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    Clinical Trial Results:
    A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Etrolizumab as an Induction And Maintenance Treatment For Patients With Moderately to Severely Active Crohn's Disease

    Summary
    EudraCT number
    		 2014-003824-36
    Trial protocol
    		 SE   EE   LT   LV   HU   DE   ES   CZ   NL   AT   SK   BE   FR   HR   RO   IT  
    Global end of trial date
    07 Sep 2021

    Results information
    Results version number
    		 v2(current)
    This version publication date
    06 Jan 2023
    First version publication date
    17 Sep 2022
    Other versions
    		 v1
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    GA29144
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03850535
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124., Basel, Switzerland, CH-4070
    Public contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com
    Scientific contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.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
    09 Sep 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    07 Sep 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Sep 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    A study evaluating the efficacy, safety, and tolerability of etrolizumab compared with placebo during induction and maintenance treatment of moderately to severely active Crohn's Disease (CD)
    Protection of trial subjects
    The study was conducted in accordance with the principles of the “Declaration of Helsinki” and Good Clinical Practice (GCP) guidelines according to the regulations and procedures described in the protocol.
    Background therapy
    		 -
    Evidence for comparator
    		 No active control
    Actual start date of recruitment
    20 Mar 2015
    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
    Argentina: 1
    Country: Number of subjects enrolled
    Austria: 15
    Country: Number of subjects enrolled
    Australia: 42
    Country: Number of subjects enrolled
    Belgium: 11
    Country: Number of subjects enrolled
    Brazil: 40
    Country: Number of subjects enrolled
    Bulgaria: 8
    Country: Number of subjects enrolled
    Canada: 64
    Country: Number of subjects enrolled
    Switzerland: 9
    Country: Number of subjects enrolled
    Czechia: 55
    Country: Number of subjects enrolled
    Germany: 29
    Country: Number of subjects enrolled
    Spain: 36
    Country: Number of subjects enrolled
    Estonia: 4
    Country: Number of subjects enrolled
    France: 58
    Country: Number of subjects enrolled
    United Kingdom: 34
    Country: Number of subjects enrolled
    Croatia: 9
    Country: Number of subjects enrolled
    Hungary: 38
    Country: Number of subjects enrolled
    Israel: 22
    Country: Number of subjects enrolled
    Italy: 22
    Country: Number of subjects enrolled
    Korea, Republic of: 34
    Country: Number of subjects enrolled
    Lithuania: 6
    Country: Number of subjects enrolled
    Latvia: 4
    Country: Number of subjects enrolled
    Mexico: 4
    Country: Number of subjects enrolled
    Netherlands: 21
    Country: Number of subjects enrolled
    New Zealand: 22
    Country: Number of subjects enrolled
    Poland: 60
    Country: Number of subjects enrolled
    Romania: 13
    Country: Number of subjects enrolled
    Russian Federation: 69
    Country: Number of subjects enrolled
    Serbia: 15
    Country: Number of subjects enrolled
    Slovakia: 13
    Country: Number of subjects enrolled
    Turkey: 12
    Country: Number of subjects enrolled
    Ukraine: 39
    Country: Number of subjects enrolled
    United States: 221
    Country: Number of subjects enrolled
    South Africa: 5
    Worldwide total number of subjects
    1035
    EEA total number of subjects
    402
    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)
    997
    From 65 to 84 years
    38
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 At the time of study closure, a total of 1035 patients were randomized into the induction phase, enrolled sequentially across Cohorts 1, 2, and 3. The final sample size for the pivotal induction Cohort 3 was lower than the 496 patients planned per the final protocol due to the early closure of the study. Cohorts below are mutually exclusive.

    Pre-assignment
    Screening details
    		 A total of 1035 participants entered the study across induction cohorts 1-3, a subset of 487 patients moved into the maintenance phase of the study.

    Period 1
    Period 1 title
    Induction Phase
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo Cohort 1
    Arm description
    		 Cohort 1 enrolled participants first before Cohorts 2 and 3 in order to conduct an exploratory analysis on induction data. Participants randomized to this arm received two SC injections of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12 (and one SC injection of etrolizumab-matching placebo at Week 2) during the 14-week Induction Phase, in order to preserve the masking.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Two SC injections of etrolizumab-matching placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo

    Arm title
    		 Etrolizumab 105mg Cohort 1
    Arm description
    		 Cohort 1 enrolled participants first before Cohorts 2 and 3 in order to conduct an exploratory analysis on induction data. Participants randomized to this arm received one SC injection of etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking, participants also received one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Etrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    One SC injection of etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week

    Arm title
    		 Etrolizumab 210mg Cohort 1
    Arm description
    		 Cohort 1 enrolled participants first before Cohorts 2 and 3 in order to conduct an exploratory analysis on induction data. Participants randomized to this arm received one SC injection of etrolizumab (210 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking, participants also received one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Etrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    One subcutaneous (SC) injection of etrolizumab (210 mg) at Weeks 0, 2, 4, 8, and 12 during the 14-week Induction Phase. In order to preserve the masking, participants also received one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.

    Arm title
    		 Etrolizumab 105mg Cohort 2
    Arm description
    		 Cohort 2 enrolled participants after Cohort 1 and was considered a "feeder" cohort to help achieve the necessary sample size for the Maintenance Phase. Participants randomized to this arm received one SC injection of open-label etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking of the dose of etrolizumab, participants also received one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Etrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    One SC injection of open-label etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking of the dose of etrolizumab, participants also received one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.

    Arm title
    		 Etrolizumab 210mg Cohort 2
    Arm description
    		 Cohort 2 enrolled participants after Cohort 1 and was considered a "feeder" cohort to help achieve the necessary sample size for the Maintenance Phase. Participants randomized to this arm received one SC injection of open-label etrolizumab (210 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking of the dose of etrolizumab, participants also received one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Etrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    one SC injection of open-label etrolizumab (210 mg) at Weeks 0, 2, 4, 8, and 12 during the 14-week Induction Phase. In order to preserve the masking for the dose of etrolizumab, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.

    Arm title
    		 Placebo Cohort 3
    Arm description
    		 Cohort 3 was the last to enroll participants (after Cohort 2) and was the pivotal cohort for the Induction Phase. Participants randomized to this arm received two SC injections of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12 (and one SC injection of etrolizumab-matching placebo at Week 2) during the 14-week Induction Phase, in order to preserve the masking.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Etrolizumab-matching placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Two SC injections of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12 (and one SC injection of etrolizumab-matching placebo at Week 2) during the 14-week

    Arm title
    		 Etrolizumab 105mg Cohort 3
    Arm description
    		 Cohort 3 was the last to enroll participants (after Cohort 2) and was the pivotal cohort for the Induction Phase. Participants randomized to this arm received one SC injection of etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking, participants also received one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Etrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    One SC injection of etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking, participants also received one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.

    Arm title
    		 Etrolizumab 210mg Cohort 3
    Arm description
    		 Cohort 3 was the last to enroll participants (after Cohort 2) and was the pivotal cohort for the Induction Phase. Participants randomized to this arm received one SC injection of etrolizumab (210 mg) at Weeks 0, 2, 4, 8, and 12 during the 14-week Induction Phase. In order to preserve the masking, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Etrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    One SC injection of etrolizumab (210 mg) at Weeks 0, 2, 4, 8, and 12 during the 14-week Induction Phase. In order to preserve the masking, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.

    Number of subjects in period 1
    		Placebo Cohort 1 Etrolizumab 105mg Cohort 1 Etrolizumab 210mg Cohort 1 Etrolizumab 105mg Cohort 2 Etrolizumab 210mg Cohort 2 Placebo Cohort 3 Etrolizumab 105mg Cohort 3 Etrolizumab 210mg Cohort 3
    Started
    59
    120
    121
    176
    174
    97
    143
    145
    Completed
    52
    104
    108
    141
    145
    80
    118
    114
    Not completed
    7
    16
    13
    35
    29
    17
    25
    31
         Lack of calculation
    -
    -
    -
    -
    -
    -
    -
    1
         Consent withdrawn by subject
    1
    2
    4
    6
    7
    4
    3
    6
         Physician decision
    -
    -
    1
    4
    -
    2
    1
    -
         Adverse Event
    2
    4
    1
    2
    5
    2
    -
    -
         Early withdrawal and roll over to different study
    -
    -
    -
    -
    -
    -
    1
    -
         Non-compliance
    -
    1
    3
    1
    3
    -
    1
    1
         Lost to follow-up
    1
    -
    -
    1
    -
    -
    1
    -
         Sponsor decision
    -
    1
    2
    -
    -
    -
    -
    -
         Technical reason
    -
    -
    -
    1
    -
    -
    -
    -
         Lack of efficacy
    3
    6
    2
    17
    14
    8
    17
    23
         Protocol deviation
    -
    2
    -
    3
    -
    1
    1
    -
    Period 2
    Period 2 title
    Maintenance Phase
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo/Placebo
    Arm description
    		 Participants who received placebo during the Induction Phase (from Cohorts 1 and 3) and achieved a CDAI-70 response at Week 14 underwent a sham randomization into the Maintenance Phase. Placebo responders from induction received blinded maintenance treatment with an SC injection of placebo once every 4 weeks (q4w) from Week 16 to Week 64.
    Arm type
    		 Placebo

    Investigational medicinal product name
    matching Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    placebo during the Induction Phase (from Cohorts 1 and 3) and achieved a CDAI-70 response at Week 14 will undergo a sham randomization into the Maintenance Phase. Placebo responders from induction will receive blinded maintenance treatment with an SC injection of placebo once every 4 weeks (q4w) from Week 16 to Week 64.

    Arm title
    		 Etrolizumab/Placebo
    Arm description
    		 Participants who received etrolizumab during the Induction Phase (from Cohorts 1-3) and achieved a CDAI-70 response at Week 14 without the use of rescue therapy were re-randomized into the Maintenance Phase. Etrolizumab responders from induction who were re-randomized to this arm received blinded maintenance treatment with an SC injection of placebo q4w from Week 16 to Week 64.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Erolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    received etrolizumab during the Induction Phase (from Cohorts 1-3) and achieved a CDAI-70 response at Week 14 without the use of rescue therapy re-randomized into the Maintenance Phase. Etrolizumab responders from induction who are re-randomized to this arm received blinded maintenance treatment with an SC injection of placebo q4w from Week 16 to Week 64.

    Arm title
    		 Etrolizumab/Etrolizumab 105mg
    Arm description
    		 Participants who received etrolizumab during the Induction Phase (from Cohorts 1-3) and achieved a CDAI-70 response at Week 14 without the use of rescue therapy were re-randomized into the Maintenance Phase. Etrolizumab responders from induction who were re-randomized to this arm received blinded maintenance treatment with an SC injection of etrolizumab (105 mg) q4w from Week 16 to Week 64.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Etrolizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants who received etrolizumab during the Induction Phase (from Cohorts 1-3) and achieved a CDAI-70 response at Week 14 without the use of rescue therapy re-randomized into the Maintenance Phase. Etrolizumab responders from induction who are re-randomized to this arm received blinded maintenance treatment with an SC injection of etrolizumab (105 mg) q4w from Week 16 to Week 64.

    Number of subjects in period 2 [1]
    		Placebo/Placebo Etrolizumab/Placebo Etrolizumab/Etrolizumab 105mg
    Started
    53
    217
    217
    Completed
    41
    175
    165
    Not completed
    12
    42
    52
         Adverse event, serious fatal
    -
    -
    1
         Physician decision
    1
    3
    2
         Adverse event, non-fatal
    1
    1
    3
         Withdrawal by Subject
    3
    12
    12
         Site closure
    -
    1
    -
         Lack of efficacy
    7
    25
    33
         Protocol deviation
    -
    -
    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: Only participants from the induction phase who had achieved a CDAI-70 response at Week 14 without the use of rescue therapy were enrolled in the maintenance phase.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo Cohort 1
    Reporting group description
    		 Cohort 1 enrolled participants first before Cohorts 2 and 3 in order to conduct an exploratory analysis on induction data. Participants randomized to this arm received two SC injections of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12 (and one SC injection of etrolizumab-matching placebo at Week 2) during the 14-week Induction Phase, in order to preserve the masking.

    Reporting group title
    Etrolizumab 105mg Cohort 1
    Reporting group description
    		 Cohort 1 enrolled participants first before Cohorts 2 and 3 in order to conduct an exploratory analysis on induction data. Participants randomized to this arm received one SC injection of etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking, participants also received one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.

    Reporting group title
    Etrolizumab 210mg Cohort 1
    Reporting group description
    		 Cohort 1 enrolled participants first before Cohorts 2 and 3 in order to conduct an exploratory analysis on induction data. Participants randomized to this arm received one SC injection of etrolizumab (210 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking, participants also received one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.

