A Bioequivalence Study of Subcutaneous Injections of Citrate-Free Mirikizumab Solution Using a 1-mL Autoinjector and an Investigational 2-mL Autoinjector in Healthy Participants
Phase: PHASE1
Conditions: Healthy
Sponsor: Eli Lilly and Company

Protocol Amendment I6T-MC-AMCB (a) 
A Bioequivalence Study of Subcutaneous Injections of Citrate-Free Mirikizumab Solution 
Using a 1-mL Autoinjector and an Investigational 2-mL Autoinjector in Healthy Participants 
NCT06475729 
Approval Date: 24-Sep-2024 

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I6T-MC-AMCB(a) 
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Title Page 
Confidential Information 
The information contained in this document is confidential and is intended for the use of clinical investigators. It is the property of 
Eli Lilly and Company or its subsidiaries and should not be copied by or distributed to persons not involved in the clinical 
investigation of mirikizumab (LY3074828) and 1-mL and investigational 2-mL autoinjectors, 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 Bioequivalence Study of Subcutaneous Injections of Citrate-Free Mirikizumab Solution Using 
a 1-mL Autoinjector and an Investigational 2-mL Autoinjector in Healthy Participants 
Protocol Number: I6T-MC-AMCB  
Amendment Number: [a] 
Compound: Mirikizumab (LY3074828) 
Brief Title: A bioequivalence study of subcutaneous injections of citrate-free mirikizumab 
solution using a 1-mL autoinjector and an investigational 2-mL autoinjector in 
healthy participants 
Study Phase: Phase 1 
Sponsor Name: Eli Lilly and Company 
Legal Registered Address: Eli Lilly and Company, Indianapolis, Indiana USA 46285 
Manufacturer: Eli Lilly and Company 
Regulatory Agency Identifier Number: IND: 125444 
Approval Date: Protocol Amendment (a) Electronically Signed and Approved by Lilly on date 
provided below.  
Document ID: VV-CLIN-145565 
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Medical Monitor Name and Contact Information will be provided separately. 
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I6T-MC-AMCB(a) 
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Protocol Amendment Summary of Changes Table  
DOCUMENT HISTORY 
Document 
Date 
Original Protocol 
21-March-2024 
Amendment [a]  
Overall rationale for the amendment 
The rationale for the amendment is to increase the approximate number of participants that may 
be enrolled.  
Section # and Name 
Description of Change 
1.1 Synopsis 
The approximate number of participants that may be 
enrolled overall has increased from 440 to 484. 
4.1 Overall Design 
9.5 Sample Size Determination 
8.2.6.1 Hepatic Safety 
Monitoring and Evaluation 
It was clarified that the actions taken for abnormal hepatic 
laboratory or clinical changes were based on participants 
with normal or near normal baseline (ALT, AST, or ALP 
<1.5 × ULN).  
10.6 Liver Safety: Suggested 
Actions and Follow-up 
Assessments 
It was clarified that if a lab did not offer total antibody 
testing, IgG and/or IgM were acceptable substitutes.  
 
 
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Table of Contents  
Protocol Amendment Summary of Changes Table ....................................................................3 
1. 
Protocol Summary ..........................................................................................................7 
1.1. 
Synopsis ............................................................................................................................7 
1.2. 
Schema ............................................................................................................................11 
1.3. 
Schedule of Activities (SoA) ..........................................................................................12 
2. 
Introduction ...................................................................................................................15 
2.1. 
Study Rationale ...............................................................................................................15 
2.2. 
Background .....................................................................................................................15 
2.2.1. 
Safety ..............................................................................................................................15 
2.2.2. 
Deaths, Serious Adverse Events, and Discontinuations Due to an 
Adverse Event .................................................................................................................16 
2.2.3. 
Other Treatment-Emergent Adverse Events ...................................................................17 
2.2.4. 
Pharmacokinetics ............................................................................................................17 
2.3. 
Benefit/Risk Assessment ................................................................................................18 
3. 
Objectives and Endpoints ............................................................................................19 
4. 
Study Design ..................................................................................................................20 
4.1. 
Overall Design ................................................................................................................20 
4.2. 
Scientific Rationale for Study Design ............................................................................21 
4.3. 
Justification for Dose ......................................................................................................22 
4.4. 
End of Study Definition ..................................................................................................22 
5. 
Study Population ...........................................................................................................23 
5.1. 
Inclusion Criteria ............................................................................................................23 
5.2. 
Exclusion Criteria ...........................................................................................................24 
5.3. 
Lifestyle Considerations .................................................................................................27 
5.3.1. 
Meals and Dietary Restrictions .......................................................................................27 
5.3.2. 
Substance Use: Caffeine, Alcohol, and Tobacco ............................................................27 
5.3.3. 
Activity ...........................................................................................................................27 
5.4. 
Screen Failures ................................................................................................................27 
5.5. 
Criteria for Temporarily Delaying 
Enrollment/Randomization/Administration of Study Intervention 
of a Participant ................................................................................................................27 
6. 
Study Intervention(s) and Concomitant Therapy .....................................................28 
6.1. 
Study Intervention(s) Administered................................................................................28 
6.1.1. 
Medical Devices, Investigational Devices, or Device 
Constituents.....................................................................................................................28 
6.2. 
Preparation, Handling, Storage, and Accountability ......................................................29 
6.3. 
Assignment to Study Intervention ..................................................................................29 
6.4. 
Study Intervention Compliance ......................................................................................29 
6.5. 
Dose Modification ..........................................................................................................29 
6.6. 
Continued Access to Study Intervention after the End of the 
Study ...............................................................................................................................30 
6.7. 
Treatment of Overdose ...................................................................................................30 
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I6T-MC-AMCB(a) 
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6.8. 
Prior and Concomitant Therapy ......................................................................................30 
6.8.1. 
Permitted Concomitant Therapy .....................................................................................30 
6.8.2. 
Prohibited Concomitant Therapy ....................................................................................31 
7. 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal........................................................................................32 
7.1. 
Discontinuation of Study Intervention ............................................................................32 
7.2. 
Participant Discontinuation/Withdrawal from the Study ................................................32 
7.3. 
Lost to Follow-up............................................................................................................32 
8. 
Study Assessments and Procedures.............................................................................33 
8.1. 
Efficacy Assessments .....................................................................................................33 
8.2. 
Safety Assessments .........................................................................................................33 
8.2.1. 
Physical Examinations ....................................................................................................33 
8.2.2. 
Vital Signs .......................................................................................................................33 
8.2.3. 
Electrocardiograms .........................................................................................................34 
8.2.4. 
Clinical Safety Laboratory Tests ....................................................................................34 
8.2.5. 
Pregnancy Testing ...........................................................................................................35 
8.2.6. 
Safety Monitoring ...........................................................................................................35 
8.2.7. 
Hypersensitivity Reactions .............................................................................................37 
8.2.8. 
Tuberculosis Testing and Monitoring .............................................................................37 
8.2.9. 
Injection-Site Reactions ..................................................................................................38 
8.3. 
Adverse Events, Serious Adverse Events, and Product 
Complaints ......................................................................................................................38 
8.3.1. 
Timing and Mechanism for Collecting Events ...............................................................39 
8.3.2. 
Collection of Pregnancy Information..............................................................................40 
8.3.3. 
Adverse Events of Special Interest .................................................................................41 
8.4. 
Pharmacokinetics ............................................................................................................42 
8.5. 
Pharmacodynamics .........................................................................................................42 
8.6. 
Genetics ..........................................................................................................................42 
8.7. 
Biomarkers ......................................................................................................................42 
8.8. 
Immunogenicity Assessments.........................................................................................42 
8.9. 
Health Economics or Medical Resource Utilization and Health 
Economics .......................................................................................................................42 
9. 
Statistical Considerations .............................................................................................43 
9.1. 
Statistical Hypothesis ......................................................................................................43 
9.2. 
Analyses Sets ..................................................................................................................43 
9.3. 
Statistical Analyses .........................................................................................................43 
9.3.1. 
General Considerations ...................................................................................................43 
9.3.2. 
Primary Endpoint Analysis .............................................................................................44 
9.3.3. 
Secondary Endpoint Analysis .........................................................................................44 
9.3.4. 
Exploratory Endpoint Analysis .......................................................................................45 
9.3.5. 
Other Safety Analyses.....................................................................................................45 
9.4. 
Interim Analysis ..............................................................................................................45 
9.5. 
Sample Size Determination ............................................................................................45 
10. 
Supporting Documentation and Operational Considerations ..................................46 
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10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ................................................................................................................46 
10.1.1. Regulatory and Ethical Considerations ...........................................................................46 
10.1.2. Financial Disclosure........................................................................................................47 
10.1.3. Informed Consent Process ..............................................................................................47 
10.1.4. Data Protection................................................................................................................47 
10.1.5. Dissemination of Clinical Study Data.............................................................................48 
10.1.6. Data Quality Assurance ..................................................................................................48 
10.1.7. Source Documents ..........................................................................................................50 
10.1.8. Study and Site Start and Closure ....................................................................................50 
10.1.9. Publication Policy ...........................................................................................................50 
10.1.10. Investigator Information .................................................................................................51 
10.1.11. Sample Retention ............................................................................................................51 
10.2. 
Appendix 2: Clinical Laboratory Tests ...........................................................................52 
10.2.1. Blood Sampling Summary ..............................................................................................54 
10.2.2. Laboratory Samples to be Obtained at the Time of a Systemic 
Hypersensitivity Event ....................................................................................................55 
10.3. 
Appendix 3: Adverse Events and Serious Adverse Events: 
Definitions and Procedures for Recording, Evaluating, Follow-
up, and Reporting ............................................................................................................56 
10.3.1. Definition of AE .............................................................................................................56 
10.3.2. Definition of SAE ...........................................................................................................57 
10.3.3. Definition of Product Complaints ...................................................................................58 
10.3.4. Recording and Follow-Up of AE and/or SAE and Product 
Complaints ......................................................................................................................58 
10.3.5. Reporting of SAEs ..........................................................................................................60 
10.3.6. Regulatory Reporting Requirements ...............................................................................60 
10.4. 
Appendix 4: Contraceptive and Barrier Guidance ..........................................................62 
10.4.1. Definitions and Guidance ...............................................................................................62 
10.4.2. Contraception Guidance..................................................................................................63 
10.5. 
Appendix 5: Genetics......................................................................................................65 
10.6. 
Appendix 6: Liver Safety: Suggested Actions and Follow-up 
Assessments ....................................................................................................................66 
10.7. 
Appendix 7: Medical Device Adverse Events (AEs), Adverse 
Device Effects (ADEs), Serious Adverse Events (SAEs) and 
Device Deficiencies: Definition and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ............................................................................68 
10.8. 
Appendix 8: Abbreviations and Definitions ...................................................................69 
10.9. 
Appendix 9: Protocol Amendment History ....................................................................72 
11. 
References ......................................................................................................................73 
 
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I6T-MC-AMCB(a) 
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1. 
Protocol Summary  
1.1. 
Synopsis  
Protocol Title: A Bioequivalence Study of Subcutaneous Injections of Citrate-Free Mirikizumab 
Solution Using a 1-mL Autoinjector and an Investigational 2-mL Autoinjector in Healthy 
Participants 
Brief Title: A bioequivalence study of subcutaneous injections of citrate-free mirikizumab 
solution using a 1-mL autoinjector and an investigational 2-mL autoinjector in healthy 
participants 
Regulatory Agency Identifier Number: IND: 125444 
Rationale: 
Study I6T-MC-AMCB (AMCB) will assess the pharmacokinetics (PK) and safety of a 200-mg 
dose of citrate-free mirikizumab (LY3074828) solution formulation administered via an 
autoinjector (AI) as 2 × 1-mL subcutaneous (SC) injections or a single 2-mL SC injection. The 
study will provide bioequivalence data on delivery of the citrate-free mirikizumab solution via 
the 2-mL AI planned to be used as the investigational AI device for subsequent studies and 
patient use. Both administrations will be evaluated at 3 different injection sites (arm, thigh, and 
abdomen). 
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
 
 To evaluate the bioequivalence of a 
200-mg SC dose of 100 mg/mL 
citrate-free mirikizumab solution using 
a 1 × 2-mL AI (test) compared to 
using 2 × 1-mL AI (reference) 
 Cmax, AUC(0-∞), and AUC(0-tlast) 
Secondary 
 
