Clinical trial NCT05644353
Conditions: Healthy
Sponsor: Eli Lilly and Company
Start date: 2022-12-05; Completion date: 2023-05-25
Enrollment: 450 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The main purpose of this study is to evaluate amount of mirikizumab (test) that gets into the blood stream and how long it takes the body to get rid of it, when given via pre-filled syringe compared to mirikizumab (reference) solution given via pre-filled syringe. The information about any adverse effects experienced will be collected and the tolerability of mirikizumab will also be evaluated.

Screening is required within 35 days prior to enrolment. For each participant, the total duration of the clinical trial will be about 17 weeks including screening.

Detailed description:

Arms: arm 1: Participants received 3 milliliter (mL) mirikizumab as 2 subcutaneous (SC) injections of 1 mL and 2 mL delivered via Pre-filled Syringe (PFS) to abdomen or arms or thighs on Day 1. arm 2: Participants received 3 mL citrate- free mirikizumab as 2 SC injections of 1 mL and 2 mL delivered via PFS to abdomen or arms or thighs on Day 1.
Interventions: intervention 1: Mirikizumab
Intervention descriptions: intervention 1: Administered SC.

Protocol documents:
Prot_000.pdf: 
Protocol I6T-MC-AMBY (b)
A Bioequivalence Study of Subcutaneous Injections of Mirikizumab Reference Solution 
Using Investigational 1-mL and 2-mL Prefilled Syringes and Mirikizumab Test Solution 
Formulation Using Investigational 1-mL and 2-mL Prefilled Syringes in Healthy 
Participants
NCT05644353
Approval Date: 01-FEB-2023


CONFIDENTIAL 
 I6T-MC-AMBY(b) 
1 
Title Page 
Confidential Information 
The information contained in this document is confidential and is intended for the use of clinical investigators. It is the property of 
Eli Lilly and Company or its subsidiaries and should not be copied by or distributed to persons not involved in the clinical 
investigation of mirikizumab (LY3074828) and the investigational 1-mL and 2-mL prefilled syringes, 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 Mirikizumab Solution 
using Investigational 1-mL and 2-mL Prefilled Syringes and Mirikizumab 
Citrate-free Solution Formulation using Investigational 1-mL and 2-mL Prefilled 
Syringes in Healthy Participants
Protocol Number: I6T-MC-AMBY 
Amendment Number: b 
Compound: Mirikizumab (LY3074828) 
Brief Title: A bioequivalence study of subcutaneous injections of mirikizumab solution and 
mirikizumab citrate-free solution using investigational 1-mL and 2-mL prefilled 
syringes in healthy participants. 
Study Phase: Phase 1 
Sponsor Name: Eli Lilly and Company 
Legal Registered Address: Eli Lilly and Company, Indianapolis, Indiana USA 46285 
Regulatory Agency Identifier Number: IND: 130052 
Approval Date: Protocol Amendment (b) Electronically Signed and Approved by Lilly on date 
provided below. 
Document ID: VV-CLIN-077573 
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 I6T-MC-AMBY(b) 
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Medical monitor name and contact information will be provided separately. 
 
 
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 I6T-MC-AMBY(b) 
3 
Protocol Amendment Summary of Changes Table 
DOCUMENT HISTORY 
Document 
Date 
Amendment (a) 
11-October-2022
Original Protocol 
21-September-2022
Amendment (b) 
This amendment is considered to be nonsubstantial. 
Overall Rationale for the Amendment: 
Protocol I6T-MC-AMBY(a) has been amended. The new protocol is indicated by amendment (b) 
and will be used to conduct the study in place of any preceding version of the protocol. 
The overall changes and rationale for the changes made to the protocol are described in the 
following table. Note that minor edits have been made throughout the protocol, which are not 
captured in the amendment summary table. 
Section # and 
Name 
Description of Change 
Brief Rationale 
Section 1.1 
Synopsis 
Section 4.1 
Overall 
Design 
Section 9.5 
Sample Size 
Determination 
Number of participants to be 
enrolled changed from 
‘approximately 410’ to 
‘approximately 440’. As such 
‘approximately 220’ participants 
will be randomized to each arm 
instead of ‘approximately 205’ 
participants, and ‘approximately 
73 participants per injection site’ 
instead of ‘approximately 
68 participants’. 
At 1 investigative site, an incorrect 
injection technique was used for 
31 participants, as the injection was 
given at a 90-degree angle rather than a 
45-degree angle. These participants will
be included in the safety analysis set but
excluded from the PK analysis set, as per
the PK analysis set exclusion criteria in
Section 9.2. Approximately 30 further
participants will therefore be enrolled in
order to achieve the PK and
immunogenicity objectives of the study.
Section 9.2 
Analyses Sets 
Clarification of PK analysis set 
exclusion criterion 
‘administration of an incorrect or 
incomplete dose’ to 
‘administration of an incorrect 
dose, incomplete dose, or 
incorrect use of procedure 
instructions’ 
The original criterion was expanded to 
clarify that the use of an incorrect 
technique or procedure of study drug 
administration warrants exclusion from 
the PK analysis set.   
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Table of Contents  
1. 
Protocol Summary ..........................................................................................................8 
1.1. 
Synopsis ............................................................................................................................8 
1.2. 
Schema ............................................................................................................................12 
1.3. 
Schedule of Activities .....................................................................................................13 
2. 
Introduction ...................................................................................................................16 
2.1. 
Study Rationale ...............................................................................................................16 
2.2. 
Background .....................................................................................................................16 
2.2.1. 
Safety ..............................................................................................................................17 
2.2.2. 
Deaths, Serious Adverse Events, and Discontinuations due to an 
Adverse Event .................................................................................................................17 
2.2.3. 
Other Treatment-Emergent Adverse Events ...................................................................18 
2.2.4. 
Pharmacokinetics ............................................................................................................18 
2.2.5. 
Immunogenicity ..............................................................................................................19 
2.3. 
Benefit/Risk Assessment ................................................................................................19 
3. 
Objectives and Endpoints ............................................................................................21 
4. 
Study Design ..................................................................................................................22 
4.1. 
Overall Design ................................................................................................................22 
4.2. 
Scientific Rationale for Study Design ............................................................................23 
4.3. 
Justification for Dose ......................................................................................................24 
4.4. 
End of Study Definition ..................................................................................................24 
5. 
Study Population ...........................................................................................................25 
5.1. 
Inclusion Criteria ............................................................................................................25 
5.2. 
Exclusion Criteria ...........................................................................................................26 
5.3. 
Lifestyle Considerations .................................................................................................29 
5.3.1. 
Meals and Dietary Restrictions .......................................................................................29 
5.3.2. 
Substance Use: Caffeine, Alcohol, and Tobacco ............................................................29 
5.3.3. 
Activity ...........................................................................................................................29 
5.4. 
Screen Failures ................................................................................................................29 
5.5. 
Criteria for Temporarily Delaying 
Enrollment/Randomization/Administration of Study Intervention 
of a Participant ................................................................................................................30 
6. 
Study Interventions and Concomitant Therapy ........................................................31 
6.1. 
Study Interventions Administered ..................................................................................31 
6.1.1. 
Devices ............................................................................................................................32 
6.2. 
Preparation, Handling, Storage, and Accountability ......................................................32 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ............................................32 
6.4. 
Study Intervention Compliance ......................................................................................33 
6.5. 
Dose Modification ..........................................................................................................33 
6.6. 
Continued Access to Study Intervention after the End of the 
Study ...............................................................................................................................33 
6.7. 
Treatment of Overdose ...................................................................................................33 
6.8. 
Concomitant Therapy .....................................................................................................33 
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7. 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal........................................................................................35 
7.1. 
Discontinuation of Study Intervention ............................................................................35 
7.2. 
Participant Discontinuation/Withdrawal from the Study ................................................35 
7.3. 
Lost to Follow-up............................................................................................................35 
8. 
Study Assessments and Procedures.............................................................................36 
8.1. 
Efficacy Assessments .....................................................................................................36 
8.2. 
Safety Assessments .........................................................................................................36 
8.2.1. 
Physical Examinations ....................................................................................................36 
8.2.2. 
Vital Signs .......................................................................................................................37 
8.2.3. 
Electrocardiograms .........................................................................................................37 
8.2.4. 
Clinical Safety Laboratory Tests ....................................................................................37 
8.2.5. 
Pregnancy Testing ...........................................................................................................38 
8.2.6. 
Safety Monitoring ...........................................................................................................38 
8.2.7. 
Tuberculosis Testing and Monitoring .............................................................................41 
8.2.8. 
Other Tests ......................................................................................................................41 
8.3. 
Adverse Events, Serious Adverse Events, and Product 
Complaints ......................................................................................................................41 
8.3.1. 
Timing and Mechanism for Collecting Events ...............................................................42 
8.3.2. 
Pregnancy ........................................................................................................................44 
8.3.3. 
Adverse Events of Special Interest .................................................................................45 
8.4. 
Pharmacokinetics ............................................................................................................45 
8.4.1. 
Bioanalysis ......................................................................................................................45 
8.5. 
Pharmacodynamics .........................................................................................................45 
8.6. 
Genetics ..........................................................................................................................46 
8.7. 
Biomarkers ......................................................................................................................46 
8.8. 
Immunogenicity Assessments.........................................................................................46 
8.9. 
Health Economics OR Medical Resource Utilization and Health 
Economics .......................................................................................................................46 
9. 
Statistical Considerations .............................................................................................47 
9.1. 
Statistical Hypotheses .....................................................................................................47 
9.2. 
Analyses Sets ..................................................................................................................47 
9.2.1. 
Study Participant Disposition .........................................................................................47 
9.2.2. 
Study Participant Characteristics ....................................................................................47 
9.3. 
Statistical Analyses .........................................................................................................47 
9.3.1. 
General Considerations ...................................................................................................47 
9.3.2. 
Primary Endpoint Analysis .............................................................................................48 
9.3.3. 
Secondary Endpoint Analysis .........................................................................................48 
9.3.4. 
Exploratory Analysis ......................................................................................................49 
9.3.5. 
Other Safety Analyses.....................................................................................................49 
9.4. 
Interim Analysis ..............................................................................................................49 
9.5. 
Sample Size Determination ............................................................................................49 
10. 
Supporting Documentation and Operational Considerations ..................................51 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ................................................................................................................51 
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6 
10.1.1. Regulatory and Ethical Considerations ...........................................................................51 
10.1.2. Financial Disclosure........................................................................................................51 
10.1.3. Informed Consent Process ..............................................................................................52 
10.1.4. Data Protection................................................................................................................52 
10.1.5. Dissemination of Clinical Study Data.............................................................................52 
10.1.6. Data Quality Assurance ..................................................................................................53 
10.1.7. Source Documents ..........................................................................................................54 
10.1.8. Study and Site Start and Closure ....................................................................................55 
10.1.9. Publication Policy ...........................................................................................................55 
10.2. 
Appendix 2: Clinical Laboratory Tests ...........................................................................56 
10.2.1. Blood Sampling Summary ..............................................................................................59 
10.2.2. Laboratory Samples to be Obtained at the Time of a Systemic 
Hypersensitivity Event ....................................................................................................60 
10.3. 
Appendix 3: Adverse Events and Serious Adverse Events: 
Definitions and Procedures for Recording, Evaluating, Follow-
up, and Reporting ............................................................................................................61 
10.3.1. Definition of Adverse Event ...........................................................................................61 
10.3.2. Definition of Serious Adverse Event ..............................................................................62 
10.3.3. Definition of Product Complaints ...................................................................................63 
10.3.4. Recording and Follow-Up of Adverse Event, Serious Adverse 
Events, and Product Complaints .....................................................................................64 
10.3.5. Reporting of Serious Adverse Events .............................................................................65 
10.3.6. Regulatory Reporting Requirements ...............................................................................66 
10.4. 
Appendix 4: Contraceptive and Barrier Guidance ..........................................................67 
10.4.1. Definitions.......................................................................................................................67 
10.4.2. Contraception Guidance..................................................................................................67 
10.5. 
Appendix 5: Genetics......................................................................................................70 
10.6. 
Appendix 6: Liver Safety: Suggested Actions and Follow-up 
Assessments ....................................................................................................................71 
10.7. 
Appendix 7: Medical Device Adverse Events, Adverse Device 
Effects, Serious Adverse Events, and Device Deficiencies: 
Definition and Procedures for Recording, Evaluating, Follow-up, 
and Reporting ..................................................................................................................73 
10.8. 
Appendix 8: Abbreviations and Definitions ...................................................................74 
10.9. 
Appendix 9: Protocol Amendment History ....................................................................78 
11. 
References ......................................................................................................................79 
 
 
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 I6T-MC-AMBY(b) 
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List of Tables 
Table 
Page 
Table AMBY.1. 
Study AMBY Weight Stratification, Formulation Randomization, and 
Injection Site Assignment ............................................................................................................. 23 
Table AMBY.2. 
Study Interventions Administered ................................................................ 31 
Table AMBY.3. 
Timing and Mechanism for Collecting Events ............................................. 42 
 
 
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 I6T-MC-AMBY(b) 
8 
1. 
Protocol Summary  
1.1. 
Synopsis  
Protocol Title: A Bioequivalence Study of Subcutaneous Injections of Mirikizumab Solution 
using Investigational 1-mL and 2-mL Prefilled Syringes and Mirikizumab Citrate-free Solution 
Formulation using Investigational 1-mL and 2-mL Prefilled Syringes in Healthy Participants 
Brief Title: A bioequivalence study of subcutaneous injections of mirikizumab solution and 
mirikizumab citrate-free solution using investigational 1-mL and 2-mL prefilled syringes in 
healthy participants. 
Regulatory Agency Identifier Number: IND: 130052 
Rationale: Study I6T-MC-AMBY (AMBY) will assess the pharmacokinetics (PK), safety, and 
tolerability of a 300-mg dose of mirikizumab (LY3074828) in: 
 solution formulation administered as 1 × 100-mg subcutaneous (SC) injection using an 
investigational 1-mL prefilled syringe (PFS) and 1 × 200-mg SC injection using an 
investigational 2-mL PFS, or  
 citrate-free solution formulation administered as 1 × 100-mg SC injection using an 
investigational 1-mL PFS and 1 × 200-mg SC injection using an investigational 2-mL 
PFS.  
The study will provide bioequivalence data on the mirikizumab citrate-free solution formulation 
planned to be used in the investigational PFS devices for use in subsequent studies and patient 
use. Both administrations will be evaluated at 3 different injection sites (arm, thigh, and 
abdomen).
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9 
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
 
 To evaluate the bioequivalence of a 
single 300-mg SC dose of 
mirikizumab in a citrate-free solution 
formulation using a 1-mL and 2-mL 
PFS (test) compared to the 
mirikizumab solution formulation 
using a 1-mL and 2-mL PFS 
(reference) 
 Cmax, AUC(0-∞), and AUC(0-tlast) 
Secondary 
 
 To describe the safety and tolerability 
of a single 300-mg SC dose of 
mirikizumab in a citrate-free solution 
formulation using a 1-mL and 2-mL 
PFS (test) compared to the 
mirikizumab solution formulation 
using a 1-mL and 2-mL PFS 
(reference) 
 TEAEs and SAEs 
Abbreviations: 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; PFS = prefilled 
syringe; SAE = serious adverse event; SC = subcutaneous; TEAE = treatment-emergent adverse event.  
 
