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    Clinical Trial Results:
    A Phase 3, Multicenter, Randomized, Double-Blind, Placebo- and Active-Controlled, Treat-Through Study to Evaluate the Efficacy and Safety of Mirikizumab in Patients with Moderately to Severely Active Crohn's Disease

    Summary
    EudraCT number
    		 2018-004614-18
    Trial protocol
    		 AT   HU   FR   GB   DE   NL   ES   PL   DK   BE   SK   LT   CZ   LV   HR   IT   RO  
    Global end of trial date
    02 Oct 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    01 Sep 2024
    First version publication date
    01 Sep 2024
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    I6T-MC-AMAM
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03926130
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Trial Number: 16590
    Sponsors
    Sponsor organisation name
    Eli Lilly and Company
    Sponsor organisation address
    Lilly Corporate Center, Indianapolis, IN, United States, 46285
    Public contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐CTLilly,
    Scientific contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐285‐4559,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    02 Oct 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    02 Oct 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The reason for this study is to see if the study drug mirikizumab is safe and effective in participants with moderately to severely active Crohn’s disease.
    Protection of trial subjects
    This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    23 Jul 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
    Türkiye: 41
    Country: Number of subjects enrolled
    United States: 117
    Country: Number of subjects enrolled
    Czechia: 57
    Country: Number of subjects enrolled
    Russian Federation: 86
    Country: Number of subjects enrolled
    Austria: 10
    Country: Number of subjects enrolled
    Latvia: 3
    Country: Number of subjects enrolled
    Netherlands: 4
    Country: Number of subjects enrolled
    Korea, Republic of: 60
    Country: Number of subjects enrolled
    China: 164
    Country: Number of subjects enrolled
    Brazil: 58
    Country: Number of subjects enrolled
    Poland: 161
    Country: Number of subjects enrolled
    Slovakia: 19
    Country: Number of subjects enrolled
    France: 7
    Country: Number of subjects enrolled
    Lithuania: 5
    Country: Number of subjects enrolled
    Serbia: 21
    Country: Number of subjects enrolled
    Croatia: 7
    Country: Number of subjects enrolled
    Argentina: 2
    Country: Number of subjects enrolled
    Romania: 13
    Country: Number of subjects enrolled
    Hungary: 34
    Country: Number of subjects enrolled
    Japan: 28
    Country: Number of subjects enrolled
    Ukraine: 88
    Country: Number of subjects enrolled
    United Kingdom: 5
    Country: Number of subjects enrolled
    Switzerland: 7
    Country: Number of subjects enrolled
    India: 25
    Country: Number of subjects enrolled
    Spain: 4
    Country: Number of subjects enrolled
    Canada: 35
    Country: Number of subjects enrolled
    Belgium: 9
    Country: Number of subjects enrolled
    Denmark: 2
    Country: Number of subjects enrolled
    Italy: 8
    Country: Number of subjects enrolled
    Mexico: 7
    Country: Number of subjects enrolled
    Israel: 15
    Country: Number of subjects enrolled
    Australia: 18
    Country: Number of subjects enrolled
    Germany: 38
    Worldwide total number of subjects
    1158
    EEA total number of subjects
    381
    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)
    6
    Adults (18-64 years)
    1119
    From 65 to 84 years
    33
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Not applicable

    Pre-assignment
    Screening details
    		 Not applicable

    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, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Participants received Placebo intravenously (IV) or subcutaneously (SC) every 4 weeks (Q4W). Any participant in the placebo arm who was considered a non-responder at Week 12 received 900 milligrams (mg) Mirikizumab IV Q4W for 3 doses, then 300 mg SC Q4W for the remainder of the study. Nonresponse is defined as failing to achieve at least a 30% decrease in stool frequency (SF) and/or abdominal pain (AP) and be no worse than baseline.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion, Solution for injection in pre-filled syringe
    Routes of administration
    Intravenous use, Subcutaneous use
    Dosage and administration details
    Participants received Placebo IV or SC Q4W. Any participant in the placebo arm who was considered a non-responder at Week 12 received 900 mg Mirikizumab IV Q4W for 3 doses, then 300 mg SC Q4W for the remainder of the study.

    Arm title
    		 Mirikizumab
    Arm description
    		 Participants received 900 mg Mirikizumab IV Q4W for 3 doses, then 300 mg SC Q4W
    Arm type
    		 Experimental

    Investigational medicinal product name
    Mirikizumab
    Investigational medicinal product code
    Other name
    LY3074828
    Pharmaceutical forms
    Solution for infusion, Suspension for injection in pre-filled syringe
    Routes of administration
    Intravenous use, Subcutaneous use
    Dosage and administration details
    Participants received 900 mg Mirikizumab IV Q4W for 3 doses, then 300 mg SC Q4W

    Arm title
    		 Ustekinumab
    Arm description
    		 Participants received 6 milligrams per kilogram (mg/kg) Ustekinumab IV for one dose, then 90 mg SC every 8 weeks (Q8W)
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Ustekinumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion, Solution for injection in pre-filled syringe
    Routes of administration
    Intravenous use, Subcutaneous use
    Dosage and administration details
    Participants received 6 mg/kg Ustekinumab IV for one dose, then 90 mg SC Q8W

    Arm title
    		 Mirikizumab (Adolescents)
    Arm description
    		 Participants received 900 mg Mirikizumab IV Q4W for 3 doses, then 300 mg SC Q4W
    Arm type
    		 Experimental

    Investigational medicinal product name
    Mirikizumab
    Investigational medicinal product code
    Other name
    LY3074828
    Pharmaceutical forms
    Solution for infusion, Suspension for injection in pre-filled syringe
    Routes of administration
    Intravenous use, Subcutaneous use
    Dosage and administration details
    Participants received open label 900 mg Mirikizumab IV Q4W for 3 doses, then 300 mg SC Q4W

    Number of subjects in period 1
    		Placebo Mirikizumab Ustekinumab Mirikizumab (Adolescents)
    Started
    212
    631
    309
    6
    Received At Least One Dose of Study Drug
    211
    630
    309
    6
    Placebo Non-Responders at Week 12
    85 [1]
    0 [2]
    0 [3]
    0 [4]
    Completed
    159
    561
    271
    4
    Not completed
    53
    70
    38
    2
         Adverse event, serious fatal
    2
    -
    1
    -
         Physician decision
    3
    2
    1
    -
         Consent withdrawn by subject
    20
    28
    18
    -
         Adverse event, non-fatal
    9
    11
    2
    -
         As Reported by Investigator
    2
    6
    6
    -
         Pregnancy
    2
    2
    1
    -
         Withdrawal by Subject
    -
    -
    -
    1
         Study Terminated by Sponsor
    1
    1
    -
    -
         Lost to follow-up
    -
    7
    1
    -
         Disposition Not Captured
    -
    2
    1
    -
         Lack of efficacy
    14
    11
    7
    1
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Milestone only shows Placebo Non-Responders; number should not be included again in count.
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Milestone only shows Placebo Non-Responders; number should not be included again in count.
    [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Milestone only shows Placebo Non-Responders; number should not be included again in count.
    [4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Milestone only shows Placebo Non-Responders; number should not be included again in count.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received Placebo intravenously (IV) or subcutaneously (SC) every 4 weeks (Q4W). Any participant in the placebo arm who was considered a non-responder at Week 12 received 900 milligrams (mg) Mirikizumab IV Q4W for 3 doses, then 300 mg SC Q4W for the remainder of the study. Nonresponse is defined as failing to achieve at least a 30% decrease in stool frequency (SF) and/or abdominal pain (AP) and be no worse than baseline.

