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Trial record 1 of 1 for:    mirikizumab | Crohn Disease | Phase 2
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A Study of Mirikizumab (LY3074828) in Participants With Active Crohn's Disease (SERENITY)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02891226
Recruitment Status : Completed
First Posted : September 7, 2016
Results First Posted : February 28, 2022
Last Update Posted : August 30, 2022
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Crohn's Disease
Interventions Drug: Mirikizumab
Drug: Placebo
Enrollment 191
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Period 1: Placebo Intravenous (IV) Every 4 Weeks (Q4W) Period 1: 200 Milligram (mg) Mirikizumab IV Q4W Period 1: 600 mg Mirikizumab IV Q4W Period 1: 1000 mg Mirikizumab IV Q4W Period 2: 200 mg Mirikizumab IV Q4W (Period 1 Mirikizumab Improvers) Period 2: 600 mg Mirikizumab IV Q4W (Period 1 Mirikizumab Improvers) Period 2: 1000 mg Mirikizumab IV Q4W (Period 1 Mirikizumab Improvers) Period 2: 300mg Mirikizumab Subcutaneous (SC) Q4W (Period 1 Mirikizumab Improvers) Period 2: 1000 mg Mirikizumab IV Q4W (Period 1 Mirikizumab Non-improvers) Period 2: 1000 mg Mirkizumab IV Q4W (Period 1 Placebo) Period 3: 300 mg Mirikizumab SC Q4W Follow-up Period: 200 mg Mirikizumab IV Q4W in Period 2 Follow-up Period: 1000 mg Mirikizumab IV Q4W in Period 2 (Period 1 Mirikizumab Improvers) Follow-up Period: 1000 mg Mirikizumab IV Q4W in Period 2 (Period 1 Mirikizumab Non-improvers) Follow-up Period: 1000 mg Mirkizumab IV Q4W in Period 2 (Placebo in Period 1) Follow-up Period: 300 mg Mirikizumab SC Q4W in Period 3
Hide Arm/Group Description Participants received placebo administered intravenously (IV) Q4W. Participants received 200 mg mirikizumab administered IV Q4W. Participants received 600 mg mirikizumab administered IV Q4W. Participants received 1000 mg mirikizumab administered IV Q4W. Participants received 200 mg mirikizumab administered IV Q4W. Participants improved on the same mirikizumab dose in Period 1. Participants received 600 mg mirikizumab administered IV Q4W. Participants improved on the same mirikizumab dose in Period 1. Participants received 1000 mg mirikizumab administered IV Q4W. Participants improved on the same mirikizumab dose in Period 1. Participants received 300 mg mirikizumab administered SC Q4W. Participants improved on any mirikizumab dose in Period 1. Participants who did not improve in Period 1 on mirikizumab (any dose) received 1000 mg mirikizumab administered IV Q4W. Participants who received placebo in period 1 received 1000 mg mirikizumab administered IV Q4W. Participants received 300 mg mirikizumab administered SC Q4W. Participants did not receive drug during the follow-up period. Group includes participants who received 200 mg mirikizumab IV Q4W during period 2. Participants did not receive drug during the follow-up period. Group includes participants who received 1000 mg mirikizumab IV Q4W during period 2 after improving on the same dose in Period 1. Participants did not receive drug during the follow-up period. Group includes participants who did not improve in period 1, and received 1000 mg mirikizumab IV Q4W during period 2. Participants did not receive drug during the follow-up period. Group includes participants who received placebo in period 1 and 1000 mg mirikizumab administered IV Q4W. Participants did not receive drug during the follow-up period. Group includes participants who received 300 mg mirikizumab administered SC Q4W during period 3.
Period Title: Period 1 (Weeks 0 to 12)
Started 64 31 32 64 0 0 0 0 0 0 0 0 0 0 0 0
Received at Least 1 Dose of Study Drug 64 31 32 64 0 0 0 0 0 0 0 0 0 0 0 0
Completed 59 29 28 60 0 0 0 0 0 0 0 0 0 0 0 0
Not Completed 5 2 4 4 0 0 0 0 0 0 0 0 0 0 0 0
Reason Not Completed
Adverse Event             4             1             3             0             0             0             0             0             0             0             0             0             0             0             0             0
Lost to Follow-up             1             1             0             0             0             0             0             0             0             0             0             0             0             0             0             0
Withdrawal by Subject             0             0             0             2             0             0             0             0             0             0             0             0             0             0             0             0
Enrollment Failure             0             0             1             0             0             0             0             0             0             0             0             0             0             0             0             0
Sponsor Decision             0             0             0             1             0             0             0             0             0             0             0             0             0             0             0             0
Lack of Efficacy             0             0             0             1             0             0             0             0             0             0             0             0             0             0             0             0
Period Title: Period 2 (Weeks 12 to 52)
Started 0 [1] 0 [1] 0 [1] 0 [1] 9 [2] 9 [2] 23 [2] 46 [2] 30 [2] 59 [2] 0 0 0 0 0 0
Completed 0 0 0 0 8 8 20 41 24 42 0 0 0 0 0 0
Not Completed 0 0 0 0 1 1 3 5 6 17 0 0 0 0 0 0
Reason Not Completed
Adverse Event             0             0             0             0             0             0             1             1             3             7             0             0             0             0             0             0
Lost to Follow-up             0             0             0             0             0             1             0             0             0             1             0             0             0             0             0             0
Withdrawal by Subject             0             0             0             0             0             0             1             2             1             6             0             0             0             0             0             0
PI decision due to Lack of Efficacy             0             0             0             0             1             0             0             0             0             0             0             0             0             0             0             0
PI and Sponsor Decision due to Subject Safety             0             0             0             0             0             0             1             0             0             0             0             0             0             0             0             0
Lack of Efficacy             0             0             0             0             0             0             0             1             1             1             0             0             0             0             0             0
PI Decision due to Lack of Efficacy             0             0             0             0             0             0             0             1             0             0             0             0             0             0             0             0
Endoscopic Procedure was not Evaluated             0             0             0             0             0             0             0             0             1             0             0             0             0             0             0             0
Lack of Efficacy and Withdrew from Study             0             0             0             0             0             0             0             0             0             1             0             0             0             0             0             0
Sponsor Decision             0             0             0             0             0             0             0             0             0             1             0             0             0             0             0             0
[1]
Participants were assigned to this arm during period 1.