 To describe the safety of a 200-mg SC 
dose of 100 mg/mL citrate-free 
mirikizumab solution using a 
1 × 2-mL AI (test) compared to using 
2 × 1-mL AI (reference) 
 TEAEs and SAEs 
Abbreviations: AI = autoinjector; AUC(0-∞) = area under the concentration versus time curve from time zero to 
infinity; AUC(0-tlast) = area under the concentration versus time curve from time zero to time t, where t is the last 
time point with a measurable concentration; Cmax = maximum observed drug concentration; SAE = serious 
adverse event; SC = subcutaneous; TEAE = treatment-emergent adverse event.  
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Overall Design: 
Study AMCB is a Phase 1, open-label, randomized, 2-arm, parallel-design, single-dose 
multi-center study of citrate-free mirikizumab administered via AI in healthy participants. 
Brief Summary: 
Screening 
All participants will be screened within 35 days prior to Day 1. 
Treatment and Assessment Period 
Eligible participants will be admitted to the clinical research unit on Day -1. Participants will be 
stratified by 1 of 3 weight categories based on their weight assessment measured on Day -1: 
 less than 75.0 kg 
 75.0 to 85.0 kg 
 more than 85.0 kg 
Participants will be stratified by weight category and randomized 1:1 to either 1 × 2-mL SC 
injection of 100 mg/mL citrate-free mirikizumab (test) or 2 × 1-mL SC injections of 100 mg/mL 
citrate-free mirikizumab (reference) with a computer-generated allocation code using an 
interactive web-response system. Injection-site location, either arm, thigh, or abdomen, will be 
assigned in an approximately equal distribution within each study arm using an interactive 
web-response system.  
Approximately 484 participants may be enrolled so that approximately 400 participants, 200 in 
each test and reference group, complete the study. Approximately 242 participants will be 
randomized to the test arm and approximately 242 participants will be randomized to the 
reference arm, with approximately 80 participants for each injection site in each study arm. 
A minimum of approximately 80 participants overall in each weight category should complete 
the study.  
On Day 1, participants will receive assigned study intervention. Participants may be allowed to 
leave the clinical research unit after completing the 4-hour safety assessments on Day 1, or later 
at the investigator’s discretion, and will return for PK sampling and safety assessments at 
predefined times up to 10 weeks postdose. Participants will be monitored for safety between 
outpatient visits by way of telephone assessment.  
Safety will be assessed through clinical chemistry, hematology, and urinalysis testing, vital signs 
measurements, recording of adverse events and product complaints, and physical examination. 
Study Population: 
Participants will 
 be overtly healthy individuals assigned male at birth or assigned female at birth who are 
individuals of childbearing potential or not of childbearing potential 
 be between 18 and 65 years of age, inclusive, at the time of signing the informed consent 
and of an acceptable age to provide informed consent, and 
 have a body mass index within the range of 18.0 to 34.0 kg/m2, inclusive. 
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I6T-MC-AMCB(a) 
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Participants may have chronic, stable medical conditions that, in the investigator’s opinion, will 
not place the participant at increased risk by participating in the study. 
Number of Participants: 
Approximately 484 participants, approximately 242 participants in each treatment arm, may be 
enrolled so that approximately 400 participants, 200 in each test and reference group, complete 
the study.  
Intervention Groups and Duration: 
All participants will be screened 35 days prior to Day 1. Mirikizumab will be administered into 
the arm, abdomen, or thigh as either: 
 1 × 2-mL SC injection of 100 mg/mL citrate-free mirikizumab (test), or  
 2 × 1-mL SC injections of 100 mg/mL citrate-free mirikizumab (reference). 
Participants will be followed through to Day 71 ± 3 days. Total study duration is up to 109 days. 
Ethical Considerations of Benefit/Risk: 
Mirikizumab-related risks 
As with other immunomodulatory therapies, mirikizumab may increase the risk of developing an 
infection or may exacerbate an existing infection. These may include opportunistic infections 
and reactivation of latent infections, such as tuberculosis and hepatitis B, although such 
infections have not been reported in healthy participant clinical trials administering mirikizumab 
to date. Therefore, participants testing positive for hepatitis B/C, human immunodeficiency 
virus, or tuberculosis at screening will not be permitted to participate in this study. 
Immunomodulatory therapies may increase the risk of malignancies; however, due to the single 
dose of mirikizumab being administered in this study, it is not considered necessary to monitor 
for such effects. 
Immediate hypersensitivity reactions, defined as anaphylactic reaction and infusion-related 
hypersensitivity reaction, including urticaria, angioedema, and anaphylaxis, have rarely been 
reported with the administration of mirikizumab. 
No other clinically significant safety or tolerability concerns have been identified to date in 
healthy participants exposed to mirikizumab up to the highest single doses given of 2400 mg 
intravenously or SC. 
There is no anticipated therapeutic benefit for the participants in this trial. However, participants 
may benefit from the screening procedures, through detection of unknown health issues, even if 
they receive no therapeutic benefit from the trial. 
AI-related risks 
As this study will use AIs, device-related safety risks will be evaluated. Possible device-related 
safety risks include local effects such as pain at the injection sites from either the needle or the 
solution entry into the SC tissue, swelling, erythema, bleeding, and bruising. These risks are 
mitigated by training of investigative site staff on proper injection techniques.  
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Data Monitoring Committee: No.
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I6T-MC-AMCB(a) 
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1.2. 
Schema  
Not applicable. 
 
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I6T-MC-AMCB(a) 
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1.3. 
Schedule of Activities (SoA)  
 
Screening 
Study Day 
Comments 
Procedure 
-35 to -2 
days prior 
to Day 1 
-1 
1 
3 
5 
±1d 
8 
±1d 
11 
±1d 
15 
±2d 
22 
±2d 
29 
±2d 
36 
±2d 
43 
±2d 
50 
±2d 
57 
±3d 
64 
±3d 
71 
±3d 
ED 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history and 
demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review and confirm 
I/E criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Admission to CRU 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Discharge from CRU 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Participants may be discharged 
after completing the 4h safety 
assessments on D1, or later at the 
investigator’s discretion. 
Outpatient visit 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
X 
 
Telephone call 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
 
X 
 
 
To check on the presence of any 
AEs and CMs. 
Randomization 
 
X 
P 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization can occur on D-1 
or D1; participants will be 
randomized as described in 
Section 4.1. 
Height, weight, and 
BMI 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Only weight will be measured on 
D-1 and D71 or ED. 
Body temperature 
X 
X 
P 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
X 
 
Physical examination 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Complete physical examination at 
either screening or D-1. 
Symptom-directed examinations 
and assessments at D71 or ED, 
and as deemed necessary by the 
investigator or designee. 
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Screening 
Study Day 
Comments 
Procedure 
-35 to -2 
days prior 
to Day 1 
-1 
1 
3 
5 
±1d 
8 
±1d 
11 
±1d 
15 
±2d 
22 
±2d 
29 
±2d 
36 
±2d 
43 
±2d 
50 
±2d 
57 
±3d 
64 
±3d 
71 
±3d 
ED 
 
Vital signs (pulse rate 
and blood pressure) 
(sitting) (hours) 
X 
X 
P, 
2 to 
4 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
D1: 2h to 4h to be conducted at 
least 2h after the last injection and 
prior to discharge at 
approximately 4h postdose. Time 
points may be added if warranted 
and agreed upon between Lilly 
and the investigator. 
Hematology, clinical 
chemistry, urinalysis 
X 
X 
P 
X 
 
 
 
X 
 
X 
 
 
 
 
 
X 
X 
See Section 10.2. 
Serology 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
See Section 10.2. 
QuantiFERON®-TB 
Gold test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
See Section 10.2. 
Breath or urine 
ethanol test and urine 
drug screen 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
May be repeated at additional time 
points at the discretion of the 
investigator. See Section 10.2. 
FSH (participants 
who are AFAB only) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
See Section 10.2. 
Pregnancy test  
(participants who are 
AFAB only) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Serum at screening and D-1. Urine 
at D71 or ED. See Section 10.2. 
Single 12-lead ECG 
(supine) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
May be obtained at additional 
times, when deemed clinically 
necessary. 
Mirikizumab 
administration  
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mirikizumab PK 
sample 
 
 
P 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
X 
See Section 10.2. 
Pharmacogenetic 
sample 
 
 
P 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
See Section 10.2. 
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I6T-MC-AMCB(a) 
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Screening 
Study Day 
Comments 
Procedure 
-35 to -2 
days prior 
to Day 1 
-1 
1 
3 
5 
±1d 
8 
±1d 
11 
±1d 
15 
±2d 
22 
±2d 
29 
±2d 
36 
±2d 
43 
±2d 
50 
±2d 
57 
±3d 
64 
±3d 
71 
±3d 
ED 
 
AE, PC, and CM 
X 
X 
X X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
If an AE of Injection-site reaction 
is reported, the investigator or 
designee will complete a 
supplemental injection-site 
reaction AE form.  
Abbreviations: AE = adverse event; AFAB = assigned female at birth; BMI = body mass index; CM = concomitant medication; CRU = clinical research unit; 
D = day; ECG = electrocardiogram; ED = early discontinuation; FSH = follicle-stimulating hormone; h = hour; I/E = inclusion/exclusion;  P = predose; 
PC = product complaint; PK = pharmacokinetics; TB = tuberculosis.  
 
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I6T-MC-AMCB(a) 
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2. 
Introduction  
2.1. 
Study Rationale  
Study I6T-MC-AMCB (AMCB) will assess the PK and safety of a 200-mg dose of citrate-free 
mirikizumab (LY3074828) solution formulation administered via an AI as 2 × 1-mL SC 
injections or a single 2-mL SC injection. The study will provide bioequivalence data on delivery 
of the citrate-free mirikizumab solution via the 2-mL AI planned to be used as the investigational 
AI device for subsequent studies and patient use. Both administrations will be evaluated at 
3 different injection sites (arm, thigh, and abdomen). 
2.2. 
Background  
Mirikizumab is a humanized immunoglobulin G4-variant monoclonal antibody that binds to the 
p19 subunit of IL-23 without binding to other members of the IL-12 cytokine family. 
Mirikizumab is being developed for the treatment of immune-mediated diseases in which the 
IL-23 pathway is thought to have a pathogenic role. Mirikizumab is approved for treatment of 
adults with moderately to severely active UC. Mirikizumab is also being developed for CD and 
was previously in development for psoriasis.  
Mirikizumab has been studied at single doses of up to 2400 mg via both IV and SC 
administration and a citrate-free formulation was developed to lessen ISRs such as pain. 
The recommended mirikizumab dose regimen for patients with UC has 2 stages: 
 an induction period with dosing of 300 mg mirikizumab infused IV for at least 
30 minutes at Weeks 0, 4, and 8, and 
 maintenance dosing of 200 mg mirikizumab injected as 2 × 1-mL SC injections every 
4 weeks, starting at Week 12. 
Administration of a SC 200-mg dose of citrate-free mirikizumab solution via a single 2-mL SC 
dose AI would provide a more convenient option for patients; thus there is a need to demonstrate 
bioequivalence of this delivery compared to 2 × 1-mL SC AI. 
2.2.1. 
Safety  
As of 22 March 2022, a total of 4898 participants in completed and ongoing mirikizumab clinical 
trials have been exposed to at least 1 dose of mirikizumab and have contributed safety data to the 
integrated analyses presented here, including 
 1088 healthy adult participants 
 2170 adult participants with psoriasis 
 1454 adult participants with UC, and 
 186 adult participants with CD. 
Phase 3 studies have been completed for psoriasis, UC, and CD. 
In biopharmaceutic and clinical pharmacology Phase 1 studies, healthy participants have been 
exposed to mirikizumab dose levels ranging from 60 mg to 2400 mg. No clinically significant 
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I6T-MC-AMCB(a) 
16 
dose-related safety or tolerability issues have been observed in completed or ongoing 
biopharmaceutic or clinical pharmacology studies. 
A mirikizumab 1-mL and/or 2-mL AI has been used in 6 completed clinical studies in healthy 
participants, all containing the mirikizumab solution formulation, including the citrate-free 
solution, and has shown acceptable safety and performance.  
Data from the mirikizumab trials that used the AI showed acceptable safety and usability based 
on the 
 PK parameters 
 TEAEs of Injection-site pain, and 
 injection-site assessment. 
Citrate-free Mirikizumab 
Citrate-free mirikizumab has been assessed in 3 completed clinical trials in healthy participants.  
Study I6T-MC-AMBV compared the safety and tolerability of mirikizumab solution formulation 
and mirikizumab citrate-free solution formulation following SC administration using PFS. The 
incidence of all TEAEs reported during the study was similar for the 2 formulations. The 
frequency of positive responses to the prospective ISR (erythema, edema, induration, pruritus, 
and pain) assessments was lower following administration of the mirikizumab citrate-free 
solution formulation (50.0%) compared to the mirikizumab solution formulation (76.7%). 
Participants who received the mirikizumab citrate-free solution formulation had a statistically 
significant lower mean VAS pain score at the 1-minute time point when compared to the 
mirikizumab solution formulation. 
Study I6T-MC-AMBT was a bioequivalence study of mirikizumab solution and citrate-free 
solution using 2 × 1-mL SC injections of 100 mg/mL mirikizumab using an AI, where both were 
well tolerated. The incidence of all TEAEs reported during the study was similar following 
administration of mirikizumab solution and citrate-free solution and between injection-site 
locations. The incidence of ISRs was lower following administration of mirikizumab citrate-free 
solution compared to mirikizumab solution.  
Study I6T-MC-AMBY was a bioequivalence study that investigated mirikizumab solution versus 
citrate-free mirikizumab SC solution in 1-mL and 2-mL PFS. A higher proportion of participants 
reported TEAEs of Injection-site reaction following administration of 300 mg mirikizumab 
solution when compared to mirikizumab citrate-free solution. Excluding Injection-site reaction, 
the incidence of all TEAEs reported during the study was similar between formulations and 
injection-site locations. 
2.2.2. 
Deaths, Serious Adverse Events, and Discontinuations Due to an Adverse Event  
No deaths have been reported in any of the completed or ongoing biopharmaceutic and clinical 
pharmacology studies. 
One participant in the Phase 1 Study I9O-MC-AABC was discontinued due to an SAE of 
malignant brain tumor (preferred term Brain neoplasm malignant). The event was considered 
unrelated to the study treatment. 
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In the Phase 1 Study I6T-MC-AMBX, 1 participant who received mirikizumab by AI reported an 
SAE of Spontaneous abortion. The SAE was severe and considered unrelated to the study 
intervention by the investigator.  
In Phase 2 and 3 studies in participants with psoriasis, UC, and CD, a total of 23 deaths have 
been reported. SAEs and discontinuations due to AEs are summarized in the IB. 
2.2.3. 
Other Treatment-Emergent Adverse Events  
Across the integrated dataset of Phase 1 studies, of the 851 healthy participants exposed to 
mirikizumab, 400 participants (47.0%) reported TEAEs. The most commonly reported TEAEs, 
reported by 5% or more of treated participants, include 
 ISRs (22.2%) 
 nasopharyngitis (7.3%), and 
 headache (7.2%). 
Administration of mirikizumab using either 1-mL or 2-mL AIs has previously shown to have an 
acceptable safety profile and usability in healthy participants, based on TEAEs and injection-site 
pain. 
2.2.4. 
Pharmacokinetics  
Studies in healthy participants and adult participants with UC found that mirikizumab exposure 
increased proportionally, and that mirikizumab has a half-life of approximately 9.3 days and SC 
absolute bioavailability of 44%. 
Body weight was identified as a covariate on the clearance of mirikizumab and BMI was 
identified as a covariate on the SC bioavailability of mirikizumab, with participants with higher 
body weight or BMI having a lower mirikizumab exposure. Although the effect size of weight or 
BMI is not considered clinically relevant, it represents a potential confounding factor for the 
bioequivalence evaluation. Therefore, participants will be stratified by weight in the current 
study.  
Citrate-free mirikizumab 
In Study AMBV, no statistically significant differences in Cmax, AUC(0-∞), and AUC(0-tlast) 
were observed following administration of the 200-mg mirikizumab solution formulation and 
mirikizumab citrate-free solution formulation as 2 × 1-mL SC injections into the arms, thighs, or 
abdomen overall nor at each injection site separately, with the 90% CIs for the ratios of 
geometric least squares means including unity. There was no statistically significant difference in 
the median tmax of mirikizumab between the formulations. 
In Study AMBT, bioequivalence was observed between the 100-mg/mL mirikizumab solution 
and citrate-free solution using 2 × 1-mL SC injections via AI, as assessed by AUC(0-tlast), 
AUC(0-∞), Cmax, and tmax. 
In Study AMBY, bioequivalence was observed between the mirikizumab solution and 
citrate-free mirikizumab SC solution in 1-mL and 2-mL PFS as assessed by AUC(0-tlast), 
AUC(0-∞), and Cmax.  
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2.3. 
Benefit/Risk Assessment  
Mirikizumab-related risks 
As with other immunomodulatory therapies, mirikizumab may increase the risk of developing an 
infection or may exacerbate an existing infection. These may include opportunistic infections 
and reactivation of latent infections, such as TB and hepatitis B, although such infections have 
not been reported in healthy participant clinical trials administering mirikizumab to date. 
Therefore, participants testing positive for hepatitis B/C, HIV, or TB at screening will not be 
permitted to participate in this study. Immunomodulatory therapies may increase the risk of 
malignancies; however, due to the single dose of mirikizumab being administered in this study, it 
is not considered necessary to monitor for such effects. 
Immediate hypersensitivity reactions, defined as anaphylactic reaction and infusion-related 
hypersensitivity reaction, including urticaria, angioedema, and anaphylaxis, have rarely been 
reported with the administration of mirikizumab. 
No other clinically significant safety or tolerability concerns have been identified to date in 
healthy participants exposed to mirikizumab up to the highest single doses given of 2400 mg IV 
or SC. 
There is no anticipated therapeutic benefit for the participants in this trial. However, participants 
may benefit from the screening procedures, through detection of unknown health issues, even if 
they receive no therapeutic benefit from the trial. 
Detailed information about the known and expected benefits, risks, SAEs, adverse drug 
reactions, and reasonably anticipated AEs of mirikizumab are described in the IB. 
Autoinjector-related risks 
As this study will use AIs, device-related safety risks will be evaluated. Possible device-related 
safety risks include local effects such as pain at the injection sites from either the needle or the 
solution entry into the SC tissue, swelling, erythema, bleeding, and bruising. These risks are 
mitigated by training of investigative site staff on proper injection techniques.  
Detailed information about the known and anticipated risks and deficiencies of the AI, and 
related anticipated adverse device effects can be found in the device IB. 
 
