A Multicenter Study With a Randomized, Double-Blind, Placebo-Controlled Induction Dosing Period Followed by a Randomized Withdrawal Maintenance Dosing Period to Evaluate the Efficacy and Safety of Mirikizumab in Patients With Moderate-to-Severe Plaque Psoriasis OASIS-1
Phase: PHASE3
Conditions: Psoriasis
Sponsor: Eli Lilly and Company

Protocol I6T-MC-AMAK (a) 
 
A Multicenter Study with a Randomized, Double-Blind, Placebo-Controlled Induction Dosing 
Period Followed by a Randomized Withdrawal Maintenance Dosing Period to Evaluate the 
Efficacy and Safety of Mirikizumab in Patients with Moderate-to-Severe Plaque Psoriasis 
OASIS-1 
 
NCT03482011 
 
Approval Date: 12-Dec-2018 

I6T-MC-AMAK(a)ClinicalProtocol
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LY3074828
Protocol I6T-MC-AMAK(a)
A Multicenter Study with a Randomized, Double-Blind, 
Placebo-Controlled Induction Dosing Period Followed by a 
Randomized Withdrawal Maintenance Dosing Period to 
Evaluate the Efficacy and Safety of Mirikizumabin Patients 
with Moderate-to-Severe Plaque Psoriasis
OASIS-1
EUDRA CTA: 2017-003298-32
Confidential Information
The information contained in this document is confidential and isintended 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.
Approval Date: 12-Dec-2018 GMT
Mirikizumab(LY3074828)
Eli Lilly and Company
Indianapolis, Indiana USA 46285
Protocol ElectronicallyS
igned andApprovedby Lilly:  25 January 2018.
Amendment (a) Electronically Signed and Approved by Lilly 
on approval date provided below.

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Table of Contents
Section
Page
Protocol I6T-MC-AMAK(a) A Multicenter Study with a Randomized, 
Double-Blind, Placebo-Controlled Induction Dosing Period Followed 
by a Randomized Withdrawal Maintenance Dosing Period to 
Evaluate the Efficacy and Safety of Mirikizumab in Patients with 
Moderate-to-Severe Plaque Psoriasis OASIS-1 ...................................................................1
Table of Contents........................................................................................................................2
1.
Synopsis .............................................................................................................................9
2.
Schedule of Activities .......................................................................................................14
3.
Introduction ......................................................................................................................22
3.1.
Study Rationale............................................................................................................22
3.2.
Background..................................................................................................................22
3.3.
Benefit/Risk Assessment..............................................................................................23
4.
Objectives and Endpoints..................................................................................................25
5.
Study Design.....................................................................................................................28
5.1.
Overall Design .............................................................................................................28
5.1.1.
Screening Period..................................................................................................28
5.1.2.
Baseline and Double-Blind Induction Period (Week 0 to 
Week 16): ............................................................................................................28
5.1.3.
Double-Blind Maintenance Period (Week 16 to Week 52 
[36 Weeks]): ........................................................................................................28
5.1.4.
Post-Treatment Follow-up Period (12 Weeks)......................................................30
5.2.
Number of Participants.................................................................................................31
5.3.
End of Study Definition ...............................................................................................31
5.4.
Scientific Rationale for Study Design...........................................................................32
5.5.
Justification for Dose ...................................................................................................32
6.
Study Population...............................................................................................................34
6.1.
Inclusion Criteria..........................................................................................................34
6.2.
Exclusion Criteria ........................................................................................................36
6.2.1.
Rationale for Exclusion of Certain Study Candidates ...........................................40
6.3.
Lifestyle Restrictions....................................................................................................40
6.4.
Screen Failures.............................................................................................................40
7.
Treatments........................................................................................................................41
7.1.
Treatments Administered .............................................................................................41
7.1.1.
Packaging and Labelling ......................................................................................42
7.2.
Method of Treatment Assignment ................................................................................42

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7.2.1.
Selection and Timing of Doses.............................................................................42
7.3.
Blinding .......................................................................................................................42
7.4.
Dosage Modification....................................................................................................43
7.5.
Preparation/Handling/Storage/Accountability...............................................................43
7.6.
Treatment Compliance .................................................................................................43
7.7.
Concomitant Therapy...................................................................................................44
7.8.
Treatment after the End of the Study............................................................................46
7.8.1.
Treatment after Study Completion........................................................................46
7.8.2.
Special Treatment Considerations ........................................................................46
Management of Hypersensitivity Events, Including 
7.8.2.1.
Injection Site Events.......................................................................................46
8.
Discontinuation Criteria ....................................................................................................48
8.1.
Discontinuation from Study Treatment.........................................................................48
8.1.1.
Permanent Discontinuation from Study Treatment ...............................................48
8.1.2.
Temporary Interruption (Withholding) of Study Treatment ..................................48
8.1.3.
Discontinuation of Inadvertently Enrolled Patients...............................................49
8.2.
Discontinuation from the Study....................................................................................49
8.3.
Lost to Follow-Up........................................................................................................51
9.
Study Assessments and Procedures ...................................................................................52
9.1.
Efficacy Assessments...................................................................................................52
9.1.1.
Primary Efficacy Assessments .............................................................................52
Static Physician’s Global Assessment.............................................................52
9.1.1.1.
Psoriasis Area and Severity Index...................................................................52
9.1.1.2.
9.1.2.
Secondary Efficacy Assessments..........................................................................52
Static Physician’s Global Assessment.............................................................52
9.1.2.1.
Psoriasis Area and Severity Index...................................................................53
9.1.2.2.
Body Surface Area .........................................................................................53
9.1.2.3.
Nail Psoriasis Severity Index ..........................................................................53
9.1.2.4.
Psoriasis Scalp Severity Index ........................................................................53
9.1.2.5.
Palmoplantar Psoriasis Severity Index ............................................................53
9.1.2.6.
Health Outcomes Assessments........................................................................53
9.1.2.7.
9.1.2.7.1.
Dermatology Life Quality Index ...............................................................53
9.1.2.7.2.
European Quality of Life–5 Dimensions–5 Levels–
Psoriasis ...................................................................................................54
9.1.2.7.3.
Work Productivity and Activity Impairment 
Questionnaire: Psoriasis............................................................................54
9.1.2.7.4.
Psoriasis Symptoms Scale.........................................................................54
9.1.2.7.5.
Medical Outcomes Study 36-Item Short-Form Health 
Survey ......................................................................................................55

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9.1.2.7.6.
16-Item Quick Inventory of Depressive 
Symptomatology-Self Report....................................................................55
9.1.2.7.7.
Treatment Satisfaction Questionnaire for Medication................................55
9.1.2.7.8.
Patient’s Global Assessment of Psoriasis ..................................................56
9.1.3.
Appropriateness of Assessments ..........................................................................56
9.2.
Adverse Events ............................................................................................................56
9.2.1.
Serious Adverse Events........................................................................................57
Suspected Unexpected Serious Adverse Reactions..........................................58
9.2.1.1.
9.2.2.
Adverse Event Monitoring with a Systematic Questionnaire ................................58
9.2.3.
Adverse Events of Special Interest .......................................................................59
9.2.4.
Complaint Handling.............................................................................................60
9.3.
Treatment of Overdose.................................................................................................60
9.4.
Safety...........................................................................................................................60
9.4.1.
Electrocardiograms ..............................................................................................60
9.4.2.
Vital Signs ...........................................................................................................61
Hypertension ..................................................................................................61
9.4.2.1.
9.4.3.
Laboratory Tests ..................................................................................................61
Pregnancy Testing ..........................................................................................61
9.4.3.1.
9.4.4.
Immunogenicity Assessments ..............................................................................62
9.4.5.
Other Tests...........................................................................................................62
Physical Examination .....................................................................................62
9.4.5.1.
Tuberculosis Screening...................................................................................62
9.4.5.2.
Chest Radiography .........................................................................................64
9.4.5.3.
Hepatitis B Screening .....................................................................................65
9.4.5.4.
Hepatitis C Screening .....................................................................................65
9.4.5.5.
9.4.6.
Safety Monitoring ................................................................................................66
Hepatic Safety Monitoring..............................................................................66
9.4.6.1.
9.5.
Pharmacokinetics .........................................................................................................66
9.6.
Pharmacodynamics ......................................................................................................67
9.7.
Pharmacogenomics ......................................................................................................67
9.7.1.
Whole Blood Sample for Pharmacogenetic Research ...........................................67
9.8.
Biomarkers...................................................................................................................67
9.9.
Medical Resource Utilization and Health Economics ...................................................68
10.
Statistical Considerations ..................................................................................................69
10.1. Sample Size Determination ..........................................................................................69
10.2. Populations for Analyses..............................................................................................70
10.3. Statistical Analyses ......................................................................................................70
10.3.1.
General Statistical Considerations ........................................................................70

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Missing Data Imputation ................................................................................71
10.3.1.1.
Multiple Comparisons/Multiplicity.................................................................72
10.3.1.2.
10.3.2.
Treatment Group Comparability...........................................................................72
Patient Disposition..........................................................................................72
10.3.2.1.
Patient Characteristics ....................................................................................72
10.3.2.2.
Concomitant Therapy .....................................................................................73
10.3.2.3.
Treatment Compliance....................................................................................73
10.3.2.4.
10.3.3.
Efficacy Analyses ................................................................................................73
Primary Analyses ...........................................................................................73
10.3.3.1.
Secondary Analyses........................................................................................73
10.3.3.2.
Exploratory Analyses .....................................................................................73
10.3.3.3.
10.3.4.
Safety Analyses....................................................................................................74
10.3.5.
Pharmacokinetic/Pharmacodynamic Analyses......................................................74
10.3.6.
Evaluation of Immunogenicity .............................................................................75
10.3.7.
Other Analyses.....................................................................................................75
Subgroup Analyses.........................................................................................75
10.3.7.1.
Psoriasis Symptoms Scale Psychometric Analysis ..........................................75
10.3.7.2.
10.3.8.
Interim Analyses ..................................................................................................76
11.
References ........................................................................................................................77
12.
Appendices .......................................................................................................................82

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List of Tables
Table
Page
Table AMAK.1. Schedule of Activities....................................................................................15
Table AMAK.2. Objectives and Endpoints...............................................................................25
Table AMAK.3. Treatment Regimens......................................................................................41
Table AMAK.4. Excluded Classes of Concomitant Medications or Classes with 
Restricted Use ...............................................................................................44

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List of Figures
Figure
Page
Figure AMAK.1. Illustration of study design for Clinical Protocol I6T-MC-AMAK. ................31

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List of Appendices
Appendix
Page
Appendix 1.
Abbreviations and Definitions........................................................................83
Appendix 2.
Clinical Laboratory Tests...............................................................................88
Appendix 3.
Study Governance Considerations..................................................................90
Appendix 4.
Examples of Infections That May Be Considered Opportunistic in the 
Setting of Biologic Therapy...........................................................................95
Appendix 5.
Risk Factors for Latent Tuberculosis Infection...............................................97
Appendix 6.
Hepatic Monitoring Tests for Treatment-Emergent Abnormality....................99
Appendix 7.
Protocol Amendment I6T-MC-AMAK(a) Summary A Multicenter 
Study with a Randomized, Double-Blind, Placebo-Controlled Induction 
Dosing Period Followed by a Randomized Withdrawal Maintenance 
Dosing Period to Evaluate the Efficacy and Safety of Mirikizumab in 
Patients with Moderate-to-Severe Plaque Psoriasis
OASIS-1......................................................................................................100

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1. Synopsis
Title of Study:
A Multicenter Study with a Randomized, Double-Blind, Placebo-Controlled Induction Dosing 
Period Followed by a Randomized Withdrawal Maintenance Dosing Period to Evaluate the 
Efficacy and Safety of Mirikizumab in Patients with Moderate-to-Severe Plaque Psoriasis.
Rationale: 
Mirikizumab (LY3074828) is a monoclonal, anti-interleukin-23 (anti-IL-23) antibody being 
developed for the treatment of immune-mediated diseases where the IL-23 pathway is thought to 
have a significant pathogenic role.  The neutralizing activity of mirikizumab is directed against
the p19 subunit of the IL-23 molecule and does not bind to IL-12.  Study I6T-MC-AMAK
(AMAK) is a confirmatory study testing mirikizumab as a treatment for plaque psoriasis and is 
intended to support registration of this indication. This Phase 3 study is designed to evaluate the 
superiority of mirikizumab versus placebo, as measured by improvement in disease severity and 
key patient-reported outcomes, and will contribute to the evaluation of the safety of 
mirikizumab.
Objective(s)/Endpoints:
Objectives
Endpoints
Primarya,b
To assess whether mirikizumab induction dosing is 
superior to placebo in the treatment of patients with 
respect to high levels of clinical response
At Week 16:

Proportion of patients with an sPGA (0,1) with at 
least a 2-point improvement from baseline

Proportion of patients achieving a 90% 
improvement in PASI from baseline (PASI 90)
Major Secondarya,b
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to an early, clinically 
meaningful response
At Week 4:

Proportion of patients achieving a 75% improvement 
in PASI (PASI 75)
To assess whether the mirikizumab induction dosing 
is superior to placebo with respect to clinically 
meaningful response and the highest levels of clinical 
response
At Week 16:

Proportion of patients achieving PASI 75

Proportion of patients achieving a 100% 
improvement in PASI (PASI 100)
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to body surface area 
(BSA) affected by psoriasis
At Week 16:

Proportion of patients with ≤1% of BSA with 
psoriasis involvement

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Objectives
Endpoints
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to patient-reported 
outcomes
At Week 16:

Proportion of patients with a PSS symptoms score of 0 
(free of itch, pain, stinging, and burning) in those with 
a PSS symptoms score 1 at baseline.

Proportion of patients achieving a DLQI total score of 
(0,1) with at least a 5-point improvement (reduction) 
from baseline in patients with a baseline DLQI total 
score 5
To assess whether 250 mg mirikizumab Q8W and 
125 mg mirikizumab Q8W maintenance dosing is 
superior to placebo with respect to maintenance of a 
high level of clinical response
At Week 52:

Proportion of patients maintaining clinical response 
(PASI 90) after re-randomization at the start of the 
randomized withdrawal period
Other Secondaryb
To compare mirikizumab to placebo with respect to 
clinical response and time to clinical response during 
the induction dosing period, and with respect to 
patient-reported outcomes during the induction 
dosing period
At Week 16 and various time points over the first 16 weeks 
of dosing:

Proportion of patients achieving PASI 90.

Change in PPASI total score in patients with 
palmoplantar involvement at baseline

Change in PSSI total score in patients with scalp 
involvement at baseline

Change in NAPSI total score in patients with 
fingernail involvement at baseline 

Change from baseline on the SF-36 physical 
component summary (PCS) and mental component 
summary (MCS) 

Change from baseline on PatGA of disease severity

Change from baseline for the WPAI-PSO scores 
(Absenteeism, Presenteeism, Work Productivity 
Loss, and Activity Impairment)

Change from baseline in QIDS-SR16 total score in 
those with a baseline QIDS-SR16 total score 11

Proportion of patients achieving a DLQI total score 
of (0,1) with at least a 5-point improvement 
(reduction) from baseline in patients with a baseline 
DLQI total score 5

Proportion of patients achieving DLQI (0,1) with 
DLQI baseline score >1

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Objectives
Endpoints
To assess whether 250 mg mirikizumab Q8W and 
125 mg mirikizumab Q8W dosing is superior to 
placebo with respect to maintenance of high and 
highest levels of clinical response among patients 
who have an PASI 90 at Week 16 and are re-
randomized
At Week 52 and at various time points during the 
Maintenance Dosing Period:

Time to relapse (the loss, at any visit, of 50% of the 
Week 16 PASI improvement from baseline).

Proportion of patients who have relapsed.

Proportion of patients maintaining clinical response 
(PASI 90) after re-randomization at the start of the 
randomized withdrawal period

Incidence of disease rebound within 12 weeks 
(worsening of psoriasis severity over baseline sPGA 
score, or worsening of psoriasis severity over 
baseline PASI score by 125%, or change in psoriasis 
phenotype [for example, from plaque to pustular]) 
after re-randomization to placebo at Week 16.
To assess the efficacy of 250 mg mirikizumab Q8W 
following relapse after re-randomization to placebo 
treatment in the Maintenance Dosing Period
During the Maintenance Dosing Period:

Proportion of patients who regained PASI 90 within 
16 weeks after mirikizumab retreatment.  
To evaluate the pharmacokinetics and 
pharmacokinetic/pharmacodynamic relationship of 
mirikizumab

Clearance and volume of distribution of 
mirikizumab

Relationship between mirikizumab exposure and 
efficacy (sPGA and PASI)
Abbreviations:  BSA = body surface area; DLQI = Dermatology Life Quality Index; MCS = mental component 
summary; NAPSI = Nail Psoriasis Severity Index; PASI = Psoriasis Area and Severity Index; 
PASI 75/90/100 = 75%/90%/100% improvement in PASI from baseline; PatGA = Patient’s Global 
Assessment of Psoriasis; PCS = physical component summary; PPASI = Palmoplantar Psoriasis Severity Index; 
PSS = Psoriasis Symptoms Scale; PSSI = Psoriasis Scalp Severity Index; Q8W = every 8 weeks; QIDS-SR16 = 
16-item Quick Inventory of Depressive Symptomatology; SF-36 = Medical Outcomes Study 36-Item Short Form 
Health Survey; sPGA = static Physician’s Global Assessment; WPAI-PSO = Work Productivity Activity 
Impairment Questionnaire–psoriasis.
a
All primary and major secondary endpoint analyses will utilize the multiplicity control technique called 
“graphical multiple testing procedure” to control the overall family-wise Type I error rate.
b
Note: A “clinically meaningful” response is a PASI 75 response, which represents at least a 75% decrease 
(improvement) from the baseline PASI score.  A “high level” of clinical response is a PASI 90 response, which 
represents at least a 90% decrease (improvement) from baseline in PASI score, or sPGA (0,1) response, which 
represents an “almost clear” response.  The “highest level” of clinical response is a PASI 100 or sPGA (0) 
response, which represents complete resolution of psoriasis.
Summary of Study Design:  
Study AMAK is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, 
parallel-group, multi-period study.  The study design includes 2 treatment periods (Induction and
Maintenance with Randomized Withdrawal), which together last for up to 52 weeks, followed by 
a 12-week Post-Treatment Follow-Up period. The study population consists of patients aged
18 years or older at the time of screening who have chronic plaque psoriasis based on a 

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confirmed diagnosis of chronic plaque psoriasis for at least 6 months, are candidates for systemic 
and/or phototherapy, and have 10% body surface area (BSA) involvement, a static Physician’s 
Global Assessment (sPGA) score of 3, and a Psoriasis Area and Severity Index (PASI) score 
12 at screening and at baseline.
Treatment Arms and Duration:
Patients will be randomized 4:1 to receive double-blind (“blinded”) subcutaneous (SC) 
administration of 250 mg mirikizumab or matching placebo at Weeks 0, 4, 8, and 12.  
Randomization will be stratified based on previous exposure to biologic therapy (yes/no), body 
weight (<100 kg or 100 kg), and geographic region (North America or Other).  Patients who 
were responders (PASI 90) in the Induction Period and who continue in the blinded 
Maintenance Period will be monitored for maintenance of response or remission, as well as 
relapse and disease rebound following treatment withdrawal, and response to retreatment 
following relapse.  Responders to mirikizumab treatment in the blinded Induction Period will be 
re-randomized 1:1:1 to 250 mg mirikizumab every 8 weeks (Q8W), 125 mg mirikizumab Q8W, 
or placebo Q8W, with treatments beginning at Week 16. Stratification in the Maintenance 
Period will be by body weight at baseline (<100 kg or 100 kg).  The duration of treatment is 
52 weeks.  The total duration of participation in this study may be up to 68 weeks as detailed 
below.
Screening Period:  Up to 4 weeks.
Treatment Period:  Approximately 52 weeks.
Post-Treatment Follow-up Period:  Approximately 12 weeks after the last visit for patients 
who discontinue treatment prior to the Week 52 assessment, or who are unable or not willing to 
participate in the long-term extension study (I6T-MC-AMAH [AMAH]).
Approximate Number of Planned Patients:
Screened:  650
Randomized:  500
Completed:  400
Statistical Analysis:
Approximately 500 patients will be randomized at a 4:1 ratio in the blinded Induction Period to 
receive 250 mg mirikizumab or placebo SC at Weeks 0, 4, 8, and 12.  Stratified block 
randomization will be performed with the following stratification factors: previous exposure to 
biologic therapy (yes/no), body weight (<100 kg or 100 kg), and geographic region (North 
America or Other). Assuming that PASI 90 responses at Week 16 are 70% for the mirikizumab
arm and 3% for the placebo arm, the planned samples size (mirikizumab, 400 patients; placebo, 
100 patients) has a power of >95% for a test of superiority of mirikizumab compared to placebo
with respect to PASI 90 at Week 16. Similarly, assuming the sPGA (0,1) responses at Week 16
are 70% for the mirikizumab arm and 5% for the placebo arm, the planned samples size has a 

I6T-MC-AMAK(a) Clinical Protocol
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power of >95% for a test of superiority of mirikizumab compared to placebo with respect to the 
sPGA (0,1) endpoint. Eli Lilly and Company (Lilly) predicts that 70% of the 
mirikizumab-treated patients will be re-randomized in the Maintenance Period at Week 16
(Visit 7) at a 1:1:1 ratio to 250 mg mirikizumab Q8W, 125 mg mirikizumab Q8W, or placebo 
using body weight at baseline (<100 kg or 100 kg) as a stratification factor. Thus, 
approximately 93 patients will be included in each Maintenance Period treatment group. The 
estimated sample size will provide a power of >95% to test superiority of 250 mg mirikizumab
Q8W against placebo, and also power of >95% to test superiority of 125 mg mirikizumab Q8W
against placebo with respect to PASI 90 at Week 52.
For assessments of the primary endpoints and other categorical efficacy and health outcomes
endpoints, the Cochran–Mantel–Haenszel (CMH) chi-square test along with Non-Responder 
Imputation (NRI) will be used to compare the treatment groups. The CMH stratification factors 
will be the same as those used in the stratified randomization scheme.  The CMH chi-square 
p-value will be provided.  In addition, the absolute treatment difference in proportions will be 
provided along with the 95% 2-sided confidence interval estimate.
Treatment comparisons of continuous efficacy and health outcome variables with multiple 
post-baseline measurements will be made using mixed-effects model for repeated measures 
(MMRM). When MMRM is used, the model will include treatment, baseline value, visit, and 
the interaction of treatment-by-visit, and the variables used for stratified randomization in 
induction/maintenance will be used as covariates.  Treatment comparisons of continuous efficacy 
and health outcome variables with a single post-baseline time point will be made using analysis 
of covariance (ANCOVA) with the following covariates in the model: treatment group, baseline 
value, and variables used for stratified randomization in induction/maintenance.
Fisher's exact test will be used for categorical safety data, including adverse events, unless 
otherwise specified.  Continuous safety data including vital sign and laboratory values will be 
analyzed using ANCOVA with treatment and baseline value in the model, unless otherwise 
specified.  Also, laboratory analytes will be presented as mean changes from baseline and as 
incidence of shift between normal and abnormal states.
The prespecified graphical multiple testing approach (Bretz et al. 2011) will be implemented to
control the overall Type I error rate at 2-sided alpha of 0.05, for the hypotheses for the primary 
and major secondary endpoints.
A Data Monitoring Committee (DMC) consisting of members external to Lilly will be 
established for interim safety monitoring across all Phase 3 trials in patients with psoriasis. A 
DMC charter will govern the role and responsibilities of DMC-related activities.