[2]
Participants were assigned to this arm during period 2.
Period Title: Period 3 (Weeks 52 to 208)
Started 0 0 0 0 0 [1] 0 [1] 0 [1] 0 [1] 0 [1] 0 [1] 137 [2] 0 0 0 0 0
Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 137 0 0 0 0 0
Reason Not Completed
Adverse Event             0             0             0             0             0             0             0             0             0             0             5             0             0             0             0             0
Lost to Follow-up             0             0             0             0             0             0             0             0             0             0             1             0             0             0             0             0
Withdrawal by Subject             0             0             0             0             0             0             0             0             0             0             14             0             0             0             0             0
Roll over to AMAX             0             0             0             0             0             0             0             0             0             0             108             0             0             0             0             0
Decided to not Participate in Extension Period (Week 104-208)             0             0             0             0             0             0             0             0             0             0             2             0             0             0             0             0
Lack of Efficacy             0             0             0             0             0             0             0             0             0             0             3             0             0             0             0             0
PI Decision as Subject Not Responding to Study Drug             0             0             0             0             0             0             0             0             0             0             2             0             0             0             0             0
Non-Compliance With Study Visit Schedule             0             0             0             0             0             0             0             0             0             0             2             0             0             0             0             0
[1]
Participants were assigned to this arm during period 2.
[2]
Participants were assigned to this arm during period 3.
Period Title: Follow-up Period
Started 0 0 0 0 0 0 0 0 0 0 0 1 [1] 2 [1] 1 [1] 1 [1] 3 [1]
Completed 0 0 0 0 0 0 0 0 0 0 0 0 2 1 0 2
Not Completed 0 0 0 0 0 0 0 0 0 0 0 1 0 0 1 1
Reason Not Completed
Withdrawal by Subject             0             0             0             0             0             0             0             0             0             0             0             1             0             0             1             1
[1]
Participants were assigned to this arm during follow-up period.
Arm/Group Title Placebo IV Q4W 200 mg Mirikizumab IV Q4W 600 mg Mirikizumab IV Q4W 1000 mg Mirikizumab IV Q4W Total
Hide Arm/Group Description Participants received placebo administered IV Q4W. Participants received 200 mg mirikizumab administered IV Q4W. Participants received 600 mg mirikizumab administered IV Q4W. Participants received 1000 mg mirikizumab administered IV Q4W. Total of all reporting groups
Overall Number of Baseline Participants 64 31 32 64 191
Hide Baseline Analysis Population Description
All randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 64 participants 31 participants 32 participants 64 participants 191 participants
39.00  (13.04) 38.10  (11.80) 40.40  (13.33) 37.70  (13.11) 38.70  (12.70)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 64 participants 31 participants 32 participants 64 participants 191 participants
Female 36 14 18 30 98
Male 28 17 14 34 93
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 64 participants 31 participants 32 participants 64 participants 191 participants
Hispanic or Latino 4 0 2 2 8
Not Hispanic or Latino 53 27 26 54 160
Unknown or Not Reported 7 4 4 8 23
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 64 participants 31 participants 32 participants 64 participants 191 participants
American Indian or Alaska Native 0 0 0 0 0
Asian 7 1 4 8 20
Native Hawaiian or Other Pacific Islander 0 0 0 0 0
Black or African American 2 2 3 4 11
White 55 28 24 52 159
More than one race 0 0 1 0 1
Unknown or Not Reported 0 0 0 0 0
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 64 participants 31 participants 32 participants 64 participants 191 participants
Australia 3 0 0 1 4
Belgium 0 1 1 4 6
Czechia 4 1 0 5 10
Hungary 3 1 0 3 7
Japan 6 1 4 7 18
Netherlands 2 3 0 2 7
Poland 6 6 3 9 24
Romania 0 0 1 4 5
Russia 6 3 2 3 14
Ukraine 4 5 4 6 19
United Kingdom 1 0 0 0 1
United States 29 10 17 20 76
1.Primary Outcome
Title Percentage of Participants Achieving Endoscopic Response at Week 12
Hide Description Endoscopic response defined as ≥ 50% reduction from baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12. The SES-CD evaluates 4 endoscopic variables: presence and size of ulcers, proportion of surface covered by ulcers, proportion of surface affected by disease, and presence and severity of stenosis. The total SES-CD calculated as sum of 4 variables for 5 bowel segments: (ileum;right,transverse,and left colon;and rectum): presence and size of ulcers (none = score 0; diameter 0.1-0.5 cm = score 1; 0.5-2 cm = score 2; >2 cm = score 3); extent of ulcerated surface (none = 0; <10% = 1;10-30% = 2;>30% = 3);extent of affected surface (none = 0; <50% = 1;50-75% = 2;>75% =3); and presence and type of narrowings (none=0; single, can be passed=1; multiple,can be passed=2; cannot be passed=3). Total SES-CD scores range from 0 to 56, with higher scores indicating more severe disease.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title Placebo IV Q4W 200 mg Mirikizumab IV Q4W 600 mg Mirikizumab IV Q4W 1000 mg Mirikizumab IV Q4W
Hide Arm/Group Description:
Participants received placebo administered IV Q4W.
Participants received 200 mg mirikizumab administered IV Q4W.
Participants received 600 mg mirikizumab administered IV Q4W.
Participants received 1000 mg mirikizumab administered IV Q4W.