    Reporting group title
    Etrolizumab 105mg Cohort 2
    Reporting group description
    		 Cohort 2 enrolled participants after Cohort 1 and was considered a "feeder" cohort to help achieve the necessary sample size for the Maintenance Phase. Participants randomized to this arm received one SC injection of open-label etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking of the dose of etrolizumab, participants also received one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.

    Reporting group title
    Etrolizumab 210mg Cohort 2
    Reporting group description
    		 Cohort 2 enrolled participants after Cohort 1 and was considered a "feeder" cohort to help achieve the necessary sample size for the Maintenance Phase. Participants randomized to this arm received one SC injection of open-label etrolizumab (210 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking of the dose of etrolizumab, participants also received one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.

    Reporting group title
    Placebo Cohort 3
    Reporting group description
    		 Cohort 3 was the last to enroll participants (after Cohort 2) and was the pivotal cohort for the Induction Phase. Participants randomized to this arm received two SC injections of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12 (and one SC injection of etrolizumab-matching placebo at Week 2) during the 14-week Induction Phase, in order to preserve the masking.

    Reporting group title
    Etrolizumab 105mg Cohort 3
    Reporting group description
    		 Cohort 3 was the last to enroll participants (after Cohort 2) and was the pivotal cohort for the Induction Phase. Participants randomized to this arm received one SC injection of etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking, participants also received one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.

    Reporting group title
    Etrolizumab 210mg Cohort 3
    Reporting group description
    		 Cohort 3 was the last to enroll participants (after Cohort 2) and was the pivotal cohort for the Induction Phase. Participants randomized to this arm received one SC injection of etrolizumab (210 mg) at Weeks 0, 2, 4, 8, and 12 during the 14-week Induction Phase. In order to preserve the masking, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.

    Reporting group values
    		 Placebo Cohort 1 Etrolizumab 105mg Cohort 1 Etrolizumab 210mg Cohort 1 Etrolizumab 105mg Cohort 2 Etrolizumab 210mg Cohort 2 Placebo Cohort 3 Etrolizumab 105mg Cohort 3 Etrolizumab 210mg Cohort 3 Total
    Number of subjects
    		 59 120 121 176 174 97 143 145 1035
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0 0 0 0 0
        Adults (18-64 years)
    		 57 116 118 169 166 93 137 141 997
        From 65-84 years
    		 2 4 3 7 8 4 6 4 38
        85 years and over
    		 0 0 0 0 0 0 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 36.5 ± 12.7 38.9 ± 13.1 38.6 ± 13.4 38.4 ± 13.3 38.2 ± 13.2 37.1 ± 13.6 38.3 ± 13.4 36.5 ± 13.1 -
    Sex: Female, Male
    Units: Participants
        Female
    		 31 57 68 80 80 38 69 69 492
        Male
    		 28 63 53 96 94 59 74 76 543
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 2 5 5 7 8 15 13 7 62
        Not Hispanic or Latino
    		 53 110 113 160 154 75 126 129 920
        Unknown or Not Reported
    		 4 5 3 9 12 7 4 9 53
    Race/Ethnicity, Customized
    race
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0 1 3 0 4
        Asian
    		 5 9 7 8 14 0 4 2 49
        Black or African American
    		 3 5 2 1 5 6 8 2 32
        White
    		 46 96 104 153 141 81 117 128 866
        Other
    		 5 10 8 14 14 9 11 13 84

    End points

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    End points reporting groups
    Reporting group title
    Placebo Cohort 1
    Reporting group description
    		 Cohort 1 enrolled participants first before Cohorts 2 and 3 in order to conduct an exploratory analysis on induction data. Participants randomized to this arm received two SC injections of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12 (and one SC injection of etrolizumab-matching placebo at Week 2) during the 14-week Induction Phase, in order to preserve the masking.

    Reporting group title
    Etrolizumab 105mg Cohort 1
    Reporting group description
    		 Cohort 1 enrolled participants first before Cohorts 2 and 3 in order to conduct an exploratory analysis on induction data. Participants randomized to this arm received one SC injection of etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking, participants also received one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.

    Reporting group title
    Etrolizumab 210mg Cohort 1
    Reporting group description
    		 Cohort 1 enrolled participants first before Cohorts 2 and 3 in order to conduct an exploratory analysis on induction data. Participants randomized to this arm received one SC injection of etrolizumab (210 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking, participants also received one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.

    Reporting group title
    Etrolizumab 105mg Cohort 2
    Reporting group description
    		 Cohort 2 enrolled participants after Cohort 1 and was considered a "feeder" cohort to help achieve the necessary sample size for the Maintenance Phase. Participants randomized to this arm received one SC injection of open-label etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking of the dose of etrolizumab, participants also received one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.

    Reporting group title
    Etrolizumab 210mg Cohort 2
    Reporting group description
    		 Cohort 2 enrolled participants after Cohort 1 and was considered a "feeder" cohort to help achieve the necessary sample size for the Maintenance Phase. Participants randomized to this arm received one SC injection of open-label etrolizumab (210 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking of the dose of etrolizumab, participants also received one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.

    Reporting group title
    Placebo Cohort 3
    Reporting group description
    		 Cohort 3 was the last to enroll participants (after Cohort 2) and was the pivotal cohort for the Induction Phase. Participants randomized to this arm received two SC injections of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12 (and one SC injection of etrolizumab-matching placebo at Week 2) during the 14-week Induction Phase, in order to preserve the masking.

    Reporting group title
    Etrolizumab 105mg Cohort 3
    Reporting group description
    		 Cohort 3 was the last to enroll participants (after Cohort 2) and was the pivotal cohort for the Induction Phase. Participants randomized to this arm received one SC injection of etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking, participants also received one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.

    Reporting group title
    Etrolizumab 210mg Cohort 3
    Reporting group description
    		 Cohort 3 was the last to enroll participants (after Cohort 2) and was the pivotal cohort for the Induction Phase. Participants randomized to this arm received one SC injection of etrolizumab (210 mg) at Weeks 0, 2, 4, 8, and 12 during the 14-week Induction Phase. In order to preserve the masking, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.
    Reporting group title
    Placebo/Placebo
    Reporting group description
    		 Participants who received placebo during the Induction Phase (from Cohorts 1 and 3) and achieved a CDAI-70 response at Week 14 underwent a sham randomization into the Maintenance Phase. Placebo responders from induction received blinded maintenance treatment with an SC injection of placebo once every 4 weeks (q4w) from Week 16 to Week 64.

    Reporting group title
    Etrolizumab/Placebo
    Reporting group description
    		 Participants who received etrolizumab during the Induction Phase (from Cohorts 1-3) and achieved a CDAI-70 response at Week 14 without the use of rescue therapy were re-randomized into the Maintenance Phase. Etrolizumab responders from induction who were re-randomized to this arm received blinded maintenance treatment with an SC injection of placebo q4w from Week 16 to Week 64.

    Reporting group title
    Etrolizumab/Etrolizumab 105mg
    Reporting group description
    		 Participants who received etrolizumab during the Induction Phase (from Cohorts 1-3) and achieved a CDAI-70 response at Week 14 without the use of rescue therapy were re-randomized into the Maintenance Phase. Etrolizumab responders from induction who were re-randomized to this arm received blinded maintenance treatment with an SC injection of etrolizumab (105 mg) q4w from Week 16 to Week 64.

    Subject analysis set title
    Maintenance Phase - Etrolizumab 105 mg/ Etrolizumab 105 mg
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    Participants who received etrolizumab during the Induction Phase (from Cohorts 1-3) and achieved a CDAI-70 response at Week 14 without the use of rescue therapy will be re-randomized into the Maintenance Phase. Etrolizumab responders from induction who are re-randomized to this arm will receive blinded maintenance treatment with an SC injection of etrolizumab (105 mg) q4w from Week 16 to Week 64.

    Subject analysis set title
    Maintenance Phase - Etrolizumab 210 mg/ Etrolizumab 105 mg
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    Participants who received etrolizumab during the Induction Phase (from Cohorts 1-3) and achieved a CDAI-70 response at Week 14 without the use of rescue therapy will be re-randomized into the Maintenance Phase. Etrolizumab responders from induction who are re-randomized to this arm will receive blinded maintenance treatment with an SC injection of etrolizumab (105 mg) q4w from Week 16 to Week 64.

    Subject analysis set title
    Etro 105mg Induction Only Cohort
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    Participants randomized to this arm will receive one SC injection of etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8 and 12

    Subject analysis set title
    Etro 210mg Induction Only Cohort
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    Participants randomized to this arm will receive one SC injection of etrolizumab (210 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8 and 12

    Subject analysis set title
    Etro 105/ Placebo Induction and Maintenance Phase Cohort
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    Participants who received etrolizumab 105 mg during the Induction Phase (from Cohorts 1-3) and achieved a CDAI-70 response at Week 14 without the use of rescue therapy that were re-randomized into the Mainetnance Phase. Etrolizumab responders from induction who re re-randomized to this arm received blinded maintenance treatment with an SC injection of placebo q4w from Week 16 to Week 64

    Subject analysis set title
    Etro 210/ Placebo Induction and Maintenance Phase
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    Participants who received etrolizumab 210 mg during the Induction Phase (from Cohorts 1-3) and achieved a CDAI-70 response at Week 14 without the use of rescue therapy that were re-randomized into the Maintenance Phase. Etrolizumab responders from induction who were re-randomized to this arm received blinded maintenance treatment with an SC injection of placebo q4w from Week 16 to Week 64

    Subject analysis set title
    Etro 105/Etro 105 Induction and Maintenance Phase
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    Participants who received etrolizumab 105mg during the Induction Phase (from Cohorts 1-3) and achieved a CDAI-70 response at Week 14 without the use of rescue therapy that were re-randomized into the Maintenance Phase. Etrolizumab responders from induction who were re-randomized to this arm received blinded maintenance treatment with an SC injection of etrolizumab 105mg q4w from Week 16 to Week 64

    Subject analysis set title
    Etro 210/Etro 105 Induction and Maintenance Phase
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    Participants who received etrolizumab 210mg during the Induction Phase (from Cohorts 1-3) and achieved CDAI-70 response at Week 14 without the use of rescue therapy that were re-randomized into the Maintenance Phase. Etrolizumab responders from induction who were re-randomized to this arm received blinded maintenance treatment with an SC injection of etrolizumab 105mg q4w from Week 16 to Week 64

    Primary: Induction Phase: Cohort 1: Percentage of Participants with Clinical Remission at Week 14

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    End point title
    		 Induction Phase: Cohort 1: Percentage of Participants with Clinical Remission at Week 14 [1] [2]
    End point description
    Clinical remission is defined as liquid/soft stool frequency (SF) mean daily score less than or equal (≤)3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit. mITT - Modified Intent to Treat population: all patients randomized who received at least one dose of study drug, grouped under the randomized treatment arm. Results for Induction Phase Cohort 2 and 3 and Maintenance Phase are not presented.
    End point type
    Primary
    End point timeframe
    Week 14
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The induction data from Cohort 1 was exploratory in nature and was evaluated prior to the commencement of enrollment to the pivotal Induction Phase of Cohort 3.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: 90% confidence interval was reported for induction phase cohort 1 participants. For induction phase cohort 2 and 3 participants, 95% confidence interval was reported, hence the data is reported as a separate outcome measure for cohort 1. The participants in the maintenance phase were not analyzed for this outcome measure.
    End point values
    		 Placebo Cohort 1 Etrolizumab 105mg Cohort 1 Etrolizumab 210mg Cohort 1
    Number of subjects analysed
    59
    120
    121
    Units: Percentage of Particiapnts
        number (confidence interval 90%)
    11.9 (6.56 to 20.51)
    20.00 (14.69 to 26.64)
    27.3 (21.16 to 34.37)
    No statistical analyses for this end point

    Primary: Induction Phase: Cohort 2 and 3: Percentage of Participants with Clinical Remission at Week 14

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    End point title
    		 Induction Phase: Cohort 2 and 3: Percentage of Participants with Clinical Remission at Week 14 [3]
    End point description
    Clinical remission is defined as liquid/soft stool frequency (SF) mean daily score less than or equal (≤)3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit. mITT - Modified Intent to Treat population: all patients randomized who received at least one dose of study drug, grouped under the randomized treatment arm. Results for Induction Phase Cohort 1 is not presented.
    End point type
    Primary
    End point timeframe
    Week 14
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: 90% confidence interval was reported for induction phase cohort 1 participants. For induction phase cohort 2 and 3 participants, 95% confidence interval was reported, hence the data is reported as a separate outcome measure for cohorts 2 and 3. The participants in the maintenance phase were not analyzed for this outcome measure.
    End point values
    		 Etrolizumab 105mg Cohort 2 Etrolizumab 210mg Cohort 2 Placebo Cohort 3 Etrolizumab 105mg Cohort 3 Etrolizumab 210mg Cohort 3
    Number of subjects analysed
    176
    174
    96
    143
    145
    Units: Percentage of Particiapnts
        number (confidence interval 95%)
    29.5 (23.30 to 36.66)
    29.3 (23.05 to 36.46)
    29.2 (21.02 to 38.92)
    30.1 (23.16 to 38.03)
    33.1 (25.97 to 41.11)
    Statistical analysis title
    		 Clinical Remission at Week 14
    Statistical analysis description
    Percentage of Participants with Clinical Remission at Week 14
    Comparison groups
    Etrolizumab 105mg Cohort 3 v Placebo Cohort 3
    Number of subjects included in analysis
    239
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [4]
    P-value
    		 = 0.8508 [5]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in rate
    Point estimate
    1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.85
         upper limit
    		 12.56
    Notes
    [4] - Difference in remission rates is adjusted using CMH weights and the 95% CIs use the Newcombes method.
    [5] - The multiplicity-adjusted p-values are presented.
    Statistical analysis title
    		 Clinical Remission at Week 14
    Statistical analysis description
    Percentage of Participants with Clinical Remission at Week 14
    Comparison groups
    Placebo Cohort 3 v Etrolizumab 210mg Cohort 3
    Number of subjects included in analysis
    241
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [6]
    P-value
    		 = 0.5235 [7]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in rate
    Point estimate
    3.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.3
         upper limit
    		 15.27
    Notes
    [6] - Difference in remission rates is adjusted using CMH weights and the 95% CIs use the Newcombes method.
    [7] - The multiplicity adjusted p-values are presented.

