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    Clinical Trial Results:
    A phase II, multicenter, randomized, double-blind, multiple dose, placebo-controlled, parallel-group study to evaluate the efficacy, pharmacokinetics, and safety of BI 655066/ABBV-066 (risankizumab), an Interleukin [IL]-23 p19 antagonist monoclonal antibody, in patients with moderately to severely active Crohn’s Disease, who are naïve to, or were previously treated with anti-Tumor Necrosis Factor [TNF] therapy

    Summary
    EudraCT number
    2013-002902-29
    Trial protocol
    BE   GB   IE   ES   NL   DE  
    Global end of trial date
    18 Nov 2016

    Results information
    Results version number
    v1(current)
    This version publication date
    01 Dec 2017
    First version publication date
    01 Dec 2017
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    1311.6
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02031276
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Boehringer Ingelheim
    Sponsor organisation address
    Binger Strasse 173, Ingelheim am Rhein, Germany, 55216
    Public contact
    QRPE Processes and Systems Coordination, Clinical Trial Information Disclosure, Boehringer Ingelheim, +1 8002430127, clintriage.rdg@boehringer-ingelheim.com
    Scientific contact
    QRPE Processes and Systems Coordination, Clinical Trial Information Disclosure, Boehringer Ingelheim, +1 8002430127, clintriage.rdg@boehringer-ingelheim.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
    13 Jan 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    22 Dec 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Nov 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This study is a proof of concept, multi-center, randomized, double-blind, placebo-controlled, parallel-group phase 2 dose-ranging study of BI 655066, an IL-23 p19 antagonist monoclonal antibody, in patients with moderately to severely active Crohn's disease.
    Protection of trial subjects
    Only subjects who met all the study inclusion and none of the exclusion criteria were to be entered in the study. All subjects were free to withdraw from the clinical trial at any time for any reason given. Close monitoring of all subjects was adhered to throughout the trial conduct. Rescue medication was allowed for all patients as required.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    25 Feb 2014
    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
    Spain: 13
    Country: Number of subjects enrolled
    United Kingdom: 16
    Country: Number of subjects enrolled
    United States: 13
    Country: Number of subjects enrolled
    Belgium: 38
    Country: Number of subjects enrolled
    Canada: 2
    Country: Number of subjects enrolled
    Germany: 9
    Country: Number of subjects enrolled
    Korea, Republic of: 15
    Country: Number of subjects enrolled
    Netherlands: 10
    Country: Number of subjects enrolled
    Poland: 5
    Worldwide total number of subjects
    121
    EEA total number of subjects
    91
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    116
    From 65 to 84 years
    5
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    Participants were randomized to 1 of 3 double-blind treatment arms in Period 1; those who achieved deep remission in Period 1 entered Period 2 washout; those who did not achieve deep remission in Period 1 entered Period 2 open-label (OL) treatment. Participants who were in clinical remission at the end of Period 2 continued to Period 3 OL treatment

    Period 1
    Period 1 title
    Double-blind IV
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator
    Blinding implementation details
    Period 1 was blinded intravenous (IV) therapy, period 2 was open label IV therapy and period 3 was open label subcutaneous (SC) therapy.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Double-blind Placebo IV (Period 1)
    Arm description
    Participants randomized to receive double-blind placebo for risankizumab by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by subcutaneous (SC) injection in Period 3.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo for risankizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Placebo for risankizumab administered by IV infusion.

    Arm title
    Double-blind Risankizumab 200 mg IV (Period 1)
    Arm description
    Participants randomized to receive double-blind risankizumab 200 mg by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by in Period 3.
    Arm type
    Experimental

    Investigational medicinal product name
    risankizumab
    Investigational medicinal product code
    Other name
    BI 655066, ABBV-066
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Risankizumab administered by IV infusion.

    Arm title
    Double-blind Risankizumab 600 mg IV (Period 1)
    Arm description
    Participants randomized to receive double-blind risankizumab 600 mg by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by subcutaneous (SC) injection in Period 3.
    Arm type
    Experimental

    Investigational medicinal product name
    risankizumab
    Investigational medicinal product code
    Other name
    BI 655066, ABBV-066
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Risankizumab administered by IV infusion.

    Number of subjects in period 1
    Double-blind Placebo IV (Period 1) Double-blind Risankizumab 200 mg IV (Period 1) Double-blind Risankizumab 600 mg IV (Period 1)
    Started
    39
    41
    41
    Completed
    33
    35
    40
    Not completed
    6
    6
    1
         Not specified
    -
    1
    -
         Adverse event, non-fatal
    6
    5
    1
    Period 2
    Period 2 title
    Open-label Risankizumab IV
    Is this the baseline period?
    No
    Allocation method
    Non-randomised - controlled
    Blinding used
    Not blinded
    Blinding implementation details
    no re-randomisation was done

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Double-blind Placebo (Period 1)
    Arm description
    Participants randomized to receive double-blind placebo for risankizumab by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by subcutaneous (SC) injection in Period 3.
    Arm type
    Experimental

    Investigational medicinal product name
    risankizumab
    Investigational medicinal product code
    Other name
    BI 655066, ABBV-066
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Risankizumab administered by IV infusion.

    Arm title
    Double-blind Risankizumab 200 mg IV (Period 1)
    Arm description
    Participants randomized to receive double-blind risankizumab 200 mg by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by in Period 3.
    Arm type
    Experimental

    Investigational medicinal product name
    risankizumab
    Investigational medicinal product code
    Other name
    BI 655066, ABBV-066
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Risankizumab administered by IV infusion.

    Arm title
    Double-blind Risankizumab 600 mg IV (Period 1)
    Arm description
    Participants randomized to receive double-blind risankizumab 600 mg by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by subcutaneous (SC) injection in Period 3.
    Arm type
    Experimental

    Investigational medicinal product name
    risankizumab
    Investigational medicinal product code
    Other name
    BI 655066, ABBV-066
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Risankizumab administered by IV infusion.