Overall Number of Participants Analyzed 64 31 32 64
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
10.9
(4.5 to 17.4)
25.8
(12.9 to 38.7)
37.5
(23.4 to 51.6)
43.8
(33.6 to 53.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo IV Q4W, 200 mg Mirikizumab IV Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.079
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.75
Confidence Interval (2-Sided) 90%
1.07 to 7.08
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo IV Q4W, 600 mg Mirikizumab IV Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.92
Confidence Interval (2-Sided) 90%
2.01 to 12.07
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo IV Q4W, 1000 mg Mirikizumab IV Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.14
Confidence Interval (2-Sided) 90%
2.81 to 13.42
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants Achieving Endoscopic Remission at Week 12
Hide Description Endoscopic remission defined as SES-CD of <4 ileal-colonic or <2 for isolated ileal disease, and no subscore >1 at week 12. The SES-CD evaluates 4 endoscopic variables: presence and size of ulcers, proportion of surface covered by ulcers, proportion of surface affected by disease, and presence and severity of stenosis. The total SES-CD is calculated as the sum of the 4 variables for the 5 bowel segments: (ileum; right, transverse, and left colon; and rectum): presence and size of ulcers (none = score 0; diameter 0.1-0.5 cm = score 1; 0.5-2 cm = score 2; greater than (>) 2 cm = score 3); extent of ulcerated surface (none = 0; less than (<) 10% = 1; 10-30% = 2; >30% = 3); extent of affected surface (none = 0; <50% = 1; 50-75% = 2; >75% = 3); and presence and type of narrowings (none=0; single, can be passed=1; multiple, can be passed=2; cannot be passed=3). Total SES-CD scores range from 0 to 56, with higher scores indicating more severe disease.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title Placebo IV Q4W 200 mg Mirikizumab IV Q4W 600 mg Mirikizumab IV Q4W 1000 mg Mirikizumab IV Q4W
Hide Arm/Group Description:
Participants received placebo administered IV Q4W
Participants received 200 mg mirikizumab administered IV Q4W.
Participants received 600 mg mirikizumab administered IV Q4W.
Participants received 1000 mg mirikizumab administered IV Q4W.
Overall Number of Participants Analyzed 64 31 32 64
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
1.6
(0.0 to 4.1)
6.5
(0.0 to 13.7)
15.6
(5.1 to 26.2)
20.3
(12.0 to 28.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo IV Q4W, 200 mg Mirikizumab IV Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.241
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.31
Confidence Interval (2-Sided) 90%
0.55 to 33.58
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo IV Q4W, 600 mg Mirikizumab IV Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.032
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 11.16
Confidence Interval (2-Sided) 90%
1.76 to 70.64
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo IV Q4W, 1000 mg Mirikizumab IV Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.009
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 16.04
Confidence Interval (2-Sided) 90%
2.82 to 91.32
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants Achieving Patient Reported Outcome Remission at Week 12
Hide Description PRO remission is defined as stool frequency (SF) ≤2.5 and abdominal pain (AP) ≤1 and no worse than baseline at week 12. SF captures the number of liquid or very soft stools. AP score is classified as 0=none, 1=mild, 2=moderate, 3=severe.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants.
Arm/Group Title Placebo IV Q4W 200 mg Mirikizumab IV Q4W 600 mg Mirikizumab IV Q4W 1000 mg Mirikizumab IV Q4W
Hide Arm/Group Description:
Participants received placebo administered IV Q4W
Participants received 200 mg mirikizumab administered IV Q4W.
Participants received 600 mg mirikizumab administered IV Q4W.
Participants received 1000 mg mirikizumab administered IV Q4W.
Overall Number of Participants Analyzed 64 31 32 64
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
6.3
(1.3 to 11.2)
12.9
(3.0 to 22.8)
28.1
(15.1 to 41.2)
21.9
(13.4 to 30.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo IV Q4W, 200 mg Mirikizumab IV Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.330
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.0
Confidence Interval (2-Sided) 90%
0.62 to 6.45
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo IV Q4W, 600 mg Mirikizumab IV Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.72
Confidence Interval (2-Sided) 90%
2.02 to 16.21
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo IV Q4W, 1000 mg Mirikizumab IV Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.029
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.52
Confidence Interval (2-Sided) 90%
1.37 to 9.07
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Mean Change From Baseline on the Patient Global Rating - Severity (PGRS) Crohn's Disease Score at Week 12
Hide Description The PGRS is a 1-item patient-rated questionnaire designed to assess the participant's rating of their disease symptom severity over the past 24 hours. Responses are graded on a 6-point scale in which a score of 1 indicates the subject has no symptoms (that is, "none") and a score of 6 indicates that the participant's symptom are "very severe." Least Squares Mean (LS Mean) was calculated using Mixed Model for Repeated Measures (MMRM) model with treatment, geographic region, geographic region, prior biologic CD therapy use (prior biologic experience versus prior biologic naive), baseline score, visit, and the interaction of treatment-by-visit and baseline-by-visit as fixed factors.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had a baseline and at least one post-baseline PGRS value.
Arm/Group Title Placebo IV Q4W 200 mg Mirikizumab IV Q4W 600 mg Mirikizumab IV Q4W 1000 mg Mirikizumab IV Q4W
Hide Arm/Group Description:
Participants received placebo administered IV Q4W
Participants received 200 mg mirikizumab administered IV Q4W.
Participants received 600 mg mirikizumab administered IV Q4W.
Participants received 1000 mg mirikizumab administered IV Q4W.
Overall Number of Participants Analyzed 58 26 29 56
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-0.44  (0.132) -1.08  (0.194) -1.27  (0.189) -0.98  (0.134)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo IV Q4W, 200 mg Mirikizumab IV Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference (Final Values)
Estimated Value -0.64
Confidence Interval (2-Sided) 90%
-1.03 to -0.25
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.234
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo IV Q4W, 600 mg Mirikizumab IV Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference (Final Values)
Estimated Value -0.83
Confidence Interval (2-Sided) 90%
-1.21 to -0.45
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.230
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo IV Q4W, 1000 mg Mirikizumab IV Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference (Final Values)
Estimated Value -0.53
Confidence Interval (2-Sided) 90%
-0.84 to -0.22
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.188
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Mean of Patient Global Rating - Change (PGRC) Crohn's Disease Score at Week 12
Hide Description The PGRC scale is a patient-rated instrument designed to assess the participant's rating of change in their symptom(s). Responses are graded on a 7-point Likert scale in which a score of 1 indicates that the participant's symptom is "very much better," a score of 4 indicates that the participant's symptom has experienced "no change," and a score of 7 indicates that the participant's symptom is "very much worse."
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had a baseline and at least one post-baseline PGRC value.