    Primary: Induction Phase: Cohort 1: Percentage of Participants with Endoscopic Improvement at Week 14

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    End point title
    		 Induction Phase: Cohort 1: Percentage of Participants with Endoscopic Improvement at Week 14 [8] [9]
    End point description
    Endoscopic improvement is defined as 50 percent (%) reduction from baseline in Simplified Endoscopic Index for Crohn’s Disease (SES-CD) score. mITT. Results for Induction Phase Cohort 2 and 3 and Maintenance Phase are not presented.
    End point type
    Primary
    End point timeframe
    Week 14
    Notes
    [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The induction data from Cohort 1 was exploratory in nature and was evaluated prior to the commencement of enrollment to the pivotal Induction Phase of Cohort 3.
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: 90% confidence interval was reported for induction phase cohort 1 participants. For induction phase cohort 2 and 3 participants, 95% confidence interval was reported, hence the data is reported as a separate outcome measure for cohort 1. The participants in the maintenance phase were not analyzed for this outcome measure.
    End point values
    		 Placebo Cohort 1 Etrolizumab 105mg Cohort 1 Etrolizumab 210mg Cohort 1
    Number of subjects analysed
    59
    120
    121
    Units: Percentage of Participants
        number (confidence interval 90%)
    3.4 (-1.74 to 8.52)
    19.5 (12.37 to 26.64)
    16.8 (10.11 to 23.50)
    No statistical analyses for this end point

    Primary: Induction Phase: Cohort 2 and 3: Percentage of Participants with Endoscopic Improvement at Week 14

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    End point title
    		 Induction Phase: Cohort 2 and 3: Percentage of Participants with Endoscopic Improvement at Week 14 [10]
    End point description
    Endoscopic improvement is defined as 50 percent (%) reduction from baseline in Simplified Endoscopic Index for Crohn’s Disease (SES-CD) score. mITT. Results for Induction Phase Cohort 1 and Maintenance Phase are not presented.
    End point type
    Primary
    End point timeframe
    Week 14
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: 90% confidence interval was reported for induction phase cohort 1 participants. For induction phase cohort 2 and 3 participants, 95% confidence interval was reported, hence the data is reported as a separate outcome measure for cohorts 2 and 3. The participants in the maintenance phase were not analyzed for this outcome measure.
    End point values
    		 Etrolizumab 105mg Cohort 2 Etrolizumab 210mg Cohort 2 Placebo Cohort 3 Etrolizumab 105mg Cohort 3 Etrolizumab 210mg Cohort 3
    Number of subjects analysed
    176
    174
    96
    143
    145
    Units: Percentage of Participants
        number (confidence interval 95%)
    20.8 (14.81 to 26.86)
    22.2 (16.02 to 28.35)
    21.6 (13.24 to 29.95)
    26.2 (18.96 to 33.44)
    27.4 (20.01 to 34.79)
    Statistical analysis title
    		 Endoscopic Improvement at Week 14
    Statistical analysis description
    Percentage of Participants With Endoscopic Improvement at Week 14
    Comparison groups
    Placebo Cohort 3 v Etrolizumab 210mg Cohort 3
    Number of subjects included in analysis
    241
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [11]
    P-value
    		 = 0.317 [12]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in rate
    Point estimate
    5.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.43
         upper limit
    		 17.05
    Notes
    [11] - Difference in response rates is adjusted using CMH weights and the 95% CIs use the Newcombes method.
    [12] - The multiplicity adjusted p-values are presented.
    Statistical analysis title
    		 Endoscopic Improvement at Week 14
    Statistical analysis description
    Percentage of Participants With Endoscopic Improvement at Week 14
    Comparison groups
    Placebo Cohort 3 v Etrolizumab 105mg Cohort 3
    Number of subjects included in analysis
    239
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [13]
    P-value
    		 = 0.7908 [14]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in rate
    Point estimate
    4.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.26
         upper limit
    		 16.11
    Notes
    [13] - Difference in response rates is adjusted using CMH weights and the 95% CIs use the Newcombes method.
    [14] - The multiplicity adjusted p-values are presented.

    Primary: Maintenance Phase: Percentage of Participants with Clinical Remission at Week 66

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    End point title
    		 Maintenance Phase: Percentage of Participants with Clinical Remission at Week 66
    End point description
    Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit. Maintenance Phase Placebo/Placebo cohort is not reported since this is an exploratory population only. Results for the Induction phase populations for cohorts 1-3 are not presented.
    End point type
    Primary
    End point timeframe
    Baseline and Week 66
    End point values
    		 Etrolizumab/Placebo Etrolizumab/Etrolizumab 105mg
    Number of subjects analysed
    217
    217
    Units: percentage of participants
        number (confidence interval 95%)
    24.00 (18.77 to 30.06)
    35.00 (28.99 to 41.58)
    Statistical analysis title
    		 Participants with Clinical Remission Week 66
    Statistical analysis description
    Percentage of Participants with Clinical Remission at Week 66
    Comparison groups
    Etrolizumab/Placebo v Etrolizumab/Etrolizumab 105mg
    Number of subjects included in analysis
    434
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [15]
    P-value
    		 = 0.0088 [16]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in rate
    Point estimate
    11.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.7
         upper limit
    		 19.65
    Notes
    [15] - Difference in response rates is adjusted using CMH weights and the 95% CIs use the Newcombes method.
    [16] - The multiplicity adjusted p-values are presented.

    Primary: Maintenance Phase: Percentage of Participants with Endoscopic Improvement at Week 66

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    End point title
    		 Maintenance Phase: Percentage of Participants with Endoscopic Improvement at Week 66
    End point description
    Endoscopic improvement is defined as 50% reduction from baseline in SES-CD score. mITT. Maintenance Phase Placebo/Placebo cohort is not reported since this is an exploratory population only. Induction Phase population for cohorts 1-3 are not included.
    End point type
    Primary
    End point timeframe
    Week 66
    End point values
    		 Etrolizumab/Placebo Etrolizumab/Etrolizumab 105mg
    Number of subjects analysed
    217
    217
    Units: Percentage of Participants
        number (confidence interval 95%)
    12.2 (7.71 to 16.69)
    23.6 (17.90 to 29.29)
    Statistical analysis title
    		 Participants with Endoscopic Improvement Week 66
    Statistical analysis description
    Percentage of Participants with Endoscopic Improvement at Week 66
    Comparison groups
    Etrolizumab/Placebo v Etrolizumab/Etrolizumab 105mg
    Number of subjects included in analysis
    434
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [17]
    P-value
    		 = 0.0026 [18]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in rate
    Point estimate
    11.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.11
         upper limit
    		 18.83
    Notes
    [17] - Difference in response rates is adjusted using CMH weights and the 95% CIs use the Newcombes method.
    [18] - The multiplicity adjusted p-values are presented.

    Secondary: Induction Phase: Cohort 1: Percentage of Participants with Clinical Remission at Week 6

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    End point title
    		 Induction Phase: Cohort 1: Percentage of Participants with Clinical Remission at Week 6 [19]
    End point description
    Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit. mITT. Results for Induction Phase Cohort 2 and 3 and Maintenance Phase are not presented.
    End point type
    Secondary
    End point timeframe
    Week 6
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: 90% confidence interval was reported for induction phase cohort 1 participants. For induction phase cohort 2 and 3 participants, 95% confidence interval was reported, hence the data is reported as a separate outcome measure for cohort 1. The participants in the maintenance phase were not analyzed for this outcome measure.
    End point values
    		 Placebo Cohort 1 Etrolizumab 105mg Cohort 1 Etrolizumab 210mg Cohort 1
    Number of subjects analysed
    59
    120
    121
    Units: Percentage of participants
        number (confidence interval 90%)
    5.1 (2.05 to 12.06)
    15.0 (10.41 to 21.13)
    24.8 (18.93 to 31.75)
    No statistical analyses for this end point

    Secondary: Induction Phase: Cohort 2 and 3: Percentage of Participants with Clinical Remission at Week 6

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    End point title
    		 Induction Phase: Cohort 2 and 3: Percentage of Participants with Clinical Remission at Week 6 [20]
    End point description
    Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit. mITT. Results for Induction Phase Cohort 1 and Maintenance Phase are not presented.
    End point type
    Secondary
    End point timeframe
    Week 6
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: 90% confidence interval was reported for induction phase cohort 1 participants. For induction phase cohort 2 and 3 participants, 95% confidence interval was reported, hence the data is reported as a separate outcome measure for cohorts 2 and 3. The participants in the maintenance phase were not analyzed for this outcome measure.
    End point values
    		 Etrolizumab 105mg Cohort 2 Etrolizumab 210mg Cohort 2 Placebo Cohort 3 Etrolizumab 105mg Cohort 3 Etrolizumab 210mg Cohort 3
    Number of subjects analysed
    176
    174
    96
    143
    145
    Units: percentage of participants
        number (confidence interval 95%)
    20.5 (15.16 to 27.01)
    21.3 (15.84 to 27.93)
    20.8 (13.91 to 30.00)
    23.8 (17.54 to 31.38)
    23.4 (17.29 to 30.97)
    Statistical analysis title
    		 Clinical Remission at Week 6
    Statistical analysis description
    Percentage of Participants With Clinical Remission at Week 6
    Comparison groups
    Placebo Cohort 3 v Etrolizumab 105mg Cohort 3
    Number of subjects included in analysis
    239
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [21]
    P-value
    		 = 1 [22]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in rate
    Point estimate
    3.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.02
         upper limit
    		 13.45
    Notes
    [21] - Difference in remission rates are adjusted using CMH weights and the 95% CIs use the Newcombes method.
    [22] - The multiplicity adjusted p-values are presented.
    Statistical analysis title
    		 Clinical Remission at Week 6
    Statistical analysis description
    Percentage of Participants With Clinical Remission at Week 6
    Comparison groups
    Placebo Cohort 3 v Etrolizumab 210mg Cohort 3
    Number of subjects included in analysis
    241
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [23]
    P-value
    		 = 0.7908 [24]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in rate
    Point estimate
    2.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.78
         upper limit
    		 12.56
    Notes
    [23] - Difference in remission rates are adjusted using CMH weights and the 95% CIs use the Newcombes method.
    [24] - The multiplicity adjusted p-values are presented.

