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    Clinical Trial Results:
    A Multicenter, Randomized, Double-Blind, Placebo Controlled Induction Study of the Efficacy and Safety of Risankizumab in Subjects With Moderately to Severely Active Crohn's Disease

    Summary
    EudraCT number
    		 2016-003123-32
    Trial protocol
    		 SK   CZ   DE   GB   PT   IE   BG   AT   LV   PL   BE   NL   EE   SE   ES   GR   NO   LT   HR   IT   RO  
    Global end of trial date
    14 Apr 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    14 Oct 2021
    First version publication date
    14 Oct 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    M16-006
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03105128
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AbbVie Deutschland GmbH & Co. KG
    Sponsor organisation address
    AbbVie House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire, United Kingdom, SL6 4UB
    Public contact
    Global Medical Services, AbbVie, 001 8006339110, abbvieclinicaltrials@abbvie.com
    Scientific contact
    Global Medical Services, AbbVie, 001 8006339110, abbvieclinicaltrials@abbvie.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
    14 Apr 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Apr 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study is to evaluate the efficacy and safety of risankizumab versus placebo during induction therapy in participants with moderately to severely active Crohn's disease (CD).
    Protection of trial subjects
    Subject and/or legal guardian read and understood the information provided about the study and gave written permission.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    10 May 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 4
    Country: Number of subjects enrolled
    Austria: 7
    Country: Number of subjects enrolled
    Belarus: 1
    Country: Number of subjects enrolled
    Belgium: 68
    Country: Number of subjects enrolled
    Bosnia and Herzegovina: 2
    Country: Number of subjects enrolled
    Brazil: 14
    Country: Number of subjects enrolled
    Bulgaria: 4
    Country: Number of subjects enrolled
    Canada: 65
    Country: Number of subjects enrolled
    Chile: 2
    Country: Number of subjects enrolled
    China: 75
    Country: Number of subjects enrolled
    Croatia: 14
    Country: Number of subjects enrolled
    Czechia: 18
    Country: Number of subjects enrolled
    Estonia: 3
    Country: Number of subjects enrolled
    Germany: 74
    Country: Number of subjects enrolled
    Greece: 12
    Country: Number of subjects enrolled
    Israel: 22
    Country: Number of subjects enrolled
    Italy: 38
    Country: Number of subjects enrolled
    Japan: 75
    Country: Number of subjects enrolled
    Korea, Democratic People's Republic of: 18
    Country: Number of subjects enrolled
    Latvia: 2
    Country: Number of subjects enrolled
    Malaysia: 1
    Country: Number of subjects enrolled
    Mexico: 2
    Country: Number of subjects enrolled
    Netherlands: 8
    Country: Number of subjects enrolled
    New Zealand: 6
    Country: Number of subjects enrolled
    Norway: 10
    Country: Number of subjects enrolled
    Poland: 63
    Country: Number of subjects enrolled
    Portugal: 14
    Country: Number of subjects enrolled
    Romania: 6
    Country: Number of subjects enrolled
    Russian Federation: 25
    Country: Number of subjects enrolled
    Serbia: 23
    Country: Number of subjects enrolled
    Singapore: 1
    Country: Number of subjects enrolled
    Slovakia: 8
    Country: Number of subjects enrolled
    South Africa: 27
    Country: Number of subjects enrolled
    Spain: 18
    Country: Number of subjects enrolled
    Sweden: 10
    Country: Number of subjects enrolled
    Switzerland: 4
    Country: Number of subjects enrolled
    Ukraine: 17
    Country: Number of subjects enrolled
    United Kingdom: 25
    Country: Number of subjects enrolled
    United States: 145
    Worldwide total number of subjects
    931
    EEA total number of subjects
    377
    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)
    9
    Adults (18-64 years)
    880
    From 65 to 84 years
    42
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Subjects were randomized to receive 600mg risankizumab, 1200mg risankizumab or placebo during the double-blind, placebo-controlled Period 1. At Week 12, subjects who do not achieve clinical response were randomized into Period 2 to receive 180mg risankizumab, 360mg risankizumab or 1200mg risankizumab. Subjects who received placebo received 1200mg.

    Pre-assignment
    Screening details
    		 A total of 931 subjects were enrolled and included in the intent-to-treat (ITT) population; 850 of those had a baseline eligible Simple Endoscopic Score for Crohn's disease (SES-CD) of ≥ 6 (≥ 4 for isolated ileal disease) excluding the narrowing component and were included in the ITT1A population.

    Period 1
    Period 1 title
    Induction Period 1
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer
    Blinding implementation details
    All AbbVie personnel with direct oversight of the conduct and management of the trial (with the exception of AbbVie's Drug Supply Management Team) the Investigator, study site personnel and the subject remained blinded to each subject's treatment throughout the blinded period of the study.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Period 1 Placebo IV
    Arm description
    		 Participants randomized to receive Placebo by intravenous (IV) infusion at Baseline, Weeks 4 and 8.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Period 1 Placebo IV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received placebo intravenously at Baseline, Week 4 and Week 8.

    Arm title
    		 Period 1 Risankizumab 600mg IV
    Arm description
    		 Participants randomized to receive risankizumab 600mg by intravenous infusion at Baseline, Weeks 4 and 8.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Period 1 Risankizumab 600mg IV
    Investigational medicinal product code
    ABBV-066
    Other name
    BI 655066, SKYRIZI
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received risankizumab 600mg intravenously at Baseline, Week 4 and Week 8.

    Arm title
    		 Period 1 Risankizumab 1200mg IV
    Arm description
    		 Participants randomized to receive risankizumab 1200mg by intravenous infusion at Baseline, Weeks 4 and 8.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Period 1 Risankizumab 1200mg IV
    Investigational medicinal product code
    ABBV-066
    Other name
    BI 655066, SKYRIZI
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received risankizumab 1200mg intravenously at Baseline, Week 4 and Week 8.

    Number of subjects in period 1
    		Period 1 Placebo IV Period 1 Risankizumab 600mg IV Period 1 Risankizumab 1200mg IV
    Started
    186
    373
    372
    Completed
    163
    365
    366
    Not completed
    23
    8
    6
         Adverse event, non-fatal
    13
    4
    3
         Other, not specified
    1
    1
    2
         COVID-19 logistical restrictions
    2
    -
    -
         Lack of efficacy
    3
    -
    1
         Withdrawal by subject
    4
    3
    -
    Period 2
    Period 2 title
    Induction Period 2
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer
    Blinding implementation details
    All AbbVie personnel with direct oversight of the conduct and management of the trial (with the exception of AbbVie's Drug Supply Management Team) the Investigator, study site personnel and the subject remained blinded to each subject's treatment throughout the blinded period of the study.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Period 2 Risankizumab 180mg SC
    Arm description
    		 Participants randomized to receive risankizumab 180mg by subcutaneous(SC) injection at Weeks 12 and 20.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Period 2 Risankizumab 180mg SC
    Investigational medicinal product code
    ABBV-066
    Other name
    BI 655066, SKYRIZI
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received risankizumab 180mg subcutaneously at Weeks 12 and 20.