Arm/Group Title Placebo IV Q4W 200 mg Mirikizumab IV Q4W 600 mg Mirikizumab IV Q4W 1000 mg Mirikizumab IV Q4W
Hide Arm/Group Description:
Participants received placebo administered IV Q4W
Participants received 200 mg mirikizumab administered IV Q4W.
Participants received 600 mg mirikizumab administered IV Q4W.
Participants received 1000 mg mirikizumab administered IV Q4W.
Overall Number of Participants Analyzed 56 29 27 57
Mean (Standard Deviation)
Unit of Measure: score on a scale
3.6  (1.11) 2.8  (1.26) 2.6  (0.97) 2.5  (0.89)
6.Secondary Outcome
Title Mean Change From Baseline on the Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 12
Hide Description The IBDQ is a 32-item self-administered questionnaire. The IBDQ has 4 dimensions: bowel symptoms (10 items), systemic symptoms (5 items), emotional function (12 items), and social function (5 items). 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." Scores range from 32 to 224; a higher score indicates a better quality of life. LS Mean was calculated using Mixed Model for Repeated Measures (MMRM) model with treatment, geographic region, geographic region, prior biologic CD therapy use (prior biologic experience versus prior biologic naive), baseline score, visit, and the interaction of treatment-by-visit and baseline-by-visit as fixed factors.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had a baseline and at least one post-baseline IBDQ value.
Arm/Group Title Placebo IV Q4W 200 mg Mirikizumab IV Q4W 600 mg Mirikizumab IV Q4W 1000 mg Mirikizumab IV Q4W
Hide Arm/Group Description:
Participants received placebo administered IV Q4W
Participants received 200 mg mirikizumab administered IV Q4W.
Participants received 600 mg mirikizumab administered IV Q4W.
Participants received 1000 mg mirikizumab administered IV Q4W.
Overall Number of Participants Analyzed 56 29 28 57
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
17.11  (3.725) 41.16  (5.311) 46.57  (5.244) 42.35  (3.770)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo IV Q4W, 200 mg Mirikizumab IV Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference (Final Values)
Estimated Value 24.05
Confidence Interval (2-Sided) 90%
13.53 to 34.56
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.358
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo IV Q4W, 600 mg Mirikizumab IV Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference (Final Values)
Estimated Value 29.46
Confidence Interval (2-Sided) 90%
18.84 to 40.08
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.421
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo IV Q4W, 1000 mg Mirikizumab IV Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference (Final Values)
Estimated Value 25.24
Confidence Interval (2-Sided) 90%
16.67 to 33.82
Parameter Dispersion
Type: Standard Error of the Mean
Value: 5.185
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Mean Change From Baseline on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 12
Hide Description The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale is a13-item, symptom-specific questionnaire that specifically assesses the participant's self-reported severity of fatigue and its impact upon daily activities and functioning. The FACIT-F uses a numeric rating scale of 0-4 associated with a range over "Not at all" to "Very much" for each item to assess fatigue and its impact in the past 7 days. Total scores range from 0 to 52, with higher scores indicating less fatigue. LS Mean was calculated using Mixed Model for Repeated Measures (MMRM) model with treatment, geographic region, geographic region, prior biologic CD therapy use (prior biologic experience versus prior biologic naive), baseline score, visit, and the interaction of treatment-by-visit and baseline-by-visit as fixed factors.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had a baseline and at least one post-baseline FACIT-F value.
Arm/Group Title Placebo IV Q4W 200 mg Mirikizumab IV Q4W 600 mg Mirikizumab IV Q4W 1000 mg Mirikizumab IV Q4W
Hide Arm/Group Description:
Participants received placebo administered IV Q4W
Participants received 200 mg mirikizumab administered IV Q4W.
Participants received 600 mg mirikizumab administered IV Q4W.
Participants received 1000 mg mirikizumab administered IV Q4W.
Overall Number of Participants Analyzed 56 29 28 57
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
2.90  (1.209) 10.81  (1.728) 9.09  (1.721) 9.62  (1.223)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo IV Q4W, 200 mg Mirikizumab IV Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference (Final Values)
Estimated Value 7.91
Confidence Interval (2-Sided) 90%
4.48 to 11.34
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.072
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo IV Q4W, 600 mg Mirikizumab IV Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference (Final Values)
Estimated Value 6.20
Confidence Interval (2-Sided) 90%
2.72 to 9.67
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.102
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo IV Q4W, 1000 mg Mirikizumab IV Q4W
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference (Final Values)
Estimated Value 6.73
Confidence Interval (2-Sided) 90%
3.94 to 9.51
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.686
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Mean Change From Baseline on the 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Week 12
Hide Description The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains:physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, 2 component scores (MCS and PCS). MCS consisted of social functioning, vitality, mental health, and role-emotional scales. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. Each domain is scored by summing individual items and transforming scores into a 0 to 100 scale with higher scores indicating better health status or functioning. LS Mean was calculated using Mixed Model for Repeated Measures (MMRM) model with treatment, geographic region, geographic region, prior biologic CD therapy use (prior biologic experience versus prior biologic naive), baseline score, visit, and the interaction of treatment-by-visit and baseline-by-visit as fixed factors.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had a baseline and at least one post-baseline PCS and MCS value.
Arm/Group Title Placebo IV Q4W 200 mg Mirikizumab IV Q4W 600 mg Mirikizumab IV Q4W 1000 mg Mirikizumab IV Q4W
Hide Arm/Group Description:
Participants received placebo administered IV Q4W
Participants received 200 mg mirikizumab administered IV Q4W.
Participants received 600 mg mirikizumab administered IV Q4W.
Participants received 1000 mg mirikizumab administered IV Q4W.