    Reporting group title
    Mirikizumab
    Reporting group description
    		 Participants received 900 mg Mirikizumab IV Q4W for 3 doses, then 300 mg SC Q4W

    Reporting group title
    Ustekinumab
    Reporting group description
    		 Participants received 6 milligrams per kilogram (mg/kg) Ustekinumab IV for one dose, then 90 mg SC every 8 weeks (Q8W)

    Reporting group title
    Mirikizumab (Adolescents)
    Reporting group description
    		 Participants received 900 mg Mirikizumab IV Q4W for 3 doses, then 300 mg SC Q4W

    Reporting group values
    		 Placebo Mirikizumab Ustekinumab Mirikizumab (Adolescents) Total
    Number of subjects
    		 212 631 309 6 1158
    Age categorical
    Units: Subjects
        <=18 years
    		 4 11 6 6 27
        Between 18 and 65 years
    		 205 598 295 0 1098
        >=65 years
    		 3 22 8 0 33
    Gender categorical
    Units: Subjects
        Female
    		 87 274 161 3 525
        Male
    		 125 357 148 3 633
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 4 8 6 0 18
        Not Hispanic or Latino
    		 16 58 25 0 99
        Unknown or Not Reported
    		 192 565 278 6 1041
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 2 2 2 0 6
        Asian
    		 44 158 78 2 282
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0
        Black or African American
    		 5 12 8 0 25
        White
    		 155 448 219 4 826
        More than one race
    		 0 3 1 0 4
        Unknown or Not Reported
    		 6 8 1 0 15
    Region of Enrollment
    Units: Subjects
        United States
    		 20 66 31 0 117
        Czechia
    		 11 29 17 0 57
        Russia
    		 22 44 20 0 86
        Austria
    		 0 7 3 0 10
        Latvia
    		 0 1 2 0 3
        Netherlands
    		 1 2 1 0 4
        South Korea
    		 7 40 11 2 60
        China
    		 31 90 43 0 164
        Brazil
    		 11 29 18 0 58
        Poland
    		 28 83 47 3 161
        Slovakia
    		 2 10 7 0 19
        France
    		 3 3 1 0 7
        Lithuania
    		 1 3 1 0 5
        Serbia
    		 8 7 6 0 21
        Croatia
    		 1 6 0 0 7
        Argentina
    		 0 2 0 0 2
        Romania
    		 1 10 2 0 13
        Hungary
    		 5 19 10 0 34
        Japan
    		 4 11 13 0 28
        Ukraine
    		 12 43 33 0 88
        United Kingdom
    		 0 4 1 0 5
        Switzerland
    		 1 3 3 0 7
        India
    		 2 13 10 0 25
        Spain
    		 1 3 0 0 4
        Canada
    		 8 19 8 0 35
        Turkey
    		 6 28 7 0 41
        Belgium
    		 2 5 2 0 9
        Denmark
    		 0 2 0 0 2
        Italy
    		 3 4 0 1 8
        Mexico
    		 1 4 2 0 7
        Israel
    		 4 9 2 0 15
        Australia
    		 8 10 0 0 18
        Germany
    		 8 22 8 0 38

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received Placebo intravenously (IV) or subcutaneously (SC) every 4 weeks (Q4W). Any participant in the placebo arm who was considered a non-responder at Week 12 received 900 milligrams (mg) Mirikizumab IV Q4W for 3 doses, then 300 mg SC Q4W for the remainder of the study. Nonresponse is defined as failing to achieve at least a 30% decrease in stool frequency (SF) and/or abdominal pain (AP) and be no worse than baseline.

    Reporting group title
    Mirikizumab
    Reporting group description
    		 Participants received 900 mg Mirikizumab IV Q4W for 3 doses, then 300 mg SC Q4W

    Reporting group title
    Ustekinumab
    Reporting group description
    		 Participants received 6 milligrams per kilogram (mg/kg) Ustekinumab IV for one dose, then 90 mg SC every 8 weeks (Q8W)

    Reporting group title
    Mirikizumab (Adolescents)
    Reporting group description
    		 Participants received 900 mg Mirikizumab IV Q4W for 3 doses, then 300 mg SC Q4W

    Subject analysis set title
    900 mg Mirikizumab IV Q4W
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received 900 mg Mirikizumab IV Q4W for 3 doses

    Subject analysis set title
    300 mg Mirikizumab SC Q4W
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received 300 mg Mirikizumab SC Q4W

    Primary: Percentage of Adult Participants Achieving Clinical Response at Week 12 and Endoscopic Response at Week 52 (Placebo and Mirikizumab)

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    End point title
    		 Percentage of Adult Participants Achieving Clinical Response at Week 12 and Endoscopic Response at Week 52 (Placebo and Mirikizumab) [1]
    End point description
    Clinical response by Patient Reported Outcome (PRO) defined as ≥30% decrease in stool frequency (SF) and/or abdominal pain (AP) & neither score worse than baseline. SF (number of liquid or very soft stools) as per Bristol Stool Scale Category 6 or 7 and AP (4-point scale: 0=none, 1=mild, 2=moderate, 3=severe). Endoscopic response defined as ≥50% reduction from baseline in total Simple Endoscopic Score for Crohn's Disease (SES-CD) score. SES-CD evaluates 4 variables assessed in 5 bowel segments, each scored from 0-3: presence & size of ulcers (none=0; diameter 0.1-0.5 cm=1; 0.5-2 cm=2; >2 cm=3); extent of ulcerated surface (none=0; <10%=1; 10% to 30%=2; >30%=3); extent of affected surface (none=0; <50%=1; 50% to 75%=2; >75%=3); presence & type of narrowing (none=0; single, can be passed=1; multiple, can be passed=2; cannot be passed=3). Total is sum of all scores across all bowel segments. Scores range from 0 to 56, with higher scores indicating more severe disease.
    End point type
    Primary
    End point timeframe
    Week 12 to Week 52 Analysis Population Description (APD): All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug.
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per Protocol, analysis only performed on Placebo and Mirikizumab arms.
    End point values
    		 Placebo Mirikizumab
    Number of subjects analysed
    199
    579
    Units: percentage of participants
        arithmetic mean (confidence interval 95%)
    9.0 (5.1 to 13.0)
    38.0 (34.0 to 42.0)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v Mirikizumab
    Number of subjects included in analysis
    778
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.000001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    28.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 23
         upper limit
    		 34.4