    Number of subjects in period 2 [1]
    Double-blind Placebo (Period 1) Double-blind Risankizumab 200 mg IV (Period 1) Double-blind Risankizumab 600 mg IV (Period 1)
    Started
    33
    35
    39
    Completed
    29
    33
    38
    Not completed
    4
    2
    1
         Withdrawal by subject
    3
    -
    -
         Not specified
    -
    2
    1
         Adverse event, non-fatal
    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: One subject did not enter Period 2 (declined open-label treatment in Period 2) in the Double-blind Risankizumab 600 mg IV group.
    Period 3
    Period 3 title
    Open-label Risankizumab SC
    Is this the baseline period?
    No
    Allocation method
    Non-randomised - controlled
    Blinding used
    Not blinded
    Blinding implementation details
    no re-randomisation was done

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Double-blind Placebo IV (Period 1)
    Arm description
    Participants randomized to receive double-blind placebo for risankizumab by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by subcutaneous (SC) injection in Period 3.
    Arm type
    Experimental

    Investigational medicinal product name
    risankizumab
    Investigational medicinal product code
    Other name
    BI 655066, ABBV-066
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Risankizumab administered by SC infusion.

    Arm title
    Double-blind Risankizumab 200 mg IV (Period 1)
    Arm description
    Participants randomized to receive double-blind risankizumab 200 mg by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by in Period 3.
    Arm type
    Experimental

    Investigational medicinal product name
    risankizumab
    Investigational medicinal product code
    Other name
    BI 655066, ABBV-066
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Risankizumab administered by SC infusion.

    Arm title
    Double-blind Risankizumab 600 mg IV (Period 1)
    Arm description
    Participants randomized to receive double-blind risankizumab 600 mg by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by subcutaneous (SC) injection in Period 3.
    Arm type
    Experimental

    Investigational medicinal product name
    risankizumab
    Investigational medicinal product code
    Other name
    BI 655066, ABBV-066
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Risankizumab administered by SC infusion.

    Number of subjects in period 3 [2]
    Double-blind Placebo IV (Period 1) Double-blind Risankizumab 200 mg IV (Period 1) Double-blind Risankizumab 600 mg IV (Period 1)
    Started
    19
    22
    21
    Completed
    16
    19
    19
    Not completed
    3
    3
    2
         Protocol deviation
    2
    -
    -
         Withdrawal by subject
    1
    1
    1
         Not specified
    -
    -
    1
         Adverse event, non-fatal
    -
    2
    -
    Notes
    [2] - 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: A total of 38 subjects did not enter Period 3 (not in clinical remission); 10 subjects in the Double-blind Placebo IV group, 11 subjects in the Double-blind Risankizumab 200 mg IV group, and 17 subjects in the Double-blind Risankizumab 600 mg IV group.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Double-blind Placebo IV (Period 1)
    Reporting group description
    Participants randomized to receive double-blind placebo for risankizumab by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by subcutaneous (SC) injection in Period 3.

    Reporting group title
    Double-blind Risankizumab 200 mg IV (Period 1)
    Reporting group description
    Participants randomized to receive double-blind risankizumab 200 mg by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by in Period 3.

    Reporting group title
    Double-blind Risankizumab 600 mg IV (Period 1)
    Reporting group description
    Participants randomized to receive double-blind risankizumab 600 mg by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by subcutaneous (SC) injection in Period 3.

    Reporting group values
    Double-blind Placebo IV (Period 1) Double-blind Risankizumab 200 mg IV (Period 1) Double-blind Risankizumab 600 mg IV (Period 1) Total
    Number of subjects
    39 41 41
    Age categorical
    Units: Subjects
    Age Continuous
    Full Analysis Set - Period 1 (FAS-P1): All randomized subjects who received at least 1 dose of study drug in the double-blind IV period (Period 1).
    Units: years
        arithmetic mean (standard deviation)
    35.5 ± 13.86 38.8 ± 13.27 39.9 ± 13.26 -
    Gender, Male/Female
    Units: Subjects
        Female
    16 15 16 47
        Male
    23 26 25 74

    End points

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    End points reporting groups
    Reporting group title
    Double-blind Placebo IV (Period 1)
    Reporting group description
    Participants randomized to receive double-blind placebo for risankizumab by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by subcutaneous (SC) injection in Period 3.

    Reporting group title
    Double-blind Risankizumab 200 mg IV (Period 1)
    Reporting group description
    Participants randomized to receive double-blind risankizumab 200 mg by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by in Period 3.

    Reporting group title
    Double-blind Risankizumab 600 mg IV (Period 1)
    Reporting group description
    Participants randomized to receive double-blind risankizumab 600 mg by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by subcutaneous (SC) injection in Period 3.
    Reporting group title
    Double-blind Placebo (Period 1)
    Reporting group description
    Participants randomized to receive double-blind placebo for risankizumab by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by subcutaneous (SC) injection in Period 3.

    Reporting group title
    Double-blind Risankizumab 200 mg IV (Period 1)
    Reporting group description
    Participants randomized to receive double-blind risankizumab 200 mg by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by in Period 3.

    Reporting group title
    Double-blind Risankizumab 600 mg IV (Period 1)
    Reporting group description
    Participants randomized to receive double-blind risankizumab 600 mg by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by subcutaneous (SC) injection in Period 3.
    Reporting group title
    Double-blind Placebo IV (Period 1)
    Reporting group description
    Participants randomized to receive double-blind placebo for risankizumab by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by subcutaneous (SC) injection in Period 3.

    Reporting group title
    Double-blind Risankizumab 200 mg IV (Period 1)
    Reporting group description
    Participants randomized to receive double-blind risankizumab 200 mg by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by in Period 3.

    Reporting group title
    Double-blind Risankizumab 600 mg IV (Period 1)
    Reporting group description
    Participants randomized to receive double-blind risankizumab 600 mg by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by subcutaneous (SC) injection in Period 3.

    Subject analysis set title
    Double-blind Placebo IV (Period 1)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants randomized to receive double-blind placebo for risankizumab by intravenous (IV) injection for 12 weeks.

    Subject analysis set title
    Double-blind Risankizumab 200 mg IV (Period 1)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants randomized to receive double-blind risankizumab 200 mg by intravenous (IV) injection for 12 weeks.

    Subject analysis set title
    Double-blind Risankizumab 600 mg IV (Period 1)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants randomized to receive double-blind risankizumab 600 mg by intravenous (IV) injection for 12 weeks.

    Subject analysis set title
    Double-blind Risankizumab 200 + 600 mg IV (Period 1)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants randomized to receive double-blind risankizumab 200 mg and 600 mg by intravenous (IV) injection for 12 weeks.

