A Multicenter, Open-Label PK Study of Mirikizumab in Pediatric Patients With Moderately to Severely Active Ulcerative Colitis
Phase: PHASE2
Conditions: Ulcerative Colitis
Sponsor: Eli Lilly and Company

 
  
 I6T-MC-AMBU(c) Clinical Protocol 
 
 
A Multicenter, Open-Label PK Study of Mirikizumab in Pediatric Patients with Moderately to 
Severely Active Ulcerative Colitis (SHINE-1) 
 
NCT04004611 
 
Approval Date: 23-Oct-2021 
 
 

I6T-MC-AMBU(c) Clinical Protocol 
Page 1 
LY3074828 
 
Protocol I6T-MC-AMBU(c) 
A Multicenter, Open-Label PK Study of Mirikizumab in 
Pediatric Patients with Moderately to Severely Active 
Ulcerative Colitis 
SHINE-1 
EUDRA CTA:  2019-001298-96 
 
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. 
Mirikizumab (LY3074828) 
Eli Lilly and Company 
Indianapolis, Indiana USA 46285 
Document ID: VV-CLIN-008288 
Amendment (c) Electronically Signed and Approved by Lilly on date provided below. 
 
 
 
 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 2 
LY3074828 
Protocol Amendment Summary of Changes Table 
 
DOCUMENT HISTORY 
Document 
Date 
Amendment b 
30-Apr-2021 
Amendment a 
26-Aug-2019 
Original Protocol 
24-Apr-2019 
Amendment c  
This amendment is considered to be nonsubstantial. 
Overall Rationale for the Amendment: 
The primary purpose of this amendment is to modify dosing instructions for the ≥20-40 kg 
participants during the maintenance period. Each participant will receive one injection of a 1 mL 
prefilled syringe instead of two 0.5 mL injections for SC maintenance dosing. 
Section # and 
Name 
Description of Change 
Brief Rationale 
Section 2. 
Schedule of 
Activities 
Updated notes for endoscopy 
with biopsies procedure  
Clarified that a medical consult is 
necessary to omit endoscopy at the ETV 
visit 
Section 1 
Synopsis and 
Section 4. 
Objectives and 
Endpoints 
Section 5.1 
Overall 
Design 
Figure AMBU.1 Study design  
 
Updated the study design figure to reflect 
the updated language in section 7.1 (see 
below) 
Section 7.1 
Treatments 
Administered, 
Table 
AMBU.3. 
Treatment 
Regimens: 
Week 12 
Clinical 
Responders 
Updated enrollment initiation 
criteria for the ≤40 kg cohort 
receiving 10 mg/kg dosing 
To correct a prior protocol error and 
clarify enrollment of the 10 mg/kg cohort 
opens after all patients in the 5 mg/kg 
cohort have enrolled AND at least 5 
patients have had 2 doses and the Week 4 
evaluation of PK samples and safety 
assessment have been completed 
Section 7.1 
Treatments 
Administered, 
Removed reference to maximum 
volume for injections  
 
 
Study site feedback indicated that 
injecting 1 mL subcutaneously in patients 
weighing 20 kg to ≤40 kg is acceptable 
and importantly, avoids 2 injections in a 
Approved on 23 Oct 2021 GMT
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 3 
LY3074828 
Section # and 
Name 
Description of Change 
Brief Rationale 
Study Drug 
Administration 
 
 
 
 
child. Therefore, the maximum volume 
limitation was removed 
 
Section 7.1.1. 
Packaging and 
Labeling 
Updated information about study 
drug supplies 
 
 
Removed pharmacy manual 
reference 
Updated content to state study drug will 
be provided as 
 
. 
 
The document name was revised 
internally; the “Pharmacy Manual” does 
not include study drug administration 
instructions  
Section 9.1.5. 
Determination 
of Responder 
Status/Loss of 
Response and 
SoA 
comments 
 
 
 
  
 
 
Section 9.4.3.1 
Pregnancy 
Testing 
More clearly define ‘women of 
childbearing potential’ and when 
urine pregnancy testing should 
be conducted 
Feedback from clinical trial sites 
suggested prior wording was unclear. 
Providing a list of the possible categories 
relevant to our study population provides 
more clarity 
Section 10.2. 
Populations 
for Analyses, 
Table 
AMBU.6. 
Population 
Definitions 
Updated description of the mITT 
population 
To clarify that  the mITT is applicable for 
both induction and maintenance periods 
Appendix 6. 
Permitted 
Medications 
with Dose 
Stabilization 
 
  
 
 
 
 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 4 
LY3074828 
Table of Contents 
Section 
Page 
Protocol I6T-MC-AMBU(c) A Multicenter, Open-Label PK Study of 
Mirikizumab in Pediatric Patients with Moderately to Severely 
Active Ulcerative Colitis SHINE-1 .........................................................................................1 
Protocol Amendment Summary of Changes Table .......................................................................2 
Table of Contents .............................................................................................................................4 
1. 
Synopsis .................................................................................................................................11 
2. 
Schedule of Activities ............................................................................................................16 
3. 
Introduction ...........................................................................................................................33 
3.1. 
Study Rationale ................................................................................................................33 
3.2. 
Background.......................................................................................................................33 
3.2.1. 
Disease State and Treatment Goals ..........................................................................33 
3.2.2. 
Currently Available Treatments and Unmet Need ...................................................34 
3.2.3. 
Interleukin-23 as a Therapeutic Target in Ulcerative Colitis ...................................35 
3.2.4. 
Preclinical and Clinical Studies of Mirikizumab .....................................................35 
3.3. 
Benefit/Risk Assessment ..................................................................................................36 
4. 
Objectives and Endpoints ......................................................................................................38 
5. 
Study Design .........................................................................................................................43 
5.1. 
Overall Design ..................................................................................................................43 
5.1.1. 
Definition of Baseline ..............................................................................................45 
5.1.2. 
Definition of Enrollment ..........................................................................................45 
5.2. 
Number of Participants .....................................................................................................45 
5.3. 
End of Study Definition....................................................................................................45 
5.4. 
Scientific Rationale for Study Design ..............................................................................45 
5.5. 
Justification for Dose ........................................................................................................46 
6. 
Study Population ...................................................................................................................49 
6.1. 
Inclusion Criteria ..............................................................................................................49 
6.2. 
Exclusion Criteria .............................................................................................................53 
6.2.1. 
Rationale for Exclusion of Certain Study Candidates .............................................59 
6.3. 
Lifestyle Restrictions ........................................................................................................59 
6.4. 
Screen Failures .................................................................................................................59 
6.4.1. 
Allowed Retesting of Screening Investigations .......................................................60 
7. 
Treatments .............................................................................................................................62 
7.1. 
Treatments Administered .................................................................................................62 
7.1.1. 
Packaging and Labelling ..........................................................................................63 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 5 
LY3074828 
7.2. 
Method of Treatment Assignment ....................................................................................64 
7.2.1. 
Selection and Timing of Doses ................................................................................64 
7.3. 
Blinding ............................................................................................................................64 
7.4. 
Dosage Modification ........................................................................................................64 
7.5. 
Preparation/Handling/Storage/Accountability .................................................................64 
7.6. 
Treatment Compliance .....................................................................................................65 
7.7. 
Concomitant Therapy .......................................................................................................65 
7.7.1. 
Corticosteroid Taper ................................................................................................66 
7.7.2. 
Vaccine Administration During the Study ...............................................................67 
7.8. 
Treatment after the End of the Study ...............................................................................67 
7.8.1. 
Study Extensions ......................................................................................................67 
7.8.2. 
Treatment after Study Completion ...........................................................................67 
7.8.3. 
Special Treatment Considerations ...........................................................................68 
7.8.3.1. 
Premedication for Infusions ...............................................................................68 
7.8.3.2. 
Management of Hypersensitivity, Infusion-Related 
Events, Infusion Site Reactions and Injection Site 
Reactions ............................................................................................................68 
8. 
Discontinuation Criteria ........................................................................................................70 
8.1. 
Discontinuation from Study Drug ....................................................................................70 
8.1.1. 
Permanent Discontinuation from Study Drug ..........................................................70 
8.1.2. 
Temporary Interruption (Withholding) of Study Drug ............................................72 
8.1.3. 
Discontinuation of Inadvertently Enrolled Patients .................................................72 
8.2. 
Discontinuation from the Study ........................................................................................73 
8.3. 
Lost to Follow-Up ............................................................................................................73 
9. 
Study Assessments and Procedures .......................................................................................74 
9.1. 
Efficacy Assessments .......................................................................................................74 
9.1.1. 
Mayo Score ..............................................................................................................75 
9.1.2. 
Endoscopy ................................................................................................................77 
9.1.3. 
Endoscopic Biopsies ................................................................................................79 
9.1.4. 
Pediatric Ulcerative Colitis Activity Index ..............................................................79 
9.1.5. 
Determination of Responder Status/Loss of Response ............................................79 
9.1.6. 
Growth and Pubertal Assessments ...........................................................................80 
9.1.6.1. 
Occipital Head Circumference ...........................................................................80 
9.1.6.2. 
Height Velocity ..................................................................................................81 
9.1.6.3. 
Assessment of Puberty .......................................................................................81 
9.1.7. 
Health Outcomes Instruments ..................................................................................81 
9.1.8. 
Histopathology Scoring Instrument .........................................................................81 
9.1.9. 
Exploratory Assessments .........................................................................................82 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 6 
LY3074828 
9.1.9.1. 
Inflammatory Biomarkers ..................................................................................82 
9.1.9.2. 
Patient-Reported Outcome/Observer-Reported Outcome 
Instruments for Exploratory Assessments ..........................................................82 
9.1.9.3. 
Extraintestinal Manifestations ............................................................................83 
9.1.9.4. 
Physician-Reported Instrument ..........................................................................83 
9.1.10. 
Appropriateness of Assessments ..............................................................................83 
9.2. 
Adverse Events .................................................................................................................83 
9.2.1. 
Serious Adverse Events ...........................................................................................84 
9.2.1.1. 
Suspected Unexpected Serious Adverse Reactions ...........................................85 
9.2.1.2. 
Regulatory Reporting Requirements for Serious Adverse 
Events .................................................................................................................85 
9.2.2. 
Adverse Events of Special Interest ..........................................................................86 
9.2.2.1. 
Opportunistic Infections .....................................................................................86 
9.2.2.2. 
Systemic Allergic Reactions and Hypersensitivity Events ................................86 
9.2.2.3. 
Injection/Infusion Site Reactions .......................................................................87 
9.2.2.4. 
Cerebro-Cardiovascular and Venous Thromboembolic 
Event Adjudication .............................................................................................87 
9.2.3. 
Complaint Handling .................................................................................................87 
9.3. 
Treatment of Overdose .....................................................................................................87 
9.4. 
Safety ................................................................................................................................88 
9.4.1. 
Vital Signs ................................................................................................................88 
9.4.2. 
Electrocardiograms ..................................................................................................88 
9.4.3. 
Laboratory Tests ......................................................................................................88 
9.4.3.1. 
Pregnancy Testing ..............................................................................................89 
9.4.3.2. 
Hormone Testing ................................................................................................89 
9.4.4. 
Immunogenicity Assessments ..................................................................................89 
9.4.5. 
Other Tests ...............................................................................................................90 
9.4.5.1. 
Physical Examination .........................................................................................90 
9.4.5.2. 
Tuberculosis Testing ..........................................................................................91 
9.4.5.3. 
Chest Radiography .............................................................................................93 
9.4.5.4. 
Hepatitis B Testing .............................................................................................94 
9.4.5.5. 
Hepatitis C Testing .............................................................................................95 
9.4.5.6. 
Depression and Suicidality .................................................................................96 
9.4.5.7. 
Stool Testing ......................................................................................................97 
9.4.6. 
Safety Monitoring ....................................................................................................98 
9.4.6.1. 
Hepatic Safety Monitoring .................................................................................98 
9.5. 
Pharmacokinetics ..............................................................................................................99 
9.6. 
Pharmacodynamics .........................................................................................................100 
9.7. 
Pharmacogenomics .........................................................................................................100 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 7 
LY3074828 
9.7.1. 
Whole Blood Sample for Pharmacogenetic Research ...........................................100 
9.8. 
Biomarkers .....................................................................................................................100 
9.9. 
Medical Resource Utilization and Health Economics ....................................................101 
10. Statistical Considerations ....................................................................................................102 
10.1. Sample Size Determination ............................................................................................102 
10.2. Populations for Analyses ................................................................................................102 
10.3. Statistical Analyses .........................................................................................................102 
10.3.1. 
General Statistical Considerations .........................................................................102 
10.3.1.1. 
Missing Data Imputation ..................................................................................103 
10.3.2. 
Treatment Group Comparability ............................................................................103 
10.3.2.1. 
Patient Disposition ...........................................................................................103 
10.3.2.2. 
Patient Characteristics ......................................................................................103 
10.3.2.3. 
Concomitant Therapy .......................................................................................103 
10.3.2.4. 
Treatment Compliance .....................................................................................103 
10.3.3. 
Efficacy Analyses ..................................................................................................104 
10.3.3.1. 
Primary Analyses .............................................................................................104 
10.3.3.2. 
Secondary Analyses .........................................................................................104 
10.3.3.3. 
Tertiary/Exploratory Analyses .........................................................................104 
10.3.4. 
Safety Analyses ......................................................................................................104 
10.3.5. 
Pharmacokinetic/Pharmacodynamic Analyses ......................................................105 
10.3.6. 
Evaluation of Immunogenicity ...............................................................................105 
10.3.7. 
Other Analyses .......................................................................................................106 
10.3.7.1. 
Subgroup Analyses ...........................................................................................106 
10.3.8. 
Data Snapshot and Interim Analyses .....................................................................106 
10.3.8.1. 
Data Snapshots .................................................................................................106 
10.3.8.2. 
Interim Analyses ..............................................................................................106 
11. References ...........................................................................................................................107 
12. Appendices ..........................................................................................................................111 
 
 
 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 8 
LY3074828 
List of Tables 
Table 
Page 
Table AMBU.1. Schedule of Activities .......................................................................................17 
Table AMBU.2. Objectives and Endpoints ..................................................................................38 
Table AMBU.3. Treatment Regimens:  Week 12 Clinical Responders .......................................62 
Table AMBU.4. Treatment Regimens:  Week 12 Clinical Nonresponders .................................63 
Table AMBU.5. Secondary Efficacy Endpoint Definitions in Study AMBU .............................75 
Table AMBU.6. Population Definitions .....................................................................................102 
 
 
 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 9 
LY3074828 
List of Figures 
Figure 
Page 
Figure AMBU.1. Illustration of study design for clinical protocol I6T-MC-AMBU. ...................44 
Figure AMBU.2. Comparison of interquartile range for average induction concentration 
for the doses planned in pediatric patients ≤40 kg relative to adults. ...............47 
Figure AMBU.3. Comparison of interquartile range for average maintenance 
concentration for the doses planned in pediatric patients relative to 
adults. ................................................................................................................48 
 
 
 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 10 
LY3074828 
List of Appendices 
Appendix 
Page 
Appendix 1. 
Abbreviations and Definitions .........................................................................112 
Appendix 2. 
Clinical Laboratory Tests ................................................................................118 
Appendix 3. 
Study Governance Considerations ..................................................................120 
 
 ..................125 
Appendix 5. 
Prohibited Medications ....................................................................................127 
Appendix 6. 
Permitted Medications with Dose Stabilization ..............................................130 
Appendix 7. 
Ulcerative Colitis Disease Activity Measures .................................................132 
Appendix 8. 
Risk Factors for Latent Tuberculosis Infection ...............................................135 
Appendix 9. 
Examples of Infections that May Be Considered Opportunistic in the 
Setting of Biologic Therapy ............................................................................137 
Appendix 10. 
Provisions for Changes in Study Conduct During Exceptional 
Circumstances .................................................................................................139 
Appendix 11. 
Protocol Amendment I6T-MC-AMBU(b) Summary  
A Multicenter, Open-Label PK Study of Mirikizumab in Pediatric 
Patients with Moderately to Severely Active Ulcerative Colitis .....................148 
 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 11 
LY3074828 
1. Synopsis 
Title of Study: 
A Multicenter, Open-Label PK Study of Mirikizumab in Pediatric Patients with Moderately to 
Severely Active Ulcerative Colitis. 
Rationale:  
Current treatments for pediatric patients with ulcerative colitis (UC) have limitations with respect 
to efficacy, safety, and tolerability; in fact clinical trial data in pediatric populations is scant or 
lacking completely.  In addition, many treatments require close monitoring for adverse effects, 
which increases undue burden to the child and family.  Thus, there is a substantial unmet need 
for the development, evaluation, and approval of efficacious, safe, and well-tolerated therapies 
for children and adolescents with UC.  Interleukin-23 (IL-23) has been implicated as a 
pro-inflammatory factor in mucosal inflammation in UC.  Study I6T-MC-AMBU (AMBU) is an 
open-label study to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and 
clinical response to mirikizumab to establish induction and maintenance doses to evaluate in 
Phase 3, in children and adolescents with UC, aged 2 to less than 18 years.  Study AMBU will 
include safety data following mirikizumab treatment for at least 1 year. 
Objective(s)/Endpoints: 
Objectives 
Endpoints 
Primary  
 
 
To evaluate the pharmacokinetics (PK) of 
mirikizumab treatment in pediatric patients 
 
Clearance and volume of distribution of mirikizumab 
Secondary 
 
 
To evaluate the effect of treatment with 
mirikizumab on achieving clinical remission at 
Week 12 and/or Week 52 
 
The proportion of patients in modified Mayo score 
(MMS) clinical remission at Week 12 
 
The proportion of patients in MMS clinical remission 
at Week 52 
 
The proportion of patients in MMS clinical remission 
at Week 52 among the MMS clinical remitters at 
Week 12 (durable clinical remission) 
 
The proportion of patients in MMS clinical remission 
at Week 52 among the MMS clinical responders from 
Week 12 
MMS clinical remission is defined as:   
 
Stool frequency (SF) subscore = 0, or SF = 1, and 
 
Rectal bleeding (RB) subscore = 0, and 
 
Endoscopic subscore (ES) = 0 or 1 (excluding 
friability) 
MMS clinical response is defined below 
 
 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 12 
LY3074828 
Objectives 
Endpoints 
 
To evaluate the effect of treatment with 
mirikizumab on achieving clinical response at 
Week 12 and/or Week 52 
 
The proportion of patients in clinical response at 
Week 12 
 
The proportion of patients in clinical response at 
Week 52 
 
The proportion of patients in clinical response at 
Week 12 who achieve clinical response at Week 52 
Clinical response is based on the MMS and is defined as: 
o 
A decrease in the MMS of ≥2 points and 
≥30% decrease from baseline, and 
o 
A decrease of ≥1 point in the RB subscore 
from baseline or a RB score of 0 or 1 
 
To evaluate the effect of treatment with 
mirikizumab on achieving corticosteroid-free 
remission without surgery among patients in 
clinical remission at Week 52 and receiving 
corticosteroids at baseline  
 
The proportion of patients who are in MMS clinical 
remission at Week 52 without the use of 
corticosteroids  
 
To evaluate the effect of treatment with 
mirikizumab on PUCAI clinical remission at 
Week 12 and/or Week 52 
 
The proportion of patients in PUCAI clinical 
remission at Week 12 
 
The proportion of patients in PUCAI clinical 
remission at Week 52 
 
The proportion of patients in PUCAI clinical 
remission at Week 12 who achieve clinical remission 
at Week 52 
 
The proportion of patients in PUCAI clinical 
response at Week 12 who achieve clinical remission 
at Week 52 
PUCAI clinical remission is defined as a PUCAI score 
of <10 points 
PUCAI clinical response is defined below 
 
To evaluate the effect of treatment with 
mirikizumab on PUCAI clinical response at 
Week 12 and/or Week 52 
 
The proportion of patients in PUCAI clinical 
response at Week 12 
 
The proportion of patients in PUCAI clinical 
response at Week 52 
 
The proportion of patients in PUCAI clinical 
response at Week 12 who achieve PUCAI clinical 
response at Week 52 
PUCAI clinical response is defined as a reduction in 
baseline PUCAI score of ≥20 points 
 
 
 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 13 
LY3074828 
Objectives 
Endpoints 
 
To evaluate the effect of treatment with 
mirikizumab on achieving endoscopic remission 
at Week 12 and/or Week 52 
 
The proportion of patients in endoscopic remission at 
Week 12  
 
The proportion of patients in endoscopic remission at 
Week 52 
 
The proportion of patients in endoscopic remission at 
Week 12 who maintain endoscopic remission at 
Week 52 (durable endoscopic remission) 
Endoscopic remission is defined as: 
o 
ES = 0 or 1 (excluding friability) 
 
To evaluate the effect of treatment with 
mirikizumab on achieving ES = 0 at Week 12 or 
Week 52  
 
The proportion of patients with ES = 0 at Week 12  
 
The proportion of patients with ES = 0 at Week 52 
 
To evaluate the effect of treatment with 
mirikizumab on symptomatic remission over 
time 
 
Proportion of patients in symptomatic remission at 
applicable study visits 
Symptomatic remission is defined as: 
o 
SF = 0, or SF = 1 with a ≥1-point decrease 
from baseline and  
o 
RB = 0 
 
To evaluate the effect of treatment with 
mirikizumab on height velocity at Weeks 12, 24, 
and 52 
 
Observed height velocity by gender and age group 
will be calculated at baseline, Week 12, Week 24, 
and Week 52 
 
To evaluate the effect of treatment with 
mirikizumab on weight throughout the trial 
 
Change from baseline in weight (kg) at all study 
visits by gender and age group 
 
To evaluate the effect of treatment with 
mirikizumab on pubertal development throughout 
the trial in appropriate patient groups 
 
Hormone levels and/or other related clinical 
measures will be evaluated 
 
 
 
 
 
To evaluate histologic-endoscopic mucosal 
remission following mirikizumab treatment at 
Week 12 or Week 52 
 
Proportion of patients with histologic-endoscopic 
mucosal remission at Week 12 
 
Proportion of patients with histologic-endoscopic 
mucosal remission at Week 52 
Histologic-endoscopic mucosal remission is defined as 
achieving both histologic remission and endoscopic 
remission.  Histologic remission will be defined in the 
SAP. 
 
 
Approved on 23 Oct 2021 GMT
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 14 
LY3074828 
Objectives 
Endpoints 
 
To evaluate the development of anti-mirikizumab 
antibodies and their effect on efficacy, safety, and 
mirikizumab exposure 
 
Proportion of patients who have treatment-emergent 
anti-drug antibodies (TEADA)  
 
Relationship between TEADA and efficacy 
 
Relationship between TEADA and safety 
 
Relationship between TEADA and mirikizumab PK 
 
 
 
 
 
 
 
Abbreviations:  NRS = numeric rating scale; PUCAI = Pediatric Ulcerative Colitis Activity Index; SAP = statistical 
analysis plan. 
 
Summary of Study Design:   
Study AMBU is a multicenter, Phase 2, open-label study designed to evaluate the safety, PK, 
PD, and clinical response of mirikizumab in pediatric patients, and to provide data for dose 
confirmation for Phase 3.  The study population includes pediatric patients with moderately to 
severely active UC, who have an inadequate response to, loss of response to, or are intolerant to 
non-biologic therapy for UC (biologic-naive), and/or those who have been exposed to at least 1 
biologic and/or Janus kinase (JAK) inhibitor therapy for UC (biologic/JAK inhibitor-
experienced). 
Treatment Arms and Duration:   
Patients weighing >40 kg will receive a mirikizumab induction dose of 300 mg via intravenous 
(IV) infusion and patients weighing ≤40 kg will receive 5 or 10 mg/kg via IV infusion at 
Weeks 0, 4, and 8.  Patients who have met the clinical response criteria at Week 12 will receive 
subcutaneous (SC) maintenance doses of 200 mg (weight >40 kg), or 100 mg (weight >20 kg to 
≤40 kg), or 50 mg (weight ≤20 kg) every 4 weeks (Q4W) from Weeks 12 to 48.  Patients who 
have not achieved clinical response at Week 12 may receive extended induction at the next 
higher dose, or will be discontinued.  In cases where there is no higher dose, patients may receive 
extended induction dosing at the current dose. 
Number of Patients:  
Approximately 60 patients with moderately to severely active UC will be screened to enroll 
approximately 30 patients.   
Statistical Analysis: 
Analyses of the PK of mirikizumab and relationships between exposure and the efficacy 
endpoints will be conducted.  For both the PK and exposure–response analyses, intrinsic and 
extrinsic factors will be evaluated to determine their impact.  Comparisons of adult and pediatric 
PK and exposure–response will be performed and may be combined if appropriate.   
The PK of mirikizumab (primary objective) will be characterized at interim analysis points using 
graphical evaluations and mixed-effect (population PK) modelling approaches using the 
available induction and maintenance mirikizumab concentration data.  The modelling will be 
used to understand the impact of factors, such as body weight and age, to estimate the exposures 
Approved on 23 Oct 2021 GMT
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 15 
LY3074828 
expected prior to enrolling the 10 mg/kg dose group in this study using interim analyses of PK 
data, and to confirm the planned doses for the Phase 3 study. 
 