Overall Number of Participants Analyzed 56 29 28 57
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
MCS 2.34  (1.133) 7.47  (1.602) 6.52  (1.592) 6.05  (1.152)
PCS 3.11  (0.774) 4.70  (1.096) 8.01  (1.108) 6.70  (0.787)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo IV Q4W, 200 mg Mirikizumab IV Q4W
Comments Mental Component Summary (MCS)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference (Final Values)
Estimated Value 5.14
Confidence Interval (2-Sided) 90%
1.95 to 8.32
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.927
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo IV Q4W, 600 mg Mirikizumab IV Q4W
Comments Mental Component Summary (MCS)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.033
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference (Final Values)
Estimated Value 4.18
Confidence Interval (2-Sided) 90%
0.96 to 7.41
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.951
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo IV Q4W, 1000 mg Mirikizumab IV Q4W
Comments Mental Component Summary (MCS)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.021
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference (Final Values)
Estimated Value 3.71
Confidence Interval (2-Sided) 90%
1.08 to 6.34
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.589
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo IV Q4W, 200 mg Mirikizumab IV Q4W
Comments Physical Component Summary (PCS)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.229
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference (Final Values)
Estimated Value 1.59
Confidence Interval (2-Sided) 90%
-0.59 to 3.77
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.319
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo IV Q4W, 600 mg Mirikizumab IV Q4W
Comments Physical Component Summary (PCS)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference (Final Values)
Estimated Value 4.91
Confidence Interval (2-Sided) 90%
2.67 to 7.14
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.349
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo IV Q4W, 1000 mg Mirikizumab IV Q4W
Comments Physical Component Summary (PCS)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean difference (Final Values)
Estimated Value 3.60
Confidence Interval (2-Sided) 90%
1.81 to 5.38
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.078
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Population Pharmacokinetics (PopPK): Mean Population Clearance of Mirikizumab
Hide Description Population mean (between-subject coefficient variance [CV %]) apparent clearance. Clearance is estimated based on concentration data collected in the time frame of 0-208 weeks.
Time Frame Week 0, 4, 8: Predose, end of infusion; Week 2; 4; 6; 8, 11-12; 12-13; 16; 20; 24; 28; 36; 44; 52; 60; 68; 76; 84; 92; 104; 108; 112; 120; 128; 136; 144; 156; 164; 172; 180; 188; 196 and 208 weeks post infusion
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and had evaluable PK data.
Arm/Group Title Mirikizumab IV Q4W
Hide Arm/Group Description:
Participants received 200 mg, 600 mg, 1000 mg mirikizumab administered IV Q4W.
Overall Number of Participants Analyzed 186
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liters per Hour (L/h)
0.0225
(30%)
10.Secondary Outcome
Title Population Pharmacokinetics (PopPK): Mean Population Volume of Distribution of Mirikizumab
Hide Description Population mean (between-subject coefficient variance [CV %]) apparent volume of distribution. Volume of distribution is estimated based on concentration data collected in the time frame of 0-208 weeks.
Time Frame Week 0, 4, 8: Predose, end of infusion; Week 2; 4; 6; 8, 11-12; 12-13; 16; 20; 24; 28; 36; 44; 52; 60; 68; 76; 84; 92; 104; 108; 112; 120; 128; 136; 144; 156; 164; 172; 180; 188; 196 and 208 weeks post infusion
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and had evaluable PK data.
Arm/Group Title Mirikizumab IV Q4W
Hide Arm/Group Description:
Participants received 200 mg, 600 mg, 1000 mg mirikizumab administered IV Q4W.
Overall Number of Participants Analyzed 186
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liters (L)
5.05
(18%)
Time Frame Baseline Up To 208 Weeks
Adverse Event Reporting Description All randomized participants who received at least 1 dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
 
Arm/Group Title Period 1: Placebo Intravenous (IV) Every 4 Weeks (Q4W) Period 1: 200 Milligram (mg) Mirikizumab IV Q4W Period 1: 600 mg Mirikizumab IV Q4W Period 1: 1000 mg Mirikizumab IV Q4W Period 2: 200 mg Mirikizumab IV Q4W (Period 1 Mirikizumab Improvers) Period 2: 600 mg Mirikizumab IV Q4W (Period 1 Mirikizumab Improvers) Period 2: 1000 mg Mirikizumab IV Q4W (Period 1 Mirikizumab Improvers) Period 2: 300mg Mirikizumab Subcutaneous (SC) Q4W (Period 1 Mirikizumab Improvers) Period 2: 1000 mg Mirikizumab IV Q4W (Period 1 Mirikizumab Non-improvers) Period 2: 1000 mg Mirkizumab IV Q4W (Period 1 Placebo) Period 3: 300 mg Mirikizumab SC Q4W Follow-up Period: 200 mg Mirikizumab IV Q4W in Period 2 Follow-up Period: 1000 mg Mirikizumab IV Q4W in Period 2 (Period 1 Mirikizumab Improvers) Follow-up Period: 1000 mg Mirikizumab IV Q4W in Period 2 (Period 1 Mirikizumab Non-improvers) Follow-up Period: 1000 mg Mirkizumab IV Q4W in Period 2 (Placebo in Period 1) Follow-up Period: 300 mg Mirikizumab SC Q4W in Period 3
Hide Arm/Group Description Participants received placebo administered intravenously (IV) Q4W. Participants received 200 mg mirikizumab administered IV Q4W. Participants received 600 mg mirikizumab administered IV Q4W. Participants received 1000 mg mirikizumab administered IV Q4W. Participants received 200 mg mirikizumab administered IV Q4W. Participants improved on the same mirikizumab dose in Period 1. Participants received 600 mg mirikizumab administered IV Q4W. Participants improved on the same mirikizumab dose in Period 1. Participants received 1000 mg mirikizumab administered IV Q4W. Participants improved on the same mirikizumab dose in Period 1. Participants received 300 mg mirikizumab administered SC Q4W. Participants improved on any mirikizumab dose in Period 1. Participants who did not improve in Period 1 on mirikizumab (any dose) received 1000 mg mirikizumab administered IV Q4W. Participants who received placebo in period 1 received 1000 mg mirikizumab administered IV Q4W. Participants received 300 mg mirikizumab administered SC Q4W. Participants did not receive drug during the follow-up period. Group includes participants who received 200 mg mirikizumab IV Q4W during period 2. Participants did not receive drug during the follow-up period. Group includes participants who received 1000 mg mirikizumab IV Q4W during period 2 after improving on the same dose in Period 1. Participants did not receive drug during the follow-up period. Group includes participants who did not improve in period 1, and received 1000 mg mirikizumab IV Q4W during period 2. Participants did not receive drug during the follow-up period. Group includes participants who received placebo in period 1 and 1000 mg mirikizumab administered IV Q4W. Participants did not receive drug during the follow-up period. Group includes participants who received 300 mg mirikizumab administered SC Q4W during period 3.