    Primary: Percentage of participants achieving CDAI Clinical Remission at week 12

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    End point title
    Percentage of participants achieving CDAI Clinical Remission at week 12
    End point description
    The CDAI is a measure of clinical response and remission. The CDAI includes 8 variables encompassing both patient-reported (symptoms, general well-being) and objective (medication usage, laboratory variables, presence of abdominal mass or complications, and weight) variables. For symptoms scores, patients keep track of daily symptoms on a diary card and the daily symptom scores are summed for the week. Each item in the CDAI is assigned a specific weight, and the weighted values of the items are totaled to produce the CDAI. Higher CDAI scores indicate greater disease activity, with a lower limit of 0 and no set upper limit: < 150 indicates remission, 150 - 219 indicates mildly active disease, 220 - 450 indicates moderately active disease, and > 450 indicates severely active disease. CDAI clinical remission is defined as CDAI < 150 at Week 12. Nonresponder Imputation (NRI): Missing values were counted as nonresponders.
    End point type
    Primary
    End point timeframe
    Week 12
    End point values
    Double-blind Placebo IV (Period 1) Double-blind Risankizumab 200 mg IV (Period 1) Double-blind Risankizumab 600 mg IV (Period 1) Double-blind Risankizumab 200 + 600 mg IV (Period 1)
    Number of subjects analysed
    39 [1]
    41 [2]
    41 [3]
    82 [4]
    Units: Percentage of participants
        number (confidence interval 95%)
    15.4 (5.9 to 30.5)
    19.5 (8.8 to 34.9)
    36.6 (22.1 to 53.1)
    28.0 (18.7 to 39.1)
    Notes
    [1] - FAS-P1
    [2] - FAS-P1
    [3] - FAS-P1
    [4] - FAS-P1
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Statistics for the difference are calculated using the Cochran-Mantel-Haenszel risk difference stratified by anti-tumor necrosis factor (anti-TNF) exposure.
    Comparison groups
    Double-blind Placebo IV (Period 1) v Double-blind Risankizumab 200 + 600 mg IV (Period 1)
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.0955
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    difference in percentage of participants
    Point estimate
    12.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.2
         upper limit
    27.5

    Secondary: Percentage of Participants Achieving CDAI Clinical Response at Week 12

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    End point title
    Percentage of Participants Achieving CDAI Clinical Response at Week 12
    End point description
    The CDAI is a measure of clinical response and remission. The CDAI includes 8 variables encompassing both patient-reported (symptoms, general well-being) and objective (medication usage, laboratory variables, presence of abdominal mass or complications, and weight) variables. For symptoms scores, patients keep track of daily symptoms on a diary card and the daily symptom scores are summed for the week. Each item in the CDAI is assigned a specific weight, and the weighted values of the items are totaled to produce the CDAI. Higher CDAI scores indicate greater disease activity, with a lower limit of 0 and no set upper limit: < 150 indicates remission, 150 - 219 indicates mildly active disease, 220 - 450 indicates moderately active disease, and > 450 indicates severely active disease. CDAI clinical response is defined as either a CDAI < 150 or a CDAI reduction from Baseline of at least 100 points at Week 12. NRI: Missing values were counted as nonresponders.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    Double-blind Placebo IV (Period 1) Double-blind Risankizumab 200 mg IV (Period 1) Double-blind Risankizumab 600 mg IV (Period 1) Double-blind Risankizumab 200 + 600 mg IV (Period 1)
    Number of subjects analysed
    39 [5]
    41 [6]
    41 [7]
    82 [8]
    Units: Percentage of participants
        number (confidence interval 95%)
    23.1 (11.1 to 39.3)
    31.7 (18.1 to 48.1)
    41.5 (26.3 to 57.9)
    36.6 (26.2 to 48.0)
    Notes
    [5] - FAS-P1
    [6] - FAS-P1
    [7] - FAS-P1
    [8] - FAS-P1
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Statistics for the difference are calculated using the Cochran-Mantel-Haenszel risk difference stratified by anti-TNF exposure.
    Comparison groups
    Double-blind Placebo IV (Period 1) v Double-blind Risankizumab 200 + 600 mg IV (Period 1)
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.1151
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    difference in percentage of participants
    Point estimate
    13.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.3
         upper limit
    30.1

    Secondary: Percentage of Participants Achieving Crohn's Disease Endoscopic Activity Index of Severity (CDEIS) Remission at Week 12

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    End point title
    Percentage of Participants Achieving Crohn's Disease Endoscopic Activity Index of Severity (CDEIS) Remission at Week 12
    End point description
    CDEIS is an index for determining the severity of Crohn's disease with endoscopic localization to ileum and colon. CDEIS considers 4 parameters (deep ulcerations, superficial ulcerations, surface involved by disease, and surface involved by ulcerations), each one evaluated in 5 pre-defined segments of the colon (ileum, ascending colon, transverse colon, descending colon and sigmoid loop, and rectum). The results of the individual segments of the colon are divided by the number of segments investigated; the presence of stenosis increases the score at the end of the computation. CDEIS remission is defined as a CDEIS ≤ 4 (or, for patients with initial isolated ileitis, a CDEIS ≤ 2) at Week 12. NRI: Missing values were counted as nonresponders.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    Double-blind Placebo IV (Period 1) Double-blind Risankizumab 200 mg IV (Period 1) Double-blind Risankizumab 600 mg IV (Period 1) Double-blind Risankizumab 200 + 600 mg IV (Period 1)
    Number of subjects analysed
    39 [9]
    41 [10]
    41 [11]
    82 [12]
    Units: Percentage of participants
        number (confidence interval 95%)
    2.6 (0.1 to 13.5)
    9.8 (2.7 to 23.1)
    19.5 (8.8 to 34.9)
    14.6 (7.8 to 24.2)
    Notes
    [9] - FAS-P1
    [10] - FAS-P1
    [11] - FAS-P1
    [12] - FAS-P1
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Statistics for the difference are calculated using the Cochran-Mantel-Haenszel risk difference stratified by anti-TNF exposure.
    Comparison groups
    Double-blind Placebo IV (Period 1) v Double-blind Risankizumab 200 + 600 mg IV (Period 1)
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.0057
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    difference in percentage of participants
    Point estimate
    12
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.5
         upper limit
    20.6