  
Efficacy analyses for the induction period and the maintenance period will be conducted on the 
modified intent-to-treat (ITT) population.  Safety analyses for the induction period and the 
maintenance period will be conducted on the induction safety population and the maintenance 
safety population, respectively.   
Descriptive summaries by treatment, by visit, and by weight group for efficacy endpoints 
(secondary objectives) will be performed using nonresponder imputation (NRI) methodology. 
Safety data will be summarized by dose.  Safety assessments will include adverse events, 
laboratory analytes, vital signs, and questionnaires to assess the existence and severity of 
depression. 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 16 
LY3074828 
2. Schedule of Activities 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 17 
LY3074828 
Table AMBU.1. 
Schedule of Activities  
 
Screening 
Treatment Period 
Notes: 
Visit No. 
V1
  
V2
  
V3 
V4 
V5 
V6
  
V7 
V8 
V9
  
V10 
Study Week 
 
Study Days 
 
Patient assent (if appropriate) 
and parent/legal guardian 
informed consent 
 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
Demographic information, 
medical and surgical history 
 
X 
 
 
 
 
 
 
 
 
 
Pre-existing (current) medical 
conditions 
X 
 
 
 
 
 
 
 
 
 
 
Review vaccine status 
X 
 
 
 
 
 
 
 
 
 
 
Concomitant medication 
review (including 
corticosteroid use) 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Review AEs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Tobacco/nicotine use 
X 
X 
 
 
 
X 
 
 
X 
 
Alcohol/caffeine use 
X 
 
 
 
 
 
 
 
 
 
Investigational Product Administration 
Assignment to treatment 
weight cohort 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 18 
LY3074828 
 
Screening 
Treatment Period 
Notes: 
Visit No. 
V1
  
V2
  
V3 
V4 
V5 
V6
  
V7 
V8 
V9
  
V10 
Study Week 
 
Study Days 
 
 
 
 
 
 
 
 
Physical Evaluation 
 
Vital signs (temperature, BP 
using an appropriately sized 
cuff, and pulse rate) 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Occipital head circumference 
 
X 
 
 
 
X 
 
 
X 
 
Weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Height 
 
X 
 
X 
 
 
 
 
X 
 
 
 
X 
 
Physical examination  
X 
X 
X 
X 
X 
X 
 
 
X 
 
Evaluate for EIMs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
12-lead ECG (locally read) 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
Laboratory Investigations 
Urinalysis  
X 
 
 
 
 
 
 
 
 
 
 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 19 
LY3074828 
 
Screening 
Treatment Period 
Notes: 
Visit No. 
V1
  
V2
  
V3 
V4 
V5 
V6
  
V7 
V8 
V9
  
V10 
Study Week 
 
Study Days 
 
 
Serum pregnancy test 
 
 
Xa 
 
 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy test  
 
 
 
 
X 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
Hormone collection 
 
 
  
 
 
 
 
 
 
 
 
 
 
HIV/HBV/HCV testing 
Xa 
 
 
 
 
 
 
 
 
 
 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 20 
LY3074828 
 
Screening 
Treatment Period 
Notes: 
Visit No. 
V1
  
V2
  
V3 
V4 
V5 
V6
  
V7 
V8 
V9
  
V10 
Study Week 
 
Study Days 
 
 
 
 
HBV DNA 
 
 
 
 
Xa 
 
 
 
 
 
 
 
 
Xa 
 
 
 
 
 
 
X 
 
 
Chemistry/Hematology 
PK assessment 
 
 
 
 
 
 
 
 
 
 
    Pre-dose PK sample 
 
 
 
X 
X 
Xa 
X 
 
X 
 
    Post-dose PK sample 
 
X 
 
 
X 
 
 
 
 
 
    PK sample 
 
 
X 
 
 
 
 
 
 
 
Immunogenicity (ADA) 
samples   
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 21 
LY3074828 
 
Screening 
Treatment Period 
Notes: 
Visit No. 
V1
  
V2
  
V3 
V4 
V5 
V6
  
V7 
V8 
V9
  
V10 
Study Week 
 
Study Days 
 
 
 
 
 
Hypersensitivity testing (if 
applicable) 
 
 
 
 
 
 
Xa 
Pharmacogenomics blood 
sample 
 
TB testing 
 
Xa 
 
 
 
 
 
 
 
 
 
C-reactive protein 
 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 22 
LY3074828 
 
Screening 
Treatment Period 
Notes: 
Visit No. 
V1
  
V2
  
V3 
V4 
V5 
V6
  
V7 
V8 
V9
  
V10 
Study Week 
 
Study Days 
Additional Safety Tests 
Chest radiography for TB 
screening (optional – see 
comment) 
 
 
X 
 
 
 
 
 
 
 
 
 
TB Monitoring 
C-SSRS 
CDI 2 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 23 
LY3074828 
 
Screening 
Treatment Period 
Notes: 
Visit No. 
V1
  
V2
  
V3 
V4 
V5 
V6
  
V7 
V8 
V9
  
V10 
Study Week 
 
Study Days 
Stool Samples 
 
 
Stool culture and Clostridium 
difficile toxin 
 
 
X 
 
 
 
 
 
 
 
 
 
Fecal sample for fecal 
calprotectin and exploratory 
biomarker sample 
Endoscopic Procedure 
Endoscopy with biopsies 
X 
 
 
 
 
X 
 
 
 
 
Tissue samples for 
exploratory biomarkers 
Ulcerative Colitis Disease Activity Assessments 
Diary dispensed 
X 
 
 
 
 
 
 
 
 
 
 
 
 diary compliance 
review 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
PGA 
PUCAI 
Health Outcomes Assessment                                                                
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 24 
LY3074828 
 
Screening 
Treatment Period 
Notes: 
Visit No. 
V1
  
V2
  
V3 
V4 
V5 
V6
  
V7 
V8 
V9
  
V10 
Study Week 
 
Study Days 
PGI-C 
 
 
 
X 
X 
X 
 
 
 
 
 
Visits 11 to Post-treatment Follow-up 
 
Treatment Period 
 
Post-treatment 
Follow-up 
Notes 
Visit No. 
V11 
V12 
V13 
V14 
V15 
V16
  
N/A
  
V997b 
V801 
V802c 
Study Week 
Study Days 
 
 
 
 
 
Concomitant medication 
review (including 
corticosteroid use) 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Review AEs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Tobacco/nicotine use 
 
 
 
 
 
 
X 
 
X 
 
X 
 
 
Investigational Product Administration 
 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 25 
LY3074828 
Visits 11 to Post-treatment Follow-up 
 
Treatment Period 
 
Post-treatment 
Follow-up 
Notes 
Visit No. 
V11 
V12 
V13 
V14 
V15 
V16
  
V801 
V802c 
Study Week 
Study Days 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Evaluation 
 
Vital signs (temperature, BP 
using appropriate size cuffs, 
and pulse rate) 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Occipital head circumference 
 
X 
 
 
 
X 
X 
 
 
 
Weight  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height  
 
 
 
 
 
X 
X 
 
 
 
Physical examination  
 
X 
 
 
X 
X 
X 
X 
X 
X 
Evaluate for EIMs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 26 
LY3074828 
Visits 11 to Post-treatment Follow-up 
 
Treatment Period 
 
Post-treatment 
Follow-up 
Notes 
Visit No. 
V11 
V12 
V13 
V14 
V15 
V16
  
V801 
V802c 
Study Week 
Study Days 
 
 
 
 
 
 
12-lead ECG (locally read) 
 
 
 
 
 
 
 
X 
 
 
X 
 
 
 
Laboratory Investigations 
 
 
 
 
Urine pregnancy test 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
 
Xb 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
Hormone collection  
 
 
 
 
 
 
 
 
 
 
 
 
 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 27 
LY3074828 
Visits 11 to Post-treatment Follow-up 
 
Treatment Period 
 
Post-treatment 
Follow-up 
Notes 
Visit No. 
V11 
V12 
V13 
V14 
V15 
V16
  
V801 
V802c 
Study Week 
Study Days 
 
 
 
 
 
 
 
 
 
HBV DNA 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
Xa 
 
 
 
 
 
Xa 
 
 
 
 
 
 
 
Xa 
 
 
Chemistry/Hematology 
 
 
 
 
 
 
 
 
 
 
 
PK assessment 
 
 
 
X 
 
 
 
 
Xa 
 
Xa 
 
 
 
Xa 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 28 
LY3074828 
Visits 11 to Post-treatment Follow-up 
 
Treatment Period 
 
Post-treatment 
Follow-up 
Notes 
Visit No. 
V11 
V12 
V13 
V14 
V15 
V16
  
V801 
V802c 
Study Week 
Study Days 
 
 
 
 
Immunogenicity (ADA) 
samples 
 
 
 
 
 
 
 
 
 
 
C-reactive protein 
 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 29 
LY3074828 
Visits 11 to Post-treatment Follow-up 
 
Treatment Period 
 
Post-treatment 
Follow-up 
Notes 
Visit No. 
V11 
V12 
V13 
V14 
V15 
V16
  
N/A
  
V802c 
Study Week 
Study Days 
 
 
 
 
 
 
 
 
 
 
 
 
Hypersensitivity testing (if 
applicable) 
 
 
 
 
 
 
 
 
Xa 
 
 
 
 
Pharmacogenomics blood 
sample 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 30 
LY3074828 
Visits 11 to Post-treatment Follow-up 
 
Treatment Period 
 
Post-treatment 
Follow-up 
Notes 
Visit No. 
V11 
V12 
V13 
V14 
V15 
V16
  
V801 
V802c 
Study Week 
Study Days 
 
 
 
 
Additional Safety Tests 
TB Monitoring 
CDI 2 
 
Stool Samples 
Fecal sample for fecal 
calprotectin and exploratory 
biomarker sample 
Endoscopy Procedure 
 
Endoscopy with biopsies 
Tissue samples for exploratory 
biomarkers 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 31 
LY3074828 
Visits 11 to Post-treatment Follow-up 
 
Treatment Period 
 
Post-treatment 
Follow-up 
Notes 
Visit No. 
V11 
V12 
V13 
V14 
V15 
V16
  
V801 
V802c 
Study Week 
Study Days 
 
 
 
 
Ulcerative Colitis Disease Activity Assessments 
 
 
 diary compliance review 
 
 
X 
 
 
   X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
 
Diary device collected 
 
 
 
 
 
X 
X 
 
 
 
PGA 
PUCAI 
Health Outcomes Assessment                                                                        
PGI-C 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 32 
LY3074828 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 33 
LY3074828 
3. Introduction 
3.1. Study Rationale 
Ulcerative colitis (UC) in pediatric patients remains a disease with high morbidity marked by a 
relapsing and remitting clinical course.  The unmet medical need for pediatric UC treatment 
exists in 3 primary areas:   
 To provide new treatments that can induce and maintain remission in patients who have 
not sufficiently responded to currently available treatment regimens.  
 To improve treatment outcomes such that the use of corticosteroids is reduced or 
eliminated, thus avoiding corticosteroid-induced adverse effects.  
 To provide new treatments with improved safety profiles.   
Mirikizumab (LY3074828) is a humanized immunoglobulin G4 monoclonal antibody that binds 
to the p19 subunit of interleukin-23 (IL-23), a cytokine that has been implicated in mucosal 
inflammation.  This study will provide dose evaluation in pediatric patients aged 2 to 17 years, 
efficacy data in induction and maintenance periods, and safety data following mirikizumab 
treatment for approximately 1 year. 
3.2. Background 
3.2.1. Disease State and Treatment Goals 
Ulcerative colitis is a chronic relapsing and remitting disease characterized by inflammation, 
ulceration, and bleeding in the colon.  Inflammation in UC is confined to the mucosal surface of 
the rectum and colon.  Ulcerative colitis is thought to be caused by a dysregulated immune 
response to host intestinal microflora.   
The prevalence of pediatric UC over time is increasing as evidenced by a population-based, 
nationwide cohort study based in Canada (Benchimol et al. 2009 [Canada]).  The prevalence of 
UC in the United States (US) pediatric population as reported in the literature ranges between 
25,459 (Betteridge et al. 2013; US Census Bureau [WWW]) and 27,923 people (Kappelman et 
al. 2013; US Census Bureau [WWW]).  In addition, although at least 1 study reported higher 
male versus female prevalence of UC (Button et al. 2010 [United Kingdom (UK)]), other studies 
reported the opposite or no significant differences between genders (Kappelman et al. 2013 [US]; 
Di Domenicantonio et al. 2014 [Italy]). 
The management of UC in children and adolescents is multifactorial and is based on treatment 
goals of:  
 induction of remission with endoscopic healing  
 maintenance of remission, and  
 longer term prevention of cancer of the affected bowel.   
 
 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 34 
LY3074828 
Other factors that influence management of pediatric patients with UC include:  
 disease severity  
 disease distribution (pancolitis, left-sided colitis, or proctitis)  
 response to and tolerance of previous treatments, and  
 comorbidities.   
Age-related considerations (for example, growth, puberty, and bone mineral density accretion) 
and patient and caregiver preferences also influence treatment plans. 
Given this information and the unmet medical need to provide an effective therapy for pediatric 
patients, this Phase 2 study is being conducted to generate pharmacokinetic (PK) and clinical 
response data to support clinical development for use of mirikizumab in pediatric patients with 
moderately to severely active UC. 
3.2.2. Currently Available Treatments and Unmet Need  
Remission rates in pediatric UC have been evaluated in pediatric clinical trials and retrospective 
reviews, and these evaluations have indicated that 29% to 50% of children with 
moderate-to-severe disease achieved steroid-free remission at 1 year (Hyams et al. 2006, 2011, 
2012; Zeisler et al. 2013).  Current treatments for pediatric patients with UC have significant 
limitations with respect to efficacy, safety, and tolerability.  In addition, many treatments require 
close monitoring for adverse effects, which increases undue burden on the child and family.  
Thus, there is a substantial unmet need for the development and approval of efficacious, safe, 
and well-tolerated therapies for children and adolescents with UC. 
To date, the anti-tumor necrosis factor (TNF) antibody, infliximab, is the only biologic therapy 
approved to treat UC in pediatric patients.  Although anti-TNF therapy has improved disease 
course in UC, lack of efficacy and loss of response continue to be a concern in this patient 
population (Hyams et al. 2012). 
The safety profile of current therapies, including infliximab, may also limit their use in some 
patients.  Treatment with infliximab is associated with an increased risk for serious infections 
leading to hospitalization or death, including tuberculosis (TB), bacterial sepsis, invasive fungal 
infection (for example, histoplasmosis), and infections caused by other opportunistic pathogens.  
Lymphoma and other malignancies, some fatal such as hepatosplenic T-cell lymphoma, have 
also been reported in children and adolescent patients treated with TNF blockers, particularly 
when these agents are used in combination with immunomodulators.  In addition, the 
development of anti-TNF antibodies is associated with acute infusion reactions, delayed 
hypersensitivity reactions, decreased serum drug levels, and loss of response (Miele et al. 2004), 
leading to potentially significant safety and efficacy concerns.   
While treatment with corticosteroids is effective in inducing clinical response or remission in the 
majority of patients, almost 50% of patients develop corticosteroid dependence and require 
additional medication to successfully discontinue corticosteroids (Jakobsen et al. 2011b).  
Corticosteroids are not effective in maintaining remission in patients with UC, and long-term 
corticosteroid therapy is limited by the potential for significant adverse effects.  Although 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 35 
LY3074828 
immunomodulatory therapies, such as azathioprine (AZA), 6-mercaptopurine (6-MP), 
tacrolimus, and methotrexate (MTX), are used in clinical practice to treat moderate-to-severe UC 
in pediatric patients, there is limited evidence of efficacy from adequate and well-controlled 
trials in pediatric patients to recommend the appropriate and safe use of these therapies. 
3.2.3. Interleukin-23 as a Therapeutic Target in Ulcerative Colitis  
Interleukin-23 is a member of the IL-12 family of cytokines.  It is a heterodimeric protein 
composed of 2 subunits:  the IL-12p40 subunit, which is shared by IL-12, and the IL-23p19 
subunit, which is specific to IL-23.   
Interleukin-23 expression is enriched in the intestine of patients with active UC.  In addition, 
genome-wide association scans identified common variants (single nucleotide polymorphisms) 
in molecules in the IL-23 signaling pathway that modify the risk of UC and/or Crohn’s disease 
(CD) in humans, including IL-23 receptor, STAT3, and Janus kinase (JAK) 2 (Jostins et al. 
2012).  Taken together, these data provide evidence for IL-23/Th17 pathway as a therapeutic 
target in UC.   
Available clinical data with mirikizumab (Study I6T-MC-AMAC [AMAC]) support such a 
hypothesis.  Published clinical data show efficacy in inflammatory bowel disease (IBD) for 
ustekinumab, risankizumab, brazikumab, and mirikizumab, and support the role of IL-23 in IBD. 
3.2.4. Preclinical and Clinical Studies of Mirikizumab 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 36 
LY3074828 
Additional preclinical data are summarized in the Investigator’s Brochure (IB). 
A number of clinical trials of mirikizumab have been completed or are currently ongoing in 
patients with psoriasis, UC, and CD.  Data from these studies are summarized in the IB.  
Ongoing studies in adult patients with UC include the Phase 2 study AMAC and the Phase 3 
LUCENT program comprising of Study I6T-MC-AMAN (AMAN; mirikizumab/placebo 
induction), Study I6T-MC-AMBG (AMBG; mirikizumab/placebo maintenance), and Study I6T-
MC-AMAP (mirikizumab open-label extension). 
Study AMAC is a Phase 2, placebo-controlled, double-blind clinical trial of mirikizumab in 
patients with moderate-to-severe UC, for which induction and maintenance results are available.  
In the 12-week induction period, mirikizumab demonstrated efficacy for both endoscopic as well 
as symptomatic indices as assessed by multiple measures (Sandborn et al. 2018).  Overall 
adverse event (AE) frequencies were similar for mirikizumab-treated and placebo-treated 
patients (Sandborn et al. 2018).  In the maintenance period through Week 52, mirikizumab 
demonstrated durable efficacy for both endoscopic, as well as symptomatic indices:  among 
patients in clinical remission at Week 12, 61.1% (every 4 weeks [Q4W]) and 38.5% (every 
12 weeks [Q12W]) remained in clinical remission at Week 52.  There were few serious adverse 
events (SAEs) and few discontinuations due to AEs over 52 weeks (D’Haens et al. 2019). 
There were no unexpected adverse findings that would preclude clinical development in pediatric 
patients aged 2 through 17 years.  
3.3. Benefit/Risk Assessment 
Ulcerative colitis remains an important public health challenge for which there are currently few 
therapies available and no cure.  Although the pathogenesis and disease course of UC show 
similarities in patients affected in childhood and adulthood, many pediatric patients with UC 
have demonstrated more extensive disease and more severe disease course compared with adult 
patients with UC (Jakobsen et al. 2011a).  Given the inevitably long-term medical problems 
caused by UC along with the adverse effects and limitations of the current therapies, more 
effective and safer treatment options are needed for pediatric patients.   
At the time of this benefit/risk assessment, mirikizumab has demonstrated efficacy in blinded, 
placebo-controlled, Phase 2 studies in UC (Sandborn et al. 2018; D’Haens et al. 2019) and 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 37 
LY3074828 
psoriasis (Reich et al. 2017).  Evaluation of unblinded safety data from the completed and 
ongoing psoriasis, UC, and CD studies with dose regimens of up to 1000 mg intravenous (IV) 
Q4W for up to 52 weeks, up to 300 mg SC Q8W for up to 104 weeks, and up to 300 mg SC 
Q4W for up to 40 weeks, have shown a safety profile generally consistent with the IL-23 
antibody class.  These data are summarized in the IB.  Across the ongoing Phase 2 mirikizumab 
studies, immediate hypersensitivity reactions, including 2 reports of immediate, infusion-related 
hypersensitivity events consistent with anaphylaxis, have been reported at the onset or during the 
IV infusion of mirikizumab.  Such reactions are considered by the sponsor to be related to 
mirikizumab and hence, have been identified as adverse drug reactions (ADRs).  The protocol 
includes specific measures for reducing the incidence and for management of study drug infusion 
rate and observation during and after infusion.  Consult the most current IB for information 
regarding ADRs and potential risks with mirikizumab.   
Given the data from the Phase 2 study in UC, data from other clinical studies completed to date, 
and the open-label design ensuring active treatment is available to all study participants, potential 
benefit to patients who receive mirikizumab while participating in Study I6T-MC-AMBU 
(AMBU) may be reasonably anticipated. 
As colonoscopies are required in this study, there are potential risks associated with the 
procedure, such as a reaction to sedation/anesthesia or the potential of perforation.  Personnel 
knowledgeable and skilled in the administration of sedation/anesthesia to children will be used to 
minimize this risk. 
In summary, the efficacy and safety data from the Phase 2 UC study AMAC support the 
continued clinical development of mirikizumab in pediatric patients with UC. 
More information about the known and expected benefits, risks, SAEs, and reasonably 
anticipated AEs of mirikizumab are found in the IB. 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 38 
LY3074828 
4. Objectives and Endpoints 
Table AMBU.2 shows the objectives and endpoints of the study. 
Table AMBU.2. 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary  
 
 
To evaluate the pharmacokinetics (PK) of 
mirikizumab treatment in pediatric patients 
 
Clearance and volume of distribution of mirikizumab 
Secondary 
 
 
To evaluate the effect of treatment with 
mirikizumab on achieving clinical remission at 
Week 12 and/or Week 52 
 
The proportion of patients in modified Mayo score 
(MMS) clinical remission at Week 12 
 
The proportion of patients in MMS clinical remission 
at Week 52 
 
The proportion of patients in MMS clinical remission 
at Week 52 among the MMS clinical remitters at 
Week 12 (durable clinical remission) 
 
The proportion of patients in MMS clinical remission 
at Week 52 among the MMS clinical responders from 
Week 12 
MMS clinical remission is defined as:   
 
Stool frequency (SF) subscore = 0, or SF = 1, and 
 
Rectal bleeding (RB) subscore = 0, and 
 
Endoscopic subscore (ES) = 0 or 1 (excluding 
friability) 
MMS clinical response is defined below 
 
To evaluate the effect of treatment with 
mirikizumab on achieving clinical response at 
Week 12 and/or Week 52 
 
The proportion of patients in clinical response at 
Week 12 
 
The proportion of patients in clinical response at 
Week 52 
 
The proportion of patients in clinical response at 
Week 12 who achieve clinical response at Week 52 
Clinical response is based on the MMS and is defined as: 
o 
A decrease in the MMS of ≥2 points and 
≥30% decrease from baseline, and 
o 
A decrease of ≥1 point in the RB subscore 
from baseline or a RB score of 0 or 1 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 39 
LY3074828 
Objectives 
Endpoints 
 
To evaluate the effect of treatment with 
mirikizumab on achieving corticosteroid-free 
remission without surgery among patients in 
clinical remission at Week 52 and receiving 
corticosteroids at baseline  
 
The proportion of patients who are in MMS clinical 
remission at Week 52 without the use of 
corticosteroids  
 
To evaluate the effect of treatment with 
mirikizumab on PUCAI clinical remission at 
Week 12 and/or Week 52 
 
The proportion of patients in PUCAI clinical 
remission at Week 12 
 
The proportion of patients in PUCAI clinical 
remission at Week 52 
 
The proportion of patients in PUCAI clinical 
remission at Week 12 who achieve clinical remission 
at Week 52 
 
The proportion of patients in PUCAI clinical 
response at Week 12 who achieve clinical remission 
at Week 52 
PUCAI clinical remission is defined as a PUCAI score 
of <10 points 
PUCAI clinical response is defined below 
 
To evaluate the effect of treatment with 
mirikizumab on PUCAI clinical response at 
Week 12 and/or Week 52 
 
The proportion of patients in PUCAI clinical 
response at Week 12 
 
The proportion of patients in PUCAI clinical 
response at Week 52 
 
The proportion of patients in PUCAI clinical 
response at Week 12 who achieve PUCAI clinical 
response at Week 52 
PUCAI clinical response is defined as a reduction in 
baseline PUCAI score of ≥20 points 
 
To evaluate the effect of treatment with 
mirikizumab on achieving endoscopic remission 
at Week 12 and/or Week 52 
 
The proportion of patients in endoscopic remission at 
Week 12  
 
The proportion of patients in endoscopic remission at 
Week 52 
 
The proportion of patients in endoscopic remission at 
Week 12 who maintain endoscopic remission at 
Week 52 (durable endoscopic remission) 
Endoscopic remission is defined as: 
o 
ES = 0 or 1 (excluding friability) 
 
To evaluate the effect of treatment with 
mirikizumab on achieving ES = 0 at Week 12 or 
Week 52  
 
The proportion of patients with ES = 0 at Week 12  
 
The proportion of patients with ES = 0 at Week 52 
 
 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 40 
LY3074828 
Objectives 
Endpoints 
 
To evaluate the effect of treatment with 
mirikizumab on symptomatic remission over 
time 
 
Proportion of patients in symptomatic remission at 
applicable study visits 
Symptomatic remission is defined as: 
o 
SF = 0, or SF =1 with a ≥ 1-point decrease 
from baseline and  
o 
RB = 0 
 
To evaluate the effect of treatment with 
mirikizumab on height velocity at Weeks 12, 24, 
and 52 
 
Observed height velocity by gender and age group 
will be calculated at baseline, Week 12, Week 24, and 
Week 52 
 
To evaluate the effect of treatment with 
mirikizumab on weight throughout the trial 
 
Change from baseline in weight (kg) at all study visits 
by gender and age group 
 
To evaluate the effect of treatment with 
mirikizumab on pubertal development throughout 
the trial in appropriate patient groups 
 
Hormone levels and/or other related clinical measures 
will be evaluated 
 
 
To evaluate histologic-endoscopic mucosal 
remission following mirikizumab treatment at 
Week 12 or Week 52 
 
Proportion of patients with histologic-endoscopic 
mucosal remission at Week 12 
 
Proportion of patients with histologic-endoscopic 
mucosal remission at Week 52 
Histologic-endoscopic mucosal remission is defined as 
achieving both histologic remission and endoscopic 
remission.  Histologic remission will be defined in the 
SAP. 
 