    Secondary: Induction Phase: Cohort 1: Percentage of Participants with SES-CD Score ≤4 (≤2 for Ileal Participants), with No Segment Having a Subcategory Score Greater than (>)1, at Week 14

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    End point title
    		 Induction Phase: Cohort 1: Percentage of Participants with SES-CD Score ≤4 (≤2 for Ileal Participants), with No Segment Having a Subcategory Score Greater than (>)1, at Week 14 [25]
    End point description
    Endoscopic Remission is defined as SES-CD total score <=4 (<=2 for ileal only patients), with no segment having a subcategory score >1. SES-CD = Simple Endoscopic Score for Crohn's Disease. A composite of four assessments, each rated from 0 to 3: size of ulcers, proportion of the surface covered by ulcers, proportion of the surface with any other lesions, and presence of narrowings (stenosis). The SES-CD total score ranges from 0 to 60, a higher score indicates worse disease activity. mITT. Results for Induction Phase Cohort 2 and 3 and Maintenance Phase are not presented.
    End point type
    Secondary
    End point timeframe
    Week 14
    Notes
    [25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: 90% confidence interval was reported for induction phase cohort 1 participants. For induction phase cohort 2 and 3 participants, 95% confidence interval was reported, hence the data is reported as a separate outcome measure for cohort 1. The participants in the maintenance phase were not analyzed for this outcome measure.
    End point values
    		 Placebo Cohort 1 Etrolizumab 105mg Cohort 1 Etrolizumab 210mg Cohort 1
    Number of subjects analysed
    59
    120
    121
    Units: Percentage of participants
        number (confidence interval 90%)
    1.7 (-2.40 to 5.79)
    13.8 (7.53 to 20.14)
    8.3 (3.29 to 13.24)
    No statistical analyses for this end point

    Secondary: Induction Phase: Cohort 2 and 3: Percentage of Participants with SES-CD Score ≤4 (≤2 for Ileal Participants), with No Segment Having a Subcategory Score Greater than (>)1, at Week 14

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    End point title
    		 Induction Phase: Cohort 2 and 3: Percentage of Participants with SES-CD Score ≤4 (≤2 for Ileal Participants), with No Segment Having a Subcategory Score Greater than (>)1, at Week 14 [26]
    End point description
    Endoscopic Remission is defined as SES-CD total score <=4 (<=2 for ileal only patients), with no segment having a subcategory score >1. SES-CD = Simple Endoscopic Score for Crohn's Disease. A composite of four assessments, each rated from 0 to 3: size of ulcers, proportion of the surface covered by ulcers, proportion of the surface with any other lesions, and presence of narrowings (stenosis). The SES-CD total score ranges from 0 to 60, a higher score indicates worse disease activity. mITT. Results for Induction Phase Cohort 1 and Maintenance Phase are not presented.
    End point type
    Secondary
    End point timeframe
    Week 14
    Notes
    [26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: 90% confidence interval was reported for induction phase cohort 1 participants. For induction phase cohort 2 and 3 participants, 95% confidence interval was reported, hence the data is reported as a separate outcome measure for cohorts 2 and 3. The participants in the maintenance phase were not analyzed for this outcome measure.
    End point values
    		 Etrolizumab 105mg Cohort 2 Etrolizumab 210mg Cohort 2 Placebo Cohort 3 Etrolizumab 105mg Cohort 3 Etrolizumab 210mg Cohort 3
    Number of subjects analysed
    176
    174
    96
    142
    145
    Units: percentage of participants
        number (confidence interval 95%)
    9.9 (5.43 to 14.42)
    12.3 (5.43 to 14.42)
    8.7 (2.84 to 14.52)
    10.2 (5.15 to 15.27)
    15.3 (9.33 to 21.29)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Percentage of Participants with SES-CD Score ≤4
    Comparison groups
    Placebo Cohort 3 v Etrolizumab 105mg Cohort 3
    Number of subjects included in analysis
    238
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [27]
    P-value
    		 = 1 [28]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in rate
    Point estimate
    1.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.51
         upper limit
    		 9.73
    Notes
    [27] - Difference in remission rates are adjusted using CMH weights and the 95% CIs use the Newcombes method.
    [28] - The multiplicity adjusted p-values are presented.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo Cohort 3 v Etrolizumab 210mg Cohort 3
    Number of subjects included in analysis
    241
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [29]
    P-value
    		 = 0.5235 [30]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in rate
    Point estimate
    6.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.24
         upper limit
    		 15.16
    Notes
    [29] - Difference in remission rates are adjusted using CMH weights and the 95% CIs use the Newcombes method.
    [30] - The multiplicity adjusted p-values are presented.

    Secondary: Induction Phase: Cohort 1: Change from Baseline in Crohn’s Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14

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    End point title
    		 Induction Phase: Cohort 1: Change from Baseline in Crohn’s Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14 [31]
    End point description
    CD-PRO/SS: Crohn's Disease Patient Reported Outcomes Signs and Symptoms. For each item, the score is taken as the average across 4-7 days eDiary data within a 9 day window from visit, else the score is considered missing. The CD-PRO/SS Bowel domain is a total score summed across 3 items and ranges from 0 - 16. The Functional domain score is a total score summed across 3 items and ranges from 0 - 12. A higher CD-PRO/SS score indicates worse quality of life. Participants are included in the analysis if they have both Baseline and at least one post-baseline score available. mITT. Data evaluable participants are included. Results for Induction Phase Cohort 2 and 3 and Maintenance Phase are not presented. Only patients with a baseline score and at least one post-baseline score are included in the analysis.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 14
    Notes
    [31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: 90% confidence interval was reported for induction phase cohort 1 participants. For induction phase cohort 2 and 3 participants, 95% confidence interval was reported, hence the data is reported as a separate outcome measure for cohort 1. The participants in the maintenance phase were not analyzed for this outcome measure.
    End point values
    		 Placebo Cohort 1 Etrolizumab 105mg Cohort 1 Etrolizumab 210mg Cohort 1
    Number of subjects analysed
    46
    76
    87
    Units: score on a scale
    least squares mean (standard error)
        CD-PRO/SS Functional Domain Score
    -0.7 ± 0.4
    -1.4 ± 0.3
    -1.6 ± 0.3
        CD-PRO/SS Bowel Domain Score
    -0.7 ± 0.4
    -1.5 ± 0.3
    -1.3 ± 0.3
    No statistical analyses for this end point

    Secondary: Induction Phase: Cohort 2 and 3: Change from Baseline in Crohn’s Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14

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    End point title
    		 Induction Phase: Cohort 2 and 3: Change from Baseline in Crohn’s Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14 [32]
    End point description
    CD-PRO/SS: Crohn's Disease Patient Reported Outcomes Signs and Symptoms. For each item, the score is taken as the average across 4-7 days eDiary data within a 9 day window from visit, else the score is considered missing. The CD-PRO/SS Bowel domain is a total score summed across 3 items and ranges from 0 - 16. The Functional domain score is a total score summed across 3 items and ranges from 0 - 12. A higher CD-PRO/SS score indicates worse quality of life. Participants are included in the analysis if they have both Baseline and at least one post-baseline score available. mITT. Data evaluable participants are included. Results for Induction Phase Cohort 1 and Maintenance Phase are not presented. Only patients with a baseline score and at least one post-baseline score are included in the analysis.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 14
    Notes
    [32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: 90% confidence interval was reported for induction phase cohort 1 participants. For induction phase cohort 2 and 3 participants, 95% confidence interval was reported, hence the data is reported as a separate outcome measure for cohorts 2 and 3. The participants in the maintenance phase were not analyzed for this outcome measure.
    End point values
    		 Etrolizumab 105mg Cohort 2 Etrolizumab 210mg Cohort 2 Placebo Cohort 3 Etrolizumab 105mg Cohort 3 Etrolizumab 210mg Cohort 3
    Number of subjects analysed
    132
    137
    91
    138
    137
    Units: score on a scale
    least squares mean (standard error)
        CD-PRO/SS Functional Domain Score
    -2.0 ± 0.2
    -2.3 ± 0.2
    -1.9 ± 0.3
    -1.6 ± 0.2
    -1.9 ± 0.2
        CD-PRO/SS Bowel Domain Score
    -2.3 ± 0.3
    -2.2 ± 0.3
    -2.0 ± 0.3
    -2.0 ± 0.3
    -2.3 ± 0.3
    Statistical analysis title
    		 Change from Baseline in CD-PRO/SS
    Statistical analysis description
    Induction Phase: Change from Baseline in Crohn’s Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14
    Comparison groups
    Placebo Cohort 3 v Etrolizumab 105mg Cohort 3
    Number of subjects included in analysis
    229
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [33]
    P-value
    		 = 1 [34]
    Method
    		 MMRM
    Parameter type
    		 Difference in LSM
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 0.9
    Notes
    [33] - Functional Domain Scale
    [34] - The multiplicity adjusted p-values are presented.
    Statistical analysis title
    		 Change from Baseline in CD-PRO/SS
    Statistical analysis description
    Induction Phase: Change from Baseline in Crohn’s Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14
    Comparison groups
    Placebo Cohort 3 v Etrolizumab 210mg Cohort 3
    Number of subjects included in analysis
    228
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [35]
    P-value
    		 = 1 [36]
    Method
    		 MMRM
    Parameter type
    		 Difference in LSM
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 0.7
    Notes
    [35] - Functional Domain Score
    [36] - The multiplicity adjusted p-values are presented.
    Statistical analysis title
    		 Change from Baseline in CD-PRO/SS
    Statistical analysis description
    Induction Phase: Change from Baseline in Crohn’s Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14
    Comparison groups
    Placebo Cohort 3 v Etrolizumab 105mg Cohort 3
    Number of subjects included in analysis
    229
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [37]
    P-value
    		 = 1 [38]
    Method
    		 MMRM
    Parameter type
    		 Difference in LSM
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 0.9
    Notes
    [37] - Bowel Domain Score
    [38] - The multiplicity adjusted p-values are presented.
    Statistical analysis title
    		 Change from Baseline in CD-PRO/SS
    Statistical analysis description
    Induction Phase: Change from Baseline in Crohn’s Disease-Patient-Reported Outcome Signs and Symptoms (CD-PRO/SS) Score at Week 14
    Comparison groups
    Placebo Cohort 3 v Etrolizumab 210mg Cohort 3
    Number of subjects included in analysis
    228
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [39]
    P-value
    		 = 1 [40]
    Method
    		 MMRM
    Parameter type
    		 Difference in LSM
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 0.5
    Notes
    [39] - Bowel Domain Score
    [40] - The multiplicity adjusted p-values are presented.

    Secondary: Maintenance Phase: Percentage of Participants with Clinical Remission at Week 66, Among Those who Achieved Clinical Remission at Week 14

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    End point title
    		 Maintenance Phase: Percentage of Participants with Clinical Remission at Week 66, Among Those who Achieved Clinical Remission at Week 14
    End point description
    Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit. mITT. Data evaluable participants are included. Placebo/Placebo Maintenance Cohort is not reported since this is an exploratory population only. Results for Induction Phase is not presented.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 14 and 66
    End point values
    		 Etrolizumab/Placebo Etrolizumab/Etrolizumab 105mg
    Number of subjects analysed
    97
    108
    Units: percentage of participants
        number (confidence interval 95%)
    39.2 (30.05 to 49.12)
    56.5 (47.07 to 65.45)
    Statistical analysis title
    		 CR at Week 66 subjects achieved CR at Week 14
    Statistical analysis description
    Percentage of Participants with Clinical Remission at Week 66, Among Those who Achieved Clinical Remission at Week 14
    Comparison groups
    Etrolizumab/Placebo v Etrolizumab/Etrolizumab 105mg
    Number of subjects included in analysis
    205
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [41]
    P-value
    		 = 0.0677 [42]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in rate
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.52
         upper limit
    		 30.27
    Notes
    [41] - Difference in remission rates is adjusted using CMH weights and the 95% CIs use the Newcombes method.
    [42] - The multiplicity adjusted p-values are presented.

    Secondary: Maintenance Phase: Percentage of Participants with Corticosteroid-Free Clinical Remission at Week 66, Among Those who Were Receiving Corticosteroids at Baseline

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    End point title
    		 Maintenance Phase: Percentage of Participants with Corticosteroid-Free Clinical Remission at Week 66, Among Those who Were Receiving Corticosteroids at Baseline
    End point description
    Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit. mITT. Maintenance Phase Cohorts only. Placebo/Placebo Maintenance Cohort is not reported since this is an exploratory population only. Only patients receiving oral corticosteroids at Baseline are included in the analysis.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 66
    End point values
    		 Etrolizumab/Placebo Etrolizumab/Etrolizumab 105mg
    Number of subjects analysed
    91
    93
    Units: percentage of participants
        number (confidence interval 95%)
    11.0 (6.08 to 19.06)
    29.0 (20.79 to 38.94)
    Statistical analysis title
    		 Participants with Corticosteroid-Free CR Week 66
    Statistical analysis description
    Maintenance Phase: Percentage of Participants with Corticosteroid-Free Clinical Remission at Week 66, Among Those who Were Receiving Corticosteroids at Baseline
    Comparison groups
    Etrolizumab/Placebo v Etrolizumab/Etrolizumab 105mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [43]
    P-value
    		 = 0.048 [44]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in rates
    Point estimate
    18.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 11.07
         upper limit
    		 25.96
    Notes
    [43] - Difference in remission rates is adjusted using CMH weights and the 95% CIs use the Newcombes method.
    [44] - The multiplicity adjusted p-values are presented.

