Clinical trial NCT04607733
Conditions: Healthy
Sponsor: Eli Lilly and Company
Start date: 2020-11-02; Completion date: 2021-05-17
Enrollment: 240 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The main purpose of this study is to compare the amount of mirikizumab that gets into the blood stream and how long it takes the body to get rid of it, when given as a solution formulation via manual prefilled syringe or autoinjector. The information about any adverse effects experienced will be collected and the tolerability of mirikizumab will also be evaluated.

Screening is required within 28 days prior to the start of the study. For each participant, the total duration of the clinical trial will be about 17 weeks, including screening.

Detailed description:

Arms: arm 1: 2× 1mL (total 200 milligrams (mg) mirikizumab) administered by subcutaneous injection (SC) via a prefilled syringe (PFS) arm 2: 2× 1mL (total 200 milligrams (mg) mirikizumab) administered by subcutaneous injection (SC) via an autoinjector (AI)
Interventions: intervention 1: Mirikizumab Prefilled Syringe intervention 2: Mirikizumab Autoinjector
Intervention descriptions: intervention 1: Administered SC by prefilled syringe intervention 2: Administered SC by autoinjector

Protocol documents:
Prot_000.pdf: 
CONFIDENTIAL
Protocol number I6T-MC-AMBW
1
Title Page
Confidential Information
The information contained in this document is confidential and is intended for the use of clinical investigators. It is the property of 
Eli Lilly and Company or its subsidiaries and should not be copied by or distributed to persons not involved in the clinical 
investigation of mirikizumab (LY3074828), unless such persons are bound by a confidentiality agreement with Eli Lilly and 
Company or its subsidiaries. 
Note to Regulatory Authorities: This document may contain protected personal data and/or commercially confidential information 
exempt from public disclosure. Eli Lilly and Company requests consultation regarding release/redaction prior to any public release. 
In the United States, this document is subject to Freedom of Information Act (FOIA) Exemption 4 and may not be reproduced or 
otherwise disseminated without the written approval of Eli Lilly and Company or its subsidiaries.
Protocol Title: A Bioequivalence Study of Injections of Mirikizumab Solution Using an 
Investigational 1-mL Pre-Filled Syringe and an Investigational 1-mL 
Autoinjector in Healthy Participants
Protocol Number: I6T-MC-AMBW
Amendment Number: This is the initial protocol
Compound: Mirikizumab (LY3074828)
Study Phase: 1
Short Title: A bioequivalence study of injections of mirikizumab solution using an 
investigational 1-mL pre-filled syringe and an investigational 1-mL autoinjector in 
healthy participants
Sponsor Name: Eli Lilly and Company
Legal Registered Address: Indianapolis, Indiana USA 46285
Regulatory Agency Identifier Number(s)
IND: 125444
Approval Date: Protocol Electronically Signed and Approved by Lilly on date provided below.
Approval Date: 14-Aug-2020 GMT


CONFIDENTIAL
Protocol number I6T-MC-AMBW
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Medical Monitor Name and Contact Information will be provided separately 


CONFIDENTIAL
Protocol number I6T-MC-AMBW
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Table of Contents
1.
Protocol Summary......................................................................................................6
1.1.
Synopsis.......................................................................................................................6
1.2.
Schema.........................................................................................................................7
1.3.
Schedule of Activities (SoA) ........................................................................................8
2.
Introduction..............................................................................................................11
2.1.
Study Rationale ..........................................................................................................11
2.2.
Background ................................................................................................................11
2.2.1.
Safety.........................................................................................................................11
2.2.2.
Deaths, Serious Adverse Events, and Discontinuations due to an 
Adverse Event ............................................................................................................12
2.2.3.
Other Treatment-Emergent Adverse Events................................................................12
2.2.4.
Pharmacokinetics........................................................................................................12
2.2.5.
Immunogenicity..........................................................................................................13
2.3.
Benefit/Risk Assessment ............................................................................................13
3.
Objectives and Endpoints.........................................................................................15
4.
Study Design .............................................................................................................16
4.1.
Overall Design............................................................................................................16
4.2.
Scientific Rationale for Study Design .........................................................................17
4.3.
Justification for Dose..................................................................................................18
4.4.
End of Study Definition..............................................................................................18
5.
Study Population ......................................................................................................19
5.1.
Inclusion Criteria........................................................................................................19
5.2.
Exclusion Criteria.......................................................................................................20
5.3.
Lifestyle Considerations .............................................................................................22
5.3.1.
Meals and Dietary Restrictions ...................................................................................22
5.3.2.
Caffeine, Alcohol, and Tobacco..................................................................................22
5.3.3.
Activity ......................................................................................................................23
5.4.
Screen Failures ...........................................................................................................23
6.
Study Intervention....................................................................................................24
6.1.
Study Intervention Administered ................................................................................24
6.1.1.
Administration Details................................................................................................24
6.1.2.
Medical Devices.........................................................................................................24
6.2.
Preparation/Handling/Storage/Accountability.............................................................25
6.3.
Measures to Minimize Bias: Randomization and Blinding..........................................25
6.4.
Study Intervention Compliance...................................................................................25
6.5.
Concomitant Therapy .................................................................................................26
6.6.
Dose Modification......................................................................................................26
6.7.
Intervention after the End of the Study........................................................................26
7.
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal....................................................................................27
7.1.
Discontinuation of Study Intervention ........................................................................27
7.2.
Participant Discontinuation/Withdrawal from the Study .............................................27


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Protocol number I6T-MC-AMBW 
 
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7.2.1. 
Discontinuation of Inadvertently Enrolled Participants ..................................................27 
7.3. 
Lost to Follow-up............................................................................................................28 
8. 
Study Assessments and Procedures.............................................................................29 
8.1. 
Efficacy Assessments .....................................................................................................29 
8.2. 
Safety Assessments .........................................................................................................29 
8.2.1. 
Physical Examinations ....................................................................................................29 
8.2.2. 
Vital Signs .......................................................................................................................30 
8.2.3. 
Electrocardiograms .........................................................................................................30 
8.2.4. 
Clinical Safety Laboratory Assessments ........................................................................30 
8.2.5. 
Other Tests ......................................................................................................................31 
8.2.6. 
Safety Monitoring ...........................................................................................................32 
8.3. 
Adverse Events and Serious Adverse Events .................................................................34 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE 
Information .....................................................................................................................34 
8.3.2. 
Method of Detecting AEs and SAEs ..............................................................................35 
8.3.3. 
Follow-up of AEs and SAEs ...........................................................................................35 
8.3.4. 
Regulatory Reporting Requirements for SAEs ...............................................................35 
8.3.5. 
Pregnancy ........................................................................................................................35 
8.3.6. 
Adverse Events of Special Interest .................................................................................36 
8.3.7. 
Product Complaints .........................................................................................................36 
8.4. 
Treatment of Overdose ...................................................................................................37 
8.5. 
Pharmacokinetics ............................................................................................................37 
8.5.1. 
Bioanalysis ......................................................................................................................38 
8.6. 
Pharmacodynamics .........................................................................................................38 
8.7. 
Genetics ..........................................................................................................................38 
8.8. 
Biomarkers ......................................................................................................................38 
8.9. 
Immunogenicity Assessments.........................................................................................38 
8.10. 
Health Economics ...........................................................................................................38 
9. 
Statistical Considerations .............................................................................................39 
9.1. 
Statistical Hypotheses .....................................................................................................39 
9.2. 
Sample Size Determination ............................................................................................39 
9.3. 
Populations for Analyses ................................................................................................39 
9.3.1. 
Study Participant Disposition .........................................................................................39 
9.3.2. 
Study Participant characteristics .....................................................................................39 
9.4. 
Statistical Analyses .........................................................................................................39 
9.4.1. 
General Considerations ...................................................................................................40 
9.4.2. 
Pharmacokinetic Analyses ..............................................................................................40 
9.4.3. 
Safety Analyses ...............................................................................................................41 
9.4.4. 
Evaluation of Immunogenicity .......................................................................................41 
9.5. 
Interim Analyses .............................................................................................................41 
9.6. 
Data Monitoring Committee (DMC) ..............................................................................41 
10. 
Supporting Documentation and Operational Considerations ..................................42 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ................................................................................................................42 
10.2. 
Appendix 2: Clinical Laboratory Tests ...........................................................................47 


CONFIDENTIAL 
Protocol number I6T-MC-AMBW 
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10.2.1.  Blood Sampling Summary ..............................................................................................49 
10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting .........................................................50 
10.3.1.  Definition of AE .............................................................................................................50 
10.3.2.  Definition of SAE ...........................................................................................................51 
10.3.3.  Recording and Follow-up of AE and/or SAE .................................................................52 
10.3.4.  Reporting of SAEs ..........................................................................................................53 
10.4. 
Appendix 4: Contraceptive Guidance and Collection of 
Pregnancy Information ...................................................................................................55 
10.5. 
Appendix 5: Genetics......................................................................................................58 
10.6. 
Appendix 6: Liver Safety: Suggested Actions and Follow-up 
Assessments ....................................................................................................................59 
10.7. 
Appendix 7: Recommended Laboratory Testing for 
Hypersensitivity Events ..................................................................................................61 
10.8. 
Appendix 8: Medical Device Adverse Events (AEs), Adverse 
Device Effects (ADEs), Serious Adverse Events (SAEs) and 
Device Deficiencies: Definition and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ............................................................................62 
10.8.1.  Definition of AE and ADE .............................................................................................62 
10.8.2.  Definition of SAE, SADE and UADE ............................................................................62 
10.8.3.  Definition of Device Deficiency .....................................................................................63 
10.8.4.  Recording and Follow-Up of AE and/or SAE and Device 
Deficiencies .....................................................................................................................63 
10.8.5.  Reporting of SAEs ..........................................................................................................65 
10.8.6.  Reporting of SADEs .......................................................................................................65 
10.8.7.  AE, ADE, SAE, SADE Determination Flow Chart ........................................................66 
10.9. 
Appendix 9: Abbreviations .............................................................................................67 
11.
References ......................................................................................................................70 


CONFIDENTIAL
Protocol number I6T-MC-AMBW
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1.
Protocol Summary
1.1.
Synopsis
Protocol Title: A Bioequivalence Study of Injections of Mirikizumab Solution Using an 
Investigational 1-mL Pre-Filled Syringe and an Investigational 1-mL Autoinjector in Healthy 
Participants
Short Title: A bioequivalence study of injections of mirikizumab solution using an 
investigational 1-mL pre-filled syringe and an investigational 1-mL autoinjector in healthy 
participants.
Rationale:
Study I6T-MC-AMBW (AMBW) will assess the pharmacokinetics (PK), safety, and tolerability 
of a 200-mg subcutaneous (SC) dose of mirikizumab (LY3074828) solution formulation 
administered using an investigational manual 1-mL pre-filled syringe (PFS) or an investigational 
1-mL autoinjector (AI). Both devices will be evaluated at 3 different injection sites (arm, thigh, 
and abdomen) in order to expand the options for administration in patient use. The study will 
provide data to bridge PFS administration of mirikizumab, with the investigational AI device 
planned for use in subsequent studies and patient use.
Objectives and Endpoints
Objectives
Endpoints
Primary

To evaluate the PK of mirikizumab 
after SC administration of 200-mg 
doses of solution formulation using a 
2× 1 mL PFS and a 2× 1 mL AI in 
healthy participants

Cmax, AUC(0-∞), and AUC(0-tlast)
Secondary

To describe the safety and tolerability 
of mirikizumab in healthy participants

TEAEs and SAEs
Abbreviations: AI = autoinjector; AUC(0-∞) = area under the concentration versus time curve from time zero to 
infinity; AUC(0-tlast) = area under the concentration versus time curve from time zero to time t, where t is the last 
time point with a measurable concentration; Cmax = maximum observed drug concentration; PFS = pre-filled 
syringe; PK = pharmacokinetics; SAE = serious adverse event; SC = subcutaneous; TEAE = treatment-emergent 
adverse event. 
Overall Design
Study AMBW is a Phase 1, open-label, 2-arm, randomized, parallel-design, single-dose, 
multi-site study in healthy participants. 


CONFIDENTIAL
Protocol number I6T-MC-AMBW
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Screening
All participants will be screened within 28 days prior to enrollment. At screening, participants 
will be stratified into 1 of 3 weight categories (less than 70 kg, 70 to 80 kg, and more than 
80 kg). 
Treatment and Assessment Period
Eligible participants will be admitted to the clinical research unit (CRU) on Day -1. 
Within the 3 weight categories, participants will be randomized using a computer-generated 
allocation code: 

1:1 to delivery device (either PFS [reference] or AI [test])

within each delivery-device group 1:1:1 to injection site (arm, thigh, or abdomen)
On Day 1, participants will receive a 2× 1mL (total 200 mg mirikizumab) SC dose delivered via 
the device and in the location assigned by the randomization. 
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 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 sign measurements, 
recording of adverse events (AEs), physical examination, and immunogenicity. 
Disclosure Statement: This is an open-label, parallel group bioequivalence study with 2 arms.
Number of Participants:
Up to approximately 240 participants may be enrolled so that approximately 216 participants 
(108 in the PFS group and 108 in the AI group) complete the study.
Intervention Groups and Duration:
All participants will be screened within 28 days prior to enrollment. A single dose of 
mirikizumab will be administered SC by either PFS or AI into the arm, thigh, or abdomen on 
Day 1 and participants will be followed through Day 85.
Data Monitoring: No
1.2.
Schema
Not applicable. 