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2. Schedule of Activities

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Table AMAK.1.
Schedule of Activities
Procedurea
Screening
Period
Baseline
Induction Period
Maintenance Period
ETVs
Follow-up
Periodt
Visit Number
V
1b
V
2
V
3
V
4
V
5
V
6
V
7
V
8
V
9
V
10
V
11
V
12
V
13
V
14
V
15
V
16
V
801
V
802
Week 
-4
0
2
4
8
12
16
20
24
28
32
36
40
44
48
52
LV 
+4W
LV
+12W
Day with Visit 
Tolerance 
Interval
≤28 days 
from V2
1
15
± 3
29
± 3
57
± 5
85
± 5
113
± 5
141
± 5
169
± 5
197
± 5
225
± 5
253
± 5
281
± 5
309
± 5
337
± 5
365
± 5
29
± 5
85
± 5
Informed 
Consent
X
Demographics
X
Height
X
Physical 
Examinationc
X
X
X
X
X
X
X
Weight
X
X
X
X
X
Inclusion/
Exclusion
Criteria  
X
X
Complete 
Medical/
Surgical
History and 
Habits
X
Concomitant 
Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Preexisting 
Conditions
X
Adverse 
Events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital Signs 
(BP, temp, and 
pulse)d
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X

I6T-MC-AMAK(a) Clinical Protocol
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LY3074828
Procedurea
Screening
Period
Baseline
Induction Period
Maintenance Period
ETVs
Follow-up
Periodt
Visit Number
V
1b
V
2
V
3
V
4
V
5
V
6
V
7
V
8
V
9
V
10
V
11
V
12
V
13
V
14
V
15
V
16
V
801
V
802
Week 
-4
0
2
4
8
12
16
20
24
28
32
36
40
44
48
52
LV 
+4W
LV
+12W
Day with Visit 
Tolerance 
Interval
≤28 days 
from V2
1
15
± 3
29
± 3
57
± 5
85
± 5
113
± 5
141
± 5
169
± 5
197
± 5
225
± 5
253
± 5
281
± 5
309
± 5
337
± 5
365
± 5
29
± 5
85
± 5
Chest 
Radiography 
for TB 
Screening
Xe
PPD/
QuantiFERON
-TB Gold/
T-SPOT.TB
(per local 
guidelines)
Xf
ECG
X
Xg
Xg
C-SSRS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Self-Harm 
Suppl. Formh
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Self-Harm 
Follow-up 
Formh
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
QIDS-SR16 
(patient 
completed)
X
X
X
X
X
X
X
IP Dosed
X
X
X
X
X
X
X
X
X
X
X
X
X
Investigator-
Completed 
Clinical 
Efficacy
Scales
PASI
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
BSA
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X

I6T-MC-AMAK(a) Clinical Protocol
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LY3074828
Procedurea
Screening
Period
Baseline
Induction Period
Maintenance Period
ETVs
Follow-up
Periodt
Visit Number
V
1b
V
2
V
3
V
4
V
5
V
6
V
7
V
8
V
9
V
10
V
11
V
12
V
13
V
14
V
15
V
16
V
801
V
802
Week 
-4
0
2
4
8
12
16
20
24
28
32
36
40
44
48
52
LV 
+4W
LV
+12W
Day with Visit 
Tolerance 
Interval
≤28 days 
from V2
1
15
± 3
29
± 3
57
± 5
85
± 5
113
± 5
141
± 5
169
± 5
197
± 5
225
± 5
253
± 5
281
± 5
309
± 5
337
± 5
365
± 5
29
± 5
85
± 5
sPGA
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Facial 
Psoriasis
X
X
X
X
PSSIi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
NAPSIi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PPASIi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Patient-
Completed 
Health 
Outcomes
Scalesj
PSS
|------------------Daily Electronic Diaryk--------------------|
X
X
X
X
DLQI
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
SF-36
X
X
X
X
PatGA
X
X
X
X
X
X
X
X
X
X
WPAI-PSO
X
X
X
X
X
X
EQ-5D-5L-
PSO
X
X
X
X
X
X
X
TSQM
X
X
X
X
X
X
Laboratory 
Tests
Hematologyl
X
X
X
X
X
X
X
X
X
X
X
X
X
Clinical 
Serum 
Chemistryl
X
X
X
X
X
X
X
X
X
X
X
X
X

I6T-MC-AMAK(a) Clinical Protocol
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LY3074828
Procedurea
Screening
Period
Baseline
Induction Period
Maintenance Period
ETVs
Follow-up
Periodt
Visit Number
V
1b
V
2
V
3
V
4
V
5
V
6
V
7
V
8
V
9
V
10
V
11
V
12
V
13
V
14
V
15
V
16
V
801
V
802
Week 
-4
0
2
4
8
12
16
20
24
28
32
36
40
44
48
52
LV 
+4W
LV
+12W
Day with Visit 
Tolerance 
Interval
≤28 days 
from V2
1
15
± 3
29
± 3
57
± 5
85
± 5
113
± 5
141
± 5
169
± 5
197
± 5
225
± 5
253
± 5
281
± 5
309
± 5
337
± 5
365
± 5
29
± 5
85
± 5
Lipid 
Panel 
(fasting)m
X
X
X
Urinalysis
X
X
X
Xu
hsCRP
X
X
X
X
X
X
X
X
HBsAg, 
HBcAb, 
HBsAb
Xn
HBV DNA 
testingn
X
X
X
X
X
X
X
X
Hepatitis C 
Antibody
X
HCV RNA 
testing
X
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Xo
Xo
HIV
X
Immuno-
genicity for 
miri p
X
X
X
X
X
X
X
X
X
X
X
X
Serum for 
miri conc
(PK)q
X
X
X
X
X
X
X
X
X
X
X
X
Serum 
Pregnancy 
Test
(WCBP 
only)
X

I6T-MC-AMAK(a)ClinicalProtocol
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LY3074828
Procedurea
Screening
Period
Baseline
InductionPeriod
Maintenance Period
ETVs
Follow-up
Periodt
Visit Number
V
1b
V
2
V
3
V
4
V
5
V
6
V
7
V
8
V
9
V
10
V
11
V
12
V
13
V
14
V
15
V
16
V
801
V
802
Week 
-4
0
2
4
8
12
16
20
24
28
32
36
40
44
48
52
LV 
+4W
LV
+12W
Day with Visit 
Tolerance 
Interval
≤28 days 
from V2
1
15
± 3
29
± 3
57
±5
85
± 5
113
± 5
141
± 5
169
± 5
197
± 5
225
± 5
253
± 5
281
± 5
309
± 5
337
± 5
365
± 5
29
± 5
85
± 5
Urine 
Pregnancy 
Test(local; 
WCBP only)
X
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
FSH
Xr
Serum/
Plasma for 
Storage/
X
X 
X
X 
X
X
Serum/
Plasma for 
Storage/
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
X
 
 
 
 
 
X
X 
X
X 
X
X
Blood for 
DNA 
Pharmaco-
genetics
X
CCI
CCI
CCI

I6T-MC-AMAK(a) Clinical Protocol
Page 20
LY3074828
Abbreviations:  BP = blood pressure; BSA = body surface area; conc = concentration; C-SSRS = Columbia–Suicide Severity Rating Scale; DLQI = Dermatology 
Life Quality Index; DNA = deoxyribonucleic acid; ECG = electrocardiogram; EQ-5D-5L-PSO = European Quality of Life–5 Dimensions–5 Levels–Psoriasis; 
ETV = early termination visit; FSH = follicle stimulating hormone; HBcAb = anti-hepatitis B core antibody; HBsAb = hepatitis B surface antibody; HBsAg = 
hepatitis B surface antigen; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus; hsCRP = high-sensitivity C-reactive 
protein; IL-19 = interleukin-19; IP = investigational product; LV = last study visit; miri = mirikizumab; NAPSI = Nail Psoriasis Severity Index; PASI = 
Psoriasis Area and Severity Index; PatGA = Patient’s Global Assessment of Psoriasis; PK = pharmacokinetic; PPASI = Palmoplantar Psoriasis Severity 
Index; PPD = purified protein derivative (skin test); PSS = Psoriasis Symptoms Scale; PSSI = Psoriasis Scalp Severity Index; QIDS-SR16 = 16-item Quick 
Inventory of Depressive Symptomatology; RNA = ribonucleic acid; SF-36 = Medical Outcomes Study 36-Item Short Form Health Survey; sPGA = static 
Physician’s Global Assessment; Suppl. = supplement; TB = tuberculosis; temp = temperature; TSQM = Treatment Satisfaction Questionnaire for Medication; 
V = visit; W = weeks; WCBP = women of childbearing potential; WPAI-PSO = Work Productivity and Activity Impairment Questionnaire: Psoriasis.
a
All activities should be completed prior to any study dose administration, unless otherwise stated.
b
Visit 1 procedures may be conducted over more than 1 day, as long as all tasks are completed within the allowable visit tolerance (at least 3 days should be 
allowed for receipt of laboratory test results).
c
One complete physical examination (excluding pelvic or rectal examinations) to include heart, lungs, peripheral lymph nodes, and abdomen, and visual 
examination of all skin areas (including genitalia and breast areas) will be performed at screening. All physical examinations throughout the study should 
include a symptom-directed evaluation as well as examination of heart, lungs, peripheral lymph nodes, and abdomen, and visual examination of all skin areas 
(including genitalia and breast areas).
d
Sitting blood pressure, temperature, and pulse will be obtained within approximately the same time frame as ECG measurements or blood sampling.  When 
multiple assessments are scheduled for the same time point, the preferred order of completion should be as follows:  ECG (if applicable), vital signs, and then 
blood sampling.
e
Chest radiography will be performed locally at screening unless it has been performed within 3 months before initial screening (provided the radiographs 
and/or formal report are available for the investigator’s review).  For additional details, see Section 9.4.5.3.
f
TB testing will be performed at screening unless it has been performed within 3 months before initial screening (provided the formal report is available for the 
investigator’s review).  It may also be performed after screening if clinically indicated.  TB testing will be performed locally using an interferon-release 
assay (IGRA; QuantiFERON®-TB Gold or T-SPOT.TB®) or a purified protein derivative (PPD) tuberculin skin test.  If PPD test is performed, patients will 
return 2 to 3 days afterwards to have their PPD test read.  For additional details on TB testing, see Exclusion Criterion [19] and Section 9.4.5.2.
g
The preferred order of completion is supine ECG prior to vital signs, blood sampling, or any other study procedures. For additional details on ECG 
collection, see Section 9.4.1. ECG should be performed at the ETV and Visit 802 only if there is early termination due to a cardiovascular event.
h
A Self-Harm Follow-Up Form is to be completed only during visits for which there is at least 1 discrete self-harm event identified on the Self-Harm 
Supplement Form (see Section 9.2.2).
i
PSSI, NAPSI, and PPASI assessments are applicable only if symptoms are present at baseline.
j
These assessments should be completed before administration of investigational product, before the patient’s clinical examination, before the patient receives 
any tests or results, and before the patient’s health, health data, or emotions are discussed.
k
Electronic diaries will be distributed at the screening visit and collected at the Week 16 visit.
l
Unscheduled hematology or blood chemistry panels may be performed at the discretion of the investigator.
m Patients should not eat or drink anything except water for 12 hours prior to sample collection.

I6T-MC-AMAK(a) Clinical Protocol
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LY3074828
n
Any enrolled patient who is HBcAb+ will undergo monitoring of HBV DNA with HBV DNA testing (see Section 9.4.5.4). Any patient with a positive HBV 
DNA test at any time must be discontinued from the study and receive appropriate follow-up medical care, including consideration for antiviral therapy.
o
Following screening, patients will not undergo monitoring for HCV RNA unless liver enzymes are elevated (see Section 9.4.5.5). Any patient with a positive 
HCV RNA test must be discontinued from the study and receive appropriate follow-up medical care, including consideration for antiviral therapy.
p
Immunogenicity samples should be collected prior to dosing on visits when mirikizumab is administered.  A sample will be obtained at unscheduled visits if a 
patient develops an acute hypersensitivity event after administration of IP (see Section 7.8.2.1).
q
Scheduled PK samples are taken as an aliquot from the immunogenicity sample.  Unscheduled PK samples, obtained if a patient develops an acute 
hypersensitivity event after administration of IP (see Section 7.8.2.1), will be collected in a separate tube.
r
FSH test is to be performed at screening for women who have had spontaneous amenorrhea for 6 to 12 months to confirm lack of childbearing potential.
s
If a patient discontinues IP early, the patient will complete the ETV and then enter the Post-Treatment Follow-up Period (V801 + V802).
t
All patients who receive IP but do not participate in Study AMAH must enter the Follow-up Period and complete V801 + V802.
u
Urinalysis assessed only for early termination due to an adverse event for which urinalysis is clinically indicated.

I6T-MC-AMAK(a) Clinical Protocol
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3. Introduction
3.1.
Study Rationale
Mirikizumab (LY3074828) is a monoclonal, anti-interleukin-23 (anti-IL-23) antibody being 
developed for the treatment of immune-mediated diseases where the IL-23 pathway is thought to 
have a significant pathogenic role.  The neutralizing activity of mirikizumab is directed against
the p19 subunit of the IL-23 molecule and does not bind to IL-12.  Study I6T-MC-AMAK
(AMAK) is a confirmatory study testing mirikizumab as a treatment for plaque psoriasis and is 
intended to support registration of this indication. This Phase 3 study is designed to evaluate the 
superiority of mirikizumab versus placebo during the Induction Period (16 weeks), as measured
by improvement in disease severity and key patient-reported outcomes.  This study period is 
followed by a randomized Maintenance Dosing Period to Week 52 to evaluate the maintenance 
of response or remission as well as relapse and rebound following treatment withdrawal, and 
response to retreatment following relapse.  The data will contribute to the evaluation of the safety 
of mirikizumab.
3.2.
Background
The worldwide prevalence of psoriasis is nearly 3% (IFPA 2017), with rates varying across 
ethnic groups, ages, gender, and geographic regions (Parisi et al. 2013).  Histologically, psoriasis 
is characterized by inflammatory infiltrate and hyperproliferative keratinocytes, which retain 
intact nuclei (parakeratosis), elongation of rete ridges, and hyperconvoluted vasculature in the 
papillary dermis.  The infiltrate consists of prominent T cells, dendritic cells, and neutrophils in 
the dermis.  The dysregulation of the immune system, especially the activation of pathogenic 
T cells, has been well demonstrated to play an important role in psoriasis development.
A typical organ-specific, T-cell-driven inflammatory disease, psoriasis had been considered a 
T helper (Th) 1-type skin disease for decades, until a new Th population, Th17, was identified 
(Lew et al. 2004; Steinman 2007; Weaver et al. 2007).  Substantial clinical and basic research 
observations now suggest that the IL-23/Th17 axis is essential in the pathogenesis of psoriasis 
(Di Cesare et al. 2009).  IL-23, a member of the IL-12 family of cytokines, is a heterodimeric 
protein comprised of 2 subunits; the p40 subunit, which it shares with IL-12, and the p19 
subunit, believed to be specific to IL-23.  IL-23 is produced by antigen-presenting cells, such as 
dendritic cells and macrophages, and plays an important role in maintenance and amplification of 
Th17 cells (Lee et al. 2004; Piskin et al. 2004).  In addition, Th17 cells and their downstream 
effector molecules, including IL-17A, IL-17F, IL-21, IL-22, and tumor necrosis factor 
(TNF)-alpha, are found at increased levels in human psoriatic skin lesions and circulation 
(Boniface et al. 2007; Lowes et al. 2008; Caruso et al. 2009; Kagami et al. 2010).
A number of IL-23 targeting molecules are being investigated for the treatment of 
immune-mediated diseases.  The first biologic to demonstrate clinical benefit through IL-23 
inhibition in such diseases was ustekinumab, which is a monoclonal antibody approved by the 
United States Food and Drug Administration (FDA; Stelara® package insert 2017) and the 
European Medicines Agency (EMA; Stelara Summary of Product Characteristics 2017) for the 
treatment of psoriasis, psoriatic arthritis, and Crohn’s disease, and is being evaluated in a Phase 3 

I6T-MC-AMAK(a) Clinical Protocol
Page 23
LY3074828
trial for the treatment of ulcerative colitis (NCT02407236).  Ustekinumab binds the p40 subunit 
common to IL-12 and IL-23; therefore, it targets both cytokines rather than IL-23 specifically.  
Blockade of the IL-12 pathway may prevent Th1 cell-induced interferon blockade of Th17 cell 
development, thus potentially limiting the clinical activity of p40-targeting antibodies.  
Experimental studies suggest that blocking the IL-23/Th17/IL-17 immune axis alone is sufficient 
to treat autoimmune inflammation (Monteleone et al. 2009). One such therapy that specifically 
targets the p19 subunit of IL-23, guselkumab, has been approved for the treatment of moderate-
to-severe plaque psoriasis by the United States FDA (Tremfyapackage insert 2017) and the 
EMA (Tremfya Summary of Product Characteristics 2017).  Other similar agents, including 
mirikizumab in Studies I6T-MC-AMAA (AMAA) and I6T-MC-AMAF (AMAF), have 
demonstrated clinical activity in plaque psoriasis (Krueger et al. 2015; Papp et al. 2015, 2017;
Reich et al. 2017b).
3.3.
Benefit/Risk Assessment
Psoriasis remains an important public health challenge.  Therefore, there is a continuing need to 
develop treatment options with mechanisms of action that differ from existing therapies.  Clinical 
data with mirikizumab (Studies AMAA and AMAF), as well as clinical data with ustekinumab,
risankizumab, tildrakizumab, and guselkumab, support the hypothesis that IL-23 plays a 
significant role in the pathogenesis of psoriasis, and these compounds appear to have a favorable
benefit/risk profile in patients with psoriasis.
To assess the nonclinical toxicity of mirikizumab and establish a margin of safety (MOS) for 
clinical studies, 4-week and 6-month general toxicity studies in normal cynomolgus monkeys 
were conducted for the evaluation of immunotoxicity, toxicokinetics, safety pharmacology (as 
part of the 4-week study), and fertility (as part of the 6-month study). The weekly administration 
of mirikizumab to cynomolgus monkeys resulted in no adverse mirikizumab-related findings at 
doses of 0 mg/kg (vehicle), 1 and 30 mg/kg (subcutaneous [SC]), or 100 mg/kg (intravenous 
[IV]) for 4 weeks, or 0, 10, and 100 mg/kg (SC) for 6 months.  Based on the lack of any toxicity 
at exposures exceeding the highest clinical exposure and lack of any tissue cross-reactivity, the 
nonclinical safety profile of mirikizumab supports clinical development.  Plasma exposure in 
monkeys at the no-observed-adverse-effect-level (NOAEL) in the 4-week and 6-month studies
provided 52- and 22-fold MOS, respectively, relative to the predicted human exposure at the 
highest proposed clinical dose and frequency of 250 mg administered SC every 4 weeks.
After 16 weeks of treatment in Study AMAF, Psoriasis Area and Severity Index (PASI) 90 
responses in all mirikizumab treatment arms were significantly higher than placebo, with the 
highest responses in the 100-mg and 300-mg dosing groups. Overall frequencies of adverse 
events (AEs) were similar for mirikizumab- and placebo-treated patients (Reich et al. 2017b).
The doses and regimens planned for Study AMAK were selected based on analyses of 
pharmacokinetic (PK), safety, and efficacy data from Phase 1 and Phase 2 studies, literature 
information for other anti-IL-23 antibodies, and nonclinical safety data.  In addition, blinded 
trial-level safety reviews will be conducted at periodic intervals throughout the study.  Interim 
safety analyses will be conducted by an external Data Monitoring Committee (DMC) to review 
unblinded safety data.  These monitoring and risk-mitigation actions, along with regular review 

I6T-MC-AMAK(a) Clinical Protocol
Page 24
LY3074828
of AEs and laboratory data, will assist in the evaluation and management of potential risks 
associated with mirikizumab administration.
Given the published literature supporting positive clinical activity following blocking IL-23 in 
autoimmune/inflammatory diseases including psoriasis, the favorable safety and PK profile of 
mirikizumab, and the initial clinical activity observed for mirikizumab in patients with psoriasis, 
the potential benefits of participating in Study AMAK are expected to outweigh the potential 
risks.
More information about the known and expected benefits, risks, serious adverse events (SAEs) 
and reasonably anticipated AEs of mirikizumab are to be found in the Investigator’s Brochure 
(IB).

I6T-MC-AMAK(a) Clinical Protocol
Page 25
LY3074828
4.
Objectives and Endpoints
Table AMAK.2 shows the objectives and endpoints of the study.
Table AMAK.2.
Objectives and Endpoints
Objectives
Endpoints
Primarya,b
To assess whether mirikizumab induction dosing is 
superior to placebo in the treatment of patients with 
respect to high levels of clinical response
At Week 16:

Proportion of patients with an sPGA (0,1) with at 
least a 2-point improvement from baseline

Proportion of patients achieving a 90% 
improvement in PASI from baseline (PASI 90)
Major Secondarya,b
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to an early, clinically 
meaningful response
At Week 4:

Proportion of patients achieving a 75% improvement 
in PASI (PASI 75)
To assess whether the mirikizumab induction dosing 
is superior to placebo with respect to clinically 
meaningful response and the highest levels of clinical 
response
At Week 16:

Proportion of patients achieving PASI 75

Proportion of patients achieving a 100% 
improvement in PASI (PASI 100)
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to body surface area 
(BSA) affected by psoriasis
At Week 16:

Proportion of patients with ≤1% of BSA with 
psoriasis involvement
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to patient-reported 
outcomes
At Week 16:

Proportion of patients with a PSS symptoms score of 0 
(free of itch, pain, stinging, and burning) in those with 
a PSS symptoms score 1 at baseline.

Proportion of patients achieving a DLQI total score of 
(0,1) with at least a 5-point improvement (reduction)
from baseline in patients with a baseline DLQI total 
score 5
To assess whether 250 mg mirikizumab Q8W and 
125 mg mirikizumab Q8W maintenance dosing is 
superior to placebo with respect to maintenance of a 
high level of clinical response
At Week 52:

Proportion of patients maintaining clinical response 
(PASI 90) after re-randomization at the start of the 
randomized withdrawal period
Other Secondaryb
To compare mirikizumab to placebo with respect to 
clinical response and time to clinical response during 
the induction dosing period, and with respect to 
patient-reported outcomes during the induction 
dosing period
At Week 16 and various time points over the first 16 weeks 
of dosing:

Proportion of patients achieving PASI 90.

Change in PPASI total score in patients with 
palmoplantar involvement at baseline

Change in PSSI total score in patients with scalp 
involvement at baseline

Change in NAPSI total score in patients with 
fingernail involvement at baseline

I6T-MC-AMAK(a) Clinical Protocol
Page 26
LY3074828
Objectives
Endpoints

Change from baseline on the SF-36 physical 
component summary (PCS) and mental component 
summary (MCS) 

Change from baseline on PatGA of disease severity

Change from baseline for the WPAI-PSO scores 
(Absenteeism, Presenteeism, Work Productivity 
Loss, and Activity Impairment)

Change from baseline in QIDS-SR16 total score in 
those with a baseline QIDS-SR16 total score 11

Proportion of patients achieving a DLQI total score 
of (0,1) with at least a 5-point improvement 
(reduction) from baseline in patients with a baseline 
DLQI total score 5

Proportion of patients achieving DLQI (0,1) with 
DLQI baseline score >1
To assess whether 250 mg mirikizumab Q8W and 
125 mg mirikizumab Q8W dosing is superior to 
placebo with respect to maintenance of high and 
highest levels of clinical response among patients 
who have an PASI 90 at Week 16 and are re-
randomized
At Week 52 and at various time points during the 
Maintenance Dosing Period:

Time to relapse (the loss, at any visit, of 50% of the 
Week 16 PASI improvement from baseline).

Proportion of patients who have relapsed.

Proportion of patients maintaining clinical response 
(PASI 90) after re-randomization at the start of the 
randomized withdrawal period

Incidence of disease rebound within 12 weeks 
(worsening of psoriasis severity over baseline sPGA 
score, or worsening of psoriasis severity over 
baseline PASI score by 125%, or change in psoriasis
phenotype [for example, from plaque to pustular]) 
after re-randomization to placebo at Week 16.
To assess the efficacy of 250 mg mirikizumab Q8W 
following relapse after re-randomization to placebo 
treatment in the Maintenance Dosing Period
During the Maintenance Dosing Period:

Proportion of patients who regained PASI 90 within 
16 weeks after mirikizumab retreatment.  
To evaluate the pharmacokinetics and 
pharmacokinetic/pharmacodynamic relationship of 
mirikizumab

Clearance and volume of distribution of 
mirikizumab

Relationship between mirikizumab exposure and 
efficacy (sPGA and PASI)
Exploratory
To evaluate the potential development of anti-
mirikizumab antibodies and their potential 
relationship with efficacy, TEAEs, and mirikizumab
exposure
At Week 16 and Week 52:

Relationship between TE-ADA and efficacy (sPGA 
and PASI)

Relationship between TE-ADA and TEAEs

Relationship between TE-ADA and mirikizumab
pharmacokinetics.

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Abbreviations: BSA = body surface area; DLQI = Dermatology Life Quality Index; MCS = mental component 
summary; NAPSI = Nail Psoriasis Severity Index; PASI = Psoriasis Area and Severity Index; 
PASI 75/90/100 = 75%/90%/100% improvement in PASI from baseline; PatGA = Patient’s Global 
Assessment of Psoriasis; PCS = physical component summary; PPASI = Palmoplantar Psoriasis Severity Index; 
PSS = Psoriasis Symptoms Scale; PSSI = Psoriasis Scalp Severity Index; Q8W = every 8 weeks; QIDS-SR16 = 
16-item Quick Inventory of Depressive Symptomatology; SF-36 = Medical Outcomes Study 36-Item Short Form 
Health Survey; sPGA = static Physician’s Global Assessment; TE-ADA = treatment-emergent anti-drug 
antibody; TEAEs = treatment-emergent adverse events; WPAI-PSO = Work Productivity Activity Impairment 
Questionnaire–psoriasis.
a
All primary and major secondary endpoint analyses will utilize the multiplicity control technique called 
“graphical multiple testing procedure” to control the overall family-wise Type I error rate.
b
Note:  A “clinically meaningful” response is a PASI 75 response, which represents at least a 75% decrease 
(improvement) from the baseline PASI score.  A “high level” of clinical response is a PASI 90 response, which 
represents at least a 90% decrease (improvement) from baseline in PASI score, or sPGA (0,1) response, which 
represents an “almost clear” response.  The “highest level” of clinical response is a PASI 100 or sPGA (0) 
response, which represents complete resolution of psoriasis.