Overall Design: 
Study AMBY is a Phase 1, participant-blind, randomized, 2-arm, 2-formulation, parallel-design, 
single-dose, multi-center study 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 clinical research unit (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, and 
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 I6T-MC-AMBY(b) 
10 
 more than 85.0 kg.  
Participants will also be randomized 1:1 to either mirikizumab solution (reference) or citrate-free 
solution (test) with a computer-generated allocation code using an interactive web-response 
system (IWRS). Injection-site location (arm, thigh, or abdomen) will be assigned in an 
approximately equal distribution within each study arm using an IWRS.  
Approximately 440 participants will be enrolled to ensure 368 completers for primary analysis. 
Approximately 220 participants will be randomized to the test arm and approximately 
220 participants will be randomized to the reference arm, with approximately 73 participants for 
each injection site in each study arm. 
A minimum of approximately 70 participants in each weight category should complete the study.  
On Day 1, participants will receive 1 × 1-mL and 1 × 2-mL SC dose of 100 mg/mL mirikizumab 
(total dose: 300 mg mirikizumab). 
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 and immunogenicity 
sampling and safety assessments at predefined times up to approximately 12 weeks postdose. 
Participants will be monitored for safety between outpatient visits by way of telephone 
assessment.  
Safety and tolerability will be assessed through clinical laboratory tests, vital signs 
measurements, recording of adverse events and product complaints, physical examination, and 
immunogenicity.  
Brief Summary: 
The purpose of this study is to evaluate the bioequivalence of a single 300-mg SC dose of 
mirikizumab in a citrate-free solution formulation (test) using investigational 1-mL and 2-mL 
PFSs compared to mirikizumab solution formulation (reference) using investigational 1-mL and 
2-mL PFSs in healthy participants. 
Study Population: 
Participants will be healthy males or females between 18 and 65 years of age, inclusive, and with 
a body mass index within the range of 18.0 and 34.0 kg/m2, inclusive. 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 440 (approximately 220 participants in the mirikizumab solution [reference] 
group and approximately 220 participants in the mirikizumab citrate-free solution [test] group) 
participants may be enrolled.  
Intervention Groups and Duration: 
All participants will be screened within 35 days prior to Day 1. A single SC dose of mirikizumab 
in either the mirikizumab solution formulation (reference) or mirikizumab citrate-free solution 
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 I6T-MC-AMBY(b) 
11 
formulation (test) will be administered as 1 × 1-mL and 1 × 2-mL injections by PFS into the arm, 
thigh, or abdomen on Day 1 and participants will be followed through Day 85, ±3 days. 
Ethical Considerations of Benefit/Risk: 
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 (TB) and hepatitis B, although such 
infections have not been reported in healthy volunteer clinical trials administering mirikizumab 
to date. Therefore, participants testing positive for hepatitis B, hepatitis C, human 
immunodeficiency virus, 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 (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 
participants exposed to mirikizumab up to the highest doses given (single 2400-mg intravenous 
and SC doses). Of note, the 2400-mg SC dose of mirikizumab was administered in conjunction 
with human recombinant hyaluronidase as an integral component of the formulation. 
There is no anticipated therapeutic benefit for the participants in this study. However, 
participants may benefit from the screening procedures (through detection of unknown health 
issues) even if they receive no therapeutic benefit from the study.   
As this study will use PFSs, 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 investigative site staff on proper injection techniques. Systemic effects may 
include sweating, feeling faint, or fever, as a sign of infection.   
Data Monitoring Committee: No. 
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 I6T-MC-AMBY(b) 
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1.2. 
Schema  
Not applicable.
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 I6T-MC-AMBY(b) 
13 
1.3. 
Schedule of Activities  
 
 
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 
85 
±3d or 
ED 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Participant 
admission to CRU 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Participant discharge 
from CRU 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Participants may be 
discharged after completing 
the 4-hour safety assessments 
on Day 1, or later at the 
investigator’s discretion. 
Outpatient visit 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
X 
 
Safety assessment 
(telephone call) 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
 
X 
 
 
To check on the presence of 
any AEs and concomitant 
medications. 
Medical history and 
demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review and confirm 
inclusion and 
exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
See Section 5 for details. 
Randomization using 
an IWRS 
 
X 
P 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
On Day -1 or Day 1, 
participants will be 
randomized 1:1 to 1 of 
2 formulations and assigned 1 
of 3 injection sites per weight 
category.  
Height, weight, and 
BMI 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Only weight will be measured 
on Day -1, Day 85, or ED. 
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 I6T-MC-AMBY(b) 
14 
 
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 
85 
±3d or 
ED 
 
Physical examination 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Complete physical 
examination at either 
screening or Day -1. 
Symptom-directed 
examinations and assessments 
at Day 85 or ED, and as 
deemed necessary by the 
investigator. 
Vital signs (pulse 
rate and blood 
pressure) (sitting) 
X 
X 
P, 
2 to 4 
hours 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
X 
Day 1: 2- to 4-hour assessment 
to be conducted at least 
2 hours after second injection 
and prior to discharge at 
approximately 4 hours 
postdose. Time points may be 
added if warranted and agreed 
on between the sponsor and 
the investigator. 
Body temperature 
X 
X 
P 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
X 
 
Clinical laboratory 
tests 
X 
X 
P 
X 
 
 
 
X 
 
X 
 
 
 
 
 
 
X 
See Appendix 2 (Section 10.2) 
for details. Performed locally 
at screening and Day -1 and 
centrally at Day 1 P and all 
postdose time points unless 
otherwise stated. 
Serology 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
See Appendix 2 (Section 10.2) 
for details. 
QuantiFERON®-TB 
Gold test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ethanol test and drug 
screen 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tests may be repeated at 
additional time points at the 
discretion of the investigator. 
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 I6T-MC-AMBY(b) 
15 
 
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 
85 
±3d or 
ED 
 
FSH 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Females only, as applicable, to 
confirm WNOCBP. See 
Appendix 4 (Section 10.4) for 
details. 
Pregnancy test  
(females only) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Serum pregnancy testing will 
be performed at screening and 
Day -1. Urine pregnancy 
testing will be performed at 
Day 85 or ED.  
Single 12-lead ECG 
(supine) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
May be obtained at additional 
times, when deemed clinically 
necessary. 
Mirikizumab 
administration 
(2 injections per 
dose) 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mirikizumab PK 
sample 
 
 
P 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
X 
 
Immunogenicity 
sample 
 
 
P 
 
 
 
 
X 
 
X 
 
 
 
 
 
 
X 
 
Pharmacogenetic 
sample 
 
 
P 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE, PC, and 
concomitant 
medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
If an AE of ISR is reported, 
the investigator or designee 
will complete a supplemental 
ISR AE form.  
Abbreviations: AE = adverse event; BMI = body mass index; CRU = clinical research unit; d = day; ECG = electrocardiogram; ED = early discontinuation; 
FSH = follicle-stimulating hormone; ISR = injection-site reaction; IWRS = interactive web-response system; P = predose; PC = product complaint; 
PK = pharmacokinetic; TB = tuberculosis; WNOCBP = women not of childbearing potential.  
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 I6T-MC-AMBY(b) 
16 
2. 
Introduction  
2.1. 
Study Rationale  
Study I6T-MC-AMBY (AMBY) will assess the PK, safety, and tolerability of a 300-mg dose of 
mirikizumab (LY3074828) in: 
 solution formulation administered as 1 × 100-mg SC injection using an investigational 
1-mL PFS and 1 × 200-mg SC injection using an investigational 2-mL PFS, or 
 citrate-free solution formulation administered as 1 × 100-mg SC injection using an 
investigational 1-mL PFS and 1 × 200-mg SC injection using an investigational 2-mL 
PFS.  
The study will provide bioequivalence data on the mirikizumab citrate-free solution formulation 
planned to be used in the investigational PFS devices for use in 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 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, including 
psoriasis, CD, and UC, in which the IL-23 pathway is thought to have a pathogenic role.  
Clinical pharmacology studies have demonstrated an acceptable safety profile in healthy 
participants following single dose IV administration up to 2400 mg and single dose SC infusion 
up to 2400 mg (see Section 2.2.1).  
Citrate has been associated with injection site pain in other injectable products (Humira 
Prescribing Information 2021; Kaiser et al. 2012; Nash et al. 2016). Evidence suggests that 
citrate chelation of endogenous divalent metal ions may lead to injection or infusion site pain 
(Krasner et al. 2012). To potentially lessen ISRs, including pain, Lilly developed a citrate-free 
solution formulation of mirikizumab that uses a different combination of buffer and tonicity 
agents to that of the mirikizumab solution formulation.  
The PFS has been used in all clinical studies, including Phase 3 studies.  
The recommended induction dosage regimen of mirikizumab for UC is 300 mg via IV infusion 
every 4 weeks for 3 doses, before a maintenance dose of 200 mg via SC injection (2 × 1-mL) 
every 4 weeks. The proposed dosage regimen of mirikizumab for moderately to severely active 
CD is 900 mg via IV infusion every 4 weeks for 3 doses, followed by a maintenance dose of 
300 mg via SC injection (1 × 1-mL and 1 × 2-mL) every 4 weeks. Multiple 300-mg SC doses 
have been investigated in Phase 2 (Study I6T-MC-AMAF and Study I6T-MC-AMAG) and 
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Phase 3 (Study I6T-MC-AMAM and Study I6T-MC-AMAX) clinical trials in adult participants 
with moderate to severe plaque psoriasis or CD. 
Ongoing Phase 3 studies investigating mirikizumab for the treatment of CD are utilizing a PFS 
and citrate-containing solution formulation. 
Administration of an SC 300-mg dose of mirikizumab as the citrate-free solution would 
potentially decrease the incidence of injection-site pain in patients with CD, thus there is a need 
to demonstrate bioequivalence of this formulation compared with the mirikizumab citrate 
solution formulation.   
2.2.1. 
Safety  
As of 06 December 2021, there have been approximately 4649 participants included in Phase 1, 
2, and 3 studies of mirikizumab. These studies include 851 healthy adult participants, 
2170 patients with psoriasis, 1442 patients with UC, and 186 patients with CD. Phase 3 studies 
have been completed for UC and plaque psoriasis and are ongoing for CD. 
In clinical pharmacology studies, single IV doses of up to 2400 mg have been administered to 
healthy Caucasian, Chinese, and Japanese participants (Study I6T-MC-AMAD and 
I6T-MC-AMBD). No dose-related safety or tolerability issues were observed in these studies or 
other ongoing clinical pharmacology studies with single SC doses ranging from 120 to 2400 mg 
(as an SC infusion in Study I9O-MC-AABA) and at multiple doses up to a maximum of 300 mg.  
Study I6T-MC-AMBV compared the safety and tolerability of mirikizumab solution formulation 
and mirikizumab citrate-free solution formulation following SC administration using PFS in 
healthy participants. 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 
(mean VAS pain score = 12.6) had a statistically significant lower mean VAS pain score at the 
1-minute time point when compared to the mirikizumab solution formulation (mean VAS pain 
score = 26.1). 
A mirikizumab PFS has been used in 7 completed clinical studies in healthy participants (all 
containing the mirikizumab solution formulation) and has shown acceptable safety and 
performance. 
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 clinical pharmacology studies. 
One participant in Phase 1 Study AABC was discontinued due to 1 SAE of Malignant brain 
neoplasm; the event was not considered to be related to study treatment by the investigator. In 
unblinded Phase 2 and 3 studies with participants having psoriasis, UC, or CD, up to 
06 December 2021, 17 deaths were reported as a result of: 
 1 disseminated intravascular coagulation, 
 1 sudden cardiac death, 
 2 myocardial infarctions, 
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 3 COVID-19 deaths, 
 3 COVID-19 pneumonia, 
 1 respiratory failure due to COVID-19 infection, 
 1 lung cancer, 
 1 colon cancer metastatic, 
 1 lymphoma,  
 1 haemorrhage intracranial, 
 1 sepsis, and 
 1 unrecorded cause.  
Three of the deaths, one each of myocardial infarction, colon cancer metastatic, and lymphoma, 
were considered to be related to study drug by the investigator. 
SAEs, ADRs, and discontinuations due to AEs are summarized in the IB. 
2.2.3. 
Other Treatment-Emergent Adverse Events  
In Phase 1 studies that were integrated for safety analyses, the most frequently reported (≥5.0%) 
TEAEs in the 851 healthy participants and participants with psoriasis treated with mirikizumab 
in clinical pharmacology studies were ISRs (including Injection-site pain; 22.2%), 
Nasopharyngitis (7.3%), and Headache (7.2%). All TEAEs were mild to moderate in severity. 
AEs reported as Injection site reaction included instances of erythema, induration, pain, pruritus, 
and edema reported postdose. Most were mild or moderate in severity. 
Administration of mirikizumab using PFSs has previously shown to be well accepted in healthy 
participants, based on TEAEs and injection-site pain, for the 1-mL PFS in Studies 
I6T-MC-AMAE, I6T-MC-AMAQ, I6T-MC-AMAR, AMBD, I6T-MC-AMBE, AMBV, and 
I6T-MC-AMBW, and the 2-mL PFS in Study AMAQ and the ongoing Study I6T-MC-AMBX. 
TEAEs in Phase 2 and 3 studies with participants having psoriasis, UC, or CD are summarized in 
the IB. 
2.2.4. 
Pharmacokinetics  
Studies in healthy participants and participants with psoriasis, UC, or CD found that systemic 
exposure of mirikizumab increases in proportion to dose, and that mirikizumab has a half-life 
of approximately 10 days and SC bioavailability of 44% across participant populations.  
Body weight and BMI were identified as covariates on the clearance and bioavailability of 
mirikizumab, respectively, 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.  
Pharmacokinetics of Mirikizumab Solution Formulation and Mirikizumab Citrate-free Solution 
Formulation via PFS 
Study AMBV investigated the relative bioavailability, safety, and tolerability of a 200-mg SC 
dose of the mirikizumab solution formulation and mirikizumab citrate-free solution formulation 
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administered via PFS. Doses were administered as 2 × 1-mL SC injections into the arms, thighs, 
or abdomen.  
Sixty healthy participants were dosed and completed the study. No statistically significant 
differences in Cmax, AUC(0-∞), and AUC(0-tlast) were observed following administration of the 
mirikizumab solution formulation and mirikizumab citrate-free solution formulation overall or 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. 
2.2.5. 
Immunogenicity  
TE-ADAs have been observed in participants in all clinical trials involving mirikizumab 
administration. In the majority of TE-ADA+ participants, titers were low and had no clear impact 
on drug exposure and, if measured, efficacy. With a few participants, titers were sufficiently high 
to impact drug exposure. There was no clear association between the development of 
immunogenicity to mirikizumab and participants reporting ISRs or hypersensitivity events.   
2.3. 
Benefit/Risk Assessment  
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 volunteer clinical trials administering mirikizumab to date. 
Therefore, participants testing positive for hepatitis B, hepatitis 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 (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 
participants exposed to mirikizumab up to the highest doses given (single 2400-mg IV and SC 
doses). Of note, the 2400-mg SC dose of mirikizumab was administered in conjunction with 
human recombinant hyaluronidase as an integral component of the formulation. 
There is no anticipated therapeutic benefit for the participants in this study. However, 
participants may benefit from the screening procedures (through detection of unknown health 
issues) even if they receive no therapeutic benefit from the study.   
As this study will use PFSs, 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 the use of proper injection techniques by investigative staff. Systemic effects may 
include sweating, feeling faint, or fever, as a sign of infection.   
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More information about the known and expected benefits, risks, SAEs, and reasonably 
anticipated AEs of mirikizumab are described in the IB. 
 