    Secondary: Maintenance Phase: Percentage of Participants with Endoscopic Improvement at Week 66 Among Participants who Achieved Endoscopic Improvement at Week 14

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    End point title
    		 Maintenance Phase: Percentage of Participants with Endoscopic Improvement at Week 66 Among Participants who Achieved Endoscopic Improvement at Week 14
    End point description
    Endoscopic improvement is defined as 50% reduction from baseline in SES-CD score. mITT. Only patients achieving endoscopic improvement at Week 14 are included in the analysis. Results for Induction Phase Cohort is not presented.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 14 and 66
    End point values
    		 Etrolizumab/Placebo Etrolizumab/Etrolizumab 105mg
    Number of subjects analysed
    58
    72
    Units: percentage of participants
        number (confidence interval 95%)
    25.3 (14.14 to 36.44)
    37.5 (26.28 to 48.72)
    Statistical analysis title
    		 Subjects with Endoscopic Improvement Week 66
    Statistical analysis description
    Etrolizumab/Placebo vs. Etrolizumab/Etrolizumab 105mg. Only patients achieving endoscopic Improvement at Week 14 are included in the analysis.
    Comparison groups
    Etrolizumab/Placebo v Etrolizumab/Etrolizumab 105mg
    Number of subjects included in analysis
    130
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [45]
    P-value
    		 = 0.121
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in rates
    Point estimate
    13.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.9
         upper limit
    		 29.94
    Notes
    [45] - Difference in response rates is adjusted using CMH weights and the 95% CIs use the Newcombes method.

    Secondary: Maintenance Phase: Percentage of Participants with SES-CD Score ≤4 (≤2 for Ileal Participants), with No Segment Having a Subcategory Score >1, at Week 66

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    End point title
    		 Maintenance Phase: Percentage of Participants with SES-CD Score ≤4 (≤2 for Ileal Participants), with No Segment Having a Subcategory Score >1, at Week 66
    End point description
    Endoscopic Remission is defined as SES-CD total score <=4 (<=2 for ileal only patients), with no segment having a subcategory score >1. SES-CD = Simple Endoscopic Score for Crohn's Disease. A composite of four assessments, each rated from 0 to 3: size of ulcers, proportion of the surface covered by ulcers, proportion of the surface with any other lesions, and presence of narrowings (stenosis). The SES-CD total score ranges from 0 to 60, a higher score indicates worse disease activity. mITT. Maintenance Phase Placebo/Placebo is not reported since this is an exploratory population only.
    End point type
    Secondary
    End point timeframe
    Week 66
    End point values
    		 Etrolizumab/Placebo Etrolizumab/Etrolizumab 105mg
    Number of subjects analysed
    217
    217
    Units: percentage of participants
        number (confidence interval 95%)
    5.9 (2.62 to 9.18)
    12.1 (7.61 to 16.54)
    Statistical analysis title
    		 Participants with SES-CD Score ≤4
    Statistical analysis description
    Maintenance Phase: Percentage of Participants with SES-CD Score ≤4 (≤2 for Ileal Participants), with No Segment Having a Subcategory Score >1, at Week 66
    Comparison groups
    Etrolizumab/Placebo v Etrolizumab/Etrolizumab 105mg
    Number of subjects included in analysis
    434
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [46]
    P-value
    		 = 0.048 [47]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in rates
    Point estimate
    6.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.54
         upper limit
    		 11.93
    Notes
    [46] - Difference in remission rates is adjusted using CMH weights and the 95% CIs use the Newcombes method.
    [47] - The multiplicity adjusted p-values are presented.

    Secondary: Maintenance Phase: Percentage of Participants with Durable Clinical Remission

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    End point title
    		 Maintenance Phase: Percentage of Participants with Durable Clinical Remission
    End point description
    Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit. Durable clinical remission was defined as clinical remission at ≥4 of the 6 in-clinic assessment visits conducted during the Maintenance Phase at Weeks 24, 28, 32, 44, 56, and 66. mITT. Maintenance Phase Placebo/Placebo arm is not reported since this is an exploratory population only. Results for Induction Phase is not presented.
    End point type
    Secondary
    End point timeframe
    Week 14 up to Week 66 (assessed at Weeks 24, 28, 32, 44, 56, and 66)
    End point values
    		 Etrolizumab/Placebo Etrolizumab/Etrolizumab 105mg
    Number of subjects analysed
    217
    217
    Units: percentage of participants
        number (confidence interval 95%)
    19.8 (15.06 to 25.62)
    30.9 (25.11 to 37.31)
    Statistical analysis title
    		 Participants with Durable CR
    Statistical analysis description
    Maintenance Phase: Percentage of Participants with Durable Clinical Remission (CR)
    Comparison groups
    Etrolizumab/Placebo v Etrolizumab/Etrolizumab 105mg
    Number of subjects included in analysis
    434
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [48]
    P-value
    		 = 0.0677 [49]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in rates
    Point estimate
    11.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.04
         upper limit
    		 19.24
    Notes
    [48] - Difference in response rates is adjusted using CMH weights and the 95% CIs use the Newcombes method.
    [49] - The multiplicity adjusted p-values are presented.

    Secondary: Maintenance Phase: Percentage of Participants with Corticosteroid-Free Clinical Remission for at Least 24 Weeks at Week 66, Among Those who Were Receiving Corticosteroids at Baseline

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    End point title
    		 Maintenance Phase: Percentage of Participants with Corticosteroid-Free Clinical Remission for at Least 24 Weeks at Week 66, Among Those who Were Receiving Corticosteroids at Baseline
    End point description
    Clinical remission is defined as SF mean daily score ≤3 and abdominal pain mean daily score ≤1, with no worsening in either subscore compared to baseline, averaged over the 7 days prior to visit. Percentage of participants with clinical remission who will be off corticosteroids for at least 24 weeks prior to Week 66 will be reported. mITT. Maintenance Phase Placebo/Placebo is arm is not reported since this is an exploratory population only. Results for Induction Phase is not presented. Only patients receiving oral corticosteroids at Baseline are included in the analysis.
    End point type
    Secondary
    End point timeframe
    Baseline and from Week 14 up to Week 66
    End point values
    		 Etrolizumab/Placebo Etrolizumab/Etrolizumab 105mg
    Number of subjects analysed
    91
    93
    Units: percentage of participants
        number (confidence interval 95%)
    9.9 (5.29 to 17.74)
    25.8 (18.00 to 35.53)
    Statistical analysis title
    		 Participants with Corticosteroid-Free CR Week 66
    Statistical analysis description
    Maintenance Phase: Percentage of Participants with Corticosteroid-Free Clinical Remission for at Least 24 Weeks at Week 66, Among Those who Were Receiving Corticosteroids at Baseline
    Comparison groups
    Etrolizumab/Placebo v Etrolizumab/Etrolizumab 105mg
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [50]
    P-value
    		 = 0.0035 [51]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in rates
    Point estimate
    16.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 8.96
         upper limit
    		 23.31
    Notes
    [50] - Difference in remission rates is adjusted using CMH weights and the 95% CIs use the Newcombes method.
    [51] - Nominal p-values are presented. No adjustment for multiplicity

    Secondary: Maintenance Phase: Change from Baseline in CD-PRO/SS Score at Week 66

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    End point title
    		 Maintenance Phase: Change from Baseline in CD-PRO/SS Score at Week 66
    End point description
    CD-PRO/SS: Crohn's Disease Patient Reported Outcomes Signs and Symptoms. For each item, the score is taken as the average across 4-7 days eDiary data within a 9 day window from visit, else the score is considered missing. The CD-PRO/SS Bowel domain is a total score summed across 3 items and ranges from 0 - 16. The Functional domain score is a total score summed across 3 items and ranges from 0 - 12. A higher CD-PRO/SS score indicates worse quality of life. Participants are included in the analysis if they have both Baseline and at least one post-baseline score available. mITT. Data evaluable participants are included. Only patients with a baseline score and at least one post-baseline score are included in the analysis. The Maintenance Phase Placebo/Placebo arm is not reported since this is an exploratory population only. Results for Induction Phase is not presented.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 66
    End point values
    		 Etrolizumab/Placebo Etrolizumab/Etrolizumab 105mg
    Number of subjects analysed
    180
    180
    Units: score on a scale
    least squares mean (standard error)
        Bowel
    -1.7 ± 0.3
    -2.0 ± 0.3
        Functional
    -1.4 ± 0.2
    -1.7 ± 0.2
    Statistical analysis title
    		 Change from Baseline in CD-PRO/SS Score Week 66
    Statistical analysis description
    Maintenance Phase: Change from Baseline in CD-PRO/SS Score at Week 66
    Comparison groups
    Etrolizumab/Placebo v Etrolizumab/Etrolizumab 105mg
    Number of subjects included in analysis
    360
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [52]
    P-value
    		 = 0.4009 [53]
    Method
    		 MMRM
    Parameter type
    		 Difference in LSM
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.9
         upper limit
    		 0.4
    Notes
    [52] - Functional Symptoms Domain
    [53] - The multiplicity adjusted p-values are presented.
    Statistical analysis title
    		 Change from Baseline in CD-PRO/SS Score at Week 66
    Statistical analysis description
    Maintenance Phase: Change from Baseline in CD-PRO/SS Score at Week 66
    Comparison groups
    Etrolizumab/Placebo v Etrolizumab/Etrolizumab 105mg
    Number of subjects included in analysis
    360
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [54]
    P-value
    		 = 0.4009 [55]
    Method
    		 MMRM
    Parameter type
    		 Difference in LSM
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 0.4
    Notes
    [54] - Bowel Symptoms Domain
    [55] - The multiplicity adjusted p-values are presented.

    Secondary: Overall Number of Participants who Experienced at Least One Adverse Event by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0)

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    End point title
    		 Overall Number of Participants who Experienced at Least One Adverse Event by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0)
    End point description
    Investigator text for AEs is coded using MedDRA version 24.0. For participants counts, multiple occurrences of AEs in the same category for an individual are counted only once. For event counts, multiple occurrences of AEs in the same category for an individual are counted separately. Severity Grades from 1 to 5. Safety Population.
    End point type
    Secondary
    End point timeframe
    From Baseline up to Week 78
    End point values
    		 Placebo Cohort 1 Placebo/Placebo Etrolizumab 105mg Cohort 1 Etrolizumab/Placebo Etrolizumab 210mg Cohort 1 Etrolizumab/Etrolizumab 105mg Etrolizumab 105mg Cohort 2 Etrolizumab 210mg Cohort 2 Placebo Cohort 3 Etrolizumab 105mg Cohort 3 Etrolizumab 210mg Cohort 3
    Number of subjects analysed
    59 [56]
    53 [57]
    120 [58]
    217 [59]
    121 [60]
    217 [61]
    176 [62]
    174 [63]
    96 [64]
    143 [65]
    145 [66]
    Units: Number of Participants
        number (not applicable)
    50
    42
    83
    190
    82
    189
    120
    115
    51
    95
    85
    Notes
    [56] - data evaluable participants are included in each Grade group
    [57] - data evaluable participants are included in each Grade group
    [58] - data evaluable participants are included in each Grade group
    [59] - data evaluable participants are included in each Grade group
    [60] - data evaluable participants are included in each Grade group
    [61] - data evaluable participants are included in each Grade group
    [62] - data evaluable participants are included in each Grade group
    [63] - data evaluable participants are included in each Grade group
    [64] - data evaluable participants are included in each Grade group
    [65] - data evaluable participants are included in each Grade group
    [66] - data evaluable participants are included in each Grade group
    No statistical analyses for this end point

    Secondary: Overall Number of Participants with Adverse Events Leading to Study Drug Discontinuation

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    End point title
    		 Overall Number of Participants with Adverse Events Leading to Study Drug Discontinuation
    End point description
    Number of participants who discontinued the study due to the adverse events is reported. Safety Population.
    End point type
    Secondary
    End point timeframe
    From Baseline up to Week 78
    End point values
    		 Placebo Cohort 1 Placebo/Placebo Etrolizumab 105mg Cohort 1 Etrolizumab/Placebo Etrolizumab 210mg Cohort 1 Etrolizumab/Etrolizumab 105mg Etrolizumab 105mg Cohort 2 Etrolizumab 210mg Cohort 2 Placebo Cohort 3 Etrolizumab 105mg Cohort 3 Etrolizumab 210mg Cohort 3
    Number of subjects analysed
    59 [67]
    53 [68]
    120 [69]
    217 [70]
    121 [71]
    217 [72]
    176 [73]
    174 [74]
    96 [75]
    143 [76]
    145 [77]
    Units: Number of Participants
        number (not applicable)
    2
    1
    4
    1
    1
    3
    2
    5
    2
    0
    0
    Notes
    [67] - data evaluable participants are included in each Grade group
    [68] - data evaluable participants are included in each Grade group
    [69] - data evaluable participants are included in each Grade group
    [70] - data evaluable participants are included in each Grade group
    [71] - data evaluable participants are included in each Grade group
    [72] - data evaluable participants are included in each Grade group
    [73] - data evaluable participants are included in each Grade group
    [74] - data evaluable participants are included in each Grade group
    [75] - data evaluable participants are included in each Grade group
    [76] - data evaluable participants are included in each Grade group
    [77] - data evaluable participants are included in each Grade group
    No statistical analyses for this end point