To evaluate the development of anti-mirikizumab 
antibodies and their effect on 
 
 
 
Proportion of patients who have treatment-emergent 
anti-drug antibodies (TEADA)  
 
 
 
 
 
 
Exploratory 
 
 
To evaluate the effect of treatment with 
mirikizumab on changes in biomarkers 
 
Change from baseline in fecal calprotectin 
 
Change from baseline in C-reactive protein 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 41 
LY3074828 
Objectives 
Endpoints 
 
 
 
To evaluate the time to symptomatic 
response 
 
Time to symptomatic response (defined as at 
least a 
 in the 
composite clinical endpoint of the sum of SF and 
RB subscores) 
 
To evaluate the time to symptomatic 
remission 
 
Time to symptomatic remission (defined as 
SF = 0, or SF = 1 with a ≥1-point decrease from 
baseline, and RB = 0) 
 
To evaluate the numerical value and change 
from baseline of individual MMS subscores 
and the composite symptom subscore over 
time in patients receiving mirikizumab  
 The numerical value and change from baseline in each 
of the following items:   
o SF (Weeks 2, 4, 8, 12, 24, 36, and 52) 
o RB (Weeks 2, 4, 8, 12, 24, 36, and 52) 
o ES (Weeks 12 and 52) 
o The composite clinical endpoint of the sum of the 
SF and RB subscores (Weeks 2, 4, 8, 12, 24, 36, 
and 52) 
 
 
 
 
 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 42 
LY3074828 
Abbreviations:  NRS = numeric rating scale; PGI-C = Patient’s Global Impression of Change; PGRS = Patient’s 
Global Rating of Severity; PUCAI = Pediatric Ulcerative Colitis Activity Index; SAP = statistical analysis plan; 
UC = ulcerative colitis. 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 43 
LY3074828 
5. Study Design 
5.1. Overall Design 
Study AMBU is a multicenter, open-label PK study designed to evaluate the safety, PK, 
pharmacodynamics (PD), and clinical response of mirikizumab in pediatric patients, and to 
provide data for dose confirmation for Phase 3.   
The study population includes patients with moderately to severely active UC who have an 
inadequate response to, loss of response to, or are intolerant to non-biologic therapy for UC 
(biologic-naive), and/or those who have been exposed to at least 1 biologic and/or JAK inhibitor 
therapy for UC (biologic/JAK inhibitor-experienced).  
Patients weighing >40 kg will receive a mirikizumab induction dose of 300 mg via IV infusion 
and patients weighing ≤40 kg will receive induction doses of 5 or 10 mg/kg via IV infusion at 
Weeks 0, 4, and 8.  Enrollment will begin with the 300 mg and 5 mg/kg dose cohorts.  Patients in 
the 10 mg/kg cohort will be enrolled after 5 patients in the 5 mg/kg dose cohort have received 4 
weeks of mirikizumab, an evaluation of the available PK in the 5 mg/kg cohort (as described in 
Section 10.3.8.1) has been conducted, and enrollment of the 5 mg/kg dose cohort has been filled. 
Patients who achieve a Modified Mayo Score (MMS) clinical response (see Table AMBU.5) at 
Week 12 will proceed to the maintenance period and receive SC doses of 200 mg (weight >40 
kg), or 100 mg (weight >20 kg to ≤40 kg), or 50 mg (weight ≤20 kg) mirikizumab Q4W through 
Week 48. 
Patients who do not meet the MMS clinical response definition at Week 12 may receive 
extended IV induction dosing (either at the same dose or for the 5 mg/kg dose cohort, escalate to 
the 10 mg/kg dose) for 12 more weeks or discontinue.  Following the completion of IV dosing at 
Week 24, if the investigator determines that the patient has improved, the patient will proceed to 
the maintenance period and receive Q4W SC doses based on weight class through Week 48.  If 
the investigator determines that sufficient improvement was not made, the patient will 
discontinue study drug and undergo procedures for early termination of the study drug, including 
post-treatment follow-up as described in the Schedule of Activities (Section 2).   
Upon completion of the maintenance period (Week 52), all patients will have the option to enter 
the 3-year long-term extension Study I6T-MC-AMAZ (AMAZ) or enter the post-treatment 
follow-up period (12 weeks following SC administration).  With sponsor approval, additional 
dosing at Week 52 and unscheduled visits (UV) beyond Week 52 may occur as needed for 
patients eligible to enroll in Study AMAZ where the clinical trial site is not yet open. Patients 
must have completed all procedures at Visit 16 and additional dosing should occur at 4-week 
intervals (±7 days) from the prior dose. Patients who discontinue while receiving IV dosing will 
undergo procedures for early termination of the study drug, including post-treatment follow-up 
for 16 weeks as described in the Schedule of Activities (Section 2).   
Figure AMBU.1 illustrates the study design  
Study governance considerations are described in detail in Appendix 3. 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 44 
LY3074828 
  
Figure AMBU.1. 
Illustration of study design for clinical protocol I6T-MC-AMBU.
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 45 
LY3074828 
5.1.1. Definition of Baseline 
Visit 2 (Week 0) is the baseline visit.  The baseline MMS is calculated from valid 
 diary 
entries obtained prior to endoscopy during the screening period and the endoscopic appearance 
of the mucosa at this screening endoscopy (Section 9.1.1).  For other efficacy, health outcomes, 
and safety assessments, baseline is defined as the last non-missing assessment recorded on or 
prior to the date of Visit 2 (Week 0). 
5.1.2. Definition of Enrollment 
A patient is considered enrolled in the study once the patient is assigned to treatment. 
5.2. Number of Participants 
Approximately 60 patients with moderately to severely active UC will be screened to enroll 
approximately 30 patients. 
5.3. End of Study Definition 
End of the study is the date of the last visit or last scheduled procedure as shown in the Schedule 
of Activities (Section 2) for the last patient. 
5.4. Scientific Rationale for Study Design 
Study AMBU is an open-label, Phase 2 study to evaluate the safety, PK, PD, and clinical 
response of mirikizumab in pediatric patients with UC, to provide data for dose regimen 
confirmation in Phase 3. 
An open-label study ensures that all patients receive active treatment while allowing the primary 
evaluation of PK of mirikizumab treatment in pediatric patients. 
The 12-week IV dosing induction period was chosen
 
 The 40-week maintenance period enables 
  The timing of the induction and 
maintenance endpoints was chosen based on characterization of the safety and efficacy of 
mirikizumab through 52 weeks of continuous treatment in Study AMAC, the Phase 2, 
placebo-controlled, double-blind adult clinical trial of mirikizumab in moderately to severely 
active UC, as well as consistency with the timing of the induction and maintenance endpoints of 
the ongoing Phase 3 adult program studies AMAN and AMBG.  
Patients are allowed to continue non-biologic background therapy throughout the study (for 
example, 5-aminosalicylic acids [5-ASAs], corticosteroids, AZAs, and 6-MPs), subject to 
concomitant medication and dose stabilization criteria.  In this context, it is anticipated that 
mirikizumab will be administered as an add-on therapy in the majority of patients.   
The selection of clinical remission at Week 52 using MMS (FDA 2016) and the Pediatric 
Ulcerative Colitis Activity Index (PUCAI) as secondary endpoints are consistent with regulatory 
guidance documents (EMA 2016a,b).  These endpoints will assess improvement in the clinical 
signs and symptoms of stool frequency (SF), rectal bleeding (RB), and abdominal pain, and 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 46 
LY3074828 
additionally assess the visual appearance of the mucosa through the endoscopic subscore (ES).  
 
 
5.5. Justification for Dose 
Dose regimens and weight categories are based on analyses of PK, exposure–response, and 
safety data from the Phase 2 adult study AMAC in patients with UC.  Study AMAC evaluated 
mirikizumab IV induction doses of 50, 200, and 600 mg administered Q4W and SC maintenance 
doses of 200 mg administered Q12W or Q4W.  The 50 mg and 200 mg IV induction dose 
cohorts included exposure-based dose adjustments that resulted in overall average induction 
doses of 100 and 250 mg, respectively.  Evaluation of unblinded safety data from the completed 
and ongoing clinical studies, which assessed mirikizumab doses up to 1000 mg IV Q4W, 
demonstrate an acceptable safety profile to date.  Based on data from Study AMAC, the doses 
selected for evaluation in adults in Phase 3 are 300 mg IV Q4W during induction and 200 mg SC 
Q4W during maintenance. 
Previous evaluations of therapeutic antibodies in pediatric subjects indicate that the primary 
factor that influences PK is body weight rather than age (Dirks and Meibohm 2010).  The range 
of adult body weights in Study AMAC was 40 to 122 kg, with a median of 75 kg.  Although 
there was a trend for decreasing mirikizumab clearance with decreasing body weight in Study 
AMAC, this relationship was not statistically significant.  However, for the purposes of initial 
dose selection for this study, an allometric relationship between body weight and mirikizumab 
clearance with an exponent of 0.8 was assumed.  This allometric relationship provides a more 
conservatively high estimate of exposure for a given body weight as compared to assuming no 
relationship, and also is consistent with historical data for other therapeutic antibodies (Bai et al. 
2012). 
Based on Study AMAC adult data and the 
 
 
  Therefore, evaluation of an IV dose of 300 mg is planned for the induction period of the 
study for patients with a body weight >40 kg.  This dose is expected to provide comparable 
induction exposures as the 300 mg IV Q4W that is being evaluated in Phase 3 adult studies. 
Pediatric patients with a body weight of ≤40 kg will receive doses using a weight-based 
approach (mg/kg) that is expected to provide comparable systemic exposures as doses evaluated 
in the adult Phase 2 study AMAC and in Phase 3.  Intravenous doses of 5 and 10 mg/kg are 
planned for the induction period for patients with a body weight of ≤40 kg to collect sufficient 
PK data over a dose range of interest and optimally support the selection of an induction dose in 
future studies that will produce exposures similar to adults. 
Figure AMBU.2 shows a comparison of the exposures projected for the weight-based doses 
relative to the 300 mg IV planned for adults in Phase 3 and the 600 mg IV dose evaluated in 
Approved on 23 Oct 2021 GMT
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 47 
LY3074828 
Study AMAC.  The planned weight-based doses are not expected to produce exposures higher 
than those evaluated in the adult Phase 2 study. 
Interim and/or real-time analyses of PK data from pediatric patients that receive the lowest 
induction doses in this study (300 mg and 5 mg/kg) will be conducted prior to enrolling the 
10mg/kg cohort, as shown above in Figure AMBU.1.  The 10 mg/kg dose level may be adjusted 
based on these analyses, but it will be no higher than the 10 mg/kg currently planned. 
Figure AMBU.2. 
Comparison of interquartile range for average induction 
concentration for the doses planned in pediatric patients ≤40 kg 
relative to adults. 
The dose regimen selected for the maintenance period of the study for patients with a body 
weight of >40 kg is 200 mg SC Q4W, and this dose is expected to provide comparable 
maintenance exposures to the 200 mg SC Q4W that is being evaluated in Phase 3 adult studies.  
The maintenance dose regimens for patients ≤40 kg are divided into 2 fixed SC doses based on 
body weight.  Patients with a body weight between >20 kg and ≤40 kg will receive a 100 mg SC 
Q4W dose, and patients with a body weight ≤20 kg will receive a 50 mg SC Q4W dose.  
Figure AMBU.3 shows a comparison of the exposures projected for these dose regimens relative 
to the 200 mg SC Q4W maintenance regimen planned for adults in Phase 3.  The planned SC 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 48 
LY3074828 
maintenance doses are expected to produce exposures similar to the 200 mg SC maintenance 
dose that was evaluated in the adult Phase 2 study. 
Figure AMBU.3. 
Comparison of interquartile range for average maintenance 
concentration for the doses planned in pediatric patients relative to 
adults. 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 49 
LY3074828 
6. Study Population 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, are not permitted.  A patient is considered enrolled into the 
study once the patient is assigned to treatment. 
6.1. Inclusion Criteria 
Patients are eligible to be included in the study only if they meet all of the following criteria 
within the screening period, which is 
, unless otherwise 
specified below: 
Informed Consent 
[1] Have given assent (if appropriate) with parent/legal guardian signed informed 
consent approved by the ethical review board (ERB) governing the site. 
Patient Characteristics 
[2] Male or female patients weighing >10 kg AND ≥2 and <18 years of age at the 
time of informed consent.  
[2a] 
 
 
 
[2b] 
 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 50 
LY3074828 
[3] 
Both the parent or legal representative and child (if capable) must agree to 
comply with the requirements of the protocol.  
[4] 
Type of Patient and Disease Characteristics 
[5] Have an established diagnosis of UC of ≥3 months in duration before 
baseline, 
 
  
[6] Have moderately to severely active UC as defined by a 
 
 within 
 before first dose of study treatment (baseline). 
[7] Have evidence of UC extending proximal to the rectum 
 
 
Prior Medication Failure Criteria 
[8] Patients must have an inadequate response to, loss of response to, or 
intolerance to at least 1 of the medications described in Criteria [8a] OR [8b].  
Documentation of dose, frequency, route of administration, and duration 
of the prior failed treatment is required.   
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 51 
LY3074828 
[8a] 
Biologic-naive patients:  Patients who have an inadequate response to, 
loss of response to, or are intolerant to at least 1 of the following 
medications:  
 Corticosteroids  
o Corticosteroid-refractory colitis, defined as signs and/or symptoms of 
active UC despite a
 Immunomodulators: 
o Signs and/or symptoms of persistently active disease despite at least 3 
months’ treatment with 1 of the following: 
 Oral AZA 
 or 6-MP
, or 
 
o History of intolerance to at least 1 immunomodulator
 
 
Discontinuation despite clinical benefit does not qualify as having failed or being 
intolerant to UC non-biologic therapy. 
[8b] Biologic/JAK inhibitor-experienced patients:  Patients who have an 
inadequate response to, 
 to biologic 
therapy for UC (such as anti-TNF antibodies or anti-
 antibodies) 
and/or to JAK inhibitors (such as tofacitinib), as described below.  
Investigators must document an adequate trial of the medication.  
Patients should fulfill at least 1 of the following criteria:   
 
 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 52 
LY3074828 
 
Inadequate response:  Signs and symptoms of persistently active disease 
despite prescribed induction treatment, or 
 
 
 
Intolerance:  History of intolerance to infliximab, adalimumab, golimumab, 
vedolizumab, tofacitinib, or other biologics or JAK inhibitors (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), or 
Dose Stabilization Inclusion Criteria 
[9] Are on stable doses of the following permitted drugs (see Appendix 6): 
[9a] 
Oral 5-ASA compounds:  if the prescribed dose has been stable for 
 
 before screening endoscopy. 
[9b] 
Oral corticosteroid therapy 
 
:  if the prescribed dose has been 
 
before the screening endoscopy.  
[9c] 
 have been prescribed 
at a stable dose for at least 
 before the screening endoscopy.  
Study Procedure Inclusion Criteria 
[10] Are willing and able to complete the scheduled study assessments, including 
endoscopy, and 
 diary entry. 
[11] Have clinically acceptable central laboratory results or local laboratory results 
reviewed and approved by sponsor medical monitor or designee during 
screening, as assessed by the investigator, including: 
 
 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 53 
LY3074828 
[11a] Hematology:   
[11b] Chemistry:   
o 
 may be allowed to enroll but cases 
must be discussed and judged not clinically significant by the sponsor 
medical monitor prior to enrollment. 
 
Patients with 
 
Retesting within the screening period is allowed for hematology and chemistry; 
see Section 6.4. 
[12] Are 
 
guidelines as noted by country specific pediatric authorities (for example, the 
American Academy of Pediatrics).  
 
 
6.2. Exclusion Criteria 
Patients will be excluded from study enrollment if they meet any of the following criteria within 
the screening period, which is 
 to the start of study drug, unless otherwise 
specified below: 
For rescreening activities within the screening period, see Section 6.4. 
Gastrointestinal Exclusion Criteria 
[13] Have a current diagnosis of CD, IBD-Unclassified (formerly known as 
indeterminate colitis), ulcerative proctitis (distal disease limited to the 
rectum), or primary sclerosing cholangitis. 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 54 
LY3074828 
[14] Have a documented history of 
 
 
[15] Previous bowel resection or intestinal or intra-abdominal surgery:  
 
Have had any small bowel or colonic surgery within 
 prior to 
baseline. 
 
Have had any non-intestinal intra-abdominal surgery within 
 of 
baseline. 
[16] Have evidence of toxic megacolon, 
 
 the small bowel or colon. 
[17] Have any history or current evidence of cancer of the gastrointestinal tract.  
Criteria for Discontinuing Prohibited Medications 
[19] Have received any of the following for treatment of UC within the timeframes 
specified below:   
[19a] Corticosteroid enemas, corticosteroid suppositories, or IV corticosteroids 
 prior to screening endoscopy. 
[19b] 5-ASA enemas or 5-ASA suppositories 
 prior to screening 
endoscopy. 
[19c]
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 55 
LY3074828 
[19d] Anti-TNF antibodies (for example, infliximab, adalimumab, or 
golimumab) within 
 prior to screening endoscopy. 
[19e] 
[19f] 
[19g] Any investigational therapy (biologic or non-biologic) within 
 
 
prior to the screening endoscopy or within 5 half-lives prior to 
the screening endoscopy, whichever is longer.   
[19h] 
 
 
[19i] 
 
[20] Have failed anti-IL12p40 antibodies (for example, ustekinumab 
[STELARA®]) or have ever received anti-IL-23p19 antibodies (for example, 
risankizumab [BI-655066/ABBV-006], brazikumab [MEDI-2070], 
guselkumab [CNTO1959], or tildrakizumab [MK-3222]) for any indication, 
including investigational use. 
Infectious Disease Exclusion Criteria 
[21] Patients who: 
[21a] Have evidence of active TB, or 
[21b] Have a past history of active TB, regardless of treatment, or 
[21c] Have a past history of latent tuberculosis infection (LTBI) and have not 
completed an appropriate TB treatment regimen (Section 9.4.5.2) or 
[21d] Are diagnosed with LTBI at screening.  
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 56 
LY3074828 
[22] 
[23] Have human immunodeficiency virus (HIV)/acquired immunodeficiency 
syndrome (AIDS), test positive for HIV antibodies at screening (see 
Section 6.2.1). 
[24] Have acute or chronic hepatitis B infection or test positive for hepatitis B 
virus (HBV) at screening, defined as:  
[24a] Positive for hepatitis B surface antigen (HBsAg+). 
OR 
[24b] Positive for anti-hepatitis B core antibody (anti-HBc+) and positive 
confirmatory PCR for HBV deoxyribonucleic acid (DNA) (see Section 
9.4.5.4). 
OR 
[24c] Detectable HBV DNA (see Section 9.4.5.4). 
[25] Have current hepatitis C infection, or test positive for hepatitis C virus (HCV) 
at screening, defined as:   
 Positive for hepatitis C antibody and detectable HCV ribonucleic acid 
(RNA) (see Section 9.4.5.5). 
 
 
[26] Had Clostridium difficile or other intestinal infection within 
 of 
screening endoscopy, or test positive at screening for C. difficile or for other 
intestinal pathogens. 
 