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3. 
Objectives and Endpoints  
Objectives 
Endpoints 
Primary 
 
 To evaluate the bioequivalence of a 
single 300-mg SC dose of 
mirikizumab in a citrate-free solution 
formulation using a 1-mL and 2-mL 
PFS (test) compared to the 
mirikizumab solution formulation 
using a 1-mL and 2-mL PFS 
(reference) 
 Cmax, AUC(0-∞), and AUC(0-tlast) 
Secondary 
 
 To describe the safety and tolerability 
of a single 300-mg SC dose of 
mirikizumab in a citrate-free solution 
formulation using a 1-mL and 2-mL 
PFS (test) compared to the 
mirikizumab solution formulation 
using a 1-mL and 2-mL PFS 
(reference) 
 TEAEs and SAEs 
Exploratory  
 
 To evaluate the effect of mirikizumab 
citrate-free solution formulation using 
a 1-mL and 2-mL PFS and of 
mirikizumab solution formulation 
using a 1-mL and 2-mL PFS on 
immunogenicity 
 To evaluate the impact of injection-site 
location (arm, thigh, or abdomen) on 
PK 
 TE-ADA 
 
 
 
 
 
 Cmax, AUC(0-∞), and AUC(0-tlast) 
Abbreviations: 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; PFS = prefilled 
syringe; PK = pharmacokinetics; SAE = serious adverse event; SC = subcutaneous; 
TE-ADA = treatment-emergent antidrug antibody; TEAE = treatment-emergent adverse event.  
 
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4. 
Study Design  
4.1. 
Overall Design  
Study AMBY is a Phase 1, participant-blind, randomized, 2-arm, 2-formulation, parallel-design, 
single-dose, multi-center study 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, and 
 more than 85.0 kg.  
Participants will also be randomized (Table AMBY.1) 1:1 to either mirikizumab 
solution (reference) or citrate-free solution (test) with a computer-generated allocation 
code (Section 6.3) using an IWRS. Injection site location (arm, thigh, or abdomen) will be 
assigned in an approximately equal distribution within each study arm using an IWRS.  
Approximately 440 participants will be enrolled to ensure 368 completers for primary analysis. 
Approximately 220 participants will be randomized to the test arm and approximately 
220 participants will be randomized to the reference arm, with approximately 73 participants for 
each injection site in each study arm. 
A minimum of approximately 70 participants in each weight category should complete the study.  
On Day 1, participants will receive 1 × 1-mL and 1 × 2-mL SC dose of 100 mg/mL mirikizumab 
(total dose: 300 mg mirikizumab). 
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 and immunogenicity 
sampling and safety assessments at predefined times up to approximately 12 weeks postdose. 
Participants will be monitored for safety between outpatient visits by way of telephone 
assessment.  
Safety and tolerability will be assessed through clinical laboratory tests, vital signs 
measurements, recording of AEs and PCs, physical examination, and immunogenicity. 
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Table AMBY.1. 
Study AMBY Weight Stratification, Formulation Randomization, and 
Injection Site Assignment  
Weight 
Category  
(Participants) 
Mirikizumab Formulationa 
Subcutaneous Injection 
Sitea,b 
Low 
<75.0 kg 
 
 
1 × 1-mL and 1 × 2-mL Solution PFS (Reference) 
Arm 
1 × 1-mL and 1 × 2-mL Citrate-free Solution PFS (Test) 
1 × 1-mL and 1 × 2-mL Solution PFS (Reference) 
Abdomen 
1 × 1-mL and 1 × 2-mL Citrate-free Solution PFS (Test) 
1 × 1-mL and 1 × 2-mL Solution PFS (Reference) 
Thigh 
1 × 1-mL and 1 × 2-mL Citrate-free Solution PFS (Test) 
Medium 
75.0 – 85.0 kg 
 
 
1 × 1-mL and 1 × 2-mL Solution PFS (Reference) 
Arm 
1 × 1-mL and 1 × 2-mL Citrate-free Solution PFS (Test) 
1 × 1-mL and 1 × 2-mL Solution PFS (Reference) 
Abdomen 
1 × 1-mL and 1 × 2-mL Citrate-free Solution PFS (Test) 
1 × 1-mL and 1 × 2-mL Solution PFS (Reference) 
Thigh 
1 × 1-mL and 1 × 2-mL Citrate-free Solution PFS (Test) 
High 
>85.0 kg 
 
 
1 × 1-mL and 1 × 2-mL Solution PFS (Reference) 
Arm 
1 × 1-mL and 1 × 2-mL Citrate-free Solution PFS (Test) 
1 × 1-mL and 1 × 2-mL Solution PFS (Reference) 
Abdomen 
1 × 1-mL and 1 × 2-mL Citrate-free Solution PFS (Test) 
1 × 1-mL and 1 × 2-mL Solution PFS (Reference) 
Thigh 
1 × 1-mL and 1 × 2-mL Citrate-free Solution PFS (Test) 
Abbreviations: PFS = prefilled syringe.  
a Using an interactive web-response system, participants will be stratified by weight, assigned an injection site, 
and randomized 1:1 to mirikizumab solution formulation or citrate-free formulation. 
 b A dose of study intervention will consist of 2 subcutaneous injections of mirikizumab into the arm, thigh, or 
abdomen. 
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 with UC, CD, and psoriasis. A 
population of healthy participants is frequently used in the assessment of the PK of both small 
and large molecules. 
Single doses of mirikizumab and the PK sampling time points have been selected to generate 
PK profiles sufficient to fulfill the study objectives. 
The mirikizumab solution formulation has been used and is currently being used in pivotal 
Phase 3 mirikizumab clinical trials. The mirikizumab citrate-free solution formulation is being 
investigated as a potential replacement for the mirikizumab solution formulation and has been 
used in a single Phase 1 clinical trial where a 200-mg dose (2 × 1-mL) was administered by 
PFS (Study AMBV) and is currently planned to be used in a Phase 1 clinical trial where a 
200-mg dose (2 × 1-mL) will be administered by autoinjector (Study I6T-MC-AMBT). 
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. 
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Participants will be assigned to receive injections in the arm, thigh, or abdomen, as injection 
location has been observed to have an impact on bioavailability in some studies 
with mirikizumab. 
Weight will be stratified into 3 categories, formulation will be randomized, and injection site will 
be assigned. The number of participants randomized to each formulation and the number of 
participants assigned to each site of injection are 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 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 
mirikizumab reference and test solution formulation. 
A parallel-group design is chosen because a crossover design is impractical for mirikizumab, 
which has a half-life of approximately 10 days across participant populations. Additionally, a 
crossover study could confound PK data if participants develop neutralizing ADAs. 
4.3. 
Justification for Dose  
The 300-mg dose of mirikizumab chosen for this study is based on: 
 300 mg being found safe and tolerable in Phase 2 and Phase 3 studies, 
 300 mg being evaluated in the Phase 3 CD development program, and 
 the volume of solution that can be delivered through a 1-mL and a 2-mL PFS and the 
concentration of mirikizumab drug product (100 mg/mL). 
The 300-mg dose administered as 1 × 1-mL and 1 × 2-mL injections is the maintenance dosing 
regimen being used in Phase 3 studies in CD patients and is anticipated for use once marketed. 
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 
of the study including the last visit shown in the SoA (Section 1.3). 
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5. 
Study Population  
Eligibility of participants for enrollment in the study will be based on the results of screening 
medical history, physical examination, vital signs, clinical laboratory tests, and ECG. The nature 
of any conditions present at the time of the physical examination and any preexisting conditions 
will be documented. 
The inclusion and exclusion criteria used to determine eligibility should be applied at screening 
or Day -1 only unless otherwise specified, and not continuously throughout the study.  
Screening may occur up to 35 days prior to Day -1. 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 (females 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 informed consent and 
of an acceptable age to provide informed consent according to local law. 
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 within the normal reference range for the population 
or 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 and Contraceptive/Barrier Requirements 
5.  are males or nonpregnant WOCBP or WNOCBP.  
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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 contraception 
requirements of this protocol, see Appendix 4 (Section 10.4). 
Informed Consent 
6. are capable of giving signed informed consent as described in Appendix 1 
(Section 10.1.3), which includes compliance with the requirements and restrictions listed 
in the ICF and this protocol. 
Other Inclusions 
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 mirikizumab, related compounds, or any components of the formulation, or a 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. 
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 immunoglobulin IgA dermatosis, toxic 
epidermal necrolysis, or exfoliative dermatitis). 
15. have a diagnosis or history of malignant disease within 5 years prior to screening, with 
the following exceptions: 
a. basal cell or squamous epithelial carcinomas of the skin that have been resected 
with no evidence of metastatic disease for 3 years, and 
b. cervical carcinoma in situ, with no evidence of recurrence within the 5 years prior 
to screening. 
16. have had breast cancer within the past 10 years. 
Prior or Concomitant Therapy 
17. 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 
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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. 
18. 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.  
19. 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. 
20. have received live vaccine(s), including attenuated live vaccines and those administered 
intranasally, within 8 weeks of screening, or intend to during the study (non-live or 
inactivated vaccinations are not allowed 2 weeks prior to, or 2 weeks after mirikizumab 
dosing, and then they must be given at an injection-site remote from mirikizumab 
administration). 
21. have been treated with oral steroids within 1 month of screening, or intend to during the 
study (mild topical steroid creams or ointments are permitted, with the exception of 
±24 hours from last injection of the study intervention as specified in Section 6.8). 
Prior or Concurrent Clinical Study Experience 
22. 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. 
23. 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. 
24. have previously completed or withdrawn from this study or any other study investigating 
mirikizumab, and have previously received mirikizumab). 
Diagnostic Assessments 
25. have an abnormality in the 12-lead ECG that, in the opinion of the investigator, increases 
the risks associated with participating in the study. 
26. have abnormal blood pressure, pulse rate, or temperature as determined by the 
investigator. 
27. show evidence of HIV infection, or positive HIV antibodies, or both. 
28. show evidence of hepatitis C virus infection or positive hepatitis C virus 
antibodies. 
29. have a current infection with hepatitis B virus (that is, positive for hepatitis B surface 
antigen and/or polymerase chain reaction positive for hepatitis B virus DNA. 
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30. infections: 
a. have had a serious infection (such as pneumonia, cellulitis, or sepsis), have 
been hospitalized, or have received IV antibiotics for an infection within 
12 weeks prior to Day 1; have had a serious bone or joint infection within 
24 weeks prior to Day 1 or have ever had an infection of an artificial joint, 
or are immunocompromised to an extent that participation in the study 
would pose an unacceptable risk to the participant as determined by the 
investigator. 
b. have or have had an infection typical of an immunocompromised host or 
that occurs with increased incidence in an immunocompromised host 
(including, but not limited to, Pneumocystis jirovecii pneumonia, 
histoplasmosis, or coccidioidomycosis) or have a known 
immunodeficiency. 
c. have or have had a herpes zoster infection or any other clinically apparent 
varicella-zoster virus infection within 12 weeks of Day 1. 
d. have had any other active or recent infection within 4 weeks of Day 1 that, 
in the opinion of the investigator, would pose an unacceptable risk to the 
participant if participating in the study; these participants may be 
rescreened (once) at least 4 weeks after documented resolution of 
symptoms. 
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 given. 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 (Section 8.2.7). 
Other Exclusions 
32. are lactating or pregnant. 
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 study screening. 
35. have an average weekly alcohol intake that exceeds 21 units per week (males) and 
14 units per week (females), have a positive test for ethanol, or are unwilling to abide by 
the alcohol restrictions described in Section 5.3.2 of 3 units per day (males) or 2 units per 
day (females) (number of units = [total volume of drink (mL) × alcohol by 
volume (%)]/1000). 
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, 
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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 and their immediate 
families. Immediate family is defined as a spouse, biological or legal guardian, child, or 
sibling. 
39. are employees of Lilly, Labcorp, or associated Contract Research Organizations involved 
in the study conduct. 
40. in the opinion of the investigator or sponsor, are unsuitable for inclusion in the study. 
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 males or 2 units per day for females.  
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 prior to any visit in which laboratory safety 
tests will occur. 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 laboratory tests during the screening period or repeating screening 
assessments to comply with the protocol-designated screening period does not constitute 
rescreening. 
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5.5. 
Criteria for Temporarily Delaying 
Enrollment/Randomization/Administration of Study Intervention 
of a Participant  
Not applicable. 
 
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6. 
Study Interventions and Concomitant Therapy  
Study intervention is defined as any investigational interventions, marketed products, placebo, or 
medical devices intended to be administered to or used by a study participant according to the 
study protocol. 
6.1. 
Study Interventions Administered  
This study involves a comparison of mirikizumab solution formulation versus citrate-free 
solution formulation using 1 × 1-mL (100 mg) and 1 × 2-mL (200 mg) SC injections of 
100 mg/mL mirikizumab using PFS into the arm, thigh, or abdomen for a total administered dose 
of 300 mg. 
Participants assigned to a group with the arm or thigh as the injection area will have: 
1. the first injection administered to the left limb using the 2-mL PFS, and  
2. the second injection administered to the corresponding (contra-lateral) right limb using 
the 1-mL PFS.  
Participants assigned to the group with the abdomen as the injection area will have: 
1. the first injection administered to the lower left quadrant using the 2-mL PFS, and 
2. the second injection administered to the lower right quadrant of the abdomen using the 
1-mL PFS.  
Whenever possible, study drug administration should be carried out by the same trained 
personnel with the use of proper injection techniques. Table AMBY.2 lists the interventions used 
in this clinical study. 
Table AMBY.2. 
Study Interventions Administered  
Intervention 
Name 
Mirikizumab solution  
in a 1-mL PFS and a 2-mL PFS 
Mirikizumab citrate-free solution  
in a 1-mL PFS and a 2-mL PFS 
Unit Dose 
Strengths/ 
Dosage Levels 
1 × 100 mg and 1 × 200 mg 
100 mg/mL 
1 × 100 mg and 1 × 200 mg 
100 mg/mL 
Route of 
Administration 
Subcutaneous 
Subcutaneous 
Dosing 
Instructions 
1 × 1-mL and 1 × 2-mL injections at 
site according to the IWRS  
1 × 1-mL and 1 × 2-mL injections at 
site according to the IWRS  
Abbreviations: IWRS = interactive web-response system; PFS = prefilled syringe.  
 
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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. 
6.1.1. 
Devices  
The Lilly-manufactured devices provided for use in this study are mirikizumab 1-mL and 2-mL 
PFSs. Pharmacy Preparation Instructions for the PFSs are part of the Study Materials provided to 
sites. All PCs (including malfunction, use error, and inadequate labeling) will be reported to the 
sponsor per instructions provided (see Section 8.3). 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 interventions received and that 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 interventions 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 separately.  In some cases, sites may destroy the material if, during the investigative 
site selection, the evaluator has verified and documented that the site has appropriate facilities 
and written procedures to dispose of clinical materials. 
Samples of the specific batches of mirikizumab used in the study will be retained. Details will be 
provided separately. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding  
This is a participant-blind, randomized study. Potential bias will be reduced by central weight 
stratification, randomization, and blinding. The site will contact the IWRS prior to the start of 
study intervention administration for each participant.  
All participants will be centrally randomized to mirikizumab solution formulation with weight 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. 
Study intervention will be dispensed at the study visits summarized in the SoA (Section 1.3).  
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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 injection 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.  
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 300 mg is considered an overdose. 
In the event of an overdose, the investigator should: 
 contact the medical monitor immediately, and 
 closely monitor the participant for any AE or SAE and laboratory abnormalities 
until mirikizumab no longer has a clinical effect or can no longer be detected 
systemically (at least 84 days postdose [Day 85]). 
6.8. 
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, hormone-replacement therapy, 
and thyroid replacement. In addition, occasional acetaminophen is acceptable at the discretion of 
the investigator. However, acetaminophen should not be administered on the dosing day within 
4 hours prior to and 4 hours after dosing. If acetaminophen (or paracetamol) treatment is needed 
for pain management, the maximal allowed dose will be 3 g per 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. 
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. 
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: 
 reason for use, 
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 dates of administration including start and end dates, and 
 dosage information including dose and frequency for concomitant therapy of 
special interest. 
The Lilly CP, CRP, or designee should be contacted if there are any questions regarding 
concomitant or prior therapy. 
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 CP, CRP, or 
designee. 
 
