A Multicenter, Phase 3b, Open-Label, Single-Arm Study to Investigate Bowel Urgency and Its Relationship With Other Outcome Measures in Adults With Moderately to Severely Active Ulcerative Colitis Treated With Mirikizumab
Phase: PHASE3
Conditions: Ulcerative Colitis, Ulcerative Colitis Chronic
Sponsor: Eli Lilly and Company

Protocol: I6T-MC-AMBZ 
 
 
A Multicenter, Phase 3b, Open-Label, Single-Arm Study to Investigate Bowel Urgency and its 
Relationship with Other Outcome Measures in Adults with Moderately to Severely Active 
Ulcerative Colitis Treated with Mirikizumab 
 
 
NCT05767021 
 
 
Approval Date: 30-Nov-2023 
 
 

CONFIDENTIAL 
I6T-MC-AMBZ(b) 
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Title Page  
Confidential Information 
The information contained in this document is confidential and is intended for the use of clinical investigators. It is the property of 
Eli Lilly and Company or its subsidiaries and should not be copied by or distributed to persons not involved in the clinical 
investigation of mirikizumab (LY3074828) unless such persons are bound by a confidentiality agreement with Eli Lilly and 
Company or its subsidiaries.  
Note to Regulatory Authorities: This document may contain protected personal data and/or commercially confidential information 
exempt from public disclosure. Eli Lilly and Company requests consultation regarding release/redaction prior to any public release. 
In the United States, this document is subject to Freedom of Information Act (FOIA) Exemption 4 and may not be reproduced or 
otherwise disseminated without the written approval of Eli Lilly and Company or its subsidiaries. 
Protocol Title: 
A Multicenter, Phase 3b, Open-Label, Single-Arm Study to Investigate Bowel Urgency and its 
Relationship with Other Outcome Measures in Adults with Moderately to Severely Active 
Ulcerative Colitis Treated with Mirikizumab 
Protocol Number: I6T-MC-AMBZ 
Amendment Number: b 
Compound: Mirikizumab (LY3074828) 
Brief Title: A Study to Investigate Bowel Urgency in Adults with Moderately to Severely 
Active Ulcerative Colitis Treated with Mirikizumab 
Study Phase: 3b 
Acronym: LUCENT-URGE 
Sponsor Name: Eli Lilly and Company 
Legal Registered Address: Indianapolis, Indiana, USA 46285 
Regulatory Agency Identifier Numbers: 
IND: 125444 
EU trial number: 2022-502393-16-00 
Approval Date: Protocol Amendment ( b) Electronically Signed and Approved by Lilly on date 
provided below. 
Document ID: 
 
 
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Medical monitor name and contact information will be provided separately. 
 
 
 
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Protocol Amendment Summary of Changes Table  
 
DOCUMENT HISTORY 
Document 
Date 
Amendment a 
16 Feb 2023 
Original Protocol 
04 Nov 2022 
Amendment [b] 
This amendment is considered to be nonsubstantial. 
Overall Rationale for the Amendment: 
The purpose of this amendment is to achieve the following: 
 
Correct and further clarify the Stool collection guidelines for stool culture/C difficile and 
fecal calprotectin testing at applicable visits 
 
Clarify and emphasize the daily diary compliance requirements for calculating UNRS, 
SF, RB, and MMS scores at applicable visits 
 
Clarify and emphasize the role of site personnel in ensuring participant understanding of 
Normal Number of Stools Questionnaire 
 
Correct and clarify the recommendations and requirements for stool cultures/C difficile 
testing in participants undergoing rescreening, after resolution of prior screen failure due 
to positive stool culture/C difficile test results 
 
Provide examples of mirikizumab “access” under related discontinuation criterion in the 
Continued Access Period (Appendix 12) 
Minor editorial changes are not included in this table. 
Section # and Name 
Description of Change 
Brief Rationale 
1.3 Schedule of 
Activities (SoA) 
Diary compliance check, “retraining as 
needed” added. Another check at V1 
added. 
Comments: added requirement of ≥4 of 7 
days prior to bowel preparation at V1, 
V6, and V10. Text regarding monitoring 
compliance and retraining removed. 
To further clarify and reinforce diary 
completion requirements at critical 
timepoints.  
Normal Number of Stools 
Comments: Modified wording to further 
address required role of site personnel.  
To further clarify and emphasize the role 
of site personnel in ensuring participant 
understanding 
Dispense Stool Collection Kit 
Comments: corrected instructions for V1 
and added detail for V1, V5, and V9 
To correct V1 instructions and clarify 
the number and type of stool collection 
kits to dispense at all relevant visits. 
Stool culture/C difficile 
Comments: added wording to describe 
timing of collection and results at V1. 
To clarify timing of sample collection 
and receipt of results at V1. 
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Section # and Name 
Description of Change 
Brief Rationale 
Fecal calprotectin 
Comments: added wording to describe 
timing of collection for V2, V6, and V10. 
To clarify timing of sample collection 
for V2, V6, and V10. 
Endoscopy with Biopsies 
Comments: Note added for diary 
completion. 
To further clarify and emphasize 
requirements for daily diary completion. 
5.1. Inclusion Criteria 
Criterion 4: Added reference to 
Section 9.3.2. 
To connect and further clarify the diary 
completion requirements for calculating 
the screening UNRS score. 
5.4.1. Allowed 
Rescreening of 
Participants after 
Initial Screen Failure 
Correction of inadvertent wording errors:  
 “(inclusive)” was removed from a 
sentence describing a time period 
within the screening period. 
‘prior to Visit 2’ was added to the 
sentence describing the full screening 
period. 
To gain consistency and further clarify 
the criteria for the two screening-visit 
time periods across several sections of 
the protocol.  
“additional” was removed from the 
sentence describing recommended testing 
of stool cultures before rescreening 
participants with prior screen failure due 
to positive results. 
To correct and gain consistency between 
recommendations made in Section 5.4. 
and in Section 8.2.10. 
8.1.1. Daily Electronic 
Diary Measures 
Wording added to indicate that  2 diary 
measures have different minimal 
completion requirements.  
To clarify this difference 
8.1.2.1. Normal 
Number of Stools 
Added text regarding the specific periods 
of time referred in this questionnaire, and 
the importance for site personnel to  
explain time periods and questions to the 
participants. Also added reference to 
Section 10.6. 
To further clarify and emphasize the 
importance of site personnel’s role in 
ensuring participants’ understanding of 
the wording and time periods used in 
this questionnaire.  
8.2.10 Screening Stool 
Testing 
Stool Culture  
Corrected and expanded the wording for 
testing stool cultures in participants 
undergoing rescreening, after resolution 
of prior screen failure due to positive 
stool-culture results. 
To correct and gain consistency with 
related wording and recommendations in 
Section 5.4., and to also further clarify 
the rescreen testing requirements in 
Section 8.2.10.  
C difficile toxin testing 
Corrected and expanded wording for C 
difficile testing in participants undergoing 
rescreening, after resolution of prior 
screen failure due to positive C difficile 
results. 
To correct and gain consistency with 
related wording and recommendations 
made in Section 5.4., and to also further 
clarify the rescreen testing requirements 
in Section 8.2.10 
9.3.2. Primary 
Endpoint Analysis 
Sentence reworded to state the minimum 
required days (4), instead of the 
maximum missing days (3).  The 
rewording did not change the meaning of 
the sentence. 
To align wording to increase consistency 
with other areas or the protocol, and to 
minimize misunderstanding.  
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Section # and Name 
Description of Change 
Brief Rationale 
10.12. Appendix 12: 
Optional Continued 
Access Period 
10.12.1 
Overview 
 
Added the phrase “and accessible,” and 
parenthetical reference to Section 10.12.7 
to the sentence about approval and 
worldwide commercial availability of 
mirikizumab. 
To connect and align content of the 
Appendix 12 Overview Section 
(10.12.1).with the more detailed content 
of the Discontinuation Section (10.12.7). 
10.12.7. 
Discontinuation of 
Study Intervention and 
Participant 
Discontinuation from 
the Study  
Added examples to the criterion including 
local access of mirikizumab 
 
The word “worldwide” added in 
statement regarding continuous access of 
mirikizumab 
To further clarify and describe the 
meaning of local “access” 
 
 
 
 
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Table of Contents  
1. 
Protocol Summary ........................................................................................................10 
1.1. 
Synopsis ..........................................................................................................................10 
 
 
1.3. 
Schedule of Activities (SoA) ..........................................................................................16 
2. 
Introduction ...................................................................................................................26 
2.1. 
Study Rationale ...............................................................................................................26 
2.2. 
Background .....................................................................................................................26 
2.3. 
Benefit/Risk Assessment ................................................................................................27 
2.3.1. 
Risk Assessment .............................................................................................................27 
2.3.2. 
Benefit Assessment .........................................................................................................28 
2.3.3. 
Overall Benefit Risk Conclusion ....................................................................................28 
3. 
Objectives, Endpoints, and Estimands .......................................................................29 
4. 
Study Design ..................................................................................................................35 
4.1. 
Overall Design ................................................................................................................35 
4.2. 
Scientific Rationale for Study Design ............................................................................35 
4.3. 
Justification for Dose ......................................................................................................36 
4.4. 
End of Study Definition ..................................................................................................37 
5. 
Study Population ...........................................................................................................38 
5.1. 
Inclusion Criteria ............................................................................................................38 
5.2. 
Exclusion Criteria ...........................................................................................................42 
5.3. 
Lifestyle Considerations .................................................................................................45 
5.4. 
Screen Failures ................................................................................................................45 
5.4.1. 
Allowed Rescreening of Participants after Initial Screen Failure ...................................45 
5.4.2. 
Allowed Retesting of Screening Procedures...................................................................46 
5.5. 
Criteria for Temporarily Delaying Enrollment of a Participant .....................................46 
6. 
Study Intervention(s) and Concomitant Therapy .....................................................47 
6.1. 
Study Intervention(s) Administered................................................................................47 
6.1.1. 
Self-Administration Training ..........................................................................................48 
6.2. 
Preparation, Handling, Storage, and Accountability ......................................................48 
6.3. 
Assignment to Study Intervention ..................................................................................48 
6.4. 
Blinding ..........................................................................................................................48 
6.5. 
Study Intervention Compliance ......................................................................................49 
6.6. 
Dose Modification ..........................................................................................................49 
6.7. 
Treatment of Overdose ...................................................................................................49 
6.8. 
Prior and Concomitant Therapy ......................................................................................49 
6.8.1. 
Corticosteroid Use and Taper .........................................................................................50 
6.8.2. 
Prohibited Medications ...................................................................................................51 
6.8.3. 
Vaccine Administration During the Study ......................................................................51 
7. 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal........................................................................................52 
7.1. 
Discontinuation of Study Intervention ............................................................................52 
7.1.1. 
Suicidal Ideation or Behavior .........................................................................................53 
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7.1.3. 
Hypersensitivity Reactions .............................................................................................54 
7.1.4. 
Temporary Discontinuation ............................................................................................54 
7.2. 
Participant Discontinuation/Withdrawal from the Study ................................................55 
7.3. 
Lost to Follow-up............................................................................................................56 
8. 
Study Assessments and Procedures.............................................................................57 
8.1. 
Efficacy Assessments .....................................................................................................57 
8.1.1. 
Daily Electronic Diary Measures ....................................................................................57 
8.1.2. 
Patient-reported Outcomes on the Electronic Tablet ......................................................59 
8.1.3. 
"4E?5/5-:P?8;.-8??1??91:@" ...........................................................................61 
8.1.4. 
Mayo Score .....................................................................................................................61 
8.1.5. 
Endoscopy .......................................................................................................................62 
8.1.6. 
Histopathology Scoring Instrument ................................................................................64 
8.2. 
Safety Assessments .........................................................................................................64 
8.2.1. 
Physical Examination......................................................................................................64 
8.2.2. 
Vital Signs .......................................................................................................................65 
8.2.3. 
Electrocardiograms .........................................................................................................65 
8.2.4. 
Clinical Safety Laboratory Tests ....................................................................................65 
8.2.5. 
Pregnancy Testing ...........................................................................................................66 
8.2.6. 
Suicidal Ideation and Behavior Risk Monitoring ...........................................................67 
8.2.7. 
Tuberculosis Testing and Monitoring .............................................................................67 
8.2.8. 
Hepatitis B and C Testing and Monitoring .....................................................................69 
 
 
8.2.10. Screening Stool Testing ..................................................................................................72 
8.3. 
Adverse Events, Serious Adverse Events, and Product 
Complaints ......................................................................................................................73 
8.3.1. 
Timing and Mechanism for Collecting Events ...............................................................74 
8.3.2. 
Pregnancy ........................................................................................................................75 
8.3.3. 
Adverse Events of Special Interest .................................................................................76 
8.4. 
Pharmacokinetics ............................................................................................................77 
8.5. 
Pharmacodynamics .........................................................................................................78 
8.6. 
Genetics ..........................................................................................................................78 
8.7. 
Biomarkers ......................................................................................................................78 
8.8. 
Immunogenicity Assessments.........................................................................................78 
 
 
9. 
Statistical Considerations .............................................................................................80 
9.1. 
Statistical Hypothesis ......................................................................................................80 
9.1.1. 
Multiplicity Adjustment ..................................................................................................80 
9.2. 
Analysis Sets ...................................................................................................................80 
9.3. 
Statistical Analyses .........................................................................................................80 
9.3.1. 
General Considerations ...................................................................................................80 
9.3.2. 
Primary Endpoint Analysis .............................................................................................80 
9.3.3. 
Secondary Endpoint Analysis .........................................................................................81 
9.3.4. 
Exploratory Analysis ......................................................................................................81 
9.3.5. 
Safety Analyses ...............................................................................................................81 
9.3.6. 
Other Analyses ................................................................................................................82 
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9.4. 
Interim Analysis ..............................................................................................................82 
9.5. 
Sample Size Determination ............................................................................................82 
10. 
Supporting Documentation and Operational Considerations ..................................83 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ................................................................................................................83 
10.1.1. Regulatory and Ethical Considerations ...........................................................................83 
10.1.2. Financial Disclosure........................................................................................................84 
10.1.3. Informed Consent Process ..............................................................................................84 
10.1.4. Data Protection................................................................................................................84 
10.1.5. Committees Structure......................................................................................................85 
10.1.6. Dissemination of Clinical Study Data.............................................................................85 
10.1.7. Data Quality Assurance ..................................................................................................86 
10.1.8. Source Documents ..........................................................................................................87 
10.1.9. Study and Site Start and Closure ....................................................................................88 
10.1.10. Publication Policy ...........................................................................................................88 
10.1.11. Investigator Information .................................................................................................89 
10.1.12. Sample Retention ............................................................................................................89 
10.2. 
Appendix 2: Clinical Laboratory Tests ...........................................................................90 
10.2.1. Laboratory Samples to be Obtained at the Time of a Systemic 
Hypersensitivity Event ....................................................................................................93 
10.3. 
Appendix 3: Adverse Events and Serious Adverse Events: 
Definitions and Procedures for Recording, Evaluating, Follow-
up, and Reporting ............................................................................................................94 
10.3.1. Definition of AE .............................................................................................................94 
10.3.2. Definition of SAE ...........................................................................................................95 
10.3.3. Definition of Product Complaints ...................................................................................96 
10.3.4. Recording and Follow-Up of AE and/or SAE and Product 
Complaints ......................................................................................................................96 
10.3.5. Reporting of SAEs ..........................................................................................................98 
10.3.6. Regulatory Reporting Requirements ...............................................................................98 
10.4. 
Appendix 4: Contraceptive and Barrier Guidance ..........................................................99 
10.4.1. Definitions.......................................................................................................................99 
10.4.2. Contraception Guidance................................................................................................100 
 
 
 
10.6. 
Appendix 6: Mayo Scoring System ..............................................................................104 
 
 
10.8. 
Appendix 8 Examples of Infections That May Be Considered 
Opportunistic in the Setting of Biologic Therapy .........................................................106 
10.9. 
Appendix 9: Tuberculosis Testing ................................................................................108 
10.10. 
Appendix 10: Permitted Concomitant Medications/Therapies .....................................109 
10.11. 
Appendix 11: Prohibited Medications ..........................................................................110 
10.12. 
Appendix 12: Optional Continued Access Period ........................................................112 
10.12.1. Overview .......................................................................................................................112 
 
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10.12.3. Schedule of Activities for Continued Access Period ....................................................114 
10.12.4. Overall Design ..............................................................................................................119 
10.12.5. Study Population ...........................................................................................................119 
10.12.6. Study Intervention .........................................................................................................122 
10.12.7. Discontinuation of Study Intervention and Participant 
Discontinuation from the Study ....................................................................................122 
10.12.8. Safety Assessments .......................................................................................................123 
10.12.9. Permitted Concomitant Medications/Therapies during Continued 
Access ...........................................................................................................................124 
10.12.10 Prohibited Concomitant Medications/Therapies during 
Continued Access..........................................................................................................126 
10.13. 
Appendix 13: Country-specific Requirements .............................................................127 
 
 
10.15. 
Appendix 15: Abbreviations and Definitions ...............................................................133 
10.16. 
Appendix 16: Protocol Amendment History ................................................................139 
11. 
References ....................................................................................................................140 
 
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1. 
Protocol Summary  
1.1. 
Synopsis  
Protocol Title: 
A Multicenter, Phase 3b, Open-Label, Single-Arm Study to Investigate Bowel Urgency and its 
Relationship with Other Outcome Measures in Adults with Moderately to Severely Active 
Ulcerative Colitis Treated with Mirikizumab 
Brief Title: 
A Study to Investigate Bowel Urgency in Adults with Moderately to Severely Active Ulcerative 
Colitis Treated with Mirikizumab 
Regulatory Agency Identifier Numbers: 
IND: 125444 
EU trial number: 2022-502393-16-00 
Rationale: 
Study I6T-MC-AMBZ (AMBZ) is a Phase 3b, open-label, single-arm study to investigate the 
relationship of bowel urgency with other outcome measures in participants with moderately to 
severely active Ulcerative Colitis (UC) treated with mirikizumab. 
Objectives, Endpoints, and Estimands: 
Objectives 
Endpoints 
Primary 
 
To assess the improvement in bowel urgency 
severity at Week 12. 
Change from baseline in bowel urgency 
severity (UNRS) score at Week 12. 
Secondary 
 
To assess the improvement in bowel urgency 
severity at Week 
. 
 
 
To assess the improvement in 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Objectives 
Endpoints 
To assess the improvement in 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
To assess the proportion of 
participants achieving clinical remission 
and a '!$%?/;>1
.  
 
 
 
 
 
 
 
To assess the proportion of participants 
achieving clinical response and 
clinically meaningful change 
in bowel urgency severity.  
 
 
 
 
 
  
To assess the association between 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
To assess associations between bowel 
urgency measures and QoL/functional 
outcome measures and UC symptom 
measures. 
 
 
 
 
 
 
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Objectives 
Endpoints 
 
 
Abbreviations: QoL = quality of life; UC = ulcerative colitis; UNRS = urgency numeric rating scale. 
Estimand 
The primary clinical question of interest is: 
What is the mean change from baseline in Urgency Numeric Rating Scale (UNRS) at Week 12  
 
 
Overall Design 
Study AMBZ is a multicenter, open-label, single-arm Phase 3b study to investigate bowel 
urgency and its relationship with other outcome measures in participants with moderately to 
severely active UC treated with mirikizumab over a 
-week period. 
The study will have 4 study periods: 
Period I (
 days) 
Participants must complete all Visit 1 screening activities within 
 days prior to Visit 2. The 
screening endoscopy must occur within 
days prior to Visit 2. 
Period II (
 weeks) 
Participants will receive 
 mg mirikizumab 
 
 
Period III (
 weeks) 
Participants will receive 
 mg mirikizumab 
 
 
Note: Participants planning to participate in continued access must complete self-administration 
training during at least 2 visits between Visits 6 and 9. 
Upon completion of all Visit 10 activities, eligible participants may enter the Continued Access 
Period. 
Period IV 
Participants who meet the following criteria should enter posttreatment follow-up, including 
completion of Visit 801: 
 
 
 
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An optional continued access will be provided for eligible participants following the completion 
of Period III. 
Brief Summary: 
Study AMBZ is designed to broadly investigate bowel urgency (severity, 
 
), and to evaluate the relationship between 
 and other 
outcome measures. 
Study Population: 
In general, an individual may take part in the study if they 
 Are H18 years and G80 years of age at the time of informed consent 
 Have an established diagnosis of UC ;2H
9;:@4?before Visit 2 (Week ), which 
includes documented endoscopic evidence of UC and a histopathology report that 
supports a diagnosis of UC 
Participants with rectal sparing on the Visit 1 screening endoscopy must have 
documentation of rectal involvement from a prior endoscopy and histopathology report to 
confirm UC diagnosis 
 Have moderately to severely active UC as defined by a modified Mayo score 
  %;2
C5@4-/1:@>-88E>1-01:0;?/;<5/
&41?/;>1?9A?@.1
based on data from @41?/>11:5:31:0;?/;<E<1>2;>910
0-E?.12;>1Visit 2 
 Have current bowel urgen/E0125:10-?-:'!$%?/;>1;2
0A>5:3?/>11:5:3 
 Have demonstrated an inadequate response, loss of response, or intolerance to 
conventional or biologic/JAK inhibitor/S1P receptor modulator 
(biologic/JAK/S1P) therapy for UC 
In general, an individual may not take part in the study if they 
 Have a current diagnosis of >;4:P? 05?1-?1 or inflammatory bowel disease-
unclassified formerly known as indeterminate colitis, or ulcerative proctitis, disease 
limited to the rectum, that is, distal to the recto-sigmoid junction, which lies 
approximately 10 to 15 cm from anal verge. 
 
 Have a history of the following bowel, intestinal or intra-abdominal surgeries: 
o extensive colonic surgery for UC or for other reasons, such as subtotal colectomy, or 
are likely to require surgery for the treatment of UC during the study, 
Participants who had limited colonic surgery for UC, such as a segmental 
resection, may be allowed in the study after discussion with the medical monitor. 
o any small bowel or colonic surgery within 6 months prior to Visit 2, or 
o any non-intestinal intra-abdominal surgery within 3 months prior to Visit 2 
 Have evidence of toxic megacolon, intra-abdominal abscess, or stricture/stenosis 
within the small bowel, colon, or rectum 
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 Have received
 
 for any indication, including investigational use. 
 Have discontinued 
 due to loss of 
response, inadequate response, or intolerance: 
Exception: if discontinuation was due to other reasons, such as a change of insurance or 
well controlled disease, -:0@410A>-@5;:;21D<;?A>1C-?GE1->;:?A8@-@5;:C5@4@41
medical monitor should occur to establish eligibility. 
Number of Participants: 
Approximately 160 participants will be assigned to study intervention. 
Intervention Groups and Duration: 
All enrolled participants will receive mirikizumab. 
Period II (
 weeks): Participants receive 
 mg mirikizumab 
. 
Period III (
 weeks): Participants receive 
 mg mirikizumab 
. 
Ethical Considerations of Benefit/Risk: 
Given both the efficacy and safety data from the Phase 3 adult studies in UC and data from other 
mirikizumab clinical studies completed to date, as well as safety data in ongoing studies of adults 
with UC, the participants receiving mirikizumab in Study AMBZ have the potential for clinical 
benefit with an acceptable safety profile. 
Data Monitoring Committee: No 
 
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a Participants who are eligible for continued access should move directly from Visit 10 to Visit 501, on the same day, if possible. Visit 801 should not be 
performed. 
b Optional Continued Access Period is described in Section 10.12. 
 