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5. Study Design
5.1.
Overall Design
Study AMAK is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, 
parallel-group, multi-period study in which approximately 500 patients will be randomized to 
treatment groups involving different mirikizumab doses and regimens or placebo.  The study is 
comprised of 2 treatment periods (Induction and Maintenance with Randomized Withdrawal),
which together last for up to 52 weeks, followed by a 12-week Post-Treatment Follow-Up 
period.
Study governance considerations are described in detail in Appendix 3.
5.1.1. Screening Period
Patients will be evaluated for study eligibility ≤28 days before the baseline visit (Visit 2).  The 
patient will sign the informed consent form (ICF) prior to any study assessments, examinations, 
or procedures being performed.  Screening procedures will be performed according to the 
Schedule of Activities (Section 2).  Electronic diary collection will begin at screening, 
approximately ≤28 days prior to Visit 2 (baseline).  All inclusion and exclusion criteria are 
provided in Sections 6.1 and 6.2, respectively.
5.1.2. Baseline and Double-Blind Induction Period (Week 0 to 
Week 16):
At Visit 2 (Week 0; baseline), patients who meet the study eligibility criteria will be randomized
4:1 to receive 250 mg mirikizumab or matching placebo (SC), respectively, at Weeks 0, 4, 8, and 
12.  Randomization will be stratified, based on previous exposure to biologic therapy (yes/no), 
body weight (<100 kg or 100 kg), and geographic region (North America or Other).
Patients who discontinue the study for any reason during this period will stop treatment and 
continue to the early termination visit (ETV) and then complete the 12-week Post-Treatment 
Follow-up Period.
5.1.3. Double-Blind Maintenance Period (Week 16 to Week 52
[36 Weeks]):
All patients who complete the Induction Period may continue in the Maintenance Period.
The Maintenance Dosing Period will be a double-blind treatment period with randomized 
withdrawal.  The first injection of study drug for this period will be at Week 16, with the last
injection at Week 48.
At Week 16 (Visit 7), patients who enter the Maintenance Period will be classified as a 
responder (PASI 90) or non-responder (<PASI 90).  Patients who are responders at Week 16 
will be monitored for maintenance of response or remission, as well as relapse and disease 
rebound following treatment withdrawal, and response to retreatment following relapse.  
Remission is defined as the achievement of PASI 100.  Relapse is defined as the loss, at any 

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visit, of 50% of the Week 16 PASI improvement from baseline. That is, a patient will have 
relapsed during the Maintenance Period if their PASI score increases to at or above the midpoint 
between their baseline and Week 16 PASI score. Rebound is defined as having one or more of 
the following: worsening of psoriasis severity over baseline static Physician’s Global 
Assessment (sPGA) score, worsening of psoriasis severity over baseline PASI score by 125%, or 
change in psoriasis phenotype (for example, from plaque to pustular) after randomization to 
placebo at Week 16.
Patients will be treated as follows:

Patients who were responders to mirikizumab in the blinded Induction Period (responder 
definition is PASI 90 at Week 16) will be re-randomized 1:1:1 to 250 mg mirikizumab
every 8 weeks (Q8W), 125 mg mirikizumab Q8W, or placebo Q8W, according to their 
randomized treatment assignment at Week 16 (see Figure AMAK.1).  Stratification for 
the re-randomization will be based on body weight at baseline (<100 kg or 100 kg).
o
Patients who relapse during the blinded Maintenance Period (see relapse criterion 
defined above) will remain on, or will be switched to, 250 mg mirikizumab for the 
remainder of the study and will be monitored for recapture of efficacy response.  
These patients will begin retreatment with mirikizumab at the visit at which 
relapse is identified and will receive another mirikizumab treatment at the next 
visit 4 weeks later.  Subsequent mirikizumab treatments will be given at Q8W 
intervals.  

Patients who received placebo in the blinded Induction Period who are responders at 
Week 16 (Visit 7) will continue to receive placebo during the Maintenance Period until 
relapse; these patients will begin treatment with 250 mg mirikizumab at the visit at which 
relapse is identified and will receive another mirikizumab treatment at the next visit 
4 weeks later.  Subsequent mirikizumab treatments will be given at Q8W intervals.

Patients who were not responders to mirikizumab in the blinded Induction Period will 
receive 250 mg mirikizumab Q8W.
o
Continued blinded treatment for nonresponders is provided so that partial or slow 
responders may remain in the study beyond Week 16, thus maintaining the study 
blind while patients continue to receive potentially beneficial longer-term 
treatment with mirikizumab.

Patients who received placebo in the blinded Induction Period who are non-responders at 
Week 16 (Visit 7) will receive 250 mg mirikizumab every 4 weeks (Q4W) for Weeks 16 
through 32 and mirikizumab treatments Q8W thereafter.  
All patients will receive injections (mirikizumab or placebo, as appropriate) Q4W at Weeks 16 
through 48 (Visits 7 through 15) in order to maintain study blind across the study treatment 
groups.

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A discontinuation criterion has been included for patients in any treatment group who remain at 
or above their baseline sPGA score at Week 16 (Visit 7) and Week 24 (Visit 9), or who remain at 
or above their baseline PASI score at Week 16 (Visit 7) and Week 24 (Visit 9), to ensure that 
patients who have not shown any benefit from study treatment are offered alternative therapies
(see Section 8.2).
At Week 52, patients will have one of the following two options:
1. Enter Study I6T-MC-AMAH (AMAH), a long-term extension study in which patients
will receive 250 mg mirikizumab Q8W (SC) or 125 mg mirikizumab Q8W (SC),
OR
2. Discontinue study treatment and complete Study AMAK’s 12-week Post-Treatment 
Follow-Up Period.
Patients who discontinue the study for any reason during this period will stop treatment and 
continue to the ETV and then complete the 12-week Post-Treatment Follow-up Period.
5.1.4. Post-Treatment Follow-up Period (12 Weeks)
Patients who do not enroll into Study AMAH or who discontinue early from study treatment in 
Study AMAK will complete the Post-Treatment Follow-Up Period (V801 and V802) of
Study AMAK.
For patients who have entered the Post-Treatment Follow-Up Period, psoriasis therapy with 
another agent(s), as determined appropriate by the investigator, is allowed.
Figure AMAK.1 illustrates the study design.

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Abbreviations: LV = last study visit; miri = mirikizumab; Q4W = every 4 weeks; 
Q8W = every 8 weeks; V = visit; w = weeks; W = week.
Note: Randomizations occur at Week 0 and Week 16.
*
Option to enter Study AMAH or to enter the Post-Treatment Follow-Up Period.
a
Patients may receive placebo injections during the Maintenance Period to 
maintain the study blind across treatment groups, as described in Section 5.1.3.
b
Patients who relapse during the Maintenance Period will be treated with 250 mg 
mirikizumab for the remainder of the study and will be monitored for recapture of 
efficacy response, as described in Section 5.1.3.
c
First Maintenance Period dosing at Week 16.
Figure AMAK.1.
Illustration of study design for Clinical Protocol I6T-MC-AMAK.
5.2.
Number of Participants
Approximately 650 participants will be screened to achieve 500 randomized participants: 
400 randomized to mirikizumab and 100 randomized to placebo.
5.3.
End of Study Definition
End of the study is the date of the last visit or last scheduled procedure for the last patient.

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5.4. Scientific Rationale for Study Design
This study will examine the effectsof 16 weeks of double-blind dosing (1 dose regimen of 
mirikizumabversus placebo) during the Induction Period.The selection of placebo as a 
comparator is justified on the basis that the most robust evaluation of efficacy can be made 
versus placebo treatment, and the duration of the 16-week primary evaluation is sufficiently short 
forpatients toreceive placebo without lasting adverse effects.
In the Maintenance with Randomized WithdrawalPeriod, double-blind dosingwith 250mg
mirikizumabQ8W, 125 mg mirikizumabQ8W, or placebo will be evaluated.  Patients who were 
not responders to LY3074828 in the Induction Period will beswitched to 250mg mirikizumab
Q8Win the Maintenance Periodso that partial or slow responders may remain in the study
beyond Week 16, thus maintaining the study blindwhile patients continueto receive longer-term
treatment with mirikizumab.  The purpose of this study periodis to determine the optimaldosing 
levelfor the maintenance of responseor remission, to evaluate relapse or rebound following 
treatment withdrawal, and to measure response to retreatment following relapse.
The Post-Treatment Follow-up Period is included for safety monitoring following the last study 
visitfor patients who do not enroll in Study AMAH or who discontinue early from 
StudyAMAK.
The dose justification for mirikizumabis outlined in Section 5.5, and the study blind will be 
maintained as described in Section 7.3.
5.5. Justification for Dose
The dose levels and regimens selected for this study were based primarily on analyses of interim 
PK, safety, and efficacy data from the Phase 2 Study AMAF, safety data from other clinical 
studies evaluating mirikizumab, and nonclinical safety data.
Safety Considerations
CCI
Single doses of up to 600 mg IV were evaluated in Study AMAA (healthy subjects and psoriasis 
patients) and up to 1200 mg IV in Study I6T-JE-AMAD (healthy subjects); no dose-related 
safety or tolerability issues were observed in either study.  Evaluation of the safety data available 
to date in the ongoing Phase2 studies in patients with ulcerative colitis (Study I6T-MC-AMAC) 
and inpatients withCrohn’s disease (Study I6T-MC-AMAG) that are evaluating higher and
more frequent dose regimens of up to 1000 mg IV Q4W for up to 52 weeks has not revealed any 
difference in the safety profile resulting from these higher exposures.
 
No dose-related safety or tolerability issues have been observed in Study AMAF, including in 
patients who were non-responders and received a third dose of 300mg SC at Week16.  
Although the proposed 250 mg Q4W induction dose regimen for this study is expected to 
produce modestly higher average concentrations than the highest dose regimen evaluated in 

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Study AMAF, the safety data collected from completed and ongoing clinical studies and from 
nonclinical toxicology studies supports the proposed dose regimens.
Efficacy Considerations
CCI
In Study AMAF, doses of 30, 100, and 300 mg mirikizumab administered Q8W SC provided 
significant efficacy relative to placebo, with 100 and 300 mg achieving greater efficacy than 
30mg at Week16.  The 300-mg dose provided the highest efficacy for the primary endpoint at 
Week 16 (PASI 90) and demonstrated a trend towards providing higher PASI 90 and PASI 100 
rates at earlier time points; the 300-mg dose also provided a more durable response following 
Week 16.  Thus, results from Study AMAF indicate that the highest dose (300 mg) provided the 
greatest efficacy.
Results from Study AMAF also suggest that additional dosing, if given during the Induction 
Period, might have further improved efficacy at Week 16.  This suggestion is based on 
incremental benefits observed following a third dose administered to Week 16 nonresponders,
when assessed within 4 week to 8 weeks of that dose.  Model-based analyses and simulations 
indicate that 250-mg doses administered at Weeks 0, 4, 8, and 12 (1000 mg total) will maximize 
efficacy at the end of the 16-weekInduction Period.
A dosing regimen of 250 mg SC Q8W during the Maintenance Period is expected to maintain or 
further enhance the efficacyachieved at the end of the Induction Period.  The 250-mg dose is 
expected to achieve exposures and efficacy that are not distinguishable from that observed with 
300-mg dosing.  A second maintenance dosing regimen of 125 mg Q8W SC was chosen to 
determine whether efficacy could be maintained with a lower dosing regimen.  This second 
dosing regimen is expected to result in mirikizumabconcentrations that have, in individual 
subjects, minimal overlap with the concentrations produced with the 250mg mirikizumabQ8W 
SC regimen.
 
 
 
 

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6.
Study Population
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, are not permitted.
6.1.
Inclusion Criteria
Patients are eligible to be included in the study only if they meet all of the following criteria 
within the screening period, which is ≤28 days prior to the start of study treatment unless 
otherwise defined:
Type of Patient and Disease Characteristics
[1]
Present with chronic plaque psoriasis based on the investigator-confirmed
diagnosis of chronic psoriasis vulgaris for at least 6 months prior to baseline, 
and meet the following criteria:
A. Plaque psoriasis involving 10% body surface area (BSA) and absolute 
PASI score 12 in affected skin at screening (Visit 1) and baseline 
(Visit 2), and
B. sPGA score of 3 at screening (Visit 1) and baseline (Visit 2).
[2]
Candidate for systemic therapy and/or phototherapy.
Patient Characteristics
[3a] Male patients:
No male contraception required except in compliance with specific local 
government study requirement.
[3b] Female patients:
Women not of childbearing potential may participate and include those who are:
A. Infertile due to surgical sterilization (hysterectomy, 
bilateral oophorectomy, or tubal ligation), congenital 
anomaly such as mullerian agenesis,
OR
B. Postmenopausal, defined as:
i.
A woman at least 50 years of age with an intact 
uterus, not on hormone therapy, who has had either:
a.
Cessation of menses for at least 1 year,
OR
b.
At least 6 months of spontaneous amenorrhea 
with a follicle stimulating hormone 
>40 mIU/mL,

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OR
ii.
A woman 55 years or older not on hormone therapy,
who has had at least 6 months of spontaneous 
amenorrhea,
OR
iii.
A woman at least 55 years of age with a diagnosis of 
menopause prior to starting hormone replacement 
therapy.
Women of childbearing potential:
A. Must test negative for pregnancy prior to initiation of treatment as 
indicated by a negative serum pregnancy test at the screening visit 
followed by a negative urine pregnancy test within 24 hours prior to 
exposure.
B. Must agree to either remain abstinent, if complete abstinence is their 
preferred and usual lifestyle, or remain in same-sex relationships, if part 
of their preferred and usual lifestyle, without sexual relationships with 
males. Periodic abstinence (for example, calendar, ovulation, 
symptothermal, post-ovulation methods), declaration of abstinence just 
for the duration of a trial, and withdrawal are not acceptable methods of 
contraception.
OR
Must use 2 effective methods of contraception for the entirety of the 
study.  Abstinence or contraception must continue for 12 weeks 
following completion of investigational product administration.
i. Two effective methods of contraception (such as male or female 
condoms with spermicide, diaphragms with spermicide or cervical 
sponges) will be used.  The patient may choose to use a double-
barrier method of contraception.  Barrier protection methods without 
concomitant use of a spermicide are not a reliable or acceptable 
method.  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.
ii.
Of note, one of the two methods of contraception may be a highly 
effective (less than 1% failure rate) method of contraception (such as 
combination oral contraceptives, implanted contraceptives or 
intrauterine devices).

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When local guidelines concerning highly effective or effective methods of birth 
control differ from the above, the local guidelines must be followed.
[4]
Are at least 18 years of age at the time of screening.
[5]
Have adequate organ function, including:
A. Hematology: 
i.
Absolute neutrophil count 1.5 x 109/L (1.5 x 103/µL or 
1.5 GI/L),
ii.
Platelet count 100 x 109/L (100 x 103/µL or 100 GI/L),
iii.
Hemoglobin level 10.0 g/dL (100 g/L),
iv.
Lymphocyte count >500 cells/µL (>0.50 x 103/µL or >0.50 GI/L),
v.
Total white blood cell count 3.0 x 109/L (3.0 x 103/µL or 
3.0 GI/L).
B. Chemistry: 
i.
Serum creatinine ≤2x the upper limit of normal (ULN),
ii.
Alanine aminotransferase (ALT) ≤2x ULN,
iii.
Aspartate aminotransferase (AST) levels ≤2x ULN,
iv.
Total bilirubin level <1.5x ULN (patients with Gilbert’s syndrome 
must have serum direct bilirubin <1.5 mg/dL or <25.7 µmol/L),
v.
Alkaline phosphatase (ALP) <1.5x ULN.
(Note:  The tests for AST and ALT may be repeated once within a week 
if the initial response exceeds this limit, and the repeat value may be 
accepted if it meets this criterion.  Other laboratory tests should not be 
repeated unless there is a technical error or clinical reasons to believe a 
result may be erroneous, and requires approval by the Eli Lilly and 
Company [Lilly]-designated medical monitor.)
[6]
Are reliable and willing to make themselves available for the duration of the 
study and are able and willing to follow study procedures, including use of 
electronic device for recording of data.
Informed Consent
[7]
Have given written informed consent as a legal adult according to local 
regulations.
6.2.
Exclusion Criteria
Patients will be excluded from study enrollment if they meet any of the following criteria at 
screening, unless otherwise specified:

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Medical Conditions
[8]
Have an abnormality in the 12-lead electrocardiogram (ECG) that, in the 
opinion of the investigator, increases the risks associated with participating in 
the study.
[9]
Have an unstable or uncontrolled illness, including but not limited to a 
cerebro-cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, 
hematologic, or neurologic disease or abnormal laboratory values at 
screening, that in the opinion of the investigator, would potentially affect 
patient safety within the study or of interfering with the interpretation of data.
[10] Presence of significant uncontrolled neuropsychiatric disorder or judged 
at-risk of suicide in the opinion of the investigator;
OR
marked “yes” to Columbia-Suicidality Severity Rating Scale (C-SSRS)
question 4 or 5 on ideation at Visit 1, or prior to dosing at Visit 2;
OR
“yes” to C-SSRS suicide behaviors question 1 month prior to Visit 1, or prior
to dosing at Visit 2;
OR
Has a history of suicide attempt within 1 month prior to screening.
[11] Have human immunodeficiency virus (HIV)/acquired immune deficiency 
syndrome (AIDS) or test positive human HIV antibodies at screening.
[12] Have hepatitis C or test positive for hepatitis C virus (HCV) at screening, 
defined as:  positive result for hepatitis C antibody and positive confirmatory 
HCV ribonucleic acid (RNA) test (see Section 9.4.5.5).  Patients in sustained 
virologic response after HCV therapy, and patients who have spontaneously 
cleared HCV infection (see Section 9.4.5.5), can be included in this study.
[13] Have hepatitis B or test positive for hepatitis B virus (HBV) at screening, 
defined as: 
A.
Positive for hepatitis B surface antigen (HBsAg+),
OR
B.
Positive for hepatitis B core antibody (HBcAb+) in conjunction with positive 
confirmatory HBV deoxyribonucleic acid (DNA) test
OR
C.
Positive HBV DNA test, regardless of anti-hepatitis B surface antibody
(HBsAb) status.

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[14] Are women who are breastfeeding or plan to breastfeed during study.
[15] Have donated blood of >500 mL within 14 days prior to baseline.
[16] Have had serious, opportunistic (see Section 9.2.3 and Appendix 4), or 
chronic/recurring infection within 3 months prior to screening.  Examples 
include, but are not limited to, infections requiring IV antibiotics, 
hospitalization, or prolonged treatment.
[17] Have received a systemic (including oral) anti-infective agent for an infection 
within 28 days of baseline (see Section 6.4 for information on rescreening). 
[18] Have had, according to the investigator, clinically significant herpes zoster 
within 3 months of screening.
[19] Have evidence of active or latent tuberculosis (TB) (refer to Section 9.4.5.2
for details on full TB exclusion criteria and Section 6.4 for information on 
rescreening).
[20] Have received a Bacillus Calmette-Guerin (BCG) vaccination within 
12 months or received live vaccine(s) (including attenuated live vaccines) 
within 12 weeks of baseline or intend to receive either during the study.
[21] Have history of hypersensitivity events to any components of the mirikizumab
product formulation.
[22] Have active or history of lymphoma, leukemia, or any 
malignancy. Exceptions: the following conditions are not 
exclusionary: successfully treated basal cell skin carcinoma, squamous cell 
skin carcinoma, or cervical carcinoma in situ, with no evidence of recurrence 
or metastatic disease within the 5 years prior to baseline.
[23] Have any other skin conditions (excluding plaque psoriasis) that would affect 
interpretation of the results (including, but not limited to, scleroderma, 
eczema, drug-induced psoriasis, guttate psoriasis, pustular psoriasis, 
parapsoriasis, or cutaneous manifestations of other autoimmune diseases such
as systemic lupus erythematosus).
Prior/Concomitant Therapy
[24] Have received systemic nonbiologic therapy (including, but not limited to, 
oral psoralen and ultraviolet A [PUVA] light therapy; cyclosporine; 
corticosteroids; methotrexate; oral retinoids; apremilast; tofacitinib; 
mycophenolate mofetil; thioguanine; hydroxyurea; sirolimus; tacrolimus; 
azathioprine; leflunomide; fumaric acid derivatives; or 1,25-dihydroxyvitamin 
D3 and analogues) or phototherapy (including either oral and topical PUVA 
light therapy, ultraviolet B, excimer laser, or self-treatment with tanning beds 
or therapeutic sunbathing) within 28 days prior to baseline.

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[25] Have received topical treatment (including, but not limited to, corticosteroids 
[mild or least potent topical steroids will be permitted for use limited to the 
face, axilla, or genitalia], crisaborole, anthralin, calcipotriene, topical 
vitamin D derivatives, retinoids, tazarotene, pimecrolimus, tacrolimus, 
emollients and other nonprescription topical products containing urea, 
>3% salicylic acid, alpha- or beta-hydroxyl acids, or medicated shampoos [for 
example, those that contain >3% salicylic acid, corticosteroids, coal tar, or 
vitamin D3 analogues]) within 14 days prior to baseline.
[26] Have received anti-TNF targeting biologics within 8 weeks prior to baseline, 
or anti-IL-17 targeting biologics within 12 weeks prior to baseline.
[27] Have previous exposure to any biologic therapy targeting IL-12/23 (p40 
subunit), or IL-23 (p19 subunit), either marketed or investigational.
[28] Are unable or unwilling to avoid excessive sun exposure or use of tanning 
booths for at least 4 weeks prior to baseline and during the study.
Prior/Concurrent Clinical Trial Experience
[29] Are currently enrolled in any other clinical study involving an investigational 
product or any other type of medical research judged not to be scientifically or 
medically compatible with this study.
[30] Have participated, within the last 30 days, in a clinical study involving an 
investigational product.
If the previous investigational product has a long half-life, 3 months or 
5 half-lives (whichever is longer) should have passed prior to screening.
[31] Have previously completed or withdrawn from this study or any other study 
investigating mirikizumab.
Other Exclusions
[32] Are investigator site personnel directly affiliated with this study and/or their 
immediate families.  Immediate family is defined as a spouse, parent, child, or 
sibling, whether biological or legally adopted.
[33] Are Lilly employees or employees of third-party organization involved with 
the study who require exclusion of their employees.
[34] Are unsuitable for inclusion in the study in the opinion of the investigator or 
Sponsor for any reason that may compromise the patient’s safety or confound 
data interpretation.

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6.2.1. Rationale for Exclusion of Certain Study Candidates
Patients less than 18 years of age are excluded from participation in this study. This is a 
confirmatory study designed to evaluate the efficacy and safety of mirikizumab as a treatment for 
plaque psoriasis and is intended to support registration of this indication in adult patients. Until 
efficacy and an adequate safety profile is developed in adult patients with psoriasis, adolescents 
and younger children with psoriasis will not be included in studies of this investigational 
product.  Patients with particular medical conditions, including serious infections or other 
uncontrolled illnesses, are excluded for patient safety and to eliminate potential confounders to 
data interpretation.  Patients taking particular concomitant medications are excluded to eliminate 
potential confounders to data interpretation.  Exclusion of patients currently or recently enrolled 
in other clinical trials, or patients affiliated with the investigator or study Sponsor, are excluded 
to meet Good Clinical Practice (GCP) initiatives for unbiased selection of patients.
6.3.
Lifestyle Restrictions
Study participants should be instructed not to donate blood or blood products during the study or 
for 12 weeks following their last dose of investigational product.
6.4.
Screen Failures
Individuals may be rescreened only 1 time for failure due to criteria [17] or [19]. Patients who 
do not qualify at screening under Exclusion Criteria [17] (recent systemic anti-infective 
treatment) may be rescreened (1 time) 4 or more weeks after documented resolution of 
underlying condition being treated.  Patients who test positive for latent TB (Exclusion Criteria 
[19]) at screening may be rescreened following appropriate treatment as described in 
Section 9.4.5.2.
Each time rescreening is performed, the individual must sign a new ICF and will be assigned a 
new identification number.
Patients who have had previous screening chest radiography and TB tests as per protocol within 
3 months of their rescreening date of consent do not need to repeat these procedures but may do 
so at the discretion of the investigator.

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7.Treatments
7.1. Treatments Administered
This study involves evaluation of mirikizumab(250 mg or 125 mg) andplacebo administered SC
during 52 weeks of double-blind treatment.  TableAMAK.3shows the treatment regimens.
TableAMAK.3.
Treatment Regimens
Regimen Group
Dosing
Description
250 mg miri Q4W
250 mg miri
At W0, 4, 8, and 12 for patients randomized to 
mirikizumab during the Induction Period
At W16, 20, 24, 28 and 32 of the Maintenance Period, for 
patients who were randomized to placebo during the 
Induction Period
250 mg miri Q8W
250 mg miri
During the Maintenance Period only, starting at W16
125 mg miri Q8W
125mg miri
 During the Maintenance Period only, starting at W16
Placebo
Placebo
 
At W0, 4, 8, and 12 for patients randomized to placebo 
during the Induction Period
At all visitsduring the Maintenance Period,as necessary,
to maintain the study blind across treatment groups
Abbreviations:  miri = mirikizumab; 
; Q4W = every 4 weeks; Q8W = every 8 weeks; W = 
Week.
Detailed instructions for investigational product administration will be provided by the Sponsor, 
and the investigational product will be administered at the site by clinical staff.
The investigator or his/her designee is responsible for the following:
Explaining the correct use of the investigational agent(s) to the site personnel,
Verifying that instructions are followed properly,
Maintaining accurate records of investigational product dispensing and 
collection,

C
C
I
At the end of the study returning all unused medication to Lilly, or its 
designee, unless the Sponsor and sites have agreed all unused medication is to 
be destroyed by the site, as allowed by local law.
C
C
I
C
C
I
CCI
C
C
I
CCI

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7.1.1. Packaging and Labelling
Mirikizumaband placebo will be supplied to the investigator by Lilly.Clinical trial materials 
will be labeled according to the country’s regulatory requirements. All investigational products 
will be stored, inventoried, reconciled, andreturned ordestroyed according to applicable 
regulations.Clinical trial materials are manufactured in accordance with current Good 
Manufacturing Practices(GMP).
Investigational productwill be supplied assingle-use,solution pre-filled syringescontaining 
mirikizumabor placebo.
Mirikizumabcannot be distinguished visually from placebo.
Investigational productwill be provided with study-specific labels. Syringes will be supplied in 
cartons, with the appropriate quantity specific to the planned dispensing schedule of the 
investigational product.
7.2. Method of Treatment Assignment
Patients who meet all criteria for enrollment will be randomized to double-blind treatment at 
Visit 2.Assignmentto treatment groups will be determined by a computer-generated random 
sequence using an interactive web-response system (IWRS).  The IWRS will be used to assign 
prefilled syringescontaining double-blind investigational product to each patient.
Investigational product will be dispensed according to the Schedule of Activities (Section2)for 
treatment of patients in the clinic.  Site personnel will confirm that they have located the correct 
carton(s)of pre-filled syringesby entering a confirmation number found on the carton(s)into the 
IWRS.
7.2.1. Selection and Timing of Doses
Study visits at which investigational productis administeredare preferred, if possible,to occur 
on the same day of the week.  In any case, the study visitsshouldoccur within the visit window 
specified onthe Schedule of Activities(see Section 2).The actual time of all dose 
administrations will be recorded in the patient’s electronic case report form (eCRF). 
7.3. Blinding
CCI
This is a double-blind study. The blinding applies to patients, sitepersonnel, and Sponsor 
personnel.
To preserve the blinding of the study, a minimum number of Lilly
 and site personnel will see the 
randomization table and treatment assignments before the study is complete.
Emergency unblinding for AEs may be performed through the IWRS.  This option may be used 
ONLY if the patient’swell-being requires knowledge ofthe patient’s treatment assignment.  All 
actions resulting in an unblinding event are recorded and reported by the IWRS.
If an investigator, site personnel performing assessments, or patient is unblinded, the patient 
must be discontinued from the study.  In cases where there are ethical reasons to have the patient 

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remain in the study, the investigator must obtain specific approval from a Lilly-designated 
medical monitor for the patient to continue in the study.
In case of an emergency, the investigator has the sole responsibility for determining if unblinding 
of a patient’s treatment assignment is warranted for medical management of the event.  The 
patient safety must always be the first consideration in making such a determination.  If a 
patient’s treatment assignment is unblinded, Lilly must be notified immediately.  If the 
investigator decides that unblinding is warranted, it is the responsibility of the investigator to 
promptly document the decision and rationale and notify Lilly as soon as possible.
7.4.
Dosage Modification
Dose adjustments are not permitted in this study except for patients who relapse during the 
Maintenance Period; these patients may be switched to 250 mg mirikizumab through the IWRS,
as described in Section 5.1.3.
7.5.
Preparation/Handling/Storage/Accountability
The investigator or his/her designee is responsible for the following:

Confirming that appropriate temperature conditions have been maintained during 
transit for all study treatment received and any discrepancies are reported and 
resolved before use of the study treatment.

