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    Clinical Trial Results:
    A Phase 3, Randomized, Double-Blind, Placebo-Controlled, 52-Week Study to Assess the Efficacy and Safety of Etrasimod in Subjects with Moderately to Severely Active Ulcerative Colitis

    Summary
    EudraCT number
    		 2018-003985-15
    Trial protocol
    		 SK   BE   DE   LV   AT   NL   LT   PT   FR   EE   HU   DK   CZ   PL   BG   ES   HR   IT   RO  
    Global end of trial date
    23 Feb 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    31 Aug 2022
    First version publication date
    31 Aug 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    APD334-301
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03945188
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Arena Pharmaceuticals, a wholly owned subsidiary of Pfizer
    Sponsor organisation address
    6154 Nancy Ridge Drive, San Diego, United States,
    Public contact
    Fabio Cataldi, Arena Pharmaceuticals, Inc., 001 8584537200, ct.gov@arenapharm.com
    Scientific contact
    Fabio Cataldi, Arena Pharmaceuticals, Inc., 001 8584537200, ct.gov@arenapharm.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-002713-PIP01-19
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    10 Mar 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Feb 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the efficacy of etrasimod on clinical remission in participants with moderately to severely active ulcerative colitis (UC) after 12 and 52 weeks of treatment.
    Protection of trial subjects
    The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with the International Council for Harmonisation Guidelines for Good Clinical Practice and applicable regulatory requirements.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    13 Jun 2019
    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
    Austria: 1
    Country: Number of subjects enrolled
    Estonia: 5
    Country: Number of subjects enrolled
    France: 2
    Country: Number of subjects enrolled
    Latvia: 3
    Country: Number of subjects enrolled
    Lithuania: 3
    Country: Number of subjects enrolled
    Poland: 45
    Country: Number of subjects enrolled
    Australia: 4
    Country: Number of subjects enrolled
    Canada: 1
    Country: Number of subjects enrolled
    Chile: 1
    Country: Number of subjects enrolled
    India: 20
    Country: Number of subjects enrolled
    Israel: 5
    Country: Number of subjects enrolled
    Korea, Republic of: 4
    Country: Number of subjects enrolled
    Mexico: 3
    Country: Number of subjects enrolled
    South Africa: 5
    Country: Number of subjects enrolled
    Thailand: 4
    Country: Number of subjects enrolled
    United States: 78
    Country: Number of subjects enrolled
    Czechia: 13
    Country: Number of subjects enrolled
    Germany: 6
    Country: Number of subjects enrolled
    Italy: 13
    Country: Number of subjects enrolled
    Bulgaria: 12
    Country: Number of subjects enrolled
    Netherlands: 1
    Country: Number of subjects enrolled
    Romania: 5
    Country: Number of subjects enrolled
    Spain: 1
    Country: Number of subjects enrolled
    Belarus: 22
    Country: Number of subjects enrolled
    Belgium: 5
    Country: Number of subjects enrolled
    Croatia: 4
    Country: Number of subjects enrolled
    Denmark: 5
    Country: Number of subjects enrolled
    Georgia: 37
    Country: Number of subjects enrolled
    Hungary: 17
    Country: Number of subjects enrolled
    Moldova, Republic of: 16
    Country: Number of subjects enrolled
    Portugal: 2
    Country: Number of subjects enrolled
    Russian Federation: 36
    Country: Number of subjects enrolled
    Serbia: 4
    Country: Number of subjects enrolled
    Slovakia: 8
    Country: Number of subjects enrolled
    Turkey: 4
    Country: Number of subjects enrolled
    Ukraine: 37
    Country: Number of subjects enrolled
    United Kingdom: 1
    Worldwide total number of subjects
    433
    EEA total number of subjects
    151
    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)
    1
    Adults (18-64 years)
    405
    From 65 to 84 years
    27
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants with moderately to severely active ulcerative colitis (UC) were enrolled in this study. Eligible participants were randomized in a 2:1 ratio to receive either etrasimod 2 milligrams (mg) once daily or matching placebo once daily for up to 52 weeks.

    Pre-assignment
    Screening details
    		 The study included a Screening Period (up to 28 days), a 12-Week Treatment Period (induction) followed by a 40-Week Treatment Period (maintenance; for which no re-randomization took place), and a 2-Week and 4-Week Follow-Up Period.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Etrasimod 2 mg
    Arm description
    		 Etrasimod 2 mg was administered orally once daily for up to 52 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Etrasimod
    Investigational medicinal product code
    Other name
    APD334
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One etrasimod tablet was to be taken each day (with water, either with or without food).

    Arm title
    		 Placebo
    Arm description
    		 Placebo was administered orally once daily for up to 52 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One matching placebo tablet was to be taken each day (with water, either with or without food).

    Number of subjects in period 1
    		Etrasimod 2 mg Placebo
    Started
    289
    144
    Completed
    161
    46
    Not completed
    128
    98
         Physician decision
    2
    2
         Withdrawal by participant or parent/guardian
    24
    10
         Adverse event, non-fatal
    10
    5
         Pregnancy
    2
    -
         Unspecified
    2
    2
         Disease worsening
    79
    73
         Lost to follow-up
    1
    2
         Lack of efficacy
    7
    4
         Protocol deviation
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Etrasimod 2 mg
    Reporting group description
    		 Etrasimod 2 mg was administered orally once daily for up to 52 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo was administered orally once daily for up to 52 weeks.

    Reporting group values
    		 Etrasimod 2 mg Placebo Total
    Number of subjects
    		 289 144 433
    Age categorical
    Units: Subjects
        Adolescents (12-17 years)
    		 0 1 1
        Adults (18-64 years)
    		 272 133 405
        From 65-84 years
    		 17 10 27
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 41.2 ( 13.97 ) 38.9 ( 14.04 ) -
    Gender categorical
    Units: Subjects
        Female
    		 137 56 193
        Male
    		 152 88 240
    Race
    Units: Subjects
        White
    		 256 129 385
        Black or African American
    		 6 3 9
        Asian
    		 22 9 31
        American Indian or Alaska Native
    		 1 3 4
        Not Reported
    		 4 0 4

    End points

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    End points reporting groups
    Reporting group title
    Etrasimod 2 mg
    Reporting group description
    		 Etrasimod 2 mg was administered orally once daily for up to 52 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo was administered orally once daily for up to 52 weeks.

