A Phase 3, Multicenter, Open-Label, Long-Term Extension Study to Evaluate the Long-Term Efficacy and Safety of Mirikizumab in Patients With Crohn's Disease
Phase: PHASE3
Conditions: Crohn's Disease
Sponsor: Eli Lilly and Company

Protocol Amendment I6T-MC-AMAX (e) 
A Phase 3, Multicenter, Open-Label, Long-Term Extension Study to Evaluate the Long-Term 
Efficacy and Safety of Mirikizumab in Patients with Crohn's Disease
NCT04232553 
Approval Date: 10-Sep-2024

CONFIDENTIAL 
Protocol I6T-MC-AMAX(e) 
1 
Title Page  
Confidential Information 
The information contained in this document is confidential and is intended for the use of clinical investigators. It is the property of 
Eli Lilly and Company or its subsidiaries and should not be copied by or distributed to persons not involved in the clinical 
investigation of mirikizumab (LY3074828), unless such persons are bound by a confidentiality agreement with Eli Lilly and 
Company or its subsidiaries. 
Note to Regulatory Authorities: This document may contain protected personal data and/or commercially confidential 
information exempt from public disclosure. Eli Lilly and Company requests consultation regarding release/redaction prior to any 
public release. In the United States, this document is subject to Freedom of Information Act (FOIA) Exemption 4 and may not be 
reproduced or otherwise disseminated without the written approval of Eli Lilly and Company or its subsidiaries. 
Protocol Title: A Phase 3, Multicenter, Open-Label, Long-Term Extension Study to Evaluate 
the Long-Term Efficacy and Safety of Mirikizumab in Patients with Crohn's Disease 
Protocol Number: I6T-MC-AMAX 
Amendment Number: e 
Compound: Mirikizumab (LY3074828) 
Brief Title: A Phase 3 Extension Study of Mirikizumab in Patients with Crohn's Disease 
Study Phase: 3 
Acronym: VIVID-2 
Sponsor Name: Eli Lilly and Company, Inc. 
Legal Registered Address: Lilly Corporate Center, Indianapolis, IN 46285 
Manufacturer: Sponsor 
Regulatory Agency Identifier Numbers: 
IND: 130052 
EU Trial Number: 2022-502841-91-00 
Approval Date: Protocol Amendment (e) Electronically Signed and Approved by Lilly on date 
provided below. 
Document ID: VV-CLIN-077269 
 
 
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CONFIDENTIAL 
Protocol I6T-MC-AMAX(e) 
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Medical Monitor Name and Contact Information will be provided separately. 
 
 
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Protocol I6T-MC-AMAX(e) 
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Protocol Amendment Summary of Changes Table  
DOCUMENT HISTORY 
Document 
Date 
I6T-MC-AMAX(d) 
06-Feb-2023 
I6T-MC-AMAX(c) 
12-Jan-2023 
I6T-MC-AMAX(b) 
03-Aug-2022 
I6T-MC-AMAX(a) 
01-Jul-2021 
I6T-MC-AMAX 
13-Dec-2019 
Amendment [e] 
This amendment is considered to be substantial. 
The amendment is considered to be substantial because it is likely to have a significant impact on 
the safety or the rights of the study participants. 
Overall rationale for the amendment 
The main rationale for this amendment is to  
 update the discontinuation language related to dysplasia, gastrointestinal lesions, and 
HBV DNA based on updated guidance, and 
 add HBV DNA monitoring time points during Years 2 and 3 for participants with 
HBcAb-positive for consistency across study 
The following table outlines a high-level description of all the changes, with a brief rationale. 
Section # and Name 
Description of Change 
Brief Rationale 
Title Page 
1.1. Synopsis 
Removed EudraCT number 
Removed, as no longer applicable 
under EU CTR 
1.1. Synopsis 
3. Objectives and 
Endpoints 
Subsection Objectives and Endpoints 
For AMAM participants
 
 removed requirement of 
 
for the AMAX 
  
To include all participants who 
 
 added “(analyzed separately)” for 
the 
 to be 
analyzed 
For clarification 
For AMAM participants
 
 
 corrected 
 
 
For correction: This 
 
was intended to be 
updated when the primary 
endpoint and the 
 
 were updated 
from PRO to CDAI in 
amendment (b) 
 added “(analyzed separately)” for 
the 
 to be 
analyzed 
For clarification 
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Protocol I6T-MC-AMAX(e) 
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Section # and Name 
Description of Change 
Brief Rationale 
1.1. Synopsis 
4.1. Overall Design 
Subsections Overall Design and 
Intervention Groups and Duration: 
 added details on continued access 
period. 
To update the study duration to 
account for continued access 
1.2. Schema 
10.13.2. Schema 
Deleted “(no post-treatment follow-up 
period)” 
This is already communicated in 
Footnote “a” of the schema 
1.3.1. Visit 1 through 
Visit 9 
 
Revised the following footnotes 
 Footnote “m”: to update details for 
follow-up for participants with 
positive HBV DNA  
To align with the updated HBV 
DNA language 
 Footnote “n”: added “Additionally” 
 Footnote “o”: to mention that the 
participants are allowed to take 
sample collection kits in advance 
for stool collections and return 
within 24 hours of producing the 
sample. 
For clarification 
 Footnote “x”: to mention that vital 
signs should be performed prior to 
endoscopy if performed on same 
day. 
To clarify the order of procedures 
if performed on same day 
1.3.2. Visit 10 through 
Visit 19 
 
“HBV DNA monitoring” row  
 added “X” for V10, V11, V13, 
V15, and V17. 
For more consistent frequency of 
HBV DNA testing 
Revised the following footnotes 
 Footnote “h”: to update details for 
follow-up for participants with 
positive HBV DNA  
To align with the updated HBV 
DNA language 
 Footnote “i”: added “Additionally” 
 Footnote “j”: to mention that the 
participants are allowed to take 
sample collection kits in advance 
for stool collections and return 
within 24 hours of producing the 
sample. 
For clarification 
 Footnote “m”: to mention that vital 
signs should be performed prior to 
endoscopy if performed on same 
day. 
To clarify the order of procedures 
if performed on same day 
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Protocol I6T-MC-AMAX(e) 
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Section # and Name 
Description of Change 
Brief Rationale 
1.3.3. Early Termination, 
 
Unscheduled 
Visits/Assessments, and 
Follow-up Visits 
Added a row for “Tobacco/Nicotine 
use” and specified as optional for 
“V997” and “UASV” 
To allow greater flexibility for 
collection of this information 
when deemed relevant 
Revised the following footnotes 
 Footnote “n”: to clarify details 
related to performing HBV DNA 
testing at ETV and to update details 
for follow-up for participants with 
positive HBV DNA 
To clarify and to align with the 
updated HBV DNA language 
 Footnote “o”: added “Additionally” 
 Footnote “r”: to mention that the 
participants are allowed to take 
sample collection kits in advance 
for stool collections and return 
within 24 hours of producing the 
sample. 
For clarification 
 Footnote “u”: added a statement for 
returning of the 14-Day paper diary 
for ETV, if the participant has 
pending diary return. 
For clarification 
 Footnote “w”: to mention that vital 
signs should be performed prior to 
endoscopy if performed on same 
day. 
To clarify the order of procedures 
if performed on same day 
2.2.5. Preclinical and 
Clinical Studies of 
Mirikizumab 
Subsection Clinical Studies in CD: 
 revised to include objectives and 
results for Study AMAM 
To update the available results 
for Study AMAM 
2.3. Benefit/Risk 
Assessment 
Replaced the citations, “D’Haens et al. 
2019; D’Haens et al. 2022; Dubinsky 
et al. 2022” with “D’Haens et al. 
2023” 
To update reference from 
conference abstracts to journal 
publication 
Deleted the sentence, “In the Phase 2 
CD study… …moderately to severely 
active CD.” 
To avoid redundancy 
Added “and Phase 3 studies” with 
citation “Ferrante et al. 2024” 
To update available Phase 3 
results 
Subsection Overall Benefit/Risk 
Conclusion 
 revised to include Phase 3 AMAM 
details 
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Protocol I6T-MC-AMAX(e) 
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Section # and Name 
Description of Change 
Brief Rationale 
3. Objectives and 
Endpoints 
Tertiary/Exploratory  
 
 
 
For clarification 
6. Study Intervention 
Updated the definition of study 
intervention 
To align with EU CTR 
requirements 
6.1. Study 
Intervention(s) 
Administered 
Table, Dosage Level(s) row: 
 categorized the dosage level based 
on the originator study of the 
participants 
For clarification   
Table, authorization row: 
 updated “Not authorized in EU” to 
“Authorized in EU and not used 
according to the marketing 
authorization” 
Per current status of mirikizumab 
in EU (mirikizumab received EU 
authorization for treatment of 
ulcerative colitis in May 2023) 
Subsection Packaging and Labeling: 
 updated to describe that study 
intervention will be supplied by the 
sponsor and labeled as appropriate 
for country requirements 
To align with EU CTR 
requirements 
6.7. Management of 
Hypersensitivity, 
Infusion-Related Events, 
Infusion Site Reactions, 
and Injection Site 
Reactions 
Subsection Hypersensitivity Events 
 Last paragraph, added 
“severe/generalized” and “(e.g., 
diffuse rash)” 
For better clarity 
Subsection Injection Site Reactions or 
Infusion Site Reactions 
 deleted the last bullet point on 
premedication. 
Clarified in subsequent section 
“Premedication for Infusions or 
Injections”.  
6.7.1. Premedication for 
Infusions or Injections 
Updated the heading to include “or 
Injections” 
For correction 
6.8.1. Treatment after 
Study Completion 
Revised to mention that mirikizumab 
will be made available to eligible 
participants after Visit 19 through the 
optional Continued Access Period  
To clarify availability of 
mirikizumab after Visit 19 
7.1.2. Permanent 
Discontinuation 
Revised the safety considerations 
related to dysplasia, gastrointestinal 
lesions, and HBV DNA 
For clarification and based on 
current recommendations. 
8.1.1.2. Endoscopy 
Revised to mention that vital signs 
should be performed prior to 
endoscopy if performed on same day 
To clarify the order of procedures 
if performed on same day 
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Protocol I6T-MC-AMAX(e) 
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Section # and Name 
Description of Change 
Brief Rationale 
8.1.2.1. Clinical 
Remission by PRO 
Deleted statement regarding PROs 
being used as primary endpoint  
For correction: The endpoints 
and objectives were updated in 
amendment (b), such that PRO is 
no longer part of the primary 
endpoint. However, this sentence 
was not updated at that time.   
8.2.8. Hepatitis B 
Testing  
 Revised the language on HBV 
DNA testing  
 Added guidance for management 
of participants with detectable 
HBV DNA. 
For clarification and based on 
current recommendations. 
8.2.10 Hepatic Safety 
Monitoring   
Subsection Close hepatic monitoring  
 Last paragraph, added a language 
to capture results from local 
hepatic monitoring tests in the 
corresponding CRFs  
For reminder 
8.3.1.1. Suspected 
Unexpected Serious 
Adverse Reactions 
 Replaced “Directive 2001/20/EC” 
with “Regulation 536/2014 
[submission of SUSARs to the 
EudraVigilance database]” 
 Revised the statement on 
processing of safety reports  
Per current EU CTR 
requirements 
8.3.4. Regulatory 
Reporting Requirements 
for SAEs 
Revised the SAE regulatory reporting 
requirements 
Per current EU CTR 
requirements and feedback 
9.4.1. General 
Considerations 
A statement has been added to describe 
the handling of missing, unused, and 
spurious data 
To align with EU CTR 
requirements 
9.4.1.1. Analyses 
Replaced “intervention received in 
Study AMAM” and related text with 
“as defined in the SAP” 
To add reference to SAP for 
details of treatment groups used 
in the analysis model. 
Replaced “the change from baseline in 
endoscopic scores for Study AMAM 
endoscopic responders” with 
“continuous endpoints with more than 
1 postbaseline timepoint” 
To clarify where the described 
methodology will be applied  
Deleted “, and geographic region 
(North America, Europe or Other)” 
To clarify that the geographic 
region is not considered as one 
covariate in the model. 
Deleted “with a single postbaseline 
time point” 
For correction 
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Protocol I6T-MC-AMAX(e) 
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Section # and Name 
Description of Change 
Brief Rationale 
9.4.1.4. Missing Data 
Imputation 
Nonresponder imputation: 
 revised the third bullet point to 
explain the reasons for 
discontinuation to consider 
participants as nonresponder for the 
NRI analysis  
 deleted last bullet point on 
concomitant CD medications 
For clarification 
Mixed-model for repeated measures: 
 deleted “primary” 
To clarify the primary analytic 
approach for continuous 
endpoints is ANCOVA. 
Replaced “No additional imputation 
methods will be applied to the MMRM 
analysis” with “Additional details will 
be provided in the SAP” 
For correction to align with 
planned estimand for this study. 
Added a bullet point for modified 
baseline observation carried forward 
with ANCOVA 
To clarify the missing data 
imputation approach used for 
ANCOVA. 
Added a paragraph “Methodology to 
address… … will be addressed in the 
SAP.” 
To clarify the methodology to 
address additional types of 
missing data 
9.4.2.1 Participant 
Disposition  
revised “ITT population” with 
“mITT/PAS population” 
For correction 
10.1.4. Data Protection 
Clarifications have been added about 
the informed consent process and 
sponsor processes to ensure 
information security, data integrity, 
and data protection 
To align with EU CTR 
requirements 
10.1.9. Study and Site 
Start and Closure 
Updated the heading and included the 
language on Study start and first act of 
recruitment 
To clarify regarding the first act 
of recruitment for this study 
10.2. Appendix 2: 
Clinical Laboratory 
Tests 
Table, Hypersensitivity Tests row  
 replaced “may” with “should”  
 added “, or severe/generalized non-
systemic hypersensitivity reactions 
involving a single organ system 
(Section 6.7)” 
For consistency with Section 6.7, 
which was clarified in this 
amendment. 
10.3.1.2. Events Meeting 
the AE Definition 
 Deleted the bullet point related to 
the overdose of study intervention.  
 Added a bullet point related to 
medication error, misuse or abuse 
of IMP. 
To align with EU CTR 
requirements 
10.3.5. Reporting of 
SAEs 
Added a reference for Section 8.3.4. 
To cross refer the regulatory 
reporting requirements for SAEs 
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Protocol I6T-MC-AMAX(e) 
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Section # and Name 
Description of Change 
Brief Rationale 
10.7. Appendix 7: 
Prohibited Medications 
Merged the rows “IV corticosteroids” 
and “Systemic corticosteroids for non-
CD indications (oral, IM, or IV)” and 
updated the drug class to read 
“Corticosteroids” 
For greater clarity 
Medicinal and recreational marijuana 
row: 
 revised the guidance to read 
“Marijuana use is prohibited for the 
duration through the end of the 
long-term extension period of the 
study. If use is identified during the 
trial prior to this time, it may…” 
For clarification with the 
continued access 
10.9. Appendix 9: 
Patient-Reported 
Outcome Instruments 
Subsection IBDQ 
 revised IBDQ score from “>170” to 
“≥170”  
 revised the citation from “Irvine et 
al. 1994” to “Irvine 2008” 
To update the IBDQ score with 
latest reference used. 
10.11. Appendix 11: 
Abbreviations and 
Definitions 
Added abbreviation for “CFR” 
Editorial update 
10.13.3. Schedule of 
Activities for Continued 
Access Period 
Subsection, Continued Access 
Treatment (Visit 501 to last dosing 
visit) 
 Added language to describe 
potential timing scenarios for V19 
and V501 activities.  
For clarification 
 
Revised the following footnotes: 
 Footnote “a”: to include 
“Additional AMAX SoA 
procedures may be… …contact 
your monitor for questions.” 
 Footnote “k”: to update details for 
follow-up for participants with 
positive HBV DNA  
To align with updated HBV DNA 
guidance 
 Footnote “o”: to include “Changes 
cannot be made to dispensing 
and… …changes to safety lab 
testing schedule).” 
For clarification 
10.13.5 Overall Design 
 Deleted “all” 
For clarification 
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Protocol I6T-MC-AMAX(e) 
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Section # and Name 
Description of Change 
Brief Rationale 
10.13.6.1. Inclusion 
Criteria 
Criterion 33: 
 deleted “all” 
Criterion 34:  
 revised to state the recommended 
duration to be no more than 8 
weeks between last dose of long-
term extension period and dosing 
in continued access.  
For clarification 
10.13.7. Study 
Intervention 
Added language to clarify that the 
caregiver or participant can administer 
injections at the study site if needed 
during the Continued Access Period.  
10.13.8. Discontinuation 
of Study Intervention 
and Participant 
Discontinuation from the 
Continued Access Period 
 Revised the sixth bullet point to 
read, “mirikizumab is locally 
commercially available and 
reimbursable (this includes patient 
access programs when and where 
available)”. 
 Last bullet point, 
o deleted “for CD” 
o added “worldwide for the 
indication in this protocol”. 
10.14.2 Inclusion 
Criteria 
Last paragraph, added
 
  
To refer to the
 
 
10.14.3. Study 
Intervention 
Last paragraph, added 
 
 and “(non-site 
staff)” 
For clarification 
 
10.14.3.1. Participant 
Training and 
Administration 
Subsection Participant training 
 Paragraph 2, added “and will 
administer the first injection” and 
“the second injection of the” 
Subsection Reporting requirements 
 added “for remote retraining” 
Subsection Remote training 
 added “If retraining needs to be 
performed and is conducted 
remotely,” 
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Section # and Name 
Description of Change 
Brief Rationale 
Subsection 
 forms 
 replaced “all visits” with “each 
 
 added “(at the training visit, the 
 
 
Subsection Independent self-
administration period 
 added “/caregivers” 
 table, Footnote “e” 
 added “If the retraining is 
performed remotely, a telemedicine 
visit must be conducted.” 
10.15.3. Czech Republic 
10.15.4. Hungary 
Updated the appendix to align with 
changes to the main protocol. 
Clarifications and to align with 
the updates to the main protocol 
10.16. Appendix 16: 
Protocol Amendment 
History 
Added amendment (d) summary of 
changes table 
To update amendment history 
11. References 
Updated the list of references.  
Editorial consistency 
Throughout the Protocol 
Minor formatting and editorial changes For correction/clarification. 
Minor, therefore not detailed 
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Protocol I6T-MC-AMAX(e) 
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Table of Contents  
Title Page ........................................................................................................................................1 
Protocol Amendment Summary of Changes Table ....................................................................3 
1. 
Protocol Summary ........................................................................................................17 
1.1. 
Synopsis ..........................................................................................................................17 
1.2. 
Schema ............................................................................................................................26 
1.3. 
Schedule of Activities (SoA) ..........................................................................................28 
1.3.1. 
Visit 1 through Visit 9 
 .................................................................................28 
1.3.2. 
Visit 10 through Visit 19 
 .......................................................................35 
1.3.3. 
Early Termination, 
 Unscheduled 
Visits/Assessments, and Follow-up Visits ......................................................................40 
1.3.4. 
Study Drug Self-Administration .....................................................................................46 
2. 
Introduction ...................................................................................................................47 
2.1. 
Study Rationale ...............................................................................................................47 
2.2. 
Background .....................................................................................................................47 
2.2.1. 
Disease State and Treatment Goals .................................................................................47 
2.2.2. 
Currently Available Treatments and Unmet Need ..........................................................48 
2.2.3. 
IL-23 as a Therapeutic Target in CD ..............................................................................48 
2.2.4. 
IL-23p19 Blockade in Crohn’s Disease ..........................................................................49 
2.2.5. 
Preclinical and Clinical Studies of Mirikizumab ............................................................49 
2.3. 
Benefit/Risk Assessment ................................................................................................52 
3. 
Objectives and Endpoints ............................................................................................53 
4. 
Study Design ..................................................................................................................60 
4.1. 
Overall Design ................................................................................................................60 
4.2. 
Scientific Rationale for Study Design ............................................................................60 
4.3. 
Justification for Dose ......................................................................................................61 
4.4. 
End of Study Definition ..................................................................................................63 
5. 
Study Population ...........................................................................................................64 
5.1. 
Inclusion Criteria ............................................................................................................64 
5.2. 
Exclusion Criteria ...........................................................................................................67 
5.3. 
Lifestyle Considerations .................................................................................................69 
5.4. 
Screen Failures ................................................................................................................69 
6. 
Study Intervention ........................................................................................................70 
6.1. 
Study Intervention(s) Administered................................................................................70 
6.1.1. 
Study Drug Administration Log .....................................................................................72 
6.2. 
Preparation/Handling/Storage/Accountability ................................................................72 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ............................................73 
6.4. 
Study Intervention Compliance ......................................................................................73 
6.5. 
Concomitant Therapy .....................................................................................................73 
6.5.1. 
Permitted Therapy ...........................................................................................................73 
6.5.2. 
Prohibited Therapy..........................................................................................................74 
6.5.3. 
Corticosteroid Taper .......................................................................................................74 
 
 
 
 
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Protocol I6T-MC-AMAX(e) 
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6.7. 
Management of Hypersensitivity, Infusion-Related Events, 
Infusion Site Reactions, and Injection Site Reactions ....................................................75 
6.7.1. 
Premedication for Infusions or Injections .......................................................................77 
6.8. 
Intervention after the End of the Study ...........................................................................77 
6.8.1. 
Treatment after Study Completion..................................................................................77 
7. 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal........................................................................................78 
7.1. 
Discontinuation of Study Intervention ............................................................................78 
7.1.1. 
Liver Chemistry Stopping Criteria ..................................................................................78 
7.1.2. 
Permanent Discontinuation .............................................................................................79 
7.1.3. 
Criteria for Temporary Interruption (Withholding) of Study Drug ................................80 
7.2. 
Participant Discontinuation/Withdrawal from the Study ................................................81 
7.3. 
Lost to Follow up ............................................................................................................81 
8. 
Study Assessments and Procedures.............................................................................82 
8.1. 
Efficacy Assessments .....................................................................................................82 
8.1.1. 
Primary Efficacy Assessment .........................................................................................83 
8.1.2. 
Secondary Efficacy Assessments ....................................................................................85 
8.1.3. 
Exploratory Assessments ................................................................................................87 
8.2. 
Safety Assessments .........................................................................................................87 
8.2.1. 
Vital Signs .......................................................................................................................87 
8.2.2. 
Physical Examinations ....................................................................................................88 
8.2.3. 
Electrocardiograms .........................................................................................................88 
8.2.4. 
Chest Radiography ..........................................................................................................88 
8.2.5. 
Stool Testing ...................................................................................................................88 
8.2.6. 
Tuberculosis Testing .......................................................................................................89 
8.2.7. 
Clinical Safety Laboratory Assessments ........................................................................92 
8.2.8. 
Hepatitis B Testing .........................................................................................................93 
8.2.9. 
Hepatitis C Testing .........................................................................................................96 
 
8.2.11. Depression, Suicidal Ideation, and Behavior Risk Monitoring ......................................99 
8.3. 
Adverse Events and Serious Adverse Events .................................................................99 
8.3.1. 
Serious Adverse Events ................................................................................................100 
8.3.2. 
Time Period and Frequency for Collecting AE and SAE 
Information ...................................................................................................................101 
8.3.3. 
Follow-Up of AEs and SAEs ........................................................................................102 
8.3.4. 
Regulatory Reporting Requirements for SAEs .............................................................102 
8.3.5. 
Pregnancy ......................................................................................................................102 
8.3.6. 
Cardiovascular and Death Events .................................................................................103 
8.3.7. 
Adverse Events of Special Interest ...............................................................................103 
8.3.8. 
Complaint Handling ......................................................................................................105 
8.4. 
Treatment of Overdose .................................................................................................105 
8.5. 
Pharmacokinetics ..........................................................................................................106 
8.6. 
Pharmacodynamics .......................................................................................................106 
8.7. 
Genetics ........................................................................................................................106 
8.8. 
Biomarkers ....................................................................................................................106 
8.9. 
Immunogenicity Assessments.......................................................................................106 
8.10. 
Medical Resource Utilization and Health Economics ..................................................107 
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Protocol I6T-MC-AMAX(e) 
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9. 
Statistical Considerations ...........................................................................................108 
9.1. 
Statistical Hypotheses ...................................................................................................108 
9.2. 
Sample Size Determination ..........................................................................................108 
9.3. 
Populations for Analyses ..............................................................................................108 
9.4. 
Statistical Analyses .......................................................................................................108 
9.4.1. 
General Considerations .................................................................................................108 
9.4.2. 
Treatment Group Comparability ...................................................................................111 
9.4.3. 
Efficacy Analyses .........................................................................................................111 
9.4.4. 
Safety Analyses .............................................................................................................112 
9.4.5. 
Pharmacokinetic Analyses ............................................................................................112 
9.4.6. 
Evaluation of Immunogenicity .....................................................................................112 
9.4.7. 
Other Analyses ..............................................................................................................113 
9.5. 
Interim Analyses ...........................................................................................................113 
9.6. 
Data Monitoring Committee .........................................................................................113 
10. 
Supporting Documentation and Operational Considerations ................................114 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ..............................................................................................................114 
10.1.1. Regulatory and Ethical Considerations .........................................................................114 
10.1.2. Financial Disclosure......................................................................................................114 
10.1.3. Informed Consent Process ............................................................................................115 
10.1.4. Data Protection..............................................................................................................115 
10.1.5. Committees Structure....................................................................................................116 
10.1.6. Dissemination of Clinical Study Data...........................................................................116 
10.1.7. Data Quality Assurance ................................................................................................117 
10.1.8. Source Documents ........................................................................................................119 
10.1.9. Study and Site Start and Closure ..................................................................................119 
10.1.10. Publication Policy .........................................................................................................120 
10.1.11. Investigator Information ...............................................................................................120 
10.2. 
Appendix 2: Clinical Laboratory Tests .........................................................................121 
10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-Up, and Reporting ......................................................125 
10.3.1. Definition of AE ...........................................................................................................125 
10.3.2. Definition of SAE .........................................................................................................126 
10.3.3. Definition of Product Complaints .................................................................................126 
10.3.4. Recording and Follow-Up of AE and/or SAE ..............................................................127 
10.3.5. Reporting of SAEs ........................................................................................................128 
10.4. 
Appendix 4: Liver Safety: Suggested Actions and Follow-Up 
Assessments ..................................................................................................................130 
10.5. 
Appendix 5: Risk Factors for Latent Tuberculosis Infection .......................................132 
10.6. 
Appendix 6: Examples of Infections that May Be Considered 
Opportunistic in the Setting of Biologic Therapy .........................................................133 
10.7. 
Appendix 7: Prohibited Medications ............................................................................135 
10.8. 
Appendix 8: Permitted Medications with Dose Stabilization .......................................137 
10.9. 
Appendix 9: Patient-Reported Outcome Instruments ...................................................138 
10.10. 
Appendix 10: Additional Information on the 
 
 
.....................................................................................141 
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Protocol I6T-MC-AMAX(e) 
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10.11. 
Appendix 11: Abbreviations and Definitions ...............................................................142 
10.12. 
Appendix 12: Provisions for Changes in Study Conduct During 
Exceptional Circumstances ...........................................................................................145 
10.13. 
Appendix 13: Optional Continued Access Period ........................................................158 
10.13.1. Overview .......................................................................................................................158 
10.13.2. Schema ..........................................................................................................................159 
10.13.3. Schedule of Activities for Continued Access Period ....................................................161 
10.13.4. Study Drug Self Administration Between Office Visits for 
Continued Access Period ..............................................................................................166 
10.13.5. Overall Design ..............................................................................................................167 
10.13.6. Study Population ...........................................................................................................167 
10.13.7. Study Intervention .........................................................................................................169 
10.13.8. Discontinuation of Study Intervention and Participant 
Discontinuation from the Continued Access Period .....................................................169 
10.13.9. Safety Assessments .......................................................................................................170 
10.13.10.Concomitant Medication/Therapy ................................................................................170 
10.14. 
Appendix 14: 
 .....................................174 
10.14.1. Overview .......................................................................................................................174 
10.14.2. Inclusion Criteria ..........................................................................................................174 
10.14.3. Study Intervention .........................................................................................................174 
10.14.4. Discontinuation of Study Intervention and Participant 
Discontinuation from the Substudy ..............................................................................179 
10.14.5. Secondary Efficacy Assessments ..................................................................................179 
10.14.6. Complaint Handling ......................................................................................................180 
10.14.7. Analyses ........................................................................................................................180 
10.15. 
Appendix 15: Country-specific Requirements .............................................................181 
10.15.1. Hungary, Latvia, and Romania .....................................................................................181 
10.15.2. Netherlands and Turkey ................................................................................................183 
10.15.3. Czech Republic .............................................................................................................183 
10.15.4. Hungary.........................................................................................................................192 
10.16. 
Appendix 16: Protocol Amendment History ................................................................196 
11. 
References ....................................................................................................................234 
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Protocol I6T-MC-AMAX(e) 
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List of Tables 
Table AMAX.1-1. Schedule of Activities - Visit 1 through Visit 9 (Year One) ....................... 28 
Table AMAX.1-2. Schedule of Activities - Visit 10 through Visit 19 (Years 2 and 3) ............ 35 
Table AMAX.1-3. Schedule of Activities - Early Termination, AMAG 3Y, Unscheduled   
Visits/Assessments, and Follow-up Visits .................................................. 40 
Table AMAX.1-4. Table for Study Drug Self-Administration not Associated with an Office 
Visit ............................................................................................................. 46 
Table AMAX.10-1 Extended Visit Windows for Exceptional Circumstances ....................... 153 
 
 
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Protocol I6T-MC-AMAX(e) 
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1. 
Protocol Summary  
1.1. 
Synopsis  
Protocol Title: A Phase 3, Multicenter, Open-Label, Long-Term Extension Study to Evaluate 
the Long-Term Efficacy and Safety of Mirikizumab in Patients with Crohn's Disease 
Brief Title: A Phase 3 Extension Study of Mirikizumab in Patients with Crohn's Disease 
Regulatory Agency Identifier Numbers:  
IND: 130052 
EU Trial Number: 2022-502841-91-00 
Rationale: 
Mirikizumab (LY3074828) is a humanized immunoglobulin G4 (IgG4) monoclonal antibody 
that binds to the p19 subunit of interleukin-23 (IL-23), a cytokine that has been implicated in 
mucosal inflammation in Crohn's disease (CD). Study I6T-MC-AMAX (AMAX) is a Phase 3 
long-term extension study designed to evaluate the long-term efficacy and safety of mirikizumab 
in treating participants from the Phase 3 study, I6T-MC-AMAM (AMAM) and the Phase 2 
study, I6T-MC-AMAG (AMAG) who meet all of the AMAX inclusion criteria and none of the 
exclusion criteria. 
 
 
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Protocol I6T-MC-AMAX(e) 
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Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
  
  
 
To assess the effect of mirikizumab on clinical 
remission by CDAI and endoscopic response  
 
 
 
Proportion of participants achieving clinical 
remission by CDAI 
 
 at Week 52 of AMAX 
 
Proportion of participants achieving endoscopic 
response (defined by 
 
 in SES-CD Total Score) at Week 52 of 
AMAX 
Secondary 
  
 
 
To assess the long-term effect of mirikizumab on 
endoscopic, PRO, and CDAI endpoints that are 
not included in the primary objective in 
participants 
 
 
 
Proportion of participants with 
 
 
 in AMAX at: 
o 
 
o 
Week 52 
o 
 
o 
 
 
Proportion of participants with clinical remission 
by CDAI in AMAX at: 
 
Proportion of participants achieving endoscopic 
response in AMAX at: 
o 
 
 
Proportion of participants achieving endoscopic 
remission (defined as SES-CD Total Score 
 
 
 in AMAX at: 
o 
Week 52 
o 
 
 
Proportion of participants with clinical response 
by PRO (
 
) in 
AMAX at: 
o 
Week 52 
o 
 
o 
 
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Objectives 
Endpoints 
 
Proportion of participants 
 
 
 
 in 
AMAX at: 
o 
Week 52 
o 
 
o 
 
 
To evaluate the effect of mirikizumab in 
 
 in 
participants from 
 
 
The following scores over time during AMAX: 
 
 
 
 
 
IBDQ in AMAX at 
 Week 52, 
 
 
 
 
 
 
 
 
 
To assess the effect of mirikizumab 
 
 endoscopic response  
 
 
 
 
 
Proportion of participants achieving endoscopic 
response in AMAX at: 
o 
Week 52 
o 
 
 
To assess the effect of mirikizumab 
 
 endoscopic remission  
 
 
 
 
 
Proportion of participants achieving endoscopic 
remission in AMAX at: 
o 
Week 52 
o 
 
 
To assess the effect of mirikizumab 
 
 of clinical response by PRO  
 
 
 
 
 
Proportion of participants achieving clinical 
response by PRO in AMAX at: 
o 
Week 52 
o 
 
o 
 
 
To assess the effect of mirikizumab 
 
 
 
 
 
 
 
Proportion of participants achieving
 
 in AMAX at: 
o 
Week 52 
o 
 
o 
 
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Objectives 
Endpoints 
 
To evaluate the effect of mirikizumab 
 
 
 
 
 
 
Proportion of participants achieving 
 
 in AMAX at: 
o 
 
o 
Week 52 
o 
 
o 
 
 
To evaluate the effect of mirikizumab 
 
 CDAI remission 
 
 
 
 
 
Proportion of participants achieving clinical 
remission by CDAI in AMAX at: 
o 
 
o 
Week 52 
o 
 
o 
  
 
To assess the effect of mirikizumab i
 
 endoscopic response  
 
 
 
 
 
Proportion of participants achieving endoscopic 
response in AMAX at: 
o 
Week 52 
o 
 
 
To assess the effect of mirikizumab 
 
 endoscopic remission  
 
 
 
 
 
Proportion of participants achieving endoscopic 
remission in AMAX at: 
o 
Week 52 
 
 
 
To assess the effect of mirikizumab 
 
clinical response by PRO  
 
 
 
 
 
Proportion of participants achieving clinical 
response by PRO in AMAX at: 
o 
Week 52 
o 
 
o 
 
 
To assess the effect of mirikizumab 
 
 
 
 
 
 
 
Proportion of participants achieving 
 
 in AMAX at: 
o 
Week 52 
o 
 
o 
 
 
To evaluate the effect of mirikizumab 
 
 clinical 
remission by CDAI or endoscopic remission in 
participants 
 
o 
 
 
o 
 
 
 
 
 
Proportion of participants who achieve clinical 
remission by CDAI or endoscopic remission 
(analyzed separately) at AMAX Week 52 
 
 
 
 
Proportion of participants who achieve clinical 
remission by CDAI or endoscopic remission 
(analyzed separately) 
 
 
 
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Protocol I6T-MC-AMAX(e) 
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Objectives 
Endpoints 
 
 
To assess the effect of mirikizumab in the 
achievement of endoscopic response  
 
 
 
 
 
Proportion of participants achieving endoscopic 
response in AMAX at: 
o 
Week 52 
o 
 
 
To assess the effect of mirikizumab in the 
achievement of endoscopic remission  
 
 
 
 
 
Proportion of participants achieving endoscopic 
remission in AMAX at: 
o 
Week 52 
o 
 
 
To assess the effect of mirikizumab on clinical 
response by PRO 
 
 
 
 
 
Proportion of participants achieving clinical 
response by PRO in AMAX at: 
o 
Week 52 
o 
 
o 
 
 
To assess the effect of mirikizumab on 
 
 
 
 
 
 
Proportion of participants achieving clinical 
remission by PRO in AMAX at: 
o 
Week 52 
o 
 
o 
 
 
To evaluate the effect of mirikizumab on 
 
 
 
 
 
 
Proportion of participants achieving clinical 
response by CDAI in AMAX at: 
o 
 
o 
Week 52 
o 
 
o 
 
 
To evaluate the effect of mirikizumab on CDAI 
remission 
 
 
 
 
 
Proportion of participants achieving clinical 
remission by CDAI in AMAX at: 
o 
 
o 
Week 52 
o 
 
o 
  
 
To assess the effect of mirikizumab on 
inflammatory biomarkers and 
 
 
 
 
 
To evaluate the following endpoints in AMAX: 
 
C-reactive protein at Week 12 
 
Fecal calprotectin at Week 12 
 
 
 
 
 
  
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Objectives 
Endpoints 
 
To assess the effect of mirikizumab in the 
achievement of endoscopic response  
 
 
 
 
 
Proportion of participants achieving endoscopic 
response in AMAX at: 
o 
Week 52 
o 
 
 
To assess the effect of mirikizumab in the 
achievement of endoscopic remission  
 
 
 
 
 
Proportion of participants achieving endoscopic 
remission in AMAX at: 
o 
Week 52 
o 
 
 
 
To assess the effect of mirikizumab in the 
achievement of clinical response by PRO  
 
 
 
 
 
Proportion of participants achieving clinical 
response by PRO in AMAX at: 
o 
Week 52 
o 
 
o 
 
 
To assess the effect of mirikizumab in the 
achievement of 
 
 
 
 
 
 
Proportion of participants achieving clinical 
 in AMAX at: 
o 
Week 52 
o 
 
o 
 
 
To evaluate the effect of mirikizumab in 
achieving 
 or 
endoscopic remission 
 
 
 
 
 
Proportion of participants achieving 
 
 or endoscopic 
remission (analyzed separately) in AMAX at: 
o 
Week 52 
o 
 
Abbreviations: AP = abdominal pain; CD = Crohn’s disease; CDAI = Crohn’s Disease Activity Index;
 
IBDQ = Inflammatory Bowel Disease Questionnaire;
 
PRO = patient-reported 
outcome; SC = subcutaneous; SES-CD = Simple Endoscopic Score for Crohn’s Disease; SF = stool frequency; 
 
Overall Design 
Study AMAX is a Phase 3, multicenter, long-term extension study evaluating the efficacy and 
safety of mirikizumab in participants with moderately-to-severely active CD who have 
participated in an originator adult mirikizumab CD study, inclusive of the Phase 3 Study AMAM 
and the Phase 2 Study AMAG. 
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Protocol I6T-MC-AMAX(e) 
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Participants who are
 
 will receive open-label mirikizumab 
subcutaneously (SC) for an extended period of time (up to 3 years) and then enter a  
12- to 16-week posttreatment follow-up period. Participants who are
 
 will receive 
 
 of mirikizumab 
  
 After completion of the long-term extension period, if mirikizumab is 
not yet locally commercially available and reimbursable, eligible participants will be provided 
with an option of continued access to open-label mirikizumab, followed by a 
 follow-up 
period. The duration of the continued access will differ by participant and country. 
Participants who meet all of the inclusion criteria and none of the exclusion criteria of AMAX, 
and who, in the opinion of the investigator, would receive benefit from open-label treatment with 
mirikizumab are eligible for enrollment into Study AMAX. It is possible that some participants 
enrolling from Study AMAM may have received placebo only in the originating study. These 
participants will receive mirikizumab for the first time in Study AMAX. 
Brief Summary: 
This is a long-term extension treatment study with participants who have been previously or are 
currently diagnosed with moderately-to-severely active CD. 
Participants from Study AMAM: All incoming participants irrespective of AMAM treatment 
assignment (mirikizumab, ustekinumab, or placebo) are 
 
 
 
 
 
 
 
 
 
Study Population: 
In general, an individual may take part in Study AMAX if the individual 
 has completed the last visit of participation in Study AMAG, remained on mirikizumab 
treatment in either the maintenance dosing period or in Study AMAG extension period, 
and in the opinion of the investigator, would derive clinical benefit from continued 
treatment with mirikizumab, OR 
 has completed Week 52 of Study AMAM, including the Week 52 endoscopy 
 
, and in the opinion of the investigator, 
would derive clinical benefit from treatment with mirikizumab. 
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Protocol I6T-MC-AMAX(e) 
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Number of Participants: 
The final sample size of Study AMAX will be determined by the number of participants who 
enroll in Study AMAX from the preceding studies (AMAM and AMAG). It is anticipated that 
approximately 50% to 70% of the participants from Studies AMAM and AMAG will enroll, 
leading to approximately 640 to 900 participants in Study AMAX. 
Intervention Groups and Duration: 
Duration of Treatment: The planned maximum duration of treatment for each participant through 
the end of the long-term extension period is 3 years, until the participant discontinues from the 
study, or until mirikizumab is commercially available in the country in which the participant 
resides, whichever occurs first. After completion of the long-term extension period, if 
mirikizumab is not yet locally commercially available and reimbursable, eligible participants will 
be provided with an option of continued access to open-label mirikizumab, and then enter a 
4-week follow-up period. The duration of the continued access will differ by participant and 
country. 
. Participants from 
Study AMAM will be eligible to enroll in Study AMAX after completing protocol-required 
procedures and assessments at Week 52, including endoscopy. Participants from Study AMAG 
will be eligible to enroll into Study AMAX after completing protocol-required Study AMAG 
procedures. 
Treatment Period through end of Long-Term Extension: 3 years maximum per participant. 
Dose Regimens: 
Participants 
 
 Participants 
: At trial entry in Study AMAX, participants will 
receive 
 during the treatment phase 
beginning with a dose at Week 0 per the Schedule of Activities. 
 Participants 
: At trial entry in Study AMAX, participants will 
receive
 
o All participants 
 
during the treatment phase of the AMAX study. 
o If the participant 
 
, then the participant is to discontinue from the study 
 and 
enter the 12- to 16-week posttreatment follow-up period. 
Participants 
: Participants who 
 
 will 
 receive 
 
 the treatment phase of Study AMAX. 
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Protocol I6T-MC-AMAX(e) 
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Ethical Considerations of Benefit/Risk: 
The efficacy and safety data from the Phase 2 CD Study AMAG support the continued clinical 
development of mirikizumab as a treatment for patients with CD, inclusive of the Phase 3 CD 
Study AMAM and Study AMAX. 
Data Monitoring Committee: Yes 
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Protocol I6T-MC-AMAX(e) 
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1.3. 
Schedule of Activities (SoA)  
1.3.1. 
Visit 1 through Visit 9 
  
Table AMAX.1-1. 
Schedule of Activities - Visit 1 through Visit 9 
 
Procedures 
Schedule of Activitiesa 
Visit Number 
V1b 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
Visit Type 
Office – 
Screening/ 
V1a 
Office - 
Dosing/V1b 
Office Office Phone Office Office Office Office Office Phone Office 
Week Relative to Study Drug Startc 
Day with Visit Tolerance Interval 
(VTI) 
All Participants (X); AMAM Rollover Participants Only (M); AMAG Rollover Participants Only (G); Optional (Opt) (See footnotes for additional key 
details) 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Preexisting conditions 
X 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
Concomitant medications 
Xae 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
Tobacco/Nicotine use 
Xf 
 
 
 
 
X 
 
 
 
 
 
X 
Demographics 
Xf 
 
 
 
 
 
 
 
 
 
 
 
AEsg (See Section 8.3) 
Xae 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
Phone Remindere 
 
 
 
 
X 
 
 
 
 
 
X 
 
Physical Evaluation 
Vital signs 
(T, PR, BP) (See Section 8.2.1.) 
Xae, ag 
Xag 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
Weight 
Xaf 
 
 
 
 
X 
 
 
 
 
 
X 
Physical examinationh (See Section 
8.2.2.) 
Xae 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
  
Xf 
Xah 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
 
Xf 
Xah 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
Clinician CDAI (See Section 8.1.2.1.) 
Xaf 
Xah 
 
 
 
X 
 
 
 
 
 
X 
TB Risk Assessment Monitoringi  
Xaf 
Xah 
X 
 
 
X 
X 
X 
X 
X 
 
X 
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Procedures 
Schedule of Activitiesa 
Visit Number 
V1b 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
Visit Type 
Office – 
Screening/ 
V1a 
Office - 
Dosing/V1b 
Office Office Phone Office Office Office Office Office Phone Office 
Week Relative to Study Drug Startc 
Day with Visit Tolerance Interval 
(VTI) 
Laboratory Tests 
Chemistry 
Xaf 
Xah 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
Hematology 
Xaf 
Xah 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
Urine Pregnancy (local)j (See 
Section 8.2.7.1.) 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
Urinalysis 
Xk 
 
 
 
 
 
 
 
 
 
 
 
HIV testing  
X 
 
 
 
 
 
 
 
 
 
 
 
HBV screeningl (Section 8.2.8.) 
X 
 
 
 
 
 
 
 
 
 
 
 
HBV DNA monitoringm 
Xaf 
Xah 
X 
 
 
X 
X 
X 
X 
X 
 
X 
HCV testing (See Section 8.2.9.) 
X 
 
 
 
 
 
 
 
 
 
 
 
PK samplen 
Xaf 
Xah 
 
 
 
X 
 
 
X 
 
 
X 
Immunogenicity (ADA) samplesn 
Xaf 
Xah 
 
 
 
X 
 
 
X 
 
 
X 
 
Xf 
Xah 
 
 
 
X 
 
 
X 
 
 
X 
Stool Samples (Note: Additional local stool testing [for example, ova and parasites] is allowed at the investigator’s discretion.) 
Fecal calprotectino 
Xf 
Xah 
 
 
 
X 
 
 
X 
 
 
X 
Dispense stool collection kito 
 
 
 
 
 
 
 
 
 
M 
 
 
Take Home Patient Diary (Electronic)p 
Patient electronic diary dispensedq  
M 
 
 
 
 
 
 
 
 
 
 
 
Patient electronic diary returnedr 
 
 
 
 
 
M 
 
 
 
 
 
 
Take Home Patient Diary (Paper)p 
Patient 14-Day paper diary dispenseds,t  
 
 
 
G 
 
 
 
 
 
X 
 
 
Patient 14-Day paper diary returned 
 
 
 
 
 
G 
 
 
 
 
 
X 
On-Site Questionnaires (Paper) 
Patient 1-Day paper diary (24-hour 
recall)t 
G 
 
G 
G 
 
 
X 
X 
X 
X 
 
 
 (See Section 8.1.2.2.) 
Mu 
Mah 
 
 
 
M 
 
 
 
 
 
 
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Procedures 
Schedule of Activitiesa 
Visit Number 
V1b 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
Visit Type 
Office – 
Screening/ 
V1a 
Office - 
Dosing/V1b 
Office Office Phone Office Office Office Office Office Phone Office 
Week Relative to Study Drug Startc 
Day with Visit Tolerance Interval 
(VTI) 
 (See Section 8.1.2.2.) 
Mu 
Mah 
M 
M 
 
M 
 
 
 
 
 
 
 (See Section 8.1.2.2.) 
Mu 
Mah 
 
 
 
M 
 
 
 
 
 
 
IBDQ 
Xv 
Xah 
 
 
 
X 
 
 
 
 
 
X 
 
Xv 
Xah 
 
 
 
X 
 
 
 
 
 
X 
 
Xv 
Xah 
 
 
 
X 
 
X 
 
 
 
X 
 (See Section 8.2.11.) 
X 
 
 
 