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3. 
Objectives and Endpoints  
Objectives 
Endpoints 
Primary 
 
 To evaluate the bioequivalence of a 
200-mg SC dose of 100 mg/mL 
citrate-free mirikizumab solution using 
a 1 × 2-mL AI (test) compared to 
using 2 × 1-mL AI (reference) 
 Cmax, AUC(0-∞), and AUC(0-tlast) 
Secondary 
 
 To describe the safety of a 200-mg SC 
dose of 100 mg/mL citrate-free 
mirikizumab solution using a 
1 × 2-mL AI (test) compared to using 
2 × 1-mL AI (reference) 
 TEAEs and SAEs 
Exploratory 
 
 To evaluate the impact of 
injection-site location on PK 
 Cmax, AUC(0-∞), and AUC(0-tlast) 
Abbreviations: AI = autoinjector; AUC(0-∞) = area under the concentration versus time curve from time zero to 
infinity; AUC(0-tlast) = area under the concentration versus time curve from time zero to time t, where t is the last 
time point with a measurable concentration; Cmax = maximum observed drug concentration; 
PK = pharmacokinetics; SAE = serious adverse event; SC = subcutaneous; TEAE = treatment-emergent adverse 
event.  
 
 
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4. 
Study Design 
4.1. 
Overall Design  
Study AMCB is a Phase 1, open-label, randomized, 2-arm, parallel-design, single-dose 
multi-center study of citrate-free mirikizumab administered via AI in healthy participants. 
Screening 
All participants will be screened within 35 days prior to Day 1. 
Treatment and Assessment Period 
Eligible participants will be admitted to the CRU on Day -1. Participants will be stratified by 1 of 
3 weight categories based on their weight assessment measured on Day -1: 
 less than 75.0 kg 
 75.0 to 85.0 kg 
 more than 85.0 kg 
Participants will be stratified by weight category and randomized as shown in Table AMCB.1 
1:1 to either 1 × 2-mL SC injection of 100 mg/mL citrate-free mirikizumab (test) or 2 × 1-mL 
SC injections of 100 mg/mL citrate-free mirikizumab (reference) with a computer-generated 
allocation code using an IWRS as described in Section 6.3. Injection-site location, either arm, 
thigh, or abdomen, will be assigned in an approximately equal distribution within each study arm 
using an IWRS.  
Approximately 484 participants may be enrolled so that approximately 400 participants, 200 in 
each test and reference group, complete the study. Approximately 242 participants will be 
randomized to the test arm and approximately 242 participants will be randomized to the 
reference arm, with approximately 80 participants for each injection site in each study arm. 
A minimum of approximately 80 participants overall in each weight category should complete 
the study.  
On Day 1, participants will receive assigned study intervention. Participants may be allowed to 
leave the CRU after completing the 4-hour safety assessments on Day 1, or later at the 
investigator’s discretion, and will return for PK sampling and safety assessments at predefined 
times up to 10 weeks postdose. Participants will be monitored for safety between outpatient 
visits by way of telephone assessment.  
Safety will be assessed through clinical chemistry, hematology, and urinalysis testing, vital signs 
measurements, recording of AEs and PCs, and physical examination. 
 
 
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Table AMCB.1. 
Study Intervention Randomization Including Weight Stratification 
and Injection Site Assignment  
Weight 
Category  
 
Administration Methoda 
Subcutaneous Injection Sitea 
Low 
<75.0 kg 
 
 
2 × 1-mL AI (Reference) 
Arm 
1 × 2-mL AI (Test) 
2 × 1-mL AI (Reference) 
Abdomen 
1 × 2-mL AI (Test) 
2 × 1-mL AI (Reference) 
Thigh 
1 × 2-mL AI (Test) 
Medium 
75.0 – 
85.0 kg 
 
 
2 × 1-mL AI (Reference) 
Arm 
1 × 2-mL AI (Test) 
2 × 1-mL AI (Reference) 
Abdomen 
1 × 2-mL AI (Test) 
2 × 1-mL AI (Reference) 
Thigh 
1 × 2-mL AI (Test) 
High 
>85.0 kg 
 
 
2 × 1-mL AI (Reference) 
Arm 
1 × 2-mL AI (Test) 
2 × 1-mL AI (Reference) 
Abdomen 
1 × 2-mL AI (Test) 
2 × 1-mL AI (Reference) 
Thigh 
1 × 2-mL AI (Test) 
Abbreviations: AI = autoinjector; SC = subcutaneous.  
a Using an interactive web-response system, participants will be stratified by weight, assigned an injection site, 
and randomized 1:1 to 1 × 2-mL SC injection or 2 × 1-mL SC injections. 
4.2. 
Scientific Rationale for Study Design  
Conducting the study in healthy participants mitigates the potential confounding effects of the 
disease state and concomitant medications in participants. A population of healthy participants is 
frequently used in the assessment of the PK of both small and large molecules. 
Single doses of citrate-free mirikizumab and the PK sampling time points have been selected to 
generate PK profiles sufficient to fulfill the study objectives. 
The mirikizumab citrate-free solution formulation is being investigated as a potential 
replacement for the mirikizumab solution formulation and has been used in 3 Phase 1 clinical 
trials (Studies I6T-MC-AMBT, I6T-MC-AMBV, and I6T-MC-AMBY). 
Due to the 5-day return of results for the QuantiFERON® TB Gold test, a 35-day screening 
period has been selected. The extension from the standard 28 days allows investigative sites 
more flexibility to screen, randomize, and dose a larger number of healthy participants. 
Weight will be stratified into 3 categories, administration methods will be randomized, and 
injection site will be assigned. The number of participants randomized to each administration 
method and the number of participants assigned to each site of injection is desired to be 
balanced. Previous population PK analyses have shown that participants with a lower body 
weight tended to have a lower clearance, central volume of distribution, or both. While the 
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effects of body weight on these PK parameters were statistically significant, it was not 
considered to be clinically relevant. However, to mitigate these potentially confounding effects, 
weight is a stratification factor to ensure that an approximately equal number of participants in 
each weight category will be randomized to each reference and test administration methods. 
A parallel-group design is chosen because a crossover design is impractical for mirikizumab, 
which has a half-life of approximately 9.3 days. Additionally, a crossover study could confound 
PK data if participants develop neutralizing anti-drug antibody. 
4.3. 
Justification for Dose  
The 200-mg dose of citrate-free mirikizumab chosen for this study is based on 200 mg 
mirikizumab being found to be effective in the completed Phase 3 UC development program and 
is the marketed SC dose for UC maintenance therapy. 
4.4. 
End of Study Definition  
The end of the study is defined as the date of the last visit of the last participant in the study. 
A participant is considered to have completed the study if the participant has completed all visits 
in the study. 
 