    Arm title
    		 Period 2 Risankizumab 360mg SC
    Arm description
    		 Participants randomized to receive risankizumab 360mg by subcutaneous injection at Weeks 12 and 20.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Period 2 Risankizumab 360mg SC
    Investigational medicinal product code
    ABBV-066
    Other name
    BI 655066, SKYRIZI
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received risankizumab 360mg subcutaneously at Weeks 12 and 20.

    Arm title
    		 Period 2 Risankizumab 1200mg IV
    Arm description
    		 Participants randomized to receive risankizumab 1200mg by intravenous infusion at Weeks 12, 16 and 20.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Period 2 Risankizumab 1200mg IV
    Investigational medicinal product code
    ABBV-066
    Other name
    BI 655066, SKYRIZI
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received risankizumab 1200mg intravenously at Weeks 12, 16, and 20.

    Arm title
    		 Period 2 Placebo/Risankizumab 1200mg IV
    Arm description
    		 Participants who received placebo in Induction Period 1 received 1200 mg risankizumab by intravenous infusion at Weeks 12, 16, and 20.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Period 2 Placebo/Risankizumab 1200mg IV
    Investigational medicinal product code
    ABBV-066
    Other name
    BI 655066, SKYRIZI
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants who received placebo in Induction Period 1 received 1200 mg risankizumab intravenously at Weeks 12, 16, and 20.

    Number of subjects in period 2 [1]
    		Period 2 Risankizumab 180mg SC Period 2 Risankizumab 360mg SC Period 2 Risankizumab 1200mg IV Period 2 Placebo/Risankizumab 1200mg IV
    Started
    67
    68
    67
    76
    Completed
    62
    65
    64
    74
    Not completed
    5
    3
    3
    2
         Adverse event, non-fatal
    -
    2
    -
    -
         Other, not specified
    -
    -
    -
    2
         COVID-19 logistical restrictions
    1
    -
    2
    -
         Lack of efficacy
    2
    -
    1
    -
         Withdrawal by subject
    2
    1
    -
    -
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: All participants who entered Induction Period 2.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Period 1 Placebo IV
    Reporting group description
    		 Participants randomized to receive Placebo by intravenous (IV) infusion at Baseline, Weeks 4 and 8.

    Reporting group title
    Period 1 Risankizumab 600mg IV
    Reporting group description
    		 Participants randomized to receive risankizumab 600mg by intravenous infusion at Baseline, Weeks 4 and 8.

    Reporting group title
    Period 1 Risankizumab 1200mg IV
    Reporting group description
    		 Participants randomized to receive risankizumab 1200mg by intravenous infusion at Baseline, Weeks 4 and 8.

    Reporting group values
    		 Period 1 Placebo IV Period 1 Risankizumab 600mg IV Period 1 Risankizumab 1200mg IV Total
    Number of subjects
    		 186 373 372 931
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 37.5 ( 13.51 ) 38.5 ( 13.22 ) 37.6 ( 13.55 ) -
    Gender categorical
    Units: Subjects
        Female
    		 93 168 173 434
        Male
    		 93 205 199 497
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 10 13 18 41
        Not Hispanic or Latino
    		 176 360 354 890
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0
        Asian
    		 32 68 75 175
        Black or African American
    		 9 10 13 32
        Native Hawaiian or Other Pacific Islander
    		 1 0 1 2
        White
    		 144 291 279 714
        More than one race
    		 0 4 4 8

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Period 1 Placebo IV
    Reporting group description
    		 Participants randomized to receive Placebo by intravenous (IV) infusion at Baseline, Weeks 4 and 8.

    Reporting group title
    Period 1 Risankizumab 600mg IV
    Reporting group description
    		 Participants randomized to receive risankizumab 600mg by intravenous infusion at Baseline, Weeks 4 and 8.

    Reporting group title
    Period 1 Risankizumab 1200mg IV
    Reporting group description
    		 Participants randomized to receive risankizumab 1200mg by intravenous infusion at Baseline, Weeks 4 and 8.
    Reporting group title
    Period 2 Risankizumab 180mg SC
    Reporting group description
    		 Participants randomized to receive risankizumab 180mg by subcutaneous(SC) injection at Weeks 12 and 20.

    Reporting group title
    Period 2 Risankizumab 360mg SC
    Reporting group description
    		 Participants randomized to receive risankizumab 360mg by subcutaneous injection at Weeks 12 and 20.

    Reporting group title
    Period 2 Risankizumab 1200mg IV
    Reporting group description
    		 Participants randomized to receive risankizumab 1200mg by intravenous infusion at Weeks 12, 16 and 20.

    Reporting group title
    Period 2 Placebo/Risankizumab 1200mg IV
    Reporting group description
    		 Participants who received placebo in Induction Period 1 received 1200 mg risankizumab by intravenous infusion at Weeks 12, 16, and 20.

    Primary: Percentage of Participants With Endoscopic Response at Week 12

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    End point title
    		 Percentage of Participants With Endoscopic Response at Week 12
    End point description
    Endoscopic response was a decrease in Simplified Endoscopic Score for Crohn's Disease (SES-CD) > 50% from Baseline (or for subjects with isolated ileal disease and a Baseline SES-CD of 4, at least a 2 point reduction from Baseline). Intent to Treat 1A Population: all randomized subjects who received at least one dose of study drug during the 12-Week Induction Period, and had baseline eligible SES-CD of ≥ 6 (≥ 4 for isolated ileal disease) excluding the narrowing component.
    End point type
    Primary
    End point timeframe
    Week 12
    End point values
    		 Period 1 Placebo IV Period 1 Risankizumab 600mg IV Period 1 Risankizumab 1200mg IV
    Number of subjects analysed
    175
    336
    339
    Units: percentage of participants
        number (not applicable)
    12.0
    40.3
    32.1
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (risankizumab - placebo).
    Comparison groups
    Period 1 Placebo IV v Period 1 Risankizumab 600mg IV
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    28.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 21.2
         upper limit
    		 35.4
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Risk difference = (risankizumab - placebo).
    Comparison groups
    Period 1 Risankizumab 1200mg IV v Period 1 Placebo IV
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    20.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 13.6
         upper limit
    		 27.1

    Primary: Percentage of Participants With Clinical Remission at Week 12

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    End point title
    		 Percentage of Participants With Clinical Remission at Week 12
    End point description
    Clinical remission is defined as using the average daily Stool Frequency (SF) ≤ 2.8 and not worse than Baseline AND average daily Abdominal Pain (AP) score ≤ 1 and not worse than Baseline. Intent to Treat 1A Population: all randomized subjects who received at least one dose of study drug during the 12-Week Induction Period, and had baseline eligible SES-CD of ≥ 6 (≥ 4 for isolated ileal disease) excluding the narrowing component.
    End point type
    Primary
    End point timeframe
    Week 12
    End point values
    		 Period 1 Placebo IV Period 1 Risankizumab 600mg IV Period 1 Risankizumab 1200mg IV
    Number of subjects analysed
    175
    336
    339
    Units: percentage of participants
        number (not applicable)
    21.7
    43.5
    41.0
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (risankizumab - placebo).
    Comparison groups
    Period 1 Placebo IV v Period 1 Risankizumab 600mg IV
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    21.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 13.8
         upper limit
    		 29.9
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Risk difference = (risankizumab - placebo).
    Comparison groups
    Period 1 Placebo IV v Period 1 Risankizumab 1200mg IV
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    18.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 10.8
         upper limit
    		 26.8