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7. 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal  
Discontinuation of specific sites or the study as a whole is handled as part of Appendix 1 
(Section 10.1). 
7.1. 
Discontinuation of Study Intervention  
This section is not applicable for this single-dose study. 
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, 
 at the request of the participant’s designee (for example, parents or legal 
guardian), 
 at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons, 
 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, or 
 if the participant, for any reason, requires treatment with a therapeutic agent that 
is prohibited by the protocol and has been demonstrated to be effective for 
treatment of the study indication. In this case, discontinuation from the study 
occurs prior to introduction of the new agent. 
At the time of discontinuing from the study, if possible, the participant will complete procedures 
for an ED visit, as shown in the SoA (Section 1.3).  
If the participant withdraws consent for disclosure of future information, the sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. If a participant 
withdraws from the study, the participant may request destruction of any samples taken and not 
tested, and the investigator must document this in the site study records. 
7.3. 
Lost to Follow-up  
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. Site personnel or designee are 
expected to make diligent attempts to contact participants who fail to return for a scheduled visit 
or are 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 (Section 1.3).  
Immediate safety concerns should be discussed with the sponsor or designee immediately on 
occurrence or awareness to determine if the participant should continue or discontinue the study. 
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.The specifications in this protocol for the timings of safety and sample collection are 
given as targets to be achieved within reasonable limits. Modifications may be made to the time 
points based on emerging clinical information. The scheduled time points may be subject to 
minor alterations; however, the actual time must be correctly recorded in the CRF. Failure or 
being late (that is, outside stipulated time allowances) to perform procedures or obtain samples 
due to legitimate clinical issues (such as equipment technical problems, venous access difficulty, 
or participant defaulting or turning up late on an agreed scheduled procedure) will not be 
considered as protocol deviations but the CRU will still be required to notify the sponsor in 
writing via a file note. 
Appendix 2 (Section 10.2) lists the laboratory tests that will be performed for this study. 
Appendix 2 (Section 10.2.1) provides a summary of the maximum number and volume of 
invasive samples, for all sampling, during the study. 
Unless otherwise stated in subsections below, all samples collected for specified laboratory tests 
will be destroyed within 60 days of receipt of confirmed test results. Certain samples may be 
retained for a longer period, if necessary, to comply with applicable laws, regulations, or 
laboratory certification standards. 
8.1. 
Efficacy Assessments  
Efficacy is not evaluated in this study. 
8.2. 
Safety Assessments  
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
8.2.1. 
Physical Examinations  
Physical examinations and routine medical assessments will be conducted as specified in the 
SoA (Section 1.3) and as clinically indicated.  
A complete physical examination will include, at a minimum, assessments of the cardiovascular, 
respiratory, gastrointestinal, neurological systems, and dermal and ear, nose, and throat 
examination. Height, weight, and BMI will also be measured and recorded at screening. Weight 
will be measured and recorded on Day -1, and Day 85 or ED. 
A symptom-directed physical examination will be performed at Day 85 or ED, as specified in the 
SoA and as deemed necessary by the investigator. 
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8.2.2. 
Vital Signs  
For each participant, vital signs and body temperature measurements should be conducted 
according to the SoA (Section 1.3). 
Blood pressure and pulse rate should be measured after at least 5 minutes sitting.  
8.2.3. 
Electrocardiograms  
For each participant, a single 12-lead digital ECG will be collected using an ECG 
machine that automatically calculates the heart rate and measures PR, QRS, and QT 
intervals, according to the SoA (Section 1.3). 
ECGs must be recorded before collecting any blood samples. Participants must be supine 
for approximately 5 to 10 minutes before ECG collection and remain supine but awake 
during ECG collection. ECGs may be obtained at additional times, when deemed 
clinically necessary. All ECGs recorded should be stored at the investigational site. 
ECGs will be interpreted by an investigator or qualified designee as soon after the time of 
ECG collection as possible, and ideally while the participant is still present, to determine 
whether the participant meets entry criteria at the relevant visits and for immediate 
participant management, should any clinically relevant findings be identified.    
If a clinically significant finding is identified (including, but not limited to, changes in 
QT/corrected QT interval from baseline) after enrollment, the investigator will determine 
if the participant can continue in the study. The investigator, or qualified designee, is 
responsible for determining if any change in participant management is needed, and must 
document his or her review of the ECG printed at the time of collection. Any new 
clinically relevant finding should be reported as an AE. 
8.2.4. 
Clinical Safety Laboratory Tests  
See Appendix 2 (Section 10.2) for the list of clinical laboratory tests to be performed and 
the SoA (Section 1.3) 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. 
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 or baseline within a period of time judged 
reasonable by the investigator, the etiology should be identified and the sponsor or 
designee notified. 
All protocol-required laboratory assessments, as defined in Appendix 2 (Section 10.2), 
must be conducted in accordance with the SoA (Section 1.3), standard collection 
requirements, and laboratory manual. 
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If laboratory values from non-protocol specified laboratory assessments performed at an 
investigator-designated local laboratory require a change in participant management or 
are considered clinically significant by the investigator (for example, SAE, AE or dose 
modification), then the information will be reported as an AE. 
8.2.5. 
Pregnancy Testing  
Pregnancy testing will be performed for all female participants at the time points detailed in the 
SoA (Section 1.3). Serum pregnancy testing will be performed at screening and Day -1. Urine 
pregnancy testing will be performed at Day 85 or ED if necessary. See Section 8.3.2 for more 
detail. 
8.2.6. 
Safety Monitoring  
The Lilly CP or CRP will monitor safety data throughout the course of the study. 
Lilly will review SAEs within time frames mandated by company procedures. The Lilly CP or 
CRP will periodically review: 
 trends in safety data, 
 laboratory analytes, and 
 AEs and PCs.  
When appropriate, the Lilly CP or CRP will consult with the functionally independent Global 
Patient Safety therapeutic area physician or clinical research scientist. 
8.2.6.1. 
Hepatic Safety  
Close hepatic monitoring 
Laboratory tests (Appendix 6; Section 10.6), including ALT, AST, ALP, TBL, direct bilirubin, 
gamma-glutamyl transferase, and creatine kinase, should be repeated within 48 to 72 hours to 
confirm the abnormality and to determine if it is increasing or decreasing if one or more of these 
conditions occur: 
If a participant with baseline results of...  develops the following elevations: 
ALT or AST <1.5× ULN 
ALT or AST ≥3× ULN 
ALP <1.5× ULN 
ALP ≥2× ULN 
TBL <1.5× ULN 
TBL ≥2× ULN (except for participants with Gilbert’s syndrome) 
ALT or AST ≥1.5× ULN 
ALT or AST ≥2× baseline 
ALP ≥1.5× ULN 
ALP ≥2× baseline 
TBL ≥1.5× ULN 
TBL ≥1.5× baseline (except for participants with Gilbert’s 
syndrome) 
Abbreviations: ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; 
TBL = total bilirubin; ULN = upper limit of normal.  
If the abnormality persists or worsens, clinical and laboratory monitoring and 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 a physical 
examination and a thorough medical history, including symptoms, recent illnesses (for example, 
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heart failure, systemic infection, hypotension, or seizures), recent travel, history of concomitant 
medications (including over-the-counter), herbal and dietary supplements, history of alcohol 
drinking and other substance abuse.  
Initially, monitoring of symptoms and hepatic biochemical tests should be done at a frequency of 
1 to 3 times weekly, based on the participant’s clinical condition and hepatic biochemical tests. 
Subsequently, the frequency of monitoring may be lowered to once every 1 to 2 weeks, if the 
participant’s clinical condition and laboratory results stabilize. Monitoring of ALT, AST, ALP, 
and TBL should continue until levels normalize or return to approximate baseline levels. 
Comprehensive hepatic evaluation 
A comprehensive evaluation should be performed to search for possible causes of liver injury if 
one or more of these conditions occur: 
If a participant with baseline results of...  develops the following elevations: 
ALT or AST <1.5× ULN 
ALT or AST ≥3× ULN with hepatic signs/symptomsa, or  
ALT or AST ≥5× ULN 
ALP <1.5× ULN 
ALP ≥3× ULN 
TBL <1.5× ULN 
TBL ≥2× ULN (except for participants with Gilbert’s syndrome) 
ALT or AST ≥1.5× ULN 
ALT or AST ≥2× baseline with hepatic signs/symptomsa, or 
ALT or AST ≥3× baseline 
ALP ≥1.5× ULN 
ALP ≥2× baseline 
TBL ≥1.5× ULN 
TBL ≥2× baseline (except for participants with Gilbert’s syndrome)  
Abbreviations: ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; 
TBL = total bilirubin; ULN = upper limit of normal.  
a Hepatic signs or symptoms are severe fatigue, nausea, vomiting, right upper quadrant abdominal pain, fever, rash, 
or eosinophilia greater than 5%. 
At a minimum, this evaluation should include a physical examination and a thorough medical 
history, as outlined above, as well as tests for prothrombin time-international normalized ratio; 
tests for viral hepatitis A, B, C, or E; tests for autoimmune hepatitis; and an abdominal imaging 
study (for example, ultrasound or computerized 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.  
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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, 
 magnetic resonance cholangiopancreatography,  
 endoscopic retrograde cholangiopancreatography, 
 cardiac echocardiogram, or  
 a liver biopsy. 
Additional hepatic data collection (hepatic safety CRF) in study participants who have 
abnormal liver tests during the study  
Additional hepatic safety data collection in the hepatic safety CRF should be performed in study 
participants who meet 1 or more of the following 4 conditions: 
1. Elevation of serum ALT to greater than or equal to 5× ULN on 2 or more consecutive 
blood tests (if baseline ALT is less than 1.5× ULN) 
➢ In participants with baseline ALT greater than or equal to 1.5× ULN, the 
threshold is ALT greater than or equal to 3× baseline on 2 or more consecutive 
tests 
2. Elevated TBL to greater than or equal to 2× ULN (if baseline TBL is less than 1.5x ULN) 
(except for cases of known Gilbert’s syndrome) 
➢ In participants with baseline TBL greater than or equal to 1.5x ULN, the threshold 
should be TBL greater than or equal to 2× baseline 
3. Elevation of serum ALP to greater than or equal to 2× ULN on 2 or more consecutive 
blood tests (if baseline ALP is less than 1.5× ULN) 
➢ In participants with baseline ALP greater than or equal to 1.5× ULN, the threshold 
is ALP greater than or equal to 2× baseline on 2 or more consecutive blood tests 
4. Hepatic event considered to be an SAE. 
Note: the interval between the 2 consecutive blood tests should be at least 2 days. 
8.2.6.2. 
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 Appendix 2 (Section 10.2.2). Laboratory results are provided to the 
sponsor via the central laboratory. 
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8.2.7. 
Tuberculosis Testing and Monitoring  
Participants will be tested as indicated in the SoA (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. 
8.2.8. 
Other Tests  
8.2.8.1. 
Injection-Site Reactions  
Although there will be no prospective collection of ISR information, spontaneously reported 
ISRs by the participant will be recorded as AEs. 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. 
The ISR CRF is used to collect supplemental data on the following specific findings:  
 erythema,  
 induration,  
 pain,  
 pruritus, and  
 edema.   
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. 
8.2.8.2. 
Bleeding and Bruising Assessment  
There will be no prospective collection of ISR information; the presence of visible bleeding or 
bruising at the injection site will be recorded on the CRF 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 the following events can be found in Appendix 3 (Section 10.3): 
 AEs, 
 SAEs, and 
 PCs. 
These events will be reported by the participant (or, when appropriate, by a caregiver, surrogate, 
or the participant's legally authorized representative). 
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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 mirikizumab study (see Section 7). 
Investigators are responsible for monitoring the safety of participants who have entered this 
study and for alerting Lilly or its designee to any event that seems unusual, even if this event 
may be considered an unanticipated benefit to the participant.  
The investigator is responsible for the appropriate medical care of participants during the study. 
Care will be taken not to introduce bias when detecting events. Open-ended and non-leading 
verbal questioning of the participant is the preferred method to inquire about event occurrences. 
After the initial report, the investigator is required to proactively follow each participant at 
subsequent visits or contacts. All SAEs and AESIs (as defined in Section 8.3.3) will be followed 
until resolution, stabilization, the event is otherwise explained, or the participant is lost to 
follow-up (as defined in Section 7.3). For PCs, the investigator is responsible for ensuring that 
follow-up includes any supplemental investigations as indicated to elucidate the nature and or 
causality, or both. Further information on follow-up procedures is provided in 
Appendix 3 (Section 10.3.4). 
8.3.1. 
Timing and Mechanism for Collecting Events  
Table AMBY.3 describes the timing, deadlines, and mechanism for collecting events. 
Table AMBY.3. 
Timing 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 informed 
consent form 
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 informed 
consent form 
start of 
intervention 
Within 24 hours of 
awareness 
SAE paper form 
SAE paper 
form 
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Event 
Collection 
Start 
Collection 
Stop 
Timing for Reporting 
to Sponsor or 
Designee 
Mechanism for 
Reporting 
Back-up 
Method of 
Reporting 
SAE and SAE 
updates – after 
start of study 
intervention 
start of 
intervention 
participation 
in study has 
ended 
Within 24 hours of 
awareness 
SAE paper form 
SAE paper 
form 
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 
Pregnancy 
Pregnancy in 
female 
participants and 
female partners 
of male 
participants 
After the 
start of study 
intervention 
Day 85 
(±3 days) or 
upon ED 
 
Within 24 hours of 
awareness (see 
Section 8.3.2) 
Pregnancy paper 
form 
Pregnancy 
paper form 
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 
 