CONFIDENTIAL
Protocol number I6T-MC-AMBW
8
1.3.
Schedule of Activities (SoA)
Study Schedule Protocol I6T-MC-AMBW
Screening
Study Day
Comments
Procedure
-28 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
±2d
71
±3d
85
±3d or 
ED
Informed consent
X
Medical history and 
demographics
X
Review and confirm 
inclusion and 
exclusion criteria
X
X
Admission to CRU
X
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.
Randomization
X
Participants will be randomized 
1:1 to 1 of 2 delivery devices and 
1:1:1 to 1 of 3 injection locations 
per delivery device. 
Height, weight, and 
BMI
X
X
Only weight will be measured on 
Day 85 or ED.
Body temperature
X
X
P
X
X
X
X
X
X
X
X
X
X
X
Physical examination
X
X
Full physical examination at 
Day -1. Symptom-directed 
examinations and assessments at 
other times, and as deemed 
necessary by the investigator.


CONFIDENTIAL
Protocol number I6T-MC-AMBW
9
Screening
Study Day
Comments
Procedure
-28 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
±2d
71
±3d
85
±3d or 
ED
Vital signs (pulse rate
and blood pressure) 
(sitting) (hours)
X
X
P,
2 to 
4
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 
upon between Lilly and the 
investigator.
Clinical laboratory 
tests
X
X
P
X
X
X
X
See Appendix 10.2, Clinical 
Laboratory Tests, for details.
Serology
X
See Appendix 10.2, Clinical 
Laboratory Tests, 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.
FSH
X
Females only. See Appendix 10.4. 
Pregnancy test 
(females only)
X
X
X
Serum pregnancy test will be 
performed at screening and 
Day -1. Urine pregnancy test will 
be performed at Day 85 or ED. 
See Appendix 10.4. 
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
See Section 6.1. 


CONFIDENTIAL
Protocol number I6T-MC-AMBW
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Screening
Study Day
Comments
Procedure
-28 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
±2d
71
±3d
85
±3d or 
ED
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 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; P = pre-dose; PK = pharmacokinetic; TB = tuberculosis.


CONFIDENTIAL
Protocol number I6T-MC-AMBW
11
2.
Introduction
2.1.
Study Rationale
Study I6T-MC-AMBW (AMBW) will assess the pharmacokinetics (PK), safety, and tolerability 
of a 200-mg subcutaneous (SC) dose of mirikizumab (LY3074828) solution formulation
administered using an investigational manual 1-mL pre-filled syringe (PFS) or an investigational
1-mL autoinjector (AI). Both devices will be evaluated at 3 different injection sites (arm, thigh,
and abdomen) in order to expand the options for administration in patient use. The study will
provide data to bridge PFS administration of mirikizumab, with the investigational AI device
planned for use in subsequent studies and patient use.
2.2.
Background
Mirikizumab is a humanized immunoglobulin G4‒variant monoclonal antibody that is directed 
against the p19 subunit of interleukin (IL)-23 and does not bind IL-12. Mirikizumab is being 
developed for the treatment of autoimmune diseases, including psoriasis, Crohn’s disease (CD), 
and ulcerative colitis (UC), in which the IL-23 pathway is thought to have a significant 
pathogenic role. 
Clinical pharmacology studies have demonstrated an acceptable safety profile in healthy subjects
following single dose IV administration up to 2400 mg (see Section 2.2.1). 
Bioavailability of mirikizumab when administered SC by either PFS or AI at different injection 
sites was evaluated in study I6T-MC-AMBE (AMBE). No statistically significant difference in 
exposure following administration with the PFS compared to the AI was noted. Comparison of 
AUC by injection location showed the highest AUC ratio was 1.5 for the PFS (thigh versus
abdomen) and 1.4 for the AI (abdomen versus arm) (see Section 2.2.4). 
Administration of a 200-mg dose via AI would improve ease of administration in patients with 
UC, thus there is a need to investigate the bioavailability of this dose administered by AI at 
various injection sites.  
2.2.1.
Safety
As of the Investigator’s Brochure (IB) cutoff date (06 February 2019), there have been
approximately 1061 participants in studies on mirikizumab. These include 236 participants with 
psoriasis, 230 participants with UC, 186 participants with CD, and 409 healthy participants who 
were exposed to either placebo or mirikizumab at single doses ranging from 5 to 2400 mg. 
Across Phase 2 studies, multiple doses of mirikizumab have been studied at a maximum of 
1000 mg intravenous (IV) and 300 mg SC. Two ongoing Phase 3 studies are being conducted in 
participants with UC, receiving an induction dose of 300 mg IV on Weeks 0, 4, and 8 (Study 
I6T-MC-AMAN) followed by maintenance dosing in those achieving clinical response of 
200 mg SC Q4W (Study I6T-MC-AMBG).  
In clinical pharmacology studies, single IV doses of up to 2400 mg have been administered to 
healthy Caucasian and Japanese participants (Study I6T-MC-AMAD). No dose-related safety or 
tolerability issues were observed in this study or in other ongoing clinical pharmacology studies


CONFIDENTIAL
Protocol number I6T-MC-AMBW
12
with single SC doses ranging from 120 to 2400 mg and at multiple doses up to a maximum of 
300 mg. 
Six completed studies (I6T-MC-AMAL [AMAL], I6T-MC-AMAE [AMAE], I6T-MC-AMAQ
[AMAQ], I6T-MC-AMAR [AMAR], I9O-MC-AABC [AABC], and AMBE) compared the 
bioavailability, safety, and tolerability of various formulations of mirikizumab delivered by 
either PFS, AI, or SC infusion. Mirikizumab was well tolerated; however, asymptomatic 
reductions in neutrophil counts were seen in a minority of participants. The incidence of 
injection-site reactions (ISRs) was highly variable across studies due to their differing designs
and treatments; however, ISRs comprised mostly mild to moderate pain and very slight to 
well-defined erythema.
2.2.2.
Deaths, Serious Adverse Events, and Discontinuations due to an Adverse Event
In Phase 1 studies with healthy participants or participants with psoriasis that were integrated for 
safety analyses, no deaths, serious adverse events (SAEs), or discontinuations due to an adverse 
event (AE) were reported. Of the studies that have completed since the IB cutoff date, there was 
1 SAE of malignant brain neoplasm that led to discontinuation of a healthy participant in Study 
AABC; the event was not considered to be related to study treatment by the investigator.  In 
Phase 2 and 3 studies with participants having psoriasis, UC, or CD, up to the IB cutoff date, 
1 death occurred from myocardial infarction and 1 death occurred from lung cancer, neither of 
which was considered related to study drug by the investigator, 
Serious adverse events 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 in the IB, the most frequently reported 
(≥5.0%) treatment-emergent adverse events (TEAEs) in the 442 healthy participants and 
participants with psoriasis treated with mirikizumab were ISRs (including injection-site pain), 
nasopharyngitis, and headache. Three of the integrated clinical pharmacology studies (AABA, 
AMAL, AMAE) and 3 subsequently completed studies (AMAR, AMBE, and AABC) actively 
observed injection sites to allow recording of events such as erythema, swelling, and induration. 
Studies AMBE and AMAQ showed that administration of mirikizumab using the 1-mL AI is
safe and well-tolerated in healthy participants based on TEAEs and injection-site pain.
Treatment-emergent adverse events 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 40%.
Study AMBE investigated the PK, safety and tolerability of and pain associated with a 125-mg
SC dose of mirikizumab solution formulation administered using the investigational manual PFS, 
or the investigational AI. Doses were administered as 1× 1-mL SC injections into the arm, thigh, 
or abdomen. When all injection sites were considered together, the study showed no statistically 


C O N FI D E N TI A L
Pr ot oc ol  n u m ber I 6 T-M C -A M B W
1 3
sig nifica nt differe nce i n e x p os ure f oll o wi n g a d mi nistrati o n wit h t he P F S c o m pare d t o t he AI ;
h o we ver, t he u p per b o u n ds of t he 9 0 % CI f or A U C( 0 -tlast), A U C( 0 -∞), a n d Cm a x were greater 
t ha n t he 1. 2 5 bi oe q ui vale nce b o u n dar y. C o m paris o n of e x p o s ure b y i njecti on l ocat i on 
d e m o nstrate d stat isticall y si g nifica nt differe nces (t hat is t he 9 0 % CI f or t he rati o of ge o metric 
least s q uares mea ns e xcl u de d u nity)  w he n c o m pari n g t he 2 a d mi nistrati o n met h o ds :

P F S a n d AI a d mi nistrati o n i nto t he a b d o me n
o
e x p os ure i ncrease d b y u p t o 6 2 % f oll o wi n g a d mi nistrati o n usi n g t he AI 
c o mpare d t o P F S
A n d f or eac h a d mi nistrati o n met h o d t he f o ll owi n g statisticall y si g nifica nt differe nces were n ote d 
bet wee n i nject i on sites:

AI a d mi nistrati o n i nt o t he ar m c o m pare d t o t he a b d o me n , 
o
ex p os ure decrease d b y u p t o 3 6 % f o ll owi n g a d mi nistratio n i nt o t he ar m  
c o mpare d t o t he a b d o m e n

P F S a d mi nistrati o n i nt o t he t hi g h c o m pare d t o t he a b d o me n.
o
e x p os ure i ncrease d b y u p t o 7 3 % f oll owi n g a d mi nistrati o n i nt o t he t hi g h
c o mpare d t o t he ab d o me n .
2. 2. 5. 
I m m u n o ge nicit y
Treat me nt -e mer ge nt a nt i dr u g a nti b o dies ( T E-A D A) ha ve bee n o bser ve d i n part ici pa nts i n all 
cli nical trials i n v o l vi n g miri kiz u ma b a d mi nistrati o n. I n t he majori t y of T E-A D A + parti ci pa nts, 
titers were lo w a n d ha d n o clear i m pact o n dr u g e x p os ure a n d, if meas ure d, efficac y. Wit h a fe w 
parti ci pa nts, titers were s ufficie ntl y hi g h t o i m pact dr u g e x p os ure. T here was n o clear ass ociat i on 
wi t h t he de vel o p me nt of i m m u n o ge nicity t o mir kiz u ma b a n d patie nts re p ortin g i nject i on site 
reactio ns/ h y p er se nsiti vity e ve nts.  
2. 3.
Be nefit/ Ris k Assess me nt
As wi t h ot her i m m u n om o d ul at or y t hera pies, miriki z u m a b ma y increase t he ri s k of de vel o pi n g a n 
i nfecti on or ma y e xacer bate a n e xist i n g i nfecti on . T hese ma y  incl u de o p p ort u nist ic i nfecti ons 
a n d react i vati on of late nt i nfecti o ns, s uc h as t u berc ul osis ( T B) a n d he pat itis B, alt ho u g h s uc h 
i nfecti ons ha ve n ot bee n re p orte d i n heal t h y v olu nteer cli nical trials a d mi nisteri n g miri kiz u ma b
t o date. T heref ore, partici pa nts testi n g p ositi ve f or he patitis B/ C, h u ma n i m m u n o deficie nc y vir us 
( HI V), or T B at scree ni n g will n ot be per mitte d t o partici pate i n t his st u d y. I m m u n om o d ul at or y 
t hera pies ma y i ncrease t he ris k of mali g na ncies; h o we ver, d ue t o t he si n gle d ose of miri kiz u ma b
bei n g a d mi nistere d i n t his st u d y , it is n ot c o nsi dere d necessar y t o mo ni t or for s uc h effects.
I mme diate h y perse nsi tivi t y reacti ons (a na p h ylact ic reactio n a n d i nf usi o n- r elate d h y perse nsit i vity 
reactio n) i ncl u di n g urticaria, a n gi oe de ma, a n d a na p h yla xis, ha ve rarel y bee n re p orte d wit h t he 
a d mi nistrati o n of miri kiz u ma b.
N o ot her cli nicall y  si g nifica nt safety or t ol era bilit y c o ncer ns ha ve bee n i de nt ifie d t o date i n 
parti ci pa nts e x p ose d t o miri kiz u ma b u p t o t he hi g hest d oses gi ve n (si n gle 2 4 0 0 -m g I V a n d S C 
d oses ). Of n ote, t he 2 4 0 0 -m g S C d ose of mir i kiz u ma b was a d mi nistere d i n c o nj u ncti on wi t h 
h u ma n rec o m bi na nt h yal ur o ni dase as a n i nte gral c o m p o ne nt of t he f or m ulat i on.


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Protocol number I6T-MC-AMBW
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Healthy participants are not expected to derive any benefit from participating in studies in which 
mirikizumab is administered.
As this study will use PFS and AIs, device-based risks will be evaluated. Possible device-based
risks include local effects such as pain at the injection sites from either the needle or the solution
entry into the SC tissue, swelling, erythema, bleeding, and bruising. These risks are mitigated by
training of investigative site staff on proper injection techniques. Systemic effects may include
sweating, feeling faint, or fever, as a sign of infection.
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of mirikizumab may be found in the IB and risks as well as reasonably anticipated 
adverse device effects of the AI are found in the device IB.