    Secondary: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Remission at Week 12

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    End point title
    		 Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Remission at Week 12
    End point description
    Crohn's Disease Activity Index (CDAI) is used to assess the symptoms of participants with Crohn's Disease. Higher CDAI scores indicate more severe disease. Clinical remission of Crohn's disease is defined as CDAI < 150. Intent to Treat IA Population: all randomized subjects who received at least one dose of study drug during the 12-Week Induction Period, and had baseline eligible Simple Endoscopic Score for Crohn's disease (SES-CD) of ≥ 6 (≥ 4 for isolated ileal disease) excluding the narrowing component.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Period 1 Placebo IV Period 1 Risankizumab 600mg IV Period 1 Risankizumab 1200mg IV
    Number of subjects analysed
    175
    336
    339
    Units: Percentage of participants
        number (not applicable)
    24.6
    45.2
    41.6
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (risankizumab - placebo).
    Comparison groups
    Period 1 Placebo IV v Period 1 Risankizumab 600mg IV
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    20.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 12.4
         upper limit
    		 29
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Risk difference = (risankizumab - placebo).
    Comparison groups
    Period 1 Risankizumab 1200mg IV v Period 1 Placebo IV
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    16.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 8.5
         upper limit
    		 24.9

    Secondary: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Response at Week 12

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    End point title
    		 Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Response at Week 12
    End point description
    Crohn's Disease Activity Index (CDAI) is used to assess the symptoms of participants with Crohn's Disease. Higher CDAI scores indicate more severe disease. Clinical response is defined as reduction of CDAI ≥ 100 points from baseline. Intent to Treat 1A Population: all randomized subjects who received at least one dose of study drug during the 12-Week Induction Period, and had baseline eligible SES-CD of ≥ 6 (≥ 4 for isolated ileal disease) excluding the narrowing component.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Period 1 Placebo IV Period 1 Risankizumab 600mg IV Period 1 Risankizumab 1200mg IV
    Number of subjects analysed
    175
    336
    339
    Units: percentage of participants
        number (not applicable)
    36.7
    59.7
    64.9
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (risankizumab - placebo).
    Comparison groups
    Period 1 Placebo IV v Period 1 Risankizumab 600mg IV
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    23.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 14.2
         upper limit
    		 31.9
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Risk difference = (risankizumab - placebo).
    Comparison groups
    Period 1 Risankizumab 1200mg IV v Period 1 Placebo IV
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    27.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 19
         upper limit
    		 36.4

    Secondary: Change From Baseline of Induction in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue at Week 12

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    End point title
    		 Change From Baseline of Induction in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue at Week 12
    End point description
    The FACIT-Fatigue scale is a 13-item tool that measures an individual's level of fatigue during their usual daily activities over the past 7 days. Each of the fatigue and impact of fatigue items are measured on a four point Likert scale. The FACIT Fatigue Scale is the sum of the individual 13 scores and ranges from 0 to 52 where higher scores indicate better the quality of life. A positive change from baseline indicates improvement. Intent to Treat 1A Population: all randomized subjects who received at least one dose of study drug during the 12-Week Induction Period, and had baseline eligible SES-CD of ≥ 6 (≥ 4 for isolated ileal disease) excluding the narrowing component.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Period 1 Placebo IV Period 1 Risankizumab 600mg IV Period 1 Risankizumab 1200mg IV
    Number of subjects analysed
    134
    302
    310
    Units: units on a scale
        least squares mean (standard error)
    6.0 ( 0.86 )
    11.2 ( 0.59 )
    10.1 ( 0.58 )
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Mean difference = (risankizumab - placebo).
    Comparison groups
    Period 1 Placebo IV v Period 1 Risankizumab 600mg IV
    Number of subjects included in analysis
    436
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed-Effect Model Repeat Measurement
    Parameter type
    		 LS Mean
    Point estimate
    5.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.2
         upper limit
    		 7.2
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Mean difference = (risankizumab - placebo).
    Comparison groups
    Period 1 Risankizumab 1200mg IV v Period 1 Placebo IV
    Number of subjects included in analysis
    444
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed-Effect Model Repeat Measurement
    Parameter type
    		 LS Mean
    Point estimate
    4.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.1
         upper limit
    		 6.1

    Secondary: Percentage of Participants With Enhanced Clinical Response and Endoscopic Response at Week 12

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    End point title
    		 Percentage of Participants With Enhanced Clinical Response and Endoscopic Response at Week 12
    End point description
    Enhanced clinical response was defined as ≥ 60% decrease in average daily Stool Frequency and/or ≥ 35% decrease in average daily Abdominal Pain score and both not worse than baseline, and/or clinical remission. Endoscopic Response was defined as a decrease in Simplified Endoscopic Score for Crohn's Disease (SES-CD) > 50% from Baseline (or for subjects with isolated ileal disease and a Baseline SES-CD of 4, at least a 2 point reduction from Baseline). Intent to Treat 1A Population: all randomized subjects who received at least one dose of study drug during the 12-Week Induction Period, and had baseline eligible SES-CD of ≥ 6 (≥ 4 for isolated ileal disease) excluding the narrowing component.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Period 1 Placebo IV Period 1 Risankizumab 600mg IV Period 1 Risankizumab 1200mg IV
    Number of subjects analysed
    175
    336
    339
    Units: percentage of participants
        number (not applicable)
    8
    30.9
    23.2
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (risankizumab - placebo).
    Comparison groups
    Period 1 Placebo IV v Period 1 Risankizumab 600mg IV
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    23.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 16.8
         upper limit
    		 29.6
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Risk difference = (risankizumab - placebo).
    Comparison groups
    Period 1 Risankizumab 1200mg IV v Period 1 Placebo IV
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    15.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 9.3
         upper limit
    		 21.2

    Secondary: Percentage of Participants With Endoscopic Remission at Week 12

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    End point title
    		 Percentage of Participants With Endoscopic Remission at Week 12
    End point description
    Endoscopic remission was defined as SES-CD ≤ 4 and at least a 2-point reduction versus baseline and no subscore greater than 1 in any individual variable. Intent to Treat 1A Population: all randomized subjects who received at least one dose of study drug during the 12-Week Induction Period, and had baseline eligible SES-CD of ≥ 6 (≥ 4 for isolated ileal disease) excluding the narrowing component.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Period 1 Placebo IV Period 1 Risankizumab 600mg IV Period 1 Risankizumab 1200mg IV
    Number of subjects analysed
    175
    336
    339
    Units: percentage of participants
        number (not applicable)
    9.1
    24.2
    23.9
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (risankizumab - placebo).
    Comparison groups
    Period 1 Placebo IV v Period 1 Risankizumab 600mg IV
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    15.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 9
         upper limit
    		 21.2
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Risk difference = (risankizumab - placebo).
    Comparison groups
    Period 1 Risankizumab 1200mg IV v Period 1 Placebo IV
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    15.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 9.4
         upper limit
    		 21.4