Ensuring that only participants enrolled in the study may receive study treatment 
and only authorized site staff may supply or administer study treatment. All study 
treatments must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area, in accordance with the labeled storage conditions 
with access limited to authorized site staff.

The investigator, institution, or the head of the medical institution (where 
applicable) is responsible for study treatment accountability, reconciliation, and 
record maintenance (such as receipt, reconciliation, and final disposition records).
Detailed instructions regarding supplies and preparation and handling of investigational products
will be provided by the Sponsor.
Investigational products will be supplied by Lilly or its representative, in accordance with current 
GMP and will be supplied with lot numbers, expiry dates, and certificates of analysis, as 
applicable.  All investigational products will be stored, inventoried, reconciled, and returned or
destroyed according to applicable regulations.
Mirikizumab and placebo should be transported and stored in refrigerated conditions 2°C to 8°C 
(36°F to 46°F).
7.6.
Treatment Compliance
All doses of study medication will be administered at the study site by site personnel.  Deviations 
from the prescribed dosage regimen should be recorded in the eCRF.

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Every attempt will be made to select patients who have the ability to understand and comply with 
study instructions.  The investigator is responsible for discussing methods to ensure high 
treatment compliance with the patient before randomization.  
If a patient is noncompliant with study procedures and/or investigational product administration, 
the investigator should assess the patient to determine the reason for noncompliance and educate
and/or manage the patient, as appropriate, to improve compliance.  Overall compliance with 
therapy is defined to be missing no more than 20% of the expected doses within the protocol-
defined dosing interval and not missing 2 consecutive doses.  If, in consultation with Lilly or its 
designee, the noncompliance is deemed to be significant or if further noncompliance occurs, the 
patient may be discontinued from the study.
7.7.
Concomitant Therapy
All concomitant medications taken during the study must be recorded on the Concomitant 
Medication eCRF. All patients should maintain their usual medication regimens for concomitant 
conditions or diseases throughout the study unless those medications are specifically excluded in 
the protocol.
Subjects taking concomitant medications should be on stable dosages at the time of baseline and 
should remain at stable dosages throughout the study unless changes need to be made because of 
AEs.  Additional systemic drugs are to be avoided during the study, unless required to treat AEs. 
If the need for concomitant medication arises for an AE or for appropriate medical management 
(including the limited use of therapeutic agents which, if used under treatment regimens other 
than for treating an AE or for appropriate medical management, might be considered psoriasis
therapies), the investigator should base decisions on the patient and clinical factors.  Other 
medications may be allowed if they are approved by the Sponsor or its designee.
Use of nonlive (killed, inactivated, or subunit) vaccinations are allowed for all patients; however, 
their efficacy with concomitant mirikizumab is unknown.  Use of live, attenuated vaccines is 
prohibited.
Classes of therapies not permitted during the course of the study, or permitted with use 
restrictions, are specified in Table AMAK.4 below (also see the Exclusion Criteria 
[Section 6.2]).
Table AMAK.4.
Excluded Classes of Concomitant Medications or Classes with 
Restricted Use
Drug Class
Allowed for 
Chronic Use
Allowed with 
Restrictions
Conditions for Allowed Use
Topical treatment for psoriasis or any
other skin condition
(for example, corticosteroids, vitamin D 
analogues, pimecrolimus, retinoids, 
salicylvaseline, salicylic acid, lactic 
acid, tacrolimus, tar, urea, -hydroxy or 
fruit acids)
N
N

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Drug Class
Allowed for 
Chronic Use
Allowed with 
Restrictions
Conditions for Allowed Use
Topical treatment for psoriasis limited to 
face, axilla, or genitalia
N
Y
Mild or least potent topical steroids will 
be permitted for use limited to the face, 
axilla, and/or genitalia, as needed.  
These topical medications should not be 
used within approximately 24 hours 
prior to study visits.
Photochemotherapy
(for example, PUVA)
N
N
Phototherapy
(for example, UVA, UVB, excimer laser)
N
N
Biological immunomodulating agents
(for example, alefacept, briakinumab, 
efalizumab, ixekizumab, secukinumab, 
etanercept, adalimumab, infliximab, 
certolizumab)
N
N
Other systemic immunomodulating 
treatments
(for example, MTX, cyclosporine A, 
corticosteroids, cyclophosphamide)
N
N
Systemic immunomodulating treatments 
(corticosteroids only)
N
Y
Limited use of systemic corticosteroids 
ONLY as needed for limited, short-term 
medical management of TEAE may be 
considered. Such drug class might be 
considered psoriasis therapy if used 
under other regimens. Limited use 
during TEAE management is considered 
to not be consistent with psoriasis 
therapy.
Systemic psoriasis therapies
(for example, retinoids, fumarates, 
apremilast) 
N
N
Bacillus Calmette-Guerin (BCG) 
vaccinations or live virus vaccinations
(BCG prohibited for 12 months before 
baseline, live vaccinations prohibited for 
12 weeks before baseline.  Both are 
prohibited throughout the study and for 
12 weeks after discontinuation of study 
drug).
N
N
Any investigational treatment
N
N
Abbreviations:  MTX = methotrexate; N = No; PUVA = psoralen and ultraviolet A; TEAE = treatment-emergent 
adverse event; UVA = ultraviolet A; UVB = ultraviolet B;  Y = Yes.
Topical therapies allowed during the study include shampoos that do not contain >3% salicylic 
acid, corticosteroids, coal tar, or vitamin D3 analogues; topical moisturizers/emollients and other 
non-prescription topical products that do not contain urea, >3% salicylic acid, alpha- or 
beta-hydroxyl acids, corticosteroids, or vitamin D3 analogues; and bath oils and oatmeal bath 
preparations.  These topical therapies are not to be used within 12 hours prior to a study visit.

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For patients who have entered the Post-Treatment Follow-Up Period, psoriasis therapy with 
another agent(s), as determined appropriate by the investigator, is allowed.
7.8.
Treatment after the End of the Study
7.8.1. Treatment after Study Completion
Mirikizumab will not be made available to patients who either discontinue early from Study 
AMAK, or complete Study AMAK but do not enroll in Study AMAH.
7.8.2. Special Treatment Considerations
Management of Hypersensitivity Events, Including Injection Site Events
7.8.2.1.
All biological agents carry the risk of systemic allergic/hypersensitivity events.  Clinical 
manifestations of these events may include, but are not limited to the following:

Skin rash

Pruritus (itching)

Urticaria (hives)

Angioedema (for example, swelling of the lips and/or tongue) 

Anaphylactic events.
Sometimes, these events can be life threatening.  Proteins may also cause redness, itching, 
swelling, or pain locally at the injection site.  Therefore, all patients should be closely monitored 
for signs or symptoms that could result from such events, educated on the signs or symptoms of 
these types of events, and instructed to contact the study site immediately if any of the symptoms 
are experienced following an injection. If a patient experiences an acute hypersensitivity event
after an injection of investigational product, he or she should be managed appropriately and 
given instructions to receive relevant supportive care.
Additionally, for an event judged by the investigator to be a potential systemic hypersensitivity 
event, blood samples will be collected for PK, immunogenicity, and exploratory hypersensitivity 
analyses at, or as close as possible to:
1. the onset of the event
2. the resolution of the event, and
3. 30 (±3) days following the event.
Exploratory hypersensitivity samples may, as appropriate for the clinical presentation,

be analyzed for tryptase (a marker of basophil/mast cell activation),

have a complement panel performed (asses immune complex formation), and

have a cytokine panel performed.
See also Section 9.4.4.

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Patients who develop clinically significant systemic hypersensitivity events following 
administration of investigational product should be discontinued from the study and not receive 
further doses of investigational product, with or without premedication (see Section 8.2).

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8.
Discontinuation Criteria
8.1.
Discontinuation from Study Treatment
8.1.1. Permanent Discontinuation from Study Treatment
Patients for whom investigational product should be permanently discontinued, irrespective of 
the reason, should complete the Post-Treatment Follow-Up and then be permanently 
discontinued from the study. Section 8.2 provides the list of criteria for permanent 
discontinuation of patients from study treatment and the study.
Patients discontinuing from the investigational product prematurely for any reason should 
complete AE and other follow-up procedures per Section 2 (Schedule of Activities),
Section 5.1.4 (Post-Treatment Follow-up Period), Section 9.2 (Adverse Events), and Section 9.4
(Safety) of this protocol.
8.1.2. Temporary Interruption (Withholding) of Study Treatment
Some possible reasons for temporarily withholding investigational product include, but are not 
limited to:

Development of:
o
Serious or opportunistic infections, as described in Section 9.2.3).
o
Hypertension (see Section 9.4.2.1).
o
Latent TB infection (LTBI) (see Section 9.4.5.2).
o
Positive HBV DNA results that are below the level of quantification (see 
Section 9.4.5.4).
o
Hepatic event or liver test abnormality: Investigational product should be 
withheld and additional testing performed following consultation with the 
Lilly-designated medical monitor, if the results of repeat tests following elevated 
ALT, ALP or total bilirubin level (TBL) include one of the following 
(Section 9.4.6.1):

ALT 3x ULN and TBL <2x ULN

ALP 2x ULN and TBL <2x ULN

TBL 2x ULN without increase from baseline in ALT/AST/ALP.

Surgery:  Patients requiring surgery at any time during the study should interrupt 
administration of the investigational product, beginning 8 weeks before the surgery or as 
early as possible within 8 weeks of surgery, and resume administration of the 
investigational product only after complete wound healing.

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Cases that may merit temporary withholding of the study treatment should be discussed with the 
medical monitor.  The medical monitor, in consultation with the investigator, will determine 
when it is appropriate to recommence study treatment.
8.1.3. Discontinuation of Inadvertently Enrolled Patients
If the Sponsor or investigator identifies a patient who did not meet enrollment criteria and was 
inadvertently enrolled, then the patient should be discontinued from study treatment, unless there 
are extenuating circumstances that make it medically necessary for the patient to continue on 
study treatment.  If the investigator and the Sponsor-designated medical monitor agree it is 
medically appropriate to continue, the investigator must obtain documented approval from the 
Sponsor medical monitor to allow the inadvertently enrolled patient to continue in the study with 
or without treatment with the investigational product. Safety follow up is as outlined in 
Section 2 (Schedule of Activities), Section 9.2 (Adverse Events), and Section 9.4 (Safety) of the 
protocol.
8.2.
Discontinuation from the Study
Patients should permanently discontinue the investigational product, complete the 
Post-Treatment Follow-up, and then permanently discontinue from the study for any of the 
following reasons:

Subject Decision
o
The patient requests to be either discontinued from the investigational product or 
withdrawn from the study.

Discontinuation due to a hepatic event or liver test abnormality.  Patients who are 
discontinued from investigational product due to a hepatic event or liver test abnormality 
should have additional hepatic safety data collected via eCRF.
Discontinuation of the investigational product for abnormal liver tests should be considered by 
the investigator when a patient meets one of the following conditions after consultation with the 
Lilly-designated medical monitor:

ALT or AST >8x ULN

ALT or AST >5x ULN for more than 2 weeks

ALT or AST >3x ULN and TBL >2x ULN or international normalized 
ratio (INR) >1.5 

ALT or AST >3x ULN, with the appearance of fatigue, nausea, vomiting, 
right upper-quadrant pain or tenderness, fever, rash, and/or eosinophilia
(>5%)

ALP >3x ULN

ALP >2.5x ULN and TBL >2x ULN

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
ALP >2.5x ULN, with the appearance of fatigue, nausea, vomiting, right 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%)

In addition, patients who meet any one of the following criteria should be 
discontinued from the investigational product, enter the Post-Treatment 
Follow-Up Period, and discontinue from the study:

Total white blood cell (WBC) count <2000 cells/L (<2.00 x 103/µL or 
<2.00 GI/L).

Lymphocyte count <500 cells/μL (<0.50 x 103/µL or <0.50 GI/L).

Platelet count <50,000 cells/μL (<50 x 103/µL or <50 GI/L). 

Changes in blood pressure (BP) (systolic BP at 160 mm Hg plus 
20 mm Hg increase from baseline [Week 0; Visit 2]; and/or diastolic BP 
at 100 mm Hg plus 10 mm Hg increase from baseline) that do not 
respond following maximal allowed intervention (further explanation in 
Section 9.4.2.1).

The patient experiences a severe AE, an SAE, or a clinically significant 
change in a laboratory value that, in the opinion of the investigator, merits 
the discontinuation of the investigational product.

Clinically significant systemic hypersensitivity event following 
administration of investigational product.

The patient becomes pregnant.

The patient develops a malignancy (Note: patients may be allowed to 
continue if they develop no more than 2 non-melanoma skin cancers during 
the study).

Any patient who has a change in disease phenotype at any time (for 
example, a change to pustular psoriasis).

If the patient remains at or above their baseline sPGA score at Week 16 (Visit 7)
and Week 24 (Visit 9), or remains at or above their baseline PASI score at 
Week 16 (Visit 7) and Week 24 (Visit 9).

It is recommended that the patient be assessed by an appropriately trained 
professional to assist in deciding whether the patient is to be discontinued 
from study treatment and the study if:
i.
The patient, at any time during the study, scores a 3 for Item 12
(Thoughts of Death or Suicide) on the 16-item Quick Inventory of 
Depressive Symptomatology (QIDS-SR16);
OR

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ii.
Develops active suicidal ideation with some intent to act with or 
without a specific plan (“yes” to question 4 or 5 on the “Suicidal 
Ideation” portion of the C-SSRS);
OR
iii.
Develops suicide-related behaviors as recorded on the C-SSRS.

The patient develops active TB or HIV/AIDS during the study.

The patient becomes HBV DNA or HCV RNA positive.  The patient 
should be referred to a specialist physician (see Sections 8.1.2 and 9.4.5.4
for HBV, and Section 9.4.5.5 for HCV).

Patients will also be permanently discontinued from study drug, complete 
Post-Treatment Follow-up, and then permanently discontinued from the study in 
the following circumstances:

Enrollment in any other clinical study involving an investigational product 
or enrollment in any other type of medical research judged not to be 
scientifically or medically compatible with this study

Participation in the study needs to be stopped for medical, safety, 
regulatory, or other reasons consistent with applicable laws, regulations, 
and GCP

Investigator decision

The investigator decides that the patient should be discontinued
from the study

If the patient, for any reason, requires treatment with another 
therapeutic agent that has been demonstrated to be effective for 
treatment of the study indication, discontinuation from the study 
occurs prior to introduction of the new agent
Patients permanently discontinuing from investigational product, completing the Post-Treatment 
Follow-Up, and permanently discontinuing from the study prematurely for any reason should 
complete AE and other safety follow-up per Section 2 (Schedule of Activities), Section 5.1.4
(Post-Treatment Follow-up Period), Section 9.2 (Adverse Events), and Section 9.4 (Safety) of 
this protocol.  
8.3.
Lost to Follow-Up
A patient will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site.  Site personnel are expected to make 
diligent attempts to contact patients who fail to return for a scheduled visit or were otherwise 
unable to be followed up by the site.

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9.
Study Assessments and Procedures
Section 2 lists the Schedule of Activities, with the study procedures and their timing (including 
tolerance limits for timing).
Appendix 2 lists the laboratory tests that will be performed for this study.
Unless otherwise stated in the subsections below, all samples collected for specified laboratory 
tests will be destroyed within 60 days of receipt of confirmed test results.  Certain samples may 
be retained for a longer period, if necessary, to comply with applicable laws, regulations, or 
laboratory certification standards.
9.1.
Efficacy Assessments
9.1.1. Primary Efficacy Assessments
The primary efficacy endpoints are the proportion of patients with an sPGA (0,1) with at least a 
2-point improvement from baseline at Week 16 and the proportion of patients achieving a 90% 
improvement in PASI from baseline (PASI 90) at Week 16.
Static Physician’s Global Assessment
9.1.1.1.
The sPGA is the physician’s global assessment of the patient’s psoriasis lesions at a given time 
point (EMA 2004).  Plaques are assessed for induration, erythema, and scaling, and an overall 
rating of psoriasis severity is given using the anchors of clear (0), minimal (1), mild (2), 
moderate (3), severe (4), or very severe (5).
Psoriasis Area and Severity Index
9.1.1.2.
The PASI is an accepted primary efficacy measurement for this phase of development of 
psoriasis treatments (EMA 2004).  The PASI combines assessments of the extent of body-surface 
involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of scaling, 
redness, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 
0 for no psoriasis to 72 for the most severe disease (Fredriksson and Pettersson 1978).  The PASI 
has been the most frequently used endpoint and measure of psoriasis severity in clinical trials 
(EMA 2004; Menter et al. 2008).  A clinically meaningful response is a PASI 75, which 
represents at least a 75% decrease (improvement) from the baseline PASI score.  Higher levels of 
clearance (PASI 90), as well as complete resolution of psoriasis (PASI 100), have become 
additional endpoints because of the increasing recognition of the association of higher clearance 
with greater health-related quality of life (HRQoL) (Puig 2015).
9.1.2. Secondary Efficacy Assessments
Secondary efficacy assessments will include the following:
Static Physician’s Global Assessment
9.1.2.1.
Both sPGA (0) and sPGA (0,1) will be assessed at various time points up to Week 52.  For 
assessment description, see Section 9.1.1.1.

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Psoriasis Area and Severity Index
9.1.2.2.
PASI 75, PASI 90, and PASI 100 will be assessed at various time points up to Week 52.  PASI 
75, 90, and 100 are the percentage improvements in PASI (75%, 90%, and 100%, respectively).  
For assessment description, see Section 9.1.1.2.
Body Surface Area
9.1.2.3.
Percent BSA will be evaluated as the percent involvement of psoriasis on each patient’s BSA on 
a continuous scale from 0% (no involvement) to 100% (full involvement), where 1% 
corresponds to the size of the patient’s hand (including the palm, fingers, and thumb) (National 
Psoriasis Foundation 2016).
Nail Psoriasis Severity Index
9.1.2.4.
The Nail Psoriasis Severity Index (NAPSI) is used to evaluate the severity of fingernail bed 
psoriasis and fingernail matrix psoriasis by area of involvement in the fingernail unit.  In this 
study, only fingernail involvement will be assessed.  The fingernail is divided with imaginary 
horizontal and longitudinal lines into quadrants.  Each fingernail is given a score for fingernail 
bed psoriasis (0 to 4) and fingernail matrix psoriasis (0 to 4) depending on the presence (score of 
1) or absence (score of 0) of any of the features of fingernail bed and fingernail matrix psoriasis
in each quadrant.  The NAPSI score of a fingernail is the sum of scores in fingernail bed and 
fingernail matrix from each quadrant (maximum of 8).  Each fingernail is evaluated, and the sum 
of all the fingernails is the total NAPSI score (range, 0 to 80).
Psoriasis Scalp Severity Index
9.1.2.5.
The Psoriasis Scalp Severity Index (PSSI) measures the affected scalp area and the severity of 
clinical symptoms.  The PSSI is a composite score derived from the sum of scores for erythema, 
induration, and desquamation multiplied by a score for the extent of scalp area involved (range,
0 to 72).  Higher scores indicate worse severity (Thaçi et al. 2015).
Palmoplantar Psoriasis Severity Index
9.1.2.6.
The Palmoplantar Psoriasis Severity Index (PPASI) is a composite score derived from the sum of 
scores for erythema, induration, and desquamation multiplied by a score for the extent of palm 
and sole area involvement (range, 0 to 72).
Health Outcomes Assessments
9.1.2.7.
The following patient-reported questionnaires will be administered according to the Schedule of 
Activities (Section 2) in countries where the questionnaires have been translated into the native 
language of the region and linguistically validated.  These assessments should be completed 
before administration of investigational product; before the patient’s clinical examination; before 
the patient receives any tests or results; and before the patient’s health, health data, or emotions 
are discussed.
9.1.2.7.1. Dermatology Life Quality Index
The Dermatology Life Quality Index (DLQI) is a validated, dermatology-specific, 
patient-reported measure that evaluates a patient’s HRQoL.  This questionnaire has 10 items that 
are grouped into 6 domains, namely symptoms and feelings, daily activities, leisure, work and 
school, personal relationships, and treatment.  The recall period of this scale is over the “last 

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week”  Response categories include “not at all,” “a little,” “a lot,” and “very much,” with 
corresponding scores of 0, 1, 2, and 3, respectively, and unanswered (“not relevant”) responses 
scored as “0.”  The total score ranges from 0 to 30 (less to more impairment) (Finlay and Khan 
1994; Basra et al. 2008).  A DLQI total score of 0 to 1 is considered as having no effect on a 
patient’s HRQoL, and a 5-point change from baseline is considered as the minimal clinically 
important difference (MCID) threshold (Khilji et al. 2002; Hongbo et al. 2005).
9.1.2.7.2. European Quality of Life–5 Dimensions–5 Levels–Psoriasis
The European Quality of Life–5 dimensions–5 levels (EQ–5D–5L) questionnaire is a widely 
used, generic questionnaire that assesses health status (EuroQol Group 1990; Herdman et al. 
2011). The questionnaire consists of 2 parts. The first part assesses 5 dimensions (mobility, 
self-care, usual activities, pain/discomfort and anxiety/depression) that have 5 possible levels of 
response (no problems, slight problems, moderate problems, severe problems, extreme problems.
This part of the EQ–5D–5L can be used to generate a health state index. The health state index 
score is calculated based on the responses to the 5 dimensions, providing a single value on a 
scale from less than 0 (where zero is a health state equivalent to death; negative values are 
valued as worse than dead) to 1 (perfect health), with higher scores indicating better health 
utility. The second part of the questionnaire consists of a visual analog scale on which the 
patient rates their perceived health state from 0 (the worst health you can imagine) to 100 (the 
best health you can imagine). The study will use the EQ–5D–5L–Psoriasis (EQ–5D–5L–PSO),
which is a version of the EQ–5D–5L with two additional items related to psoriasis: skin 
irritation and self-confidence (Swinburn et al. 2013).
9.1.2.7.3. Work Productivity and Activity Impairment Questionnaire: Psoriasis
The Work Productivity and Activity Impairment-Psoriasis (WPAI-PSO) Questionnaire is a 
patient-reported instrument developed to measure the impact on work productivity and regular 
activities attributable to a specific health problem (psoriasis). It contains 6 items that measure:
1) employment status, 2) hours missed from work due to the psoriasis, 3) hours missed from 
work for other reasons, 4) hours actually worked, 5) degree of health affected-productivity while 
working, and 6) degree of health affected-productivity in regular unpaid activities. Four scores 
are calculated from the responses to these 6 items: absenteeism, presenteeism, work productivity 
loss, and activity impairment. Scores are calculated as impairment percentages (Reilly et al. 
1993), with higher numbers indicating greater impairment and less productivity, that is, worse 
outcomes.
9.1.2.7.4. Psoriasis Symptoms Scale
The Psoriasis Symptoms Scale (PSS) is a patient-administered assessment of 4 symptoms (itch, 
pain, stinging, and burning); 3 signs (redness, scaling, and cracking); and 1 item on discomfort 
related to symptoms/signs.  Respondents are asked to answer the questions based on their 
psoriasis symptoms.
The overall severity for each individual symptom/sign from the patient’s psoriasis is indicated by 
selecting the number from a numeric rating scale (NRS) of 0 to 10 that best describes the worst 
level of each symptom/sign in the past 24 hours, where 0=no symptom/sign and 10=worst 
imaginable symptom/sign.