[27] Have a current or recent acute, active nonserious extraintestinal infection for 
which signs and/or symptoms are present or treatment, if indicated, is not yet 
complete 
 prior to screening. 
[28] Patients with serious, opportunistic or chronic/recurring extraintestinal 
infections should be adequately treated and off antibiotics for 
 without 
recurrence of symptoms prior to screening.  Serious extraintestinal infections 
include but are not limited to the following: 
[28a] Infections requiring IV antibiotics. 
[28b] Infections requiring hospitalization. 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 57 
LY3074828 
[28c] Infections that are considered “opportunistic” (examples are listed in 
Appendix 9).  
[28d] Chronic, recurrent infections (for example, osteomyelitis and recurring 
cellulitis).  
Patients with an opportunistic infection or chronic, recurrent infection 
 
 should be discussed on a case-by-case basis with the medical monitor.   
[29] Have evidence of active/infectious herpes zoster infection or primary varicella 
zoster infection 
 prior to screening.  Infections are considered active 
until all vesicles are crusted over. 
General Exclusion Criteria 
[30] Have had lymphoma, leukemia, or any malignancy within 
 of 
screening.  
Exceptions:  The following conditions are not exclusionary:   
a) Basal cell or squamous epithelial carcinoma of the skin that has been adequately 
treated with no evidence of metastatic disease for at least 
 
b) Cervical carcinoma in situ that has been adequately treated with no evidence of 
recurrence within 
 of baseline. 
[31] 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. 
[32] Are Eli Lilly and Company (Lilly) employees or employees of third-party 
organizations involved with the study. 
[33] 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. 
[34] Have previously completed or withdrawn from this study or any other study 
investigating mirikizumab after receiving study drug.  This criterion does not 
apply to patients undergoing rescreening procedures. 
[35] Have had extra-abdominal surgery and have not recovered fully following 
surgery, including complete wound healing, before screening.  
[36] Have presence of significant uncontrolled neuropsychiatric disorder or judged 
at risk of suicide in the opinion of the investigator;  
OR 
For patients
 
during the screening 
period prior to dosing at Visit 2;  
OR 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 58 
LY3074828 
 
AND 
 
[37] Have an unstable or uncontrolled illness, including but not limited to a 
cardiovascular, respiratory, gastrointestinal (excluding UC), neurological or 
neuropsychiatric disorders, that would potentially affect patient safety within 
the study or confound efficacy assessment. 
[38] Have a known hypersensitivity to any component of mirikizumab or 
monoclonal antibodies. 
[39] Have a solid organ transplant or hematopoietic stem cell transplantation.  
[40] Are unwilling or unable to comply with the use of a data collection device to 
directly record data from the subject. 
[41] Are unsuitable for inclusion in the study in the opinion of the investigator or 
sponsor for any reason that may compromise the subject’s safety or confound 
data interpretation. 
[42] Are pregnant, lactating, or planning pregnancy (both males and females) while 
enrolled in the study or within 
 
 after receiving the last dose of study drug. 
[43] Have current or history of alcohol dependence and/or illicit drug abuse within the last 
year. 
[44] Have abnormal 12-lead electrocardiogram (ECG) that, in the opinion of the 
investigator or sponsor, increases the risks associated with participating in the study. 
[45] Use marijuana (both recreational and medicinal uses including cannabidiol [CBD] 
oil]).  Marijuana use must be stopped prior to screening and is prohibited for the 
duration of the study. 
[46] Had a blood transfusion in the last 
 prior to hematology blood sample 
collection.  
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 59 
LY3074828 
6.2.1. Rationale for Exclusion of Certain Study Candidates 
Children younger than 2 years of age are excluded from this study due to the difficulty in 
obtaining a definitive diagnosis of UC in children/infants younger than 2 years of age and the 
potential for lack of efficacy in this age group.  
 
6.3. Lifestyle Restrictions 
If applicable, study participants should be instructed not to donate blood or blood products 
during the study or for 
 following their last dose.  In order to participate in the study, 
patients must agree to the contraception, reproduction, and breastfeeding criteria detailed in 
study entry criteria (Section 6.1 and Section 6.2). 
6.4. Screen Failures 
Allowed rescreening of patients after initial screen failure 
Patients who have failed screening because of the following Inclusion/Exclusion Criteria may be 
rescreened when the reason for screen failure has resolved:   
 [5] 
 [6] 
 [7] 
 [8] 
 [9] 
 [11] 
 [12] 
 [15] 
 [18c] (once polyps have been removed) 
 [19] 
 [22] 
 [27] to [30] 
 [35]  
 [42] 
 [45], and 
 [46]. 
Individuals may be rescreened up to 2 times, for a maximum total of 3 screens unless additional 
rescreening is approved via sponsor’s medical monitor or designee.   
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 60 
LY3074828 
Participants who have failed screening because of Exclusion Criterion [21c] 
 
 may be rescreened 1 time 
(see Section 9.4.5.2). 
Participants who have failed screening because of Exclusion Criterion [26] may be rescreened 
1 time for C. difficile stool toxin.  Additionally, a participant may be rescreened 1 time for stool 
culture or ova parasite.  In either situation, participant rescreening should only occur after the 
reason for screen failure has resolved.  It is recommended that the investigator confirms the 
participant has a negative C. difficile stool toxin/stool culture/stool ova parasite (as applicable) 
before performing additional rescreening investigations (see also Section 9.4.5.7).  The interval 
between rescreening visits should be at
 unless a shorter interval has been agreed 
with the study’s medical monitor.  Each time rescreening is performed the participant, 
parent/guardian must sign a new informed consent form (ICF) and will be assigned a new 
identification number. 
Participants who screen fail because they are unable to complete their endoscopy prior to Visit 2 
will not be required to undergo repeat TB testing, chest X-ray (CXR) or computed tomography 
(CT), HIV, HBV, and HCV testing stool cultures, and C. difficile testing if these were normal or 
negative during screening after discussion with sponsor medical monitor or designee.  These 
tests should be repeated if based on the investigator’s judgment the patient has risk factors and/or 
signs and symptoms of illness.  Participants may undergo repeat rescreening sooner than
between screen failure and rescreening. 
Disallowed rescreening of patients after initial screen failure 
Patients who have failed screening because of the following Exclusion Criteria may not be 
rescreened:   
 [10] 
 [13] 
 [14] 
 [16] 
 [18a] and [18b] 
 [20] 
 [21a] and [21b] (if current or past history of active TB) 
 [23] to [25] 
 [31] to [34] 
 [36] to [41] 
 [43], and 
 [44]. 
6.4.1. Allowed Retesting of Screening Investigations 
The screening investigations specified below may be retested once without the need for 
rescreening at the discretion of the investigator.   
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 61 
LY3074828 
 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 an interferon-γ release assay (IGRA):  for 
example, QuantiFERON®-TB Gold or T-SPOT® assay) in selected patients as part of 
screening for LTBI (see Section 9.4.5.2 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 investigations should be discussed with the medical monitor 
prior to retesting. 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 62 
LY3074828 
7. Treatments 
7.1. Treatments Administered 
In this study, mirikizumab is administered by IV or SC routes to pediatric patients in a staggered 
approach based on dose level as per Table AMBU.3.  Assignment to weight classes will be based 
on body weight at enrollment for induction period dosing and Week 12 for dosing at Week 12 
and beyond; patients will continue in the assigned weight group throughout the duration of the 
study. 
Patients in the high weight cohort will receive flat dosing, while patients in the low weight 
cohort will receive weight-tiered dosing in order to obtain similar exposures as flat dose 
regimens in the higher weight cohort. 
Patients who achieve clinical response at Week 12 will follow the treatment regimens described 
in Table AMBU.3.  Patients who do not achieve clinical response at Week 12 will follow the 
treatment regimens described in Table AMBU.4.   
If any patient experiences loss of response and meets the criteria for loss of response in 
Section 9.1.5 at or after Week 16 and up to Week 40, they may receive rescue or discontinue the 
study based on their physician’s discretion.  Rescue treatment is IV mirikizumab Q4W for 
3 doses based on their weight cohort.  Once IV loss of response dosing is complete, patients who, 
in the opinion of the investigator, are receiving clinical benefit from mirikizumab therapy may 
continue with further SC dosing.  Patients who are not considered by the investigator to be 
receiving clinical benefit from mirikizumab IV rescue therapy, will be discontinued and proceed 
to post-treatment follow-up. 
Table AMBU.3. 
Treatment Regimens:  Week 12 Clinical Responders  
Weight 
Cohort 
Dose 
Weeks 0, 4, and 8 
Dose 
Weeks 12 through 48 
 
Enrollment Initiation 
>40 kg 300 mg mirikizumab IV 
200 mg mirikizumab Q4W SC 
≤40 kg 5 mg/kg mirikizumab IV ≤20 kg:  50 mg mirikizumab Q4W SC 
>20 to ≤40 kg:  100 mg mirikizumab 
Q4W SC 
 
≤40 kg 
10 mg/kg mirikizumab 
IV 
≤20 kg:  50 mg mirikizumab Q4W SC 
>20 to ≤40 kg:  100 mg mirikizumab 
Q4W SC 
Abbreviations:  IV = intravenous; PK = pharmacokinetics; Q4W = every 4 weeks; SC = subcutaneous. 
 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 63 
LY3074828 
Table AMBU.4. 
Treatment Regimens:  Week 12 Clinical Nonresponders  
Weight 
Cohort 
Dose 
Weeks 0, 4, and 8 
Dose 
Weeks 12 through 48 
>40 kg 
300 mg mirikizumab IV 
≤40 kg 
5 mg/kg mirikizumab IV 
≤40 kg 
10 mg/kg mirikizumab IV 
Abbreviations:  IV = intravenous; Q4W = every 4 weeks; SC = subcutaneous. 
 
Study Drug Administration  
Intravenous infusion of mirikizumab will occur over at 
 
  All patients should be monitored for 
 or longer following IV 
administration, according to investigator practice or local standard of care.  Sites must have 
resuscitation equipment, emergency medications, and appropriately trained staff available during 
the infusion and monitoring period.  Detailed instructions for investigational product 
administration will be provided separately by the sponsor.    
Subcutaneous administration of mirikizumab will be given 
.  
Patients should be monitored according to investigator practice or local standard of care.  
Acceptable locations for SC administration include the abdomen, front upper thighs, upper arms, 
and buttocks. 
The investigator or his/her designee is responsible for the following: 
 Explaining the correct use of the investigational agent to the site personnel  
 Verifying that instructions are followed properly 
 Maintaining accurate records of investigational product dispensing and collection 
 At the end of the study returning all unused medication to Lilly, or its designee, 
unless the sponsor and sites have agreed that all unused medication is to be 
destroyed by the site, as allowed by local law 
7.1.1. Packaging and Labelling 
Mirikizumab will be supplied to the investigator by Lilly or its designee.  Clinical trial materials 
will be labeled according to the country’s regulatory requirements.  All investigational products 
will be stored, inventoried, reconciled, and destroyed according to applicable regulations.  
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 64 
LY3074828 
Clinical trial materials are manufactured in accordance with current Good Manufacturing 
Practices (GMP). 
Study drug will be supplied as:  
 Single use solution pre-filled syringe containing mirikizumab.  The 
 syringe of 
mirikizumab is manufactured to deliver 
   
 Single use solution vial containing mirikizumab.  The 
 vial of mirikizumab is 
manufactured to  deliver 
   
Study drug will be provided with study-specific labels.  Syringes and vials will be supplied in 
cartons, with the appropriate quantity specific to the planned dispensing schedule of the 
investigational product.   
7.2. Method of Treatment Assignment 
Study AMBU is open-label and patients will be assigned to mirikizumab dose groups based on 
weight at Visit 2.   
An interactive web-response system (IWRS) will be used to assign investigational product to 
each patient.  Site personnel will confirm that they have located the correct investigational 
product package by entering a confirmation number found on the package into the IWRS. 
At Week 12, patients who meet the clinical response criteria (see Table AMBU.5) may proceed 
to the maintenance period and will continue with open-label mirikizumab SC dosing based on 
current body weight. 
Nonresponding patients (see Section 9.1.5) may enter into extended induction dosing via IV 
administration for the next 12 weeks or discontinue the study.   
7.2.1. Selection and Timing of Doses 
Patients who meet all criteria will be assigned to treatment and will receive their assigned study 
drug as outlined in Sections 7.1 and 7.2.  The actual time of all dose administrations will be 
recorded in the patient’s electronic case report form (eCRF).  
7.3. Blinding 
This is an open-label study. 
7.4. Dosage Modification 
Dose adjustments, other than 
 
 
, are not permitted in this study.  
7.5. Preparation/Handling/Storage/Accountability 
The investigator or his/her designee is responsible for the following: 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 65 
LY3074828 
 Confirming that appropriate temperature conditions have been maintained during 
transit for all study drug received and any discrepancies are reported and resolved 
before use of the study drug. 
 Ensuring that only participants enrolled in the study may receive study drug and 
only authorized site staff may supply or administer study drug.  All study drugs 
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 site staff. 
 The investigator, institution, or the head of the medical institution (where 
applicable) is responsible for study drug accountability, reconciliation, and record 
maintenance (such as receipt, reconciliation, and final disposition records). 
Mirikizumab will be supplied by Lilly or its designee, in accordance with current GMP and will 
be supplied with lot numbers, expiry dates, and certificates of analysis, as applicable. 
Mirikizumab should be stored in refrigerated conditions 
. 
Detailed instructions regarding supplies, preparation, and handling of mirikizumab will be 
provided by the sponsor.  
7.6. Treatment Compliance 
All doses of study medication will be administered at the study site by site personnel.  Deviations 
from the prescribed dosage regimen should be recorded in the eCRF. 
Every attempt will be made to select patients and caregivers who have the ability to understand 
and comply with study instructions.  The investigator is responsible for discussing methods to 
ensure high treatment compliance with the patient and caregiver before study enrollment.   
In particular, the investigator is responsible for ensuring that study participants and caregivers 
receive adequate training on and appropriate understanding of: 
 the review of caregiver remission SF value as a critical data point 
 how to evaluate their UC symptoms and to record them on the 
 diary, and 
 the importance of being compliant with the 
 diary recording. 
If a patient is noncompliant with study procedures and/or investigational product administration, 
the investigator should assess the patient to determine the reason for noncompliance and educate 
and/or manage the patient as appropriate to improve compliance.  Overall compliance with 
therapy is defined in the statistical analysis plan (SAP).  If, in consultation with Lilly or its 
designee, the noncompliance is deemed to be significant or if further noncompliance occurs, the 
patient may be discontinued from the study. 
7.7. Concomitant Therapy 
The list of prohibited medications and the list of permitted medications with dose stabilization 
guidance are provided in Appendix 5 and Appendix 6, respectively. 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 66 
LY3074828 
All concomitant medications (including medications for bowel preparations) taken during the 
study must be recorded in the Concomitant Medication eCRF.  This includes concomitant 
medications for UC as well as for underlying conditions or diseases, and for AEs.  All patients 
are encouraged to maintain their usual medication regimens for concomitant conditions or 
diseases throughout the study, unless those medications are specifically excluded (Appendix 5).   
Stable doses of permitted UC concomitant medications (other than oral corticosteroids) are 
encouraged, unless dose modification is required due to AEs, or dose modification is otherwise 
specified in Appendix 6.  Patients taking oral corticosteroids are to follow the corticosteroid 
taper instructions described in Section 7.7.1.   
Administration of prohibited UC medications for the management of symptoms 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 patient safety.  
Patients who require a prohibited medication to treat their UC (see Appendix 5) need to be 
discontinued from study drug and complete an early termination visit (ETV) and post-treatment 
follow-up visits. 
If a concomitant medication is needed to treat an AE or for appropriate medical management, the 
investigator should base decisions on patient and clinical factors.  Local administration of 
corticosteroids (for example, intranasal, inhaled, intraarticular) are allowed as required for the 
management of pre-existing conditions and AEs.  A patient who initiates a prohibited medication 
for a non-UC indication should be discussed with the medical monitor. 
Patients are allowed to continue or initiate any concomitant medication for non-UC conditions, 
diseases, or AEs, insofar that the medication is not specifically prohibited (Appendix 5) and use 
of the medication complies with the dosing requirements as described in Appendix 6. 
7.7.1. Corticosteroid Taper 
The investigator should use clinical judgement of the benefit/risk of steroid tapering for each 
individual subject as corticosteroids should be tapered as soon as possible following the 
recommended tapering regimen per local practice.  Patients who enter Study AMBU on 
corticosteroid therapy for treatment of UC
 
 may initiate corticosteroid tapering 
based on the investigator’s discretion.  
 who have not already 
begun tapering corticosteroid therapy should initiate corticosteroid tapering no later than 
  
 with mirikizumab will 
begin 
 is achieved at any time after starting 
  
Symptomatic response is defined as at least a 
 from baseline in the composite 
clinical endpoint of the sum of SF and RB subscores. 
The recommended tapering schedule for oral corticosteroids (other than budesonide) is 
as follows: 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 67 
LY3074828 
  In situations where the steroid tapering is 
paused, the tapering regimen (as described above) should be reinitiated within 
 of 
interruption of taper if possible, with a goal to complete tapering 
 
7.7.2. Vaccine Administration During the Study 
Every effort should be made to vaccinate patients with standard of care vaccines prior to entry in 
the trial.   
7.8. Treatment after the End of the Study 
7.8.1. Study Extensions 
Patients who complete this study through Week 52 and achieve clinical benefit may be eligible 
to participate in Study AMAZ.  Patients who do not meet enrollment criteria for Study AMAZ or 
do not opt to continue into Study AMAZ, will be asked to complete the post-treatment follow-up 
period, as described in the Schedule of Activities (Section 2), which will complete their study 
participation. 
7.8.2. Treatment after Study Completion 
Mirikizumab will not be made available to patients after conclusion of the study, except through 
enrollment in the long-term extension trial, Study AMAZ. 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 68 
LY3074828 
7.8.3. Special Treatment Considerations 
7.8.3.1. Premedication for Infusions 
  Any premedication for 
infusions or injections should be discussed with the medical monitor.  Any premedication given 
should be documented as a concomitant therapy. 
Other Infusion-Related Events  
If a patient experiences a reaction consisting of 
 
during or up to 6 
 after an infusion of study drug, the following guidance should be followed: 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 69 
LY3074828 
Injection Site Reactions or Infusion Site Reactions 
If a patient experiences an injection site reaction or an infusion site reaction, such as pain, 
erythema, urticaria, pruritus, or angioedema localized to the SC injection or infusion site (in the 
absence of systemic hypersensitivity signs or symptoms), the following guidance should be 
followed: 
Approved on 23 Oct 2021 GMT
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 70 
LY3074828 
8. Discontinuation Criteria 
8.1. Discontinuation from Study Drug 
8.1.1. Permanent Discontinuation from Study Drug 
Study drug may be permanently discontinued during the study.  Patients who discontinue study 
drug early will undergo early termination procedures, which include an ETV and post-treatment 
follow-up visits.   
The investigator will also complete any AE reporting and follow-up that may be required (if 
applicable, see Section 9.2).   
If a patient’s study drug is discontinued before the end of the study, the patient should complete 
the ETV and post-treatment follow-up period as follows: 
 Patients who discontinue investigational product during 
 
 will return for post-treatment follow-up visits 
(Visits 801 and 802) 
 after the end-of-treatment visit.  
 Patients who discontinue study drug
 
will return for post-treatment follow-up 
visits (Visits 801 and 802) 
 after the end-of-treatment visit. 
Possible reasons leading to permanent discontinuation of investigational product include the 
following (list is not exhaustive): 
Patient Decision 
 The patient or the patient’s designee, for example, parents or legal guardian, requests to 
discontinue investigational product. 
   
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 71 
LY3074828 
Disease Worsening  
 The patient requires rescue therapy for exacerbation of UC at doses higher than those 
specified in the “dose stabilization” inclusion criterion (for example, prednisone 
 Inclusion Criterion [9]), or with medications specified in the “prohibited 
medications” exclusion criterion (for example, IV corticosteroids, infliximab, or IV 
cyclosporine; Exclusion Criterion [19]) (see also Appendix 5). 
Safety Criteria for Study Drug Discontinuation 
 The patient has a diagnosis of any of the following during the study: 
o Cancer other than squamous cell or basal cell carcinoma of the skin 
o Polypoid or non-polypoid dysplasia that is endoscopically visible or invisible 
o Active TB (see Section 9.4.5.2) 
o HIV/AIDS 
o Hepatitis B or development of detectable HBV DNA (see Section 9.4.5.4) 
o Hepatitis C or development of detectable HCV RNA (see Section 9.4.5.5). 
 The patient requires a colectomy during the study. 
 The patient has a systemic hypersensitivity event or anaphylaxis to mirikizumab 
(Section 7.8.3.2).  Study drug should be discontinued after a systemic hypersensitivity 
event or anaphylaxis. 
 The patient becomes pregnant.  Pregnant patients will not undergo an endoscopy/flexible 
sigmoidoscopy at the ETV.   
 The patient has absolute lymphocyte count 
 after retesting 
(see Section 8.1.2). 
 The patient is non-compliant with LTBI treatment (see Section 9.4.5.2). 
 The patient experiences an AE or SAE that, in the opinion of the investigator or sponsor, 
would preclude him/her from continuing to receive study drug or if they experience 
disease worsening that requires rescue therapy with protocol excluded medications. 
Other Reasons for Study Drug Discontinuation 
 The investigator determines that the patient is repeatedly noncompliant with study 
procedures and/or study drug (see Section 7.6). 
 Inadvertent enrollment (see Section 8.1.3). 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 72 
LY3074828 
Patients discontinuing from the investigational product prematurely for any reason should 
complete AE and other follow-up procedures per Section 2 (Schedule of Activities), Section 9.2 
(Adverse Events), and Section 9.4 (Safety). 
8.1.2. Temporary Interruption (Withholding) of Study Drug 
Some possible reasons for temporarily withholding the investigational product include (but are 
not limited to): 
 Patient develops C. difficile, or other clinically important intestinal or extraintestinal 
infection during the study (including LTBI), see Section 6.2. 
 Patient requires major surgery (administration of the investigational product may be 
restarted only after adequate wound healing). 
 Patient develops a confirmed absolute neutrophil count 
 
 
 Patient develops absolute lymphocyte count 
 
 must be discontinued, if applicable, for a confirmed 
absolute lymphocyte count 
 (2 assessments below this threshold).  The 
hematology must be repeated in 
.  If the absolute lymphocyte count remains 
, the hematology will be repeated again in 
 (that is, prior to the next 
dose of study drug).  If the absolute lymphocyte count remains 
, the next dose 
of study drug will not be administered.  The hematology will be repeated again in  
  If the absolute lymphocyte count remains 
, study drug will be 
permanently discontinued.  White blood cell and lymphocyte counts will be followed for 
these patients until they return to an acceptable level. 
 The patient has other laboratory abnormalities that may lead investigator to hold the 
study drug until resolution of the abnormalities. 
Cases that may merit temporary withholding of the study drug should be discussed with the 
medical monitor.  The medical monitor, in consultation with the investigator, will determine 
when it is appropriate to recommence study drug.   
8.1.3. Discontinuation of Inadvertently Enrolled Patients 
If the sponsor or investigator identifies a patient who did not meet enrollment criteria and was 
inadvertently enrolled, then the patient should be discontinued from study drug, unless there are 
extenuating circumstances that make it medically appropriate for the patient to continue on study 
drug.  If the investigator and the sponsor agree it is medically appropriate to continue, the 
investigator must obtain documented approval from the sponsor to allow the 
inadvertently-enrolled patient to continue in the study with or without treatment with the 
investigational product.  Patients who are discontinued from study drug should have safety 
follow-up as outlined in Section 2 (Schedule of Activities), Section 9.2 (Adverse Events), and 
Section 9.4 (Safety), including ETV and post-treatment follow-up visits (Visit 801 and 
Visit 802). 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 73 
LY3074828 
8.2. Discontinuation from the Study 
Patients will be discontinued (withdrawn) from the study in the following circumstances:  
 
Enrollment in any other clinical study involving an investigational product or 
enrollment in any other type of medical research judged not to be 
scientifically or medically compatible with this study 
 Participation in the study needs to be stopped for medical, safety, regulatory, 
or other reasons consistent with applicable laws, regulations, and good clinical 
practices 
 Investigator decision 
o The investigator decides that the patient should be discontinued from the 
study 
o If the patient, for any reason, requires treatment with another therapeutic 
agent that has been demonstrated to be effective for treatment of the study 
indication, discontinuation from the study will occur prior to introduction 
of the new agent 
o For patients who develop a condition, require a live vaccine, or begin a 
therapy that would have excluded entry into the study, the investigator 
must consult with Lilly-designated medical monitor to decide whether the 
patient can continue taking study drug and remain in the study. 
 Patient decision 
o The patient or the patient’s designee, for example, parents or legal 
guardian requests to be withdrawn from the study 
Patients discontinuing from the study prematurely for any reason should complete AE and other 
safety follow-up specified per ETV, as outlined in Section 2 (Schedule of Activities), Section 9.2 
(Adverse Events), and Section 9.4 (Safety). 
8.3. Lost to Follow-Up 
A patient 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 are expected to make 
diligent attempts to contact patients who fail to return for a scheduled visit or are otherwise 
unable to be followed up by the site. 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 74 
LY3074828 
9. Study Assessments and Procedures 
Section 2 lists the Schedule of Activities, with the study procedures and their timing (including 
tolerance limits for timing).  Adherence to the study design requirements, including those 
specified in the Schedule of Activities, is essential and required for study conduct. 
Appendix 2 lists the laboratory tests that will be performed for this study. 
A summary of the maximum number and volume of invasive samples for all sampling during the 
study will be provided separately. 
Unless otherwise stated in the subsections below, all samples collected for specified laboratory 
tests will be destroyed within 
 of receipt of confirmed test results.  Certain samples may 
be retained for a longer period, if necessary, to comply with applicable laws, regulations, or 
laboratory certification standards. 
9.1. Efficacy Assessments 
Efficacy endpoints are found in Table AMBU.2.  Secondary efficacy endpoint definitions are 
found in Table AMBU.5.  Additional details are provided below. 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 75 
LY3074828 
Table AMBU.5. 
Secondary Efficacy Endpoint Definitions in Study AMBU 
Endpoint 
Definition 
Modified Mayo Score (MMS) 
clinical remission 
 
Stool frequency (SF) subscore = 0, or SF = 1, and 
 
Rectal bleeding (RB) subscore = 0; and 
 
Endoscopic subscore (ES) = 0 or 1 (excluding friability) 
MMS clinical response 
 
A decrease in the MMS of ≥2 points and ≥30% decrease from 
baseline, and  
 
A decrease of ≥1 point in the RB subscore from baseline or a RB 
score of 0 or 1 
Corticosteroid-free remission 
without surgery 
Pediatric Ulcerative Colitis 
Activity Index (PUCAI) clinical 
remission 
 
A PUCAI score of <10 points 
PUCAI clinical response 
 
A reduction in baseline PUCAI score of ≥20 points 
Endoscopic remission 
 
ES = 0 or 1 (excluding friability) 
Symptomatic remission 
 
SF = 0, or SF = 1 with ≥1-point decrease from baseline, and 
 
RB = 0 
Histologic-endoscopic mucosal 
remission 
 
Defined as achieving both histologic remission and endoscopic 
remission.  Histologic remission will be specified in the statistical 
analysis plan (SAP). 
Loss of clinical response 
 
Week 12 responders:  An increase from the Week 12 Partial Mayo 
score of 
 (with 
confirmation of negative C. difficile testing) or 
 
Week 12 nonresponders who had extended induction:  An 
increase from the Week 24 Partial Mayo score of 
 
 (with confirmation of 
negative C. difficile testing) 
Symptomatic response 
 
 from baseline in the composite clinical endpoint of 
the sum of SF and RB subscores 
9.1.1. Mayo Score 
This study utilizes components and permutations of the Mayo score (Schroeder et al. 1987) to 
assess UC disease activity for the primary and secondary endpoints (see Appendix 7).  Complete 
and accurate recording of the Mayo SF and RB subscores by patients or their 
parent/caregiver in their daily electronic diary is necessary for the success of the study.  
Adequate bowel preparation and an endoscopy with adequate visualization of the mucosa will 
enable calculation of the Mayo ES.   
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 76 
LY3074828 
Note:  The investigator is responsible for ensuring that study participants receive adequate 
training on and appropriate understanding of: 
 the importance of complete bowel preparation prior to endoscopies/flexible 
sigmoidoscopies 
 how to record “remission/ normal” SF at the beginning of the study 
 how to evaluate their UC symptoms and to record them on the 
 diary, and 
 the importance of being compliant with the 
 diary recording. 
The Mayo score is a composite instrument comprised of the following 4 subscores: 
Stool Frequency (SF):  The SF subscore is a patient-reported measure.  This item reports the 
number of stools in a 
, relative to the normal number of stools for that patient in 
the same period, on a 4-point scale (see Appendix 7). 
 