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3.
Objectives and Endpoints
Objectives
Endpoints
Primary

To evaluate the PK of mirikizumab after SC 
administration of 200-mg doses of solution 
formulation using a 2× 1-mL PFS and a 
2× 1-mL AI in healthy participants

Cmax, AUC(0-∞), and AUC(0-tlast)
Secondary

To describe the safety and tolerability of 
mirikizumab in healthy participants

TEAEs and SAEs
Tertiary/Exploratory

To evaluate the effect of mirikizumab delivery 
device on immunogenicity

To evaluate the impact of injection-site 
location on PK

TE-ADA

Cmax, AUC(0-∞), and AUC(0-tlast)
Abbreviations: AI = autoinjector; AUC(0-∞) = area under the concentration versus time curve from time zero to 
infinity; AUC(0-tlast) = area under the concentration versus time curve from time zero to time t, where t is the last 
time point with a measurable concentration; Cmax = maximum observed drug concentration; PFS = pre-filled 
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 AMBW is a Phase 1, open-label, 2-arm, randomized, parallel-design, single-dose, 
multi-site study in healthy participants. 
Screening
All participants will be screened within 28 days prior to enrollment. At screening, participants 
will be stratified into 1 of 3 weight categories (less than 70 kg, 70 to 80 kg, and more than 
80 kg). 
Treatment and Assessment Period
Eligible participants will be admitted to the clinical research unit (CRU) on Day -1. 
Within the 3 weight categories, participants will be randomized (Table AMBW.1) using a 
computer-generated allocation code (Section 6.3):

1:1 to delivery device (either PFS [reference] or AI [test])

within each delivery-device group 1:1:1 to injection site (arm, thigh, or abdomen)
On Day 1, participants will receive a 2× 1mL (total 200 mg mirikizumab) SC dose delivered via 
the device and in the location assigned by the randomization. 
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 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 sign measurements, 
recording of AEs, physical examination, and immunogenicity. 


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Protocol number I6T-MC-AMBW
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Table AMBW.1.
Study AMBW Stratification and Randomization Plan
Weight Category 
(Participants)
Injection Device
Subcutaneous Injection 
Locationa
Desired Number 
of Participants
Low
<70 kg
(72 participants)
2 x 1-mL PFS (Reference)
Arm
12
2 x 1-mL AI (Test)
12
2 x 1-mL PFS (Reference)
Abdomen
12
2 x 1-mL AI (Test)
12
2 x 1-mL PFS (Reference)
Thigh
12
2 x 1-mL AI (Test)
12
Medium
70 – 80 kg
(72 participants)
2 x 1-mL PFS (Reference)
Arm
12
2 x 1-mL AI (Test)
12
2 x 1-mL PFS (Reference)
Abdomen
12
2 x 1-mL AI (Test)
12
2 x 1-mL PFS (Reference)
Thigh
12
2 x 1-mL AI (Test)
12
High
>80 kg
(72 participants)
2 x 1-mL PFS (Reference)
Arm
12
2 x 1-mL AI (Test)
12
2 x 1-mL PFS (Reference)
Abdomen
12
2 x 1-mL AI (Test)
12
2 x 1-mL PFS (Reference)
Thigh
12
2 x 1-mL AI (Test)
12
Abbreviations: AI = autoinjector; PFS = prefilled syringe. 
a.
A dose of study intervention will consist of 2 subcutaneous injections of mirikizumab into the arm, thigh, 
or abdomen. All doses will be administered by trained site staff. 
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. 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.
Participants will be randomized 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.
Previous population PK analyses have shown that patients with a lower body weight tended to 
have a lower clearance and/or central volume of distribution. 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, approximately equal numbers of 
participants in each weight category are proposed to avoid a large difference in mean weight 
between the test and the reference delivery-device groups. A participant population of 72 per 
weight group is an approximate target with the recommended weight categories selected based 
on the distribution of weights in prior studies. The number of participants assigned to each 
delivery device and the number of participants assigned to each site of injection is desired to be 
balanced. 


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A parallel-group design is chosen because a crossover design is impractical for mirikizumab,
which has a half-life of approximately 10.5 days. Additionally, a crossover study could confound
PK data if participants develop neutralizing antidrug antibodies (ADAs).
4.3.
Justification for Dose
The 200-mg dose of mirikizumab chosen for this study is based on

200 mg being found safe and tolerable in Phase 2 studies,

200 mg being evaluated in the Phase 3 UC development program, and

the volume of solution that can be delivered through 2 PFS/AI (1 mL per PFS/AI) and the 
solubility of mirikizumab (100 mg/mL).
The 200-mg dose administered as 2× 1-mL injections is the maintenance dosing regimen being 
used in Phase 3 studies and anticipated for use once marketed.
4.4.
End of Study Definition
A participant is considered to have completed the study if he/she has completed all required 
phases of the study including the last visit shown in the Schedule of Activities (SoA; 
Section 1.3).
The end of the study is defined as the date of the last visit of the last participant in the study.


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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 
electrocardiogram (ECG). The nature of any conditions present at the time of the physical 
examination and any preexisting conditions will be documented.
Screening may occur up to 28 days prior to enrollment. Participants who are not enrolled within 
28 days of screening may undergo an additional medical assessment and/or clinical 
measurements to confirm their eligibility. In such instances, repeat the following screening tests 
and procedures: weight, 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 and Sex
1. are between 18 and 65 years of age 
2. are males or non-pregnant females of childbearing or non-childbearing potential. 

Reproductive definitions and contraceptive requirements are provided in 
Appendix 4 (Section 10.4)
Weight
3. have body mass index (BMI) within the range 18.0 to 32.0 kg/m2 (inclusive)
Type of Participant and Disease Characteristics
4. participants who are overtly healthy, as determined by medical evaluation including:

medical history

physical examination

clinical laboratory tests,

ECG and

vital signs.
5. have clinical laboratory test results within 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
6. have venous access sufficient to allow for blood sampling as per the protocol
7. agree not to donate blood or plasma until after the end of their participation in the study
8. are reliable and willing to make themselves available for the duration of the study and are 
willing to follow study procedures


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Protocol number I6T-MC-AMBW
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Informed Consent
9. capable of giving signed informed consent as described in Appendix 1 (Section 10.1) 
which includes compliance with the requirements and restrictions listed in the informed 
consent form (ICF) and in this protocol.
5.2.
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
10. have known allergies to mirikizumab, related compounds, or any components of 
the formulation, or history of significant atopy
11. have self-perceived dullness or loss of sensation in either arm or thigh or on either 
side of the abdomen
12. have an abnormality in the 12-lead ECG that, in the opinion of the investigator, 
increases the risks associated with participating in the study
13. have an abnormal blood pressure, pulse rate, or temperature determined to be 
clinically significant by the investigator
14. have a history or presence of cardiovascular, respiratory, hepatic, renal, 
gastrointestinal, endocrine, hematological, neurological, or dermatological
disorders capable of significantly altering the absorption, metabolism, or 
elimination of drugs; of constituting a risk when taking the study intervention; or 
of interfering with the interpretation of data
15. Infections:
a.
have had a serious infection (such as, pneumonia, cellulitis, sepsis); 
have been hospitalized or have received intravenous 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 
and/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.
16. have known or ongoing psychiatric disorders deemed clinically significant by the 
investigator


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17. regularly use known drugs of abuse and/or show positive findings on 
drug screening
18. show evidence of HIV infection and/or positive HIV antibodies
19. show evidence of hepatitis C and/or positive hepatitis C antibody
20. show evidence of hepatitis B and/or positive hepatitis B surface antigen or 
hepatitis B core antibody
21. are females who are pregnant or lactating
22. 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
23. have significant allergies to humanized monoclonal antibodies
24. have clinically significant multiple or severe drug allergies, or intolerance to
topical corticosteroids, or severe posttreatment hypersensitivity 
reactions (including, but not limited to, erythema multiforme major, 
linear immunoglobulin A dermatosis, toxic epidermal necrolysis, or exfoliative 
dermatitis)
25. have had lymphoma, leukemia, or any malignancy within the past 5 years, except 
for basal cell or squamous epithelial carcinomas of the skin that have been 
resected with no evidence of metastatic disease for 3 years
26. have had breast cancer within the past 10 years
Prior/Concomitant Therapy
27. intend or are likely to use over-the-counter or prescription medication within 7 days prior 
to dose administration. Participants on stable doses of some medications (such as, statins 
and antihypertensives) may be eligible for enrolment following discussion with the 
sponsor (Section 6.5)
28. have ever received anti-IL-12p40 antibodies (eg, ustekinumab [Stelara®]) or 
anti-IL-23p19 antibodies (eg, risankizumab [BI-655066], brazikumab [MEDI2070], 
guselkumab [CNTO 1959], or tildrakizumab [MK-3222]) for any indication, including 
investigational use
29. 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)
30. have been treated with oral steroids within 1 month of screening, or intend to during the 
study (mild topical steroid creams/ointments are permitted, with the exception of the 
injection day as specified in Section 6.5)


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Prior/Concurrent Clinical Study Experience
31. 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
32. have participated in a clinical trial involving an investigational product within 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 
Day 1
33. have previously completed or withdrawn from this study or any other study investigating 
mirikizumab, and have previously received mirikizumab
Other Exclusions
34. 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
35. are Lilly or Covance employees
36. have donated blood or plasma of more than 500 mL within 1 month prior to screening 
37. 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) (1 unit = 12 oz or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 
45 mL of distilled spirits)
38. have a tobacco consumption of more than 10 cigarettes per day (or equivalent), or who 
are unwilling to abide by the CRU smoking guidelines described in Section 5.3.2
39. have excessive tattoos, scars, moles, skin hyperpigmentation, birth marks, or stretch 
marks over either arm, either thigh, or either side of the abdomen that would interfere 
with injection site assessments
40. in the opinion of the investigator, 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.
Caffeine, Alcohol, and Tobacco
Caffeine
Participants will not be allowed to consume caffeinated products during study visits and while 
resident at the CRU, but otherwise participants will be allowed to maintain their regular caffeine 
consumption.


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Protocol number I6T-MC-AMBW
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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/exercise; 
however, they should not undertake vigorous or prolonged exercise within 48 hours prior to any 
visit in which laboratory safety tests will occur (Day -1, Day 1, Day 3, Day 15, Day 29, and Day 
85). While certain study procedures are in progress at the site, participants may be required to 
remain recumbent or sitting.
5.4.
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but do 
not meet all inclusion/exclusion criteria, are not alternates, and subsequently are not enrolled in 
the study.
Individuals who do not meet the criteria for participation in this study (screen failure) may not be 
rescreened, unless stated in Section 5. Repeating of 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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6.
Study Intervention
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to/used by a study participant 
according to the study protocol.
6.1.
Study Intervention Administered
This study involves a comparison of 21-mL (100 mg) SC injections of mirikizumab using PFS 
and AI into the arm, thigh, or abdomen for a total administered dose of 200 mg.
Table AMBW.2.
Study Interventions Administered
Study Intervention 
Mirikizumab PFS
Mirikizumab AI
Dosage Formulation
Solution for injection
Solution for injection
Unit Dose 
Strength(s)/Dosage Level(s)
100 mg/mL in a 1-mL PFS 
100 mg/mL in a 1-mL AI
Route of Administration
Subcutaneous
Subcutaneous
Dosing Instructions
2× 1-mL injections at site according to the 
randomization
2× 1-mL injections at site according to 
the randomization
Abbreviations: AI = autoinjector; PFS = prefilled syringe. 
6.1.1.
Administration Details 
Participants randomized to a group with the arm or thigh as the injection area will have 
1. the first injection administered to the left limb, and 
2. the second injection administered to the corresponding (contra-lateral) right limb. 
Participants randomized to the group with the abdomen as the injection area will have 
1. the first injection administered to the lower left quadrant, and
2. the second injection administered to the lower right quadrant of the abdomen. 
6.1.2.
Medical Devices
1. The Lilly-manufactured medical devices (or devices manufactured for Lilly by a third 
party) provided for use in this study are 
a.
The fully assembled mirikizumab 1-mL PFS
b. The fully assembled mirikizumab 1-mL AI.
2. Instructions for medical device use will be provided as part of the Study Materials 
provided to investigators and sites.


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3. All device deficiencies (including malfunction, use error, and inadequate labelling) shall 
be documented and reported by the investigator throughout the clinical investigation (see 
Section 8.3.7) and appropriately managed by the sponsor.
4. Each device will be labelled according to the country’s regulatory requirements.
6.2.
Preparation/Handling/Storage/Accountability
1. The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received and any discrepancies are 
reported and resolved before use of the study intervention.
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study intervention 
must be stored in a secure, environmentally controlled, and monitored (manual or 
automated) area in accordance with the labeled storage conditions with access limited to 
the investigator and authorized site staff.
3. The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(that is, receipt, reconciliation, and final disposition records).
4. Further guidance and information for the final disposition of unused study interventions 
are provided separately.
Note: 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 an open-label randomized study. Potential bias will be reduced by central randomization. 
On Day 1, participants will be assigned a unique number (randomization number). The 
randomization number encodes the participant’s assignment, within their weight stratification 
category, to one of the 2 possible delivery devices (PFS or AI) and 3 possible injection sites 
(arm, thigh, or abdomen), according to the randomization schedule generated prior to the study 
by the Statistics Department at Covance. Each participant will be dispensed study intervention 
labeled with his/her unique randomization number. 
6.4.
Study Intervention Compliance
Participants are dosed at the site; they will receive study intervention directly from the 
investigator or designee, under medical supervision. The date, time, and location of each dose 
administered in the clinic will be recorded in the source documents and recorded in the electronic 
case report form (eCRF). The dose of study intervention and study participant identification will 
be confirmed at the time of dosing by a member of the study site staff other than the person 
administering the study intervention. 