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5. 
Study Population  
Participant eligibility for enrollment in the study is based on the criteria listed in this section. The 
inclusion and exclusion criteria used to determine eligibility should only apply at screening or 
other specified visits, and not continuously throughout the study. 
Participants who are not enrolled within 35 days of screening may undergo additional medical 
assessments, clinical measurements, or both to confirm their eligibility. In such instances, the 
following screening tests and procedures will be repeated: vital signs, ECG, clinical laboratory 
tests, and pregnancy test for participants who are assigned female at birth only. 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
5.1. 
Inclusion Criteria  
Participants are eligible to be included in the study only if all of the following criteria apply: 
Age 
1. are between 18 and 65 years of age, inclusive, at the time of signing the informed consent 
and of an acceptable age to provide informed consent. 
Type of participant and disease characteristics 
2. are overtly healthy as determined by medical evaluation including: 
 medical history 
 physical examination 
 clinical laboratory tests 
 ECG, and  
 vital signs. 
Note: participants may have chronic, stable medical conditions that, in the investigator’s opinion, 
will not place the participant at increased risk by participating in the study, and will not interfere 
with interpretation of the data, for example, treated controlled mild hypertension, 
hypercholesterolemia, gastroesophageal reflux disease. 
3. have clinical laboratory test results at screening and Day -1 
 within normal reference range for the population, or 
 within normal reference range for the investigative site, or  
 results with acceptable deviations that are judged to be not clinically significant by 
the investigator. 
Weight 
4. have a BMI within the range of 18.0 to 34.0 kg/m2, inclusive.  
Sex assigned at birth and contraceptive/barrier requirements 
5. are individuals assigned male at birth or assigned female at birth who are individuals of 
childbearing potential or individuals not of childbearing potential. 
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Contraceptive use by participants should be consistent with local regulations regarding the 
methods of contraception for those participating in clinical studies. For the definitions and 
additional requirements related to contraception requirements of this protocol, see 
Section 10.4. 
Informed consent 
6. are capable of giving signed informed consent as described in Section 10.1.3, which 
includes compliance with the requirements and restrictions listed in the ICF and in this 
protocol. 
Other inclusion criteria 
7. have venous access sufficient to allow for blood sampling as per the protocol. 
8. are reliable and willing to make themselves available for the duration of the study and are 
willing to follow study procedures.  
9. agree not to donate blood or plasma until after the end of their participation in the study. 
5.2. 
Exclusion Criteria  
Participants are excluded from the study if any of the following criteria apply: 
Medical conditions 
10. have significant allergies to humanized monoclonal antibodies or known allergies to 
citrate-free mirikizumab, related compounds or any components of the formulation, or 
history of significant atopy. 
11. have self-perceived dullness or loss of sensation in either arm or thigh or on either 
side of the abdomen. 
12. have significant previous or current history of comorbidities capable of significantly 
altering the absorption, metabolism, or elimination of drugs; of constituting a risk when 
taking the investigational product; or of interfering with the interpretation of data. 
Uncomplicated cholecystectomy, appendectomy, or hernia repair will not be 
exclusionary.  
13. have known or ongoing psychiatric disorders deemed clinically significant by the 
investigator. 
14. have clinically significant multiple or severe drug allergies, or intolerance to topical 
corticosteroids, or severe post-treatment hypersensitivity reactions, including, but not 
limited to, erythema multiforme major, linear IgA dermatosis, toxic epidermal necrolysis, 
or exfoliative dermatitis. 
15. have a diagnosis or history of malignant disease within 5 years prior to baseline, with the 
following exceptions: 
 basal cell or squamous epithelial carcinomas of the skin that have been resected with 
no evidence of metastatic disease for 3 years. 
 cervical carcinoma in situ, with no evidence of recurrence within the 5 years prior to 
baseline. 
 history of breast cancer will be exclusionary. 
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Prior/concomitant therapy 
16. intend to use over-the-counter or prescription medication, including herbal medications 
and traditional medications, within 7 days prior to dosing. Participants on stable doses of 
some medications, such as statins and antihypertensives, may be eligible for enrolment 
following discussion with the sponsor or designee. Specific medications listed in 
Section 6.8 may be allowed. 
17. have received treatment with biologic agents, such as monoclonal antibodies, including 
marketed drugs, within 3 months or 5 half-lives, whichever is longer, prior to dosing. 
18. have ever received anti-IL-12p40 antibodies, for example, ustekinumab (Stelara®), or 
anti-IL-23p19 antibodies, for example risankizumab (BI 655066), brazikumab 
(MEDI2070), guselkumab (CNTO 1959), or tildrakizumab (MK 3222), for any 
indication, including investigational use. 
19. have received any live vaccine (that is, live attenuated) within less than 4 weeks or 
inactivated vaccine within less than 2 weeks before randomization, or intend to receive a 
live vaccine during the study or an inactivated vaccine 2 weeks postdose, and then they 
must be given at an injection site remote from mirikizumab administration. 
20. have been treated with oral steroids within 1 month of screening or intend to during the 
study. Mild potency topical steroid creams or ointments are permitted, with the exception 
of ± 24 hours from injection of the study intervention as specified in Section 6.8. 
Prior/concurrent clinical study experience 
21. are currently enrolled in a clinical study involving an investigational product or any other 
type of medical research judged not to be scientifically or medically compatible with this 
study. 
22. have participated in a clinical study involving an investigational product within the last 
30 days or 5 half-lives, whichever is longer, prior to screening. If the clinical trial 
involved treatment with biologic agents, such as monoclonal antibodies, including 
marketed drugs, at least 3 months or 5 half-lives, whichever is longer, should have 
elapsed prior to dosing. 
23. have previously completed or withdrawn from this study or any other study investigating 
mirikizumab, and have previously received mirikizumab. 
Diagnostic assessments 
24. have an abnormality in the 12-lead ECG that, in the opinion of the investigator, increases 
the risks associated with participating in the study. 
25. have clinically significant blood pressure, pulse rate, or body temperature as determined 
by the investigator. 
26. have HIV infection. 
27. have a current infection with hepatitis C virus, that is, positive for hepatitis C virus RNA. 
28. have a current infection with hepatitis B virus, that is, positive for hepatitis B surface 
antigen or polymerase chain reaction positive for hepatitis B virus DNA. 
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29. have a current or recent acute, active infection. For at least 30 days before screening and 
up to randomization, participants must have no symptoms or signs of confirmed or 
suspected infection, and must have completed any appropriate anti-infective treatment. 
30. have had any of the following types of infection within 3 months prior to screening or 
develops any of these infections before the randomization: 
a. Serious: Requiring hospitalization, or IV or equivalent oral antibiotic treatment, or 
both. 
b. Opportunistic: As defined in Winthrop et al. 2015. Note: Herpes zoster is 
considered active and ongoing until all vesicles are dry and crusted over. 
c. Chronic: Duration of symptoms, signs, and/or treatment of 6 weeks or longer. 
d. Recurring: Including, but not limited to, herpes simplex, herpes zoster, 
recurring cellulitis, chronic osteomyelitis. 
31. show evidence of active or latent TB, as documented through medical history, 
examination, and TB testing (positive [not indeterminate] QuantiFERON TB 
Gold test; if a repeat test is also indeterminate, the participant will not be eligible); 
or have had household contact with a person with active TB, unless appropriate 
and documented prophylaxis treatment has been completed at least 3 months prior 
to treatment. Participants with any history of active TB are excluded from the 
study, regardless of previous or current TB treatments. Participants that have or 
have had latent TB infection that has not been treated with a complete course of 
appropriate therapy as defined by the World Health Organization and the United 
States Centers for Disease Control and Prevention, unless such treatment is 
underway, are excluded as described in Section 8.2.8. 
Other exclusion criteria 
32. are pregnant, or intend to become pregnant or to breastfeed during the study. 
33. regularly use known drugs of abuse or show positive findings on drug screening. 
34. have donated blood of more than 500 mL within 1 month of screening. 
35. have alcohol intake that exceeds recommended average weekly alcohol consumption 
limits per local regulation, or an amount deemed significant by the investigator. 
36. smoke more than 10 cigarettes per day, or equivalent, or are unable to abide by 
investigative site smoking restrictions described in Section 5.3.2. 
37. have 2 or more of the injection sites (arm, thigh, or abdomen) obscured by tattoos, scars, 
moles, skin hyperpigmentation, birth marks, or stretch marks that would interfere with 
injection site assessments. 
38. are investigative site personnel directly affiliated with this study or their immediate 
families. Immediate family is defined as a spouse, parent, child, or sibling, whether 
biological or legally adopted. 
39. are Lilly employees or are employees of third party organizations involved in the study 
conduct. 
40. in the opinion of the investigator or sponsor, are unsuitable for inclusion in the study. 
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5.3. 
Lifestyle Considerations  
5.3.1. 
Meals and Dietary Restrictions  
Participants will receive a light breakfast on the morning of Day 1 prior to dosing. Standard 
meals will be provided at all other times while participants are resident at the CRU, per the 
CRU’s policy. 
5.3.2. 
Substance Use: Caffeine, Alcohol, and Tobacco  
Caffeine 
Participants will follow clinic caffeine restrictions while resident at the CRU, but otherwise 
participants will be allowed to maintain their regular caffeine consumption. 
Alcohol 
Alcohol consumption is not permitted while participants are resident at the CRU and for 
24 hours prior to each study visit. Alcohol intake during outpatient periods should not exceed 
3 units per day for participants who are assigned male at birth or 2 units per day for participants 
who are assigned female at birth. 
Tobacco 
Participants must abide by the CRU smoking restrictions during study visits and while resident at 
the CRU. 
5.3.3. 
Activity  
Participants will be advised to maintain their regular levels of physical activity and exercise but 
will abstain from strenuous exercise for 48 hours before each blood collection for clinical 
laboratory tests. Participants may participate in light recreational activities during the study, for 
example, watching television, or reading. While certain study procedures are in progress at the 
site, participants may be required to remain recumbent or sitting. 
5.4. 
Screen Failures  
A screen failure occurs when a participant who consents to participate in the clinical study is not 
subsequently enrolled in the study. 
Individuals who do not meet the criteria for participation in this study (screen failure) may not be 
rescreened. Repeating of laboratory tests during the screening period or repeating screening 
assessments to comply with the protocol-designated screening period does not constitute 
rescreening.  
5.5. 
Criteria for Temporarily Delaying 
Enrollment/Randomization/Administration of Study Intervention of 
a Participant  
Not applicable. 
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6. 
Study Intervention(s) and Concomitant Therapy  
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  
Whenever possible, study intervention administration should be carried out by the same trained 
personnel. 
This table lists the interventions used in this clinical study. 
Intervention 
Name 
Mirikizumab citrate-free solution 
in a 1-mL AI (reference) 
Mirikizumab citrate-free solution 
in a 2-mL AI (test) 
Dosage Level(s) 
2 × 100 mg 
100 mg/mL 
1 × 200 mg 
100 mg/mL 
Route of 
Administration 
Subcutaneous injection into the 
arm, abdomen, or thigh 
Subcutaneous injection into the 
arm, abdomen, or thigh 
Dosing 
Instructions 
2 × 1-mL injections at site 
according to the IWRS 
1 × 2-mL injection at site 
according to the IWRS  
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. 
Participants randomized to the 1 × 2-mL SC injections into the abdomen will be administered in 
the lower quadrants of the abdomen.  
Participants randomized to the 2 × 1-mL SC injections will be administered as shown.  
 
First injection 
Second injection 
Arm or thigh 
left limb 
corresponding (contra-lateral) right limb 
Abdomen 
lower left quadrant 
lower right quadrant 
6.1.1. 
Medical Devices, Investigational Devices, or Device Constituents  
The sponsor-manufactured medical devices provided for use in this study are 1-mL and 2-mL 
AIs containing 100 mg/mL citrate-free mirikizumab. 
Instructions for medical device use are provided as part of the study materials provided to 
investigators and sites. 
All PCs, including malfunction, use error, and inadequate labelling, shall be documented and 
reported by the investigator throughout the clinical investigation as described in Section 8.3 and 
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appropriately managed by the sponsor. Each device will be labeled as appropriate for country 
requirements. 
6.2. 
Preparation, Handling, Storage, and Accountability  
The investigator or designee must confirm appropriate storage conditions have been maintained 
during transit for all study intervention received and any discrepancies are reported and resolved 
before use of the study intervention. 
Only participants enrolled in the study may receive study intervention. Only authorized study 
personnel may supply, prepare, or administer study intervention.  
All study intervention must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area in accordance with the labeled storage conditions with access limited 
to the investigator and authorized study personnel. 
The investigator or authorized study personnel are responsible for study intervention 
accountability, reconciliation, and record maintenance, that is, receipt, reconciliation, and final 
disposition records. 
Further guidance and information for the final disposition of unused study interventions are 
provided in the pharmacy manual. 
Samples of the specific batches of mirikizumab used in the study will be retained; details will be 
provided separately. 
6.3. 
Assignment to Study Intervention  
 This is an open-label study. Potential bias will be reduced by central weight category 
stratification and randomization. The site will contact the IWRS prior to the start of study 
intervention administration for each participant.  
All participants will be assigned a unique participant identifier and randomized to citrate-free 
mirikizumab administration methods with weight category as a stratification factor and injection 
site assignment using an IWRS. Before the study is initiated, the log in information and 
directions for the IWRS will be provided to each site. The site will record the intervention 
assignment on the applicable CRF, if required.  
6.4. 
Study Intervention Compliance  
Participants are dosed at the site. Study intervention will be administered under medical 
supervision by the investigator or designee. The dose of study intervention and study participant 
identification will be confirmed prior to the time of dosing by a member of the study site staff 
other than the person administering the study intervention. The date, time, and injection location 
of each dose administered will be recorded in the source documents and will be provided to the 
sponsor as requested. 
6.5. 
Dose Modification  
Not applicable for this single-dose study.  
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6.6. 
Continued Access to Study Intervention after the End of the Study  
Not applicable. 
6.7. 
Treatment of Overdose  
For this study, any dose of mirikizumab greater than 200 mg will be considered an overdose. 
The sponsor does not recommend specific treatment for an overdose. 
In the event of an overdose, the investigator should 
 contact the medical monitor immediately, and 
 closely monitor the participant for any AE/SAE and laboratory abnormalities 
as medically appropriate until, for example, until mirikizumab no longer has a 
clinical effect or can no longer be detected systemically (at least 71 days 
postdose). 
6.8. 
Prior and Concomitant Therapy  
Any medication or vaccine, including over-the-counter or prescription medicines, vitamins, 
and/or herbal supplements, that the participant is receiving at the time of enrollment or receives 
during the study must be recorded along with the 
 reason for use 
 dates of administration including start and end dates, and 
 dosage information including dose and frequency for concomitant therapy of 
special interest. 
The medical monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
6.8.1. 
Permitted Concomitant Therapy  
Participants on stable concomitant medication at the time of study entry should continue their 
regular, unchanged dose throughout the study. Permitted concomitant medications, at the 
discretion of the investigator, include  
 hormonal contraceptives 
 thyroid-replacement therapy 
 hormone-replacement therapy, and 
 occasional acetaminophen (or paracetamol). Acetaminophen should not be administered 
on the dosing day within 4 hours prior to and 4 hours after dosing. If acetaminophen 
treatment is needed for pain management, the maximal allowed dose will be 3 g/day from 
all acetaminophen-containing medicinal products.  
Inclusion of participants on any other concomitant medication (for example, statins and 
anti-hypertensives) is contingent upon approval following consultation with the sponsor or 
designee. 
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If the need for any additional concomitant medication arises, inclusion or continuation of the 
participant may be at the discretion of the investigator after consultation with a Lilly clinical 
pharmacologist, clinical research physician, or designee. 
6.8.2. 
Prohibited Concomitant Therapy  
Participants must abstain from taking the medications described in Section 5.2 until completion 
of the last follow-up visit, unless, in the opinion of the investigator and sponsor, the medication 
will not interfere with the study. 
Participants will be restricted from applying any creams or lotions on the arm, thigh, or 
abdominal skin within 24 hours prior to or after the injections and participants should not receive 
any additional SC injections at the site of mirikizumab administration for the duration of the 
study. 
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7. 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal  
Discontinuation of specific sites or of the study as a whole are handled as part of Section 10.1. 
7.1. 
Discontinuation of Study Intervention  
Not applicable.  
7.2. 
Participant Discontinuation/Withdrawal from the Study  
Discontinuation is expected to be uncommon. 
A participant may withdraw from the study 
 at any time at the participant’s own request for any reason or without 
providing any reason 
 at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons, or 
 if enrolled in any other clinical study involving an investigational product, or 
enrolled in any other type of medical research judged not to be scientifically 
or medically compatible with this study. 
At the time of discontinuing from the study, if possible, the participant will complete procedures 
for an early discontinuation visit as shown in the SoA in Section 1.3. If the participant has not 
already discontinued the study intervention, the participant will be permanently discontinued 
from the study intervention at the time of the decision to discontinue the study. 
If the participant withdraws consent for disclosure of future information, the sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. If a participant 
withdraws from the study, the participant may request destruction of any samples taken and not 
tested, and the investigator must document this in the site study records. 
7.3. 
Lost to Follow-up  
A participant will be considered lost to follow-up if they repeatedly fail to return for scheduled 
visits and are unable to be contacted by the study site. Site personnel or designee are expected to 
make diligent attempts to contact participants who fail to return for a scheduled visit or were 
otherwise unable to be followed up by the site.  
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8. 
Study Assessments and Procedures  
Study procedures and their timing are summarized in the SoA in Section 1.3.  
Immediate safety concerns should be discussed with the sponsor immediately upon occurrence or 
awareness to determine if the participant should continue or discontinue study intervention. 
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct. 
All screening evaluations must be completed and reviewed to confirm that potential participants 
meet all eligibility criteria. The investigator will maintain a screening log to record details of all 
participants screened and to confirm eligibility or record reasons for screening failure, as 
applicable.  
Further details are provided in the sections shown. 
Section 10.2 
List of laboratory tests that will be performed 
Section 10.2.1 
Summary of the maximum number and volume of invasive samples 
Section 10.1.11 
Details about sample retention and custody 
8.1. 
Efficacy Assessments  
Efficacy is not evaluated in this study. 
8.2. 
Safety Assessments  
Planned time points for all safety assessments are provided in the SoA in Section 1.3. 
8.2.1. 
Physical Examinations  
Physical examinations, height, weight, and BMI will be conducted according to the SoA in 
Section 1.3. 
A complete physical examination will include, at a minimum, assessments of the dermatological, 
cardiovascular, respiratory, gastrointestinal, and neurological systems.  
Symptom-directed physical examinations will also be performed. 
Investigators should pay special attention to clinical signs related to previous serious illnesses. 
8.2.2. 
Vital Signs  
For each participant, vital signs measurements should be conducted according to the SoA in 
Section 1.3. If warranted, additional vital signs may be measured. 
Blood pressure and pulse rate should be measured after at least 5 minutes sitting. When possible, 
measurements of blood pressure and pulse rate should be performed at approximately the same 
time of day at each scheduled time point. 
If orthostatic measurements are required, participants should be supine for at least 5 minutes and 
measurement obtained between 2 to 3 minutes after standing. 
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If the participant feels unable to stand, supine vital signs only will be recorded.  
Unscheduled orthostatic vital signs should be assessed, if possible, during any AE of Dizziness or 
posture-induced symptoms. Additional vital signs may be measured throughout the study per 
investigator discretion. 
8.2.3. 
Electrocardiograms  
For each participant, a single 12-lead digital ECG will be collected according to the SoA in 
Section 1.3. All single ECGs recorded should be stored at the investigational site. ECGs may be 
obtained at additional times when deemed clinically necessary, for example, to assess 
participants’ safety. 
During the study, ECGs should be recorded before collecting any blood samples. Participants 
must be supine for at least 5 to 10 minutes before ECG collection, and remain supine and awake 
during ECG collection.  
Any clinically significant findings from ECGs that result in a diagnosis and that occur after the 
participant receives the first dose of study intervention should be reported to the sponsor, or its 
designee, as an AE via the eCRF. 
ECGs will be interpreted by the investigator (a physician or qualified designee) at the site as 
soon after the time of ECG collection as practical, and ideally while the participant is still 
present, to determine whether the participant meets entry criteria at the relevant visit(s) and for 
immediate participant management, should any clinically relevant findings be identified. 
8.2.4. 
Clinical Safety Laboratory Tests  
See Section 10.2 for the list of clinical laboratory tests to be performed and the SoA for the 
timing and frequency. 
The investigator must review the laboratory results, document this review, and report any 
clinically relevant changes occurring during the study as an AE. The laboratory results must be 
retained with source documents unless a source document agreement or comparable document 
cites an electronic location that accommodates the expected retention duration.  
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 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, must be conducted in 
accordance with the SoA, standard collection requirements, and laboratory manual. 
If laboratory values from non-protocol specified laboratory assessments performed at an 
investigator-designated local laboratory require a change in participant management or are 
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considered clinically significant by the investigator, for example, SAE or AE or dose 
modification, then report the information as an AE.  
8.2.5. 
Pregnancy Testing  
Pregnancy testing will be performed as detailed in the SoA in Section 1.3. 
8.2.6. 
Safety Monitoring  
8.2.6.1. 
Hepatic Safety Monitoring and Evaluation  
This table summarizes actions to take based on abnormal hepatic laboratory or clinical changes. 
Participants with normal or near normal baseline (ALT, AST, or ALP <1.5 × ULN) 
If this laboratory value is observed… 
Then… 
Initiate or continue 
 close hepatic 
monitoring 
Initiate  
comprehensive 
evaluation 
ALT or AST ≥3 × ULN 
X 
 