    Primary: Percentage of Adult Participants Achieving Clinical Response at Week 12 and Clinical Remission at Week 52 (Placebo and Mirikizumab)

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    End point title
    		 Percentage of Adult Participants Achieving Clinical Response at Week 12 and Clinical Remission at Week 52 (Placebo and Mirikizumab) [2]
    End point description
    Clinical response by PRO defined as ≥ 30% decrease in SF and/or AP and neither score worse than baseline. SF (number of liquid or very soft stools) as per Bristol Stool Scale Category 6 or 7 and AP (4-point scale: 0=none, 1=mild, 2=moderate, 3=severe). Clinical remission defined as Crohn’s Disease Activity Index (CDAI) total score <150. The CDAI is an 8-item disease activity measure comprised of a composite of 3 patient-reported items: AP (4-point scale: 0=none, 1=mild, 2=moderate, 3=severe); SF (number of liquid or very soft stools) as per Bristol Stool Scale Category 6 or 7; and general well-being (0=generally well, 1=slightly under par, 2=poor, 3=very poor, 4=terrible) and 5 physician-reported/laboratory items (physical signs and a laboratory parameter [hematocrit]). Total score range of 0 to 600 points. APD: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug.
    End point type
    Primary
    End point timeframe
    Week 12 to Week 52
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per Protocol, analysis only performed on Placebo and Mirikizumab arms.
    End point values
    		 Placebo Mirikizumab
    Number of subjects analysed
    199
    579
    Units: percentage of participants
        arithmetic mean (confidence interval 95%)
    19.6 (14.1 to 25.1)
    45.4 (41.4 to 49.5)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v Mirikizumab
    Number of subjects included in analysis
    778
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.000001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    25.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 18.8
         upper limit
    		 32.7

    Secondary: Percentage of Adult Participants Achieving Endoscopic Response at Week 12 (Placebo and Mirikizumab)

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    End point title
    		 Percentage of Adult Participants Achieving Endoscopic Response at Week 12 (Placebo and Mirikizumab) [3]
    End point description
    Endoscopic Response defined as ≥50% reduction from baseline in total SES-CD score. SES-CD evaluates 4 variables assessed in 5 bowel segments, each scored from 0-3: presence & size of ulcers (none = 0; diameter 0.1-0.5 cm = 1; 0.5-2 cm = 2; >2 cm = 3); extent of ulcerated surface (none = 0; <10% = 1; 10% to 30% = 2; >30% = 3); extent of affected surface (none = 0; <50% = 1; 50% to 75% = 2; >75% = 3); presence & type of narrowing (none = 0; single, can be passed = 1; multiple, can be passed = 2; cannot be passed =3). Total is sum of all scores across all bowel segments. Scores range from 0 to 56, with higher scores indicating more severe disease. APD: All randomized participants in the Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per Protocol, analysis only performed on Placebo and Mirikizumab arms.
    End point values
    		 Placebo Mirikizumab
    Number of subjects analysed
    199
    579
    Units: percentage of participants
        arithmetic mean (confidence interval 95%)
    12.6 (8.0 to 17.2)
    32.5 (28.7 to 36.3)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v Mirikizumab
    Number of subjects included in analysis
    778
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.000001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    19.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 13.7
         upper limit
    		 25.6

    Secondary: Percentage of Adult Participants Achieving Endoscopic Response at Week 52

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    End point title
    		 Percentage of Adult Participants Achieving Endoscopic Response at Week 52 [4]
    End point description
    Endoscopic Response defined as ≥50% reduction from baseline in total SES-CD score. SES-CD evaluates 4 variables assessed in 5 bowel segments, each scored from 0-3: presence & size of ulcers (none = 0; diameter 0.1-0.5 cm = 1; 0.5-2 cm = 2; >2 cm = 3); extent of ulcerated surface (none = 0; <10% = 1; 10% to 30% = 2; >30% = 3); extent of affected surface (none = 0; <50% = 1; 50% to 75% = 2; >75% = 3); presence & type of narrowing (none = 0; single, can be passed = 1; multiple, can be passed = 2; cannot be passed =3). Total is sum of all scores across all bowel segments. Scores range from 0 to 56, with higher scores indicating more severe disease. APD: All randomized participants who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug per protocol.
    End point type
    Secondary
    End point timeframe
    Week 52
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per Protocol, analysis only performed on Placebo, Mirikizumab, Ustekinumab arms.
    End point values
    		 Placebo Mirikizumab Ustekinumab
    Number of subjects analysed
    199
    579
    287
    Units: percentage of participants
        arithmetic mean (confidence interval 95%)
    9.0 (5.1 to 13.0)
    48.4 (44.3 to 52.4)
    46.3 (40.6 to 52.1)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v Mirikizumab
    Number of subjects included in analysis
    778
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.000001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    39.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 33.4
         upper limit
    		 44.8
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Mirikizumab v Ustekinumab
    Number of subjects included in analysis
    866
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.513623
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    2.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.7
         upper limit
    		 9.3

    Secondary: Percentage of Adult Participants Achieving Clinical Remission at Week 12 (Placebo and Mirikizumab)

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    End point title
    		 Percentage of Adult Participants Achieving Clinical Remission at Week 12 (Placebo and Mirikizumab) [5]
    End point description
    Clinical remission defined as CDAI total score <150. The CDAI is an 8-item disease activity measure comprised of a composite of 3 patient-reported items: AP (4-point scale: 0=none, 1=mild, 2=moderate, 3=severe); SF (number of liquid or very soft stools) as per Bristol Stool Scale Category 6 or 7; and general well-being (0=generally well, 1=slightly under par, 2=poor, 3=very poor, 4=terrible), and 5 physician-reported/laboratory items (physical signs and a laboratory parameter [hematocrit]). Total score range of 0 to 600 points. APD: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per Protocol, analysis only performed on Placebo and Mirikizumab arms.
    End point values
    		 Placebo Mirikizumab
    Number of subjects analysed
    199
    579
    Units: percentage of participants
        arithmetic mean (confidence interval 95%)
    25.1 (19.1 to 31.2)
    37.7 (33.7 to 41.6)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v Mirikizumab
    Number of subjects included in analysis
    778
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.001431
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    12.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.3
         upper limit
    		 19.6