    Secondary: Overall Number of Participants who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0

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    End point title
    		 Overall Number of Participants who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0
    End point description
    Participants who Experienced at Least One Infection-Related Adverse Event by Severity, According to NCI-CTCAE v4.0 are reported. Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = Death. Safety Population.
    End point type
    Secondary
    End point timeframe
    From Baseline up to Week 78
    End point values
    		 Placebo Cohort 1 Placebo/Placebo Etrolizumab 105mg Cohort 1 Etrolizumab/Placebo Etrolizumab 210mg Cohort 1 Etrolizumab/Etrolizumab 105mg Etrolizumab 105mg Cohort 2 Etrolizumab 210mg Cohort 2 Placebo Cohort 3 Etrolizumab 105mg Cohort 3 Etrolizumab 210mg Cohort 3
    Number of subjects analysed
    59 [78]
    53 [79]
    120 [80]
    217 [81]
    121 [82]
    217 [83]
    176 [84]
    174 [85]
    96 [86]
    143 [87]
    145 [88]
    Units: Number of Participants
    number (not applicable)
        Grade 1 (n=11,30,32,66,50,16,40,42,22,121,106)
    8
    9
    10
    44
    16
    42
    38
    21
    8
    25
    21
        Grade 2 (n=11,30,32,66,50,16,40,42,22,121,106)
    2
    11
    17
    65
    24
    53
    23
    20
    7
    12
    20
        Grade 3 (n=11,30,32,66,50,16,40,42,22,121,106)
    1
    2
    2
    11
    2
    10
    5
    8
    1
    2
    1
        Grade 4 (n=11,30,32,66,50,16,40,42,22,121,106)
    0
    0
    1
    1
    0
    0
    0
    1
    0
    1
    0
        Grade 5 (n=11,30,32,66,50,16,40,42,22,121,106)
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Notes
    [78] - data evaluable participants are included in each Grade group
    [79] - data evaluable participants are included in each Grade group
    [80] - data evaluable participants are included in each Grade group
    [81] - data evaluable participants are included in each Grade group
    [82] - data evaluable participants are included in each Grade group
    [83] - data evaluable participants are included in each Grade group
    [84] - data evaluable participants are included in each Grade group
    [85] - data evaluable participants are included in each Grade group
    [86] - data evaluable participants are included in each Grade group
    [87] - data evaluable participants are included in each Grade group
    [88] - data evaluable participants are included in each Grade group
    No statistical analyses for this end point

    Secondary: Overall Number of Participants who Experienced at Least One Infection-Related Serious Adverse Event

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    End point title
    		 Overall Number of Participants who Experienced at Least One Infection-Related Serious Adverse Event
    End point description
    Safety Population
    End point type
    Secondary
    End point timeframe
    From Baseline up to Week 78
    End point values
    		 Placebo Cohort 1 Placebo/Placebo Etrolizumab 105mg Cohort 1 Etrolizumab/Placebo Etrolizumab 210mg Cohort 1 Etrolizumab/Etrolizumab 105mg Etrolizumab 105mg Cohort 2 Etrolizumab 210mg Cohort 2 Placebo Cohort 3 Etrolizumab 105mg Cohort 3 Etrolizumab 210mg Cohort 3
    Number of subjects analysed
    59 [89]
    53 [90]
    120 [91]
    217 [92]
    121 [93]
    217 [94]
    176 [95]
    174 [96]
    96 [97]
    143 [98]
    145 [99]
    Units: Number of Participants
        number (not applicable)
    2
    1
    4
    13
    1
    12
    2
    5
    1
    2
    2
    Notes
    [89] - data evaluable participants are included in each Grade group
    [90] - data evaluable participants are included in each Grade group
    [91] - data evaluable participants are included in each Grade group
    [92] - data evaluable participants are included in each Grade group
    [93] - data evaluable participants are included in each Grade group
    [94] - data evaluable participants are included in each Grade group
    [95] - data evaluable participants are included in each Grade group
    [96] - data evaluable participants are included in each Grade group
    [97] - data evaluable participants are included in each Grade group
    [98] - data evaluable participants are included in each Grade group
    [99] - data evaluable participants are included in each Grade group
    No statistical analyses for this end point

    Secondary: Overall Number of Participants who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0

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    End point title
    		 Overall Number of Participants who Experienced at Least One Injection-Site Reaction by Severity, According to NCI-CTCAE v4.0
    End point description
    Investigator test for AEs is coding using MedDRA version 24.0. Injection-Site Reactions are identified by eCRF checkbox for local injection site reactions, and/or primary or secondary HLT Injection Site Reactions. Multiple occurrences of AEs for an individual are counted only once, under the worst grade reported. Safety Population. Result data evaluable participants are included.
    End point type
    Secondary
    End point timeframe
    From Baseline up to Week 78
    End point values
    		 Placebo Cohort 1 Placebo/Placebo Etrolizumab 105mg Cohort 1 Etrolizumab/Placebo Etrolizumab 210mg Cohort 1 Etrolizumab/Etrolizumab 105mg Etrolizumab 105mg Cohort 2 Etrolizumab 210mg Cohort 2 Placebo Cohort 3 Etrolizumab 105mg Cohort 3 Etrolizumab 210mg Cohort 3
    Number of subjects analysed
    59 [100]
    53 [101]
    120 [102]
    217 [103]
    121 [104]
    217 [105]
    176 [106]
    174 [107]
    96 [108]
    143 [109]
    145 [110]
    Units: Number of Participants
    number (not applicable)
        Grade 1 (n=4,7,4,10,9,1,11,6,3,18,9)
    4
    3
    7
    18
    3
    8
    10
    8
    1
    10
    6
        Grade 2 (n=4,7,4,10,9,1,11,6,3,18,9)
    0
    0
    0
    0
    1
    1
    0
    1
    0
    1
    0
        Grade 3 (n=4,7,4,10,9,1,11,6,3,18,9)
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Grade 4 (n=4,7,4,10,9,1,11,6,3,18,9)
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Grade 5 (n=4,7,4,10,9,1,11,6,3,18,9)
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Notes
    [100] - data evaluable participants are included in each Grade group
    [101] - data evaluable participants are included in each Grade group
    [102] - data evaluable participants are included in each Grade group
    [103] - data evaluable participants are included in each Grade group
    [104] - data evaluable participants are included in each Grade group
    [105] - data evaluable participants are included in each Grade group
    [106] - data evaluable participants are included in each Grade group
    [107] - data evaluable participants are included in each Grade group
    [108] - data evaluable participants are included in each Grade group
    [109] - data evaluable participants are included in each Grade group
    [110] - data evaluable participants are included in each Grade group
    No statistical analyses for this end point

    Secondary: Overall Number of Participants who Experienced at Least One Hypersensitivity Reaction by Severity, According to NCI-CTCAE v4.0

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    End point title
    		 Overall Number of Participants who Experienced at Least One Hypersensitivity Reaction by Severity, According to NCI-CTCAE v4.0
    End point description
    Investigator text for AEs is coded using MedDRA version 24.0. Multiple occurrences of AEs for an individual are counted only once, under the worst grade reported. Safety Population. Result data evaluable participants are included.
    End point type
    Secondary
    End point timeframe
    From Baseline up to Week 78
    End point values
    		 Placebo Cohort 1 Placebo/Placebo Etrolizumab 105mg Cohort 1 Etrolizumab/Placebo Etrolizumab 210mg Cohort 1 Etrolizumab/Etrolizumab 105mg Etrolizumab 105mg Cohort 2 Etrolizumab 210mg Cohort 2 Placebo Cohort 3 Etrolizumab 105mg Cohort 3 Etrolizumab 210mg Cohort 3
    Number of subjects analysed
    59 [111]
    53 [112]
    120 [113]
    217 [114]
    121 [115]
    217 [116]
    176 [117]
    174 [118]
    96 [119]
    143 [120]
    145 [121]
    Units: Number of Participants
    number (not applicable)
        Grade 1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
        Grade 2
    2
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
        Grade 3
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Grade 4
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Grade 5
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Notes
    [111] - data evaluable participants are included in each Grade group
    [112] - data evaluable participants are included in each Grade group
    [113] - data evaluable participants are included in each Grade group
    [114] - data evaluable participants are included in each Grade group
    [115] - data evaluable participants are included in each Grade group
    [116] - data evaluable participants are included in each Grade group
    [117] - data evaluable participants are included in each Grade group
    [118] - data evaluable participants are included in each Grade group
    [119] - data evaluable participants are included in each Grade group
    [120] - data evaluable participants are included in each Grade group
    [121] - data evaluable participants are included in each Grade group
    No statistical analyses for this end point

    Secondary: Overall Number of Participants who Develop Malignancies

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    End point title
    		 Overall Number of Participants who Develop Malignancies
    End point description
    Participants with malignancies are reported. Malignancies are identified by SMQ Malignant and unspecified tumors (narrow). Safety Population.
    End point type
    Secondary
    End point timeframe
    From Baseline up to Week 78
    End point values
    		 Placebo Cohort 1 Placebo/Placebo Etrolizumab 105mg Cohort 1 Etrolizumab/Placebo Etrolizumab 210mg Cohort 1 Etrolizumab/Etrolizumab 105mg Etrolizumab 105mg Cohort 2 Etrolizumab 210mg Cohort 2 Placebo Cohort 3 Etrolizumab 105mg Cohort 3 Etrolizumab 210mg Cohort 3
    Number of subjects analysed
    59 [122]
    53 [123]
    120 [124]
    217 [125]
    121 [126]
    217 [127]
    176 [128]
    174 [129]
    96 [130]
    143 [131]
    145 [132]
    Units: Number of Participants
        number (not applicable)
    0
    0
    1
    2
    1
    1
    0
    1
    0
    0
    0
    Notes
    [122] - data evaluable participants are included in each Grade group
    [123] - data evaluable participants are included in each Grade group
    [124] - data evaluable participants are included in each Grade group
    [125] - data evaluable participants are included in each Grade group
    [126] - data evaluable participants are included in each Grade group
    [127] - data evaluable participants are included in each Grade group
    [128] - data evaluable participants are included in each Grade group
    [129] - data evaluable participants are included in each Grade group
    [130] - data evaluable participants are included in each Grade group
    [131] - data evaluable participants are included in each Grade group
    [132] - data evaluable participants are included in each Grade group
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab

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    End point title
    		 Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Etrolizumab
    End point description
    Participants who received at least one dose of study treatment and had at least one baseline or post-baseline ATA result. Induction: treatment groups were pooled across cohorts 1-3. Maintenance: treatment group is stratified by induction dose
    End point type
    Secondary
    End point timeframe
    Baseline, Pre-dose (Hour 0) on Weeks 4, 14, 24, 32, 44, 66 or early termination, 12 weeks after last dose (up to Week 78)
    End point values
    		 Etro 105mg Induction Only Cohort Etro 210mg Induction Only Cohort Etro 105/ Placebo Induction and Maintenance Phase Cohort Etro 210/ Placebo Induction and Maintenance Phase Etro 105/Etro 105 Induction and Maintenance Phase Etro 210/Etro 105 Induction and Maintenance Phase
    Number of subjects analysed
    222 [133]
    223 [134]
    108 [135]
    109 [136]
    109 [137]
    108 [138]
    Units: Percentage of participants
    number (not applicable)
        Baseline (positive ADA) n=217,218,107,108,107,108
    4.1
    2.8
    2.8
    5.6
    2.8
    0
        Treatment emergent ADA n=213,216,108,109,109,108
    23
    22.7
    23.1
    33.9
    33.9
    21.3
    Notes
    [133] - Data evaluable participants are included in each group
    [134] - Data evaluable participants are included in each group
    [135] - Data evaluable participants are included in each group
    [136] - Data evaluable participants are included in each group
    [137] - Data evaluable participants are included in each group
    [138] - Data evaluable participants are included in each group
    No statistical analyses for this end point