 
 
 
 
 
 
 
 
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Protocol I6T-MC-AMAX(e) 
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Abbreviations: ADA = antidrug antibody; AE = adverse event; AESI = adverse event of special interest; 
 
AP = abdominal pain; 
; BP = blood pressure; CDAI = Crohn’s Disease Activity Index; CDAI-AP = Crohn’s Disease Activity 
Index – Abdominal Pain; CDAI-SF = Crohn’s Disease Activity Index – Stool Frequency; 
 CT = computed 
tomography; CXR = chest x-ray; 
 
; HBcAb = hepatitis B core antibody; HBV = hepatitis B virus; HCV = hepatitis 
C virus; HIV = human immunodeficiency virus; 
 IBDQ = Inflammatory Bowel Disease Questionnaire; 
IGRA = interferon gamma release assay; IP = investigative product; IV = intravenous; NA = Not applicable; NRS = numeric rating scale; 
 
; PI = principle investigator; PK = pharmacokinetic; PR = pulse rate; 
 
 SC = subcutaneous; 
 
 SoA = Schedule of Activities; T = temperature; TB = tuberculosis; TST = tuberculin skin test; V = Visit; VTI = visit tolerance interval; 
. 
a Please see detailed instructions provided by the sponsor for calculation of visit dates. Also, note that unscheduled assessments can be performed during 
scheduled visits, see Table AMAX.1-3 for details.  
b V1 is a split visit, occurring on at least 2 office visits on different dates. Screening procedures are to be performed at the first part of V1, called 
Screening/V1a, in order to have results available to confirm eligibility prior to dosing. For AMAM-originating participants, it is recommended that V1a 
screening procedures be on the same date as AMAM V17. V1 dosing is performed at the Dosing/V1b visit. For both AMAM and AMAG-originating 
participants, the timing for AMAX V1a and V1b must allow for first AMAX dosing (V1b) within no more than 
 from the last dosing in the 
originating study. It is required that all screening assessments, including laboratory test results are reviewed to confirm eligibility from both the final visit of 
the originating study as well as AMAX V1a, as applicable, prior to dosing at V1b. For participants originating from AMAM, the 
 
 Note that some assessments may be required at both V1a and V1b. Refer to 
footnotes for details. To accommodate potential lab delays and/or needs for retesting, please plan for at least 10 business days to obtain lab results after initial 
samples are received at the laboratory, and up to 5 business days for endoscopy results after receipt of video. 
c All activities should be completed prior to any study drug administration unless otherwise stated. 
d See footnote b for definitions of the V1 Screening visit (V1a) and the V1 Dosing visit (V1b). V1 dosing (V1b) is defined as Day 1. All V1 screening activities 
need to be performed prior to dosing, including all assessment retesting (if needed), with results available prior to dosing such that the total interval from last 
dose in the originating study to first dose in AMAX is no more than 
. Please see detailed instructions provided by the sponsor for calculation of 
subsequent visit dates. 
e Site to remind participant to complete 14-Day diary and/or bowel prep, as appropriate. Phone reminder must occur at least 15 days prior to actual next visit 
date to ensure the participant begins the collection of diary data in time. 
f Data should be collected at V1 from the AMAG originating participants. Demographic data from the originator study can be used for AMAM participants. 
For all other items with AMAM participants: if data were collected at the final visit in AMAM, those data can be used in AMAX; otherwise, data should be 
collected at V1a. 
g For AESIs, additional data are collected (Section 8.3.7). 
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h Includes a symptom-directed evaluation as well as examination of eyes, heart, lungs, abdomen, and visual examination of the skin (Section 8.2.2). 
i At V1 and throughout the study, participants will be assessed for risk factors for TB (Section 10.5, Appendix 5). If the participant has a risk factor(s) or any 
TB-related signs or symptoms identified as part of the discussions of preexisting conditions or AEs, or as part of the standard physical exam, the investigator 
should conduct a thorough exam to evaluate for TB, including examination of peripheral lymph nodes and documentation of body temperature. If there are 
relevant physical findings or other factors that the investigator feels requires testing and imaging, an IGRA or TST and a CXR should be performed 
(Table AMAX.1-3 Unscheduled assessments). A CT scan can be performed as an alternative to the CXR, based on regional standard of practice 
(Section 8.2.6). 
j To be performed only on women of child-bearing potential. Done locally and at screening, as well as prior to each dosing (Section 8.2.7.1). 
k Data should be collected from the AMAM originating participants. If data were collected at the final visit in AMAG for AMAG-originating participants, they 
can be used, and there is no need to recollect at V1 in AMAX. 
l Participants testing HBcAb+ in the originator study do not need to have HBV full screening at V1 but they will need to have HBV DNA testing at screening 
and continue HBV DNA monitoring throughout the trial. All other participants should have the full HBV screening at V1a. 
m Perform only if participant had ongoing monitoring for HBV DNA during their originator study, or for participants who were found to be HBcAb+ in AMAX 
and met the requirements to continue in the study as described in Section 8.2.8. Such participants will undergo monitoring of HBV DNA at specified 
intervals. Any participants not meeting the requirements to continue in the study at any time must be discontinued from the study and receive appropriate 
follow-up medical care (Section 8.2.8). 
n Samples will be collected predose on the days specified in the SoA. Additionally, in the event of a systemic allergic/hypersensitivity event, blood samples will 
be collected for PK, ADA,
 at the following time points: as close as possible to: (1) the onset of the systemic 
allergic/hypersensitivity event, (2) the resolution of the systemic allergic/hypersensitivity event, 
 
 
o Participants must adhere to proper stool incubation requirements and return stool to site within 24 hours of producing sample. AMAG and AMAM 
participants dispensed pre-endoscopy stool collection kit per SoA. AMAG participants should also receive stool collection kit at the visit prior to the 
endoscopy performed at 
. Instruct participants to collect stool samples up to 3 days prior to beginning bowel prep for endoscopy. For stool 
collection for testing associated with other visits, the sample collection kits may be sent home in earlier visits. This allows the participants to collect samples 
within 24 hours prior to their visit and bring to the site on the day of visit. If samples are not collected before or on the day of the visit, the collection kit 
should be sent home with the participant on the day of the visit, and sample should be collected as soon as possible and returned to the site within 24 hours of 
producing the sample. For AMAG-originating participants at V1, the collection may be performed at the first day of screening and must be collected prior to 
dosing. 
p Visits will differ for participant collections via paper diary or electronic diary capture. See Section 8.1.2.2 for instructions. 
q Dispensed at V1a to AMAM participants only. Includes 
 CDAI-SF with Bristol Stool Scale, CDAI-AP, CDAI well-being, 
 
 (See Section 8.1.2.2). 
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r Collected only from AMAM participants. 
s The 
 endoscopy should be performed for AMAG-originating participants 
 (See 
Table AMAX.1-3) and is notated here under V1 only as a reminder, since it could occur over a wide window of time within the AMAX schedule. At the visit 
prior to the 
 endoscopy, the site should provide the participant with one 14-Day paper diary to be returned at the next regularly scheduled office 
visit. The 14-Day diary should be completed in the 14 days leading up to the next regularly scheduled office visit and may begin before or after the 
endoscopy, depending on endoscopy timing (See Table AMAX.1-3) 
t The 14-Day paper diaries and 1-Day paper diaries both include: 
 CDAI-SF with Bristol Stool Scale, CDAI-AP, CDAI well-being, 
 
 (See Section 8.1.2.2.). 
u Collections required only for participants from AMAM. Collect at AMAX V1a if data were not collected at the final visit in the originator study. 
v Collect at AMAX V1a if data were not collected at the final visit in the originator study. 
w At V1a of AMAX, participants from AMAM should be administered the 
. Participants from AMAG should be administered the 
 
x 
y 
z Visit procedures and assessments must be completed prior to dosing. For both AMAM and AMAG-originating participants, dosing at V1b should occur no 
later than 
 after the participant’s last dose in the originator study. 
aa Dispense study drug at each office visit for the next 
 dose(s) as needed, noting that the visit schedule changes from every 
 
 Also, see Table AMAX.1-4 and Section 6.1 regarding timing for administrations between scheduled 
office visits and participants who choose not to self-administer. At Visit 4, provide ancillary supplies. Continue to dispense ancillary supplies at each visit as 
needed. Note that any used or unused study drug may be returned as an optional unscheduled activity at subsequent visits (Table AMAX.1-3). 
ab Site to complete training with the participant using the Patient Study Drug Administration Training Log at Visit 4. If training does not occur at Visit 4, the 
participant should be trained at the earliest opportunity based on the PI’s discretion. Additionally, participants may be retrained on how to self-administer the 
investigational product, if needed. 
ac Site to complete and dispense Patient Study Drug Administration Log. Provide syringes for next dosing, inform participant of dosing date for self-injection, 
and provide ancillary supplies to participant. 
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ad Participant to return the Patient Study Drug Administration Log at the next visit. 
ae Assessments are scheduled to be performed at the last visit of the originating study and will only need to be performed separately for AMAX V1a if these 
visits do not occur on the same date. 
af Collect/assess at AMAX V1a if not performed at the last visit of the originator study. 
ag Vitals should be assessed at both V1a and V1b. However, only vitals data from V1b should be entered into Inform for V1. 
ah If more than 
 will have elapsed between last collection/assessment and the first AMAX dosing, additional procedures must be performed again prior 
to the V1b dosing. See sponsor guidance regarding sample collection kits or data entry for items that need to be collected again at V1b. Investigator medical 
judgment should be used regarding whether the repeat lab results should be available and reviewed prior to dosing (review prior to dosing not needed for PK, 
immunogenicity, 
 or fecal calprotectin).  
 
 
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Protocol I6T-MC-AMAX(e) 
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1.3.2. 
Visit 10 through Visit 19 
  
Table AMAX.1-2. 
Schedule of Activities - Visit 10 through Visit 19 
 
Procedures 
Schedule of Activitiesa 
Visit Number 
V10 
V11 
V12 
V13 
V14 
V15 
V16 
V17 
V18 
V19r 
Visit Type 
Office 
Office 
Phone 
Office 
Office  Phone 
Office 
Office 
Phone 
Office 
Office 
Office 
Phone 
Office 
Week Relative to Study 
Drug Startb 
Day with Visit 
Tolerance Interval 
(VTI) 
All Participants (X); AMAM Rollover Participants Only (M); AMAG Rollover Participants Only (G); Optional (Opt) (See footnotes for additional 
key details) 
Concomitant medications 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
X 
 
X 
Tobacco/Nicotine use 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
AEsd (See Section 8.3)  
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
X 
 
X 
Phone Reminderc 
 
 
X 
 
 
X 
 
 
X 
 
 
 
X 
 
Physical Evaluation 
Vital signs  
(T, PR, BP) (See 
Section 8.2.1.) 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
X 
 
X 
Weight 
 
 
 
X 
 
 
X 
 
 
X 
 
 
 
X 
Physical examinatione 
(See Section 8.2.2.) 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
X 
 
X 
  
.)  
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
X 
 
X 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
X 
 
X 
Clinician CDAI  
(See Section 8.1.2.1.) 
 
 
 
X 
 
 
X 
 
 
X 
 
 
 
X 
TB Risk Assessment 
Monitoringf  
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
X 
 
X 
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Procedures 
Schedule of Activitiesa 
Visit Number 
V10 
V11 
V12 
V13 
V14 
V15 
V16 
V17 
V18 
V19r 
Visit Type 
Office 
Office 
Phone 
Office 
Office  Phone 
Office 
Office 
Phone 
Office 
Office 
Office 
Phone 
Office 
Week Relative to Study 
Drug Startb 
Day with Visit 
Tolerance Interval 
(VTI) 
Laboratory Tests 
Chemistry 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
X 
 
X 
Hematology 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
X 
 
X 
Urine pregnancy (local)g  
(See Section 8.2.7.1.) 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
X 
 
X 
HBV DNA monitoringh 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
X 
 
X 
PK samplei 
 
 
 
X 
 
 
X 
 
 
X 
 
 
 
X 
Immunogenicity (ADA) 
samplesi 
 
 
 
X 
 
 
X 
 
 
X 
 
 
 
X 
 
 
 
 
X 
 
 
X 
 
 
X 
 
X 
 
X 
Stool Samples (Note: Additional local stool testing [for example, ova and parasites] is allowed at the investigator’s discretion.) 
 
 
 
 
X 
 
 
X 
 
 
X 
 
X 
 
X 
Dispense stool collection 
kitj 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Take Home Patient Diary (Paper) 
Patient 14-Day paper 
diary dispensedk,l 
 
X 
 
 
X 
 
 
X 
 
 
 
X 
 
 
Patient 14-Day paper 
diary returned 
 
 
 
X 
 
 
X 
 
 
X 
 
 
 
X 
On-Site Questionnaires (Paper) 
 
Patient 1-Day paper diary 
(24-hour recall)l 
X 
X 
 
 
X 
 
 
X 
 
 
X 
X 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
X 
 
 
X 
 
 
X 
 
X 
 
X 
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Procedures 
Schedule of Activitiesa 
Visit Number 
V10 
V11 
V12 
V13 
V14 
V15 
V16 
V17 
V18 
V19r 
Visit Type 
Office 
Office 
Phone 
Office 
Office  Phone 
Office 
Office 
Phone 
Office 
Office 
Office 
Phone 
Office 
Week Relative to Study 
Drug Startb 
Day with Visit 
Tolerance Interval 
(VTI) 
Abbreviations: ADA = antidrug antibody; AE = adverse event; AESI = adverse event of special interest; A
 
; BP = blood pressure; CDAI = Crohn’s Disease Activity Index; CDAI-AP = Crohn’s Disease Activity Index – Abdominal 
Pain; CDAI-SF = Crohn’s Disease Activity Index – Stool Frequency; CT = computed tomography; CXR = chest x-ray; 
 
ETV = early termination visit; 
; HBcAb = hepatitis B core antibody; 
HBV = hepatitis B virus; 
; IBDQ = Inflammatory Bowel Disease Questionnaire; IGRA = interferon gamma 
release assay; IP = investigational product; 
; PK = pharmacokinetic; PR = pulse rate; 
 
 
SoA = Schedule of Activities; T = temperature; TB = tuberculosis; TST = tuberculin skin test; V = visit. 
a Please see detailed instructions provided by the sponsor for calculation of visit dates. Also, note that unscheduled assessments can be performed during 
scheduled visits, see Table AMAX.1-3 for details. Please refer to Section 10.13.3 for continued access period details.  
b All activities should be completed prior to any study drug administration unless otherwise stated. 
c Site to remind participant to complete 14-Day diary and/or bowel prep, as appropriate. Phone reminder must occur at least 15 days prior to actual next visit 
date to ensure the participant begins the collection of diary data in time. 
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Protocol I6T-MC-AMAX(e) 
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d For AESIs, additional data are collected (See Section 8.3.7). 
e Includes a symptom-directed evaluation as well as examination of eyes, heart, lungs, abdomen, and visual examination of the skin (Section 8.2.2). 
f Throughout the study, participants will be assessed for risk factors for TB (Section 10.5, Appendix 5). If the participant has a risk factor(s) or any TB-related 
signs or symptoms identified as part of the discussions of AEs or as part of the standard physical exam, the investigator should conduct a thorough exam to 
evaluate for TB, including examination of peripheral lymph nodes and documentation of body temperature. If there are relevant physical findings or other 
factors that the investigator feels warrant testing and imaging, an IGRA or TST and CXR should be performed (Table AMAX.1-3 Unscheduled assessments). 
A CT scan can be performed as an alternative to the CXR based on regional standard of practice (Section 8.2.6). 
g To be performed only on women of child-bearing potential. Done locally and prior to dosing (Section 8.2.7.1). Between visits, urine pregnancy tests are to be 
performed prior to monthly at-home dosing. 
h Perform only if participant had ongoing monitoring for HBV DNA during their originator study, or for participants who were found to be HBcAb+ in AMAX 
and met the requirements to continue in the study as described in Section 8.2.8. Such participants will undergo monitoring of HBV DNA at specified 
intervals. Any participant not meeting the requirements to continue in the study at any time must be discontinued from the study and receive appropriate 
follow-up medical care (Section 8.2.8). 
i Samples will be collected predose on the days specified in the SoA. Additionally, in the event of a systemic allergic/hypersensitivity event, blood samples will 
be collected for PK, ADA, 
 at the following time points: as close as possible to: (1) the onset of the systemic 
allergic/hypersensitivity event, (2) the resolution of the systemic allergic/hypersensitivity event, 
 
 
j Participants must adhere to proper stool incubation requirements and return stool to site within 24 hours of producing sample. AMAG-originating participants 
should receive stool collection kits in AMAX at the visit 
, AMAG- and AMAM-originating 
participants are dispensed a stool collection kit per SoA. Instruct participants to collect stool samples up to 3 days prior to beginning bowel prep for 
endoscopy. For stool collection for testing associated with other visits, the sample collection kits may be sent home in earlier visits.  This allows the 
participants to collect samples within 24 hours prior to their visit and bring to the site on the day of visit.  If samples are not collected before or on the day of 
the visit, the collection kit should be sent home with the participant on the day of this visit, and sample should be collected as soon as possible and returned to 
the site within 24 hours of producing the sample. 
k At the visit 
, the site should provide the participant with one 14-Day paper diary to be collected at the next regularly 
scheduled office visit. The 14-Day diary should be completed in the 14 days leading up to the next regularly scheduled office visit and may begin before or 
after the endoscopy, depending on endoscopy timing (see Table AMAX.1-3). 
l The 14-Day paper diaries and 1-Day paper diaries both include: 
 CDAI-SF with Bristol Stool Scale, CDAI-AP, CDAI well-being, 
 
 (See Section 8.1.2.2.) 
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m 
n Visit procedures and assessments must be completed prior to dosing. 
o Dispense study drug at each office visit for the next 
 as needed, noting that the visit schedule changes from every 
 
 Also, see Table AMAX.1-4 and Section 6.1 regarding timing for administrations between scheduled 
office visits and participants who choose not to self-administer. Continue to dispense ancillary supplies at each visit as needed. Note that any used or unused 
study drug may be returned as an optional unscheduled activity at subsequent visits (see Table AMAX.1-3). 
p Site to complete and dispense Patient Study Drug Administration Log. Provide syringes for next dosing, inform participant of dosing date for self-injection, 
and provide ancillary supplies to participant. 
q Participant to return the Patient Study Drug Administration Log at the next visit. 
r Participants who are eligible for continued access should move directly from Visit 19 to Visit 501, on the same day, if possible. Visit 801 and Visit 802 should 
not be performed for these participants. 
 
 
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1.3.3. 
Early Termination, 
 Unscheduled Visits/Assessments, and Follow-up Visits  
Table AMAX.1-3. 
Schedule of Activities - Early Termination, 
, Unscheduled Visits/Assessments, and Follow-
up Visits 
Procedures 
 
Schedule of Activitiesa 
Visit Number 
ETV 
 
V997c 
UASVd 
V801y 
V802y 
Visit Type 
Office 
Visit Tolerance Interval 
N/A 
All Participants (X); AMAM Rollover Participants Only (M); AMAG Rollover Participants Only (G); Optional (Opt) (See footnotes for additional 
key details) 
Concomitant Medications 
X 
 
 
 
X 
 
X 
X 
Tobacco/Nicotine use 
 
 
 
 
Opt 
Opt 
 
 
AEse (Section 8.3.7.) 
X 
 
 
 
X 
 
X 
X 
Phone Reminderf 
 
G 
 
 
 
 
 
 
Physical Evaluation 
Vital signs (T, PR, BP) 
(See Section 8.2.1.) 
X 
  
 
 
Opt 
 
X 
X 
Weight 
X 
 
 
G 
Opt 
Opt 
  
  
Physical examinationg  
(See Section 8.2.2.) 
X 
  
 
 
Opt 
 
X 
X 
  
 
X 
  
 
 
Opt 
 
X 
X 
 
X 
  
 
 
Opt 
 
X 
X 
Clinician CDAI  
(See Section 8.1.2.1) 
X 
 
 
G 
  
 
  
  
12-lead ECG (local)  
(See Section 8.2.3.) 
  
  
 
 
Opt 
Opt 
  
  
TB Risk Assessment 
Monitoringh 
 
 
 
 
Opt 
Opt 
 
 
CXR (local)i 
  
  
 
 
Opt 
Opt 
  
  
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Protocol I6T-MC-AMAX(e) 
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Procedures 
 
Schedule of Activitiesa 
Visit Number 
ETV 
 
V997c 
UASVd 
V801y 
V802y 
Visit Type 
Office 
Phone 
Endoscopy 
Office 
Office 
Office 
Office 
Office 
Visit Tolerance Interval 
Laboratory Tests 
Chemistry 
X 
 
 
 
Opt 
Opt 
X 
X 
Hematology 
X 
 
 
 
Opt 
Opt 
X 
X 
Hematocrit Only 
 
 
 
Gj 
Opt 
Opt 
 
 
Lipid panel (fasting) 
 
 
 
 
Opt 
Opt 
 
 
FSH  
 
 
 
 
Opt 
Opt 
 
 
Urine pregnancy (local)k 
(See Section 8.2.7.1.) 
X 
 
 
 
Opt 
Opt 
X 
X 
Urinalysis 
 
 
 
 
Opt 
Opt 
 
 
TB testingl (Section 8.2.6.) 
 
 
 
 
Opt 
Opt 
 
 
HIV testing 
 
 
 
 
Opt 
Opt 
 
 
HBV screeningm  
(See Section 8.2.8.) 
 
 
 
 
Opt 
Opt 
 
 
HBV DNA monitoringn 
X 
 
 
 
Opt 
Opt 
 
X 
HCV testing  
(See Section 8.2.9.) 
 
 
 
 
Opt 
Opt 
 
 
PK sampleo 
X 
 
 
 
Opt 
Opt 
 
X 
Immunogenicity (ADA) 
sampleo 
X 
 
 
 
Opt 
Opt 
 
X 
 
X 
 
 
Gj 
Opt 
Opt 
 
 
Hypersensitivity kit 
(tryptase, PK, and 
immunogenicity) 
 
 
 
 
See 
footnotep 
See 
footnotep 
 
 
Hepatic kit 
 
 
 
 
See 
footnoteq 
See 
footnoteq 
 
 
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Protocol I6T-MC-AMAX(e) 
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Procedures 
 
Schedule of Activitiesa 
Visit Number 
ETV 
 
V997c 
UASVd 
V801y 
V802y 
Visit Type 
Office 
Phone 
Endoscopy 
Office 
Office 
Office 
Office 
Office 
Visit Tolerance Interval 
Stool Samples (Note: Additional local stool testing [for example, ova and parasites] is allowed at the investigator’s discretion.) 
Stool culture 
 
 
 
 
Opt 
Opt 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
G 
 
Opt 
Opt 
 
 
Dispense stool collection 
kitr 
 
 
G 
 
Opt 
Opt 
 
 
Take Home Patient Diary (Electronic)s 
Patient electronic diary 
returnedt 
M 
 
 
 
 
 
 
 
Take Home Patient Diary (Paper)s 
Patient 14-Day paper diary 
dispensedu,v 
 
 
 
 
 
 
 
 
Patient 14-Day paper diary 
returnedu 
X 
 
 
G 
 
 
 
 
On-Site Questionnaires (Paper) 
Patient 1-Day paper diary 
(24-hour recall)v 
X 
 
 
G 
Opt 
Opt  
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
Opt 
Opt 
 
 
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Protocol I6T-MC-AMAX(e) 
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Procedures 
 
Schedule of Activitiesa 
Visit Number 
ETV 
 
V997c 
UASVd 
V801y 
V802y 
Visit Type 
Office 
Phone 
Endoscopy 
Office 
Office 
Office 
Office 
Office 
Visit Tolerance Interval 
Abbreviations: ADA = antidrug antibody; AE = adverse event; AESI = adverse event of special interest;
 
 BP = blood pressure; CDAI = Crohn’s Disease Activity Index; CDAI-AP = Crohn’s Disease Activity Index – Abdominal 
Pain; CDAI-SF = Crohn’s Disease Activity Index – Stool Frequency; CRF = case report form; CT = computed tomography; CXR = chest x-ray; 
ECG = electrocardiogram; 
; ETV = early termination visit; 
 
 FSH = follicle-stimulating hormone; HBcAb = hepatitis B core antibody; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human 
immunodeficiency virus; 
; IBDQ = Inflammatory Bowel Disease Questionnaire; IGRA = interferon gamma 
release assay; IP = investigative product; LV = last visit; N/A = not applicable; 
; PK = pharmacokinetic; PR = pulse 
rate; 
 
SoA = Schedule of Activities; T = temperature; TB = tuberculosis; TST = tuberculin skin test; UASV = Unscheduled Assessments during a Scheduled Visit; 
V = Visit. 
a Please see detailed instructions provided by the sponsor for calculation of visit dates. Please refer to Section 10.13.3 for continued access period details.  
b The 
 should be associated in the electronic data capture system with the next regularly scheduled office visit. The 14-Day diary should 
be completed in the 14 days leading up to that next office visit and may begin before or after t
 
 
c Unscheduled visits (997) may be performed at the discretion of the investigator between protocol visits. During all unscheduled 997 visits, concomitant 
medications and AEs must be completed. Other assessments are considered optional (defined as Opt) and if performed, require documentation via the 
appropriate standard (CRF, laboratory requisition or source documentation). 
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d Unscheduled assessments may be performed during a scheduled visit at the discretion of the investigator and are considered part of that protocol scheduled 
visit. The optional assessments (defined as Opt) if performed, require documentation via the appropriate standard (CRF, laboratory requisition and/or source 
documentation). 
e For AESIs, additional data are collected (Section 8.3.7). 
f  Site to remind participant to complete 14-Day diary, stool collection, 
. Phone reminder must occur 
 
 at least 15 days prior to actual next office visit date to ensure the participant begins each item in time. 
g Includes a symptom-directed evaluation as well as examination of eyes, heart, lungs, abdomen, and visual examination of the skin (Section 8.2.2). 
h At the discretion of the investigator, participants may be assessed for risk factors for TB (Section 10.5, Appendix 5) as an additional optional assessment. If 
the participant has a risk factor(s) or any TB-related signs or symptoms identified as part of the discussions of AEs or as part of the standard physical exam, 
the investigator should conduct a thorough exam to evaluate for TB, including examination of peripheral lymph nodes and documentation of body 
temperature. If there are relevant TB-related physical findings or other factors that the investigator feels warrant testing and imaging, an IGRA or TST and 
CXR should be performed. See Footnotes i and l for additional details. A CT scan can be performed as an alternative to the CXR based on regional standard 
of practice. 
i If there are relevant TB-related physical findings or other factors that the investigator feels warrant testing and imaging, a CXR should be performed. A CT 
scan can be performed as an alternative to the CXR. An IGRA or TST should also be performed (see footnote l). 
j 
Sample to be collected for 
 office visit occurs at a regularly scheduled visit that does not already 
collect that sample. 
k To be performed only on women of child-bearing potential. Done locally and prior to dosing. 
l TB testing is required for participants who have relevant physical findings or other factors that the investigator feels warrant testing and imaging. Participants 
who had a TST must return 48 to 72 hours after placement to have their test results read (Section 8.2.6). A CXR should also be performed (see Footnote i). 
m Participants previously testing HBcAb+ do not need to be retested for HBV serology (Section 8.2.8). 
n Perform at ETV only if participant had ongoing monitoring for HBV DNA previously or was found to be HBcAb+ by the time of the ETV. Any enrolled 
participant who is HBcAb+ and meets the requirements to continue in the study as described in Section 8.2.8 will undergo monitoring of HBV DNA at 
specified intervals. Any participant not meeting the requirements to continue in the study  at any time must be discontinued from the study and receive 
appropriate follow-up medical care (Section 8.2.8). 
o Samples will be collected predose per the SoA. Additionally, in the event of a systemic allergic/hypersensitivity event (Section 6.7), blood samples will be 
collected for PK, ADA, 
 at the following time points: as close as possible to: (1) the onset of the systemic 
allergic/hypersensitivity event, (2) the resolution of the systemic allergic/hypersensitivity event, 
 
 
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p In the event of a systemic allergic/hypersensitivity event, blood samples will be collected for PK, ADA, 
 at the 
following time points: as close as possible to: (1) the onset of the systemic allergic/hypersensitivity event, (2) the resolution of the systemic 
allergic/hypersensitivity event, 
 
q 
 
r Participants must adhere to proper stool incubation requirements and return stool to site within 24 hours of producing sample. AMAG-originating participants 
should receive stool collection kits in AMAX at the visit 
 Instruct participants to collect stool samples 
 
. Fecal calprotectin is only tested at the 
 office visit does not coincide 
with a regularly scheduled visit that already collects this lab. For stool collection at the ETV and at optional timepoints, the sample collection kits may be sent 
home in earlier visits. This allows the participants to collect the samples within 24 hours prior to their visit and bring to the site on the day of visit. If samples 
are not collected before or on the day of the visit, the collection kit should be sent home with the participant on the day of the visit, and sample should be 
collected as soon as possible and returned to the site within 24 hours of producing the sample. 
s Visits will differ for participant collections via paper or electronic diary capture (Section 8.1.2.2). 
t Collected from AMAM participants only. 
u Return of the 14-Day paper diary only applies for the ETV if participant has a pending diary return. At the visit prior to 
, the site 
should provide the participant with one 14-Day paper diary to be collected at the next regularly scheduled office visit (also see Footnote b). 
v The 14-Day paper diaries and 1-Day paper diaries both include: 
 CDAI-SF with Bristol Stool Scale, CDAI-AP, CDAI well-being, 
 
 (See Section 8.1.2.2.). 
w 
, as indicated in the table. For each visit with an endoscopy, it is 
recommended that the endoscopy be performed on a separate day from the vital signs and study questionnaires, and IP administration, within the visit 
window, with the endoscopy preceding the other activities. However, if they must be performed on the same day due to logistical issues, the following period 
order of procedures must be followed: (1) Measurement of vital signs and collection of responses to questionnaires; (2) Administration of IP with protocol-
specific observation (at least 1 hour); (3) Performance of endoscopy with or without sedation. An ETV endoscopy should only be performed if the ETV 
occurs at least 16 weeks after the last endoscopy. An ETV endoscopy will not be performed during the follow-up period. 
x Participant to return the Patient Study Drug Administration Log at the next visit. 
y Participants who are eligible for continued access should move directly from Visit 19 to Visit 501, on the same day, if possible. Visit 801 and Visit 802 should 
not be performed for these participants. 
 
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1.3.4. 
Study Drug Self-Administration  
Table AMAX.1-4. 
Table for Study Drug Self-Administration not Associated with an Office Visit 
Procedures 
 
Name of Visit Interval 
 
Week Relative to Study Drug Start 
Days Relative to Study Drug Start and 
Visit Interval Tolerance (Days) 
Study Drug Self-Administrationb 
a 
b Complete Patient Study Drug Administration Log at time of administration. Also, see Section 6.1 regarding participants who choose not to self-administer. In 
this case, the Patient Study Drug Administration Log must still be completed, and dose administrations would be performed on these specified weeks in the 
office by site staff. 
 
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2. 
Introduction  
2.1. 
Study Rationale  
Mirikizumab (LY3074828) is a humanized immunoglobulin G4 (IgG4) monoclonal antibody 
that binds to the p19 subunit of interleukin-23 (IL-23), a cytokine that has been implicated in 
mucosal inflammation. 
Study I6T-MC-AMAX (AMAX) is an open-label, long-term extension for adult participants in 
studies I6T-MC-AMAM (AMAM) and I6T-MC-AMAG (AMAG). Study AMAX is a Phase 3 
clinical trial designed to evaluate the long-term safety and efficacy of mirikizumab in 
participants with moderately-to-severely active Crohn’s disease (CD) who have previously 
participated in Studies AMAM and AMAG. 
2.2. 
Background  
2.2.1. 
Disease State and Treatment Goals  
Crohn’s disease is a chronic disease of unknown etiology with environmental, genetic, and 
immunologic influences. Transmural inflammation affecting any part of the gastrointestinal tract 
from the mouth to the anus, usually appearing as discontinuous lesions, is a normal characteristic 
for CD (Baumgart and Sandborn 2007). Symptoms include chronic diarrhea (often bloody and 
containing pus or mucus), abdominal pain (AP), weight loss, fever, fatigue, anemia, rectal 
bleeding, and a feeling of fullness in the abdomen. Symptoms depend on the severity of the 
disease and location of the disease, with most patients experiencing an abscess, fistula, stricture, 
or an obstruction requiring surgical intervention. Relapsing–remitting symptoms, meaning that 
many patients have intermittent disease flares that are interspersed with periods of remission, are 
very common in CD (Lichtenstein et al. 2018). 
Treatment goals in clinical practice are control of symptoms and healing of the intestinal 
mucosa. In clinical trials, these goals are reflected by assessing induction of response (typically 
within a 6-week to 12-week period) and maintenance of remission in the longer term (over 
52 weeks and beyond of continuous treatment) as assessed by patient-reported outcomes (PROs), 
including a reduction in stool frequency (SF) and AP. In both clinical practice and in clinical 
trials, assessment of the response to therapeutic interventions includes endoscopy to assess 
improvement in the endoscopic appearance of the mucosa and healing of ulcers. 
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2.2.2. 
Currently Available Treatments and Unmet Need  
Medications used for the treatment of CD may include aminosalicylic acid (5-ASA)–containing 
medications (sulfasalazine, mesalazine, balsalazide, and olsalazine), corticosteroids or 
budesonide, immunomodulators (example: azathioprine [AZA], 6-mercaptopurine [6-MP], and 
methotrexate [MTX]), antimicrobial therapy specific for CD and diet, and antitumor necrosis 
factor (TNF) agents (infliximab, adalimumab, and certolizumab pegol) for treatment of CD 
resistant to treatment with corticosteroids or refractory to MTX or thiopurine therapy. Agents 
targeting leukocyte trafficking such as vedolizumab (an anti-integrin) are currently used in 
patients who have failed other therapies. Ustekinumab, an IL-12/23 (anti-p40) antibody, is 
recommended in patients who have failed prior treatments with corticosteroids, 
immunomodulators, or anti-TNF agents. Adalimumab and certolizumab pegol are recommended 
for treatment of perianal fistulas. 
A sizable proportion of the population with moderately-to-severely active CD is unresponsive to, 
fails to tolerate, or loses response to conventional therapies or approved biologic therapies. The 
estimated rates of clinical remission in patients who failed conventional therapy range from 
approximately 20% to 50% depending on the biologic therapy evaluated. The estimated rates of 
clinical remission in the biologic-failure population are around 20% in all treated patients at 
12 months (Kamm et al. 2011). Thus, there remains considerable unmet medical need for new 
treatment options, especially therapies with novel mechanisms of action that have the potential to 
have improved efficacy and maximize the proportion of patients who achieve long-term clinical 
remission while maintaining a reassuring safety profile. 
2.2.3. 
IL-23 as a Therapeutic Target in CD  
The contribution of IL-12 and IL-23 in driving the pathophysiology of CD has been explored in 
genetic and animal model studies. These studies would suggest that IL-23 plays a predominant 
role in inflammatory bowel disease (IBD), and blocking IL-23 alone may be a more effective 
strategy than blocking both IL-12 and IL-23. 
A number of observations suggest that CD is mediated by IL-12 and/or IL-23, potentially 
through the Th1 and Th17 pathways they induce (Monteleone et al. 1997; Berrebi et al. 1998; 
Parrello et al. 2000). Moreover, the predominant role for IL-23 in CD has been suggested by 
genomics studies (Duerr et al. 2006; Barrett et al. 2008). The role of IL-23 in driving intestinal 
inflammation has been shown in several mouse models of IBD (Hue et al. 2006; Uhlig et al. 
2006; Elson et al. 2007; Maxwell et al. 2015), and mice with a genetic deletion of the p19 
subunit of IL-23 have been shown to be protected in several models of intestinal inflammation 
(Hue et al. 2006; Kullberg et al. 2006; Yen et al. 2006). 
The relative contribution of IL-12 and IL-23 to disease pathology in IBD has been explored in 
several studies. The results of these studies would indicate that IL-23, but not IL-12, promotes 
intestinal inflammation (Hue et al. 2006; Kullberg et al. 2006; Uhlig et al. 2006; Yen et al. 2006). 
Data from murine models of psoriasis demonstrating a protective role in dermatologic 
inflammation (Kulig et al. 2016), as well as clinical trials (Blauvelt et al. 2017; Reich et al. 
2019), would imply that IL-12 blockade may actually be counterproductive to the control of 
intestinal inflammation. These data suggest that the efficacy obtained with IL-12/23p40 blockade 
may be through the inhibition of IL-23 and provide a strong rationale for inhibiting IL-23 in CD, 
inclusive of long-term efficacy and safety. 
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2.2.4. 
IL-23p19 Blockade in Crohn’s Disease  
The efficacy of IL-23p19 blockade in CD has been demonstrated in Phase 2 studies evaluating 
the short-term efficacy and safety of different IL-23p19 monoclonal antibodies, including 
brazikumab induction (Sands et al. 2017), guselkumab induction and maintenance (Danese et al. 
2022; Sandborn et al. 2022), and recent Phase 3 studies of risankizumab induction and 
maintenance (D’Haens et al. 2022; Ferrante et al. 2022). The data from these studies showed 
significant efficacy of anti-IL-23 p19 biologics in patients with moderately to severe Crohn’s 
disease with favorable safety profiles. 
2.2.5. 
Preclinical and Clinical Studies of Mirikizumab  
Mirikizumab binds the IL-23p19 subunit of human IL-23 and prevents binding of IL-23 to the 
IL-23 receptor, neutralizing the activity of human IL-23 in vitro. Mirikizumab also neutralizes 
human IL-23 in vivo, ameliorating the development of psoriasis-like skin inflammation in mice 
following subcutaneous (SC) injection of human IL-23. Mirikizumab does not prevent IL-12 
signaling in vitro. 
Several clinical studies of mirikizumab have been completed or are currently ongoing in patients 
with psoriasis, ulcerative colitis (UC), and CD. 
Clinical Studies in UC 
Study I6T-MC-AMAC (AMAC) was 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% Q4W and 38.5% every 12 weeks 
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). 
The Phase 3 LUCENT program comprises of Study I6T-MC-AMAN (AMAN), a 12-week 
double-blind, placebo-controlled, Phase 3 induction study of mirikizumab in participants with 
moderate to severe UC who had failed conventional and/or biologic treatments (D’Haens et al. 
2022) and Study I6T-MC-AMBG, a double-blind, randomized withdrawal maintenance study in 
patients who responded to mirikizumab induction therapy in AMAN (Dubinsky et al. 2022). In 
Study AMAN, mirikizumab met the primary endpoint of clinical remission at Week 12 
compared to placebo (p<.0001). At Week 12, mirikizumab when compared to placebo also 
achieved highly statistically significant p-values, including reduced bowel urgency, clinical 
response, endoscopic remission, symptomatic remission, and improvement in endoscopic 
histologic inflammation.  
The incidence of TEAEs and SAEs among participants treated with mirikizumab was consistent 
with that of the previous Phase 2 mirikizumab study in UC and studies with the anti-IL-23p19 
antibody class. The most common AEs ≥3% in any treatment group included nasopharyngitis, 
anemia, and headache for both placebo and mirikizumab-treated participants (D’Haens et al. 
2022). 
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The Phase 3 LUCENT program also includes I6T-MC-AMAP (mirikizumab open-label 
extension) in patients with moderately-to-severely active UC; this study is ongoing at the time of 
this writing. 
Clinical Studies in CD 
Study I6T-MC-AMAG (AMAG) was a Phase 2, placebo-controlled, double-blind clinical trial of 
mirikizumab in participants with active CD. Unblinded results are available from the completed 
12-week induction period and 52-week maintenance data. The primary efficacy objective is to 
test the hypothesis that treatment with mirikizumab is superior to placebo in the proportion of 
patients with endoscopic response at Week 12, defined as a 50% reduction from baseline in 
Simple Endoscopic Score for Crohn’s Disease (SES-CD) Total Score. At Week 12, endoscopic 
response was significantly higher by the predefined 2-sided significance level of 0.1 for all 
mirikizumab groups compared with placebo (200 mg: 25.8%, 8/31, 95% CI, 10.4-41.2, p = .079; 
600 mg: 37.5%, 12/32, 95% CI, 20.7-54.3, p = .003; 1000 mg: 43.8%, 28/64, 95% CI, 31.6-
55.9, p < .001; placebo: 10.9 %, 7/64, 95% CI, 3.3-18.6). Endoscopic response at Week 52 was 
58.5% (24/41) and 58.7% (27/46) in the combined IV group and the SC group, respectively. 
Thus, mirikizumab effectively induced endoscopic response after 12 weeks in participants with 
moderate-to-severe CD and demonstrated durable efficacy to Week 52. Frequencies of AEs in 
the mirikizumab groups were similar to placebo. Treatment with mirikizumab has shown 
clinically relevant and consistent treatment effect in reducing or resolving endoscopic 
inflammation and patient-reported symptoms in participants with moderately to severely active 
CD. Through Week 52, frequencies of TEAEs were similar across all groups. Frequencies of 
SAEs and discontinuations due to AEs were higher in the nonrandomized maintenance cohort, 
consisting of Week 12 endoscopic nonimprovers, and participants who received placebo in the 
first 12 Weeks followed by mirikizumab for the remainder of the trial. There were no deaths in 
any study period, and no malignancies or instances of veno-occlusive disease (including 
pulmonary embolism) reported in the induction or maintenance period of the study (Sands et al. 
2022). 
Study AMAM was a Phase 3, multicenter, randomized, double-blind, double-dummy, parallel 
group, and active- and placebo-controlled, treat-through clinical trial of mirikizumab in 
participants with moderately to severely active CD. Participants who had an inadequate response 
to, loss of response to, or were intolerant to corticosteroid or immunomodulator therapy for CD 
(termed “conventional-failed”), and those who had an inadequate response to, loss of response 
to, or were intolerant to biologic therapy for CD (termed “biologic-failed”) were included in the 
study. The primary objective was to test the hypothesis that mirikizumab is superior to placebo 
as assessed by the following co-primary endpoints:  
 PRO clinical response at Week 12 and endoscopic response at Week 52, and  
 PRO clinical response at Week 12 and clinical remission by CDAI at Week 52.  
A significantly greater percentage of participants achieved both co-primary endpoints at Week 
52 in the mirikizumab group (endoscopic response: 38.0%, 220 of 579 participants, p<0.000001; 
clinical remission: 45.4%, 263 of 579 participants, p<0.000001) compared with the placebo 
group (endoscopic response: 9.0%, 18 of 199 participants; clinical remission: 19.6%, 39 of 199 
participants).  
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Thus, mirikizumab demonstrated statistically significant and clinically meaningful improvements 
for both co-primary endpoints compared to placebo. Overall, higher frequencies of TEAEs were 
reported in the placebo group compared with the mirikizumab group. Most TEAEs were 
mild-to-moderate in severity. Frequency of SAEs and discontinuation due to AEs were higher in 
placebo group compared with the mirikizumab group. Three participant deaths were reported in 
this study (1 in the placebo group due to pulmonary embolism, 1 in the ustekinumab group due 
to sepsis, and 1 due to CD in the placebo nonresponder group who switched to mirikizumab at 
Week 12). 
Additional nonclinical and clinical trial data are summarized in the Investigator’s Brochure (IB). 
 