All-Cause Mortality
Period 1: Placebo Intravenous (IV) Every 4 Weeks (Q4W) Period 1: 200 Milligram (mg) Mirikizumab IV Q4W Period 1: 600 mg Mirikizumab IV Q4W Period 1: 1000 mg Mirikizumab IV Q4W Period 2: 200 mg Mirikizumab IV Q4W (Period 1 Mirikizumab Improvers) Period 2: 600 mg Mirikizumab IV Q4W (Period 1 Mirikizumab Improvers) Period 2: 1000 mg Mirikizumab IV Q4W (Period 1 Mirikizumab Improvers) Period 2: 300mg Mirikizumab Subcutaneous (SC) Q4W (Period 1 Mirikizumab Improvers) Period 2: 1000 mg Mirikizumab IV Q4W (Period 1 Mirikizumab Non-improvers) Period 2: 1000 mg Mirkizumab IV Q4W (Period 1 Placebo) Period 3: 300 mg Mirikizumab SC Q4W Follow-up Period: 200 mg Mirikizumab IV Q4W in Period 2 Follow-up Period: 1000 mg Mirikizumab IV Q4W in Period 2 (Period 1 Mirikizumab Improvers) Follow-up Period: 1000 mg Mirikizumab IV Q4W in Period 2 (Period 1 Mirikizumab Non-improvers) Follow-up Period: 1000 mg Mirkizumab IV Q4W in Period 2 (Placebo in Period 1) Follow-up Period: 300 mg Mirikizumab SC Q4W in Period 3
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/64 (0.00%)      0/31 (0.00%)      0/32 (0.00%)      0/64 (0.00%)      0/9 (0.00%)      0/9 (0.00%)      0/23 (0.00%)      0/46 (0.00%)      0/30 (0.00%)      0/59 (0.00%)      0/136 (0.00%)      0/1 (0.00%)      0/2 (0.00%)      0/1 (0.00%)      0/1 (0.00%)      0/3 (0.00%)    
Hide Serious Adverse Events
Period 1: Placebo Intravenous (IV) Every 4 Weeks (Q4W) Period 1: 200 Milligram (mg) Mirikizumab IV Q4W Period 1: 600 mg Mirikizumab IV Q4W Period 1: 1000 mg Mirikizumab IV Q4W Period 2: 200 mg Mirikizumab IV Q4W (Period 1 Mirikizumab Improvers) Period 2: 600 mg Mirikizumab IV Q4W (Period 1 Mirikizumab Improvers) Period 2: 1000 mg Mirikizumab IV Q4W (Period 1 Mirikizumab Improvers) Period 2: 300mg Mirikizumab Subcutaneous (SC) Q4W (Period 1 Mirikizumab Improvers) Period 2: 1000 mg Mirikizumab IV Q4W (Period 1 Mirikizumab Non-improvers) Period 2: 1000 mg Mirkizumab IV Q4W (Period 1 Placebo) Period 3: 300 mg Mirikizumab SC Q4W Follow-up Period: 200 mg Mirikizumab IV Q4W in Period 2 Follow-up Period: 1000 mg Mirikizumab IV Q4W in Period 2 (Period 1 Mirikizumab Improvers) Follow-up Period: 1000 mg Mirikizumab IV Q4W in Period 2 (Period 1 Mirikizumab Non-improvers) Follow-up Period: 1000 mg Mirkizumab IV Q4W in Period 2 (Placebo in Period 1) Follow-up Period: 300 mg Mirikizumab SC Q4W in Period 3
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/64 (10.94%)      0/31 (0.00%)      3/32 (9.38%)      2/64 (3.13%)      0/9 (0.00%)      0/9 (0.00%)      0/23 (0.00%)      2/46 (4.35%)      3/30 (10.00%)      9/59 (15.25%)      15/136 (11.03%)      0/1 (0.00%)      0/2 (0.00%)      0/1 (0.00%)      0/1 (0.00%)      0/3 (0.00%)    
Cardiac disorders                                 
Cardiac failure  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 1/136 (0.74%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Gastrointestinal disorders                                 
Abdominal pain  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 1/64 (1.56%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/136 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Crohn's disease  1  3/64 (4.69%)  3 0/31 (0.00%)  0 1/32 (3.13%)  1 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 1/46 (2.17%)  1 1/30 (3.33%)  1 1/59 (1.69%)  1 2/136 (1.47%)  2 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Ileal perforation  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 1/46 (2.17%)  1 0/30 (0.00%)  0 0/59 (0.00%)  0 0/136 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Ileal stenosis  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 1/136 (0.74%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Ileus  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 1/136 (0.74%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Intestinal obstruction  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 1/59 (1.69%)  1 0/136 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Intestinal perforation  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 1/136 (0.74%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Large intestinal stenosis  1  0/64 (0.00%)  0 0/31 (0.00%)  0 1/32 (3.13%)  1 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/136 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Large intestine perforation  1  0/64 (0.00%)  0 0/31 (0.00%)  0 1/32 (3.13%)  1 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/136 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Lower gastrointestinal haemorrhage  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 1/136 (0.74%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Pneumatosis intestinalis  1  1/64 (1.56%)  1 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/136 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Small intestinal stenosis  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 1/136 (0.74%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
General disorders                                 
Malaise  1  1/64 (1.56%)  1 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/136 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Non-cardiac chest pain  1  0/64 (0.00%)  0 0/31 (0.00%)  0 1/32 (3.13%)  1 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 1/59 (1.69%)  1 0/136 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Pyrexia  1  1/64 (1.56%)  1 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 1/136 (0.74%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Immune system disorders                                 
Anaphylactic reaction  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 2/59 (3.39%)  2 0/136 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Infusion related hypersensitivity reaction  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 1/59 (1.69%)  1 0/136 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Infections and infestations                                 