    Secondary: Percentage of Adult Participants Achieving Clinical Remission at Week 52

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    End point title
    		 Percentage of Adult Participants Achieving Clinical Remission at Week 52 [6]
    End point description
    Clinical remission defined as CDAI total score <150. The CDAI is an 8-item disease activity measure comprised of a composite of 3 patient-reported items: AP (4-point scale: 0=none, 1=mild, 2=moderate, 3=severe); SF (number of liquid or very soft stools) as per Bristol Stool Scale Category 6 or 7; and general well-being (0=generally well, 1=slightly under par, 2=poor, 3=very poor, 4=terrible), and 5 physician-reported/laboratory items (physical signs and a laboratory parameter [hematocrit]). Total score range of 0 to 600 points. APD: All randomized participants who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug per protocol.
    End point type
    Secondary
    End point timeframe
    Week 52
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per Protocol, analysis only performed on Placebo, Mirikizumab, Ustekinumab arms.
    End point values
    		 Placebo Mirikizumab Ustekinumab
    Number of subjects analysed
    199
    579
    287
    Units: percentage of participants
        arithmetic mean (confidence interval 95%)
    19.6 (14.1 to 25.1)
    54.1 (50.0 to 58.1)
    48.4 (42.7 to 54.2)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v Mirikizumab
    Number of subjects included in analysis
    778
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.000001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    34.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 27.7
         upper limit
    		 41.4
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Mirikizumab v Ustekinumab
    Number of subjects included in analysis
    866
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 < 0.0001
    Method
    		 Z test
    Parameter type
    		 Risk difference (RD)
    Point estimate
    5.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 12.8

    Secondary: Percentage of Adult Participants Achieving Endoscopic Remission at Week 12 (Placebo and Mirikizumab)

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    End point title
    		 Percentage of Adult Participants Achieving Endoscopic Remission at Week 12 (Placebo and Mirikizumab) [7]
    End point description
    Endoscopic remission SES-CD ≤4 is defined as SES-CD Total Score ≤4 and at least a 2-point reduction from baseline and no subscore >1. SES-CD evaluates 4 variables assessed in 5 bowel segments, each scored from 0-3: presence & size of ulcers (none = 0; diameter 0.1-0.5 cm = 1; 0.5-2 cm = 2; >2 cm = 3); extent of ulcerated surface (none = 0; <10% = 1; 10% to 30% = 2; >30% = 3); extent of affected surface (none = 0; <50% = 1; 50% to 75% = 2; >75% = 3); presence & type of narrowing (none = 0; single, can be passed = 1; multiple, can be passed = 2; cannot be passed =3). Total is sum of all scores across all bowel segments. Scores range from 0 to 56, with higher scores indicating more severe disease. APD: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug.
    End point type
    Secondary
    End point timeframe
    Week 12
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per Protocol, analysis only performed on Placebo and Mirikizumab arms.
    End point values
    		 Placebo Mirikizumab
    Number of subjects analysed
    199
    579
    Units: percentage of participants
        arithmetic mean (confidence interval 95%)
    4.0 (1.3 to 6.7)
    10.9 (8.3 to 13.4)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Mirikizumab v Placebo
    Number of subjects included in analysis
    778
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.003414
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    6.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.2
         upper limit
    		 10.5

    Secondary: Change from Baseline in Urgency Numeric Rating Scale (NRS) at Week 12 in Adult Participants (Placebo and Mirikizumab)

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    End point title
    		 Change from Baseline in Urgency Numeric Rating Scale (NRS) at Week 12 in Adult Participants (Placebo and Mirikizumab) [8]
    End point description
    The Urgency NRS is a single patient-reported item that measures the severity for the urgency (sudden or immediate need) to have a bowel movement in the past 24 hours using an 11-point NRS ranging from 0 (no urgency) to 10 (worst possible urgency). APD: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per Protocol, analysis only performed on Placebo and Mirikizumab arms.
    End point values
    		 Placebo Mirikizumab
    Number of subjects analysed
    199
    579
    Units: score on a scale
        least squares mean (standard error)
    -1.58 ± 0.168
    -2.44 ± 0.099
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v Mirikizumab
    Number of subjects included in analysis
    778
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.000011
    Method
    		 ANCOVA
    Parameter type
    		 Least Squares (LS) Mean Difference (Net)
    Point estimate
    -0.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.24
         upper limit
    		 -0.48

    Secondary: Change from Baseline in Urgency NRS at Week 52 in Adult Participants (Placebo and Mirikizumab)

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    End point title
    		 Change from Baseline in Urgency NRS at Week 52 in Adult Participants (Placebo and Mirikizumab) [9]
    End point description
    The Urgency NRS is a single patient-reported item that measures the severity for the urgency (sudden or immediate need) to have a bowel movement in the past 24 hours using an 11-point NRS ranging from 0 (no urgency) to 10 (worst possible urgency). APD: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per Protocol, analysis only performed on Placebo and Mirikizumab arms.
    End point values
    		 Placebo Mirikizumab
    Number of subjects analysed
    199
    579
    Units: score on a scale
        least squares mean (standard error)
    -1.23 ± 0.180
    -3.24 ± 0.106
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v Mirikizumab
    Number of subjects included in analysis
    778
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.000001
    Method
    		 ANCOVA
    Parameter type
    		 LSMean Difference (Net)
    Point estimate
    -2.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.42
         upper limit
    		 -1.6

    Secondary: Percentage of Adult Participants Achieving Clinical Response at Week 12 and Clinical Remission by PRO at Week 52 (Placebo and Mirikizumab)

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    End point title
    		 Percentage of Adult Participants Achieving Clinical Response at Week 12 and Clinical Remission by PRO at Week 52 (Placebo and Mirikizumab) [10]
    End point description
    Clinical Response by PRO defined as ≥30% decrease in SF and/or AP & neither score worse than baseline. SF (number of liquid or very soft stools) as per Bristol Stool Scale Category 6 or 7 and AP (4-point scale: 0=none, 1=mild, 2=moderate, 3=severe). Clinical Remission by PRO defined as defined as SF≤3 and not worse than baseline (as per Bristol Stool Scale Category 6 or 7) and AP ≤1 and no worse than baseline. APD: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug.
    End point type
    Secondary
    End point timeframe
    Week 12 to Week 52
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per Protocol, analysis only performed on Placebo and Mirikizumab arms.
    End point values
    		 Placebo Mirikizumab
    Number of subjects analysed
    199
    579
    Units: percentage of participants
        arithmetic mean (confidence interval 95%)
    19.6 (14.1 to 25.1)
    45.4 (41.4 to 49.5)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v Mirikizumab
    Number of subjects included in analysis
    778
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.000001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    25.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 18.9
         upper limit
    		 32.6