ALP ≥2 × ULN  
X 
 
TBL ≥2 × ULNb 
X 
 
ALT or AST ≥5 × ULN 
X 
X 
ALP ≥2.5 × ULN 
X 
X 
ALT or AST ≥3 × ULN with hepatic signs or symptomsa  
X 
X 
ALT or AST ≥3 × ULN and TBL ≥2 × ULNb or INR ≥ 1.5 
X 
X 
a Examples of hepatic signs or symptoms: severe fatigue, nausea, vomiting, right upper quadrant abdominal pain, 
fever, rash, and/or eosinophilia >5%. 
b In participants with Gilbert’s syndrome the threshold for TBL may be higher. 
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8.2.6.1.1. Close Hepatic Monitoring  
If a participant develops any one of these changes, initiate close hepatic monitoring: 
ALT or AST ≥3 × ULN or 
ALP ≥2 × ULN or 
TBL ≥2 × ULNb 
b In participants with Gilbert’s syndrome the threshold for TBL may be higher. 
Close hepatic monitoring should include these actions: 
 Laboratory tests detailed in Section 10.6, including ALT, AST, alkaline phosphatase, 
TBL, direct bilirubin, gamma-glutamyl transferase, creatine kinase, and complete blood 
count with differential, should be checked within 48 to 72 hours of the detection of 
elevated liver tests to confirm the abnormality and to determine if it is increasing or 
decreasing. 
 If the abnormality persists, clinical and laboratory monitoring should continue at a 
frequency of 2 to 3 times weekly until levels normalize or return to approximate baseline 
values.  
 In addition to laboratory tests, basic evaluation for possible causes of abnormal liver tests 
should be initiated by the investigator in consultation with the Lilly-designated medical 
monitor. At a minimum, this evaluation should include physical examination and a 
thorough medical history, including current symptoms, recent illnesses (for example, 
heart failure, systemic infection, hypotension, or seizures), recent travel, concomitant 
medications (including over-the-counter), herbal and dietary supplements, history of 
alcohol drinking and other substance abuse. 
8.2.6.1.2. Comprehensive Hepatic Monitoring  
If a participant develops any one of the following laboratory or clinical changes, initiate a 
comprehensive hepatic evaluation:  
ALT or AST ≥5 × ULN or 
ALP ≥2.5 × ULN or 
ALT or AST ≥3 × ULN with hepatic signs or symptomsa or 
ALT or AST ≥3 × ULN and TBL ≥2 × ULNb or INR≥ 1.5 
a Examples of hepatic signs or symptoms: severe fatigue, nausea, vomiting, right upper quadrant abdominal pain, 
fever, rash, and/or eosinophilia >5%. 
b In participants with Gilbert’s syndrome the threshold for TBL may be higher. 
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Comprehensive hepatic evaluation should include these actions: 
 At a minimum, comprehensive hepatic evaluation should include physical examination 
and a thorough medical history, as outlined above, as well as tests for prothrombin 
time-INR; tests for viral hepatitis A, B, C, and E; tests for autoimmune hepatitis; and an 
abdominal imaging study (for example, ultrasound or computed tomography scan).  
 Based on the participant’s history and initial results, further testing should be considered 
in consultation with the Lilly-designated medical monitor, including tests for hepatitis D 
virus, cytomegalovirus, Epstein-Barr virus, acetaminophen levels, acetaminophen protein 
adducts, urine toxicology screen, Wilson’s disease, blood alcohol levels, urinary ethyl 
glucuronide, and blood phosphatidylethanol.  
 Based on the circumstances and the investigator’s assessment of the participant’s clinical 
condition, the investigator should consider referring the participant for a hepatologist or 
gastroenterologist consultation, and additional tests including magnetic resonance 
cholangiopancreatography, endoscopic retrograde cholangiopancreatography, cardiac 
echocardiogram, or a liver biopsy. 
 Clinical and laboratory monitoring should continue at a frequency of 1 to 2 times weekly 
until levels normalize or return to approximate baseline values.  
 All the medical information and test results related to the hepatic monitoring and 
comprehensive hepatic evaluation should be collected and recorded in a hepatic safety 
CRF.  
8.2.7. 
Hypersensitivity Reactions  
Many drugs, including oral agents and biologic agents, carry the risk of systemic hypersensitivity 
reactions. If such a reaction occurs, additional data should be provided to the sponsor in the 
designated CRFs. 
Sites should have appropriately trained medical staff and appropriate medical equipment 
available when study participants are receiving study intervention. It is recommended that 
participants who experience a systemic hypersensitivity reaction be treated per national and 
international guidelines. 
In the case of a suspected systemic hypersensitivity event, additional blood samples should be 
collected as described in Section 10.2.2. Laboratory results are provided to the sponsor via the 
central laboratory. 
8.2.8. 
Tuberculosis Testing and Monitoring  
Participants will be tested as indicated in the SoA, in Section 1.3, for evidence of active or latent 
TB using the QuantiFERON-TB Gold test. If the test is indeterminate, 1 retest is allowed. If the 
retest is indeterminate, the participant will be excluded from the study. 
Participants who have had household contact with a person with active TB must be excluded, 
unless appropriate and documented prophylaxis treatment for TB has been completed at least 
3 months prior to treatment. 
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Participants with any history of active TB are excluded from the study, regardless of previous or 
current TB treatments. 
8.2.9. 
Injection-Site Reactions  
Although there will be no prospective collection of ISR information, spontaneously reported 
ISRs by the participant will be recorded as AEs, with the ISR CRF used to collect supplemental 
data on the following specific findings:  
 induration  
 pain 
 edema  
 pruritus, and  
 erythema. 
The findings of ISR for a specific injection will be captured as a single AE of Injection-site 
reaction, if 1 or more than 1 of the findings is positive, and the severity that is recorded on the 
ISR AE form will be the highest severity across the findings at each applicable visit. 
If injection-site pain is reported at any time during the study, the intensity of pain will be 
quantified using the 100-mm validated pain VAS. The VAS is a well validated tool (Williamson 
and Hoggart 2005) to assess injection-site pain; it is presented as a 100-mm line anchored by 
verbal descriptors, usually “no pain” and “worst imaginable pain.” The participant will be asked 
to rate any pain at the injection site on a scale of 0 to 100 on the line as soon as is practical 
following reporting of the event. 
Injection-site assessments should be conducted at the next planned visit following the reporting 
of an injection-related AE. 
8.2.9.1. 
Bleeding and Bruising Assessment  
The presence of visible bleeding or bruising at the injection site will be recorded on the eCRF as 
applicable and will be recorded as an AE if judged to be more severe than expected with a 
typical SC administration.  
A bandage may be placed on the injection site after assessment. 
8.3. 
Adverse Events, Serious Adverse Events, and Product Complaints  
The definitions of AEs, SAEs, and PCs can be found in Section 10.3. 
These events will be reported by the participant, or, when appropriate, by a caregiver, surrogate, 
or the participant's legally authorized representative. 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet these definitions and remain responsible for following up events that 
are serious, considered related to the study intervention or study procedures, or that caused the 
participant to discontinue the study as described in Section 7. 
Care will be taken not to introduce bias when detecting events. Open-ended and non-leading 
verbal questioning of the participant is the preferred method to inquire about event occurrences. 
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After the initial report, the investigator is required to proactively follow each participant at 
subsequent visits or contacts. All SAEs and AEs of special interest as defined in Section 8.3.3 
will be followed until resolution, stabilization, the event is otherwise explained, or the participant 
is lost to follow-up as defined in Section 7.3.  
For PCs, the investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature or causality. Further information on follow-up 
procedures is provided in Section 10.3. 
8.3.1. 
Timing and Mechanism for Collecting Events  
This table describes the timing, deadlines, and mechanism for collecting events. 
Event 
Collection Start 
Collection 
Stop 
Timing for 
Reporting to 
Sponsor or 
Designee 
Mechanism 
for 
Reporting 
Back-up 
Method 
of 
Reporting 
Adverse Event 
AE 
Signing of the ICF  
Participation in 
study has 
ended 
As soon as 
possible upon 
site 
awareness 
AE CRF 
N/A 
Serious Adverse Event 
SAE and SAE updates – 
prior to start of study 
intervention and deemed 
reasonably possibly 
related to study 
procedures 
Signing of the ICF 
Start of 
intervention 
Within 
24 hours of 
awareness 
SAE paper 
form 
N/A 
SAE and SAE updates – 
after start of study 
intervention 
Start of 
intervention 
Participation in 
study has 
ended 
Within 
24 hours of 
awareness 
SAE paper 
form 
N/A 
SAE* – after 
participant’s study 
participation has ended 
and the investigator 
becomes aware 
After participant’s 
study participation 
has ended 
N/A 
Promptly 
SAE paper 
form 
N/A 
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Event 
Collection Start 
Collection 
Stop 
Timing for 
Reporting to 
Sponsor or 
Designee 
Mechanism 
for 
Reporting 
Back-up 
Method 
of 
Reporting 
Pregnancy 
Pregnancy in participants 
and partners of 
participants 
After the start of 
study intervention 
Day 71 
(±3 days) or 
upon early 
discontinuation 
 