    Primary: Percentage of participants achieving clinical remission at Week 12

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    End point title
    		 Percentage of participants achieving clinical remission at Week 12
    End point description
    Clinical remission was based on the modified Mayo score (MMS). The MMS is a composite score of 3 assessments consisting of participant-reported symptoms using daily eDiary and centrally read endoscopy: stool frequency (SF), rectal bleeding (RB) and endoscopic score (ES). Clinical remission was defined as SF subscore = 0 (or = 1 with a ≥ 1-point decrease from Baseline), RB subscore = 0, and ES ≤ 1 (excluding friability). Each component subscore ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease. Analysis was performed using the Full Analysis Set (FAS, consisting of all randomized participants who received at least 1 dose of study treatment) with actual Baseline MMS 5 to 9.
    End point type
    Primary
    End point timeframe
    At Week 12
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    274
    135
    Units: Percentage of participants
        number (not applicable)
    27.0
    7.4
    Statistical analysis title
    		 Clinical Remission at Week 12
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    19.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 12.88
         upper limit
    		 26.63

    Primary: Percentage of participants achieving clinical remission at Week 52

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    End point title
    		 Percentage of participants achieving clinical remission at Week 52
    End point description
    Clinical remission was based on the MMS which is a composite score of 3 assessments: SF, RB and ES. Clinical remission was defined as SF subscore = 0 (or = 1 with a ≥ 1-point decrease from Baseline), RB subscore = 0, and ES ≤ 1 (excluding friability). Each component subscore ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease. Analysis was performed using the FAS with actual Baseline MMS 5 to 9.
    End point type
    Primary
    End point timeframe
    At Week 52
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    274
    135
    Units: Percentage of participants
        number (not applicable)
    32.1
    6.7
    Statistical analysis title
    		 Clinical Remission at Week 52
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    25.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 18.42
         upper limit
    		 32.36

    Secondary: Percentage of participants achieving endoscopic improvement at Week 12

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    End point title
    		 Percentage of participants achieving endoscopic improvement at Week 12
    End point description
    Endoscopic improvement was defined as an ES ≤ 1 (excluding friability). The ES ranged from 0 to 3 (where 0 = normal/inactive disease and 3 = severe disease). Analysis was performed using the FAS with actual Baseline MMS 5 to 9.
    End point type
    Secondary
    End point timeframe
    At Week 12
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    274
    135
    Units: Percentage of participants
        number (not applicable)
    35.0
    14.1
    Statistical analysis title
    		 Endoscopic Improvement at Week 12
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    21.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 13.03
         upper limit
    		 29.32

    Secondary: Percentage of participants achieving endoscopic improvement at Week 52

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    End point title
    		 Percentage of participants achieving endoscopic improvement at Week 52
    End point description
    Endoscopic improvement was defined as an ES ≤ 1 (excluding friability). The ES ranged from 0 to 3 (where 0 = normal/inactive disease and 3 = severe disease). Analysis was performed using the FAS with actual Baseline MMS 5 to 9.
    End point type
    Secondary
    End point timeframe
    At Week 52
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    274
    135
    Units: Percentage of participants
        number (not applicable)
    37.2
    10.4
    Statistical analysis title
    		 Endoscopic Improvement at Week 52
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    26.69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 18.99
         upper limit
    		 34.39

    Secondary: Percentage of participants achieving symptomatic remission at Week 12

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    End point title
    		 Percentage of participants achieving symptomatic remission at Week 12
    End point description
    Symptomatic remission was defined as an SF subscore = 0 (or = 1 with a ≥ 1-point decrease from Baseline) and RB subscore = 0. The SF subscore ranged from 0 to 3 (where 0 = normal number of stools and 3 = at least 5 stools more than normal) and RB subscore ranged from 0 to 3 (where 0 = no blood and 3 = blood alone passes). Higher scores indicate more severe disease. Analysis was performed using the FAS with actual Baseline MMS 5 to 9.
    End point type
    Secondary
    End point timeframe
    At Week 12
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    274
    135
    Units: Percentage of participants
        number (not applicable)
    46.0
    21.5
    Statistical analysis title
    		 Symptomatic Remission at Week 12
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    24.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 15.46
         upper limit
    		 33.63

    Secondary: Percentage of participants achieving symptomatic remission at Week 52

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    End point title
    		 Percentage of participants achieving symptomatic remission at Week 52
    End point description
    Symptomatic remission was defined as an SF subscore = 0 (or = 1 with a ≥ 1-point decrease from Baseline) and RB subscore = 0. The SF subscore ranged from 0 to 3 (where 0 = normal number of stools and 3 = at least 5 stools more than normal) and RB subscore ranged from 0 to 3 (where 0 = no blood and 3 = blood alone passes). Higher scores indicate more severe disease. Analysis was performed using the FAS with actual Baseline MMS 5 to 9.
    End point type
    Secondary
    End point timeframe
    At Week 52
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    274
    135
    Units: Percentage of participants
        number (not applicable)
    43.4
    18.5
    Statistical analysis title
    		 Symptomatic Remission at Week 52
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    24.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 16.17
         upper limit
    		 33.6

    Secondary: Percentage of participants with mucosal healing at Week 12

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    End point title
    		 Percentage of participants with mucosal healing at Week 12
    End point description
    Mucosal healing was defined as an ES ≤ 1 (excluding friability) with histologic remission measured by a Geboes Index score < 2.0. The ES ranged from 0 to 3 (where 0 = normal/inactive disease and 3 = severe disease). The Geboes score grading system is a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher Geboes score indicates more severe disease. Analysis was performed using the FAS with actual Baseline MMS 5 to 9.
    End point type
    Secondary
    End point timeframe
    At Week 12
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    274
    135
    Units: Percentage of participants
        number (not applicable)
    21.2
    4.4
    Statistical analysis title
    		 Mucosal Healing at Week 12
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    16.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 10.78
         upper limit
    		 22.98

    Secondary: Percentage of participants with mucosal healing at Week 52

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    End point title
    		 Percentage of participants with mucosal healing at Week 52
    End point description
    Mucosal healing was defined as an ES ≤ 1 (excluding friability) with histologic remission measured by a Geboes Index score < 2.0. The ES ranged from 0 to 3 (where 0 = normal/inactive disease and 3 = severe disease). The Geboes score grading system is a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher Geboes score indicates more severe disease. Analysis was performed using the FAS with actual Baseline MMS 5 to 9.
    End point type
    Secondary
    End point timeframe
    At Week 52
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    274
    135
    Units: Percentage of participants
        number (not applicable)
    26.6
    8.1
    Statistical analysis title
    		 Mucosal Healing at Week 52
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    18.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 11.39
         upper limit
    		 25.39

    Secondary: Percentage of participants achieving corticosteroid-free clinical remission at Week 52

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    End point title
    		 Percentage of participants achieving corticosteroid-free clinical remission at Week 52
    End point description
    Corticosteroid-free clinical remission was defined as an SF subscore = 0 (or = 1 with a ≥ 1-point decrease from Baseline), RB subscore = 0, ES ≤ 1 (excluding friability), and have not received corticosteroids for ≥ 12 weeks in the 40-Week Treatment Period. Each component subscore ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease. Analysis was performed using the FAS with actual Baseline MMS 5 to 9.
    End point type
    Secondary
    End point timeframe
    At Week 52
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    274
    135
    Units: Percentage of participants
        number (not applicable)
    32.1
    6.7
    Statistical analysis title
    		 Corticosteroid-Free Clinical Remission
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    25.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 18.42
         upper limit
    		 32.36