    Secondary: Observed Trough Serum Concentration (Ctrough) of Etrolizumab

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    End point title
    		 Observed Trough Serum Concentration (Ctrough) of Etrolizumab [139]
    End point description
    Serum etrolizumab trough concentration. mITT. All participants who received at least one dose of study drug and had evaluable PK data.
    End point type
    Secondary
    End point timeframe
    Induction Phase at Weeks 10 and 14, Maintenance Phase at Weeks 16, 24, 28, 32, 44, and 66
    Notes
    [139] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Serum etrolizumab trough concentration was analyzed.
    End point values
    		 Etrolizumab 105mg Cohort 1 Etrolizumab 210mg Cohort 1 Etrolizumab 105mg Cohort 2 Etrolizumab 210mg Cohort 2 Etrolizumab 105mg Cohort 3 Etrolizumab 210mg Cohort 3 Maintenance Phase - Etrolizumab 105 mg/ Etrolizumab 105 mg Maintenance Phase - Etrolizumab 210 mg/ Etrolizumab 105 mg
    Number of subjects analysed
    117 [140]
    121 [141]
    175 [142]
    172 [143]
    138 [144]
    141 [145]
    109 [146]
    108 [147]
    Units: microgram/mL
    arithmetic mean (standard deviation)
        Week 10 (n=104, 112,158,160,124,126,0,0)
    9.39 ± 4.59
    25.1 ± 11.6
    10.3 ± 5.07
    25.7 ± 11.9
    9.78 ± 4.63
    25.5 ± 11.0
    0 ± 0
    0 ± 0
        Week 14 (n=96, 103, 148,144,115,120,0,0)
    10.2 ± 5.27
    23.2 ± 10.6
    11.0 ± 5.04
    24.1 ± 11.4
    10.8 ± 5.43
    24.6 ± 9.53
    0 ± 0
    0 ± 0
        Week 16 (n=0,0,0,0,0,0,102,94)
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
    6.15 ± 4.20
    14.8 ± 10.5
        Week 24 (n=0,0,0,0,0,0,96,97)
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
    6.58 ± 4.59
    8.20 ± 6.34
        Week 28 (n=0,0,0,0,0,0,88,82)
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
    7.29 ± 8.45
    8.07 ± 5.81
        Week 32 (n=0,0,0,0,0,0,85,81)
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
    7.13 ± 9.76
    7.89 ± 5.96
        Week 44 (n=0,0,0,0,0,0,68, 73)
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
    6.68 ± 3.75
    8.31 ± 6.68
        Week 66 (n=0,0,0,0,0,0,61,63)
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
    0 ± 0
    11.7 ± 5.82
    12.2 ± 6.44
    Notes
    [140] - Data evaluable participants are included in each cohort
    [141] - Data evaluable participants are included in each cohort
    [142] - Data evaluable participants are included in each cohort
    [143] - Data evaluable participants are included in each cohort
    [144] - Data evaluable participants are included in each cohort
    [145] - Data evaluable participants are included in each cohort
    [146] - Data evaluable participants are included in each cohort
    [147] - Data evaluable participants are included in each cohort
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From Baseline up to a maximum of 78 weeks
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.0
    Reporting groups
    Reporting group title
    Etrolizumab 105mg Cohort 1
    Reporting group description
    		 Cohort 1 enrolled participants first before Cohorts 2 and 3 in order to conduct an exploratory analysis on induction data. Participants randomized to this arm will receive one SC injection of etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.

    Reporting group title
    Placebo Cohort 1
    Reporting group description
    		 Cohort 1 enrolled participants first before Cohorts 2 and 3 in order to conduct an exploratory analysis on induction data. Participants randomized to this arm will receive two SC injections of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12 (and one SC injection of etrolizumab-matching placebo at Week 2) during the 14-week Induction Phase, in order to preserve the masking.

    Reporting group title
    Etrolizumab 105mg Cohort 2
    Reporting group description
    		 Cohort 2 is enrolling participants after Cohort 1 and is considered a "feeder" cohort to help achieve the necessary sample size for the Maintenance Phase. Participants randomized to this arm will receive one SC injection of open-label etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking of the dose of etrolizumab, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.

    Reporting group title
    Etrolizumab 210mg Cohort 1
    Reporting group description
    		 Cohort 1 enrolled participants first before Cohorts 2 and 3 in order to conduct an exploratory analysis on induction data. Participants randomized to this arm will receive one subcutaneous (SC) injection of etrolizumab (210 mg) at Weeks 0, 2, 4, 8, and 12 during the 14-week Induction Phase. In order to preserve the masking, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.

    Reporting group title
    Etrolizumab 210mg Cohort 2
    Reporting group description
    		 Cohort 2 is enrolling participants after Cohort 1 and is considered a "feeder" cohort to help achieve the necessary sample size for the Maintenance Phase. Participants randomized to this arm will receive one SC injection of open-label etrolizumab (210 mg) at Weeks 0, 2, 4, 8, and 12 during the 14-week Induction Phase. In order to preserve the masking for the dose of etrolizumab, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.

    Reporting group title
    Etrolizumab/Placebo
    Reporting group description
    		 Participants who received etrolizumab during the Induction Phase (from Cohorts 1-3) and achieved a CDAI-70 response at Week 14 without the use of rescue therapy will be re-randomized into the Maintenance Phase. Etrolizumab responders from induction who are re-randomized to this arm will receive blinded maintenance treatment with an SC injection of placebo q4w from Week 16 to Week 64

    Reporting group title
    Placebo/Placebo
    Reporting group description
    		 Participants who received placebo during the Induction Phase (from Cohorts 1 and 3) and achieved a CDAI-70 response at Week 14 will undergo a sham randomization into the Maintenance Phase. Placebo responders from induction will receive blinded maintenance treatment with an SC injection of placebo once every 4 weeks (q4w) from Week 16 to Week 64.

    Reporting group title
    Etrolizumab 105mg Cohort 3
    Reporting group description
    		 Cohort 3 is the last to enroll participants (after Cohort 2) and will be the pivotal cohort for the Induction Phase. Participants randomized to this arm will receive one SC injection of etrolizumab (105 mg) at Weeks 0, 4, 8, 12 and one SC injection of etrolizumab-matching placebo at Week 2 during the 14-week Induction Phase. In order to preserve the masking, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.

    Reporting group title
    Etrolizumab 210mg Cohort 3
    Reporting group description
    		 Cohort 3 is the last to enroll participants (after Cohort 2) and will be the pivotal cohort for the Induction Phase. Participants randomized to this arm will receive one SC injection of etrolizumab (210 mg) at Weeks 0, 2, 4, 8, and 12 during the 14-week Induction Phase. In order to preserve the masking, participants will also receive one SC injection of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12.

    Reporting group title
    Placebo Cohort 3
    Reporting group description
    		 Cohort 3 is the last to enroll participants (after Cohort 2) and will be the pivotal cohort for the Induction Phase. Participants randomized to this arm will receive two SC injections of etrolizumab-matching placebo at Weeks 0, 4, 8, and 12 (and one SC injection of etrolizumab-matching placebo at Week 2) during the 14-week Induction Phase, in order to preserve the masking.

    Reporting group title
    Etrolizumab/Etrolizumab 105mg
    Reporting group description
    		 Participants who received etrolizumab during the Induction Phase (from Cohorts 1-3) and achieved a CDAI-70 response at Week 14 without the use of rescue therapy will be re-randomized into the Maintenance Phase. Etrolizumab responders from induction who are re-randomized to this arm will receive blinded maintenance treatment with an SC injection of etrolizumab (105 mg) q4w from Week 16 to Week 64.