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6.5.
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. No more than 3 g of acetaminophen will be permitted 
in any 24-hour period. Inclusion of participants on any other concomitant medication (eg, statins 
and anti-hypertensives) is contingent upon approval following consultation with the sponsor.
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

dates of administration including start and end dates

dosage information including dose and frequency for concomitant therapy of 
special interest.
The Lilly clinical pharmacologist (CP) or clinical research physician (CRP) 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 or CRP.
6.6.
Dose Modification
Not applicable for this single-dose study. 
6.7.
Intervention after the End of the Study
Not applicable for this study.


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7.
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal
7.1.
Discontinuation of Study Intervention
Not applicable for this single-dose study. 
7.2.
Participant Discontinuation/Withdrawal from the Study
A participant may withdraw from the study:

at any time at his/her own request 

at the request of his/her designee (for example, parents or legal guardian)

at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons

if the participant becomes pregnant during the study

if enrolled in any other clinical study involving an investigational product or 
enrollment in any other type of medical research judged not to be 
scientifically or medically compatible with this study
Discontinuation is expected to be uncommon.
At the time of discontinuing from the study, if possible, an early discontinuation visit should be 
conducted, as shown in the SoA (Section 1.3). See SoA for data to be collected at the time of 
study discontinuation and follow-up and for any further evaluations that need to be completed. 
The participant will be permanently discontinued from the study at that time.
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, he/she may request destruction of any samples taken and not tested,
and the investigator must document this in the site study records.
7.2.1.
Discontinuation of Inadvertently Enrolled Participants
If the sponsor or investigator identify a participant who did not meet enrollment criteria and was 
inadvertently enrolled, then the participant should be discontinued unless there are extenuating 
circumstances that make it medically necessary for the participant to continue in the study. 
If the investigator and the sponsor CP agree it is medically appropriate to continue, the 
investigator must obtain documented approval from the sponsor CP to allow the inadvertently 
enrolled participant to continue in the study. The documented approval must contain the 
benefit/risk assessment and a robust clinical justification that continuing in the study will not 
jeopardize the participant’s safety. All inadvertently enrolled participants will complete safety 
follow-up as outlined in Section 1.3 (SoA), Section 8.2 (Safety Assessments), and Section 8.3
(Adverse Events and Serious Adverse Events) of the protocol.


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7.3.
Lost to Follow-up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. Site personnel are expected to 
make diligent attempts to contact participants who fail to return for a scheduled visit or were 
otherwise unable to be followed up by the site.


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8.
Study Assessments and Procedures
Study procedures and their timing are summarized in the SoA (Section 1.3). 
Protocol waivers or exemptions are not allowed.
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 upon emerging clinical information. The scheduled time points may be subject to minor 
alterations; however, the actual time must be correctly recorded in the eCRF. 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
A complete physical examination will be conducted on Day -1 and will include, at a minimum, 
assessments of the cardiovascular, respiratory, gastrointestinal, and neurological systems. Height 
and weight will also be measured and recorded at screening.
A symptom-directed physical examination will be performed at other visits, 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 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.
Unscheduled orthostatic vital signs should be assessed, if possible, during any AE of dizziness or 
posture-induced symptoms. Additional vital signs may be measured during the study, if 
warranted. 
If orthostatic measurements are required, participants should be supine for at least 5 minutes and 
stand for at least 3 minutes.
If the participant feels unable to stand, supine vital signs only will be recorded. 
8.2.3.
Electrocardiograms
For each participant, a single 12-lead digital ECG will be collected according to the SoA 
(Section 1.3). Electrocardiograms 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. Electrocardiograms may be obtained at additional 
times, when deemed clinically necessary. All ECGs recorded should be stored at the 
investigational site.
Electrocardiograms will be interpreted by a qualified investigator (the physician or qualified 
designee) at the site as soon after the time of ECG collection as possible, and ideally while the 
participant is still present, to determine whether the participant meets entry criteria at the relevant 
visit(s) and for immediate participant management, should any clinically relevant findings be 
identified. 
Any new clinically relevant finding should be reported as an AE.
8.2.4.
Clinical Safety Laboratory Assessments
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 report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the eCRF. 
The laboratory reports must be filed with the source documents. 
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 CP.
If such values do not return to normal/baseline within a period of time judged reasonable by the 
investigator, the etiology should be identified and the sponsor notified.
All protocol-required laboratory assessments, as defined in Appendix 2 (Section 10.2), must be 
conducted in accordance with the laboratory manual and the SoA.
If laboratory values from non-protocol-specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 


C O N FI D E N TI A L
Pr ot oc ol  n u m ber I 6 T-M C -A M B W
3 1
cli nicall y si g nifica nt b y t he i n vestigat or ( f or e xa m ple, S A E or A E), t he n t he res ults must be 
rec or de d i n t he eC R F .
If a ce ntral ve n d or is use d f or t he st u d y, Lill y or its desig nee will  pr o vi de t he i n vesti gat or wit h 
t he res ults of la b orat or y tests a nal yze d b y a ce ntral ve n d or.
8. 2. 4. 1.
T u berc ul osis Testi n g
P arti cip a nts will be teste d as i n dicate d i n t he S o A ( Secti o n 1. 3 ) for e vi de nce of acti ve or late nt 
T B usi n g t he Q ua nt i F E R O N-T B G ol d test . If t he test is i n deter mi nate, 1 retest is all o we d. If t he 
retest is i n deter mi nate, t he parti ci pa nt will be e xcl u de d fr o m t he st u d y.
P arti cip a nts w h o ha ve ha d h o use h o l d c o ntact wit h a pers o n wit h acti ve T B m ust be e xcl u de d, 
u nless a p pr o priate a n d d oc u me nte d pr o p h yla xis treat me nt f or T B has bee n c o m p lete d.
P articip a nts wi t h a n y hist or y of acti ve T B are e xcl u de d fr om t he st u d y, re gar dless of pre vi o us or 
c urre nt T B treat me nts.
8. 2. 5.
Ot her Tests
8. 2. 5. 1.
I njecti o n-Site Re acti o ns
Alt h o u g h t here will be n o pr os pecti ve c ollect i on of I S R i nf or mati on, s p o nta ne o usl y  re p orte d 
I S Rs b y t he participa nt will  be rec or de d as A Es, with t he I S R C R F use d t o c ollect s u p ple me ntal 
data o n t he f o ll owi n g s pecific fi n di n gs:

i n d urati o n, 

pai n, 

e de ma, 

pr uri t us, a n d 

er yt he ma.
T he fi n di n gs of I S R f or a s pecific i njecti o n will be ca pt ure d as a si n gle A E of  inject i on- sit e 
reactio n , if 1 or m o re t ha n 1 of t he fi n di n gs is p ositi ve, a n d t he se verity t hat is rec or de d o n t he 
I S R A E f or m will be t he hi g hest se verity acr oss t he fi n di n gs at eac h a p plica ble visit.
If i njecti on- site pai n is re p orte d at a n y time d uri n g t he st u d y , t he i nte nsity of  pai n will be
q ua nt ifie d usi n g t he 1 0 0-m m vali date d p ai n vis ual a nal o g scale ( V A S) . T he V A S is a
well -vali date d t o ol ( Willia ms o n a n d H o g gart 2 0 0 5) t o assess i nject i on- site pai n; it is prese nte d as
a 1 0 0-m m li ne a nc h ore d b y ver bal descri pt ors, us uall y “ n o pai n ”
a n d “ w orst ima gi na ble
pai n. ”
T he parti ci pa nt will be as ke d t o rate a n y  pai n at t he i njecti on site o n a scale of 0 t o 1 0 0 
o n t he li ne as s o o n as is practical f oll o wi n g re p orti n g of t he e ve nt.
I njecti on -site assess me nts s h o uld be c o n d ucte d at t he ne xt pla n ne d visit f o ll owi n g t he re p orti n g
of  a n i njecti on- r elate d A E.
8. 2. 5. 2.
Blee di n g/ Br uisi n g Assess me nt
T he prese nce of visi ble blee di n g / br uisi n g at t he i njectio n si te will be rec or de d o n t he e C R F as 
a p plica ble a n d will be rec or de d as a n A E if j u d ge d t o be m ore se vere t ha n e x pecte d wit h a 
t ypical S C a d mi nistrati o n. 


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A bandage may be placed on the injection site after assessment.
8.2.6.
Safety Monitoring
The Lilly CP or clinical research physician/scientist 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.
When appropriate, the Lilly CP or CRP will consult with the functionally independent Global 
Patient Safety medical physician or clinical research scientist.
8.2.6.1.
Hepatic Safety
Close hepatic monitoring
Laboratory tests (Appendix 6, Section 10.6), including alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBL), and direct bilirubin, 
should be repeated within 48 to 72 hours if possible with additional testing for 
gamma-glutamyltransferase and creatine kinase, to confirm the abnormality and to determine if it 
is increasing or decreasing, if 1 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 ≥2× baseline (except for participants with 
Gilbert’s syndrome)
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 CP. At a minimum, this evaluation should include physical examination and 
a thorough medical history, including symptoms, recent illnesses (for example, 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. 


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Subsequently, the frequency of monitoring may be lowered to once every 1 to 2 weeks, if the 
participant’s clinical condition and lab 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 1
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/symptoms*, 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/symptoms*, or
ALT or AST ≥3× baseline
ALP ≥1.5× ULN
ALP ≥2× baseline
TBL ≥1.5× ULN
TBL ≥1.5× baseline (except for participants with Gilbert’s 
syndrome) 
* Hepatic signs/symptoms are severe fatigue, nausea, vomiting, right upper quadrant abdominal 
pain, fever, rash, and/or eosinophilia >5%.
At a minimum, this evaluation should include physical examination and a thorough medical 
history, as outlined above, as well as tests for prothrombin time - international normalized ratio 
(PT-INR); tests for viral hepatitis A, B, C, or E; tests for autoimmune hepatitis; and an abdominal 
imaging study (for example, ultrasound or computerized tomography [CT] scan). 
Based on the participant’s history and initial results, further testing should be considered in 
consultation with the Lilly-designated CP, including tests for hepatitis D virus (HDV), 
cytomegalovirus (CMV), Epstein-Barr virus (EBV), acetaminophen levels, acetaminophen 
protein adducts, urine toxicology screen, Wilson’s disease, blood alcohol levels, urinary ethyl 
glucuronide, and serum phosphatidylethanol. Based on the circumstances and the investigator’s 
assessment of the participant’s clinical condition, the investigator should consider referring the 
participant for a hepatologist or gastroenterologist consultation, magnetic resonance 
cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), 
cardiac echocardiogram, or a liver biopsy. 
Additional hepatic data collection (hepatic safety eCRF) in study participants who have 
abnormal liver tests during the study 
Additional hepatic safety data collection in the hepatic safety eCRF should be performed in study 
participants who meet 1 or more of the following 5 conditions:


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1. Elevation of serum ALT to ≥5× ULN on 2 or more consecutive blood tests (if baseline 
ALT <1.5× ULN)

In participants with baseline ALT ≥1.5× ULN, the threshold is ALT ≥3× baseline 
on 2 or more consecutive tests
2. Elevated TBL to ≥2× ULN (if baseline TBL <1.5× ULN) (except for cases of known 
Gilbert’s syndrome)

In participants with baseline TBL ≥1.5× ULN, the threshold should be TBL ≥2x 
baseline
3. Elevation of serum ALP to ≥2× ULN on 2 or more consecutive blood tests (if baseline 
ALP <1.5× ULN)

In participants with baseline ALP ≥1.5× ULN, the threshold is ALP ≥2× baseline 
on 2 or more consecutive blood tests
4. Hepatic event considered to be an SAE
5. Discontinuation of study drug due to a hepatic event 
Note: The interval between the 2 consecutive blood tests should be at least 2 days.
8.3.
Adverse Events and Serious Adverse Events
The definitions of device-related safety events, (adverse device effects [ADEs], unanticipated 
adverse device effects [UADEs], and serious adverse device effects [SADEs]), can be found in 
Appendix 8 (Section 10.8). Product complaints are covered in Section 8.3.7.
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant's legally authorized representative).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up AEs that are serious, considered related to the study intervention or study procedures, or that 
caused the participant to discontinue the 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.
8.3.1.
Time Period and Frequency for Collecting AE and SAE Information
All AEs and SAEs will be collected from the time of signing of the ICF until participation in 
study has ended.
Adverse events that begin before the start of study intervention but after signing of the ICF will 
be recorded on the Adverse Event eCRF.
Although all AEs after signing the ICF are recorded by the site in the eCRF/electronic data entry, 
SAE reporting to sponsor begins after the participant has signed the ICF and has received 
mirikizumab. However, if an SAE occurs after signing the ICF, but prior to receiving 
mirikizumab, it needs to be reported ONLY if it is considered reasonably possibly related to 
study procedures.