    Secondary: Percentage of participants achieving sustained clinical remission at both Weeks 12 and 52

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    End point title
    		 Percentage of participants achieving sustained clinical remission at both Weeks 12 and 52
    End point description
    Sustained clinical remission was defined as an SF subscore = 0 (or = 1 with a ≥ 1-point decrease from Baseline), RB subscore = 0, and ES ≤ 1 (excluding friability) at both Week 12 and Week 52. Each component subscore ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease. Analysis was performed using the FAS with actual Baseline MMS 5 to 9.
    End point type
    Secondary
    End point timeframe
    At Weeks 12 and 52
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    274
    135
    Units: Percentage of participants
        number (not applicable)
    17.9
    2.2
    Statistical analysis title
    		 Sustained Clinical Remission
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    15.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 10.66
         upper limit
    		 21.03

    Secondary: Percentage of participants achieving clinical response at Week 12

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    End point title
    		 Percentage of participants achieving clinical response at Week 12
    End point description
    Clinical response was based on the MMS which is a composite score of 3 assessments: SF, RB and ES. Clinical response was defined as a ≥ 2-point and ≥ 30% decrease from Baseline MMS, and a ≥ 1-point decrease from Baseline in RB subscore or an absolute RB subscore ≤ 1. Each component subscore ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease. Analysis was performed using the FAS with actual Baseline MMS 5 to 9.
    End point type
    Secondary
    End point timeframe
    At Week 12
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    274
    135
    Units: Percentage of participants
        number (not applicable)
    62.4
    34.1
    Statistical analysis title
    		 Clinical Response at Week 12
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    28.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 18.51
         upper limit
    		 38.02

    Secondary: Percentage of participants achieving clinical response at Week 52

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    End point title
    		 Percentage of participants achieving clinical response at Week 52
    End point description
    Clinical response was based on the MMS which is a composite score of 3 assessments: SF, RB and ES. Clinical response was defined as a ≥ 2-point and ≥ 30% decrease from Baseline MMS, and a ≥ 1-point decrease from Baseline in RB subscore or an absolute RB sub-score ≤ 1. Each component subscore ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease. Analysis was performed using the FAS with actual Baseline MMS 5 to 9.
    End point type
    Secondary
    End point timeframe
    At Week 52
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    274
    135
    Units: Percentage of participants
        number (not applicable)
    48.2
    23.0
    Statistical analysis title
    		 Clinical Response at Week 52
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    24.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 15.79
         upper limit
    		 34.07

    Secondary: Percentage of participants achieving clinical response at both Weeks 12 and 52

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    End point title
    		 Percentage of participants achieving clinical response at both Weeks 12 and 52
    End point description
    Clinical response was based on the MMS which is a composite score of 3 assessments: SF, RB and ES. Clinical response was defined as a ≥ 2-point and ≥ 30% decrease from Baseline MMS, and a ≥ 1-point decrease from Baseline in RB subscore or an absolute RB subscore ≤ 1. Each component subscore ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease. Analysis was performed using the FAS with actual Baseline MMS 5 to 9.
    End point type
    Secondary
    End point timeframe
    At Weeks 12 and 52
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    274
    135
    Units: Percentage of participants
        number (not applicable)
    44.9
    18.5
    Statistical analysis title
    		 Clinical Response at Both Weeks 12 and 52
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    26.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 17.48
         upper limit
    		 34.84

    Secondary: Percentage of participants with mucosal healing at both Weeks 12 and 52

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    End point title
    		 Percentage of participants with mucosal healing at both Weeks 12 and 52
    End point description
    Mucosal healing was defined as an ES ≤ 1 (excluding friability) with histologic remission measured by a Geboes Index score < 2.0. The ES ranged from 0 to 3 (where 0 = normal/inactive disease and 3 = severe disease). The Geboes score grading system is a validated score for evaluating histologic disease activity in UC as follows: grade 0 = structural and architectural changes; grade 1 = chronic inflammatory infiltrate; grade 2 = lamina propria neutrophils and eosinophils; grade 3 = neutrophils in the epithelium; grade 4 = crypt destruction; grade 5 = erosions or ulceration. A higher Geboes score indicates more severe disease. Analysis was performed using the FAS with actual Baseline MMS 5 to 9.
    End point type
    Secondary
    End point timeframe
    At Weeks 12 and 52
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    274
    135
    Units: Percentage of participants
        number (not applicable)
    13.5
    2.2
    Statistical analysis title
    		 Mucosal Healing at Both Weeks 12 and 52
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    11.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.49
         upper limit
    		 16.14

    Secondary: Percentage of participants achieving endoscopic normalization at Week 12

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    End point title
    		 Percentage of participants achieving endoscopic normalization at Week 12
    End point description
    Endoscopic normalization was defined as an ES = 0. The ES ranged from 0 to 3 (where 0= normal/inactive disease and 3= severe disease). Analysis was performed using the FAS with actual Baseline MMS 5 to 9.
    End point type
    Secondary
    End point timeframe
    At Week 12
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    274
    135
    Units: Percentage of participants
        number (not applicable)
    14.6
    4.4
    Statistical analysis title
    		 Endoscopic Normalization at Week 12
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    10.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.73
         upper limit
    		 15.73

    Secondary: Percentage of participants achieving endoscopic normalization at Week 52

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    End point title
    		 Percentage of participants achieving endoscopic normalization at Week 52
    End point description
    Endoscopic normalization was defined as an ES = 0. The ES ranged from 0 to 3 (where 0= normal/inactive disease and 3= severe disease). Analysis was performed using the FAS with actual Baseline MMS 5 to 9.
    End point type
    Secondary
    End point timeframe
    At Week 52
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    274
    135
    Units: Percentage of participants
        number (not applicable)
    26.3
    5.9
    Statistical analysis title
    		 Endoscopic Normalization at Week 52
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    20.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 13.79
         upper limit
    		 26.98

    Secondary: Percentage of participants achieving endoscopic normalization at both Weeks 12 and 52

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    End point title
    		 Percentage of participants achieving endoscopic normalization at both Weeks 12 and 52
    End point description
    Endoscopic normalization was defined as an ES = 0. The ES ranged from 0 to 3 (where 0= normal/inactive disease and 3= severe disease). Analysis was performed using the FAS with actual Baseline MMS 5 to 9.
    End point type
    Secondary
    End point timeframe
    At Weeks 12 and 52
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    274
    135
    Units: Percentage of participants
        number (not applicable)
    10.6
    1.5
    Statistical analysis title
    		 Endoscopic Normalization at Both Weeks 12 and 52
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    9.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.93
         upper limit
    		 13.38