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The symptom severity scores, ranging from 0 to 10, are the values of the selected numbers 
indicated by the patient on the instrument’s horizontal scale.  Each of the 8 individual items will 
receive a score of 0 to 10 and will be reported as item scores for itch, pain, stinging, burning, 
redness, scaling, cracking, and discomfort.  In addition, a symptoms score ranging from 0 (no 
symptoms) to 40 (worst imaginable symptoms), and a signs score of 0 (no signs) to 30 (worst 
imaginable signs) will be reported.
9.1.2.7.5. Medical Outcomes Study 36-Item Short-Form Health Survey
The Medical Outcomes Study 36-Item Short-Form Health Survey (SF 36) is a patient-reported, 
generic, HRQoL instrument originally published in 1992, with some item wordings and response 
options revised in 2000 (Ware and Sherbourne 1992; Ware 2000). It consists of 36 questions 
measuring 8 health domains: physical functioning, bodily pain, role limitations due to physical 
problems, role limitations due to emotional problems, general health perceptions, mental health, 
social function, and vitality. The patient’s responses are solicited using Likert scales that vary in 
length, with 3–6 response options per item. The SF-36 can be scored into the 8 health domains 
named above and two overall summary scores: physical component summary (PCS) and mental 
component summary (MCS) scores. The domain and summary scores range from 0 to 100; 
higher scores indicate better levels of function and/or better health. The SF-36 version 2 (acute 
version) will be used, which utilizes the recall period of “the past week” (Ware 2000).
9.1.2.7.6. 16-Item Quick Inventory of Depressive Symptomatology-Self Report
The QIDS-SR16 is a self-administered, 16-item instrument intended to assess the existence and 
severity of symptoms of depression as listed in the American Psychiatric Association’s 
Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) (American 
Psychiatric Association 2013).  A patient is asked to consider each statement as it relates to the 
way they have felt for the past 7 days.  There is a 4-point scale for each item ranging from 0 to 3.  
The 16 items corresponding to 9 depression domains are summed to give a single score ranging 
from 0 to 27, with higher scores denoting greater symptom severity.  The domains assessed by 
the instrument include:  (1) sad mood, (2) concentration, (3) self-criticism, (4) suicidal ideation, 
(5) interest, (6) energy/fatigue, (7) sleep disturbance (initial, middle, and late insomnia or 
hypersomnia), (8) decrease/increase in appetite/weight, and (9) psychomotor 
agitation/retardation.
This instrument will also be used for AE monitoring (see Section 9.2.2).
9.1.2.7.7. Treatment Satisfaction Questionnaire for Medication
The Treatment Satisfaction Questionnaire for Medication (TSQM) is a self-administered 9-item 
measure to evaluate patient treatment satisfaction with medication in the domains of 
effectiveness (3 items), convenience (3 items), and global satisfaction (3 items). The recall 
period is the last 2-3 weeks or since the medication was last taken. Item formats include both a 
1- to 7-point and a 1- to 5-point Likert scale. Higher scores indicate greater satisfaction
(Bharmal et al. 2009).

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9.1.2.7.8. Patient’s Global Assessment of Psoriasis
The Patient’s Global Assessment of Psoriasis (PatGA) is a patient-reported, single-item scale on 
which patients are asked to rank, by selecting a number on a 0 to 5 NRS, the severity of their 
psoriasis “today,” from 0 (clear/no psoriasis) to 5 (severe).
9.1.3. Appropriateness of Assessments
The clinical safety parameters in this study are standard elements of clinical health assessment 
and Phase 3 drug development.  The disease activity and health outcome measurements are used 
both in clinical practice and psoriasis clinical trials.  Psoriasis is associated with numerous skin-
based symptoms and HRQoL impairment, which justifies the use of the psoriasis symptom 
severity, as well as dermatologic and generic HRQoL assessments used in this study (EMA 
2004; Kimball et al. 2005).
9.2.
Adverse Events
Investigators are responsible for monitoring the safety of patients who have entered this study 
and for alerting Lilly or its designee to any event that seems unusual, even if this event may be 
considered an unanticipated benefit to the patient.
The investigator is responsible for the appropriate medical care of patients during the study.
Investigators must document their review of each laboratory safety report.
The investigator remains responsible for following, through an appropriate health care option, 
AEs that are serious or otherwise medically important, considered related to the investigational 
product or the study, or that caused the patient to discontinue the investigational product before 
completing the study.  The patient should be followed until the event resolves, stabilizes with 
appropriate diagnostic evaluation, or is reasonably explained.  The frequency of follow-up 
evaluations of the AE is left to the discretion of the investigator.
Lack of drug effect is not an AE in clinical studies, because the purpose of the clinical study is to 
establish treatment effect.
After the ICF is signed, study site personnel will record via eCRF the occurrence and nature of 
each patient’s preexisting conditions, including clinically significant signs and symptoms of the 
disease under treatment in the study.  In addition, site personnel will record any change in the 
condition(s) and any new conditions as AEs. Investigators should record their assessment of the 
potential relatedness of each AE to protocol procedure or investigational product via eCRF.
The investigator will interpret and document whether or not an AE has a reasonable possibility 
of being related to study treatment, study device, or a study procedure, taking into account the 
disease, concomitant treatment or pathologies.
A “reasonable possibility” means that there is a cause and effect relationship between the 
investigational product, study device, and/or study procedure and the AE.
The investigator answers yes/no when making this assessment.

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Planned surgeries and nonsurgical interventions should not be reported as AEs unless the 
underlying medical condition has worsened during the course of the study.
If a patient’s investigational product is discontinued as a result of an AE, study site personnel 
must report this to Lilly or its designee via eCRF, clarifying if possible, the circumstances 
leading to any dosage modifications, or discontinuations of treatment.
9.2.1. Serious Adverse Events
An SAE is any AE from this study that results in one of the following outcomes:

Death

Initial or prolonged inpatient hospitalization

A life-threatening experience (that is, immediate risk of dying)

Persistent or significant disability/incapacity

Congenital anomaly/birth defect

Important medical events that may not be immediately life threatening or result in 
death or hospitalization, but may jeopardize the patient or may require 
intervention to prevent one of the other outcomes listed in the definition above.  
Examples of such medical events include allergic bronchospasm requiring 
intensive treatment in an emergency room or at home, blood dyscrasias or 
convulsions that do not result in inpatient hospitalization, or the development of 
drug dependency or drug abuse.

When a condition related to the prefilled syringes necessitates medical or surgical 
intervention to preclude either permanent impairment of a body function or 
permanent damage to a body structure, the serious outcome of “required 
intervention” will be assigned.
All AEs occurring after signing the ICF are recorded in the eCRF and assessed for serious 
criteria.  The SAE reporting to the Sponsor begins after the patient has signed the ICF and has 
received investigational product.  However, if an SAE occurs after signing the ICF but prior to 
receiving investigational product, the SAE should be reported to the Sponsor as per SAE 
reporting requirements and timelines (see Section 9.2) if it is considered reasonably possibly 
related to study procedure.
Study site personnel must alert Lilly or its designee of any SAE within 24 hours of investigator 
awareness of the event via a Sponsor-approved method.  If alerts are issued via telephone, they 
are to be immediately followed with official notification on study-specific SAE forms.  This 
24-hour notification requirement refers to the initial SAE information and all follow-up SAE 
information. Patients with a serious hepatic AE should have additional data collected using the 
eCRF.
Pregnancy (during maternal or paternal exposure to investigational product) does not meet the 
definition of an AE.  However, to fulfill regulatory requirements, any pregnancy should be 
reported following the SAE process to collect data on the outcome for both mother and fetus.

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Investigators are not obligated to actively seek AEs or SAEs in patients once they have 
discontinued and/or completed the study (the patient disposition CRF has been completed).  
However, if the investigator learns of any SAE, including a death, at any time after a patient has 
been discharged from the study, and he/she considers the event reasonably possibly related to the 
study treatment or study participation, the investigator must promptly notify Lilly.
Suspected Unexpected Serious Adverse Reactions
9.2.1.1.
Suspected unexpected serious adverse reactions (SUSARs) are serious events that are not listed 
in the IB and that the investigator identifies as related to investigational product or procedure.  
United States 21 CFR 312.32 and European Union Clinical Trial Directive 2001/20/EC and the 
associated detailed guidances or national regulatory requirements in participating countries 
require the reporting of SUSARs.  Lilly has procedures that will be followed for the 
identification, recording and expedited reporting of SUSARs that are consistent with global 
regulations and the associated detailed guidances.
9.2.2. Adverse Event Monitoring with a Systematic Questionnaire
The C-SSRS captures the occurrence, severity, and frequency of suicidal ideation and/or 
behavior during the assessment period.  The scale includes suggested questions to solicit the type 
of information needed to determine if suicidal ideation and/or behavior occurred.  The C-SSRS is 
administered by an appropriately trained health care professional with at least 1 year of patient 
care/clinical experience.  The tool was developed by the National Institute of Mental Health trial 
group for the purpose of being a counterpart to the Columbia Classification Algorithm of Suicide 
Assessment categorization of suicidal events.  For this study, the scale has been adapted (with 
permission from the scale authors) to include only the portion of the scale that captures the 
occurrence of the 11 preferred ideation and behavior categories.
The nonleading AE collection should occur prior to the collection of the C-SSRS.  If a 
suicide-related event is discovered during the C-SSRS but was not captured during the 
nonleading AE collection, sites should not change the AE form.  If an event is serious or leads to 
discontinuation, this is an exception where the SAE and/or AE leading to discontinuation should 
be included on the AE form and the process for reporting SAEs should be followed.
Suicide-related events (behavior and/or ideations) will be assessed and evaluated at every visit 
with the administration of the C-SSRS and the Self-Harm Supplement Form.  The Self-Harm 
Supplement Form is a single question to enter the number of suicidal behavior events, possible 
suicide behaviors, or nonsuicidal self-injurious behaviors.  If the number of behavioral events is 
greater than zero, it will lead to the completion of the Self-Harm Follow-Up Form.  The 
Self-Harm Follow-Up Form is a series of questions that provides a more detailed description of 
the behavior cases.
The QIDS-SR16 instrument (for description, see Section 9.1.2.7.6) will be used to collect 
patient-reported data on signs and symptoms related to depression.

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9.2.3. Adverse Events of Special Interest
Adverse events of special interest (AESIs) are AEs which the Sponsor specifies as being of 
special interest based on standard drug registration topics, safety findings from previous studies 
in development program, potential risks associated with biologic immunomodulators as noted in 
product labels and published literature, and comorbidities and risk factors prevalent in the 
studied populations.  The AESIs for this study are defined in the statistical analysis plan (SAP), 
and may include, but not be limited to the following:

Infections, including opportunistic infections

Hypersensitivity events, including anaphylaxis

Injection site events

Cerebro-cardiovascular events

Malignancies

Depression, or suicidal ideation or behaviors

Hepatic AEs.
For some AESIs, sites should provide additional information regarding the event, as instructed 
on the eCRF.
Infections, Including Opportunistic Infections
Drugs that modulate the immune system may increase the risk of infection, including serious or 
opportunistic infections.
Infections will be categorized by Lilly as opportunistic according to Opportunistic Infections and 
Biologic Therapies in Immune-Mediated Inflammatory Diseases: Consensus Recommendations 
for Infection Reporting during Clinical Trials and Postmarketing Surveillance by Winthrop et al. 
(2015).  Examples are listed in Appendix 4.
Hypersensitivity Events 
Site personnel should educate patients and/or caregivers about the symptoms and signs of 
hypersensitivity events and provide instructions on dealing with these events.  A blood sample 
will be collected when possible for any patient who experiences an AE of hypersensitivity during 
the study.
Cerebro-Cardiovascular Adjudication
Data collected regarding a potential or actual cerebro-cardiovascular AE will be provided to, and 
adjudicated by, an independent, external adjudication committee.  The role of the committee is to 
adjudicate the reported cardiovascular AEs in a blinded, consistent, and unbiased manner 
throughout the course of the study, thereby ensuring that all such reported events are evaluated 
uniformly.

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9.2.4. Complaint Handling
Lilly collects product complaints on investigational products and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and to 
facilitate process and product improvements.
Patients will be instructed to contact the investigator as soon as possible if he or she has a 
complaint or problem with the investigational product or prefilled syringes so that the situation 
can be assessed.
•
Complaints must be reported by site staff within 24 hours of study/site personnel becoming 
aware of a product issue, regardless of the availability of the complaint sample.
•
Investigational product should be retained under appropriate storage conditions, if available 
or when obtained, until instructed to return it to Lilly or its designee.
•
Product complaints for non-Lilly products (including concomitant drugs) that do not have a 
Lilly Product Batch or Control number are reported directly to the manufacturer per product 
label.
•
Instructions outlined in the Product Complaint Form should be followed for other reporting 
requirements.
9.3.
Treatment of Overdose
Investigators should remain vigilant for unknown effects related to mirikizumab overdose.  In 
case of suspected overdose, hematology, chemistry, vital signs, and oxygen saturation should be 
monitored and supportive care provided as necessary.  There is no known antidote for 
mirikizumab.
9.4.
Safety
9.4.1. Electrocardiograms
For each patient, ECGs should be collected according to the Schedule of Activities (Section 2).  
Electrocardiograms should be recorded according to the study-specific recommendations and 
read locally for evaluation of study eligibility and safety monitoring. 
Patients should be supine for approximately 5 to 10 minutes before ECG collection, and remain 
supine but awake during ECG collection.  Sitting BP, temperature, and pulse (see Section 9.4.2)
should be obtained at approximately the same time as ECG measurements or blood sampling.  
When multiple assessments are scheduled for the same time point, the preferred order of 
completion should be as follows:  ECG, vital signs, and then blood sampling.
Any clinically significant findings from ECGs that result in a diagnosis and that occur after the 
patient receives the first dose of the investigational product should be reported to Lilly or its 
designee as an AE via eCRF.

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9.4.2. Vital Signs
For each patient, vital signs measurements should be conducted according to the Schedule of 
Activities (Section 2).
Sitting vital signs (BP, temperature, and pulse) will be measured after resting for a minimum of 
10 minutes at times indicated in the Schedule of Activities (Section 2), and prior to blood 
sampling or administration of the investigational product. 
Any clinically significant findings from vital signs measurement that result in a diagnosis and 
that occur after the patient receives the first dose of investigational product should be reported to 
Lilly or its designee as an AE via eCRF.
Hypertension
9.4.2.1.
Patients who experience changes in BP (systolic BP at 160 mm Hg plus 20 mm Hg increase 
from baseline [Week 0; Visit 2]; and/or diastolic BP at 100 mm Hg plus 10 mm Hg increase 
from baseline) on 2 consecutive visits are to receive intervention for the management of 
hypertension.  Intervention may begin with lifestyle changes and could lead to the maximal 
intervention of withholding the dose of investigational product (see Section 8.1.2) and/or the 
introduction of antihypertensive agent(s) as medically appropriate.
9.4.3. Laboratory Tests
For each patient, laboratory tests (detailed in Appendix 2) should be conducted according to the 
Schedule of Activities (Section 2).
With the exception of laboratory test results that may unblind the study, Lilly or its designee will 
provide the investigator with the results of laboratory tests analyzed by a central vendor, if a 
central vendor is used for the clinical trial.
Any clinically significant findings from laboratory tests that result in a diagnosis and that occur 
after the patient receives the first dose of investigational product should be reported to Lilly or its 
designee as an AE via eCRF.
Pregnancy Testing
9.4.3.1.
Pregnancy testing is to be performed only on women of childbearing potential.
Serum pregnancy test will be done at screening only and will be performed centrally. Patients 
determined to be pregnant will be excluded from the study.
Patients will undergo urine pregnancy testing at the clinic during designated scheduled visits (see 
Section 2), which will be performed locally.  Result will be read prior to administration of the 
investigational product.  The urine pregnancy test at Week 0 must be performed within 24 hours 
prior to exposure to the investigational product.
Urine pregnancy testing may be performed at additional time points during the treatment period 
and/or follow-up period, at the discretion of the investigator or if this is required by local 
regulations.  Patients determined to be pregnant will be discontinued from the study.
If a urine pregnancy test is not available, a serum pregnancy test is an acceptable alternative.

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9.4.4. Immunogenicity Assessments
At the visits and times specified in the Schedule of Activities (Section 2), venous bloodsamples 
will be collected to determine antibody production against mirikizumab.  To interpret the results 
of immunogenicity, abloodsample for PK analysiswillbe collected at the same time points.All 
samples for immunogenicity should be taken predose when applicable. With reports of
hypersensitivityevents(immediate or non-immediate), additional samples will be collectedas 
close to the onset of the eventas possible, at the resolution of the event, and 30days following 
resolution of the event.  Samples will be evaluated for PK, anti-drug antibodies(ADAs),   
  Instructions for the 
collection and handling of blood samples willbe provided by the Sponsor.  The actual date and 
time (24-hour clock time) of each sampling will be recorded.
Immunogenicity will be assessed by a validated assay
 designed to detect ADAs in the presence 
of mirikizumabat a laboratory approved by the Sponsor. Patient samples willbeanalyzed using 
a 4-tiered approach.  All samples will beassessed in Tier 1 (screening).  Samples above the 
disease state screening assay cut point factor (Tier 1) will beassessed in Tier 2 (confirmation).  
Any samples confirmed as positive for anti-mirikizumabantibodies in Tier2 will be reported as 
“detected.”  All samples below the screening assay cut point factor in Tier1 or not confirmed in 
Tier 2 will bereported as “not detected.”  Any “detected” sample in Tier2 will beassessed in 
Tier 3 (titer assessment; values reported) and Tier 4 (neutralizing ADA assay).  Any samples 
above the disease state Tier 4 cut point will bereported as “detected”for neutralizing antibodies; 
samples below the disease state Tier 4 cut point will bereported as “not detected”for 
neutralizing antibodies.
Samples will be retained at a facility selected by the Sponsorfor a maximum of 15 years after the 
last patient visit, or for a shorter period if local regulations and/orEthical Review Boards (ERBs) 
require.  The duration allows the Sponsor to respond to future regulatory requests related to 
mirikizumab.  Any samples remaining after 15 y
ears will be destroyed.
9.4.5. Other Tests
Physical Examination
9.4.5.1.
Physical examination will be performed as specified in the Schedule of Activities (Section2).  
One complete physical examination (excluding pelvic or rectal examinations),which includes
heart, lungs, peripheral lymph nodes, and abdomen,and visual examination of all skin areas 
(including genitalia and breast areas),will be performed at screening. All physical examinations 
throughout the study should include a symptom-directed evaluation,as well as examination of 
heart, lungs, peripheral lymph nodes, and abdomen,and visual examination of all skin areas 
(including genitalia and breast areas).
Tuberculosis Screening
9.4.5.2.
Screening:
Screening foractive orlatent TB (LTBI) willinclude a history, physical examination 
(Section9.4.5.1), chest x-ray (Section 9.4.5.3
CCI
),and, except as noted below under “Prior 

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Treatment for LTBI or TB,” testing by an interferon-release assay (IGRA; QuantiFERON®-TB 
Gold or T-SPOT.TB®) or a purified protein derivative (PPD) tuberculin skin test.
In people aged 5 years and over, IGRA is the preferred screening test for LTBI.  In countries 
where the PPD is available and is preferred (in the judgment of the investigator) as an alternative 
screening test for LTBI, that test may be used instead of an IGRA.
Patients with documentation of a negative IGRA or PPD within 3 months before initial screening 
may not need to repeat TB testing at screening, based on the judgment of the investigator.  
Source documentation must include the original laboratory report (for IGRA) or a record of the 
size in millimeters of the induration response (for PPD).  A PPD recorded as negative without 
documenting the size of induration in millimeters, will not be acceptable and will require a retest.
Monitoring:
After initial screening, tuberculosis testing will only be required based on clinical assessment of 
TB risk (symptoms/signs/known or suspected TB exposure), and according to local regulations 
and/or local standard of care.  Such clinical assessments should be conducted periodically, at 
least every 4 months.
Interpretation of Screening Tests for LTBI
The QuantiFERON-TB Gold assay will be reported as negative, indeterminate, or positive.  The 
T-SPOT.TB assay will be reported as negative, borderline, or positive.
A positive PPD is indicated with a skin test response 5 mm of induration, documented between 
approximately 48 and 72 hours after test application (regardless of BCG vaccination history).  
Patients who do not return within 48 to 72 hours of test administration will be required to have 
the test repeated and then interpreted within this time frame.  
Patients with a diagnosis of LTBI, based on a positive IGRA test result or a positive PPD 
response 5 mm of induration and no evidence of active TB, may be rescreened once after they 
meet the following requirements:

Have received at least 4 weeks of appropriate ongoing prophylactic therapy for LTBI as 
per local standard of care, and

Have no evidence of treatment hepatotoxicity (ALT and AST levels must remain 
≤2x ULN) upon retesting of serum ALT and AST levels before randomization.
Such patients must continue and complete appropriate LTBI therapy during the course of the 
study to remain eligible and must continue to meet all other inclusion and exclusion criteria for 
participation.
Re-Testing and Confirmatory Testing
One retest is allowed for patients with an “indeterminate” QuantiFERON-TB Gold assay or 
“borderline” T-SPOT.TB assay.  Patients with 2 indeterminate QuantiFERON-TB Gold assays 
or 2 borderline T-SPOT.TB assays will be excluded.  

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Confirmatory testing with an IGRA is allowed for selected patients who have a positive 
QuantiFERON-TB Gold assay, positive T-SPOT.TB assay, or positive PPD, who meet all of the 
following criteria and are assessed and documented by the investigator as likely to have a false-
positive test result:  no risk factors for LTBI, no risk factors for increased likelihood of 
progressing from LTBI to active TB, and have never resided in a high-burden country (detailed 
in Appendix 5).  If the confirmatory test is positive, the patient will be excluded from the study 
unless they complete at least 4 weeks of appropriate therapy for LTBI, based on national or 
international guidelines (as defined above), have no evidence of hepatotoxicity (ALT and AST 
levels must remain ≤2x ULN) upon retesting of serum ALT and AST levels after at least 4 weeks 
of LTBI treatment.  Such patients must continue and complete appropriate full course of LTBI 
therapy during the course of the study to remain eligible to participate.  If the confirmatory test is 
negative, these results will be discussed with the medical monitor in order to determine 
eligibility for the study.  
Diagnosis of LTBI During Study
Patients diagnosed with LTBI during the study will temporarily discontinue the investigational 
product and will be offered treatment by the referring physician.  These patients can be 
considered for resumption of investigational product after completing the first 4 weeks of 
appropriate treatment and no evidence of treatment hepatotoxicity, as described above.  These 
patients must continue and complete a full course of treatment for LTBI in order to continue on 
investigational product.
Prior Treatment for LTBI or TB
Patients who have a documented history of completing an appropriate TB prophylaxis or 
treatment regimen (consistent with World Health Organization and/or United States Centers for 
Disease Control at the time of treatment), with no history of re-exposure since their treatments 
were completed and no evidence of active TB, are eligible to participate in the study; these 
patients should not undergo TB testing unless advised to do so based on local guidelines.  
Active TB 
Patients diagnosed with active TB at screening will be excluded. 
Patients diagnosed with active TB during the study will be discontinued and should be referred 
for appropriate treatment.
Chest Radiography
9.4.5.3.
Posterior-anterior (PA) chest x-ray (CXR) will be obtained at screening (Visit 1) unless, in the 
opinion of the investigator or based on local standard of care, both PA and lateral views are 
indicated.
A CXR does not have to be performed if the patient has had a CXR that is sufficient for TB 
evaluation according to local standard of care within 3 months of screening, and the CXR film(s) 
or a radiology report is available to the investigator for review.

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Hepatitis B Screening
9.4.5.4.
Patients who test HBsAg+, test HBcAb+ in conjunction with positive confirmatory HBV DNA 
test, or have positive HBV DNA test, regardless of HBsAb status, at screening will be excluded.
Any enrolled patient who is HBcAb+ will undergo periodic monitoring of HBV DNA as per the 
Schedule of Activities (Section 2).  
In addition to the above, any enrolled patient who is HBcAb+ and who experiences an elevated 
ALT or AST level >3x ULN must undergo HBV DNA testing.  If the HBV DNA test is 
negative, the investigator should consult with the Lilly-designated medical monitor regarding 
further management of the patient.  
If the result of the HBV DNA test is positive but below quantification, study drug should be 
withheld and a repeat test done immediately.  The Lilly-designated medical monitor should be 
contacted regarding study status of the patient.  If the result of the HBV DNA test is positive and 
quantifiable, the patient must be discontinued from the study and should receive appropriate 
follow-up medical care, including consideration for antiviral therapy.  A specialist physician in 
the care of patients with hepatitis (for example, infectious disease or hepatologist subspecialists) 
should be consulted, and the patient should potentially be started on antiviral therapy prior to 
discontinuation of any immunosuppressant therapy (including study drug). Timing of 
discontinuation from the study treatment, the study, and of any immunosuppressant therapy 
(including study drug) needs to be based on the recommendations of the consulting specialist 
physician in conjunction with the investigator and medical guidelines/standard of care.  
Hepatitis C Screening
9.4.5.5.
Patients who test positive for HCV antibody and have a positive confirmatory HCV RNA test at 
screening will be excluded.
Patients with a previous diagnosis of hepatitis C who have been treated with antiviral therapy 
and achieved a sustained virologic response may be eligible for inclusion in the study, provided 
they have no detectable RNA on the screening HCV RNA test for this protocol.  A sustained 
virologic response is defined as an undetectable HCV RNA level, 12 weeks after completion of a 
full, documented course of an approved antiviral therapy for HCV.  
Patients who have spontaneously cleared HCV infection, defined as (i) a positive HCV antibody 
test and (ii) a negative HCV RNA test, with no history of anti-HCV treatment, may be eligible 
for inclusion in the study, provided they have no detectable HCV RNA on screening for this 
study.
Any patient with a history of HCV infection who develops elevated ALT >3xULN will be tested 
for HCV RNA.
Anyone diagnosed with hepatitis C during the study will be discontinued from the study and 
should receive appropriate follow-up medical care. 