    Secondary: Percentage of Participants With Enhanced Clinical Response at Week 12

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    End point title
    		 Percentage of Participants With Enhanced Clinical Response at Week 12
    End point description
    Enhanced clinical response was defined as ≥ 60% decrease in average daily Stool Frequency and/or ≥ 35% decrease in average daily Abdominal Pain score and both not worse than baseline, and/or clinical remission. Intent to Treat 1A Population: all randomized subjects who received at least one dose of study drug during the 12-Week Induction Period, and had baseline eligible SES-CD of ≥ 6 (≥ 4 for isolated ileal disease) excluding the narrowing component.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Period 1 Placebo IV Period 1 Risankizumab 600mg IV Period 1 Risankizumab 1200mg IV
    Number of subjects analysed
    175
    336
    339
    Units: percentage of participants
        number (not applicable)
    41.9
    62.8
    64.3
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (risankizumab - placebo).
    Comparison groups
    Period 1 Placebo IV v Period 1 Risankizumab 600mg IV
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 12.2
         upper limit
    		 29.9
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Risk difference = (risankizumab - placebo).
    Comparison groups
    Period 1 Risankizumab 1200mg IV v Period 1 Placebo IV
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    21.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 12.8
         upper limit
    		 30.4

    Secondary: Percentage of Participants With Ulcer-Free Endoscopy at Week 12

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    End point title
    		 Percentage of Participants With Ulcer-Free Endoscopy at Week 12
    End point description
    Ulcer-free endoscopy was defined as SES-CD ulcerated surface subscore of 0 in subjects with SES-CD ulcerated surface subscore ≥ 1 at baseline. Intent to Treat 1A Population: all randomized subjects who received at least one dose of study drug during the 12-Week Induction Period, and had baseline eligible SES-CD of ≥ 6 (≥ 4 for isolated ileal disease) excluding the narrowing component.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Period 1 Placebo IV Period 1 Risankizumab 600mg IV Period 1 Risankizumab 1200mg IV
    Number of subjects analysed
    173
    336
    338
    Units: percentage of participants
        number (not applicable)
    7.6
    21.0
    16.4
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (risankizumab - placebo).
    Comparison groups
    Period 1 Placebo IV v Period 1 Risankizumab 600mg IV
    Number of subjects included in analysis
    509
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    13.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 7.9
         upper limit
    		 19.5
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Risk difference = (risankizumab - placebo).
    Comparison groups
    Period 1 Risankizumab 1200mg IV v Period 1 Placebo IV
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    9.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.7
         upper limit
    		 14.5

    Secondary: Percentage of Participants With Resolution of Extra-Intestinal Manifestations (EIMs) at Week 12, in Participants With EIMs at Baseline

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    End point title
    		 Percentage of Participants With Resolution of Extra-Intestinal Manifestations (EIMs) at Week 12, in Participants With EIMs at Baseline
    End point description
    Manifestations of Crohn's disease in areas of the body other than the digestive tract, including eyes, skin, joints, mouth, and liver. Intent to Treat 1A Population: all randomized subjects who received at least one dose of study drug during the 12-Week Induction Period, and had baseline eligible SES-CD of ≥ 6 (≥ 4 for isolated ileal disease) excluding the narrowing component.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Period 1 Placebo IV Period 1 Risankizumab 600mg IV Period 1 Risankizumab 1200mg IV
    Number of subjects analysed
    64
    140
    158
    Units: percentage of participants
        number (not applicable)
    20.5
    38.1
    43.7
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (risankizumab - placebo).
    Comparison groups
    Period 1 Placebo IV v Period 1 Risankizumab 600mg IV
    Number of subjects included in analysis
    204
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.022
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    14.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.1
         upper limit
    		 27
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Risk difference = (risankizumab - placebo).
    Comparison groups
    Period 1 Risankizumab 1200mg IV v Period 1 Placebo IV
    Number of subjects included in analysis
    222
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    23.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 11.1
         upper limit
    		 36.3

    Secondary: Percentage of Participants With CD-Related Hospitalization through Week 12

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    End point title
    		 Percentage of Participants With CD-Related Hospitalization through Week 12
    End point description
    Participants with at least one admission to the hospital due to Crohn’s Disease Intent to Treat 1A Population: all randomized subjects who received at least one dose of study drug during the 12-Week Induction Period, and had baseline eligible SES-CD of ≥ 6 (≥ 4 for isolated ileal disease) excluding the narrowing component.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Period 1 Placebo IV Period 1 Risankizumab 600mg IV Period 1 Risankizumab 1200mg IV
    Number of subjects analysed
    175
    336
    339
    Units: percentage of participants
        number (not applicable)
    12
    3.3
    1.8
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (risankizumab - placebo).
    Comparison groups
    Period 1 Placebo IV v Period 1 Risankizumab 600mg IV
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    -8.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.9
         upper limit
    		 -3.5
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Risk difference = (risankizumab - placebo).
    Comparison groups
    Period 1 Risankizumab 1200mg IV v Period 1 Placebo IV
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    -10.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15.2
         upper limit
    		 -5.2

    Secondary: Percentage of Participants Without Draining Fistulas at Week 12 in Participants With Draining Fistulas at Baseline

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    End point title
    		 Percentage of Participants Without Draining Fistulas at Week 12 in Participants With Draining Fistulas at Baseline
    End point description
    Participants without draining fistulas at Week 12 in participants who had draining fistulas at baseline. Intent to Treat 1A Population: all randomized subjects who received at least one dose of study drug during the 12-Week Induction Period, and had baseline eligible SES-CD of ≥ 6 (≥ 4 for isolated ileal disease) excluding the narrowing component.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Period 1 Placebo IV Period 1 Risankizumab 600mg IV Period 1 Risankizumab 1200mg IV
    Number of subjects analysed
    9
    18
    24
    Units: percentage of participants
        number (not applicable)
    22.2
    27.8
    29.2
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (risankizumab - placebo).
    Comparison groups
    Period 1 Placebo IV v Period 1 Risankizumab 600mg IV
    Number of subjects included in analysis
    27
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 1
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    5.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -28.6
         upper limit
    		 39.7
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Risk difference = (risankizumab - placebo).
    Comparison groups
    Period 1 Risankizumab 1200mg IV v Period 1 Placebo IV
    Number of subjects included in analysis
    33
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 1
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    6.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -25.7
         upper limit
    		 39.6

    Secondary: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Response at Week 4