    Secondary: Percentage of participants achieving symptomatic remission by study visit

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    End point title
    		 Percentage of participants achieving symptomatic remission by study visit
    End point description
    Symptomatic remission was defined as an SF subscore = 0 (or = 1 with a ≥ 1-point decrease from Baseline) and RB subscore = 0. The SF subscore ranged from 0 to 3 (where 0 = normal number of stools and 3 = at least 5 stools more than normal) and RB subscore ranged from 0 to 3 (where 0 = no blood and 3 = blood alone passes). Higher scores indicate more severe disease. Analysis was performed using the FAS with actual Baseline MMS 5 to 9.
    End point type
    Secondary
    End point timeframe
    At Weeks 2, 4, 8, 16, 20, 24, 32, 40, and 48
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    274
    135
    Units: Percentage of participants
    number (not applicable)
        Week 2
    15.3
    8.9
        Week 4
    28.1
    13.3
        Week 8
    37.6
    20.7
        Week 16
    43.1
    21.5
        Week 20
    43.8
    20.0
        Week 24
    44.9
    23.7
        Week 32
    44.5
    18.5
        Week 40
    42.0
    18.5
        Week 48
    42.0
    15.6
    Statistical analysis title
    		 Symptomatic Remission At Week 2
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.049
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    6.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.02
         upper limit
    		 12.95
    Statistical analysis title
    		 Symptomatic Remission At Week 4
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    15.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 7.32
         upper limit
    		 22.74
    Statistical analysis title
    		 Symptomatic Remission At Week 8
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    16.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 8.06
         upper limit
    		 25.63
    Statistical analysis title
    		 Symptomatic Remission At Week 16
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    21.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 12.71
         upper limit
    		 30.61
    Statistical analysis title
    		 Symptomatic Remission At Week 20
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    23.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 14.98
         upper limit
    		 32.51
    Statistical analysis title
    		 Symptomatic Remission At Week 24
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    21.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 11.83
         upper limit
    		 30.24
    Statistical analysis title
    		 Symptomatic Remission At Week 32
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    25.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 17.08
         upper limit
    		 34.56
    Statistical analysis title
    		 Symptomatic Remission At Week 40
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    23.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 14.8
         upper limit
    		 32.14
    Statistical analysis title
    		 Symptomatic Remission At Week 48
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    26.37
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 17.92
         upper limit
    		 34.82

    Secondary: Percentage of participants achieving complete symptomatic remission by study visit

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    End point title
    		 Percentage of participants achieving complete symptomatic remission by study visit
    End point description
    Complete symptomatic remission was defined as an SF subscore = 0 and RB subscore = 0. The SF subscore ranged from 0 to 3 (where 0 = normal number of stools and 3 = at least 5 stools more than normal) and RB subscore ranged from 0 to 3 (where 0 = no blood and 3 = blood alone passes). Higher scores indicate more severe disease. Analysis was performed using the FAS with actual Baseline MMS 5 to 9.
    End point type
    Secondary
    End point timeframe
    At Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48 and 52
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    274
    135
    Units: Percentage of participants
    number (not applicable)
        Week 2
    5.8
    2.2
        Week 4
    11.3
    4.4
        Week 8
    16.8
    6.7
        Week 12
    23.0
    6.7
        Week 16
    21.2
    5.9
        Week 20
    22.3
    4.4
        Week 24
    22.3
    8.1
        Week 32
    23.0
    3.0
        Week 40
    21.2
    5.9
        Week 48
    19.7
    2.2
        Week 52
    24.5
    4.4
    Statistical analysis title
    		 Complete Symptomatic Remission at Week 2
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.057
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    3.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.11
         upper limit
    		 7.3
    Statistical analysis title
    		 Complete Symptomatic Remission at Week 4
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.007
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    6.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.86
         upper limit
    		 11.9
    Statistical analysis title
    		 Complete Symptomatic Remission at Week 8
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    10.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.09
         upper limit
    		 16.2
    Statistical analysis title
    		 Complete Symptomatic Remission at Week 12
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    16.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 9.89
         upper limit
    		 22.83
    Statistical analysis title
    		 Complete Symptomatic Remission at Week 16
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    15.37
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 9.23
         upper limit
    		 21.52
    Statistical analysis title
    		 Complete Symptomatic Remission at Week 20
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    17.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 11.85
         upper limit
    		 23.75
    Statistical analysis title
    		 Complete Symptomatic Remission at Week 24
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    14.24
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 7.45
         upper limit
    		 21.04
    Statistical analysis title
    		 Complete Symptomatic Remission at Week 32
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    20.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 14.25
         upper limit
    		 25.81
    Statistical analysis title
    		 Complete Symptomatic Remission at Week 40
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    15.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 8.91
         upper limit
    		 21.35
    Statistical analysis title
    		 Complete Symptomatic Remission at Week 48
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    17.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 12.16
         upper limit
    		 22.87
    Statistical analysis title
    		 Complete Symptomatic Remission at Week 52
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    19.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 13.75
         upper limit
    		 25.98

    Secondary: Percentage of participants achieving non-invasive clinical response by study visit

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    End point title
    		 Percentage of participants achieving non-invasive clinical response by study visit
    End point description
    Non-invasive clinical response was defined as a ≥ 30% decrease from Baseline in composite RB and SF subscores, and a ≥ 1-point decrease from Baseline in RB subscore or RB subscore ≤ 1. The SF subscore ranged from 0 to 3 (where 0 = normal number of stools and 3 = at least 5 stools more than normal) and RB subscore ranged from 0 to 3 (where 0 = no blood and 3 = blood alone passes). The composite RB and SF score range was from 0 to 6, with higher scores indicating more severe disease. Analysis was performed using the FAS with actual Baseline MMS 5 to 9.
    End point type
    Secondary
    End point timeframe
    At Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    274
    135
    Units: Percentage of participants
    number (not applicable)
        Week 2
    38.3
    33.3
        Week 4
    56.2
    39.3
        Week 8
    63.1
    43.0
        Week 12
    65.7
    42.2
        Week 16
    55.5
    30.4
        Week 20
    57.3
    28.1
        Week 24
    56.6
    30.4
        Week 32
    54.0
    25.2
        Week 40
    51.5
    23.0
        Week 48
    51.1
    21.5
        Week 52
    50.4
    23.7
    Statistical analysis title
    		 Non-invasive Clinical Response at Week 2
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.336
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    4.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.01
         upper limit
    		 14.68
    Statistical analysis title
    		 Non-invasive Clinical Response at Week 4
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    17.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 7.06
         upper limit
    		 27.15
    Statistical analysis title
    		 Non-invasive Clinical Response at Week 8
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    20.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 10.15
         upper limit
    		 30.19
    Statistical analysis title
    		 Non-invasive Clinical Response at Week 12
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    23.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 13.45
         upper limit
    		 33.43
    Statistical analysis title
    		 Non-invasive Clinical Response at Week 16
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    25.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 15.67
         upper limit
    		 34.83
    Statistical analysis title
    		 Non-invasive Clinical Response at Week 20
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    29.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 19.77
         upper limit
    		 38.64
    Statistical analysis title
    		 Non-invasive Clinical Response at Week 24
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    26.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 16.47
         upper limit
    		 35.69
    Statistical analysis title
    		 Non-invasive Clinical Response at Week 32
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    28.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 19.35
         upper limit
    		 38.02
    Statistical analysis title
    		 Non-invasive Clinical Response at Week 40
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    28.43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 19.3
         upper limit
    		 37.55
    Statistical analysis title
    		 Non-invasive Clinical Response at Week 48
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    29.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 20.55
         upper limit
    		 38.64
    Statistical analysis title
    		 Non-invasive Clinical Response at Week 52
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    26.43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 17.18
         upper limit
    		 35.68