    Secondary: Percentage of Participants Achieving CDEIS Response at Week 12

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    End point title
    Percentage of Participants Achieving CDEIS Response at Week 12
    End point description
    CDEIS is an index for determining the severity of Crohn's disease with endoscopic localization to ileum and colon. CDEIS considers 4 parameters (deep ulcerations, superficial ulcerations, surface involved by disease, and surface involved by ulcerations), each one evaluated in 5 pre-defined segments of the colon (ileum, ascending colon, transverse colon, descending colon and sigmoid loop, and rectum). The results of the individual segments of the colon are divided by the number of segments investigated; the presence of stenosis increases the score at the end of the computation. CDEIS response is defined as defined as ≥ 50% reduction of CDEIS from Baseline to Week 12. NRI: Missing values were counted as nonresponders.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    Double-blind Placebo IV (Period 1) Double-blind Risankizumab 200 mg IV (Period 1) Double-blind Risankizumab 600 mg IV (Period 1) Double-blind Risankizumab 200 + 600 mg IV (Period 1)
    Number of subjects analysed
    39 [13]
    41 [14]
    41 [15]
    82 [16]
    Units: Percentage of participants
        number (confidence interval 95%)
    12.8 (4.3 to 27.4)
    26.8 (14.2 to 42.9)
    36.6 (22.1 to 53.1)
    31.7 (21.9 to 42.9)
    Notes
    [13] - FAS-P1
    [14] - FAS-P1
    [15] - FAS-P1
    [16] - FAS-P1
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Statistics for the difference are calculated using the Cochran-Mantel-Haenszel risk difference stratified by anti-TNF exposure.
    Comparison groups
    Double-blind Placebo IV (Period 1) v Double-blind Risankizumab 200 + 600 mg IV (Period 1)
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.0104
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    difference in percentage of participants
    Point estimate
    18.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    4.4
         upper limit
    33

    Secondary: Percentage of Participants Achieving Mucosal Healing at Week 12

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    End point title
    Percentage of Participants Achieving Mucosal Healing at Week 12
    End point description
    Mucosal healing was defined as the absence of mucosal ulceration, i.e., a CDEIS ulceration sub-score (deep ulceration, superficial ulceration, ulcerated stenosis) of 0 at Week 12. NRI: Missing values were counted as nonresponders.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    Double-blind Placebo IV (Period 1) Double-blind Risankizumab 200 mg IV (Period 1) Double-blind Risankizumab 600 mg IV (Period 1) Double-blind Risankizumab 200 + 600 mg IV (Period 1)
    Number of subjects analysed
    39 [17]
    41 [18]
    41 [19]
    82 [20]
    Units: Percentage of participants
        number (confidence interval 95%)
    2.6 (0.1 to 13.5)
    2.4 (0.1 to 12.9)
    7.3 (1.5 to 19.9)
    4.9 (1.3 to 12.0)
    Notes
    [17] - FAS-P1
    [18] - FAS-P1
    [19] - FAS-P1
    [20] - FAS-P1
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Statistics for the difference are calculated using the Cochran-Mantel-Haenszel risk difference stratified by anti-TNF exposure.
    Comparison groups
    Double-blind Placebo IV (Period 1) v Double-blind Risankizumab 200 + 600 mg IV (Period 1)
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.4977
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    difference in percentage of participants
    Point estimate
    2.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.5
         upper limit
    9.2

    Secondary: Percentage of Participants Achieving Deep Remission at Week 12

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    End point title
    Percentage of Participants Achieving Deep Remission at Week 12
    End point description
    Deep remission is defined as clinical remission (CDAI < 150) AND CDEIS remission (CDEIS ≤ 4, or ≤ 2 in participants with initial isolated ileitis) at Week 12. NRI: missing values were counted as nonresponders.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    Double-blind Placebo IV (Period 1) Double-blind Risankizumab 200 mg IV (Period 1) Double-blind Risankizumab 600 mg IV (Period 1) Double-blind Risankizumab 200 + 600 mg IV (Period 1)
    Number of subjects analysed
    39 [21]
    41 [22]
    41 [23]
    82 [24]
    Units: Percentage of participants
        number (confidence interval 95%)
    0 (0.0 to 9.0)
    2.4 (0.1 to 12.9)
    12.2 (4.1 to 26.2)
    7.3 (2.7 to 15.2)
    Notes
    [21] - FAS-P1
    [22] - FAS-P1
    [23] - FAS-P1
    [24] - FAS-P1
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Statistics for the difference are calculated using the Cochran-Mantel-Haenszel risk difference stratified by tumor necrosis factor (TNF)-exposure.
    Comparison groups
    Double-blind Placebo IV (Period 1) v Double-blind Risankizumab 200 + 600 mg IV (Period 1)
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.0107
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    difference in percentage of participants
    Point estimate
    7.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.7
         upper limit
    13

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Treatment-emergent AEs (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 15 weeks after the last dose of study drug (up to 67 weeks).
    Adverse event reporting additional description
    TEAEs and TESAEs: AEs and SAEs with onset/worsening from the first dose of DB study drug until either the first dose of OL risankizumab or 15 weeks after the last dose of DB study drug (up to 27 weeks); for All Risankizumab, from the first dose of DB or OL risankizumab until 15 weeks after the last dose of risankizumab (up to 67 weeks).
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    Double-blind Placebo IV (Period 1)
    Reporting group description
    Participants received double-blind placebo for risankizumab by intravenous (IV) injection for 12 weeks.

    Reporting group title
    Double-blind Risankizumab 200 mg IV (Period 1)
    Reporting group description
    Participants received double-blind risankizumab 200 mg by intravenous (IV) injection for 12 weeks.

    Reporting group title
    Double-blind Risankizumab 600 mg IV (Period 1)
    Reporting group description
    Participants administered double-blind risankizumab 600 mg by intravenous (IV) injection for 12 weeks.

    Reporting group title
    Open-label Risankizumab 600 mg IV (Period 2)
    Reporting group description
    Participants administered open-label risankizumab 600 mg by intravenous (IV) injection for 12 weeks.

    Reporting group title
    Open-label Risankizumab 180 mg SC (Period 3)
    Reporting group description
    Participants administered open-label risankizumab 600 mg by subcutaneous (SC) injection for 12 weeks.

    Reporting group title
    All Risankizumab
    Reporting group description
    Participants administered at least one dose of risankizumab.