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    End point title
    		 Percentage of Participants With Crohn's Disease Activity Index (CDAI) Clinical Response at Week 4
    End point description
    Crohn's Disease Activity Index (CDAI) is used to assess the symptoms of participants with Crohn's Disease. Higher CDAI scores indicate more severe disease. Clinical response is defined as reduction of CDAI ≥ 100 points from baseline. Intent to Treat 1A Population: all randomized subjects who received at least one dose of study drug during the 12-Week Induction Period, and had baseline eligible SES-CD of ≥ 6 (≥ 4 for isolated ileal disease) excluding the narrowing component.
    End point type
    Secondary
    End point timeframe
    Week 4
    End point values
    		 Period 1 Placebo IV Period 1 Risankizumab 600mg IV Period 1 Risankizumab 1200mg IV
    Number of subjects analysed
    175
    336
    339
    Units: percentage of participants
        number (not applicable)
    25.2
    40.8
    37.2
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (risankizumab - placebo)
    Comparison groups
    Period 1 Placebo IV v Period 1 Risankizumab 600mg IV
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    15.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 7.2
         upper limit
    		 23.7
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Risk difference = (risankizumab - placebo)
    Comparison groups
    Period 1 Risankizumab 1200mg IV v Period 1 Placebo IV
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.007
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    11.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.1
         upper limit
    		 19.2

    Secondary: Percentage of Participants With Enhanced Clinical Response at Week 4

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    End point title
    		 Percentage of Participants With Enhanced Clinical Response at Week 4
    End point description
    Enhanced clinical response was defined as ≥ 60% decrease in average daily Stool Frequency and/or ≥ 35% decrease in average daily Abdominal Pain score and both not worse than baseline, and/or clinical remission. Intent to Treat 1A Population: all randomized subjects who received at least one dose of study drug during the 12-Week Induction Period, and had baseline eligible SES-CD of ≥ 6 (≥ 4 for isolated ileal disease) excluding the narrowing component.
    End point type
    Secondary
    End point timeframe
    Week 4
    End point values
    		 Period 1 Placebo IV Period 1 Risankizumab 600mg IV Period 1 Risankizumab 1200mg IV
    Number of subjects analysed
    175
    336
    339
    Units: percentage of participants
        number (not applicable)
    31
    46
    43.4
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (risankizumab - placebo)
    Comparison groups
    Period 1 Risankizumab 600mg IV v Period 1 Placebo IV
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    14.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.2
         upper limit
    		 23.5
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Risk difference = (risankizumab - placebo)
    Comparison groups
    Period 1 Risankizumab 1200mg IV v Period 1 Placebo IV
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.007
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    11.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.2
         upper limit
    		 20.3

    Secondary: Change from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) total score at Week 12

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    End point title
    		 Change from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) total score at Week 12
    End point description
    The IBDQ is a 32-item (ranges 1 – 7) self-report questionnaire for patients with IBD to evaluate the patient reported outcomes across 4 dimensions: bowel symptoms (loose stools, abdominal pain), systemic symptoms (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). The IBDQ total Score ranges from 32 to 224 with a higher score indicating better outcome. Intent to Treat 1A Population: all randomized subjects who received at least one dose of study drug during the 12-Week Induction Period, and had baseline eligible SES-CD of ≥ 6 (≥ 4 for isolated ileal disease) excluding the narrowing component.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Period 1 Placebo IV Period 1 Risankizumab 600mg IV Period 1 Risankizumab 1200mg IV
    Number of subjects analysed
    134
    302
    310
    Units: units on a scale
        least squares mean (standard error)
    23.6 ( 2.72 )
    44.3 ( 1.87 )
    43 ( 1.85 )
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Mean difference = (risankizumab - placebo).
    Comparison groups
    Period 1 Placebo IV v Period 1 Risankizumab 600mg IV
    Number of subjects included in analysis
    436
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed-Effect Model Repeat Measurement
    Parameter type
    		 LS Mean
    Point estimate
    20.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 14.3
         upper limit
    		 27.1
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Mean difference = (risankizumab - placebo).
    Comparison groups
    Period 1 Placebo IV v Period 1 Risankizumab 1200mg IV
    Number of subjects included in analysis
    444
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed-Effect Model Repeat Measurement
    Parameter type
    		 LS Mean
    Point estimate
    19.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 13.1
         upper limit
    		 25.8

    Secondary: Change from baseline in Work Productivity and Impairment Questionnaire – Crohn's disease (WPAI-CD) Overall Work Impairment at Week 12

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    End point title
    		 Change from baseline in Work Productivity and Impairment Questionnaire – Crohn's disease (WPAI-CD) Overall Work Impairment at Week 12
    End point description
    WPAI: CD is a questionnaire used to evaluate lost productivity due to CD ; scores are presented as percentages (multiplying the scores by 100), with 0% representing no impact on productivity and 100% representing complete impact on productivity. Total work productivity impairment takes into account both hours missed due to CD symptoms and the patient's assessment of the degree to which CD affected their productivity while working (overall work impairment [OWI]). WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity. Intent to Treat 1A Population: all randomized subjects who received at least one dose of study drug during the 12-Week Induction Period, and had baseline eligible SES-CD of ≥ 6 (≥ 4 for isolated ileal disease) excluding the narrowing component.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Period 1 Placebo IV Period 1 Risankizumab 600mg IV Period 1 Risankizumab 1200mg IV
    Number of subjects analysed
    65
    156
    162
    Units: units on a scale
        least squares mean (standard error)
    -8.344 ( 3.5640 )
    -17.930 ( 2.3446 )
    -20.485 ( 2.3112 )
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Period 1 Placebo IV v Period 1 Risankizumab 600mg IV
    Number of subjects included in analysis
    221
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.024
    Method
    		 Mixed-Effect Model Repeat Measurement
    Parameter type
    		 LS Mean
    Point estimate
    -9.586
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -17.89
         upper limit
    		 -1.282
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Period 1 Placebo IV v Period 1 Risankizumab 1200mg IV
    Number of subjects included in analysis
    227
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.004
    Method
    		 Mixed-Effect Model Repeat Measurement
    Parameter type
    		 LS Mean
    Point estimate
    -12.141
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -20.39
         upper limit
    		 -3.892

    Secondary: Change from baseline in Short Form-36 (SF-36) Physical Component Summary (PCS) score at Week 12

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    End point title
    		 Change from baseline in Short Form-36 (SF-36) Physical Component Summary (PCS) score at Week 12
    End point description
    The Short Form-36 Health Survey determined participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 comprise the physical component of the SF-36. Scores on each item were summed and averaged (range = 0-100); a positive change from Baseline indicates improvement. Intent to Treat 1A Population: all randomized subjects who received at least one dose of study drug during the 12-Week Induction Period, and had baseline eligible SES-CD of ≥ 6 (≥ 4 for isolated ileal disease) excluding the narrowing component.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Period 1 Placebo IV Period 1 Risankizumab 600mg IV Period 1 Risankizumab 1200mg IV
    Number of subjects analysed
    134
    302
    309
    Units: units on a scale
        least squares mean (standard error)
    5.482 ( 0.5985 )
    8.394 ( 0.4107 )
    8.756 ( 0.4071 )
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Period 1 Placebo IV v Period 1 Risankizumab 600mg IV
    Number of subjects included in analysis
    436
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed-Effect Model Repeat Measurement
    Parameter type
    		 LS Mean
    Point estimate
    2.913
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.512
         upper limit
    		 4.313
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Period 1 Placebo IV v Period 1 Risankizumab 1200mg IV
    Number of subjects included in analysis
    443
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Mixed-Effect Model Repeat Measurement
    Parameter type
    		 LS Mean
    Point estimate
    3.275
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.877
         upper limit
    		 4.672