    Secondary: Percentage of participants achieving symptomatic response by study visit

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    End point title
    		 Percentage of participants achieving symptomatic response by study visit
    End point description
    Symptomatic response was defined as a ≥ 30% decrease from Baseline in composite RB and SF subscores. The SF subscore ranged from 0 to 3 (where 0= normal number of stools and 3= at least 5 stools more than normal) and RB subscore ranged from 0 to 3 (where 0= no blood and 3= blood alone passes). The composite RB and SF score range was from 0 to 6, with higher scores indicating more severe disease. Analysis was performed using the FAS with actual Baseline MMS 5 to 9.
    End point type
    Secondary
    End point timeframe
    At Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    274
    135
    Units: Percentage of participants
    number (not applicable)
        Week 2
    39.4
    33.3
        Week 4
    57.3
    40.0
        Week 8
    64.6
    43.7
        Week 12
    66.4
    42.2
        Week 16
    55.5
    31.1
        Week 20
    57.7
    28.1
        Week 24
    56.9
    30.4
        Week 32
    54.7
    25.2
        Week 40
    51.8
    23.0
        Week 48
    51.5
    21.5
        Week 52
    50.7
    23.7
    Statistical analysis title
    		 Symptomatic Response at Week 2
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.24
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    5.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.96
         upper limit
    		 15.81
    Statistical analysis title
    		 Symptomatic Response at Week 4
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    17.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 7.48
         upper limit
    		 27.53
    Statistical analysis title
    		 Symptomatic Response at Week 8
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    20.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 10.92
         upper limit
    		 30.94
    Statistical analysis title
    		 Symptomatic Response at Week 12
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    24.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 14.15
         upper limit
    		 34.1
    Statistical analysis title
    		 Symptomatic Response at Week 16
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    24.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 14.89
         upper limit
    		 34.13
    Statistical analysis title
    		 Symptomatic Response at Week 20
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    29.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 20.13
         upper limit
    		 39.01
    Statistical analysis title
    		 Symptomatic Response at Week 24
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    26.45
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 16.88
         upper limit
    		 36.02
    Statistical analysis title
    		 Symptomatic Response at Week 32
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    29.35
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 20.01
         upper limit
    		 38.68
    Statistical analysis title
    		 Symptomatic Response at Week 40
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    28.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 19.71
         upper limit
    		 37.95
    Statistical analysis title
    		 Symptomatic Response at Week 48
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    30
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 20.97
         upper limit
    		 39.03
    Statistical analysis title
    		 Symptomatic Response at Week 52
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    409
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    26.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 17.6
         upper limit
    		 36.07

    Secondary: Percentage of participants achieving 4-week corticosteroid-free clinical remission at Week 52 among participants receiving corticosteroids at Baseline

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    End point title
    		 Percentage of participants achieving 4-week corticosteroid-free clinical remission at Week 52 among participants receiving corticosteroids at Baseline
    End point description
    Four-week corticosteroid-free clinical remission was defined as an SF subscore = 0 (or = 1 with a ≥ 1-point decrease from Baseline), RB subscore = 0, and ES ≤ 1, and have not received corticosteroids for ≥ 4 weeks in the 40-Week Treatment Period. Each component subscore ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease. Analysis was performed using the FAS with actual Baseline MMS 5 to 9. Only participants receiving corticosteroids at study entry and who had not been receiving corticosteroids for ≥ 4 weeks prior to Week 52 were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Week 52
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    87
    40
    Units: Percentage of participants
        number (not applicable)
    31.0
    7.5
    Statistical analysis title
    		 4-Week Corticosteroid-Free Clinical Remission
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    127
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    23.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 10.2
         upper limit
    		 35.9

    Secondary: Percentage of participants achieving clinical remission at Week 52 among participants in clinical response at Week 12

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    End point title
    		 Percentage of participants achieving clinical remission at Week 52 among participants in clinical response at Week 12
    End point description
    Clinical remission and clinical response were based on the MMS which is a composite of 3 assessments: SF, RB and ES. Clinical remission was defined as an SF subscore = 0 (or = 1 with a ≥ 1-point decrease from Baseline), RB subscore = 0, and ES ≤ 1 (excluding friability). Clinical response was defined as a ≥ 2-point and ≥ 30% decrease from Baseline MMS, and a ≥ 1-point decrease from Baseline in RB subscore or an absolute RB subscore ≤ 1. Each component subscore ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease. Analysis was performed using the FAS with actual Baseline MMS 5 to 9.
    End point type
    Secondary
    End point timeframe
    At Week 52
    End point values
    		 Etrasimod 2 mg Placebo
    Number of subjects analysed
    171
    46
    Units: Percentage of participants
        number (not applicable)
    49.1
    17.4
    Statistical analysis title
    		 Clinical Remission at Week 52
    Statistical analysis description
    Clinical remission at Week 52 among participants in clinical response at Week 12
    Comparison groups
    Etrasimod 2 mg v Placebo
    Number of subjects included in analysis
    217
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    31.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 18.45
         upper limit
    		 45.28

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 56 weeks (12-Week and 40-Week Treatment Periods plus Follow-up). Treatment-emergent adverse events (TEAEs) were collected from first dose of study treatment up to 30 days following discontinuation of the study treatment.
    Adverse event reporting additional description
    TEAEs, defined as those adverse events that started or worsened in severity after the first dose of study treatment, are reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Placebo was administered orally once daily for up to 52 weeks.

    Reporting group title
    Etrasimod 2 mg
    Reporting group description
    		 Etrasimod 2 mg was administered orally once daily for up to 52 weeks.