    Serious adverse events
    Double-blind Placebo IV (Period 1) Double-blind Risankizumab 200 mg IV (Period 1) Double-blind Risankizumab 600 mg IV (Period 1) Open-label Risankizumab 600 mg IV (Period 2) Open-label Risankizumab 180 mg SC (Period 3) All Risankizumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    13 / 39 (33.33%)
    10 / 41 (24.39%)
    4 / 41 (9.76%)
    11 / 101 (10.89%)
    7 / 62 (11.29%)
    31 / 115 (26.96%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    Vascular disorders
    CIRCULATORY COLLAPSE
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    1 / 101 (0.99%)
    0 / 62 (0.00%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DEEP VEIN THROMBOSIS
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    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
    Surgical and medical procedures
    ABORTION INDUCED
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    1 / 101 (0.99%)
    0 / 62 (0.00%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    ANAPHYLACTIC REACTION
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    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
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    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
    PAIN
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 41 (2.44%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PYREXIA
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    1 / 101 (0.99%)
    0 / 62 (0.00%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    PSYCHIATRIC DECOMPENSATION
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    1 / 62 (1.61%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    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
    SUICIDE ATTEMPT
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    1 / 62 (1.61%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    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
    Investigations
    BLOOD MAGNESIUM DECREASED
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 41 (0.00%)
    1 / 41 (2.44%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    TACHYCARDIA
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    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
    Respiratory, thoracic and mediastinal disorders
    PNEUMOTHORAX
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    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
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    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
    NEUTROPENIA
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    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
    Nervous system disorders
    CEREBROSPINAL FLUID LEAKAGE
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    1 / 101 (0.99%)
    0 / 62 (0.00%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HEADACHE
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    1 / 101 (0.99%)
    0 / 62 (0.00%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HEMIPARESIS
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    1 / 62 (1.61%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    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
    MIGRAINE
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    1 / 62 (1.61%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    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
    Eye disorders
    BLINDNESS TRANSIENT
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    1 / 101 (0.99%)
    0 / 62 (0.00%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    DIPLOPIA
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 41 (2.44%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    SUDDEN HEARING LOSS
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    1 / 62 (1.61%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    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
    Gastrointestinal disorders
    ANAL FISTULA
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    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
    APHTHOUS ULCER
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    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
    CROHN'S DISEASE
         subjects affected / exposed
    5 / 39 (12.82%)
    2 / 41 (4.88%)
    1 / 41 (2.44%)
    3 / 101 (2.97%)
    1 / 62 (1.61%)
    7 / 115 (6.09%)
         occurrences causally related to treatment / all
    2 / 6
    0 / 2
    0 / 1
    1 / 4
    0 / 1
    1 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INTESTINAL OBSTRUCTION
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    2 / 101 (1.98%)
    1 / 62 (1.61%)
    3 / 115 (2.61%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INTESTINAL PERFORATION
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 41 (2.44%)
    0 / 41 (0.00%)
    1 / 101 (0.99%)
    0 / 62 (0.00%)
    2 / 115 (1.74%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PROCTALGIA
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    1 / 101 (0.99%)
    0 / 62 (0.00%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SMALL INTESTINAL OBSTRUCTION
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 41 (2.44%)
    0 / 41 (0.00%)
    2 / 101 (1.98%)
    0 / 62 (0.00%)
    3 / 115 (2.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    ACUTE KIDNEY INJURY
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 41 (2.44%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RENAL COLIC
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 41 (2.44%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RENAL FAILURE
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 41 (2.44%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    CHOLELITHIASIS
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    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
    Musculoskeletal and connective tissue disorders
    INTERVERTEBRAL DISC PROTRUSION
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    1 / 62 (1.61%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    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
    Metabolism and nutrition disorders
    HYPOKALAEMIA
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 41 (0.00%)
    1 / 41 (2.44%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPONATRAEMIA
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 41 (2.44%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPOPHOSPHATAEMIA
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 41 (0.00%)
    1 / 41 (2.44%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    MALNUTRITION
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 41 (2.44%)
    0 / 41 (0.00%)
    1 / 101 (0.99%)
    0 / 62 (0.00%)
    2 / 115 (1.74%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    METABOLIC ACIDOSIS
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 41 (2.44%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    ABDOMINAL ABSCESS
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    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
    ANAL ABSCESS
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 41 (0.00%)
    1 / 41 (2.44%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    APPENDICITIS
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    1 / 62 (1.61%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    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
    INCISION SITE ABSCESS
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    1 / 101 (0.99%)
    0 / 62 (0.00%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    OSTEOMYELITIS
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 41 (0.00%)
    1 / 41 (2.44%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 41 (2.44%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    1 / 115 (0.87%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RECTAL ABSCESS
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    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
    VAGINAL ABSCESS