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All SAEs reported after a participant has received mirikizumab will be recorded and reported to 
the sponsor or designee immediately and under no circumstance should this exceed 24 hours, as 
indicated in Appendix 3 (Section 10.3). The investigator will submit any updated SAE data to 
the sponsor or designee within 24 hours of it being available. 
Investigators are not obligated to actively seek AEs or SAEs after conclusion of the study 
participation. However, if the investigator learns of any SAE, including a death, at any time after 
a participant has been discharged from the study, and he/she considers the event to be reasonably 
related to the study intervention or study participation, the investigator must promptly notify the 
sponsor.
8.3.2.
Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Appendix 3 (Section 10.3).
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about AE
occurrences.
8.3.3.
Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts. All SAEs, and AEs of special interest (as defined in Section 8.3.6) 
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). Further information on follow-up procedures is 
provided in Appendix 3 (Section 10.3).
8.3.4.
Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a study 
intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, Institutional Review Boards (IRB)/Independent Ethics Committees 
(IEC), and investigators.
An investigator who receives an investigator safety report describing an SAE or other specific 
safety information (for example, summary or listing of SAEs) from the sponsor will review and 
then file it along with the IB and will notify the IRB/IEC, if appropriate according to local 
requirements.
8.3.5.
Pregnancy
Details of all pregnancies in female participants will be collected after the start of study 
intervention and until study end.
If a pregnancy is reported, the investigator should inform the sponsor within 24 hours of learning 
of the pregnancy and should follow the procedures outlined in Appendix 10.4.


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Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, congenital
anomalies, ectopic pregnancy) are considered SAEs.
Pregnancy (maternal or paternal exposure to study intervention) does not meet the definition of 
an AE. However, to fulfill regulatory requirements, any pregnancy should be reported following 
the SAE process described in Appendix 10.4 (Section 10.4) to collect data on the outcome for 
both mother and fetus.
8.3.6. Adverse Events of Special Interest 
The following AEs of special interest will be used to determine the safety and tolerability of 
mirikizumab administered through PFS or AI in this clinical study:

infection

systemic allergic/hypersensitivity reactions.
If infections or allergic/hypersensitivity reactions are reported, site staff will provide details on 
these events as instructed on the eCRF. A PK, immunogenicity, and hypersensitivity cytokine 
panel (Appendix 7, Section 10.7) will be collected when possible for any participant who 
experiences an AE of systemic allergic/hypersensitivity reaction during the study.
8.3.7. Product Complaints
A product complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, durability, reliability, safety, effectiveness, or performance of a 
trial intervention. 
The sponsor collects product complaints on study interventions and drug delivery systems used 
in clinical studies in order to ensure the safety of study participants, monitor quality, and to 
facilitate process and product improvements.
Participants will be instructed to contact the investigator as soon as possible if he or she has a 
complaint or problem with the investigational product or drug delivery system so that the 
situation can be assessed.
Note: AEs/SAEs that are associated with a product complaint will also follow the processes 
outlined in Section 8.3.3 and Appendix 3 (Section 10.3) of the protocol.
8.3.7.1.
Time Period for Detecting Product Complaints
Product complaints that result in an AE will be detected, documented, and reported to the 
sponsor during all periods of the study in which the drug/device is used.
If the investigator learns of any product complaint at any time after a participant has been 
discharged from the study, and such incident is considered reasonably related to a 
drug/device provided for the study, the investigator will promptly notify the sponsor. The 
method of documenting Medical Device Deficiency is provided in Appendix 8 
(Section 10.8). 
8.3.7.2. Prompt Reporting of Product Complaints to Sponsor
Product complaints will be reported to the sponsor within 24 hours after the investigator 
becomes aware of the complaint.


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Device deficiencies will be reported to the sponsor within 72 hours after the investigator 
determines that the event meets the definition of a medical device deficiency.
The Product Complaint Form will be sent to the sponsor by the method provided in the 
form. If the primary method is unavailable, then an alternative method provided in the 
form should be utilized.
8.3.7.3.
Follow-up of Product Complaints
Follow-up applies to all participants.
The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the product 
complaint.
New or updated information will be recorded on the originally completed form with all 
changes signed and dated by the investigator and submitted to the sponsor.
8.3.7.4. Regulatory Reporting Requirements for Product Complaints
The investigator will promptly report all device related product complaints to the sponsor 
to facilitate timely regulatory reporting.
As required by local regulations, the investigator will report to their IRB/IEC any 
unanticipated adverse device effect or UADE (unanticipated problem that resulted in an 
SAE), or any product complaint that could have led to an SAE had precautions not been 
taken.
8.4.
Treatment of Overdose
For this study, any dose of mirikizumab greater than 200 mg will be considered an overdose.
The sponsor does not recommend specific treatment for an overdose. 
In the event of an overdose, the investigator/treating physician should:
1. Contact the CP immediately.
2. Closely monitor the participant for any AE/SAE and laboratory abnormalities.
8.5.
Pharmacokinetics
Blood samples of approximately 3 mL will be collected for measurement of serum
concentrations of mirikizumab as specified in the SoA (Section 1.3.). 
A maximum of 3 samples may be collected at additional time points during the study if 
warranted and agreed upon between the investigator and the sponsor. The timing of 
sampling may be altered during the course of the study based on newly available data to 
ensure appropriate monitoring. 
Instructions for the collection and handling of biological samples will be provided by the 
sponsor. The actual date and time (24-hour clock time) of each sample will be recorded.


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8.5.1.
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 (ELISA) 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, and/or bioanalytical method cross-validation.
8.6.
Pharmacodynamics
Pharmacodynamic parameters are not evaluated in this study.
8.7.
Genetics
A blood sample for DNA isolation will be collected from participants. 
See Appendix 5 (Section 10.5) for information regarding genetic research. 
8.8.
Biomarkers
Biomarkers are not evaluated in this study.
8.9.
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.
Treatment-emergent ADAs are defined in Section 9.4.4.
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 will 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.
8.10.
Health Economics
This section is not applicable for this study. 


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9.
Statistical Considerations
9.1.
Statistical Hypotheses
The primary objective of this study is to evaluate PK following administration using PFS and AI. 
9.2.
Sample Size Determination
Up to approximately 240 participants may be enrolled so that approximately 216 participants 
(108 in the PFS [reference] group and 108 in the AI [test] group) complete the study. 
A sample size of 108 participants per treatment group will provide approximately 90% power 
that the 90% confidence interval (CI) of the geometric mean ratio of maximum observed drug 
concentration (Cmax) and area under the concentration versus time curve (AUC) between groups 
will fall within 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 percent coefficients of 
variation (%CV) of Cmax and AUC are approximately 40% (based on previous trials), the 
expected ratio of geometric means is 1.07, and the %CV are the same for participants from each 
treatment group.
Participants who are randomized but not administered treatment and participants who do not 
complete PK sampling through Day 85 may be replaced to ensure that approximately 
216 participants (108 in each group) complete the study.
9.3.
Populations for Analyses
The following populations are defined:
Population
Description
Enrolled
All participants randomly assigned to study intervention.
Safety
All participants randomly assigned to study intervention and who 
receive study intervention. Participants will be analyzed 
according to the intervention they actually received.
Pharmacokinetic Analysis
All enrolled participants who receive a full dose of study 
intervention and have evaluable PK data.
9.3.1.
Study Participant Disposition
A detailed description of participant disposition will be provided at the end of the study. 
9.3.2.
Study Participant characteristics
The participants’ age, sex, weight, height, BMI, race, and other demographic characteristics will 
be recorded and summarized using descriptive statistics.
9.4.
Statistical Analyses
Statistical analysis of this study will be the responsibility of the sponsor or its designee.


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Any change to the data analysis methods described in the protocol will require an amendment,
only if it changes a principal feature of the protocol. Any other change to the data analysis 
methods described in the protocol, and the justification for making the change, will be described 
in the statistical analysis plan (SAP) and the clinical study report. Additional exploratory 
analyses of the data will be conducted as deemed appropriate.
The SAP will be finalized prior to the first participant visit and it will include a more technical 
and detailed description of the statistical analyses described in this section. This section is a 
summary of the planned statistical analyses of the most important endpoints including primary 
and key secondary endpoints.
9.4.1. General Considerations
Additional exploratory analyses of the data will be conducted as deemed appropriate. Study 
results may be pooled with the results of other studies for population PK analysis purposes to 
avoid issues with post hoc analyses and incomplete disclosures of analyses.
No adjustments for multiple comparisons will be made.
9.4.2.
Pharmacokinetic Analyses
9.4.2.1.
Pharmacokinetic Parameter Estimation
Pharmacokinetic parameter estimates for mirikizumab will be calculated using standard 
noncompartmental methods of analysis.
The primary parameters for analysis will be the Cmax, AUC 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]) of mirikizumab. The secondary parameter for analysis will be the 
time to maximum observed drug concentration (tmax) of mirikizumab. Other noncompartmental 
parameters, such as half-life associated with the terminal rate constant (t1/2), apparent total body 
clearance of drug calculated after extra-vascular administration (CL/F), and apparent volume of 
distribution during the terminal phase after extra-vascular administration (Vz/F), may be 
reported.
9.4.2.2.
Pharmacokinetic Statistical Inference
The Cmax, AUC(0-∞), and AUC(0-tlast), will be log-transformed and analyzed using a linear
fixed-effects model. The model will include delivery device, injection location, and weight 
stratification as fixed effects. The dosing regimen differences between AI and PFS 
administrations 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 delivery devices and 
then between the 3 injection locations.
The 2 delivery devices will be considered bioequivalent if the 90% CIs of the ratio of geometric 
least squares means fall within 0.8 to 1.25. 
The tmax of mirikizumab between AI and PFS administrations 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.


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Additional PK analyses may be conducted if deemed appropriate.
9.4.3.
Safety Analyses
9.4.3.1.
Clinical Evaluation of Safety
All study intervention and protocol procedure AEs and product complaints will be listed, and, if 
the frequency of events allows, safety data will be summarized using descriptive methodology.
The incidence of symptoms for each treatment will be presented by severity and by association
with study intervention as perceived by the investigator. Symptoms reported to occur prior to 
study entry will be distinguished from those reported as new or increased in severity during the 
study. Each symptom will be classified by the most suitable term from the medical regulatory 
dictionary.
The number of study intervention- and device-related SAEs and any related product complaints 
will be reported.
9.4.3.2.
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 analyses will be performed if
warranted upon review of the data.
9.4.4.
Evaluation of Immunogenicity
Results from immunogenicity testing will be listed. The frequency and percentage of participants 
with preexisting ADAs and with TE-ADAs that are positive (TE-ADA+) to mirikizumab will be 
tabulated. Treatment-emergent ADAs are defined as those with a titer 2-fold (1 dilution) or 
greater than the minimum required dilution if no ADAs were detected at baseline (treatment-
induced ADA) or those with a 4-fold or greater (2 dilutions) increase in titer compared to 
baseline if ADAs were detected at baseline (treatment-boosted ADA). For the TE-ADA+ 
participants, the distribution of maximum titers will be described. The frequency of neutralizing 
antibodies will also be tabulated in TE-ADA+ participants.
The relationship between the presence of antibodies and PK and safety parameters of 
mirikizumab may be assessed.
9.5.
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.
9.6.
Data Monitoring Committee (DMC)
No data monitoring committee is required for this study. 


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10.
Supporting Documentation and Operational Considerations
10.1.
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations
10.1.1.
Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines 
including the Declaration of Helsinki and Council for International 
Organizations of Medical Sciences (CIOMS) International Ethical 
Guidelines

Applicable International Council for Harmonisation (ICH) Good Clinical 
Practice (GCP) Guidelines

Applicable laws and regulations
The protocol, protocol amendments, ICF, IB, and other relevant documents (such as
advertisements) must be submitted to an IRB/IEC by the investigator and reviewed and 
approved by the IRB/IEC before the study is initiated.
Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an 
immediate hazard to study participants.
The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/IEC 
annually or more frequently in accordance with the requirements, policies, 
and procedures established by the IRB/IEC

Notifying the IRB/IEC of SAEs and/or UADEs or other significant safety 
findings as required by IRB/IEC procedures

Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 Code of Federal Regulations (CFR), ICH guidelines, 
the IRB/IEC, European regulation 536/2014 for clinical studies (if 
applicable), and all other applicable local regulations
Investigator sites are compensated for participation in the study as detailed in the clinical 
trial agreement (CTA).
10.1.2.
Informed Consent Process
The investigator or his/her representative will explain the nature of the study, including the risks 
and benefits, to the participant or his/her legally authorized representative and answer all 
questions regarding the study.
Participants must be informed that their participation is voluntary. Participants or their legally 
authorized representative will be required to sign a statement of informed consent that meets the 
requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance Portability and 
Accountability Act (HIPAA) requirements, where applicable, and the IRB/IEC or study center.


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The medical record must include a statement that written informed consent was obtained before 
the participant was entered in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF.
Participants must be re-consented 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. 
10.1.3.
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 his/her 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 his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities.
The sponsor has processes in place to ensure 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.
10.1.4.
Dissemination of Clinical Study Data
Communication of Suspended or Terminated Dosing
If a decision is taken to suspend or terminate dosing in the trial due to safety findings, this 
decision will be communicated by Lilly to all investigators (for example, by phone and/or 
email) as soon as possible. It will be a requirement that investigators respond upon 
receipt to confirm that they understand the communication and have taken the appropriate 
action prior to further dosing any participants with study intervention. Any investigator 
not responding will be followed up by Lilly personnel prior to any further planned 
dosing. If a dose is planned imminently, Lilly personnel will immediately, and 
continually, use all efforts to reach investigators until contact is made and instructions 
verified.
Reports
The sponsor will disclose a summary of study information, including tabular study 
results, on publicly available websites where required by local law or regulation.
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.