    Secondary: Percentage of Adult Participants Achieving Clinical Response at Week 12 and Endoscopic Remission at Week 52 (Placebo and Mirikizumab)

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    End point title
    		 Percentage of Adult Participants Achieving Clinical Response at Week 12 and Endoscopic Remission at Week 52 (Placebo and Mirikizumab) [11]
    End point description
    Clinical Response by PRO defined as ≥30% decrease in SF and/or AP & neither score worse than baseline. SF (number of liquid or very soft stools) as per Bristol Stool Scale Category 6 or 7 and AP (4-point scale: 0=none, 1=mild, 2=moderate, 3=severe). Endoscopic remission SES-CD ≤4 is defined as SES-CD Total Score ≤4 and at least a 2-point reduction from baseline and no subscore >1. SES-CD evaluates 4 variables assessed in 5 bowel segments, each scored from 0-3: presence & size of ulcers (none=0; diameter 0.1-0.5 cm=1; 0.5-2 cm=2; >2 cm=3); extent of ulcerated surface (none = 0; <10% = 1; 10% to 30% = 2; >30% = 3); extent of affected surface (none = 0; <50% = 1; 50% to 75% = 2; >75% = 3); presence & type of narrowing (none =0; single, can be passed=1; multiple, can be passed=2; cannot be passed=3). Total is sum of all scores across all bowel segments. Scores range from 0 to 56, with higher scores indicating more severe disease.
    End point type
    Secondary
    End point timeframe
    Week 12 to Week 52 APD: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug.
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per Protocol, analysis only performed on Placebo and Mirikizumab arms.
    End point values
    		 Placebo Mirikizumab
    Number of subjects analysed
    199
    579
    Units: percentage of participants
        arithmetic mean (confidence interval 95%)
    2.0 (0.1 to 4.0)
    15.9 (12.9 to 18.9)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v Mirikizumab
    Number of subjects included in analysis
    778
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.000001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    13.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 10.2
         upper limit
    		 17.4

    Secondary: Percentage of Adult Participants Achieving Clinical Response at Week 12 and Corticosteroid-free AND either in Clinical Remission or Endoscopic Remission at Week 52 (Placebo and Mirikizumab)

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    End point title
    		 Percentage of Adult Participants Achieving Clinical Response at Week 12 and Corticosteroid-free AND either in Clinical Remission or Endoscopic Remission at Week 52 (Placebo and Mirikizumab) [12]
    End point description
    APD: Zero participants analyzed. Analysis not completed as FDA recommended modification of endpoint.
    End point type
    Secondary
    End point timeframe
    Week 12 to Week 52
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per Protocol, analysis planned only on Placebo and Mirikizumab arms.
    End point values
    		 Placebo Mirikizumab
    Number of subjects analysed
    0 [13]
    0 [14]
    Units: percentage of participants
        arithmetic mean (confidence interval 95%)
    ( to )
    ( to )
    Notes
    [13] - Zero participants analyzed. Analysis not completed as FDA recommended modification of endpoint.
    [14] - Zero participants analyzed. Analysis not completed as FDA recommended modification of endpoint.
    No statistical analyses for this end point

    Secondary: Percentage of Adult Participants Achieving Clinical Response at Week 12 and Corticosteroid-free Clinical Remission at Week 52 (Placebo and Mirikizumab)

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    End point title
    		 Percentage of Adult Participants Achieving Clinical Response at Week 12 and Corticosteroid-free Clinical Remission at Week 52 (Placebo and Mirikizumab) [15]
    End point description
    Clinical response by PRO defined as ≥30% decrease in SF and/or AP and neither score worse than baseline. SF (number of liquid or very soft stools) as per Bristol Stool Scale Category 6 or 7 and AP (4-point scale: 0=none, 1=mild, 2=moderate, 3=severe). Clinical remission defined as CDAI total score <150. The CDAI is an 8- item disease activity measure comprised of a composite of 3 patient-reported items: AP (4-point scale: 0=none, 1=mild, 2=moderate, 3=severe); SF (number of liquid or very soft stools) as per Bristol Stool Scale Category 6 or 7; and general well-being (0=generally well, 1=slightly under par, 2=poor, 3=very poor, 4=terrible), and 5 physician-reported/laboratory items (physical signs and a laboratory parameter [hematocrit]). Total score range of 0 to 600 points. Corticosteroid-free clinical remission by CDAI is defined as achieving clinical remission by CDAI at Week 52 and being corticosteroid free from Week 40 to Week 52.
    End point type
    Secondary
    End point timeframe
    Week 12 to Week 52 APD: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug.
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per Protocol, analysis only performed on Placebo and Mirikizumab arms.
    End point values
    		 Placebo Mirikizumab
    Number of subjects analysed
    199
    579
    Units: percentage of participants
        arithmetic mean (confidence interval 95%)
    18.6 (13.2 to 24.0)
    43.7 (39.7 to 47.7)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v Mirikizumab
    Number of subjects included in analysis
    778
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.000001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 18.2
         upper limit
    		 31.8

    Secondary: Change from Baseline in C-Reactive Protein (CRP) at Week 52 in Adult Participants (Placebo and Mirikizumab)

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    End point title
    		 Change from Baseline in C-Reactive Protein (CRP) at Week 52 in Adult Participants (Placebo and Mirikizumab) [16]
    End point description
    Change from baseline in CRP APD: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per Protocol, analysis only performed on Placebo and Mirikizumab arms.
    End point values
    		 Placebo Mirikizumab
    Number of subjects analysed
    199
    579
    Units: milligram per liter (mg/L)
        least squares mean (standard error)
    -0.08 ± 0.087
    -0.93 ± 0.051
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v Mirikizumab
    Number of subjects included in analysis
    778
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.000001
    Method
    		 ANCOVA
    Parameter type
    		 LSMean Difference (Net)
    Point estimate
    -0.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.05
         upper limit
    		 -0.65

    Secondary: Change from Baseline in Fecal Calprotectin at Week 52 in Adult Participants (Placebo and Mirikizumab)

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    End point title
    		 Change from Baseline in Fecal Calprotectin at Week 52 in Adult Participants (Placebo and Mirikizumab) [17]
    End point description
    Change from baseline in Fecal Calprotectin APD: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug and had baseline fecal calprotectin.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per Protocol, analysis only performed on Placebo and Mirikizumab arms.
    End point values
    		 Placebo Mirikizumab
    Number of subjects analysed
    199
    579
    Units: micrograms per gram (μg/g)
        least squares mean (standard error)
    -0.19 ± 0.117
    -1.41 ± 0.067
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Mirikizumab v Placebo
    Number of subjects included in analysis
    778
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.000001
    Method
    		 ANCOVA
    Parameter type
    		 LSMean Difference (Net)
    Point estimate
    -1.22
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.48
         upper limit
    		 -0.95