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9.4.6. Safety Monitoring
Lilly will periodically review evolving aggregate safety data within the study by appropriate 
methods.
In the event that safety monitoring uncovers an issue that needs to be addressed by unblinding at 
the group level, members of the DMC, consisting of members external to Lilly (see 
Section 10.3.8), and/or the Lilly Global Patient Safety (GPS) Safety Internal Review Committee 
(SIRC), consisting of GPS reviewers outside the study team, when appropriate, can view 
unblinded data and conduct additional analyses of the unblinded safety data.  The SIRC and the 
GPS expedited reporting team can also unblind at the individual SAE case level, when 
appropriate.
Hepatic Safety Monitoring
9.4.6.1.
If a study patient experiences elevated ALT 3x ULN, ALP 2x ULN, or elevated TBL 
2x ULN, liver testing (Appendix 6) should be repeated within 3 to 5 days including ALT, AST, 
ALP, TBL, direct bilirubin, gamma-glutamyl transferase, and creatine kinase to confirm the 
abnormality and to determine if it is increasing or decreasing.  If the abnormality persists or 
worsens, clinical and laboratory monitoring should be initiated by the investigator and in 
consultation with the study medical monitor. Monitoring of ALT, AST, TBL, and ALP should 
continue until levels normalize or return to approximate baseline levels.
Hepatic Safety Data Collection
Additional safety data should be collected via the eCRF if 1 or more of the following conditions 
occur: 

Elevation of serum ALT to 5x ULN on 2 or more consecutive blood tests

Elevated serum TBL to 2x ULN (except for cases of known Gilbert’s syndrome)

Elevation of serum ALP to 2x ULN on 2 or more consecutive blood tests

Patient discontinued from treatment due to a hepatic event or abnormality of liver 
tests

Hepatic event considered to be a SAE
9.5.
Pharmacokinetics
At the visits and times specified in the Schedule of Activities (Section 2), venous blood samples 
will be collected to determine the serum concentrations of mirikizumab.
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.
Drug concentration information that may unblind the study will not be reported to investigative 
sites or blinded personnel.
Bioanalytical samples collected to measure investigational product concentration will be retained 
for a maximum of 1 year following last patient visit for the study.

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9.6. Pharmacodynamics
Not applicable.
9.7. Pharmacogenomics
9.7.1. Whole Blood Sample for Pharmacogenetic Research
A whole blood sample will be collected for pharmacogenetic analysis as specified in the 
Schedule of Activities (Section 2
CCI
)where local regulations allow.  
Samples will notbe used to conduct unspecified disease or population genetic research either 
now or in the future.  Samples will be used to investigate variable response to mirikizumaband 
to investigate genetic variants thought to play a role in psoriasis.  Assessment of variable 
response may include evaluation of AEs or differences in efficacy.  
All samples will be coded with the patient number.  These samples and any data generated can 
be linked back to the patient only by the investigator site personnel.  
Samples will be retained at a facility selected by Lilly or its designee for a maximum of 15years 
after the last patient visit for the study, or for a shorter period if local regulations and/or 
ERBs/investigational review boards impose shorter time limits.  This retention period enables 
use of new technologies, response to regulatory questions, and investigation of variable response 
that may not be observed until later in the development of mirikizumabor after mirikizumab
becomescommercially available.
Molecular technologies are expected to improve during the 15-year storage period and therefore 
cannot be specifically named.  However, existing approaches include whole genome or exome 
sequencing, genome wide association studies, and candidate gene studies.  Regardless of the 
technology utilized,genotyping data generated will be used only for the specific research scope 
described in this section.
 
 
 
 
 
 
 
 
 

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9.9. Medical Resource Utilization and Health Economics
CCI
Health Economics and Medical Resource Utilization parameters willnot be evaluated in this 
study.

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10. Statistical Considerations
10.1. Sample Size Determination
Approximately 500 patients will be randomized at a 4:1 ratio in the blinded Induction Period to 
receive 250 mg mirikizumab or placebo SC at Weeks 0, 4, 8, and 12.  Stratified block 
randomization will be performed with the following stratification factors: previous exposure to 
biologic therapy (yes/no), body weight (<100 kg or 100 kg), and geographic region (North 
America or Other).
There are multiple primary endpoints in this study:  sPGA (0,1) and PASI 90 at Week 16.  The 
assumed sPGA (0,1) responses are 70% for the mirikizumab arm and 5% for the placebo arm.
The assumed PASI 90 responses are 70% for the mirikizumab arm and 3% for the placebo arm.  
These assumptions are based upon the results of the mirikizumab Phase 2 Study AMAF (Reich 
et al. 2017b) and review of historical clinical studies in psoriasis (Langley et al. 2014; Gordon et 
al. 2016; Blauvelt et al. 2017; Papp et al. 2017; Reich et al. 2017a).
With a total sample size of 500 patients, randomizing 400 patients to the mirikizumab arm and 
100 patients to the placebo arm, this study has power of >95% for testing superiority of 
mirikizumab to placebo based on a 2-sided chi-square test with alpha of 5% on sPGA(0,1).  It 
also provides a power of >95% for testing superiority of mirikizumab to placebo on PASI 90
based on a 2-sided chi-square test with alpha of 5%.
In order to account for multiple testing for the comparisons of 2 mirikizumab groups against the 
placebo group in the Maintenance Period, a 2-sided chi-square test at the 0.025 level is assumed.
Assuming 70% of the mirikizumab patients are re-randomized in the Maintenance Period at 
Week 16 (Visit 7) at a 1:1:1 ratio to 250 mg mirikizumab Q8W, 125 mg mirikizumab Q8W or 
placebo, approximately 93 patients will be included in each treatment group. Stratified block 
randomization will be performed with the stratification factor of body weight at baseline
(<100 kg or 100 kg).  This sample size will provide >95% power to test the difference in the 
proportion of patients maintaining PASI 90 from Week 16 (Visit 7) after re-randomization at the 
start of the Maintenance Dosing Period to Week 52 (Visit 16) between each mirikizumab dosing 
interval and placebo, assuming the proportions of patients maintaining PASI 90 are 80% for 
250 mg mirikizumab Q8W, 70% for 125 mg mirikizumab Q8W, and 10% for placebo.  

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10.2. Populations for Analyses
For purposes of analysis, the following populations are defined:
Population
Description
Induction ITT
All randomized patients, even if the patient does not take the assigned 
treatment, does not receive the correct treatment, or otherwise does not follow 
the protocol. Patients will be analyzed according to the treatment to which 
they were assigned.  Unless otherwise noted, efficacy and health outcomes 
analyses for the Induction Period will be conducted on this population.
Induction Safety
All randomized patients who received at least 1 dose of the study treatment. 
Patients will be analyzed according to the treatment to which they were 
assigned.  Safety analyses for the Induction Period will be conducted on this 
population.
Re-randomized Maintenance ITT
All ITT patients who received at least 1 induction dose of the study treatment
and have been re-randomized at Week 16.  Efficacy and health outcomes 
analyses for the Maintenance Period will be conducted on this population.
Re-randomized Maintenance
Safety
All ITT patients who received at least 1 induction dose of the study treatment, 
have been re-randomized at Week 16, and have received at least 1 maintenance 
dose.  Safety analyses for the Maintenance Period will be conducted on this 
population.
Abbreviation:  ITT = intent-to-treat.
Additional analysis populations will be described in the SAP as deemed appropriate.
10.3. Statistical Analyses
10.3.1. General Statistical Considerations
Statistical analysis of this study will be the responsibility of Lilly or its designee.
Any change to the data analysis methods described in the protocol will require an amendment 
ONLY if it changes a principal feature of the protocol.  Any other change to the data analysis 
methods described in the protocol, and the justification for making the change, will be described 
in the clinical study report (CSR).  Additional exploratory analyses of the data will be conducted 
as deemed appropriate.
Efficacy analysis for induction outcomes will be conducted on the Induction intent-to-treat (ITT) 
population, while efficacy analysis for the maintenance outcomes will be conduction on the re-
randomized maintenance population as defined in Section 10.2. The induction and maintenance 
safety analysis will be performed on the induction safety and re-randomized  maintenance safety 
populations, respectively. Additional safety and efficacy analysis of the patients who are not re-
randomized for the maintenance portion of the study will be defined in the SAP.
Continuous data will be summarized in terms of the mean, standard deviation, minimum, 
maximum, median, and number of observations.  Categorical data will be summarized as 
frequency counts and percentages. Unless otherwise specified, all hypothesis tests will be 
2-sided with alpha of 0.05. Multiple testing will be controlled as described in Section 10.3.1.2.

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Unless otherwise specified, baseline for efficacy and health outcomes endpoints during both the 
Induction and Maintenance Periods will be defined as the last available value before the initial 
randomization during the Induction Period, which in most cases will be the measure recorded at 
Week 0 (Visit 2).  Detailed definitions of baseline for safety-related analyses will be described in 
the SAP. 
Unless otherwise specified, the statistical analysis models for the Induction Period will adjust for 
the covariates: previous exposure to biologic therapy (yes/no), body weight (<100 kg or
100 kg), and geographic region (North America or Other). Similarly, unless otherwise 
specified, the statistical analysis models for the Maintenance Period will adjust for the covariate
body weight (<100 kg or 100 kg).
For assessments of the primary endpoints and other categorical efficacy and health outcomes 
endpoints, the Cochran–Mantel–Haenszel (CMH) chi-square test will be used to compare the 
treatment groups with the stratification factors mentioned above.  The CMH chi-square p-value 
will be provided.  In addition, the absolute treatment difference in proportions will be provided 
along with the 95% 2-sided confidence interval estimate.
Treatment comparisons of continuous efficacy and health outcome variables with multiple 
post-baseline measurements will be made using mixed-effects model for repeated measures 
(MMRM).  When MMRM is used, the model includes treatment, baseline value, visit, the 
interaction of treatment-by-visit as fixed factors, and the induction/maintenance covariates 
mentioned above.  The covariance structure to model the within-patient errors will be 
unstructured.  If the unstructured covariance matrix results in a lack of convergence, the 
heterogeneous Toeplitz covariance structure, followed by the heterogeneous autoregressive 
covariance structure will be used.  The Kenward-Roger method will be used to estimate the 
denominator degrees of freedom.  Type III tests for the least squares means will be used for the 
statistical comparison; the 95% confidence interval will also be reported.
Treatment comparisons of continuous efficacy and health outcome variables with a single 
post-baseline time point will be made using analysis of covariance (ANCOVA) with the 
following in the model: treatment group, baseline value, and Induction Period/Maintenance
Period covariates mentioned above.  Type III tests for least-square (LS) means will be used for 
statistical comparison between treatment groups.  The LS mean difference, standard error, p-
value, and 95% confidence interval, unless otherwise specified, will also be reported.  Missing 
data imputation method for ANCOVA model will be specified in the SAP.
Fisher's exact test will be used for categorical safety data including AEs, unless otherwise 
specified.  Continuous safety data including vital sign and laboratory values will be analyzed 
using ANCOVA with treatment and baseline value in the model, unless otherwise specified. 
Also, laboratory analytes will be presented as mean changes from baseline and as incidence of 
shift between normal and abnormal states.
Missing Data Imputation
10.3.1.1.
The following methods for imputation of missing data will be used:

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
Non-Responder Imputation (NRI) for Binary Clinical Response:  Patients will be 
considered non-responders for the NRI analysis if they do not meet the clinical response 
criteria or have missing clinical response data at the analysis time point. Randomized 
subjects without at least 1 postbaseline observation will also be defined as 
non-responders for the NRI analysis.

Mixed-Effects Model for Repeated Measures (MMRM):  It will be the primary analysis 
method for longitudinal continuous measurements.  It assumes missing at random and the 
bias caused by missing data can be attenuated by modelling random effects using the 
within-patient error correlation structure. 
Additional missing data imputation methodologies, for example, modified baseline observation 
carried forward (mBOCF), may be considered as sensitivity analyses and will be detailed in the 
SAP.  By using mBOCF, for patients discontinuing study treatment due to an AE, the baseline 
observation will be carried forward to the corresponding primary endpoint for evaluation.  For 
patients discontinuing investigational product for any other reason, the last nonmissing 
postbaseline observation before discontinuation will be carried forward to the corresponding 
primary endpoint for evaluation.
Multiple Comparisons/Multiplicity
10.3.1.2.
The prespecified graphical multiple testing approach (Bretz et al. 2011) will be implemented to
control the overall Type I error rate at 2-sided alpha of 0.05, for the hypotheses for the primary 
and major secondary endpoints.  The graphical approach is a closed testing procedure; hence, it 
strongly controls the family-wise error rate across all endpoints (Alosh et al. 2014).
The Week 16 endpoints of sPGA (0,1) and PASI 90 represent a primary endpoint family.  The 
graphical testing scheme will sequentially test sPGA (0,1) first, followed by PASI 90 before 
proceeding to test the major secondary endpoints. Details of the specific graphical testing 
scheme (including testing order, interrelationships, Type I error allocation for the major 
secondary endpoints, and the associated propagation) will be pre-specified in the SAPs prior to 
the first unblinded analysis.
10.3.2. Treatment Group Comparability
Patient Disposition
10.3.2.1.
A detailed description of patient disposition will be provided at the end of the study.
Patient disposition will be summarized for each treatment period.  Reasons for discontinuation 
from the study will be summarized.
Patient Characteristics
10.3.2.2.
Patient characteristics and baseline clinical measures will be summarized for each treatment 
period.  Baseline characteristics will include gender, age, age category, weight, race, geographic 
region, baseline disease severity, duration of disease, prior exposure to biologic therapy, previous 
nonbiologic systemic therapy, and previous biologic therapy.  Baseline clinical measurements 
will include sPGA score, PASI score, BSA, PSSI, PSS symptom and sign scores, PatGA, DLQI 
total score, SF-36 (PCS), and SF-36 (MCS).

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Concomitant Therapy
10.3.2.3.
Previous and concomitant medications will be summarized for patientswho enter each treatment 
period and will be presented using the latest version of the World Health Organization (WHO) 
drug dictionary. 
Treatment Compliance
10.3.2.4.
Treatment compliance with investigational product will be summarized for patientswho enter 
the Induction and Maintenance Periods.  A patientwill be considered as having missed thevisit 
if he or she fails to attend for administration of the investigational product within the required 
treatment window as defined in the Schedule of Activities (Section 2).  Overall compliance with 
therapy is defined to be missing no more than 20% of the expected doses within the protocol-
defined dosing interval and not missing 2consecutive doses.  The proportion of patientswho 
demonstrate overall compliance during the Induction Period will be compared between treatment 
groups using Fisher’s exact test.
10.3.3.Efficacy Analyses
Primary and secondary analyses will be based on the InductionITT populationand Maintenance 
ITT population as defined in Section 10.2.
Primary Analyses
10.3.3.1.
Treatment comparisons between mirikizumaband placebo in the proportion of patientsachieving 
sPGA (0,1) with at least a 2-point improvement frombaselineatWeek 16 will be analyzed using 
the CMH methodwith NRI as described in Section 10.3.1.Also, treatment comparisons between 
mirikizumaband placebo in the proportion of patientsachieving PASI 90 at Week 16 will be 
analyzed using the CMH methodwith NRI as described in Section 10.3.1.
Secondary Analyses
10.3.3.2.
Protocol-definedsecondary efficacy and health outcome endpoints of the trial are presented in 
TableAMAK.2.Details of the analysis methods that will be utilized are provided in 
Section10.3.1.As noted in Section 10.3.1.2
CCI
,our graphical testing approach to multiplicity 
control will require both primary endpoints to be successful before proceeding to the major 
secondary endpoints.
Additional analyses of secondary efficacy and health outcome endpoints may
 be considered and 
will be fully detailed in the SAP.  Additional endpoints may be pre-specified in the SAP.
 
 

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10.3.4. Safety Analyses
Safety assessments will include AEs, SAEs, AESIs, laboratory analytes, vital signs, QIDS-SR16, 
and C-SSRS.
The Induction Period safety analyses will compare mirikizumab to placebo using the methods 
described in Section 10.3.1.  The Maintenance Period safety analyses will summarize safety 
measures by treatment. 
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities
(MedDRA) and summarized by system organ class, preferred term, severity, and relationship to 
investigational product.  A treatment-emergent adverse event (TEAE) is defined as an event that 
first occurred or worsened in severity after baseline.  For each event classification term, the 
number of patients experiencing a TEAE with that classification term will be tabulated.  
Treatment-related TEAEs are defined as events that are indicated by the investigator on the 
eCRF to be related to treatment.  If a patient reports the occurrence of a particular event more 
than once, the most severe of those events will be included in the summary tables of TEAEs, and 
the most severe of the most related of those events will be included in the summary tables of 
treatment-related events.  For events that are gender specific, the denominator and computation 
of the percentage will only include patients from the given gender.
Adverse events of special interest are defined in Section 9.2.3 and the analysis plan will be 
described in the Program Safety Analysis Plan and SAP.
10.3.5. Pharmacokinetic/Pharmacodynamic Analyses
The PK of mirikizumab will be characterized using visualization/graphical evaluations and 
mixed-effect (population PK) modeling approaches.  Various structural and error models will be 
evaluated.  Intrinsic factors (such as age, body weight, gender, immunogenicity) and extrinsic 
factors (such as co-medications) will be investigated to assess their influence on model 
parameters.  Model evaluation will include a visual predictive check.  Estimates of PK model 
parameters and covariate effects and corresponding 90% confidence intervals will be reported.
Analyses of exposure-response relationships will be conducted using both exploratory 
visualization/graphical approaches and model-based approaches. Exploratory 
visualization/graphical analysis approaches for categorical clinical endpoints (for example, PASI 
90, sPGA [0,1]) may consist of graphs showing the percentage of patients who achieve the 
clinical endpoint at different percentiles (for example, quartiles) of exposure of mirikizumab at 
Weeks 16 and 52. Measures of exposure may include population PK estimated average 
concentrations (Cavg), or estimated or observed trough concentrations at the time of the clinical 
endpoint. Model-based analyses of the binary clinical endpoints will utilize population 
exposure-response logistic regression models, where maximum effect (Emax) or other model 
structures may be used to relate exposure to the probability of achieving the endpoint. These 
models may be used to evaluate patient factors that may impact the relationship between 
exposure and the probability of achieving the endpoint. Longitudinal exposure-response models 

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for PASI scores or response rates may be developed, which relate the time course and magnitude 
of mirikizumabexposure to the time course and magnitude of the PASI response.
Additional analyses may be conducted,if they are deemed appropriate.  Data from this study 
may be combined with other study data, if appropriate.  Further details on PK and PK/PD 
analyses will be provided in the PK/PD analysis plan.
10.3.6.Evaluation of Immunogenicity
The frequencyand percentageof patients with pre-existing (baseline) ADA, ADA at any time 
post baseline, and with treatment-emergent ADA(TE-ADA)to mirikizumabwill be tabulated. 
The frequency of neutralizing antibodies will also betabulated.
The relationship between the presence of antibodies and the PKparameters and PDresponse,
including safety and efficacy to mirikizumab,willbe assessed.
10.3.7.Other Analyses
 
 
Psoriasis Symptoms ScalePsychometric Analysis
10.3.7.2.
CCI
Psychometric analysis of PSS will be defined in a separate health outcomes SAP.  The analyses 
will evaluate the validity, responsiveness, and interpretability of the PSS.

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10.3.8. Interim Analyses
One DMC consisting of members external to Lilly will be established for interim safety
monitoring across all Phase 3 trials in patients with psoriasis. This committee will consist of a
minimum of 3 members, including a physician with expertise in dermatology and a statistician. 
No member of the DMC may have contact with study sites. A Statistical Analysis Center (SAC)
will prepare and provide unblinded safety data to the DMC. The SAC members may be Lilly 
employees or from third-party organizations designated by Lilly.  However, they will be external 
to the study team and will have no contact with sites and no privileges to influence change in the 
ongoing study. Access to the unblinded safety data will be limited to the DMC and the SAC or 
their designees. The study team will not have access to the unblinded data. Only the DMC is 
authorized to evaluate unblinded data. The purpose of the DMC is to advise Lilly regarding 
continuing patient safety; however, the DMC may request key efficacy data to put safety 
observations into context and to confirm a reasonable benefit/risk profile for ongoing patients in 
the study. Hence, there will be no alpha adjustment for these interim assessments. Study sites 
will receive information about interim assessments ONLY if they need to know for the safety of
their patients. This committee will make recommendations as to whether it is scientifically and
ethically appropriate to continue enrollment, discontinue a treatment group, or discontinue the
study. Details outlining the roles and responsibilities of the DMC will be finalized in the DMC 
charter and an associated DMC analysis plan prior to the first unblinded assessment. 
In addition to the DMC interim assessments for safety, a limited number of Lilly employees or 
their designees not in direct contact with the clinical sites will be provided access to the data 
from this study once all randomized patients either complete the assessments for primary 
endpoints at Week 16 (Visit 7) or discontinue from the study. The purpose of providing this 
access to a small group is to initiate work related to regulatory submission upon completion of 
the study. The study will not be terminated prematurely on the basis of either efficacy or futility 
following the Week 16 interim analysis. Although this is an interim analysis with respect to the 
entire study, it is the only and final analysis for the primary endpoint. Therefore, no alpha 
adjustment for this interim analysis is planned.
In addition, a limited number of pre-identified internal Lilly personnel that are not in contact 
with clinical sites may gain access to unblinded PK data, as specified in the unblinding plan, 
prior to final database lock, in order to initiate the final population PK model development 
processes.  Unblinding details will be provided in the unblinding plan.

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J Invest Dermatol. 2008;128(5):1207-1211.
Menter A, Gottlieb A, Feldman SR, VanVoorhees AS, Leonardi CL, Gordon KB, Lebwohl M, 
Koo JY, Elmets CA, Korman NJ, Beutner KR, Bhushan R. Guidelines of care for the 
management of psoriasis and psoriatic arthritis: section 1. Overview of psoriasis and 
guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. 
2008;58(5):826-850.
Monteleone I, Pallone F, Monteleone G. Interleukin-23 and Th17 cells in the control of gut 
inflammation. Mediators Inflamm. 2009;2009:297645.
National Psoriasis Foundation. The psoriasis and psoriatic arthritis pocket guide – treatment 
algorithms and management options (4th ed.). 2016. Available at: 
https://www.psoriasis.org/pocket-guide. Accessed January 19, 2018.
Papp KA, Blauvelt A, Bukhalo M, Gooderham M, Krueger J, Lacour J-P, Menter A, Philipp S, 
Sofen H, Tyring S, Berner BR, Visvanathan S, Pamulapati C, Bennett N, Flack M, Scholl P, 
Padula SJ. Risankizumab versus ustekinumab for moderate-to-severe plaque psoriasis. N Engl 
J Med. 2017;376(16):1551-1560.
Papp K, Thaçi D, Reich K, Riedl E, Langley RG, Krueger JG, Gottlieb AB, Nakagawa H, 
Bowman EP, Mehta A, Li Q, Zhou Y, Shames R. Tildrakizumab (MK-3222) an 
anti-interleukin-23p19 monoclonal antibody, improves psoriasis in a phase IIb randomized 
placebo-controlled trial. Br J Dermatol. 2015;173(4):930-939.
Parisi R, Symmons DP, Griffiths CE, Ashcroft DM; Identification and Management of Psoriasis 
and Associated ComorbidiTy (IMPACT) project team. Global epidemiology of psoriasis: a 
systematic review of incidence and prevalence. J Invest Dermatol. 2013;133(2):377-385.
Piskin G, Tursen U, Sylva-Steenland RM, Bos JD, Teunissen MB. Clinical improvement in 
chronic plaque-type psoriasis lesions after narrow-band UVB therapy is accompanied by a 
decrease in the expression of IFN-gamma inducers -- IL-12, IL-18 and IL-23. Exp Dermatol.
2004;13(12):764-772.

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Puig L. PASI90 response: the new standard in therapeutic efficacy for psoriasis. J Eur Acad 
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Accessed January 16, 2018.