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10.1.5.
Data Quality Assurance
Investigator responsibilities
All participant data relating to the study will be recorded on printed or electronic CRF 
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. Source data may include laboratory tests, medical 
records, and clinical notes.
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents.
Data management and monitoring
The Monitoring Plan includes

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

requirements

handling of noncompliance issues 

monitoring techniques.
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).
Study monitors will perform ongoing source data verification to confirm that data entered 
into the eCRF 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 retention and audits
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 CTA unless local 
regulations or institutional policies require a longer retention period. 
No records may be destroyed during the retention period without the written approval of 
the sponsor. No records may be transferred to another location or party without written 
notification to the sponsor.


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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 sponsor 
or its representatives, and/or regulatory agencies at any time. Investigators will be given 
notice before an audit occurs.
Data Capture System
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness 
of the data reported to the sponsor.
An electronic data capture (EDC) system will be used in this study for the collection of CRF 
data. The investigator maintains a separate source for the data entered by the investigator or 
designee into the sponsor-provided EDC system. The investigator is responsible for the 
identification of any data to be considered source and for the confirmation that data reported are 
accurate and complete by signing the CRF.
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 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 sponsor will be encoded and stored in the global 
product complaint management system.
10.1.6.
Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site.
Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on the 
study. Also, current medical records must be available.
The definition of what constitutes source data can be found in 10.1.6. 
10.1.7.
Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
Site Closure
The sponsor 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.


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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:

Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP 
guidelines

Inadequate recruitment of participants by the investigator

Discontinuation of further study intervention development.
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The investigator shall promptly inform the participant and assures 
appropriate participant therapy and/or follow-up.
10.1.8.
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 will be performed by the central laboratory or by the local laboratory, as detailed in the 
table below.
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 each laboratory safety report.


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Safety Laboratory Testsa
Hematology
Clinical Chemistry
Hematocrit
Sodium
Hemoglobin
Potassium
Erythrocyte count (RBC)
Bicarbonate
Mean cell volume 
Chloride
Mean cell hemoglobin 
Calcium
Mean cell hemoglobin concentration 
Phosphorous
Leukocytes (WBC) 
Glucose (random)
BUN
Cell morphology
Uric acid
Absolute counts and % of:
Total cholesterol
Neutrophils
Total protein
Lymphocytes
Albumin
Monocytes
Total bilirubin
Eosinophils
Direct bilirubin
Basophils
ALP
Platelets
AST
ALT
Urinalysis
Creatinine
Specific gravity
pH
Protein
Other Tests
Glucose
Ethanol testingc
Ketones
Urine drug screenc
Bilirubin
Pregnancy test (females only)d
Urobilinogen
FSH (females only)b
Blood
QuantiFERON®-TB Goldb
Nitrite
Microscopy (if dipstick abnormal; blood, protein, 
nitrites, or leukocyte esterase positive)
Serology
Hepatitis B surface antigenb
Hepatitis B core antibodyb
Hepatitis C antibodyb
HIVb
Abbreviations: ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; 
BUN = blood urea nitrogen; FSH = follicle-stimulating hormone; HIV = human immunodeficiency virus; 
RBC = red blood cell; TB = tuberculosis; WBC = white blood cell.
a. Performed locally at Screening and Day -1 and centrally at Day 1 predose and all postdose timepoints unless 
otherwise stated.
b
Performed at screening only.
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-AMBW Sampling Summary
Purpose
Maximum Blood Volume 
per Sample (mL)
Number of Blood 
Samples
Total Volume 
(mL)
Screening testsa
45
1
45
Local clinical laboratory 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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10.3.
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting
10.3.1.
Definition of AE
AE Definition

An AE is any untoward medical occurrence in a patient or clinical study participant, 
temporally associated with the use of study intervention, whether or not considered 
related to the study intervention.

NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g., ECG, radiological scans, vital signs measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator (i.e., not related to progression of 
underlying disease).

Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.

New conditions 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.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent. Such overdose should be reported regardless of sequelae.
Events NOT Meeting the AE Definition

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition.

Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).


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
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.
10.3.2.
Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (e.g., hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease).
An SAE is defined as any untoward medical occurrence that, at any dose:
a.
Results in death
b.
Is life-threatening
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, which 
hypothetically might have caused death, if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization

In general, hospitalization signifies that the participant has been admitted to hospital
for observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during hospitalization 
are AEs. If a complication prolongs hospitalization or fulfills any other serious criteria, 
the event is serious. When in doubt as to whether “hospitalization” occurred or was 
necessary, the AE should be considered serious.

Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from baseline is not considered an AE.
d.
Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, 
and accidental trauma (e.g., sprained ankle) which may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE reporting 
is appropriate in other situations such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
participant or may require medical or surgical intervention to prevent one of the other 


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outcomes listed in the above definition. These events should usually be considered 
serious.

Examples of such events include invasive or malignant cancers, intensive treatment in 
an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency or 
drug abuse.
10.3.3.
Recording and Follow-up of AE and/or SAE
AE and SAE Recording

When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory reports, and diagnostics 
reports) related to the event.

The investigator will then record all relevant AE/SAE information in the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to sponsor or designee in lieu of completion of the AE/SAE CRF page.

There may be instances when copies of medical records for certain cases are requested 
by sponsor or designee. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to sponsor or designee.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported during 
the study and assign it to 1 of the following categories:

Mild: An event that is easily tolerated by the participant, causing minimal discomfort 
and not interfering with everyday activities.

Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.

Severe: An event that prevents normal everyday activities. An AE that is assessed as 
severe should not be confused with a SAE. Severe is a category utilized for rating the 
intensity of an event; both AEs and SAEs can be assessed as severe.
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE.


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
The investigator will consider any AEs, SAEs, and clinically important laboratory 
abnormalities as related to the study intervention unless there is clear evidence that the 
event is not related.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the IB and/or Product Information, for marketed 
products, in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred, and the investigator has 
minimal information to include in the initial report to sponsor or designee. However, it 
is very important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to sponsor or designee.

The investigator may change his/her opinion of causality in light of follow-up 
information and send a SAE follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
Follow-up of AEs and SAEs

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by sponsor or 
designee to elucidate the nature and/or causality of the AE or SAE as fully as possible. 
This may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other health care professionals.

If a participant dies during participation in the study or during a recognized follow-up 
period, the investigator will provide sponsor or designee with a copy of any 
post-mortem findings including histopathology. 

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to sponsor or designee within 24 
hours of receipt of the information.
10.3.4.
Reporting of SAEs
SAE Reporting via SAE Report

Facsimile transmission of the SAE paper CRF 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 CRF pages within the designated reporting time frames.


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
Contacts for SAE reporting can be found in the SAE report.


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10.4.
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information
Definitions:
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile (see below).
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study intervention, additional evaluation should be considered.
Women in the following categories are considered not of childbearing potential:
A. infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, bilateral 
salpingectomy, bilateral tubal occlusion, or bilateral tubal ligation), congenital anomaly 
such as mullerian agenesis; or 
B. post-menopausal – defined as either
i.
A woman at least 40 years of age with an intact uterus, not on hormone therapy, who 
has cessation of menses for at least 1 year without an alternative medical cause, AND 
a follicle-stimulating hormone >40 mIU/mL; or
ii.
A woman 55 or older not on hormone therapy, who has had at least 12 months of 
spontaneous amenorrhea; or
iii.
A woman at least 55 years of age with a diagnosis of menopause prior to starting 
hormone-replacement therapy.
Contraception Guidance:
Females
All female participants must test negative for pregnancy prior to initiation of treatment, as 
indicated by negative serum pregnancy test at the screening visit and Day -1 prior to exposure to 
mirikizumab

Women of childbearing potential who are abstinent (if this is complete abstinence, 
as their preferred and usual lifestyle) or in a same-sex relationship (as part of their 
preferred and usual lifestyle) must agree to either remain abstinent or stay in a 
same-sex relationship without sexual relationships with males. Periodic 
abstinence (eg, calendar, ovulation, symptothermal, postovulation methods), 
declaration of abstinence for the duration of the study, and withdrawal are not 
acceptable methods of contraception. 

Otherwise, women of childbearing potential participating in this study must agree 
to use 1 highly effective method (<1% failure rate) of contraception or a 
combination of 2 effective methods of contraception from the time of signing the 
ICF to 12 weeks following dosing with the study intervention)
o
Either 1 highly effective method of contraception (such as combination 
oral contraceptives, implanted contraceptives, an intrauterine device, or 
vaginal ring) or a combination of 2 effective methods of contraception 


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(such as male or female condoms with spermicide, diaphragms with 
spermicide, or cervical sponges) will be used. The participant may choose 
to use a double-barrier method of contraception. Barrier protection 
methods without concomitant use of a spermicide are not reliable or 
acceptable methods. Thus, each barrier method must include use of a 
spermicide. It should be noted that the use of male and female condoms 
as a double-barrier method is not considered acceptable due to the high 
failure rate when these methods are combined

Women not of childbearing potential may participate.
Males
No male contraception required, except in compliance with specific local government study 
requirements.
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 obtaining the necessary signed informed consent from the pregnant female partner directly, 
the investigator will record pregnancy information on the appropriate form and submit it to the 
sponsor within 24 hours of learning of the partner’s pregnancy. 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 
including fetal status (presence or absence of anomalies) and 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, including 
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 still birth (occurring 
at greater than 20 weeks gestational age) is always considered to be an SAE and will be reported 
as such. 


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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 8.3.4. 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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10.5.
Appendix 5: Genetics
Use/Analysis of DNA
Genetic variation may impact a participant’s response to study intervention, susceptibility to, and 
severity and progression of disease. Variable response to study intervention may be due to 
genetic determinants that impact drug absorption, distribution, metabolism, and excretion; 
mechanism of action of the drug; disease etiology; and/or molecular subtype of the disease being 
treated. Therefore, where local regulations and IRB/IEC allow, a blood sample will be collected 
for DNA analysis from consenting participants.
The DNA samples will be used for research related to mirikizumab or IL-23-mediated 
autoimmune disease, and related diseases. They may also be used to develop tests/assays 
including diagnostic tests related to mirikizumab and/or interventions of this drug class and 
IL-23-mediated autoimmune disease. Genetic research may consist of the analysis of one or 
more candidate genes or the analysis of genetic markers throughout the genome or analysis of 
the entire genome.
The samples may be analyzed as part of a multi-study assessment of genetic factors involved in 
the response to mirikizumab or study interventions of this class to understand study disease or 
related conditions.
The results of genetic analyses may be reported in the clinical study report or in a separate study 
summary.
The sponsor will store the DNA samples in a secure storage space with adequate measures to 
protect confidentiality.
The samples will be retained while research on mirikizumab continues but no longer than 
15 years or other period as per local requirements.


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10.6.
Appendix 6: Liver Safety: Suggested Actions and Follow-up 
Assessments
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, International Normalized Ratio
(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)
Hepatis 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 d
Anti-actin antibody b
Hepatis C virus (HCV) testing:
Epstein-Barr virus (EBV) testing:
    HCV antibody
    EBV antibody
    HCV RNA d
    EBV DNA d
Hepatitis D virus (HDV) testing:
Cytomegalovirus (CMV) testing:
    HDV antibody
    CMV antibody
Hepatitis E virus (HEV) testing:
    CMV DNA d
    HEV IgG antibody
Herpes simplex virus (HSV) testing:
    HEV IgM antibody
    HSV (Type 1 and 2) antibody 
    HEV RNA d
    HSV (Type 1 and 2) DNA d
Microbiology c
Liver kidney microsomal type 1 (LKM-1) antibody
Culture:
    Blood
    Urine
a
Not required if anti-actin antibody is tested.
b
Not required if anti-smooth muscle antibody (ASMA) is tested.
c
Assayed ONLY by investigator-designated local laboratory; no central testing available.
d
Reflex/confirmation dependent on regulatory requirements, testing availability, or both.


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Protocol number I6T-MC-AMBW
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10.7.
Appendix 7: Recommended Laboratory Testing for Hypersensitivity 
Events
Laboratory assessments should be performed if the participant experiences generalized urticaria 
or if anaphylaxis is suspected.

Collect sample after the participant has been stabilized, and within 1 to 2 hours of the
event; however, samples may be obtained as late as 12 hours after the event as analytes
can remain altered for an extended period of time. Record the time at which the sample
was collected.

Obtain a follow-up sample after approximately 4 weeks.
Clinical Lab Tests for Hypersensitivity Events
Hypersensitivity Tests
Notes
Selected test may be obtained in the event of anaphylaxis or 
systemic allergic/hypersensitivity reactions.
LY3819253 anti-drug 
antibodies 
(immunogenicity/ADA)
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
LY3819253 concentrations 
(PK)
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
Tryptase
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
Urine N-methylhistamine testing is performed in addition to 
tryptase testing. Collect the first void urine following the event. 
Collect a follow-up urine sample after approximately 4 weeks.
Note: If a tryptase sample is obtained more than 2 hours after the 
event (that is, within 2 to 12 hours), or is not obtained because more 
than 12 hours have lapsed since the event, collect a urine sample for 
N-methylhistamine testing.
N-methylhistamine
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
Basophil activation test
Will be performed if a validated assay is available.
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
NOTE: The basophil activation test is an in vitro cell based assay 
that only requires a serum sample. It is a surrogate assay for 
drug-specific IgE but is not specific for IgE.
Complement (C3, C3a and 
C5a)
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
Cytokine panel
Assayed by Lilly-designated laboratory. 
Results will not be provided to the investigative sites.
Abbreviations: IgE = immunoglobulin E; PK = pharmacokinetic.