 
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2.3. 
Benefit/Risk Assessment  
At the time of the last benefit/risk assessment, evaluation of unblinded safety data from the 
completed or ongoing clinical studies has not revealed any dose-related safety or tolerability 
concerns. Mirikizumab has demonstrated efficacy in blinded, placebo-controlled Phase 2 and 
Phase 3 studies in psoriasis (Reich et al. 2019; Papp et al. 2020), Phase 2 and 3 studies in UC 
(Sandborn et al. 2018; D’Haens et al. 2023), and Phase 2 and Phase 3 studies in CD (Sands et al. 
2022; Ferrante et al. 2024). Evaluation of unblinded safety data in studies in psoriasis, UC, and 
CD with dose regimens of up to 1000 mg IV Q4W for up to 52 weeks and up to 300 mg SC 
Q4W for up to 104 weeks have shown a safety profile generally consistent with the IL-23 
antibody class. These data are summarized in the IB. Given the data from the Phase 2 and  
Phase 3 studies in CD and data from other clinical studies completed to date, potential benefits to 
participants who receive mirikizumab while participating in Study AMAX are reasonably 
anticipated. 
In Phase 2 mirikizumab studies where mirikizumab in a lyophilized solution was administered 
intravenously over no less than 30 minutes, immediate hypersensitivity reactions, including 2 
reports of immediate, infusion-related hypersensitivity events consistent with anaphylaxis and 
AEs that resulted in study drug discontinuation, were reported. In response, the duration of 
mirikizumab administration was increased. After this change was implemented, no additional 
events consistent with anaphylaxis were reported, and no anaphylactic reactions have been 
reported in participants who received the current Phase 3 formulation of mirikizumab (planned 
for commercial use). Infusion-related hypersensitivity reaction is an ADR for mirikizumab. 
Based on unblinded Phase 3 data, the following additional ADRs have been identified: injection 
site reactions, upper respiratory tract infections, alanine amino transferase increased, aspartate 
aminotransferase increased, headaches, and rashes. Consult the IB for information regarding 
ADRs and potential risks with mirikizumab. 
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 
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, are noted in Section 8.3.7 of this protocol. For all AESIs, including 
hypersensitivity events, the protocol and IB provide monitoring and management guidance to the 
investigator. In addition, an independent, external data monitoring committee (DMC) will review 
clinical trial data at prespecified, regular intervals during the study (Section 10.1.5). This 
independent assessment of clinical trial data will contribute to the overall ongoing evaluation and 
management of potential risks associated with mirikizumab administration. 
Overall Benefit/Risk Conclusion 
In summary, the efficacy and safety data from the Phase 2 CD Study AMAG and the Phase 3 CD 
Study AMAM support the continued clinical development of mirikizumab as a treatment for 
patients with CD in the ongoing Phase 3 CD Study AMAX. 
More information about the known and expected benefits, risks, SAEs, and reasonably 
anticipated AEs of mirikizumab can be found in the IB. 
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3. 
Objectives and Endpoints  
Objectives 
Endpoints 
Primary 
  
  
 
To assess the effect of mirikizumab on clinical 
remission by CDAI and endoscopic response  
 
  
 
Proportion of participants achieving clinical 
remission by CDAI 
 
at Week 52 of AMAX 
 
Proportion of participants achieving endoscopic 
response (defined by 
 
SES-CD Total Score) at Week 52 of 
AMAX 
Secondary 
  
 
 
To assess the long-term effect of mirikizumab on 
endoscopic, PRO, and CDAI endpoints that are 
not included in the primary objective in 
participants 
 
 
 
Proportion of participants with 
 
 
 in AMAX at: 
o 
Week 12 
o 
Week 52 
o 
 
o 
 
 
Proportion of participants with clinical remission 
by CDAI in AMAX at: 
 
Proportion of participants achieving endoscopic 
response in AMAX at: 
o 
 
 
Proportion of participants achieving endoscopic 
remission (defined as SES-CD Total Score ≤4 
 
 in AMAX at: 
o 
Week 52 
o 
 
 
Proportion of participants with clinical response 
by PRO 
 
 in 
AMAX at: 
o 
Week 52 
o 
 
o 
 
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Objectives 
Endpoints 
 
Proportion of participants 
 
 
 
 in 
AMAX at: 
o 
Week 52 
o 
 
o 
 
 
To evaluate the effect of mirikizumab in 
 
 in 
participants 
 
 
The following scores over time during AMAX: 
 
 
 
 
 
IBDQ in AMAX at 
 Week 52, 
 
 
 
 
To assess the effect of mirikizumab
 
endoscopic response
 
 
 
 
 
 
Proportion of participants achieving endoscopic 
response in AMAX at: 
o 
Week 52 
o 
 
 
To assess the effect of mirikizumab 
 
endoscopic remission  
 
 
 
 
 
Proportion of participants achieving endoscopic 
remission in AMAX at: 
o 
Week 52 
o 
 
 
To assess the effect of mirikizumab 
 
 clinical response by 
 
 
 
 
 
 
Proportion of participants achieving clinical 
response by PRO in AMAX at: 
o 
Week 52 
o 
 
o 
 
 
To assess the effect of mirikizumab 
 
 
 
 
 
 
 
Proportion of participants 
 
in AMAX at: 
o 
Week 52 
o 
 
o 
 
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Objectives 
Endpoints 
 
To evaluate the effect of mirikizumab 
 
 
 
 
 
 
Proportion of participants achieving 
 
 in AMAX at: 
o 
 
o 
Week 52 
o 
 
o 
 
 
To evaluate the effect of mirikizumab 
 
 CDAI remission 
 
 
 
 
 
Proportion of participants achieving clinical 
remission by CDAI in AMAX at: 
o 
 
o 
Week 52 
o 
 
o 
  
 
To assess the effect of mirikizumab i
 
 endoscopic response  
 
 
 
 
 
Proportion of participants achieving endoscopic 
response in AMAX at: 
o 
Week 52 
o 
 
 
To assess the effect of mirikizumab 
 
endoscopic remission  
 
 
 
 
 
Proportion of participants achieving endoscopic 
remission in AMAX at: 
o 
Week 52 
o 
 
 
To assess the effect of mirikizumab 
 
 clinical response by PRO  
 
 
 
 
 
Proportion of participants achieving clinical 
response by PRO in AMAX at: 
o 
Week 52 
o 
 
o 
 
 
To assess the effect of mirikizumab 
 
 
 
 
 
 
 
Proportion of participants achieving 
 
 in AMAX at: 
o 
Week 52 
o 
 
o 
 
 
To evaluate the effect of mirikizumab 
 
 clinical 
remission by CDAI or endoscopic remission in 
participants 
: 
o 
o 
 
Proportion of participants who achieve clinical 
remission by CDAI or endoscopic remission 
(analyzed separately) at AMAX Week 52 
 
 
 
 
Proportion of participants who achieve clinical 
remission by CDAI or endoscopic remission 
(analyzed separately) 
 
 
 
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Objectives 
Endpoints 
AMAM participants not achieving endpoints at Week 52 of AMAM: 
 
To assess the effect of mirikizumab in the 
achievement of endoscopic response  
 
 
 
 
 
Proportion of participants achieving endoscopic 
response in AMAX at: 
o 
Week 52 
o 
 
 
To assess the effect of mirikizumab in the 
achievement of endoscopic remission  
 
 
 
 
 
Proportion of participants achieving endoscopic 
remission in AMAX at: 
o 
Week 52 
o 
 
 
To assess the effect of mirikizumab on clinical 
response by PRO 
 
 
 
 
 
Proportion of participants achieving clinical 
response by PRO in AMAX at: 
o 
Week 52 
o 
 
o 
 
 
To assess the effect of mirikizumab 
 
 
 
 
 
 
Proportion of participants achieving clinical 
remission by PRO in AMAX at: 
o 
Week 52 
o 
 
o 
 
 
To evaluate the effect of mirikizumab on 
 
 
 
 
 
 
Proportion of participants achieving clinical 
response by CDAI in AMAX at: 
o 
 
o 
Week 52 
o 
 
o 
 
 
To evaluate the effect of mirikizumab on CDAI 
remission
 
 
 
 
 
Proportion of participants achieving clinical 
remission by CDAI in AMAX at: 
o 
 
o 
Week 52 
o 
 
o 
  
 
To assess the effect of mirikizumab on 
inflammatory biomarkers 
 
 
 
 
 
To evaluate the following endpoints in AMAX: 
 
C-reactive protein at Week 12 
 
Fecal calprotectin at Week 12 
 
 
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Objectives 
Endpoints 
 
To assess the effect of mirikizumab in the 
achievement of endoscopic response  
 
 
 
 
 
Proportion of participants achieving endoscopic 
response in AMAX at: 
o 
Week 52 
o 
 
 
To assess the effect of mirikizumab in the 
achievement of endoscopic remission  
 
 
 
 
 
Proportion of participants achieving endoscopic 
remission in AMAX at: 
o 
Week 52 
o 
 
 
 
To assess the effect of mirikizumab in the 
achievement of clinical response by PRO  
 
 
 
 
 
Proportion of participants achieving clinical 
response by PRO in AMAX at: 
o 
Week 52 
o 
 
o 
 
 
To assess the effect of mirikizumab in the 
achievement of 
 
 
 
 
 
 
Proportion of participants achieving 
 
 in AMAX at: 
o 
Week 52 
o 
 
o 
 
 
To evaluate the effect of mirikizumab in 
achieving 
 
endoscopic remission 
 
 
 
 
 
Proportion of participants achieving 
 
 or endoscopic 
remission (analyzed separately) in AMAX at: 
o 
Week 52 
o 
 
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Abbreviations: AP = abdominal pain; CD = Crohn’s disease; CDAI = Crohn’s Disease Activity Index; 
; IBDQ = Inflammatory Bowel 
Disease Questionnaire;
 
 PRO = patient-reported outcome; SC = subcutaneous; SES-CD = Simple 
Endoscopic Score for Crohn’s Disease; SF = stool frequency; 
 
 
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4. 
Study Design  
4.1. 
Overall Design  
Study AMAX is a long-term study of adult participants completing studies AMAM or AMAG 
(see schema in Section 1.2). 
Two intervention groups will be studied in participants with moderate-to-severe CD: 
 
Mirikizumab 
 
 
Mirikizumab 
. 
Study participants will receive mirikizumab for an extended period of time (approximately 
3 years or until commercial availability of mirikizumab, whichever comes first) and then enter a 
12- to 16-week posttreatment follow-up period. After completion of long-term extension period, 
if mirikizumab is not yet locally commercially available and reimbursable, eligible participants 
will be provided with an option of continued access to open-label mirikizumab, and then enter a 
 follow-up period (Section 10.13, Appendix 13). The duration of the continued access 
will differ by participant and country.  
AMAM participants will require an endoscopy to be performed at Week 52, 
 
) in the AMAX study. 
AMAG participants who are entering AMAX after completing 
 
 into AMAX. Participants who have not yet 
completed
 
 
 
See Section 8.1.1.2 for details. 
4.2. 
Scientific Rationale for Study Design  
Study AMAX is designed to accumulate data on the long-term safety of mirikizumab and 
evaluate the efficacy of mirikizumab in 
 for up to 
3 years of treatment in participants with moderately-to-severely active CD. The primary 
objective of Study AMAX is to evaluate the long-term effect of mirikizumab in clinical 
remission and endoscopic response at Week 52 of treatment in Study AMAX. Clinical remission 
is defined as achieving 
. Endoscopic response is defined as 
 
 
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Endpoints 
To evaluate the effect of mirikizumab on clinical improvement of CD and decreasing intestinal 
mucosa inflammation, the following measures will be used for the primary objectives of Study 
AMAX: CDAI and SES-CD Total Score. 
For participants transitioning from AMAM, the SES-CD will be determined at Week 52 of 
AMAM, at Week 52 (Year 1) of AMAX, 
 
), with evaluation of 
endoscopic response
) at 
Week 52 AMAX as a primary endpoint. 
 
 
 
 
 
 
 
 
 
 
To evaluate the effect of mirikizumab on decreasing symptoms of CD, AP and SF will be 
assessed. Qualitative patient research, clinical gastroenterological expert opinion, and a review of 
the peer-reviewed literature assert that AP and SF are the most important and clinically relevant 
symptoms associated with moderate-to-severe CD (Baumgart and Sandborn 2007; Khanna et al. 
2015; Kim et al. 2015). Both AP and frequent bowel movements with the consistency of liquid 
or soft stools have a significant impact on the day-to-day function and life of a patient with 
moderate-to-severe CD. 
To assess the effect of mirikizumab on SF and AP, 
 will be measured 
in Study AMAX at time points detailed in the Schedule of Activities (SoA) (Section 1.3). 
Participants transitioning from AMAM will be provided with an electronic daily diary during 
Week 0-Week 12 of the study to record their signs and symptoms on a daily basis. 
To measure the number of liquid or very soft stools in the past 24 hours, participants will use the 
SF item of the Crohn’s Disease Activity Index (CDAI) (unweighted). To further define “liquid or 
very soft stools,” participants will be referred to the Bristol Stool Scale Category 6 and/or 7, 
which provides a pictorial and verbal description of stool consistency and form, for example, 
liquid or watery stool. To measure the participant’s AP, participants will be asked to record AP 
using the 4-point scale. 
4.3. 
Justification for Dose  
The mirikizumab 
 dose regimens 
selected for this study were 
 and were based primarily on 
analyses of interim pharmacokinetics (PK), safety, and efficacy data from the Phase 2 Study 
AMAG, safety data from other clinical studies evaluating mirikizumab, and nonclinical safety 
data. 
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Safety Considerations 
The safety data collected for mirikizumab in completed and ongoing clinical studies and in 
nonclinical toxicology studies support the proposed dose regimen. As noted in Section 2.3, in the 
Phase 2 Study AMAG, the incidences of SAEs and TEAEs were similar between placebo and 
mirikizumab treatment groups, with no dose relationship noted in the first 12 weeks (Period 1). 
In Period 2 (Weeks 12 to 52), comparative data are limited. The incidence of overall TEAEs was 
similar across all mirikizumab dose groups and were generally mild to moderate in severity. 
Patients exposed to 1000 mg mirikizumab IV had a higher number of SAEs, including 2 reports 
of immediate, infusion-related hypersensitivity events consistent with anaphylaxis. For IV dose 
administration, mitigation measures that include slowing the infusion rate and monitoring during 
and after drug infusion have been implemented. There were no deaths during Study AMAG. As 
noted in Section 2.3, for all AESIs, including hypersensitivity events, the protocol and IB 
provide monitoring and management guidance to the investigator. 
Single IV doses of up to 
 mg were evaluated in Study AMAA (healthy participants and 
participants with psoriasis) and up to 
 mg in Study I6T-JE-AMAD (AMAD) (healthy 
participants). No dose-related safety or tolerability issues were observed in either study. 
Evaluation of the unblinded safety data available to date in the ongoing Phase 2 study in patients 
with psoriasis (Study AMAF) and of the unblinded safety data available to date in the ongoing 
Phase 2 study of mirikizumab in patients with UC (Study AMAC) has not revealed a safety 
concern that differs from the safety findings noted above for Study AMAG. 
The nonclinical safety profile of mirikizumab supports the proposed dose regimens in this study 
on the basis of the no-observed-adverse-effect levels (NOAELs) established in studies in 
monkeys. The margins of safety for the 
 dose regimens 
proposed relative to the NOAEL level in the 6-month nonclinical toxicology study in 
cynomolgus monkeys are 
, respectively, based on area under the plasma concentration 
versus time curve. 
Considerations of Efficacy and Exposure–Response Relationships 
Significant efficacy of mirikizumab relative to placebo was observed in the 600 mg and 1000 mg 
IV Q4W treatment groups in Study AMAG based on the Week 12 endoscopic response endpoint, 
with the highest rates observed in the 1000 mg treatment group. Significant efficacy relative to 
placebo was also observed at Week 12 for the PRO remission endpoints and indicated 
near-maximal efficacy between the 600 mg and 1000 mg doses. 
A model-based analysis of the relationship between individual subject mirikizumab systemic 
exposures and Week 12 endoscopic response revealed a significant relationship, with higher 
mirikizumab exposures associated with higher rates of endoscopic response. The 900 mg IV 
induction dose in the ongoing phase 3 AMAM study is expected to produce near-maximal effect 
based on this exposure-response analysis.
 
 
 
 
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In the Week 12 to Week 52 maintenance period of Study AMAG, the mirikizumab dose 
regimens that were evaluated ranged from 300 mg SC Q4W to 1000 mg IV Q4W.
 
 The Week 52 endoscopic response
 across the 
maintenance treatment groups were similar and did not appear to have any relationship to dose or 
mirikizumab exposure within any of the doses and range of exposures evaluated in 
Study AMAG.
 
 
 
In summary, the totality of the available data for both efficacy and safety supports the proposed 
 
4.4. 
End of Study Definition  
The end of the study is the date of the last visit or last scheduled procedure shown in the SoA 
(Section 1.3) for the last participant. 
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5. 
Study Population  
Study AMAX is a continuation of originator Studies AMAM and AMAG. Adult participants 
may enter into Study AMAX directly from Studies AMAM and AMAG after they sign a 
study-specific Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved 
informed consent. A participant is considered enrolled into the study once the eligibility of the 
participant is verified (see Section 8). Participants who sign informed consent to enter 
Study AMAX but do not meet eligibility criteria should return to the originator trial for safety 
follow-up (see Section 5.4). Data collected during the last visit of the originator studies, 
including laboratory evaluations, endoscopy, and patient-reported data, may be used to review 
entry criteria, assess the suitability of a participant for entering this long-term extension trial, and 
serve as part of Visit 1 for AMAX. (Note that AMAX V1 is a split visit. See SoA Table 
AMAX.1-1 footnote d for additional details.) Prior to study entry, participants who do not meet 1 
or more hepatic or hematologic laboratory enrollment criteria may have these blood measures 
repeated 1 time at the investigator’s discretion to assess participant eligibility. 
Participants who discontinued from Study AMAM for any reason are not eligible to enter study 
AMAX. AMAG participants who discontinued from the AMAG study or addendum or 
permanently discontinued treatment prior to the time of enrollment in Study AMAX are not 
eligible to enter Study AMAX. 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, are not permitted. 
5.1. 
Inclusion Criteria  
Participants are eligible to be included in the study only if all of the following criteria apply. 
Criteria below apply to all AMAX participants, regardless of their originating study, unless a 
specific originator study (AMAM or AMAG) is specified: 
Informed Consent 
[1] 
Have given written informed consent approved by the ethical review board (ERB) 
governing the site. 
Type of Participant and Disease Characteristics 
[2] 
Participants from the Phase 2 Study AMAG who: 
 completed the last visit of participation in the AMAG study and remained on 
mirikizumab treatment in either the maintenance dosing period 3 or in the AMAG 
extension period, and 
 in the opinion of the investigator, would derive clinical benefit from 
continued treatment with mirikizumab. 
It is recommended that participants receive the first dose of AMAX study drug 
within approximately
 of the last dosing visit in AMAG. A maximum 
of 
 will be allowed between the last dose in AMAG and the first dose in 
AMAX to accommodate situations where due to circumstances outside the 
patient’s control, a patient may not be able to complete all required assessments 
within the recommended shorter window. 
OR 
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[3] 
Participants from the Phase 3 Study AMAM who: 
 
completed Week 52 of the AMAM study, including the Week 52 endoscopy 
 
, and in the opinion of the 
investigator would derive clinical benefit from treatment with mirikizumab. 
It is recommended that participants receive the first dose of AMAX study drug 
within approximately 
 after the last dosing visit in AMAM. A 
maximum of 
 will be allowed between the last dose in AMAM and the 
first dose in AMAX to accommodate situations where due to circumstances 
outside the patient’s control, a patient may not be able to complete all required 
assessments within the recommended shorter window. 
Note: Participants who have completed the AMAM adolescent addendum are not 
eligible for the AMAX trial, but may be eligible for the pediatric IBD long-term 
extension trial. 
Participant Characteristics 
[4] 
Are willing and able to complete the scheduled study assessments, including endoscopy, 
self-administer investigational product (or have caregiver administer investigational 
product), and complete patient electronic and paper diary (See Section 8.1.2.2). 
Note: Self-administration is a key long-term convenience factor for participants, and it is 
important that participants are well-supported in becoming comfortable with learning to 
take this step toward greater independence. Additional support will be available for 
training if participants express concerns about self-administration. The sponsor may 
approve exceptions regarding self-administration, depending on circumstances. Please 
contact your medical monitor. Patients who cannot carry out or do not feel comfortable 
with self-administration of study drug will not be excluded from participation in this trial. 
[5] 
Have clinically acceptable central laboratory test results at study entry which would not 
have resulted in permanent discontinuation of treatment in the originator study. 
Prior to study entry, patients whose hepatic or hematologic laboratory values meet 
discontinuation criteria in the originator study may have these blood measures repeated 
1 time at the investigator’s discretion to assess participant’s eligibility for AMAX. 
Participants with a diagnosis of Gilbert’s syndrome (requires source documentation 
showing isolated unconjugated hyperbilirubinemia, with no evidence of hemolysis) can 
be included with elevated serum total bilirubin levels. 
[6] 
Contraception: Contraceptive use by men or women should be consistent with local 
regulations regarding the methods of contraception for those participating in clinical 
studies. 
a. Male Participants: 
No male contraception is required except in compliance with specific local government 
study requirements. 
b. Female Participants: 
Women of childbearing potential (WOCBP, defined as all adult females unless they are 
WNOCBP as defined below) may participate if they meet the following criteria: 
A. must test negative for pregnancy prior to initiation of treatment as indicated by a 
negative urine pregnancy test at Visit 1/Week 0 of this study 
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AND 
B. must agree to either remain abstinent, if complete abstinence is their preferred and 
usual lifestyle, or remain in same-sex relationships, if part of their preferred and usual 
lifestyle, without sexual relationships with males. Periodic abstinence (for example, 
calendar, ovulation, symptothermal, or postovulation methods), declaration of 
abstinence just for the duration of a trial, and withdrawal are not acceptable methods 
of contraception, 
OR 
must use a combination of 2 effective methods of contraception or 1 highly effective 
method of contraception for the entirety of the study. Abstinence or contraception 
must continue following completion of study drug administration for 16 weeks. 
i. 
Effective methods of contraception may include barrier methods such as male or 
female condoms with spermicide, diaphragms with spermicide, or cervical 
sponges (which usually are made with spermicide). The barrier method must 
include use of a spermicide to be counted as one effective method. 
ii. Highly effective (<1% failure rate) methods of contraception include 
 female sterilization 
 combination oral contraceptive pill 
 progestin-only contraceptive pill (mini-pill) 
 implanted contraceptives 
 injectable contraceptives 
 contraceptive patch (only women <198 pounds or 90 kg) 
 vasectomy (if only sexual partner) 
 fallopian tube implants (if confirmed by hysterosalpingogram) 
 combined contraceptive vaginal ring, or 
 intrauterine devices. 
iii. Ineffective forms of contraception, whether used alone or in any combination, 
include 
 spermicide alone 
 periodic abstinence 
 fertility awareness (calendar method, temperature method, cervical mucus, or 
symptothermal) 
 withdrawal 
 postcoital douche, or 
 lactational amenorrhea. 
Women not of childbearing potential (WNOCBP) may participate and include those 
who are: 
A. infertile due to surgical sterilization (total hysterectomy, bilateral salpingo-
oophorectomy, bilateral salpingectomy, bilateral oophorectomy, or tubal ligation)a, have 
a congenital anomaly such as Müllerian agenesis, 
OR 
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B. postmenopausalb – defined as either: 
i. a woman at least 40 years of age with an intact uterus, not on hormone therapy, 
who has had either: 
 cessation of menses for at least 1 year, without an alternative medical cause 
 at least 6 months of spontaneous amenorrhea with a follicle-stimulating 
hormone (FSH) level >40 mIU/mL 
ii. a woman 55 years or older not on hormone therapy, who has had at least 6 months 
of spontaneous amenorrhea, or 
iii. a woman at least 55 years of age with a diagnosis of menopause prior to starting 
hormone replacement therapy.  
a 
Note that if it has been less than 6 weeks post-surgical bilateral oophorectomy 
with or without hysterectomy, she will be required to use contraception until she has 
reached 6 weeks since the procedure. 
b 
For the purpose of defining the length of time of amenorrhea to determine 
postmenopausal status, only count time in which the woman was not taking 
medications such as oral contraceptives, hormones, gonadotropin-releasing hormone, 
anti-estrogens, SERMs, or chemotherapy that could induce transient amenorrhea. 
5.2. 
Exclusion Criteria  
Participants are excluded from the study if any of the following criteria apply: 
Type of Participant and Disease Characteristics 
[7] 
Exclusion criterion [7] has been deleted due to redundancy with Inclusion Criteria [2] and 
[3]. 
[8] 
Exclusion criterion [8] has been deleted due to redundancy with Inclusion Criterion [3]. 
[9] 
Had a reported SAE in originator study or developed other condition prior to AMAX 
Week 0 that would disqualify them from treatment with mirikizumab according to 
originator study criteria. 
[10] 
Had permanently discontinued study drug in the originator study or had a temporary 
interruption of study drug in originator study such that, in the opinion of the investigator 
or sponsor, restarting of mirikizumab would pose an unacceptable risk for the participant 
in Study AMAX. 
Medical Conditions 
[11] 
Presence of significant uncontrolled neuropsychiatric disorder or judged at risk of suicide 
in the opinion of the investigator 
OR 
marked “yes” to 
 on 
ideation prior to dosing at Week 0 
OR 
marked “yes” to suicide behaviors prior to dosing at Week 0 
AND 
the ideation or behavior occurred within the past month. 
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[12] 
Have an unstable or uncontrolled illness, including, but not limited to, cerebro-
cardiovascular, respiratory, gastrointestinal (excluding CD), hepatic, renal, endocrine, 
hematologic or neurological disorders, or abnormal laboratory values that developed 
prior to dosing at Visit 1 that, in the opinion of the investigator or sponsor, would pose an 
unacceptable risk to the participant if investigational product continues to be 
administered. 
[13] 
Are diagnosed with any medical condition (or signs or symptoms thereof), including 
developing malignancy or suspicion of active malignant disease prior to dosing at Visit 1 
of AMAX, which would have precluded enrollment in the prior originator study or would 
have required discontinuation. 
[14] 
Have been diagnosed with serious infection (including, but not limited to, hepatitis B, 
hepatitis C, human immunodeficiency virus (HIV), and active tuberculosis [TB]) during 
the originator study or prior to dosing at Visit 1 of AMAX. 
 
Note: Participants with a history of active TB with documentation of treatment by the 
World Health Organization (WHO) and/or Centers for Disease Control and Prevention 
(CDC) criteria prior to the originator study are not excluded from the study. 
[15] 
Have been diagnosed with latent tuberculosis infection (LTBI) during an originator study 
or prior to dosing at Visit 1 of AMAX and is not willing to comply with completing TB 
treatment as appropriate (see Section 8.2.6 for TB prophylaxis details). 
[16] 
Have a known hypersensitivity to any component of mirikizumab or has experienced an 
acute systemic hypersensitivity event with previous study drug administration in the 
originating study that precludes mirikizumab therapy. 
[17] 
Have any other condition that, in the opinion of the investigator, renders the participant 
unable to understand the nature, scope, and possible consequences of the study or 
precludes the participant from attending study visits, completing study procedures, or 
adhering to prohibited concomitant medication requirements (See Section 10.7, 
Appendix 7). 
General Exclusion Criteria 
[18] 
Are pregnant, lactating, or planning to become pregnant while enrolled in the study or 
within 16 weeks after receiving the last dose of study drug. 
[19] 
Exclusion criterion [19] has been deleted since surgical interventions of concern during 
originator trials would have been addressed previously. 
[20] 
Intend to receive a Bacillus Calmette Guerin (BCG) vaccination or a live attenuated 
vaccine during the study.  
[21] 
Have any history or current evidence of cancer of the gastrointestinal tract. 
[22] 
Have any current sporadic colonic adenomatous polypa ≤10 mm that has not been 
removed. Once completely removed, the participant may be eligible for the study 
provided the histology report confirms no or low-grade dysplasia and absence of 
malignancy. 
 
a pedunculated or sessile polypoid, with a dome-shaped and symmetric contour, smooth 
surface, and well-delineated border in the non-colitic area 
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[23] 
Have any adenomatous polyp (including sporadic) >10 mm, dysplasia (low grade* or 
high grade) in GI tract, or presence of any serrated lesion (with or without dysplasia). 
 
*Note: except for low-grade sporadic colonic adenomatous polypa ≤10 mm once 
completely removed (per [22] above) 
 
a pedunculated or sessile polypoid, with a dome-shaped and symmetric contour, smooth 
surface, and well-delineated border which occurred in the non-colitic area 
[24] 
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. 
[25] 
Requires parenteral nutrition delivered by central vein and/or central venous catheter for 
venous access or receives enteral feeding as the primary source of their diet with limited 
oral intake. 
[26] 
Are a Lilly employee, employee of a third-party organization involved with the study, or 
investigator site personnel directly affiliated with this study and/or their immediate 
families. 
[27] 
Are unsuitable for inclusion in the study in the opinion of the investigator or sponsor for 
any reason that may compromise the participant’s safety or confound data interpretation. 
This includes participants who use marijuana (both recreational and medicinal uses 
[including cannabidiol oil]). Marijuana use must be stopped prior to screening and is 
prohibited for duration of the long-term extension period of the study. 
5.3. 
Lifestyle Considerations  
In order to participate in the study, the participants must agree to the contraception, reproduction, 
and breastfeeding criteria detailed in the inclusion and exclusion criteria. Study participants 
should be instructed not to donate blood or blood products during the study or for 16 weeks 
following study drug administration. 
5.4. 
Screen Failures  
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently enrolled in the study due to failing one or more eligibility criteria. A minimal 
set of screen failure information is required to ensure transparent reporting of screen failure 
participants to meet the Consolidated Standards of Reporting Trials publishing requirements and 
to respond to queries from regulatory authorities. Minimal information includes demography, 
screen failure details, eligibility criteria, and any SAE. 
Participants who sign informed consent to enter Study AMAX but do not subsequently enroll 
should receive safety follow-up per the originator trial protocol. 
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6. 
Study Intervention  
Study intervention is defined as any medicinal product(s) or medical device(s) intended to be 
administered to or used by a study participant according to the study protocol. 
6.1. 
Study Intervention(s) Administered  
The doses and routes of administration reflect the multipart study design (Section 4.1). 
This table lists the intervention used in this clinical study 
Intervention Name 
Mirikizumab 
Dosage Level(s) 
Route of Administration 
IV infusion or SC injection 
Authorized as defined by EU 
Clinical Trial Regulation 
Authorized in EU and not used according to the marketing 
authorization 
Packaging and Labeling 
Study interventions will be supplied by the sponsor in accordance with current Good 
Manufacturing Practice. Study interventions will be labeled as appropriate for country 
requirements. 
All investigational products will be stored, inventoried, reconciled, and destroyed according to 
applicable regulations. Clinical trial materials are manufactured in accordance with current Good 
Manufacturing Practices. 
 
Single-use solution vial containing mirikizumab with study-specific labels. 
o The 
 vial of mirikizumab is manufactured to deliver 
 
 
Single-use solution prefilled syringe containing mirikizumab. 
o The 
 syringe of mirikizumab is manufactured to deliver 
 
o The 
 syringe of mirikizumab is manufactured to deliver 
 
Vials and syringes will be supplied in cartons, with the appropriate quantity specific to the 
planned dispensing schedule. Investigational product will be provided with study-specific labels. 
Preparation and Administration 
Sites must have resuscitation equipment, emergency medications, and appropriately trained staff 
available during the infusion and monitoring period. All participants should be monitored for 
1 hour or longer after IV dosing, according to investigator practice or local standard of care. 
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Detailed instructions for investigational product administration will be provided by the sponsor, 
and the investigational product will be administered at the site only by clinical staff until Visit 4, 
at which time site staff will train participants on self-injection and will provide them with a log 
to track their doses at home. If the participant or caregiver is not able or willing to administer any 
dose throughout the study, the study site staff may administer that injection. Also, as noted in 
Inclusion Criterion 4, the sponsor may approve a general exception for self-administration for a 
participant depending on circumstances. In this situation, the reason will be documented. 
Participants will return to the site for administration by site staff, and will complete the Patient 
Study Drug Administration Log. 
For those participants who choose self-administration of syringes, at Visit 4, site personnel will 
administer the first injection, and then the participant/caregiver will administer the second 
injection with guidance from the site personnel. Following Visit 4, injections will be self-
administered SC by the participant or caregiver as specified in the SoA (Section 1.3). 
Participants will self-administer 
 
. Following training, injections will be 
self-administered per the study schedule without clinical intervention and participants will 
document information related to dosing in the provided Patient Study Drug Administration Log. 
The log will collect information including whether the participants were able to successfully 
self-administer the full dose of mirikizumab
 
). Participants will 
record the time when each of the 2 injections were administered. 
In the AMAX clinical study, a product usability study is being conducted on a subset of 
participants to assess the effectiveness of self-administration of mirikizumab by participants or 
caregivers in a home/office setting. 
Refer to the appropriate Manual Syringe Directions for Use provided by the sponsor for the 
investigational product. Note that in the case a study drug injection is performed in an arm, it is 
not to be given in the same arm from which participant blood samples, including PK samples, are 
drawn at relevant visits. 
Study Drug Administration Logs will be dispensed to each participant for recording pertinent 
data about each injection; details of the use of these logs are provided in Section 6.1.1. Possible 
injection sites are identified in the Manual Syringe Directions for Use. The injection site may be 
rotated to another area for subsequent doses. 
Time of Doses 
The actual time of all dose administrations will be recorded in the participant’s electronic case 
report form (eCRF). 
Investigator Responsibilities 
The investigator or his or her designee is responsible for the following, in addition to the study 
intervention responsibilities listed in Sections 6.1.1, 6.2, and 6.4: 
 
explaining the correct use of the investigational interventions to the site personnel 
 
ensuring that participants are dosed with the correct 
 
 Please refer to the 
supplemental training materials. 
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 
verifying that instructions are followed properly 
 
maintaining accurate records of investigational product dispensing and collection, and 
 
at the end of the study, returning all unused medication to Lilly or its designee, unless the 
sponsor and sites have agreed all unused medication is to be destroyed by the site as 
allowed by local law. 
6.1.1. 
Study Drug Administration Log  
Training for self-administration will begin at Visit 4 (or earliest opportunity if not at Visit 4).  
A paper Study Drug Administration Training Log will be completed at training. Subsequent 
injections will be self-administered SC by the participant or caregiver as specified in the SoA 
(Section 1.3). If the participant or caregiver is not able to administer any dose throughout the 
study, the study site staff may administer that injection. 
If an injection is missed, sites should contact their clinical research associate for further 
instructions. 
A paper Study Drug Administration Log (or Study Drug Administration Training Log for the 
training visit) will be completed for each injection from Week 12 of study participation. The data 
from the Log must be transcribed into the eCRF by site personnel. 
Participants will be instructed to contact their study site in the event of an injection problem. In 
addition, site personnel will review all Study Drug Administration Logs at each visit to identify 
any product complaints, and they will complete a product complaint form for each operation 
failure reported on a Study Drug Administration Log (see Section 8.3.8 for additional 
instructions regarding complaint handling). 
6.2. 
Preparation/Handling/Storage/Accountability  
The investigator or his or her designee is responsible for the following: 
 
confirming appropriate temperature conditions have been maintained during transit for all 
study treatment received and any discrepancies are reported and resolved before use of 
the study treatment 
 
ensuring that only participants enrolled in the study may receive study treatment and only 
authorized site staff may supply or administer study treatment when applicable. All study 
treatments 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, and 
 
the investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study treatment accountability, reconciliation, and record maintenance 
(such as receipt, reconciliation, and final disposition records). 
Detailed instructions regarding supplies and preparation and handling of mirikizumab will be 
provided by the sponsor. 
Investigational products (interventions) will be supplied in accordance with current GMP and 
will be supplied with lot numbers, expiry dates, and certificates of analysis, as applicable. 
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6.3. 
Measures to Minimize Bias: Randomization and Blinding  
This is an open-label study. 
6.4. 
Study Intervention Compliance  
Detailed instructions for investigational product administration, including infusion rate and SC 
injections, will be provided separately by the sponsor. 
Every attempt will be made to select participants 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 participant. 
In particular, the investigator is responsible for ensuring that study participants receive adequate 
training on and appropriate understanding of 
 
the importance of complete bowel prep prior to colonoscopies 
 
how to evaluate their CD symptoms and to record them on the eDiary, paper diary, or 
questionnaires. 
 
the importance of being compliant with the daily eDiary or paper diary recording, and 
 
SC self-administration by the participant or caregiver. 
If a participant is noncompliant with study procedures and/or investigational product 
administration, the investigator should assess the participant to determine the reason for 
noncompliance and educate and/or manage the participant, as appropriate, to improve 
compliance. 
If, in consultation with Lilly or its designee, the noncompliance is deemed to be significant or if 
further noncompliance occurs, the participant may be discontinued. See Section 7.1.2 for 
treatment noncompliance leading to permanent discontinuation from study drug. 
6.5. 
Concomitant Therapy  
Recording of Information about Concomitant Medications 
All concomitant medications, including vaccinations and endoscopy preparation medications 
taken during the study, must be recorded on the Concomitant Medication eCRF. This includes 
concomitant medications for CD, underlying conditions or diseases, and AEs. 
Use of Concomitant Medications during the Study 
All participants are encouraged to maintain their usual medication regimens for concomitant 
conditions or diseases throughout the study unless those medications are specifically prohibited 
(Section 10.7, Appendix 7). 
6.5.1. 
Permitted Therapy  
Participants taking permitted CD concomitant medications other than oral corticosteroids are 
recommended to keep doses stable unless modifications are needed due to AEs or for appropriate 
medical management. For participants entering AMAX on corticosteroids for CD, corticosteroids 
should remain stable until Week 12 unless modifications are needed due to medical necessity. 
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After Week 12, corticosteroid tapering will occur as described in Section 6.5.3. Instructions 
regarding guidance for use are detailed in Section 10.8, Appendix 8. 
6.5.2. 
Prohibited Therapy  
Use of prohibited medications should not be withheld if, in the opinion of the investigator, 
failure to prescribe them would compromise participant safety. Participants who require a 
prohibited medication should be discontinued from study drug as described in Section 7.1.2 and 
should complete an early termination visit (ETV) and posttreatment follow-up visits as described 
in the SoA (Section 1.3). Some exceptions (IV corticosteroid, systemic corticosteroids for 
non-CD indications, and marijuana) may not necessarily result in discontinuation. Consult the 
medical monitor prior to discontinuing the participant (see Section 10.7, Appendix 7). 
If a concomitant medication is needed to treat an AE or for appropriate medical management, the 
investigator should base decisions on the participant and clinical factors, considering the list of 
prohibited medication. 
Vaccinations 
Use of BCG vaccination is prohibited throughout the duration of the study and for 12 months 
after discontinuation of study drug. 
Use of live, attenuated vaccines are prohibited during the study and for 3 months after 
discontinuation of study drug. 
Use of nonlive (killed, inactivated, subunit, and RNA-based) vaccinations are allowed; however, 
their efficacy with concomitant mirikizumab is unknown. 
For More Information 
The list of prohibited medications is provided in Section 10.7, Appendix 7. 
The list of permitted medications with dose stabilization guidance is provided in Section 10.8, 
Appendix 8. 
6.5.3. 
Corticosteroid Taper  
For participants who enter AMAX on corticosteroids, corticosteroid tapering as described below 
should be initiated or continued for participants who at the discretion of the investigator have 
achieved clinical response at Week 12. Instructions regarding guidance for use are detailed in 
Section 10.8, Appendix 8. For participants who cannot tolerate the corticosteroid taper without 
recurrence of clinical symptoms, corticosteroid taper may be paused and/or corticosteroid dose 
may be increased up to the original dose at baseline. The oral corticosteroid dose, however, may 
not be increased above the baseline dose in originator study unless due to medical necessity. 
For participants who previously have tapered off corticosteroids but have recurrence of 
symptoms during study AMAX necessitating reintroduction of corticosteroids, this is allowed, 
however the dose may not be increased above the baseline dose in originator study, unless due to 
medical necessity. 
Additionally, for participants who were not on oral corticosteroids during the originator study, 
oral corticosteroids may not be initiated, unless due to medical necessity. 
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For participants who have not begun corticosteroid tapering at Week 12 or participants who start 
corticosteroids after Week 12, tapering should be considered over the course of the study as soon 
as the participant demonstrates clinical response. Investigators must contact the Study Medical 
Monitor to discuss any participant who does not initiate CS tapering upon achieving clinical 
response. 
The recommended tapering schedule for oral corticosteroids (other than budesonide) is as 
follows; however, investigators may taper steroids as clinically feasible and appropriate: 
 
Dose >10 mg/day prednisone or equivalent: taper daily dose by 5 mg/week until 
receiving 10 mg/day, and then continue tapering at 2.5 mg/week until 0 mg/day. 
 
Dose ≤10 mg/day prednisone or equivalent: taper daily dose by 2.5 mg/week until 
0 mg/day. 
For participants receiving oral budesonide, the recommended tapering schedule is having their 
dose tapered by 3 mg every 3 weeks until 0 mg/day. 
6.7. 
Management of Hypersensitivity, Infusion-Related Events, Infusion 
Site Reactions, and Injection Site Reactions  
During and after study drug administration, participants should be closely monitored for signs or 
symptoms of AEs, including hypersensitivity events, other infusion-related events, and infusion 
or injection site reactions. See Section 8.3.7.2 for more information about blood sampling and 
data collection. 
Hypersensitivity Events 
If a participant experiences a systemic hypersensitivity reaction involving 2 or more organ 
systems (that is, mucocutaneous, respiratory, cardiovascular, or gastrointestinal systems) during 
or up to 6 hours after an infusion of study drug, the following guidance should be followed: 
 
Study drug infusion should be stopped immediately, and appropriate supportive care 
provided according to local standard practice (for example, administration of epinephrine, 
antihistamine, systemic steroids, and/or bronchodilators). 
 
After the participant’s stabilization, blood samples should be obtained as described in the 
SoA (Section 1.3). 
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Note: Results from PK, immunogenicity, 
 are not 
intended for participant management and will not be provided to investigative sites. The 
participant should be monitored until resolution or stabilization of the symptoms, as 
clinically appropriate. 
 
Study drug should be discontinued (Section 7.1.2). The participant should undergo an 
ETV and posttreatment follow-up procedures after study drug discontinuation. 
For severe/generalized nonsystemic hypersensitivity reactions involving a single organ system 
(e.g., diffuse rash), all of the above should be followed, except the participant may be allowed to 
continue in the study. Continuation of a participant in the clinical study based on the 
investigator’s assessment of the event must be discussed and agreed upon with the medical 
monitor. If it is agreed the participant can continue, premedication prior to subsequent study drug 
administration may be considered, if judged by the investigator to be appropriate for the 
individual participant. 
Other Infusion-Related Events 
If a participant experiences a reaction consisting of headache, rigors, and/or temperature >38°C 
(in the absence of signs or symptoms of a systemic hypersensitivity reaction) during or up to 
6 hours after an infusion of study drug, the following guidance should be followed: 
 
The study drug infusion should be interrupted, and appropriate medical care should be 
administered (for example, non-steroidal anti-inflammatory drugs, antipyretics, or 
antihistamines). 
 
Blood samples should be obtained as described in Section 8.3.7.2 or the SoA 
(Section 1.3). 
 
Resumption of study drug infusion after interruption, possibly at a slower rate of 
administration, can be considered if symptoms resolve and it is deemed to be medically 
appropriate based on the investigator’s discretion and considering the risk/benefit of 
readministration. 
 
Premedication prior to subsequent study drug administration may be considered if judged 
by the investigator to be appropriate for the individual participant. 
 
If the participant develops systemic hypersensitivity symptoms or signs, he or she should 
be managed as described above for a systemic hypersensitivity reaction. The participant 
should remain in observation, as is clinically appropriate for the participant’s symptoms. 
Injection Site Reactions or Infusion Site Reactions 
If a participant experiences an injection site reaction or an infusion site reaction, such as pain, 
erythema, urticaria, pruritus, or edema localized to the SC injection or infusion site (in the 
absence of systemic hypersensitivity signs or symptoms), the following guidance should be 
followed: 
 
The participant should be instructed to contact the study site to report any symptoms 
experienced following a SC injection or an infusion site reaction. 
 
If the participant develops systemic hypersensitivity symptoms, he or she should be 
managed as described above for a systemic hypersensitivity reaction. 
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6.7.1. 
Premedication for Infusions or Injections 
Premedication for the study drug infusions or injections is not planned. Any premedication for 
infusions or injections should be discussed with the medical monitor. Any premedication given 
will be documented as a concomitant therapy (Section 6.5). Systemic corticosteroids may be 
permitted if deemed necessary by the investigator. 
6.8. 
Intervention after the End of the Study  
6.8.1. 
Treatment after Study Completion  
Mirikizumab will be made available by sponsor to eligible study participants, who complete 
Visit 19 
 through the optional Continued Access Period until local commercial 
availability of mirikizumab and reimbursement, including patient access programs, when and 
where available. Refer to Section 10.13 for more information on continued access. 
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7. 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal  
These sections describe reasons for: 
 
permanent or temporary discontinuation of study drug, or 
 
participant’s discontinuation (withdrawal) from the study. 
Discontinuation of the study as a whole or of particular study sites is described in Section 10.1.9. 
7.1. 
Discontinuation of Study Intervention  
Study drug may be permanently discontinued or temporarily withheld during the study. 
Participants who permanently discontinue study drug early will undergo ET procedures, which 
include: 
 
an ETV, and 
 
posttreatment follow-up visits (Visit 801 and Visit 802). 
The investigator will complete any AE reporting and necessary follow-up (Section 8.3). 
7.1.1. 
Liver Chemistry Stopping Criteria  
Participants who are discontinued from study drug because of a hepatic event or liver test 
abnormality should have additional hepatic safety data collected via the hepatic eCRF packet. 
Interrupting study drug based on elevated liver tests 
The study drug should be interrupted and 
 
if one or more of these conditions occur: 
Elevation 
Exception 
ALT or AST >8x ULN 
 
ALT or AST >5x ULN for more than 2 weeks 
 
ALT or AST >3x ULN and either TBL >2x ULN or 
INR >1.5  
For participants with Gilbert’s syndrome:  
If baseline direct bilirubin is >0.5 mg/dL, then 
doubling of direct bilirubin should be used for drug 
interruption decisions rather than TBL>2x ULN. 
ALT or AST >3x ULN with the appearance of fatigue, 
nausea, vomiting, right upper quadrant pain or 
tenderness, fever, rash, and/or eosinophilia (>5%) 
 
ALP >3x ULN, when the source of increased ALP is 
the liver 
 
ALP >2.5x ULN and TBL > 2x ULN  
For participants with Gilbert’s syndrome:  
If baseline direct bilirubin is >0.5 mg/dL, then 
doubling of direct bilirubin should be used for drug 
interruption decisions rather than TBL>2x ULN. 
ALP >2.5x ULN with the appearance of fatigue, 
nausea, vomiting, right upper quadrant pain or 
tenderness, fever, rash, and/or eosinophilia (>5%) 
 
Source: FDA Guidance for Industry: Drug-Induced Liver Injury: Premarketing Clinical Evaluation, July 2009 
and other consensus guidelines, with minor modifications 
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Resuming study drug after elevated liver tests 
Resumption of the study drug can be considered only in consultation with the Lilly-designated 
medical monitor and only if the liver test results return to baseline and if a self-limited non-drug 
etiology is identified. Otherwise, the study drug should be discontinued. 
7.1.2. 
Permanent Discontinuation  
Possible reasons leading to permanent discontinuation of study drug include, but are not limited 
to: 
Subject Decision 
 
The participant requests to discontinue the study drug. 
Disease Worsening 
 
The participant requires treatment with a specified prohibited CD medication 
(Section 10.7, Appendix 7). 
 
The participant undergoes surgery for CD (with the exception of drainage of a perianal or 
other cutaneous abscess or seton placement). 
Safety Considerations 
 
The participant 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 any colonic adenomatous polyp with low grade dysplasia, not completely 
removed,  
o any adenomatous polyp with high grade dysplasia   
o evidence of dysplasia in non-polypoid mucosa (indefinite for dysplasia, low 
grade, or high-grade dysplasia) in the GI tract 
o active TB (Section 8.2.6) 
o HIV/acquired immunodeficiency syndrome (AIDS) 
o hepatitis B or development of detectable hepatitis B virus (HBV) DNA under 
specified circumstances (Section 8.2.8), or 
o hepatitis C or development of detectable hepatitis C virus (HCV) RNA 
(Section 8.2.9). 
 
If the investigator determines that a systemic hypersensitivity reaction has occurred 
related to study intervention administration, the participant may be permanently 
discontinued from the study intervention, and the sponsor’s designated medical monitor 
should be notified. If the investigator is uncertain about whether a systemic 
hypersensitivity reaction has occurred and whether discontinuation of study intervention 
is warranted, the investigator may consult the sponsor. 
 
The participant has absolute lymphocyte count <0.5 × 103/μL after retesting (see 
Section 7.1.3). 
 
The participant has liver chemistry levels outside acceptable ranges that fail to meet the 
criteria for resumption of study drug as described in Section 7.1.1. 
 
The participant becomes pregnant. Pregnant participants will not undergo an endoscopy 
at the ETV (Section 8.1.1.2). 
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 
Noncompliance with LTBI treatment (see Section 8.2.6). 
 
The participant has an AE or SAE which, in the opinion of the investigator or sponsor, 
would preclude the participant from continuing to receive study drug. 
 
It is recommended that the participant be assessed by an appropriately trained 
professional to assist in deciding whether the participant is to be discontinued if: 
o 
 
 
 
o the participant reports suicidal ideation or suicidal behaviors during the study. 
Other Reasons 
 
Treatment noncompliance:
 
(Section 6.4). 
 