 The total number of stools passed 
 will be recorded by the 
patient or caregiver in a daily electronic diary.  The reference “normal” SF for that patient will be 
recorded electronically at the screening visit.  Normal SF for that patient is based on reported SF 
when the patient was in remission or reported SF before initial onset of signs and symptoms of 
UC.  Study software will use the patient-reported daily SF and the reference normal SF to 
automatically calculate the Mayo SF subscore.  Further details on the analysis of 
 diary 
items are contained in the SAP.   
Rectal Bleeding (RB):  The RB subscore is a patient-reported measure.  This item reports the 
most severe amount of blood passed with stool for a given day, on a 4-point scale (see Appendix 
7).  The patient or caregiver will record this in a 
 electronic diary. 
Endoscopic Subscore (ES):  The ES is a physician-reported measure that reports the worst 
appearance of the mucosa on flexible sigmoidoscopy or colonoscopy, on a 4-point scale (see 
Appendix 7).  Determination of the ES is further detailed in Section 9.1.2.  Consistent with 
current clinical practice and regulatory advice, this study subscore excludes friability from the 
definition of an ES of 1.  Also consistent with best clinical trial practice, endoscopy scores will 
be determined from blinded central readers.  The 
 endoscopy score is collected on paper and 
) in the eCRF.  The entry 
of the local endoscopy is critical to initiate the blinded central reading process. 
Physician’s Global Assessment (PGA):  The Physician’s Global Assessment (PGA) is a 
physician-reported measure that summarizes the investigator’s assessment of the patient’s UC 
disease activity on a 4-point scale (see Appendix 7).  The investigator will record the PGA 
electronically as source data in the tablet device at appropriate study visits.  Consistent with 
regulatory guidance, the PGA will not be used solely for efficacy assessment in this study. 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 77 
LY3074828 
Each subscore is scored on a 4-point scale, ranging from 0 to 3, to give a maximum Mayo score 
of 12.  The study will use the following permutation of the Mayo score: 
 Modified Mayo score (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 
Additional permutations of the Mayo score have been described and may be used in analyzing 
data from this study. 
Observer-reported outcomes will be used in place of patient-reported outcomes for children less 
than 8 years of age.  To maintain consistency in reporting of SF and RB data, the patient’s age at 
baseline will determine whether an observer-reported method (ages 2 through 7 years) or a 
patient-reported method (ages 8 through 17 years) will be used, irrespective of patient’s age at 
later study visits.  Efficacy assessments will be conducted in study population age range for 
which the scale/instrument was validated. 
9.1.2. Endoscopy  
Endoscopy will be used to determine the Mayo ES at 
 
  Site and blinded central reading of endoscopies will be used to determine ES. 
A flexible sigmoidoscopy or colonoscopy will be performed on all patients during screening, 
within 
 to Visit 2.  The endoscopy report and histopathology report (if biopsies are 
sent to the local histopathology laboratory) must be available in the source documents.  Prior to 
performing the screening endoscopy, investigators should ensure that patients have SF and RB 
scores that suggest they will meet entry criteria (see Inclusion Criterion [6]) and clinically 
acceptable laboratory test results, including stool tests that are “negative” for C. difficile and 
other intestinal pathogens (see Inclusion Criterion [11] and Exclusion Criteria [21] and [23] to 
[26]). 
Flexible sigmoidoscopy is generally recommended.  However, full colonoscopy may be 
appropriate in some patients (for example, those with mild-to-moderate pan-colitis).  The choice 
of flexible sigmoidoscopy or full colonoscopy is at the investigator’s discretion.  Other situations 
that may warrant a full colonoscopy at screening include: 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 78 
LY3074828 
In these patients, the investigator can obtain additional biopsies to surveille for dysplasia 
at the screening colonoscopy.  This screening colonoscopy will be performed according 
to local guidelines and biopsies will be sent to the local histopathology laboratory.  
Chromoendoscopy may be an acceptable method of targeting biopsies, if allowed 
according to local guidelines.   
 Patients requiring screening for colorectal cancer, who do not have a current screening 
colonoscopy according to local guidelines.  This may include: 
o Personal history indicating increased colorectal cancer risk, for example, previous 
adenomatous polyps. 
o Patients with other known risk factors. 
 Where, in the opinion of the investigator, a colonoscopy is indicated at screening, for 
example, to confirm that a recent removal of an adenomatous polyp is complete prior to 
study enrollment.   
 Patients who do not have the report of a completed, full colonoscopy available in source 
documents. 
Patients who undergo colonoscopy at screening do not require a separate flexible sigmoidoscopy. 
Patients will undergo a 
 
  The endoscopy report and histopathology report (if biopsies are sent to the local 
histopathology laboratory) must be available in the source documents.  Patients who discontinue 
the study drug because of pregnancy will not undergo a flexible sigmoidoscopy or full 
colonoscopy at their ETV. 
The endoscopist will be a
 
  Investigators may delegate endoscopy 
to other members of the study team.  However, all study staff performing endoscopy must 
 
 at each endoscopy and it will be 
recorded in the eCRF.   
All endoscopic procedures will be video recorded using a storage medium provided by the 
sponsor or designee.  The video images will 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, and the qualifications required of the central reader.   
The central readers will determine the centrally-read Mayo ES at each 
 
 in a blinded manner, as detailed in the image review charter.   
The procedure to address disagreement between the site readers and central readers is detailed in 
the image review charter.  The final Mayo ES will be provided to the site prior to being enrolled 
at Visit 2 to enable determination of the MMS for eligibility. 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 79 
LY3074828 
9.1.3. Endoscopic Biopsies 
A histopathology report supporting the diagnosis of UC must be available in the source 
documents prior to study enrollment, in order to satisfy Inclusion Criterion [5].  If a 
histopathology report is not available, the investigator can obtain additional biopsies for this 
purpose at the screening endoscopy (sent to the local histopathology laboratory).   
Biopsies will be obtained at each endoscopy to support assessment of the histopathology 
endpoints in this study and, where permitted, 
.  In 
rare circumstances, the investigator may consider it unsafe to collect all required biopsies; in this 
situation, fewer biopsies may be collected so as not to jeopardize patient safety.  Biopsies will be 
sent to the central study laboratory for processing.  A detailed biopsy reference guide from the 
central reading laboratory will provide the number of biopsies to be collected, and outline the 
procedures to be used for secure specimen transfer, processing, slide preparation, and digitization 
of slides for histopathologic scoring.  These results will not be made available to study sites.   
9.1.4. Pediatric Ulcerative Colitis Activity Index 
The PUCAI (Turner et al. 2007) is a clinician-administered, 6-item questionnaire that measures:  
abdominal pain; RB; stool consistency; number of stools; nocturnal stools; and activity level (see 
Appendix 7).  All items are answered as an average over the ‘past 2 days’.  A total disease 
activity score is calculated from 0 to 85, with severe:  65-85, moderate:  35-60, mild:  10-30, and 
none:  <10.  The clinician will record the patient or caregiver/legal guardian responses for the 
PUCAI electronically as source data in the tablet device at appropriate visits. 
9.1.5. Determination of Responder Status/Loss of Response 
At Week 12, patients who achieve an MMS clinical response as defined in Table AMBU.5 may 
move into the maintenance period.   
Week 12 Nonresponders are defined as those that do not meet the following criteria: 
 A decrease in the MMS of 
 from baseline, and 
 A decrease of 
 in the RB subscore from baseline or a RB score 
. 
Nonresponding patients may receive extended induction dosing via IV infusion Q4W for 12 
weeks as noted in Table AMBU.4. 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 80 
LY3074828 
9.1.6. Growth and Pubertal Assessments 
9.1.6.1. Occipital Head Circumference 
Occipital head circumference measurements will be performed on patients less than 3 years of 
age at baseline.  Measurements will be taken at baseline and then approximately Q12W 
thereafter, until the patient reaches the age of 3 years. 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 81 
LY3074828 
9.1.6.2. Height Velocity 
Height will be collected 3 times per visit at the visits indicated in Section 2 using a stadiometer 
or other instrument of equivalent measuring capacity.  Observed height velocity by gender and 
age group will be calculated at 
, based on height 
measurements from the 3 to 12 months (preferably 4 to 6 months) preceding the study (from 
screening) or those obtained at baseline according to the following formula:  
 (Present Height [cm] - Previous Height [cm])/Interval (months) Between Measurements 
× 12 
Age-specific z-scores for height velocity by gender and age group will be calculated for each 
patient with reference to standard height velocity tables according to the following formula:  
 (Observed Height Velocity [cm/y] - Mean Height Velocity for Age and Sex 
[cm/y])/(Standard Deviation of the Mean) 
Full details on height velocity analyses can be found in the SAP. 
9.1.6.3. Assessment of Puberty 
 
 
 
  The date of onset of menstruation will also be collected. 
9.1.7. Health Outcomes Instruments 
Observer-reported outcomes will be used in place of patient-reported outcomes for children less 
than 
 for the following scales.  The patient’s age at entry into the study will 
determine which scale/instrument is used and this will not change as the patient ages during the 
study.   
Abdominal Pain Numeric Rating Scale:  The abdominal pain numeric rating scale (NRS) is a 
single item that measures the “worst abdominal pain in the past 24 hours” using a Pain NRS 
ranging from 0 to 5 (8-11 years old) and 0 to 10 (12-17 years old).  For children less than 8 years 
old, caregivers will complete an observer-reported outcome ranging from 0 to 10.  Patients or 
caregivers will be provided with an electronic diary tool during screening to record information 
daily pertaining to the patient’s worst abdominal pain experience. 
Urgency Numeric Rating Scale:  
 
 
 
  
 
9.1.8. 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 histopathology charter. 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 82 
LY3074828 
9.1.9. Exploratory Assessments 
Exploratory endpoints are found in Table AMBU.2.  Additional details are provided below. 
9.1.9.1. Inflammatory Biomarkers 
Fecal calprotectin:  Fecal calprotectin is a complex consisting of the calcium-binding proteins 
S100A8 and S100A9.  It is expressed by activated neutrophils (and to a lesser extent by 
macrophages and monocytes), and fecal levels correlate with the number of neutrophils in the 
gut (Sands 2015).  It is used as a biomarker of intestinal inflammation in clinical practice.  Fecal 
calprotectin will be obtained at time points described in the Schedule of Activities (Section 2).   
C-reactive protein (CRP):  C-reactive protein is an acute phase protein expressed by 
hepatocytes in response to inflammatory cytokines, particularly IL-6, TNF, and IL-1β 
(Sands 2015).  C-reactive protein will be obtained at the time points described in the Schedule of 
Activities (Section 2).   
9.1.9.2. Patient-Reported Outcome/Observer-Reported Outcome Instruments for 
Exploratory Assessments 
Observer-reported outcomes will be used in place of patient-reported outcomes for children less 
than 
 of age.   
Approved on 23 Oct 2021 GMT
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 83 
LY3074828 
9.1.9.3. Extraintestinal Manifestations 
Review of extraintestinal manifestations (EIMs) will be performed at the time points described in 
the Schedule of Activities (Section 2).  Extraintestinal manifestations that occur prior to baseline 
or existing EIMs that change in severity or resolve during the study will be documented on the 
appropriate eCRF.  Extraintestinal manifestations include, but are not limited to:  
 
 
 
9.1.9.4. Physician-Reported Instrument 
9.1.10. Appropriateness of Assessments 
All of the clinical and safety assessments in this study are standard, widely used, and generally 
recognized as reliable, accurate, and relevant.  The disease activity measurements are used in 
clinical practice and UC clinical trials, and the health outcomes measures will allow assessment 
of symptoms and quality of life that are important to patients and their caregivers.  
Immunogenicity monitoring will provide information for future development of mirikizumab. 
9.2. Adverse Events 
Investigators are responsible for monitoring the safety of patients who have entered this study 
and for alerting Lilly or its designee to any event that seems unusual, even if this event may be 
considered an unanticipated benefit to the patient. 
The investigator is responsible for the appropriate medical care of patients during the study. 
Investigators must document their review of each laboratory safety report. 
The investigator remains responsible for following, through an appropriate health care option, 
AEs that are serious or otherwise medically important, considered related to the investigational 
product or the study, or that caused the patient to discontinue the investigational product before 
completing the study.  The patient should be followed until the event resolves, stabilizes with 
appropriate diagnostic evaluation, or is reasonably explained.  The frequency of follow-up 
evaluations of the AE is left to the discretion of the investigator.  The investigator will record all 
relevant AE/SAE information in the eCRF. 
Lack of drug effect is not an AE in clinical studies, because the purpose of the clinical study is to 
establish treatment effect. 
After the ICF is signed, study site personnel will record via eCRF the occurrence and nature of 
each patient’s preexisting conditions, including clinically significant signs and symptoms of the 
Approved on 23 Oct 2021 GMT
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 84 
LY3074828 
disease under treatment in the study.  In addition, site personnel will record any change in the 
condition(s) and any new conditions as AEs.  Investigators should record their assessment of the 
potential relatedness of each AE to protocol procedure or investigational product, via eCRF.  
The investigator will interpret and document whether or not an AE has a reasonable possibility 
of being related to study drug, study device, or a study procedure, taking into account the 
disease, concomitant treatment, or pathologies. 
A “reasonable possibility” means that there is a cause and effect relationship between the 
investigational product, study device and/or study procedure and the AE.  The investigator 
answers yes/no when making this assessment. 
Planned surgeries and nonsurgical interventions should not be reported as AEs unless the 
underlying medical condition has worsened during the course of the study. 
If a patient’s investigational product is discontinued as a result of an AE, study site personnel 
must report this to Lilly or its designee via eCRF, clarifying if possible, the circumstances 
leading to any dosage modifications, or discontinuations of treatment.  
Care will be taken not to introduce bias when detecting AEs or SAEs.  Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences. 
Cardiovascular and venous thromboembolic AEs and other events leading to death are collected 
as described in Section 9.2.1 and its subsections; also see Section 9.2.2.4. 
9.2.1. Serious Adverse Events 
An SAE is any AE from this study that results in one of the following outcomes: 
 Death 
 Initial or prolonged inpatient hospitalization 
 A life-threatening experience (that is, immediate risk of dying) 
 Persistent or significant disability/incapacity 
 Congenital anomaly/birth defect 
 Important medical events that may not be immediately life-threatening or result in 
death or hospitalization but may jeopardize the patient or may require intervention 
to prevent one of the other outcomes listed in the definition above.  Examples of 
such medical events include allergic bronchospasm requiring intensive treatment 
in an emergency room or at home, blood dyscrasias or convulsions that do not 
result in inpatient hospitalization, or the development of drug dependency or drug 
abuse. 
All AEs occurring after signing the ICF are recorded in the eCRF, assessed for serious criteria, 
and all serious criteria that are met are recorded in the eCRF.  The required timeframe for SAE 
reporting to the sponsor begins after the patient has signed the ICF and has received 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 85 
LY3074828 
investigational product.  However, if an SAE occurs after signing the ICF, but prior to receiving 
investigational product, the SAE should be reported to the sponsor as per SAE reporting 
requirements and timelines (see Section 9.2) if it is considered reasonably possibly related to 
study procedure. 
Study site personnel must alert Lilly or its designee of any SAE within 24 hours of investigator’s 
awareness of the event via a sponsor-approved method.  If alerts are issued via telephone, they 
are to be immediately followed with official notification on study-specific SAE forms.  This 
24-hour notification requirement refers to the initial SAE information and all follow-up SAE 
information.  Patients with a 
 should have additional data collected using the 
hepatic eCRF. 
Pregnancy (during maternal or paternal exposure to investigational product) does not meet the 
definition of an AE.  However, to fulfill regulatory requirements, any pregnancy that begins at 
any point after the start of study drug and until at least 
 after the participant’s last dose 
of study drug should be reported following the SAE process to collect data on the outcome for 
both mother and fetus.   
Investigators are not obligated to actively seek AEs or SAEs in subjects once they have 
discontinued and/or completed the study (that is, the patient disposition case report form has 
been completed).  However, if the investigator learns of any SAE, including a death, at any time 
after a subject has been discharged from the study, and he/she considers the event reasonably 
possibly related to the study drug or study participation, the investigator must promptly notify 
Lilly. 
9.2.1.1. Suspected Unexpected Serious Adverse Reactions 
Suspected unexpected serious adverse reactions (SUSARs) are serious events that are not listed 
in the IB and that the investigator identifies as related to investigational product or procedure.  
United States 21 CFR 312.32 and European Union Clinical Trial Directive 2001/20/EC and the 
associated detailed guidances or national regulatory requirements in participating countries 
require the reporting of SUSARs.  Lilly has procedures that will be followed for the 
identification, recording, and expedited reporting of SUSARs that are consistent with global 
regulations and the associated detailed guidances. 
9.2.1.2. Regulatory Reporting Requirements for Serious Adverse Events 
Prompt notification by the investigator to the sponsor of an SAE as stated in Section 9.2.1 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.  The 
sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, Institutional Review Boards (IRBs)/Independent Ethics Committees 
(IECs), and investigators. 
Approved on 23 Oct 2021 GMT
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 86 
LY3074828 
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators as necessary. 
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. 
9.2.2. Adverse Events of Special Interest 
Adverse events of special interest (AESIs), which are not necessarily ADRs but are of special 
interest based on standard drug registration topics, safety findings from previous studies in the 
development program, potential risks associated with biologic immunomodulators as noted in 
product labels and published literature, and comorbidities and risk factors prevalent in the 
studied populations.  The AESIs for this study are defined in the SAP, and may include but are 
not limited to: 
Additional samples and data will be collected for hypersensitivity events (Section 2).  For some 
AESIs, sites should provide additional information regarding the event, as instructed on the 
eCRF.  For all AESIs, including hypersensitivity events, the protocol and IB provide monitoring 
and management guidance to the investigator. 
Approved on 23 Oct 2021 GMT
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 87 
LY3074828 
9.2.3. Complaint Handling 
Lilly collects product complaints on investigational products and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and to 
facilitate process and product improvements. 
Patients will be instructed to contact the investigator as soon as possible if he or she has a 
complaint or problem with the investigational product so that the situation can be assessed. 
9.3. Treatment of Overdose  
In case of suspected overdose, participants should be monitored for any signs or symptoms of 
adverse reactions or effects, and hematology, chemistry, vital signs, and oxygen saturation 
should be monitored; supportive care should be provided as necessary.  The medical monitor and 
sponsor must be informed as soon as possible when an overdose has been identified, and all AEs 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 88 
LY3074828 
associated with the overdose will be recorded in the eCRF.  
 