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Abbreviations: AE = adverse event; CRF = case report form; ED = early discontinuation; N/A = not applicable; 
PC = product complaint; SAE = serious adverse event. 
* SAEs should not be reported unless the investigator deems them to be possibly related to study treatment or study 
participation. 
8.3.2. 
Pregnancy  
Collection of pregnancy information 
Male participants with partners who become pregnant 
The investigator will attempt to collect pregnancy information on any male participant’s female 
partner who becomes pregnant while the male participant is in this study. This applies only to 
male participants who receive mirikizumab. 
After learning of a pregnancy in the female partner of a study participant, the investigator will 
attempt to: 
 obtain consent to release information from the pregnant female partner directly, and 
 within 24 hours after obtaining this consent will record pregnancy information on the 
appropriate form and submit it to the sponsor.  
The female partner will also be followed to determine the outcome of the pregnancy. Information 
on the status of the mother and child will be forwarded to the sponsor. Generally, the follow-up 
will be no longer than 6 to 8 weeks following 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. 
Female participants who become pregnant 
The investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study. The initial information will be recorded on the 
appropriate form and submitted to the sponsor within 24 hours of learning of a participant's 
pregnancy.  
The participant will be followed to determine the outcome of the pregnancy. The investigator 
will collect follow-up information on the participant and the neonate and the information will be 
forwarded to the sponsor. Generally, follow-up will not be required for longer than 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 less than 20 weeks gestational age) or stillbirth (occurring 
at equal to or more than 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, he or 
she may learn of an SAE through spontaneous reporting. 
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Any female participant who becomes pregnant while participating in the study may be 
withdrawn from the study. If the participant is discontinued from the study, the standard 
discontinuation process should be followed, and the participant should continue directly to the 
ED visit. The follow-up on the pregnancy outcome should continue independent of intervention 
or study discontinuation.   
8.3.3. Adverse Events of Special Interest  
AESIs for this program include: 
 hepatic safety, 
 infections, including opportunistic and serious infections, 
 hypersensitivity reactions, 
 ISRs, 
 cerebro-cardiovascular events, 
 malignancies, and 
 suicidal ideation or behavior and depression. 
If any of these AESIs are reported, sites will be prompted to collect additional details and data. A 
PK, immunogenicity, and hypersensitivity cytokine panel (Appendix 2; Section 10.2.2) will be 
collected when possible for any participant who experiences an AE of hypersensitivity reaction 
during the study. 
8.4. 
Pharmacokinetics  
At the visits and times specified in the SoA (Section 1.3), venous blood samples of 
approximately 3 mL each will be collected to determine the serum concentrations of 
mirikizumab. A maximum of 3 samples may be collected at additional time points during 
the study if warranted and agreed on between both the investigator and sponsor. 
Instructions for the collection and handling of blood samples will be provided by the 
sponsor. The actual date and time (24-hour clock time) of each sampling will be 
recorded. 
8.4.1. 
Bioanalysis  
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 enzyme-linked immunosorbent 
assay method. 
Bioanalytical samples collected to measure mirikizumab concentrations will be retained for a 
maximum of 1 year following the last participant visit for the study. During this time, samples 
remaining after the bioanalyses may be used for exploratory analyses such as metabolism work, 
protein binding, bioanalytical method cross-validation, or all. 
8.5. 
Pharmacodynamics  
Pharmacodynamic parameters are not evaluated in this study. 
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8.6. 
Genetics  
A blood sample for DNA isolation will be collected from participants.  
See Appendix 5 (Section 10.5) for information regarding genetic research. 
8.7. 
Biomarkers  
Biomarkers are not evaluated in this study. 
8.8. 
Immunogenicity Assessments  
At the visits and times specified in the SoA (Section 1.3), venous blood samples of 
approximately 10 mL each will be collected to determine antibody production against 
mirikizumab. To interpret the results of immunogenicity, venous blood samples will be collected 
at the same time points to determine the serum concentrations of mirikizumab. Instructions for 
the collection and handling of blood samples will be provided by the sponsor. The actual date 
and time (24-hour clock time) of each sampling will be recorded. 
TE-ADAs are defined in Section 9.3.4.1. 
Immunogenicity will be assessed using a validated assay designed to detect ADAs in the 
presence of mirikizumab at a laboratory approved by the sponsor. Antibodies may be evaluated 
for their ability to neutralize the activity of mirikizumab. 
Samples will be retained for a maximum of 15 years after the last participant visit, or for a 
shorter period if local regulations and IRBs allow, at a facility selected by the sponsor. The 
duration allows the sponsor to respond to future regulatory requests related to mirikizumab. Any 
samples remaining after 15 years will be destroyed. 
8.9. 
Health Economics OR Medical Resource Utilization and Health 
Economics  
This section is not applicable for this study.  
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9. 
Statistical Considerations  
The SAP 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. 
9.1. 
Statistical Hypotheses  
The primary objective of this study is to evaluate bioequivalence of the mirikizumab citrate-free 
solution formulation compared to the mirikizumab solution formulation, administered using a 
1-mL and 2-mL PFS.  
9.2. 
Analyses Sets  
For the purposes of analysis, the following analysis sets are defined: 
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. 
Participants may be excluded from the PK analysis set in the event of: 
 a device malfunction, 
 administration of only 1 of the 2 PFS doses, or 
 administration of an incorrect dose, incomplete dose, or incorrect use of procedure 
instructions. 
9.2.1. 
Study Participant Disposition  
A detailed description of participant disposition will be provided at the end of the study. 
9.2.2. 
Study Participant Characteristics   
The participants’ age, sex, weight, height, BMI, race, and other demographic characteristics will 
be recorded and summarized using descriptive statistics.  
9.3. 
Statistical Analyses  
9.3.1. General Considerations  
Statistical analysis of this study will be the responsibility of the sponsor or its designee. 
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PK analyses will be conducted for the PK analysis set according to the actual mirikizumab 
formulation. Safety analyses will be conducted for the safety analysis set.  
Additional exploratory analyses of the data will be conducted as deemed appropriate. Study 
results may be pooled with the results of other studies for safety and population PK analysis 
purposes. 
Handling of missing, unused, and spurious data is addressed prospectively in the overall 
statistical methods described in the protocol and in the SAP, where appropriate. Adjustments to 
the planned analyses will be described in the final clinical study report. 
9.3.2. 
Primary Endpoint Analysis  
PK 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 t1/2, CL/F, and Vz/F, may be reported. 
9.3.2.1. 
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 solution formulation, injection 
location, and weight category stratification as fixed effects. The solution formulation 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 solution formulations and then 
between the 3 injection locations. 
The 2 solution formulations will be considered bioequivalent if the 90% CIs of the ratio of 
geometric least squares means fall within 0.8 to 1.25.  
In addition, the tmax of mirikizumab between the solution formulations will be analyzed using a 
Wilcoxon rank sum test. Estimates of the median difference, 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. 
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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, will be listed, and 
summarized using standard descriptive statistics. Additional analysis will be performed if 
warranted upon review of the data. 
9.3.4. 
Exploratory Analysis  
9.3.4.1. 
Evaluation of Immunogenicity  
The frequency and percentage of participants with preexisting ADAs and with TE-ADA may be 
tabulated. TE-ADAs are defined as those with a titer 2-fold (1 dilution) or greater than the 
minimum required dilution if no ADAs are detected at baseline (treatment-induced ADA) or 
those with a 4-fold or greater (2 dilutions) increase in titer compared to baseline if ADAs are 
detected at baseline (treatment-boosted ADA). For the TE-ADA+ participants, the distribution of 
maximum titers may be described. The frequency of neutralizing antibodies may also be 
tabulated in TE-ADA+ participants. 
The relationship between the presence of antibodies to mirikizumab and the PK parameters and 
pharmacodynamic response including safety and efficacy may be assessed. 
9.3.4.2. 
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 SAP. 
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 440 (approximately 220 participants in the mirikizumab solution [reference] 
group and approximately 220 participants in the mirikizumab citrate-free solution [test] group) 
participants may be enrolled. This is to ensure that approximately 368 participants 
(184 participants in the mirikizumab solution [reference] group and 184 participants in the 
mirikizumab citrate-free solution [test] group) complete the study for the primary analysis.  
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Within each weight category, participants will be assigned to an SC injection site of either the 
arm, thigh, or abdomen (approximately 73 participants per injection site for the reference and test 
arms).  
A sample size of 184 participants per treatment group will provide approximately 90% power 
that the 90% CI of the geometric mean ratio of Cmax and AUC between groups will fall within 
the equivalence range of 0.8 to 1.25. This sample size calculation was based on the assumptions 
that the PK parameters have log-normal distribution, the %CV of Cmax and AUC are 
approximately 44% (based on the PFS arm of Study AMBX), the expected ratio of geometric 
means is 0.91 (based on the results of Study I6T-MC-AMBV), and the %CV is the same for 
participants from each treatment group. 
 
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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, 
 ISO 14155, 
 applicable ICH GCP guidelines, and 
 applicable laws and regulations. 
The protocol, protocol amendments, ICF, IB, and other relevant documents (for example, 
advertisements) must be submitted to an IRB by the investigator and reviewed and approved by 
the IRB before the study is initiated. 
Any amendments to the protocol will require IRB 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 annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB, 
 notifying the IRB of SAEs or other significant safety findings as required by IRB 
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, 
European regulation 536/2014 for clinical studies (if applicable), and all other applicable 
local regulations, and 
 reporting to the sponsor or designee significant issues related to participant safety, 
participant rights, or data integrity. 
Investigator sites are compensated for participation in the study as detailed in the clinical trial 
agreement. 
10.1.2. 
Financial Disclosure  
Investigators and sub-investigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
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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 participant or the participant’s legally authorized 
representative and answer all questions regarding the study. 
Participants must be informed that their participation is voluntary. Participants or their legally 
authorized representatives 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 or study center. 
The medical record must include a statement that written informed consent was obtained before 
the participant was entered into the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF. 
Participants must be reconsented to the most current version of the ICF(s) during their 
participation in the study. 
A copy of the ICF(s) must be provided to the participant or the participant’s legally authorized 
representative and is kept on file. 
10.1.4. 
Data Protection  
Participants will be assigned a unique identifier by the sponsor. Any participant records, datasets, 
or tissue samples that are transferred to the sponsor will contain the identifier only; participant 
names or any information which would make the participant identifiable will not be transferred. 
The participant must be informed that the participant’s personal study-related data will be used 
by the sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant who will be required to give consent for their data to be used as 
described in the informed consent.  
The participant must be informed that their medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB members, and by inspectors from regulatory authorities. 
The sponsor has processes in place to ensure data protection, information security, and data 
integrity. These processes include appropriate contingency plan(s) for appropriate and timely 
response in the event of a data security breach. 
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 study due to safety findings, this 
decision will be communicated by Lilly to all investigators (for example, by phone or email) as 
soon as possible. It will be a requirement that investigators respond upon receipt to confirm that 
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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 data set 
would result in analyses lacking scientific rigor (for example, underpowered) or compromise the 
integrity of the overall analyses (for example, trial not yet unblinded), the summary of results 
will be submitted within 1 year after the end of the study globally or as soon as available, 
whichever is earlier. 
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. 
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. 
Source data may include laboratory tests, medical records, and clinical notes.  
The investigator must permit study-related monitoring, audits, IRB review, and regulatory 
agency inspections and provide direct access to source documents. 
Monitoring details describing strategy (for example, risk-based initiatives in operations and 
quality such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities, and requirements, including handling of noncompliance issues and 
monitoring techniques are provided in the Monitoring Plan. 
The sponsor or designee is responsible for the data management of this study including quality 
checking of the data. 
The sponsor assumes accountability for actions delegated to other individuals (for example, 
contract research organizations). 
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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, regulatory agencies, or all, 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 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 system(s) will be stored at third parties. The 
investigator will have continuous access to the data during the study and until decommissioning 
of the data capture 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 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. 
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 transcribed from source documents must be 
consistent with the source documents or the discrepancies must be explained. The investigator 
may need to request previous medical records or transfer records, depending on the study. Also, 
current medical records must be available. 
Definition of what constitutes source data can be found in Section 10.1.6. 
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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: 
o discontinuation of further study intervention development. 
 for site termination: 
o failure of the investigator to comply with the protocol, the requirements of the 
IRB 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, and 
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 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, follow-up, or both. 
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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10.2. 
Appendix 2: Clinical Laboratory Tests  
The tests detailed in the table below will be performed by the central laboratory or by the local 
laboratory, as detailed in the table below. 
In circumstances where the sponsor approves local laboratory testing in lieu of central laboratory 
testing (in the table below), the local laboratory must be qualified in accordance with applicable 
local regulations. 
Protocol-specific requirements for inclusion or exclusion of participants are detailed in Section 5 
of the protocol. 
Additional tests may be performed at any time during the study as determined necessary by the 
investigator or required by local regulations. 
Pregnancy testing will be conducted as detailed in the SoA (Section 1.3). 
Investigators must document their review of the laboratory safety results. 
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Safety Laboratory Testsa 
Hematology 
Clinical Chemistry 
Hematocrit 
Sodium 
Hemoglobin 
Potassium 
Erythrocyte count (RBC) 
Calcium 
Mean cell volume  
Phosphorous 
Mean cell hemoglobin  
Glucose (random) 
Mean cell hemoglobin concentration  
Blood urea nitrogen 
Leukocytes (WBC)  
Uric acid 
 
Total cholesterol 
Cell morphology 
Total protein 
Absolute counts and/or % of: 
Albumin 
Neutrophils 
Total bilirubin 
Lymphocytes 
Direct bilirubin 
Monocytes 
Alkaline phosphatase 
Eosinophils 
Aspartate aminotransferase 
Basophils 
Alanine aminotransferase 
Platelets 
Creatinine 
 
 
Urinalysis 
 
Specific gravity 
 
pH 
 
Protein 
Other Tests 
Glucose 
Ethanol testingc 
Ketones 
Urine drug screenc 
Bilirubin 
Pregnancy test (females only)d 
Urobilinogen 
Leukocytes 
FSH (females only, as applicable)b 
Blood 
QuantiFERON®-TB Goldb 
Nitrite 
 
Microscopy (if dipstick abnormal; blood, protein, 
nitrites, or leukocyte esterase is positive) 
 
 
 
Serology 
 
Hepatitis B surface antigenb 
 
Hepatitis B DNAb 
 
Hepatitis C antibodyb 
 
HIVb 
 
Abbreviations: FSH = follicle-stimulating hormone; HIV = human immunodeficiency virus; RBC = red blood cell; 
TB = tuberculosis; WBC = white blood cell. 
Note: Results of these assays will be validated by the local or central laboratory at the time of testing. Additional 
tests may be performed or auto-calculated by the laboratory as part of its standard panel that cannot be removed. 
Some of the above parameters are calculated from measured values. Omission of calculated values will not be 
considered as a protocol violation. 
a Performed locally at screening and Day -1 and centrally at Day 1 predose and all postdose time points unless 
otherwise stated. 
b Performed at screening only. 
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c Urine drug screen and ethanol tests may be repeated locally at additional time points at the discretion of the 
investigator. 
d Serum pregnancy test to be performed at screening and Day -1. Urine pregnancy test to be performed locally at 
Day 85 or early discontinuation. 
 
 
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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. 
Protocol I6T-MC-AMBY Sampling Summary 
 
Purpose 
Blood Volume per 
Sample (mL) 
Number of Blood 
Samples 
Total Volume 
(mL) 
Screening testsa 
45 
1 
45 
Local clinical laboratory tests and 
pregnancy testsa 
12 
1 
12 
Central clinical laboratory testsa 
4.5 
5 
22.5 
Pharmacokinetics  
3 
15b 
45 
Immunogenicity 
10 
4 
40 
Pharmacogenetics 
10 
1 
10 
Total 
174.5 
Total for clinical purposes 
180 
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 test 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 Test a 
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) ADA 
mirikizumab (LY3074828) concentration 
Abbreviations: ADA = antidrug antibodies; IL = interleukin. 
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 ISO 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 Adverse Event  
Adverse Event Definition 
 An AE is any untoward medical occurrence in a participant administered a 
pharmaceutical product and that does not necessarily have a causal relationship with the 
study intervention. An AE can therefore be any unfavourable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a medicinal (investigational) product, whether or 
not related to the medicinal (investigational) product. 
 An AE is any untoward medical occurrence, unintended disease or injury, or untoward 
clinical signs (including abnormal laboratory findings) in study participants, users, or 
other persons, whether or not related to the investigational medical device. This 
definition includes events related to the investigational medical device or comparator 
and events related to the procedures involved except for events in users or other 
persons, which only include events related to investigational devices. 
Events Meeting the Adverse Event Definition 
 Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (for example, ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, are 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, intensity of the condition, or both. 
 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. 
 