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10.8.Appendix 8: Medical Device Adverse Events (AEs), Adverse Device 
Effects (ADEs), Serious Adverse Events (SAEs) and Device Deficiencies: 
Definition and Procedures for Recording, Evaluating, Follow-up, and 
Reporting
●
The definitions and procedures detailed in this appendix are in accordance with 
International Organization for Standardization (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.
10.8.1. Definition of AE and ADE
AE and ADE Definition

An AE is defined as any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory finding) in study participants, 
users, or other persons, whether or not related to the investigational 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.

An adverse device effect (ADE) is defined as an adverse event related to the use of an 
investigational medical device. This definition includes any adverse events resulting 
from insufficient or inadequate instructions for use, deployment, implantation, 
installation, or operation; any malfunction of the investigational medical device as well 
as any event resulting from use error or from intentional misuse of the investigational 
medical device.
10.8.2. Definition of SAE, SADE and UADE
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (e.g., hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease).
An SAE is an AE that:
a.
Led to death 
b. Led to serious deterioration in the health of the participant, that either resulted in:
1. A life-threatening illness or injury. 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.
2. A permanent impairment of a body structure or a body function.


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3. Inpatient or prolonged hospitalization. Planned hospitalization for a pre-existing
condition, or a procedure required by the protocol, without serious deterioration in
health, is not considered an SAE.
4. Medical or surgical intervention to prevent life-threatening illness or injury or
permanent impairment to a body structure or a body function
c.
Led to fetal distress, fetal death, or a congenital abnormality or birth defects.
d. Any device deficiency that might have led to serious adverse event if appropriate action
had not been taken, intervention had not occurred, or circumstances had been less
fortunate.
SADE definition

A SADE is defined as an adverse device effect that has resulted in any of the
consequences characteristic of an SAE.
UADE definition

A UADE is a SADE which by its nature, incidence, severity or outcome has not been 
identified in the current version of the risk analysis report (see section 2.3).
10.8.3. Definition of Device Deficiency
Device Deficiency definition

A device deficiency is an inadequacy of a medical device with respect to its identity,
quality, durability, reliability, safety, or performance. Device deficiencies include
malfunctions, use errors, and inadequate labeling.
10.8.4. Recording and Follow-Up of AE and/or SAE and Device Deficiencies
AE, SAE and Device Deficiency Recording

When an AE/SAE/device deficiency occurs, it is the responsibility of the investigator
to review all documentation (e.g., hospital progress notes, laboratory reports, and
diagnostics reports) related to the event.

The investigator will then record all relevant AE/SAE/device deficiency information in
the participant’s medical records, in accordance with the investigator’s normal clinical
practice and on the appropriate CRF or the Product Complaint Form.

It is not acceptable for the investigator to send photocopies of the participant’s medical
records to sponsor or designee in lieu of completion of the AE/SAE/device deficiency
CRF or the Product Complaint Form.

There may be instances when copies of medical records for certain cases are requested
by sponsor or designee. In this case, all participant identifiers, with the exception of the
participant number, will be redacted on the copies of the medical records before
submission to sponsor or designee.


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Protocol number I6T-MC-AMBW
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
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE/SAE reported during the 
study and assign it to one of the following categories:

Mild: An event that is easily tolerated by the participant, causing minimal discomfort 
and not interfering with everyday activities.

Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.

Severe: An event that prevents normal everyday activities. An AE that is assessed as 
severe should not be confused with an SAE. Severe is a category utilized for rating the 
intensity of an event, and both AEs and SAEs can be assessed as severe.

An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE.

The investigator will consider any AEs, SAEs, and clinically important laboratory 
abnormalities as related to the study intervention unless there is clear evidence that the 
event is not related.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the IB in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to sponsor or designee. However, it 
is very important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to sponsor or designee.

The investigator may change his/her opinion of causality in light of follow-up 
information and send a SAE follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.


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Follow-up of AE/SAE

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by sponsor or 
designee to elucidate the nature and/or causality of the AE/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 sponsor or designee with a copy of any 
post-mortem findings including histopathology.

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to sponsor or designee within 
24 hours of receipt of the information.
10.8.5. Reporting of SAEs
SAE Reporting via SAE Report

Facsimile transmission of the SAE paper CRF 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 CRF pages within the designated reporting time frames.

Contacts for SAE reporting can be found in the SAE report.
10.8.6. Reporting of SADEs
SADE Reporting
NOTE: There are additional reporting obligations for medical device incidents that are 
potentially related to SAEs that must fulfill the legal responsibility to notify appropriate 
regulatory authorities and other entities about certain safety information relating to 
medical devices being used in clinical studies.

Any device deficiency that is associated with an SAE must be reported to the sponsor 
within 24 hours after the investigator determines that the event meets the definition of a 
device deficiency.

The sponsor shall review all device deficiencies and determine and document in 
writing whether they could have led to an SAE. These shall be reported to the 
regulatory authorities and IRBs/IECs as required by national regulations.

Contacts for SAE reporting can be found in the SAE report.


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Protocol number I6T-MC-AMBW
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10.8.7. AE, ADE, SAE, SADE Determination Flow Chart
Note: Adverse event reporting for countries other than the USA and EU must follow the 
regulatory and ethical requirements for that country.


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Protocol number I6T-MC-AMBW
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10.9.
Appendix 9: Abbreviations
Term
Definition
ADA
antidrug antibody
ADE
adverse device effect
AE
adverse event
AI
autoinjector
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
CD
Crohn’s disease
CFR
Code of Federal Regulations
CI
confidence interval
Cmax
maximum observed drug concentration
complaint
A complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, purity, durability, reliability, safety or effectiveness, or 
performance of a drug or drug delivery system.
compliance
Adherence to all study-related, good clinical practice (GCP), and applicable regulatory 
requirements.
CP
clinical pharmacologist
CRF
case report form
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
CTA
clinical trial agreement


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CV
coefficient of variation
device deficiencies
Equivalent to product complaint.
ECG
electrocardiogram
eCRF
electronic case report form
EDC
electronic data capture
enroll
The act of assigning a participant to a treatment. Participants who are enrolled in the 
study are those who have been assigned to a treatment.
enter
Participants entered into a study are those who sign the informed consent form directly 
or through their legally acceptable representatives.
GCP
good clinical practice
HIV
human immunodeficiency virus
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonisation
IEC
Independent Ethics Committees
IL
interleukin
Informed consent
A process by which a participant voluntarily confirms his or her willingness to 
participate in a particular study, after having been informed of all aspects of the study 
that are relevant to the participant’s decision to participate. Informed consent is 
documented by means of a written, signed and dated informed consent form.
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
ISR
injection-site reaction
IV
intravenous
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
PFS
pre-filled syringe
PK
pharmacokinetics


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SADE
serious adverse device effect
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
TB
tuberculosis
TBL
total bilirubin level
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.
tmax
time to maximum observed drug concentration
UADE
unanticipated adverse device effect
UC
ulcerative colitis
ULN
upper limit of normal
VAS
visual analog scale


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11.
References
Cornelissen F, Asmawidjaja PS, Mus AM, Corneth O, Kikly K, Lubberts E. IL-23 dependent and 
independent stages of experimental arthritis: no clinical effect of therapeutic IL-23p19 
inhibition in collagen-induced arthritis. PLoS One. 2013;8(2):e57553.
Ruutu M, Thomas G, Steck R, Degli-Esposti MA, Zinkernagel MS, Alexander K, Velasco J, 
Strutton G, Tran A, Benham H, Rehaume L, Wilson RJ, Kikly K, Davies J, Pettit AR, 
Brown MA, McGuckin MA, Thomas R. β-glucan triggers spondylarthritis and Crohn’s 
disease-like ileitis in SKG mice. Arthritis Rheum. 2012;64(7):2211-2222.
Williamson A, Hoggart B. Pain: a review of three commonly used pain rating scales. J Clin 
Nurs. 2005;14(7):798-804.


Leo Document ID = 036c4557-9cc7-4d79-8cea-e5efaa82487d
Approver: 
Approval Date & Time: 14-Aug-2020 04:13:42 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 14-Aug-2020 13:21:23 GMT
Signature meaning: Approved
PPD
PPD

SAP_001.pdf: 
Final, 12 October 2020
Page 1 of 17
STATISTICAL ANALYSIS PLAN
A Bioequivalence Study of Injections of Mirikizumab Solution Using an Investigational 
1-mL Pre-Filled Syringe and an Investigational 1-mL Autoinjector in Healthy Participants
Statistical Analysis Plan Status: Final
Statistical Analysis Plan Date: 12-October-2020
Study Drug: LY3074828
Sponsor Reference: I6T-MC-AMBW
Covance CRU Study: 1000071 - 8442497
Clinical Phase I
Approval Date: 19-Oct-2020 GMT
Approval Date: 19-Oct-2020 GMT


Final, 12 October 2020
Page 2 of 17
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8442497
Sponsor Reference I6T-MC-AMBW
1. TABLE OF CONTENTS
1.
TABLE OF CONTENTS .....................................................................................................2
2.
ABBREVIATIONS..............................................................................................................4
3.
INTRODUCTION ...............................................................................................................6
4.
STUDY OBJECTIVES AND ENDPOINTS ........................................................................6
4.1
Primary Objective and Endpoints ..................................................................................6
4.2
Secondary Objective and Endpoints...............................................................................7
4.3
Exploratory Objectives and Endpoints...........................................................................7
5.
STUDY DESIGN.................................................................................................................7
6.
TREATMENTS...................................................................................................................8
7.
SAMPLE SIZE JUSTIFICATION .......................................................................................8
8.
DEFINITION OF ANALYSIS POPULATIONS..................................................................8
9.
STATISTICAL METHODOLOGY .....................................................................................9
9.1
General..........................................................................................................................9
9.2
Demographics and Participant Disposition.....................................................................9
9.3
Pharmacokinetic Assessment.........................................................................................9
9.3.1
Pharmacokinetic Analysis.....................................................................................9
9.3.2
Pharmacokinetic Statistical Methodology ...........................................................13
9.4
Safety and Tolerability Assessments............................................................................14
9.4.1
Adverse events ...................................................................................................14
9.4.2
Concomitant medication.....................................................................................14
9.4.3
Clinical laboratory parameters............................................................................15
9.4.4
Vital signs ..........................................................................................................15
9.4.5
Body Temperature..............................................................................................15
9.4.6
Electrocardiogram (ECG)...................................................................................15
9.4.7
Hepatic Monitoring ............................................................................................15
9.4.8
Immunogenicity Assessments.............................................................................15
9.4.9
Hypersensitivity reactions...................................................................................16
9.4.10
Injection-Site Reactions......................................................................................16
9.4.11
Visual Analog Scale (VAS) Pain ........................................................................16
9.4.12
Bleeding/Bruising Assessment............................................................................16
9.4.13
Other assessments...............................................................................................16


Final, 12 October 2020
Page 3 of 17
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8442497
Sponsor Reference I6T-MC-AMBW
10. INTERIM ANALYSES .....................................................................................................17
11. CHANGES FROM THE PROTOCOL SPECIFIED STATISTICAL ANALYSES ............17
12. REFERENCES ..................................................................................................................17
13. DATA PRESENTATION ..................................................................................................17
13.1 Derived Parameters .....................................................................................................17
13.2 Missing Data ...............................................................................................................17
13.3 Insufficient Data for Presentation ................................................................................17


Final, 12 October 2020
Page 4 of 17
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8442497
Sponsor Reference I6T-MC-AMBW
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
Antidrug antibody
ADE
Adverse device effect
AE
Adverse event
AI
Autoinjector
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 lower limit of quantification
CI
Confidence interval
CL/F
Apparent total body clearance of drug calculated after extra-vascular 
administration
Clast
Last quantifiable drug concertation
Cmax
Maximum observed drug concentration
CRU
Clinical Research Unit
CSR
Clinical Study Report
CV
Coefficient of variation
CV%
Percent coefficient of variation
ECG
Electrocardiogram
ICH
International Conference on Harmonisation
ISR
Injection-site reaction
MedDRA
Medical Dictionary for Regulatory Activities
PFS
Pre-filled syringe
PK
Pharmacokinetic
SADE
Serious adverse device effect
SAE
Serious adverse event
SAP
Statistical Analysis Plan
SC
Subcutaneous
SD
Standard deviation 


Final, 12 October 2020
Page 5 of 17
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8442497
Sponsor Reference I6T-MC-AMBW
t1/2
Half-life associated with the terminal rate constant (λz) in 
non-compartmental analysis
TE ADA
Treatment-emergent antidrug antibody
TFLs
Tables, Figures, and Listings
tmax
Time of maximum observed drug concentration
UADE
Unanticipated adverse device effect
ULN
Upper limit of normal
VAS
Visual analog scale
Vss/F
Apparent volume of distribution at steady state after extra-vascular 
administration
Vz/F
Apparent volume of distribution during the terminal phase after extra-
vascular administration
WHO
World Health Organization