Within 
24 hours (see 
Section 8.3.2) 
Pregnancy 
paper form 
N/A 
Product Complaints 
PC associated with an 
SAE or might have led to 
an SAE 
Start of study 
intervention 
End of study 
intervention 
Within 
24 hours of 
awareness 
Product 
Complaint 
form 
N/A 
PC not associated with 
an SAE 
Start of study 
intervention 
End of study 
intervention 
Within 
1 business 
day of 
awareness 
Product 
Complaint 
form 
N/A 
Updated PC information 
— 
— 
As soon as 
possible upon 
site 
awareness 
Originally 
completed 
Product 
Complaint 
form with all 
changes 
signed and 
dated by the 
investigator 
N/A 
PC (if investigator 
becomes aware) 
Participation in 
study has ended 
N/A 
Promptly 
Product 
Complaint 
form 
- 
* SAEs should not be reported unless the investigator deems them to be possibly related to study treatment or study 
participation. 
8.3.2. 
Collection of Pregnancy Information 
8.3.2.1. 
Participants Who Become Pregnant  
The investigator will collect pregnancy information on any participant who becomes pregnant 
while participating in this study. The initial information will be recorded on the appropriate form 
and submitted to the sponsor within 24 hours of learning of a participant's pregnancy.  
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The participant will be followed to determine the outcome of the pregnancy. The investigator 
will collect follow-up information on the participant and the neonate and the information will be 
forwarded to the sponsor. Generally, follow-up will not be required for longer than 6 to 8 weeks 
beyond the estimated delivery date. Any termination of pregnancy will be reported, regardless of 
gestational age, fetal status, presence or absence of anomalies, or indication for the procedure. 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be reported as an AE or SAE.  
A spontaneous abortion (occurring at <20 weeks gestational age) or still birth (occurring at 
≥20 weeks gestational age) is always considered to be an SAE and will be reported as such.  
Any post-study pregnancy-related SAE considered reasonably related to the study intervention 
by the investigator will be reported to the sponsor as described in Section 8.3.1. While the 
investigator is not obligated to actively seek this information in former study participants, the 
investigator may learn of an SAE through spontaneous reporting. 
Any participant who becomes pregnant while participating in the study may be withdrawn from 
the study. If the participant is discontinued from the study, follow the standard discontinuation 
process and continue directly to the follow-up phase. The follow-up on the pregnancy outcome 
should continue independent of intervention or study discontinuation. 
8.3.2.2. 
Participants With Partners Who Become Pregnant  
When to collect pregnancy information 
In most circumstances, the investigator will attempt to collect pregnancy information from a 
participant’s partner who becomes pregnant while the participant is in this study.  
After learning about a pregnancy in the partner of a study participant, the investigator  
 will obtain a consent to release information from the pregnant partner directly, and 
 within 24 hours after obtaining this consent will record pregnancy information on the 
appropriate form and submit it to the sponsor.  
The partner will be followed to determine the outcome of the pregnancy. Information on the 
status of the mother and neonate will be forwarded to the sponsor. Generally, the follow-up will 
be no longer than 6 to 8 weeks after the estimated delivery date. Any termination of the 
pregnancy will be reported regardless of gestational age, fetal status, presence or absence of 
anomalies, or indication for the procedure. 
When not to collect pregnancy information 
It is not necessary to collect information about a pregnancy in the partner of a study participant 
in these circumstances: 
 the partner of the study participant was not exposed to the study intervention, or 
 the participant did not contribute the sperm or ova that resulted in the pregnancy. 
8.3.3. Adverse Events of Special Interest  
AEs of special interest for this program include: 
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 infection and 
 systemic allergic/hypersensitivity reactions. 
If infections or allergic/hypersensitivity reactions are reported, site staff will provide details on 
these events as instructed on the eCRF. A PK and hypersensitivity cytokine panel will be 
collected, as detailed in Section 10.2.2, when possible, for any participant who experiences an 
AE of systemic allergic/hypersensitivity reaction during the study. 
8.4. 
Pharmacokinetics  
At the visits and times specified in the SoA in Section 1.3, venous blood samples will be 
collected from all participants to determine the serum concentrations of mirikizumab. Samples 
will be analyzed at a laboratory approved by the sponsor and stored at a facility designated by 
the sponsor. Concentrations of mirikizumab will be assayed using a validated bioanalytical 
assay.  
A maximum of 3 samples may be collected at additional time points during the study if 
warranted and agreed upon between the investigator and the sponsor. The timing of sampling 
may be altered during the course of the study based on newly available data to ensure appropriate 
monitoring. 
Instructions for the collection and handling of blood samples will be provided by the sponsor.  
The actual date and time (24-hour clock time) of each sample must be recorded.  
Further details on sample retention are described in Section 10.1.11. 
8.5. 
Pharmacodynamics  
Pharmacodynamic parameters are not evaluated in this study. 
8.6. 
Genetics  
A blood sample for DNA isolation will be collected from participants.  
See Section 10.5 for information regarding genetic research and Section 10.1.11 for details about 
sample retention and custody.  
8.7. 
Biomarkers  
Biomarkers are not evaluated in this study. 
8.8. 
Immunogenicity Assessments  
Immunogenicity is not evaluated in this study. 
8.9. 
Health Economics or Medical Resource Utilization and Health 
Economics  
Health economics or medical resource utilization and health economics parameters are not 
evaluated in this study. 
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9. 
Statistical Considerations  
The statistical analysis plan will be finalized prior to first participant first visit, and it will include 
a more technical and detailed description of the statistical analyses described in this section. This 
section is a summary of the planned statistical analyses of the most important endpoints, 
including primary and secondary endpoints. 
9.1. 
Statistical Hypothesis  
The primary objective of this study is to evaluate the bioequivalence of a single 2-mL SC dose of 
citrate-free mirikizumab solution in AI compared to 2 × 1-mL SC doses of citrate-free 
mirikizumab solution in AI. 
9.2. 
Analyses Sets  
Participant Analysis Set 
Description 
Enrolled 
All participants randomly assigned to study intervention. 
Safety analysis set 
All participants who are exposed to study intervention. 
Participants will be analyzed according to the intervention they 
actually received. 
PK analysis set 
All enrolled participants who receive a dose of study intervention 
and have evaluable PK data according to the study intervention 
actually received. 
Participants may be excluded from the PK analysis set in the event of 
 a device malfunction 
 administration of only 1 of the 2 × 1-mL AI doses, or  
 administration of an incorrect or incomplete dose. 
9.3. 
Statistical Analyses  
Statistical analysis of this study will be the responsibility of the sponsor or designee. 
Safety analyses will be conducted for all enrolled participants who were administered study 
intervention, whether or not they completed all protocol requirements. 
Additional exploratory analyses of the data will be conducted as appropriate. Study results may 
be pooled with the results of other studies for safety and population PK analysis purposes, for 
totality of evidence. 
9.3.1. General Considerations  
Handling of missing, unused, and spurious data is addressed prospectively in the overall 
statistical methods described in the protocol and in the statistical analysis plan, where 
appropriate. Adjustments to the planned analyses will be described in the final clinical study 
report. 
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9.3.2. 
Primary Endpoint Analysis   
9.3.2.1. 
Pharmacokinetic Parameter Estimation  
Pharmacokinetic parameter estimates for mirikizumab will be calculated using standard 
noncompartmental methods of analysis. 
The primary parameters for analysis will be the Cmax, AUC(0-∞), and AUC(0-tlast) of 
mirikizumab. The secondary parameter for analysis will be the tmax of mirikizumab. Other 
noncompartmental parameters, such as half-life associated with the terminal rate constant, 
apparent clearance, and apparent volume of distribution, may be reported. 
9.3.2.2. 
Pharmacokinetic Statistical Inference  
The Cmax, AUC(0-∞), and AUC(0-tlast) will be log-transformed and analyzed using a linear 
fixed-effects model. The model will include mirikizumab administration method (2 × 1-mL SC 
injections of 100 mg/mL citrate-free mirikizumab as reference, and 1 × 2-mL SC injections of 
100 mg/mL citrate-free mirikizumab as test), injection location, and weight category 
stratification as fixed effects. The administration method differences will be back-transformed to 
present the ratios of geometric least squares means and the corresponding 90% CI. Comparisons 
will be made between the 2 administration methods.   
The 2 administration methods will be considered bioequivalent if the 90% CIs of the ratio of 
geometric least squares means fall within 0.80 to 1.25.  
In addition, the tmax of mirikizumab between the administration methods will be analyzed using 
a Wilcoxon rank sum test. Estimates of the median difference, approximately 90% CIs, and 
p-values from the Wilcoxon rank sum test will be calculated. 
Additional PK analyses may be conducted if deemed appropriate. 
9.3.3. 
Secondary Endpoint Analysis  
9.3.3.1. 
Clinical Evaluation of Safety  
All investigational product and protocol procedure AEs and PCs will be listed, and if the 
frequency of events allows, safety data will be summarized using descriptive methodology.  
A TEAE is defined as an AE which occurs postdose or which is present prior to dosing and 
becomes more severe postdose. The incidence of TEAEs for each treatment will be presented by 
severity and by association with investigational product as perceived by the investigator. AEs 
reported to occur prior to study entry will be distinguished from those reported as new or 
increased in severity during the study. Each AE will be classified by the most suitable term from 
the medical regulatory dictionary. 
The number of SAEs will be reported. 
9.3.3.2. 
Statistical Evaluation of Safety  
Safety parameters that will be assessed include clinical laboratory parameters and vital signs. 
The parameters and changes from baseline (predose), where appropriate, may be listed and 
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summarized using standard descriptive statistics. Additional analysis will be performed if 
warranted upon review of the data. 
9.3.4. 
Exploratory Endpoint Analysis  
9.3.4.1. 
Pharmacokinetic Parameter Estimation – Injection-site Location  
See Section 9.3.2.1. Additional exploratory analyses may be conducted, and the details will be 
included in the statistical analysis plan. 
9.3.5. 
Other Safety Analyses  
9.3.5.1. 
Injection-site Assessments  
If available, any incidence of erythema, induration, pain, pruritus, edema, bleeding, and bruising 
will be listed. 
9.4. 
Interim Analysis  
No interim analyses are planned for this study. If an unplanned interim analysis is deemed 
necessary for reasons other than a safety concern, the protocol must be amended. 
9.5. 
Sample Size Determination  
Approximately 484 participants, approximately 242 participants in each treatment arm, may be 
enrolled so that approximately 400 participants, 200 in each test and reference group, complete 
the study.  
Within each weight category, participants will be assigned to an SC injection site of either the 
arm, thigh, or abdomen, approximately 80 participants per injection site for the reference and test 
arms. 
A sample size of 200 participants per treatment group will provide approximately 
90% probability that the 90% CI of the geometric mean ratio of Cmax and AUC between groups 
will fall within the equivalence boundary of 0.80 to 1.25. This sample size calculation was based 
on the assumptions that the coefficient of variation of PK parameters is up to 41.8% for each 
treatment group and the expected ratio of geometric means is between 0.9 and 1.1. 
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10. 
Supporting Documentation and Operational Considerations  
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations  
10.1.1. 
Regulatory and Ethical Considerations  
This study will be conducted in accordance with the protocol and with the following: 
 Consensus ethical principles derived from international guidelines 
including the Declaration of Helsinki and Council for International 
Organizations of Medical Sciences International Ethical Guidelines 
 Applicable ICH GCP Guidelines 
 International Organization for Standardization 14155 
 Applicable laws and regulations. 
The protocol, protocol amendments, ICF, IB, and other relevant documents, for example, 
advertisements, must be submitted to an IRB/IEC by the investigator and reviewed and approved 
by the IRB/IEC before the study is initiated. 
Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants. 
Protocols and any substantial amendments to the protocol will require health authority approval 
prior to initiation except for changes necessary to eliminate an immediate hazard to study 
participants. 
The investigator will be responsible for the following 
 providing written summaries of the status of the study to the IRB/IEC 
annually or more frequently in accordance with the requirements, policies, 
and procedures established by the IRB/IEC 
 notifying the IRB/IEC of SAEs or other significant safety findings as 
required by IRB/IEC procedures 
 providing oversight of study conduct for participants under their 
responsibility and adherence to requirements of 21 Code of Federal 
Regulations, ICH guidelines, the IRB/IEC, European regulation 536/2014 
for clinical studies (if applicable), and all other applicable local 
regulations 
 reporting to the sponsor or designee significant issues related to participant 
safety, participant rights, or data integrity. 
Investigator sites are compensated for participation in the study as detailed in the clinical trial 
agreement. 
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10.1.2. 
Financial Disclosure  
Investigators and sub-investigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study. 
10.1.3. 
Informed Consent Process  
The investigator or the investigator’s representative will explain the nature of the study, 
including the risks and benefits, to the potential participant and answer all questions regarding 
the study. 
Potential participants must be informed that their participation is voluntary. Participants will be 
required to sign a statement of informed consent that meets the requirements of 21 Code of 
Federal Regulations 50, local regulations, ICH guidelines, privacy and data protection 
requirements, where applicable, and the IRB/IEC or study center. 
The medical record must include a statement that written informed consent was obtained before 
the participant was entered in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF. 
Revised consents must be appropriately obtained using the correct approved ICFs for applicable 
study participants in accordance with sponsor and IRB/IEC consenting guidance. 
A copy of the ICF(s) must be provided to the participant and 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. 
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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 EU General Data Protection Regulation. 
10.1.5. 
Dissemination of Clinical Study Data  
Communication of Suspended or Terminated Dosing 
If a decision is taken to suspend or terminate dosing in the trial due to safety findings, this 
decision will be communicated by Lilly to all investigators (for example, by phone and/or email) 
as soon as possible. It will be a requirement that investigators respond upon receipt to confirm 
that they understand the communication and have taken the appropriate action prior to further 
dosing any participants with study intervention. Any investigator not responding will be 
followed up by Lilly personnel prior to any further planned dosing. If a dose is planned 
imminently, Lilly personnel will immediately, and continually, use all efforts to reach 
investigators until contact is made and instructions verified. 
Reports 
The sponsor will disclose a summary of study information, including tabular study results, on 
publicly available websites where required by local law or regulation. 
The summary of results will be posted within the time frame specified by local law or regulation. 
If the study remains ongoing in some countries and a statistical analysis of an incomplete dataset 
would result in analyses lacking scientific rigor (for example, underpowered) or compromise the 
integrity of the overall analyses (for example, trial not yet unblinded), the summary of results 
will be submitted within 1 year after the end of the study globally or as soon as available, 
whichever is earlier. 
Data 
The sponsor does not proactively share data from Phase 1 clinical trials. Requests for access to 
Phase 1 clinical trial data are evaluated on a case-by-case basis taking into consideration the 
ability to anonymize the data and the nature of the data collected.  
10.1.6. 
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. This includes laboratory tests, medical records, and clinical 
notes. 
The investigator must review and confirm that data entries are accurate and complete throughout 
the duration of the study, by physically or electronically signing the CRF, as instructed by the 
sponsor. All completed CRFs must be signed prior to archival. 
The investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct or remote access to source documents. 
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Monitoring details describing strategy, for example, risk-based initiatives in operations and 
quality such as risk management and mitigation strategies and analytical risk-based monitoring, 
methods, responsibilities and requirements, including handling of noncompliance issues and 
monitoring techniques are provided in the Monitoring Plan. 
The sponsor or designee is responsible for the data management of this study including quality 
checking of the data. 
The sponsor assumes accountability for actions delegated to other individuals, for example, 
contract research organizations. 
The sponsor or designee will perform monitoring to confirm that data transcribed into the CRF 
by authorized site personnel are accurate, complete, and verifiable from source documents; that 
the safety and rights of participants are being protected; and that the study is being conducted in 
accordance with the currently approved protocol and any other study agreements, ICH GCP, and 
all applicable regulatory requirements. 
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 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, the 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 the 
sponsor or its representatives, 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 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 electronic data capture 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. 
Data collected via the sponsor-provided data capture systems 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 systems. Prior to decommissioning, the investigator will receive or access an 
archival copy of pertinent data for retention. 
Data managed by a central vendor, such as laboratory test data, will be stored electronically in 
the central vendor’s database system and reports/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. 
Data from complaint forms submitted to the sponsor will be encoded and stored in the global PC 
management system. 
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10.1.7. 
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 or entered in the CRF and are transcribed from source documents must be 
consistent with the source documents or the discrepancies must be explained. The investigator 
may need to request previous medical records or transfer records, depending on the study. Also, 
current medical records must be available. 
Definition of what constitutes source data can be found in the site confirmation of source data. 
10.1.8. 
Study and Site Start and Closure  
First act of recruitment 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
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 due to discontinuation of further study intervention development 
 for site termination due to 
o 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 
o inadequate recruitment, evaluated after a reasonable amount of time of 
participants by the investigator, or 
o total number of participants included earlier than expected. 
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up. 
10.1.9. 
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 if the results are deemed to be of significant medical 
importance. 
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10.1.10. 
Investigator Information  
Researchers with appropriate education, training, and experience, as determined by the sponsor, 
will participate as investigators in this clinical trial. 
10.1.11. 
Sample Retention  
Sample retention enables use of new technologies, response to regulatory questions, and 
investigation of variable response that may not be observed until later in the development 
of mirikizumab or after mirikizumab becomes commercially available. 
Sample Type 
Custodian 
Retention Period After Last 
Participant Visit 
Pharmacokinetics 
Sponsor or designee 
1 year 
Pharmacogenetic 
Sponsor or designee 
15 years 
Clinical laboratory tests (not 
otherwise specified) 
Sponsor or designee 
After completion of testing or 
60 days 
 
 
 
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10.2. 
Appendix 2: Clinical Laboratory Tests  
The tests detailed in the table below will be performed by the central or local laboratory as 
specified below. 
In circumstances where the sponsor approves local laboratory testing in lieu of central laboratory 
testing (in the table below), the local laboratory must be qualified in accordance with applicable 
local regulations. 
Protocol-specific requirements for inclusion or exclusion of participants are detailed in Section 5 
of the protocol. 
Additional tests may be performed at any time during the study as determined necessary by the 
investigator or required by local regulations. 
Investigators must document their review of the laboratory safety results. 
Clinical Laboratory Tests  
Comments 
Hematology 
Performed locally at screening and Day -1 
and centrally at Day 1 predose and all 
postdose time points unless otherwise 
stated. 
 