 
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1.3. 
Schedule of Activities (SoA)  
Period I 
Completion of the Visit 1 screening activities requires more than 1 day. 
Period II 
Visit 3 is a telephone visit. All safety assessments should be performed by telephone. 
Period III 
Upon completion of all Visit 10 activities, eligible participants may enter the Continued Access Period. These participants will move 
directly from Visit 10 to Visit 501 of the Continued Access Period if they meet requirements detailed in Section 10.12. 
Period IV 
Visit 801, a telephone visit, should be performed 
 days after the participantPs last visit, either Visit 10 or the ED visit. 
Visit 801 may be performed onsite when onsite activities are required or at 5:B1?@53-@;>P?discretion. 
Early discontinuation (ED) visit 
Required for all participants who discontinue mirikizumab treatment prior to Visit 10. 
Unscheduled visits (UV) 
May occur as needed, on any day without regard to visit interval. Required activities are indicated in the SoA. Additional procedures 
may be performed at the 5:B1?@53-@;>P? discretion. 
 
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I 
II 
III 
 
IV 
Comments 
Visit number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
ED 
UV 
801 
Dosing visits: complete all visit 
activities before administration of 
mirikizumab. 
Weeks from 
treatment assignment 
 
Study day 
 
Visit interval 
tolerance (days) 
 
Visit location 
O 
O 
T 
O 
O 
O 
O 
O 
O 
O 
O 
O 
T 
O = Onsite, T = Telephone 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
The informed consent form (ICF) 
must be signed before any protocol-
specific activities are performed. 
See Section 10.1.3. 
Inclusion and exclusion 
criteria, review and 
confirm eligibility 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Confirm before Visit 2 assignment 
and administration of first dose. 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Includes year of birth, sex, race, and 
ethnicity (where permissible). 
Preexisting conditions 
and medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Collect all ongoing conditions; 
relevant surgical or medical history. 
Prespecified medical 
history (UC and history 
of interest) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Collect additional data for UC and 
comorbidities of interest. 
Prior treatments for UC 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Substance use 
including alcohol, 
caffeine, tobacco, 
nicotine  
X 
 
 
 
 
X 
 
 
 
X 
X 
 
X 
 
Concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Refer to Section 6.8. 
Adverse events (AEs) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
See Sections 8.3.1 and 8.3.3.  
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I 
II 
III 
 
IV 
Comments 
Visit number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
ED 
UV 
801 
Dosing visits: complete all visit 
activities before administration of 
mirikizumab. 
Weeks from 
treatment assignment 
 
Study day 
 
Visit interval 
tolerance (days) 
 
Visit location 
O 
O 
T 
O 
O 
O 
O 
O 
O 
O 
O 
O 
T 
O = Onsite, T = Telephone 
Pre-endoscopy 
instructions and 
reminders 
X 
 
 
 
X 
 
 
 
X 
 
 
 
 
Includes diary compliance, dates, 
and bowel preparation/procedure 
Physical Evaluation 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
 
 
 
X 
 
 
 
X 
X 
 
 
 
Vital signs 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
XW 
W optional per investigator 
discretion. See Section 8.2.2.  
Physical examination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.1. 
Symptom-directed 
physical assessment 
 
X 
 
May perform at any visit, per investigator 
discretion 
X 
X 
X 
XW 
W;<@5;:-8<1>5:B1?@53-@;>
discretion. See Section 8.2.1. 
Evaluate for EIMs 
X 
X 
 
May perform at any visit, per investigator 
discretion 
X 
X 
 
 
See Section 8.2.1. 
Tuberculosis (TB) 
evaluation 
 
X 
 
 
 
X 
 
X 
 
X 
X 
 
 
Risk factors and symptoms of active 
TB. See Section 8.2.7.  
Chest X-ray 
X 
 
 
 
 
 
 
 
 
 
 
 
 
For instructions and exceptions, see 
Section 8.2.7.1. 
12-lead ECG (local) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.3. 
Participant Diary (Electronic) 
Diary dispensed 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Explain use of device and each 
measure. See Section 8.1.1. 
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I 
II 
III 
 
IV 
Comments 
Visit number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
ED 
UV 
801 
Dosing visits: complete all visit 
activities before administration of 
mirikizumab. 
Weeks from 
treatment assignment 
 
Study day 
 
Visit interval 
tolerance (days) 
 
Visit location 
O 
O 
T 
O 
O 
O 
O 
O 
O 
O 
O 
O 
T 
O = Onsite, T = Telephone 
Diary compliance 
check, retraining as 
needed 
XZ 
X 
X 
X 
X 
XZ 
X 
X 
X 
XZ 
X 
 
 
 
XZ: Site personnel must ensure 
diary completed on 4 or more (H4) 
of 7 days prior to bowel preparation 
at V1, V6, and V10. See Section 
8.1.1. 
Diary returned 
 
 
 
 
 
 
 
 
 
X 
X 
 
 
 
Patient-Reported Outcomes (Electronic tablet)  
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
X 
X 
X 
 
 
 
X 
X 
 
 
 
 
 
X 
 
 
 
X 
 
X 
 
X 
X 
 
 
 
 
 
X 
 
 
 
X 
 
X 
 
X 
X 
 
 
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I 
II 
III 
 
IV 
Comments 
Visit number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
ED 
UV 
801 
Dosing visits: complete all visit 
activities before administration of 
mirikizumab. 
Weeks from 
treatment assignment 
 
Study day 
 
Visit interval 
tolerance (days) 
 
Visit location 
O 
O 
T 
O 
O 
O 
O 
O 
O 
O 
O 
O 
T 
O = Onsite, T = Telephone 
 
X 
 
 
 
X 
 
X 
 
X 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
 
 
Clinician-Administered Assessments  
 
 
 
Baseline/Screening 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Complete on electronic tablet, by 
site staff trained on C-SSRS. See 
Section 8.2.6.1. 
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I 
II 
III 
 
IV 
Comments 
Visit number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
ED 
UV 
801 
Dosing visits: complete all visit 
activities before administration of 
mirikizumab. 
Weeks from 
treatment assignment 
 
Study day 
 
Visit interval 
tolerance (days) 
 
Visit location 
O 
O 
T 
O 
O 
O 
O 
O 
O 
O 
O 
O 
T 
O = Onsite, T = Telephone 
"4E?5/5-:P?8;.-8
Assessment (PGA) 
 
X 
 
 
 
X 
 
 
 
X 
X 
 
 
Complete on electronic tablet. See 
Section 8.1.3. 
Laboratory Tests and Sample Collections 
Hematology  
X 
X 
 
X 
X 
X 
 
X 
 
X 
X 
XW 
XW 
W Optional per investigator 
discretion 
Clinical chemistry 
X 
X 
 
X 
X 
X 
 
X 
 
X 
X 
XW 
XW 
W Optional per investigator 
discretion 
Urinalysis 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy 
X 
 
 
 
 
 
 
 
 
 
 
 
 
For WOCBP. See Section 8.2.5. 
Urine pregnancy (local) 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
WOCBP; negative test required 
prior to dosing at marked visits. See 
Section 8.2.5. 
Follicle Stimulating 
Hormone (FSH) 
XW 
XW 
 
 
 
W Optional per investigator 
discretion , to confirm 
postmenopausal status. See Section 
8.2.5. 
Tuberculosis (TB) 
Testing 
  
X 
 
 
 
 
 
 
 
 
XU 
 
 
 
QuantiFERON®-TB Gold; central 
or local laboratory. See Section 
8.2.7. 
U Visit 10: Perform only if 
necessary, per local requirements.  
HIV screening test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
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I 
II 
III 
 
IV 
Comments 
Visit number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
ED 
UV 
801 
Dosing visits: complete all visit 
activities before administration of 
mirikizumab. 
Weeks from 
treatment assignment 
 
Study day 
 
Visit interval 
tolerance (days) 
 
Visit location 
O 
O 
T 
O 
O 
O 
O 
O 
O 
O 
O 
O 
T 
O = Onsite, T = Telephone 
Hepatitis C virus 
(HCV) screening tests 
X 
 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.8.2. 
Hepatitis B virus 
(HBV) screening tests 
X 
 
 
 
 
 
 
 
 
 
 
 
 
See Section 8.2.8.1. 
HBV DNA 
 
 
 
 
 
X 
 
X 
 
 
X 
X 
 
Only if positive serology at 
screening. See Section 8.2.8.1. 
Immunogenicity 
(ADA) samples: 
predose 
 
X  
 
 
 
 
 
 
 
 
 
 
 
 
Immunogenicity 
(ADA) samples 
 
In the event of 
 
 related event- Collect PK and ADA samples 
 
 
Collect PK and ADA samples as 
detailed in Section 10.2. 
Pharmacokinetic (PK) 
samples 
 
 
 
Stool Sample Collection and Testing 
Dispense stool 
collection kit 
X 
 
 
 
X 
 
 
 
X 
 
 
 
 
V1 = 2 kits: Stool culture/C difficile 
and fecal calprotectin  
V5/V9 = 1 kit: fecal calprotectin   
See Section 8.2.10. 
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I 
II 
III 
 
IV 
Comments 
Visit number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
ED 
UV 
801 
Dosing visits: complete all visit 
activities before administration of 
mirikizumab. 
Weeks from 
treatment assignment 
 
Study day 
 
Visit interval 
tolerance (days) 
 
Visit location 
O 
O 
T 
O 
O 
O 
O 
O 
O 
O 
O 
O 
T 
O = Onsite, T = Telephone 
Stool culture 
 
oxin 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Instruct participant to collect their 
stool sample as soon as possible 
during screening/V1,  to allow for 
receipt of test results prior to V1 
endoscopy. The test results must be 
negative at screening. See Section 
8.2.10. 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
Instruct participant to collect their 
stool sample as follows: 
V2: After V1 endoscopy and before 
V2 dosing.  
V6/V10: 3 or less (G
) days prior to 
day of bowel prep 
Endoscopy Procedures and Sample Collection 
 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
See Section 8.1.5. 
Note: For eligibility, diary must be 
completed for 4 or more (H4) of the 
7 days prior to bowel preparation 
for endoscopy 
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I 
II 
III 
 
IV 
Comments 
Visit number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
ED 
UV 
801 
Dosing visits: complete all visit 
activities before administration of 
mirikizumab. 
Weeks from 
treatment assignment 
 
Study day 
 
Visit interval 
tolerance (days) 
 
Visit location 
O 
O 
T 
O 
O 
O 
O 
O 
O 
O 
O 
O 
T 
O = Onsite, T = Telephone 
Stored Samples 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
See Sections 8.7 and 8.1.5.4. 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
 
Registration and Dosing 
Register visit with 
IWRS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
Assign Treatment with 
IWRS 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Dispense mirikizumab 
via IWRS 
 
X 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
See Section 6.1. 
Administer 
mirikizumab 
 
X 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
See Section 6.1. 
Self-Administration Training 
Provide training on 
self-administration  
 
 
 
 
 
X* 
X* 
X* 
X* 
 
 
 
 
*Completion of training required for 
Continued Access Period. See 
Section 6.1.1. 
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Abbreviations: ADA = anti-drug antibody DNA = deoxyribonucleic acid; ECG = electrocardiogram; ED = early discontinuation; EIM = extraintestinal 
manifestation; HIV = human immunodeficiency virus; IWRS = interactive web-response system; UC = ulcerative colitis; UV = Unscheduled Visit; V = visit; 
WOCBP = woman of childbearing potential. 
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2. 
Introduction  
2.1. 
Study Rationale  
Study I6T-MC-AMBZ (AMBZ) is a Phase 3b, open-label, single-arm study to investigate the 
relationship of bowel urgency with other outcome measures in participants with moderately to 
severely active UC treated with mirikizumab. 
2.2. 
Background  
Disease state 
UC is a chronic relapsing and remitting disease characterized by inflammation, ulceration, and 
bleeding in the colon and rectum. Symptoms include diarrhea; RB; bowel urgency; and 
tenesmus, a feeling of incomplete evacuation of the rectum after defecation, even though there is 
no remaining stool to expel. UC has a relapsing–remitting course, meaning that many individuals 
have intermittent disease flares that are interspersed with periods of remission. 
Treatment goals 
Treatment goals in UC traditionally include induction of remission, typically within a 6- to 12-
week time frame, and maintenance of remission in the longer term as assessed over 52 weeks of 
continuous treatment in clinical studies. 
In both clinical practice and clinical studies, clinical response and clinical remission are assessed 
by a combination of improvement in the endoscopic appearance of the mucosa and healing of 
ulcers and patient-reported outcomes, including a reduction in SF and a resolution of RB 
(Levesque et al. 2015). Control of intestinal inflammation in UC is associated with a reduction in 
corticosteroid use, risk of hospitalization, colectomy and, in the longer term, UC-associated 
dysplasia and colorectal cancer. 
Importance of bowel urgency 
More than 80% of individuals with UC experience bowel urgency (Petryszyn et al. 2018; 
Nóbrega et al. 2018; Newton et al. 2019; Dulai et al. 2020) and 50% experience bowel urgency 
at least once a day (Petryszyn et al. 2018). More than 40% of individuals experience bowel 
urgency, even when SF and RB measure scores are 0 (Hibi et al. 2020). An estimated 36% to 
54% of individuals with UC report having a deferral time (make it to the bathroom on time) of 
less than 5 minutes and nearly 18% have less than 2 minutes. In severe cases, individuals have 
less than 30 seconds to make it to the bathroom. These data demonstrate that bowel urgency has 
a significant negative impact on the QoL, and the functional ability of individuals with UC. 
The American College of Gastroenterology clinical guidelines specifically highlight the need to 
evaluate urgency of defecation when diagnosing and assessing disease severity, driving a 
growing need to characterize this endpoint for clinical practice. Regulatory bodies are also 
interested in defining and validating patient-reported outcomes beyond SF and RB, with bowel 
urgency being one of the most relevant symptoms to patients (Danese et al. 2019). 
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I6T-MC-AMBZ(b) 
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Despite its significant impact, robust examination of bowel urgency has only recently been 
incorporated into clinical investigations and is now increasingly considered an emerging 
endpoint in clinical studies. 
Mirikizumab 
Mirikizumab (LY3074828) is a humanized immunoglobulin G4 monoclonal antibody that binds 
to the p19 subunit of IL-23, a cytokine associated with mucosal inflammation (Croxford et al. 
2014; Gheita et al. 2014; Globig et al. 2014; El-Bassat et al. 2016). 
Preclinical and clinical data to date support the development of mirikizumab as a treatment for 
moderately to severely active UC. 
A detailed description of the chemistry, pharmacology, nonclinical and clinical efficacy, and 
safety of mirikizumab is provided in the IB. 
See Section 4.3 for results from the Phase 3 studies in participants with moderately to severely 
active UC. 
2.3. 
Benefit/Risk Assessment  
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of mirikizumab may be found in the IB. 
2.3.1. 
Risk Assessment  
Risks due to Common Study Procedures 
Potential Risks of Clinical 
Significance 
Summary of Data/ 
Rationale for Risk 
Mitigation Strategy 
Risk associated with the 
endoscopic procedures 
including bleeding and 
colonic perforation. 
These risks are considered 
rare but are recognized risks 
for endoscopic procedures. 
(Rabeneck et al. 2008; Arora 
et al. 2009) 
Trained and experienced 
endoscopists will be 
performing endoscopic 
assessments. 
Blood collection volumes 
may exceed usual standard of 
care volume for a single visit. 
 
Blood volumes are calculated 
for every visit and where 
potentially problematic, 
sample collections may be 
eliminated based on 
prioritization guidance. 
Evaluation of safety data from mirikizumab clinical studies examining psoriasis, UC, and CD, 
shows a safety profile consistent with the anti-IL-23 p19 antibody class. 
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I6T-MC-AMBZ(b) 
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2.3.2. Benefit Assessment  
At the time of this benefit/risk assessment, mirikizumab has demonstrated efficacy in 
 Phase 3, placebo-controlled studies in adults with 
o psoriasis (Papp et al. 2020), and 
o UC (D’Haens et al. 2022) 
 Phase 2 studies in adults with 
o psoriasis (Reich et al. 2019) 
o UC (Sandborn et al. 2018; D’Haens et al. 2019), and 
o CD (Sands et al. 2019, 2020). 
The potential benefits from participation in this study include 
 clinical remission 
 reduced bowel urgency 
 clinical response 
 endoscopic remission 
 symptomatic remission, and 
 improvement in endoscopic histologic inflammation. 
2.3.3. Overall Benefit Risk Conclusion  
Given both the efficacy and safety data from the Phase 3 adult studies in UC and data from other 
mirikizumab clinical studies completed to date, as well as safety data in ongoing studies of adults 
with UC, the participants receiving mirikizumab in Study AMBZ have the potential for clinical 
benefit with an acceptable safety profile. 
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3. 
Objectives, Endpoints, and Estimands  
Objectives 
Endpoints 
Primary 
 
To assess the improvement in bowel 
urgency severity at Week 12. 
Change from baseline in bowel urgency severity (UNRS) 
score at Week 12. 
Secondary 
 
To assess the improvement in bowel 
urgency severity at Week 
. 
To assess the improvement in 
 
 
 
To assess the improvement in 
 
 
 
To assess the proportion of 
participants achieving clinical 
remission and a '!$%?/;>1
.  
To assess the proportion of 
participants achieving clinical 
response and clinically meaningful 
change in bowel urgency severity.  
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To assess the association 
between 
. 
To assess associations 
between bowel urgency measures 
and QoL/functional outcome 
measures and UC symptom 
measures. 
 
Exploratory 
 
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Abbreviations: QoL = quality of life, UC = ulcerative colitis, UNRS = urgency numeric rating scale. 
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4. 
Study Design  
4.1. 
Overall Design  
This is a multicenter, open-label, single-arm Phase 3b study to investigate bowel urgency and its 
relationship with other outcome measures in participants with moderately to severely active UC 
treated with mirikizumab over a 
-week period. 
Design 
The study will have 4 study periods: 
Period I (
 days) 
Participants must complete all Visit 1 screening activities within 
 days prior to Visit 2. The 
screening endoscopy must occur within 
 days prior to Visit 2. 
Period II (
 weeks) 
Participants will receive 
 mg mirikizumab 
. 
Period III (
 weeks) 
Participants will receive 
 mg mirikizumab 
 
. 
Note: Participants planning to participate in continued access must complete self-administration 
training during at least 2 visits between Visits 6 and 9 (see Section 6.1.1). Upon completion of all 
Visit 10 activities, eligible participants may enter the Continued Access Period. 
Period IV 
Participants who meet the following criteria should enter posttreatment follow-up, including 
completion of Visit 801: 
 
 
 
An optional continued access will be provided for eligible participants following the completion 
of Period III. See Section 10.12. 
See 
 Section 1.3 for the SoA. 
4.2. 
Scientific Rationale for Study Design  
Study AMBZ is designed to broadly investigate bowel urgency (severity, 
 
), and to evaluate the relationship between the components of bowel urgency and other 
outcome measures. 
In Studies I6T-MC-AMAN and I6T-MC-AMBG, improvement in bowel urgency severity was 
reported as early as Week 2 after the first induction dose of mirikizumab, and this improvement 
became statistically significant compared to placebo at Week 12 of induction dosing. The 
mirikizumab treatment group continued to have incremental improvement in bowel urgency 
severity through Week 20 (Week 8 of SC mirikizumab maintenance dosing) and then plateaued 
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for the remainder of the maintenance period. These results support the use of a 
-week 
mirikizumab 
 induction period and a 
-week mirikizumab 
 dosing period in this study. 
Primary and secondary endpoints 
See Section 2.2 for the background rationale for the primary endpoint. 
The bowel urgency endpoint (UNRS) in Studies AMAC, AMAN and AMBG was constructed in 
alignment with FDA guidance to assess mean change of severity. Mean change from baseline in 
UNRS was added as a gated endpoint to the LUCENT clinical program based on results of the 
binary analysis of bowel urgency in the Phase 2 Study AMAC.  
The results from the LUCENT clinical program suggest that while the mean change in bowel 
urgency severity is a relevant, differentiating endpoint at the population level, there is a need to 
further characterize bowel urgency with 
 
. In addition to investigating a broader characterization of bowel urgency in 
UC, providing a better understanding of the association between bowel urgency and other 
clinical outcomes would further advance the scientific understanding of urgency and inform the 
clinical community. 
Collection of demographic information 
In this study, collection of demographic information includes race and ethnicity (where 
permissible). The scientific rationale is based on the need to assess variable response of the 
endpoints based on race or ethnicity. This question can be answered only if all the relevant data 
are collected. 
4.3. 
Justification for Dose  
The induction and maintenance dose levels and regimens in Study AMBZ were based on 
analyses of PK, safety, and efficacy data from the following studies of mirikizumab in 
participants with moderate to severe UC: 
 AMAC: Phase 2 study with a 12-week IV 5:0A/@5;:-:0G	-week SC maintenance 
 AMAN (LUCENT-1): Phase 3 induction study with a 12-week IV treatment duration 
o Active dosing regimen: 300 mg mirikizumab IV Q4W, and 
 AMBG (LUCENT-2): Phase 3 maintenance study with a 40-week SC treatment duration. 
o Active dosing regimen: 200 mg mirikizumab SC Q4W. 
Study AMAN was a Phase 3, randomized, double-blind, placebo-controlled study designed to 
evaluate the safety and efficacy of mirikizumab over a 12-week induction period. Responders to 
mirikizumab induction treatment in AMAN were re-randomized to receive blinded mirikizumab 
200 mg or placebo subcutaneously Q4W for 40 weeks in the AMBG study. 
Study AMBG was a Phase 3, randomized, double-blind, placebo-controlled study evaluating the 
safety and efficacy of mirikizumab 200 mg SC Q4W in maintaining treatment response after 52 
weeks of continuous study intervention treatment. 
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Efficacy results from Studies AMAN and AMBG 
Studies AMAN and AMBG demonstrated that both the induction and maintenance dosing 
regimens provided clinically meaningful and statistically significant efficacy. 
Study AMAN demonstrated that mirikizumab induction dosing of 300 mg mirikizumab IV Q4W 
was consistently superior to placebo in the treatment of moderately to severely active UC for all 
primary and major secondary endpoints.  
Study AMBG demonstrated that 200 mg mirikizumab SC Q4W was superior to placebo at 
achieving the primary endpoint of clinical remission and all major secondary endpoints at Week 
40, which was representative of 52 weeks of continuous treatment.  
In both the induction and maintenance studies, the mirikizumab treatment groups were 
consistently superior to placebo across clinical, symptomatic, QoL, endoscopic, and histologic 
measures. 
 