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12.
Appendices

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Appendix 1.
Abbreviations and Definitions
Term
Definition
AIDS
acquired immune deficiency syndrome
ADA
anti-drug antibody
AE
adverse event:  Any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product that does not necessarily have a causal 
relationship with this treatment.  An adverse event can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a medicinal (investigational) product, whether or 
not related to the medicinal (investigational) product.
AESI
adverse event of special interest
ANCOVA
analysis of covariance
ALP
alkaline phosphatase
ALT
alanine aminotransferase
AST
aspartate aminotransferase
blinding/masking
A single-blind study is one in which the investigator and/or his staff are aware of the 
treatment but the patient is not, or vice versa, or when the Sponsor is aware of the 
treatment but the investigator and/his staff and the patient are not.
A double-blind study is one in which neither the patient nor any of the investigator or 
Sponsor staff who are involved in the treatment or clinical evaluation of the patients are 
aware of the treatment received.
BCG
Bacillus Calmette-Guerin
BP
blood pressure
BSA
body surface area
CIOMS
Council for International Organizations of Medical Sciences
CMH
Cochran-Mantel-Haenszel
complaint
A complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, purity, durability, reliability, safety or effectiveness, or 
performance of a drug or drug delivery system.
compliance
Adherence to all study-related, good clinical practice (GCP), and applicable regulatory 
requirements.
CRF
case report form

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CSR
clinical study report
C-SSRS
Columbia-Suicide Severity Rating Scale
CXR
chest x-ray
DLQI
Dermatology Life Quality Index
DMC
Data Monitoring Committee
DNA
deoxyribonucleic acid
ECG
electrocardiogram
eCOA
electronic clinical outcome assessments
eCRF
electronic case report form
EMA
European Medicines Agency
enroll
The act of assigning a patient to a treatment.  Patients who are enrolled in the study are 
those who have been assigned to a treatment.
enter
Patients entered into a study are those who sign the informed consent form directly or 
through their legally acceptable representatives.
EQ-5D-5L-PSO
European Quality of Life–5 Dimensions–5 Levels–Psoriasis
ERB
Ethical Review Board
ETV
early termination visit
FDA
United States Food and Drug Administration
GCP
Good Clinical Practice
GMP
Good Manufacturing Practice
GPS
Global Patient Safety
HBcAb
hepatitis B core antibody
HBsAb
hepatitis B surface antibody
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HIV
human immunodeficiency virus
HRQoL
health-related quality of life

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IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonisation
IGRA
interferon-release assay
informed consent
A process by which a patient voluntarily confirms his or her willingness to participate 
in a particular study, after having been informed of all aspects of the study that are 
relevant to the patient’s decision to participate.  Informed consent is documented by 
means of a written, signed and dated informed consent form.
interim analysis
An interim analysis is an analysis of clinical study data, separated into treatment groups, 
that is conducted before the final reporting database is created/locked.
IL-23
interleukin-23
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.
INR
international normalized ratio
ITT
intention to treat:  The principle that asserts that the effect of a treatment policy can be 
best assessed by evaluating on the basis of the intention to treat a patient (that is, the 
planned treatment regimen) rather than the actual treatment given.  It has the 
consequence that patients allocated to a treatment group should be followed up, 
assessed, and analyzed as members of that group irrespective of their compliance to the
planned course of treatment.
IV
intravenous
IWRS
interactive web-response system
LTBI
latent tuberculosis infection
LS
least-squares
mBOCF
modified baseline observation carried forward
MCID
minimal clinically important difference
MCS
mental component summary of the SF-36
medical monitor
Individual responsible for the medical conduct of the study.  Responsibilities of the 
medical monitor may be performed by a physician, clinical research scientist, global 
safety physician, or other medical officer.
MedDRA
Medical Dictionary for Regulatory Activities
MMRM
mixed-effects model for repeated measures

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MOS
margin of safety
NAPSI
Nail Psoriasis Severity Index
NOAEL
no-observed-adverse-effect-level
NRI
non-responder imputation
NRS
numeric rating scale
PA
posterior-anterior (chest x-ray)
PASI
Psoriasis Area and Severity Index
PatGA
Patient’s Global Assessment of Psoriasis
PCS
physical component summary of the SF-36
PD
pharmacodynamics(s)
PK
pharmacokinetic(s)
PK/PD
pharmacokinetics/pharmacodynamics
PPASI
Palmoplantar Psoriasis Severity Index
PPD
purified protein derivative (skin test)
PSS
Psoriasis Symptoms Scale
PSSI
Psoriasis Scalp Severity Index
PUVA
psoralen and ultraviolet A
Q4W
every 4 weeks
Q8W
every 8 weeks
QIDS-SR16
16-item Quick Inventory of Depressive Symptomatology
RNA
ribonucleic acid
SAC
Statistical Analysis Center
SAP
statistical analysis plan
SC
subcutaneous
SAE
serious adverse event
screen
The act of determining if an individual meets minimum requirements to become part of 
a pool of potential candidates for participation in a clinical study. 
SF-36
Medical Outcomes Study 36-item Short-Form Health Survey

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SIRC
Safety Internal Review Committee
sPGA
static Physician’s Global Assessment
SUSARs
suspected unexpected serious adverse reactions
TB
tuberculosis
TBL
total bilirubin level
TE-ADA
treatment-emergent anti-drug antibody
TEAE
Treatment-emergent adverse event:  An untoward medical occurrence that emerges 
during a defined treatment period, having been absent pretreatment, or worsens relative 
to the pretreatment state, and does not necessarily have to have a causal relationship 
with this treatment.
Th
T helper
TNF
tumor necrosis factor
TSQM
Treatment Satisfaction Questionnaire for Medication
ULN
upper limit of normal
WBC
white blood cell
WHO
World Health Organization
WPAI-PSO
Work Productivity and Activity Impairment Questionnaire: Psoriasis

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Appendix 2.
Clinical Laboratory Tests
Clinical Laboratory Tests
Hematologya
Clinical (Serum) Chemistrya
Other
Hemoglobin
Serum Concentrations of:
Human immunodeficiency virus (HIV)b
Hematocrit
Sodium
Hepatitis B surface antigen (HBsAg)b
Erythrocyte count (RBC)
Potassium
Hepatitis B core antibody (HBcAb)b
Mean cell volume
Total bilirubin
Hepatitis B surface antibody (HBsAb)b
Mean cell hemoglobin
Total protein
HBV DNA testc
Mean cell hemoglobin 
concentration
Direct bilirubin
Hepatitis C antibodyb
Leukocytes (WBC)
Alkaline phosphatase (ALP)
HCV RNA testc
Cell morphology
Alanine aminotransferase (ALT)
Pregnancy Test (females only)
Absolute Counts and 
Percentage of:
Aspartate aminotransferase (AST)
Serumb
Neutrophils, segmented
Gamma-glutamyl transferase (GGT)
Urine (assayed locally by clinical study 
site)
Lymphocytes
Blood urea nitrogen (BUN)
Follicle-stimulating hormone (FSH)b
Monocytes
Creatinine
PPD or QuantiFERON-TB Gold test or T-
SPOT.TB testd
Eosinophils
Uric acid
Exploratory storage samples (DNA)
Basophils
Calcium
Exploratory storage samples (serum, 
plasma, whole blood,
RNA)
Absolute Counts of:
Glucose
Anti-mirikizumab antibodies 
(immunogenicity)a
Platelets
Albumin
Serum mirikizumab concentration (PK)a
Cholesterol (total)
Tryptasea
Triglycerides
Complement panel (C3 and C4)a

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Urinalysis
Creatine kinase (CK)
Cytokine panela
Specific gravity
High-sensitivity C-reactive protein 
(hsCRP)
pH
Lipid Panel (fasting)
Protein
Low-density lipoprotein (LDL)
Glucose
High-density lipoprotein (HDL)
Ketones
Very-low-density lipoprotein (VLDL)
Bilirubin
Urobilinogen
Blood
Nitrite
Urine leukocyte esterase
Microscopic examination 
of sediment
Abbreviations:  DNA = deoxyribonucleic acid; HBV = hepatitis B virus; HCV = hepatitis C virus; 
PK = pharmacokinetic(s); PPD = purified protein derivative (skin test); RBC = red blood cells; 
RNA = ribonucleic acid; TB = tuberculosis; WBC = white blood cells.
a
Unscheduled hematology or blood chemistry panels may be performed at the discretion of the investigator. If a 
patient develops an acute hypersensitivity event after administration of IP, blood samples will be collected for 
pharmacokinetic, immunogenicity, and exploratory hypersensitivity analyses.
b
Performed at screening only.
c
Following screening, patients will not undergo monitoring for Hepatitis C unless liver enzymes are elevated.
Hepatitis B monitoring will be performed at protocol-specified intervals in patients who test positive for 
anti-hepatitis B core antibody.
d
TB testing will be performed locally using an interferon-release assay (IGRA, for example
QuantiFERON®-TB Gold or T-SPOT.TB) or a PPD tuberculin skin test.  If PPD test is performed, patients will 
return 2 to 3 days afterwards to have their PPD test read.

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Appendix 3.
Study Governance Considerations

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Appendix 3.1. Regulatory and Ethical Considerations, Including the 
Informed Consent Process
Appendix 3.1.1.
Informed Consent
The investigator is responsible for:

Ensuring that the patient understands the nature of the study, the potential 
risks and benefits of participating in the study, and that their participation is 
voluntary.

Ensuring that informed consent is given by each patient or legal 
representative.  This includes obtaining the appropriate signatures and dates 
on the informed consent form (ICF) prior to the performance of any protocol 
procedures and prior to the administration of investigational product.

Answering any questions the patient may have throughout the study and 
sharing in a timely manner any new information that may be relevant to the 
patient’s willingness to continue his or her participation in the study.

Ensuring that a copy of the ICF is provided to the participant or the 
participant’s legal representative and is kept on file.

Ensuring that the medical record includes a statement that written informed 
consent was obtained before the participant was enrolled in the study and the 
date the written consent was obtained. The authorized person obtaining the 
informed consent must also sign the ICF.
Appendix 3.1.2.
Recruitment
Lilly or its designee is responsible for the central recruitment strategy for patients.  Individual 
investigators may have additional local requirements or processes.
Appendix 3.1.3.
Ethical Review
The investigator or an appropriate local representative must give assurance that the ethical 
review board (ERB) was properly constituted and convened as required by International Council
for Harmonisation (ICH) guidelines and other applicable laws and regulations.
Documentation of ERB approval of the protocol and the ICF must be provided to Lilly before the 
study may begin at the investigative site(s).  Lilly or its representatives must approve the ICF, 
including any changes made by the ERBs, before it is used at the investigative site(s).  All ICFs 
must be compliant with the ICH guideline on Good Clinical Practice (GCP).
The study site’s ERB(s) should be provided with the following:

The protocol and related amendments and addenda, current IB and updates 
during the course of the study

Informed consent form

Other relevant documents (for example, curricula vitae, advertisements)

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Appendix 3.1.4.
Regulatory Considerations
This study will be conducted in accordance with the protocol and with the:

Consensus ethics principles derived from international ethics guidelines, 
including the Declaration of Helsinki and Council for International Organizations
of Medical Sciences (CIOMS) International Ethical Guidelines

Applicable ICH GCP Guidelines

Applicable laws and regulations
Some of the obligations of the Sponsor will be assigned to a third party.
Appendix 3.1.5.
Investigator Information
Physicians with a specialty in dermatology or other relevant specialties with appropriate 
experience in diagnosis and treatment of patients with psoriasis will participate as investigators 
in this clinical trial.
Appendix 3.1.6.
Protocol Signatures
The Sponsor’s responsible medical officer and statistician will approve the protocol, confirming 
that, to the best of his or her knowledge, the protocol accurately describes the planned design and 
conduct of the study.
After reading the protocol, each principal investigator will sign the protocol signature page and 
send a copy of the signed page to a Lilly representative.
Appendix 3.1.7.
Final Report Signature
The clinical study report (CSR) coordinating investigator will sign the final CSR for this study, 
indicating agreement that, to the best of his or her knowledge, the report accurately describes the 
conduct and results of the study.
The CSR coordinating investigator will be selected by the Sponsor.  If this investigator is unable 
to fulfill this function, another investigator will be chosen by Lilly to serve as the CSR 
coordinating investigator.
The Sponsor’s responsible medical officer and statistician will approve the final CSR for this 
study, confirming that, to the best of his or her knowledge, the report accurately describes the 
conduct and results of the study.
Appendix 3.2.
Data Quality Assurance
To ensure accurate, complete, and reliable data, Lilly or its representatives will do the following:

Provide instructional material to the study sites, as appropriate

Sponsor start-up training to instruct the investigators and study coordinators.  This 
training will give instruction on the protocol, the completion of the case report 
forms (CRFs), and study procedures.

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
Make periodic visits to the study site

Be available for consultation and stay in contact with the study site personnel by 
mail, telephone, and/or fax

Review and evaluate CRF data and use standard computer edits to detect errors in 
data collection

Conduct a quality review of the database
In addition, Lilly or its representatives will periodically check a sample of the patient data 
recorded against source documents at the study site.  The study may be audited by Lilly or its 
representatives, and/or regulatory agencies at any time.  Investigators will be given notice before 
an audit occurs.
The investigator will keep records of all original source data.  This might include laboratory 
tests, medical records, and clinical notes.  If requested, the investigator will provide the Sponsor, 
applicable regulatory agencies, and applicable ERBs with direct access to original source 
documents.
Appendix 3.2.1.
Data Capture System
An electronic case report form (eCRF) system will be used in this study.  The site maintains a 
separate source for the data entered by the site into the Sponsor-provided eCRF system.  Case 
report form data will be encoded and stored in a clinical trial database.
Electronic clinical outcome assessments (eCOA) measures (questionnaires, scales, self-reported 
diary data, etc.) will be collected by the patients and site personnel at the time that the 
information is obtained.  In these instances, where there is no prior written or electronic source 
data at the site, the eCOA data record will serve as the source. The eCOA data will be stored at a 
third party site.  Investigator sites will have continuous access to the source documents during 
the study and will receive an archival copy at the end of the study for retention.  Any data for 
which the eCOA instrument record will serve to collect source data will be identified and 
documented by each site in that site’s study file.
Data managed by a central vendor, such as laboratory test data, will be stored electronically in 
the central vendor’s database system.  Data will subsequently be transferred from the central 
vendor to the Lilly data warehouse.
Data from complaint forms submitted to Lilly will be encoded and stored in the global product 
complaint management system.
Appendix 3.3.
Study and Site Closure
Appendix 3.3.1.
Discontinuation of Study Sites
Study site participation may be discontinued if Lilly or its designee, the investigator, or the ERB 
of the study site judges it necessary for medical, safety, regulatory, or other reasons consistent 
with applicable laws, regulations, and GCP.

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Appendix 3.3.2.
Discontinuation of the Study
The study will be discontinued if Lilly or its designee judges it necessary for medical, safety, 
regulatory, or other reasons consistent with applicable laws, regulations, and GCP.
Appendix 3.4.
Publication Policy
The publication policy for Study I6T-MC-AMAK is described in the letters of agreement 
between the Sponsor and the investigators and institutions.

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Appendix 4.
Examples of Infections That May Be 
Considered Opportunistic in the Setting of Biologic 
Therapy

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Bacterial
Bartonellosis (disseminated disease only)
Campylobacteriosis (invasive disease only)
Legionellosis
Listeria monocytogenes (invasive disease only)
Nocardiosis
Tuberculosis
Non-tuberculous mycobacterial disease 
Salmonellosis (invasive disease only) 
Shigellosis (invasive disease only)
Vibriosis (invasive disease due to Vibrio vulnificus)
Viral
BK virus disease including polyomavirus-associated nephropathy
Cytomegalovirus disease
Hepatitis B virus reactivation
Hepatitis C virus progression
Herpes simplex (invasive disease only)
Herpes zoster (any form)
Post-transplant lymphoproliferative disorder (Epstein-Barr virus)
Progressive multifocal leukoencephalopathy (PML), John Cunningham (JC) virus [excluded from the study]
Fungal
Aspergillosis (invasive disease only)
Blastomycosis
Candidiasis (invasive disease or pharyngeal)
Coccidioidomycosis
Cryptococcosis
Histoplasmosis
Paracoccidioides infections
Penicillium marneffei
Pneumocystis jirovecii (formerly Pneumocystis carinii)
Sporothrix schenckii
Other invasive fungi: Mucormycosis (zygomycosis) (Rhizopus, Mucor and Lichtheimia), 
Scedosporium/Pseudallescheria boydii, Fusarium
Protozoan
Leishmaniasis (visceral only)
Microsporidiosis
Toxoplasmosis
Trypanosoma cruzi infection (Chagas’ disease) (disseminated disease only)
Source:  Adapted from Winthrop et al. (2015).
This table is provided to aid the investigator in recognizing infections that may be considered opportunistic in the 
context of biologic therapy, for the purposes of Exclusion Criterion [16].  This list is not exhaustive.  
Investigators should use their clinical judgement, as well as discussion with the Lilly-designated medical 
monitor, in determining if other infections may be considered opportunistic, for the purposes of Exclusion 
Criterion [16].  
Winthrop et al. (2015) consider tuberculosis (TB) and non-TB mycobacterial disease to be opportunistic infections 
in the context of biologic therapy.  See Section 9.4.5.2 for the approach to screening for latent TB infection
within the study.

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Appendix 5.
Risk Factors for Latent Tuberculosis 
Infection

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Risk Factors for Latent Tuberculosis Infection
Household contact or recent exposure to an active case
Mycobacterial laboratory personnel
Birth or residency in a high burden country (>20/100,000)
Residents and employees of high risk congregate settings, for example, prisons, homelessness, intravenous drug use
Source:  Adapted from Horsburgh and Rubin (2011) and Lewinsohn et al. (2017).
Risk Factors for Increased Likelihood of Progression from LTBI to Active TB
Household contact or close contact with an active case
HIV
Radiographic evidence of old, healed TB that was not treated
Silicosis
Treatment with 15 mg prednisone (or equivalent) per day
Children <5 years of age
Chronic renal failure
Treatment with an anti-TNF antibody
Poorly controlled diabetes
Intravenous drug use
Weight 10% below normal
Smoking
Abbreviations:  HIV = human immunodeficiency virus; LTBI = latent tuberculosis infection; TB = tuberculosis; 
TNF = tumor necrosis factor.
Source:  Adapted from Horsburgh and Rubin (2011) and Lewinsohn et al. (2017).
World Health Organization List of High Burden Countries
Angola
India
Peru
Azerbaijan
Indonesia
Philippines
Bangladesh
Kenya
Russian Federation
Belarus
Kazakhstan
Sierra Leone
Botswana
Democratic People’s Republic of Korea
Somalia
Brazil
Kyrgyzstan
South Africa
Cambodia
Lesotho
Swaziland
Cameroon
Liberia
Tajikistan
Central African Republic
Malawi
United Republic of Tanzania
Chad
Moldova
Thailand
China
Mozambique
Uganda
Congo
Myanmar
Ukraine
Democratic Republic of the Congo
Namibia
Uzbekistan
Ethiopia
Nigeria
Vietnam
Ghana
Pakistan
Zambia
Guinea-Bissau
Papua New Guinea
Zimbabwe
Source:  WHO (2015).

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Appendix 6.
Hepatic Monitoring Tests for 
Treatment-Emergent Abnormality
Selected tests may be obtained in the event of a treatment-emergent hepatic abnormality and may 
be required in follow-up with patients in consultation with the Lilly-designated medical monitor.
Hepatic Monitoring Tests
Hepatic Hematologya
Haptoglobina
Hemoglobin
Hematocrit
Hepatic Coagulationa
Red blood cells (RBC)
Prothrombin time
White blood cells (WBC)
Prothrombin time, INR
Neutrophils, segmented
Lymphocytes
Hepatic Serologiesa,b
Monocytes
Hepatitis A antibody, total
Eosinophils
Hepatitis A antibody, IgM
Basophils
Hepatitis B surface antigen
Platelets
Hepatitis B surface antibody
Hepatitis B Core antibody
Hepatic Chemistrya
Hepatitis C antibody
Total bilirubin
Hepatitis E antibody, IgG
Direct bilirubin
Hepatitis E antibody, IgM
Alkaline phosphatase (ALP)
Alanine aminotransferase (ALT)
Anti-Nuclear Antibodya
Aspartate aminotransferase (AST)
Gamma-glutamyl transferase (GGT)
Alkaline Phosphatase Isoenzymesa
Creatine phosphokinase (CPK)
Anti-Smooth Muscle Antibody (or Anti-Actin 
Antibody)a
Abbreviations:  Ig = immunoglobulin; INR = international normalized ratio.
a
Assayed by Lilly-designated or local laboratory.
b
Reflex/confirmation dependent on regulatory requirements and/or testing availability.

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Appendix 7.
Protocol Amendment I6T-MC-AMAK(a)
Summary A Multicenter Study with a Randomized, 
Double-Blind, Placebo-Controlled Induction Dosing 
Period Followed by a Randomized Withdrawal 
Maintenance Dosing Period to Evaluate the Efficacy and 
Safety of Mirikizumab in Patients with 
Moderate-to-Severe Plaque Psoriasis
OASIS-1
Overview
Protocol I6T-MC-AMAK (A Multicenter Study with a Randomized, Double-Blind, 
Placebo-Controlled Induction Dosing Period Followed by a Randomized Withdrawal 
Maintenance Dosing Period to Evaluate the Efficacy and Safety of Mirikizumab in Patients with 
Moderate-to-Severe Plaque Psoriasis [OASIS-1]) has been amended.  The new protocol is 
indicated by amendment (a) and will be used to conduct the study in place of any preceding 
version of the protocol.  The primary changes in this amendment are:

The major secondary endpoint of DLQI (0,1) response at Week 16 has been revised
per FDA feedback.  Previously, DLQI (0,1) response was to be assessed in patients 
with baseline DLQI >1.  Now, DLQI (0,1) response will include a 5-point reduction 
and be assessed in patients with baseline DLQI 5.

Stricter discontinuation language for clinically significant systemic hypersensitivity 
events has been applied throughout the protocol.
The overall changes and rationale for the changes made to this protocol are described in the 
following table:

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Amendment Summary for Protocol I6T-MC-AMAK Amendment (a)
Section # and Name
Description of Change
Brief Rationale
Global
Global
Various typos fixed and clarifications made
Section 1
Section 1.  Synopsis
Revised to align with changes in protocol body
Section 2
Section 2.  Schedule of Activities
1.
In header, moved line separating Induction and 
Maintenance to the center of Visit 7
2.
Added “temp” to Vital Signs
3.
Added peripheral lymph nodes examination to 
the physical examination
4.
Added that TB testing may be performed after
screening if clinically indicated
5.
If PPD test is performed, patients will return 2
to 3 days afterwards Visit 1 to have their PPD
test read.  (also amended in Appendix 2)
1.
Alignment with other studies in program
2.
Regulatory request from US FDA
3.
New safety guideline and alignment with other 
studies in program
4.
New patient safety guidelines
5.
Allows PPD to be performed at visits other
than Visit 1
Section 4
Section 4.  Objectives and Endpoints
1.
Revised major secondary endpoint so that 
DLQI (0,1) response will include a 5-point 
reduction and be assessed in patients with 
baseline DLQI 5 (also included this endpoint 
at other times as Other Secondary endpoint)
2.
Moved DLQI (0,1) response assessed in 
patients with baseline DLQI >1 to Other 
Secondary objectives
3.
Changed PPASI, PSSI, and NAPSI endpoints 
from “percent change” to “change.”
1.
FDA feedback
2.
As it is no longer a major secondary objective, 
but Lilly would still like to perform indirect 
and direct comparisons
3.
To give flexibility to report both absolute and 
percentage change

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Section # and Name
Description of Change
Brief Rationale
Section 5
Section 5.1.4.  Post-Treatment Follow-Up Period 
(12 Weeks)
Added ability for patients to receive psoriasis
therapy with another agent(s)
Allow patients not receiving benefit from study
drug to access other treatments more quickly
Section 6
Section 6.1.  Inclusion Criteria
Added that local contraception guidelines must be 
followed
Allow sites to meet local regulatory requirements
Section 7
Section 7.7.  Concomitant Therapy
1.
BCG prohibited for 12 months before baseline, 
live vaccinations prohibited for 12 weeks 
before baseline.  Both are prohibited 
throughout the study and for 12 months or 12 
weeks, respectively, after discontinuation of 
study drug
2.
Added paragraph on allowed topical therapies
1.
Error in original protocol
2.
Clarification and alignment with other studies 
in program
Section 7.8.2.1. Management of Hypersensitivity
Events, Including Injection Site Events
1.
Added that if a patient experiences an acute 
hypersensitivity event after an injection of the 
investigational product, blood samples will be 
collected for PK, immunogenicity, and 
exploratory hypersensitivity analyses. (also 
amended in Appendix 2)
2.
Patients who develop clinically significant 
systemic hypersensitivity events following 
administration of investigational product,who 
do not respond to symptomatic medication, or 
whose event results in clinical sequelae (for 
example, hospitalization), should be 
discontinued from the study.
1.
To align this section with the rest of the 
protocol
2.
Commitment to FDA

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Section # and Name
Description of Change
Brief Rationale
Section 8
Section 8.2.  Discontinuation from the Study (sixth 
subbullet of third bullet point)
Clinically significant systemic hypersensitivity 
event following administration of investigational 
productthat does not respond to symptomatic 
medication or results in clinical sequelae.
Commitment to FDA
Section 9
Section 9.4.1. Electrocardiograms and 
Section9.4.2. Vital Signs
Added temperature to list of vital signs
Alignment with Schedule of Activities
Section 9.4.4. Immunogenicity Assessments
Added that immunogenicity samples will be
evaluated for PK, ADA, 
To provide information in the event of a
hypersensitivity event
Section 9.4.5.1.  Physical Examination
Added peripheral lymph nodes to list for 
symptom-directed evaluation
New safety guideline
Section 9.4.5.2.  Tuberculosis Screening
1. Added Monitoringsubsectionbeneaththe 
Screening subsection
2. Removed sentence “Follow-up TB testing with 
IGRA or PPD, tailored in accordance with a 
person’s risk (for example, hospital care
worker, residence in a high risk location), may
be performed according to local guidelines.”
3. Added prior treatment for TB to subsection on 
prior treatment for LTBI
1. New safety guideline
2. Redundant with new monitoring language
3. Clarification and alignment with other studies 
in program
Appendices
Appendix 2.  Clinical Laboratory Tests
1. Added “Gamma-glutamyl transferase (GGT)”
to list of clinical chemistry
1. Regulatory request from FDA
 
CCI
C
C
I
C
C
I

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Section # and Name
Description of Change
Brief Rationale
Appendix 4. Examples of Infections That May Be
Considered Opportunistic in the Setting of Biologic
Therapy
Removed statement that patients with any history of 
active TB are excluded from the study
Error in original protocol

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Revised Protocol Sections
Note:
Deletions have been identified by strikethroughs.
Additions have been identified by the use of underscore.
Section 1.  Synopsis
Objective(s)/Endpoints:
Objectives
Endpoints
Major Secondarya,b
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to patient-reported 
outcomes
At Week 16:

Proportion of patients with a PSS symptoms score of 0 
(free of itch, pain, stinging, and burning) in those with 
a PSS symptoms score 1 at baseline.

Proportion of patients achieving a DLQI total score of 
(0,1) with at least a 5-point improvement (reduction) 
from baseline in those patients with a baseline DLQI
baseline total score 5>1
Other Secondaryb
To compare mirikizumab to placebo with respect to 
clinical response and time to clinical response during 
the induction dosing period, and with respect to 
patient-reported outcomes during the induction 
dosing period
At Week 16 and various time points over the first 16 weeks 
of dosing:

Proportion of patients achieving PASI 90.