    Serious adverse events
    		 Placebo Etrasimod 2 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 144 (6.25%)
    20 / 289 (6.92%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Investigations
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Breast conserving surgery
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Intracranial pressure increased
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Anembryonic gestation
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 144 (0.69%)
    2 / 289 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Allergy to arthropod bite
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis ulcerative
         subjects affected / exposed
    3 / 144 (2.08%)
    6 / 289 (2.08%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mucosal prolapse syndrome
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Proctitis
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    COVID-19 pneumonia
         subjects affected / exposed
    1 / 144 (0.69%)
    1 / 289 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    1 / 144 (0.69%)
    1 / 289 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Campylobacter infection
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Placebo Etrasimod 2 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    77 / 144 (53.47%)
    204 / 289 (70.59%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Colon adenoma
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 144 (0.69%)
    8 / 289 (2.77%)
         occurrences all number
    1
    8
    Hypertensive crisis
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Hot flush
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Flushing
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Varicose vein
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Peripheral arterial occlusive disease
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Deep vein thrombosis
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    6 / 144 (4.17%)
    14 / 289 (4.84%)
         occurrences all number
    7
    15
    Asthenia
         subjects affected / exposed
    2 / 144 (1.39%)
    7 / 289 (2.42%)
         occurrences all number
    2
    7
    Fatigue
         subjects affected / exposed
    2 / 144 (1.39%)
    5 / 289 (1.73%)
         occurrences all number
    3
    6
    Chest discomfort
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Oedema peripheral
         subjects affected / exposed
    1 / 144 (0.69%)
    2 / 289 (0.69%)
         occurrences all number
    1
    2
    Pain
         subjects affected / exposed
    1 / 144 (0.69%)
    2 / 289 (0.69%)
         occurrences all number
    1
    2
    Peripheral swelling
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Vaccination site pain
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    3
    Discomfort
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Drug intolerance
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Influenza like illness
         subjects affected / exposed
    1 / 144 (0.69%)
    1 / 289 (0.35%)
         occurrences all number
    1
    1
    Non-cardiac chest pain
         subjects affected / exposed
    2 / 144 (1.39%)
    1 / 289 (0.35%)
         occurrences all number
    2
    1
    Chest pain
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Chills
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Infusion site reaction
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Malaise
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    2 / 144 (1.39%)
    0 / 289 (0.00%)
         occurrences all number
    2
    0
    Reproductive system and breast disorders
    Breast mass
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Endometriosis
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Heavy menstrual bleeding
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Amenorrhoea
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Penile curvature
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Rhinitis allergic
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Dyspnoea exertional
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Cough
         subjects affected / exposed
    2 / 144 (1.39%)
    2 / 289 (0.69%)
         occurrences all number
    2
    2
    Dyspnoea
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Nasal congestion
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Rhinorrhoea
         subjects affected / exposed
    0 / 144 (0.00%)
    4 / 289 (1.38%)
         occurrences all number
    0
    4
    Pulmonary mass
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Bronchial obstruction
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Oropharyngeal pain
         subjects affected / exposed
    2 / 144 (1.39%)
    1 / 289 (0.35%)
         occurrences all number
    2
    1
    Epistaxis
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Obstructive airways disorder
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Painful respiration
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Sinus congestion
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Sneezing
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Wheezing
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Insomnia
         subjects affected / exposed
    1 / 144 (0.69%)
    2 / 289 (0.69%)
         occurrences all number
    1
    2
    Agitation
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Attention deficit hyperactivity disorder
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Depression
         subjects affected / exposed
    2 / 144 (1.39%)
    1 / 289 (0.35%)
         occurrences all number
    2
    1
    Sleep disorder
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Panic attack
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 144 (0.69%)
    5 / 289 (1.73%)
         occurrences all number
    1
    5
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 144 (1.39%)
    8 / 289 (2.77%)
         occurrences all number
    2
    12
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    2 / 144 (1.39%)
    5 / 289 (1.73%)
         occurrences all number
    2
    5
    Transaminases increased
         subjects affected / exposed
    0 / 144 (0.00%)
    3 / 289 (1.04%)
         occurrences all number
    0
    4
    Aspartate aminotransferase increased
         subjects affected / exposed
    3 / 144 (2.08%)
    3 / 289 (1.04%)
         occurrences all number
    3
    5
    SARS-CoV-2 test positive
         subjects affected / exposed
    1 / 144 (0.69%)
    3 / 289 (1.04%)
         occurrences all number
    1
    3
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Serum ferritin decreased
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Blood triglycerides increased
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 144 (0.69%)
    2 / 289 (0.69%)
         occurrences all number
    1
    2
    Blood cholesterol increased
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Weight increased
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Weight decreased
         subjects affected / exposed
    1 / 144 (0.69%)
    2 / 289 (0.69%)
         occurrences all number
    1
    2
    Blood glucose increased
         subjects affected / exposed
    1 / 144 (0.69%)
    1 / 289 (0.35%)
         occurrences all number
    1
    1
    Blood iron decreased
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Blood pressure increased
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Haemoglobin decreased
         subjects affected / exposed
    1 / 144 (0.69%)
    1 / 289 (0.35%)
         occurrences all number
    1
    1
    C-reactive protein increased
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Blood triglycerides abnormal
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Blood thyroid stimulating hormone increased
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Blood thyroid stimulating hormone decreased
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    International normalised ratio increased
         subjects affected / exposed
    1 / 144 (0.69%)
    1 / 289 (0.35%)
         occurrences all number
    1
    1
    Urine ketone body
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Forced expiratory volume decreased
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Bacterial test positive
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Spirometry abnormal
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    FEV1/FVC ratio decreased
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Platelet count increased
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Lung diffusion test decreased
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Liver function test increased
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Prothrombin time prolonged
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Pulmonary arterial pressure decreased
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Arthropod bite
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Arthropod sting
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Contusion
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Injury corneal
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Fall
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Ligament sprain
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Patella fracture
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Limb injury
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Post lumbar puncture syndrome
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Muscle strain
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Vaccination complication
         subjects affected / exposed
    1 / 144 (0.69%)
    1 / 289 (0.35%)
         occurrences all number
    1
    1
    Peripheral nerve injury
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Wound
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Lower limb fracture
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Cardiac failure chronic