Study participants and physicians may discontinue the study participation if they perceive 
no clinical benefit. 
Participants discontinuing from the study drug prematurely for any reason will complete AE and 
other follow-up procedures as specified in the SoA (Section 1.3), Section 8.2 (Safety 
Assessments), and Section 8.3 (Adverse Events and Serious Adverse Events), including ETV 
and posttreatment follow-up visits (Visit 801 and Visit 802). 
7.1.3. 
Criteria for Temporary Interruption (Withholding) of Study Drug  
Cases that may merit temporary withholding of study drug must be discussed with the medical 
monitor. The medical monitor, in consultation with the investigator, will determine when it is 
appropriate to recommence study drug. 
Some possible reasons for temporarily withholding of study drug include, but are not limited to: 
 
The participant develops a clinically important intestinal or extraintestinal infection 
(including LTBI) during the study (see Section 5.2). 
 
The participant requires major surgery. Administration of study drug may be restarted 
only after adequate wound healing. 
 
The participant develops a confirmed absolute neutrophil count <1 × 109/L (<1 × 103/μL 
or <1 GI/L (2 assessments below this threshold). 
 A participant who develops an absolute lymphocyte count <500 cells/µL (<0.5 × 103/µL 
or <0.50 GI/L) will be retested every 2 weeks for up to 8 weeks unless the lymphocyte 
count becomes ≥0.5 × 103/µL or ≥0.50 GI/L. 
o Azathioprine, methotrexate, or 6-mercaptopurine must be discontinued, if 
applicable, after the first retest confirming absolute lymphocyte count 
<0.5 × 103/L (second assessment below threshold), and the next dose of study 
drug held. The participant must be retested in approximately 2 weeks. 
o The third retest (fourth assessment below threshold) should occur prior to the 
next monthly dosing and if still below <0.5 × 103/L, the next dose of study drug 
should also be held. The participant must be retested in approximately 2 weeks. 
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o After the fourth retest (fifth assessment below threshold), the participant may be 
permanently discontinued. Consult the medical monitor. White blood cell and 
lymphocyte counts will be followed for these participants until they return to an 
acceptable level. 
 
The participant has laboratory abnormalities that may lead the investigator to hold the 
study drug until resolution of the abnormalities. 
7.2. 
Participant Discontinuation/Withdrawal from the Study  
Participants 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 practice (GCP) 
 
the investigator decides that the participant should be discontinued from the study 
 
all participants from originator Study AMAM 
 
 
 and enter the 12- to 16-week 
posttreatment follow-up period, or 
 
the participant requests to be withdrawn from the study. 
Participants discontinuing from the study prematurely for any reason should have AE and other 
safety follow-up specified for the ETV. See Section 1.3 (Schedule of Activities), Section 8.2 
(Safety Assessments), and Section 8.3 (Adverse Events and Serious Adverse Events). 
7.3. 
Lost to Follow up  
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. Site personnel are expected to 
make diligent attempts to contact participants who fail to return for a scheduled visit or were 
otherwise unable to be followed up by the site. 
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8. 
Study Assessments and Procedures  
Study procedures and their timing, including tolerance limits for timing, are listed in the SoA 
(Section 1.3). Adherence to the study design requirements, including those specified in the SoA, 
is essential and required for study conduct. 
The disease activity measurements are used in clinical practice and CD clinical trials. 
The safety parameters in this study are routine elements of clinical health assessment and 
Phase 3 drug development. 
Safety concerns should be discussed with the sponsor immediately upon occurrence or awareness 
to determine whether the participant should continue or discontinue study drug. 
All screening criteria evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. Timing to receive results and to retest if needed should be 
considered when scheduling. If the available screening laboratory results are from samples taken 
more than 
 prior to Visit 1 dosing, new labs should be collected again prior to dosing. 
The investigator will maintain a screening log to record details of all participants screened and to 
confirm eligibility or record reasons for screening failure, as applicable. 
Unless otherwise stated in the subsections below, all samples collected for specified laboratory 
tests will be destroyed within 60 days 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. 
8.1. 
Efficacy Assessments  
The following table defines efficacy endpoints used in this study. 
Endpoint 
Definition 
Endoscopic 
response 
Endoscopic 
remission 
 
Clinical remission 
by PRO 
Clinical response 
by PRO 
Clinical remission 
by CDAI 
 
Abbreviations: 
; CDAI = Crohn’s Disease Activity Index; PRO = patient-reported outcome; 
. 
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8.1.1. 
Primary Efficacy Assessment  
The primary endpoints are clinical remission by CDAI and endoscopic response by SES-CD at 
Week 52 of AMAX. 
Clinical Remission 
The CDAI is an 8-item disease activity measure comprised of a composite of 3 patient-reported 
and 5 physician-reported/laboratory items (physical signs and a laboratory parameter 
[hematocrit]). Patient responses are summed over a 7-day period, and all items are subsequently 
weighted, yielding a total score range of 0 to 600 points. See Section 10.9, Appendix 9, for 
additional descriptions of PROs (CDAI-SF, CDAI-AP, and CDAI-well-being). 
Endoscopic Response 
Endoscopic response is based on the SES-CD score (Vuitton et al. 2016) and is defined in the 
table in Section 8.1. 
The SES-CD tool will be utilized by central readers to evaluate the endoscopy video that is 
collected during the participant’s endoscopic examination. The SES-CD is discussed further in 
Section 8.1.1.1. 
Refer to Sections 8.1.1.2 and 8.1.1.3 for more information on endoscopy and endoscopic 
biopsies. 
8.1.1.1. 
Simple Endoscopic Score for Crohn’s Disease  
The SES-CD (Daperno et al. 2004) is an endoscopic scoring system for CD based on 
4 endoscopic variables (presence and size of ulcers, proportion of surface covered by ulcers, 
proportion of surface affected by disease, and presence and severity of stenosis) which are 
assessed in 5 ileocolonic bowel segments (ileum, right colon, transverse colon, left colon, and 
rectum). Each of the 4 endoscopic variables is scored from 0 to 3: presence and size of ulcers 
(none = score 0; diameter 0.1 cm to 0.5 cm = score 1; 0.5 cm to 2 cm = score 2; >2 cm = score 
3), extent of ulcerated surface (none = 0; <10% = 1; 10% to 30% = 2; >30% = 3), extent of 
affected surface (none = 0; <50% = 1; 50% to 75% = 2; >75% = 3), and presence and type of 
narrowing (none = 0; single, can be passed = 1; multiple, can be passed = 2; cannot be 
passed = 3). The grand total is obtained as the sum of all endoscopic scores across all bowel 
segments. Scores range from 0 to 56, with higher scores indicating more severe disease. 
8.1.1.2. 
Endoscopy  
The endoscopy completed at Week 52 of AMAM 
 
 
Endoscopies will be performed on all AMAM participants at Week 52 a
 
of Study AMAX. 
AMAG participants who are entering AMA
 
 participants will 
have an endoscopy performed 
 of Study 
AMAX. 
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Investigators may use these endoscopies to perform surveillance for dysplasia or colorectal 
cancer locally, according to national and international guidelines. 
For both AMAG and AMAM participants, an ET endoscopy should only be performed if the 
visit occurs 
 after the last endoscopy. An ET endoscopy will not be performed 
during the follow-up period. 
Unscheduled endoscopies can be performed at the principal investigator’s discretion if deemed 
clinically appropriate. 
To ensure quality data and standardization, endoscopy will be performed locally at clinical sites 
per the study schedules and use the same endoscopist throughout the trial wherever possible. The 
endoscopist will be a licensed physician who is qualified by education, training, and experience 
to perform colonoscopies. Investigators may delegate endoscopy to other members of the study 
team. 
The SES-CD will be determined by central readers blinded to study treatment f
 
 and for evaluation of 
endoscopic efficacy endpoints during the trial. A detailed imaging review charter from the 
central reading laboratory will outline the endoscopic procedures, video recordings, and 
equipment to be used for video capture and transmission of endoscopic recordings. For each 
participant, video recording of the entire endoscopic procedure will be performed using a storage 
medium provided by the sponsor or designee. The endoscopic recordings will be read centrally 
in a blinded manner by qualified gastroenterologists according to the image review charter. 
For each visit with an endoscopy, it is recommended that the endoscopy be performed on a 
separate day from the vital signs and study questionnaires, and IP administration, within the visit 
window, with the endoscopy (with or without sedation) preceding the other activities. However, 
if they must be performed on the same day due to logistical issues, the following order of 
procedures must be followed: (1) Measurement of vital signs and collection of responses to 
questionnaires; (2) Administration of IP with protocol-specific observation period (at least 1 
hour); (3) Performance of endoscopy with or without sedation. 
If a participant becomes pregnant during the study, no additional endoscopies will be performed. 
8.1.1.3. 
Endoscopic Biopsies  
Biopsies will be collected during the endoscopy procedure. Biopsies will be used to support 
assessment of the 
 (Section 8.1.3). The biopsy samples will be sent to 
the central study laboratory for processing. To ensure quality data and standardization, bowel 
tissue 
 The details of biopsy 
sample collection will be provided in both the imaging manual and laboratory manual. Detailed 
endoscopy and 
 charters outline the procedures to be used for secure specimen 
transfer, 
 
These results will not be made available to study sites during the study. 
At the scheduled endoscopies, additional biopsies may be taken as clinically indicated for 
participant management. These specimens will be sent to a local laboratory. Any clinically 
significant findings must be recorded as an AE on the eCRF. 
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Samples will be retained at a facility selected by Lilly or its designee for a maximum 15 years 
after the last participant visit for the study, or for a shorter period if local regulations and ERBs 
impose shorter time limits. 
8.1.2. 
Secondary Efficacy Assessments  
8.1.2.2. 
PROs  
Participants Originating from AMAM 
The following PROs will be collected from Week 0 through Week 12: 
 
Daily via patient eDiary 
o 
 
o CDAI-SF 
Note: Bristol Stool Scale is used as a reference to complete CDAI-SF 
o CDAI-AP 
o CDAI-well-being 
o 
o 
o 
 
At scheduled visits via paper questionnaire 
o 
 
o Inflammatory Bowel Disease Questionnaire (IBDQ) 
o 
o 
o 
Participants Originating from AMAG 
The following PROs will be collected at scheduled visits from Week 0 through Week 12: 
 
via patient 1-Day and/or 14-Day paper diary or paper questionnaire 
o 
 
o CDAI-SF 
Note: Bristol Stool Scale is used as a reference to complete CDAI-SF. 
o CDAI-AP 
o CDAI-well-being 
o 
o 
o IBDQ. 
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All Participants from AMAG and AMAM 
The following PROs will be collected at scheduled visits from Week 16 through study 
completion: 
 
via patient 1-Day and/or 14-Day paper diary or paper questionnaire 
o 
 
o CDAI-SF 
Note: Bristol Stool Scale is used as a reference to complete CDAI-SF. 
o CDAI-AP 
o CDAI-well-being 
o 
o 
o 
o IBDQ. 
As noted in Section 6.4, the investigator is responsible for ensuring that study participants 
receive adequate training on the eDiary, paper diary, and paper questionnaires, and have 
appropriate understanding of how to evaluate their CD symptoms and to record them. 
See Section 10.9, Appendix 9 for details on the above PROs. 
8.1.2.3. 
Inflammatory Biomarkers  
High-Sensitivity C-Reactive Protein 
High-sensitivity 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). 
High-sensitivity C-reactive protein will be obtained at time points described in the SoA 
(Section 1.3). 
Investigators will be blinded to high-sensitivity C-reactive protein results until after AMAM 
database lock. 
Fecal Calprotectin 
Fecal calprotectin is a complex consisting of the calcium-binding proteins S100A8 and S100A9 
(Sands 2015). It is expressed by activated neutrophils (and to a lesser extent by macrophages and 
monocytes), and fecal calprotectin levels correlate with the number of neutrophils in the gut. It is 
used as a biomarker of intestinal inflammation in clinical practice. Fecal calprotectin will be 
obtained at time points described in the SoA (Section 1.3). 
Investigators will be blinded to fecal calprotectin results until after AMAM database lock. 
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8.1.3. 
Exploratory Assessments  
Other exploratory endpoints, including 
, will be defined in the statistical 
analysis plan (SAP). 
8.2. 
Safety Assessments  
Visits and Order of Safety Assessments 
Safety assessments occur at visits specified in the SoA (Section 1.3). When multiple assessments 
are scheduled for the same visit, the preferred order of completion is: 
 
vital signs first 
 
electrocardiogram (ECG) (if applicable), and then 
 
blood sampling last. 
Adverse event collection should occur before the collection of the 
 
(Section 8.2.11 and Section 8.3.2.1). 
Data Collection and Reporting 
The AE data collection and reporting requirements are described in Section 8.3. The additional 
requirements for collection of data regarding AESIs are noted in Section 8.3.7. 
Safety Monitoring 
The sponsor will periodically review evolving aggregate safety data within the study by 
appropriate methods. In the event that safety monitoring uncovers an issue that needs to be 
addressed by unblinding at the individual or group level, additional analyses of the safety data 
can be performed by members of the DMC (Section 10.1.5, Appendix 1) or by the sponsor 
through its internal review committee process. 
8.2.1. 
Vital Signs  
Measurements of vital signs (body temperature, blood pressure, and pulse rate) will be conducted 
at the study visits specified in the SoA (Section 1.3). 
Sitting blood pressure and pulse rate should be measured after the participant has been sitting for 
at least 5 minutes. Sitting blood pressure and pulse rate should be obtained at approximately the 
same time of day as ECG measurements and/or blood sampling. When multiple assessments are 
scheduled for the same visit, the preferred order of completion is: Vital signs, ECG (if 
applicable), then blood sampling. 
Any clinically significant findings from vital sign measurements that result in a diagnosis and/or 
treatment that occur after the participant receives the first dose of study drug should be reported 
to Lilly or its designee as an AE via eCRF. 
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8.2.2. 
Physical Examinations  
Physical examinations are mandated and will be performed as specified in the SoA (Section 1.3). 
Physical examinations can also be performed at the discretion of the investigator at any 
additional time points; for example, to assist in the evaluation of a new symptom during the 
study. 
Physical examinations should include a symptom-directed evaluation as well as an examination 
of eyes, heart, lungs, abdomen, and a visual examination of the skin. 
For participants with a risk factor, a thorough exam to evaluate for TB will be performed 
(Section 8.2.6). 
Any clinically significant findings from physical examination that result in a diagnosis and/or 
treatment and that occurs after the participant receives the first dose of study drug should be 
reported to Lilly or its designee as an AE via eCRF. 
8.2.3. 
Electrocardiograms  
Electrocardiograms (12-lead) will be conducted at the study visits specified in the SoA 
(Section 1.3). 
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. 
Electrocardiograms will be read locally. 
Any clinically significant findings from ECGs that result in a diagnosis and that occur after the 
participant receives the first dose of study drug should be reported to Lilly or its designee as an 
AE via eCRF. 
8.2.4. 
Chest Radiography  
A posterior-anterior chest x-ray (CXR), interpreted and reported by a radiologist or 
pulmonologist, will be obtained if there are relevant TB-related physical findings or other factors 
that the investigator feels warrant testing and imaging, as specified in the SoA (Section 1.3) and 
Section 8.2.6. A lateral CXR can also be obtained if, in the opinion of the investigator, a lateral 
view is indicated. A computed tomography (CT) scan can be performed as an alternative to the 
CXR based on regional standard of practice. An IGRA or TST should also be performed 
(Section 8.2.6). 
8.2.5. 
Stool Testing  
Stool Culture 
Stool culture/testing is allowed at the investigator’s discretion. 
C. difficile Toxin 
A stool sample for C. difficile toxin (toxins A and B, and glutamate dehydrogenase, with reflex 
to polymerase chain reaction testing as needed) is allowed at the investigator’s discretion. 
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8.2.6. 
Tuberculosis Testing  
Initial Screening 
All participants will be evaluated for risk factors for LTBI at rollover from their originator 
studies during the AMAX Visit 1 (Section 10.5, Appendix 5). If the participant has risk factors 
or any TB-related signs or symptoms are identified as part of the discussions of preexisting 
conditions or as part of the standard physical exam, the investigator should conduct a thorough 
physical examination, including body temperature measurement and assessment of peripheral 
lymph nodes. For participants with relevant TB-related physical findings or other factors that the 
investigator feels warrant testing and imaging: 
 a TB test should be performed: 
o IGRA (for example, QuantiFERON-TB Gold or TSPOT.TB), or 
o Tuberculin skin test (TST; also called a purified protein derivative [PPD] or 
Mantoux test). 
Note: 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. 
If participant has a history of positive TB test result with prophylaxis, TB testing should 
not be performed unless advised to do so based on local guidelines (See also section on 
Prior Treatment for LTBI). 
 a CXR should be performed, as described in Section 8.2.4. A CT scan may be performed 
as an alternative to the CXR based on regional standard of practice. 
Tests for Immune Response to Mycobacterial Antigens 
In people aged 5 years and over, IGRA is the preferred screening test for LTBI and should be 
performed for LTBI screening in this study in preference to the TST. Interferon gamma release 
assay is also the preferred screening test for LTBI in participants who have received a BCG 
vaccination. In countries where the TST is available and is preferred (in the judgment of the 
investigator) as an alternative screening test for LTBI, that test may be used instead of an IGRA 
for appropriate participants. 
Interpretation of Tests for LTBI 
The QuantiFERON-TB Gold assay will be reported as negative, indeterminate, or positive. The 
T-SPOT.TB assay will be reported as negative, borderline, or positive. 
The TST should be read 48 to 72 hours after test application. Skin induration ≥5 mm in diameter 
is interpreted as positive for the purpose of this study, regardless of BCG vaccination history. 
Retesting and Confirmatory Testing 
One retest is allowed for participants with an “indeterminate” QuantiFERON-TB Gold assay or 
“borderline” T-SPOT.TB assay. Participants with 2 indeterminate QuantiFERON-TB Gold 
assays, 2 borderline T-SPOT.TB assays, or 1 indeterminate QuantiFERON-TB Gold assay plus 
1 borderline T-SPOT.TB assay will be excluded. 
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Confirmatory testing with an IGRA is allowed for selected participants who have a positive 
QuantiFERON-TB Gold assay, positive T-SPOT.TB assay, or positive TST who meet all 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 Section 10.5, Appendix 5. 
If the confirmatory test is positive, the participants will be excluded from the study unless he or 
she completes at least 4 weeks of appropriate therapy for LTBI (see TB Screening Outcomes and 
Enrollment below). If the confirmatory test is negative, these results will be discussed with the 
medical monitor in order to determine eligibility for the study. 
Participants with a negative TST or IGRA can be retested 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. 
TB Screening Outcomes and Enrollment 
Participants who are negative for LTBI and active TB may be enrolled in the trial (Section 5.2). 
Participants diagnosed with LTBI at screening, based on a positive IGRA test result or a positive 
purified protein derivative response ≥5 mm of induration, and no evidence of active TB, may be 
enrolled in the study if treatment with mirikizumab is initially withheld and 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 4 weeks of appropriate ongoing prophylactic therapy for LTBI 
based on national or international guidelines, for example, United States CDC (2016) or 
the WHO (2018), with documentation of having completed the appropriate TB 
prophylaxis regimen 
 
no evidence of reactivation of LTBI, and 
 
no evidence of hepatotoxicity (ALT and AST levels must remain ≤2 × ULN) upon 
retesting of serum ALT and AST levels after at least 4 weeks of prophylaxis, before 
mirikizumab dosing. 
Such participants 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. 
Participants diagnosed with active TB at screening will be excluded (see Active TB section 
below). 
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Monitoring for TB during the Study 
For all participants, monitoring for TB is to be continuous throughout the study. Every 2 to 
3 months as indicated in the SoA, the participants will be assessed for risk factors for TB 
(Section 10.5, Appendix 5). If the participant has a risk factor or any TB-related signs or 
symptoms identified as part of the AE discussions or standard physical exam, the investigator 
should conduct a thorough exam to evaluate for TB, including examination of peripheral lymph 
nodes and documentation of body temperature. If there are relevant physical findings or other 
factors that the investigator feels warrant testing and imaging, an IGRA OR TST and CXR 
should be performed. A CT scan can be performed as an alternative to the CXR, based on 
regional standard of practice. 
Participants diagnosed with active TB during the study will be discontinued and should be 
referred for appropriate treatment (see Active TB section below). 
Diagnosis of LTBI During the Study 
Participants diagnosed with LTBI after enrollment in the study, based on a positive IGRA test 
result or a positive purified protein derivative response ≥5 mm of induration, and no evidence of 
active TB, will temporarily discontinue investigational product and be offered treatment, if 
clinically appropriate. These participants can be considered for resumption of investigational 
product after completing the first 4 weeks of appropriate ongoing prophylactic therapy for LTBI 
based on national or international guidelines (for example, United States CDC [2016] or the 
WHO [2018]) and if they have no evidence of treatment hepatotoxicity (ALT and AST levels 
must remain ≤2 × ULN). These participants must continue with and complete a full course of 
treatment for LTBI in order to continue investigational product. Noncompliance with LTBI 
treatment during the study is a reason for permanent discontinuation from study drug. 
Household Contact 
Throughout the study, participants who have had household contact with a person with active TB 
must be evaluated for TB infection. 
Prior Treatment for LTBI 
Participants 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 participants should not 
undergo TST or IGRA testing unless advised to do so based on local guidelines. 
Active TB 
Participants with a past history of active TB without documented treatment by WHO and/or 
CDC criteria are excluded from the study (Section 5.2). 
Participants diagnosed with active TB at screening will be excluded (Section 5.2) and should be 
referred by the investigator for appropriate TB treatment and follow-up. 
If a participant is diagnosed with active TB during the study, the study drug will be permanently 
discontinued (Section 7.1.2), and the participant will undergo an ETV and then enter the 12- to 
16-week posttreatment follow-up period. The participant should also be referred by the 
investigator for appropriate TB treatment and follow-up. 
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8.2.7. 
Clinical Safety Laboratory Assessments  
Visits and Times 
The clinical laboratory tests listed in Section 10.2 will be conducted at the study visits specified 
in the SoA (Section 1.3). 
Retesting for study entry is allowed 1 time prior to dosing at Visit 1 of Study AMAX. 
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. 
Except where otherwise stated, samples for laboratory tests should be collected prior to dosing. 
Central and Local Testing 
Unless noted as locally performed (for example, urine pregnancy tests), clinical laboratory tests 
will be sent to a central laboratory for testing. 
Provision of Laboratory Test Results 
With the exception of laboratory test results that may unblind the originator Study AMAM 
(Section 8.1.2.3), Lilly or its designee will provide the investigator with the results of laboratory 
tests analyzed by a central vendor. 
Investigator Responsibilities 
The investigator must review the laboratory reports in a timely manner throughout the study. 
Investigators must document this review and record any clinically relevant changes occurring 
after the participant receives the first dose of study drug in the AE section of the CRF. 
The laboratory reports must be filed with the source documents. Clinically significant abnormal 
laboratory findings are those which are not associated with the underlying disease, unless judged 
by the investigator to be more severe than expected for the participant's condition. All laboratory 
tests with values considered clinically significantly abnormal during participation in the study or 
during the 12- to 16-week follow-up period should be repeated until the values return to normal 
or baseline or are no longer considered clinically significant by the investigator or medical 
monitor. If such values do not return to normal/baseline within a period of time judged 
reasonable by the investigator, the etiology should be identified, and the sponsor notified. 
All protocol-required laboratory assessments, as defined in Section 10.2, Appendix 2, must be 
conducted in accordance with the laboratory manual and the SoA. If laboratory values from 
nonprotocol specified laboratory assessments performed at the institution’s local laboratory 
require a change in participant management or are considered clinically significant by the 
investigator (for example, SAE, AE, or dose modification), then the results must be recorded in 
the case report form (CRF). 
8.2.7.1. 
Pregnancy Testing  
Pregnancy testing is to be performed on all women unless they meet the criteria describing 
women not of childbearing potential, as outlined in Section 5.1. Participants who are pregnant 
will be discontinued from the study (Section 7.1.2). 
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Visits and Times 
Urine pregnancy testing will be performed locally during designated scheduled visits through 
Week 156. The urine pregnancy test must be “negative” within 24 hours prior to administration 
of study drug. 
Between visits, urine pregnancy tests are to be performed prior to monthly at-home dosing. 
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 local serum pregnancy test is an acceptable 
alternative. 
Assessment of follicle-stimulating hormone levels can assist in determining if a woman meets 
the definition of “postmenopausal” as outlined in Section 5.1. Follicle-stimulating hormone can 
be optionally obtained during study entry procedures at the discretion of the investigator. 
Follicle-stimulating hormone can also be optionally obtained during the study to determine 
postmenopausal status (see Section 1.3). 
8.2.8. 
Hepatitis B Testing  
HBV Screening and Interpretation 
Participants with acute or chronic hepatitis B infection are excluded from the study (see 
Section 5.2). 
Screening for HBV in this study is performed as follows: an initial test for hepatitis B surface 
antigen (HBsAg) and hepatitis B core antibody (HBcAb), followed by a test for HBV DNA in 
participants who are HBsAg-, HBcAb+. Participants testing HBcAb+ in the originator study do 
not need to have HBV full screening at Visit 1, but they will need to have HBV DNA testing at 
screening, as well as HBV DNA monitoring throughout the trial, as described below. 
Exclusion Based on HBV Serology and HBV DNA Testing 
Participants with the following screening test results will be excluded from the study 
(Section 5.2). 
 
HBsAg+, irrespective of HBcAb result, or 
 
HBsAg-, HBcAb+ with detectable HBV DNA. 
Participants Potentially Allowed into the Study, Based on HBV Serology and HBV DNA 
Testing 
Participants with the following screening test results may be eligible for inclusion, provided they 
meet the other study entry criteria: 
 
HBsAg-, HBcAb-, or 
 
HBsAg-, HBcAb+ with no HBV DNA detected. 
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Management of participants with the following HBV serology from the originator study or at 
Week 0 of AMAX (or found to have the following serology at any time during AMAX) will 
undergo HBV DNA monitoring as described in the SoA (Section 1.3): 
 
HBsAg-, HBcAb+, HBV DNA not detected   
In addition, if such participants experience an elevated ALT or AST level >3 × ULN during the 
study, they must have an HBV DNA test and be managed appropriately based on the results of 
that test. 
Management of Participants with Detectable HBV DNA during the Study 
Please contact medical monitor for any scenarios not covered below. 
If a participant develops detectable but not quantifiable HBV DNA: 
 
Withhold the study drug.  
 
Repeat HBV DNA, HBsAg, ALT, AST, TBL within 2 weeks and again 2 weeks later, at the central 
laboratory, if possible. However, if central laboratory collection is not possible due to extenuating 
circumstances, and after consultation with the medical monitor, local laboratories may be used to 
facilitate the patient’s compliance. Results should be reported in the Local Laboratory Tests CRFs 
under the Hepatic visit for tests where data collection fields exist. 
 
If the repeat HBV DNA is undetectable, or detectable but not quantifiable, on 2 consecutive retests 
(for a total of 3 consecutive tests), and the participant remains asymptomatica with no elevation in 
liver testsb, the study drug can be resumed with close monitoring of HBV DNA and liver tests.  
 
The investigator should wait for the results of both HBV DNA tests before making a decision on 
resuming the study drug.  
 
HBV DNA, ALT, AST, TBL should be monitored at least once-monthly in the 3 months after the 
last detectable HBV DNA result and every 3 months thereafter.  
 
If one of the subsequent HBV DNA results again becomes detectable and not quantifiable, but the 
participant remains asymptomatic with normal liver tests, continue the study drug, and increase 
monitoring frequency of HBV DNA, ALT, AST, and TBL to once-monthly.  
 
If one of the repeat HBV DNA results is detectable and quantifiable, follow the instructions below, 
for participants with detectable and quantifiable HBV DNA. 
If a participant develops detectable and quantifiable HBV DNA: 
If the participant is asymptomatica and liver 
tests are not elevatedb:  
 
Withhold the study drug.  
 
Repeat HBV DNA, HBsAg, ALT, AST, 
and TBL within 2 weeks.  
 
Inform the Lilly-designated medical 
monitor.  
 
Refer to a hepatologistc for further 
management, including initiation of a 
nucleoside/nucleotide analog (NA). 
If the participant is symptomatica, or if ALT, AST, or 
TBL are elevatedb:  
 
Withhold the study drug.  
 
Repeat HBsAg, ALT, AST, and TBL within 48 to 
72 hours to determine if the levels are increasing 
or decreasing.  
 
Continue monitoring liver tests 1 to 3 times 
weekly according to the protocol requirements for 
treatment-emergent abnormal liver tests.  
 
Inform the Lilly-designated medical monitor. 
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 
Continue monitoring HBV DNA, HBsAg, 
ALT, AST, and TBL every 2 weeks. If 
HBV DNA is undetectable in 3 consecutive 
tests, and liver tests are not elevatedb, 
monitoring frequency can decrease to once 
every 1 to 2 months. 
 
Refer to a hepatologist for further management, 
including initiation of a nucleoside/nucleotide 
analog (NA).  
 
Continue monitoring HBV DNA, and HBsAg, 
every 2 weeks. If liver tests are back to baseline, 
and HBV DNA is undetectable in 3 consecutive 
tests, monitoring frequency can decrease to 
once-monthly. 
Resumption of the study drug in participants with detectable and quantifiable HBV DNA:  
Resumption of the study drug after interruption for detectable and quantifiable HBV DNA, can be 
considered only:  
 
in asymptomatica participants without concurrent elevatedb liver tests, or in whom there was a 
clear alternative cause for the elevations, and they have returned to baseline  
 
in consultation with the Lilly-designated medical monitor, and  
 
only after the participant was seen by a hepatologistc and NA has been initiated.  
If the above criteria are met:  
 
the study drug can be restarted 7 days after NA initiation.  
 
If NA was initiated and the study drug was resumed, HBV DNA, HBsAg, ALT, AST, and TBL 
should be monitored at least monthly initially.  
 
After HBV DNA is undetectable in 3 consecutive tests, monitoring frequency can be decreased to 
every 2 to 3 months.  
Permanent discontinuation of the study drug in participants with detectable and quantifiable 
HBV DNA: 
The study drug should be permanently discontinued if any of the following occurs: 
 
HBV DNA is detectable and quantifiable with concurrent elevationb of ALT, AST, or TBL for 
which there is no clear alternate cause.  
 
HBV DNA is detectable and quantifiable with concurrent symptomsa that are considered by the 
investigator to be related to HBV reactivation.  
 
HBV DNA viral load is >100 IU/mL on 2 or more tests. 
HBV DNA is detectable and quantifiable, but participant does not start NA treatment. 
Duration of HBV DNA monitoring and NA prophylaxis in participants with detectable and 
quantifiable HBV DNA: 
 
HBV DNA monitoring should continue for at least 6 months after the last dose of the study drug.  
 
If NA was initiated and the study drug was resumed, NA treatment and HBV DNA monitoring 
should continue for at least 6 months after the last dose of the study drug.  
 
The participant should be referred to a hepatologistc for continued follow-up and management 
after study participation.  
a Symptoms may include worsening fatigue, nausea, vomiting, abdominal discomfort, jaundice, fever, or rash.  
b ALT, AST, or TBL elevation refers to elevations ≥2x ULN in participants with normal baseline or near normal 
baseline (i.e., <1.5x ULN) or elevation ≥2x baseline in participants with elevated baseline (i.e., ≥1.5x ULN). In 
participants with Gilbert’s syndrome, isolated hyperbilirubinemia may be up to 3x ULN provided that direct 
bilirubin is no higher than 30% of the total.  
c A hepatologist may include a health care provider with recognized expertise in the assessment and management 
of viral hepatitis. 
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If the study drug must be discontinued per guidelines above, the participant will have an ETV. 
The participant will then enter the posttreatment follow-up period (Section 7.1). Prior to 
discontinuing investigational product (IP), the sponsor recommends that a hepatologist (or a 
physician with expertise in viral hepatitis) is consulted and that it is determined whether it is 
appropriate to start antiviral therapy prior to discontinuation of IP or any immunosuppressant or 
immunomodulatory therapy. However, study drug should not be administered until this 
consultation has been completed and after discussion with the medical monitor. Such participants 
should also receive appropriate follow-up medical care. 
If HBV DNA is detected during the study, the investigator should consider using one of the 
following terms to report the AE: 
 
“Detectable HBV DNA” if HBV DNA is detected without an increase in 
aminotransferase levels. 
 
“Reactivation of hepatitis B” if HBV DNA is detected and quantifiable in concert with an 
increase in aminotransferase levels and/or symptoms and signs of liver disease. 
8.2.9. 
Hepatitis C Testing  
Participants with current hepatitis C infection are excluded from the study (see Section 5.2). 
Screening for HCV in this study is performed as follows: an initial test for HCV antibody, 
followed by a test for HCV RNA if the HCV antibody test is positive. Participants with a 
positive HCV antibody test and detectable HCV RNA will be excluded from the study 
(Section 5.2). 
Participants who test negative for HCV antibody will not be tested for HCV RNA and may be 
eligible for inclusion in the study. 
Participants who have spontaneously cleared hepatitis C infection, defined as: 
 
a positive HCV antibody test, and 
 
a negative HCV RNA test, with no history of anti-HCV treatment, 
may be eligible for inclusion in the study, provided they have no detectable HCV RNA on 
screening for this study. 
Any participant with a history of hepatitis C infection who develops elevated ALT >3 × ULN 
within the study will be tested for HCV RNA. 
Participants with a previous diagnosis of hepatitis C who have been treated with antiviral therapy 
and achieved a sustained virologic response may be eligible for inclusion in the study, provided 
they have no detectable HCV RNA at screening. Sustained virologic response is defined as an 
undetectable HCV RNA level 24 weeks after completion of a full, documented course of an 
approved, potentially curative antiviral therapy for HCV. 
If a participant is diagnosed with hepatitis C during the study (detectable HCV RNA), the study 
drug will be discontinued, and the participant will have an ETV. The participant will then enter 
the posttreatment follow-up period (Section 7.1). Such participants should also receive 
appropriate follow-up medical care. 
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8.2.11. 
Depression, Suicidal Ideation, and Behavior Risk Monitoring  
Suicide-related events (behavior and/or ideations) will be assessed at screening with the 
administration of the 
 
Depressive symptomology will be assessed with the 
at the visits specified in the 
SoA (Section 1.3). 
These assessments are described below, and further information is provided in Section 10.9, 
Appendix 9. 
See Section 8.3.2.1 for information about AE collection relative to collection of the 
 
 
See Section 7.1.2 for information regarding discontinuation of study drug for participants who 
have suicidal ideation or suicidal behaviors. 
8.3. 
Adverse Events and Serious Adverse Events  
Investigators are responsible for monitoring the safety of participants 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 participant. 
The investigator is responsible for the appropriate medical care of participants during the study. 
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 participant to discontinue the investigational product 
before completing the study. The participant should be followed until the event resolves, 
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stabilizes with appropriate diagnostic evaluation, or is otherwise reasonably explained. The 
frequency of follow-up evaluations of the AE is left to the discretion of the investigator. 
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 informed consent form (ICF) is signed, study site personnel will record via eCRF the 
occurrence and nature of each participant’s pre-existing conditions, including clinically 
significant signs and symptoms of the disease under treatment in the study. 
In addition, after the first dose of study drug, site personnel will record any change in the 
condition(s), including exacerbation of CD, and any new conditions as AEs. Also, if an AE 
occurs after signing the AMAX ICF, but prior to receiving investigational product, and is 
considered reasonably possibly related to an AMAX study procedure, the AE should be reported 
as an AE in AMAX. Any other events/diagnoses that start after signing AMAX consent but 
before first AMAX dosing should be recorded in the AMAX MH eCRF. 
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 treatment, 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 participant’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 (see Section 8.3.2.1). 
8.3.1. 
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, or 
 
important medical events that may not be immediately life-threatening or result in death 
or hospitalization, but may jeopardize the participant 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 
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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. 
As described in Section 8.3, all AEs occurring after the participant receives the first dose of 
AMAX study drug are recorded as AEs in the AMAX eCRF and they will be assessed for 
serious criteria. The SAE reporting to the sponsor begins after the participant has signed the 
AMAX ICF and has received AMAX investigational product. However, if an SAE occurs after 
signing the AMAX ICF, but prior to receiving investigational product, the SAE should be 
reported to the sponsor as per SAE reporting requirements and timelines (see Section 8.3.2) if it 
is considered reasonably possibly related to an AMAX study procedure. 
Study site personnel must alert Lilly or its designee of any SAE within 24 hours of investigator 
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. Participants with a serious hepatic AE should have additional data collected using 
the hepatic eCRF packet (see Section 8.2.10). 
Pregnancy (during maternal or paternal exposure to investigational product) does not meet the 
definition of an AE. However, for tracking purposes, any pregnancy should be reported 
following the SAE process to collect data on the outcome for both mother and fetus through the 
pregnancy outcome, generally no longer than 6 to 8 weeks past the estimated due date. 
8.3.1.1. 
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, European Union Clinical Trial Regulation 536/2014 [submission 
of SUSARs to the EudraVigilance database], and the associated detailed guidance or national 
regulatory requirements in participating countries require the reporting of SUSARs. The sponsor 
has processes for safety reports for the identification, recording, and expedited reporting of 
SUSARs according to EU regulatory requirements. 
8.3.2. 
Time Period and Frequency for Collecting AE and SAE Information  
Adverse events occurring after the participant has signed the AMAX ICF, but prior to AMAX 
study drug administration, will be recorded as AEs in the originating study and transcribed as 
pre-existing/medical history in the AMAX eCRF (except where reasonably possibly related to an 
AMAX study procedure, as described in Section 8.3). All AEs occurring after the participant 
receives the first dose of AMAX study drug are recorded as AEs in the AMAX eCRF and 
assessed for serious criteria. Investigators are not obligated to actively seek AEs or SAEs in 
participants once the participant has discontinued and/or completed the study (the participant 
disposition eCRF has been completed). However, if the investigator learns of any SAE, including 
a death, at any time after a participant has been discharged from the study and the investigator 
considers the event reasonably possibly related to the study treatment or study participation, the 
investigator must promptly notify Lilly. 
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8.3.2.1. 
AE Monitoring with a Systematic Questionnaire  
Spontaneous AE collection should occur prior to the collection of the 
 
If a suicide-related event is discovered during the 
 but was not captured during the 
spontaneous AE collection, sites should not change the AE form. However, if an event is serious 
or leads to discontinuation, the event should be included on the AE form, and the process for 
reporting SAEs, if applicable, should be followed. 
8.3.3. 
Follow-Up of AEs and SAEs  
The investigator responsibility for follow-up of AEs sand SAEs is described in Section 8.3. 
8.3.4. 
Regulatory Reporting Requirements for SAEs  
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a study 
intervention under clinical investigation are met. 
The sponsor has a legal responsibility to notify all applicable regulatory agencies about the safety 
of a study intervention under clinical investigation. The sponsor will evaluate the reported SAEs, 
including confirmation of relatedness and assessment of expectedness. The sponsor will comply 
with applicable regulatory requirements relating to safety reporting to the regulatory authority 
(United States 21 CFR 312.32, European Union Clinical Trial Regulation 536/2014 [submission 
of SUSARs to the EudraVigilance database], and national regulatory requirements in other 
participating countries), IRB/IEC, and investigators in the participating regions and countries. 
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators as necessary. Refer to Section 
8.3.1.1 for details for regulatory reporting requirements of SUSARs. 
An investigator who receives an investigator safety report describing a SAE or other specific 
safety information (e.g., summary or listing of SAEs) from the sponsor will review and then file 
it along with the appropriate Reference Safety Information, for example, in the IB, and will 
notify the IRB/IEC, if appropriate, according to existing requirements.  
8.3.5. 
Pregnancy  
 
For all pregnancies occurring at any point after the start of study intervention in AMAX 
and until at least 16 weeks after the participant’s last dose of study drug, in both female 
participants and female partners of male participants, details will be collected 
(Section 8.3.1). 
 
After learning of a pregnancy in the female partner of a male study participant, 
the investigator will attempt to obtain a consent to release information from the 
pregnant female partner directly as required by local guidelines. 
 
The guidelines in some geographies may require additional consent from pregnant 
female participants. 
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 
If a pregnancy is reported, the investigator should record pregnancy information on the 
appropriate form and inform the sponsor within 24 hours of learning of the pregnancy. In 
addition, investigator should follow the procedures outlined in Section 10.3.5, 
Appendix 3 for SAEs (even though pregnancy is not considered an AE as described in 
Section 8.3.1). 
 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, or ectopic pregnancy) are considered SAEs. 
8.3.6. 
Cardiovascular and Death Events  
Cardiovascular AEs and other events leading to death are collected as described in Section 8.3 
and its subsections. 
. 
8.3.7. 
Adverse Events of Special Interest  
The AESIs for this program may include but are not limited to: 
Sites should collect additional details and data regarding AESIs, as instructed on the applicable 
eCRFs. 
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8.3.8. 
Complaint Handling  
A product complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, durability, reliability, safety, effectiveness, or performance of a 
trial intervention. 
Lilly collects product complaints on investigational products used in clinical studies in order to 
ensure the safety of study participants, monitor quality, and facilitate process and product 
improvements. 
Participants will be instructed to contact the investigator as soon as possible if the participant has 
a complaint or problem with the investigational product so that the situation can be assessed. 
NOTE: AEs/SAEs that are associated with a product complaint will also follow the processes 
outlined in Section 8.3 and Section 10.3 of the protocol. 
8.3.8.1. 
Follow-Up of Product Complaints  
 
Follow-up applies to all participants, including those who discontinue study intervention. 
 
The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the deficiency. 
 
New or updated information will be recorded on the originally completed form with all 
changes signed and dated by the investigator. 
8.3.8.2. 
Prompt Reporting of Product Complaints to Sponsor  
Product complaints will be reported to the sponsor according to the instructions in the product 
complaints form after the investigator determines that the event meets the protocol definition of a 
product complaint. 
8.4. 
Treatment of Overdose  
In the event of a suspected overdose, the investigator should 
1. contact the medical monitor and sponsor immediately 
2. closely monitor the participant for any AE/SAE and laboratory abnormalities 
(hematology, chemistry, vital signs, and oxygen saturation); supportive care should be 
provided as necessary, and 
3. document all AEs associated with the overdose in the eCRF. 
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant. 
There is no known antidote for mirikizumab. 
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8.5. 
Pharmacokinetics  
Visits and Times 
At the visits and times specified in the SoA (Section 1.3), venous blood samples will be collected 
to determine the serum concentrations of mirikizumab. 
 
Predose will be obtained per the SoA. 
 
The actual date and time (24-hour clock time) of dosing and sample collection will be 
recorded. 
Collection, Handling, and Storage of Samples 
Instructions for the collection and handling of blood samples will be provided by the sponsor. 
Samples will be analyzed at a laboratory approved by the sponsor and stored at a facility 
designated by the sponsor. Serum concentrations of mirikizumab will be determined using a 
validated enzyme-linked immunosorbent assay. The results will not be provided to the 
investigator. 
Additional Samples 
 
 
 In the case of systemic 
allergic/hypersensitivity reactions (Section 8.3.7.2), additional blood samples will be obtained, as 
described in the SoA (Section 1.3). 
Sample Retention 
Bioanalytical samples collected to measure investigational product concentration will be retained 
for a maximum of 1 year following the last participant visit for the study. 
8.6. 
Pharmacodynamics  
Pharmacodynamic parameters are not evaluated in this study. 
8.7. 
Genetics  
Genetics are not evaluated in this study. 
8.8. 
Biomarkers  
Biomarkers are listed in Section 10.2, Appendix 2. 
8.9. 
Immunogenicity Assessments  
Visits and Times 
At the visits and times specified in the SoA (Section 1.3), venous blood samples will be collected 
to determine antibody production against mirikizumab. 
 
Predose samples will be obtained per the SoA. 
 
The actual date and time (24-hour clock time) of each sample collection will be recorded. 
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To aid interpretation of these results, a predose blood sample for PK analysis will be collected at 
the same time points. 
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. Samples may be further evaluated for 
antibodies that neutralize the activity of mirikizumab. 
Treatment-emergent (TE) ADAs are defined in Section 9.4.6. 
Sample Retention 
Samples will be retained for a maximum of 15 years after the last participant visit, or for a 
shorter period if local regulations and ethical review boards 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 15 years will be destroyed. 
8.10. 
Medical Resource Utilization and Health Economics  
Sites should provide information regarding healthcare visits, including hospitalizations and 
surgeries for CD, as instructed on the eCRF. 
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9. 
Statistical Considerations  
9.1. 
Statistical Hypotheses  
No formal hypothesis testing will be conducted in this open-label trial. 
9.2. 
Sample Size Determination  
The sample size of Study AMAX will be determined by the number of participants who enroll in 
Study AMAX from the preceding studies (AMAM and AMAG). It is anticipated that 
approximately 50% to 70% of the participants from Study AMAM and Study AMAG will be 
enrolled. Based on this assumption, 640 to 900 participants are expected to enroll in Study 
AMAX. 
9.3. 
Populations for Analyses  
For purposes of analysis, the following populations are defined. 
Intent-to-Treat (ITT) Population 
The ITT population is defined as all participants who enter Study AMAX and receive a treatment 
assignment, even if the participant does not receive the correct treatment or otherwise does not 
follow the protocol. Participants will be analyzed according to the treatment to which they were 
assigned. 
Modified Intent-to-Treat (mITT) Population 
All participants from the ITT population who take at least 1 dose of study drug in Study AMAX. 
Primary Analysis Set 
All patients from the mITT population who h
 
 
Safety Population 
Same as mITT. 
9.4. 
Statistical Analyses  
9.4.1. 
General Considerations  
Statistical analysis of this study will be the responsibility of Lilly or its designee. 
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, such as the analysis method for the 
primary objective. 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. 
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The first version of the SAP will be finalized prior to First Patient Visit and it will include a 
more technical and detailed description of the statistical analyses described in this section. The 
SAP may be modified, as required, during the trial. This section is a summary of the planned 
statistical analyses of the most important endpoints, including primary and secondary endpoints. 
This is an open-label extension study with no randomization. Participants
 
r mirikizumab SC or to mirikizumab IV
 
 
herefore, no intervention 
comparisons will be done. Analyses and summaries will be focused on point estimates and 
confidence intervals. 
Efficacy summaries will be provided 
 using the primary 
analysis set (as described in Section 9.3) and will be summarized by intervention group and by 
the intervention received in the originating study. Select efficacy summaries may also be 
conducted in the mITT population. 
Safety summaries will be provided using the safety population (as described in Section 9.3) and 
will be summarized by originating study, intervention group, and the intervention received in the 
originating study. 
Handling of missing, unused, and spurious data is addressed prospectively in the overall 
statistical methods described in the protocol and in the SAP, where appropriate. Adjustments to 
the planned analyses are described in the final CSR. 
9.4.1.1. 
Analyses  
Continuous data will be summarized in terms of mean, standard deviation, median, and 
minimum and maximum values; categorical data will be summarized as frequency counts and 
percentages. 
For assessment of categorical efficacy and health outcome endpoints for participants from Study 
AMAM, proportions for each intervention group will be summarized by the intervention groups 
as defined in the SAP. The 95% confidence intervals will also be reported using the Wilson 
Score method (Wilson 1927, Newcombe 1998). Categorical repeated measure analyses such as 
the generalized linear model may be explored for selected endpoints. 
For continuous endpoints with more than 1 postbaseline timepoint, the least squares mean from a 
restricted maximum likelihood-based mixed-effects model of repeated measures (MMRM) with 
the corresponding 95% confidence interval may be summarized. The MMRM model will include 
baseline value, visit, intervention group as defined in the SAP, and visit by intervention group 
interaction. Alternative versions of MMRM may be implemented as deemed appropriate. Least 
squares means will be reported along with the 95% confidence interval. 
For continuous efficacy and health outcome variables for participants 
, the 
mean response will be estimated using analysis of covariance, including baseline value and 
intervention group as defined in the SAP. Least squares means will be reported along with the 
95% confidence intervals. Missing data imputation method for the analysis of covariance model 
will be specified in the SAP. 
Utilizing visualization tools will also be used to summarize the data as deemed appropriate. 
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9.4.1.2. 
Definition of Baseline  
Unless otherwise specified, all references to baseline for efficacy and health-outcome-related 
endpoints in this study refer to baseline values of the originating study (that is, the study in which 
the participant received their first dose for this program). Further details about baseline 
definitions along with any supportive analysis will be described in the SAP. 
9.4.1.3. 
Estimand  
The estimand (International Council for Harmonisation [ICH] 2017) associated with each 
endpoint/analysis is documented in the following places: 
 
The population of interest is described in the inclusion/exclusion criteria (Section 5.1 and 
Section 5.2) and in “Populations for Analyses” (Section 9.3) 
 
The endpoints are listed in Objectives and Endpoints (Section 3) 
 
The handling of intercurrent events is summarized in “Missing Data Imputation” 
(Section 9.4.1.4), and 
 
Population summary measures are described in “General Considerations” (Section 9.4.1) 
Additional details will be provided in the SAP. 
9.4.1.4. 
Missing Data Imputation  
While every effort will be made to reduce missing data, the missing data imputation methods 
described below will be used to assess the efficacy endpoints when participants are permanently 
discontinued from study drug or otherwise have missing data. 
 