Clostridium difficile infection  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 1/59 (1.69%)  1 0/136 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Peritonitis  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 1/46 (2.17%)  1 0/30 (0.00%)  0 0/59 (0.00%)  0 0/136 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Pneumonia  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 1/30 (3.33%)  1 0/59 (0.00%)  0 0/136 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Pyelonephritis  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 1/46 (2.17%)  1 0/30 (0.00%)  0 0/59 (0.00%)  0 0/136 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Injury, poisoning and procedural complications                                 
Concussion  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 1/136 (0.74%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Intestinal anastomosis complication  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 1/59 (1.69%)  1 0/136 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Maternal exposure during pregnancy  1  0/36 (0.00%)  0 0/14 (0.00%)  0 0/18 (0.00%)  0 0/30 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 1/13 (7.69%)  1 0/33 (0.00%)  0 0/61 (0.00%)  0 0/1 (0.00%)  0 0/0  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0
Paternal exposure during pregnancy  1  0/28 (0.00%)  0 0/17 (0.00%)  0 0/14 (0.00%)  0 0/34 (0.00%)  0 0/5 (0.00%)  0 0/5 (0.00%)  0 0/11 (0.00%)  0 0/23 (0.00%)  0 0/17 (0.00%)  0 0/26 (0.00%)  0 2/75 (2.67%)  2 0/0  0 0/2 (0.00%)  0 0/0  0 0/0  0 0/2 (0.00%)  0
Investigations                                 
Blood potassium decreased  1  1/64 (1.56%)  1 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/136 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Metabolism and nutrition disorders                                 
Dehydration  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 1/46 (2.17%)  1 0/30 (0.00%)  0 0/59 (0.00%)  0 0/136 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Hypokalaemia  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 1/46 (2.17%)  1 0/30 (0.00%)  0 0/59 (0.00%)  0 0/136 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Musculoskeletal and connective tissue disorders                                 
Back pain  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 1/64 (1.56%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/136 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Osteoarthritis  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 1/59 (1.69%)  1 0/136 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Rotator cuff syndrome  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 1/136 (0.74%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                                 
Gastrointestinal tract adenoma  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 1/136 (0.74%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Pregnancy, puerperium and perinatal conditions                                 
Abortion spontaneous  1  0/36 (0.00%)  0 0/14 (0.00%)  0 0/18 (0.00%)  0 0/30 (0.00%)  0 0/4 (0.00%)  0 0/4 (0.00%)  0 0/12 (0.00%)  0 0/23 (0.00%)  0 1/13 (7.69%)  1 0/33 (0.00%)  0 0/61 (0.00%)  0 0/1 (0.00%)  0 0/0  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0
Renal and urinary disorders                                 
Renal colic  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 1/136 (0.74%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Respiratory, thoracic and mediastinal disorders                                 
Pulmonary embolism  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 1/136 (0.74%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Vascular disorders                                 
Deep vein thrombosis  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 1/136 (0.74%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
1
Term from vocabulary, MedDRA 23.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Period 1: Placebo Intravenous (IV) Every 4 Weeks (Q4W) Period 1: 200 Milligram (mg) Mirikizumab IV Q4W Period 1: 600 mg Mirikizumab IV Q4W Period 1: 1000 mg Mirikizumab IV Q4W Period 2: 200 mg Mirikizumab IV Q4W (Period 1 Mirikizumab Improvers) Period 2: 600 mg Mirikizumab IV Q4W (Period 1 Mirikizumab Improvers) Period 2: 1000 mg Mirikizumab IV Q4W (Period 1 Mirikizumab Improvers) Period 2: 300mg Mirikizumab Subcutaneous (SC) Q4W (Period 1 Mirikizumab Improvers) Period 2: 1000 mg Mirikizumab IV Q4W (Period 1 Mirikizumab Non-improvers) Period 2: 1000 mg Mirkizumab IV Q4W (Period 1 Placebo) Period 3: 300 mg Mirikizumab SC Q4W Follow-up Period: 200 mg Mirikizumab IV Q4W in Period 2 Follow-up Period: 1000 mg Mirikizumab IV Q4W in Period 2 (Period 1 Mirikizumab Improvers) Follow-up Period: 1000 mg Mirikizumab IV Q4W in Period 2 (Period 1 Mirikizumab Non-improvers) Follow-up Period: 1000 mg Mirkizumab IV Q4W in Period 2 (Placebo in Period 1) Follow-up Period: 300 mg Mirikizumab SC Q4W in Period 3
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   24/64 (37.50%)      11/31 (35.48%)      12/32 (37.50%)      27/64 (42.19%)      7/9 (77.78%)      5/9 (55.56%)      14/23 (60.87%)      30/46 (65.22%)      16/30 (53.33%)      30/59 (50.85%)      89/136 (65.44%)      0/1 (0.00%)      1/2 (50.00%)      1/1 (100.00%)      0/1 (0.00%)      0/3 (0.00%)    
Blood and lymphatic system disorders                                 
Anaemia  1  1/64 (1.56%)  1 2/31 (6.45%)  2 1/32 (3.13%)  1 2/64 (3.13%)  2 1/9 (11.11%)  1 0/9 (0.00%)  0 1/23 (4.35%)  2 2/46 (4.35%)  2 2/30 (6.67%)  2 5/59 (8.47%)  6 7/136 (5.15%)  8 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Endocrine disorders                                 
Hypothyroidism  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 1/136 (0.74%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Eye disorders                                 
Lacrimation increased  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 1/23 (4.35%)  1 0/46 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/136 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Gastrointestinal disorders                                 