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    0 / 115 (0.00%)
         occurrences causally related to treatment / all
    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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Double-blind Placebo IV (Period 1) Double-blind Risankizumab 200 mg IV (Period 1) Double-blind Risankizumab 600 mg IV (Period 1) Open-label Risankizumab 600 mg IV (Period 2) Open-label Risankizumab 180 mg SC (Period 3) All Risankizumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    28 / 39 (71.79%)
    25 / 41 (60.98%)
    21 / 41 (51.22%)
    48 / 101 (47.52%)
    31 / 62 (50.00%)
    80 / 115 (69.57%)
    Injury, poisoning and procedural complications
    INFUSION RELATED REACTION
         subjects affected / exposed
    2 / 39 (5.13%)
    1 / 41 (2.44%)
    0 / 41 (0.00%)
    3 / 101 (2.97%)
    0 / 62 (0.00%)
    4 / 115 (3.48%)
         occurrences all number
    3
    1
    0
    3
    0
    4
    Respiratory, thoracic and mediastinal disorders
    COUGH
         subjects affected / exposed
    4 / 39 (10.26%)
    1 / 41 (2.44%)
    0 / 41 (0.00%)
    3 / 101 (2.97%)
    3 / 62 (4.84%)
    7 / 115 (6.09%)
         occurrences all number
    5
    1
    0
    3
    3
    7
    OROPHARYNGEAL PAIN
         subjects affected / exposed
    1 / 39 (2.56%)
    2 / 41 (4.88%)
    1 / 41 (2.44%)
    4 / 101 (3.96%)
    2 / 62 (3.23%)
    8 / 115 (6.96%)
         occurrences all number
    1
    2
    1
    4
    2
    9
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 41 (0.00%)
    3 / 41 (7.32%)
    2 / 101 (1.98%)
    1 / 62 (1.61%)
    6 / 115 (5.22%)
         occurrences all number
    2
    0
    4
    2
    1
    7
    Nervous system disorders
    DIZZINESS
         subjects affected / exposed
    1 / 39 (2.56%)
    1 / 41 (2.44%)
    3 / 41 (7.32%)
    5 / 101 (4.95%)
    1 / 62 (1.61%)
    9 / 115 (7.83%)
         occurrences all number
    1
    1
    4
    5
    1
    11
    HEADACHE
         subjects affected / exposed
    5 / 39 (12.82%)
    6 / 41 (14.63%)
    5 / 41 (12.20%)
    7 / 101 (6.93%)
    6 / 62 (9.68%)
    22 / 115 (19.13%)
         occurrences all number
    6
    7
    7
    10
    7
    31
    LETHARGY
         subjects affected / exposed
    3 / 39 (7.69%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    2 / 101 (1.98%)
    1 / 62 (1.61%)
    2 / 115 (1.74%)
         occurrences all number
    4
    0
    0
    2
    1
    3
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    2 / 39 (5.13%)
    4 / 41 (9.76%)
    2 / 41 (4.88%)
    3 / 101 (2.97%)
    1 / 62 (1.61%)
    9 / 115 (7.83%)
         occurrences all number
    3
    5
    2
    3
    1
    11
    FATIGUE
         subjects affected / exposed
    3 / 39 (7.69%)
    0 / 41 (0.00%)
    2 / 41 (4.88%)
    2 / 101 (1.98%)
    5 / 62 (8.06%)
    8 / 115 (6.96%)
         occurrences all number
    3
    0
    2
    2
    5
    9
    INFLUENZA LIKE ILLNESS
         subjects affected / exposed
    2 / 39 (5.13%)
    1 / 41 (2.44%)
    2 / 41 (4.88%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    3 / 115 (2.61%)
         occurrences all number
    2
    1
    2
    0
    0
    3
    MALAISE
         subjects affected / exposed
    0 / 39 (0.00%)
    0 / 41 (0.00%)
    1 / 41 (2.44%)
    4 / 101 (3.96%)
    2 / 62 (3.23%)
    7 / 115 (6.09%)
         occurrences all number
    0
    0
    1
    4
    2
    7
    PERIPHERAL SWELLING
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    0 / 115 (0.00%)
         occurrences all number
    4
    0
    0
    0
    0
    0
    PYREXIA
         subjects affected / exposed
    3 / 39 (7.69%)
    3 / 41 (7.32%)
    3 / 41 (7.32%)
    6 / 101 (5.94%)
    3 / 62 (4.84%)
    14 / 115 (12.17%)
         occurrences all number
    3
    4
    3
    7
    3
    17
    Psychiatric disorders
    INSOMNIA
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 41 (2.44%)
    3 / 41 (7.32%)
    1 / 101 (0.99%)
    2 / 62 (3.23%)
    6 / 115 (5.22%)
         occurrences all number
    0
    1
    3
    1
    2
    7
    SLEEP DISORDER
         subjects affected / exposed
    2 / 39 (5.13%)
    1 / 41 (2.44%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    0 / 62 (0.00%)
    1 / 115 (0.87%)
         occurrences all number
    2
    1
    0
    0
    0
    1
    Gastrointestinal disorders
    ABDOMINAL PAIN
         subjects affected / exposed
    5 / 39 (12.82%)
    6 / 41 (14.63%)
    4 / 41 (9.76%)
    11 / 101 (10.89%)
    5 / 62 (8.06%)
    21 / 115 (18.26%)
         occurrences all number
    5
    6
    4
    12
    6
    28
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    0 / 39 (0.00%)
    2 / 41 (4.88%)
    1 / 41 (2.44%)
    2 / 101 (1.98%)
    3 / 62 (4.84%)
    8 / 115 (6.96%)
         occurrences all number
    0
    2
    1
    2
    3
    8
    CROHN'S DISEASE
         subjects affected / exposed
    1 / 39 (2.56%)
    0 / 41 (0.00%)
    0 / 41 (0.00%)
    0 / 101 (0.00%)
    4 / 62 (6.45%)
    4 / 115 (3.48%)
         occurrences all number
    1
    0
    0
    0
    4
    4
    DIARRHOEA
         subjects affected / exposed
    2 / 39 (5.13%)
    2 / 41 (4.88%)
    3 / 41 (7.32%)
    4 / 101 (3.96%)
    1 / 62 (1.61%)
    9 / 115 (7.83%)
         occurrences all number
    3
    2
    3
    5
    1
    11
    HAEMATOCHEZIA
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 41 (0.00%)
    2 / 41 (4.88%)
    2 / 101 (1.98%)
    1 / 62 (1.61%)
    4 / 115 (3.48%)
         occurrences all number
    2
    0
    2
    2
    2
    6
    NAUSEA
         subjects affected / exposed
    4 / 39 (10.26%)
    9 / 41 (21.95%)
    4 / 41 (9.76%)
    6 / 101 (5.94%)
    1 / 62 (1.61%)
    18 / 115 (15.65%)
         occurrences all number
    4
    9
    4
    6
    1
    20
    VOMITING
         subjects affected / exposed
    4 / 39 (10.26%)
    4 / 41 (9.76%)
    2 / 41 (4.88%)
    7 / 101 (6.93%)
    0 / 62 (0.00%)
    11 / 115 (9.57%)
         occurrences all number
    4
    4
    2
    8
    0
    14
    Skin and subcutaneous tissue disorders
    ALOPECIA
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 41 (0.00%)
    1 / 41 (2.44%)
    3 / 101 (2.97%)
    0 / 62 (0.00%)
    4 / 115 (3.48%)
         occurrences all number
    2
    0
    1
    3
    0
    4
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    4 / 39 (10.26%)
    6 / 41 (14.63%)
    8 / 41 (19.51%)
    7 / 101 (6.93%)
    6 / 62 (9.68%)
    25 / 115 (21.74%)
         occurrences all number
    4
    6
    10
    7
    6
    29
    BACK PAIN
         subjects affected / exposed
    2 / 39 (5.13%)
    1 / 41 (2.44%)
    3 / 41 (7.32%)
    3 / 101 (2.97%)
    2 / 62 (3.23%)
    9 / 115 (7.83%)
         occurrences all number
    2
    1
    5
    3
    2
    11
    PAIN IN EXTREMITY
         subjects affected / exposed
    2 / 39 (5.13%)
    2 / 41 (4.88%)
    1 / 41 (2.44%)
    1 / 101 (0.99%)
    0 / 62 (0.00%)
    4 / 115 (3.48%)
         occurrences all number
    2
    2
    1
    1
    0
    4
    Metabolism and nutrition disorders
    DECREASED APPETITE
         subjects affected / exposed
    2 / 39 (5.13%)
    0 / 41 (0.00%)
    1 / 41 (2.44%)
    1 / 101 (0.99%)
    1 / 62 (1.61%)
    3 / 115 (2.61%)
         occurrences all number
    2
    0
    1
    1
    1
    3
    HYPOKALAEMIA
         subjects affected / exposed
    3 / 39 (7.69%)
    0 / 41 (0.00%)
    1 / 41 (2.44%)
    2 / 101 (1.98%)
    0 / 62 (0.00%)
    2 / 115 (1.74%)
         occurrences all number
    3
    0
    1
    2
    0
    3
    Infections and infestations
    NASOPHARYNGITIS
         subjects affected / exposed
    3 / 39 (7.69%)
    2 / 41 (4.88%)
    2 / 41 (4.88%)
    8 / 101 (7.92%)
    9 / 62 (14.52%)
    18 / 115 (15.65%)
         occurrences all number
    4
    3
    2
    9
    13
    27
    SINUSITIS
         subjects affected / exposed
    0 / 39 (0.00%)
    1 / 41 (2.44%)
    1 / 41 (2.44%)
    2 / 101 (1.98%)
    3 / 62 (4.84%)
    7 / 115 (6.09%)
         occurrences all number
    0
    1
    1
    2
    3
    7