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Events NOT Meeting the Adverse Event Definition 
 Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
 The disease 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. 
 Medical or surgical procedure (for example, endoscopy, appendectomy): the condition 
that leads to the procedure is the AE. 
 Situations in which an untoward medical occurrence did not occur (social, convenience 
admission to a hospital, or both). 
 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 Serious Adverse Event  
An SAE is defined as any untoward medical occurrence that, at any dose, meets one or 
more of the criteria listed: 
a. Results in death 
b. Is life-threatening 
The term life-threatening in the definition of serious refers to an event in which the participant 
was at risk of death at the time of the event. It does not refer to an event, which hypothetically 
might have caused death, if it were more severe. 
c. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
 In general, hospitalization signifies that the participant has been admitted to 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. 
 Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from baseline is not considered an AE. 
d. Results in persistent disability or incapacity 
 The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
 This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, 
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and accidental trauma (for example, sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 
e. 
Is a congenital anomaly or birth defect 
 Abnormal pregnancy outcomes (for example, spontaneous abortion, fetal death, 
stillbirth, congenital anomalies, ectopic pregnancy) are considered SAEs. 
f. 
Other situations: 
 Medical or scientific judgment should be exercised 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. 
 
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.  
g. 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: 
o Deficiencies in labeling information, and 
o Use errors for device or drug-device combination products due to ergonomic 
design elements of the product. 
 PCs related to study interventions used in clinical trials are collected to ensure the 
safety of participants, monitor quality, and to facilitate process and product 
improvements. 
 Investigators will instruct participants to contact the site as soon as possible if he or she 
has a PC or problem with the study intervention so that the situation can be assessed. 
 An event may meet the definition of both a PC and an AE or SAE. In such cases, it 
should be reported as both a PC and as an AE or SAE. 
 
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10.3.4. 
Recording and Follow-Up of Adverse Event, Serious Adverse Events, and 
Product Complaints  
AE, SAE, and Product Complaint Recording 
 When an AE, SAE, or 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, or PC information in the 
participant’s medical records, in accordance with the investigator’s normal clinical 
practice. AE or 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 or SAE. In such 
cases, it should be reported as both a PC and as an AE or SAE. 
 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 or 
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 or 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, 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. 
 
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Assessment of Causality 
 The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE or SAE. The investigator will use clinical judgment to 
determine the relationship. 
 A “reasonable possibility” of a relationship conveys that there are facts, evidence, and 
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, Product Information, or both for marketed 
products, in their assessment. 
 For each AE or SAE, the investigator must document in the medical notes that he or 
she has reviewed the AE or SAE and has provided an assessment of causality. 
 There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor or designee. 
However, it is very important that the investigator always make an assessment of 
causality for every event before the initial transmission of the SAE data to the sponsor 
or designee. 
 The investigator may change 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 Adverse Events and Serious Adverse Events 
 The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and evaluations as medically indicated or as requested by the sponsor or 
designee to elucidate the nature, causality, or both 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 
post-mortem findings including histopathology. 
10.3.5. 
Reporting of Serious Adverse Events  
Serious Adverse Event Reporting via SAE Report 
 Facsimile transmission of the SAE Report is the preferred method to transmit this 
information to the sponsor or designee.  
 Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE Report within the designated reporting time frames.  
 Contacts for SAE reporting can be found in the SAE Report. 
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10.3.6. 
Regulatory Reporting Requirements  
Serious Adverse Event Regulatory Reporting 
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
study intervention under clinical investigation are met. 
 The sponsor has a legal responsibility to notify both the local regulatory 
authority and other regulatory agencies about the safety of a study intervention 
under clinical investigation. The sponsor will comply with country-specific 
regulatory requirements relating to safety reporting to the regulatory authority, 
IRB, and investigators. 
 An investigator who receives an investigator safety report describing an SAE or 
other specific safety information (for example, summary or listing of SAEs) 
from the sponsor will review and then file it along with the IB and will notify 
the IRB, if appropriate according to local requirements. 
 
 
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10.4. 
Appendix 4: Contraceptive and Barrier Guidance  
10.4.1. 
Definitions  
Women of childbearing potential 
Adult females are considered WOCBP unless they are WNOCBP. 
Women not of childbearing potential 
Females are considered WNOCBP if they: 
 have a congenital anomaly such as Müllerian agenesis,  
 are infertile due to surgical sterilization, or  
 are postmenopausal. 
Examples of surgical sterilization include total hysterectomy, bilateral salpingo-oophorectomy, 
bilateral salpingectomy, bilateral tubal ligation, bilateral tubal occlusion, or bilateral 
oophorectomy. Determination can come from the site personnel’s review of the participant’s 
medical records, medical examination, or medical history interview. 
Postmenopausal state 
The postmenopausal state is defined as a woman: 
 at any age at least 6 weeks post-surgical bilateral oophorectomy with or without 
hysterectomy, confirmed by operative note, medical history, or physical examination; or  
 aged at least 40 years and up to 55 years with an intact uterus, not on hormone therapy*, 
who has had cessation of menses for at least 12 consecutive months without an 
alternative medical cause, AND with a follicle-stimulating hormone greater than 
40 mIU/mL; or  
 55 years or older not on hormone therapy, who has had at least 12 months of spontaneous 
amenorrhea, or 
 aged at least 55 years with a diagnosis of menopause prior to starting hormone 
replacement therapy. 
*Women should not be taking medications during amenorrhea such as oral contraceptives, 
hormones, gonadotropin-releasing hormone, anti-estrogens, selective estrogen receptor 
modulators, or chemotherapy that could induce transient amenorrhea. 
10.4.2. 
Contraception Guidance  
Male Participants 
No male contraception is required except in compliance with specific local government study 
requirements. 
Female Participants 
Women not of childbearing potential 
WNOCBP are not required to use contraception. 
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Women of childbearing potential 
WOCBP who are completely abstinent as their preferred and usual lifestyle, or in a same-sex 
relationship as their preferred and usual lifestyle: 
Must… 
Must not… 
agree to either 
remain abstinent or 
stay in a same-sex 
relationship without 
sexual relationships 
with males 
 use periodic abstinence methods 
o calendar  
o ovulation  
o symptothermal, or 
o post-ovulation  
 declare abstinence just for the duration of a trial, or 
 use the withdrawal method 
 
WOCBP who are NOT completely abstinent as their preferred and usual lifestyle, or NOT in a 
same-sex relationship as their preferred and usual lifestyle, must do the following: 
Topic 
Condition 
Contraception 
Agree to use 1 highly effective method of contraception or a combination 
of 2 effective methods of contraception. 
 
These forms of contraception must be used for the duration of the study. 
 
All females will receive pregnancy testing and must have a negative serum test result at 
screening followed by a negative serum result within 24 hours prior to treatment exposure. See 
the protocol SoA (Section 1.3) for subsequent pregnancy testing requirements. 
 
Examples of different forms of contraception:  
Methods 
Examples 
Highly effective 
contraception (less than 
1% failure rate) 
 combination oral contraceptive pill, 
 progestin-only contraceptive pill (mini-pill), 
 implanted contraceptives, 
 injectable contraceptives, 
 contraceptive patch (only women less than 198 pounds or 
90 kg), 
 total abstinence, 
 vasectomy (if only sexual partner), 
 fallopian tube implants (if confirmed by hysterosalpingogram), 
 combined contraceptive vaginal ring, or  
 intrauterine devices. 
Effective contraception 
 male or female condoms with spermicide, or  
 diaphragms with spermicide or cervical sponges 
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Note: The barrier method must include use of a spermicide (that is, 
condom with spermicide, diaphragm with spermicide, or female 
condom with spermicide) to be considered effective. Use of male and 
female condoms as a double barrier method is not considered effective. 
Ineffective forms of 
contraception whether 
used alone or in any 
combination 
 spermicide alone 
 periodic abstinence 
 fertility awareness (calendar method, temperature method, 
cervical mucus, or symptothermal) 
 withdrawal 
 postcoital douche, or 
 lactational amenorrhea 
 
 
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10.5. 
Appendix 5: Genetics  
Use or 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 molecular subtype of 
the disease being treated. Therefore, where local regulations and IRB 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 or 
assays including diagnostic tests related to mirikizumab, interventions of this drug class 
and IL-23-mediated autoimmune disease, or all. Genetic research may consist of the 
analysis of 1 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 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 or study interventions of this 
class or indication continues but no longer than 15 years or amother 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 must complete the analysis of all selected testing except 
for microbiology testing. 
Local testing may be performed in addition to central testing when necessary for immediate 
participant management. 
Results will be reported if a validated test or calculation is available. 
Hematology 
Clinical Chemistry 
Hemoglobin 
Total bilirubin 
Hematocrit 
Direct bilirubin 
Erythrocytes (RBCs - red blood cells) 
Alkaline phosphatase (ALP) 
Leukocytes (WBCs - white blood cells) 
Alanine aminotransferase (ALT) 
Differential: 
Aspartate aminotransferase (AST) 
    Neutrophils, segmented 
Gamma-glutamyl transferase (GGT) 
    Lymphocytes 
Creatine kinase (CK) 
    Monocytes 
Other Chemistry 
    Basophils 
Acetaminophen 
    Eosinophils 
Acetaminophen protein adducts 
Platelets 
Alkaline phosphatase isoenzymes 
Cell morphology (RBC and WBC) 
Ceruloplasmin 
Coagulation 
Copper 
Ethyl alcohol (EtOH) 
Prothrombin time, INR (PT-INR) 
Haptoglobin 
Serology 
Immunoglobulin IgA (quantitative) 
Hepatitis A virus (HAV) testing: 
Immunoglobulin IgG (quantitative) 
    HAV total antibody 
Immunoglobulin IgM (quantitative) 
    HAV IgM antibody 
Phosphatidylethanol (PEth) 
Hepatitis B virus (HBV) testing: 
Urine Chemistry 
    Hepatitis B surface antigen (HBsAg) 
Drug screen 
    Hepatitis B surface antibody (anti-HBs) 
Ethyl glucuronide (EtG) 
    Hepatitis B core total antibody (anti-HBc) 
Other Serology 
    Hepatitis B core IgM antibody 
Anti-nuclear antibody (ANA) 
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    Hepatitis B core IgG antibody 
Anti-smooth muscle antibody (ASMA) a 
    HBV DNA b 
Anti-actin antibody c 
Hepatitis C virus (HCV) testing: 
Epstein-Barr virus (EBV) testing: 
    HCV antibody 
    EBV antibody 
    HCV RNA b 
    EBV DNA b 
Hepatitis D virus (HDV) testing: 
Cytomegalovirus (CMV) testing: 
    HDV antibody 
    CMV antibody 
Hepatitis E virus (HEV) testing: 
    CMV DNA b 
    HEV IgG antibody 
Herpes simplex virus (HSV) testing: 
    HEV IgM antibody 
    HSV (Type 1 and 2) antibody 
    HEV RNA b 
    HSV (Type 1 and 2) DNA b 
Microbiology d 
Liver kidney microsomal type 1 (LKM-1) antibody 
Culture: 
 
    Blood 
 
    Urine 
 
Abbreviations: Ig = immunoglobulin; INR = international normalization ratio.  
a Not required if anti-actin antibody is tested. 
b Reflex or confirmation dependent on regulatory requirements, testing availability, or both. 
c Not required if anti-smooth muscle antibody is tested. 
d Assayed ONLY by investigator-designated local laboratory; no central testing available. 
 
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10.7. Appendix 7: Medical Device Adverse Events, Adverse Device Effects, 
Serious Adverse Events, and Device Deficiencies: Definition and 
Procedures for Recording, Evaluating, Follow-up, and Reporting  
Refer to Appendix 3 (Section 10.3) 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 
%CV 
percent coefficients of variation 
abuse 
Use of a study intervention for recreational purposes or to maintain an addiction or 
dependence 
ADA 
antidrug antibody 
AE 
adverse event 
AESI 
adverse event of special interest 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
AUC 
area under the concentration versus time curve 
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 
blinding 
A single-blind study is one in which the investigator, the investigator’s staff, or both are 
aware of the treatment but the participant is not, or vice versa, or when the sponsor is 
aware of the treatment but the investigator, investigator’s staff, or both and the 
participant are not. 
CD 
Crohn’s disease 
CI 
confidence interval 
CL/F 
apparent total body clearance of drug calculated after extra-vascular administration 
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. 
COVID-19 
coronavirus disease-19 
CP 
clinical pharmacologist 
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CRF 
case report form; a printed, optical, or electronic document designed to record all of the 
protocol-required information to be reported to the sponsor for each trial participant. 
CRP 
clinical research physician: Individual responsible for the medical conduct of the study.  
Responsibilities of the CRP may be performed by a physician, clinical research 
scientist, global safety physician or other medical officer. 
CRU 
clinical research unit 
device deficiencies 
Equivalent to product complaint 
ECG 
electrocardiogram 
ED 
early discontinuation 
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 
IB 
investigator’s brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IL 
interleukin 
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. 
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. 
IRB 
institutional review board 
ISO 
International Organization for Standardization 
ISR 
injection-site reaction 
IV 
intravenous 
IWRS 
interactive web-response system 
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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 5 rights, the following may also represent medication errors:  
• dose omission associated with an AE or a product complaint 
• dispensing or use of expired medication 
• use of medication past the recommended in-use date 
• dispensing or use of an improperly stored medication 
• use of an adulterated dosage form or administration technique inconsistent with the 
medication's labeling (for example, Summary of Product Characteristics, IB, local 
label, protocol), or 
• shared use of cartridges, prefilled pens, or both. 
misuse 
Use of a study intervention for self-treatment that either is inconsistent with the 
prescribed dosing regimen, indication, or both, or is obtained without a prescription 
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 
SAP 
statistical analysis plan 
SC 
subcutaneous 
screen 
The act of determining if an individual meets minimum requirements to become part of 
a pool of potential candidates for participation in a clinical study.  
SoA 
Schedule of Activities 
t1/2 
half-life associated with the terminal rate constant 
TB 
tuberculosis 
TBL 
total bilirubin 
TE-ADA 
treatment-emergent antidrug antibodies 
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. 
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tmax 
time to maximum observed drug concentration 
UC 
ulcerative colitis 
ULN 
upper limit of normal 
WNOCBP 
women not of childbearing potential 
WOCBP 
women of childbearing potential 
VAS 
visual analog scale 
Vz/F 
apparent volume of distribution during the terminal phase after extra-vascular 
administration 
 
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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. 
Amendment (a): 11 October 2022 
Overall Rationale for the Amendment: 
 
Amendment (a) corrects an error in the IND number shown on the cover page and in the 
Synopsis (Section 1). 
 