Nonresponder imputation (NRI): For analysis of categorical efficacy and health outcomes 
variables, missing data will be imputed using an NRI method. Participants will be 
considered a Nonresponder for the NRI analysis if they 
o do not achieve the endpoint(s) being analyzed 
o have missing data at the time point of interest that results in nonassessment of 
(an) endpoint(s) at the time point of interest, or  
o discontinue treatment prior to the time point of interest due to reasons other than 
participants switching to commercially available mirikizumab or extraordinary 
circumstances, e.g., inability to supply study drug to a particular region 
 
Mixed-model for repeated measures: For continuous variables, the analysis may include 
the MMRM with the missing-at-random assumption for handling missing data. This 
analysis takes into account both missingness of data and the correlation of the repeated 
measurements. Additional details will be provided in the SAP.  
 
Modified Baseline Observation Carried Forward with ANCOVA: For continuous 
variables, single imputation will be used based on carrying the baseline observation 
forward. Additional details will be provided in the SAP. 
Additional details and sensitivity analyses, including imputed and observed data, will be 
specified in the SAP. 
Methodology to address missing data due to participants switching to commercially available 
mirikizumab or extraordinary circumstances, e.g., inability to supply study drug to a particular 
region, will be addressed in the SAP. 
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9.4.1.5. 
Multiple Comparisons/Multiplicity  
The data analyses and summaries will not include hypotheses testing, so no multiple 
comparisons adjustments will be considered for this open-label study. 
9.4.2. 
Treatment Group Comparability  
9.4.2.1. 
Participant Disposition  
The number of participants in the mITT/PAS population will be summarized for each originating 
study by AMAX study intervention and by the intervention assigned in the originating study. 
Frequency counts and percentages of all participants who complete the study or who discontinue 
the study or treatment intervention early will be presented. Reasons for early discontinuation of 
the study intervention or of the study will be summarized. 
9.4.2.2. 
Participant Characteristics  
Demographic and baseline characteristics will be summarized by intervention group and by the 
intervention in the originating study for the mITT population and primary analysis set; no testing 
will be performed for baseline characteristics. 
9.4.2.3. 
Concomitant Therapy  
Concomitant therapy will be collected at each visit, and the reported term will be classified by 
the WHO drug dictionary. A summary of preferred names of concomitant medication by study 
intervention group will be generated for the mITT population and primary analysis set. 
9.4.2.4. 
Treatment Compliance  
Deviations from the prescribed dosage regimen will be described in a patient listing. Additional 
details will be described in the SAP. 
9.4.3. 
Efficacy Analyses  
9.4.3.1. 
Primary Efficacy Analyses  
Primary efficacy analyses will be performed in the primary analysis set 
 
 
The co-primary objective is in participants who completed treatment 
 
Study AMAM and is comprised of two separate endpoints: 
 Proportion of participants achieving clinical remission by CDAI at Week 52 of AMAX 
 Proportion of participants achieving endoscopic response at Week 52 of AMAX 
Clinical remission by CDAI is defined as 
 where CDAI is calculated as a 
weighted sum of its 8 subscores: 3 patient-reported and 5 physician-reported/laboratory items. 
Endoscopic response is defined 
 
where the SES-CD Total Score will be calculated as the sum of its 5 subscores: ileum; right 
colon, transverse colon, left colon, and rectum. If at least 1 subscore is nonmissing, missing 
subscores will be imputed with a zero value when deriving the SES-CD Total Score. 
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The proportion of responders with associated confidence intervals will be provided following the 
methods specified in Section 9.4.1.1. 
9.4.3.2. 
Secondary Efficacy Analyses  
The secondary endpoints are specified in Section 3. 
Secondary endpoints will be analyzed following the methods described in Section 9.4.1.1. 
Additional analyses of the secondary efficacy and health outcome endpoints may be considered 
and will be fully detailed in the SAP. Additional endpoints may be prespecified in the SAP. 
9.4.4. 
Safety Analyses  
Safety endpoints are better assessed in the context of combining the safety data from the 
originating study with the safety data from this study. All safety data from this study will be used 
as part of integrated summaries. 
For the purposes of the CSR for Study AMAX alone, a listing and summary of SAEs and AEs 
leading to permanent discontinuation of study intervention will be created. 
The primary safety objective of the study is to accumulate long-term safety data for inclusion in 
integrated assessments of mirikizumab. 
Safety analyses will be performed in the safety population. 
The safety data from this study will also be used as part of ongoing safety reviews. 
9.4.5. 
Pharmacokinetic Analyses  
Analyses of PK data will be limited to graphical or tabular summaries of mirikizumab 
concentrations. No model-based analyses of the data are planned unless deemed necessary based 
on unanswered questions raised in preceding studies. Exploratory evaluations of the relationships 
between mirikizumab exposure and efficacy and safety may be performed. 
Additional analyses may be conducted if they are deemed appropriate. Data from this study may 
be combined with other study data, if appropriate. Further details on PK analyses will be 
provided in the PK analysis plan. 
9.4.6. 
Evaluation of Immunogenicity  
Immunogenicity will be evaluated cumulatively, using data both from the participant’s 
originating study and from the present study. Baseline for ADA assessment will be the baseline 
ADA assessment from the originating study, and postbaseline will be time after initiation of 
mirikizumab. 
The frequency and percentage of participants with pre-existing (baseline) ADA, ADA 
postbaseline, and with TE ADA to mirikizumab will be tabulated. If no ADAs are detected at 
baseline, TE ADAs are defined as those with a titer 2-fold (1 dilution) greater than the minimum 
required dilution of the assay. For samples with ADAs detected at baseline, TE ADAs are 
defined as those with a 4-fold (2 dilutions) increase in titer compared to baseline. For participants 
who have TE ADAs, the distribution of maximum titers will be described. 
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The frequency of neutralizing antibodies will also be tabulated. The relationship between the 
presence of antibodies and the PK parameters and pharmacodynamic response, including safety 
and efficacy to mirikizumab, will be assessed as deemed appropriate. 
9.4.7. 
Other Analyses  
9.4.7.1. 
Health Economics  
The health outcome and quality of life measures, including 
 
 and IBDQ, will be analyzed using methods described for continuous data 
as described for efficacy measures in Section 9.4.1.1. 
9.5. 
Interim Analyses  
Since this study is open-label, any permanent data snapshot or database lock will not require 
unblinding. PK, immunogenicity, biomarker, and hypersensitivity values taken prior to Week 12 
for AMAM originating participants are blinded in data transfer before AMAM primary endpoint 
database lock. Details can be found in the Blinding and Unblinding Plan. 
At least 1 interim analysis is planned to be conducted 
 
 Additional interim analyses 
may be performed as deemed appropriate or to fulfill the need of regulatory interactions or 
publication purposes. The final database lock will occur after the last participant has completed 
Study AMAX. 
Additionally, a DMC consisting of members external to Lilly will be established for interim 
safety monitoring across all the sponsor’s Phase 3 studies in participants with CD. See 
Section 10.1.5 for more information. 
9.6. 
Data Monitoring Committee  
For details on the DMC, refer to Section 10.1.5. 
A DMC consisting of members external to Lilly will be established for interim safety monitoring 
across all the sponsor’s Phase 3 studies in participants with CD. See Section 10.1.5 for more 
information. 
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10. 
Supporting Documentation and Operational Considerations  
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations  
10.1.1. 
Regulatory and Ethical Considerations  
 
This study will be conducted in accordance with the protocol and with 
o Consensus ethical principles derived from international guidelines, including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences International Ethical Guidelines 
o Applicable ICH GCP Guidelines 
o Applicable laws and regulations 
 
The protocol, protocol amendments, ICF, IB, and other relevant documents (e.g., 
advertisements) must be submitted to an IRB/IEC by the investigator and reviewed and 
approved by the IRB/IEC before the study is initiated. 
 
Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an 
immediate hazard to study participants. 
 
Protocols and any substantial amendments to the protocol will require health authority 
approval prior to initiation except for changes necessary to eliminate an immediate 
hazard to study participants. 
 
The investigator will be responsible for 
o Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC 
o Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
o Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local 
regulations. 
o Reporting to the sponsor or designee significant issues related to participant 
safety, participant rights, or data integrity. 
 
Investigator sites are compensated for participation in the study as detailed in the clinical 
trial agreement.  
10.1.2. 
Financial Disclosure  
Investigators and sub-investigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study. 
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10.1.3. 
Informed Consent Process  
 
The investigator or the investigator’s representative will explain the nature of the study to 
the participant or his or her legally authorized representative, explain the risks and 
benefits of participating in the study, and answer all questions regarding the study. 
 
Participants must be informed that their participation is voluntary. Participants or their 
legally authorized representative will be required to sign a statement of informed consent 
that meets the requirements of 21 CFR 50, local regulations, ICH guidelines, Health 
Insurance Portability and Accountability Act requirements, where applicable, and the 
IRB/IEC or study center. 
 
The medical record must include a statement that written informed consent was obtained 
before the participant participated in any study procedure or received the investigational 
intervention. The statement must include the date on which the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the 
ICF(s). 
 
Participants must be reconsented to the most current version of the ICF(s) during their 
participation in the study. 
 
A copy of each ICF must be provided to the participant or the participant’s legally 
authorized representative. A copy of each ICF is kept on file. 
10.1.4. 
Data Protection  
 
Participants will be assigned a unique identifier by the sponsor to protect the participant’s 
personal data. Any participant information, such as records, datasets, or tissue samples 
that are transferred to the sponsor will contain the identifier only. Participant names or 
any information which would make the participant identifiable will not be transferred. 
 
The participant must be informed that the participant’s personal study-related data will be 
used by the sponsor in accordance with local data protection law. The level of disclosure 
must also be explained to the participant who will be required to give consent for their 
data to be used as described in the informed consent. This is done by the site personnel 
through the informed consent process. 
 
The participant must be informed through the informed consent by the site personnel that 
their medical records may be examined by Clinical Quality Assurance auditors or other 
authorized personnel appointed by the sponsor, by appropriate IRB/IEC members, and by 
inspectors from regulatory authorities. 
 
The sponsor has processes in place to ensure information security, data integrity, and data 
protection. These processes address management of data transfer, and prevention and 
management of unauthorized access, disclosure, dissemination, alteration or loss of 
information or personal data. These processes include appropriate contingency plan(s) for 
appropriate and timely response in the event of a data security breach. 
 
The transfer of personal data is subject to appropriate safeguards through contractual 
agreements and processes. The sponsor’s processes are compliant with local privacy laws 
and relevant legislations, including the General Data Protection Regulation. 
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10.1.5. 
Committees Structure  
 
 
DMC 
A DMC consisting of members external to Lilly will be established. The purpose of the DMC is 
to conduct periodic monitoring of clinical trial data for the Phase 3 CD program. The DMC will 
consist of a minimum of 3 members, including a physician with expertise in gastroenterology 
and a statistician. 
No member of the DMC will have contact with study sites. A statistical analysis center (SAC) 
will prepare and provide unblinded data to the DMC. The SAC members may be Lilly 
employees or from third-party organizations designated by Lilly. The SAC members will be 
external to the study team and will have no contact with sites and no privileges to influence 
changes to the ongoing studies. The timing and frequency of the periodic clinical trial data 
review by the DMC will be detailed in a DMC charter. 
The DMC is authorized to evaluate unblinded interim efficacy and safety analyses. In addition, 
the DMC may request key efficacy data to put safety observations into context and to assess a 
reasonable benefit/risk profile for ongoing participants in the study. The DMC will make a 
recommendation to the Lilly Research Laboratories Senior Management Designee, who may 
order the immediate implementation of the DMC recommendation or may convene an internal 
review committee (IRC), which is independent from the study team, to review the 
recommendation according to standard Lilly policy. Study sites will receive information about 
interim results ONLY if it is required for the safety of their participants. 
10.1.6. 
Dissemination of Clinical Study Data  
Report Preparation 
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. 
Public Access to Reports and Data 
Reports 
The sponsor will disclose a summary of study information, including tabular study results, on 
publicly available websites where required by local law or regulation. 
The summary of results will be posted within the time frame specified by local law or regulation. 
If the study remains ongoing in some countries and a statistical analysis of an incomplete data set 
would result in analyses lacking scientific rigor (for example, underpowered) or compromise the 
integrity of the overall analyses (for example, trial not yet unblinded), the summary of results 
will be submitted within 1 year after the end of the study globally or as soon as available, 
whichever is earlier. 
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Data 
The sponsor provides access to all individual participant data collected during the trial, after 
anonymization, with the exception of PK data.  
Data are available to request 6 months after the indication studied has been approved in the US 
and EU and after primary publication acceptance, whichever is later. No expiration date of data 
requests is currently set once data are made available.  
Access is provided after a proposal has been approved by an independent review committee 
identified for this purpose and after receipt of a signed data sharing agreement.  
Data and documents, including the study protocol, SAP, CSR, and blank or annotated CRFs, will 
be provided in a secure data sharing environment for up to 2 years per proposal.  
For details on submitting a request, see the instructions provided at www.vivli.org. 
Publications 
For policies on publications, see Section 10.1.10. 
10.1.7. 
Data Quality Assurance  
 All participant data relating to the study will be recorded on printed or electronic 
CRFs unless transmitted to the sponsor or designee electronically (for example, 
laboratory data). The investigator is responsible for verifying that data entries are 
accurate and correct by physically or electronically signing the CRF. 
 The investigator must maintain accurate documentation (source data) that 
supports the information entered in the CRF. 
 The investigator must permit study-related monitoring, audits, IRB/IEC review, 
and regulatory agency inspections and provide direct access to source data 
documents. 
 Quality tolerance limits (QTLs) will be predefined to identify systematic issues 
that can impact participant safety and/or reliability of study results. These 
predefined parameters will be monitored during the study and important 
excursions from the QTLs and remedial actions taken will be summarized in the 
CSR. 
 Monitoring details describing strategy (for example, risk-based initiatives in 
operations and quality such as risk management and mitigation strategies and 
analytical risk-based monitoring), methods, responsibilities and requirements, 
including handling of noncompliance issues, and monitoring techniques are 
provided in the Monitoring Plan. 
 The sponsor or designee is responsible for the data management of this study 
including quality checking of the data. 
 The sponsor assumes accountability for actions delegated to other individuals (for 
example, contract research organizations). 
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 Study monitors will perform ongoing source data verification to confirm that data 
entered into the CRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of participants are 
being protected; and that the study is being conducted in accordance with the 
currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements. 
 Records and documents, including signed ICFs, pertaining to the conduct of this 
study must be retained by the investigator for the time period outlined in the 
Clinical Trial Agreement (CTA) unless local regulations or institutional policies 
require a longer retention period. No records may be destroyed during the 
retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. 
 In addition, sponsor or its representatives will periodically check a sample of the 
participant data recorded against source documents at the study site. The study 
may be audited by sponsor or its representatives, and/or regulatory agencies at 
any time. Investigators will be given notice before an audit occurs. 
Data Capture System 
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness 
of the data reported to the sponsor. 
An 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 (participant-focused outcome instrument) will be 
collected by the participant and investigator site personnel via a paper source document and will 
be transcribed by the investigator site personnel into the EDC system. See the SoA, Section 1.3, 
for which instruments are administered via paper source document. 
Additionally, electronic Clinical Outcome Assessment (eCOA) data (participant-focused 
outcome instrument) will be directly recorded by the participant and investigator site personnel 
into an instrument (for example, handheld smart phone or tablet). The eCOA data will serve as 
the source documentation and the investigator does not maintain a separate written or electronic 
record of these data. See the SoA, Section 1.3, for which instruments are administered via an 
eCOA instrument. 
Data collected via the sponsor-provided data capture system(s) will be stored at third parties. The 
investigator will have continuous access to the data during the study and until decommissioning 
of the data capture system(s). Prior to decommissioning, the investigator will receive an archival 
copy of pertinent data for retention. 
Data managed by a central vendor, such as laboratory test data, will be stored electronically in 
the central vendor’s database system and reports/electronic transfers will be provided to the 
investigator for review and retention. Data will subsequently be transferred from the central 
vendor to the sponsor data warehouse. 
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Data from complaint forms submitted to the sponsor will be encoded and stored in the global 
product complaint management system. 
10.1.8. 
Source Documents  
 
Source documents provide evidence for the existence of the participant and substantiate 
the integrity of the data collected. Source documents are filed at the investigator’s site. 
 
Data reported on the CRF or entered in the eCRF that are transcribed from source 
documents must be consistent with the source documents, or the discrepancies must be 
explained. The investigator may need to request previous medical records or transfer 
records, depending on the study. Also, current medical records must be available. 
 
The definition of what constitutes source data can be found in Section 10.1.7. 
10.1.9. 
Study and Site Start and Closure  
Study start 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
First act of recruitment 
The first act of recruitment is the opening of the first site. 
Study or site termination 
The sponsor or sponsor’s designee reserves the right to close the study site or terminate the study 
at any time for any reason at the sole discretion of the sponsor. Study sites will be closed upon 
study completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to: 
For study termination: 
 
Discontinuation of further study intervention development 
For site termination:  
 
Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the sponsor's procedures, or GCP guidelines 
 
Inadequate recruitment of participants by the investigator, or 
 
Total number of participants enrolled earlier than expected. 
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If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up. 
10.1.10. 
Publication Policy  
In accordance with the sponsor’s publication policy, the results of this study will be submitted 
for publication by a peer-reviewed journal. 
10.1.11. 
Investigator Information  
Researchers with appropriate education, training, and experience, as determined by the sponsor, 
will participate as investigators in this clinical trial. 
 
 
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10.2. 
Appendix 2: Clinical Laboratory Tests  
 
The tests detailed below will be performed by the central or local laboratory (see the 
SoA, Section 1.3). 
 
Protocol-specific requirements for inclusion or exclusion of participants are detailed in 
Section 5 of the protocol. 
 
Additional tests may be performed at any time during the study as determined necessary 
by the investigator or required by local regulations. 
 
Urine pregnancy testing will be local prior to dosing. If a urine pregnancy test is not 
available, a local serum pregnancy test is an acceptable alternative. Between visits, 
urine pregnancy tests are to be performed prior to monthly home dosing (see 
Section 8.2.7.1). 
Investigators must document their review of each laboratory safety report. 
Laboratory and/or analyte results that could unblind the study will not be reported to 
investigative sites or other blinded personnel. 
Clinical Laboratory Tests 
Comments  
Clinical Chemistry 
Assayed by Lilly-designated laboratory. 
Sodium 
  
Potassium 
  
Chloride 
  
Bicarbonate 
  
Total bilirubin 
  
Direct bilirubin 
  
ALP 
  
ALT 
  
AST 
  
GGT 
  
BUN 
  
Creatinine  
  
CK 
  
Uric acid 
  
Total protein 
  
Albumin 
  
Calcium 
  
Glucose 
Random 
Glucose 
Fasting 
Cholesterol  
  
Triglycerides 
  
  
  
Hematology 
Assayed by Lilly-designated laboratory. 
Hemoglobin 
  
Hematocrit 
  
Erythrocyte count (RBCs) 
  
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Clinical Laboratory Tests 
Comments  
Mean cell volume  
  
Mean cell hemoglobin 
  
Mean cell hemoglobin concentration  
  
Leukocytes (WBCs)  
  
Absolute neutrophil count (segmented and 
bands) (calculated) 
 
Absolute count of: 
  
Neutrophils, segmented 
  
Neutrophils, bands (if detected) 
 
Lymphocytes 
  
Monocytes 
  
Eosinophils 
  
Basophils 
  
Platelets 
  
Cell morphology  
  
Reticulocyte count 
  
  
  
Lipid Panel 
Assayed by Lilly-designated laboratory. Participant should not eat 
or drink anything except water for 12 hours before the test. 
HDL-C 
  
LDL-C 
  
  
  
Urinalysis 
Assayed by Lilly-designated laboratory. 
Specific gravity 
  
pH 
  
Protein 
  
Glucose 
  
Ketones 
  
Bilirubin 
  
Urobilinogen 
  
Blood 
  
Nitrite 
  
Urine leukocyte esterase 
  
Microscopic examination of sediment 
  
  
  
Hormones (Female) 
  
Pregnancy test (serum) 
Optional - Evaluated locally.  
Pregnancy test (urine) 
Evaluated locally. 
FSH 
Assayed by Lilly-designated laboratory. Optional, performed as 
needed to confirm participant’s postmenopausal status. 
  
  
Serology 
Assayed by Lilly-designated laboratory. 
TB testing: 
See the protocol (Section 8.2.6) for more information about TB 
testing. 
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Clinical Laboratory Tests 
Comments  
QuantiFERON-TB Gold test  
Assayed by Lilly-designated laboratory OR locally. 
T-SPOT or TST 
Evaluated locally.  
HIV testing  
Assayed by Lilly-designated laboratory.  
HCV testing: 
Assayed by Lilly-designated laboratory. Will be confirmed with 
an additional testing method.  
HCV antibody  
Hepatitis C RNA PCR 
Participants with a previous diagnosis of hepatitis C who have 
been treated with antiviral therapy and achieved a sustained 
virologic response may be eligible for inclusion in the study, 
provided they have no detectable HCV RNA at study entry. 
Sustained virologic response is defined as an undetectable HCV 
RNA level 24 weeks after completion of a full, documented 
course of an approved, potentially curative antiviral therapy for 
HCV.  
HBV testing:  
Assayed by Lilly-designated laboratory. 
HBV DNA  
Performed only for participants who test positive for HBcAb. 
HBcAb  
  
HBsAg 
  
  
  
PK Samples – LY3074828 concentration 
Assayed by Lilly-designated laboratory. Results will not be 
provided to the investigative sites. 
  
  
Stool Sample 
  
Stool culture 
  
Clostridium difficile testing 
C. difficile Toxins A and B, and GDH, with reflex Toxin PCR. 
  
Biomarkers 
Assayed by Lilly-designated laboratory. Results from samples 
taken prior to AMAX Week 12 will not be provided to the 
investigative sites until AMAM database lock or later. 
 
  
Fecal calprotectin 
  
  
  
Immunogenicity Samples 
Assayed by Lilly-designated laboratory. Results will not be 
provided to the investigative sites. 
Anti-LY3074828 antibodies  
  
Anti-LY3074828 antibodies neutralization 
  
  
Hypersensitivity Tests 
Selected test should be obtained in the event of anaphylaxis, 
systemic allergic/hypersensitivity reactions, or severe/generalized 
non-systemic hypersensitivity reactions involving a single organ 
system (Section 6.7). Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites. 
Anti-LY antibodies (Immunogenicity) 
  
LY Concentrations (PK) 
  
Tryptase 
  
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Abbreviations: ALP = alkaline phosphatase; ALT = alanine aminotransferase; HBcAb = hepatitis B core antibody; 
AST = aspartate aminotransferase; BUN = blood urea nitrogen; CK = creatine kinase; FSH = follicle-stimulating 
hormone; GDH = glutamate dehydrogenase; GGT = gamma-glutamyl transferase; HBsAg = hepatitis B surface 
antigen; HBV = hepatitis B virus; HCV = hepatitis C virus; HDL-C = high-density lipoprotein-cholesterol; HIV 
= human immunodeficiency virus; 
; LDL-C = low-density 
lipoprotein-cholesterol; PCR = polymerase chain reaction ; PK = pharmacokinetic; RBC = red blood cell; TB = 
tuberculosis; TST = tuberculin skin test; WBC = white blood cell. 
 
 
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10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-Up, and Reporting  
10.3.1. 
Definition of AE  
10.3.1.1. AE Definition  
 
An AE is any untoward medical occurrence in a participant or clinical study participant, 
temporally associated with the use of study intervention, whether or not considered 
related to the study intervention. 
Note: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study intervention. 
10.3.1.2. Events Meeting the AE Definition  
 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g., ECG, radiological scans, or vital signs measurements), 
including those that worsen from baseline, considered clinically significant in the medical 
and scientific judgment of the investigator (that is, not related to progression of 
underlying disease). 
 
Exacerbation of a chronic or intermittent pre-existing condition, including either an 
increase in frequency and/or intensity of the condition. 
 
New condition detected or diagnosed after study intervention administration, even though 
it may have been present before the start of the study. 
 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
 
Medication error, misuse, or abuse of IMP, including signs, symptoms, or clinical 
sequelae. 
10.3.1.3. Events Not Meeting the AE Definition  
 
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
 
The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition. 
 
Planned surgeries and nonsurgical interventions should not be reported as AEs unless the 
underlying medical condition has worsened during the course of the study. 
 
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or detected 
at the start of the study that do not worsen. 
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10.3.2. 
Definition of SAE  
An SAE is defined as any untoward medical occurrence that, at any dose: 
a. Results in Death 
b. Is Life-Threatening 
 The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event which 
hypothetically might have caused death if it were more severe. 
c. Requires Inpatient Hospitalization or Prolongation of Existing Hospitalization 
 
In general, hospitalization signifies that the participant has been admitted to the hospital 
for observation and/or treatment that would not have been appropriate in the physician’s 
office or outpatient setting. Complications that occur during hospitalization are AEs. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious. 
 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline of the originating study is not considered an AE. 
d. Results in Persistent Disability/Incapacity 
 
The term disability means a substantial disruption of a person’s ability to conduct normal 
life functions. 
 
This definition is not intended to include experiences of relatively minor medical 
significance, such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and 
accidental trauma (e.g., sprained ankle), which may interfere with or prevent everyday 
life functions but do not constitute a substantial disruption. 
e. Is a Congenital Anomaly/Birth Defect or Other Abnormal Pregnancy Outcome 
Abnormal pregnancy outcomes (for example, spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs. 
f. Other Situations: 
 
Medical or scientific judgment should be exercised in deciding whether SAE reporting is 
appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
participant or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition. These events should usually be considered 
serious. 
 
Examples of such events include invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions 
that do not result in hospitalization, or development of drug dependency or drug abuse. 
10.3.3. 
Definition of Product Complaints  
See Section 8.3.8. 
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10.3.4. 
Recording and Follow-Up of AE and/or SAE  
10.3.4.1. AE and SAE Recording  
 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory reports, and diagnostics reports) 
related to the event. 
 
The investigator will then record all relevant AE/SAE information in the CRF. 
 
It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to sponsor or designee in lieu of completion of the AE/SAE CRF page. 
 
There may be instances when copies of medical records for certain cases are requested by 
the sponsor or designee. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to the sponsor or designee. 
 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE. 
10.3.4.2. Assessment of Intensity  
The investigator will make an assessment of intensity for each AE and SAE reported during the 
study and assign it to one of the following categories: 
 
Mild: An event that is easily tolerated by the participant, causing minimal discomfort, 
and not interfering with everyday activities. 
 
Moderate: An event that causes sufficient discomfort and interferes with normal everyday 
activities. 
 
Severe: An event that prevents normal everyday activities. An AE that is assessed as 
severe should not be confused with an SAE. Severe is a category utilized for rating the 
intensity of an event, and both AEs and SAEs can be assessed as severe. 
 
An event is defined as ‘serious’ when it meets at least one of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe. 
10.3.4.3. Assessment of Causality  
 
The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE. 
 
A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
 
The investigator will use clinical judgment to determine the relationship. 
 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 
 
The investigator will also consult the IB and/or Product Information for marketed 
products in his/her assessment. 
 
For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
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 
There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to the sponsor or designee. However, it is very 
important that the investigator always make an assessment of causality for every event 
before the initial transmission of the SAE data to the sponsor or designee. 
 
The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment. 
 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
10.3.4.4. Follow-Up of AEs and SAEs  
 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations, as medically indicated or as requested by the sponsor 
or designee, to elucidate the nature and/or causality of the AE or SAE as fully as possible. 
This may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other health care professionals. 
 
If a participant dies during participation in the study or during a recognized follow-up 
period, the investigator will provide the sponsor or designee with a copy of any 
postmortem findings, including histopathology. 
 
New or updated information will be recorded in the originally completed CRF. 
 
The investigator will submit any updated SAE data to the sponsor or designee within 24 
hours of receipt of the information. 
10.3.5. 
Reporting of SAEs  
Note that pregnancies (during maternal or paternal exposure to investigational product) are also 
reported using the SAE reporting process for tracking purposes (even though pregnancy is not 
considered an AE/SAE as described in Section 8.3.1). Refer to Section 8.3.4 for regulatory 
reporting requirements for SAEs. 
10.3.5.1. SAE Reporting via an Electronic Data Collection Tool  
 
The primary mechanism for reporting an SAE will be the electronic data collection tool. 
 
If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours. 
 
The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
 
After the study is completed at a given site, the electronic data collection tool will be 
taken offline to prevent the entry of new data or changes to existing data. 
 
If a site receives a report of a new SAE from a study participant or receives updated data 
on a previously reported SAE after the electronic data collection tool has been taken 
offline, then the site can report this information on a paper SAE form (see next section) 
or to the medical monitor by telephone. 
 
Contacts for SAE reporting can be found in site training documents. 
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10.3.5.2. SAE Reporting via Paper CRF  
 
Facsimile transmission of the SAE paper CRF is the preferred method to transmit this 
information to the sponsor. 
 
Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE CRF pages within the designated reporting time frames. 
Contacts for SAE reporting can be found in site training documents.  
 
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10.4. 
Appendix 4: Liver Safety: Suggested Actions and Follow-Up 
Assessments  
Hepatic Evaluation Testing 
 
The Lilly-designated central laboratory should complete the analysis of all selected testing 
except when testing is required at an increased frequency and a local laboratory must be used for 
feasibility for the patient (with sponsor approval) 
, or for testing 
listed in the investigator-designated local laboratory table. The central laboratory will report 
results if a validated test or calculation is available. 
Notes for the use of local labs: 
 
The local laboratory must be qualified in accordance with applicable local regulations.  
 
Site personnel should update documentation per local requirements and sponsor guidance. 
 Assay results and reference ranges should be collected and documented as per sponsor 
guidance.  
Local testing may also be performed in addition to central testing when necessary for immediate 
participant management. 
Tests assayed by Lilly-designated central laboratory 
Hepatic Hematology Panel 
Hepatitis A virus (HAV) testing 
Hemoglobin 
 HAV total antibody 
Hematocrit 
 HAV IgM antibody 
Erythrocytes (RBCs - red blood cells) 
Hepatitis B virus (HBV) testing 
Leukocytes (WBCs - white blood cells) 
 Hepatitis B surface antigen (HBsAg) 
Differential: 
 Hepatitis B surface antibody (anti-HBs) 
 Neutrophils, segmented 
 Hepatitis B core total antibody (anti-HBc) 
 Lymphocytes 
 Hepatitis B core IgM antibody 
 Monocytes 
 Hepatitis B core IgG antibody 
 Basophils 
 HBV DNA b 
 Eosinophils 
Hepatitis C virus (HCV) testing 
Platelets 
 HCV antibody 
Cell morphology (RBC and WBC) 
 HCV RNA b 
Hepatic Clinical Chemistry Panel 
Hepatitis D virus (HDV) testing 
Total bilirubin 
 HDV antibody 
Direct bilirubin 
Hepatitis E virus (HEV) testing 
Alkaline phosphatase (ALP) 
 HEV IgG antibody 
Alanine aminotransferase (ALT) 
 HEV IgM antibody 
Aspartate aminotransferase (AST) 
 HEV RNA b 
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Gamma-glutamyl transferase (GGT) 
Anti-nuclear antibody (ANA) 
Creatine kinase (CK) 
Anti-smooth muscle antibody (ASMA) a 
Hepatic Coagulation Panel 
Anti-actin antibody c 
Prothrombin time, INR (PT-INR) 
Immunoglobulin IgA (quantitative) 
Urine Chemistry 
Immunoglobulin IgG (quantitative) 
Drug screen 
Immunoglobulin IgM (quantitative) 
Haptoglobin 
Epstein-Barr virus (EBV) testing 
 
EBV antibody 
Tests assayed ONLY by investigator-designated local laboratory 
Acetaminophen 
Epstein-Barr virus (EBV) testing 
Acetaminophen protein adducts 
 EBV DNA b 
Alkaline phosphatase isoenzymes 
Cytomegalovirus (CMV) testing: 
Ceruloplasmin 
 CMV antibody 
Copper 
 CMV DNA b 
Ethyl alcohol (EtOH) 
Herpes simplex virus (HSV) testing: 
 
 HSV (Type 1 and 2) antibody 
 
 HSV (Type 1 and 2) DNA b 
 
Liver kidney microsomal type 1 (LKM-1) 
ib d
 
Microbiology  
Phosphatidylethanol (PEth) 
Culture: 
Urine Chemistry 
 Blood 
Ethyl glucuronide (EtG) 
 Urine 
 
 
a Not required if anti-actin antibody is tested. 
b Reflex/confirmation dependent on regulatory requirements, testing availability, or both. 
c Not required if anti-smooth muscle antibody (ASMA) is tested. 
 
 
 
 
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10.5. 
Appendix 5: Risk Factors for Latent Tuberculosis Infection  
Risk Factors for LTBI 
Household contact or recent exposure to an active case 
Birth or residency in a high burden country (>20/100,000) 
Residents and employees of high-risk congregate settings, for example, prisons, homelessness, IV drug use 
Abbreviations: IV = intravenous; LTBI = latent tuberculosis infection. 
Source: Adapted from Horsburgh and Rubin 2011 and Lewinsohn et al. 2017. 
 
Risk Factors for Increased Likelihood of Progression from LTBI to Active TB 
Household contact or close contact with an active case 
HIV 
Radiographic evidence of old, healed TB that was not treated 
Silicosis 
Treatment with ≥15 mg prednisone (or equivalent) per day 
Children <5 years of age 
Chronic renal failure 
Treatment with an anti-TNF antibody 
Poorly controlled diabetes 
IV drug use 
Weight ≥10% below normal 
Smoking 
Abbreviations: HIV = human immunodeficiency virus; IV = intravenous; LTBI = latent tuberculosis infection; 
TB = tuberculosis; TNF = tumor necrosis factor. 
Source: Adapted from Horsburgh and Rubin 2011. 
 
WHO List of High Burden Countries 
Angola 
India 
Peru 
Azerbaijan 
Indonesia 
Philippines 
Bangladesh 
Kenya 
Russian Federation 
Belarus 
Kazakhstan 
Sierra Leone 
Botswana 
Democratic People’s Republic of 
Korea 
Somalia 
Brazil 
Kyrgyzstan 
South Africa 
Cambodia 
Lesotho 
Swaziland 
Cameroon 
Liberia 
Tajikistan 
Central African Republic 
Malawi 
United Republic of 
Tanzania 
Chad 
Republic of Moldova 
Thailand 
China 
Mozambique 
Uganda 
Congo 
Myanmar 
Ukraine 
Democratic Republic of the 
Congo 
Namibia 
Uzbekistan 
Ethiopia 
Nigeria 
Vietnam 
Ghana 
Pakistan 
Zambia 
Guinea-Bissau 
Papua New Guinea 
Zimbabwe 
Abbreviation: WHO = World Health Organization. 
Source: WHO 2015. 
 
 
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10.6. 
Appendix 6: Examples of Infections that May Be Considered 
Opportunistic in the Setting of Biologic Therapy  
This table is provided to aid the investigator in recognizing infections that may be considered 
opportunistic in the context of biologic therapy, for the purposes of exclusion criteria. This list is 
not exhaustive. Investigators should use their own clinical judgement in determining if other 
infections may be considered opportunistic for the purposes of exclusion criteria. Winthrop et al. 
(2015) consider TB and non-TB mycobacterial disease to be opportunistic infections in the 
context of biologic therapy. 
Bacterial 
 
Bartonellosis (disseminated disease only) 
 
Campylobacteriosis (invasive disease only) 
 
Legionellosis 
 
Listeriosis (invasive disease only) 
 
Nocardiosis 
 
TB 
 
Non-TB mycobacterial disease  
 
Salmonellosis (invasive disease only)  
 
Shigellosis (invasive disease only) 
 
Vibriosis (invasive disease due to Vibrio vulnificus) 
Viral 
 
BK virus disease including polyomavirus-associated nephropathy 
 
Cytomegalovirus disease 
 
HBV reactivation 
 
HCV progression 
 
Herpes simplex (invasive disease only) 
 
Herpes zoster (any form) 
 
Posttransplant lymphoproliferative disorder (Epstein-Barr virus) 
 
PML, JC virus  
Fungal 
 
Aspergillosis (invasive disease only) 
 
Blastomycosis 
 
Candidiasis (invasive disease or oropharyngeal, esophageal. Not isolated lingual) 
 
Coccidioidomycosis 
 
Cryptococcosis 
 
Histoplasmosis 
 
Paracoccidioides infections 
 
Penicilliosis 
 
Pneumocystosis 
 
Sporotrichosis 
 
Other invasive molds: Mucormycosis (zygomycosis) (Rhizopus, Mucor, and Lichtheimia), 
Scedosporium/Pseudallescheria boydii, Fusarium 
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Parasitic 
 
Leishmaniasis (visceral only) 
 
Strongyloidosis (hyperinfection syndrome or disseminated disease) 
 
Microsporidiosis 
 
Toxoplasmosis 
 
Trypanosoma cruzi infection (Chagas’ disease progression) (disseminated disease only) 
 
Cryptosporidiosis (chronic disease only) 
Abbreviations: HBV = hepatitis B virus; HCV = hepatitis C virus; JC = John Cunningham; 
PML = progressive multifocal leukoencephalopathy; TB = tuberculosis. 
Source: Adapted from Winthrop et al. 2015.  
 
 
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10.7. 
Appendix 7: Prohibited Medications  
This section outlines medications that are prohibited during both the originator studies and the 
AMAX study. 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 
Guidance for Use 
The following medications are prohibited 
throughout duration of study: 
 
Anti-TNF antibodies (for example, infliximab, 
adalimumab, or certolizumab pegol) 
Prohibited throughout duration of study. 
Anti-integrin antibodies: 
  
Natalizumab 
Prohibited throughout duration of study. 
Other anti-integrin antibodies (for example, 
vedolizumab) 
Prohibited throughout duration of study. 
Agents depleting B or T cells (for example, 
rituximab, alemtuzumab, or visilizumab) 
Prohibited throughout duration of study. 
Immunomodulatory medications, including 
oral cyclosporine, IV cyclosporine, tacrolimus, 
mycophenolate mofetil, thalidomide, or JAK 
inhibitors (other than topical) 
Prohibited throughout duration of study. 
Rectally administered 5-ASA therapies 
(enemas or suppositories) 
Prohibited throughout duration of study. 
Rectally administered corticosteroids (enemas 
or suppositories) 
Prohibited throughout duration of study. 
Corticosteroids 
 
A course of IV corticosteroids is prohibited throughout 
duration of study, except for use as premedication for 
infusion or for short-term treatment of acute non-CD events 
(for example, allergic reactions). IV corticosteroids used for 
CD may result in discontinuation, therefore consult your 
medical monitor. 
 
From Week 0 to Week 12, initiation or adjustment of 
systemic corticosteroids for non-CD indications is 
prohibited unless needed due to AEs or for appropriate 
medical management.  
 
After Week 12, participants may transiently initiate or 
increase doses (that is, for <4 weeks) of corticosteroids for 
reasons other than loss of response to treatment for CD (for 
example, premedication for infusions, and stress doses of 
corticosteroids for surgery, asthma, and allergic reaction).  
 
Locally administered corticosteroids (for example, inhaled, 
intranasal, intra-articular, or topical) are allowed.  
 
Systemic corticosteroid use is allowed for adrenocortical 
insufficiency (Section 6.5 and 6.7.1). 
Any investigational therapy (biologic or 
nonbiologic) 
Prohibited throughout duration of study. 
Interferon therapy 
Prohibited unless medically necessary for short-term 
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Drug Class 
Guidance for Use 
Leukocyte apheresis (leukapheresis, for 
example, Adacolumn) 
Prohibited throughout duration of study. 
Anti-IL-23p19 antibodies (for example, 
risankizumab [BI-655066], brazikumab 
[MEDI-2070], guselkumab [CNTO1959], or 
tildrakizumab [MK-3222]) for any indication, 
including investigational use 
Prohibited throughout duration of study. 
Anti-IL 12/23p40 antibodies (for example, 
ustekinumab) 
Prohibited throughout duration of study. 
BCG vaccine 
BCG vaccination prohibited throughout the duration of the 
study and for 12 months after discontinuation of study 
drug. 
Live attenuated vaccines 
Live attenuated vaccines are prohibited throughout the 
duration of the study and for 3 months after discontinuation 
of study drug. 
Medicinal and recreational marijuana (includes 
CBD Oil) 
Marijuana use is prohibited through the end of the long-
term extension period of the study. If use is identified prior 
to this time, it may result in discontinuation, consult the 
medical monitor. 
Abbreviations: 5-ASA = 5-aminosalicyclic acid; AE = adverse event; BCG = Bacillus Calmette Guerin; 
CBD = cannabidiol; CD = Crohn’s disease; COVID = coronavirus disease; IL = interleukin; IM = intramuscular; 
IV = intravenous; JAK = Janus kinase; TNF = tumor necrosis factor. 
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10.8. 
Appendix 8: Permitted Medications with Dose Stabilization  
Drug Class 
Guidance for Use 
Oral 5-ASAs (for example, 
mesalamine, balsalazide, or 
olsalazine) 
Prescribed dose should remain stable for the duration of the study 
unless modifications are needed due to AEs or for appropriate medical 
management.  
Oral corticosteroids (prednisone 
≤30 mg/day or equivalent or 
budesonide 9 mg/day) 
Prescribed dose should remain stable until Week 12 unless 
modifications are needed due to medical necessity. 
After Week 12, see Section 6.5.3. 
If doses above 30 mg/day are felt to be necessary, please consult 
sponsor. 
Immunomodulators (for example, 
AZA, 6-MP, or methotrexate) 
Doses should remain stable throughout study unless medication is 
discontinued due to a toxicity related to the medication or 
modifications are needed due to AEs or for appropriate medical 
management.  
Antibiotics being used specifically 
for the treatment of CD (for 
example: rifaximin or Cipro) 
Prescribed dose must remain stable for the duration of the study unless 
modifications are needed due to AEs or for appropriate medical 
management. 
Antidiarrheals (for example, 
loperamide or diphenoxylate with 
atropine) 
May continue during study with stable doses encouraged. 
Low-dose or baby aspirin (75 mg to 
162.5 mg) 
Daily use for cardiovascular prophylaxis permitted. 
Nonlive (killed, inactivated, or 
subunit) vaccines (including RNA-
based) 
Allowed during the study. Must be reported as concomitant 
medications, and the verbatim for any associated adverse events 
should note the relationship to vaccination. The efficacy of nonlive 
vaccinations with concomitant mirikizumab treatment is unknown. 
Abbreviations: 5-ASA = 5-aminosalicyclic acid; 6-MP = 6-mercaptopurine; AE = adverse event; AZA = 
azathioprine; CD = Crohn’s disease. 
 
 
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10.9. 
Appendix 9: Patient-Reported Outcome Instruments  
This appendix describes PRO instruments used in this study. For the physician items of the 
CDAI and other clinician efficacy assessments, see Section 8.1. 
Daily Diary (eDiary/Paper Diary – including 1-Day and 14-Day) 
Paper Questionnairesa 
 
CDAI-SF/Bristol Stool Scale (Reference to Types 6 & 7) 
CDAI-AP 
IBDQ 
CDAI-well-being 
 
Abbreviations: AP = abdominal pain; 
; CDAI = Crohn’s Disease Activity Index; 
CDAI-AP = Crohn’s Disease Activity Index – Abdominal Pain; CDAI-SF = Crohn’s Disease Activity Index – 
Stool Frequency;
 
IBDQ = Inflammatory Bowel Disease Questionnaire; 
 
 
 SF = stool frequency; 
 
 
a 
Not including 1-Day or 14-Day paper diary. 
 