    Secondary: Percentage of Participants With Clinical Remission at Week 4

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    End point title
    		 Percentage of Participants With Clinical Remission at Week 4
    End point description
    Clinical remission is defined as using the average daily Stool Frequency (SF) ≤ 2.8 and not worse than Baseline AND average daily Abdominal Pain (AP) score ≤ 1 and not worse than Baseline. Intent to Treat 1A Population: all randomized subjects who received at least one dose of study drug during the 12-Week Induction Period, and had baseline eligible SES-CD of ≥ 6 (≥ 4 for isolated ileal disease) excluding the narrowing component.
    End point type
    Secondary
    End point timeframe
    Week 4
    End point values
    		 Period 1 Placebo IV Period 1 Risankizumab 600mg IV Period 1 Risankizumab 1200mg IV
    Number of subjects analysed
    175
    336
    339
    Units: percentage of participants
        number (not applicable)
    9.1
    21.0
    21.2
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (risankizumab - placebo).
    Comparison groups
    Period 1 Placebo IV v Period 1 Risankizumab 600mg IV
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    11.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.4
         upper limit
    		 17.5
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Risk difference = (risankizumab - placebo).
    Comparison groups
    Period 1 Placebo IV v Period 1 Risankizumab 1200mg IV
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    11.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.7
         upper limit
    		 17.8

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study drug until 140 days following last dose of study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    Period 1 Risankizumab 1200mg IV
    Reporting group description
    		 Participants randomized to receive risankizumab 1200mg by intravenous infusion at Baseline, Weeks 4 and 8.

    Reporting group title
    Period 1 Placebo IV
    Reporting group description
    		 Participants randomized to receive Placebo intravenous by intravenous infusion at Baseline, Weeks 4 and 8.

    Reporting group title
    Period 1 Risankizumab 600mg IV
    Reporting group description
    		 Participants randomized to receive risankizumab 600mg by intravenous infusion at Baseline, Weeks 4 and 8.

    Reporting group title
    Period 1 Risankizumab total
    Reporting group description
    		 -

    Reporting group title
    Period 2 Risankizumab 360mg SC
    Reporting group description
    		 Participants randomized to receive risankizumab 360mg by subcutaneous injection at Weeks 12 and 20.

    Reporting group title
    Period 2 Risankizumab 180mg SC
    Reporting group description
    		 Participants randomized to receive risankizumab 180mg by subcutaneous injection at Weeks 12 and 20.

    Reporting group title
    Period 2 Risankizumab 1200mg IV
    Reporting group description
    		 Participants received risankizumab 1200mg by intravenous infusion at Weeks 12, 16, and 20.

    Reporting group title
    Period 2 Risankizumab total
    Reporting group description
    		 -

    Reporting group title
    Period 2 Placebo/Risankizumab 1200mg IV
    Reporting group description
    		 Participants who received placebo in Induction Period 1 received 1200 mg risankizumab by intravenous infusion at Weeks 12, 16, and 20.