 
9.4. Safety 
When multiple safety assessments are scheduled for the same visit, the preferred order of 
completion is as follows:   
9.4.1. Vital Signs 
Measurements of vital signs (body temperature, blood pressure, and pulse rate) will be conducted 
at the study visits specified in the Schedule of Activities (Section 2).   
Sitting blood pressure and pulse rate should be measured after the patient has been sitting for at 
least 5 minutes. 
Any clinically significant findings from vital signs measurement that result in a diagnosis and 
that occur after the patient receives the first dose of study drug should be reported to Lilly or its 
designee as an AE via eCRF. 
9.4.2. Electrocardiograms 
Electrocardiograms (
) should be collected according to the Schedule of Activities 
(Section 2).   
Electrocardiograms should be completed prior to any blood draw.  Participants should be supine 
for approximately 5 to 10 minutes before ECG collection and should remain supine and awake 
during ECG collection. 
Evaluation of ECGs should be performed by appropriately trained personnel with experience in 
reading pediatric ECGs.  Electrocardiograms will be read locally by a health care professional 
trained in the reading of pediatric ECGs. 
Any clinically significant findings from ECGs that result in a diagnosis and that occur after the 
patient receives the first dose of the investigational treatment should be reported to Lilly or its 
designee as an AE via eCRF. 
9.4.3. Laboratory Tests 
Laboratory tests detailed in Appendix 2 should be conducted according to the Schedule of 
Activities (Section 2).  
Retesting is allowed during the screening period (see Section 6.4.1). 
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.   
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 89 
LY3074828 
Except where otherwise stated (for example, 
), samples for laboratory 
tests should be collected prior to dosing. 
Unless noted as locally performed (for example, urine pregnancy tests), clinical laboratory tests 
will be sent to a central laboratory for testing. 
Lilly or its designee will provide the investigator with the results of laboratory tests analyzed by 
a central vendor, where appropriate. 
Any clinically significant findings from laboratory tests that result in a diagnosis and that occur 
after the patient receives the first dose of investigational product should be reported to Lilly or its 
designee as an AE via eCRF. 
9.4.3.1. Pregnancy Testing 
Female subjects of childbearing potential will undergo a urine pregnancy test at the clinic 
 
 during scheduled visits through Week 52.  
Childbearing potential is defined as females meeting one or more of the following criteria: 
Serum pregnancy test will be done at screening only and results will be confirmed by the central 
laboratory.  Patients determined to be pregnant will be discontinued from the study. 
Urine pregnancy testing will be performed locally during designated scheduled visits through 
Week 52.  The urine pregnancy test must be “negative” within 24 hours prior to administration 
of study drug at every study visit. 
Urine pregnancy testing may be performed at additional time points during the treatment period 
and/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. 
9.4.3.2. Hormone Testing 
 will be collected to assess the onset of puberty in patients 
aged 
 and older who have not attained full maturation by Visit 1 and at other visits 
specified in the Schedule of Activities (Section 2). 
9.4.4. Immunogenicity Assessments 
At the visits and times specified in the Schedule of Activities (Section 2), venous blood samples 
will be collected to determine antibody production against mirikizumab.   
 Pre-dose samples will be obtained per the Schedule of Activities. 
 The actual date and time (24-hour clock time) of each sample collection will be recorded. 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 90 
LY3074828 
To aid interpretation of these results, a pre-dose blood sample for PK analysis will be collected at 
the same time points. 
In the event of a systemic allergic/hypersensitivity reaction (Section 9.2.2.2), additional blood 
samples will be obtained as specified in the Schedule of Activities (Section 2). 
Sample collection, handling, and use 
Instructions for the collection and handling of blood samples will be provided by the sponsor. 
Immunogenicity will be assessed by a validated assay designed to detect ADAs in the presence 
of mirikizumab at a laboratory approved by the sponsor.  Antibodies will be further evaluated for 
their ability to neutralize the activity of mirikizumab. 
Sample retention 
Samples will be retained for a maximum of 
 after the last patient visit, or for a shorter 
period if local regulations and ERBs allow, at a facility selected by the sponsor.  The duration 
allows the sponsor to respond to future regulatory requests related to mirikizumab.  Any samples 
remaining after 
 will be destroyed.   
9.4.5. Other Tests 
9.4.5.1. Physical Examination 
Physical examinations are mandated and will be performed as specified in the Schedule of 
Activities (Section 2).  Physical examinations can also be performed at the discretion of the 
investigator at any additional timepoints, for example, to assist in the evaluation of a new 
symptom during the study.   
At screening, 1 complete physical examination (excluding pelvic, rectal, and breast 
examinations) will be performed and will include an assessment of peripheral lymph nodes. 
After screening, physical examinations should include a symptom-directed evaluation, as well as 
examination of eyes, heart, lungs, abdomen, and skin.  For all participants, a thorough exam to 
evaluate for TB will be performed (Section 9.4.5.2). 
Any clinically significant findings from physical examinations that result in a diagnosis and that 
occur after the patient receives the first dose of investigational product should be reported to 
Lilly or its designee as an AE via eCRF.  
Approved on 23 Oct 2021 GMT
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 91 
LY3074828 
9.4.5.2. Tuberculosis Testing 
Initial Screening 
All patients will be screened for active TB and LTBI.  Screening for LTBI (Visit 0) will include 
the following: 
 Thorough medical and social history to determine risk factors for TB infection over 
lifetime, symptoms or signs of active TB, and physical examination, including body 
temperature measurement and assessment of peripheral lymph nodes, as described in 
Section 9.4.5.1. 
 Two tests to assess immune response to mycobacterial antigens (unless patient has a 
history of a positive IGRA): 
o IGRA (for example, QuantiFERON-TB Gold or T-SPOT.TB), and 
o Tuberculin skin test (TST, also called a purified protein derivative [PPD] or 
Mantoux test). 
 CXR, as described in Section 9.4.5.3. 
This testing paradigm follows the recommendation from NASPGHAN for pediatric patients with 
IBD starting on anti-TNF therapy (Ardura et al. 2016).  
Tests for Immune Response to Mycobacterial Antigens 
Patients with documentation of a “negative” IGRA or TST within 
 before initial 
screening may not need to repeat TB testing at screening, based on judgment of the investigator.  
Source documentation must include the original laboratory report (for IGRA) or a record of the 
size in millimeters of the induration response (for TST).  A TST recorded as “negative” without 
documenting the size of induration in millimeters will not be acceptable and will require a retest.  
Interpretation of Screening Tests for LTBI 
The QuantiFERON-TB Gold assay will be reported as negative, indeterminate, or positive.  The 
T-SPOT assay will be reported as negative, borderline, or positive. 
The TST should be read 48 to 72 hours after test application.  Skin induration 
 in diameter 
is interpreted as positive in patients without a BCG vaccination history.  In patients with a prior 
BCG vaccination history, a positive result shall be defined using local criteria 
recommendation/guidelines.  Any questions should be referred to the medical monitor. 
Patients with a diagnosis of LTBI based on a positive IGRA test result or a positive TST 
response, and no evidence of active TB on medical history, physical examination, and CXR, may 
be evaluated as described in Retesting and Confirmatory testing or rescreened once, as indicated 
in Section 6.4.  
Patients may be enrolled in the study if they are treated for LTBI and meet the following 
requirements: 
 No history of risk of re-exposure since their treatments were completed 
 Have received at least 
 of appropriate ongoing prophylactic therapy for LTBI, 
based on national or international guidelines, for example, United States Centers for 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 92 
LY3074828 
Disease Control and Prevention (CDC 2016); or the World Health Organization (WHO 
2018), with documentation of having completed the appropriate TB prophylaxis regimen, 
 No evidence of reactivation of LTBI, and 
 Have no evidence of hepatotoxicity (ALT and AST levels must remain ≤2xAAULN) 
upon retesting of serum ALT and AST levels before treatment assignment). 
Such patients must meet all other inclusion and exclusion criteria for participation, and also must 
continue and complete appropriate LTBI therapy during the course of the study to remain 
eligible to participate.   
Retesting and Confirmatory Testing 
One retest is allowed for patients with an “indeterminate” QuantiFERON-TB Gold assay or 
“borderline” T-SPOT assay.  Patients with 2 indeterminate QuantiFERON-TB Gold assays or 2 
borderline T-SPOT assays will be required to have a CXR (see Section 9.4.5.3).  If both the CXR 
and TST are negative and there are no other risk factors for TB exposure present, the patient is 
eligible to be enrolled in the study. 
Confirmatory testing with an IGRA is allowed for selected patients who have a positive TST, 
positive QuantiFERON-TB Gold assay or positive T-SPOT assay who meet all of the following 
criteria, and are assessed by the investigator as likely having a false-positive test result:  
 No risk factors for LTBI  
 No risk factors for increased likelihood of progressing from LTBI to active TB, and  
 Have never resided in a high-burden country, as detailed in Appendix 8.   
If the confirmatory test is positive, the patient will be excluded from the study unless they 
complete at least 
 of appropriate therapy for LTBI based on national or international 
guidelines (as defined above), and have no evidence of hepatotoxicity 
 
 upon retesting of serum 
 of 
LTBI treatment.  Such patients must continue and complete appropriate full course of LTBI 
therapy during the course of the study to remain eligible to participate in the study.  If the 
confirmatory test is negative, these results will be discussed with the medical monitor in order to 
determine eligibility for the study.  
Patients with a negative TST or IGRA can be re-tested with an IGRA where, in the judgement of 
the investigator, the initial test result may be a false negative, for example, due to a technical 
difficulty in administering the TST or due to concomitant immunosuppressant therapy. 
Monitoring for TB During the Study 
For all patients, monitoring for TB is to be continuous throughout the study.  At a minimum, 
each participant is to have the following documented at least every 
  
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 93 
LY3074828 
If the patient has a risk factor (Appendix 8), the investigator should collect 
, as described 
in Section 9.4.5.3 
Diagnosis of LTBI During Study 
Patients diagnosed with LTBI during the study 
 
  If treatment for LTBI is considered to be appropriate, the patient must 
complete 
 of appropriate therapy for LTBI, based on national or international 
guidelines (as defined above), and have no evidence of hepatotoxicity 
 
upon retesting of serum ALT and AST levels after at least 
 of 
LTBI treatment.  Such patients may then resume study drug and must continue with and 
complete a full course of treatment for LTBI in order to continue on study drug.  Non-
compliance with LTBI treatment during the study is a reason for permanent discontinuation from 
study drug (Section 8.1.1).  
Household Contact 
Throughout the study, patients who have had household contact with a person with active TB 
must be evaluated for TB infection. 
Prior Treatment for LTBI  
Patients who have a documented history of completing an appropriate TB prophylaxis regimen 
with no history of risk of re-exposure since their treatments were completed and no evidence of 
active TB are eligible to participate in the study.  These patients should not undergo TST or 
IGRA testing unless advised to do so based on local guidelines.   
Active TB  
Patients with a past history of active TB, without documented treatment by WHO and/or CDC 
criteria are excluded from the study (Section 6.2). 
Patients diagnosed with active TB at screening will be excluded (Section 6.2) and should be 
referred by the investigator for appropriate TB treatment and follow-up. 
If a patient is diagnosed with active TB during the study, the study drug will be permanently 
discontinued (Section 8.1.1), and the patient will undergo an ETV and then enter the post-
treatment follow-up period.  The patient should also be referred by the investigator for 
appropriate TB treatment and follow-up. 
9.4.5.3. Chest Radiography 
A posterior-anterior chest x-ray (CXR), interpreted and reported by a radiologist or 
pulmonologist, may be obtained at screening, as specified in the Schedule of Activities 
(Section 2) if both the TST and QuantiFERON-TB Gold assay or T-Spot assay are indeterminate 
or borderline.  A CXR may be taken at any time in the study at the discretion of the investigator 
when clinically indicated, for example, as part of an evaluation for active TB and LTBI.  A 
lateral CXR can also be obtained, if in the opinion of the investigator, a lateral view is indicated.  
The CXR will be performed and interpreted locally.  
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 94 
LY3074828 
A CT scan can be performed as an alternative to the CXR based on regional standard of practice.  
The CT scan will be performed and interpreted locally. 
If the CXR or CT is performed for TB evaluation, it should be interpreted and reported by a 
radiologist or physician who specializes in the treatment of TB. 
Certain findings from CXR may be consistent with a condition that excludes a participant from 
the study; see Section 6.2.   
9.4.5.4. Hepatitis B Testing 
HBV Screening and Interpretation 
Exclusion Based on HBV Serology and HBV DNA Testing 
Patients Potentially Allowed into the Study, Based on HBV Serology and HBV DNA 
Testing 
Management of Patients with the Following HBV Serology at Baseline:  HBsAg-, 
anti-HBc+, HBV DNA Not Detected 
Management of Patients with a Newly Positive anti-HBc Test During the Study 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 95 
LY3074828 
Management of Patients with Detectable HBV DNA During the Study 
9.4.5.5. Hepatitis C Testing 
Patients with current hepatitis C infection are excluded from the study. 
Approved on 23 Oct 2021 GMT
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 96 
LY3074828 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 97 
LY3074828 
9.4.5.7. Stool Testing 
Stool Culture  
A stool sample for culture will be obtained at screening.   
Patients must have a “negative” stool culture from which no enteric pathogens are isolated in 
order to be enrolled.   
Retesting is allowed within the same screening period if there is a technical difficulty in 
performing or reporting the stool culture assay, as stated in Section 6.4.1.  
Patients who have a “positive” stool culture result can be re-screened once, as stated in 
Section 6.4, provided that the following conditions have been met: 
 The patient has been adequately treated, and 
o if antibiotics were prescribed, patient has been off antibiotics for 
, or 
o if antibiotics were not prescribed, 
 or more has elapsed since resolution of 
acute symptoms and signs associated with the underlying intestinal infection. 
The stool culture should be retested prior to rescreening.  
Additional local stool culture/testing is allowed at the investigator’s discretion. 
Participants with a positive stool culture result are excluded from the study (see Section 6.2). 
C. difficile  
A stool sample for testing C. difficile will be obtained at screening.   
This assay may be tested locally (if available for antigen, toxin, and PCR reflex evaluation) or 
centrally for the presence of C. difficile antigen (GDH) and toxin (toxin A and toxin B), followed 
by a possible reflex to PCR confirmatory test for C. difficile gene expression in the stool sample.  
See flow chart below.   
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 98 
LY3074828 
Retesting is allowed within the screening period if there is a technical difficulty in performing or 
reporting the C. difficile result, as stated in Section 6.4.1. 
Patients who test positive at screening for C. difficile can be rescreened once, as stated in 
Section 6.4, provided that the following conditions have been met: 
 The patient has been adequately treated, and 
 The patient has been off antibiotics for 
. 
Patients who have been adequately treated for C. difficile with fecal microbial transplantation or 
IV immunoglobulin therapy can be rescreened once for the study, 
 after completing their 
therapy.   
A C. difficile stool toxin assay should be repeated prior to rescreening.  
Patients with a positive test for C. difficile toxin are excluded from the study (Section 6.2). 
9.4.6. Safety Monitoring 
Lilly will periodically review evolving aggregate safety data within the study by appropriate 
methods. 
9.4.6.1. Hepatic Safety Monitoring 
If a study patient experiences elevated 
, or 
 
, liver testing (described in Appendix 4) should be repeated within 3 to 5 days, 
including 
 
 to confirm the abnormality and to determine if it is increasing or decreasing.  If the 
abnormality persists or worsens, clinical and laboratory monitoring should be initiated by the 
investigator and in consultation with the study medical monitor.  Monitoring of 
 
 should continue until levels normalize or return to approximate baseline levels.  
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 99 
LY3074828 
If a study patient experiences an 
 and 
 or 
international normalized ratio 
, the study medical monitor should be consulted as soon as 
possible for further guidance on evaluation of the laboratory abnormalities. 
Hepatic Safety Data Collection 
Additional safety data should be collected via the hepatic eCRF if 1 or more of the following 
conditions occur:  
 Elevation of serum ALT to 
 on 2 or more consecutive blood tests 
 Elevated serum TBL to 
 (except for cases of known Gilbert’s 
syndrome)  
 Elevation of serum ALP to 
 on 2 or more consecutive blood tests 
 Patient discontinued from treatment due to a hepatic event or abnormality of 
liver tests 
 Hepatic event considered to be a SAE 
 Patient with a history of HCV infection develops elevated ALT 
.  Patient 
will be tested for HCV RNA. 
9.5. Pharmacokinetics 
At the visits and times specified in the Schedule of Activities (Section 2), venous blood samples 
will be collected to determine the serum concentrations of mirikizumab.  Pre-dose samples can 
be collected at any time prior to dosing during the visit, and post-dose samples should be 
collected within 
 after dosing. 
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.   
Additional samples 
A maximum of 3 additional samples may be collected at additional time points during the study 
if warranted and agreed upon between both the investigator and sponsor.  In the case of systemic 
allergic/hypersensitivity reactions (Section 9.2.2.2), additional blood samples will be obtained, as 
described in the Schedule of Activities (Section 2). 
 
 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 100 
LY3074828 
Sample retention 
Bioanalytical samples collected to measure investigational product concentration will be retained 
for a maximum of 
 following last patient visit for the study. 
9.6. Pharmacodynamics 
See Section 9.8. 
9.7. Pharmacogenomics  
 
 
  
 
 
 
   
 
 
may be tested.  These are genetic markers that are related to 
the biology of inflammatory and autoimmune disease. 
All samples will be coded with the patient number.  These samples and any data generated can 
be linked back to the patient only by the investigator site personnel.   
Sample retention 
Samples will be retained at a facility selected by Lilly or its designee for a maximum of 
 
after the last patient visit for the study, or for a shorter period if local regulations and/or ERBs 
impose shorter time limits.  This retention period 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 becomes commercially available. 
Molecular technologies are expected to improve during the 
 and therefore, 
cannot be specifically named.  However, existing approaches include whole genome or exome 
sequencing, genome wide association studies, and candidate gene studies.  Regardless of the 
technology utilized, genotyping data generated will be used only for the specific research scope 
described in this section. 
9.8. Biomarkers 
 
 
 
 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 101 
LY3074828 
Sample use 
Biomarker research is performed to address questions of relevance to drug disposition, target 
engagement, PD, mechanism of action, variability of patient response (including safety), and 
clinical outcome.  Sample collection is incorporated into clinical studies to enable examination of 
these questions through measurement of biomolecules, including DNA, RNA, proteins, lipids, 
and other cellular elements. 
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, and/or 
research method, or in validating diagnostic tools or assays related to UC.   
All samples will be coded with the patient number.  These samples and any data generated can 
be linked back to the patient only by the investigator site personnel.   
Sample retention 
Samples will be retained at a facility selected by Lilly or its designee for a maximum of 
 
after the last patient visit for the study, or for a shorter period if local regulations and ERBs 
impose shorter time limits.  This retention period 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 becomes commercially available. 
9.9. Medical Resource Utilization and Health Economics 
Sites should provide information regarding healthcare visits, including hospitalizations and 
surgeries for UC, as instructed on the eCRF. 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 102 
LY3074828 
10. Statistical Considerations 
10.1. Sample Size Determination 
Lilly plans to enroll approximately 30 patients into Study AMBU, to achieve at least 25 
evaluable patients with respect to evaluating mirikizumab PK.  The enrollment target includes 
approximately 
 patients in the >40 kg category and approximately 
 patients in the ≤40 kg 
category.  
This sample size is considered adequate to evaluate the PK of mirikizumab treatment in pediatric 
patients. 
10.2. Populations for Analyses 
For purposes of analysis, the populations are defined in Table AMBU.6. 
Table AMBU.6. 
Population Definitions 
Population 
Description 
Modified Intent-to-Treat 
(mITT) Population 
All enrolled patients that took at least 1 dose of treatment, even if the patient 
does not receive the correct treatment, or otherwise does not follow the 
protocol.  Patients will be analyzed according to the treatment to which they 
were assigned.  Unless otherwise noted, efficacy and health outcomes analyses 
will be conducted on this population. 
Induction Safety 
All Induction ITT patients who received at least 1 dose of the study drug.  
Patients will be analyzed according to the treatment to which they were 
assigned.  Safety analyses for the induction period will be conducted on this 
population.  
Maintenance Safety 
All Maintenance ITT patients who have received at least 1 maintenance dose.  
Safety analyses for the maintenance period will be conducted on this 
population. 
PK evaluable 
All patients who received at least 1 dose of investigational product and have 
sufficient blood sampling to allow for PK evaluation. 
Abbreviations:  ITT = intent-to-treat; PK = pharmacokinetic. 
 
Additional populations will be defined in the SAP. 
10.3. Statistical Analyses 
10.3.1. General Statistical Considerations 
Statistical analysis of this study will be the responsibility of Lilly or its designee. 
Efficacy analyses for the induction period and the maintenance period will be conducted on the 
modified ITT population.  Safety analyses for the induction period and the maintenance period 
will be conducted on the induction safety population and the maintenance safety population, 
respectively.   
Approved on 23 Oct 2021 GMT
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 103 
LY3074828 
Summary statistics for continuous variables will include mean, standard deviation, median, and 
minimum and maximum values; categorical variables will be presented as counts and 
percentages.   
Any change to the data analysis methods described in the protocol will require an amendment 
ONLY if it changes a principal feature of the protocol.  Any other change to the data analysis 
methods described in the protocol, and the justification for making the change, will be described 
in the clinical study report (CSR).  Additional exploratory analyses of the data will be conducted 
as deemed appropriate.  Full details of these analyses will be provided in the SAP.  
10.3.1.1. Missing Data Imputation 
While every effort will be made to reduce missing data, the missing data imputation method of 
NRI will be used when patients are permanently discontinued from study drug or otherwise have 
missing data. 
For analysis of categorical efficacy and health outcomes variables, missing data will be imputed 
using an NRI method.  Patients will be considered a nonresponder for the NRI analysis if they do 
not meet the categorical response criteria or have missing clinical response data at a time point of 
interest.   
Imputation details based on NRI will be provided in the SAP.  Additional missing data 
imputation methodologies may be considered and will also be fully detailed in the SAP. 
10.3.2. Treatment Group Comparability 
10.3.2.1. Patient Disposition 
The number of enrolled patients will be summarized.  Frequency counts and percentages of all 
patients who are enrolled and completing the study or discontinue the study drug/study early will 
be presented.  Reasons for discontinuing the study drug/study will be summarized. 
10.3.2.2. Patient Characteristics 
Full date of birth (unless prohibited by local law), sex, weight, height, smoking habits, previous 
biologic therapy, corticosteroid use, and other demographic characteristics will be recorded.  Age 
and body mass index will be calculated.  Demographic and baseline characteristics will be 
summarized for each treatment group.  Certain characteristics, such as weight, that are collected 
after baseline, will be reported as a listing.   
10.3.2.3. Concomitant Therapy 
Concomitant therapy will be collected at each visit, and the reported term will be classified by 
the World Health Organization drug dictionary.  Previous concomitant therapy (reported before 
study enrollment) and current concomitant therapy (reported after study enrollment) will be 
presented separately in frequency tables by drug name for all enrolled patients. 
10.3.2.4. Treatment Compliance 
Patients who are noncompliant will be listed by treatment.  A contingency table of numbers of 
noncompliant patients by treatment will be provided. 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 104 
LY3074828 
10.3.3. Efficacy Analyses 
10.3.3.1. Primary Analyses 
The primary objective of this study is to evaluate the PK of mirikizumab treatment in pediatric 
patients.  See Section 10.3.5 for a description of PK analyses. 
10.3.3.2. Secondary Analyses 
The secondary efficacy endpoint of clinical remission will be assessed using the MMS, a 9-point 
instrument that includes the SF, RB, and ES subscores of the Mayo Score. 
The SF and RB subscores of the Mayo Score will be calculated from daily electronic diary data 
by averaging the most recent 
 (possibly non-consecutive) prior to the Week 52 visit or 
 prior to the Week 52 bowel preparation/endoscopy.  If data from fewer than 
 are 
available from the 
 to Week 52 visit, the subscores will be considered as missing.  
The 
 of patient diary data must exclude data from days when bowel preparation or 
endoscopic exam (flexible proctosigmoidoscopy/colonoscopy) occur and exclude data from the 
day after the endoscopic exam.   
To calculate the SF subscore, the reference SF will be subtracted from the 
 averaged SF.  
The subtracted SF value will then be rounded to the nearest integer and then mapped to obtain 
Mayo SF subscore.   
To calculate the RB subscore, the 
 RB scores will be averaged and the RB subscore will be 
rounded to the nearest integer.  Rates of clinical remission at Week 12, as defined in 
Section 9.1.1, will be analyzed.  Patients who do not achieve clinical remission or who do not 
reach the Week 12 assessment will be considered to be nonremitters.  
Descriptive summaries by treatment, by visit, and by weight group for this endpoint, as well as 
for the rest of the secondary efficacy endpoints described in Table AMBU.2 will be performed 
using NRI methodology. 
Additional analyses of the secondary endpoint may be considered and details will be provided in 
the SAP. 
10.3.3.3. Tertiary/Exploratory Analyses 
The exploratory endpoints of the trial are presented in Table AMBU.2.  Details of the analyses of 
exploratory endpoints, as well as additional exploratory endpoints will be described in the SAP. 
10.3.4. Safety Analyses 
Safety data will be summarized by dose.  Safety and tolerability including but not limited to AEs, 
infections, injection site reactions, clinical chemistry, hematology, immunogenicity, tolerability 
and acceptability of SC injection volumes of 
, and questionnaires to assess the existence 
and severity of depression will be assessed.   
For AEs, the number of treatment-emergent adverse events (TEAEs), as well as the number and 
percentage of patients who reported at least 1 TEAE will be summarized using Medical 
Dictionary for Regulatory Activities (MedDRA) for each system organ class and preferred term.  
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 105 
LY3074828 
Serious adverse events (including deaths), treatment-emergent AESIs, and AEs that lead to 
treatment discontinuation will also be summarized using MedDRA for each system organ class 
and preferred term. 
For laboratory analytes and vital signs, treatment-emergent abnormal shifts to low/high will be 
presented. 
Summary tables or listings for 
 will be produced as needed. 
Immunization history will be recorded at baseline, and any unexpected outcomes or effects 
related to standard of care vaccination during the study will be summarized. 
Further analyses may be performed as deemed appropriate and will be detailed in the SAP. 
10.3.5. Pharmacokinetic/Pharmacodynamic Analyses 
Analyses of the PK of mirikizumab and relationships between exposure and the efficacy 
endpoints will be conducted.  For both the PK and exposure-response analyses, intrinsic and 
extrinsic factors will be evaluated to determine their impact.  Comparisons of adult and pediatric 
PK and exposure-response will be performed and may be combined if appropriate. 
The PK of mirikizumab will be characterized 
 