The following are descriptions of additional PRO instruments for this study, using Patient eDiary 
and/or paper diary and paper questionnaire (listed in order of administration). 
CDAI-(SF, AP: abdominal pain, and general well-being): CDAI is an 8-item disease activity 
measure that includes 3 patient-reported items: AP (4-point scale: 0=none, 1=mild, 2=moderate, 
3=severe); SF (number of liquid or very soft stools); and general well-being (0=generally well, 
1=slightly under par, 2=poor, 3=very poor, 4=terrible). 
Bristol Stool Scale (used as a reference for CDAI-SF): The Bristol Stool Scale provides a 
pictorial and verbal description of stool consistency and form ranging from Type 1 (Hard 
Lumps) to Type 7 (Watery/Liquid). To further define “liquid or very soft stools,” when 
responding to the CDAI-SF item, patients will be referred to the Bristol Stool Scale Category 6 
and/or 7, that is liquid or watery stool. 
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IBDQ: A 32-item patient-completed questionnaire that measures 4 aspects of patients’ lives: 
symptoms directly related to the primary bowel disturbance, systemic symptoms, emotional 
function, and social function (Guyatt et al.1989; Irvine et al. 1994; Irvine et al. 1996). Responses 
are graded on a 7-point Likert scale in which 7 denotes “not a problem at all” and 1 denotes “a 
very severe problem.” Scores range from 32 to 224; a higher score indicates a better quality of 
life. In general, patients in symptomatic remission have an IBDQ score ≥170 (Irvine 2008). 
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10.11. 
Appendix 11: Abbreviations and Definitions  
Term 
Definition 
abuse 
use for recreational purposes or to maintain an addiction or dependence 
ADA 
antidrug antibody 
ADR 
adverse drug reaction 
AE 
adverse event: Any untoward medical occurrence in a participant 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 event of special interest 
AIDS 
acquired immunodeficiency syndrome 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AP 
abdominal pain 
AST 
aspartate aminotransferase 
BCG 
Bacillus Calmette Guerin 
 
 
CBD 
cannabidiol 
CD 
Crohn’s disease 
CDAI 
Crohn’s Disease Activity Index 
CDAI-AP 
Crohn’s Disease Activity Index – Abdominal Pain 
CDAI-SF 
Crohn’s Disease Activity Index – Stool Frequency 
CDC 
Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CK 
creatine kinase 
CMV 
cytomegalovirus 
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, and applicable regulatory 
requirements. 
CRF/eCRF 
case report form/electronic case report form designed to record protocol-required 
information to be reported to the sponsor for each trial participant 
CSR 
clinical study report 
 
 
CT 
computed tomography 
CXR 
chest x-ray 
D. Bil 
direct bilirubin 
DMC 
data monitoring committee. A data monitoring committee or data monitoring board is a 
group of independent scientists who are appointed to monitor the safety and scientific 
integrity of a human research intervention and to make recommendations to the sponsor 
regarding the stopping of a study for efficacy, harms, or futility. The composition of the 
committee is dependent upon the scientific skills and knowledge required for monitoring 
the particular study. 
DNA 
deoxyribonucleic acid 
EBV 
Epstein-Barr virus 
ECAV 
extended continued access visits 
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Term 
Definition 
ECG 
electrocardiogram 
eCOA 
electronic Clinical Outcome Assessment 
EDC 
electronic data capture 
 
 
enroll 
The act of assigning a participant to a treatment. Participants who are enrolled in the study 
are those who have been assigned to a treatment. 
enter 
Participants entered into a study are those who sign the informed consent form directly or 
through their legally acceptable representatives. 
 
 
ERCP 
endoscopic retrograde cholangiopancreatography 
ET 
early termination 
ETV 
early termination visit 
 
 
GCP 
good clinical practice 
GGT 
gamma-glutamyltransferase 
HBcAb  
hepatitis B core antibody 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HDV 
hepatitis D virus 
HIV 
human immunodeficiency virus 
IB 
Investigator’s Brochure 
IBD 
inflammatory bowel disease 
IBDQ 
Inflammatory Bowel Disease Questionnaire 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IGRA 
interferon gamma release assay 
IL 
interleukin 
informed 
consent 
A process by which a participant 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 participant’s decision to participate. Informed consent is documented by means of a 
written, signed, and dated informed consent form. 
INR 
international normalized ratio 
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, marketed 
products used for an unauthorized indication, or marketed products used to gain further 
information about the authorized form.  
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 participant (that is, the 
planned treatment regimen) rather than the actual treatment given. It has the consequence 
that participants 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/intravenously 
LTBI 
latent tuberculosis infection 
mITT 
modified intent-to-treat 
MMRM 
mixed-effects model for repeated measures 
MRCP 
magnetic resonance cholangiopancreatography 
NOAEL 
no-observed-adverse-effect level 
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Term 
Definition 
NRI 
nonresponder imputation 
 
 
participant 
Equivalent to Clinical Data Interchange Standards Consortium term “subject”: an 
individual who participates in a clinical trial, either as recipient of an investigational 
medicinal product or as a control. 
 
 
 
PK  
pharmacokinetic(s) 
PRO 
patient-reported outcome 
PT 
prothrombin time 
 
 
 
SAC 
statistical analysis center 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SDALs 
study drug administration logs 
 
 
SC 
subcutaneous/subcutaneously 
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.  
SERMs 
selective estrogen receptor modulators 
SES-CD 
Simple Endoscopic Score for Crohn’s Disease 
SF 
stool frequency 
SoA 
Schedule of Activities 
SUSARs 
suspected unexpected serious adverse reactions 
TB 
tuberculosis 
TBL 
total bilirubin level 
TE 
treatment-emergent 
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 
TST 
tuberculin skin test 
UC 
ulcerative colitis 
ULN 
upper limit of normal 
WHO 
World Health Organization 
WNOCBP 
women not of childbearing potential 
WOCBP 
women of childbearing potential 
 
 
 
 
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10.12. 
Appendix 12: 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 GCP, enabling 
participants to continue safely in the study and maintaining the integrity of the study. 
Informed consent 
Additional consent from the participant will be obtained, if required, for: 
 participation in remote visits, as defined in Section “Remote visits” below, 
 a change in the method of study intervention administration, 
 alternate delivery of study intervention and ancillary supplies, and 
 provision of their personal or medical information required prior to implementation of 
these activities. 
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. Further, the flexibilities outlined may not be available in each site 
location and will be determined by the sponsor in accordance with applicable local regulations. 
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The following changes in study conduct will not be considered protocol deviations. 
Remote visits 
In source documents and the CRF, the study site should capture the visit method, with a specific 
explanation for any data missing because of missed in-person site visits. 
Regardless of the type of remote visits implemented, the protocol requirements regarding the 
reporting of AEs, SAEs, and product complaints remain unchanged. Furthermore, every effort 
should be made to enable participants to return to on-site visits as soon as reasonably possible 
while ensuring the safety of both the participants and the site staff. 
Types of remote visits 
Telemedicine: Telephone or technology-assisted virtual visits, or both, are acceptable to 
complete appropriate assessments. Assessments to be completed in this manner include, but are 
not limited to: 
 Concomitant medication reviews 
 Tobacco/nicotine use 
 AE reviews 
 Review of diary compliance 
 Questionnaires will be collected by verbal reporting from the participant to the site for 
entry on paper, and then entry into the eCRF. 
 Product complaint (if applicable) 
 Verification of negative pregnancy test (if applicable) 
 Status/observation of self-administration of IP where applicable 
Mobile healthcare: Healthcare visits may be performed by a mobile healthcare provider at 
locations other than the study site when participants cannot travel to the site due to an 
exceptional circumstance if written approval is provided by the sponsor. Procedures performed at 
such visits may include, but are not limited to: 
 Coordination of signature needed for study documents 
 Concomitant medication reviews 
 Tobacco/nicotine use 
 AE collection 
 Vital signs (T, PR, BP), weight 
 Laboratory collection (including stool collections) 
 Review of diary compliance 
 Coordinate questionnaire administration (must be collected by site via telemedicine, see 
section above) 
 Dosing (SC only) 
 Study drug self-administration training 
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 Delivery of required ancillary supplies or IP product for self-administration 
 Urine pregnancy test (as applicable) 
The below procedures also may be performed, but may require additional qualifications and 
sponsor approval: 
 Physical exam 
 
 
 
 
 Clinician CDAI 
 TB Monitoring 
Other alternative locations: The sponsor should be made aware of temporary site relocations as 
soon as possible. Alternate locations for study conduct must be approved for appropriateness 
considering participant privacy and participant/site staff safety. Study visits or assessments may 
be done at an alternate location under exceptional circumstances, if allowed by local authorities. 
In instances where an alternate facility is required, sites may continue to perform all procedures 
as feasible. This will include utilizing alternate endoscopy suites and performing central 
laboratory collection, infusion of IP, or SC injection of IP by a trained healthcare professional. 
 Alternate facilities for central or local laboratory sample collection. Where available, 
participants should utilize laboratory facilities affiliated with the study’s central 
laboratory vendor. 
Data capture 
In source documents and the CRF, the study site should capture the visit method, with a specific 
explanation for any data missing because of missed in-person site visits. 
Safety reporting 
Regardless of the type of remote visits implemented, the protocol requirements regarding the 
reporting of AEs, SAEs, and product complaints remain unchanged. 
Return to on-site visits 
Every effort should be made to enable participants to return to on-site visits as soon as 
reasonably possible, while ensuring the safety of both the participants and the site staff. 
Local laboratory testing option 
 Local laboratory testing may be conducted in lieu of central laboratory testing for safety 
labs including chemistry, hematology, and HBV DNA. Local laboratories may also be 
used for HBV serology, HCV, and HIV testing and for urinalysis. However, only central 
laboratory testing should be used for 
 PK, immunogenicity, hypersensitivity tests, 
fecal calprotectin, 
 to support endpoints. The local 
laboratory must be qualified in accordance with applicable local regulations. Site 
personnel should update documentation per local requirements and sponsor guidance. 
Assay results and reference ranges should be collected and documented as per sponsor 
guidance. Investigators must document their review of each laboratory safety result and 
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retain in the source documentation. Any clinically significant findings from laboratory 
tests that result in a diagnosis and that occur after the participant receives the first dose of 
study drug should be reported to Lilly or its designee as an AE via eCRF. 
 Laboratory testing may be performed locally if needed. Local laboratory collections will 
be used for immediate patient management and safety but will not be included in the data 
for analysis, except for hematocrit which may be included at key timepoints as needed to 
calculate CDAI if central lab results are not available. (Local labs may also be used for 
follow-up monitoring of hepatic lab abnormalities as described in Section 8.2.10, and in 
this case may be included in hepatic safety analyses.) See information related to local 
laboratory testing options below. 
Study intervention and ancillary supplies (including participant diaries) 
When a participant is unable to go to the site to receive study supplies during normal on-site 
visits, the site should work with the sponsor to determine appropriate actions. These actions may 
include: 
 asking the participant to go to the site and receive study supplies from site staff without 
completion of a full study visit, 
 asking the participant’s designee to go to the site and receive study supplies on a 
participant’s behalf, 
 arranging delivery of study supplies, and 
 working with the sponsor to determine how study intervention that is typically 
administered on site will be administered to the participant; for example, during a mobile 
healthcare visit, at an alternate location such as an infusion center, or by self-
administration of SC injections after appropriate training. 
o Dosing can proceed only if central or local safety labs have been performed 
within 14 weeks (or within a shorter timeframe for participants with previous 
abnormal lab results, as medically indicated) prior to dosing, and lab results do 
not require study drug discontinuation or temporary interruption. 
o For participants who have had abnormal laboratory values at a prior lab 
collection, the investigator may ask the participant to have local or central labs 
obtained to confirm that protocol requirements for IP administration are met. Any 
clinically significant laboratory abnormality should be discussed with the medical 
monitor before at-home administration can proceed. 
These requirements must be met before action is taken: 
 Alternate delivery of study intervention should be performed in a manner that ensures 
product integrity. The existing protocol requirements for product accountability remain 
unchanged, including verification of participant’s receipt of study supplies. 
 When delivering supplies to a location other than the study site (for example, 
participant’s home), the investigator, sponsor, or both should ensure oversight of the 
shipping process to ensure accountability and product quality (that is, storage conditions 
maintained and intact packaging upon receipt). 
 Instructions may be provided to the participant or designee on the final disposition of any 
unused or completed study supplies. 
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In addition, if study intervention will be administered to the participant during a mobile 
healthcare visit or at an alternate location, these additional requirements must be met: 
 Only authorized study personnel may supply, prepare, or administer study intervention. 
 If IV administration occurs at an alternate location, resuscitation equipment, emergency 
medications, and appropriately trained staff must be available during the infusion and 
monitoring period. All participants should be monitored for 1 hour or longer after IV 
dosing, according to investigator practice or local standard of care. 
 Adherence to the detailed instructions for investigational product administration, 
including infusion rate and SC injections, provided by the sponsor must continue to be 
followed. Maintain accurate records of study drug dispensing and collection. 
 Site staff will document the IP package numbers that are dispensed and shipped for home 
administration on the Study Drug Administration Log. 
o Participants will complete Study Drug Administration Logs to document the 
doses administered and return this documentation to the site at the next on-site 
visit. 
o Instruct participants to retain sharps container with used IP, as well as any 
unused IP in order to return to the site at the next on-site visit. 
 For doses intended to be performed at the office according to the SoA, the site staff will 
reassess the ability of the participant to receive study drug in office for the next scheduled 
visit before a subsequent dose will be shipped to the participant’s home. 
 All unused medication must be returned to Lilly or its designee unless the sponsor and 
sites have agreed unused medication is to be destroyed by the site, as allowed by local 
law. 
Concomitant therapy 
Steroid Tapering: During the first 12 weeks of the study, the principal investigator should use 
clinical judgement of the benefit/risk of tapering for each individual participant, and consider 
Gastrointestinal Society guidance, to determine if corticosteroid dosage adjustment is indicated 
for their patients during the exceptional circumstances. If the investigator believes steroid 
tapering is in the best interest of the study participant, dosages above 15 mg of prednisone (or 
equivalent) may be reduced to a dose of 15 mg 
 following 
the recommended tapering regimen in the protocol, per local practice, or per Gastrointestinal 
Society guidance. After Week 12, see Section 6.5.3. 
Use of prohibited medications in exceptional circumstances, and continuation in the study, 
should be discussed with your medical monitor. 
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Screening period guidance 
To ensure safety of study participants, screening laboratory values and other eligibility 
assessments are valid for a maximum of 
. In exceptional circumstances, if one or more 
screening laboratory assessments cannot be performed at AMAM Visit 17 (for AMAM-
originating participants) or at AMAX Visit 1, if valid results had been obtained for other 
visits/purposes for that assessment within 
 prior to AMAX first dosing, those results 
can be used to confirm eligibility. This situation must be reported to the sponsor, and that 
assessment must be performed again as soon as it is available and could result in discontinuation 
if the delay raises safety concerns. The following rules will be applied for consented rollover 
participants prior to receiving the first dose in AMAX whose participation in the study must be 
paused due to exceptional circumstances: 
 An extension from 
 for the maximum dosing interval between last 
dose in the originator trial (AMAG or AMAM) and the first dose in AMAX may be 
allowed (for example but not limited to, due to prolonged turnaround time for screening 
labs, endoscopy suite backlogs for participants originating from AMAM needing AMAM 
Week 52 endoscopy, and site closure and inability to dose). The total screening window 
may also be extended as needed, but must occur within the allowed interdosing interval. 
o The site should conduct the next visit if the participant’s eligibility criteria are 
confirmed, and the site should document the reason for delay in the source 
documentation. 
o Due to the pause in screening, sites should also reconfirm the impacted 
participant’s consent and document this confirmation in the source 
documentation. 
Adjustments to visit windows 
Whenever possible and safe to do so, as determined by the investigator’s discretion, participants 
should complete the usual SoA. 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. 
There are no plans for an increase in number of IP doses or increase in exposure to IP. 
In order for IP to be administered during visit window adjustments, the following must be done 
at a minimum and in compliance with the protocol requirements: 
 Urine pregnancy test complete with negative result 
 Review of AEs 
 Review of concomitant medications 
 Review of previous labs obtained 
 Safety labs must have been obtained and reviewed within the previous 
 (or 
within a shorter timeframe for participants with previous abnormal lab results, as 
medically indicated). Collections may utilize either local or central labs 
 Follow the protocol regarding administration of IP, including temporary holding of IP for 
safety issues as per protocol 
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There must be a minimum of 
 between IP doses. 
The following describes the allowed adjustments to visit windows. See Table AMAX.10-1 for 
additional details. 
Visits 1 through 3 
 Extending the visit window to the beginning of the next visit window will be allowed. 
If the patient visit exceeds the extended window, the visit must occur at the earliest 
opportunity. 
 Timeframes for future participant visits must be adjusted to bring the participant back 
into compliance with the protocol defined visit windows, while keeping all doses at 
least 
 apart. 
 Sites should remind AMAM-originating participants to continue to record all daily 
eDiary data through Visit 4. 
Visit 4 through end of trial 
 Beginning with Visit 4, at which self-administration may begin, the visit window may 
extend to the beginning of the next dosing window. If the participant visit exceeds the 
extended window, the visit must occur at the earliest opportunity. 
 Timeframes for future participant visits and self-administration of dosing, where 
applicable, must be adjusted to bring the participant back into compliance with the 
protocol defined visit windows, while keeping all doses at least 
 apart. 
Throughout trial 
 A urine pregnancy test (if applicable) must be obtained prior to each IP 
administration. 
 If a 14-Day paper diary is in use and the subsequent visit is delayed, the participant 
should continue to record the daily data, even beyond 14 days, until the next visit 
occurs (guidance will be provided for ensuring sufficient forms are available). 
 Note: Per protocol, participants who miss 
 must be considered 
for ET. 
Endoscopies 
 For 
, the window for the
 
 If the 
 
 cannot be performed within the extended window, the
 
 should be performed as soon as possible. 
 For 
, if the AMAX Week 52 
 endoscopy 
cannot be performed within the extended V9 window, the site should still perform all 
other assessments and may continue with dosing. The Week 52 endoscopy should be 
performed as soon as possible. At the time of the endoscopy, an unscheduled fecal-
calprotectin stool sample should be collected. 
 If the 
 endoscopy cannot be performed within the extended 
 window, the site should still perform all other assessments. The 
 
 should be performed as soon as possible. At the time of the endoscopy, an 
unscheduled fecal-calprotectin stool sample should be collected. 
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 The overall length of exposure will not be extended for this trial. 
Posttreatment Follow-Up Visits 801 and 802 
 Visit 801: Visit window may be extended up to 2 weeks earlier or less than 12 weeks 
from the last visit (LV) or ETV (LV/ETV + 2 weeks to <12 weeks). 
 Visit 802: Visit window may be extended up to 4 weeks earlier (provided Visit 802 is 
at least 4 weeks from Visit 801) or 8 weeks later than the protocol visit date 
(LV/ETV + 8 weeks to 24 weeks). If additional time is required, a discussion with the 
sponsor should take place. 
Documentation 
Changes to study conduct will be documented: 
 Sites will identify and document the details of how participants, visits, 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 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. 
The table below describes the mitigations to allow for expanded visit windows during 
exceptional circumstances. See “Adjustments to visit windows” above for further details. There 
must be a minimum of 
 between study drug doses. 
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Table AMAX.10-1 
Extended Visit Windows for Exceptional Circumstances 
Study 
Visit/ 
Dosea 
Study 
Week 
Protocol 
Specified  
Day 
Protocol Specified 
Visit Tolerance 
Interval  
Mitigation Extension 
of Visit Interval 
Tolerance 
Mitigation Study 
Day Range 
Notes 
V1 
Total interval from 
last dose in the 
originating study to 
first dose in 
AMAX is no more 
than 
 
Total interval from 
last dose in the 
originating study to 
first dose in AMAX is 
no more than 
 
V1 is a split visit. V1 dosing is defined as 
Day 1. Most other V1 activities may be 
erformed in prior days and must be 
ompleted prior to dosing. 
V2 
±7 days 
-7 to +20 days 
 
V3 
±7 days 
-7 to +20 days 
When AMAG-originating participants are 
rovided the 14-Day paper diaries to 
omplete prior to their next visit, additional 
opies should be provided in case the visit 
may need to move out. In that situation, the 
articipant should continue to record the daily 
ata, even beyond 14 days, until the actual 
ext visit occurs. 
V4 Phone 
At least 15 days 
prior to actual next 
visit date 
At least 15 days prior 
to actual next visit 
date 
Phone reminder must occur at least 15 days 
rior to intended next visit to ensure 
ollection of 14-Day diary data. 
V4 Office 
±7 days 
-7 to +20 days 
 
 
±7 days 
-7 to +20 days 
 
V5 
±7 days 
-7 to +20 days 
 
 
±7 days 
-7 to +20 days 
 
V6 
±7 days 
-7 to +20 days 
 
 
±7 days 
-7 to +20 days 
 
V7 
±7 days 
-7 to +20 days 
 
 
±7 days 
-7 to +20 days 
 
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Study 
Visit/ 
Dosea 
Study 
Week 
Protocol 
Specified  
Day 
Protocol Specified 
Visit Tolerance 
Interval  
Mitigation Extension 
of Visit Interval 
Tolerance 
Mitigation Study 
Day Range 
Notes 
V8 
±7 days 
-7 to +20 days 
When participants are provided the 14-Day 
paper diaries to complete prior to their next 
visit, additional copies should be provided in 
case the visit may need to move out. In that 
situation, the participant should continue to 
record the daily data, even beyond 14 days, 
until the actual next visit occurs.  
 
±7 days 
-7 to +20 days 
 
V9 Phone 
At least 15 days 
prior to actual next 
visit date 
At least 15 days prior 
to actual next visit 
date 
Phone reminder must occur at least 15 days 
prior to intended next visit to ensure 
collection of 14-Day diary data. 
V9 Office 
±7 days 
-7 to +20 days 
 
±7 days 
-7 to +20 days 
 
V10 Office 
±7 days 
-7 to +20 days 
 
 
±7 days 
-7 to +20 days 
 
V11 Office 
±7 days 
-7 to +20 days 
When participants are provided the 14-Day 
paper diaries to complete prior to their next 
visit, additional copies should be provided in 
case the visit may need to move out. In that 
situation, the participant should continue to 
record the daily data, even beyond 14 days, 
until the actual next visit occurs. 
 
±7 days 
-7 to +20 days 
 
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Study 
Visit/ 
Dosea 
Study 
Week 
Protocol 
Specified  
Day 
Protocol Specified 
Visit Tolerance 
Interval  
Mitigation Extension 
of Visit Interval 
Tolerance 
Mitigation Study 
Day Range 
Notes 
V12 Phone 
At least 15 days 
prior to actual next 
visit date 
At least 15 days prior 
to actual next visit 
date 
Phone reminder must occur at least 15 days 
prior to intended next visit to ensure 
collection of 14-Day diary data. 
V12 Office 
±7 days 
-7 to +20 days 
 
 
±7 days 
-7 to +20 days 
 
 
±7 days 
-7 to +20 days 
 
V13 Office 
±7 days 
-7 to +20 days 
When participants are provided the 14-Day 
paper diaries to complete prior to their next 
visit, additional copies should be provided in 
case the visit may need to move out. In that 
situation, the participant should continue to 
record the daily data, even beyond 14 days, 
until the actual next visit occurs. 
 
±7 days 
-7 to +20 days 
 
 
±7 days 
-7 to +20 days 
 
V14 Phone 
At least 15 days 
prior to actual next 
visit date 
At least 15 days prior 
to actual next visit 
date 
Phone reminder must occur at least 15 days 
prior to intended next visit to ensure 
collection of 14-Day diary data.  
V14 Office 
±7 days 
-7 to +20 days 
 
 
±7 days 
-7 to +20 days 
 
 
±7 days 
-7 to +20 days 
 
V15 Office 
±7 days 
-7 to +20 days 
When participants are provided the 14-Day 
paper diaries to complete prior to their next 
visit, additional copies should be provided in 
case the visit may need to move out. In that 
situation, the participant should continue to 
record the daily data, even beyond 14 days, 
until the actual next visit occurs. 
 
±7 days 
-7 to +20 days 
 
 
±7 days 
-7 to +20 days 
 
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Study 
Visit/ 
Dosea 
Study 
Week 
Protocol 
Specified  
Day 
Protocol Specified 
Visit Tolerance 
Interval  
Mitigation Extension 
of Visit Interval 
Tolerance 
Mitigation Study 
Day Range 
Notes 
V16 Phone 
At least 15 days 
prior to actual next 
visit date 
At least 15 days prior 
to actual next visit 
date 
Phone reminder must occur at least 15 days 
prior to intended next visit to ensure 
collection of 14-Day diary data. 
V16 Office 
±7 days 
-7 to +20 days 
 
 
±7 days 
-7 to +20 days 
 
 
±7 days 
-7 to +20 days 
 
V17 Office 
±7 days 
-7 to +20 days 
 
 
±7 days 
-7 to +20 days 
 
 
±7 days 
-7 to +20 days 
 
V18 Office 
±7 days 
-7 to +20 days 
When participants are provided the 14-Day 
paper diaries to complete prior to their next 
visit, additional copies should be provided in 
case the visit may need to move out. In that 
situation, the participant should continue to 
record the daily data, even beyond 14 days, 
until the actual next visit occurs. 
 
±7 days 
-7 to +20 days 
 
V19 Phone 
At least 15 days 
prior to actual next 
visit date 
At least 15 days prior 
to actual next visit 
date 
Phone reminder must occur at least 15 days 
prior to intended next visit to ensure 
collection of 14-Day diary data. 
V19 Office 
±7 days 
-7 to +20 days 
If the Week 156 endoscopy cannot be 
performed within the extended V19 window, 
the site should still perform all other 
assessments. The Week 156 endoscopy 
should be performed as soon as possible. At 
the time of the endoscopy, an unscheduled 
fecal-calprotectin stool sample should be 
collected. 
V801 
±10 days 
LV/ETV + 2 weeks to 
<12 weeks 
 
V802 
 
LV/ETV + 8 weeks to 
24 weeks 
V802 must occur at least 4 weeks after V801. 
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Study 
Visit/ 
Dosea 
Study 
Week 
Protocol 
Specified  
Day 
Protocol Specified 
Visit Tolerance 
Interval  
Mitigation Extension 
of Visit Interval 
Tolerance 
Mitigation Study 
Day Range 
Notes 
Abbreviations: 
; ETV = early termination visit; LV = last visit; V = Visit. 
a If a visit occurs after the extended visit window, the visit should be conducted at the earliest possible timepoint. Future participant visits must be adjusted to 
bring the participant back into compliance with the protocol defined visit windows. Doses must occur at least 
 apart. See “Adjustments to Visit 
Windows” above for further details. 
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10.13. 
Appendix 13: Optional Continued Access Period  
10.13.1. 
Overview  
This appendix will provide optional continued access to open-label mirikizumab for eligible patients following the completion of the long-
term extension period of AMAX.  
The duration of the Continued Access Period will differ by participant and country. 
Efficacy data will not be collected during the Continued Access Period. Participants will continue to be followed for safety throughout 
their participation in this Continued Access Period. 
 
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10.13.3. 
Schedule of Activities for Continued Access Period  
Throughout this appendix, “self-administration” refers to injection of mirikizumab by the 
participant or caregiver. 
All visits 
Office visits will generally occur every 
. Self-administration of mirikizumab 
 
 is required, regardless if the dosing is onsite or remote (refer to Section 10.13.7 for 
more detail). All other visit activities should be completed prior to self-administration of 
mirikizumab, unless otherwise stated below. 
Continued Access Treatment (Visit 501 to last dosing visit) 
Visit 501 activities should occur on the same day as Visit 19 of the long-term extension period if 
possible. It is recommended that the Visit 19 endoscopy be performed first, on a prior date within 
the Visit 19 window, followed by a combined Visit 19/ Visit 501 office visit on a later day also 
within the Visit 19 window.  
If this is not possible, the Visit 19 endoscopy can be performed on the same day as the Visit 19 
office visit, with Visit 501 being performed on a later date within window. Ensure all Visit 19 
activities are completed prior to starting Visit 501 activities and dosing. 
If Visit 19 and Visit 501 do not occur on same day, Visit 501 activities may need to be repeated, 
as detailed in the continued access period SoA. 
If Visit 19 and Visit 501 occur more than 2 weeks apart, the following laboratory tests must be 
repeated: hematology, clinical chemistry, and HBV DNA. 
Extended continued access visits (ECAV) 
After Visit 502 (
), ECAV continue until criteria for the final visit occurs (outlined in 
Section 10.13.8). 
Onsite ECAV Visits occur every 
 
Visit numbers will be registered sequentially after Visit 502. This table provides an example of 
the ECAV visit structure that will continue until the final visit. 
Visit Number 
Visit ID 
Weeks from AMAX Visit 1 
502 
502 
ECAV 
503 
ECAV 
504 
ECAV 
505, 506, 507… 
ECAV will continue until criteria for final visit occurs 
Discontinuation (DC) visit 
All participants who discontinue mirikizumab treatment after Visit 501 should complete this DC 
Visit. 
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Continued Access Period follow-up (4 weeks) 
Visit 901 
All participants will complete this visit following their DC visit or at the end of their 
participation in the Continued Access Period of the study. 
V901 may be performed onsite when onsite activities are required or at investigator’s discretion. 
Unscheduled visits 
Unscheduled visits may occur as needed, on any day without regard to visit interval. Required 
activities are indicated in the SoA. Additional procedures may be performed at the investigator’s 
discretion. 
 
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Procedures 
AMAX Continued Access Period Schedule of Activitiesa 
Visit Number 
501 
502 
ECAV 
DC 
UV 
V901 
Visit Type 
Office 
Office 
Office 
Office 
Office 
Phone 
Week Relative to Study Drug Startb 
Visit Tolerance Interval (VTI) in days 
All Participants (X); Optional (Opt) (See footnotes for additional key details) 
Confirmation of Informed consent  
X 
 
 
 
 
 
Inclusion and exclusion criteria 
X 
 
 
 
 
 
Concomitant medications 
Xc 
X 
X 
X 
X 
X 
Tobacco/Nicotine use 
 
 
Xd 
 
 
 
AEse (See Section 8.3)  
Xc 
X 
X 
X 
X 
X 
Physical Evaluation 
Vital signs  
(T, PR, BP) (See Section 8.2.1) 
Xc 
X 
X 
X 
X 
 
Weight 
Xc 
X 
X 
X 
X 
 
Physical examinationf (See Section 8.2.2) 
Xc 
X 
X 
X 
X 
 
TB Risk Assessment Monitoringg  
Xc 
X 
X 
X 
 
 
Participant Education 
Self-administration retraining 
Opth 
 
Opth 
 
Laboratory Tests 
Chemistry 
Xi 
X 
X 
Opt 
Opt 
 
Hematology 
Xi 
X 
X 
Opt 
Opt 
 
Urine pregnancy (local)j  
(See Section 8.2.7.1) 
Xc 
X 
X 
X 
 
X 
HBV DNA monitoringk 
Xi 
X 
X 
X 
 
 
Hypersensitivity kit (tryptase, PK, and 
immunogenicity) 
Xl 
 
On-Site Questionnaires (Paper) 
QIDS-SR16 
 
 
Xm 
X 
Opt 
 
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Procedures 
AMAX Continued Access Period Schedule of Activitiesa 
Visit Number 
501 
502 
ECAV 
DC 
UV 
V901 
Visit Type 
Office 
Office 
Office 
Office 
Office 
Phone 
Week Relative to Study Drug Startb 
Visit Tolerance Interval (VTI) in days 
 
CXR = chest x-ray; DC = discontinue; ECAV = extended continued access visits, FSH = follicle-stimulating hormone; HBcAb = hepatitis B core antibody; 
HBV = hepatitis B virus; IGRA = interferon gamma release assay; IP = investigational product; IWRS = Interactive Web Response Systems; PK = 
pharmacokinetic; PR = pulse rate; 
); SoA = schedule of activities; 
T = temperature; TB = tuberculosis; TST = tuberculin skin test; UV = unscheduled visit; V = visit. 
a Please see detailed instructions provided by the sponsor for calculation of visit dates. Additional AMAX SoA procedures may be performed during Continued 
Access at other timepoints at the investigator’s discretion (for example HBV DNA monitoring, urine pregnancy tests, TB Risk Assessment Monitoring, or 
others). Please contact your monitor for questions. 
b All activities should be completed prior to any study drug administration unless otherwise stated. ECAV visits will occur every 
 until patient meets 
discontinuation criteria.  
c If visits 501 and V19 do not occur on the same day, these activities must be repeated 
d Tobacco/Nicotine use data will be collected yearly. 
e For AESIs, additional data are collected (See Section 8.3.7). 
f Includes a symptom-directed evaluation as well as examination of eyes, heart, lungs, abdomen, and visual examination of the skin (Section 8.2.2). 
g Throughout the study, participants will be assessed for risk factors for TB (Section 10.5, Appendix 5). If the participant has a risk factor(s) or any TB-related 
signs or symptoms identified as part of the discussions of AEs or as part of the standard physical exam, the investigator should conduct a thorough exam to 
evaluate for TB, including examination of peripheral lymph nodes and documentation of body temperature. If there are relevant physical findings or other 
factors that the investigator feels warrant testing and imaging, an IGRA or TST and CXR should be performed (Table AMAX.1-3 Unscheduled assessments). 
A CT scan can be performed as an alternative to the CXR based on regional standard of practice (Section 8.2.6). 
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h Complete at the investigator’s discretion. See Section 10.13.7. 
i If there are not results available from safety laboratory collections within 
 of Visit 501, these laboratory tests must be repeated and results reviewed 
prior to dosing. 
j To be performed only on women of child-bearing potential. Done locally and prior to dosing (Section 8.2.7.1). Between visits, urine pregnancy tests are to be 
performed prior to monthly at-home dosing. Optional FSH may be performed as needed to confirm postmenopausal status in female participants. See  
Section 5.1 
k Perform only if participant had ongoing monitoring for HBV DNA during the long-term extension period of Study AMAX, or for participants in the 
Continued Access period who were found to be HBcAb+ and meet the requirements to continue in the study as described in Section 8.2.8. Such participants 
will undergo monitoring of HBV DNA at specified intervals. Any participant not meeting the requirements to continue in the study at any time must be 
discontinued from the study and receive appropriate follow-up medical care (Section 8.2.8). 
l In the event of a systemic allergic/hypersensitivity event, blood samples will be collected for PK, ADA, 
 at the 
following time points: as close as possible to: (1) the onset of the systemic allergic/hypersensitivity event, (2) the resolution of the systemic 
allergic/hypersensitivity event, 
 
m 
 to be administered every 6 months during continued access period. 
n Visit procedures and assessments must be completed prior to dosing. 
o Dispense study drug at each office visit 
 Changes cannot be made to dispensing and planned office visit schedules without prior sponsor 
approval (and potentially changes to safety lab testing schedule). Continue to dispense ancillary supplies at each visit as needed. Note that any used or unused 
study drug may be returned as an optional unscheduled activity at subsequent visits (see Table AMAX.1-3). 
p Site to complete and dispense Patient Study Drug Administration Log. Provide syringes for next dosing, inform participant of dosing date for self-injection, 
and provide ancillary supplies to participant. 
q Participant to return the Patient Study Drug Administration Log at the next visit. 
 
 
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10.13.4. 
Study Drug Self Administration Between Office Visits for Continued Access Period  
Procedures 
 
Name of Visit Interval at which Study Drug Administration Occursa 
501a 
501b 
502a 
502b 
ECAVa 
ECAVb 
Week Relative to Study Drug Start 
Days Relative to Study Drug Start and Visit Interval Tolerance (Days) 
 
a This table shows administration intervals between office visits. Please complete the Patient Study Drug Administration Log. If the participant is a woman of 
childbearing potential, a urine pregnancy test must be performed before dosing. Phone visits can be performed if needed to provide additional 
support/guidance. 
 
.
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10.13.5. 
Overall Design  
Transition of participants from the AMAX long-term extension period to optional 
Continued Access period 
A participant will 
 complete AMAX Visit 19 activities, including the Visit 19 study endoscopy with 
biopsies, and 
 complete the Continued Access section of the main AMAX study consent form and Visit 
501 activities of the Continued Access Period. 
o If a potentially eligible participant does not meet all inclusion and exclusion 
criteria at Visit 501, that participant should enter the posttreatment follow-up 
period of the main study protocol and complete Visits 801 and 802 as indicated in 
Section 1.3. 
o If a potentially eligible participant meets all inclusion and exclusion criteria at 
Visit 501, that participant should continue visits and procedures according to the 
SoA in Section 10.13.3 
10.13.6. 
Study Population  
The inclusion and exclusion criteria in this section are specific to this optional Continued Access 
Appendix, in addition to the inclusion and exclusion criteria listed in Section 5.  
10.13.6.1. Inclusion Criteria  
Participants are eligible to enter the Continued Access Period only if all the following criteria 
apply. 
Informed consent 
32. Have given signed informed consent to take part in the Continued Access Period prior to any 
procedures specific to Continued Access Period being completed. 
Participant and disease characteristics 
33. Have completed the AMAX long-term extension period, including 
 Visit 19 activities, including the 
 with biopsies without early termination 
of mirikizumab in main AMAX study, and 
 in the opinion of the investigator, would continue to derive benefit from treatment with 
mirikizumab. 
34. Have the ability to complete Visit 501, including the first dose of mirikizumab of the 
Continued Access Period, on the same day as Visit 19, or within approximately 
 after 
Visit 19. 
 It is strongly recommended that no more than 
 occur between the last dose in the 
long-term extension period 
 and the Visit 501 dosing of the Continued Access 
Period. Participants requiring a longer duration for entry into the Continued Access 
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Period, but not to exceed approximately 
, must be discussed on an individual 
basis with the medical monitor. 
35. Are willing and able to complete the SoA for the Continued Access Period, including 
self-administration of mirikizumab (by participant or caregiver). Also, in the opinion 
of the investigator, are able to reliably perform remote, self-administration 
procedures, and related required documentation. 
10.13.6.2. Exclusion Criteria  
Participants are excluded from the Continued Access Period if any of the following criteria 
apply: 
Gastrointestinal exclusion criteria 
36. Had a reported AE or SAE in the long-term extension period prior to Visit 501 that would 
disqualify them from treatment with mirikizumab according to originator study and/or long-
term extension criteria. 
37. Had permanently discontinued study drug in the long-term extension period or had a 
temporary interruption of study drug in the long-term extension period such that, in the 
opinion of the investigator or sponsor, restarting of mirikizumab would pose an unacceptable 
risk for the participant in Study AMAX. 
38. Meet any of the exclusion criteria from the AMAX long-term extension during the long-term 
extension period prior to Visit 501 (see Section 5.2) 
39. Are likely to require surgery for the treatment of worsening CD during the Continued Access 
Period. 
Other exclusion criteria 
40. Have been diagnosed with a condition, underwent a surgical procedure, received prohibited 
treatment, or experienced a laboratory abnormality that met criteria for permanent 
discontinuation from mirikizumab treatment prior to Visit 501 of the Continued Access 
Period. See Section 7.1. 
41. Currently meet temporary discontinuation of study intervention criteria (see Section 7.1). 
Note: Once resolution of the condition or appropriate treatment is met, the participant may be 
eligible for the Continued Access Period if the maximum roll-over period to enter the 
Continued Access Period has not been exceeded. 
42. Have initiated a new prohibited medication (see Section 10.7) prior to Visit 501 of the 
Continued Access Period. 
43. Have an underlying disease, or surgical, physical, or medical condition that, in the opinion of 
the investigator, would potentially affect participant safety within the Continued Access 
Period. 
44. Are pregnant or planning pregnancy (females only) while enrolled in the continued access 
period, or within 16 weeks after receiving the last dose SC dose of mirikizumab. 
45. Have enrolled or plan to enroll in any other clinical study involving an investigational 
product or any other type of medical research judged not to be scientifically or medically 
compatible with this study.  
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46. Are unsuitable for inclusion in the Continued Access Period in the opinion of the investigator 
or sponsor for any reason that may compromise the subject’s safety or confound the safety 
data interpretation. 
10.13.7. 
Study Intervention  
All participants in the Continued Access Period will self-administer 
 mirikizumab 
 
 
Administration of mirikizumab should always be done after completion of all other visit 
activities, as specified in SoA (Section 10.13.3). 
If self-administration is not possible, the study site staff may administer the dose at the study site 
and provide source documentation for the reason. If self-administration is not possible for 
repeated visits, study site should contact the medical monitor. Also note that the caregiver or 
participant may be allowed to administer limited injections at the study site, if needed. 
Reporting requirements 
All required self-administration dosing information must be documented on the relevant SDALs 
for each visit. Deviations from the prescribed dosing regimen should be documented by the 
participant on the SDAL and recorded by site staff in the CRF. 
Following review of the completed SDALs, and returned mirikizumab syringe cartons, including 
any unused syringes, if the site staff identifies any deviations from correct procedures, 
incomplete doses administered, product complaints, and/or injection concerns from participant, 
appropriate corrective actions, including retraining, should be completed. 
Treatment compliance 
Compliance with study intervention will be assessed at each visit. Compliance will be assessed 
by direct questioning, counting unused syringes, review of SDALs, and documented in the 
source documents. 
If a participant is noncompliant with self-administration procedures, the investigator should 
determine the reason for noncompliance and educate or manage the participant as appropriate to 
improve compliance. 
If, in consultation with the medical monitor, the noncompliance is deemed to be significant such 
that it affects the safety of the participant or the evaluation of the safety data during the 
Continued Access Period, the participant should be discontinued from the Continued Access 
Period. 
10.13.8. 
Discontinuation of Study Intervention and Participant Discontinuation from the 
Continued Access Period  
In addition to the study intervention discontinuation requirements in Section 7.1, the following 
also apply to the Continued Access Period: 
 a safety concern assessed by investigator as being related to study intervention, that 
should result in drug discontinuation 
 loss of response as assessed by the investigator 
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 
 
 
 investigator’s assessment that another clinical trial is appropriate for the participant 
 
 
 
 mirikizumab is locally commercially available and reimbursable (this includes patient 
access programs when and where available) 
 once a participant stops the Continued Access Period, they would not be eligible to 
resume, and 
 
 
Following discontinuation from mirikizumab during the Continued Access Period, the 
participant should complete both the discontinuation visit and Visit 901, as indicated in the 
Continued Access Period SoA (Section 10.13.3). 
10.13.9. 
Safety Assessments  
During the Continued Access Period, all AEs, SAEs, and mirikizumab exposure will be reported 
on the CRF. SAEs will also be reported to the sponsor. In the event that an SAE occurs, the 
sponsor may request additional information to evaluate the reported SAE. 
Investigators will perform any other standard procedures and tests needed to treat and evaluate 
participants. However, the choice and timing of the tests will be at the investigator’s discretion. 
The sponsor will not routinely collect the results of these assessments. 
See Sections, 8.2, 8.3, and 10.3 for more details. 
10.13.10. Concomitant Medication/Therapy  
10.13.10.1.Permitted Concomitant Medications/Therapies during Continued Access  
At the discretion of the investigator, any permitted concomitant medication may have the dose 
modified, be discontinued, or be re-started during the Continued Access Period. If there are any 
questions on these permitted medications, please contact the medical monitor. 
Drug Class (examples) 
Comments 
Oral corticosteroids (including oral 
budesonide or beclomethasone) for treatment 
of CD 
 
prednisone ≤30 mg/day or 
equivalent 
 
budesonide ≤9 mg/day, or 
 
beclomethasone dipropionate ≤5 
mg/day (gastro-resistant prolonged-
release tablet)  
Short courses of corticosteroids, including budesonide, are 
permitted with tapering to begin as soon as clinically feasible, 
with a goal of discontinuing within 3 months. 
Participants who require increasing doses and repeated courses or 
are intolerant to tapering of corticosteroids should be considered 
for treatment discontinuation and termination from the Continued 
Access Period 
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Drug Class (examples) 
Comments 
Corticosteroids for non-CD indications 
Permitted as follows: 
 
continued use to treat adrenal insufficiency 
 
locally administered use, e.g., inhaled, intranasal, 
intra-articular, and topical 
 
single doses (oral or IV) corticosteroids as 
premedication for miri self-administered injection 
 
limited use for acute conditions per investigator 
discretion, and 
 
possible use for chronic conditions must be discussed 
with medical monitor 
Rectally administered corticosteroids 
(enemas or suppositories) 
Permitted with the goal of tapering as soon as clinically feasible 
or discontinuing within 3 months. 
Immunomodulators for CD 
(oral AZA, 6-MP, or methotrexate) 
Permitted 
Antibiotics being used specifically for the 
treatment of CD (for example: rifaximin or 
Cipro) 
Permitted 
 
Oral 5-ASAs (mesalamine, balsalazide, 
olsalazine) and sulfasalazine for CD 
Permitted 
Rectally administered 5-ASAs 
(enemas or suppositories) 
Permitted 
Topical JAK inhibitors and topical 
calcineurin inhibitors 
Permitted 
Antidiarrheals 
(loperamide, diphenoxylate with atropine) 
Permitted 
Low-dose or baby aspirin (75 to 162.5 mg) 
Daily use for cardiovascular prophylaxis permitted 
Non-live vaccines 
(killed, inactivated, subunit, or RNA-based)  
Permitted 
Complementary alternative medicine for CD 
and non-CD indications 
(dietary/herbal supplements, vitamins, 
probiotics) 
Permitted 
Abbreviations: 5-ASA = 5-aminosalicylic acid; 6-MP = 6-mercaptopurine; AZA = azathioprine; 
CD = Crohn’s disease; IV = intravenous; JAK = Janus kinase. 
 
 
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10.13.10.2.Prohibited Concomitant Medications/Therapies during Continued Access  
This section outlines medications that, if initiated, require treatment and study discontinuation 
(Section 10.13.8) during the AMAX Continued Access Period, if applicable. If there are any 
questions on medications, please contact the medical monitor.  
Drug Class (examples) 
Continued Access Period 
Comments and Guidelines 
IV corticosteroids for CD 
Course of IV corticosteroids prohibited  
Systemic corticosteroids for non-CD indication, oral or IV 
Allowed exceptions: See Section 10.13.10.1 
Prohibited  
Immunomodulatory medications, oral or IV: 
Cyclosporine, mycophenolate mofetil, thalidomide, tacrolimus 
Other immunomodulatory medications should be discussed with 
medical monitor prior to use 
Prohibited 
Agents depleting B or T cells 
(alemtuzumab, rituximab, visilizumab) 
Prohibited  
Interferon therapy 
Prohibited unless medically necessary for 
short term COVID treatment 
Leukocyte apheresis, leukapheresis (Adacolumn) 
Prohibited  
Bacillus Calmette-Guerin (BCG) vaccination  
Use prohibited during study and ≤12M after 
last dose of mirikizumab 
Live or attenuated vaccines 
(for measles, mumps, rubella, or varicella) 
Use prohibited during study and ≤3M after 
last dose of mirikizumab 
Abbreviations: CD = Crohn’s disease; COVID = coronavirus disease; IV = intravenous; M = month. 
 