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Atrioventricular block first degree
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Atrial fibrillation
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Tachycardia
         subjects affected / exposed
    1 / 144 (0.69%)
    2 / 289 (0.69%)
         occurrences all number
    1
    2
    Bradycardia
         subjects affected / exposed
    0 / 144 (0.00%)
    4 / 289 (1.38%)
         occurrences all number
    0
    4
    Atrioventricular block second degree
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Palpitations
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    7 / 144 (4.86%)
    24 / 289 (8.30%)
         occurrences all number
    12
    36
    Dizziness
         subjects affected / exposed
    1 / 144 (0.69%)
    15 / 289 (5.19%)
         occurrences all number
    1
    17
    Head discomfort
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Migraine
         subjects affected / exposed
    0 / 144 (0.00%)
    3 / 289 (1.04%)
         occurrences all number
    0
    8
    Carotid arteriosclerosis
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Parkinson's disease
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Sciatica
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Post herpetic neuralgia
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Asterixis
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Somnolence
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Dizziness exertional
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Tension headache
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Dizziness postural
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Hypoaesthesia
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Syncope
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    14 / 144 (9.72%)
    24 / 289 (8.30%)
         occurrences all number
    17
    31
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Thrombocytosis
         subjects affected / exposed
    1 / 144 (0.69%)
    2 / 289 (0.69%)
         occurrences all number
    1
    2
    Hypocoagulable state
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Lymphadenopathy
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Lymphopenia
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Eye disorders
    Papilloedema
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Vision blurred
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    3
    Cataract
         subjects affected / exposed
    1 / 144 (0.69%)
    3 / 289 (1.04%)
         occurrences all number
    1
    3
    Myopia
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Amblyopia
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Astigmatism
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Blepharitis
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Eyelid pain
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Dry eye
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Eyelid cyst
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Macular oedema
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Eye swelling
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Visual impairment
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Visual acuity reduced
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Keratitis
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Uveitis
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Retinal haemorrhage
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Eye pain
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Maculopathy
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Colitis ulcerative
         subjects affected / exposed
    10 / 144 (6.94%)
    17 / 289 (5.88%)
         occurrences all number
    10
    18
    Nausea
         subjects affected / exposed
    2 / 144 (1.39%)
    9 / 289 (3.11%)
         occurrences all number
    2
    11
    Diarrhoea
         subjects affected / exposed
    1 / 144 (0.69%)
    5 / 289 (1.73%)
         occurrences all number
    1
    5
    Flatulence
         subjects affected / exposed
    0 / 144 (0.00%)
    6 / 289 (2.08%)
         occurrences all number
    0
    6
    Abdominal pain
         subjects affected / exposed
    5 / 144 (3.47%)
    11 / 289 (3.81%)
         occurrences all number
    6
    13
    Abdominal distension
         subjects affected / exposed
    3 / 144 (2.08%)
    4 / 289 (1.38%)
         occurrences all number
    4
    5
    Haemorrhoids
         subjects affected / exposed
    0 / 144 (0.00%)
    7 / 289 (2.42%)
         occurrences all number
    0
    8
    Vomiting
         subjects affected / exposed
    0 / 144 (0.00%)
    5 / 289 (1.73%)
         occurrences all number
    0
    5
    Dyspepsia
         subjects affected / exposed
    2 / 144 (1.39%)
    3 / 289 (1.04%)
         occurrences all number
    2
    3
    Constipation
         subjects affected / exposed
    1 / 144 (0.69%)
    4 / 289 (1.38%)
         occurrences all number
    1
    4
    Abdominal pain lower
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Anal pruritus
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Stomatitis
         subjects affected / exposed
    0 / 144 (0.00%)
    3 / 289 (1.04%)
         occurrences all number
    0
    3
    Gastritis
         subjects affected / exposed
    0 / 144 (0.00%)
    3 / 289 (1.04%)
         occurrences all number
    0
    3
    Aphthous ulcer
         subjects affected / exposed
    1 / 144 (0.69%)
    2 / 289 (0.69%)
         occurrences all number
    1
    2
    Abdominal pain upper
         subjects affected / exposed
    3 / 144 (2.08%)
    1 / 289 (0.35%)
         occurrences all number
    3
    1
    Abdominal tenderness
         subjects affected / exposed
    1 / 144 (0.69%)
    1 / 289 (0.35%)
         occurrences all number
    1
    1
    Proctalgia
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Large intestine polyp
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Anal fissure
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Dry mouth
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Diverticulum intestinal
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Enteritis
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    2
    Epigastric discomfort
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Eructation
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Haematochezia
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Melaena
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    2
    Inguinal hernia
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Mucosal prolapse syndrome
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Rectal tenesmus
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Paraesthesia oral
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Rectal polyp
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Small intestine polyp
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Tooth impacted
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Umbilical hernia
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Defaecation urgency
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Food poisoning
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Mouth ulceration
         subjects affected / exposed
    3 / 144 (2.08%)
    0 / 289 (0.00%)
         occurrences all number
    4
    0
    Hepatobiliary disorders
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Cholestasis
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Hepatic steatosis
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Cholangitis sclerosing
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Primary biliary cholangitis
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    1 / 144 (0.69%)
    3 / 289 (1.04%)
         occurrences all number
    2
    3
    Acne
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Rash
         subjects affected / exposed
    3 / 144 (2.08%)
    5 / 289 (1.73%)
         occurrences all number
    4
    5
    Erythema
         subjects affected / exposed
    1 / 144 (0.69%)
    2 / 289 (0.69%)
         occurrences all number
    1
    2
    Eczema
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Night sweats
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Alopecia scarring
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Dermatitis
         subjects affected / exposed
    1 / 144 (0.69%)
    1 / 289 (0.35%)
         occurrences all number
    2
    1
    Psoriasis
         subjects affected / exposed
    1 / 144 (0.69%)
    2 / 289 (0.69%)
         occurrences all number
    1
    2
    Dry skin
         subjects affected / exposed
    2 / 144 (1.39%)
    1 / 289 (0.35%)
         occurrences all number
    2
    1
    Ecchymosis
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Rash pruritic
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Ephelides
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Dermatitis contact
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Purpura senile
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Xanthelasma
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Urticaria
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    Nephrolithiasis
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Pollakiuria
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Chromaturia
         subjects affected / exposed
    1 / 144 (0.69%)
    1 / 289 (0.35%)
         occurrences all number
    1
    1
    Renal cyst
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Haematuria
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Proteinuria
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Micturition frequency decreased
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Renal impairment
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Urine abnormality
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    1 / 144 (0.69%)
    2 / 289 (0.69%)