 
 
   
Analyses of exposure-response relationships may be conducted using both exploratory graphical 
approaches and model based approaches.  Exploratory graphical analysis approaches may consist 
of graphs showing the change in
versus exposure of mirikizumab.  Model based analyses may utilize population exposure-
response models, where maximum effect (Emax) or other model structures may be used to relate 
mirikizumab exposure to the probability of achieving clinical response, clinical remission, 
endoscopic healing, or change in the MMS score.  These models may be used to evaluate patient 
factors that may impact the exposure-response relationships.  Similar graphical and model based 
analyses relating mirikizumab exposure to 
 
 may also be conducted.  
Additional analyses may be conducted if they are deemed appropriate.  Data from this study may 
be combined with other study data, if appropriate.  Comparison of data in this study with data 
from adult studies will be addressed in a separate analysis plan.  Further details on PK and 
exposure-response analyses will be provided in the PK/PD analysis plan. 
10.3.6. Evaluation of Immunogenicity  
The frequency and percentage of patients with preexisting (baseline) ADA, ADA at any time 
post baseline, and with treatment-emergent anti-drug antibody (TEADA) to mirikizumab will be 
tabulated.  If no ADAs are detected at baseline, TEADAs are defined as those with a 
 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 106 
LY3074828 
 greater than the minimum required dilution (MRD) of the assay.  For samples with 
ADA detected at baseline, TEADAs are defined as those with a 
 increase in 
titer compared to baseline.  For patients who have TEADA, the distribution of maximum titers 
will be described.  The frequency of neutralizing antibodies will also be tabulated. 
The relationship between the presence of antibodies and the PK parameters and PD response 
including safety and efficacy to mirikizumab will be assessed. 
10.3.7. Other Analyses 
10.3.7.1. Subgroup Analyses 
Subgroup analyses may be conducted for select secondary endpoints.  Subgroups to be evaluated 
may include sex, age 
, weight (≥40 kg versus <40 kg), race, 
geographic region, baseline disease severity, duration of disease, previous use of biologic 
therapy, and no previous use of biologic therapy.  Details of the subgroups and associated 
analyses (including any additional subgroups) will be defined in the SAP. 
10.3.8. Data Snapshot and Interim Analyses 
The planned data snapshot and interim analyses are described as follows. 
10.3.8.1. Data Snapshots 
There will be 2 data snapshots taken of PK and safety data: 
 The first snapshot will be taken when at least  patients reach Week 4.  This will provide 
an early assessment of PK and safety data.  This analysis is planned to enable dose 
confirmation for the Phase 3 study for patients >40 kg. 
 The second snapshot will be taken when approximately  patients in the ≤40 kg group 
(5 mg/kg IV Q4W) reach Week 4.  This analysis is planned to enable the enrollment of 
the 10 mg/kg treatment group. 
10.3.8.2. Interim Analyses 
 An interim analysis is planned when approximately 
 patients in the ≤40 kg group reach 
Week 12.  This analysis will allow confirmation of dose for patients ≤40 kg to begin the 
Phase 3 study. 
No multiplicity adjustment will be made due to multiple comparisons or due to interim analyses. 
Additional data snapshots and/or interim analyses may be performed as deemed necessary, based 
on emerging data from the study. 
Study sites will receive information about interim results ONLY if it is required for the safety of 
their patients. 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 107 
LY3074828 
11. References 
Ardura MI, Toussi SS, Siegel JD, Lu Y, Bousvaros A, Crandall W. NASPGHAN clinical report: 
surveillance, diagnosis, and prevention of infectious diseases in pediatric patients with 
inflammatory bowel disease receiving tumor necrosis factor-α inhibitors. J Pediatr 
Gastroenterol Nutr. 2016;63(1):130-155. 
Bai S, Jorga K, Xin Y, Jin D, Zheng Y, Damico-Beyer LA, Gupta M, Tang M, Allison DE, Lu 
D, Zhang Y, Joshi A, Dresser MJ. A guide to rational dosing of monoclonal antibodies. Clin 
Pharmacokinet. 2012;51(2):119-135. 
Benchimol EI, Guttmann A, Griffiths AM, Rabeneck L, Mack DR, Brill H, Howard J, Guan J, 
To T. Increasing incidence of paediatric inflammatory bowel disease in Ontario, Canada: 
evidence from health administrative data. Gut. 2009;58(11):1490-1497. 
Betteridge JD, Armbruster SP, Maydonovitch C, Veerappan GR. Inflammatory bowel disease 
prevalence by age, gender, race, and geographic location in the U.S. military health care 
population. Inflamm Bowel Dis. 2013;19(7):1421-1427. 
Buse E. Development of the immune system in the cynomolgus monkey: the appropriate model 
in human targeted toxicology? J Immunotoxicol. 2005;2(4):211-216. 
Button LA, Roberts SE, Goldacre MJ, Akbari A, Rodgers SE, Williams JG. Hospitalized 
prevalence and 5-year mortality for IBD: Record linkage study. World J Gastroenterol. 
2010;16(4):431-438. 
[CDC] Centers for Disease Control and Prevention. Treatment regimens for latent TB infection 
(LTBI). CDC webpage. Available at: https://www.cdc.gov/tb/topic/treatment/ltbi.htm. April 
2016. Accessed April 16, 2019.  
[CUIMC] Columbia University Irving Medical Center. Columbia-Suicide Severity Rating Scale 
(C-SSRS). Available at: https://cssrs.columbia.edu/. Published 2016. Accessed December 14, 
2020. 
D’Haens G, Sanborn WJ, Ferrante M, Bhandari BR, Berliba E, Hibi T, Tuttle J, Canavan JB, 
Friedrich S, Durante M, Arora V, Feagan B. OP38 maintenance treatment with mirikizumab, a 
p19-directed IL-23 antibody: 52-week results in patients with moderate-to-severely active 
ulcerative colitis. J Crohns Colitis. 2019;13:S026-S027. 
Di Domenicantonio R, Cappai G, Arca M, Agabiti N, Kohn A, Vernia P, Biancone L, Armuzzi 
A, Papi C, Davoli M. Occurrence of inflammatory bowel disease in central Italy: A study 
based on health information systems. Dig Liver Dis. 2014;46(9):777-782. 
Dirks NL, Meibohm B. Population pharmacokinetics of therapeutic monoclonal antibodies. Clin 
Pharmacokinet. 2010;49(10):633–659.  
Ekbom A, Helmick C, Zack M, Adami HO. Ulcerative colitis and colorectal cancer. A 
population-based study. N Engl J Med. 1990;323(18):1228-1233. 
[EMA] European Medicines Agency. Qualification opinion Paediatric Ulcerative Colitis Activity 
Index (PUCAI). CHMP/SAWP/801872/2015. Available at: 
http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideli
ne/2016/01/WC500200026.pdf. January 2016a. Accessed April 10, 2019. 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 108 
LY3074828 
[EMA] European Medicines Agency. Guideline on the development of new medicinal products 
for the treatment of Ulcerative Colitis. CHMP/EWP/18463/2006 Rev. 1. Available at: 
http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2016/07/WC50
0211431.pdf. 2 July 2016b. Accessed April 10, 2019. 
[FDA] Food and Drug Administration. Ulcerative Colitis: Clinical Trial Endpoints, Draft 
Guidance for Industry. Available at: 
https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/u
cm515143.pdf. August 2016. Accessed April 10, 2019. 
Horsburgh CR, Rubin EJ. Latent tuberculosis infection in the United States. N Engl J Med. 
2011;364(15):1441-1448. 
Hyams J, Markowitz J, Lerer T, Griffiths A, Mack D, Bousvaros A, Otley A, Evans J, 
Pfefferkorn M, Rosh J, Rothbaum R, Kugathasan S, Mezoff A, Wyllie R, Tolia V, delRosario 
JF, Moyer MS, Oliva-Hemker M, Leleiko N; Pediatric Inflammatory Bowel Disease 
Collaborative Research Group. The natural history of corticosteroid therapy for ulcerative 
colitis in children. Clin Gastroenterol Hepatol. 2006;4(9):1118-1123. 
Hyams JS, Lerer T, Mack D, Bousvaros A, Griffiths A, Rosh J, Otley A, Evans J, Stephens M, 
Kay M, Keljo D, Pfefferkorn M, Saeed S, Crandall W, Michail S, Kappelman MD, Grossman 
A, Samson C, Sudel B, Oliva-Hemker M, Leleiko N, Markowitz J; Pediatric Inflammatory 
Bowel Disease Collaborative Research Group Registry. Outcome following thiopurine use in 
children with ulcerative colitis: a prospective multicenter registry study. Am J Gastroenterol. 
2011;106(5):981-987. 
Hyams J, Damaraju L, Blank M, Johanns J, Guzzo C, Winter HS, Kugathasan S, Cohen S, 
Markowitz J, Escher JC, Veereman-Wauters G, Crandall W, Baldassano R, Griffiths A; T72 
Study Group. Induction and maintenance therapy with infliximab for children with moderate 
to severe ulcerative colitis. Clin Gastroenterol Hepatol. 2012;10(4):391-399. 
Illumina. Infinium® ImmunoArray-24 v2.0 BeadChip product information sheet. 2015. 
Webpage. Available at: https://www.illumina.com/content/dam/illumina-
marketing/documents/products/product_information_sheets/infinium-human-immunoarray-24-
product-info-sheet-370-2015-002.pdf. Accessed April 10, 2019.  
Jakobsen C, Bartek J Jr., Wewer V, Vind I, Munkholm P, Groen R, Paerregaard A. Differences 
in phenotype and disease course in adult and paediatric inflammatory bowel disease–a 
population-based study. Aliment Pharmacol Ther. 2011a;34(10):1217-1224. 
Jakobsen C, Munkholm P, Paerregaard A, Wewer V. Steroid dependency and pediatric 
inflammatory bowel disease in the era of immunomodulators–a population-based study. 
Inflamm Bowel Dis. 2011b;17(8):1731-1740. 
Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, Lee JC, Schumm LP, 
Sharma Y, Anderson CA, Essers J, Mitrovic M, Ning K, Cleynen I, Theatre E, Spain SL, 
Raychaudhuri S, Goyette P, Wei Z, Abraham C, Achkar JP, Ahmad T, Amininejad L, 
Ananthakrishnan AN, Andersen V, Andrews JM, Baidoo L, Balschun T, Bampton PA, 
Bitton A, Boucher G, Brand S, Büning C, Cohain A, Cichon S, D’Amato M, De Jong D, 
Devaney KL, Dubinsky M, Edwards C, Ellinghaus D, Ferguson LR, Franchimont D, 
Fransen K, Gearry R, Georges M, Gieger C, Glas J, Haritunians T, Hart A, Hawkey C, 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 109 
LY3074828 
Hedl M, Hu X, Karlsen TH, Kupcinskas L, Kugathasan S, Latiano A, Laukens D, 
Lawrance IC, Lees CW, Louis E, Mahy G, Mansfield J, Morgan AR, Mowat C, Newman W, 
Palmieri O, Ponsioen CY, Potocnik U, Prescott NJ, Regueiro M, Rotter JI, Russell RK, 
Sanderson JD, Sans M, Satsangi J, Schreiber S, Simms LA, Sventoraityte J, Targan SR, 
Taylor KD, Tremelling M, Verspaget HW, De Vos M, Wijmenga C, Wilson DC, 
Winkelmann J, Xavier RJ, Zeissig S, Zhang B, Zhang CK, Zhao H; International IBD 
Genetics Consortium (IIBDGC), Silverberg MS, Annese V, Hakonarson H, Brant SR, 
Radford-Smith G, Mathew CG, Rioux JD, Schadt EE, Daly MJ, Franke A, Parkes M, 
Vermeire S, Barrett JC, Cho JH. Host-microbe interactions have shaped the genetic 
architecture of inflammatory bowel disease. Nature. 2012;491(7422):119-124. 
Kappelman MD, Moore KR, Allen JK, Cook SF. Recent trends in the prevalence of Crohn’s 
disease and ulcerative colitis in a commercially insured US population. Dig Dis Sci. 
2013;58(2):519-525. 
Kovacs M. Children’s depression inventory (CDI 2) (2nd edition). Journal of Psychoeducational 
Assessment. 2012;30(3):304-308. 
Lewinsohn DM, Leonard MK, LoBue PA, Cohn DL, Daley CL, Desmond E, Keane J, 
Lewinsohn DA, Loeffler AM, Mazurek GH, O’Brien RJ, Pai M, Richeldi L, Salfinger M, 
Shinnick TM, Sterling TR, Warshauer DM, Woods GL. Official American Thoracic 
Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention 
Clinical Practice Guidelines: diagnosis of tuberculosis in adults and children. Clin Infect Dis. 
2017;64(2):111-115. 
Miele E, Markowitz JE, Mamula P, Baldassano RN. Human antichimeric antibody in children 
and young adults with inflammatory bowel disease receiving infliximab. J Pediatr 
Gastroenterol Nutr. 2004;38(5):502-508. 
Reich K, Armstrong AW, Foley P, Song M, Wasfi Y, Randazzo B, Li S, Shen YK, Gordon KB. 
Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared 
with adalimumab for the treatment of patients with moderate to severe psoriasis with 
randomized withdrawal and retreatment: Results from the phase III, double-blind, placebo- 
and active comparator-controlled VOYAGE 2 trial. J Am Acad Dermatol. 2017;76(3):418-431. 
Rosen MJ, Dhawan A, Saeed SA. Inflammatory bowel disease in children and adolescents. 
JAMA Pediatr. 2015;169(11):1053-1060. 
Sandborn WJ, Ferrante M, Bhandari BR, D’Haens GR, Berliba E, Feagan BG, Laskowski J, 
Friedrich S, Durante M, Tuttle J. Efficacy and safety of anti-interleukin-23 therapy with 
mirikizumab (LY3074828) in patients with moderate-to-severe ulcerative colitis in a phase 2 
study. Gastroenterology. 2018;154(6):S1360-S1361. 
Sands BE. Biomarkers of inflammation in inflammatory bowel disease. Gastroenterology. 
2015;149(5):1275-1285.e2. 
Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly 
to moderately active ulcerative colitis. A randomized study. N Engl J Med. 
1987;317(26):1625-1629. 
Turner D, Otley AR, Mack D, Hyams J, de Bruijne J, Uusoue K, Walters TD, Zachos M, 
Mamula P, Beaton DE, Steinhart AH, Griffiths AM. Development, validation, and evaluation 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 110 
LY3074828 
of a pediatric ulcerative colitis activity index: a prospective multicenter study. 
Gastroenterology. 2007;133(2):423–432. 
US Census Bureau population division website. Annual estimates of the resident population for 
selected age groups by sex for the United States, states, counties and Puerto Rico 
commonwealth and municipios: April 1, 2010 to July 1, 2015. Available at: 
https://factfinder.census.gov/faces/tableservices/j sf/pages/productview.xhtml?src=bkmk. 
Accessed January 13, 2017.   
Uhlig HH, Schwerd T, Koletzko S, Shah N, Kammermeier J, Elkadri A, Ouahed J, Wilson DC, 
Travis SP, Turner D, Klein C, Snapper SB, Muise AM; COLORS in IBD Study Group and 
NEOPICS. The diagnostic approach to monogenic very early onset inflammatory bowel 
disease. Gastroenterology. 2014;147(5):990-1007. 
[WHO] World Health Organization. Use of high burden country lists for TB by WHO in the 
post-2015 era. Available at: 
http://www.who.int/tb/publications/global_report/high_tb_burdencountrylists2016-2020.pdf. 
Accessed April 10, 2019. 
[WHO] World Health Organization. Latent tuberculosis infection: updated and consolidated 
guidelines for programmatic management. WHO webpage. Available at: 
https://apps.who.int/iris/bitstream/handle/10665/260233/9789241550239-
eng.pdf;jsessionid=E70CB8EF5698843C11B55E8D24622809?sequence=1. 2018. Accessed 
April 16, 2019.  
Winthrop KL, Novosad SA, Baddley JW, Calabrese L, Chiller T, Polgreen P, Bartalesi F, 
Lipman M, Mariette X, Lortholary O, Weinblatt ME, Saag M, Smolen J. Opportunistic 
infections and biologic therapies in immune-mediated inflammatory diseases: consensus 
recommendations for infection reporting during clinical trials and postmarketing surveillance. 
Ann Rheum Dis. 2015;74(12):2107-2116. 
Zeisler B, Lerer T, Markowitz J, Mack D, Griffiths A, Bousvaros A, Keljo D, Rosh J, Evans J, 
Kappelman M, Otley A, Kay M, Grossman A, Saeed S, Carvalho R, Oliva-Hemker M, 
Faubion W, Sudel B, Pfefferkorn M, Ashai-Khan F, Leleiko N, Hyams J; Pediatric 
Inflammatory Bowel Disease Collaborative Research Group. Outcome following 
aminosalicylate therapy in children newly diagnosed as having ulcerative colitis. J Pediatr 
Gastroenterol Nutr. 2013;56(1):12-18. 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 111 
LY3074828 
12. Appendices 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 112 
LY3074828 
Appendix 1. 
Abbreviations and Definitions 
 
 
 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 113 
LY3074828 
Term 
Definition 
5-ASA 
5-aminosalicylic acid 
6-MP 
6-mercaptopurine 
AAULN 
age-adjusted upper limit of normal 
ADA 
anti-drug antibody 
ADR 
adverse drug reaction 
AE 
adverse event:  Any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product that does not necessarily have a causal 
relationship with this treatment.  An adverse event can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a medicinal (investigational) product, whether or 
not related to the medicinal (investigational) product. 
AESI 
adverse events of special interest 
AIDS 
acquired immunodeficiency syndrome 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
anti-HBc 
hepatitis B core antibody 
AST 
aspartate aminotransferase 
AZA 
azathioprine 
CD 
Crohn’s disease 
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. 
CRF 
case report form 
CSR 
clinical study report 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 114 
LY3074828 
CT 
computed tomography 
CXR 
chest x-ray 
DNA 
deoxyribonucleic acid 
ECG 
electrocardiogram 
eCOA 
electronic clinical outcome assessment 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EIM 
extraintestinal manifestation 
enroll 
The act of assigning a patient to a treatment.  Patients who are enrolled in the study are 
those who have been assigned to a treatment. 
enter 
Patients entered into a study are those who sign the informed consent form directly or 
through their legally acceptable representatives. 
ePPND 
enhanced pre- and postnatal development 
ERB 
ethical review board 
ES 
endoscopic subscore 
ETV 
early termination visit 
GDH 
C. difficile antigen 
GMP 
Good Manufacturing Practice 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
hs-CRP 
high-sensitivity C-reactive protein 
IB 
Investigator’s Brochure 
IBD 
inflammatory bowel disease 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 115 
LY3074828 
IEC 
Independent Ethics Committee 
IGRA 
interferon-γ release assay 
IL 
interleukin 
informed consent 
A process by which a patient voluntarily confirms his or her willingness to participate 
in a particular study, after having been informed of all aspects of the study that are 
relevant to the patient’s decision to participate.  Informed consent is documented by 
means of a written, signed and dated informed consent form. 
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/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 
gain further information about the authorized form. 
IP 
investigational product 
IRB 
Institutional Review Board 
ITT 
intent-to-treat:  The principle that asserts that the effect of a treatment policy can be best 
assessed by evaluating on the basis of the intention to treat a patient (that is, the planned 
treatment regimen) rather than the actual treatment given.  It has the consequence that 
patients allocated to a treatment group should be followed up, assessed, and analyzed as 
members of that group irrespective of their compliance to the planned course of 
treatment. 
IV 
intravenous 
IWRS 
interactive web-response system 
JAK 
Janus kinase 
LTBI 
latent tuberculosis infection 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMS 
Modified Mayo Score 
MTX 
methotrexate 
NIMH 
National Institute of Mental Health 
NOS 
not otherwise specified  
NRI 
nonresponder imputation 
NRS 
numeric rating scale 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 116 
LY3074828 
PCR 
Polymerase Chain Reaction 
PD 
pharmacodynamics 
PGA 
Physician’s Global Assessment 
PGI-C 
Patient’s Global Impression of Change 
PGRS 
Patient’s Global Rating of Severity 
PK 
pharmacokinetics 
PPD 
purified protein derivative 
PRN 
as needed 
PUCAI 
Paediatric Ulcerative Colitis Activity Index 
Q4W 
every 4 weeks 
Q12W 
every 12 weeks 
RB 
rectal bleeding 
RNA 
ribonucleic acid 
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.  
SF 
stool frequency 
SUSARs 
suspected unexpected serious adverse reactions 
TASA 
Treatment of Adolescent Suicide Attempters 
TB 
tuberculosis 
TBL 
total bilirubin level 
TEADA 
treatment-emergent anti-drug antibody 
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 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 117 
LY3074828 
TST 
tuberculin skin test 
UC 
ulcerative colitis 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 118 
LY3074828 
Appendix 2. 
Clinical Laboratory Tests 
 
 
 
 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 119 
LY3074828 
 
Selected tests may be obtained in the event of systemic allergic/hypersensitivity events. 
Hypersensitivity Testsa 
Immunogenicity testing (ADA) 
Tryptase  
Serum mirikizumab concentration (PK) 
Complement  
 
Cytokine Panel 
Abbreviations:  ADA = anti-drug antibody; PK = pharmacokinetics. 
a 
Assayed by Lilly-designated laboratory and for immediate hypersensitivity events only. 
 