 
Safety results from Studies AMAN and AMBG 
The proportion of participants with TEAEs was similar between mirikizumab and placebo 
groups during both AMAN and AMBG studies. 
The frequency of SAEs and discontinuations of study treatment due to AEs were numerically 
lower in the mirikizumab group compared to placebo in both studies. 
More detailed information about the safety and dosing rationale for mirikizumab may be found 
in the IB. 
4.4. 
End of Study Definition  
The end of the study is defined as the date of last visit for the last participant in the study 
globally. 
A participant is considered to have completed the main study if the participant has completed 
study periods I-III and all required procedures for Visit 801 or Visit 501 as outlined in Sections 
1.3 and 10.12.3, respectively. 
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5. 
Study Population  
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
5.1. 
Inclusion Criteria  
Participants are eligible to be included in the study only if all the following criteria apply: 
Age 
1. Are H18 years -:0G80 years of age at the time of signing the informed consent. 
Type of participant and disease characteristics 
2. Have an established diagnosis of UC for H
9;:@4?.12;>1Visit 2 (Week ), which includes 
documented endoscopic evidence of UC and a histopathology report that supports diagnosis 
of UC (see Section 8.1.5.4). 
Participants with rectal sparing on the Visit 1 screening endoscopy must have 
documentation of rectal involvement from a prior endoscopy and histopathology report to 
confirm UC diagnosis. 
3. Have moderately to severely active UC as defined by a MMS of 
 with a centrally read 
. The scores must be based on data from the screening endoscopy performed G14 days 
before Visit 2 (see Section 8.1.5.4). 
4. Have current bowel urgency, defined as an UNRS score of  or more 
 during screening 
(see Section 9.3.2). 
5. Have evidence of UC extending proximal to the rectum. 
6. Participants with a history of UC for 
 years have had a surveillance colonoscopy with 
biopsies completed within 
 prior to Visit 2, with documented negative results for 
colorectal dysplasia and cancer. 
Participants with primary sclerosing cholangitis, regardless of duration of UC diagnosis, 
have had a surveillance colonoscopy with biopsies completed within  year prior to Visit 2, 
with documented negative results for colorectal dysplasia and cancer. 
For participants who do not have documented negative results for colorectal dysplasia and 
cancer from a surveillance colonoscopy with biopsies completed as above, the investigator 
should perform a colonoscopy with biopsies as the endoscopic procedure at Visit 1 to meet 
this inclusion criteria and other study requirements. A documented negative result is needed 
prior to Visit 2 to meet this inclusion criterion. See detailed requirements in Section 8.1.5.2. 
Surveillance biopsies should be collected and sent to a local laboratory for testing and 
documentation of results. 
Sex and contraceptive/barrier requirements 
7. Are male or female and agree to adhere to the contraception requirements for the study. 
Contraceptive use by participants should be consistent with local regulations regarding 
the methods of contraception for those participating in clinical studies. For the 
contraception requirements of this protocol, see Section 10.4. 
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Informed consent 
8. Are capable of giving signed informed consent as described in Section 10.1.3, which 
includes compliance with the requirements and restrictions listed in the ICF and in this 
protocol. 
Prior medication use 
9. Have met conditions for either conventional-failure or biologic/JAK inhibitor/S1P receptor 
modulator (biologic/JAK/S1P) failure stated in 9a OR 9b. Documentation of dose, 
frequency, route of administration, and duration of use for the prior failed treatment is 
required. 
9a. Conventional-failed participants 
A conventional-failed participant is one who had an inadequate response to, a loss 
of response to, or an intolerance to at least 1 of the conventional medications 
described in the table below 
Conventional 
Medication  
Criteria for Inadequate Response, Loss of Response, or 
Intolerance 
Corticosteroid 
 
 
Corticosteroid-refractory colitis defined as 
 
signs or symptoms of active UC despite taking oral prednisone, or 
equivalent oral corticosteroid, at doses of ≥30 mg/day for ≥2 
weeks. 
Exception: budesonide MMX and beclomethasone dipropionate 
gastro-resistant prolonged-release tablet are not included in this 
category. 
Corticosteroid-dependent colitis defined as 
 
an inability to taper or reduce corticosteroid dose below the 
equivalent of prednisone 10 mg/day within 3 months of starting 
corticosteroids without a return of signs or symptoms of active 
UC, or 
 
a relapse ≤3 months after completing a course of corticosteroids. 
History of intolerance of corticosteroids defined as AEs including, but 
not limited to 
 
cataracts 
 
Cushing’s syndrome 
 
hyperglycemia 
 
hypertension 
 
osteopenia/osteoporosis, or 
 
neuropsychiatric AEs, including insomnia 
Immunomodulator 
 
Signs or symptoms of persistently active UC despite ≥3 months 
treatment with 1 of the following:  
 oral AZA (≥1.5 mg/kg/day) or 6-MP (≥0.75 mg/kg/day) 
 oral AZA or 6-MP within a therapeutic range as judged by 
thioguanine metabolite testing, or 
 a combination of a thiopurine and allopurinol within a therapeutic 
range as judged by thioguanine metabolite testing. 
History of intolerance to at least 1 immunomodulator listed above 
defined as AEs including, but not limited to 
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nausea/vomiting 
 
abdominal pain 
 
pancreatitis 
 
liver function test abnormalities, and 
 
lymphopenia/blood dyscrasias 
 
Additionally,
 
 
 
 
 
9b. Biologic/JAK/S1P-failed participants 
A biologic/JAK/S1P-failed participant is one who had an inadequate response to, 
a loss of response to, or an intolerance to 1 of the medications listed below. 
 
Medications used to qualify the participant for entry into this category must be 
approved in the US, UK, or European Union for the treatment of 
UC. Investigators must be able to document an adequate course of the medication. 
 
Biologic/JAK/S1P-failed 
Categories 
Criteria for Inadequate Response, Loss of Response, or 
Intolerance 
Anti-TNF 
for example, 
adalimumab, golimumab, 
infliximab 
 
JAK inhibitor 
for example, tofacitinib, 
upadacitinib 
 
Anti-integrin 
vedolizumab only 
 
S1P receptor modulator 
for example, ozanimod 
Signs and symptoms of persistently active disease despite 
completion of the induction dosing regimen that is indicated in the 
relevant product label. 
Recurrence of signs and symptoms of active disease after prior 
clinical benefit during approved maintenance dosing. 
History of intolerance, including but not limited to infusion-related 
event, demyelination, congestive heart failure, or any other drug-
related AE that led to a reduction in dose or discontinuation of the 
medication. 
Note: Participants who discontinue these therapies for reasons other than stated above do not 
qualify for criterion 9b. 
 
 
 
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Participants previously exposed to investigational therapies for the treatment of 
UC must still meet conditions stated in 9a OR 9b. 
 
10. If participants are receiving 1 of these permitted therapies, they should continue the stable 
dose regimen during Study Periods I and II, as detailed in Section 10.10. 
 
Oral 5-aminosalicylic acid and sulfasalazine therapy if the prescribed dose has been 
stable for 
 prior to the screening endoscopy. 
 
Oral corticosteroid therapy (prednisone G20 mg/day or equivalent, or budesonide 
extended->181-?1G930-E@-.81@?+.A01?;:501  *,, or beclomethasone 
dipropionate [gastro-resistant, prolonged-release tablet] 5 mg/day) if the prescribed 
dose has been stable for 
 before the screening endoscopy. 
 
AZA, 6-MP, and methotrexate if the prescribed dose has been stable for 
 
before the screening endoscopy. 
11. Agree to abstain from recreational or medicinal marijuana use during the study. 
Study procedures 
12. Are willing and able to complete the scheduled study assessments and procedures, including 
venous access sufficient to allow blood sampling, endoscopy procedures, and completion of 
daily diary entries and study site questionnaires. 
13. Have clinically acceptable central laboratory results during screening, as defined in the 
 
 
Retesting within the screening period is allowed for hematology and chemistry; see Section 5.4. 
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5.2. 
Exclusion Criteria  
Participants are excluded from the study if any of the following criteria apply: 
Gastrointestinal exclusion criteria 
14. Have a current diagnosis of 
 
CD 
 
inflammatory bowel disease-unclassified, formerly known as indeterminate colitis, 
or 
 
ulcerative proctitis, disease limited to the rectum, that is, distal to the recto-sigmoid 
junction, which lies approximately 10 to 15 cm from anal verge. 
15. Have an inherited immunodeficiency syndrome or a monogenic cause of UC-like colonic 
inflammation. 
16. Have a history of the following bowel, intestinal or intra-abdominal surgeries 
 
extensive colonic surgery for UC or for other reasons, such as subtotal colectomy, or 
are likely to require surgery for the treatment of UC during the study. 
o Participants who had limited colonic surgery for UC, such as a segmental 
resection, may be allowed in the study after discussion with the medical monitor. 
 
any small bowel or colonic surgery within  months prior to Visit 2, or 
 
any non-intestinal intra-abdominal surgery within  months prior to Visit 2. 
17. Have evidence of toxic megacolon, intra-abdominal abscess, or stricture/stenosis within the 
small bowel, colon, or rectum. 
Adenoma, dysplasia, and gastrointestinal cancer 
18. Have any history or current evidence of cancer of the gastrointestinal tract. 
19. Have any current sporadic adenoma without dysplasia (adenomatous polyps occurring 
proximal to known areas of colitis), that has not been removed. If completely removed, this 
criterion would no longer apply. 
20. Have any history or current evidence of colonic dysplasia, including 
 
polypoid or non-polypoid lesion(s) of colonic mucosa in an area which is 
endoscopically visible or invisible, and 
 
histopathology report of M5:0125:5@12;>0E?<8-?5-N8;C-grade dysplasia, or high-
grade dysplasia. 
Prohibited medications 
21. Have received any medication prohibited within the required screening washout period, as 
described in Section 10.11. 
22. Have received 
 
for any indication, including investigational use. 
23. Have discontinued 
 due to loss of response, inadequate 
response, or intolerance: 
Exception: if discontinuation was due to other reasons, such as a change of insurance or 
well controlled disease, and the 0A>-@5;:;21D<;?A>1C-?
E1->. Consultation with the 
medical monitor should occur to establish eligibility. 
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24. Have failed >3 
. 
Note: originator and biosimilar count as 1 therapy (for example, 
 
biosimilar). 
Infectious disease exclusion criteria 
25. Have active TB (Section 8.2.7). 
26. Have or have had LTBI that has not been treated with a complete course of appropriate 
therapy as defined by the WHO or the US CDC, unless such treatment is underway (Section 
8.2.7). 
27. Have received any live vaccine (that is, live attenuated) within 3 months prior to Visit 2, or 
intend to receive a live attenuated vaccine during the study. See Section. 6.8.3. 
28. Have received a BCG vaccination or treatment within 
 months prior to Visit 2 or intend to 
receive BCG vaccination or treatment during the study. 
29. Have HIV infection. 
30. Have a current infection with HBV, that is, positive for HBsAg and/or PCR positive for 
HBV DNA (see Section 8.2.8). 
31. Have a current infection with HCV, that is, positive for HCV RNA (see Section 8.2.8). 
Exception: Participants with a previous HCV infection that was successfully 
treated with antiviral therapy are not excluded. 
32. Have Clostridioides difficile or other intestinal infection within 
days of screening 
endoscopy, or test positive at screening for C difficile or for other intestinal pathogens. 
Participants with a confirmed diagnosis of cytomegalovirus-associated colitis should have 
adequate treatment and resolution of symptoms at least  months prior to screening 
endoscopy. 
33. Have a current or recent acute, active nonserious extraintestinal infection for which signs or 
symptoms are present, or if current treatment is not completed  weeks prior to screening. 
34. Have had any of the following types of infection within 
 days prior to Visit 1, or develops 
any of these infections before Visit 2: 
 
Serious: requiring hospitalization, IV or equivalent oral antibiotic treatment, or both. 
 
Opportunistic: see Section 10.8. 
Note: Herpes zoster is considered active and ongoing until all vesicles are dry and 
crusted over. 
 
Chronic: defined as duration of symptoms, signs, or treatment of 6 weeks or longer. 
 
Recurring: including, but not limited to, herpes simplex, herpes zoster, recurring 
cellulitis, and chronic osteomyelitis. 
Note: Participants with only recurrent mild and uncomplicated orolabial herpes, or 
genital herpes, or both may be discussed with the medical monitor and considered for 
enrollment if other study eligibility criteria are met. 
35. Have serious, opportunistic, or chronic/recurring extraintestinal infections who are not 
adequately treated and off antibiotics for 
 days without recurrence of symptoms prior to 
Visit 1. 
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36. Have evidence of active/infectious herpes zoster infection or primary varicella zoster 
infection 
C117?<>5;>@;Visit 1. Infections are considered active until all vesicles are 
crusted over. 
Other exclusion criteria 
37. Are investigator site personnel directly affiliated with this study and/or their immediate 
families. Immediate family is defined as a spouse, parent, child, or sibling, whether 
biological or legally adopted. 
38. Are Eli Lilly and Company employees or employees of third-party organizations involved 
with the study. 
39. Are currently enrolled in any other clinical study involving an investigational product or any 
other type of medical research judged not to be scientifically or medically compatible with 
this study. 
40. Have previously completed or withdrawn from this study or any other study investigating 
mirikizumab after receiving study intervention. This criterion does not apply to participants 
undergoing rescreening procedures. 
41. Have had extra-abdominal surgery and have not recovered fully following surgery, 
43. Have lymphoma, leukemia, or any malignancy within 10 years prior to Visit 2. 
Exceptions: 
 
Basal cell or squamous epithelial carcinoma of the skin that has been adequately 
treated without recurrence evidence of metastatic disease for at least  year prior to 
Visit 2. 
 
Cervical carcinoma in situ that has been adequately treated without evidence of 
recurrence within  years of prior to Visit 2. 
44. Have a history or presence of an underlying disease, or surgical, physical, or medical 
condition that, in the opinion of the investigator, would potentially affect participant safety 
within the study or interfere with the interpretation of data. 
45. Have a known hypersensitivity to any component of mirikizumab or monoclonal antibodies. 
46. Have a solid organ transplant or hematopoietic stem cell transplantation. 
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47. Have a blood transfusion in the last 
 days prior to hematology blood sample collection. 
48. Are pregnant, lactating, or planning pregnancy (females only) while enrolled in the study or 
within 
 weeks 
 or 
 weeks 
 after receiving the last dose of 
study intervention. 
49. Have used either recreational or medicinal marijuana within 2 weeks prior to screening 
endoscopy. 
50. Have current or history of chronic alcohol abuse or illicit drug abuse within 1 year before 
Visit 1. 
51. Are unsuitable for inclusion in the study in the opinion of the investigator or sponsor for any 
reason that may compromise the <->@5/5<-:@P? safety or confound data interpretation. 
5.3. 
Lifestyle Considerations  
Study participants should not donate blood or blood products during the study or for up to 16 
weeks following their last dose. 
To participate in the study, participants must agree to the contraception, reproduction, and 
breastfeeding criteria detailed in study entry criteria (Sections 5.1, 5.2 and 10.4). 
5.4. 
Screen Failures  
A screen failure occurs when a participant who consents to participate in the clinical study is not 
subsequently enrolled in the study. A minimal set of screen failure information is required to 
ensure transparent reporting of screen failure participants to meet the Consolidated Standards of 
Reporting Trials (CONSORT) publishing requirements and to respond to queries from regulatory 
authorities. Minimal information includes demography, screen failure details, and any SAE 
related to study procedures. 
5.4.1. 
Allowed Rescreening of Participants after Initial Screen Failure  
Individuals who have failed screening because of the following inclusion/exclusion criteria 
detailed in Section 5 may be rescreened when the reason for screen failure has resolved: 
Criterion 2 to 6, 9 to 13, 16, 19, 21, 26 to 28, 32 to 36, 39, 41, 43, 44, 47 to 50. 
Participants may be rescreened up to 2 times, for a maximum total of 3 screening visits. The 
interval between rescreening visits should be at least 4 weeks unless a shorter interval has been 
agreed upon with the medical monitor. Each time rescreening is performed the individual must 
sign a new ICF and be assigned a new identification number. 
Participants who fail screening because they are unable to complete their endoscopy within 14 
days prior to Visit 2 or were unable to complete all visit procedures within the required screening 
C5:0;C;2G	0-E? prior to Visit 2, may repeat screening procedures sooner than 4 weeks 
between screen failure and rescreening. These participants are not required to repeat HIV or TB 
testing, CXR, stool cultures or C difficile testing if results were normal or negative during prior 
screening and done within the prior 3 months. However, C difficile retesting should be 
reconsidered if there is a suspicion of infection. 
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Participants who fail screening because of exclusion criterion 32 may be rescreened once when 
the reason for screen failure has resolved. It is recommended that the investigator first confirm 
the participant has a negative C difficile stool toxin/stool culture/stool ova parasite (as 
applicable) before performing rescreening investigations (see Section 8.2.10). 
Requests to rescreen participants for eligibility criteria other than those listed above must be 
discussed with the medical monitor prior to rescreening. 
5.4.2. 
Allowed Retesting of Screening Procedures  
The screening procedures below may be retested once within the screening period at the 
discretion of the investigator: 
 Screening hematology and chemistry blood tests: where 1 or more results are outside the 
acceptable range for inclusion in the study but may be within the acceptable range for 
inclusion on retesting, due to test-retest variability. 
 Stool testing: if there is a technical difficulty in performing or reporting the C difficile or 
stool culture assays. 
 Retesting or confirmatory testing with 
 Gold test in selected 
participants as part of screening for LTBI (see Section 10.9 for details). 
 
 Endoscopy: where the endoscopist is unable to adequately visualize the mucosa (for 
example, due to poor bowel preparation, technical issues with equipment) or where the 
central reader is unable to determine the centrally read Mayo ES (for example, failure of 
the recording equipment). 
Retesting of all other screening procedures within the screening period must be discussed with 
the medical monitor prior to retesting. 
5.5. 
Criteria for Temporarily Delaying Enrollment of a Participant  
This section is not applicable for this study. 
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6. 
Study Intervention(s) and Concomitant Therapy  
Study intervention is defined as any medicinal products or medical device(s) intended to be 
administered to/used by a study participant according to the study protocol. 
In this study, the study intervention is mirikizumab. 
6.1. 
Study Intervention(s) Administered  
All enrolled participants will receive mirikizumab. 
Detailed instructions for mirikizumab administration, 
 
will be provided separately by the sponsor or designee. 
Sites must have resuscitation equipment, emergency medications, and appropriately trained 
personnel available during the 
 monitoring period. 
Administration of mirikizumab should always be done after all other visit assessments are 
completed, as specified in SoA (see Section 1.3). 
Returned study intervention should not be re-dispensed to the participants. 
This table provides information about mirikizumab administration in this clinical study. 
Intervention Name 
Mirikizumab 
Study Period 
II 
III 
Dosage Level(s) 
 mg 
 
 mg
  
Route of Administration 
 
 via 
mL 
 
Administration 
 onsite 
 by authorized study personnel 
only 
 maximum rate of 10 mg/min by 
 over no less than 30 
min.  
 onsite 
 by authorized study personnel, or via self-
administration by participant or caregiver, 
as indicated in the SoA (Section 1.3) 
Participant 
Monitoring 
 hour following 
 administration. 
Note: Longer monitoring is allowed 
when required by investigator 
practice or local standard of care  
According to investigator practice or local 
standard of care 
 
Authorized as Defined by 
EU Clinical Trial 
Regulation 
Not authorized in EU 
Not authorized in EU 
Abbreviations: EU = European Union; 
 
 SoA = Schedule of Activities; 
 