    Secondary: Percentage of Adult Participants Achieving Clinical Response at Week 12 and Resolution of Baseline Extraintestinal Manifestations (EIMs) at Week 52 (Placebo and Mirikizumab)

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    End point title
    		 Percentage of Adult Participants Achieving Clinical Response at Week 12 and Resolution of Baseline Extraintestinal Manifestations (EIMs) at Week 52 (Placebo and Mirikizumab) [18]
    End point description
    Clinical response by PRO defined as ≥30% decrease in SF and/or AP and neither score worse than baseline. SF (number of liquid or very soft stools) as per Bristol Stool Scale Category 6 or 7 and AP (4-point scale: 0=none, 1=mild, 2=moderate, 3=severe). APD: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug and had at least one EIM at baseline.
    End point type
    Secondary
    End point timeframe
    Week 12 to Week 52
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per Protocol, analysis only performed on Placebo and Mirikizumab arms.
    End point values
    		 Placebo Mirikizumab
    Number of subjects analysed
    41
    132
    Units: percentage of participants
        number (not applicable)
    14.6
    43.2
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Mirikizumab v Placebo
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Percentage of Adult Participants Achieving Clinical Response at Week 12 and ≥50% Reduction in Number of Draining Cutaneous Fistulae at Week 52 in Participants with Draining Cutaneous Fistulae at Baseline (Placebo and Mirikizumab)

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    End point title
    		 Percentage of Adult Participants Achieving Clinical Response at Week 12 and ≥50% Reduction in Number of Draining Cutaneous Fistulae at Week 52 in Participants with Draining Cutaneous Fistulae at Baseline (Placebo and Mirikizumab) [19]
    End point description
    Clinical response by PRO defined as ≥ 30% decrease in SF and/or AP and neither score worse than baseline. SF (number of liquid or very soft stools) as per Bristol Stool Scale Category 6 or 7 and AP (4-point scale: 0=none, 1=mild, 2=moderate, 3=severe). APD: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug and had at least one draining cutaneous fistulae at baseline.
    End point type
    Secondary
    End point timeframe
    Week 12 to Week 52
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per Protocol, analysis only performed on Placebo and Mirikizumab arms.
    End point values
    		 Placebo Mirikizumab
    Number of subjects analysed
    18
    38
    Units: percentage of participants
        arithmetic mean (confidence interval 95%)
    16.7 (0.0 to 33.9)
    21.1 (8.1 to 34.0)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Mirikizumab v Placebo
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.732715
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    4.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -18
         upper limit
    		 26.1

    Secondary: Change from Baseline in Health Related Quality of Life at Week 52 in Adult Participants: Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score (Placebo and Mirikizumab)

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    End point title
    		 Change from Baseline in Health Related Quality of Life at Week 52 in Adult Participants: Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score (Placebo and Mirikizumab) [20]
    End point description
    The IBDQ is a 32-item patient completed questionnaire that measures 4 aspects of patients’ lives: symptoms directly related to the primary bowel disturbance, systemic symptoms, emotional function, and social function. Responses are graded on a 7-point Likert scale in which 7 denotes “not a problem at all” and 1 denotes “a very severe problem.” IBDQ total score is calculated as the sum of all questions. Scores range from 32 to 224; a higher score indicates a better quality of life. APD: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per Protocol, analysis only performed on Placebo and Mirikizumab arms.
    End point values
    		 Placebo Mirikizumab
    Number of subjects analysed
    199
    579
    Units: score on a scale
        least squares mean (standard error)
    15.9 ± 2.316
    43.82 ± 1.365
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v Mirikizumab
    Number of subjects included in analysis
    778
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.000001
    Method
    		 ANCOVA
    Parameter type
    		 LSMean Difference (Net)
    Point estimate
    27.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 22.67
         upper limit
    		 33.18

    Secondary: Adult Population Pharmacokinetics (PopPK): Area Under the Concentration Time Curve (AUC) of Mirikizumab

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    End point title
    		 Adult Population Pharmacokinetics (PopPK): Area Under the Concentration Time Curve (AUC) of Mirikizumab
    End point description
    PopPK: AUC of Mirikizumab APD: All randomized participants who received at least one dose of study drug and had evaluable PK data.
    End point type
    Secondary
    End point timeframe
    Week 4, 8, 12, 16, 24, 36: Predose; Week 4, Day 1: Postdose; Week 52
    End point values
    		 900 mg Mirikizumab IV Q4W 300 mg Mirikizumab SC Q4W
    Number of subjects analysed
    711
    711
    Units: micrograms*day per milliliter(ug*day/mL)
        geometric mean (geometric coefficient of variation)
    1820 ± 38.1
    220 ± 55.9
    No statistical analyses for this end point

    Post-hoc: Percentage of Adult Participants Achieving Endoscopic Remission at Week 12 (Placebo and Mirikizumab)

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    End point title
    		 Percentage of Adult Participants Achieving Endoscopic Remission at Week 12 (Placebo and Mirikizumab) [21]
    End point description
    Endoscopic remission SES-CD ≤4 is defined as SES-CD Total Score ≤4 and at least a 2-point reduction from baseline and no subscore >1 in any individual variable. SES-CD evaluates 4 variables assessed in 5 bowel segments, each scored from 0-3: presence & size of ulcers (none = 0; diameter 0.1-0.5 cm = 1; 0.5-2 cm = 2; >2 cm = 3); extent of ulcerated surface (none = 0; <10% = 1; 10% to 30% = 2; >30% = 3); extent of affected surface (none = 0; <50% = 1; 50% to 75% = 2; >75% = 3); presence & type of narrowing (none = 0; single, can be passed = 1; multiple, can be passed = 2; cannot be passed =3). Total is sum of all scores across all bowel segments. Scores range from 0 to 56, with higher scores indicating more severe disease. APD: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug.
    End point type
    Post-hoc
    End point timeframe
    Week 12
    Notes
    [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per Protocol, analysis only performed on Placebo and Mirikizumab arms.
    End point values
    		 Placebo Mirikizumab
    Number of subjects analysed
    199
    579
    Units: percentage of participants
        arithmetic mean (confidence interval 99.5%)
    7.0 (1.9 to 12.1)
    17.6 (13.2 to 22.1)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v Mirikizumab
    Number of subjects included in analysis
    778
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.000213
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    10.6
    Confidence interval
         level
    		 99.5%
         sides
    2-sided
         lower limit
    		 4.1
         upper limit
    		 17.2

    Post-hoc: Percentage of Adult Participants Achieving Clinical Response at Week 12 and Endoscopic Remission at Week 52 (Placebo and Mirikizumab)

