all number
    0
    0
    7
    1
    6
    0
    2
    3
    Urinary tract infection
         subjects affected / exposed
    2 / 98 (2.04%)
    0 / 25 (0.00%)
    6 / 85 (7.06%)
    1 / 41 (2.44%)
    3 / 84 (3.57%)
    2 / 20 (10.00%)
    0 / 76 (0.00%)
    1 / 37 (2.70%)
         occurrences all number
    2
    0
    7
    2
    3
    2
    0
    1
    Viral infection
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 25 (0.00%)
    2 / 85 (2.35%)
    2 / 41 (4.88%)
    2 / 84 (2.38%)
    1 / 20 (5.00%)
    3 / 76 (3.95%)
    1 / 37 (2.70%)
         occurrences all number
    1
    0
    2
    2
    2
    1
    6
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    1 / 85 (1.18%)
    1 / 41 (2.44%)
    0 / 84 (0.00%)
    0 / 20 (0.00%)
    0 / 76 (0.00%)
    2 / 37 (5.41%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    2
    Magnesium deficiency
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Vitamin B12 deficiency
         subjects affected / exposed
    0 / 98 (0.00%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    0 / 41 (0.00%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Vitamin D deficiency
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    1 / 41 (2.44%)
    1 / 84 (1.19%)
    1 / 20 (5.00%)
    1 / 76 (1.32%)
    1 / 37 (2.70%)
         occurrences all number
    1
    0
    0
    1
    1
    1
    1
    1
    Zinc deficiency
         subjects affected / exposed
    1 / 98 (1.02%)
    0 / 25 (0.00%)
    0 / 85 (0.00%)
    2 / 41 (4.88%)
    0 / 84 (0.00%)
    1 / 20 (5.00%)
    0 / 76 (0.00%)
    0 / 37 (0.00%)
         occurrences all number
    1
    0
    0
    2
    0
    1
    0
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    14 Jun 2012
    Amendment 1 introduced changes that incorporated feedback received from regulatory authorities in Europe and the US on a phase 2 study in subjects with Ulcerative Colitis. Briefly: - The subject population at study entry was refined to subjects who had an inadequate response to, loss of response to, or intolerance to immunomodulators and/or anti-TNF agents. - A list of highly effective methods of birth control was added. - Topical aminosalicylic acid or corticosteroids, and IV or intramuscular corticosteroids were added to the exclusion criteria. - The safety follow-up period was extended from 12 months to 24 months. - The use of concomitant medications during the study was clarified. - Immunomodulators were to be withdrawn in all subjects at week 8. - Recommendations for withdrawal of open-label AMG 181 in subjects who did not achieve adequate disease control or had recurrence of significant symptoms was added. - Hepatotoxicity rules on stopping of and rechallenge with investigational product were added. - In the statistical section, the statistical method proposed for the continuous or ordinal endpoints was changed to an IPW GEE model to handle missing data. The ANCOVA model after missing data was imputed by the last observation carried forward approach was demoted to a sensitivity analysis. 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: - Results from phase 3 studies of vedolizumab had recently been made publicly available (subsequent full publication = Sands et al, 2014). These results suggested that the effect on disease activity might increase further beyond week 8. The study endpoints were therefore updated to include additional key secondary, other secondary, and exploratory endpoints, mainly at week 12, in order to assess disease activity at this time point as well as at week 8. Moreover, the statistical section was updated to reflect the changes in assumptions of the treatment effect size according to recent results and the addition of key secondary endpoints. The overall type I error rate was adjusted to a 2-sided alpha level of 0.10. - The enrollment of subjects with any prior exposure to anti-TNF agents was limited to approximately 80% in order to ensure recruitment of anti-TNF-naïve subjects in the study and generation of efficacy data in that population in addition to those for the core population of anti-TNF-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 secondary packaging and the IPIM occurred. As a consequence, 89 subjects enrolled prior to Protocol Amendment 3 were randomly assigned to treatment groups at ratios different from those stipulated in the double-blind period as outlined in Protocol. Approximately 74 subjects were expected to have received the IVRS randomized dose and 15 subjects received an incorrect dose such that a greater proportion of subjects than stipulated in the Protocol received placebo. All subjects received a dose level defined by the Protocol. No increased safety risks were identified for subjects who received a different protocol-defined dose than that to which they were randomly assigned. Changes to the Statistical Considerations were made accordingly, as summarized below: -- Full Analysis Set and Analysis of Key Endpoints: Neither the randomization nor study blind was compromised and therefore 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. However, 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. -- Sample Size Considerations: Minor adjustments were made to the sample size assumptions. - Clarifications to Study Design were done. - Inclusion Criteria was 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. This change allowed for testing of AMG 181 in a broader patient population and facilitated subject recruitment in regions outside of the US. - Minor clarifications and corrections to Study Procedures and Schedule of Assessments were done.

    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 21 mg dose cohort. 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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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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