DOCUMENT HISTORY 
Document 
Date 
Amendment (a) 
11-October-2022 
Original Protocol 
21-September-2022 
 
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11. 
References  
Humira [Prescribing Information]. North Chicago, IL: AbbVie Inc; 2021. 
https://www.rxabbvie.com/pdf/humira.pdf. 
Kaiser C, Knight A, Nordström D, et al. Injection-site reactions upon Kineret (anakinra) 
administration: experiences and explanations. Rheumatol Int. 2012;32:295-299. 
https://doi.org/10.1007/s00296-011-2096-3 
Krasner A, Pohl R, Simms P, et al. A review of a family of ultra-rapid-acting insulins: 
formulation development. J Diabetes Sci Technol. 2012;6(4):786-796. 
https://doi.org/10.1177/193229681200600408  
Nash P, Vanhoof J, Hall S, et al. Randomized crossover comparison of injection site pain with 
40 mg/0.4 or 0.8 mL formulations of adalimumab in participants with rheumatoid arthritis. 
Rheumatol Ther. 2016;3:257-270. https://doi.org/10.1007/s40744-016-0041-3  
Williamson A, Hoggart B. Pain: a review of three commonly used pain rating scales. J Clin 
Nurs. 2005;14:(7)798-804. https://doi.org/10.1111/j.1365-2702.2005.01121  
 
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SAP_001.pdf: 
Statistical Analysis Plan Version 2.0 I6T-MC-AMBY
A Bioequivalence Study of Subcutaneous Injections of Mirikizumab Reference 
Solution Using Investigational 1-mL and 2-mL Prefilled Syringes and Mirikizumab 
Test Solution Formulation Using Investigational 1-mL and 2-mL Prefilled Syringes 
in Healthy Participants
NCT05644353
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STATISTICAL ANALYSIS PLAN 
A Bioequivalence Study of Subcutaneous Injections of Mirikizumab Solution using 
Investigational 1-mL and 2-mL Prefilled Syringes and Mirikizumab Citrate-free Solution 
Formulation using Investigational 1-mL and 2-mL Prefilled Syringes in Healthy 
Participants 
Statistical Analysis Plan Status: Final 
Statistical Analysis Plan Version: 2.0 
Statistical Analysis Plan Date: 05MAR2023 
Investigational Medicinal Product: Mirikizumab (LY3074828) 
Protocol Reference: I6T-MC-AMBY  
Labcorp Drug Development Study: 8499240 
Clinical Phase I 
 
 
 
 
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CONFIDENTIAL 
Labcorp Drug Development Study: 8499240  
Protocol Reference: I6T-MC-AMBY 
1. TABLE OF CONTENTS 
1. 
TABLE OF CONTENTS ................................................................................................... 2 
2. 
ABBREVIATIONS ............................................................................................................ 4 
3. 
INTRODUCTION .............................................................................................................. 6 
4. 
STUDY OBJECTIVES AND ENDPOINTS ...................................................................... 7 
5. 
STUDY DESIGN ............................................................................................................... 7 
6. 
BLINDING ......................................................................................................................... 8 
7. 
TREATMENTS .................................................................................................................. 8 
8. 
SAMPLE SIZE JUSTIFICATION ..................................................................................... 9 
9. 
DEFINITION OF ANALYSIS POPULATIONS .............................................................. 9 
10. STATISTICAL METHODOLOGY ................................................................................... 9 
10.1 General ......................................................................................................................... 9 
10.2 Demographics and Participant Disposition ............................................................... 10 
10.3 Pharmacokinetic Assessment ..................................................................................... 10 
10.3.1 Pharmacokinetic Analysis ................................................................................ 10 
10.3.2 Pharmacokinetic Statistical Methodology ........................................................ 14 
10.4 Safety and Tolerability Assessments ......................................................................... 15 
10.4.1 Adverse events ................................................................................................. 15 
10.4.2 Concomitant medication ................................................................................... 15 
10.4.3 Clinical laboratory parameters ......................................................................... 15 
10.4.4 Vital signs ......................................................................................................... 15 
10.4.5 Electrocardiogram (ECG) ................................................................................. 16 
10.4.6 Hepatic Monitoring .......................................................................................... 16 
10.4.7 Immunogenicity Assessments .......................................................................... 16 
10.4.8 Visual Analog Scale (VAS) Pain Scores .......................................................... 16 
10.4.9 Injection Site Reactions .................................................................................... 17 
10.4.10 Hypersensitivity reactions ................................................................................ 17 
10.4.11 Bleeding and Bruising Assessment .................................................................. 17 
10.4.12 Other assessments ............................................................................................. 17 
10.4.13 Safety and Tolerability Statistical Methodology .............................................. 17 
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11. INTERIM ANALYSES .................................................................................................... 17 
12. CHANGES FROM THE PROTOCOL SPECIFIED STATISTICAL ANALYSES ....... 17 
13. REFERENCES ................................................................................................................. 18 
14. DATA PRESENTATION ................................................................................................ 18 
14.1 Derived Parameters .................................................................................................... 18 
14.2 Missing Data .............................................................................................................. 18 
14.3 Insufficient Data for Presentation .............................................................................. 18 
15. APPENDICES .................................................................................................................. 19 
Appendix 1: Document History .......................................................................................... 19 
 
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Labcorp Drug Development Study: 8499240  
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2. ABBREVIATIONS  
Abbreviations pertain to the Statistical Analysis Plan (SAP) only (not the tables, figures and 
listings [TFLs]). 
%AUC(tlast-∞) 
Percentage of AUC(0-∞) extrapolated 
ADA 
Anti-drug antibody 
AE 
Adverse event 
AUC 
Area under the concentration versus time curve 
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 
BQL 
Below the quantifiable lower limit of the assay 
CI 
Confidence interval 
CL/F 
Apparent total body clearance of drug calculated after extra-vascular 
administration 
Clast 
Last quantifiable drug concentration 
Cmax 
Maximum observed drug concentration 
CRU 
Clinical Research Unit 
CSR 
Clinical Study Report 
CV 
Coefficient of variation 
DMP 
Data Management Plan 
ECG 
Electrocardiogram 
ICH 
International Conference on Harmonisation 
IWRS 
Interactive web response system 
LS 
Least square 
MedDRA 
Medical Dictionary for Regulatory Activities 
PC 
Product complaints 
PFS 
Prefilled syringe 
PK 
Pharmacokinetic 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SC 
Subcutaneous 
SD 
Standard deviation  
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SOP 
Standard Operating Procedure 
t1/2 
Half-life associated with the terminal rate constant (λz) in non-compartmental 
analysis 
TEAE 
Treatment emergent adverse event 
TFLs 
Tables, Figures, and Listings 
tmax 
Time of maximum observed drug concentration 
VAS 
Visual analog scale 
Vss/F 
Apparent volume of distribution at steady state after extravascular 
administration 
Vz/F 
Apparent volume of distribution during the terminal phase after extra-
vascular administration 
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3. INTRODUCTION  
This SAP has been developed after review of the Clinical Study Protocol (final version dated 
01 February 2023). 
This SAP describes the planned analysis of the safety, tolerability, and pharmacokinetic (PK) 
data from this study. A detailed description of the planned TFLs to be presented in the clinical 
study report (CSR) is provided in the accompanying TFL shell document. 
The intent of this document is to provide guidance for the statistical and PK analyses of data. In 
general, the analyses are based on information from the protocol, unless they have been modified 
by agreement with Eli Lilly and Company. A limited amount of information concerning this 
study (e.g., objectives, study design) is given to help the reader’s interpretation. This SAP must 
be finalized prior to first participant visit. When the SAP and TFL shells are agreed upon and 
finalized, they will serve as the template for this study’s CSR. 
This SAP supersedes the statistical considerations identified in the protocol; where 
considerations are substantially different, they will be so identified. If additional analyses are 
required to supplement the planned analyses described in this SAP, they may be performed and 
will be identified in the CSR. Any substantial deviations from this SAP will be agreed upon with 
Eli Lilly and Company and identified in the CSR. Any minor deviations from the TFLs may not 
be documented in the CSR. 
This SAP is written with consideration of the recommendations outlined in the International 
Conference on Harmonisation (ICH) E9 Guideline entitled Guidance for Industry: Statistical 
Principles for Clinical Trials1 and the ICH E3 Guideline entitled Guidance for Industry: Structure 
and Content of Clinical Study Reports2. 
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4. STUDY OBJECTIVES AND ENDPOINTS  
Objectives 
Endpoints 
Primary 
 
 To evaluate the bioequivalence of a 
single 300-mg subcutaneous (SC) 
dose of mirikizumab in a citrate-free 
solution formulation using a 1-mL 
and 2-mL prefilled syringe (PFS) 
(test) compared to the mirikizumab 
solution formulation using a 1-mL 
and 2-mL PFS (reference)  
 Maximum observed drug concentration 
(Cmax), area under the concentration 
versus time curve (AUC) from time zero 
to infinity (AUC[0-∞]), and AUC from 
time zero to time t, where t is the last 
time point with a measurable 
concentration (AUC[0-tlast]) 
Secondary 
 
 To describe the safety and 
tolerability of a single 300-mg SC 
dose of mirikizumab in a citrate-free 
solution formulation using a 1-mL 
and 2-mL PFS (test) compared to 
the mirikizumab solution 
formulation using a 1-mL and 2-mL 
PFS (reference) 
 Treatment-emergent adverse events 
(TEAEs) and serious adverse event 
(SAEs)  
Exploratory 
 
 To evaluate the effect of 
mirikizumab citrate-free solution 
formulation using a 1-mL and 2-mL 
PFS and of mirikizumab solution 
formulation using a 1-mL and 2-mL 
PFS on immunogenicity 
 To evaluate the impact of 
injection-site location (arm, thigh, or 
abdomen) on PK 
 Treatment-emergent antidrug antibody 
[TE-ADA]  
 
 
 
 
 Cmax, AUC(0-∞), and AUC(0-tlast) 
 
5. STUDY DESIGN  
Study I6T-MC-AMBY (AMBY) is a Phase 1, participant-blind, randomized, 2-arm, 
2-formulation, parallel-design, single-dose, multi-center study 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 clinical 
research unit (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 
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Participants will also be randomized in a 1:1 ratio to either mirikizumab solution (reference) or 
citrate-free solution (test) with a computer-generated allocation code using an Interactive Web 
Response Systems (IWRS). Injection site location (arm, thigh, or abdomen) will be assigned in 
an approximately equal distribution within each study arm using an IWRS. 
Approximately 440 participants will be enrolled to ensure 368 completers. Approximately 220 
participants will be randomized to the test arm and approximately 220 participants will be 
randomized to the reference arm, with approximately 73 participants for each injection site in 
each study arm. 
A minimum of approximately 70 participants in each weight category should complete the study. 
On Day 1, participants will receive 1×1-mL and 1 × 2-mL SC dose of 100 mg/mL mirikizumab 
(total dose: 300 mg mirikizumab). 
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 and immunogenicity 
sampling and safety assessments at predefined times up to approximately 12 weeks postdose. 
Participants will be monitored for safety between outpatient visits by way of telephone 
assessment.  
Safety and tolerability will be assessed through clinical laboratory tests, vital signs 
measurements, recording of AEs and product complaints (PCs), physical examination, and 
immunogenicity. 
6. BLINDING  
This is a randomized participant-blind study. Only the participants will be blinded to treatment 
assignment. 
The Labcorp biometrics and Eli Lilly study teams will be unblinded throughout the study. 
7. TREATMENTS  
The following is a list of the study treatment labels that will be used in the TFLs. 
Study Treatment Name 
Injection 
Site 
Abbreviation 
Treatment 
order in TFL 
1 × 1-mL (100 mg) and 1 × 2-mL 
(200 mg) Mirikizumab Solution SC 
PFS (Reference) 
Abdomen 
Solution PFS (Reference) (Abdomen) 
1 
Arm 
Solution PFS (Reference) (Arm) 
2 
Thigh 
Solution PFS (Reference) (Thigh) 
3 
1 × 1-mL (100 mg) and 1 × 2-mL 
(200 mg) Mirikizumab Citrate-free 
Solution SC PFS (Test) 
Abdomen 
CF Solution PFS (Test) (Abdomen)  
4 
Arm 
CF Solution PFS (Test) (Arm) 
5 
Thigh 
CF Solution PFS (Test) (Thigh) 
6 
Abbreviations: CF = citrate-free; PFS = prefilled syringe; SC = subcutaneous 
 
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8. SAMPLE SIZE JUSTIFICATION  
Approximately 410 (approximately 205 participants in the mirikizumab solution [reference] 
group and approximately 205 participants in the mirikizumab citrate-free solution [test] group) 
participants may be enrolled. This is to ensure that approximately 368 participants (184 
participants in the mirikizumab solution [reference] group and 184 participants in the 
mirikizumab citrate-free solution [test] 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 68 participants per injection site for the reference and test arms). 
A sample size of 184 participants per treatment group will provide approximately 90% power 
that the 90% confidence interval (CI) of the geometric mean ratio of Cmax and AUC between 
groups will fall within the equivalence range of 0.8 to 1.25. This sample size calculation was 
based on the assumptions that the PK parameters have log-normal distribution, the % coefficient 
of variation (CV) of Cmax and AUC are approximately 44% (based on the PFS arm of Study 
I6T-MC-AMBX), the expected ratio of geometric means is 0.91 (based on the results of Study 
I6T-MC-AMBV), and the %CV is the same for participants from each treatment group. 
9. DEFINITION OF ANALYSIS POPULATIONS  
The “Enrolled” population will consist of all participants randomly assigned to mirikizumab. 
The “Safety” population will consist of all participants who are exposed to mirikizumab. 
Participants will be analyzed according to the mirikizumab they actually received. 
The “Pharmacokinetic” population will consist of all enrolled participants who receive a dose of 
mirikizumab and have evaluable PK data. 
Participants may be excluded from the PK analysis set in the event of: 
 a device malfunction, 
 administration of only 1 of the 2 PFS doses, or 
 administration of an incorrect dose, incomplete dose or incorrect use of procedure 
instructions. 
All protocol deviations that occur during the study will be considered for their severity/impact 
and will be taken into consideration when participants are assigned to analysis populations. 
10. 
STATISTICAL METHODOLOGY  
10.1 
General  
Data listings will be provided for all data that is databased. Summary statistics and statistical 
analysis will only be presented for data where detailed in this SAP. For continuous data, 
summary statistics will include the arithmetic mean, arithmetic standard deviation (SD), median, 
minimum, maximum and number of observations; for log-normal data (e.g. the PK parameters: 
AUCs and Cmax) the geometric mean and geometric CV% will also be presented. For categorical 
data, frequency count and percentages will be presented. Data listings will be provided for all 
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participants up to the point of withdrawal, with any participants excluded from the relevant 
population highlighted. Summary statistics and statistical analyses will generally only be 
performed for participants included in the relevant analysis population. For the calculation of 
summary statistics and statistical analysis, unrounded data will be used.  
For change from baseline summary statistics, each individual change from baseline will be 
calculated by subtracting the individual participant’s baseline value from the value at that time 
point. The individual participants’ change from baseline values will be used to calculate the 
summary statistics (arithmetic mean, arithmetic SD, median, minimum, maximum and number 
of observations) using a SAS procedure such as Proc Univariate. 
Data analysis will be performed using SAS® Version 9.4 or greater. 
10.2 
Demographics and Participant Disposition  
Participant disposition will be listed. The demographic variables age, sex, race, ethnicity, country 
of enrolment, site ID, body weight, body weight category, height, and body mass index will be 
summarized by treatment, injection site, and overall (overall for each treatment arm and overall), 
and listed. All other demographic variables will be listed only. 
10.3 
Pharmacokinetic Assessment  
10.3.1 Pharmacokinetic Analysis  
PK parameter estimates will be determined using non-compartmental procedures in validated 
software program (Phoenix WinNonlin Version 8.1.1 or later). 
Serum concentrations of mirikizumab will be used to determine the following PK parameters, 
when possible:   
Parameter 
Units 
Definition 
AUC(0-tlast) 
day*µg/mL area under the concentration versus time curve from time zero to time t, 
where t is the last time point with a measurable concentration 
AUC(0-∞) 
day*µg/mL area under the concentration versus time curve from time zero to infinity 
%AUC(tlast-) 
% 
percentage of AUC(0-∞) extrapolated 
Cmax 
µg/mL 
maximum observed drug concentration 
tmax 
day 
time of maximum observed drug concentration 
t½ 
day 
half-life associated with the terminal rate constant (λz) in 
non-compartmental analysis 
CL/F 
L/day 
apparent total body clearance of drug calculated after extra-vascular 
administration 
Vz/F 
L 
apparent volume of distribution during the terminal phase after 
extra-vascular administration 
Vss/F 
L 
apparent volume of distribution at steady state after extra-vascular 
administration 
 
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Additional PK parameters such as weight-normalized PK parameter estimates may be calculated, 
as appropriate. The software and version used for the final analyses will be specified in the CSR.  
Any exceptions or special handling of data will be clearly documented within the final CSR. 
 