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    End point title
    		 Percentage of Adult Participants Achieving Clinical Response at Week 12 and Endoscopic Remission at Week 52 (Placebo and Mirikizumab) [22]
    End point description
    Clinical Response by PRO defined as ≥30% decrease in SF and/or AP & neither score worse than baseline. SF (number of liquid or very soft stools) as per Bristol Stool Scale Category 6 or 7 and AP (4- point scale: 0=none, 1=mild, 2=moderate, 3=severe). Endoscopic remission SES-CD ≤4 is defined as SES-CD Total Score ≤4 and at least a 2-point reduction from baseline and no subscore >1 in any individual variable. SES-CD evaluates 4 variables assessed in 5 bowel segments, each scored from 0-3: presence & size of ulcers (none=0; diameter 0.1-0.5 cm=1; 0.5-2 cm=2; >2 cm=3); extent of ulcerated surface (none = 0; <10% = 1; 10% to 30% = 2; >30% = 3); extent of affected surface (none = 0; <50% = 1; 50% to 75% = 2; >75% = 3); presence & type of narrowing (none =0; single, can be passed=1; multiple, can be passed=2; cannot be passed=3). Total is sum of all scores across all bowel segments. Scores range from 0 to 56, with higher scores indicating more severe disease.
    End point type
    Post-hoc
    End point timeframe
    Week 12 to Week 52 APD: All randomized participants in Placebo and Mirikizumab arms who have baseline SES-CD ≥7 (or ≥4 for isolated ileal disease) and received at least one dose of study drug.
    Notes
    [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per Protocol, analysis only performed on Placebo and Mirikizumab arms.
    End point values
    		 Placebo Mirikizumab
    Number of subjects analysed
    199
    579
    Units: percentage of participants
        arithmetic mean (confidence interval 99.5%)
    4.0 (0.1 to 7.9)
    23.5 (18.5 to 28.4)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v Mirikizumab
    Number of subjects included in analysis
    778
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 < 0.000001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Risk difference (RD)
    Point estimate
    19.4
    Confidence interval
         level
    		 99.5%
         sides
    2-sided
         lower limit
    		 13.1
         upper limit
    		 25.7

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline through follow up (up to 68 weeks)
    Adverse event reporting additional description
    All randomized participants who received one dose of study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received Placebo IV or SC Q4W

    Reporting group title
    Placebo Non-Responders
    Reporting group description
    		 Any participant in the placebo arm who was considered a non-responder at Week 12 received 900 mg Mirikizumab IV Q4W for 3 doses, then 300 mg SC Q4W for the remainder of the study.

    Reporting group title
    Mirikizumab
    Reporting group description
    		 Participants received 900 mg Mirikizumab IV Q4W for 3 doses, then 300 mg SC Q4W

    Reporting group title
    Ustekinumab
    Reporting group description
    		 Participants received 6 mg/kg Ustekinumab IV for one dose, then 90 mg SC Q8W

    Reporting group title
    Mirikizumab (Adolescents)
    Reporting group description
    		 Participants received 900 mg Mirikizumab IV Q4W for 3 doses, then 300 mg SC Q4W