Packaging and labeling 
Study intervention, mirikizumab, will be supplied by the sponsor or its designee in accordance 
with current Good Manufacturing Practice. Study intervention will be labeled as appropriate for 
country requirements. 
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6.1.1. 
Self-Administration Training  
In this protocol, self-administration is defined as the 
 of 
 mg mirikizumab 
 by the 
participant or caregiver. 
Completion of self-administration training is required for eligibility in the Continued Access 
Period. 
It is recommended that self-administration training starts at Visit 6 (Week 
). Training must 
occur during at least 2 visits and start no later than Visit 8 (Week 
) for participants planning to 
complete self-administration training. See SoA in Section 1.3. 
During self-administration, the site staff should use the Study Drug Administration Training Log 
to train participants on the completion of the SDAL. 
After completion of self-administration training at 2 or more visits, trained participants may self-
administer 
 mg mirikizumab 
 and complete the SDALs at any remaining dosing visits. At 
these visits, the site staff should observe the self-administration of mirikizumab and review the 
completion of the SDAL 
. If deviations in self-administration procedures or in 
SDAL completion are identified, the site staff should take corrective actions, including retraining 
as appropriate. 
6.2. 
Preparation, Handling, Storage, and Accountability  
The investigator or designee must confirm appropriate storage conditions have been maintained 
during transit for all study intervention received and any discrepancies are reported and resolved 
before use of the study intervention. 
Only participants enrolled in the study may receive study intervention. Only authorized study 
personnel may supply, prepare, and administer study intervention. Exception: participants or 
caregivers may administer mirikizumab injections at dosing visits during or following self-
administration training. 
All study intervention must be stored in a secure, environmentally controlled, and 
monitored (manual or automated) area in accordance with the labeled storage conditions 
with access limited to the investigator and authorized study personnel. 
The investigator or authorized study personnel are responsible for study intervention 
accountability, reconciliation, and record maintenance (that is, receipt, reconciliation, and final 
disposition records). 
Further guidance and information for the final disposition of unused study interventions are 
provided in the Pharmacy Manual. 
6.3. 
Assignment to Study Intervention  
All participants will be centrally assigned to mirikizumab using an interactive web-response 
system. Before the study is initiated, the log in information and directions for the interactive 
web-response system  will be provided to each site. 
6.4. 
Blinding  
This is an open-label study and all participants will receive mirikizumab. There is no blinding. 
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6.5. 
Study Intervention Compliance  
Period II: 
 dosing 
 mg mirikizumab 
 must be administered under medical supervision by the investigator or 
designee. The date and time of each dose administered will be recorded in the source documents 
and will be provided to the sponsor as requested. 
Period III: 
 dosing 
 mg mirikizumab 
 must be administered by authorized study personnel or self-
administered by the participant or caregiver, per protocol training procedures. The date and time 
of each dose administered should be recorded in the source documents and provided to the 
sponsor as requested. 
6.6. 
Dose Modification  
Dose modifications are not permitted in this study. 
6.7. 
Treatment of Overdose  
There is no known antidote for mirikizumab. 
In the event of an overdose, the investigator should: 
 Contact the medical monitor immediately. 
 Initiate supportive treatment according to the participantPs clinical signs and 
symptoms. 
 Closely monitor the participant for any AE/SAE and laboratory abnormalities 
(hematology and chemistry), as well as vital signs and oxygen saturation. 
 Evaluate the participant to determine, in consultation with the medical monitor, 
whether study intervention should be interrupted. 
6.8. 
Prior and Concomitant Therapy  
Section 10.10 provides the list of permitted medications with dose stabilization guidance. 
Section 10.11 provides the list of prohibited medications. 
Section 6.8.1 provides corticosteroid taper instructions for participants taking oral 
corticosteroids. 
The medical monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
Continued use of nonprescription herbal supplements/medicines that are taken specifically for 
the treatment of UC should be discussed with the medical monitor. 
The medical monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
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All participants should maintain their usual medication regimens for concomitant conditions or 
diseases throughout the study, unless those medications are specifically prohibited (Section 
10.11). 
Stable doses of permitted UC medications, other than oral corticosteroids, should be continued, 
unless dose modification is required due to AEs, or dose modification is otherwise specified in 
Section 10.10. Other medications may be allowed if they are approved by the medical monitor. 
If a medication is needed to treat an AE or for appropriate medical management, the investigator 
should base decisions on participant and clinical factors. 
Reporting of prior or concomitant therapy 
Any medication or vaccine, including over-the-counter or prescription medicines, bowel 
preparations, vitamins, and herbal supplements; or other specific categories of interest, that the 
participant is receiving at the time of enrollment or receives during the study must be recorded in 
the concomitant medication CRF, along with: 
T Reason for use 
T Dates of administration including start and end dates, and 
T Dosage information including dose and frequency for concomitant therapy of 
special interest. 
6.8.1. 
Corticosteroid Use and Taper  
Local administration of corticosteroids, for example, intranasal, inhaled, and intra-articular, is 
allowed if required for the management of preexisting conditions and AEs. 
Periods I and II 
For participants who enter the study on corticosteroid therapy, the prescribed dose must have 
been stable for at least 2 weeks before the screening endoscopy. The prescribed dose should 
remain stable for the duration Study Periods I and II. 
Period III 
For participants who enter the Study Period III on corticosteroids, tapering of corticosteroid 
therapy may be initiated at Visit 6 (Week 
). 
The investigator should use clinical judgment of the benefit/risk of steroid tapering for each 
individual participant as corticosteroids should be tapered as soon as possible following the 
recommended tapering regimen below or as preferred per local practice. 
The recommended tapering schedule for oral corticosteroids (other than budesonide extended-
release tablets [budesonide MMX]) is as follows: 
 Dose >10 mg/day prednisone or equivalent: taper daily dose by 
 until 
receiving 10 mg/day, and then continue tapering at 
 until 0 mg/day. 
 D;?1G930-E<>10:5?;:1;>1=A5B-81:@@-<1>0-58E0;?1.E
A:@58
0 mg/day. 
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The tapering schedule for oral budesonid1  *G930-E5?@;
;2@-.81@?
from daily to every other day for 
, followed by every third day for 
, and then 
discontinue. 
The recommended tapering schedule for participant receiving oral beclomethasone dipropionate 
(gastro-resistant prolonged-release tablet)  mg/day is to reduce tablets to  mg every other day 
for 
, and then discontinue. 
In participants who cannot tolerate the corticosteroid taper without recurrence of clinical 
symptoms, 
 
 are needed, consult the medical monitor. 
In situations where the steroid tapering is paused, the tapering regimen (as described above) 
should be 
, if possible. 
6.8.2. 
Prohibited Medications  
Administration of prohibited medications for the treatment of UC, approved or investigational, 
constitutes treatment failure. Use of such medications should not be withheld if, in the opinion of 
the investigator, failure to prescribe them would compromise participant safety. Participants who 
require a prohibited medication to treat their UC must be discontinued from study intervention, 
complete an ED visit, and a posttreatment follow-up visit. 
A participant who requires a prohibited medication for a non-UC indication should be discussed 
with the medical monitor. 
Section 10.11 provides the list of prohibited medications and details. 
6.8.3. 
Vaccine Administration During the Study  
Prohibited vaccines 
Use of BCG vaccination is prohibited throughout the duration of the study and for 12 months 
after discontinuation of study intervention. 
Live attenuated vaccines such as measles, mumps, rubella, or varicella are prohibited during the 
study and for 3 months after the last dose of study intervention. Use of emergency vaccinations 
(such as rabies or tetanus vaccinations) is allowed with no timing restriction. 
Allowed vaccines 
Use of non-live (killed, inactivated, subunit, or RNA-based) vaccinations is allowed for all 
participants; however, their efficacy with concomitant mirikizumab is unknown. If a permitted 
non-live vaccine is needed, it is recommended that study intervention not be administered on the 
same day as a vaccination. 
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7. 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal  
Discontinuation of specific sites or of the study as a whole are handled as part of Section 10.1.9. 
7.1. 
Discontinuation of Study Intervention  
When necessary, a participant may be permanently discontinued from mirikizumab. If so, the 
participant will discontinue mirikizumab and will remain in the study to complete procedures for 
an ED visit, if applicable, and posttreatment follow-up, as shown in the SoA. 
A participant should be permanently discontinued from study intervention (mirikizumab) if 
● the participant becomes pregnant during the study 
● in the opinion of the investigator, the participant should permanently discontinue the 
study intervention for safety reasons 
 the participant has a lack of clinical benefit or disease worsening and 
o requires treatment with medication(s) at doses higher than those specified in Sections 
10.10 and 10.11. 
or 
o requires treatment with prohibited medications specified in Section 10.11. 
 the participant undergoes surgery for active UC 
 the participant has a systemic hypersensitivity reaction (Section 7.1.3) 
 the participant has a diagnosis of the following during the study: 
o malignancy (except for successfully treated basal or squamous cell skin carcinoma), 
or 
o intestinal dysplasia 
 the participant develops HIV infection. 
 the participant develops active TB or has untreated LTBI (Section 8.2.7). 
 HBV or HCV: the participant tests positive for HBV DNA (see Section 8.2.8.1) or tests 
positive for HCV RNA (Section 8.2.8.2)  
Note: The HBV DNA result is to be confirmed if initial test result is positive but below 
the level of quantification (Section 8.2.8.1). 
Prior to discontinuation of any immunomodulatory and/or immunosuppressive therapy 
due to hepatitis, including study intervention, it is recommended that the participant is to 
be referred to, evaluated, and managed by a specialist physician with expertise in 
evaluation and management of viral hepatitis. 
 
The timing of discontinuation from study intervention relative to the initiation of any 
antiviral treatment for hepatitis is to be based on the recommendation of the consulting 
specialist physician, in conjunction with the investigator, and aligned with medical 
guidelines and standard of care. 
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7.1.1. 
Suicidal Ideation or Behavior  
It is recommended that the participant be assessed by an appropriately trained professional to 
assist in deciding whether the participant is to be discontinued from study intervention if 
 the participant scores a 3 for Item 12 (thoughts of death or suicide) on the 
 at 
any time in the study, or 
 the participant reports suicidal ideation or suicidal behaviors during the study. 
A psychiatrist or appropriately trained professional may assist in the decision to discontinue the 
participant or assist in preparing a safety monitoring plan for the participant should they continue 
in the study. 
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7.1.3. 
Hypersensitivity Reactions  
If the investigator determines that a systemic hypersensitivity reaction has occurred related to 
study intervention administration, the participant may be permanently discontinued from the 
?@A0E5:@1>B1:@5;:-:0@41?<;:?;>P?01?53:-ted medical monitor should be notified. If the 
investigator is uncertain about whether a systemic hypersensitivity reaction has occurred and 
whether discontinuation of study intervention is warranted, the investigator should consult the 
medical monitor. 
7.1.4. 
Temporary Discontinuation  
Temporary withholding of study intervention is required if the participant meets any of the 
following infection-related criteria during the study. 
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Criteria for temporary discontinuation  
of study intervention 
Next steps 
Infection-related criteria 
Serious or opportunistic infections, as 
defined in Section 5.2  
Withhold until resolution of all acute clinical signs and symptoms, 
and completion of all appropriate anti-infective treatment. If 
participant is diagnosed with LTBI, see Section 8.2.7. 
A participant diagnosed with LTBI during 
the study 
Permanently discontinue from study intervention unless 
the participant is a candidate for LTBI treatment, and is 
treated for LTBI as follows: 
S 
Study intervention is temporarily held for at least 
the 
 weeks of LTBI treatment. 
S 
After receiving at least  weeks of appropriate 
LTBI therapy (as per WHO or US CDC 
guidelines), if there is no evidence of 
41<-@;@;D5/5@E&%&9A?@>19-5:G	@591?
ULN) or other treatment intolerance, study 
intervention may be resumed. 
S 
The participant must complete appropriate LTBI therapy to 
remain eligible to receive study intervention. 
HBV DNA results that are reported as 
positive, or as detecting HBV DNA, but 
HBV DNA is below the level of 
quantification 
Contact medical monitor. 
Repeat HBV DNA testing as soon as is feasible. 
If HBV DNA is confirmed as positive, then study intervention 
must be permanently discontinued. 
Hematology Laboratory Criteria 
 
Platelet count < 50.0 x 109/L 
 
WBC <2.0 x 109/L (leukopenia) 
 
Absolute Neutrophil Count <1.0 x 
109/L (< 1.0 × 103/μL or < 
1.0 GI/L) (neutropenia) 
 
Lymphocyte count <500 cells/uL 
(<0.5 x 103/μL or <0.5 GI/L) 
(lymphopenia) 
Contact medical monitor. 
Discuss timing of repeat hematology laboratory panel and term for 
withholding intervention. 
7.2. 
Participant Discontinuation/Withdrawal from the Study  
Discontinuation is expected to be uncommon. 
A participant may withdraw from the study: 
T at any time at @41<->@5/5<-:@P? own request for any reason or without providing 
any reason 
 -@@41>1=A1?@;2@41<->@5/5<-:@P?01?53:112;>1D-9<81<->1:@? or legal 
guardian) 
T at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons 
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● if enrolled in any other clinical study involving an investigational product, or 
enrolled in any other type of medical research judged not to be scientifically or 
medically compatible with this study 
● if the participant, for any reason, requires treatment with a therapeutic agent that 
is prohibited by the protocol and has been demonstrated to be effective for 
treatment of the study indication. In this case, discontinuation from the study 
occurs prior to introduction of the new agent. 
At the time of discontinuing from the study, if possible, the participant should complete 
procedures for an ED visit and posttreatment follow-up, if applicable, as shown in the SoA (see 
Section 1.3). If the participant has not already discontinued the study intervention, the participant 
will be permanently discontinued from the study intervention at the time of the decision to 
discontinue the study. 
If the participant withdraws consent for disclosure of future information, the sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. If a participant 
withdraws from the study, the participant may request destruction of any samples taken and not 
tested, and the investigator must document this in the site study records. 
7.3. 
Lost to Follow-up  
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. Site personnel or designee are 
expected to make diligent attempts to contact participants who fail to return for a scheduled visit 
or were otherwise unable to be followed up by the site. 
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8. 
Study Assessments and Procedures  
Study procedures and their timing are summarized in the SoA. 
Immediate safety concerns should be discussed with the sponsor immediately upon occurrence or 
awareness to determine if the participant should continue or discontinue study intervention. 
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct. 
All screening evaluations must be completed and reviewed to confirm that potential participants 
meet all eligibility criteria. The investigator should maintain a screening log to record details of 
all participants screened and to confirm eligibility or record reasons for screening failure, as 
applicable. 
8.1. 
Efficacy Assessments  
8.1.1. 
Daily Electronic Diary Measures  
Participants must use an electronic diary to complete these patient-reported measures daily. 
1. Urgency NRS 
The investigator should monitor electronic diary compliance throughout the study and provide 
retraining to participants as needed. 
For this study, O?@;;8P5?0125:10-?-@>5<@;@41@;581@C41:@41<->@5/5<-:@4-?-.;C18
movement; or passes blood alone; or passes blood and mucus; or passes mucus only. 
If the participant is not compliant with
 
 
8.1.1.1. 
Urgency NRS  
Urgency NRS is a patient-reported, single-item measure of the severity for the urgency (sudden 
or immediate need) to have a bowel movement in the past 24 hours using an 11-point NRS 
>-:35:32>;9M:;A>31:/EN@;MC;>?@<;??5.81A>31:/EN 
 
  
 
 
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8.1.2. 
Patient-reported Outcomes on the Electronic Tablet  
The following patient-reported measures will be completed using an electronic tablet at onsite 
visits, as designated in the SoA. 
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8.1.3. 
Physician’s Global Assessment (PGA)  
The PGA is a physician->1<;>@1091-?A>1@4-@?A99->5F1?@415:B1?@53-@;>P?-??1??91:@;2@41
participantP?'05?1-?1-/@5B5@E;:--point scale (see Section 10.6). Consistent with regulatory 
guidance, the PGA will not be used as an efficacy assessment in this study. 
8.1.4. 
Mayo Score  
The Mayo score (adapted from Schroeder et al. 1987) is a composite instrument reported by 
participants and the physician and is comprised of the following 4 subscores: 
 SF subscore (described below) 
 RB subscore 
 
 ES (described below), and 
 PGA (see Section 8.1.3). 
The SF subscore is the number of stools reported in a 24-hour period, relative to the Normal 
Number of Stools for that participant in the same period, on a 4-point scale. 
The ES is a physician-reported measure that indicates the worst appearance of the mucosa on 
flexible sigmoidoscopy or colonoscopy, on a 4-point scale. Determination of the ES is further 
detailed in Section 10.6. Consistent with current clinical practice and regulatory advice, the ES 
excludes friability from the definition of an ES of 1. Also consistent with best clinical study 
practice, endoscopy scores will be determined from blinded central readers. 
The local endoscopy score is collected on paper and should be transcribed immediately, no more 
than 24 hours after reading, in the CRF. The entry of the local endoscopy is critical to initiate the 
blinded central reading process. 
The Mayo score is 
 If the 
participant is not compliant 
 for at least  days in the -days 
prior to bowel preparation, the Mayo score cannot be calculated. 
Scoring 
Each subscore is scored on a 4-point scale, ranging from 0 to 3, to give a maximum Mayo score 
of 12. See Section 10.6. for more details about the Mayo scoring system. 
The following permutations of the Mayo score will be used in this study: 
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 MMS: a sum of the Mayo SF, RB, and ES, giving a maximum MMS of 9 
 Partial Mayo score: a sum of the Mayo SF, RB, and PGA, giving a maximum partial 
Mayo score of 9 
8.1.5. 
Endoscopy  
Standard procedures 
Flexible sigmoidoscopy is the standard endoscopic procedure for assessment of endoscopic 
disease activity in this study, except when a full colonoscopy is indicated. 
A colonoscopy can be performed instead of flexible sigmoidoscopy within this study for 
surveillance, or for other clinically indicated reasons, per investigator discretion (see Section 
8.1.5.2). 
8.1.5.1. 
Study-required Endoscopies  
Endoscopies will be used to determine the Mayo ES at the time points described in the SoA 
(Section 1.3). 
Visit 1 screening 
It is highly recommended that the investigator confirm the participant meets other screening 
criteria for inclusion in the study before performing the Visit 1 screening endoscopy (see 
Sections 5.1 and 5.2). 
Visit 6 
The investigator should ensure the participant is compliant with electronic diary daily 
completion, particularly during the 7 days prior to bowel preparation. 
Visit 10 
The investigator should ensure the participant is compliant with electronic diary daily 
completion, particularly during the 7 days prior to bowel preparation. 
For participants otherwise eligible for the Continued Access Period, the Visit 10 endoscopy must 
be completed prior to initiating Visit 501 (see Section 10.12). 
8.1.5.2. 
Surveillance Colonoscopy Requirements  
Requirements for a surveillance colonoscopy with biopsies for colorectal dysplasia and cancer, 
with documented negative results, are as follows: 
 Participants with a history of UC for 
 years are to have had a surveillance colonoscopy 
with biopsies completed within the past  years prior to Visit 2. 
 Participants with primary sclerosing cholangitis, regardless of duration of UC diagnosis, 
are to have had a surveillance colonoscopy with biopsies completed within the 
 year 
prior to Visit 2. 
If a potential participant has not had a surveillance colonoscopy with biopsies, as described 
above, or does not have the required documentation of negative results for colorectal dysplasia 
and cancer, the investigator should perform a colonoscopy with biopsies as the endoscopic 
procedure at Visit 1 to meet surveillance eligibility criteria and study requirements. 
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Surveillance biopsies should be collected and sent to a local laboratory for testing and 
documentation of results. 
Participants should remain up-to-date with their surveillance colonoscopy requirement during the 
study, including the Continued Access Period if relevant. If needed for continued eligibility, 
colonoscopy with biopsies should be the endoscopic procedure at Visit 10 (Week 
) to meet 
both surveillance eligibility criteria and study requirements. 
8.1.5.3. 
Procedural Requirements for Endoscopies  
Endoscopist qualifications 
The endoscopist must be a licensed physician who is qualified by education, training, and 
experience to perform endoscopies. 
Investigators may delegate endoscopy to other qualified individuals. 
Anyone performing endoscopy must receive training from the sponsor or designee in the 
determination and calculation of the Mayo ES. 
Video procedures 
All study endoscopies and endoscopic procedures should be video recorded using a storage 
medium provided by the sponsor or designee. The video images must be sent for independent 
central reading. An endoscopy video instruction manual from the central reading laboratory will 
outline the standard study procedures used to capture and transmit video recordings of 
endoscopic procedures throughout the study. 
The central readers will determine the Mayo ES at each endoscopy in a blinded manner. 
Disagreement between the site readers and central readers will be resolved using an established 
adjudication process. 
The central reading laboratory must provide the final Mayo ES to the sites prior to Visit 2 for 
determination of the MMS to confirm study eligibility (see Section 5.1). 
8.1.5.4. 
Endoscopic Biopsies  
Eligibility requirements 
A histopathology report supporting the diagnosis of UC must be available in the source 
documents prior to study enrollment, to satisfy the inclusion criteria for this study. 
If a histopathology report is not available, the investigator may obtain additional biopsies for this 
purpose at the screening endoscopy and send these to the local histopathology laboratory. 
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Study endoscopic biopsies 
Biopsies will be obtained at each endoscopy to support assessment of the exploratory 
histopathology endpoints and their association with gene expression in this study and, where 
permitted by local regulations and ERBs, for the assessment of exploratory biomarkers. 
 
Endoscopic Biopsy Sample Collection 
Sample number, 
segment, and purpose 
N = 
 biopsy samples collected per endoscopy (Visits 1, 6, and 10) 
 
 (for exploratory biomarker analyses) 
 
 (for exploratory biomarker analyses) 
Sample segment and 
area, by visit  
Visit 1: 
 
within the defined segment 
 collect from worst affected area 
Visits 6 and 10 
 
 
within the defined segment 
 collect from worst affected area, 
even if area within the segment is not the same as Visit 1/screening. 
 
 if no affected area is visible within the defined segment, collect from same 
general area as screening. 
 
In rare circumstances, the investigator may consider it unsafe to collect all required biopsies. In 
this situation, fewer biopsies may be collected. 
Biopsies will be sent to the central study laboratory for processing. A detailed biopsy reference 
guide from the central reading laboratory will outline the procedures to be used for biopsy 
collection, secure specimen transfer, processing, slide preparation, and digitization of slides for 
histopathologic scoring. These results will not be made available to study sites. 
8.1.6. 
Histopathology Scoring Instrument  
The histopathology instruments that will be used for the evaluation of microscopic inflammation 
and histopathologic disease activity will be specified in the SAP. 
8.2. 
Safety Assessments  
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
8.2.1. 
Physical Examination  
The physical examination should include evaluation of the heart, lungs, abdomen, 
peripheral lymph nodes and visual examination of the skin, and exclude pelvic, rectal, 
and breast examinations unless clinically indicated. 
Symptom-directed physical assessments should be performed as specified in the SoA to evaluate 
specific symptoms reported by the participant. 
A physical examination may be repeated at the 5:B1?@53-@;>P?05?/>1@5;:-@-:E@591-
participant presents with physical complaints. 
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Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
Extraintestinal manifestations 
Review of extraintestinal manifestations will be performed at the time points described in the 
SoA (Section 1.3). Extraintestinal Manifestations include 
 ankylosing spondylitis  
 osteoporosis 
 aphthous stomatitis  
 pancreatitis 
 arthralgia  
 peripheral arthritis 
 autoimmune hepatitis  
 primary sclerosing cholangitis 
 cholelithiasis  
 pyoderma gangrenosum 
 deep vein thrombosis 
 nephrolithiasis 
 episcleritis 
 sacroiliitis 
 erythema nodosum 
 skin vasculitis, and 
 iritis 
 uveitis 
 osteopenia 
 