         occurrences all number
    1
    2
    Cushingoid
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Autoimmune thyroiditis
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Thyroid cyst
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    3 / 144 (2.08%)
    13 / 289 (4.50%)
         occurrences all number
    3
    16
    Back pain
         subjects affected / exposed
    3 / 144 (2.08%)
    7 / 289 (2.42%)
         occurrences all number
    4
    7
    Neck pain
         subjects affected / exposed
    0 / 144 (0.00%)
    3 / 289 (1.04%)
         occurrences all number
    0
    4
    Muscle spasms
         subjects affected / exposed
    0 / 144 (0.00%)
    5 / 289 (1.73%)
         occurrences all number
    0
    5
    Osteoarthritis
         subjects affected / exposed
    1 / 144 (0.69%)
    3 / 289 (1.04%)
         occurrences all number
    1
    3
    Pain in extremity
         subjects affected / exposed
    2 / 144 (1.39%)
    2 / 289 (0.69%)
         occurrences all number
    2
    2
    Tendonitis
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Ankle deformity
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Joint stiffness
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Arthropathy
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Groin pain
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Musculoskeletal stiffness
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Muscle twitching
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Joint swelling
         subjects affected / exposed
    1 / 144 (0.69%)
    1 / 289 (0.35%)
         occurrences all number
    1
    1
    Myalgia
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Periarthritis
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Osteochondrosis
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Spondyloarthropathy
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Flank pain
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Limb mass
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    8 / 144 (5.56%)
    19 / 289 (6.57%)
         occurrences all number
    8
    29
    Respiratory tract infection viral
         subjects affected / exposed
    2 / 144 (1.39%)
    6 / 289 (2.08%)
         occurrences all number
    2
    6
    Urinary tract infection
         subjects affected / exposed
    3 / 144 (2.08%)
    6 / 289 (2.08%)
         occurrences all number
    3
    8
    COVID-19 pneumonia
         subjects affected / exposed
    1 / 144 (0.69%)
    4 / 289 (1.38%)
         occurrences all number
    1
    4
    Cystitis
         subjects affected / exposed
    0 / 144 (0.00%)
    4 / 289 (1.38%)
         occurrences all number
    0
    4
    Bronchitis
         subjects affected / exposed
    0 / 144 (0.00%)
    3 / 289 (1.04%)
         occurrences all number
    0
    3
    Pharyngitis
         subjects affected / exposed
    0 / 144 (0.00%)
    3 / 289 (1.04%)
         occurrences all number
    0
    4
    Nasopharyngitis
         subjects affected / exposed
    4 / 144 (2.78%)
    3 / 289 (1.04%)
         occurrences all number
    4
    3
    Anal abscess
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 144 (1.39%)
    3 / 289 (1.04%)
         occurrences all number
    3
    4
    Herpes zoster
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Candida infection
         subjects affected / exposed
    1 / 144 (0.69%)
    2 / 289 (0.69%)
         occurrences all number
    1
    2
    Hordeolum
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Oral herpes
         subjects affected / exposed
    1 / 144 (0.69%)
    2 / 289 (0.69%)
         occurrences all number
    1
    2
    Pustule
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Conjunctivitis
         subjects affected / exposed
    4 / 144 (2.78%)
    1 / 289 (0.35%)
         occurrences all number
    6
    1
    Abscess limb
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Acne pustular
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Helicobacter infection
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Clostridium difficile infection
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Liver abscess
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Helminthic infection
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Pneumonia viral
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Herpes simplex
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Pulpitis dental
         subjects affected / exposed
    1 / 144 (0.69%)
    1 / 289 (0.35%)
         occurrences all number
    1
    1
    Respiratory tract infection
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Rhinitis
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Otitis externa
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Sinusitis
         subjects affected / exposed
    1 / 144 (0.69%)
    1 / 289 (0.35%)
         occurrences all number
    1
    1
    Tinea infection
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 144 (0.69%)
    1 / 289 (0.35%)
         occurrences all number
    1
    1
    Tonsillitis
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Ear infection staphylococcal
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Tracheitis
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Gastroenteritis
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Vaginal infection
         subjects affected / exposed
    1 / 144 (0.69%)
    1 / 289 (0.35%)
         occurrences all number
    1
    1
    Vulval abscess
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Gastroenteritis viral
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Pneumonia
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Skin infection
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Influenza
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Tooth abscess
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Tooth infection
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Tuberculosis
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Vulvovaginal mycotic infection
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    1 / 144 (0.69%)
    4 / 289 (1.38%)
         occurrences all number
    1
    4
    Hypercholesterolaemia
         subjects affected / exposed
    0 / 144 (0.00%)
    6 / 289 (2.08%)
         occurrences all number
    0
    6
    Decreased appetite
         subjects affected / exposed
    1 / 144 (0.69%)
    1 / 289 (0.35%)
         occurrences all number
    1
    1
    Vitamin D deficiency
         subjects affected / exposed
    0 / 144 (0.00%)
    2 / 289 (0.69%)
         occurrences all number
    0
    2
    Dehydration
         subjects affected / exposed
    1 / 144 (0.69%)
    2 / 289 (0.69%)
         occurrences all number
    1
    2
    Iron deficiency
         subjects affected / exposed
    1 / 144 (0.69%)
    2 / 289 (0.69%)
         occurrences all number
    1
    2
    Diabetes mellitus
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Hypertriglyceridaemia
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Hyperkalaemia
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 144 (0.69%)
    0 / 289 (0.00%)
         occurrences all number
    0
    0
    Hypophosphataemia
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1
    Lipomatosis
         subjects affected / exposed
    0 / 144 (0.00%)
    1 / 289 (0.35%)
         occurrences all number
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    05 Mar 2019
    Amendment 1.0: Changed stratification factor from failed biologic or Janus kinase (JAK) inhibitor therapy to naïve to biologic or JAK inhibitor therapy; updated inclusion/exclusion criteria for hematological function, prior medication, and hospitalization for UC; added a section "Guidance for Cardiac Monitoring Following Treatment Initiation or Re-Initiation" and added a 12-lead electrocardiogramn (ECG) at Week 12 and Week 52; updated safety precautions for cardiovascular events; renamed the analysis sets; added a section on subgroup analyses.
    20 Dec 2019
    Amendment 2.0: Updated entry criteria for open-label extension (OLE) study for participants who experience UC worsening after Week 12 and prior to Week 52. Amendment provided additional guidance to the Investigator regarding required endoscopic evaluation to confirm eligibility for OLE prior to Week 52. Updated eligibility criteria (list of prior therapy failures or non-response, contraception use, cardiovascular disease history, and prior therapy washout period); added a 4-Week Follow-Up Visit; provided additional instructions for safety monitoring related to 12-lead ECG, pulmonary function tests (PFTs), ophthalmoscopy and optical coherence tomography (OCT), and Quantiferon tuberculosis Gold and tuberculin skin tests.
    07 Feb 2020
    Amendment 3.0: Provided clarification and further instructions for tuberculosis testing and updated the tuberculosis screening questionnaire; updated entry criteria for enrollment in the OLE study; added lack of efficacy as a reason a participant may discontinue from double-blind treatment. Added that if the Early Termination or Study Completion visit is ≥ 2 weeks after the last dose of study treatment, the 2-Week Follow-Up visit is not required; however, the 4-Week Follow-up visit should be scheduled and completed. If the Early Termination or Study Completion visit is ≥ 4 weeks after the last dose of study treatment, the 4-Week Follow-Up visit is not required.
    22 Dec 2020
    Amendment 4.0: Updated the participant enrollment number and guidance for conducting virtual and offsite visits; added information on anti-arrhythmic drugs to prohibited concomitant therapies; updated the corticosteroid-free remission secondary endpoint; updated language regarding timing of screening OCTs and PFTs; added an exclusion criterion covering treatment with topical rectal Chinese medicine, enemas, or suppositories.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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