*reported as required.  
Hematocrit 
Hemoglobin 
Erythrocyte count  
Mean cell volume  
Mean cell hemoglobin  
Mean cell hemoglobin concentration  
Leukocytes  
Cell morphology* 
Platelets 
Absolute counts and/or % of: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
Clinical Chemistry 
Performed locally at screening and Day -1 
and centrally at Day 1 predose and all 
postdose time points unless otherwise 
stated. 
 
Sodium 
Potassium 
Calcium 
Phosphorous 
Glucose (random) 
Blood urea nitrogen 
Uric acid 
Total cholesterol 
Total protein 
Albumin 
Total bilirubin 
Direct bilirubin 
Alkaline phosphatase 
Aspartate aminotransferase 
Alanine aminotransferase 
Creatinine 
Urinalysis 
Performed locally at screening and Day -1 
and centrally at Day 1 predose and all 
postdose time points unless otherwise 
stated. 
  
Specific gravity 
pH 
Protein 
Glucose 
Ketones 
Leukocyte esterase 
Bilirubin 
Urobilinogen 
Blood 
Nitrite 
Microscopy (if dipstick 
abnormal; blood, protein, 
nitrites, or leukocyte esterase 
is positive) 
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Clinical Laboratory Tests  
Comments 
Hormones (participants assigned female at birth) 
Performed by a local laboratory. 
Serum and urine pregnancy test 
Follicle-stimulating hormone 
test 
Other 
Performed by a local laboratory. 
Breath or urine ethanol test 
Urine drug screen 
TB, HIV, and hepatitis serology 
Performed by a local laboratory. 
a If hepatitis B core antibody is positive, 
further testing for hepatitis B DNA will be 
performed.  
b If hepatitis C antibody is positive, 
further testing for hepatitis C virus RNA 
will be performed.  
Hepatitis B surface antigen 
Hepatitis B core antibodya 
Hepatitis C antibodyb 
HIV 
QuantiFERON® TB Gold 
Pharmacokinetic samples  
Performed by Lilly-designated laboratory.  
Results will not be provided to the 
investigative sites. 
Mirikizumab concentration 
Pharmacogenetic sample 
Performed by Lilly-designated laboratory.  
Results will not be provided to the 
investigative sites. 
 
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10.2.1. 
Blood Sampling Summary  
This table summarizes the approximate number of venipunctures and blood volumes for all 
blood sampling (screening, safety laboratories, and bioanalytical assays) during the study. 
 
Purpose 
Blood Volume 
per Sample (mL) 
Number of 
Blood Samples 
Total Volume 
(mL) 
Screening testsa 
45 
1 
45 
Local hematology, clinical 
chemistry, and pregnancy testsa 
12 
1 
12 
Central hematology and 
chemistrya 
4.5 
5 
22.5 
Pharmacokinetics  
3 
14b 
42 
Pharmacogenetics 
10 
1 
10 
Total 
131.5 
Total for clinical purposes  
140 
a Additional samples may be drawn if needed for safety purposes. 
b   Includes additional 3 samples, if required. 
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10.2.2. 
Laboratory Samples to be Obtained at the Time of a Systemic Hypersensitivity 
Event  
Purpose of collecting samples after a systemic hypersensitivity event 
The samples listed in this appendix are not collected for acute study participant management. 
The sponsor will use the laboratory tests results from these samples to characterize 
hypersensitivity events across the clinical development program. 
When to collect samples after a systemic hypersensitivity event occurs 
Collect the samples listed below if a systemic hypersensitivity event is suspected. The timing 
should be as designated in the table, assuming the participant has been stabilized. 
Obtain follow-up samples at the next regularly scheduled laboratory sample collection to assess 
post-event return-to-baseline values. 
Timing 
Laboratory Testa 
Collect from 30 minutes to 4 hours after 
the start of the event. 
 Note: The optimal collection time is 
from 1 to 2 hours after the start of 
event. 
total tryptase 
complements (C3, C3a, and C5a) 
cytokine panel (IL-6, IL-1β, IL-10, or any 
cytokine panel that includes these 3 cytokines) 
Collect only if not already collected on the 
same day as the event. 
 Note: If collecting, collect up to 
12 hours after the start of the event. 
mirikizumab (LY3074828) concentration  
 
a All samples for hypersensitivity testing will be assayed by Lilly-designated laboratory. Results will not be 
provided to the study site. If samples are not collected or are collected outside the specified time period, this will 
not be considered a protocol deviation. 
What information to record 
Record the date and time when the samples are collected. 
Allowed additional testing for participant management 
The investigator may perform additional tests locally, if clinically indicated, for acute study 
participant management. 
 
 
 
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10.3. 
Appendix 3: Adverse Events and Serious Adverse Events: Definitions 
and Procedures for Recording, Evaluating, Follow-up, and 
Reporting  
The definitions and procedures detailed in this appendix are in accordance with International 
Organization for Standardization 14155. 
Both the investigator and the sponsor will comply with all local medical device reporting 
requirements. 
The detection and documentation procedures described in this protocol apply to all sponsor 
medical devices provided for use in the study. See Section 6.1.1 for the list of sponsor medical 
devices. 
10.3.1. 
Definition of AE 
 An AE is any untoward medical occurrence in a participant administered a 
pharmaceutical product and which does not necessarily have a causal relationship with 
the study intervention. An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a medicinal (investigational) product, or 
investigational combination product, whether or not related to the medicinal 
(investigational) product or investigational combination product. 
 An AE is any untoward medical occurrence, unintended disease or injury, or untoward 
clinical signs (including abnormal laboratory finding) in study participants, users, or 
other persons, whether or not related to the investigational device.  
Events meeting the AE definition 
 Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments, for example, ECG, radiological scans, and vital 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 investigational medicinal product, including signs, 
symptoms, or clinical sequelae. 
Events NOT meeting the AE definition 
 Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
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 The disease or disorder being studied or expected progression, signs, or symptoms of the 
disease or disorder being studied, unless more severe than expected for the participant’s 
condition. 
 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. 
10.3.2. 
Definition of SAE  
An SAE is defined as any untoward medical occurrence that, at any dose, meets one or 
more of the criteria listed: 
 Results in death 
 Is life-threatening 
o The term life-threatening in the definition of serious refers to an event in which 
the participant was at risk of death at the time of the event. It does not refer to an 
event, which hypothetically might have caused death, if it were more severe. 
 Requires inpatient hospitalization or prolongation of existing hospitalization 
o In general, hospitalization signifies that the participant has been admitted to 
hospital or emergency ward (usually involving at least an overnight stay) for 
observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfills any 
other serious criteria, the event is serious. When in doubt as to whether 
hospitalization occurred or was necessary, the AE should be considered serious. 
o Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE. 
 Results in persistent disability/incapacity 
o The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
o This definition is not intended to include experiences of relatively minor medical 
significance, such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma, for example, sprained ankle, which may 
interfere with or prevent everyday life functions but do not constitute a substantial 
disruption. 
 Is a congenital anomaly/birth defect 
o Abnormal pregnancy outcomes, for example, spontaneous abortion, fetal death, 
stillbirth, congenital anomalies, and ectopic pregnancy, are considered SAEs. 
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 Other situations: 
o Medical or scientific judgment should be exercised by the investigator in deciding 
whether SAE reporting is appropriate in other situations such as important 
medical events that may not be immediately life-threatening or result in death or 
hospitalization but may jeopardize the participant or may require medical or 
surgical intervention to prevent one of the other outcomes listed in the above 
definition. These events should usually be considered serious. 
o Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse. 
 Resulted in medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function.  
10.3.3. 
Definition of Product Complaints  
Product complaint 
A PC is any written, electronic, or oral communication that alleges deficiencies related to the 
identity, quality, durability, reliability, safety, effectiveness or performance of a study 
intervention. When the ability to use the study intervention safely is impacted, the following are 
also PCs: 
 deficiencies in labeling information, and 
 use errors for device or drug-device combination products due to ergonomic design 
elements of the product. 
Product complaints related to study interventions used in clinical trials are collected to ensure the 
safety of participants, monitor quality, and to facilitate process and product improvements. 
If the participant identifies a PC or a problem with the study intervention, investigators will 
instruct participants to contact the site as soon as possible so that the situation can be assessed. 
An event may meet the definition of both a PC and an AE/SAE. In such cases, it should be 
reported as both a PC and as an AE/SAE. 
10.3.4. 
Recording and Follow-Up of AE and/or SAE and Product Complaints  
AE, SAE, and product complaint recording 
When an AE/SAE/PC occurs, it is the responsibility of the investigator to review all 
documentation (for example, hospital progress notes, laboratory reports, and diagnostics reports) 
related to the event. 
The investigator will then record all relevant AE/SAE/PC information in the participant’s 
medical records, in accordance with the investigator’s normal clinical practice. AE/SAE 
information is reported on the appropriate CRF page and PC information is reported on the 
Product Complaint Form. 
Note: An event may meet the definition of both a PC and an AE/SAE. In such cases, it should be 
reported as both a PC and as an AE/SAE. 
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It is not acceptable for the investigator to send photocopies of the participant’s medical records 
to the sponsor or designee in lieu of completion of the CRF page for AE/SAE and the Product 
Complaint Form for PCs. 
There may be instances when copies of medical records for certain cases are requested by 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. 
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: A type of AE that is usually transient and may require only minimal treatment or 
therapeutic intervention. The event does not generally interfere with usual activities of 
daily living. 
 Moderate: A type of AE that is usually alleviated with additional specific therapeutic 
intervention. The event interferes with usual activities of daily living, causing discomfort 
but poses no significant or permanent risk of harm to the research participant. 
 Severe: A type of AE that interrupts usual activities of daily living, or significantly 
affects clinical status, or may require intensive therapeutic intervention. An AE that is 
assessed as severe should not be confused with an SAE. Severe is a category utilized for 
rating the intensity of an event, and both AEs and SAEs can be assessed as severe. 
An event is defined as “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. 
Assessment of causality 
The investigator is obligated to assess the relationship between study intervention and each 
occurrence of each AE/SAE. The investigator will use clinical judgment to determine the 
relationship. 
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. 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as 
well as the temporal relationship of the event to study intervention administration will be 
considered and investigated. 
The investigator will also consult the IB in their assessment. 
The investigator must review and provide an assessment of causality for each AE/SAE and 
document this in the medical notes. 
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 
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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 their opinion of causality in light of follow-up information and send 
an SAE follow-up report with the updated causality assessment. 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
Follow-up of AEs and SAEs 
 The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by 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. 
10.3.5. 
Reporting of SAEs  
SAE reporting via paper form 
Facsimile transmission of the SAE paper form is the preferred method to transmit this 
information to the sponsor and designee. 
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 the Global Patient Safety Clinical Trial SAE 
Transmission Cover Sheet and Form. 
10.3.6. 
Regulatory Reporting Requirements  
SAE regulatory reporting 
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of 
a study intervention under clinical investigation are met. 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will evaluate the reported SAEs, including confirmation of relatedness and assessment 
of expectedness. The sponsor has processes for safety reports for identification, recording, and 
expedited reporting of suspected unexpected serious adverse reactions according to local 
regulatory requirements. The sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, IRBs/IECs, and investigators. 
An investigator who receives an investigator safety report describing an SAE or other specific 
safety information (for example, summary or listing of SAEs) from the sponsor will review and 
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then file it along with the IB and will notify the IRB/IEC, if appropriate according to local 
requirements.  
 