8.2.2. 
Vital Signs  
Measurements of vital signs (body temperature, blood pressure, and pulse rate) should be 
conducted at the study visits specified in the SoA. Measure vital signs with the participant in the 
seated position with feet on the floor, after sitting quietly for at least 5 minutes. 
Any clinically significant findings from vital sign measurement that result in a diagnosis and that 
occur after the participant receives the first dose of mirikizumab should be reported as an AE via 
CRF. 
8.2.3. 
Electrocardiograms  
Collect the screening ECG at least 30 minutes prior to blood sample collections. The participant 
should be supine for approximately 5 to 10 minutes before ECG collection and remain supine but 
awake during the ECG. 
If deemed clinical necessary, ECGs may be obtained at additional times. 
ECGs should be interpreted by the investigator or qualified designee at the study site as soon 
after the time of ECG collection as possible, and ideally while the participant is still present, to 
determine whether the participant meets the study entry criteria and for immediate participant 
management, if any clinically relevant findings are identified. 
8.2.4. 
Clinical Safety Laboratory Tests  
● See Section 10.2 for the list of clinical laboratory tests to be performed and the 
SoA for the timing and frequency. 
● Unless noted as locally performed (for example, urine pregnancy tests), clinical 
laboratory tests will be sent to a central laboratory for testing. 
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T The investigator must review the laboratory results, document this review, and 
report any clinically relevant changes occurring during the study as an AE. The 
laboratory results must be retained with source documents unless a source 
document agreement or comparable document cites an electronic location that 
accommodates the expected retention duration. 85:5/-88E?53:525/-:@-.:;>9-8
8-.;>-@;>E25:05:3?->1@4;?1C45/4->1:;@-??;/5-@10C5@4@41A:01>8E5:305?1-?1
A:81??6A0310.E@415:B1?@53-@;>@;.19;>1?1B1>1@4-:1D<1/@102;>@41
<->@5/5<-:@P?/;:05@5;: 
T All laboratory tests with values considered clinically significantly abnormal 
during participation in the study including the 
 post-treatment follow-up 
period should be repeated until the values return to normal or baseline or are no 
longer considered clinically significant by the investigator or medical monitor. 
S If such values do not return to normal/baseline within a period of time judged 
reasonable by the investigator, the etiology should be identified, and the 
medical monitor and sponsor notified. 
S All protocol-required laboratory assessments, as defined in Section 10.2, must 
be conducted in accordance with the SoA, standard collection requirements, 
and laboratory manual. 
T If laboratory values from non-protocol specified laboratory assessments 
performed at an investigator-designated local laboratory require a change in 
participant management or are considered clinically significant by the investigator 
(for example, SAE or AE or dose modification), then report the information as an 
AE. 
 Additional clinical laboratory tests, including local tests, may be performed at any time 
during the study as determined necessary by the investigator for immediate participant 
management or safety or as required by local regulations. 
8.2.5. 
Pregnancy Testing  
Serum pregnancy test should be done at screening only and results should be confirmed by the 
central laboratory. 
Female participants of childbearing potential should undergo a urine pregnancy test, performed 
locally, at visits indicated in the SoA through Week 
. The urine pregnancy test must be 
M:13-@5B1N within 24 hours prior to administration of mirikizumab at every study visit. 
Urine pregnancy testing may be performed at additional time points during the treatment period 
or follow-up period, at the discretion of the investigator, or if this is required by local 
regulations. 
If a urine pregnancy test is not available, a serum pregnancy test is an acceptable alternative. 
Assessment of FSH levels can assist in determining if a woman meets the definition of 
M<;?@91:;<-A?-8N as outlined in Section 10.4. FSH levels can be optionally obtained during 
screening or during the study, at the discretion of the investigator to determine postmenopausal 
status (see Section 1.3). 
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8.2.6. 
Suicidal Ideation and Behavior Risk Monitoring  
Suicide ideation and behavior will be assessed at screening with the administration of the 
. Depressive symptomology will be assessed with the 
 during the study, at 
visits specified in the SoA (Section 1.3). 
These assessments are described below, and further information is provided in Section 10.7. 
Participants should be monitored appropriately and observed closely for suicidal ideation and 
behavior or any other unusual changes in behavior, especially at the beginning and end of the 
course of study intervention. Participants who experience signs of suicidal ideation and behavior 
should undergo a risk assessment. All factors contributing to suicidal ideation and behavior 
should be evaluated and consideration should be given to discontinuation of the study 
intervention. 
8.2.7. 
Tuberculosis Testing and Monitoring  
Screening 
During screening, all participants will be assessed for risk factors, symptoms, and signs of TB 
with all of the following: 
 Thorough history to determine the lifetime risk factors for TB infection, for TB 
progression, and for symptoms or signs of active TB. 
 Signs of previous or active TB by means of 
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o Thorough physical examination for signs of active TB, including measurement of 
body temperature and assessment of peripheral lymph nodes. 
o A high-quality CXR (PA, including a lateral view if needed) interpreted and reported 
by a radiologist or pulmonologist (see Section 8.2.7.1). 
All participants with no history of LTBI or active TB, and no history of positive Mantoux 
tuberculin skin test using purified protein derivative or positive Mycobacterium tuberculosis  
, must have an 
 for M 
tuberculosis, using 
 gold test. For details about these tests, see Section 10.9. 
Participants diagnosed with LTBI 
Guidance when participants are diagnosed with LTBI during screening 
Participants diagnosed with LTBI are excluded (Section 5.2) unless they are candidates for LTBI 
treatment, are treated for LTBI, and the following criterion are met: 
 After receiving at least 4 weeks of appropriate LTBI therapy (as per WHO or the United 
States CDC guidelines), there is no evidence of hepatotoxicity (ALT/AST must remain 
G	@591?'!;>;@41>@>1-@91:@5:@;81>-:/1:@45?/-?1@41<->@5/5<-:@9-E.1
rescreened (Section 5.4) and is not excluded due to LTBI. 
Guidance when participants are diagnosed with LTBI during the study 
 The participant must continue and complete appropriate LTBI therapy to remain eligible 
to continue to receive study intervention (Sections 7.1 and 7.1.4) 
Monitoring during the study 
For all participants, monitoring for TB will be continuous throughout the study. At a minimum, 
each participant will have the following documented at least every 3 months 
 thorough history to determine any risk factors for TB infection and for TB progression, 
symptoms, or signs of active TB, and 
 thorough physical examination that includes assessment for signs of active TB, including 
measurement of body temperature and assessment of peripheral lymph nodes. 
8.2.7.1. 
Chest Imaging  
Collect a high-quality CXR (PA view and, if needed, a lateral view), interpreted and reported by 
a radiologist or pulmonologist as specified in the SoA (Section 1.3). 
Exception: Participants do not need to have a CXR at screening if, in the opinion of the 
investigator, both of these 2 conditions are met: 
 a CXR was performed within 3 months before initial screening, and 
 documentation of the CXR, read by a qualified radiologist or pulmonologist, is sufficient 
for TB evaluation according to local standard of care. 
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For each participant, the CXR films, images, or a radiology report must be available to the 
investigator for review before the participant is assigned treatment. 
Note: Results of a chest computed tomography scan or other imaging study similar to a CXR 
may be used instead of the CXR for TB evaluation, in consultation with the sponsor’s medical 
monitor. 
8.2.8. 
Hepatitis B and C Testing and Monitoring  
8.2.8.1. 
Hepatitis B Testing and Monitoring  
As specified in the SoA (Section 1.3), initial testing for HBV infection includes HBsAg and 
anti-HBc. 
 If HBsAg is positive, the participant is excluded. 
 If HBsAg is negative and anti-HBc is negative, the participant is not excluded. 
 If HBsAg is negative and anti-HBc is positive, further testing for HBV DNA is required. 
o If the screening HBV DNA is positive, the participant is excluded. 
o If the screening HBV DNA is negative, the participant is not excluded. Repeat 
testing for HBV DNA is required at least every 3 months during the study. 
Management of enrolled participants with detectable HBV DNA during the study 
If HBV DNA is detected, study intervention will be temporarily withheld or permanently 
discontinued, as described in Section 7.1, and the participant should receive appropriate follow-
up medical care. 
8.2.8.2. 
Hepatitis C Testing  
As specified in the SoA (Section 1.3), initial testing for HCV infection includes testing for 
anti-HCV. 
 If anti-HCV is positive, a test for circulating HCV RNA is required. 
 If HCV RNA test is negative, the participant is not excluded. 
 If HCV RNA test is positive, the participant is excluded (see Section 5.2). 
Participants who have had HCV infection and have been successfully treated, defined as a 
sustained virologic response (HCV RNA by PCR negative for at least 24 weeks following 
treatment completion) are not excluded on the basis of HCV as long as HCV RNA test is 
negative at screening. 
If HCV RNA is detected during the study, the study intervention will be discontinued (Section 
7.1), and the participant should receive appropriate follow-up medical care. 
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8.2.10. 
Screening Stool Testing  
Stool culture 
Participants must have a negative stool culture from which no enteric pathogens are isolated to 
participate in the study. 
Retesting is allowed within the screening period if there is a technical difficulty in performing or 
reporting the stool culture assay, as stated in Section 5.4. 
"->@5/5<-:@?C4;4-B1-M<;?5@5B1N?@;;8/A8@A>1>1?A8t can be rescreened once, as stated in 
Section 5.4, provided that the following conditions have been met: 
 the participant has been adequately treated, and 
o if antibiotics were prescribed, participant has been off antibiotics for 
 days, or 
o if antibiotics were not prescribed, 
 days or more has elapsed since resolution of 
acute symptoms and signs associated with the underlying intestinal infection. 
To confirm that the reason for screen failure (positive stool culture) has resolved, it is 
recommended that the investigator performs a local stool culture test before rescreening. Upon 
rescreen (Visit 1), a negative stool culture result from the central lab is required to meet this 
eligibility criterion. 
005@5;:-88;/-8?@;;8/A8@A>1@1?@5:35?-88;C10-@@415:B1?@53-@;>P?05?/>1@5;: or based on 
country requirements. 
C difficile toxin testing 
This assay tests for the presence of C difficile toxin protein, followed by a confirmatory test for C 
difficile toxin gene expression in the stool sample. 
Participants should test negative for C difficile to receive mirikizumab. Retesting is allowed 
within the same screening period if there is a technical difficulty in performing or reporting the C 
difficile assays, or if in the judgment of the investigator, the participa:@P?symptoms or signs are 
not consistent with C difficile infection. 
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Participants who test positive at screening for C difficile can be rescreened once for the study, 
once they have been adequately treated and off antibiotics for 
 days. 
Participants who have been adequately treated for C difficile with fecal microbial transplantation 
or IV immunoglobulin therapy can be rescreened once for the study 
 days after completing 
their therapy. 
To confirm that the reason for screen failure (positive C difficile) has resolved, it is 
recommended that the investigator performs a local C difficile test before rescreening. Upon 
rescreen (Visit 1), a negative C difficile result from the central lab is required to meet this 
eligibility criterion. 
8.3. 
Adverse Events, Serious Adverse Events, and Product Complaints  
The definitions of the following events can be found in Section 10.3, Appendix 3: 
 AEs 
 SAEs 
 PCs 
These events will be reported by the participant (or, when appropriate, by a caregiver, surrogate, 
or the participantPs legally authorized representative). 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet these definitions and remain responsible for following up events that 
are serious, considered related to the study intervention or study procedures, or that caused the 
participant to discontinue the study intervention (see Section 7.1). 
Care will be taken not to introduce bias when detecting events. Open-ended and non-leading 
verbal questioning of the participant is the preferred method to inquire about event occurrences. 
After the initial report, the investigator is required to proactively follow each participant at 
subsequent visits/contacts. All SAEs and AEs of special interest (as defined in Section 8.3.3) will 
be followed until resolution, stabilization, the event is otherwise explained, or the participant is 
lost to follow-up (as defined in Section 7.3). For PCs, the investigator is responsible for ensuring 
that follow-up includes any supplemental investigations as indicated to elucidate the nature 
and/or causality. Further information on follow-up procedures is provided in Section 10.3. 
 
 
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8.3.1. 
Timing and Mechanism for Collecting Events  
This table describes the timing, deadlines, and mechanism for collecting events. 
Event 
Collection 
Start 
Collection 
Stop 
Timing for Reporting 
to Sponsor or 
Designee 
Mechanism for 
Reporting 
Back-up 
Method of 
Reporting 
Adverse Event 
AE 
Signing of 
the ICF 
Participation 
in study has 
ended 
As soon as possible 
upon site awareness 
AE CRF 
N/A 
Serious Adverse Event 
SAE and SAE 
updates – prior 
to start of study 
intervention and 
deemed 
reasonably 
possibly related 
to study 
procedures 
Signing of 
the ICF 
Start of 
intervention 
Within 24 hours of 
awareness 
SAE paper form 
SAE paper 
form 
SAE and SAE 
updates – after 
start of study 
intervention 
Start of 
intervention 
Participation 
in study has 
ended 
Within 24 hours of 
awareness 
SAE paper form 
SAE paper 
form 
SAEa – after 
participant’s 
study 
participation has 
ended and the 
investigator 
becomes aware 
After 
participant’s 
study 
participation 
has ended 
N/A 
Promptly 
SAE paper form 
N/A 
Pregnancy 
Pregnancy in 
female 
participants and 
female partners 
of male 
participants 
After the 
start of study 
intervention 
16 weeks 
after the last 
dose 
Within 24 hours (see 
Section 8.3.2) 
Pregnancy paper 
form 
Pregnancy 
paper form 
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Event 
Collection 
Start 
Collection 
Stop 
Timing for Reporting 
to Sponsor or 
Designee 
Mechanism for 
Reporting 
Back-up 
Method of 
Reporting 
Product Complaints 
PC associated 
with an SAE or 
might have led 
to an SAE 
Start of study 
intervention 
End of study 
intervention 
Within 24 hours of 
awareness 
PC form 
N/A 
PC not 
associated with 
an SAE 
Start of study 
intervention 
End of study 
intervention 
Within 1 business day 
of awareness 
PC form 
N/A 
Updated PC 
information 
L 
L 
As soon as possible 
upon site awareness 
Originally 
completed PC form 
with all changes 
signed and dated by 
the investigator 
N/A 
PC (if 
investigator 
becomes aware) 
Participation 
in study has 
ended 
N/A 
Promptly 
PC form 
 
AE = adverse event; CRF = case report form; ICF = informed consent form; N/A = Not applicable; PC = product 
complaint; SAE = serious adverse event 
a Serious adverse events should not be reported unless the investigator deems them to be possibly related to study 
treatment or study participation. 
8.3.2. 
Pregnancy  
Collection of pregnancy information 
Male participants with partners who become pregnant 
&415:B1?@53-@;>C588-@@19<@@;/;881/@<>13:-:/E5:2;>9-@5;:;:-:E9-81<->@5/5<-:@P?219-81
partner who becomes pregnant while the male participant is in this study. This applies only to 
male participants who receive mirikizumab. 
After learning of a pregnancy in the female partner of a study participant, the investigator will 
 obtain a consent to release information from the pregnant female partner directly, and 
 within 24 hours after obtaining this consent will record pregnancy information on the 
appropriate form and submit it to the sponsor. 
The female partner will also be followed to determine the outcome of the pregnancy. Information 
on the status of the mother and child will be forwarded to the sponsor. Generally, the follow-up 
will be no longer than 
 weeks following the estimated delivery date. Any termination of the 
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pregnancy will be reported regardless of gestational age, fetal status (presence or absence of 
anomalies) or indication for the procedure. 
Female participants who become pregnant 
The investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study. The initial information will be recorded on the 
appropriate form and submitted to the sponsor within 24 hours of learning of a participantPs 
pregnancy. 
The participant will be followed to determine the outcome of the pregnancy. The investigator 
will collect follow-up information on the participant and the neonate and the information will be 
forwarded to the sponsor. Generally, follow-up will not be required for longer than 
 weeks 
beyond the estimated delivery date. Any termination of pregnancy will be reported, regardless of 
gestational age, fetal status (presence or absence of anomalies) or indication for the procedure. 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be reported as an AE or SAE. 
A spontaneous abortion (occurring at 
 weeks gestational age) or still birth (occurring at 
 
weeks gestational age) is always considered to be an SAE and will be reported as such. 
Any post-study pregnancy related SAE considered reasonably related to the study intervention 
by the investigator will be reported to the sponsor as described in protocol Section 8.3.1. While 
the investigator is not obligated to actively seek this information in former study participants, he 
or she may learn of an SAE through spontaneous reporting. 
Any female participant who becomes pregnant while participating in the study will discontinue 
study intervention. If the participant is discontinued from the study, follow the standard 
discontinuation process and continue directly to the follow-up phase. The follow-up on the 
pregnancy outcome should continue independent of intervention or study discontinuation. 
If a participant becomes pregnant during the study, no additional endoscopies will be performed. 
8.3.3. Adverse Events of Special Interest  
The AESIs for this program may include but are not limited to: 
Sites should collect additional details and data regarding AESIs, as instructed on the applicable 
CRFs. 
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8.4. 
Pharmacokinetics  
In the event of a potential systemic drug hypersensitivity reaction or 
 related 
event, venous blood samples approximately 
 eachwill be collected to determine the serum 
concentrations of mirikizumab. 
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Collection, handling, and storage of samples 
Instructions for the collection and handling of blood samples will be provided by the sponsor. 
The actual date and time (24-hour clock time) of each sampling will be recorded. Samples will 
be analyzed at a laboratory approved by the sponsor and stored at a facility designated by the 
sponsor. Serum concentrations of mirikizumab will be determined using a validated enzyme 
linked immunosorbent assay. 
The sample retention is described in Section 10.1.12. 
8.5. 
Pharmacodynamics  
Pharmacodynamic parameters are not evaluated in this study. 
8.6. 
Genetics  
Genetics are not evaluated in this study. 
8.7. 
Biomarkers  
Whole blood, stool, and endoscopic biopsy tissue samples for exploratory biomarker research 
will be collected at the times specified in the SoA (Section 1.3) where local regulations allow. 
See Section 8.1.5.4 for details on endoscopic biopsy tissue samples. 
Exploratory biomarker research is performed to address questions of relevance to drug 
disposition, target engagement, pharmacodynamics, mechanism of action, variability of 
participant response (including safety), and clinical outcome. Sample collection is incorporated 
into clinical studies to enable examination of these questions through measurement of 
 
Samples will be used for research on the drug target, disease process, variable response to 
mirikizumab, pathways associated with UC, mechanism of action of mirikizumab, or research 
method, or in validating diagnostic tools or assays related to UC. 
Sample retention is described in Section 10.1.12. 
8.8. 
Immunogenicity Assessments  
In the event of a potential 
 or an 
 
reaction and at visits and times specified in SoA (Section 1.3), venous blood samples will be 
collected to determine antibody production against mirikizumab. Additional samples may be 
collected at the final visit from participants who discontinued mirikizumab or were withdrawn 
from the study due to a 
 event or an 
 reaction. 
Antibodies may be further characterized for their ability to neutralize the activity of 
mirikizumab. 
To interpret the results of immunogenicity, a venous blood PK sample will be collected at the 
same time points to determine the concentrations of mirikizumab. 
Sample retention is described in Section 10.1.12. 
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9. 
Statistical Considerations  
The SAP will be finalized prior to first participant visit, and it will include a more technical and 
detailed description of the statistical analyses described in this section. This section is a summary 
of the planned statistical analyses of the most important endpoints, including primary and key 
secondary endpoints. 
9.1. 
Statistical Hypothesis  
The primary objective is to assess the improvement from baseline in UNRS in participants 
treated with mirikizumab at Week 
. No formal hypothesis testing will be performed on the 
primary endpoint. 
9.1.1. 
Multiplicity Adjustment  
Multiplicity control is not applicable for this study. 
9.2. 
Analysis Sets  
For purposes of analysis, the following analysis sets are defined: 
Population 
Description 
Full Analysis 
Set  
All participants who are assigned to treatment and receive at least 1 (partial or 
complete) dose of study treatment 
Safety Analysis 
Set 
All participants who are assigned to treatment and receive at least 1 (partial or 
complete) dose of study treatment 
9.3. 
Statistical Analyses  
9.3.1. 
General Considerations  
Statistical analysis of this study will be the responsibility of the sponsors or their designees. 
Handling of missing, unusable, and spurious data will be addressed prospectively in the overall 
statistical methods described in the protocol and in the SAP, where appropriate. Any change to 
the data analysis methods in the protocol will require an amendment only if it changes a principal 
feature of the protocol. Additional exploratory analyses of the data will be conducted as deemed 
appropriate. 
When reported, descriptive statistics will include the number of participants; mean, standard 
deviation, median, minimum, and maximum for continuous measures; frequency counts and 
percentages for categorical measures; and estimates and 95% confidence intervals for correlation 
coefficients. 
9.3.2. 
Primary Endpoint Analysis  
As described in Section 3, the primary endpoint is change from baseline in UNRS score at Week 
. The UNRS score at each time point (baseline and Week 
) will be summarized as a 
continuous measure for each participant as the average daily diary score over a -day period. The 
difference between the UNRS score at Week 
 and at baseline will be calculated for each 
participant and averaged. Diary data from at least  of the  days from the specified period are 
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required to calculate the average UNRS score and change from baseline, otherwise these 
endpoints will be considered missing. Further details regarding the primary estimand are 
described in Section 3. 
 
 
9.3.3. 
Secondary Endpoint Analysis  
Secondary endpoints and estimands are presented in Section 3. Descriptive summaries and 
confidence intervals will be provided for continuous and binary secondary endpoints as indicated 
in Section 9.3.1. Further details regarding endpoint definitions and analysis methods will be 
described in the SAP. 
9.3.4. 
Exploratory Analysis  
Exploratory endpoints are presented in Section 3. Details of the analyses of these endpoints, as 
well as additional exploratory analyses, will be described in the SAP or additional supplemental 
SAP, as appropriate. 
9.3.5. 
Safety Analyses  
Safety will be assessed by describing the following: including, but not limited to, AEs, 
laboratory analytes, vital signs, participant characteristics, and AESIs (Section 8.3.3). 
The AEs will be coded according to the MedDRA. A TEAE is defined as an event that first 
occurred or worsened in severity after baseline. The MedDRA Lowest Level Terms will be used 
in the treatment-emergent computation. If a participant reports the occurrence of a particular 
event more than once, the most severe of those events will be included in the summary tables of 
TEAEs. 
In an overview table, the number and percentage of participants with at least 1 TEAE, SAE, fatal 
SAE, or discontinuation from study treatment due to an AE will be summarized. TEAEs (all and 
by maximum severity), SAEs, including deaths, and AEs that lead to treatment discontinuation 
will be summarized and analyzed by MedDRA system organ class and PT or by PT alone. 
Laboratory and vital sign measurements will be summarized using boxplot displays and 
treatment-emergent shifts to low/high tables. Further analyses may be performed as deemed 
necessary. Potential AESIs will be identified by 1 or more Standardized MedDRA Queries by a 
Lilly-defined MedDRA PT listing based upon the review of the most current MedDRA version, 
or by treatment-emergent relevant laboratory changes. Definitions of the AESIs and associated 
analyses will be described in the SAP. 
This study also includes assessment of tolerability and acceptability of the 
 dose 
regimen through the summarization of AEs reported as 
 reactions and pain, as well 
as treatment discontinuations as defined in the SAP. Reports of 
 pain will include 
the assessment of severity (mild, moderate, or severe). Data from these assessments will be 
reviewed regularly throughout the study by the medical team as part of the trial level safety 
reviews. 
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All safety analyses will be fully detailed in the SAP. 
9.3.6. 
Other Analyses  
9.3.6.1. 
Subgroup Analyses  
Subgroup analyses for selected endpoints in Section 3 may be conducted. Subgroups to be 
evaluated may include
 