    Serious adverse events
    		 Etrolizumab 105mg Cohort 1 Placebo Cohort 1 Etrolizumab 105mg Cohort 2 Etrolizumab 210mg Cohort 1 Etrolizumab 210mg Cohort 2 Etrolizumab/Placebo Placebo/Placebo Etrolizumab 105mg Cohort 3 Etrolizumab 210mg Cohort 3 Placebo Cohort 3 Etrolizumab/Etrolizumab 105mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    20 / 120 (16.67%)
    8 / 59 (13.56%)
    18 / 176 (10.23%)
    12 / 121 (9.92%)
    20 / 174 (11.49%)
    33 / 217 (15.21%)
    9 / 53 (16.98%)
    12 / 143 (8.39%)
    8 / 145 (5.52%)
    8 / 96 (8.33%)
    30 / 217 (13.82%)
         number of deaths (all causes)
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    1
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma pancreas
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    1 / 174 (0.57%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    1 / 174 (0.57%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral embolism
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    1 / 217 (0.46%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Removal of foreign body from gastrointestinal tract
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    1 / 174 (0.57%)
    1 / 217 (0.46%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    1 / 217 (0.46%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Granuloma
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    1 / 217 (0.46%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Female genital tract fistula
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    2 / 217 (0.92%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Pelvic pain
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    1 / 121 (0.83%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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 / 0
    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 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax spontaneous
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 59 (1.69%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (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
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Liver function test abnormal
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    1 / 121 (0.83%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Gastrointestinal anastomotic leak
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Procedural intestinal perforation
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    1 / 143 (0.70%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thermal burn
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    1 / 217 (0.46%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    1 / 176 (0.57%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral gas embolism
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Tremor
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 59 (1.69%)
    0 / 176 (0.00%)
    1 / 121 (0.83%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    1 / 53 (1.89%)
    2 / 143 (1.40%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    2 / 217 (0.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leukocytosis
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    1 / 143 (0.70%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Acute vestibular syndrome
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vertigo positional
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Optic neuropathy
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 59 (1.69%)
    2 / 176 (1.14%)
    2 / 121 (1.65%)
    2 / 174 (1.15%)
    2 / 217 (0.92%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    2 / 145 (1.38%)
    1 / 96 (1.04%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 2
    0 / 2
    0 / 2
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Crohn's disease
         subjects affected / exposed
    12 / 120 (10.00%)
    6 / 59 (10.17%)
    5 / 176 (2.84%)
    7 / 121 (5.79%)
    10 / 174 (5.75%)
    14 / 217 (6.45%)
    4 / 53 (7.55%)
    7 / 143 (4.90%)
    5 / 145 (3.45%)
    3 / 96 (3.13%)
    4 / 217 (1.84%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 9
    0 / 6
    0 / 7
    0 / 11
    0 / 15
    0 / 4
    0 / 8
    0 / 5
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    1 / 217 (0.46%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal fistula
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    1 / 174 (0.57%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    3 / 217 (1.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    1 / 176 (0.57%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterocutaneous fistula
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    1 / 217 (0.46%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterovesical fistula
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    1 / 53 (1.89%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    1 / 96 (1.04%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileal stenosis
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    1 / 174 (0.57%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal fistula
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    1 / 176 (0.57%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    2 / 174 (1.15%)
    2 / 217 (0.92%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    1 / 53 (1.89%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mechanical ileus
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Proctitis
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    1 / 217 (0.46%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    1 / 174 (0.57%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 59 (0.00%)
    1 / 176 (0.57%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    1 / 145 (0.69%)
    0 / 96 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal perforation
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    1 / 53 (1.89%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subileus
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    1 / 176 (0.57%)
    0 / 121 (0.00%)
    1 / 174 (0.57%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Acute febrile neutrophilic dermatosis
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    1 / 174 (0.57%)
    1 / 217 (0.46%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Erythema nodosum
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    1 / 174 (0.57%)
    1 / 217 (0.46%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Excessive granulation tissue
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Scar pain
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Chronic kidney disease
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    1 / 217 (0.46%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    1 / 217 (0.46%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    1 / 96 (1.04%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 59 (1.69%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    1 / 217 (0.46%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fistula
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    1 / 217 (0.46%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myositis
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    1 / 217 (0.46%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal abscess
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    1 / 217 (0.46%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    1 / 96 (1.04%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal wall abscess
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    1 / 176 (0.57%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abscess intestinal
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    1 / 217 (0.46%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal abscess
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    1 / 176 (0.57%)
    0 / 121 (0.00%)
    1 / 174 (0.57%)
    1 / 217 (0.46%)
    0 / 53 (0.00%)
    1 / 143 (0.70%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    3 / 217 (1.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    1 / 217 (0.46%)
    0 / 53 (0.00%)
    1 / 143 (0.70%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (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
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asymptomatic COVID-19
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    1 / 145 (0.69%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    1 / 121 (0.83%)
    1 / 174 (0.57%)
    1 / 217 (0.46%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    1 / 174 (0.57%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    2 / 217 (0.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis norovirus
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    1 / 217 (0.46%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 120 (0.00%)
    1 / 59 (1.69%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    1 / 217 (0.46%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal infection
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    1 / 174 (0.57%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    1 / 176 (0.57%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    1 / 217 (0.46%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Meningitis listeria
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    1 / 176 (0.57%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pilonidal cyst
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    1 / 176 (0.57%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    1 / 217 (0.46%)
    1 / 53 (1.89%)
    0 / 143 (0.00%)
    1 / 145 (0.69%)
    0 / 96 (0.00%)
    2 / 217 (0.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    1 / 217 (0.46%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal abscess
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    1 / 121 (0.83%)
    2 / 174 (1.15%)
    1 / 217 (0.46%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    1 / 174 (0.57%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 120 (0.83%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    1 / 143 (0.70%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    1 / 217 (0.46%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    1 / 176 (0.57%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    1 / 217 (0.46%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    1 / 176 (0.57%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    1 / 176 (0.57%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Electrolyte imbalance
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    0 / 174 (0.00%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    1 / 96 (1.04%)
    0 / 217 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 120 (0.00%)
    0 / 59 (0.00%)
    0 / 176 (0.00%)
    0 / 121 (0.00%)
    1 / 174 (0.57%)
    0 / 217 (0.00%)
    0 / 53 (0.00%)
    0 / 143 (0.00%)
    0 / 145 (0.00%)
    0 / 96 (0.00%)
    1 / 217 (0.46%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Etrolizumab 105mg Cohort 1 Placebo Cohort 1 Etrolizumab 105mg Cohort 2 Etrolizumab 210mg Cohort 1 Etrolizumab 210mg Cohort 2 Etrolizumab/Placebo Placebo/Placebo Etrolizumab 105mg Cohort 3 Etrolizumab 210mg Cohort 3 Placebo Cohort 3 Etrolizumab/Etrolizumab 105mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    61 / 120 (50.83%)
    32 / 59 (54.24%)
    80 / 176 (45.45%)
    52 / 121 (42.98%)
    68 / 174 (39.08%)
    154 / 217 (70.97%)
    33 / 53 (62.26%)
    65 / 143 (45.45%)
    45 / 145 (31.03%)
    35 / 96 (36.46%)
    147 / 217 (67.74%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    13 / 120 (10.83%)
    4 / 59 (6.78%)
    20 / 176 (11.36%)
    7 / 121 (5.79%)
    20 / 174 (11.49%)
    27 / 217 (12.44%)
    4 / 53 (7.55%)
    14 / 143 (9.79%)
    8 / 145 (5.52%)
    7 / 96 (7.29%)
    22 / 217 (10.14%)
         occurrences all number
    14
    5
    27
    10
    22
    43
    4
    20
    15
    10
    27
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 120 (2.50%)
    2 / 59 (3.39%)
    0 / 176 (0.00%)
    2 / 121 (1.65%)
    5 / 174 (2.87%)
    10 / 217 (4.61%)
    2 / 53 (3.77%)
    5 / 143 (3.50%)
    4 / 145 (2.76%)
    2 / 96 (2.08%)
    11 / 217 (5.07%)
         occurrences all number
    3
    2
    0
    2
    5
    11
    2
    5
    4
    2
    12
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    4 / 120 (3.33%)
    1 / 59 (1.69%)
    6 / 176 (3.41%)
    3 / 121 (2.48%)
    2 / 174 (1.15%)
    10 / 217 (4.61%)
    1 / 53 (1.89%)
    4 / 143 (2.80%)
    5 / 145 (3.45%)
    3 / 96 (3.13%)
    13 / 217 (5.99%)
         occurrences all number
    4
    1
    7
    3
    2
    11
    1
    5
    6
    5
    15
    Injection site erythema
         subjects affected / exposed
    5 / 120 (4.17%)
    3 / 59 (5.08%)
    9 / 176 (5.11%)
    3 / 121 (2.48%)
    7 / 174 (4.02%)
    14 / 217 (6.45%)
    2 / 53 (3.77%)
    6 / 143 (4.20%)
    5 / 145 (3.45%)
    0 / 96 (0.00%)
    7 / 217 (3.23%)
         occurrences all number
    12
    5
    18
    7
    14
    41
    4
    8
    9
    0
    16
    Pyrexia
         subjects affected / exposed
    4 / 120 (3.33%)
    0 / 59 (0.00%)
    5 / 176 (2.84%)
    4 / 121 (3.31%)
    5 / 174 (2.87%)
    16 / 217 (7.37%)
    3 / 53 (5.66%)
    6 / 143 (4.20%)
    4 / 145 (2.76%)
    2 / 96 (2.08%)
    7 / 217 (3.23%)
         occurrences all number
    4
    0
    5
    4
    5
    18
    3
    8
    4
    2
    7
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    6 / 120 (5.00%)
    1 / 59 (1.69%)
    14 / 176 (7.95%)
    10 / 121 (8.26%)
    10 / 174 (5.75%)
    24 / 217 (11.06%)
    9 / 53 (16.98%)
    10 / 143 (6.99%)
    6 / 145 (4.14%)
    13 / 96 (13.54%)
    27 / 217 (12.44%)
         occurrences all number
    7
    1
    16
    12
    16
    29
    12
    11
    6
    15
    34
    Crohn's disease
         subjects affected / exposed
    9 / 120 (7.50%)
    12 / 59 (20.34%)
    13 / 176 (7.39%)
    8 / 121 (6.61%)
    7 / 174 (4.02%)
    63 / 217 (29.03%)
    13 / 53 (24.53%)
    7 / 143 (4.90%)
    8 / 145 (5.52%)
    3 / 96 (3.13%)
    37 / 217 (17.05%)
         occurrences all number
    12
    14
    13
    9
    7
    66
    13
    8
    9
    3
    43
    Diarrhoea
         subjects affected / exposed
    2 / 120 (1.67%)
    1 / 59 (1.69%)
    1 / 176 (0.57%)
    3 / 121 (2.48%)
    2 / 174 (1.15%)
    12 / 217 (5.53%)
    2 / 53 (3.77%)
    3 / 143 (2.10%)
    6 / 145 (4.14%)
    3 / 96 (3.13%)
    21 / 217 (9.68%)
         occurrences all number
    2
    1
    1
    3
    2
    15
    2
    3
    7
    3
    22
    Dyspepsia
         subjects affected / exposed
    5 / 120 (4.17%)
    2 / 59 (3.39%)
    4 / 176 (2.27%)
    0 / 121 (0.00%)
    2 / 174 (1.15%)
    11 / 217 (5.07%)
    2 / 53 (3.77%)
    3 / 143 (2.10%)
    1 / 145 (0.69%)
    1 / 96 (1.04%)
    8 / 217 (3.69%)
         occurrences all number
    5
    2
    4
    0
    2
    11
    2
    3
    1
    1
    8
    Frequent bowel movements
         subjects affected / exposed
    1 / 120 (0.83%)
    1 / 59 (1.69%)
    1 / 176 (0.57%)
    0 / 121 (0.00%)
    1 / 174 (0.57%)
    2 / 217 (0.92%)
    3 / 53 (5.66%)
    1 / 143 (0.70%)
    0 / 145 (0.00%)
    1 / 96 (1.04%)
    1 / 217 (0.46%)
         occurrences all number
    2
    2
    1
    0
    1
    2
    5
    1
    0
    1
    1
    Nausea
         subjects affected / exposed
    7 / 120 (5.83%)
    4 / 59 (6.78%)
    6 / 176 (3.41%)
    8 / 121 (6.61%)
    11 / 174 (6.32%)
    13 / 217 (5.99%)
    3 / 53 (5.66%)
    6 / 143 (4.20%)
    6 / 145 (4.14%)
    8 / 96 (8.33%)
    21 / 217 (9.68%)
         occurrences all number
    8
    4
    6
    14
    14
    16
    7
    6
    7
    11
    28
    Vomiting
         subjects affected / exposed
    7 / 120 (5.83%)
    2 / 59 (3.39%)
    4 / 176 (2.27%)
    6 / 121 (4.96%)
    3 / 174 (1.72%)
    12 / 217 (5.53%)
    0 / 53 (0.00%)
    4 / 143 (2.80%)
    4 / 145 (2.76%)
    2 / 96 (2.08%)
    14 / 217 (6.45%)
         occurrences all number
    9
    2
    5
    8
    3
    22
    0
    4
    4
    3
    16
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 120 (1.67%)
    2 / 59 (3.39%)
    2 / 176 (1.14%)
    1 / 121 (0.83%)
    1 / 174 (0.57%)
    4 / 217 (1.84%)
    3 / 53 (5.66%)
    1 / 143 (0.70%)
    2 / 145 (1.38%)
    4 / 96 (4.17%)
    7 / 217 (3.23%)
         occurrences all number
    2
    3
    2
    1
    1
    5
    3
    1
    2
    4
    7
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    6 / 120 (5.00%)
    2 / 59 (3.39%)
    12 / 176 (6.82%)
    10 / 121 (8.26%)
    9 / 174 (5.17%)
    25 / 217 (11.52%)
    9 / 53 (16.98%)
    11 / 143 (7.69%)
    7 / 145 (4.83%)
    7 / 96 (7.29%)
    27 / 217 (12.44%)
         occurrences all number
    6
    2
    13
    10
    11
    30
    12
    12
    8
    7
    32
    Back pain
         subjects affected / exposed
    3 / 120 (2.50%)
    1 / 59 (1.69%)
    4 / 176 (2.27%)
    4 / 121 (3.31%)
    1 / 174 (0.57%)
    10 / 217 (4.61%)
    5 / 53 (9.43%)
    2 / 143 (1.40%)
    0 / 145 (0.00%)
    3 / 96 (3.13%)
    4 / 217 (1.84%)
         occurrences all number
    3
    1
    4
    4
    1
    10
    5
    2
    0
    3
    5
    Infections and infestations
    Influenza
         subjects affected / exposed
    2 / 120 (1.67%)
    2 / 59 (3.39%)
    4 / 176 (2.27%)
    1 / 121 (0.83%)
    7 / 174 (4.02%)
    15 / 217 (6.91%)
    2 / 53 (3.77%)
    2 / 143 (1.40%)
    0 / 145 (0.00%)
    1 / 96 (1.04%)
    6 / 217 (2.76%)
         occurrences all number
    2
    2
    4
    1
    7
    16
    2
    2
    0
    1
    6
    Nasopharyngitis
         subjects affected / exposed
    7 / 120 (5.83%)
    2 / 59 (3.39%)
    11 / 176 (6.25%)
    9 / 121 (7.44%)
    7 / 174 (4.02%)
    27 / 217 (12.44%)
    3 / 53 (5.66%)
    7 / 143 (4.90%)
    9 / 145 (6.21%)
    4 / 96 (4.17%)
    32 / 217 (14.75%)
         occurrences all number
    7
    2
    12
    13
    7
    35
    3
    9
    9
    4
    42
    Sinusitis
         subjects affected / exposed
    1 / 120 (0.83%)
    1 / 59 (1.69%)
    2 / 176 (1.14%)
    2 / 121 (1.65%)
    4 / 174 (2.30%)
    6 / 217 (2.76%)
    2 / 53 (3.77%)
    4 / 143 (2.80%)
    2 / 145 (1.38%)
    1 / 96 (1.04%)
    13 / 217 (5.99%)
         occurrences all number
    1
    1
    2
    2
    4
    9
    2
    4
    2
    1
    16
    Upper respiratory tract infection
         subjects affected / exposed
    6 / 120 (5.00%)
    3 / 59 (5.08%)
    11 / 176 (6.25%)
    1 / 121 (0.83%)
    7 / 174 (4.02%)
    26 / 217 (11.98%)
    3 / 53 (5.66%)
    5 / 143 (3.50%)
    4 / 145 (2.76%)
    1 / 96 (1.04%)
    16 / 217 (7.37%)
         occurrences all number
    6
    3
    13
    1
    7
    30
    3
    5
    6
    1
    19
    Urinary tract infection
         subjects affected / exposed
    3 / 120 (2.50%)
    0 / 59 (0.00%)
    8 / 176 (4.55%)
    6 / 121 (4.96%)
    1 / 174 (0.57%)
    13 / 217 (5.99%)
    1 / 53 (1.89%)
    1 / 143 (0.70%)
    2 / 145 (1.38%)
    0 / 96 (0.00%)
    11 / 217 (5.07%)
         occurrences all number
    3
    0
    9
    7
    1
    13
    1
    1
    2
    0
    18

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    14 Oct 2014
    V2
    09 Dec 2014
    V3
    07 Oct 2015
    V4
    18 Nov 2016
    V5
    31 Aug 2017
    v6
    24 Apr 2019
    v7

    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

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/34467254
    http://www.ncbi.nlm.nih.gov/pubmed/32445184
    http://www.ncbi.nlm.nih.gov/pubmed/32464142
    For support, Contact us.
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    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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