 
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10.4. 
Appendix 4: Contraceptive and Barrier Guidance 
10.4.1. 
Definitions and Guidance  
Word/Phrase 
Definition 
Individuals 
assigned female 
at birth 
Individuals assigned the female sex based on external genitalia and/or 
genetic or medical information. In addition, if these individuals are of 
reproductive potential, they are potentially capable of gestating a fetus, and 
thus are capable of exposing an egg, embryo, or fetus to study drug or drug 
effects. 
Individuals 
assigned male at 
birth 
Individuals assigned the male sex based on external genitalia and/or genetic 
or medical information. In addition, if these individuals are of reproductive 
potential, they are not capable of gestating a fetus, but are capable of 
exposing a fetus to study drug or drug effects via their semen. Individuals 
assigned male at birth are considered to be not of reproductive potential if 
they have had orchiectomy (orchidectomy) with or without penectomy, 
confirmed by operative note. 
Individuals of 
childbearing 
potential 
(IOCBP) a 
Adult individuals assigned female at birth are considered IOCBP unless 
they are INOCBP. 
Note: Adolescent or adult individuals assigned female at birth who are 
receiving hormone therapy as part of gender transition are considered 
IOCBP unless they meet the conditions outlined below for INOCBP. 
Individuals not 
of childbearing 
potential 
(INOCBP) b 
Individuals assigned female at birth are considered INOCBP if they are not 
capable of producing ova or embryo, and/or are not capable of potentially 
gestating a fetus. Such individuals include those who  
 have a congenital anomaly such as Müllerian agenesis, resulting in 
confirmed infertility  
 are infertile due to surgical sterilization, or  
 are menopausal. 
Acceptable surgical sterilization methods are hysterectomy, bilateral 
salpingo-oophorectomy, bilateral salpingectomy, or bilateral oophorectomy. 
Menopausal 
state c 
The menopausal state is defined as an individual: 
 at any age at least 6 weeks post-surgical bilateral oophorectomy 
with or without hysterectomy, confirmed by operative note; or  
 aged at least 40 years and up to 55 years with an intact uterus, not 
on hormone therapyc, who has had cessation of menses for at least 
12 consecutive months without an alternative medical cause, AND 
with a follicle-stimulating hormone ≥40 mIU/mL; or  
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 55 years or older not on hormone therapy, who has had at least 
12 months of spontaneous amenorrhea, or 
 aged at least 55 years with a diagnosis of menopause prior to 
starting HRT. 
a IOCBP is inclusive of the concept of women of childbearing potential, a term often used in literature and 
regulatory guidance documents. 
b INOCBP is inclusive of the concept of women not of childbearing potential. 
c The individual should not be taking medications during amenorrhea such as oral contraceptives, HRT, 
gonadotropin-releasing hormone, anti-estrogens, selective estrogen receptor modulators, or chemotherapy that 
could induce transient amenorrhea. Individuals on HRT and those whose menopausal status cannot be confirmed 
will be required to comply with the protocol contraception requirements if they wish to continue HRT during the 
study. Otherwise they must discontinue HRT to allow confirmation of menopausal status before study 
enrollment. 
10.4.2. 
Contraception Guidance  
Individuals Assigned Male at Birth 
For individuals assigned male at birth, no contraception is required except in compliance with 
specific local government study requirements. 
Individuals Assigned Female at Birth 
IOCBP who are completely abstinent as their preferred and usual lifestyle, or exclusively engage 
in sexual relations with other individual(s) who are assigned female at birth as their preferred and 
usual lifestyle must follow the rules in this table. 
Must… 
Must not…  
agree to either remain abstinent or 
exclusively engage in sexual 
relations with other individual(s) 
who are assigned female at birth, 
and not plan a pregnancy during 
the study 
 use periodic abstinence methods 
o calendar 
o ovulation 
o symptothermal, or  
o post-ovulation 
 declare abstinence just for the duration of a trial, or 
 use the withdrawal method 
IOCBP who are NOT completely abstinent as their preferred and usual lifestyle, or who do NOT 
exclusively engage in sexual relations with other individual(s) who are assigned female at birth 
as their preferred and usual lifestyle, must follow the rules in this table. 
Must… 
Agree to use 1 highly effective method of contraception, or a combination of 2 effective 
methods of contraception. 
These methods of contraception must be used for the duration of the study. 
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Examples of different methods of contraception: 
Methods 
Examples 
Highly effective 
contraception (less 
than 1% failure 
rate) 
 
 fallopian tubal sterilization methods other than bilateral 
salpingectomy (laparoscopic bipolar electrocoagulation, plastic 
ring application on the uterine tubes, fallopian tube ligation, 
hysteroscopic sterilization). Note: Bilateral salpingectomy is 
indicative of permanent sterilization. Please see the INOCBP 
definition above 
 combination oral contraceptive pill 
 progestin-only contraceptive pill (mini-pill) 
 implanted contraceptives  
 injected contraceptives 
 contraceptive patch (only individuals <198 pounds or 90 kg) 
 total abstinence 
  sexual relationships exclusively between individuals who are 
assigned the same sex at birth 
 vasectomy – for individuals assigned male at birth in clinical trials 
and for the partner of an individual assigned female at birth (if 
only sexual partner) 
 fallopian tube implants (if confirmed by hysterosalpingogram) 
 vaginal ring containing combination hormone medication, or  
 intrauterine devices 
Effective 
contraception 
  penile condom with spermicide 
 vaginal condom with spermicide  
 diaphragm with spermicide 
 cervical sponge with spermicide, or  
 cervical cap with spermicide  
Note: Penile and vaginal condoms should not be used in combination 
Ineffective 
methods of 
contraception 
whether used 
alone or in any 
combination 
 spermicide alone 
 periodic abstinence 
 fertility awareness (calendar method, temperature method, cervical 
mucus, or symptothermal) 
 withdrawal 
 postcoital douche, or  
 lactational amenorrhea 
 
 
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10.5. 
Appendix 5: Genetics  
Use/Analysis of DNA 
Genetic variation may impact a participant’s response to study intervention, susceptibility to, and 
severity and progression of disease. Variable response to study intervention may be due to 
genetic determinants that impact drug absorption, distribution, metabolism, and excretion; 
mechanism of action of the drug; disease etiology; and/or molecular subtype of the disease being 
treated.  
Therefore, where local regulations and IRB/IEC allow, a blood sample will be collected for DNA 
analysis from consenting participants. 
DNA samples will be used for research related to mirikizumab or IL-23-mediated autoimmune 
disease, and related diseases. They may also be used to develop tests/assays including diagnostic 
tests related to mirikizumab and/or interventions of this drug class and IL-23-mediated 
autoimmune disease. Genetic research may consist of the analysis of one or more candidate 
genes or the analysis of genetic markers throughout the genome or analysis of the entire genome 
(as appropriate). 
The samples may be analyzed as part of a multi-study assessment of genetic factors involved in 
the response to mirikizumab or study interventions of this class to understand study disease or 
related conditions. 
The results of genetic analyses may be reported in the clinical study report or in a separate study 
summary. 
The sponsor will store the DNA samples in a secure storage space with adequate measures to 
protect confidentiality. 
The samples will be retained while research on mirikizumab continues but no longer than 
15 years or other period as per local requirements. 
 
 
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10.6. 
Appendix 6: Liver Safety: Suggested Actions and Follow-up 
Assessments  
Hepatic Evaluation Testing 
See Section 8.2.6.1 for guidance on appropriate test selection. 
The Lilly-designated central laboratory should complete the analysis of all selected testing 
except for testing listed in the investigator-designated local laboratory table. The central 
laboratory will report results if a validated test or calculation is available. 
Local testing may be performed in addition to central testing when necessary for immediate 
participant management. The local laboratory must be qualified in accordance with applicable 
local regulations. If testing is not available in certain regions based on local requirements, 
consult with Lilly-designated medical monitor. 
Tests assayed by Lilly-designated central laboratory 
Hepatic Hematology Panel 
Hepatitis A virus (HAV) testing: 
   Hemoglobin 
    HAV total antibody a 
   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 
    Hepatitis B core total antibody (anti-HBc) 
       Lymphocytes 
    Hepatitis B core IgM antibody 
       Monocytes 
    HBV DNA b 
       Basophils 
Hepatitis C virus (HCV) testing: 
       Eosinophils 
    HCV total antibody a 
   Platelets 
    HCV RNA b 
   Cell morphology (RBC and WBC) 
Hepatitis D virus (HDV) testing: 
Hepatic Clinical Chemistry Panel 
    HDV total antibody a 
   Total bilirubin 
    HDV IgM antibody 
   Direct bilirubin 
    HDV RNA b 
   Alkaline phosphatase (ALP) 
Hepatitis E virus (HEV) testing: 
   Alanine aminotransferase (ALT) 
    HEV IgG antibody 
   Aspartate aminotransferase (AST) 
    HEV IgM antibody 
   Gamma-glutamyl transferase (GGT) 
    HEV RNA b 
   Creatine kinase (CK) 
Anti-nuclear antibody (ANA) 
Hepatic Coagulation Panel 
Anti-smooth muscle antibody (ASMA) or anti-
actin antibody 
   Prothrombin time, INR (PT-INR) 
Immunoglobulin IgA (quantitative) 
Urine Chemistry 
Immunoglobulin IgG (quantitative) 
   Drug screen 
Immunoglobulin IgM (quantitative) 
Haptoglobin 
 
 
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Tests assayed ONLY by investigator-designated local laboratory  
Acetaminophen 
Cytomegalovirus (CMV) testing: 
Acetaminophen protein adducts c 
    CMV antibody 
Alkaline phosphatase isoenzymes 
    CMV DNA b 
Ceruloplasmin 
Herpes simplex virus (HSV) testing: 
Copper 
    HSV (Type 1 and 2) antibody 
Ethyl alcohol (ethanol, EtOH) 
    HSV (Type 1 and 2) DNA b 
Phosphatidylethanol (PEth) 
Liver kidney microsomal type 1 (LKM-1) 
antibody 
Urine Chemistry 
Microbiology Culture: 
    Ethyl glucuronide (EtG) 
    Blood 
Epstein-Barr virus (EBV) testing: 
    Urine 
    EBV antibody 
    
    EBV DNA b 
 
a If lab does not offer total antibody testing, IgG and/or IgM are acceptable substitutes 
b Reflex/confirmation dependent on regulatory requirements, testing availability, or both.  
c Availability of acetaminophen protein adducts testing is limited, so testing may be performed at central labs, if 
needed. 
 
 
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10.7. 
Appendix 7: Medical Device Adverse Events (AEs), Adverse Device 
Effects (ADEs), Serious Adverse Events (SAEs) and Device 
Deficiencies: Definition and Procedures for Recording, Evaluating, 
Follow-up, and Reporting  
Refer to Appendix 3 for definitions and procedures for recording, evaluating, follow-up, and 
reporting of all events. 
 
 
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10.8. 
Appendix 8: Abbreviations and Definitions  
Term 
Definition 
abuse 
Use of a study intervention for recreational purposes or to maintain an addiction or 
dependence 
AE 
adverse event 
AI 
autoinjector 
ALT 
alanine aminotransferase 
ALP 
alkaline phosphatase 
AST 
aspartate aminotransferase 
AUC(0-∞) 
area under the concentration versus time curve from time zero to infinity 
AUC(0-tlast) 
area under the concentration versus time curve from time zero to time t, where t is the 
last time point with a measurable concentration 
BMI 
body mass index 
CD 
Crohn’s disease 
CI 
confidence interval 
Cmax 
maximum observed drug concentration 
complaint 
A complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, purity, durability, reliability, safety or effectiveness, or 
performance of a drug or drug delivery system. 
compliance 
Adherence to all study-related, good clinical practice (GCP), and applicable regulatory 
requirements. 
CRF 
case report form; a printed, optical, or electronic document designed to record all of the 
protocol-required information to be reported to the sponsor for each trial participant. 
CRU 
clinical research unit 
device deficiencies 
Equivalent to product complaint 
ECG 
electrocardiogram 
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. 
GCP 
good clinical practice 
HIV 
human immunodeficiency virus 
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HRT 
hormone replacement therapy 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
independent ethics committee 
IL 
interleukin 
INR 
international normalized ratio  
informed consent 
A process by which a participant voluntarily confirms their willingness to participate in 
a particular study, after having been informed of all aspects of the study that are 
relevant to the participant’s decision to participate. Informed consent is documented by 
means of a written, signed and dated informed consent form. 
INOCBP 
individuals not of childbearing potential 
investigational 
product 
A pharmaceutical form of an active ingredient or placebo being tested or used as a 
reference in a clinical trial, including products already on the market when used or 
assembled (formulated or packaged) in a way different from the authorized form, or 
marketed products used for an unauthorized indication, or marketed products used to 
gain further information about the authorized form.  
IOCBP 
individuals of childbearing potential 
IRB 
institutional review board 
ISR 
injection-site reaction 
IV 
intravenous(ly) 
IWRS 
interactive web-response system 
medication error 
Errors in the prescribing, dispensing, or administration of a study intervention, 
regardless of whether or not the medication is administered to the participant or the 
error leads to an AE. Medication error generally involve a failure to uphold one or more 
of the five “rights” of medication use: the right participant, the right drug, the right 
dose, right route, at the right time. 
In addition to the core five rights, the following may also represent medication errors:  
• dose omission associated with an AE or a product complaint 
• dispensing or use of expired medication 
• use of medication past the recommended in-use date 
• dispensing or use of an improperly stored medication 
• use of an adulterated dosage form or administration technique inconsistent with the 
medication's labeling (for example, Summary of Product Characteristics, IB, local 
label, protocol), or 
• shared use of cartridges, prefilled pens, or both. 
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misuse 
Use of a study intervention for self-treatment that either is inconsistent with the 
prescribed dosing regimen, indication, or both, or is obtained without a prescription 
participant 
Equivalent to CDISC term “subject”: an individual who participates in a clinical trial, 
either as recipient of an investigational medicinal product or as a control 
PC 
product complaint 
PFS 
prefilled syringe 
PK 
pharmacokinetics 
SAE 
serious adverse event 
SC 
subcutaneous(ly) 
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.  
SoA 
schedule of activities 
TB 
tuberculosis 
TBL 
total bilirubin 
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. 
tmax 
time of maximum observed drug concentration 
UC 
ulcerative colitis 
ULN 
upper limit of normal 
VAS 
visual analog scale 
 
 
 
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10.9. 
Appendix 9: Protocol Amendment History  
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents. 
 
 
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11. 
References  
Williamson A, Hoggart B. Pain: a review of three commonly used pain rating scales. J Clin 
Nurs. 2005;14:(7)798-804 
Winthrop KL, Novosad SA, Baddley JW, et al. Opportunistic infections and biologic therapies in 
immune-mediated inflammatory diseases: consensus recommendations for infection reporting 
during clinical trials and postmarketing surveillance. Ann Rheum Dis. 2015;74(12):2107-2116. 
https://doi.org/10.1136/annrheumdis-2015-207841 
 
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