    Serious adverse events
    		 Placebo Placebo Non-Responders Mirikizumab Ustekinumab Mirikizumab (Adolescents)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    32 / 126 (25.40%)
    12 / 85 (14.12%)
    65 / 630 (10.32%)
    35 / 309 (11.33%)
    0 / 6 (0.00%)
         number of deaths (all causes)
    1
    1
    0
    1
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    breast cancer
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    colorectal adenoma
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    1 / 309 (0.32%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    haemorrhage
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    hypotension
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    peripheral arterial occlusive disease
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    1 / 309 (0.32%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    anal fistula repair
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ileectomy
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    abortion spontaneous
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    1 / 309 (0.32%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    oedema
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pyrexia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    swelling
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    anaphylactic reaction
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    1 / 309 (0.32%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    infusion related hypersensitivity reaction
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 85 (1.18%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    chronic obstructive pulmonary disease
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 85 (1.18%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pulmonary embolism
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    panic disorder
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    anastomotic stenosis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    1 / 309 (0.32%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    post procedural haemorrhage
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    procedural intestinal perforation
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 85 (1.18%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    rib fracture
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    tibia fracture
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    hydrocele
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed [1]
    0 / 77 (0.00%)
    0 / 48 (0.00%)
    0 / 356 (0.00%)
    1 / 148 (0.68%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    atrial fibrillation
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    angina pectoris
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    1 / 309 (0.32%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cardiac arrest
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cardio-respiratory arrest
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cardiac failure acute
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    cerebrovascular accident
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    1 / 309 (0.32%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    headache
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    loss of consciousness
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    myoclonic epilepsy
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    syncope
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    anaemia macrocytic
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    1 / 309 (0.32%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    anaemia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    2 / 630 (0.32%)
    1 / 309 (0.32%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    sudden hearing loss
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    1 / 309 (0.32%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    abdominal pain
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 126 (0.79%)
    1 / 85 (1.18%)
    2 / 630 (0.32%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    anal fistula
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    4 / 126 (3.17%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    1 / 309 (0.32%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    abdominal pain upper
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    abdominal pain lower
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 85 (1.18%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    anorectal disorder
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    1 / 309 (0.32%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    enterocolonic fistula
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    enteritis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    diarrhoea haemorrhagic
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    gastrointestinal disorder
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    crohn's disease
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    12 / 126 (9.52%)
    4 / 85 (4.71%)
    12 / 630 (1.90%)
    11 / 309 (3.56%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    3 / 12
    1 / 4
    2 / 12
    4 / 16
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    colitis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    diarrhoea
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    2 / 630 (0.32%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    gastrointestinal perforation
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    1 / 309 (0.32%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ileal stenosis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ileus
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 85 (1.18%)
    2 / 630 (0.32%)
    1 / 309 (0.32%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    inguinal hernia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    large intestine perforation
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    2 / 630 (0.32%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    intestinal perforation
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    1 / 85 (1.18%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    intestinal obstruction
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 126 (0.79%)
    1 / 85 (1.18%)
    3 / 630 (0.48%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    1 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    nausea
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    obstruction gastric
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pancreatitis acute
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    rectal stenosis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    small intestinal obstruction
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 85 (0.00%)
    4 / 630 (0.63%)
    1 / 309 (0.32%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 5
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    subileus
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    2 / 309 (0.65%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    bile duct stone
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    2 / 126 (1.59%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cholelithiasis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    1 / 309 (0.32%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cholecystitis acute
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    1 / 309 (0.32%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cholecystitis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cholangitis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    hydronephrosis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    arthralgia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    chondrocalcinosis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    intervertebral disc degeneration
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    sacroiliitis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    abdominal abscess
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    2 / 630 (0.32%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    anal abscess
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    2 / 630 (0.32%)
    2 / 309 (0.65%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    abscess limb
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    1 / 309 (0.32%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    abscess intestinal
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    covid-19
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 85 (0.00%)
    2 / 630 (0.32%)
    2 / 309 (0.65%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    covid-19 pneumonia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    appendicitis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    1 / 309 (0.32%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    clostridium difficile colitis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    1 / 309 (0.32%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    cellulitis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    gastroenteritis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    fournier's gangrene
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    clostridium difficile infection
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    1 / 309 (0.32%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    liver abscess
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pneumonia aspiration
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pneumonia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    peritonitis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    pelvic abscess
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    salpingitis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed [2]
    0 / 49 (0.00%)
    1 / 37 (2.70%)
    0 / 274 (0.00%)
    0 / 161 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    sepsis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    1 / 309 (0.32%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    septic shock
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    urinary tract infection
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    1 / 309 (0.32%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    urosepsis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    dehydration
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    1 / 309 (0.32%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    malnutrition
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    0 / 309 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
    [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo Placebo Non-Responders Mirikizumab Ustekinumab Mirikizumab (Adolescents)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    72 / 126 (57.14%)
    48 / 85 (56.47%)
    319 / 630 (50.63%)
    145 / 309 (46.93%)
    5 / 6 (83.33%)
    Investigations
    sars-cov-2 test positive
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    1 / 630 (0.16%)
    1 / 309 (0.32%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    1
    1
    Injury, poisoning and procedural complications
    road traffic accident
    alternative dictionary used: MedDRA 26.0
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    1
    Nervous system disorders
    headache
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    6 / 126 (4.76%)
    4 / 85 (4.71%)
    41 / 630 (6.51%)
    15 / 309 (4.85%)
    1 / 6 (16.67%)
         occurrences all number
    10
    5
    58
    15
    2
    Blood and lymphatic system disorders
    anaemia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    10 / 126 (7.94%)
    11 / 85 (12.94%)
    43 / 630 (6.83%)
    15 / 309 (4.85%)
    0 / 6 (0.00%)
         occurrences all number
    11
    12
    48
    20
    0
    General disorders and administration site conditions
    injection site pain
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    8 / 126 (6.35%)
    0 / 85 (0.00%)
    20 / 630 (3.17%)
    11 / 309 (3.56%)
    0 / 6 (0.00%)
         occurrences all number
    37
    0
    131
    66
    0
    fatigue
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    10 / 126 (7.94%)
    2 / 85 (2.35%)
    23 / 630 (3.65%)
    7 / 309 (2.27%)
    0 / 6 (0.00%)
         occurrences all number
    12
    2
    32
    7
    0
    pyrexia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    5 / 126 (3.97%)
    6 / 85 (7.06%)
    27 / 630 (4.29%)
    9 / 309 (2.91%)
    1 / 6 (16.67%)
         occurrences all number
    5
    8
    35
    13
    1
    Immune system disorders
    hypersensitivity
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 85 (0.00%)
    3 / 630 (0.48%)
    2 / 309 (0.65%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    4
    2
    1
    Gastrointestinal disorders
    abdominal pain
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    7 / 126 (5.56%)
    8 / 85 (9.41%)
    26 / 630 (4.13%)
    10 / 309 (3.24%)
    0 / 6 (0.00%)
         occurrences all number
    10
    8
    29
    14
    0
    gastrooesophageal reflux disease
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    1 / 126 (0.79%)
    0 / 85 (0.00%)
    11 / 630 (1.75%)
    2 / 309 (0.65%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    11
    2
    1
    crohn's disease
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    21 / 126 (16.67%)
    7 / 85 (8.24%)
    17 / 630 (2.70%)
    14 / 309 (4.53%)
    1 / 6 (16.67%)
         occurrences all number
    22
    8
    17
    16
    1
    diarrhoea
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    8 / 126 (6.35%)
    3 / 85 (3.53%)
    33 / 630 (5.24%)
    12 / 309 (3.88%)
    1 / 6 (16.67%)
         occurrences all number
    8
    3
    35
    16
    1
    vomiting
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    2 / 126 (1.59%)
    2 / 85 (2.35%)
    24 / 630 (3.81%)
    6 / 309 (1.94%)
    1 / 6 (16.67%)
         occurrences all number
    2
    2
    25
    6
    1
    Musculoskeletal and connective tissue disorders
    arthralgia
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    10 / 126 (7.94%)
    4 / 85 (4.71%)
    41 / 630 (6.51%)
    8 / 309 (2.59%)
    1 / 6 (16.67%)
         occurrences all number
    11
    4
    48
    9
    1
    Infections and infestations
    gastroenteritis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    5 / 126 (3.97%)
    0 / 85 (0.00%)
    15 / 630 (2.38%)
    8 / 309 (2.59%)
    1 / 6 (16.67%)
         occurrences all number
    5
    0
    18
    9
    1
    epstein-barr virus infection
    alternative dictionary used: MedDRA 26.0
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    1
    covid-19
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    21 / 126 (16.67%)
    13 / 85 (15.29%)
    103 / 630 (16.35%)
    46 / 309 (14.89%)
    1 / 6 (16.67%)
         occurrences all number
    22
    14
    106
    48
    1
    pustule
    alternative dictionary used: MedDRA 26.0
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    1
    pharyngotonsillitis
    alternative dictionary used: MedDRA 26.0
         subjects affected / exposed
    0 / 126 (0.00%)
    0 / 85 (0.00%)
    0 / 630 (0.00%)
    0 / 309 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    1
    nasopharyngitis
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    8 / 126 (6.35%)
    2 / 85 (2.35%)
    36 / 630 (5.71%)
    19 / 309 (6.15%)
    0 / 6 (0.00%)
         occurrences all number
    10
    2
    52
    20
    0
    upper respiratory tract infection
    alternative dictionary used: MedDRA 26.1
         subjects affected / exposed
    7 / 126 (5.56%)
    9 / 85 (10.59%)
    38 / 630 (6.03%)
    22 / 309 (7.12%)
    0 / 6 (0.00%)
         occurrences all number
    10
    10
    43
    24
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Apr 2020
    -Prolonged Screening period by 1 week -Updated inclusion and exclusion criteria -Revised other secondary endpoints
    18 Dec 2020
    -Added Provisions for Changes in Study Conduct During Exceptional Circumstances -Updated Prohibited Medications -Revised restrictions on screen failures
    01 Apr 2021
    -Updated inclusion criteria
    23 Feb 2022
    -Revised objectives and endpoints in response to FDA feedback

    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.
    After enrolling 6 participants, sponsor elected to stop enrollment of adolescents in study AMAM and enroll pediatric participants in a separate, pediatric study. The 6 enrolled participants were allowed to continue treatment and finish the study.
    For support, Contact us.
    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
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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