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    02 Jan 2014
    The protocol amendment included. [a] Replaced “Week 26” by “visit E1” when appropriate, removed “Drug screening”, added evaluation of Adverse Event (AE) at visit 1.1 [Flow Chart A (Blinded Intravenous Therapy (Period 1))], added “during period 1” to footnote 1 of Flow Chart A, added assessment of eligibility at visit 2, added fecal samples in the list of other sampling and testing. [b] Replaced “months” by “weeks”. [c] Exclusion criterion number 21 added per Health Authority request. [d] Reference to section 5.1.2 (Assessment of Efficacy) was added to clarify which hematocrit result should be used for calculation of Crohn’s Disease Activity Index (CDAI). [e] Clarification was added to footnote 6 of Flow Chart A. [f] The amendment included “Assessment of AE after subcutaneous injections will also include assessment of local tolerability. The assessment of local tolerability should be done just before the patient leaves the investigator site.” [g] If, in the investigator’s opinion, the patient required additional medical therapy for their Crohn’s Disease due to persistently high disease activity or worsening based on CDAI score (>450, or an increase by 100 points from baseline), the study treatment may be stopped and patients may receive conventional treatment for active disease as per investigator’s judgment. [h] Section 4.1.3 (Selection of doses in the trial) was amended. [i] Replaced “normal saline (0.9% NaCl)” by “5% Dextrose in Water (D5W)”. [j] The detailed procedures for preparing and handling the study drug were provided in Investigator Site File (ISF). [k] Section 5.6 [Biomarker (s)] was amended. [l] Additional unscheduled visits for the purpose of re-testing of laboratory parameters or AE monitoring were included as deemed necessary by the investigator. [m] To remove CDAI, Inflammatory Bowel Disease Questionnaire (IBDQ) and Crohn’s Disease Endoscopic Index of Severity (CDEIS) from the protocol.
    27 May 2014
    The protocol amendment included. a) Contact detail for Nasri Abdallah was updated and Ivona Herichova was added as Trial Clinical Monitor (TCM). b) Reference to ISF added. Intravenous (IV) infusions, as detailed in the Instructions for Preparation and Handling of BI 655066/Placebo in the Investigator Site File. c) Instruction how to proceed in case of Infusion reaction added. In case of infusion reactions emerging during or after infusion of BI 655066 or Placebo, the investigator should consider in accordance with severity of the reaction and local standard of care to 1) Immediately interrupt the infusion 2) Treat with systemic anti-histamines and intravenous steroids. Based on patient`s clinical course and medical judgment, the infusion may be re-initiated in case of mild or moderate reactions (according to RCTC grading in appendix 10.3) at lower speed with gradual increase to complete the infusion as detailed out in the Instructions for Preparation and Handling of BI 655066/Placebo in the Investigator Site File. d) Added recommendations in case of infusion reaction. In case of an infusion reaction monitor the patient per standard of care, grade the intensity of the reaction according to RCTC grading and proceed as described in Section 4.2.1 (Rescue medication, emergency procedures, and additional treatment(s)).
    30 Jul 2014
    The protocol amendment included. a) Change in TCM, TCM Nasri Abdallah was replaced by Ivona Herichova. b) Endoscopic remission criterion added for patients with initial isolated ileitis. c) Inclusion Criterion for Period 3 more specified. d) To add inclusion criteria for roll-over trial. e) To add CDEIS threshold for patients with initial isolated ileitis. f) Update on start point of oral corticosteroids tapering. g) To specify inclusion criteria (CDEIS score) for patients with isolated ileitis. h) The inclusion criteria for treatment experienced patients was simplified to clarify that stopping of previous anti-TNF treatment for other reason is not exclusionary. i) Editorial change - to add restriction on concomitant medication into the exclusion criteria. j) Editorial change – Deletion of the exclusion criteria #20 since is already added to exclusion criteria #4. k) To specify inclusion criteria (CDEIS score) for patients with isolated ileitis as is stated in rationale for change 7. l) This exclusion criterion #21 is added due to a harmonization across the project. m) To update secondary efficacy endpoints. To update other efficacy endpoint, rationale as for change 14. n) To fecal calprotectin and lactoferrin are collected for the analysis of biomarkers. o) The times of visit clarification. p) To add eligibility criteria and timing for roll-over from trial 1311.6 to 1311.20. q) To exclude assessments obligation. r) Justification of CDEIS scoring for patients with isolated ileitis. s) Reasoning for adding SES-CD and PRO-2. t) To add opioids to restricted medication. u) To add Guidelines on tapering of corticosteroids. v) To add PRO-2 description, which is likely to be the new FDA requested primary endpoint in CD trials. w) To clarify procedure in case of CDEIS/SES-CD discrepancies.
    04 Dec 2014
    The protocol amendment included. a) Information about roll over trial inserted in Clinical Trial Protocol (CTP) version 3 was deleted considering postponing of roll over study start. b) Emphasize that CDEI assessment is mandatory at visits R0 or E1only at certain circumstances. c) Administrative change: Reformulation of footnotes 6 and 7 wording to make them more clear for the readers. d) Sponsor decision on CDEIS score rounding. e) To cover intra-articular administration. f) Sponsor decision to not apply unblinding rules. g) Administrative change: Inconsistency correction, to be compliant with section 3.1 [Overall trial design and plan]. h) Administrative change: correction of incorrect statement. i) Sponsor decision to allow re-screening for specified patients. j) Administrative change: More appropriate name assignment to differentiate between Clinical and PRO response.
    14 Apr 2015