    Serious adverse events
    		 Period 1 Risankizumab 1200mg IV Period 1 Placebo IV Period 1 Risankizumab 600mg IV Period 1 Risankizumab total Period 2 Risankizumab 360mg SC Period 2 Risankizumab 180mg SC Period 2 Risankizumab 1200mg IV Period 2 Risankizumab total Period 2 Placebo/Risankizumab 1200mg IV
    Total subjects affected by serious adverse events
         subjects affected / exposed
    14 / 372 (3.76%)
    28 / 186 (15.05%)
    27 / 373 (7.24%)
    41 / 745 (5.50%)
    3 / 68 (4.41%)
    3 / 67 (4.48%)
    4 / 67 (5.97%)
    14 / 278 (5.04%)
    4 / 76 (5.26%)
         number of deaths (all causes)
    0
    2
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    2
    0
    0
    0
    0
    0
    0
    0
    Vascular disorders
    DEEP VEIN THROMBOSIS
         subjects affected / exposed
    1 / 372 (0.27%)
    0 / 186 (0.00%)
    0 / 373 (0.00%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPERTENSION
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    1 / 373 (0.27%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    ABORTION INDUCED
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    1 / 373 (0.27%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    0 / 372 (0.00%)
    1 / 186 (0.54%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    SYSTEMIC INFLAMMATORY RESPONSE SYNDROME
         subjects affected / exposed
    1 / 372 (0.27%)
    0 / 186 (0.00%)
    0 / 373 (0.00%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    FOOD ALLERGY
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    1 / 373 (0.27%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    ASTHMA
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    1 / 373 (0.27%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PULMONARY EMBOLISM
         subjects affected / exposed
    1 / 372 (0.27%)
    0 / 186 (0.00%)
    0 / 373 (0.00%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    MENTAL DISORDER
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 278 (0.36%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    OBSESSIVE-COMPULSIVE DISORDER
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    1 / 278 (0.36%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Investigations
    BODY TEMPERATURE INCREASED
         subjects affected / exposed
    1 / 372 (0.27%)
    0 / 186 (0.00%)
    0 / 373 (0.00%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HAEMOGLOBIN DECREASED
         subjects affected / exposed
    1 / 372 (0.27%)
    0 / 186 (0.00%)
    0 / 373 (0.00%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    WEIGHT DECREASED
         subjects affected / exposed
    0 / 372 (0.00%)
    1 / 186 (0.54%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Injury, poisoning and procedural complications
    FALL
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    1 / 373 (0.27%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FOREARM FRACTURE
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    1 / 373 (0.27%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    VENTRICULAR TACHYCARDIA
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    1 / 373 (0.27%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    DIZZINESS
         subjects affected / exposed
    0 / 372 (0.00%)
    1 / 186 (0.54%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    SYNCOPE
         subjects affected / exposed
    0 / 372 (0.00%)
    1 / 186 (0.54%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    1 / 372 (0.27%)
    1 / 186 (0.54%)
    0 / 373 (0.00%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    RETINAL DISORDER
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 278 (0.36%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    Gastrointestinal disorders
    ABDOMINAL HERNIA
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    1 / 278 (0.36%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    ABDOMINAL PAIN
         subjects affected / exposed
    0 / 372 (0.00%)
    2 / 186 (1.08%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COLITIS
         subjects affected / exposed
    0 / 372 (0.00%)
    1 / 186 (0.54%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    CROHN'S DISEASE
         subjects affected / exposed
    2 / 372 (0.54%)
    15 / 186 (8.06%)
    5 / 373 (1.34%)
    7 / 745 (0.94%)
    0 / 68 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    1 / 278 (0.36%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    2 / 16
    0 / 7
    1 / 9
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DIARRHOEA
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    1 / 373 (0.27%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GASTROINTESTINAL HAEMORRHAGE
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    1 / 373 (0.27%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GASTROINTESTINAL INFLAMMATION
         subjects affected / exposed
    0 / 372 (0.00%)
    1 / 186 (0.54%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    GASTROINTESTINAL NECROSIS
         subjects affected / exposed
    0 / 372 (0.00%)
    1 / 186 (0.54%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    1 / 278 (0.36%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ILEAL PERFORATION
         subjects affected / exposed
    0 / 372 (0.00%)
    1 / 186 (0.54%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ILEAL STENOSIS
         subjects affected / exposed
    1 / 372 (0.27%)
    0 / 186 (0.00%)
    0 / 373 (0.00%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ILEUS
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    2 / 373 (0.54%)
    2 / 745 (0.27%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INTESTINAL ISCHAEMIA
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    1 / 278 (0.36%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    INTESTINAL OBSTRUCTION
         subjects affected / exposed
    0 / 372 (0.00%)
    2 / 186 (1.08%)
    1 / 373 (0.27%)
    1 / 745 (0.13%)
    1 / 68 (1.47%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    3 / 278 (1.08%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 1
    0 / 1
    0 / 1
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INTESTINAL STENOSIS
         subjects affected / exposed
    0 / 372 (0.00%)
    2 / 186 (1.08%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LARGE INTESTINE PERFORATION
         subjects affected / exposed
    1 / 372 (0.27%)
    0 / 186 (0.00%)
    1 / 373 (0.27%)
    2 / 745 (0.27%)
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 278 (0.36%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 2
    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
    0 / 0
    NAUSEA
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    1 / 373 (0.27%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PANCREATITIS ACUTE
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    1 / 373 (0.27%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SMALL INTESTINAL OBSTRUCTION
         subjects affected / exposed
    1 / 372 (0.27%)
    1 / 186 (0.54%)
    1 / 373 (0.27%)
    2 / 745 (0.27%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    1 / 278 (0.36%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 1
    1 / 2
    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
    0 / 0
    SUBILEUS
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 278 (0.36%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    TERMINAL ILEITIS
         subjects affected / exposed
    1 / 372 (0.27%)
    0 / 186 (0.00%)
    0 / 373 (0.00%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    VOMITING
         subjects affected / exposed
    0 / 372 (0.00%)
    1 / 186 (0.54%)
    1 / 373 (0.27%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    1 / 278 (0.36%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    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
    0 / 0
    Hepatobiliary disorders
    BILE DUCT STONE
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    1 / 373 (0.27%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CHOLANGITIS
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    1 / 373 (0.27%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CHOLECYSTITIS ACUTE
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    1 / 278 (0.36%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    HEPATIC FUNCTION ABNORMAL
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    1 / 373 (0.27%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LIVER DISORDER
         subjects affected / exposed
    1 / 372 (0.27%)
    0 / 186 (0.00%)
    0 / 373 (0.00%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    RASH
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    1 / 373 (0.27%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    CALCULUS URINARY
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    0 / 68 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    1 / 278 (0.36%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYDRONEPHROSIS
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    1 / 373 (0.27%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NEPHROLITHIASIS
         subjects affected / exposed
    1 / 372 (0.27%)
    1 / 186 (0.54%)
    0 / 373 (0.00%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 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
    0 / 0
    URETEROLITHIASIS
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    2 / 373 (0.54%)
    2 / 745 (0.27%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    1 / 278 (0.36%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    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
    0 / 0
    Musculoskeletal and connective tissue disorders
    ANKYLOSING SPONDYLITIS
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    1 / 373 (0.27%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ARTHRALGIA
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    1 / 373 (0.27%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FIBROMYALGIA
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    1 / 373 (0.27%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FISTULA
         subjects affected / exposed
    1 / 372 (0.27%)
    0 / 186 (0.00%)
    0 / 373 (0.00%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SPONDYLITIS
         subjects affected / exposed
    0 / 372 (0.00%)
    1 / 186 (0.54%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Infections and infestations
    ABDOMINAL WALL ABSCESS
         subjects affected / exposed
    0 / 372 (0.00%)
    1 / 186 (0.54%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    ABSCESS INTESTINAL
         subjects affected / exposed
    0 / 372 (0.00%)
    1 / 186 (0.54%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    ANAL ABSCESS
         subjects affected / exposed
    0 / 372 (0.00%)
    1 / 186 (0.54%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    APPENDICITIS
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    1 / 373 (0.27%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GASTROENTERITIS
         subjects affected / exposed
    0 / 372 (0.00%)
    1 / 186 (0.54%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GASTROENTERITIS NOROVIRUS
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 278 (0.36%)
    1 / 76 (1.32%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LEPTOSPIROSIS
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    1 / 373 (0.27%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LOWER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    1 / 373 (0.27%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PERITONITIS
         subjects affected / exposed
    0 / 372 (0.00%)
    0 / 186 (0.00%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    1 / 68 (1.47%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    1 / 278 (0.36%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    PNEUMONIA
         subjects affected / exposed
    1 / 372 (0.27%)
    1 / 186 (0.54%)
    0 / 373 (0.00%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    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 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PULMONARY SEPSIS
         subjects affected / exposed
    0 / 372 (0.00%)
    1 / 186 (0.54%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PYELONEPHRITIS
         subjects affected / exposed
    0 / 372 (0.00%)
    1 / 186 (0.54%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    TONSILLITIS
         subjects affected / exposed
    0 / 372 (0.00%)
    1 / 186 (0.54%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    URINARY TRACT INFECTION
         subjects affected / exposed
    1 / 372 (0.27%)
    0 / 186 (0.00%)
    0 / 373 (0.00%)
    1 / 745 (0.13%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    VULVAL CELLULITIS
         subjects affected / exposed
    0 / 372 (0.00%)
    1 / 186 (0.54%)
    0 / 373 (0.00%)
    0 / 745 (0.00%)
    0 / 68 (0.00%)
    0 / 67 (0.00%)
    0 / 67 (0.00%)
    0 / 278 (0.00%)
    0 / 76 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Period 1 Risankizumab 1200mg IV Period 1 Placebo IV Period 1 Risankizumab 600mg IV Period 1 Risankizumab total Period 2 Risankizumab 360mg SC Period 2 Risankizumab 180mg SC Period 2 Risankizumab 1200mg IV Period 2 Risankizumab total Period 2 Placebo/Risankizumab 1200mg IV
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    58 / 372 (15.59%)
    35 / 186 (18.82%)
    67 / 373 (17.96%)
    125 / 745 (16.78%)
    7 / 68 (10.29%)
    4 / 67 (5.97%)
    4 / 67 (5.97%)
    27 / 278 (9.71%)
    12 / 76 (15.79%)
    Nervous system disorders
    HEADACHE
         subjects affected / exposed
    20 / 372 (5.38%)
    8 / 186 (4.30%)
    24 / 373 (6.43%)
    44 / 745 (5.91%)
    3 / 68 (4.41%)
    1 / 67 (1.49%)
    2 / 67 (2.99%)
    11 / 278 (3.96%)
    5 / 76 (6.58%)
         occurrences all number
    27
    8
    25
    52
    3
    2
    3
    13
    5
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    9 / 372 (2.42%)
    5 / 186 (2.69%)
    11 / 373 (2.95%)
    20 / 745 (2.68%)
    2 / 68 (2.94%)
    0 / 67 (0.00%)
    1 / 67 (1.49%)
    7 / 278 (2.52%)
    4 / 76 (5.26%)
         occurrences all number
    9
    5
    11
    20
    2
    0
    1
    7
    4
    Gastrointestinal disorders
    CROHN'S DISEASE
         subjects affected / exposed
    4 / 372 (1.08%)
    10 / 186 (5.38%)
    5 / 373 (1.34%)
    9 / 745 (1.21%)
    1 / 68 (1.47%)
    2 / 67 (2.99%)
    0 / 67 (0.00%)
    3 / 278 (1.08%)
    0 / 76 (0.00%)
         occurrences all number
    4
    10
    5
    9
    1
    2
    0
    3
    0
    NAUSEA
         subjects affected / exposed
    13 / 372 (3.49%)
    10 / 186 (5.38%)
    16 / 373 (4.29%)
    29 / 745 (3.89%)
    0 / 68 (0.00%)
    1 / 67 (1.49%)
    0 / 67 (0.00%)
    4 / 278 (1.44%)
    3 / 76 (3.95%)
         occurrences all number
    13
    10
    17
    30
    0
    1
    0
    4
    3
    Infections and infestations
    NASOPHARYNGITIS
         subjects affected / exposed
    22 / 372 (5.91%)
    5 / 186 (2.69%)
    22 / 373 (5.90%)
    44 / 745 (5.91%)
    1 / 68 (1.47%)
    1 / 67 (1.49%)
    1 / 67 (1.49%)
    5 / 278 (1.80%)
    2 / 76 (2.63%)
         occurrences all number
    24
    5
    24
    48
    1
    1
    1
    5
    2