 
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10.13.10.3.Alternative Treatment after Discontinuation of Mirikizumab in the Continued 
Access Period  
When investigator or sponsor assess, based on current evidence, that an alternative treatment is 
an acceptable option and is available locally, the participant should be discontinued from the 
Continued Access Period. 
Examples of alternative treatment for CD after discontinuation are described in this table.  
Drug Class (examples) 
Continued Access Period 
Comments and Guidelines 
Anti-TNF antibodies 
(adalimumab, golimumab, infliximab)  
May use after discontinuation of 
mirikizumab 
Anti-IL-12/23p40 antibodies 
(ustekinumab) 
Anti-IL-23p19 antibodies 
(risankizumab, brazikumab, guselkumab, tildrakizumab) 
Anti-integrin antibodies 
(vedolizumab) 
JAK inhibitors, oral (tofacitinib, upadacitinib) 
Small-molecule S1P receptor modulator (ozanimod) 
Any investigational therapy, biologic or non-biologic 
 Abbreviations: CD = Crohn’s disease; IL= interleukin; JAK = Janus kinase; S1P = Sphingosine-1-phosphate; 
TNF = tumor necrosis factor. 
 
 
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10.14. 
Appendix 14: Optional 
 Substudy  
10.14.1. 
Overview  
This substudy is optional for participants who are active in the main study. This substudy is 
being conducted on a subset of participants to assess 
 for 
self-administration by participants or caregivers.  
The 
 that is used to deliver mirikizumab. The 
ePFS represents an eventual commercial presentation of the combination product, which is 
 
Informed consent will be obtained from participants and caregivers participating in the optional 
 self-administration substudy. 
This appendix must be followed for all participants in the optional 
 substudy, in addition to 
all procedures required by Protocol AMAX or any subsequent amendments to that protocol, as 
applicable. 
10.14.2. 
Inclusion Criteria  
) Self-Administration Eligibility 
Participation in this 
 self-administration substudy is voluntary. 
Participants are eligible to perform self-administration of investigational product using the 
 
if they are appropriately trained and they meet the following criteria: 
47. Participants must have given the written informed consent for the optional 
 self-
administration substudy that has been approved by the ethical review board governing the 
site prior to 
 self-administration training. 
48. Participants must have successfully completed (according to the investigator) at least 1 visit 
with training on 
 self-administration prior to performing independent self-administration 
of 
 
Note that participants are not required to train on 
 prefilled syringe (PFS) prior 
to 
 self-administration training, nor are participants required to train on ePFS prior 
to self-administration training for 
 PFS. 
10.14.3. 
Study Intervention  
The study intervention used in the main AMAX study is mirikizumab administered by IV or SC 
injection.  
Subcutaneous injection for this substudy will be administered with 
  
The doses and routes of administration reflect the multipart study design (Section 4.1). 
Each dose will consist of
 
 
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For the purpose of the participant’s convenience, the independent 
 self-administration by 
the participant or caregiver (non-site staff) may be performed at home or at the study site, 
simulating home use.  
Injection location 
Possible injection sites are identified in the instructions provided by the sponsor for the 
investigational product. The injection site may be rotated to another area for subsequent doses. 
Note that in the case a study drug injection is performed in an arm, it is not to be given in the 
same arm from which participant blood samples, including pharmacokinetic samples, are drawn 
at relevant visits. 
Study Drug Administration Logs  
Study Drug Administration Logs will be dispensed to each participant for recording pertinent 
data about each injection. Details of the use of these logs are provided in Section 6.1.1. 
Packaging and Labeling 
Clinical trial materials will be labeled for the study and according to the country’s regulatory 
requirements. All investigational products will be stored, inventoried, reconciled, and destroyed 
according to applicable regulations. Clinical trial materials are manufactured in accordance with 
current GMP. 
 
The 
 will provide a single injection of mirikizumab. 
o The 
 is manufactured to deliver
 
o The 
 is manufactured to deliver 
 
The 
 will be supplied with the appropriate quantity specific to the planned dispensing 
schedule. Investigational product will be provided with study-specific labels. 
10.14.3.1. Participant Training and Administration  
General guidance 
Detailed instructions for investigational product administration will be provided by the sponsor, 
and the investigational product will be administered at the site by clinical staff for the first 
administration of Training Visit 1. At this visit, site staff will train participants on self-injection 
with 
 and will provide them with a log to track their doses at home. 
All administrations for the following three visits will be done by the participant or caregiver. 
Participant training 
The participant (and/or caregiver) will begin training on the use of the 
 at a 
regularly scheduled office visit, once the 
 and the
 
 become available.  
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At the training session, site personnel will train the participant and/or caregiver to perform the 
injections using the 
 and will administer the first injection. The participant and/or caregiver 
will then administer the second injection of the dose using an 
 while the site personnel 
provide oversight and instruction. 
Additional training may occur at any time during the substudy, as needed. 
Reporting requirements 
Site staff must complete the Patient Study Drug Administration Training Log during each 
Training Visit, including any telemedicine visits for remote retraining (see 
 dosing table 
below for documentation required by site). 
Remote training 
If retraining needs to be performed and is conducted remotely, telemedicine visits with the 
participant must be conducted during the administration of the dose in order to provide additional 
guidance, if needed, and to confirm dosing completion. 
 
During each 
 dosing, the participant/caregiver must complete an 
 form for 
each set of injections that they administer (at the training visit, the 
 responses should 
only refer to the injection that is given by the participant/caregiver). The participant will need to 
report product complaints, any user error or use issues, issues with the instructions for use, label 
deficiencies, etc. to the Investigator. 
Independent self-administration period 
During the 
 independent self-administration period, participants/caregivers will perform the 
next 
 with the 
.  
The Patient Study Drug Administration Log must be completed by participants during each self-
administration. See table below for documentation required by participant.  
 
 
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 Dosing 1a,b,c,d 
 Dosing 2e 
 Dosing 3e 
 Dosing 4e,f 
Type of Visit 
Training 
Independent Self-
Administration 
Independent Self-
Administration 
Independent Self-
Administration 
Home or Office 
Office 
Office or Home 
Office or Home 
Office or Home 
Investigational 
Productg 
Mirikizumab 
 
Mirikizumab 
 
Mirikizumab 
 
Mirikizumab 
 
First 
 
Injection 
Administeredb 
HCP 
Participant and/ or 
Caregiver 
Participant and/ or 
Caregiver 
Participant and/ or 
caregiver 
Second 
 
Injection 
Administeredb 
Participant and/or 
Caregiver 
Participant and/ or 
Caregiver 
Participant and/or 
Caregiver 
Participant and/or 
Caregiver 
Documentation 
Required by 
Participant 
and  
PATIENT 
STUDY DRUG 
ADMINISTRATI
ON LOG 
and 
PATIENT STUDY 
DRUG 
ADMINISTRATION 
LOG 
and 
PATIENT STUDY 
DRUG 
ADMINISTRATION 
LOG 
Documentation 
Required by Site 
PATIENT STUDY 
DRUG 
ADMINISTRATIO
N TRAINING 
LOGh 
N/A 
N/A 
N/A 
Abbreviations: 
; HCP = health care provider; PFS = prefilled syringe;
 
 SDATL = Study Drug Administration Training Log. 
a 
 training must start on a regularly scheduled office visit and must begin no earlier than V4 and no later than 
V16. 
 substudy will not be allowed to start at V11. If 
 training starts at Visits 12-16, participants who 
were not previously trained on PFS self-administration will be required to come onsite for the next PFS dosings 
after they complete the 
 dosings, in order to receive PFS training or to have PFS dosings administered by 
site staff. Please see additional details provided separately by the sponsor for scenarios based on beginning 
 
training at each of the allowed visits. 
b If the investigator, participant, or caregiver judges at any time during the 
 period that self-administration 
cannot be performed independently, the participant will no longer participate in the 
 self-administration 
substudy. If the investigator judges that the participant or caregiver is able to successfully self-administer the 
PFS, the participant may continue use of PFS self-administration independently. 
c 
 informed consent must be obtained before any 
 Visit 1 Procedures. 
d Site to complete training with participant using the Patient Study Drug Administration Training Log. ePFS 
training may begin once the 
 and the 
 forms become available. 
 training will be 
completed after the participant meets eligibility criteria.  
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e At any time after the training visit, the participant or caregiver may be retrained on how to self-administer 
investigational product, if needed. If the retraining is performed remotely, a telemedicine visit must be 
conducted. 
f After the participant completes 3 independent self-administration occurrences with 
 the participant will 
return to using the 
, either by self-administration with the required prior training or administered 
by the HCP if the participant or caregiver is unable. 
g 
 injections 
 can be administered in any order.  
h If subsequent Training Visits are required, site personnel to complete the SDATL at those visits. 
 
 
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Returning to use of 
 PFS 
After the participant/caregiver completes the third independent self-administration dosing with 
the 
 the participant will return to using the 
l PFS. 
The participant may continue the use of PFS self-administration independently if the investigator 
judges that the participant is able to perform this successfully and PFS training is completed. 
If the participant/caregiver was previously trained on self-administration with the PFS, the site 
staff may perform re-training as needed. If the participant/caregiver has not been trained on using 
the PFS, they should be offered training.  
If the participant is unable/unwilling to self-administer with PFS, the sponsor may approve a 
general exception for self-administration for a participant depending on circumstances (See 
Section 5.1, Criterion #4). 
10.14.4. Discontinuation of Study Intervention and Participant Discontinuation from the 
Substudy  
If the investigator or the participant/caregiver judges that 
 training is unsuccessful or the 
self-administration dosings cannot be performed independently, the participant will no longer 
participate in the 
 self-administration substudy 
10.14.5. 
Secondary Efficacy Assessments  
10.14.5.1. PROs  
All Participants from AMAG and AMAM  
The 
 will be collected for each set of 
 injections performed by a 
participant/caregiver for both training and independent administrations. 
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10.14.6. 
Complaint Handling  
See Section 8.3.8.  
10.14.7. 
Analyses  
Analyses presented for this substudy will be descriptive, including frequency counts and 
percentages, and use the modified intent-to-treat population in participants who have enrolled in 
the 
 substudy.  
In participants who have completed 
 training, analyses of successful administration with an 
 may be presented by administration attempt. 
 
 
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10.15. 
Appendix 15: Country-specific Requirements  
This appendix is applicable for sites in EU-member states and Turkey. 
Note: Deletions to the main protocol sections are identified by strikethrough format and 
additions by underlined text.  
10.15.1. 
Hungary, Latvia, and Romania  
This section describes protocol changes applicable for participants in study sites in Hungary, 
Latvia, and Romania 
This table describes the changes and provides a rationale for the changes 
Protocol Section Number and Name 
Description of the Change 
Brief Rationale 
5.1 Inclusion Criteria  
Updated inclusion criterion [6]  
To align with contraceptive use for 
all sites in Hungary, Latvia, and 
Romania 
The revised text in the following sections show the changes applicable for participants at study 
sites in Hungary, Latvia, and Romania.  
5.1 
Inclusion Criteria 
[6] 
Contraception: Contraceptive use by men or women should be consistent with local 
regulations regarding the methods of contraception for those participating in clinical studies. 
a. Male Participants: 
No male contraception is required except in compliance with specific local government 
study requirements. Agree to use a reliable method of birth control during the study and 
for at least 16 weeks following the last dose of the study drug. 
b. Female Participants: 
Women of childbearing potential (WOCBP, defined as all adult females unless they are 
WNOCBP as defined below) may participate if they meet the following criteria: 
A. must test negative for pregnancy prior to initiation of treatment as indicated by a 
negative urine pregnancy test at Visit 1/Week 0 of this study 
AND 
B. must agree to either remain abstinent, if complete abstinence is their preferred and 
usual lifestyle, or remain in same-sex relationships, if part of their preferred and usual 
lifestyle, without sexual relationships with males. Periodic abstinence (for example, 
calendar, ovulation, symptothermal, or postovulation methods), declaration of 
abstinence just for the duration of a trial, and withdrawal are not acceptable methods 
of contraception, 
OR 
must use a combination of 2 effective methods of contraception or 1 highly effective 
method of contraception for the entirety of the study, where at least 1 method must be 
highly effective and the other method is effective or highly effective. Abstinence or 
cContraception must continue for 16 weeks following completion of study drug 
administration for 16 weeks. 
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i. 
Effective methods of contraception may include barrier methods such as male or 
female condoms with spermicide, diaphragms with spermicide, or cervical 
sponges (which usually are made with spermicide). The barrier method must 
include use of a spermicide to be counted as one effective method. 
ii. Highly effective (<1% failure rate) methods of contraception (at least one of 
which must be used) include 
 female sterilization  
 combination oral contraceptive pill 
 progestin-only contraceptive pill (mini-pill) 
 implanted contraceptives 
 injectable contraceptives 
 contraceptive patch (only women <198 pounds or 90 kg) 
 vasectomy (if only sexual partner) 
 fallopian tube implants (if confirmed by hysterosalpingogram) 
 combined contraceptive vaginal ring, or  
 intrauterine devices 
iii. Ineffective forms of contraception, whether used alone or in any combination, 
include 
 spermicide alone 
 periodic abstinence 
 fertility awareness (calendar method, temperature method, cervical mucus, 
or symptothermal) 
 withdrawal 
 postcoital douche or 
 lactational amenorrhea 
Women not of childbearing potential (WNOCBP) may participate and include those 
who are: 
A. infertile due to surgical sterilization (total hysterectomy, bilateral 
salpingo-oophorectomy, bilateral salpingectomy, bilateral oophorectomy, or tubal 
ligation)a, have a congenital anomaly such as Müllerian agenesis 
OR 
B. postmenopausalb – defined as either: 
i. a woman at least 40 years of age with an intact uterus, not on hormone therapy, 
who has had either: 
 cessation of menses for at least 1 year, without an alternative medical cause 
 at least 6 months of spontaneous amenorrhea with a follicle-stimulating 
hormone level >40 mIU/mL 
ii. a woman 55 years or older not on hormone therapy, who has had at least 6 months 
of spontaneous amenorrhea, or 
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iii. a woman at least 55 years of age with a diagnosis of menopause prior to starting 
hormone replacement therapy. 
a 
Note that if it has been less than 6 weeks post-surgical bilateral oophorectomy 
with or without hysterectomy, she will be required to use contraception until she has 
reached 6 weeks since the procedure. 
b 
For the purpose of defining the length of time of amenorrhea to determine 
postmenopausal status, only count time in which the woman was not taking 
medications such as oral contraceptives, hormones, gonadotropin-releasing hormone, 
anti-estrogens, SERMs, or chemotherapy that could induce transient amenorrhea. 
10.15.2. 
Netherlands and Turkey  
This section describes protocol changes applicable for adult participants in study sites in 
Netherlands and Turkey 
This table describes the changes and provides a rationale for the changes 
Protocol Section Number and Name 
Description of the Change 
Brief Rationale 
7.2. Participant Discontinuation/Withdrawal 
from the Study 
Added information about 
inadvertently enrolled 
participants 
To remove inadvertently 
enrolled participants from the 
study 
The revised text in the following sections show the changes applicable for adult participants at 
study sites in Netherlands and Turkey.  
7.2 
Participant Discontinuation/Withdrawal from the Study 
If the sponsor or investigator identifies a participant who did not meet enrollment criteria and 
was inadvertently enrolled into AMAX, the participant must be withdrawn from the study in 
order to comply with local regulations. 
10.15.3. 
Czech Republic  
This section describes protocol changes applicable for adult participants in study sites in the 
Czech Republic. 
 
 
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This table describes the changes and provides a rationale for the changes 
Protocol Section Number and Name 
Description of the Change 
Brief Rationale 
1.3 Schedule of Activities  
Updated tuberculosis risk 
assessment and yearly 
screening for active and latent 
TB in participants 
Updated in accordance with 
regulatory requirements in the 
Czech Republic 
5.1 Inclusion Criteria 
Updated inclusion criteria [6] b 
Revised in accordance with 
regulatory requirements in the 
Czech Republic 
8.2.4 Chest Radiography 
Added Czech Republic-specific 
details for chest radiography 
Updated in accordance with 
regulatory requirements in the 
Czech Republic 
8.2.6 Tuberculosis Testing 
Added Czech Republic-specific 
details for tuberculosis testing 
and removed general 
instructions for initial screening 
test 
Updated in accordance with 
regulatory requirements in the 
Czech Republic 
The revised text in the following sections show the changes applicable for adult participants at 
study sites in the Czech Republic. 
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1.3 
Schedule of Activities (SoA) 
1.3.1 Visit 1 through Visit 9 
 
Table AMAX.1 1. 
Schedule of Activities - Visit 1 through Visit 9 (
 
Procedures 
Schedule of Activitiesa 
Visit Number 
V1b 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
Visit Type 
Office – 
Screening/ 
V1a 
Office - 
Dosing/V1b Office Office Phone Office Office Office Office Office Phone Office 
Week Relative to Study Drug Startc 
Day with Visit Tolerance Interval (VTI) 
All Participants (X); AMAM Rollover Participants Only (M); AMAG Rollover Participants Only (G); Optional (Opt) (See footnotes for additional key 
details) 
TB Risk Assessment Monitoringi 
Xaf 
Xah 
X 
 
 
X 
X 
X 
X 
X 
 
X 
Yearly screening for active and latent TB in 
participants in the Czech Republic* 
X 
 
 
 
 
 
 
 
 
 
 
X 
Abbreviations: AEs = adverse events; CT = computed tomography; CXR = chest x-ray; 
; IGRA = interferon gamma 
release assay; NA = Not applicable; PK = pharmacokinetic; TB = tuberculosis; TST = tuberculin skin test; V = Visit 
* Participants from the Czech Republic will be screened for active and latent TB infection annually, including at Visits 1 and 9. This will include the assessment 
of medical history, AEs, and clinical risk, physical examination, and a TB test as described Tuberculosis Testing section (Section 8.2.6 of main protocol and 
Section 8.2.6 of this appendix). Participants who had a TST must return 48 to 72 hours after placement to have their test results read by a pulmonologist. A 
chest X-ray may be performed if clinically indicated. A CT scan may be performed as an alternative based on regional standard of practice 
a Please see detailed instructions provided by the sponsor for calculation of visit dates. Also, note that unscheduled assessments can be performed during 
scheduled visits, see Table AMAX.1-3 for details.  
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b V1 is a split visit, occurring on at least 2 office visits on different dates. Screening procedures are to be performed at the first part of V1, called 
Screening/V1a, in order to have results available to confirm eligibility prior to dosing. For AMAM-originating participants, it is recommended that V1a 
screening procedures be on the same date as AMAM V17. V1 dosing is performed at the Dosing/V1b visit. For both AMAM and AMAG-originating 
participants, the timing for AMAX V1a and V1b must allow for first AMAX dosing (V1b) within no more than 
 from the last dosing in the 
originating study. It is required that all screening assessments, including laboratory test results are reviewed to confirm eligibility from both the final visit of 
the originating study as well as AMAX V1a, as applicable, prior to dosing at V1b. For participants originating from AMAM, 
 
. Note that some assessments may be required at both V1a and V1b. Refer to 
footnotes for details. To accommodate potential lab delays and/or needs for retesting, please plan for at least 10 business days to obtain lab results after initial 
samples are received at the laboratory, and up to 5 business days for endoscopy results after receipt of video. 
c All activities should be completed prior to any study drug administration unless otherwise stated. 
d See footnote b for definitions of the V1 Screening visit (V1a) and the V1 Dosing visit (V1b). V1 dosing (V1b) is defined as Day 1. All V1 screening activities 
need to be performed prior to dosing, including all assessment retesting (if needed), with results available prior to dosing such that the total interval from last 
dose in the originating study to first dose in AMAX is no more than 
. Please see detailed instructions provided by the sponsor for calculation of 
subsequent visit dates. 
i At V1 and t Throughout the study, participants will be assessed for risk factors for TB (Section 10.5, Appendix 5). If the participant has a risk factor(s) or any 
TB-related signs or symptoms identified as part of the discussions of preexisting conditions or AEs, or as part of the standard physical exam, the investigator 
should conduct a thorough exam to evaluate for TB, including examination of peripheral lymph nodes and documentation of body temperature. If there are 
relevant physical findings or other factors that the investigator feels requires testing and imaging, an IGRA or TST and a CXR should be performed 
(Table AMAX.1-3 Unscheduled assessments). A CT scan can be performed as an alternative to the CXR, based on regional standard of practice 
(Section 8.2.6). 
af Collect/assess at AMAX V1a if not performed at the last visit of the originator study. 
ah If more than 14 weeks will have elapsed between last collection/assessment and the first AMAX dosing, additional procedures must be performed again prior 
to the V1b dosing. See sponsor guidance regarding sample collection kits or data entry for items that need to be collected again at V1b. Investigator medical 
judgment should be used regarding whether the repeat lab results should be available and reviewed prior to dosing (review prior to dosing not needed for PK, 
immunogenicity,
, or fecal calprotectin).  
 
 
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1.3.2 Visit 10 through Visit 19 
 
Table AMAX.1 2. 
Schedule of Activities - Visit 10 through Visit 19 
 
Procedures 
Schedule of Activitiesa 
Visit Number 
V10 
V11 
V12 
V13 
V14 
V15 
V16 
V17 
V18 
V19 
Visit Type 
Office 
Office 
Phone 
Office 
Office  Phone 
Office 
Office 
Phone 
Office 
Office 
Office 
Phone 
Office 
Week Relative to Study 
Drug Startb 
Day with Visit 
Tolerance Interval 
(VTI) 
All Participants (X); AMAM Rollover Participants Only (M); AMAG Rollover Participants Only (G); Optional (Opt) (See footnotes for additional 
key details) 
TB Risk Assessment 
Monitoringf 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
X 
 
X 
Yearly screening for active 
and latent TB in participants 
in the Czech Republic* 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
Abbreviations: AEs = adverse events; CT = computed tomography; CXR = chest x-ray; IGRA = interferon gamma release assay; TB = tuberculosis; TST = 
tuberculin skin test; V = visit. 
* Participants from the Czech Republic will be screened for active and latent TB infection annually, including at Visits 14 and 19. This will include assessment 
of medical history, AEs and clinical risk, physical examination, and a TB test as described in Tuberculosis Testing section (Section 8.2.6 of main protocol and 
Section 8.2.6 of this appendix). Participants who had a TST must return 48 to 72 hours after placement to have their test results read by a pulmonologist. A 
chest X-ray may be performed if clinically indicated. A CT scan may be performed as an alternative based on regional standard of practice. 
a Please see detailed instructions provided by the sponsor for calculation of visit dates. Also, note that unscheduled assessments can be performed during 
scheduled visits, see Table AMAX.1-3 for details. Please refer to Section 10.13.3 for the optional continued access period details. Participants from the Czech 
Republic will continue to be screened for active and latent TB infection annually during continued access if they participate. 
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b All activities should be completed prior to any study drug administration unless otherwise stated. 
c Site to remind participant to complete 14-Day diary and/or bowel prep, as appropriate. Phone reminder must occur at least 15 days prior to actual next visit 
date to ensure the participant begins the collection of diary data in time. 
f Throughout the study, participants will be assessed for risk factors for TB (Section 10.5, Appendix 5). If the participant has a risk factor(s) or any TB-related 
signs or symptoms identified as part of the discussions of AEs or as part of the standard physical exam, the investigator should conduct a thorough exam to 
evaluate for TB, including examination of peripheral lymph nodes and documentation of body temperature. If there are relevant physical findings or other 
factors that the investigator feels warrant testing and imaging, an IGRA or TST and CXR should be performed (Table AMAX.1-3 Unscheduled assessments). 
A CT scan can be performed as an alternative to the CXR based on regional standard of practice (Section 8.2.6). 
 
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5.1 
Inclusion Criteria 
[6] b. Female Participants: 
Women of childbearing potential (WOCBP, defined as all adult females unless they are 
WNOCBP as defined below) may participate if they meet the following criteria: 
A. must test negative for pregnancy prior to initiation of treatment as indicated by a 
negative urine pregnancy test at Visit 1/Week 0 of this study within 24 hours prior to 
exposure 
AND 
B. must agree to either remain abstinent, if complete abstinence is their preferred and 
usual lifestyle, or remain in same-sex relationships, if part of their preferred and usual 
lifestyle, without sexual relationships with males. Periodic abstinence (for example, 
calendar, ovulation, symptothermal, or postovulation methods), declaration of 
abstinence just for the duration of a trial, and withdrawal are not acceptable methods 
of contraception, 
OR 
must use a combination of 2 effective methods of contraception or 1 highly effective 
method of contraception for the entirety of the study, where at least 1 method must be 
highly effective and the other method is effective or highly effective. Abstinence or 
contraception must continue following completion of study drug administration for 16 
weeks. 
i. 
Effective methods of contraception may include barrier methods such as male or 
female condoms with spermicide, diaphragms with spermicide, or cervical 
sponges (which usually are made with spermicide). The barrier method must 
include use of a spermicide to be counted as one effective method. 
ii. At least one highly effective method of contraception must be used. A highly 
effective method of contraception is defined as one with a Pearl index <1 (which 
is used to measure the reliability of birth control methods), such as male or female 
sterilization, hormonal birth control like the Pill (with the exception of Mini Pill), 
3-month injection, hormone implantation, hormone loop, vaginal ring, or 
transdermal patch. Highly effective (<1% failure rate) methods of contraception 
include 
 female sterilization 
 combination oral contraceptive pill 
 progestin-only contraceptive pill (mini-pill) 
 implanted contraceptives 
 injectable contraceptives 
 contraceptive patch (only women <198 pounds or 90 kg) 
 vasectomy (if only sexual partner) 
 fallopian tube implants (if confirmed by hysterosalpingogram) 
 combined contraceptive vaginal ring, or 
 intrauterine devices. 
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iii. Ineffective forms of contraception, whether used alone or in any combination, 
include 
 spermicide alone 
 periodic abstinence 
 fertility awareness (calendar method, temperature method, cervical mucus, or 
symptothermal) 
 withdrawal 
 postcoital douche, or 
 lactational amenorrhea. 
Women not of childbearing potential (WNOCBP) may participate and include those who 
are: 
A. infertile due to surgical sterilization (total hysterectomy, bilateral salpingo-
oophorectomy, bilateral salpingectomy, bilateral oophorectomy, or tubal ligation)a, have 
a congenital anomaly such as Müllerian agenesis,  
OR 
B. postmenopausalb – defined as either: 
i. a woman at least 40 years of age with an intact uterus, not on hormone therapy, 
who has had either 
 cessation of menses for at least 1 year, without an alternative medical cause 
 at least 612 months of spontaneous amenorrhea with a follicle-stimulating 
hormone (FSH) level >40 mIU/mL 
ii. a woman 55 years or older not on hormone therapy, who has had at least 
612 months of spontaneous amenorrhea, or 
iii a woman at least 55 years of age with a diagnosis of menopause prior to starting 
hormone replacement therapy. 
a 
Note that if it has been less than 6 weeks post-surgical bilateral oophorectomy 
with or without hysterectomy, she will be required to use contraception until she has 
reached 6 weeks since the procedure. 
b 
For the purpose of defining the length of time of amenorrhea to determine 
postmenopausal status, only count time in which the woman was not taking 
medications such as oral contraceptives, hormones, gonadotropin-releasing hormone, 
anti-estrogens, SERMs, or chemotherapy that could induce transient amenorrhea. 
8.2.4 Chest Radiography 
A posterior-anterior chest x-ray (CXR), interpreted and reported by a radiologist or 
pulmonologist, will be obtained if there are relevant TB-related physical findings or other factors 
that the investigator feels warrant testing and imaging, as specified in the SoA (Section 1.3), and 
Section 8.2.6 of main protocol and Section 8.2.6 in this appendix. A posterior-anterior CXR may 
be obtained at Visit 1 at the investigator’s discretion, if clinically indicated for TB infection. A 
lateral chest x-ray can also be obtained if, in the opinion of the investigator, a lateral view is 
indicated. Patients with documentation of a CXR, read by a qualified radiologist, that is 
sufficient for TB evaluation according to local standard of care, performed within 3 months 
before initial screening, may not need to repeat CXR at screening, based on the judgement of the 
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investigator. In either case, the CXR film(s)/image(s) or a radiology report must be available to 
the investigator for review. A computed tomography (CT) scan can be performed as an 
alternative to the CXR based on regional standard of practice. An IGRA or TST should also be 
performed (Section 8.2.6 of main protocol and Section 8.2.6 in this appendix). 
8.2.6. Tuberculosis Testing 
Initial Screening 
All participants will be evaluated for risk factors for LTBI at rollover from their originator 
studies during the AMAX Visit 1 (Section 10.5, Appendix 5). If the participant has risk factors 
or any TB-related signs or symptoms are identified as part of the discussions of preexisting 
conditions or as part of the standard physical exam, the investigator should conduct a thorough 
physical examination, including body temperature measurement and assessment of peripheral 
lymph nodes. For participants with relevant TB-related physical findings or other factors that the 
investigator feels warrant testing and imaging: 
 a TB test should be performed: 
o IGRA (for example, QuantiFERON-TB Gold or TSPOT.TB), or 
o Tuberculin skin test (TST; also called a purified protein derivative [PPD] or 
Mantoux test). 
Participants from the Czech Republic will be screened for active and latent TB infection (LTBI) 
at Visit 1. This will include the following: 
 Medical history of ongoing adverse events from originator study (Visit 1). 
 Clinical assessment of risk (Section 10.5, Appendix 5). 
 Physical examination as described in Section 8.2.2, and include body temperature 
measurement and assessment of peripheral lymph nodes. 
 A test to assess immune response to mycobacterial antigens such as interferon- release 
assay (interferon gamma release assay [IGRA], for example, QuantiFERON-TB Gold or 
T-SPOT.TB). 
 If a tuberculin skin test (TST) or purified protein derivative test is performed, the test will 
be at a designated location (a pulmonary outpatient clinic) and read by a pulmonologist. 
Note: 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. 
If participant has a history of positive TB test result with prophylaxis, TB testing should 
not be performed unless advised to do so based on local guidelines (See also section on 
Prior Treatment for LTBI). 
 a CXR may should be performed if clinically indicated, as described in Section 8.2.4. A 
CT scan may be performed as an alternative to the CXR based on regional standard of 
practice. 
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Monitoring for TB during the study 
For all participants, monitoring for TB is to be continuous throughout the study. Every 2 to 
3 months as indicated in the SoA, the participants will be assessed for risk factors for TB 
(Section 10.5, Appendix 5). If the participant has a risk factor or any TB-related signs or 
symptoms identified as part of the AE discussions or standard physical exam, the investigator 
should conduct a thorough exam to evaluate for TB, including examination of peripheral lymph 
nodes and documentation of body temperature. If there are relevant physical findings or other 
factors that the investigator feels warrant testing and imaging, an IGRA OR TST and CXR 
should be performed. A CT scan can be performed as an alternative to the CXR, based on 
regional standard of practice. 
Participants from the Czech Republic will also be screened for active and latent TB infection at 
yearly interval visits V9, V14, and V19 over the duration of the study (and throughout continued 
access if they participate), following all steps described above for Initial Screening, with medical 
assessment of all ongoing adverse events and with testing. 
10.15.4. 
Hungary  
This section describes protocol changes applicable for participants in study sites in Hungary. 
This table describes the changes and provides a rationale for the changes 
Protocol Section Number and Name 
Description of the Change 
Brief Rationale 
1.1 Synopsis 
Added additional information 
for participants in Hungary 
who were in the placebo 
group at Week 52 of AMAM 
and considered responders at 
Week 52 of AMAM 
Updated in accordance the 
comments from the Medical 
Research Council, Ethics 
Committee for Clinical 
Pharmacology of Hungary 
4.1 Overall Design 
Added additional information 
for participants in Hungary 
who were in the placebo 
group at Week 52 of AMAM 
and considered responders at 
Week 52 of AMAM 
Updated in accordance the 
comments from the Medical 
Research Council, Ethics 
Committee for Clinical 
Pharmacology of Hungary 
7.2 Participant Discontinuation/Withdrawal 
from the study 
Added AMAX participant 
discontinuation/withdrawal 
from study details for 
participants in Hungary who 
were in the placebo group at 
Week 52 of AMAM and 
considered responders at 
Week 52 of AMAM 
Updated in accordance the 
comments from the Medical 
Research Council, Ethics 
Committee for Clinical 
Pharmacology of Hungary 
The revised text in the following sections show the changes applicable for adult participants at 
study sites in Hungary.  
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1.1. 
Synopsis 
Overall Design 
Study AMAX is a Phase 3, multicenter, long-term extension study evaluating the efficacy and 
safety of mirikizumab in participants with moderately-to-severely active CD who have 
participated in an originator adult mirikizumab CD study, inclusive of the Phase 3 Study AMAM 
and the Phase 2 Study AMAG. 
Participants who are
 
for an extended period of time (up to 3 years) and then enter a 12- to 16-
week posttreatment follow-up period. Participants who are 
 
 
fter completion of the long-term extension period, if mirikizumab is not yet 
locally commercially available and reimbursable, eligible participants will be provided with an 
option of continued access to open-label mirikizumab, followed by a 4-week follow-up period. 
The duration of the continued access will differ by participant and country. 
Participants who meet all of the inclusion criteria and none of the exclusion criteria of AMAX, 
and who, in the opinion of the investigator, would receive benefit from open-label treatment with 
mirikizumab are eligible for enrollment into Study AMAX. It is possible that some participants 
enrolling from Study AMAM may have received placebo only in the originating study. These 
participants will receive mirikizumab for the first time in Study AMAX. After the AMAM final 
database lock, the sponsor will unblind the treatment assignments of Hungary participants from 
Study AMAM. To comply with the response from the Medical Research Council, Ethics 
Committee for Clinical Pharmacology of Hungary, any Hungary sites that have participants who 
were in the placebo intervention group at Week 52 of Study AMAM and were considered 
responders at Week 52 of Study AMAM will receive a notification through the investigator to 
discontinue the participant from Study AMAX. These participants will complete the AMAX 
Early Termination Visit (ETV) and enter the posttreatment Follow-up Period.  
4.1. 
Overall Design 
Study AMAX is a long-term study of adult participants completing studies AMAM or AMAG 
(see schema in Section 1.2). 
Two intervention groups will be studied in participants with moderate-to-severe CD: 
 
Mirikizumab 
 
 
Mirikizumab 
 
. After the AMAM final database lock, the 
sponsor will unblind the treatment assignments of Hungary participants from Study AMAM. To 
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comply with the response from the Medical Research Council, Ethics Committee for Clinical 
Pharmacology of Hungary, any Hungary sites that have participants who were in the placebo 
intervention group at Week 52 of Study AMAM and were considered responders at Week 52 of 
Study AMAM will receive a notification through the investigator to discontinue the participant 
from Study AMAX. These participants will complete the AMAX ETV and enter the 
posttreatment Follow-up Period.  
Study participants will receive mirikizumab for an extended period of time (approximately 
3 years or until commercial availability of mirikizumab, whichever comes first) and then enter a 
12- to 16-week posttreatment follow-up period. After completion of long-term extension period, 
if mirikizumab is not yet locally commercially available and reimbursable, eligible participants 
will be provided with an option of continued access to open-label mirikizumab, and then enter a 
4-week follow-up period (Section 10.13, Appendix 13). The duration of the continued access 
will differ by participant and country. 
AMAM participants will require an endoscopy to be performed at Week 52, 
 
 in the AMAX study. 
AMAG participants who are entering AMAX after completing 
 
 into AMAX. Participants who have not yet 
completed
 
See Section 8.1.1.2 for details. 
7.2. 
Participant Discontinuation/Withdrawal from the Study 
Participants 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 practice (GCP) 
 
the investigator decides that the participant should be discontinued from the study 
 
all participants from originator Study AMAM 
 
 
 and enter the 12- to 16-week 
posttreatment follow-up period, or 
 
following the final database lock in Study AMAM, all participants in Hungary who were 
in the placebo intervention group at Week 52 of Study AMAM and who were considered 
responders at Week 52 of Study AMAM will be discontinued from Study AMAX 
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through a notification to the investigator and will complete the ETV and enter the 
posttreatment Follow-up Period, or 
 
the participant requests to be withdrawn from the study. 
Participants discontinuing from the study prematurely for any reason should have AE and other 
safety follow-up specified for the ETV. See Section 1.3 (Schedule of Activities), Section 8.2 
(Safety Assessments), and Section 8.3 (Adverse Events and Serious Adverse Events). 
 
 
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10.16. Appendix 16: Protocol Amendment History  
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents (TOC). 
Note: Due to the short time between approval of amendment [c] and amendment [d], it is 
expected that amendment [c] will not be implemented at sites, and they will instead move 
directly to amendment [d] once all requirements are met. To facilitate identifying changes from 
the last amendment version in use, the Summary of Changes Table includes the cumulative 
changes made in amendment [c] and amendment [d]. Section 10.16 includes a table of the 
changes made specifically to amendment [c]. 
Amendment [c]: 12-Jan-2023 
Amendment [c] is considered to be substantial because it is likely to have a significant impact on 
the safety or the rights of the study participants. 
Overall Rationale for Amendment [c]: 
The changes include 
 the addition of an optional Continued Access appendix 
 the addition of an optional 
 that may be conducted on a subset of 
participants to assess the 
, and 
 protocol addenda approved by EU Member States have been incorporated into 
appendices for the purpose of creating a consolidated protocol that will support the 
transition to the EU Clinical Trial Regulation. 
Amendment [d]: 06-Feb-2023 
The changes that are specific to amendment [d] are considered nonsubstantial and primarily 
impact the new Continued Access appendix incorporated in amendment [c], which has not yet 
been implemented.   
Overall Rationale for Amendment [d]: 
The changes include 
 changes to the Continued Access appendix Schedule of Activities, and  
 removal of the Netherlands from Appendix 10.15.1 since it was determined that this 
appendix is not applicable to and was not implemented in the Netherlands. 
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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 1.1 
Synopsis 
Updated word from short 
title to brief title, deleted 
acronym, added regulatory 
agency identified 
numbers, replaced 
disclosure statement with 
brief summary, and added 
study population and 
ethical considerations of 
benefit/risk 
To align with current sponsor protocol 
template 
Section 1.2 Schema Updated schema with 
continued access period 
details 
Updated to include continued access period 
details 
Section 1.3.1 Visit 
1 through Visit 9 
 
Added Chemistry and 
Hematology labs at Visit 3 
The addition of chemistry and hematology 
at Visit 3 (office visit) was included to 
continue hepatic safety monitoring 
 
for the first 12 weeks of the study and to 
have an additional hematocrit value close 
to Week 
 if needed for CDAI purposes. 
Section 1.3.2 Visit 
10 through Visit 19 
 
Footnote “a” was updated 
 
 
Footnote “r” was added 
 
 
Footnote “g” was updated 
A cross-reference to Section 10.13.3 was 
added to provide more details on continued 
access period 
To note that patients moving to continued 
access should move directly from V19 to 
V501, and not perform V801 or V802 
 
Updated for clarity in Amendment [d] 
Section 1.3.3 Early 
Termination, 
 
Unscheduled 
Visits/Assessments, 
and Follow-up 
Visits 
Removed “G” at office 
visit following Endoscopy 
in Patient 14-Day paper 
diary dispensed row 
Footnote “a” was updated 
 
 
 
Footnote “y” was added 
To clarify that 14-day diary is not 
dispensed on the same day as it is returned. 
 
 
A cross-reference to Section 10.13.3 was 
added to provide more details on continued 
access period 
 
To note that patients moving to continued 
access should move directly from V19 to 
V501, and not perform V801 or V802 
Section 1.3.4 Study 
Drug Self-
Administration 
Updated table name and 
footnote “a” 
Updated for clarity 
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Section 2.2.4 IL-
23p19 Blockade in 
Crohn’s Disease 
Updated efficacy of IL-
23p19 blockade in 
Crohn’s disease 
information per recent 
data 
Updated per recent data 
Section 2.3 
Benefit/Risk 
Assessment 
Added AMAX in overall 
benefit/risk conclusion 
Updated to include AMAX information 
Section 5.2 
Exclusion Criteria 
Updated wording from 
duration of the study to 
duration of the long-term 
extension period of the 
study 
Update to clarify that marijuana is 
prohibited during long-term extension of 
the study 
Section 6.1 Study 
Intervention(s) 
Administered 
Removed text and added 
tables that lists the 
interventions in the study 
To align with current sponsor protocol 
template 
Section 8.1.2.3 
Inflammatory 
Biomarkers 
Removed “from samples 
taken prior to Week 12 of 
AMAX”  
To clarify that no 
 or fecal 
calprotectin results will be shared until 
after database lock 
Section 9.5 Interim 
Analyses 
Added additional 
information for 
clarification  
Update for clarity 
Section 10.1.1 
Regulatory and 
Ethical 
Considerations 
Added additional 
information per template  
To align with current sponsor protocol 
template 
Section 10.1.2 
Financial 
Disclosure 
Added this section per 
template 
To align with current sponsor protocol 
template 
Section 10.1.3 
Informed Consent 
Process 
Updated language per 
template 
To align with current sponsor protocol 
template 
Section 10.1.4 Data 
Protection 
Added additional 
information per template 
To align with current sponsor protocol 
template 
Section 10.1.6 
Dissemination of 
Clinical Study Data 
Added additional 
information per template 
To align with current sponsor protocol 
template 
Section 10.1.9 
Study and Site 
Closure 
Added additional 
information per template 
To align with current sponsor protocol 
template 
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Section 10.1.11 
Investigator 
Information 
Added the investigator 
information section per 
template 
Added per template 
Section 10.3.1.2 
Events Meeting the 
AE definition 
Removed lack of efficacy 
details 
Removed as lack of efficacy is not 
considered as an adverse event in this study 
Section 10.7 
Appendix 7: 
prohibited 
Medications 
Updated guidance for use 
for interferon therapy 
Updated for clarity 
Section 10.11 
Appendix 11: 
Abbreviations and 
Definitions 
Added abbreviations and 
definitions as per changes 
in the document 
Added per updated information 
Section 10.13 
Appendix 13: 
Optional Continued 
Access Period 
Added Optional 
Continued Access Period 
details 
Added Continued Access Period in 
Amendment [c]. Made changes to the 
Overview, Schedule of Activities, and 
Study Intervention language for the 
planned Continued Access Period and 
removed some of the phone visits for 
Continued Access Period in Amendment 
[d] 
Section 10.14 
Appendix 14: 
 
Added 
 
details 
Added an optional 
 substudy in 
amendment [c] that may be offered to a 
subset of participants to assess the
 
 
Corrected the word from addendum to 
substudy in Section 10.14.2 in Amendment 
[d] 
Section 10.15 
Appendix 15: 
Country-specific 
requirements 
Added EU countries 
addenda into this appendix 
Protocol addenda approved by EU Member 
States were incorporated into appendices in 
amendment [c] for the purpose of creating 
a consolidated protocol that will support 
the transition to the EU Clinical Trial 
Regulation. The Netherlands was removed 
from Appendix 10.15.1 in Amendment [d] 
since it was determined that this appendix 
is not applicable to and was not 
implemented in the Netherlands 
Throughout the 
protocol 
Changed the
 
 
Updated to make the screening labs 
interval consistent through the document 
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Throughout the 
protocol 
Minor editorial changes 
Modified for clarity 
Section 10.16 
Appendix 16: 
Protocol 
Amendment 
History 
Added Amendment (c) 
summary of changes table 
Addition of amendment (c) details 
Section 11 
References 
Updated reference as per 
the changes in protocol 
Updated as per protocol changes 
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Amendment [c]: 12-Jan-2023 
This amendment is considered to be substantial. 
The amendment is considered to be substantial because it is likely to have a significant impact on 
the safety or the rights of the study participants. 
Overall Rationale for the Amendment: 
The changes in this amendment include 
 the addition of a Continued Access appendix 
 the addition of an optional 
 that may be conducted on a subset of 
participants to assess the 
, and 
 all protocol addenda approved by EU Member States, which have been incorporated into 
appendices for the purpose of creating a consolidated protocol that will support the 
transition to the EU Clinical Trial Regulation. 
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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 1.1 
Synopsis 
Updated word from short 
title to brief title, deleted 
acronym, added regulatory 
agency identified 
numbers, replaced 
disclosure statement with 
brief summary, and added 
study population and 
ethical considerations of 
benefit/risk 
To align with the current sponsor protocol 
template 
Section 1.2 Schema Updated schema with 
Continued Access Period 
details 
Updated to include Continued Access 
Period details 
Section 1.3.1 Visit 
1 through Visit 9 
 
Added Chemistry and 
Hematology labs at Visit 3 
The addition of chemistry and hematology 
at Visit 3 (office visit) was included to 
continue hepatic safety monitoring 
 
for the first 12 weeks of the study and to 
have an additional hematocrit value close 
to 
 if needed for CDAI purposes 
Section 1.3.2 Visit 
10 through Visit 19 
 
Footnote “a” was updated 
 
 
 
Footnote “r” was added 
A cross-reference to Section 10.13.3 was 
added to provide more details on 
Continued Access Period 
 
To note that patients moving to Continued 
Access should move directly from V19 to 
V501 and not perform V801 or V802 
Section 1.3.3 Early 
Termination, 
 
Unscheduled 
Visits/Assessments, 
and Follow-up 
Visits 
Removed “G” at office 
visit following Endoscopy 
in Patient 14-Day paper 
diary dispensed row 
Footnote “a” was updated 
 
 
 
Footnote “y” was added 
To clarify that 14-day diary is not 
dispensed on the same day as it is returned 
 
 
A cross-reference to Section 10.13.3 was 
added to provide more details on 
Continued Access Period 
 
To note that patients moving to continued 
access should move directly from V19 to 
V501 and not perform V801 or V802 
Section 1.3.4 Study 
Drug Self-
Administration 
Updated table name and 
footnote “a” 
Updated for clarity 
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Section 2.2.4 IL-
23p19 Blockade in 
Crohn’s Disease 
Updated efficacy of IL-
23p19 blockade in 
Crohn’s disease 
information per recent 
data 
Updated per recent data 
Section 2.3 
Benefit/Risk 
Assessment 
Added AMAX in overall 
benefit/risk conclusion 
Updated to include AMAX information 
Section 5.2 
Exclusion Criteria 
Updated wording from 
duration of the study to 
duration of the long-term 
extension period of the 
study 
Update to clarify that marijuana is 
prohibited during long-term extension of 
the study 
Section 6.1 Study 
Intervention(s) 
Administered 
Removed text and added 
tables that lists the 
interventions in the study 
To align with the current sponsor protocol 
template 
Section 8.1.2.3 
Inflammatory 
Biomarkers 
Removed “from samples 
taken prior to Week 12 of 
AMAX”  
To clarify that no 
 or fecal 
calprotectin results will be shared until 
after database lock 
Section 9.5 Interim 
Analyses 
Added additional 
information for 
clarification  
Update for clarity 
Section 10.1.1 
Regulatory and 
Ethical 
Considerations 
Added additional 
information per template  
To align with the current sponsor protocol 
template 
Section 10.1.2 
Financial 
Disclosure 
Added this section per 
template 
To align with the current sponsor protocol 
template 
Section 10.1.3 
Informed Consent 
Process 
Updated language per 
template 
To align with the current sponsor protocol 
template 
Section 10.1.4 Data 
Protection 
Added additional 
information per template 
To align with the current sponsor protocol 
template 
Section 10.1.6 
Dissemination of 
Clinical Study Data 
Added additional 
information per template 
To align with the current sponsor protocol 
template 
Section 10.1.9 
Study and Site 
Closure 
Added additional 
information per template 
To align with the current sponsor protocol 
template 
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Section 10.1.11 
Investigator 
Information 
Added the investigator 
information section per 
template 
Added per template 
Section 10.3.1.2 
Events Meeting the 
AE definition 
Removed lack of efficacy 
details 
Removed as lack of efficacy is not 
considered as an adverse event in this study 
Section 10.7 
Appendix 7: 
prohibited 
Medications 
Updated guidance for use 
for infection therapy 
Updated for clarity 
Section 10.11 
Appendix 11: 
Abbreviations and 
Definitions 
Added abbreviations and 
definitions as per changes 
in the document 
Added per updated information 
Section 10.13 
Appendix 13: 
Optional Continued 
Access Period 
Added Optional 
Continued Access Period 
details 
Added Continued Access Period details 
Section 10.14 
Appendix 14: 
 