Abdominal distension  1  0/64 (0.00%)  0 0/31 (0.00%)  0 2/32 (6.25%)  2 1/64 (1.56%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 1/23 (4.35%)  1 3/46 (6.52%)  3 0/30 (0.00%)  0 0/59 (0.00%)  0 1/136 (0.74%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Abdominal pain  1  1/64 (1.56%)  1 0/31 (0.00%)  0 1/32 (3.13%)  1 0/64 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 2/23 (8.70%)  2 3/46 (6.52%)  3 0/30 (0.00%)  0 3/59 (5.08%)  3 8/136 (5.88%)  10 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Anal incontinence  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 2/136 (1.47%)  2 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Crohn's disease  1  6/64 (9.38%)  7 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 1/23 (4.35%)  1 3/46 (6.52%)  3 0/30 (0.00%)  0 1/59 (1.69%)  1 8/136 (5.88%)  10 0/1 (0.00%)  0 0/2 (0.00%)  0 1/1 (100.00%)  1 0/1 (0.00%)  0 0/3 (0.00%)  0
Diarrhoea  1  1/64 (1.56%)  1 1/31 (3.23%)  1 0/32 (0.00%)  0 2/64 (3.13%)  2 0/9 (0.00%)  0 1/9 (11.11%)  1 0/23 (0.00%)  0 3/46 (6.52%)  3 1/30 (3.33%)  1 0/59 (0.00%)  0 6/136 (4.41%)  7 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Flatulence  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 1/64 (1.56%)  1 0/9 (0.00%)  0 1/9 (11.11%)  1 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/136 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Haemorrhoids  1  1/64 (1.56%)  1 1/31 (3.23%)  1 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/23 (0.00%)  0 1/46 (2.17%)  1 1/30 (3.33%)  1 1/59 (1.69%)  1 1/136 (0.74%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Intestinal obstruction  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/136 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Nausea  1  2/64 (3.13%)  2 0/31 (0.00%)  0 2/32 (6.25%)  2 2/64 (3.13%)  2 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 1/30 (3.33%)  2 3/59 (5.08%)  3 6/136 (4.41%)  8 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Rectal polyp  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 1/59 (1.69%)  1 0/136 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
General disorders                                 
Fatigue  1  3/64 (4.69%)  3 0/31 (0.00%)  0 0/32 (0.00%)  0 1/64 (1.56%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 1/23 (4.35%)  1 1/46 (2.17%)  1 0/30 (0.00%)  0 4/59 (6.78%)  4 7/136 (5.15%)  7 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Infusion site reaction  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 1/9 (11.11%)  2 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/136 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Injection site pain  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  15 1/23 (4.35%)  1 4/46 (8.70%)  64 1/30 (3.33%)  7 3/59 (5.08%)  16 8/136 (5.88%)  162 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Injection site reaction  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  4 0/23 (0.00%)  0 3/46 (6.52%)  4 0/30 (0.00%)  0 1/59 (1.69%)  2 18/136 (13.24%)  114 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Pyrexia  1  1/64 (1.56%)  1 0/31 (0.00%)  0 3/32 (9.38%)  3 1/64 (1.56%)  1 1/9 (11.11%)  1 0/9 (0.00%)  0 0/23 (0.00%)  0 2/46 (4.35%)  2 2/30 (6.67%)  2 1/59 (1.69%)  1 6/136 (4.41%)  6 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Infections and infestations                                 
Cystitis  1  0/64 (0.00%)  0 2/31 (6.45%)  2 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 2/136 (1.47%)  2 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Epididymitis  1  0/28 (0.00%)  0 0/17 (0.00%)  0 0/14 (0.00%)  0 0/34 (0.00%)  0 0/5 (0.00%)  0 0/5 (0.00%)  0 1/11 (9.09%)  2 0/23 (0.00%)  0 0/17 (0.00%)  0 0/26 (0.00%)  0 0/75 (0.00%)  0 0/0  0 0/2 (0.00%)  0 0/0  0 0/0  0 0/2 (0.00%)  0
Erysipelas  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 1/59 (1.69%)  1 1/136 (0.74%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Gastroenteritis viral  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 1/9 (11.11%)  1 1/9 (11.11%)  1 1/23 (4.35%)  1 0/46 (0.00%)  0 1/30 (3.33%)  1 1/59 (1.69%)  1 1/136 (0.74%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Human anaplasmosis  1  0/64 (0.00%)  0 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/23 (0.00%)  0 0/46 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/136 (0.00%)  0 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Influenza  1  0/64 (0.00%)  0 0/31 (0.00%)  0 1/32 (3.13%)  1 0/64 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/23 (0.00%)  0 1/46 (2.17%)  1 1/30 (3.33%)  1 1/59 (1.69%)  1 5/136 (3.68%)  5 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Nasopharyngitis  1  1/64 (1.56%)  1 0/31 (0.00%)  0 2/32 (6.25%)  2 4/64 (6.25%)  4 0/9 (0.00%)  0 0/9 (0.00%)  0 2/23 (8.70%)  2 6/46 (13.04%)  7 3/30 (10.00%)  3 4/59 (6.78%)  6 25/136 (18.38%)  33 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Respiratory tract infection viral  1  1/64 (1.56%)  1 1/31 (3.23%)  1 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 1/46 (2.17%)  1 0/30 (0.00%)  0 1/59 (1.69%)  1 2/136 (1.47%)  2 0/1 (0.00%)  0 0/2 (0.00%)  0 1/1 (100.00%)  1 0/1 (0.00%)  0 0/3 (0.00%)  0
Sinusitis  1  1/64 (1.56%)  1 0/31 (0.00%)  0 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 1/46 (2.17%)  1 1/30 (3.33%)  1 3/59 (5.08%)  3 5/136 (3.68%)  8 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Upper respiratory tract infection  1  2/64 (3.13%)  2 1/31 (3.23%)  1 0/32 (0.00%)  0 2/64 (3.13%)  2 1/9 (11.11%)  1 0/9 (0.00%)  0 1/23 (4.35%)  1 3/46 (6.52%)  4 2/30 (6.67%)  2 3/59 (5.08%)  3 14/136 (10.29%)  18 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Urinary tract infection  1  1/64 (1.56%)  1 1/31 (3.23%)  1 0/32 (0.00%)  0 0/64 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/23 (0.00%)  0 1/46 (2.17%)  1 1/30 (3.33%)  1 3/59 (5.08%)  3 1/136 (0.74%)  1 0/1 (0.00%)  0 0/2 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/3 (0.00%)  0
Vulvovaginal mycotic infection  1  1/36 (2.78%)  1 0/14 (0.00%)  0 0/18 (0.00%)  0 0/30 (0.00%)  0 0/4 (0.00%)  0 1/4 (25.00%)  1 0/12 (0.00%)  0 0/23 (0.00%)  0 0/13 (0.00%)  0 2/33 (6.06%)  2 2/61 (3.28%)  2 0/1 (0.00%)  0 0/0  0 0/1 (0.00%)  0 0/1 (0.00%)  0 0/1 (0.00%)