A detailed description of the subgroup variables and analyses will be provided 
in the SAP. 
Analyses specifically requested by regulatory agencies will be identified and implemented as 
deemed appropriate. 
9.3.6.2. 
Pharmacokinetic Analyses  
No pharmacokinetic analysis will be conducted for this study. 
9.4. 
Interim Analysis  
No interim analyses are planned for this study. However, if needed for regulatory interactions or 
publication purposes, an interim analysis may be performed after completion of Period II. 
9.5. 
Sample Size Determination  
Approximately 160 participants will be assigned to study intervention. The sample size was 
determined by considering the precision of the estimated correlation between endpoints. 
Simulations were performed for both binary and continuous measures where the true correlation 
varied between 
 The average half width of the 95% confidence intervals for the 
correlations at Week 
 varied between 
 under considered assumptions for an 
overall sample size of 160. The average half width of the 95% confidence intervals varied 
between 
 for endpoints during the maintenance period under the assumption that 
of participants could discontinue early from the study. 
Additionally, the proposed sample size of 160 participants is considered sufficient to have 
 
power to detect a significant (non-zero) change from baseline in UNRS at Week 
 (primary 
endpoint). 
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10. 
Supporting Documentation and Operational Considerations  
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations  
10.1.1. 
Regulatory and Ethical Considerations  
● This study will be conducted in accordance with the protocol and with the 
following: 
○ consensus ethical principles derived from international guidelines including 
the Declaration of Helsinki and Council for International Organizations of 
Medical Sciences (CIOMS) International Ethical Guidelines 
○ applicable ICH Good Clinical Practice (GCP) Guidelines, and 
○ applicable laws and regulations 
● The protocol, protocol amendments, ICF, Investigator Brochure, and other 
relevant documents (for example, advertisements) must be submitted to an 
IRB/IEC by the investigator and reviewed and approved by the IRB/IEC before 
the study is initiated. 
● Any amendments to the protocol will require IRB/IEC approval before 
implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to study participants. 
● Protocols and any substantial amendments to the protocol will require health 
authority approval prior to initiation except for changes necessary to eliminate an 
immediate hazard to study participants. 
● The investigator will be responsible for the following: 
○ Providing written summaries of the status of the study to the IRB/IEC 
annually or more frequently in accordance with the requirements, policies, and 
procedures established by the IRB/IEC 
○ Notifying the IRB/IEC of SAEs or other significant safety findings as required 
by IRB/IEC procedures 
○ Providing oversight of study conduct for participants under their responsibility 
and adherence to requirements of 21 Code of Federal Regulations (CFR), ICH 
guidelines, the IRB/IEC, European regulation 536/2014 for clinical studies (if 
applicable), and all other applicable local regulations 
○ Reporting to the sponsor or designee significant issues related to participant 
safety, participant rights, or data integrity 
● Investigator sites are compensated for participation in the study as detailed in the 
clinical trial agreement. 
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10.1.2. 
Financial Disclosure  
Investigators and sub-investigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study. 
10.1.3. 
Informed Consent Process  
● The investigator or the investigator’s representative will explain the nature of the 
study, including the risks and benefits, to the potential participant and answer all 
questions regarding the study. 
● Potential participants must be informed that their participation is voluntary. 
Participants will be required to sign a statement of informed consent that meets 
the requirements of 21 CFR 50, local regulations, ICH guidelines, privacy and 
data protection requirements, where applicable, and the IRB/IEC or study center. 
● The medical record must include a statement that written informed consent was 
obtained before the participant was entered in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent must 
also sign the ICF. 
● Participants must be reconsented to the most current version of the ICF(s) during 
their participation in the study. 
● A copy of the ICF(s) must be provided to the participant and is kept on file. 
Participants who are rescreened are required to sign a new ICF. 
10.1.4. 
Data Protection  
● Participants will be assigned a unique identifier by the sponsor. Any participant 
records, datasets or tissue samples that are transferred to the sponsor will contain 
the identifier only; participant names or any information which would make the 
participant identifiable will not be transferred. 
● The participant must be informed that the participant’s personal study-related data 
will be used by the sponsor in accordance with local data protection law. The 
level of disclosure must also be explained to the participant who will be required 
to give consent for their data to be used as described in the informed consent. This 
is done by the site personnel through the informed consent process. 
● The participant must be informed through the informed consent by the site 
personnel that their medical records may be examined by Clinical Quality 
Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
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● The sponsor has processes in place to ensure data protection, information security, 
and data integrity, including data transfer, unauthorized access, disclosure, 
dissemination, alteration, or loss of information or personal data. These processes 
include appropriate contingency plan(s) for appropriate and timely response in the 
event of a data security breach. The transfer of personal data is subject to 
appropriate safeguards through contractual agreements and processes. These 
processes are compliant with General Data Protection Regulation (GDPR) data 
privacy regulations and the European Clinical Trial Regulation (CTR) (articles 
56, 57, 58). 
10.1.5. 
Committees Structure  
Clinical event committee 
An independent Clinical Event Committee with membership external to the sponsor will be 
responsible for cerebro-cardiovascular event adjudication. The committee will include experts 
with appropriate expertise in cardiovascular medicine. 
The Clinical Event Committee charter will contain the final membership and detailed event 
definitions used for adjudication. 
10.1.6. 
Dissemination of Clinical Study Data  
Reports 
The sponsor will disclose a summary of study information, including tabular study results, on 
publicly available websites where required by local law or regulation. 
The summary of results will be posted within the time frame specified by local law or regulation. 
If the study remains ongoing in some countries and a statistical analysis of an incomplete dataset 
would result in analyses lacking scientific rigor (for example, underpowered) or compromise the 
integrity of the overall analyses (for example, trial not yet unblinded), the summary of results 
will be submitted within 1 year after the end of the study globally or as soon as available, 
whichever is earlier. 
Data 
The sponsor provides access to all individual participant data collected during the trial, after 
anonymization, with the exception of pharmacokinetic or genetic data. 
Data are available to request 6 months after the indication studied has been approved in the US 
and EU and after primary publication acceptance, whichever is later. No expiration date of data 
requests is currently set once data are made available. 
Access is provided after a proposal has been approved by an independent review committee 
identified for this purpose and after receipt of a signed data sharing agreement. 
Data and documents, including the study protocol, statistical analysis plan, clinical study report, 
and blank or annotated case report forms, will be provided in a secure data sharing environment 
for up to 2 years per proposal. 
For details on submitting a request, see the instructions provided at www.vivli.org. 
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10.1.7. 
Data Quality Assurance  
 All participant data relating to the study will be recorded on printed or 
electronic CRFs unless transmitted to the sponsor or designee electronically, 
for example, laboratory data. The investigator is responsible for verifying that 
data entries are accurate and correct by physically or electronically signing the 
CRF. 
 The investigator must maintain accurate documentation (source data) that 
supports the information entered in the CRF. 
 The investigator must review and confirm that data entries are accurate and 
complete throughout the duration of the study, by physically or electronically 
signing the CRF, as instructed by the sponsor. All completed CRFs must be 
signed prior to archival. 
 The investigator must permit study-related monitoring, audits, IRB/IEC 
review, and regulatory agency inspections and provide direct access to source 
documents. 
 Quality tolerance limits will be pre-defined to identify systematic issues that 
can impact participant safety and/or reliability of study results. These pre-
defined parameters will be monitored during the study, and important 
excursions from the quality tolerance limits and remedial actions taken will be 
summarized in the clinical study report. 
 Monitoring details describing strategy (for example, risk-based initiatives in 
operations and quality, such as risk management and mitigation strategies and 
analytical risk-based monitoring), methods, responsibilities, and requirements, 
including handling of noncompliance issues and monitoring techniques, are 
provided in the Monitoring Plan. 
 The sponsor or designee is responsible for the data management of this study, 
including quality checking of the data. 
 The sponsor assumes accountability for actions delegated to other individuals 
(for example, contract research organizations). 
 The sponsor or designee will perform monitoring to confirm that data 
transcribed into the CRF by authorized site personnel are accurate, complete, 
and verifiable from source documents; that the safety and rights of 
participants are being protected; and that the study is being conducted in 
accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements. 
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 Records and documents, including signed ICFs, pertaining to the conduct of 
this study must be retained by the investigator for the time period outlined in 
the clinical trial agreement (CTA) unless local regulations or institutional 
policies require a longer retention period. No records may be destroyed during 
the retention period without the written approval of the sponsor. No records 
may be transferred to another location or party without written notification to 
the sponsor. 
 In addition, Sponsor or its representatives will periodically check a sample of 
the participant data recorded against source documents at the study site. The 
study may be audited by Sponsor or its representatives, and/or regulatory 
agencies at any time. Investigators will be given notice before an audit occurs. 
Data capture system 
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness 
of the data reported to the sponsor. 
An EDC will be used in this study for the collection of CRF data. The investigator maintains a 
separate source for the data entered by the investigator or designee into the sponsor-provided 
EDC system. The investigator is responsible for the identification of any data to be considered 
source and for the confirmation that data reported are accurate and complete by signing the CRF. 
Additionally, clinical outcome assessment data (participant-focused outcome instrument) and 
other data, such as SDAL, will be collected by the participant, via a paper source document, and 
will be transcribed by the authorized study personnel into the EDC system. 
Additionally, electronic clinical outcome assessment data (participant-focused outcome 
instrument) will be directly recorded by the participant or investigator site personnel, into an 
instrument, for example, handheld smart phone or tablet). The electronic clinical outcome 
assessment data will serve as the source documentation and the investigator does not maintain a 
separate written or electronic record of these data. 
Data collected via the sponsor-provided data capture system(s) will be stored at third parties. The 
investigator will have continuous access to the data during the study and until decommissioning 
of the data capture system(s). Prior to decommissioning, the investigator will receive or access 
an archival copy of pertinent data for retention. 
Data managed by a central vendor, such as laboratory test data, will be stored electronically in 
the central vendor’s database system, and reports will be provided to the investigator for review 
and retention. Data will subsequently be transferred from the central vendor to the Sponsor data 
warehouse. 
Data from complaint forms submitted to the Sponsor will be encoded and stored in the global 
product complaint management system. 
10.1.8. 
Source Documents  
 Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site. 
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 Data reported on or entered in the CRF and are transcribed from source documents 
must be consistent with the source documents, or the discrepancies must be 
explained. The investigator may need to request previous medical records or transfer 
records, depending on the study. Also, current medical records must be available. 
 Definition of what constitutes source data can be found in Section 10.1.7. 
10.1.9. 
Study and Site Start and Closure  
First act of recruitment 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
The first act of recruitment is the first site open. 
Study or site termination 
The sponsor or sponsor’s designee reserves the right to close the study site or terminate the study 
at any time for any reason at the sole discretion of the sponsor. Study sites will be closed upon 
study completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study site closure visit has been performed. 
The investigator may initiate study site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to 
For study termination 
 discontinuation of further study intervention development 
 For site termination 
 failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines 
 inadequate recruitment (evaluated after a reasonable amount of time) of 
participants by the investigator, and 
 total number of participants included earlier than expected. 
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up. 
10.1.10. 
Publication Policy  
In accordance with the sponsor’s publication policy, the results of this study will be submitted 
for publication by a peer-reviewed journal. 
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10.1.11. 
Investigator Information  
Researchers with appropriate education, training, and experience, as determined by the sponsor, 
will participate as investigators in this clinical trial. 
10.1.12. 
Sample Retention  
Sample retention enables use of new technologies, response to regulatory questions, and 
investigation of variable response that may not be observed until later in the development of 
mirikizumab or after mirikizumab become(s) commercially available for ulcerative colitis. 
 
Sample Type 
Custodian 
Retention Period after Last Participant 
Visita 
Exploratory biomarkers  
Sponsor or Designee 
Pharmacokinetic  
Sponsor or Designee 
Immunogenicity  
Sponsor or Designee 
a Retention periods may differ locally. 
 
 
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10.2. 
Appendix 2: Clinical Laboratory Tests  
 The tests detailed in the table below will be performed by the Lilly-designated 
laboratory or by the local laboratory as specified in the table below. 
 In circumstances where the sponsor approves local laboratory testing in lieu of central 
laboratory testing (in the table below), the local laboratory must be qualified in 
accordance with applicable local regulations. 
 Protocol-specific requirements for inclusion or exclusion of participants are detailed 
in Section 5 of the protocol. 
 Additional tests may be performed at any time during the study as determined 
necessary by the investigator or required by local regulations. 
 Investigators must document their review of the laboratory safety results. 
Clinical Laboratory Tests 
Comments 
Hematology 
Assayed by Lilly-designated laboratory 
Hemoglobin 
  
Hematocrit 
  
Erythrocyte count (RBCs - red blood cells) 
  
Mean cell volume  
  
Mean cell hemoglobin 
  
Mean cell hemoglobin concentration 
 
Leukocytes (WBCs - white blood cells)  
  
Absolute neutrophil count (segmented and bands) 
(calculated) 
  
Absolute count of 
 
  Neutrophils, segmented 
  
  Neutrophils, bands (if detected) 
 
  Lymphocytes 
  
  Monocytes 
  
  Eosinophils 
  
  Basophils 
  
Platelets 
  
Cell morphology (RBC and WBC) 
 
Clinical Chemistry 
Assayed by Lilly-designated laboratory 
Sodium 
  
Potassium 
  
Chloride 
  
Bicarbonate 
  
Total bilirubin 
  
Direct bilirubin 
  
Alkaline phosphatase (ALP) 
  
Alanine aminotransferase (ALT) 
  
Aspartate aminotransferase (AST) 
  
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Clinical Laboratory Tests 
Comments 
Gamma-glutamyl transferase (GGT) 
Blood urea nitrogen (BUN) 
  
Creatinine  
  
Creatine kinase (CK) 
 
Uric acid 
 
Total protein 
  
Albumin 
  
Calcium 
Glucose 
  
Cholesterol 
 
Urinalysis 
Assayed by Lilly-designated laboratory 
Specific gravity 
 
pH 
 
Protein 
 
Glucose 
 
Ketones 
 
Blood 
 
Nitrite 
 
Urine leukocyte esterase 
 
Hormones (female) 
Urine pregnancy 
Evaluated locally 
Serum pregnancy 
Assayed by Lilly-designated laboratory 
Follicle stimulating hormone (FSH) 
Assayed by Lilly-designated laboratory 
HIV, hepatitis serology, and TB 
 
HIV testing: 
 
  HIV antibody 
Assayed by Lilly-designated laboratory 
  HIV RNA 
Assayed by Lilly-designated laboratory 
Hepatitis C Virus (HCV) testing: 
  
  HCV antibody  
Assayed by Lilly-designated laboratory 
  HCV RNA 
Assayed by Lilly-designated laboratory 
Hepatitis B Virus (HBV) testing: 
 
  Hepatitis B core antibody (Anti-HBc)  
Assayed by Lilly-designated laboratory 
  Hepatitis B surface antigen (HBsAg)  
Assayed by Lilly-designated laboratory 
  HBV DNA 
Assayed by Lilly-designated laboratory. 
Performed only for participants who test positive for 
Anti-HBc 
Tuberculosis (TB) testing: 
 
  
Gold test 
Assayed by Lilly-designated laboratory (preferred) or 
if available, by local laboratory 
Pharmacokinetic samples  
Assayed by Lilly-designated laboratory 
Mirikizumab concentration 
 
Immunogenicity samples 
Assayed by Lilly-designated laboratory 
Anti-mirikizumab antibodies  
 
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Clinical Laboratory Tests 
Comments 
  
 
Stool Samples 
Assayed by Lilly-designated laboratory. Additional 
local testing (for example, for ova and parasites) is 
-88;C10-@@415:B1?@53-@;>P?05?/>1@5;: 
Stool Culture 
 
Clostridioides difficile (C difficile) testing 
Assayed by Lilly-designated laboratory. Confirmed 
by a test for C difficile toxin gene expression 
Fecal calprotectin 
Assayed by Lilly-designated laboratory. Results will 
not be provided to the investigative sites 
Exploratory biomarker storage samples 
Assayed by Lilly-designated laboratory.  
Results will not be provided to the investigative sites 
 
 
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10.2.1. 
Laboratory Samples to be Obtained at the Time of a Systemic Hypersensitivity 
Event  
Purpose of collecting samples after a systemic hypersensitivity event 
The samples listed in this appendix are not collected for acute study participant management. 
The sponsor will use the laboratory tests results from these samples to characterize 
hypersensitivity events across the clinical development program. 
When to collect samples after a systemic hypersensitivity event occurs 
Collect the samples listed below if a systemic hypersensitivity event is suspected. The timing 
should be as designated in the table, assuming the participant has been stabilized. 
Obtain follow-up predose samples at the next regularly scheduled laboratory sample collection 
(ideally prior to the next dose after the event) to assess post-event return to baseline values. 
Timing 
Laboratory Testa 
Collect from 
 hour after the start 
of the event. 
T 
Note: The optimal collection time is 
from 
 hr after the start of event. 
Collect only if not already collected on the 
same day as the event. 
T 
Note: If collecting, collect up to 
 hr 
after the start of the event. 
Abbreviation: 
 
a All samples for hypersensitivity testing will be assayed by Lilly-designated laboratory. Results will not be provided 
to the study site. If samples are not collected or are collected outside the specified time period, this will not be 
considered a protocol deviation. 
What information to record 
Record the date and time when the samples are collected. 
Allowed additional testing for participant management 
The investigator may perform additional tests locally, if clinically indicated, for acute study 
participant management. 
 
 
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10.3. 
Appendix 3: Adverse Events and Serious Adverse Events: Definitions 
and Procedures for Recording, Evaluating, Follow-up, and 
Reporting  
10.3.1. 
Definition of AE  
AE definition 
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product 
and which does not necessarily have a causal relationship with the study intervention. An AE can 
therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal 
(investigational) product, whether or not related to the medicinal (investigational) product. 
Events meeting the AE definition 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other 
safety assessments (for example, ECG, radiological scans, and vital sign measurements), 
including those that worsen from baseline, considered clinically significant in the medical and 
scientific judgment of the investigator (that is, not related to progression of underlying disease). 
Exacerbation of a chronic or intermittent preexisting condition, including either an increase in 
frequency and/or intensity of the condition. 
New condition detected or diagnosed after study intervention administration even though it may 
have been present before the start of the study. 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
Medication error, misuse, or abuse of study intervention, including signs, symptoms, or clinical 
sequelae. 
Lack of efficacy or failure of expected pharmacological action per se will not be reported as an 
AE or SAE. Such instances will be captured in the efficacy measures. However, the signs, 
symptoms, and/or clinical sequelae resulting from lack of efficacy will be reported as AE or SAE 
if they fulfill the definition of an AE or SAE. 
Events NOT Meeting the AE Definition 
Any clinically significant abnormal laboratory findings or other abnormal safety assessments that 
are associated with the underlying disease, unless judged by the investigator to be more severe 
than expected for the participant’s condition. 
The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s condition. 
Medical or surgical procedure, for example, endoscopy and appendectomy: the condition that 
leads to the procedure is the AE. 
Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present or detected 
at the start of the study that do not worsen. 
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10.3.2. 
Definition of SAE  
An SAE is defined as any untoward medical occurrence that, at any dose, meets 1 or more 
of the criteria listed: 
 Results in death 
 Is life-threatening 
o The term life-threatening in the definition of serious refers to an event in which 
the participant was at risk of death at the time of the event. It does not refer to an 
event, which hypothetically might have caused death, if it were more severe. 
 Requires inpatient hospitalization or prolongation of existing hospitalization 
o In general, hospitalization signifies that the participant has been admitted to 
hospital or emergency ward (usually involving at least an overnight stay) for 
observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfills any 
other serious criteria, the event is serious. When in doubt as to whether 
hospitalization occurred or was necessary, the AE should be considered serious. 
o Hospitalization for elective treatment of a preexisting condition that did not 
worsen from baseline is not considered an AE. 
 Results in persistent disability/incapacity 
o The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
o This definition is not intended to include experiences of relatively minor medical 
significance, such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma, for example, sprained ankle, which may 
interfere with or prevent everyday life functions but do not constitute a substantial 
disruption. 
 Is a congenital anomaly/birth defect 
o Abnormal pregnancy outcomes, for example, spontaneous abortion, fetal death, 
stillbirth, congenital anomalies, and ectopic pregnancy, are considered SAEs. 
 Other situations 
o Medical or scientific judgment should be exercised by the investigator in deciding 
whether SAE reporting is appropriate in other situations, such as important 
medical events that may not be immediately life-threatening or result in death or 
hospitalization but may jeopardize the participant or may require medical or 
surgical intervention to prevent one of the other outcomes listed in the above 
definition. These events should usually be considered serious. 
o Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
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dyscrasias, or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse. 
10.3.3. 
Definition of Product Complaints  
Product complaint 
 A PC is any written, electronic, or oral communication that alleges deficiencies related to 
the identity, quality, durability, reliability, safety, effectiveness, or performance of a 
study intervention. When the ability to use the study intervention safely is impacted, the 
following are also PCs: 
o deficiencies in labeling information, and 
o use errors for device or drug-device combination products due to ergonomic 
design elements of the product. 
 PCs related to study interventions used in clinical trials are collected to ensure the safety 
of participants, monitor quality, and to facilitate process and product improvements. 
 Investigators will instruct participants to contact the site as soon as possible if he or she 
has a PC or problem with the study intervention so that the situation can be assessed. 
 An event may meet the definition of both a PC and an AE/SAE. In such cases, it should 
be reported as both a PC and as an AE/SAE. 
10.3.4. 
Recording and Follow-Up of AE and/or SAE and Product Complaints  
AE, SAE, and product complaint recording 
 When an AE/SAE/PC occurs, it is the responsibility of the investigator to review all 
documentation (for example, hospital progress notes, laboratory reports, and diagnostics 
reports) related to the event. 
 The investigator will then record all relevant AE/SAE/PC information in the participant’s 
medical records, in accordance with the investigator’s normal clinical practice. AE/SAE 
information is reported on the appropriate CRF page and PC information is reported on 
the Product Complaint Form. 
 Note: An event may meet the definition of both a PC and an AE/SAE. In such cases, it 
should be reported as both a PC and as an AE/SAE. 
 It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to Sponsor or designee in lieu of completion of the CRF page for AE/SAE and 
the Product Complaint Form for PCs. 
 There may be instances when copies of medical records for certain cases are requested by 
Sponsor or designee. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to Sponsor or designee. 
 The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not the 
individual signs or symptoms) will be documented as the AE/SAE. 
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Assessment of intensity 
The investigator will make an assessment of intensity for each AE and SAE reported during the 
study and assign it to 1 of the following categories: 
 Mild: A type of adverse event that is usually transient and may require only minimal 
treatment or therapeutic intervention. The event does not generally interfere with usual 
activities of daily living. 
 Moderate: A type of adverse event that is usually alleviated with additional specific 
therapeutic intervention. The event interferes with usual activities of daily living, causing 
discomfort but poses no significant or permanent risk of harm to the research participant. 
 Severe: A type of adverse event that interrupts usual activities of daily living, or 
significantly affects clinical status, or may require intensive therapeutic intervention. An 
AE that is assessed as severe should not be confused with an SAE. Severe is a category 
utilized for rating the intensity of an event, and both AEs and SAEs can be assessed as 
severe. 
An event is defined as MseriousN when it meets at least 1 of the pre-defined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe. 
Assessment of causality 
 The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE. The investigator will use clinical judgment to 
determine the relationship. 
 