Added 
 
 details 
Addition of an optional 
 
substudy that may be offered to a subset of 
participants to assess the 
 
 
Section 10.15 
Appendix 15: 
Country-specific 
requirements 
Added all EU countries 
addenda into this appendix 
All protocol addenda approved by EU 
Member States have been incorporated into 
appendices for the purpose of creating a 
consolidated protocol that will support the 
transition to the EU Clinical Trial 
Regulation 
Throughout the 
protocol 
Changed the
 
 
 
 
Updated to make the screening labs 
interval consistent through the document 
Throughout the 
protocol 
Minor editorial changes 
Modified for clarity 
Section 10.16 
Appendix 16: 
Protocol 
Amendment 
History 
Added Amendment (b) 
summary of changes table 
Addition of amendment (b) details 
Section 11 
References 
Updated reference as per 
the changes in protocol 
Updated as per protocol changes 
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Amendment [b]: 03-Aug-2022 
This amendment is considered to be substantial. 
The amendment is considered to be substantial because it is likely to have a significant impact on 
the 
● safety or the rights of the study participants, and 
● reliability and robustness of the data generated in the clinical study. 
Overall Rationale for the Amendment: 
The primary rationale for this amendment is to revise the objectives and endpoints for the study 
in alignment with changes made to the originator AMAM study. Revisions based on new 
standard safety language are also being incorporated. 
Section # and Name 
Description of Change 
Brief Rationale 
Section 1.1 Synopsis 
and Section 3 
Objectives and 
Endpoints 
Updated objectives and 
endpoints 
To align with changes to AMAM 
protocol to place more emphasis on 
clinical outcomes 
Section 1.2 Schema 
Added “Frequency” row 
To clarify the time between visits 
Section 1.3.1 Schedule 
of Activities - Visit 1 
through Visit 9 
 
 
Added additional column for 
V1 Office - Dosing and 
defined V1 screening as V1a 
and V1 Dosing as V1b 
To clarify that V1 has procedures 
both on screening and dosing dates 
Removed “Data from 
Originator Study (R)” and 
added “See footnotes for 
additional key details” 
To co-locate the details regarding 
when each procedure is required in 
the footnotes 
Added 
 in 
footnote t to the 14-Day and 
1-Day paper diaries for all 
patients 
To collect 
 data in addition to 
the data collected from AMAM-
originating patients in the first 12 
weeks by the eDiary 
Added footnote ah, which 
requires that if more than 
 
 have elapsed at the 
time of rollover to AMAX 
between the last procedures 
in AMAM and the first 
dosing in AMAX, additional 
procedures must be 
performed prior to the first 
AMAX dosing at V1b 
To ensure information at the time of 
first AMAX dosing is sufficiently 
current 
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Section # and Name 
Description of Change 
Brief Rationale 
Updated reference to 
footnotes throughout table. 
For clarification 
Updated footnotes b, d, f, j, l, 
q, u, v, w, and z. 
Added footnotes ae, af, and 
ag. 
For clarification and to provide 
additional information. 
Section 1.3.2 Schedule 
of Activities - Visit 10 
through Visit 19 
  
Removed “Data from 
Originator Study (R)” and 
added “See footnotes for 
additional key details” 
To co-locate the details regarding 
when each procedure is required in 
the footnotes 
Added chemistry and 
hematology at additional 
office visits 
To monitor safety labs at 
approximately 
 intervals 
through the 
 of 
this long-term extension study 
Added 
 in 
footnote l to the 14-Day and 
1-Day paper diaries for all 
patients 
To collect 
 data in addition to 
the data collected from AMAM-
originating patients in the first 
 
 by the eDiary 
Section 1.3.3 Schedule 
of Activities - Early 
Termination, 
 
, Unscheduled 
Visits/Assessments, 
and Follow-up Visits 
Removed “Data from 
Originator Study (R)” and 
added “See footnotes for 
additional key details” 
To co-locate the details regarding 
when each procedure is required in 
the footnotes 
Added chemistry and 
hematology at additional 
office visits 
To monitor safety labs at 
approximately 
 intervals 
through the 
 of 
this long-term extension study 
Removed “complement, 
cytokine panel” from 
Hypersensitivity kit row 
These tests no longer need to be 
considered as part of the 
hypersensitivity assessment, based on 
updated sponsor guidelines 
Added 
 in 
footnote v to the 14-Day and 
1-Day paper diaries for all 
patients 
To collect 
 data in addition to 
the data collected from AMAM-
originating patients in the first 
 
 by the eDiary 
Section 2.2.5 
Preclinical and 
Clinical Studies of 
Mirikizumab 
Updated information added  
To align with updated Investigator’s 
Brochure and Risk Profile and 
disclosures 
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Section # and Name 
Description of Change 
Brief Rationale 
Section 2.3 
Benefit/Risk 
Assessment 
Updated information added 
To align with updated Investigator’s 
Brochure and Risk Profile and 
disclosures 
Section 4.2 Scientific 
Rationale for Study 
Design 
Updated primary objectives 
and endpoint information 
To align with Section 1.1 and Section 
3 
Section 5 Study 
Population 
Added information 
explaining V1 split visit 
For clarification 
Section 5.1 Inclusion 
Criteria 
Inclusion criteria [2] and [3]: 
Updated “preferred” to 
“recommended” and added 
additional information about 
situations where participants 
may not be able to complete 
all assessments within the 
recommended visit window 
For clarification 
Inclusion criterion [5]: 
Removed “an established” 
 
Updated “elevated bilirubin 
levels” to “elevated serum 
total bilirubin levels” 
To allow for enrollment of 
participants who are diagnosed with 
Gilbert’s syndrome during screening 
For clarification 
Inclusion criterion [6]: 
Updated contraception 
guidance for female 
participants 
To align with current standard safety 
language 
Section 5.2 Exclusion 
Criteria 
Exclusion criterion [22]: 
Removed adenoma without 
dysplasia, added colonic 
adenomatous polyp, and 
revised criteria to include 
size, dysplasia grade, and 
being in a non-colitic area 
To reflect most recent data 
Exclusion criterion [23]: 
Removed colonic dysplasia, 
added adenomatous polyp, 
and revised criteria to 
include size, dysplasia grade, 
presence of any serrated 
To reflect most recent data 
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Section # and Name 
Description of Change 
Brief Rationale 
lesion, and being in a non-
colitic area 
Exclusion criterion [27]: 
Updated to include “are 
unsuitable for inclusion in 
the study in the opinion of 
the investigator or sponsor 
for any reason that may 
compromise the participant’s 
safety or confound data 
interpretation” 
To align with parent study AMAM. 
Section 5.3 Lifestyle 
Considerations 
Removed instruction for 
participants not to donate 
sperm during the study or for 
16 weeks following study 
participation 
This is not necessary for 
mirikizumab. 
Updated instruction for 
participants not to donate 
blood or blood products 
during the study or for 16 
weeks following study “drug 
administration” instead of 
study “participation” 
For clarification and to align with 
eligibility criteria 
Section 5.4 Screen 
Failures 
Updated definition of screen 
failures to specify 
participants who are not 
enrolled due to failing one or 
more eligibility criteria 
For clarification 
Updated instructions for 
participants who do not 
“meet eligibility criteria” to 
not “subsequently enroll” 
For clarification 
Section 6.1 Study 
Intervention(s) 
Administered 
Preparation and 
Administration: 
Added instructions for 
participants who choose self-
administration of syringes, at 
Visit 4 the site personnel will 
administer the first injection 
and the participant will 
administer the second 
injection 
For clarification 
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Section # and Name 
Description of Change 
Brief Rationale 
Updated instructions for 
recording the timing of 
injections from “taken to 
confirm the full dose was 
achieved within the given 
time range” to 
“administered” 
For clarification 
Investigator Responsibilities: 
Added bullet point about 
ensuring that participants are 
dosed with the correct 
combination of prefilled 
syringes 
To emphasize that there are two 
different sizes of syringes 
Section 6.1.1 Study 
Drug Administration 
Log 
Updated information about 
Study Drug Administration 
Training Log 
For clarification 
Section 6.5.1 
Permitted Therapy 
Added information about 
modifications needed due to 
medical necessity 
For clarification 
Section 6.5.3 
Corticosteroid Taper 
Added instruction for 
participants who have not 
begun corticosteroid tapering 
at Week 12 or those who 
start corticosteroids after 
Week 12 
For clarification 
Section 6.7 
Management of 
Hypersensitivity, 
Infusion-Related 
Events, Infusion Site 
Reactions, and 
Injection Site 
Reactions 
“Injection Site Reactions or 
Infusion Site Reactions”: 
Changed “angioedema” to 
“edema” 
For accuracy 
Section 7.1.1 Liver 
Chemistry Stopping 
Criteria 
This section has been added 
to replace the section for 
Hepatic Event or Liver Test 
Abnormality. The rest of 
Section 7.1 has been 
renumbered to reflect this 
change 
To align with the current protocol 
template 
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Section # and Name 
Description of Change 
Brief Rationale 
Section 7.1.2 
Permanent 
Discontinuation 
This section has been 
renumbered. 
Removed intestinal dysplasia 
and added any colonic 
adenomatous polyp, 
dysplasia in GI tract, or 
presence of any serrated 
lesion in safety 
considerations 
To reflect most recent data 
Updates made throughout 
section 
To align with current standard safety 
language 
Updated treatment 
noncompliance bullet point 
in “Other Reasons” 
For clarification 
Section 7.1.3 Criteria 
for Temporary 
Interruption 
(Withholding) of 
Study Drug 
This section has been 
renumbered 
Updated “should” to “must”: 
“Cases that may merit 
temporary withholding of 
study drug must be discussed 
with the medical monitor” 
To ensure this important 
communication occurs 
Section 7.1.3 
Discontinuation of 
Inadvertently Enrolled 
Participants 
This section has been 
removed 
Deleted as internal process will be 
followed for inadvertent enrollment 
Section 8 Study 
Assessments and 
Procedures 
Updated instructions for 
collecting new screening 
labs prior to dosing for 
samples taken more than 
 
 prior to dosing  
For clarification 
Section 8.1.1 Primary 
Efficacy Assessment 
Updated primary endpoint 
information. 
Added Clinical Remission 
and CDAI information that 
was previously in Section 
8.1.2 
The remaining sections of 
8.1.2 have been renumbered. 
To align with Sections 1.1 and 3 
Section 8.1.2.2 PROs 
Added 
 to list 
of PROs collected in all 
The 
 is being added to 
the paper diary 
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Section # and Name 
Description of Change 
Brief Rationale 
participants from AMAG 
and AMAM  
Section 8.2.5 Stool 
Testing 
C. difficile Toxin updated to 
include “(toxins A and B, 
and glutamate 
dehydrogenase, with reflex 
to polymerase chain reaction 
testing as needed)” 
For clarification 
Section 8.3 Adverse 
Events and Serious 
Adverse Events 
Added information, “Any 
other events/diagnoses that 
start after signing AMAX 
consent but before first 
AMAX dosing should be 
recorded in the AMAX MH 
eCRF” 
For clarification 
Section 8.3.1 Serious 
Adverse Events and 
Section 10.3.5. 
Appendix 3 Reporting 
of SAEs 
Updated “to fulfill regulatory 
requirements” to “for 
tracking purposes” for 
pregnancy reporting 
For clarification 
Added text, “through the 
pregnancy outcome, 
generally no longer than 6 to 
8 weeks past the estimated 
due date” to the pregnancy 
reporting information 
To align with current standard safety 
language 
Section 8.3.5 
Pregnancy 
Updated the following 
language: 
 obtaining a consent from 
the female partner of a 
male study participant 
 recording pregnancy 
information on the 
appropriate form, and 
 clarifying that pregnancy 
is not considered an AE 
although SAE reporting 
procedure is used 
For clarity, per current Lilly protocol 
template 
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Section # and Name 
Description of Change 
Brief Rationale 
Section 8.5 
Pharmacokinetics 
Added information that 
results of additional samples 
will not be provided to the 
investigator. 
For clarification 
Section 9.3 Population 
for Analyses 
Added primary analysis set 
to be the population for 
efficacy analyses 
To maintain continuity between study 
AMAM and study AMAX 
populations used for analyses. 
9.4.1 General 
Considerations 
Revised to clarify that the 
SAP may be modified during 
the trial 
While the first version of the SAP is 
finalized prior to FPV, revisions may 
be made during the study prior to 
final DBL 
Modified text to add the 
primary analysis set as the 
population for efficacy 
analysis 
To maintain continuity between study 
AMAM and study AMAX 
populations used for analyses 
Added text that select 
efficacy summaries may also 
be conducted in the mITT 
population 
To allow for conduct of other 
relevant analyses 
Section 9.4.2.2. 
Participant 
Characteristics and 
Section 9.4.2.3 
Concomitant Therapy 
Added “and primary analysis 
set” to the populations being 
summarized 
To align with Section 9.3 
Section 9.4.3 Primary 
Efficacy Analyses 
Changed “mITT population” 
to “primary analysis set” 
To align with Section 9.4.1 
Updated information to 
reflect the new co-primary 
objectives 
To align with Sections 1.1 and 3 
Section 10.2 Appendix 
2: Clinical Laboratory 
Tests 
Added “Absolute neutrophil 
count (segmented and bands) 
(calculated)” and 
“Neutrophils, bands (if 
detected)” to Clinical 
Laboratory Tests 
For clarification 
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Section # and Name 
Description of Change 
Brief Rationale 
Added “Toxins A and B, and 
GDH, with reflex Toxin 
PCR” to C. difficile testing 
and removed “Confirmed by 
a test for C. difficile toxin 
gene expression” 
For clarification 
Removed Cytokine panel 
and Complement (C3 and 
C4) 
These tests no longer need to be 
considered as part of the 
hypersensitivity assessment, based on 
updated sponsor guidelines 
Section 10.3.1.3 
Appendix 3: Events 
Not Meeting the AE 
Definition 
Updated information about 
planned surgeries and 
nonsurgical interventions not 
being reported as AEs unless 
the underlying medical 
condition has worsened 
during the course of the 
study 
For clarification 
Section 10.3.2 
Appendix 3: 
Definition of SAE 
Updated to add that other 
Abnormal Pregnancy 
Outcomes are also 
considered SAEs 
For clarification 
Section 10.3.3 
Appendix 3: 
Definition of Product 
Complaint 
This section has been added 
to reference Section 8.3.8 for 
the definition of product 
complaint 
The rest of Section 10.3 has 
been renumbered to reflect 
this change 
To align with current template 
Section 10.3.5 
Appendix 3: Reporting 
of SAEs 
Added text that pregnancies 
are also reported using the 
SAE reporting process for 
tracking purposes 
To align with current standard safety 
language 
Section 10.4 Appendix 
4: Liver Safety: 
Suggested Actions and 
Follow-Up 
Assessments 
This section has been 
updated 
To align with current standard safety 
language 
Section 10.7 Appendix 
7: Prohibited 
Medications 
Clarified that topical JAK 
inhibitors are allowed 
For clarification 
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Section # and Name 
Description of Change 
Brief Rationale 
Section 10.8 Appendix 
8: Permitted 
Medications and Dose 
Stabilization 
This section has been 
updated 
For clarification 
Section 10.9 Appendix 
9: Patient-Reported 
Outcome Instruments 
Removed language 
indicating that the 
 
 is in the eDiary only 
Updated footnote a to add 
14-Day paper diary 
 is being added to the 
paper diaries 
 
For clarification 
Section 10.12 
Appendix 12: 
Provisions for 
Changes in Study 
Conduct During 
Exceptional 
Circumstances 
Added text that flexibilities 
outlined will be determined 
by the sponsor in accordance 
with applicable local 
regulations 
For clarification 
Added text about remote 
visits data collection and 
reporting of AEs, SAEs, and 
product complaints 
For clarification 
Added text that every effort 
should be made to enable 
participants to return to on-
site visits as soon as 
reasonably possible 
To ensure that study conduct returns 
to align with the requirements of the 
main protocol when possible 
Updated local laboratory 
testing option information. 
Added text that local 
laboratories may also be 
used for HBV serology, 
HCV and HIV testing and 
for urinalysis 
For clarification 
Added text that site 
personnel should update 
documentation per local 
requirements and sponsor 
guidance. 
To provide additional detail 
Updated text that local 
laboratory testing may be 
performed locally if needed. 
Removed information about 
logistics related to sample 
For clarification 
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Section # and Name 
Description of Change 
Brief Rationale 
stability and feasibility to 
collect at alternate location 
Added text that hematocrit 
results from local labs may 
be included in analyses at 
key timepoints as needed to 
calculate CDAI if central lab 
results are not available 
To provide additional flexibility to 
collect key information in exceptional 
circumstances 
Updated screening period 
guidance for screening 
laboratory assessments 
To provide additional 
accommodation for screening labs if 
needed 
Section 10.13 
Appendix 13: Protocol 
Amendment History 
This section has been added 
To include the revision history for the 
previous amendment 
Throughout 
Editorial corrections 
Minor, therefore not described 
 
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Amendment [a]: 01-Jul-2021 
This amendment is considered to be substantial because it is likely to have a significant impact 
on the safety or physical/mental integrity of participants and/or the scientific value of the study. 
Overall Rationale for the Amendment: 
The primary rationale for this amendment is the addition of Appendix 12: Provisions for 
Changes in Study Conduct During Exceptional Circumstances. 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 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. 
Other minor typographical corrections and clarifications or semantic changes not affecting 
content have also been made in the document. 
Secondary updates for this amendment include the revision of the Schedule of Activities office 
visits changing from every 
) in the study. As 
this is a long-term extension study, the participants should benefit from having fewer office visits 
and allowing for participants to self-administer at home during 
 of the 
study while still monitoring participant health and long-term safety data. 
Changes specific to certain protocol sections and a brief rationale are provided in the table 
below. 
Section # and Name 
Description of Change 
Brief Rationale 
1.1 Synopsis 
 Updated to match revisions in 
Section 3. 
 Revised text to clarify 
 
 
 To improve clarity and 
completeness. 
 Clarification 
1.2 Schema 
 Updated schema. 
 To incorporate change in 
visit schedule from 
every 
 
1.3 Schedule of 
Activities 
 Reformatted SoA, created footnotes 
from Notes column of previous 
version, and split into separate 
subsections containing tables by 
year(s) (Table AMAX.1-1, Table 
AMAX.1-2, and Table AMAX.1-
3). Table AMAX.1-4 placed in its 
own subsection. 
 Throughout SoA: 
 Simplification 
 
 
 
 
 
 
 
 
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Section # and Name 
Description of Change 
Brief Rationale 
o Added footnotes asking that 
sites see detailed instructions 
provided by the sponsor for 
calculation of visit dates. 
o Added “monitoring” to HBV 
DNA test. 
o Included footnotes adding 
“14-Day” to Take Home Patient 
Diary (Paper) dispensed. 
o Added footnotes specifying 
“24-hour recall” for Patient 
1-Day paper diary. 
o Corrected phone visit days and 
tolerance intervals. 
o Added footnotes specifying that 
a CT scan may be performed in 
lieu of a CXR. 
o Clarified that the routine PK 
samples will be collected 
predose. 
o Changed visits from every 
 
 
o Patient Study Drug 
Administration Training Log 
made optional as an 
unscheduled assessment. 
o Noted that unscheduled 
assessments may be performed 
at the discretion of the 
investigator during a scheduled 
visit (UASV). 
 Table AMAX.1-1.: 
 Clarification 
 
 
 Clarification 
 Clarification 
 
 Clarification 
 
 
 Clarification 
 
 To allow flexibility to 
align with local practice 
for TB evaluation 
 Clarification 
 
 
 To reduce participant 
burden 
 
 Investigators may train 
the participant at any 
visit at their discretion. 
 
 Clarification 
 
 
 
 
 
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Section # and Name 
Description of Change 
Brief Rationale 
o TB testing (an IGRA or TST) 
and a CXR will only be 
performed at screening based 
on physical findings and other 
factors that the investigator 
feels warrant testing and 
imaging. Clarified the schedule 
and requirements for TB 
monitoring throughout study. 
Also, see Footnote i. 
o Added collection of 
 on-
site questionnaires at Visit 1 
Day 1 (for participants 
originating from AMAM only) 
o 
 
 Clarification and 
alignment with current 
recommendations for 
long-term extension 
studies 
 
 
 
 
 
 Clarification 
 
 
 
 To shorten and simplify 
SoA 
 
 
 To allow more time to 
obtain necessary 
screening results  
 
 
 
 
 
 
 
 
 Clarification 
 
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o Created footnotes from Notes 
column of previous version of 
SoA. Changes/additions to 
previous text as follows: 
▪ Footnote b: Revised text to 
note that up to 
 is 
now allowed between last 
dose in originator study and 
first dose in AMAX. 
Emphasized that all 
screening results must be 
reviewed prior to dosing 
and must be from samples 
from within 
 prior 
to the Visit 1 dose. 
▪ Footnote d: Revised text to 
clarify that Visit 1 dosing is 
defined as Day 1. 
▪ Footnote l: Revised text to 
clarify requirements for 
HBV screening. 
▪ Footnote m: Revised text to 
clarify when HBV DNA 
monitoring shall occur. 
▪ Footnote o: Added text to 
clarify timing for collection 
of stool sample associated 
with endoscopies and office 
visits. 
▪ Footnote s: Added timing 
details for providing, 
completing, and returning 
14-Day paper diary for the 
. 
▪ Footnote x: Added 
recommendations and 
requirements regarding the 
order for performing 
procedures at visits 
associated with 
endoscopies. 
▪ Footnote ab: Added text 
clarifying that study drug 
self-administration training 
may occur at 
 Clarification 
 
 
 Clarification 
 
 
 Clarification 
 
 
 
 Clarification  
 
 
 
 Clarification 
 
 
 
 
 Clarification 
 
 
 
 
 
 
 Clarification and 
alignment with current 
recommendations for 
long-term extension 
studies 
 
 To shorten and simplify 
SoA 
 
 
 Clarification 
 
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alternate/additional visits if 
necessary. 
 Table AMAX.1-2.: 
o Clarified the schedule and 
requirements for TB monitoring 
throughout study. Also, see 
Footnote f. Adjusted timing of 
procedures as needed to 
accommodate new visit 
schedule after V12. 
o Created footnotes from Notes 
column of previous version of 
SoA. Changes/additions to 
previous text as follows: 
▪ Footnote h: Clarified text 
regarding HBcAb+ and 
HBV DNA monitoring. 
▪ Footnote j: Provided 
additional detail regarding 
stool sample collection. 
▪ Footnote k: Timepoints 
added for providing, 
returning, and completing 
patient 14-Day paper diary. 
▪ Footnote m: Added 
recommendations and 
requirements regarding the 
order for performing 
procedures at visits 
associated with endoscopies. 
 Table AMAX.1-3.: 
o Added unscheduled assessments 
during a scheduled visit 
(UASV). 
 
o Split out the components of the 
 in the table and 
provided additional details 
regarding lab collection and 
performance of procedures. 
o Added 10-day window for Visit 
801. 
 Clarification 
 
 
 Clarification 
 
 
 
 Clarification 
 
 
 
 
 
 
 To allow for additional 
optional data collection 
for UASV 
 Clarification 
 
 
 
 To rectify previous 
omission 
 Clarification and 
alignment with current 
recommendations for 
long-term extension 
studies  
 
 
 
 To increase visibility 
regarding labs that may 
be needed on an 
unscheduled basis 
 To shorten and simplify 
SoA 
 
 Clarification 
 
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Section # and Name 
Description of Change 
Brief Rationale 
o TB testing and CXR will only be 
performed at screening and other 
visits based on physical findings 
and other factors that the 
investigator feels warrant testing 
and imaging. Clarified the 
schedule and requirements for 
TB monitoring throughout 
study. Also, see footnotes h, i, 
and l. 
o Added Hypersensitivity kit and 
Hepatic kit to table. 
 
 
o Created footnotes from Notes 
column of previous version of 
SoA. Changes/additions to 
previous text as follows: 
▪ Footnote a: Added 
recommendation to see 
sponsor instructions for 
calculation of visit dates. 
▪ Footnote c: Added 
instructions for conducting 
unscheduled visits (997). 
▪ Footnote d: Added 
instructions for conducting 
optional assessments during 
unscheduled visits. 
▪ Footnote m: Clarification 
regarding HBV testing. 
▪ Footnote n: Clarification 
regarding HBV DNA 
monitoring. 
▪ Footnote r: Provided 
additional detail regarding 
fecal calprotectin and stool 
sample collection and 
testing. 
 
 
 Clarification 
 
 
 Clarification 
 
  
 
 Clarification 
 
 Clarification 
 
 Clarification 
 
 
 
 Clarification 
 
 
 
 
 
 
 
 
 
 Clarification 
 
 
 
 
 
 
 To align with schedule 
change 
  
  
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Section # and Name 
Description of Change 
Brief Rationale 
▪ Footnote u: Added 
instructions specifying that 
the Patient 14-Day paper 
diary provided by the site at 
the visit prior to 
 
will be collected 
at next scheduled office visit 
(and per footnote b, should 
be completed in the 14 days 
leading up to that next 
scheduled office visit). 
▪ Footnote w: Added 
recommendations and 
requirements regarding the 
order for performing 
procedures at visits 
associated with endoscopies. 
 Table AMAX.1-4.: 
o Revised visit schedule to allow  
 
 
2.2.2. Currently 
Available Treatments 
and Unmet Need 
 Modified text regarding the 
estimated rates of clinical remission 
in participants failing conventional 
therapy and in the biologic-failure 
population. 
 Clarification 
2.3 Benefit/Risk 
Assessment 
 Changed 
 
in reference to 
other ongoing studies. 
 To correct a 
typographical error 
3. Objectives and 
Endpoints 
 Revised text throughout to clarify 
whether timepoints are with respect 
to AMAG, AMAM, or AMAX as 
applicable. 
 Secondary Endpoints: 
 
o Effect of mirikizumab 
 
 Modified Objective 
and Endpoint text. 
 To indicate to which trial 
each timepoint refers 
 
 
 
 
 
 To clarify specific study 
conditions in the 
analysis  
 
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Section # and Name 
Description of Change 
Brief Rationale 
 Secondary Endpoints: 
o Moved secondary endpoint “To 
evaluate the effect of 
mirikizumab in achieving 
 
from Section
 
 
 to Section 
 
 
 
 
 To clarify specific study 
conditions in the 
analysis 
 
4.1 Overall Design 
 Modified text regarding how long 
study participants will receive 
mirikizumab. 
 Clarification 
4.3 Justification for 
Dose 
 Removed “based on preliminary 
data at the time of this writing”. 
 Data are no longer 
preliminary 
5. Study Population 
 Added text to specify the study 
population as adult participants. 
 Clarification 
5.1 Inclusion Criteria 
 Added text to clarify that the 
inclusion criteria apply to all 
AMAX participants regardless of 
their originating study unless a 
specific originator study (AMAM 
or AMAG) is specified. 
 Criterion [2]: 
o Clarified regarding completion 
of last visit in originating trial. 
o Preferred interval between final 
dose in AMAG and first 
AMAX dose changed to
 
 
 
o Maximum interval between 
final dose in AMAG and first 
AMAX dose changed from 
 
. 
 Criterion [3]: 
o Clarified regarding completion 
of last visit in originating trial. 
 Clarification 
 
 
 
 
 
 Clarification 
 
 Changed to allow greater 
flexibility to 
accommodate screening 
requirements 
 Changed to allow greater 
flexibility to 
accommodate screening 
requirements 
 
 Clarification 
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Section # and Name 
Description of Change 
Brief Rationale 
o Preferred interval between final 
dose in AMAM and first 
AMAX dose changed to 
 
 
 
o Maximum interval between 
final dose in AMAM and first 
AMAX dose changed from 
 
. 
o Added note specifying 
adolescent participants who 
complete AMAM cannot enroll 
in AMAX, but may be eligible 
for the pediatric extension 
study. 
 Criterion [4]: Added note regarding 
additional support for IP self-
administration, and option for a 
general exception to self-
administration depending on 
circumstances. 
 Criterion [6]: 
o Period of abstinence or 
contraception following last 
dose of study drug changed to 
16 weeks. 
o Definition of postmenopausal 
women changed to ≥ 40 years 
of age. Cessation of menses 
must have occurred without an 
alternative medical cause. 
 Changed to allow greater 
flexibility for timing to 
accommodate screening 
requirements 
 Changed to allow greater 
flexibility for timing to 
accommodate screening 
requirements 
 Clarified extension study 
for adolescents 
 
 
 
 Clarification that 
participants will not be 
excluded from trial if 
they will not self-
administer 
 
 
 For greater consistency 
across trials for 
participants on 
mirikizumab 
 To reflect most recent 
internal safety guidance 
 
5.2 Exclusion Criteria  
 Criterion [7]: Deleted 
 
 
 Criterion [8]: Deleted 
 
 Redundancy with 
Inclusion Criteria [2] 
and [3] 
 Redundancy with 
Inclusion Criterion [3] 
 Clarification 
 
 
 
 
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Section # and Name 
Description of Change 
Brief Rationale 
 Criterion [14]: Added note that 
participants with a history of active 
TB with documentation of 
treatment by WHO and/or CDC 
criteria prior to the originator study 
are not excluded from the study. 
 Criterion [15]: Added reference to 
Section 8.2.6. 
 Criterion [16]: Modified text. 
 
 Criterion [18]: Period in which 
women may not enroll if planning 
to become pregnant changed from 
within 12 weeks to within 16 weeks 
of last dose. 
 Criterion [19]: Deleted 
 
 
 
 
 Criterion [25]: Updated text 
regarding delivery of parenteral 
nutrition. 
 
 
 
 Criterion [27]: Added new criterion 
on prohibited marijuana use and 
updated Appendix 7 (Prohibited 
Medications) accordingly. 
 For TB prophylaxis 
details 
 Clarification regarding 
hypersensitivity 
 For greater consistency 
across trials for 
participants on 
mirikizumab 
 
 Participants would have 
been discontinued during 
originator trial if surgery 
was deemed to be an 
issue. 
 Parenteral and enteral 
nutrition as primary 
source of diet are 
excluded due to potential 
to confound efficacy 
assessments. 
 To avoid potential 
impact on protocol 
assessments as 
cannabinoids have 
shown a potential role in 
inflammation and 
mucosal permeability of 
the gastrointestinal tract  
5.3 Lifestyle 
Considerations 
 Modified text to include instruction 
to study participants regarding 
sperm donation. 
 To be more 
comprehensive  
5.4 Screen Failures 
 Added text for participants who 
sign informed consent to enter 
Study AMAX but do not meet 
eligibility criteria.  
 To provide clarification 
regarding safety follow-
up for participants who 
screen fail in AMAX 
6.1. Study 
Intervention(s) 
Administered 
 Added text regarding need for 
resuscitation equipment, 
emergency medication, and safety 
monitoring. 
 To match the AMAM 
protocol 
 
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Section # and Name 
Description of Change 
Brief Rationale 
 Added text that the sponsor may 
approve a general exception for 
self-administration for a 
participant, as noted in Inclusion 
Criterion 4. 
 To clarify that 
participants may be 
exempted from self-
administration in the 
entire study, not just for 
a single dose 
6.5. Concomitant 
Therapy 
 
 Added subsection headings under 
concomitant therapies and 
prohibited medications and 
renumbered subsequent sections. 
 Clarification 
6.5.1. Permitted 
Therapy 
 
 Modified text to add that 
participants taking permitted CD 
concomitant medications are 
recommended to keep doses stable 
unless modifications are needed for 
appropriate medical management. 
 Clarified that for participants 
entering AMAX on corticosteroids 
the doses should remain stable until 
Week 12, and after Week 12 
corticosteroid tapering will occur as 
described in Section 6.5.3. 
 Clarification 
 
 
 
 
 
 Clarification 
 
 
6.5.2. Prohibited 
Therapy 
 
 Added exceptions to prohibited CD 
medications, IV corticosteroid, 
systemic corticosteroids for 
non-CD indications, and marijuana 
use. 
 Added exception to vaccinations 
allowing RNA-based vaccinations. 
 To align with the 
AMAM protocol and to 
improve clarity 
 
 The introduction of 
RNA-based COVID-19 
vaccines has made it 
necessary to clarify that 
these are permitted. 
6.5.3. Corticosteroid 
Taper 
 
 Clarified that for participants who 
enter AMAX on corticosteroids, 
tapering should be initiated or 
continued for participants who at 
the discretion of the investigator 
have achieved clinical response at 
Week 12, with reference to 
Section 10.8. 
 Clarification 
 
 
 
 
 
 
 Clarification 
 
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Section # and Name 
Description of Change 
Brief Rationale 
 Clarified that oral corticosteroid 
dose may not be increased above 
the baseline dose in originator 
study unless due to medical 
necessity. 
6.7. Management of 
Hypersensitivity, 
Infusion-Related 
Events, Infusion Site 
Reactions, and 
Injection Site 
Reactions 
 Hypersensitivity Events: Added a 
note regarding PK, 
immunogenicity, 
 
 lab results. 
 
 
 Noted that same steps should be 
performed for nonsystemic 
hypersensitivity reactions as with 
systemic hypersensitivity reactions, 
except that continued trial 
participation may be allowed.  
 Clarification that these 
lab results are not 
intended for participant 
management and will 
not be shared with 
investigative sites 
 Clarification 
 
7.1.1. Permanent 
Discontinuation 
 Clarified that drainage specifically 
of a perianal or other cutaneous 
abscess is an allowed surgery. 
 Clarification 
 
7.1.2. Criteria for 
Temporary 
Interruption 
(Withholding) of 
Study Drug 
 Revised the text for management of 
participants who develop decreased 
absolute lymphocyte count. 
 To increase clarity on 
participant management 
7.2 Participant 
Discontinuation/With
drawal from the Study 
 Removed redundant language 
regarding investigator or 
participant decision.  
 Redundant  
8.1.1.2 Endoscopy 
 
 Modified text to clarify that 
AMAG-originating participants 
who have reached the
 
 
 
 Added paragraph regarding 
recommendation for endoscopies to 
be performed on a different day 
than collection of questionnaire 
responses and IP administration or 
if on the same day, regarding 
sequence of assessments. 
 Clarifications/correction
s 
 
 
 
 
 
 
 Clarifications/correction
s 
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Section # and Name 
Description of Change 
Brief Rationale 
8.1.1.3 Endoscopic 
Biopsies 
 Revised text referencing source of 
details of biopsy sample collection. 
 Added statement on biopsy sample 
retention. 
 Clarifications/correction
s 
 
 Clarifications/correction
s 
8.1.2.3 PROs 
 Revised terminology regarding 
questionnaires/diaries for greater 
clarity.  
 Modified to match other 
changes in the protocol 
where references to 1- 
and 14-Day paper diaries 
and questionnaires are 
used. 
8.1.2.4. Inflammatory 
Biomarkers 
 Modified text to clarify that 
investigators will be blinded to 
 results and fecal 
calprotectin results from samples 
taken prior to Week 12 of AMAX 
until after AMAM database lock. 
 To improve clarity of 
sample blinding and 
timing for unblinding 
 
8.2.4. Chest 
Radiography 
 Modified text to clarify when 
imaging is required and that a CT 
scan can be performed as an 
alternative to the CXR. Noted also 
that an IGRA or TST should be 
performed.  
 Clarification  
8.2.6 Tuberculosis 
Testing 
 Reorganized section. 
 
 
 
 
 Added Section ‘Initial screening’. 
 Specified that if there are relevant 
physical findings or other factors 
that the investigator feels warrant 
testing and imaging, either at 
screening or at monitoring during 
the trial, an IGRA OR TST and 
CXR should be performed. 
 Reorganized so that 
procedures would be 
listed in order of 
occurrence for greater 
clarity. 
 Clarification 
 Clarification and 
alignment with current 
recommendations for 
long-term extension 
studies 
 
 
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Section # and Name 
Description of Change 
Brief Rationale 
 Added that participants with 
1 indeterminate QuantiFERON-TB 
Gold assay plus 1 borderline T-
SPOT.TB assay will be excluded. 
Added Section ‘TB Screening 
Outcomes and Enrollment’. Moved 
Section ‘Diagnosis of LTBI During 
the Study’. 
 Clarification 
 
 
 
 
 
 
8.2.8. Hepatitis B 
Testing 
 Noted that participants who were 
HBcAb+ in the originator study 
only need HBV DNA testing, not 
full HBV screening, and will 
require continued HBV DNA 
monitoring. 
 Management of participants with 
detectable HBV DNA: Added 
language regarding consultation 
with medical monitor. 
 Clarification 
 
 
 
 
 Clarification that any 
subsequent study drug 
administration following 
HBV DNA positive 
result requires approval 
of the medical monitor 
8.2.11. Depression, 
Suicidal Ideation, and 
Behavior Risk 
Monitoring 
 Removed text regarding Self Harm 
Supplement Form and Self Harm 
“Follow-Up” Form.  
 
 
 Modified text on administration of 
 
 Removed text that the tablet device 
is used to electronically capture the 
data for 
 
 Information currently 
collected via safety 
reporting provides 
sufficient information on 
self-harm cases. 
 Clarification 
 
 
 is only on 
paper. No tablet is used. 
 
8.3 Adverse Events 
and Serious Adverse 
Events 
 Noted that AEs occurring after 
signing the AMAX ICF, but prior 
to dosing, if considered reasonably 
possibly related to an AMAX study 
procedure, should be reported as an 
AE in AMAX. 
 Clarification 
8.3.1. Serious 
Adverse Events 
 Revised language to refer to 
Section 8.3 for details regarding 
general AE collection.  
 Clarification 
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Section # and Name 
Description of Change 
Brief Rationale 
8.3.5. Pregnancy 
 Modified text on collecting details 
for pregnancies, including change 
to follow-up of pregnancies 
occurring until at least 16 weeks 
after last dose (rather than 20 
weeks). 
 Alignment with other 
time intervals related to 
pregnancy and 
contraception, as well as 
general clarification 
9.4.1.1 Analyses 
 
 Least squares mean from a 
restricted maximum likelihood-
based model of MMRM substituted 
for estimation of mean response 
over time for the change from 
baseline in endoscopic scores for 
 
 
 Alternative versions of MMRM 
may be implemented as deemed 
appropriate substituted for 
specified statistical analyses. 
 For continuous efficacy and health 
outcome variables for participants 
from Study AMAM, deleted 
restriction of estimation using 
analysis of covariance in 
‘intervention group by intervention 
received in originating study 
interaction’. 
 For all: Changes to 
modeling are to provide 
flexibility in modeling 
and align with the SAP 
9.4.1.4 Missing Data 
Imputation 
 Revised text to clarify that 
participants will be considered a 
Nonresponder for the NRI analysis 
if they have specified changes in 
concomitant CD medications. 
 Revised text: Including the MMRM 
with missing-at-random assumption 
for handling missing data in the 
primary analysis is optional. 
 For both: To provide 
flexibility considering 
medications may change 
over the course of a 
long-term extension 
study 
Appendix 1: 
10.1.6. Data Quality 
Assurance 
 Updated text, including noting that 
investigator document retention 
requirements are outlined in the 
Clinical Trial Agreement (rather 
than specifically 15 years).  
 To provide up-to-date 
guidance 
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Section # and Name 
Description of Change 
Brief Rationale 
Appendix 2: 
10.2 Clinical 
Laboratory Tests 
 Modified to include that 
QuantiFERON-TB Gold test may 
be done locally. 
 Clarified that 
 and fecal 
calprotectin results from samples 
taken prior to AMAX Week 12 will 
not be provided to sites until 
AMAM database lock or later.  
 To allow flexibility for 
local testing in 
alignment with AMAM 
 To improve clarity 
Appendix 3: 
10.3.1.2 Definition of 
AE  
 Deleted lack of efficacy from list of 
events meeting AE definition. 
 To align with language 
in Section 8.3 
Appendix 3: 
10.3.2 Definition of 
SAE 
 Deleted statement implying that 
events such as hospitalization for 
signs/symptoms of the disease 
under study or death due to 
progression of disease may not be 
SAEs. 
 Clarification 
Appendix 3: 
10.3.4.1 
SAE Reporting via an 
Electronic Data 
Collection Tool 
 Noted that SAEs occurring after 
shutdown of the electronic data 
collection tool may also be reported 
via phone call to the medical 
monitor. 
 Clarification 
Appendix 7 
10.7 Prohibited 
Medications 
 
 Listed that IV corticosteroids may 
be used as infusion premedication 
or short-term treatment for acute 
non-CD events. 
 Added text to include information 
on IV corticosteroid used for CD 
that may result in discontinuation.  
 
 Added text to include information 
regarding initiation or adjustment 
of systemic corticosteroids for non-
CD indications. 
 Added text to include information 
on systemic corticosteroid used for 
adrenal insufficiency. 
 Broadened language to include any 
anti-IL 12/23p40 antibodies. 
 Incorporation of content 
from the body of the 
protocol 
 
 To allow medical 
discretion to prevent 
unnecessary 
discontinuation 
 Clarification 
 
 
 Clarification 
 
 
 To match the AMAM 
protocol 
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Section # and Name 
Description of Change 
Brief Rationale 
 Added text to include information 
on prohibited marijuana use. 
 To avoid potential 
impact on protocol 
assessments as 
cannabinoids have 
shown a potential role in 
inflammation and 
mucosal permeability of 
the gastrointestinal tract 
Appendix 8: 
10.8 Permitted 
Medications with 
Dose Stabilization 
 Modified dose of permitted 
prednisone to ≤30 mg/day. 
 Noted that oral corticosteroid doses 
for CD should be kept stable until 
Week 12 and should follow 
guidance in Section 6.5.3 
thereafter. 
 Added text allowing RNA-based 
vaccines. 
 To match the AMAM 
protocol. 
 Clarification. 
 
 
 
 Due to the introduction 
of RNA-based vaccines 
for COVID-19 
Appendix 9: 
10.9 Patient-Reported 
Outcome Instruments 
 Removed text that the tablet device 
is used to electronically capture the 
data for 
 and other indicated 
PROs.  
 The PROs listed are only 
on paper. No tablet is 
used. 
Appendix 12: 
10.12 Provisions for 
Changes in Study 
Conduct During 
Exceptional 
Circumstances 
 Added appendix. 
 Provides for temporary 
changes to procedures 
intended to be used only 
during specific time 
periods as directed by 
the sponsor in 
partnership with the 
investigator. 
Throughout 
 Minor editorial changes  
 Corrections/clarification
s 
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Protocol I6T-MC-AMAX(e) 
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Abbreviations: AE = adverse event; AMAG = I6T-MC-AMAG protocol; 
 
; AMAM = I6T-MC-AMAM protocol; AMAX = I6T-MC-AMAX protocol; CD = Crohn’s disease; 
CDC = Centers for Disease Control and Prevention; COVID-19 = Coronavirus Disease 2019; 
CS = corticosteroid; 
; CT = computed tomography; 
CXR = chest x-ray; DNA = deoxyribonucleic acid; HBcAb = hepatitis B core antibody; HBV =hepatitis B virus; 
; ICF = informed consent form; IGRA = interferon gamma release 
assay; IL = interleukin; IP = investigative product; IV = intravenous; LTBI = latent tuberculosis infection; 
MMRM = mixed-effects model for repeated measures; mRNA = messenger ribonucleic acid; 
NRI = nonresponder imputation; 
; PK = pharmacokinetics; 
PRO = patient-reported outcome; 
 
; RNA = ribonucleic acid; SAE = serious adverse event; 
SAP = Statistical Analysis Plan; SC = subcutaneous; SoA = Schedule of Activities; TB = tuberculosis; 
TST = tuberculin skin test; UASV = unscheduled assessments during a scheduled visit, WHO = World Health 
Organization. 
 
 
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11. 
References  
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fifth edition (DSM-V). Arlington, VA: American Psychiatric Publishing. 2013. 
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Taylor KD, Barmada MM, Bitton A, Dassopoulos T, Datta LW, Green T, Griffiths AM, 
Kistner EO, Murtha MT, Regueiro MD, Rotter JI, Schumm LP, Steinhart AH, Targan SR, 
Xavier RJ; NIDDK IBD Genetics Consortium, Libioulle C, Sandor C, Lathrop M, Belaiche J, 
Dewit O, Gut I, Heath S, Laukens D, Mni M, Rutgeerts P, Van Gossum A, Zelenika D, 
Franchimont D, Hugot JP, de Vos M, Vermeire S, Louis E; Belgian-French IBD Consortium; 
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Gwilliam R, Tremelling M, Deloukas P, Mansfield J, Jewell D, Satsangi J, Mathew CG, 
Parkes M, Georges M, Daly MJ. Genome-wide association defines more than 30 distinct 
susceptibility loci for Crohn’s disease. Nat Genet. 2008;40(8):955-962. 
Baumgart DC, Sandborn WJ. Inflammatory bowel disease: clinical aspects and established and 
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Berrebi D, Besnard M, Fromont-Hankard G, Paris R, Mougenot JF, De Lagausie P, Emilie D, 
Cezard JP, Navarro J, Peuchmaur M. Interleukin-12 expression is focally enhanced in the 
gastric mucosa of pediatric patients with Crohn’s disease. Am J Pathol. 1998;152(3):667-672. 
Blauvelt A, Papp KA, Griffiths CE, Randazzo B, Wasfi Y, Shen YK, Li S, Kimball AB. Efficacy 
and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with 
adalimumab for the continuous treatment of patients with moderate to severe psoriasis: Results 
from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 
trial. J Am Acad Dermatol. 2017;76(3):405-417. 
[CDC] Centers for Disease Control and Prevention. Treatment regiments for latent TB infection 
(LTBI). April 2016. CDC webpage. Available at: 
https://www.cdc.gov/tb/topic/treatment/ltbi.htm. Accessed 9 March 2019. 
 
 
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