    The protocol amendment included. a) Vedolizumab deleted from the list of drugs requiring 6 months of wash-out in exclusion criterion #4. b) Rewording as per request from Korean HA to make the statement more clear: Rectal 5-ASA compounds, parenteral or rectal corticosteroids must have been discontinued at least 4 weeks prior to visit 2. Rectal 5-ASA compounds, parenteral or rectal corticosteroids within 4 weeks prior to visit 2. c) Change in calculation, weekly weighted average instead of daily weighted average. d) Additional other efficacy endpoints added. e) Added: “The trial bioanalyst (TBA) and bioanalytical laboratory will be unblinded and provided with randomization codes in order to support PK/ADA sample bioanalysis.” f) Cannabis added to restricted medication list due to rather common use in the population and the interference with key efficacy endpoints. g) Clarification of alternative treatment added: “1). Re-screening of patients will not be allowed unless they have received and failed alternative treatment after first SF now meet eligibility criteria. “ changed to: “Re-screening of patients will not be allowed unless they have received and failed alternative treatment (not limited to Anti-TNF) and started to meet eligibility criteria.”
    30 Jul 2015
    The protocol amendment included. a) Administrative change: Sponsor includes the changes implemented in the Investigator’s Brochure (IB), version 6, dated 03 June 2015. b) Administrative change, sponsor decision on efficacy endpoints categorization c) Administrative change: correction of mistake in definition of CDEIS response and the typo correction in the week of endoscopic assessment should be week 52. d) Administrative change: typo correction - mistake in the week of endoscopic assessment, should be week 52. e) Deleted endpoints: Change in SES-CD at week 26. Change in CDEIS at week 26. f) Added information about blinding procedure for the Interim analysis: An interim analysis for planning purposes only will be performed when approximately 90 out of 120 patients will complete week 12 assessment. The Trial Statistical Analysis Plan (TSAP) will be approved before the interim analysis snapshot BI personnel specified in the Interim Analysis Logistic plan will have access to selected unblinded information necessary to perform and interpret the Interim analysis Internal Planning. The results of this interim analysis will be used for planning purposes only. g) Analysis for Internal Planning. An interim analysis for efficacy will be performed for the first approximately 90 patients out of the 120 targeted patients who complete the week 12 visit. This analysis is for internal planning purposes only to facilitate further substance development. No need to account for an alpha penalty since this analysis is for internal planning only, it will not affect the conduct of the current trial and the conclusion of the trial will be based on the primary analysis. Details of this interim analysis are specified in the interim analysis logistic plan which will be finalized before the fast track approval snapshot will be performed. The results will be documented separately, no interim analysis CTR will be written.
    13 Nov 2015
    The protocol amendment included. a) Patients fulfilling eligibility criteria for long term extension roll-over trial (1311.20) can be entered directly to 1311.20 trial after completion either visit E1 or E5 in 1311.6. b) Boolean remission endpoint added because it is a new way grouping CDAI subscores which was defined in the statistical plan. The analysis by visit was added for CDAI and PRO-2 which means a more detailed look at the data. c) The primary efficacy endpoint is the clinical remission of Crohn’s Disease defined as a CDAI score of below 150 after 12 weeks. Changed to: The primary efficacy endpoint is the clinical remission of Crohn’s Disease after 12 weeks, defined as a CDAI score of below 150. d) Added wording: The Simple Endoscopic Score in Crohn`s Disease (SES-CD) (R14-2969), has also been validated for CD and correlates closely with CDEIS, despite its reduced complexity. e) Follow up period is 15 weeks after the last administration of study medication. Changed to: Follow up period is 15 weeks after the last administration of study medication. Patients rolling over to 1311.20 trial are not requested to complete follow up period and are not counted as premature discontinuations. f) The statistical model for the binary endpoint is a stratified Cochran-Mantel-Haenszel test with randomisation factor of naïve or experienced to TNF antagonists as the stratification variable. There are three treatment arms, A is BI 655066 600 mg IV, B is BI 655066 200 mg IV, while C is the placebo arm. Changed to: The statistical model for the binary endpoint is a stratified Cochran-Mantel-Haenszel test with naïve or experienced to TNF antagonists as the stratification variable. There are three treatment arms, A is BI 655066 600 mg IV, B is BI 655066 200 mg IV, while C is the placebo arm. g) Adding comparison against placebo for clarification. Also, due to anticipated low number of patients in the TNF naïve group, an additional analysis is mentioned.
    14 Oct 2016
    The protocol amendment included. a) Changed “Boehringer Ingelheim” into “AbbVie/Boehringer Ingelheim”. b) Added ABBV-066 (risankizumab) after BI 655066. c) “The trial is sponsored by Boehringer Ingelheim (BI)” was changed to “The trial is sponsored by AbbVie in the US and Boehringer Ingelheim (BI) ex-US. (d) “Data Management and Statistical Evaluation will be done by BI according to BI SOPs” was changed to “Data Management will be done by BI according to BI SOPs and the Statistical Evaluation will be done by AbbVie according to their SOPs.” e) The sample for DNA banking will be stored at Boehringer Ingelheim for 15 years after the end of the clinical trial or until there is no more material available for tests” was changed to “The sample for DNA banking will be stored at AbbVie or a third party delegate (e.g. Boehringer Ingelheim Pharma GmbH & Co. KG; Birkendorfer Str. 65, 88397 Biberach, Germany).” for 15 years after the end of the clinical trial or until there is no more material available for tests.

    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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