 
 
 Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 
 The investigator will also consult the IB in their assessment. 
 For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
 There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to Sponsor or designee. However, it is very 
important that the investigator always make an assessment of causality for every event 
before the initial transmission of the SAE data to Sponsor or designee. 
 The investigator may change their opinion of causality in light of follow-up information 
and send an SAE follow-up report with the updated causality assessment. 
 The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
Follow-up of AEs and SAEs 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by Sponsor or designee 
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to elucidate the nature and/or causality of the AE or SAE as fully as possible. This may include 
additional laboratory tests or investigations, histopathological examinations, or consultation with 
other health care professionals. 
10.3.5. 
Reporting of SAEs  
SAE reporting via paper form 
 Facsimile transmission of the SAE paper form is the preferred method to transmit this 
information to the sponsor. 
 Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE CRF pages within the designated reporting time frames. 
 Contacts for SAE reporting can be found in SAE paper form. 
10.3.6. 
Regulatory Reporting Requirements  
SAE regulatory reporting 
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of 
a study intervention under clinical investigation are met. 
 The sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study intervention under clinical 
investigation. Investigator safety reports will be prepared for SUSARs according to local 
regulatory requirements and sponsor policy. The sponsor will comply with country-
specific regulatory requirements relating to safety reporting to the regulatory authority, 
IRB/IEC, and investigators. 
 An investigator who receives an investigator safety report describing an SAE or other 
specific safety information, for example, summary or listing of SAEs, from the sponsor 
will review and then file it along with the IB and will notify the IRB/IEC, if appropriate 
according to local requirements. 
 Consistent with the EU CTR (536/2014), the sponsor has procedures that will be 
followed for the identification, recording, and expedited reporting of SUSARs. Upon an 
investigator’s report of an SAE, the sponsor will evaluate the data, including 
confirmation of relatedness and assessment of expectedness. The sponsor will submit any 
qualifying reports to the EudraVigilance database within the required time frame. 
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and will be forwarded to investigators as necessary. 
 
 
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10.4. 
Appendix 4: Contraceptive and Barrier Guidance  
10.4.1. 
Definitions  
Word/Phrase 
Definition 
Women of 
childbearing 
potential 
(WOCBP) 
Adult females are considered WOCBP unless they are WNOCBP. 
Women not of 
childbearing 
potential 
(WNOCBP) 
Females are considered WNOCBP if they 
 have a congenital anomaly, such as Müllerian agenesis 
 are infertile due to surgical sterilization, or 
 are postmenopausal. 
Examples of surgical sterilization include total hysterectomy, bilateral 
salpingo-oophorectomy, bilateral salpingectomy, or bilateral oophorectomy. 
Postmenopausal 
state 
The postmenopausal state is defined as a woman: 
 at any age at least 6 weeks post-surgical bilateral oophorectomy 
with or without hysterectomy, confirmed by operative note or 
 aged at least 40 years and up to 55 years with an intact uterus, not 
on hormone therapya, who has had cessation of menses for at least 
12 consecutive months without an alternative medical cause, AND 
with a follicle stimulating hormone 
 or 
 55 years or older not on hormone therapy, who has had at least 12 
months of spontaneous amenorrhea, or 
 aged at least 55 years with a diagnosis of menopause prior to 
starting hormone replacement therapy. 
a Women should not be taking medications during amenorrhea, such as oral 
contraceptives, hormones, gonadotropin-releasing hormone, anti-estrogens, 
selective estrogen receptor modulators, or chemotherapy that could induce 
transient amenorrhea. 
 
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10.4.2. 
Contraception Guidance  
WOCBP and WNOCBP may participate in this trial. See Section 10.4.1 for definitions and 
additional requirements related to contraception. 
WOCBP who are completely abstinent as their preferred and usual lifestyle, or in a same-sex 
relationship as their preferred and usual lifestyle: 
Must…  
Must not…  
agree to either 
remain abstinent or 
stay in a same-sex 
relationship without 
sexual relationships 
with males 
 use periodic abstinence methods 
o calendar 
o ovulation 
o symptothermal, or 
o post-ovulation 
 declare abstinence just for the duration of a trial, or 
 use the withdrawal method 
 
WOCBP who are NOT completely abstinent as their preferred and usual lifestyle, or NOT in a 
same-sex relationship as their preferred and usual lifestyle, must do the following: 
Topic 
Condition 
Pregnancy testing 
 Have a negative serum test result at screening. 
 At each dosing visit, have a negative urine test result within 24 
hours prior to treatment exposure. 
See the protocol SoA for subsequent pregnancy testing requirements. 
Contraception 
 Agree to use 1 highly effective method of contraception, or a 
combination of 2 effective methods of contraception. 
 
 These forms of contraception must be used for the duration of 
the study. 
 
 
 
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Examples of different forms of contraception: 
Methods 
Examples 
Highly effective 
contraception (less 
than 1% failure rate) 
 female sterilization 
 combination oral contraceptive pill 
 progestin-only contraceptive pill (mini-pill) 
 implanted contraceptives 
 injectable contraceptives 
 contraceptive patch (only women <198 pounds or 90 kg) 
 total abstinence (in compliance with local requirements) 
 vasectomy (if only sexual partner) 
 fallopian tube implants (if confirmed by 
hysterosalpingogram) 
 combined contraceptive vaginal ring, or 
 intrauterine devices 
Effective 
contraception 
 male or female condoms with spermicide 
 diaphragms with spermicide or cervical sponges 
 barrier method with use of a spermicide 
o condom with spermicide 
o diaphragm with spermicide, or 
o female condom with spermicide 
Ineffective forms of 
contraception whether 
used alone or in any 
combination 
 spermicide alone 
 periodic abstinence 
 fertility awareness (calendar method, temperature method, 
cervical mucus, or symptothermal) 
 withdrawal 
 postcoital douche, or 
 lactational amenorrhea 
Guidance for all men 
Males may participate in this trial. 
No male contraception is required except in compliance with specific local government study 
requirements. 
 
 
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cal 
dical 
s. 
or 
 
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10.6. 
Appendix 6: Mayo Scoring System  
This table describes the Mayo Scoring System for the assessment of UC disease activity. 
Stool Frequency 
Score 
Normal number of stools for subject 
0 
1 to 2 stools more than normal 
1 
3 to 4 stools more than normal 
2 
5 or more stools than normal 
3 
Rectal Bleeding  
Score 
No blood seen 
0 
Streaks of blood with stool less than half of the time 
1 
Obvious blood (more than just streaks) or streaks of blood with 
stool most of the time 
2 
Blood alone passed 
3 
Endoscopic Subscore 
Score 
Normal or inactive disease 
0 
Mild disease (erythema, decreased vascular pattern) 
1 
Moderate disease (marked erythema, absent vascular pattern, 
friability, erosions) 
2 
Severe disease (spontaneous bleeding, ulceration) 
3 
Physician’s Global Assessment 
Score 
Normal 
0 
Mild disease 
1 
Moderate disease 
2 
Severe disease 
3 
Mayo Score = Stool Frequency + Rectal Bleeding + Endoscopic Subscore + Physician’s Global Assessment 
Note: The Mayo score ranges from 0 to 12, with higher scores indicating more severe disease. The partial Mayo 
score excludes endoscopy and ranges from 0 to 9, while the modified Mayo score excludes the Physician’s Global 
Assessment and also ranges from 0 to 9. The original description of the Mayo score included friability in the 
definition of an endoscopic subscore of 1. Consistent with current clinical practice and regulatory guidance, this 
study excludes friability from the definition of an endoscopic subscore of 1. 
Source: Adapted from Schroeder et al. (1987). 
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10.8. 
Appendix 8 Examples of Infections That May Be Considered 
Opportunistic in the Setting of Biologic Therapy  
This table lists examples of infections that may be considered opportunistic in the context of 
biologic therapy. This table is provided to aid the investigator in recognizing infections that may 
be considered opportunistic. This list is not exhaustive. For data analysis, infections will be 
categorized by Lilly as opportunistic according to the article by 
. 
Examples of infections that may be considered opportunistic in the setting of biologic 
therapy 
Bacterial 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
Viral 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
Fungal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Parasitic 
 
 
 
 
 
 
 
 
 
 
Source: Based on 
. 
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10.9. 
Appendix 9: Tuberculosis Testing  
This table describes recommendations for performing and interpreting TB tests. It also provides 
recommendations on TB retesting. 
TB test type 
How to perform the test 
How to interpret the test 
When to retest 
 
M tuberculosis 
Ensure that specimen handling, 
transport, timing, and 
laboratory procedures meet all 
requirements per package 
insert. 
Results are provided by the 
laboratory assaying the test. 
The investigator may 
discuss retesting with the 
?<;:?;>P?01?53:-@10
medical monitor if 
T the investigator suspects 
a false-positive 
 Gold 
test result in a participant 
with no increased risk of 
TB infection during 
lifetime, and 
T there is no evidence of 
prior or current TB on 
physical examination 
and/or on CXR 
interpreted by radiologist 
and/or pulmonologist 
(investigator assessment 
by history and physical 
examination, and with 
documented CXR 
report). 
Abbreviation: CXR = chest X-ray. 
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10.10. 
Appendix 10: Permitted Concomitant Medications/Therapies  
Drug Class (examples)  
Comments by Study Period 
Screening and Washout 
Treatment 
I 
II 
III 
Oral 5-ASAs (mesalamine, balsalazide, 
olsalazine) and sulfasalazine for UC 
 
if participant is on a stable prescribed dose 
 weeks before screening endoscopy 
If continuing stable screening dose, 
prescribed dose must remain stable until 
Visit 6 (Week 
) 
May continue 
with stable dose 
encouraged 
Oral corticosteroids for UC 
 
<>10:5?;:1
mg/day or equivalent, or 
 
extended-release budesonide tablets 
(budesonide MMX) 
 mg/day, or 
 
beclomethasone dipropionate  mg/day 
(gastro-resistant, prolonged-release tablet) 
 
if participant on stable prescribed dose 
 weeks before screening endoscopy 
If continuing stable screening dose, 
prescribed dose must remain stable until 
Visit 6 (Week 
) 
Tapering of dose 
may begin at Visit 
6 (Week 
). 
See Section 6.8.1 
Corticosteroids for non-UC indications 
Stable doses encouraged 
 
continued use/regimen to treat adrenal insufficiency 
 
locally administered use, e.g., inhaled, intranasal, intra-
articular, topical, and 
 
single doses, oral or IV, as premedication for mirikizumab 
administration in participants with prior 
mirikizumab/other biologic administration reactions 
Oral AZA, 6-MP, MTX for UC indication 
 
if participant on stable prescribed dose 
weeks before screening endoscopy 
If continuing stable screening dose, prescribed dose must 
remain stable throughout the study unless modifications are 
needed due to AEs related to the medication 
Topical JAK inhibitors and calcineurin 
inhibitors 
As needed 
Antidiarrheals 
(loperamide, diphenoxylate with atropine) 
Stable doses encouraged 
Low-dose or baby aspirin (
 mg) 
Daily use of a stable dose for cardiovascular prophylaxis 
Non-live vaccines 
(killed, inactivated, subunit, or RNA-based)  
If a non-live vaccine is needed, it is recommended that study 
intervention not be administered on the same day of the 
vaccination 
Complementary alternative medicine for non-
UC indications (dietary or herbal supplements, 
vitamins, probiotics) 
Stable regimen and doses encouraged. 
Other nonprescription medicines in this category may be 
permitted following discussion with the medical monitor 
Abbreviations: 5-ASA = 5-aminosalicylic acid; 6-MP = 6-mercaptopurine; AE = adverse event; AZA = 
azathioprine; IV = intravenous; JAK = Janus kinase; MMX = Multi matrix colonic delivery technology; MTX = 
methotrexate; UC = ulcerative colitis. 
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10.11. 
Appendix 11: Prohibited Medications  
This section outlines medications that are prohibited during the treatment phase of the study and 
during washout periods prior to the screening endoscopy, if applicable. Use of the medications 
listed in this appendix is allowed at the discretion of the investigator after a participant 
discontinues study intervention and completes the ED visit. 
Drug Class (examples)  
Comments by Study Period 
Screening and Washout  
Treatment 
 
I 
II 
III  
Biologics, JAK inhibitors, Immunomodulators 
Anti-TNF antibodies 
(adalimumab, golimumab, infliximab)  
DC 
 prior to screening 
endoscopy 
Prohibited  
 
DC 
 prior to screening 
endoscopy. See Section 5.2. 
Prohibited  
Anti-integrin antibodies 
(vedolizumab) 
DC 
 prior to screening 
endoscopy 
Prohibited  
JAK inhibitors, oral 
(tofacitinib, upadacitinib) 
DC 
 prior to screening 
endoscopy 
Prohibited  
 
 
DC 
 prior to screening 
endoscopy 
Prohibited 
Immunomodulators for UC: oral AZA, 6-MP, 
MTX  
Initiation or increase above the stable dose at screening is 
prohibited during the study 
Immunomodulatory medications, oral or IV: 
cyclosporine, mycophenolate mofetil, 
thalidomide, tacrolimus. 
Other immunomodulatory medications should 
be discussed with medical monitor prior to use 
DC 
 prior to screening 
endoscopy 
Prohibited 
Corticosteroids 
Rectally administered corticosteroids, 
enemas or suppositories 
DC 
 prior to screening 
endoscopy 
Prohibited  
Oral corticosteroids for UC  
Initiation or increase above the stable oral dose at screening is 
prohibited during the study 
Oral budesonide standard formulation 
- 
Note: this is not budesonide MMX 
DC 
 prior to screening 
endoscopy 
Prohibited 
IV corticosteroids for UC 
DC 
 prior to screening 
endoscopy 
Course of IV corticosteroids 
prohibited  
Systemic corticosteroids for non-UC indication, 
oral or IV. Allowed exceptions: See Section 
10.10. 
DC 
 prior to screening 
endoscopy 
Prohibited  
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Drug Class (examples)  
Comments by Study Period 
Screening and Washout  
Treatment 
 
I 
II 
III  
Other 
Rectally administered 5-ASA therapies - 
enemas, suppositories 
DC 
 prior to screening 
endoscopy 
Prohibited 
Agents depleting B or T cells (alemtuzumab, 
rituximab, visilizumab) 
DC 
 prior to screening 
endoscopy 
Prohibited 
Any investigational therapy, biologic or 
non-biologic 
DC 
 or  half-lives, 
whichever is longer, prior to 
screening endoscopy 
Prohibited 
Rectally administered investigational 
preparations for UC (arsenic) 
DC 
 prior to screening 
endoscopy 
Prohibited  
Interferon therapy 
DC 
 prior to screening 
endoscopy 
Prohibited 
Leukocyte apheresis, leukapheresis 
(Adacolumn) 
DC 
 prior to screening 
endoscopy 
Prohibited 
BCG vaccination  
!;@
<>5;>@;(5?5@	 
Prohibited, also 
-2@1>8-?@
dose of mirikizumab 
Live or attenuated vaccines (for measles, 
mumps, rubella, or varicella). 
See Section 6.8.3. 
!;@
<>5;>@;(5?5@	 
Prohibited, also 
-2@1>8-?@
dose of mirikizumab 
Nonprescription complementary alternative 
medicines for UC indication (dietary/herbal 
supplements, vitamins, probiotics) 
 
Prohibited during study. 
May consult with medical monitor 
Medicinal and recreational marijuana  
DC 
 prior to screening 
endoscopy 
Prohibited 
Abbreviations: 5-ASA = 5-aminosalicylic acid; 6-MP = 6-mercaptopurine; AZA = azathioprine; BCG = Bacillus 
Calmette-Guerin; DC = discontinue; IL= interleukin; IV = intravenous; JAK = Janus kinase; M = month; 
MMX = multi matrix colonic delivery technology; MTX = methotrexate; S1P = Sphingosine-1-phosphate; TNF 
= tumor necrosis factor; UC = ulcerative colitis; W = weeks. 
 
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10.12. 
Appendix 12: Optional Continued Access Period  
10.12.1. 
Overview  
The Continued Access Period is offered to sites with eligible study participants who complete 
AMBZ Study Periods I to III. 
The duration of the Continued Access Period will differ by participant and country. 
 
 
 
 
Efficacy data will not be collected during the Continued Access Period. Participants will 
continue to be followed for safety throughout their participation in this Continued Access Period. 
Study activities and procedures described in this appendix are in addition to the requirements of 
the main AMBZ protocol, unless otherwise specified. Some information from the main AMBZ 
protocol is repeated for clarity. 
 
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a Participants who are eligible for Continued Access should move directly from Visit 10 to Visit 501, on the same day, if possible. Visit 801 should not be 
performed. 
 
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10.12.3. 
Schedule of Activities for Continued Access Period  
Throughout this appendix, Mself-administrationN refers to 
 of mirikizumab by the participant or caregiver. 
All visits 
Self-administration of mirikizumab 
 mg 
 is required at all visits, regardless if the visit is onsite, or telehealth or remote. 
All activities should be completed prior to self-administration of mirikizumab, unless otherwise stated below. 
Continued Access Treatment (Visit 501 to last dosing visit) 
Visit 501 activities should occur on the same day as Visit 10 of Study Period III. 
Complete all Visit 10 activities before starting Visit 501 activities and dosing. 
If Visit 10 and Visit 501 do not occur on same day, Visit 501 activities may need to be repeated, as detailed in the continued access 
period SoA. 
If Visit 10 and Visit 501 occur more than 2 weeks apart, the following laboratory tests must be repeated: hematology, clinical 
chemistry, and HBV DNA. 
Extended continued access visits (ECAV) 
After Visit 507 (Week 
), ECAV continue until criteria for the final visit occurs. 
Visits ECAVa, ECAVb, and ECAVc occur every  weeks. 
Visit ECAVa and ECAVb represent telehealth or remote visits that occur every weeks, and follow an onsite visit. 
Visit ECAVc represents the quarterly onsite visit. 
Visit numbers will be registered sequentially after Visit 507. This table provides an example of the visit structure that will continue 
until the final visit. 
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Visit Number 
Visit ID 
Weeks from Visit 2 
507 
507 
ECAVa 
508 
ECAVb 
509 
ECAVc 
510 
ECAVa 
511 
ECAVb 
512 
ECAVc 
513 
 
Discontinuation (DC) visit 
All participants who discontinue mirikizumab treatment after Visit 501 should complete this DC Visit. 
Continued Access Period follow-up (  weeks) 
Visit 901 
All participants will complete this visit following their DC visit or at the end of their participation in the Continued Access Period of 
the study. 
Visit 901 may be performed onsite when onsite activities are required or -@5:B1?@53-@;>P?05?/>1@5;: 
Unscheduled visits 
Unscheduled visits may occur as needed, on any day without regard to visit interval. Required activities are indicated in the SoA. 
005@5;:-8<>;/10A>1?9-E.1<1>2;>910-@@415:B1?@53-@;>P?05?/>1@5;: 
 
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AMBZ Continued Access Period 
 
 
Comments 
Visit number 
501 
502 
503 
504 
505 
506 
507 
ECA
Va 
ECA
Vb 
ECA
Vc 
DC 
UV 
V901 
ECAV = extended continued access visit 
DC = discontinuation visit 
 
 
 
Visit conduct 
O 
T 
T 
O 
T 
T 
O 
T 
T 
O 
O 
O 
T 
O = onsite; T = telehealth/remote visit 
Z = If Visit 10 and Visit 501 do not occur on 
same day, these activities must be repeated 
ZZ2(5?5@-:0(5?5@;//A>>2 weeks 
apart,  these laboratory tests must be repeated 
Informed 
consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
ICF must be signed before any continued access-
specific activities are performed. 
Inclusion and 
exclusion 
criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Review and confirm specific inclusion and 
exclusion criteria before V501 activities and 
dosing.  
Substance use, 
including alcohol, 
caffeine, tobacco, 
nicotine 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
Concomitant 
medications 
*Z 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Adverse events 
(AEs) 
*Z 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
See Sections 8.3.1 and 8.3.3.  
Physical evaluation 
Weight 
*Z 
 
 
X 
 
 
X 
 
 
X 
X 
 
 
 
Vital signs 
*Z 
 
 
X 
 
 
X 
 
 
X 
X 
 
 
See Section 8.2.2.  
Symptom-
directed 
physical 
assessment 
*Z 
 
 
X 
 
 
X 
 
 
X 
X 
 
 
See Section 8.2.1. 
Evaluate for 
EIMs 
*Z 
 
 
X 
 
 
X 
 
 
X 
X 
 
 
See Section 8.2.1. 
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Tuberculosis 
(TB) evaluation 
*Z 
 
 
X 
 
 
X 
 
 
X 
X 
 
 
TB risk factors; symptoms of active TB. See 
Section 8.2.7. 
Participant education 
Self-
administration 
retraining 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Complete a@@415:B1?@53-@;>P?05?/>1@5;: See 
Section 10.12.6. 
Laboratory tests 
Hematology  
*ZZ 
 
 
X 
 
 
X 
 
 
X 
X 
XW 
XW 
WOptional per investigator discretion. 
Clinical 
Chemistry 
*ZZ 
 
 
X 
 
 
X 
 
 
X 
X 
XW 
XW 
WOptional per investigator discretion. 
Urine pregnancy 
(local) 
*Z 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Must be performed, with negative result 
available, prior to dosing at each visit, for 
WOCBP. 
Follicle 
stimulating 
hormone (FSH) 
X 
 
 
 
Optional, perform as needed to confirm 
postmenopausal status in female participants. 
See Section 8.2.5. 
HBV DNA 
X 
 
 
X 
 
 
X 
 
 
X 
X 
 
 
Only required for participants with positive HBV 
serology at screening. See Section 8.2.8. 
Pharmacokinetic 
(PK) samples 
Collect PK and ADA samples in the event of a potential systemic drug 
hypersensitivity reaction 
 reaction. 
 
 
Collect PK and ADA samples as detailed in 
Section 10.2. 
Immunogenicity 
(ADA) samples 
 
 
Endoscopy Procedures 
Endoscopy 
Not required, may perform p1>5:B1?@53-@;>P?05?/>1@5;:. 
 