Laboratory Test Prioritization 
Care should be taken to safeguard study participants with regard to the amount of blood drawn 
for study procedures.  All efforts have been made to minimize required sampling in this protocol; 
however, in the case of younger and lower body weight patients, the following guidance is 
provided.  Importantly, sites should follow local institutional review board guidelines, where 
applicable.  Patients 
 old with body weight lower than 
 will require reduced blood 
volume collection, and some tests will need to be excluded.  In the situation where blood volume 
is limited and all tubes cannot be collected, the following sample tubes should be removed in this 
order: 
Please refer to the lab manual for collection tube volumes for each of the above mentioned tests.  
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 120 
LY3074828 
Appendix 3. 
Study Governance Considerations 
 
 
 
 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 121 
LY3074828 
Appendix 3.1. Regulatory and Ethical Considerations, Including the 
Informed Consent Process 
Appendix 3.1.1. 
Informed Consent 
The investigator is responsible for: 
 Ensuring that the patient/patient’s legal representative understands the nature of 
the study, the potential risks and benefits of participating in the study, and that 
their participation is voluntary. 
 Ensuring that informed consent is given by each patient or legal representative.  
This includes obtaining the appropriate signatures and dates on the informed 
consent form (ICF) prior to the performance of any protocol procedures and prior 
to the administration of investigational product. 
 Ensuring that informed consent is given by pediatric participants for continued 
participation once the patient reaches the age of legal consent. 
 Answering any questions the patient/patient’s legal representative may have 
throughout the study and sharing in a timely manner any new information that 
may be relevant to the patient’s/patient’s legal representative’s willingness to 
continue his or her participation in the study. 
 Ensuring that a copy of the ICF is provided to the participant or the participant’s 
legal representative and is kept on file. 
 Ensuring that the medical record includes a statement that written informed 
consent was obtained before the participant was enrolled in the study and the date 
the written consent was obtained.  The authorized person obtaining the informed 
consent must also sign the ICF.   
A legal representative must give informed consent for a child to participate in this study.  In 
addition to the informed consent given by the legal representative, the child may be required to 
give documented assent, if capable. 
Appendix 3.1.2. 
Recruitment 
Eli Lilly and Company (Lilly) or its designee is responsible for the central recruitment strategy 
for patients.  Individual investigators may have additional local requirements or processes. 
Appendix 3.1.3. 
Ethical Review 
The investigator must give assurance that the ethical review board (ERB) was properly 
constituted and convened as required by International Council for Harmonisation (ICH) 
guidelines and other applicable laws and regulations. 
Documentation of ERB approval of the protocol and the ICF and Assent Form must be provided 
to Lilly before the study may begin at the investigative site(s).  Lilly or its representatives must 
approve the ICF, including any changes made by the ERBs, before it is used at the investigative 
site(s).  All ICFs must be compliant with the ICH guideline on Good Clinical Practice (GCP). 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 122 
LY3074828 
The study site’s ERB(s) should be provided with the following: 
 The protocol and related amendments and addenda, current Investigator’s 
Brochure and updates during the course of the study 
 Informed consent form and Assent Form 
 Other relevant documents (for example, curricula vitae and advertisements) 
Appendix 3.1.4. 
Regulatory Considerations 
This study will be conducted in accordance with the protocol and with the: 
 Consensus ethics principles derived from international ethics guidelines, 
including the Declaration of Helsinki and Council for International Organizations 
of Medical Sciences International Ethical Guidelines 
 Applicable ICH GCP Guidelines 
 Applicable laws and regulations 
Some of the obligations of the sponsor will be assigned to a third party. 
Appendix 3.1.5. 
Investigator Information 
Physicians with a specialty in pediatric gastroenterology and/or at least 
 of experience 
with pediatric patients may participate as investigators in this clinical trial. 
Appendix 3.1.6. 
Protocol Signatures 
The sponsor’s responsible medical officer will approve the protocol, confirming that, to the best 
of his or her knowledge, the protocol accurately describes the planned design and conduct of the 
study. 
After reading the protocol, each principal investigator will sign the protocol signature page and 
send a copy of the signed page to a Lilly representative. 
Appendix 3.1.7. 
Final Report Signature 
The CSR coordinating investigator will sign the final CSR for this study, indicating agreement 
that, to the best of his or her knowledge, the report accurately describes the conduct and results 
of the study. 
An investigator will be chosen by Lilly to serve as the CSR coordinating investigator. 
The sponsor’s responsible medical officer and statistician will approve the final CSR for this 
study, confirming that, to the best of his or her knowledge, the report accurately describes the 
conduct and results of the study. 
Appendix 3.2. 
Data Quality Assurance 
To ensure accurate, complete, and reliable data, Lilly or its representatives will do the following: 
 Provide instructional material to the study sites, as appropriate 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 123 
LY3074828 
 Provide sponsor start-up training to instruct the investigators and study 
coordinators.  This training will give instruction on the protocol, the completion 
of the case report forms (CRFs), and study procedures. 
 Make periodic visits to the study site 
 Be available for consultation and stay in contact with the study site personnel by 
mail, telephone, and/or fax 
 Review and verify data reported to detect potential errors  
In addition, Lilly or its representatives will periodically check a sample of the patient data 
recorded against source documents at the study site.  The study may be audited by Lilly or its 
representatives, and/or regulatory agencies at any time.  Investigators will be given notice before 
an audit occurs. 
The investigator will keep records of all original source data.  This might include laboratory 
tests, medical records, and clinical notes.  If requested, the investigator will provide the sponsor, 
applicable regulatory agencies, and applicable ERBs with direct access to original source 
documents. 
Appendix 3.2.1. 
Data Capture System 
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness 
of the data reported to the sponsor.  
An electronic data capture (EDC) system 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 (questionnaires, scales, self-reported diary data, 
etc.) will be collected by the investigator site personnel, via a paper source document and will be 
transcribed by the investigator site personnel into the EDC system. 
Additionally, electronic clinical outcome assessment (eCOA) data (questionnaires, scales, self-
reported diary data, etc.) will be directly recorded by the subject/caregiver/investigator site 
personnel into an instrument (for example, hand held smart phone or tablet, or by means of an 
interactive voice/web system).  The eCOA data will serve as the source documentation and the 
investigator will 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 a third party.  
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 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 electronic transfers will be provided to the investigator 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 124 
LY3074828 
for review and retention.  Data will subsequently be transferred from the central vendor to the 
Lilly data warehouse.  
Data from compliant forms submitted to Lilly will be encoded and stored in the global product 
compliant management system. 
Appendix 3.3. 
Study and Site Closure 
Appendix 3.3.1. 
Discontinuation of Study Sites 
Study site participation may be discontinued if Lilly or its designee, the investigator, or the ERB 
of the study site judges it necessary for medical, safety, regulatory, or other reasons consistent 
with applicable laws, regulations, and GCP. 
Appendix 3.3.2. 
Discontinuation of the Study 
The study will be discontinued if Lilly or its designee judges it necessary for medical, safety, 
regulatory, or other reasons consistent with applicable laws, regulations, and GCP. 
Appendix 3.4. 
Publication Policy 
The publication policy for Study I6T-MC-AMBU (AMBU) is described in the letters of 
agreement between the sponsor and the investigators and institutions. 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 125 
LY3074828 
 
 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 126 
LY3074828 
 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 127 
LY3074828 
Appendix 5. 
Prohibited Medications 
 
 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 128 
LY3074828 
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 drug and completes the ETV. 
Drug Class 
Comments 
Anti-TNF antibodies (for example, infliximab, adalimumab 
or golimumab)  
Discontinue at least 
prior to screening 
endoscopy and prohibited throughout duration 
of study 
Anti-integrin antibodies (for example, vedolizumab) 
Discontinue at least
prior to screening 
endoscopy and prohibited throughout duration 
of study 
Agents depleting B or T cells (for example, rituximab, 
alemtuzumab, or visilizumab) 
Discontinue at least 
prior to 
baseline; patients remain excluded if evidence 
of persistent targeted lymphocyte depletion at 
the time of screening endoscopy 
Immunomodulatory medications, including oral cyclosporine, 
IV cyclosporine, tacrolimus, mycophenolate mofetil, 
thalidomide, or Janus kinase (JAK) inhibitors (for example, 
tofacitinib)  
Discontinue at least
 prior to screening 
endoscopy and prohibited throughout duration 
of study 
Intravenous corticosteroids 
Discontinue at least 
prior to screening 
endoscopy and prohibited throughout duration 
of study 
Systemic corticosteroids for non-UC indications (oral or IV) 
Patients requiring systemic corticosteroids for 
 for non-UC conditions are excluded.  
Exceptions include 
 
 
 
 
 
Topical corticosteroids and 5-ASA therapies (enemas or 
suppositories) 
Discontinue at least 
 prior to screening 
endoscopy and prohibited throughout duration 
of study 
Any investigational therapy (biologic or non-biologic)  
 
Discontinue at least 
, or 5 half-lives 
whichever is longer, prior to screening 
endoscopy and prohibited throughout duration 
of study 
Anti-IL12p40 antibodies (for example, ustekinumab 
[Stelara®]) or anti-IL-23p19 antibodies (for example, 
risankizumab [BI-655066/ABBV-066], brazikumab 
[MEDI-2070], guselkumab [CNTO1959], tildrakizumab 
[MK-3222]) for any indication, including investigational use 
Patients with any previous exposure of p19 
antibodies are not eligible to be enrolled 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 129 
LY3074828 
Drug Class 
Comments 
Medicinal and recreational marijuana (includes cannabidiol 
[CBD] oil) 
Must be stopped prior to enrollment.  
Marijuana use is prohibited for the duration of 
the study.  If use is identified during the trial, it 
may result in discontinuation; consult the 
medical monitor. 
Abbreviations:  5-ASA = 5-aminosalicyclic acid; IV = intravenous; TNF = tumor necrosis factor; UC = ulcerative 
colitis. 
 
Approved on 23 Oct 2021 GMT
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 130 
LY3074828 
Appendix 6. 
Permitted Medications with Dose 
Stabilization 
 
 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 131 
LY3074828 
Drug Class 
Comments 
Oral 5-ASAs (for example, mesalamine, 
balsalazide, olsalazide) 
May continue during study with stable doses encouraged 
Oral corticosteroids 
 
Responder patients who are receiving oral corticosteroids at 
the start of Study AMBU will start corticosteroid taper at 
 
will begin corticosteroid tapering 
if symptomatic response or symptomatic improvement based 
on investigator discretion is achieved at any time after 
starting extended induction (see Corticosteroid Taper in 
Section 7.7.1. 
Corticosteroids for non-UC indications:  
corticosteroids to treat adrenal insufficiency, as 
premedication for investigational product 
infusion, or locally administered corticosteroids 
(e.g., inhaled, intranasal, intra-articular, topical) 
May continue corticosteroids to treat adrenal insufficiency or 
locally administered corticosteroids during study with stable 
dose encouraged.  
 corticosteroids 
as premedication to investigational product administration are 
allowed in patients with prior investigational product or other 
previous biologic injection reactions.  A short course 
 
 is allowed to treat non-UC conditions. 
Immunomodulators (for example, AZA, 6-MP, 
or MTX) 
Prescribed dose will remain 
 unless 
medication is discontinued due to a toxicity related to the 
medication. 
 
 at the discretion of the investigator unless 
medication is discontinued due to a toxicity related to the 
medication 
Antidiarrheals (for example, loperamide, 
diphenoxylate with atropine) 
May continue during study with stable doses encouraged 
Non-live (killed, inactivated or subunit) vaccines 
Allowed during the study.  The efficacy of non-live 
vaccinations with concomitant mirikizumab treatment is 
unknown.  If a non-live vaccine is needed, it is recommended 
that study drug not be administered on the same day as a 
vaccination.   
Homeopathic and alternative treatments 
Vitamins and probiotics are allowed.  Other non-prescription 
drug therapies may be permitted following discussion with 
the sponsor.  The dose of medication should remain constant 
for the 52-week duration of the study 
Abbreviations:  5-ASA = 5-aminosalicylic acid; 6-MP = 6-mercaptopurine; AZA = azathioprine; IV = intravenous; 
MMX = multi matrix colonic delivery technology; MTX = methotrexate; UC = ulcerative colitis. 
 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 132 
LY3074828 
Appendix 7. 
Ulcerative Colitis Disease Activity 
Measures 
 
 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 133 
LY3074828 
Mayo Scoring System for the Assessment of Ulcerative Colitis Disease Activity 
 
 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 134 
LY3074828 
PUCAI:  Pediatric Ulcerative Colitis Activity Index 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 135 
LY3074828 
Appendix 8. 
Risk Factors for Latent Tuberculosis 
Infection 
 
 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 136 
LY3074828 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 137 
LY3074828 
Appendix 9. 
Examples of Infections that May Be 
Considered Opportunistic in the Setting of Biologic 
Therapy 
 
 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 138 
LY3074828 
 
 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 139 
LY3074828 
Appendix 10. 
Provisions for Changes in Study Conduct 
During Exceptional Circumstances 
Implementation of this appendix 
The changes to procedures described in this appendix are temporary measures intended to be 
used only during specific time periods as directed by the sponsor in partnership with the 
investigator. 
Exceptional circumstances 
Exceptional circumstances are rare events that may cause disruptions to the conduct of the study.  
Examples include pandemics or natural disasters.  These disruptions may limit the ability of the 
investigators, participants, or both to attend on-site visits or to conduct planned study procedures. 
Implementing changes under exceptional circumstances 
In an exceptional circumstance, after receiving the sponsor’s written approval, sites may 
implement changes if permitted by local regulations.  
After approval by local Ethical Review Boards, regulatory bodies, and any other relevant local 
authorities, implementation of these exceptional circumstance changes will not typically require 
additional notification to these groups, unless they have specific requirements in which 
notification is required (for example, upon implementation and suspension of changes).  All 
approvals and notifications must be retained in the study records. 
If the sponsor grants written approval for changes in study conduct, the sponsor will also provide 
additional written guidance, if needed. 
Considerations for making a change 
The prevailing consideration for making a change is ensuring the safety of study participants.  
Additional important considerations for making a change are compliance with Good Clinical 
Practice, enabling participants to continue safely in the study and maintaining the integrity of the 
study.  
Informed consent 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 140 
LY3074828 
Changes in study conduct during exceptional circumstances 
Changes in study conduct not described in this appendix, or not consistent with applicable local 
regulations, are not allowed.   
The following changes in study conduct will not be considered protocol deviations. 
Approved on 23 Oct 2021 GMT
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 141 
LY3074828 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 142 
LY3074828 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 143 
LY3074828 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 144 
LY3074828 
Screening period guidance  
To ensure safety of study participants, laboratory values and other eligibility assessments taken 
at the screening visit are valid for a maximum of 
.  The following rules will be applied 
for active, nonrandomized participants whose participation in the study must be paused due to 
exceptional circumstances: 
 If screening is paused for less than 
 from screening/lead-in visits to 
randomization visit:  the participant will proceed to the study visit per the usual 
Schedule of Activities, provided that randomization visit must be conducted within 
 from first screening procedure.  
o The site should conduct the randomization visit if the participant’s eligibility 
criteria are confirmed, and the site should document the reason for delay. 
o Due to the pause in screening, sites should also reconfirm the impacted 
participant’s legal guardian consent, participants assent if not of legal age and 
document this confirmation in the source documentation. 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 145 
LY3074828 
 If screening is paused for more than 
 from screening/lead-in visits to 
randomization visit and without an endoscopy procedure completed:  the participant 
must be discontinued because of screening interruption due to an exceptional 
circumstance.  This is documented as a screen failure in the CRF.  The participant can 
reconsent and be rescreened as a new participant.  [This rescreen is in addition to the 
one allowed by the main protocol.]  The screening procedures per the usual Schedule 
of Activities should be followed, starting at screening visit to ensure participant 
eligibility prior to randomization visit. 
Adjustments to Visit Windows  
Whenever possible and safe to do so, as determined by the investigator’s discretion, participants 
should complete the usual Schedule of Activities.  To maximize the possibility that these visits 
can be conducted as on-site visits, the windows for visits may be adjusted, upon further guidance 
from the sponsor.  This minimizes missing data and preserves the intended conduct of the study. 
This table describes the allowed adjustments to visit windows. 
Table 1:  Extended Visit Windows  
Approved on 23 Oct 2021 GMT
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 146 
LY3074828 
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 147 
LY3074828 
For participants whose visits have extended windows, additional study intervention may need to 
be provided to avoid interruption and maintain overall integrity of the study.  
Documentation 
Changes to study conduct will be documented 
 Sites will identify and document the details of how participants, visits types, and 
conducted activities were affected by exceptional circumstances.  
Dispensing/shipment records of study intervention and relevant communications, 
including delegation, should be filed with site study records. 
Source documents at alternate locations 
 Source documents generated at a location other than the study site should be part of 
the investigator’s source documentation and should be transferred to the site in a 
secure and timely manner.  
Approved on 23 Oct 2021 GMT
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 148 
LY3074828 
Appendix 11. 
Protocol Amendment I6T-MC-AMBU(b) 
Summary  
A Multicenter, Open-Label PK Study of Mirikizumab in 
Pediatric Patients with Moderately to Severely Active 
Ulcerative Colitis 
Overview 
Protocol I6T-MC-AMBU(a) A Multicenter, Open-Label PK Study of Mirikizumab in Pediatric 
Patients with Moderately to Severely Active Ulcerative Colitis has been amended.  The new 
protocol is indicated by amendment (b) and will be used to conduct the study in place of any 
preceding version of the protocol. 
The overall changes and rationale for the changes made to this protocol are described in the 
following table: 
 
Approved on 23 Oct 2021 GMT

I6T-MC-AMBU(c) Clinical Protocol 
Page 149 
LY3074828 
Amendment Summary for Protocol I6T-MC-AMBU Amendment (b) 
Section # and Name 
Description of Change 
Brief Rationale 
Section 1. Synopsis 
Section 4. Objectives and Endpoints 
Section 9.1 Efficacy Assessments, Table AMBU 5 
Revised secondary objective wording for MMS 
clinical remission definition 
Endpoint has been updated based on revised 
regulatory expectations. 
Updated secondary objective mucosal healing 
endpoint 
Endpoint has been updated for clarity from 
mucosal healing to histologic-endoscopic mucosal 
remission to align with other mirikizumab 
protocols. 
Section 2. Schedule of Activities 
TB monitoring language was clarified 
Clarification of TB monitoring process to align 
with sponsor safety guidance for TB assessments 
and other mirikizumab protocols. 
Addition of language for Stool culture and 
Clostridium difficile toxin  
In some cases, local laboratory testing results may 
be available sooner than the central lab results. 
Given the need to shorten the screening period for 
these sick children, the protocol will now allow 
specific C. difficile local laboratory tests for 
screening into the study. 
Approved on 23 Oct 2021 GMT
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 150 
LY3074828 
Section 2. Schedule of Activities 
Section 5.1. Overall Design 
Additional footnote and language added for 
unscheduled visits  
Footnote b was added to the SoA to allow, with 
prior Sponsor approval, additional dosing at 
Week 52 and beyond, after completing Visit 16 
procedures if participant is waiting for regulatory 
and/or ethics approval to enroll into Study AMAZ. 
This provision was also added to the overall study 
design for clarity. 
Section 2. Schedule of Activities 
Section 9.1.6.3. Assessment of Puberty 
Section 9.4.3.2. Hormone Testing 
 
 
  
Section 5.1. Overall Design 
Addition of wording to clarify intended use of data 
snapshot and how it pertains to the opening of 
 
 group for enrollment 
Addition of wording to clarify intended use of data 
snapshot and provide alignment with updates in 
Section 10.3.8.1. Data Snapshots 
Section 6.1. Inclusion Criteria 
Addition of wording in inclusion criterion [2b] for 
female contraception 
Clarification that 2 effective methods of 
contraception must continue 
 
 
 
Revision of language in hemoglobin inclusion 
criterion [11a] 
Update of language to reference additional 
exclusion criterion [46] clarifying a hematology 
blood sample cannot be drawn within 
 of a 
blood transfusion. 
Section 6.2. Exclusion Criteria 
Revised language in exclusion criteria [19d], 
[19e], and [19i]  
Clarification that therapies must be discontinued 
within designated time window prior to screening 
endoscopy.  
Removal of wording in exclusion criterion [23] 
Removal of redundant wording on primary 
immune deficiencies as this is previously noted in 
exclusion criterion [14]. 
Additional language in exclusion criterion [26] 
Further clarification for C difficile, other intestinal 
pathogens, and
 
   
Revised language in exclusion criterion [42] 
Clarification of timing for enrollment for 
participants to require
 
after receiving last dose of study drug  
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 151 
LY3074828 
Clarification with addition of exclusion criterion 
[45]  
Clarification to separate marijuana from illicit 
drugs exclusion criterion [43] to avoid potential 
confusion. 
Clarification with addition of exclusion criterion 
[46] 
By requiring that hematology blood samples 
cannot be collected within 
 
 
 
 
 
Section 6.4. Screen Failures 
Clarification of inclusion/exclusion criteria 
numbers and language related to rescreening  
Clarification of Inclusion/Exclusion criteria 
numbers that weren’t previously documented as 
allowed or disallowed for rescreening in the event 
of a screen failure. 
Section 6.4.1. Allowed Retesting of Screening 
Investigations  
Removal of first paragraph and additional 
language added 
Paragraph was removed to avoid redundancy and 
language was added for clarity. 
Section 7.1. Treatments Administered 
Correction of typo for timing IV administration of 
mirikizumab and sentence removal  
Correction of typo for IV administration time for 
mirikizumab to be 
 to align with 
investigational product administration instructions 
provided to the sites and removal of sentence for 
clarity. 
Section 7.6. Treatment Compliance 
Section 9.1.1. Mayo Score 
Clarification language added and paragraphs 
moved from Section 7.6 to Section 9.1.1  
Clarification of investigator responsibility for 
training of participant and paragraphs moved to 
align with section in protocol discussing bowel 
preparation and UC symptom diary recording. 
Section 7.7.1. Corticosteroid Taper 
Clarification language was added 
Clarification that steroids can be tapered before 
following investigator judgement.  
Section 7.7.2. Vaccine Administration During the 
Study 
 
 
 
 
.  
Section 8.1.1. Permanent Discontinuation from 
Study Drug 
 
 
 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 152 
LY3074828 
Section 9.1.2. Endoscopy 
Clarification of timing from baseline for those 
requiring full colonoscopy and additional wording 
for central readers 
Timing for participants who require surveillance 
colonoscopy for UC associated dysplasia and 
malignancy noted to be within 
 of 
baseline to align with surveillance guidance.  Also, 
clarification of procedures for central readers 
Section 9.1.9.3. Extraintestinal Manifestations 
Clarification of diagnoses 
Updates for content regarding extraintestinal 
manifestation diagnoses. 
Section 9.4.5.1. Physical Examination 
Clarification of language for TB screening 
physical examination 
Clarification of physical examination for TB at 
screening for all participants.  
Section 9.4.5.2. Tuberculosis Testing 
Clarification of language for monitoring for TB 
during the study 
Clarification for interpretation of screening test for 
LBTI for patients with BCG vaccination history.  
Updated guidance for TB monitoring to be 
documented at least every 
 for each 
participant:  (1) to determine any risk factors for 
TB infection and progression; (2) and thorough 
physical examination for signs of active TB.  
Additions were made to align with updated Lilly 
safety guidance.  
Section 9.4.5.3. Chest Radiography 
Clarification of language for CXR and allowance 
of a CT Scan in place of CXR 
Clarified guidelines for CXR and additional 
language to allow CT Scan based on regional 
standard of practice.  Additional guidance for the 
CXR or CT Scan for TB evaluation to be 
interpreted and reported by a radiologist or 
physician specialized in the treatment of TB. 
Section 9.4.5.4. Hepatitis B Testing 
Clarification of language for patient management 
Clarification for Management of Patients with a 
Newly Positive anti-HBc Test During the Study to 
give guidance for management of this potential 
patient population during the study. 
Section 9.4.5.6. Depression and Suicidality 
Section 11 References 
Approved on 23 Oct 2021 GMT
CCI
CCI
CCI
CCI

I6T-MC-AMBU(c) Clinical Protocol 
Page 153 
LY3074828 
Section 9.4.5.7. Stool Testing 
Additional language and flow chart for C. difficile 
testing 
Clarification on C. difficile screening using local 
and central testing.  A flow chart was added to 
clarify process for determining results for C. 
difficile infection.  
Section 10.3.8.1. Data Snapshots 
Updated language 
Clarification of data snapshots for patients >40 kg.   
Section 10.3.8.2. Interim Analyses 
Updated language 
Clarification of interim analysis timing based on 
number of patients in the ≤40 kg group necessary 
to make a dosing decision to enable Phase 3 trial. 
Appendix 2 Clinical Laboratory Tests 
Addition of language for hypersensitivity tests 
Clarification of Lilly-designated laboratory to be 
used for immediate hypersensitivity events only. 
Appendix 5. Prohibited Medications 
Revised language in comments section for 
anti-TNF antibodies, anti-
 antibodies, and 
  
Clarification that therapies must be discontinued 
within specified time window prior to screening 
endoscopy to align with exclusion criteria. 
Clarification of BCG and live attenuated vaccine 
and marijuana use including CBD oil 
Clarification of prohibited medications to align 
with other mirikizumab protocols. 
Appendix 6. Permitted Medications and Dose 
Stabilization 
Clarification regarding rectally administered 
medications 
Clarification of guidance for rectally administered 
5-ASAs and rectally administered corticosteroids 
to align with other mirikizumab protocols. 
Addition of language for non-live vaccines  
Addition of recommendation noting study drug 
should not be administered on the same day as a 
vaccination.  
Appendix 10. Provision for Changes in Study 
Conduct During Exceptional Circumstances 
Addition of appendix 
Provisions were added in the event of exceptional 
circumstances that may cause study disruptions 
and sites needing additional flexibility. 
Throughout 
Minor typographical corrections, clarifications, or 
semantic changes 
Changes do not affect content. 
 
Approved on 23 Oct 2021 GMT
CCI
CCI

Signature Page for VV-CLIN-008288 v1.0
Signature Page for VV-CLIN-008288 v1.0
Approval
22-Oct-2021 20:48:56 GMT+0000
Approval
23-Oct-2021 00:58:37 GMT+0000
Approved on 23 Oct 2021 GMT
PPD
PPD