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    05 Jul 2017
    Major changes included: Added CDAI criteria to the inclusion criteria. Updated instructions on which hematocrit (Hct) value to use in calculating the CDAI for inclusion. Added "psychological or psychiatric cause" to Exclusion Criterion 29. Updated information on discontinuation of individual subjects for subjects who were not responders at Week 12. Updated contraception recommendations and criteria. Clarification of the blind-breaking process. Updated latent tuberculosis (TB) requirements. Updated pregnancy reporting timing. Added assent information for subjects less than 18 years old.
    29 Sep 2017
    Major changes included: Added an anaphylaxis adjudication committee. Revised to allow for local regulations for the difference in minimum age for adults. Updated of Inclusion Criterion 6 for immunomodulators (IMM) use. Updated of Exclusion Criterion 18 for CD related complications. Updated of prohibited medications. Added international normalized ratio (INR) and anaphylaxis testing. Added details for additional hepatitis testing and anaphylaxis testing. Added endoscopic remission to ranked secondary endpoints and Patient Global Impression of Severity (PGIS) and Patient Global Impression of Change (PGIC) to non ranked secondary endpoints. Added clinical and endoscopic remission over time as endpoints. Updated criteria for discontinuation of individual subjects. Revised to align with Common Toxicity Criteria for Adverse Events (CTCAE) grading criteria for adverse events (AEs). Revised to allow for additional types of anaphylactic reactions and to provide Investigators with guidance on reporting of events. Updated for alignment with template requirements and for consistency across the risankizumab programs. Clarifications of sample size calculation. Updated to reflect the most recent subject diary entries and addition of patient-reported outcome (PRO) for collection. Updated in the schedule of activities to reflect changes made in the body of the protocol. Addition of information on the sample collection schedule. Revised to align with regulatory agency feedback.
    09 Jul 2018
    Major changes included: Extension of the AE collection period duration, final follow-up call, and period for prohibition of vaccines. Modified benefits and risks to align with the IB. Added blood collection for tryptase following a suspected drug administration hypersensitivity reaction. Added "worsening" CD to common AEs associated with underlying disease. Added "intramuscular" as possible route of administration for prohibited anti-infectives. Exclusion of subjects who receive exclusive enteral nutrition to treat CD. Clarification and explanation of inclusion requirements for oral locally acting steroids, IV or oral systemic steroids. Added height measurement for pediatric subjects. Prohibition of local, routine testing for fecal calprotectin and high-sensitivity C-reactive protein. Modified contraception language. Removed stool sample collection for fecal-calprotectin (FCP) at screening. Clarified repeat screening tests and the qualifications for a screening period extension.
    22 Feb 2019
    Major changes included: Documentation of the DMC opinion to continue the trial and enroll 16-17 year olds. Added language to allow single repeat testing of transient exclusionary laboratory values during the screening period. Clarified the types of prohibited corticosteroids. Modified permit enrollment of not more than 20% subjects with prior exposure, including intolerance or inadequate response, to ustekinumab Specification that enrollment of subjects with Baseline SES-CD of ≥ 3 to < 6 for ileocolonic or colonic disease or Baseline SES-CD of 3 for isolated ileal disease would be no more than 10% of the total population. Added stratification factor of Baseline SES-CD. Updated definitions of endoscopic remission and endoscopic response. Revised to allow a commercially available assay to determine approved biologic washout. Clarified that TB prophylaxis is permissible. Revised the order and addition of ranked secondary endpoints, update of ranked secondary endpoints to non ranked secondary endpoints, and addition of non-ranked secondary endpoint. Updated statistical assumptions for sample size determination. Added details of multiplicity adjustment and subgroup analysis for Bio-IR and non Bio-IR population. Updated of the missing imputation methodology to remove last observation carried forward (LOCF).
    19 Dec 2019
    Major changes included: Specified total N of 855 for the primary intent-to-treat (ITT) population used for efficacy analysis, that the number of subjects with lower SES-CD will be no more than 85, and that data collected from subjects with the lower SES-CD will be analyzed as an exploratory efficacy analysis. Specified that Hct from the preceding visit may be used to calculate the CDAI if there are technical issues. Revised the definition of endoscopic remission. Revised the term "endoscopic healing" to "ulcer-free endoscopy". Updated of secondary endpoint ranking and combining and adding new ranked secondary endpoints. Clarified timing of DBL Removed the missing imputation method OC from the sensitivity analysis of the continuous efficacy variables. Added missing data handling methods. Clarified the way continuous laboratory and vital signs would be summarized. Removed Fisher's exact test for risankizumab treatment group differences versus placebo for AEs.
    28 Jul 2020
    Major changes included: Revised language throughout due to the Coronavirus disease – 2019 (COVID-19) pandemic, including benefit and risk, criteria to exclude subjects with active COVID-19, addition of COVID-19 AE data collection process, modification of study visits/protocol-specified procedures impacted by changes in local regulations, protocol deviations, missing data, data monitoring, and COVID-19 testing. Added language regarding site responsibility. Clarified HIV results language.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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