 
 
If performed, conduct local read. 
Registration and dosing 
Register visit 
with IWRS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
Dispense 
mirikizumab via 
IWRS 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
 
 
Self-administer 
mirikizumab 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
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ICF = Informed consent form; IWRS = interactive web response system; SDAL = Study Drug Administration Log; V= Visit; WOCBP = women of childbearing 
potential  
Provide self-
administration 
materials for 
remote dosing 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
 
Materials include mirikizumab; SDALs; and 
ancillary supplies, including urine pregnancy 
tests for WOCBP. 
Review SDALs 
and mirikizumab 
 cartons  
X 
 
 
X 
 
 
X 
 
 
X 
 
 
 
See Section 10.12.6. 
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10.12.4. 
Overall Design  
Transition of participants from the main study to continued access 
A participant will 
 complete all AMBZ Visit 10 activities, including the Visit 10 study endoscopy with 
biopsies, and 
 complete Visit 501 of the Continued Access Period. 
o If a potentially eligible participant does not meet all inclusion and exclusion 
criteria at Visit 501, that participant should enter the posttreatment follow-up 
period of the main study protocol and complete Visit 801 as indicated in Section 
1.3. 
o If a potentially eligible participant meets all inclusion and exclusion criteria at 
Visit 501, that participant should continue visits and procedures according to the 
SoA in Section 10.12.3. 
10.12.5. 
Study Population  
The inclusion and exclusion criteria in this section are specific to this Continued Access 
Appendix. 
The inclusion and exclusion criteria stated in Section 5 do not apply to participant eligibility for 
continued access, unless that criterion is re-stated below. 
10.12.5.1. Inclusion Criteria  
Participants are eligible to enter the Continued Access Period only if all the following criteria 
apply. 
Informed consent 
52. Are capable of giving signed informed consent to take part in the continued access period, 
prior to any procedures specific to Continued Access Period being completed. 
Participant and disease characteristics 
53. Have completed AMBZ Study Periods I to III, including 
 all Visit 10 activities, including the endoscopy with biopsies 
 administration of at least 
 mg mirikizumab
 doses, without early 
termination of mirikizumab in Study Period III 
 self-administration training, or demonstrate willingness and ability to complete training 
and/or retraining, and 
 in the opinion of the investigator, would continue to derive benefit from treatment with 
mirikizumab 
54. Have the ability to complete Visit 501, including the first dose of mirikizumab of the 
Continued Access Period, on the same day as Visit 10, or within approximately 4 weeks after 
Visit 10. 
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 It is strongly recommended that no more than  weeks occur between Visit 9 of Period III 
and Visit 501 of the Continued Access Period. Participants requiring a longer duration for 
entry into the Continued Access Period, but not to exceed approximately 
 weeks, must 
be discussed on an individual basis with the medical monitor. 
55. Are up-to-date with surveillance colonoscopy requirement per Section 8.1.5.2, with 
documented negative results for colorectal dysplasia and cancer. If needed, a colonoscopy 
with biopsies should be the endoscopic procedure performed at Visit 10 (Week 
). 
56. Are willing and able to complete the scheduled visit activities for the Continued Access 
Period, including self-administration of mirikizumab (by participant or caregiver). Also, in 
the opinion of the investigator, are able to reliably perform remote, self-administration 
procedures and related required documentation. 
Sex and contraceptive/barrier requirements 
57. Agree to adhere to the contraception requirements specified in Section 10.4. 
10.12.5.2. Exclusion Criteria  
Participants are excluded from the Continued Access Period if any of the following criteria 
apply: 
Gastrointestinal exclusion criteria 
58. Have been diagnosed with CD, inflammatory bowel disease-unclassified, formerly known as 
indeterminate colitis. 
59. Have had bowel resection or other surgery for the treatment of UC or are likely to require 
surgery for the treatment of UC during the Continued Access Period. 
60. Have had evidence of toxic megacolon, intra-abdominal abscess, or stricture or stenosis 
within the small bowel or colon prior to Visit 501 of the Continued Access Period. 
61. Have evidence of cancer of the gastrointestinal tract prior to Visit 501 of the Continued 
Access Period. 
62. Have evidence of current sporadic adenoma without dysplasia (adenomatous polyps 
occurring proximal to known areas of colitis), that has not been removed. If completely 
removed prior to Visit 501, this exclusion criterion would no longer apply.  
Note: Once removed, the participant may be eligible for the Continued Access Period, after 
confirming no dysplasia or malignancy on local histology report; and the maximum roll-over 
period to enter the Continued Access Period has not been exceeded. 
63. Have current evidence of colonic dysplasia prior to Visit 501, including 
 polypoid or non-polypoid lesion(s) of colonic mucosa in an area which is endoscopically 
visible or invisible, and 
 histopathology report of M5:0125:5@12;>0E?<8-?5-N8;C-grade dysplasia, or high-grade 
dysplasia. 
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Infectious disease exclusion criteria 
64. Have been diagnosed with a clinically important infection including, but not limited to, 
hepatitis B, hepatitis C, HIV/AIDS, and active tuberculosis (TB) prior to Visit 501 of the 
Continued Access Period. 
65. Have detectable hepatitis B virus (HBV) DNA detected at any time prior to Visit 501 of the 
Continued Access Period. 
66.  Have been diagnosed with LTBI prior to Visit 501 of the Continued Access Period and are 
not willing to comply with completing TB treatment as appropriate. 
67.  Intend to receive a Bacillus Calmette-Guerin (BCG) vaccination or live attenuated 
vaccine(s) during the Continued Access Period. 
Other exclusion criteria 
68. Have been diagnosed with a condition, underwent a surgical procedure, received prohibited 
treatment, or experienced a laboratory abnormality that met criteria for permanent 
discontinuation from mirikizumab treatment prior to Visit 501 of the Continued Access 
Period. See Section 7.1. 
69. Currently meet temporary discontinuation of study intervention criteria (see Section 7.1.4). 
Note: Once resolution of the condition or appropriate treatment is met, the participant may be 
eligible for the Continued Access Period if the maximum roll-over period to enter the 
Continued Access Period has not been exceeded. 
70. Have initiated a new prohibited medication (see Section 10.11) prior to Visit 501 of the 
Continued Access Period. 
71. Have had evidence of alcohol dependence or illicit drug abuse prior to Visit 501 of the 
Continued Access Period. 
72. Have had the presence of a hepatic or hematologic laboratory abnormality prior to Visit 501 
of the Continued Access Period, that would require permanent discontinuation from 
mirikizumab treatment. See Section 7.1. 
73. Have an underlying disease, or surgical, physical, or medical condition that, in the opinion of 
the investigator, would potentially affect participant safety within the continued access 
period. 
74. Have a known systemic hypersensitivity to any component of mirikizumab, or have 
experienced an acute systemic hypersensitivity event with previous mirikizumab treatment 
administration, that precludes mirikizumab treatment. 
75. Are pregnant or planning pregnancy (females only) while enrolled in the continued access 
period, or within 
 weeks after receiving the last dose 
 dose of mirikizumab. 
76. Became part of the investigator site personnel directly affiliated with this study or their 
immediate families prior to Visit 501 of the Continued Access Period. 
77. Became a Lilly employee or an employee of third-party organizations involved with the 
study prior to Visit 501 of the Continued Access Period. 
78. Have enrolled in any other clinical study involving an investigational product or any other 
type of medical research judged not to be scientifically or medically compatible with this 
study. 
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79. Are unsuitable for inclusion in the continued access period in the opinion of the investigator 
;>?<;:?;>2;>-:E>1-?;:@4-@9-E/;9<>;95?1@41?A.61/@P??-21@E 
10.12.6. 
Study Intervention  
All participants enrolled in the Continued Access Period will self-administer 
 mg 
mirikizumab 
. 
Administration of mirikizumab should always be done after completion of all other visit 
activities, as specified in SoA (Section 10.12.3). 
At all telehealth or remote dosing visits, self-administration of mirikizumab should be performed 
immediately following completion of the telephone-portion of the visit. 
If self-administration is not possible at a visit, the study site staff may administer the dose at the 
study site and provide source documentation for the reason. If self-administration is not possible 
for repeated visits, study site should contact the medical monitor. 
Reporting requirements 
All required self-administration dosing information must be documented on the relevant SDALs 
for each visit. Deviations from the prescribed dosing regimen should be documented by the 
participant on the SDAL and recorded by site staff in the CRF. 
Following review of the completed SDALs, and returned mirikizumab 
 cartons, including 
any unused 
, if the site staff identifies any deviations from correct procedures, 
incomplete doses administered, PCs, and/or 
 concerns from participant, appropriate 
corrective actions, including retraining, should be completed. 
Treatment compliance 
Compliance with study intervention will be assessed at each visit. Compliance will be assessed 
by direct questioning, counting unused syringes, review of SDALs, and documented in the 
source documents. 
If a participant is noncompliant with self-administration procedures, the investigator should 
determine the reason for noncompliance and educate or manage the participant as appropriate to 
improve compliance. 
If, in consultation with the medical monitor, the noncompliance is deemed to be significant such 
that it affects the safety of the participant or the evaluation of the safety data during the 
Continued Access Period, the participant should be discontinued from the Continued Access 
Period. 
10.12.7. 
Discontinuation of Study Intervention and Participant Discontinuation from the 
Study  
In addition to the study intervention discontinuation requirements in Section 7.1, the following 
also apply to the continued access period: 
 
 
 
 
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Following discontinuation from mirikizumab during the continued access period, the participant 
should complete both the discontinuation visit and Visit 901, as indicated in the Continued 
Access Period SoA (Section 10.12.3). 
10.12.8. 
Safety Assessments  
During the Continued Access Period, all AEs, SAEs, and mirikizumab exposure will be reported 
on the CRF. SAEs will also be reported to the sponsor. In the event that an SAE occurs, the 
sponsor may request additional information to evaluate the reported SAE. 
Investigators will perform any other standard procedures, and tests needed to treat and evaluate 
participants; however, the choice and timing of the tests will be at the inves@53-@;>P?05?/>1@5;:
The sponsor will not routinely collect the results of these assessments. 
See Sections 10.12.1, and Sections 8.2 and 8.3 for more details. 
 
 
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10.12.9. 
Permitted Concomitant Medications/Therapies during Continued Access  
Note: At the discretion of the investigator, any permitted concomitant medication may have the 
dose modified, be discontinued, or be re-started during the Continued Access Period. If there are 
any questions on these permitted medications, please contact the medical monitor. 
Drug Class (examples) 
Comments 
Oral corticosteroids or oral budesonide 
(standard or extended-release formulation 
[budesonide MMX]) for UC 
 
prednisone 
 mg/day or equivalent 
 
budesonide   *
930-E;> 
 
beclomethasone 05<>;<5;:-@1
930-E
(gastro-resistant prolonged-release 
tablet)  
Short courses of corticosteroids, including budesonide, are 
permitted with tapering to begin as soon as clinically feasible, 
with a goal of discontinuing within 3 months. 
Participants who require increasing doses and repeated courses or 
are intolerant to tapering of corticosteroids should be considered 
for treatment discontinuation and termination from the Continued 
Access Period 
Corticosteroids for non-UC indications 
Permitted as follows: 
 
continued use to treat adrenal insufficiency 
 
locally administered use, e.g., inhaled, intranasal, 
intraarticular, and topical 
 
single doses (oral or IV) corticosteroids as premedication for 
miri self-administered 
 and 
 
limited use for acute conditions per investigator discretion 
Rectally administered corticosteroids 
(enemas or suppositories) 
Permitted with the goal of tapering as soon as clinically feasible 
or discontinuing within 3 months. 
Participants who require continuous use of steroid enemas or 
suppositories or are intolerant to tapering should be considered 
for treatment discontinuation and early termination from the 
Continued Access Period 
Immunomodulators for UC 
(oral AZA, 6-MP, or methotrexate) 
Permitted 
Oral 5-ASAs (mesalamine, balsalazide, 
olsalazine) and sulfasalazine for UC 
Permitted 
Rectally administered 5-ASAs 
(enemas or suppositories) 
Permitted 
Topical JAK inhibitors and calcineurin 
inhibitors 
Permitted 
Antidiarrheals 
(loperamide, diphenoxylate with atropine) 
Permitted 
Low-0;?1;>.-.E-?<5>5:@;	X93 
Daily use for cardiovascular prophylaxis permitted 
Non-live vaccines 
(killed, inactivated, subunit, or RNA-based)  
Permitted 
Complementary alternative medicine for UC 
and non-UC indications 
Permitted 
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(dietary/herbal supplements, vitamins, 
probiotics) 
Abbreviations: 5-ASA = 5-aminosalicylic acid; 6-MP = 6-mercaptopurine; AZA = azathioprine; IV = intravenous; 
JAK = Janus kinase; MMX = Multi-matrix system; UC = ulcerative colitis. 
 
 
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10.12.10 Prohibited Concomitant Medications/Therapies during Continued Access  
This section outlines medications that are prohibited during the continued access period of the 
study. Use of the medications in this table is allowed at the discretion of the investigator after a 
participant discontinues study intervention and completes the DC visit. 
Drug Class (examples) 
Continued Access Period 
Comments and Guidelines 
Biologics, JAK inhibitors, Immunomodulators 
Anti-TNF antibodies 
(adalimumab, golimumab, infliximab)  
Prohibited  
 
Prohibited  
Anti-integrin antibodies 
(vedolizumab) 
Prohibited  
 
Prohibited  
Small-molecule S1P receptor modulator (ozanimod) 
Prohibited  
Immunomodulatory medications, oral or IV: 
 Cyclosporine, mycophenolate mofetil, thalidomide, tacrolimus. 
Other immunomodulatory medications should be discussed with 
medical monitor prior to use 
Prohibited  
Corticosteroids 
Oral corticosteroids for UC 
Initiation or increase above the oral dose 
at screening is prohibited  
IV corticosteroids for UC 
Course of IV corticosteroids prohibited  
Systemic corticosteroids for non-UC indication, oral or IV 
Allowed exceptions: See Section 10.12.9. 
Prohibited  
Other 
Agents depleting B or T cells 
(alemtuzumab, rituximab, visilizumab) 
Prohibited  
Any investigational therapy, biologic or non-biologic 
Prohibited  
Rectally administered investigational preparations for UC 
(arsenic) 
Prohibited 
Interferon therapy 
Prohibited  
Leukocyte apheresis, leukapheresis 
(Adacolumn) 
Prohibited  
Bacillus Calmette-Guerin (BCG) vaccination  
Use prohibited, also 
-2@1>8-?@0;?1
of mirikizumab 
Live or attenuated vaccines 
(for measles, mumps, rubella, or varicella. See Section 6.8.3.) 
Use prohibited, also 
-2@1>8-?@0;?1
of mirikizumab 
Abbreviations: DC = discontinue; IL= Interleukin; IV = intravenous; M = month; S1P = Sphingosine-1-phosphate; 
TNF = tumor necrosis factor; UC = ulcerative colitis. 
 
 
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10.13. 
Appendix 13: Country-specific Requirements  
For sites in EU member states 
This appendix is not applicable at this time. 
For sites outside of EU member states 
Country-specific requirements, if any, will be described in a separate protocol addendum. 
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10.15. 
Appendix 15: Abbreviations and Definitions  
Term 
Definition 
6-MP 
6-mercaptopurine 
abuse 
Use of a study intervention for recreational purposes or to maintain an addiction or 
dependence 
ADA 
anti-drug antibody 
AE 
adverse event 
AESI 
adverse event of special interest 
AIDS 
acquired immunodeficiency syndrome 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
Anti-HBc 
Antibodies to hepatitis B core antigen 
AST 
aspartate aminotransferase 
authorized IMP 
Applicable to the EU only: a medicinal product authorized in accordance with 
Regulation (EC) No 726/2004 or in any Member State concerned in accordance with 
Directive 2001/83/EC, irrespective of changes to the labeling of the medicinal 
product, which is used as an investigational medicinal product 
AZA 
azathioprine 
BCG 
Bacillus Calmette-Guerin 
C difficile 
Clostridioides difficile 
CD 
Crohn’s disease 
CDC 
Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
CIOMS 
Council for International Organizations of Medical Sciences 
CK 
creatine kinase 
complaint 
A complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, purity, durability, reliability, safety or effectiveness, or 
performance of a drug or drug delivery system 
compliance 
Adherence to all study-related, good clinical practice (GCP), and applicable 
regulatory requirements 
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Term 
Definition 
CRF 
case report form; a printed, optical, or electronic document designed to record all of 
the protocol-required information to be reported to the sponsor for each trial 
participant 
CRP 
clinical research physician: individual responsible for the medical conduct of the 
study. Responsibilities of the CRP may be performed by a physician, clinical research 
scientist, global safety physician, or other medical officer 
 
 
CTA 
Clinical Trial Agreement 
CTR 
Clinical Trial Regulation 
CXR 
Chest X-ray 
D.Bil 
Direct bilirubin 
Device deficiencies 
equivalent to product complaint 
ECAV 
extended continued access visit 
ECG 
electrocardiogram 
ED 
early discontinuation 
EDC 
electronic data capture 
EIM 
extraintestinal manifestation 
enroll 
The act of assigning a participant to a treatment. Participants who are enrolled in the 
study are those who have been assigned to a treatment 
enter 
Participants entered into a study are those who sign the informed consent form 
directly or through their legally acceptable representatives 
ERB 
Ethical Review Board 
ES 
endoscopic subscore 
FSH 
follicle stimulating hormone 
 
 
GCP 
good clinical practice 
GGT 
gamma-glutamyl transferase 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B Virus 
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Term 
Definition 
HCV 
hepatitis C Virus 
HIV 
human immunodeficiency virus 
IB 
:B1?@53-@;>P?>;/4A>1 
 
 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IL 
interleukin 
IMP 
:B1?@53-@5;:-8 105/5:-8">;0A/@?11-8?;M5:B1?@53-@5;:-8<>;0A/@N 
A medicinal product which is being tested or used as a reference, including as a 
placebo, in a clinical trial 
informed consent 
A process by which a participant voluntarily confirms their willingness to participate 
in a particular study, after having been informed of all aspects of the study that are 
>181B-:@@;@41<->@5/5<-:@P?01/5?5;:@;<->@5/5<-@1:2;>910/;:?1:@5?0;/A91:@10
by means of a written, signed, and dated informed consent form 
INR 
international normalized ratio 
interim analysis 
An interim analysis is an analysis of clinical study data, separated into treatment 
groups, that is conducted before the final reporting database is created or locked 
investigational product 
A pharmaceutical form of an active ingredient or placebo being tested or used as a 
reference in a clinical trial, including products already on the market when used or 
assembled (formulated or packaged) in a way different from the authorized form, or 
marketed products used for an unauthorized indication, or marketed products used to 
3-5:2A>@41>5:2;>9-@5;:-.;A@@41-A@4;>5F102;>9%11-8?;M "N 
IRB 
Institutional Review Board 
IV 
intravenous 
IWRS 
interactive web-response system 
JAK 
Janus Kinase 
LTBI 
latent tuberculosis infection 
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Term 
Definition 
medication error 
Errors in the prescribing, dispensing, or administration of a study intervention, 
regardless of whether or not the medication is administered to the participant or the 
error leads to an AE. Medication error generally involves a failure to uphold 1 or more 
of the 5 M>534@?N;29105/-@5;:A?1@41>534@<->@5/5<-:@@41>534@0>A3@41>534@0;?1
right route, at the right time. 
In addition to the core 5 rights, the following may also represent medication errors: 
 
dose omission associated with an AE or a product complaint 
 
dispensing or use of expired medication 
 
use of medication past the recommended in-use date 
 
dispensing or use of an improperly stored medication 
 
use of an adulterated dosage form or administration technique inconsistent 
with the medicationPs labeling (for example, Summary of Product 
Characteristics, IB, local label, and protocol), or 
 
shared use of cartridges or prefilled pens, or both 
Misuse 
Use of a study intervention for self-treatment that either is inconsistent with the 
prescribed dosing regimen, indication, or both, or is obtained without a prescription 
MMS 
Modified Mayo Score 
MMX 
multi matrix colonic delivery technology 
MTX 
methotrexate 
NRS 
numeric rating scale 
PA 
posteriorKanterior 
Participant 
=A5B-81:@@;%@1>9M?A.61/@N-:5:05B50A-8C4;<->@5/5<-@1?5:-/85:5/-8@>5-8
either as recipient of an investigational medicinal product or as a control 
PC 
product complaint 
PCR 
polymerase chain reaction 
PGA 
"4E?5/5-:P?8;.-8??1??91:@ 
 
 
 
 
PK 
Pharmacokinetics 
PRO/ePRO 
patient-reported outcomes or electronic patient-reported outcomes 
PT 
Prothrombin Time 
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Term 
Definition 
Q4W 
once every 4 weeks 
 
 
QoL 
quality of life 
RB 
rectal bleeding 
RNA 
ribonucleic acid 
S1P 
Sphingosine-1-phosphate 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SC 
Subcutaneous 
Screen 
The act of determining if an individual meets minimum requirements to become part 
of a pool of potential candidates for participation in a clinical study  
SDAL 
Study Drug Administration Log 
SF 
stool frequency 
SoA 
Schedule of Activities 
SUSAR 
suspected unexpected serious adverse reaction 
TB 
tuberculosis 
TBL 
total bilirubin level 
TEAE 
Treatment-emergent adverse event: An untoward medical occurrence that emerges 
during a defined treatment period, having been absent pretreatment, or worsens 
relative to the pretreatment state, and does not necessarily have to have a causal 
relationship with this treatment 
TNF 
tumor necrosis factor 
UC 
ulcerative colitis 
ULN 
upper limit of normal 
UNRS 
urgency numeric rating scale 
UV 
unscheduled visit 
WBC 
white blood cell 
WHO 
World Health Organization 
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Term 
Definition 
WNOCBP 
women not of childbearing potential 
WOCBP 
women of childbearing potential 
 
 
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10.16. 
Appendix 16: Protocol Amendment History   
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents (TOC). 
 
Amendment [a] 
Overall Rationale for the Amendment: 
The purpose of this amendment is to clarify the surveillance colonoscopy requirements and to 
update protocol wording to align with current regulatory requirements. 
Minor editorial changes are not included in this table. 
Section # and Name 
Description of Change 
Brief Rationale 
1.3. Schedule of Activities 
Removed the OXP indicator for 
 at ED visit. 
To align with the analysis strategy. 
5.1. Inclusion Criteria 
Criterion 6: Added specific 
surveillance colonoscopy criteria 
to clarify the requirements for 
eligibility prior to Visit 2. 
To clarify the surveillance colonoscopy 
requirements.  
6. Study Intervention(s) and 
Concomitant Therapy 
Reworded the definition of study 
intervention. 
To improve alignment with regulatory 
definitions. 
8.1.5.2. Surveillance 
Colonoscopy Requirements 
Added specific surveillance 
colonoscopy criteria to clarify 
the requirements for eligibility 
prior to Visit 2; and removed 
subsection on minimum 
colonoscopy biopsy procedural 
requirements. 
To maintain consistency with revisions 
in Section 5.1, and to allow for regional 
differences in biopsy requirements for 
surveillance colonoscopies in 
participants with moderately to severely 
active UC. 
10.1.4. Data Protection 
Added statements to clarify 
methods for protection of 
personal data and handling of 
data security breach. 
To address an EU CTR (536/2014) 
requirement. 
10.3.6. Regulatory Reporting 
Requirements 
Added a description of the 
reporting of SUSARs. 
To address an EU CTR (536/2014) 
requirement. 
10.12.1. Overview (of 
Appendix 12: Optional 
Continued Access Period) 
Clarified that the Continued 
Access Period may be stopped if 
sponsor discontinues plans for 
?1175:3>13A8-@;>E-<<>;B-8M5:
any 9->71@?N>-@41>@4-:MC5@45:
@41<->@5/5<-:@P?/;A:@>EN 
To maintain consistency with statement 
in Section 10.12.7. 
10.12.3. Schedule of Activities 
for Continued Access Period 
Removed the footnote indicator 
on HBV DNA cell for Visit 501. 
To correct a typographical error. 
10.12.5.1. Inclusion Criteria (of 
Appendix 12: Optional 
Continued Access Period) 
Revised Criterion 55. 
To maintain consistency with other 
sections of the protocol. 
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