Formatting of tables, figures and abbreviations will follow the Eli Lilly Global PK/PD/TS Tool: 
NON-COMPARTMENTAL PHARMACOKINETIC STYLE GUIDE. The version of the tool 
effective at the time of PK analysis will be followed. 
General PK Parameter Rules 
 Actual sampling times will be used in the final analyses of individual PK parameters, 
except for non-bolus pre-dose sampling times which will be set to zero.  
 Cmax and tmax will be reported from observed values. If Cmax occurs at more than one time 
point, tmax will be assigned to the first occurrence of Cmax.  
 AUC parameters will be calculated using a combination of the linear and logarithmic 
trapezoidal methods (linear-log trapezoidal rule). The linear trapezoidal method will be 
applied up to tmax and then the logarithmic trapezoidal method will be used after tmax. The 
minimum requirement for the calculation of AUC will be the inclusion of at least three 
consecutive concentrations above the lower limit of quantification, with at least one of 
these concentrations following Cmax. 
 AUC(0-) values where the percentage of the total area extrapolated is more than 20% 
will be flagged. Any AUC(0-) value excluded from summary statistics will be noted in 
the footnote of the summary table. 
 Half-life (t1/2) will be calculated, when appropriate, based on the apparent terminal 
log-linear portion of the concentration-time curve. The start of the terminal elimination 
phase for each participant will be defined by visual inspection and generally will be the 
first point at which there is no systematic deviation from the log-linear decline in serum 
concentrations. Half-life will only be calculated when a reliable estimate for this 
parameter can be obtained comprising of at least 3 data points. If t1/2 is estimated over a 
time window of less than 2 half-lives, the values will be flagged in the data listings. Any 
t1/2 value excluded from summary statistics will be documented in the footnote of the 
summary table.  
 A uniform weighting scheme will be used in the regression analysis of the terminal 
log-linear portion of the concentration-time curve. 
 The parameters based on observed last quantifiable drug concentration (Clast) will be 
reported. 
Individual PK Parameter Rules 
 Only quantifiable concentrations will be used to calculate PK parameters with the 
exception of special handling of certain concentrations reported below the lower limit of 
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quantitation (BQL). Serum concentrations reported as BQL will be set to a value of zero 
when all of the following conditions are met:  
o The compound is non-endogenous. 
o The samples are from the initial dose period for a participant or from a subsequent 
dose period following a suitable wash-out period. 
o The time points occur before the first quantifiable concentration. 
 All other BQL concentrations that do not meet the above criteria will be set to missing.  
 Also, where two or more consecutive concentrations are BQL towards the end of a 
profile, the profile will be deemed to have terminated and therefore any further 
quantifiable concentrations will be set to missing for the calculation of the PK parameters 
unless it is considered to be a true characteristic of the profile of the drug. 
Individual Concentration vs. Time Profiles 
 Individual concentrations will be plotted utilizing actual sampling times. 
 The terminal point selections will be indicated on a semi-logarithmic plot. 
Average Concentration vs. Time Profiles 
 The average concentration profiles will be graphed using scheduled (nominal) sampling 
times.  
 The average concentration profiles will be graphed using arithmetic average 
concentrations. 
 The pre-dose average concentration for single-dose data from non-endogenous 
compounds will be set to zero. Otherwise, only quantifiable concentrations will be used 
to calculate average concentrations. 
 Concentrations at a sampling time exceeding the sampling time window specified in the 
protocol, or ± 10%, will be excluded from the average concentration profiles. 
 Concentrations excluded from the mean calculation will be documented in the final CSR. 
 A concentration average will be plotted for a given sampling time only if 2/3 of the 
individual data at the time point have quantifiable measurements that are within the 
sampling time window specified in the protocol or ± 10%. An average concentration 
estimated with less than 2/3 but more than 3 data points may be displayed on the mean 
concentration plot if determined to be appropriate and will be documented within the 
final CSR. 
 
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Treatment of Outliers during PK Analysis 
Application of this procedure to all PK analyses is not a requirement. Rather, this procedure 
provides justification for exclusion of data when scientifically appropriate. This procedure 
describes the methodology for identifying an individual value as an outlier for potential 
exclusion, but does not require that the value be excluded from analysis. The following 
methodology will not be used to exclude complete profiles from analysis. 
Data within an Individual Profile 
A value within an individual profile may be excluded from analysis if any of the following 
criteria are met: 
 For any questionable datum that does not satisfy the above criteria, the profile will be 
evaluated and results reported with and without the suspected datum.  
Data between Individual Profiles 
1. If n6, then an objective outlier test will be used to compare the atypical value to other 
values included in that calculation: 
a. Transform all values in the calculation to the logarithmic domain. 
b. Find the most extreme value from the arithmetic mean of the log transformed 
values and exclude that value from the dataset. 
c. Calculate the lower and upper bounds of the range defined by the arithmetic mean 
±3*SD of the remaining log-transformed values. 
d. If the extreme value is within the range of arithmetic mean ±3*SD, then it is not 
an outlier and will be retained in the dataset. 
e. If the extreme value is outside the range of arithmetic mean ±3*SD, then it is an 
outlier and will be excluded from analysis. 
If the remaining dataset contains another atypical datum suspected to be an outlier and n ≥ 6 
following the exclusion, then repeat step 2 above. This evaluation may be repeated as many 
times as necessary, excluding only one suspected outlier in each iteration, until all data 
remaining in the dataset fall within the range of arithmetic mean ±3*SD of the log-transformed 
values. 
Reporting of Excluded Values 
Individual values excluded as outliers will be documented in the final CSR. Approval of the final 
CSR will connote approval of the exclusion.Insert from PKAP (note PKAP should detail 
WinNonlin version) 
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Labcorp Drug Development Study: 8499240  
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10.3.2 Pharmacokinetic Statistical Methodology  
The PK parameters will be summarized by treatment. Additionally, the PK parameters will also 
be summarized by treatment and injection site location. 
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 solution formulation, injection site 
location, and weight category stratification as fixed effects. The least squares (LS) mean 
differences between citrate-free solution PFS (Test) and solution PFS (Reference) 
administrations (across all locations) will be back-transformed to present the ratios of geometric 
LS means and the corresponding 90% CI. 
Example SAS Code: 
proc mixed data=xxx; 
by parameter; 
class formulation location strat_weight; 
model log_pk = formulation location strat_weight / residual; 
lsmeans formulation / alpha=0.1 cl pdiff; 
lsmeans location / alpha=0.1 cl pdiff; 
ods output lsmeans=lsmeans diffs=diffs; 
run; 
The 2 solution formulations will be considered bioequivalent if the 90% CIs of the ratio of 
geometric LS means fall within 0.800 to 1.250. 
Using the same model, the following exploratory comparisons will also be made: 
 The 2 solution formulations compared separately at each injection location (injection 
location will be removed from the model above) 
 The 3 injection locations (arm versus abdomen and thigh versus abdomen) separately for 
each solution formulations (solution formulations will be removed from the model above) 
In addition, the tmax of mirikizumab between the solution formulations will be analyzed using a 
Wilcoxon rank-sum test. Estimates of the median, the median difference, 90% CIs, and p-values 
from the Wilcoxon rank-sum test will be reported.  
Example SAS code: 
proc npar1way data = xxx hl(refclass=”xx”) alpha = 0.1; 
  by parameter; 
  class formulation; 
  var pk; 
  exact wilcoxon hl;  
  ods output wilcoxontest = Wilcoxon;  
  ods output HodgesLehmann=hl; 
run; 
Additional PK analyses may be conducted if deemed appropriate. 
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Labcorp Drug Development Study: 8499240  
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10.4 
Safety and Tolerability Assessments  
10.4.1 Adverse events  
Where changes in severity are recorded in the Case Report Form, each separate severity of the 
adverse event (AE) will be reported in the listings, only the most severe will be used in the 
summary tables. A pre-existing condition is defined as a condition that starts before the 
participant has provided written informed consent and is ongoing at consent. A non-treatment 
emergent AE is defined as an AE which starts after informed consent but prior to dosing. A 
treatment-emergent AE is defined as an AE which occurs postdose or which is present prior to 
dosing and becomes more severe postdose.  
All AEs will be listed. TEAEs will be summarized by treatment, injection site location, severity 
and relationship to the study drug. The frequency (the number of AEs, the number of participants 
experiencing an AE and the percentage of participants experiencing an AE) of TEAEs will be 
summarized by treatment, injection site location, Medical Dictionary for Regulatory Activities 
(MedDRA) (version is documented in the Data Management Plan [DMP]) system organ class 
and preferred term. The summary and frequency AE tables will be presented for all causalities 
and those considered related to the study drug by the investigator. Any SAEs and PCs will be 
listed. Adverse events of special intrest (protocol section 8.3.3) will be listed.  
Discontinuations due to AEs will be listed. 
10.4.2 Concomitant medication  
Concomitant medication will be coded using the WHO drug dictionary (version is documented 
in the DMP). Concomitant medication will be listed. 
10.4.3 Clinical laboratory parameters  
All clinical chemistry and hematology data will be summarized by parameter, treatment overall, 
treatment subset by injection location, and overall and timepoint together with changes from 
baseline, where baseline is defined as the Day 1 predose assessment. All clinical chemistry, 
hematology and urinalysis data will be listed. Additionally, clinical chemistry, hematology and 
urinalysis data outside the reference ranges will be listed and flagged on individual participant 
data listings. 
10.4.4 Vital signs  
Vital signs data will be summarized by parameter, treatment overall, treatment subset by 
injection location, and overall and time point, together with changes from baseline, where 
baseline is defined as the Day 1 predose assessment.  
Values for individual participants will be listed. 
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10.4.5 Electrocardiogram (ECG)  
ECGs will be performed for safety monitoring purposes only and will not be presented. Any 
clinically significant findings from ECGs will be reported as an AE. 
10.4.6 Hepatic Monitoring  
If a participant experiences elevated hepatic laboratory parameters, as detailed in Section 8.2.6.1 
of the protocol, additional tests will be performed to confirm the abnormality. Additional safety 
data may be collected if required, as defined in the protocol. Where applicable, the following will 
be presented. 
The participants’ liver disease history and associated person liver disease history data will be 
listed. Use of acetaminophen during the study, which has potential for hepatotoxicity, will be 
listed. Results from any hepatic monitoring procedures, such as a magnetic resonance 
elastography scan, and biopsy assessments will be listed, if performed. 
Hepatic risk factor assessment data will be listed. Liver related signs and symptoms data will be 
summarized by treatment and listed. Alcohol and recreational drug use data will also be listed. 
All hepatic chemistry, hematology, coagulation, and serology data will be listed. Values outside 
the reference ranges will be flagged on the individual participant data listings. 
10.4.7 Immunogenicity Assessments  
Immunogenicity data will be listed and frequency tables will be presented if analysed. The 
frequency and percentage of participants with pre-existing antidrug antibody (ADA) and with 
TE-ADAs will be presented. TE-ADAs are those that are boosted or induced by exposure to 
study drug, with a 4-fold increase in titer compared to baseline if ADAs were detected at 
baseline or a titer 2-fold greater than the minimum required dilution (1:10) if no ADAs were 
detected at baseline, where baseline is defined as Day 1 predose. For the TE-ADA+ participants, 
the distribution of maximum titers may be described. 
The frequency and percentage of participants with neutralizing antibodies, if measured, may also 
be tabulated for participants with TE ADA.  
The relationship between the presence of antibodies and PK parameters of mirikizumab may be 
assessed if deemed appropriate. 
10.4.8 Visual Analog Scale (VAS) Pain Scores  
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. 
Injection-site assessments should be conducted at the next planned visit following the reporting 
of an injection-related AE. 
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The participants’ maximum post-dose pain scores will be summarized by treatment and injection 
site location. Participants who do not report paint will be included with a score of 0. 
Additionally, maximum post-dose pain score will also be summarized by category, treatment and 
injection site location. The pain categories of VAS for presentation in the TFLs will be no pain 
(VAS pain score = 0), mild pain (VAS pain score > 0 and ≤ 30), moderate pain (VAS pain score 
> 30 and ≤ 70), and severe pain (VAS pain score > 70). 
All data collected will be listed. 
10.4.9 Injection Site Reactions  
Although no prospective collection, spontaneously reported will be captured as an AE of 
Injection-site reaction and additional info will be recorded. 
Injection-site reaction data (erythema, induration, categorical pain, pruritus, and edema) will be 
listed and summarized by treatment overall, treatment subset by injection location, and overall in 
frequency tables.  
10.4.10 Hypersensitivity reactions  
For all drug hypersensitivity reactions that occur, additional follow-up data will be collected to 
assess the participant’s medical history, alternative causes, and symptoms. 
These data will be listed. 
10.4.11 Bleeding and Bruising Assessment  
The presence of visible bleeding/bruising at the injection site will be recorded as an AE if judged 
to be more severe than expected with a typical SC administration. 
If available, any bleeding/bruising data will be listed. 
10.4.12 Other assessments  
All other safety assessments not detailed in this section will be listed but not summarized or 
statistically analyzed. 
10.4.13 Safety and Tolerability Statistical Methodology  
No inferential statistical analyses are planned. 
11. 
INTERIM ANALYSES  
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. 
12. 
CHANGES FROM THE PROTOCOL SPECIFIED STATISTICAL ANALYSES  
There were no changes from the protocol specified statistical analyses. 
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13. 
REFERENCES  
1. International Conference on Harmonization of Technical Requirements for Registration of 
Pharmaceuticals for Human Use, ICH Harmonized Tripartite Guideline, Statistical Principles 
for Clinical Trials (E9), 5 February 1998. 
2. International Conference on Harmonization of Technical Requirements for Registration of 
Pharmaceuticals for Human Use, ICH Harmonized Tripartite Guideline, Structure and 
Content of Clinical Study Reports (E3), 30 November 1995. 
14. 
DATA PRESENTATION  
14.1 
Derived Parameters  
Individual derived parameters (e.g. PK parameters) and appropriate summary statistics will be 
reported to three significant figures. Observed concentration data, e.g. Cmax, should be reported 
as received. Observed time data, e.g. tmax, should be reported as received. Number of 
observations and percentage values should be reported as whole numbers. Median values should 
be treated as an observed parameter and reported to the same number of decimal places as 
minimum and maximum values. 
14.2 
Missing Data  
Missing data will not be displayed in listings. 
14.3 
Insufficient Data for Presentation  
Some of the TFLs may not have sufficient numbers of participants or data for presentation. If 
this occurs, the blank TFL shell will be presented with a message printed in the center of the 
table, such as, “No serious adverse events occurred for this study.” 
 
 
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15. 
APPENDICES  
Appendix 1: Document History  
Status and Version 
Date of Change 
Summary/Reason for Changes 
Final Version 1.0 
NA 
NA; the first version. 
Final Version 2.0 
05 March 2023 
Incorporated Protocol amendment (b) dated 01 Feb 2023 
NA = not applicable 
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Signature Page for VV-CLIN-089798 v1.0
Signature Page for VV-CLIN-089798 v1.0
Approval
06-Mar-2023 15:05:31 GMT+0000
Approval
06-Mar-2023 16:23:32 GMT+0000
Approval
07-Mar-2023 15:52:24 GMT+0000
Approval
07-Mar-2023 18:53:11 GMT+0000
Approved on 07 Mar 2023 GMT
PPD
PPD
PPD
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