Final, 12 October 2020
Page 6 of 17
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8442497
Sponsor Reference I6T-MC-AMBW
3. INTRODUCTION
This SAP has been developed after review of the Clinical Study Protocol (final version dated
14 August 2020).
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 signed off prior to first participant visit for this study. 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. 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.
4. STUDY OBJECTIVES AND ENDPOINTS
4.1
Primary Objective and Endpoints
The primary objective of this study is to evaluate the PK of mirikizumab after subcutaneous (SC)
administration of 200-mg doses of solution formulation using a 2×1-mL pre-filled syringe (PFS)
and a 2×1-mL autoinjector (AI) in healthy participants.
The primary endpoints for this study are:

Maximum observed drug concentration (Cmax)

Area under the concentration versus time curve from time zero to infinity (AUC [0-∞])

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-tlast])


Final, 12 October 2020
Page 7 of 17
Statistical Analysis Plan 
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Covance Clinical Study No. 1000071-8442497
Sponsor Reference I6T-MC-AMBW
4.2
Secondary Objective and Endpoints
The secondary objective of this study is to describe the safety and tolerability of mirikizumab in 
healthy participants.
The secondary endpoints of this study are:

Treatment emergent adverse events

Serious adverse events (SAEs)
4.3
Exploratory Objectives and Endpoints
The exploratory objectives and endpoints for this study are:

To evaluate the effect of mirikizumab delivery device on immunogenicity
o
Treatment-emergent antidrug antibody (TE ADA)

To evaluate the impact of injection-site location on PK
o
Cmax
o
AUC (0-∞)
o
AUC(0-tlast)
5. STUDY DESIGN
Study AMBW is a Phase 1, open-label, 2-arm, randomized, parallel-design, single-dose,
multi-site study in healthy participants. At screening, participants will be stratified into 1 of 3 
weight categories (less than 70 kg, 70 to 80 kg, and more than 80 kg).
Eligible participants will be admitted to the clinical research unit (CRU) on Day -1.
Within the 3 weight categories, participants will be randomized using a computer-generated 
allocation code:

1:1 to delivery device (either PFS [reference] or AI [test])

within each delivery-device group 1:1:1 to injection site (abdomen, arm, or thigh)
On Day 1, participants will receive a 2×1 mL (total 200 mg mirikizumab) SC dose delivered via 
the device and in the location assigned by the randomization.
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 12 weeks postdose. Participants will 
be monitored for safety between outpatient visits by way of telephone assessment.


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Safety and tolerability will be assessed through clinical laboratory tests, vital sign measurements, 
recording of AEs, physical examination, and immunogenicity.
6. TREATMENTS
The following is a list of the study treatment abbreviations that will be used in the TFLs.
Study Treatment Name
Injection Site
Abbreviation
Treatment order in TFL
200 mg Mirikizumab 2 x 1-mL 
(100 mg/mL) PFS (Reference)
Abdomen
Reference (Abdomen)
1
Arm
Reference (Arm)
2
Thigh
Reference (Thigh)
3
200 mg Mirikizumab 2 x 1-mL
(100 mg/mL) AI (Test)
Abdomen
Reference (Abdomen)
4
Arm
Reference (Arm)
5
Thigh
Reference (Thigh)
6
7. SAMPLE SIZE JUSTIFICATION
Up to approximately 240 participants may be enrolled so that approximately 216 participants 
(108 in the PFS [reference] group and 108 in the AI [test] group) complete the study.
A sample size of 108 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 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 percent coefficients 
of variation (CV%) of Cmax and AUC are approximately 40% (based on previous trials), the 
expected ratio of geometric means is 1.07, and the CV% are the same for participants from each 
treatment group.
Participants who are randomized but not administered treatment, and participants who do not 
complete PK sampling through Day 85, may be replaced to ensure that approximately 216 
participants (108 in each group) complete the study.
8. DEFINITION OF ANALYSIS POPULATIONS
The “Enrolled” population will consist of all participants randomly assigned to the study 
intervention (mirikizumab).
The “Safety” population will consist of all participants randomly assigned and who received
study intervention (mirikizumab). Participants will be analyzed according to the intervention 
they actually received.
The “Pharmacokinetic” population will consist of all enrolled participants who receive a full 
dose of study intervention (mirikizumab) and have evaluable PK data.
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.


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9. STATISTICAL METHODOLOGY
9.1
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 N; 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 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. 
Mean change from baseline is the mean of all individual participants’ change from baseline 
values. Each individual change from baseline will be calculated by subtracting the individual 
participant’s baseline value from the value at the timepoint. The individual participant’s change 
from baseline values will be used to calculate the mean change from baseline using a SAS 
procedure such as Proc Univariate.
Data analysis will be performed using SAS® Version 9.4 or greater.
9.2
Demographics and Participant Disposition
Participant disposition will be summarized and listed. The demographic variables age, sex, race, 
ethnicity, country of enrolment, site ID, body weight, height and body mass index will be 
summarized by treatment, and listed. All other demographic variables will be listed only.
9.3
Pharmacokinetic Assessment
9.3.1
Pharmacokinetic Analysis
Noncompartmental methods applied with a validated software program (WinNonlin Phoenix 
v8.1 or later) to the serum concentrations of LY3074828 will be used to determine the following 
PK parameters, when possible: 


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Parameter
Units
Definition
AUC(0-tlast)
µg*day/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-∞)
µg*day/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
t1/2
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
Additional PK parameters 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 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 predose sampling times which will be set to zero.

Cmax and tmax will be reported from observed values. If Cmax occurs at more than 
one timepoint, 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 plasma concentrations above the lower limit of quantification, with at least 
one of these concentrations following Cmax. The 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 plasma 


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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 except for
special handling of certain concentrations reported below the lower limit of quantification 
(BQL). Plasma concentrations reported as BQL will be set to a value of zero when all the 
following conditions are met:  
○
The compound is non-endogenous.
○
The samples are from the initial dose period for a participant or from a subsequent 
dose period following a suitable wash-out period.
○
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 and arithmetic average concentrations.

The predose 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.


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
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 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 
CSR.
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 PK profiles during multiple dosing, the concentration of the predose sample exceeds 
all measured concentrations for that individual in the subsequent post-dose samples.

For PK profiles during single dosing of non-endogenous compounds, the concentration in 
a predose sample is quantifiable.

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 the dataset is too small to conduct a reliable range test. Data will be analyzed 
with and without the atypical value, and both sets of results will be reported. 
2. 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.


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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 CSR. Approval of the CSR will 
connote approval of the exclusion.
9.3.2
Pharmacokinetic Statistical Methodology
The Cmax, AUC (0-∞), and AUC(0-tlast), will be log-transformed and analyzed using a linear 
fixed-effects model. The model will include delivery device, injection location, and weight 
stratification as fixed effects. The dosing regimen differences between AI and PFS 
administrations will be back-transformed to present the ratios of geometric least squares means 
and the corresponding 90% CI. 
Example SAS Code:
proc mixed data=xxx;
by parameter;
class device location strat_weight;
model log_pk = device location strat_weight / residual;
lsmeans device / alpha=0.1 cl pdiff;
ods output lsmeans=lsmeans diffs=diffs;
run;
The tmax of mirikizumab between the AI (Test) and PFS (Reference) administrations 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 comparisons will be made between:

The 2 delivery devices (AI [Test] versus PFS [Reference]) separately at each injection 
location (injection location will be removed from the model above)


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Statistical Analysis Plan 
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Covance Clinical Study No. 1000071-8442497
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
The 3 injection locations (arm [Test] versus abdomen [Reference] and thigh [Test] versus 
abdomen [Reference]) separately for each device (device will be removed from the model 
above)
The 2 delivery devices (AI [Test] versus PFS [Reference]) will be considered bioequivalent if the 
90% CI of the ratio of geometric least squares means of Cmax, AUC (0-∞), and AUC(0-tlast) fall 
within 0.8 to 1.25. There would not be power in the model to achieve bioequivalence boundaries 
for any specific injection location, therefore the bioequivalence for the 3 injection locations will 
not be determined. 
PK parameters may be normalized by body weight for summarizing data. Additional PK 
analyses may be conducted if deemed appropriate.
9.4
Safety and Tolerability Assessments
9.4.1
Adverse events
Where changes in severity are recorded in the case report form, each separate severity of the 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 an AE 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. 
An adverse device effect (ADE) is defined as an AE related to the use of an investigational 
medical device.  A serious adverse device effect (SADE) is defined as an adverse device 
effect (ADE) that has resulted in any of the consequences characteristic of an SAE. An 
unanticipated ADE (UADE) is a SADE which by its nature, incidence, severity, or outcome has 
not been identified in the current version of the Lilly risk analysis report.
All AEs will be listed. Treatment-emergent AEs will be summarized by treatment, 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 
treatment-emergent AEs will be summarized by treatment, Medical Dictionary for Regulatory 
Activities (MedDRA) version 23.0 (or higher if upversioned during the study) 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. All SAEs, SADEs, and 
UADEs will be listed.
Discontinuations due to AEs will be listed.
9.4.2
Concomitant medication
Concomitant medication will be coded using the WHO drug dictionary version MAR20B3 (or 
higher if upversioned during the study). Concomitant medication will be listed.


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9.4.3
Clinical laboratory parameters
All clinical chemistry and hematology data will be summarized by parameter and treatment, and 
listed. Urinalysis data will be listed. Changes from baseline (predose) will also be presented. 
Additionally, clinical chemistry, hematology and urinalysis data outside the reference ranges will 
be listed and flagged on individual participant data listings.
9.4.4
Vital signs
Vital signs data will be summarized by treatment together with changes from baseline (predose),
and values for individual participants will be listed.
9.4.5
Body Temperature
Body temperature data will be summarized by parameter and treatment, and listed. Changes from 
baseline (predose) will also be presented. Figures of mean body temperature will be presented by 
treatment, over all timepoints.
9.4.6
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.
9.4.7
Hepatic Monitoring
If a participant experiences elevated alanine aminotransferase ≥3× upper limit of normal (ULN), 
alkaline phosphatase ≥2× ULN, or elevated total bilirubin ≥2× ULN, liver 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. Any concomitant medications that have potential for hepatotoxicity, including 
acetaminophen 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.
9.4.8
Immunogenicity Assessments
The frequency and percentage of participants with pre-existing antidrug antibody (ADA) and 
with TE ADAs to mirikizumab will be tabulated and listed. 
For participants who are ADA negative at baseline, TE ADAs are defined as those with a titer 
2-fold (1 dilution) or greater than the minimum required dilution of the assay (1:10). For 


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Statistical Analysis Plan 
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participants who are ADA positive at baseline, TE ADAs are defined as those with a 4-fold 
(2 dilution) or greater increase in titer compared to baseline. 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 and safety parameters of 
mirikizumab may be assessed.
9.4.9
Hypersensitivity reactions
For all drug hypersensitivity reactions that occur, additional follow-up data will be collected to 
assess the patient’s medical history, alternative causes, and symptoms.
These data will be listed.
9.4.10
Injection-Site Reactions
Although there will be no prospective collection of injection-site reaction (ISR) information, any 
spontaneously reported ISR by the participant will be reported as AEs. 
Any ISR data (including erythema, induration, pain, pruritus, and edema) will be summarized by 
treatment, and listed.
9.4.11
Visual Analog Scale (VAS) Pain
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 visual analog scale (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 
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). 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.
If available, this data will be summarized by treatment and timepoint, and listed.
9.4.12
Bleeding/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 bruising or bleeding data will be listed.
9.4.13
Other assessments
All other safety assessments not detailed in this section will be listed but not summarized or 
statistically analyzed.


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10.
INTERIM ANALYSES
No interim statistical analyses are planned.
11.
CHANGES FROM THE PROTOCOL SPECIFIED STATISTICAL ANALYSES
There were no changes from the protocol specified statistical analyses.
12.
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.
3. Williamson A, Hoggart B. Pain: a review of three commonly used pain rating scales. J Clin 
Nurs. 2005;14(7):798-804.
13.
DATA PRESENTATION
13.1
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. N 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.
13.2
Missing Data
Unless otherwise stated, there are no plans to impute missing data. Any missing data will not be 
displayed in listings.
13.3
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.”


Leo Document ID = d140ad03-ba18-43f4-aac0-d87e0fc34e5d
Approver: 
Approval Date & Time: 14-Oct-2020 07:42:16 GMT
Signature meaning: Approved
Approver: 
  
Approval Date & Time: 15-Oct-2020 15:53:22 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 19-Oct-2020 14:23:28 GMT
Signature meaning: Approved
Approver:
Approval Date & Time: 19-Oct-2020 14:27:09 GMT
Signature meaning: Approved
PPD
PPD
PPD
PPD


Leo Document ID = d140ad03-ba18-43f4-aac0-d87e0fc34e5d
Approver: 
Approval Date & Time: 19-Oct-2020 15:18:26 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 19-Oct-2020 15:18:56 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 19-Oct-2020 15:49:18 GMT
Signature meaning: Approved
Approver:
Approval Date & Time: 19-Oct-2020 16:05:00 GMT
Signature meaning: Approved
PPD
PPD
PPD
PPD