Percent cChange in PPASI total score in patients 
with palmoplantar involvement at baseline

Percent cChange in PSSI total score in patients with 
scalp involvement at baseline

Percent cChange in NAPSI total score in patients 
with fingernail involvement at baseline 

Change from baseline on the SF-36 physical 
component summary (PCS) and mental component 
summary (MCS) 

Change from baseline on PatGA of disease severity

Change from baseline for the WPAI-PSO scores 
(Absenteeism, Presenteeism, Work Productivity 
Loss, and Activity Impairment)

Change from baseline in QIDS-SR16 total score in 
those with a baseline QIDS-SR16 total score 11

Proportion of patients achieving a DLQI total score 
of (0,1) with at least a 5-point improvement 
(reduction) from baseline in patients with a baseline 
DLQI total score 5

Proportion of patients achieving DLQI (0,1) with 
DLQI baseline score >1
Abbreviations:  BSA = body surface area; DLQI = Dermatology Life Quality Index; MCS = mental component 
summary; NAPSI = Nail Psoriasis Severity Index; PASI = Psoriasis Area and Severity Index; 
PASI 75/90/100 = 75%/90%/100% improvement in PASI from baseline; PatGA = Patient’s Global 
Assessment of Psoriasis; PCS = physical component summary; PPASI = Palmoplantar Psoriasis Severity Index; 
PSS = Psoriasis Symptoms Scale; PSSI = Psoriasis Scalp Severity Index; Q8W = every 8 weeks; QIDS-SR16 = 

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16-item Quick Inventory of Depressive Symptomatology; SF-36 = Medical Outcomes Study 36-Item Short Form 
Health Survey; sPGA = static Physician’s Global Assessment; WPAI-PSO = Work Productivity Activity 
Impairment Questionnaire–psoriasis.
a
All primary and major secondary endpoint analyses will utilize the multiplicity control technique called 
“graphical multiple testing procedure” to control the overall family-wise Type I error rate.
b
Note:  A “clinically meaningful” response is a PASI 75 response, which represents at least a 75% decrease 
(improvement) from the baseline PASI score. A “high level” of clinical response is a PASI 90 response, which 
represents at least a 90% decrease (improvement) from baseline in PASI score, or sPGA (0,1) response, which 
represents an “almost clear” response.  The “highest level” of clinical response is a PASI 100 or sPGA (0) 
response, which represents complete resolution of psoriasis.
Section 2.  Schedule of Activities (overleaf)

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Table AMAK.1.
Schedule of Activities
Procedurea
Screening
Period
Baseline
Induction Period
Maintenance Period
ETVs
Follow-up
Periodt
Visit Number
V
1b
V
2
V
3
V
4
V
5
V
6
V
7
V
8
V
9
V
10
V
11
V
12
V
13
V
14
V
15
V
16
V
801
V
802
Week 
-4
0
2
4
8
12
16
20
24
28
32
36
40
44
48
52
LV 
+4W
LV
+12W
Day with Visit 
Tolerance 
Interval
≤28 days 
from V2
1
15
± 3
29
± 3
57
± 5
85
± 5
113
± 5
141
± 5
169
± 5
197
± 5
225
± 5
253
± 5
281
± 5
309
± 5
337
± 5
365
± 5
29
± 5
11285
± 5
Vital Signs 
(BP, temp, and 
Ppulse)d
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Abbreviations:  BP = blood pressure; BSA = body surface area; conc = concentration; C-SSRS = Columbia–Suicide Severity Rating Scale; DLQI = Dermatology 
Life Quality Index; DNA = deoxyribonucleic acid; ECG = electrocardiogram; EQ-5D-5L-PSO = European Quality of Life–5 Dimensions–5 Levels–Psoriasis; 
ETV = early termination visit; FSH = follicle stimulating hormone; HBcAb = anti-hepatitis B core antibody; HBsAb = hepatitis B surface antibody; HBsAg = 
hepatitis B surface antigen; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus; hsCRP = high-sensitivity C-reactive 
protein; IL-19 = interleukin-19; IP = investigational product; LV = last study visit; miri = mirikizumab; NAPSI = Nail Psoriasis Severity Index; PASI = 
Psoriasis Area and Severity Index; PatGA = Patient’s Global Assessment of Psoriasis; PK = pharmacokinetic; PPASI = Palmoplantar Psoriasis Severity 
Index; PPD = purified protein derivative (skin test); PSS = Psoriasis Symptoms Scale; PSSI = Psoriasis Scalp Severity Index; QIDS-SR16 = 16-item Quick 
Inventory of Depressive Symptomatology; RNA = ribonucleic acid; SF-36 = Medical Outcomes Study 36-Item Short Form Health Survey; sPGA = static 
Physician’s Global Assessment; Suppl. = supplement; TB = tuberculosis; temp = temperature; TSQM = Treatment Satisfaction Questionnaire for Medication; 
V = visit; W = weeks; WCBP = women of childbearing potential; WPAI-PSO = Work Productivity and Activity Impairment Questionnaire: Psoriasis.
a
All activities should be completed prior to any study dose administration, unless otherwise stated.
b
Visit 1 procedures may be conducted over more than 1 day, as long as all tasks are completed within the allowable visit tolerance (at least 3 days should be 
allowed for receipt of laboratory test results).
c
One complete physical examination (excluding pelvic or rectal examinations) to include heart, lungs, peripheral lymph nodes, and abdomen, and visual 
examination of all skin areas (including genitalia and breast areas) will be performed at screening.  All physical examinations throughout the study should 
include a symptom-directed evaluation as well as examination of heart, lungs, peripheral lymph nodes, and abdomen, and visual examination of all skin areas 
(including genitalia and breast areas).
d
Sitting blood pressure, temperature, and pulse will be obtained within approximately the same time frame as ECG measurements or blood sampling.  When 
multiple assessments are scheduled for the same time point, the preferred order of completion should be as follows:  ECG (if applicable), vital signs, and then 
blood sampling.
e
Chest radiography will be performed locally at screening unless it has been performed within 3 months before initial screening (provided the radiographs 
and/or formal report are available for the investigator’s review).  For additional details, see Section 9.4.5.3.

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f
TB testing will be performed at screening unless it has been performed within 3 months before initial screening (provided the formal report is available for the 
investigator’s review).  It may also be performed after screening if clinically indicated.  TB testing will be performed locally using an interferon-release 
assay (IGRA; QuantiFERON®-TB Gold or T-SPOT.TB®) or a purified protein derivative (PPD) tuberculin skin test.  If PPD test is performed, patients will 
return 2 to 3 days afterwards Visit 1 to have their PPD test read.  For additional details on TB testing, see Exclusion Criterion [19] and Section 9.4.5.2.
g
The preferred order of completion is sSupine ECGs should preferably be completed prior to vital signs, blood sampling, or any other study procedures. For 
additional details on ECG collection, see Section 9.4.1. ECG should be performed at the ETV and Visit 802 only if there is early termination due to a 
cardiovascular event.
h
A Self-Harm Follow-Up Form is to be completed only during visits for which there is at least 1 discrete self-harm event identified on the Self-Harm 
Supplement Form (see Section 9.2.2).
i
PSSI, NAPSI, and PPASI assessments are applicable only if symptoms are present at baseline.
j
These assessments should be completed before administration of investigational product, before the patient’s clinical examination, before the patient receives 
any tests or results, and before the patient’s health, health data, or emotions are discussed.
k
Electronic diaries will be distributed at the screening visit and collected at the Week 16 visit.
l
Unscheduled hematology or blood chemistry panels may be performed at the discretion of the investigator.
m Patients should not eat or drink anything except water for 12 hours prior to sample collection.
n
Any enrolled patient who is HBcAb+ will undergo monitoring of HBV DNA with HBV DNA testing (see Section 9.4.5.4).  Any patient with a positive HBV 
DNA test at any time must be discontinued from the study and receive appropriate follow-up medical care, including consideration for antiviral therapy. 
o
Following screening, patients will not undergo monitoring for HCV RNA unless liver enzymes are elevated (see Section 9.4.5.5).  Any patient with a positive 
HCV RNA test must be discontinued from the study and receive appropriate follow-up medical care, including consideration for antiviral therapy.
p
Immunogenicity samples should be collected prior to dosing on visits when mirikizumab is administered.  A sample will be obtained at unscheduled visits if a 
patient develops an acute hypersensitivity event after administration of IP (see Section 7.8.2.1).
q
Scheduled PK samples are taken as an aliquot from the immunogenicity sample.  Unscheduled PK samples, obtained if a patient develops an acute 
hypersensitivity event after administration of IP (see Section 7.8.2.1), will be collected in a separate tube.
r
FSH test is to be performed at screening for women who have had spontaneous amenorrhea for 6 to 12 months to confirm lack of childbearing potential.
s
If a patient discontinues IP early, the patient will complete the ETV and then enter the Post-Treatment Follow-up Period (V801 + V802).
t
All patients who receive IP but do not participate in Study AMAH must enter the Follow-up Period and complete V801 + V802.
u
Urinalysis assessed only for early termination due to an adverse event for which urinalysis is clinically indicated.

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Section 4.  Objectives and Endpoints
Table AMAK.2.
Objectives and Endpoints
Objectives
Endpoints
Major Secondarya,b
To assess whether mirikizumab induction dosing is 
superior to placebo with respect to patient-reported 
outcomes
At Week 16:

Proportion of patients with a PSS symptoms score of 0 
(free of itch, pain, stinging, and burning) in those with 
a PSS symptoms score 1 at baseline.

Proportion of patients achieving a DLQI total score of 
(0,1) with at least a 5-point improvement (reduction) 
from baseline in those patients with a baseline DLQI
baseline total score 5>1
Other Secondaryb
To compare mirikizumab to placebo with respect to 
clinical response and time to clinical response during 
the induction dosing period, and with respect to 
patient-reported outcomes during the induction 
dosing period
At Week 16 and various time points over the first 16 weeks 
of dosing:

Proportion of patients achieving PASI 90.

Percent cChange in PPASI total score in patients 
with palmoplantar involvement at baseline

Percent cChange in PSSI total score in patients with 
scalp involvement at baseline

Percent cChange in NAPSI total score in patients 
with fingernail involvement at baseline 

Change from baseline on the SF-36 physical 
component summary (PCS) and mental component 
summary (MCS) 

Change from baseline on PatGA of disease severity

Change from baseline for the WPAI-PSO scores 
(Absenteeism, Presenteeism, Work Productivity 
Loss, and Activity Impairment)

Change from baseline in QIDS-SR16 total score in 
those with a baseline QIDS-SR16 total score 11

Proportion of patients achieving a DLQI total score 
of (0,1) with at least a 5-point improvement 
(reduction) from baseline in patients with a baseline 
DLQI total score 5

Proportion of patients achieving DLQI (0,1) with 
DLQI baseline score >1
Abbreviations: BSA = body surface area; DLQI = Dermatology Life Quality Index; MCS = mental component 
summary; NAPSI = Nail Psoriasis Severity Index; PASI = Psoriasis Area and Severity Index; 
PASI 75/90/100 = 75%/90%/100% improvement in PASI from baseline; PatGA = Patient’s Global 
Assessment of Psoriasis; PCS = physical component summary; PPASI = Palmoplantar Psoriasis Severity Index; 
PSS = Psoriasis Symptoms Scale; PSSI = Psoriasis Scalp Severity Index; Q8W = every 8 weeks; QIDS-SR16 = 
16-item Quick Inventory of Depressive Symptomatology; SF-36 = Medical Outcomes Study 36-Item Short Form 
Health Survey; sPGA = static Physician’s Global Assessment; TE-ADA = treatment-emergent anti-drug 
antibody; TEAEs = treatment-emergent adverse events; WPAI-PSO = Work Productivity Activity Impairment 
Questionnaire–psoriasis.
a
All primary and major secondary endpoint analyses will utilize the multiplicity control technique called 
“graphical multiple testing procedure” to control the overall family-wise Type I error rate.

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b
Note:  A “clinically meaningful” response is a PASI 75 response, which represents at least a 75% decrease 
(improvement) from the baseline PASI score. A “high level” of clinical response is a PASI 90 response, which 
represents at least a 90% decrease (improvement) from baseline in PASI score, or sPGA (0,1) response, which 
represents an “almost clear” response.  The “highest level” of clinical response is a PASI 100 or sPGA (0) 
response, which represents complete resolution of psoriasis.
Section 5.1.4.  Post-Treatment Follow-up Period (12 Weeks)
Patients who do not enroll into Study AMAH or who discontinue early from study treatment in 
Study AMAK will complete the Post-Treatment Follow-Up Period (V801 and V802) of 
Study AMAK.
For patients who have entered the Post-Treatment Follow-Up Period, psoriasis therapy with 
another agent(s), as determined appropriate by the investigator, is allowed.
Section 6.1.  Inclusion Criteria
Patient Characteristics
[3b] Female patients:
Women of childbearing potential:
A. Must test negative for pregnancy prior to initiation of treatment as 
indicated by a negative serum pregnancy test at the screening visit 
followed by a negative urine pregnancy test within 24 hours prior to 
exposure.
B. Must agree to either remain abstinent, if complete abstinence is their 
preferred and usual lifestyle, or remain in same-sex relationships, if part 
of their preferred and usual lifestyle, without sexual relationships with 
males.  Periodic abstinence (for example, calendar, ovulation, 
symptothermal, post-ovulation methods), declaration of abstinence just 
for the duration of a trial, and withdrawal are not acceptable methods of 
contraception.
OR
Must use 2 effective methods of contraception for the entirety of the 
study. Abstinence or contraception must continue for 12 weeks 
following completion of investigational product administration.

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i.
Two effective methods of contraception (such as male or female 
condoms with spermicide, diaphragms with spermicide or cervical 
sponges) will be used. The patient may choose to use a double-
barrier method of contraception. Barrier protection methods 
without concomitant use of a spermicide are not a reliable or 
acceptable method. 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.
ii.
Of note, one of the two methods of contraception may be a highly 
effective (less than 1% failure rate) method of contraception (such 
as combination oral contraceptives, implanted contraceptives or 
intrauterine devices).
When local guidelines concerning highly effective or effective methods of birth 
control differ from the above, the local guidelines must be followed.
[5]
Have adequate organ function, including:
A. Hematologyic: 
Section 6.2.  Exclusion Criteria
Prior/Concomitant Therapy
[24] Have received systemic nonbiologic therapy (including, but not limited to, 
oral psoralen and ultraviolet A [PUVA] light therapy; cyclosporine; 
corticosteroids; methotrexate; oral retinoids; apremilast; tofacitinib; 
mycophenolate mofetil; thioguanine; hydroxyurea; sirolimus; tacrolimus; 
azathioprine; leflunomidelefludimide; fumaric acid derivatives; or 
1,25-dihydroxyvitamin D3 and analogues) or phototherapy (including either 
oral and topical PUVA light therapy, ultraviolet B, excimer laser, or self-
treatment with tanning beds or therapeutic sunbathing) within 28 days prior to 
baseline.

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Section 7.7.  Concomitant Therapy
Table AMAK.4.
Excluded Classes of Concomitant Medications or Classes with 
Restricted Use
Drug Class
Allowed for 
Chronic Use
Allowed with 
Restrictions
Conditions for Allowed Use
Biological immunomodulating agents
(for example, alefacept, briakinumab, 
efalizumab, ixekizumab, secukinumab, 
etanercept, adalimumab, infliximab, 
certolizumabamb)
N
N
Systemic immunomodulating treatments 
(corticosteroids only)
N
Y
Limited use of systemtic corticosteroids 
ONLY as needed for limited, short-term 
medical management of TEAE may be 
considered.  Such drug class might be 
considered psoriasis therapy if used 
under other regimens.  Limited use 
during TEAE management is considered 
to not be consistent with psoriasis 
therapy.
Bacillus Calmette-Guerin (BCG) 
vaccinations or live virus vaccinations 
(BCG prohibited for 12 months before 
baseline, live vaccinations prohibited for 
12 weeks before baseline.  Both are 
prohibited throughout the study and for 
12 months or 12 weeks, respectively,
after discontinuation of study drug).
N
N
Any investigational treatment
N
N
Abbreviations:  MTX = methotrexate; N = No; PUVA = psoralen and ultraviolet A; TEAE = treatment-emergent 
adverse event; UVA = ultraviolet A; UVB = ultraviolet B;  Y = Yes.
Topical therapies allowed during the study include shampoos that do not contain >3% salicylic 
acid, corticosteroids, coal tar, or vitamin D3 analogues; topical moisturizers/emollients and other 
non-prescription topical products that do not contain urea, >3% salicylic acid, alpha- or 
beta-hydroxyl acids, corticosteroids, or vitamin D3 analogues; and bath oils and oatmeal bath 
preparations.  These topical therapies are not to be used within 12 hours prior to a study visit.  
For patients who have entered the Post-Treatment Follow-Up Period, psoriasis therapy with 
another agent(s), as determined appropriate by the investigator, is allowed.
Section 7.8.2.1.  Management of Hypersensitivity Events, Including Injection Site Events
All biological agents carry the risk of systemic allergic/hypersensitivity events.  Clinical 
manifestations of these events may include, but are not limited to the following:

Skin rash

Pruritus (itching)

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
Urticaria (hives)

Angioedema (for example, swelling of the lips and/or tongue) 

Anaphylactic events.
Sometimes, these events can be life threatening.  Proteins may also cause redness, itching, 
swelling, or pain locally at the injection site.  Therefore, all patients should be closely monitored 
for signs or symptoms that could result from such events, educated on the signs or symptoms of 
these types of events, and instructed to contact the study site immediately if any of the symptoms 
are experienced following an injection. If a patient experiences an acute hypersensitivity event
after an injection of investigational product, he or she should be managed appropriately and 
given instructions to receive relevant supportive care.  
Additionally, for an event judged by the investigator to be a potential systemic hypersensitivity 
event, blood samples will be collected for PK, immunogenicity, and exploratory hypersensitivity 
analyses at, or as close as possible to:
1. the onset of the event
2. the resolution of the event, and
3. 30 (±3) days following the event.
Exploratory hypersensitivity samples may, as appropriate for the clinical presentation,

be analyzed for tryptase (a marker of basophil/mast cell activation),

have a complement panel performed (asses immune complex formation), and

have a cytokine panel performed.
a blood sample should be drawn to test for anti-drug antibodies (ADAs; sSee also Section 9.4.4).
Patients who develop clinically significant systemic hypersensitivity events following 
administration of investigational product, who do not respond to symptomatic medication or 
whose event results in clinical sequelae (for example, hospitalization), should be discontinued 
from the study and not receive further doses of investigational product, with or without 
premedication (see Section 8.2).
Section 8.2.  Discontinuation from the Study

In addition, patients who meet any one of the following criteria should be 
discontinued from the investigational product, enter the Post-Treatment 
Follow-Up Period, and discontinue from the study:

Clinically significant systemic hypersensitivity event following 
administration of investigational product that does not respond to 
symptomatic medication or results in clinical sequelae.

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Section 9.2.3.  Adverse Events of Special Interest
Adverse events of special interest (AESIs) are AEs which the Sponsor specifies as being of 
special interest based on standard drug registration topics, safety findings from previous studies 
in development program, potential risks associated with biologic immunomodulators as noted in 
product labels and published literature, and comorbidities and risk factors prevalent in the 
studied populations.  The AESIs for this study are defined in the statistical analysis plan (SAP), 
and may include, but not be limited to the following:

Infections, including Oopportunistic infections

Hypersensitivity events, including anaphylaxis

Injection site events

Cerebro-cardiovascular events

Malignancies

Depression, or suicidal ideation and or behaviors

Hepatic AEs.
For some AESIs, sites should provide additional information regarding the event, as instructed 
on the eCRF.
Infections, Including Opportunistic Infections
Drugs that modulate the immune system may increase the risk of infection, including serious or 
opportunistic infections.
Infections will be categorized by Lilly as opportunistic according to Opportunistic Infections and 
Biologic Therapies in Immune-Mediated Inflammatory Diseases: Consensus Recommendations 
for Infection Reporting during Clinical Trials and Postmarketing Surveillance by Winthrop et al. 
(2015).  Examples are listed in Appendix 4.
Hypersensitivity Events 
Site personnel should educate patients and/or caregivers about the symptoms and signs of 
hypersensitivity events and provide instructions on dealing with these events.  A blood sample 
will be collected when possible for any patient who experiences an AE of hypersensitivity events 
during the study.
Section 9.4.1.  Electrocardiograms
For each patient, ECGs should be collected according to the Schedule of Activities (Section 2).  
Electrocardiograms should be recorded according to the study-specific recommendations and 
read locally for evaluation of study eligibility and safety monitoring. 
Patients should be supine for approximately 5 to 10 minutes before ECG collection, and remain 
supine but awake during ECG collection.  Sitting BP, temperature, and pulse (see Section 9.4.2)
should be obtained at approximately the same time as ECG measurements or blood sampling.  

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When multiple assessments are scheduled for the same time point, the preferred order of 
completion should be as follows:  ECG, vital signs, and then blood sampling.
Any clinically significant findings from ECGs that result in a diagnosis and that occur after the 
patient receives the first dose of the investigational product should be reported to Lilly or its 
designee as an AE via eCRF.
Section 9.4.2.  Vital Signs
For eachpatient,vital signs measurements should be conducted according to the Schedule of 
Activities (Section 2).
Sitting vital signs (BP, temperature,and pulse) will be measured after resting for a minimum of 
10 minutesat times indicated in the Schedule of Activities (Section 2),and prior to blood 
sampling or administration of the investigational product. 
Any clinically significant findings from vital signs measurement that result in a diagnosis and 
that occur after the patient receives the first dose of investigational product should be reported to 
Lilly or its designee as an AE via eCRF.
Section 9.4.4.  Immunogenicity Assessments
At the visits and times specified in the Schedule of Activities (Section 2), venous bloodsamples 
will be collected to determine antibody production against mirikizumab.  To interpret the results 
of immunogenicity, abloodsample for PK analysiswillbe collected at the same time points.All 
samples for immunogenicity should be taken predose when applicable. With reports of
hypersensitivityevents(immediate or non-immediate), additional samples will be collectedas 
close to the onset of the eventas possible, at the resolution of the event, and 30days following 
resolution of the event.  Samples will be evaluated for PK, anti-drug antibodies (ADAs),   
CCI
  Instructions for the 
collection and handling of blood sampleswill be provided by the Sponsor.  The actual date and 
time (24-hour clock time) of each sampling will be recorded.
Immunogenicity will be assessed by a validated assay designed to detect ADAs in the presence 
of mirikizumabat a laboratory approved by the Sponsor. Patient samples will beanalyzed using 
a 4-tiered approach.  All samples will beassessed in Tier 1 (screening).  Samples above the 
disease state screening assay cut point factor (Tier 1) will beassessed in Tier 2 (confirmation).  
Any samples confirmed as positive for anti-mirikizumabantibodies in Tier2 will be reported as 
“detected.”  All samples below the screening assay cut point factor in Tier1 or not confirmed in 
Tier 2 will bereported as “not detected.”  Any “detected” sample in Tier2 will beassessed in 
Tier 3 (titer assessment; values reported) and Tier 4 (neutralizing ADA assay).  Any samples 
above the disease state Tier 4 cut point will bereported as “detected”for neutralizing antibodies; 
samples below the disease state Tier 4 cut point will bereported as “not detected”for 
neutralizing antibodies.

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Samples will be retained at a facility selected by the Sponsor for a maximum of 15 years after the 
last patient visit, or for a shorter period if local regulations and/or Ethical Review Boards (ERBs) 
requireallow, 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.
Section 9.4.5.1.  Physical Examination
Physical examination will be performed as specified in the Schedule of Activities (Section 2).  
One complete physical examination (excluding pelvic or rectal examinations), which includes
heart, lungs, peripheral lymph nodes, and abdomen, and visual examination of all skin areas 
(including genitalia and breast areas), will be performed at screening. All physical examinations 
throughout the study should include a symptom-directed evaluation, as well as examination of 
heart, lungs, peripheral lymph nodes, and abdomen, and visual examination of all skin areas 
(including genitalia and breast areas).
Section 9.4.5.2.  Tuberculosis Screening
Initial Screening:
Screening for active or latent TB (LTBI) will include a history, physical examination 
(Section 9.4.5.1), chest x-ray (Section 9.4.5.3), and, except as noted below under “Prior 
Treatment for LTBI or TB,” testing by an interferon-release assay (IGRA; QuantiFERON®-TB 
Gold or T-SPOT.TB®) or a purified protein derivative (PPD) tuberculin skin test.
In people aged 5 years and over, IGRA is the preferred screening test for LTBI.  In countries 
where the PPD is available and is preferred (in the judgment of the investigator) as an alternative 
screening test for LTBI, that test may be used instead of an IGRA.
Patients with documentation of a negative IGRA or PPD within 3 months before initial screening 
may not need to repeat TB testing at screening, based on the judgment of the investigator.  
Source documentation must include the original laboratory report (for IGRA) or a record of the 
size in millimeters of the induration response (for PPD).  A PPD recorded as negative without 
documenting the size of induration in millimeters, will not be acceptable and will require a retest.
Monitoring:
After initial screening, tuberculosis testing will only be required based on clinical assessment of 
TB risk (symptoms/signs/known or suspected TB exposure), and according to local regulations 
and/or local standard of care.  Such clinical assessments should be conducted periodically, at 
least every 4 months.

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Interpretation of Screening Tests for LTBI
The QuantiFERON-TB Gold assay will be reported as negative, indeterminate, or positive.  The 
T-SPOT.TB assay will be reported as negative, borderline, or positive.
A positive PPD is indicated with a skin test response 5 mm of induration, documented between 
approximately 48 and 72 hours after test application (regardless of BCG vaccination history).  
Patients who do not return within 48 to 72 hours of test administration will be required to have 
the test repeated and then interpreted within this time frame.
Patients with a diagnosis of LTBI, based on a positive IGRA test result or a positive PPD 
response 5 mm of induration and no evidence of active TB, may be rescreened once if after 
they meet the following requirements:

Have received at least 4 weeks of appropriate ongoing prophylactic therapy for LTBI as 
per local standard of care, and

Have no evidence of treatment hepatotoxicity (ALT and AST levels must remain 
≤2x ULN) upon retesting of serum ALT and AST levels before randomization.)
Such patients must continue and complete appropriate LTBI therapy during the course of the 
study to remain eligible and must continue to meet all other inclusion and exclusion criteria for 
participation.  Follow-up TB testing with IGRA or PPD, tailored in accordance with a person’s 
risk (for example, hospital care worker, residence in a high risk location), may be performed 
according to local guidelines.
Prior Treatment for LTBI or TB
Patients who have a documented history of completing an appropriate TB prophylaxis or 
treatment regimen (consistent with World Health Organization and/or United States Centers for 
Disease Control at the time of treatment), with no history of re-exposure since their treatments 
were completed and no evidence of active TB, are eligible to participate in the study; these 
patients should not undergo TB testing unless advised to do so based on local guidelines.  
Section 9.4.5.5.  Hepatitis C Screening
Patients who test positive for HCV antibody and have a positive confirmatory HCV RNA test at 
screening will be excluded.
Patients with a previous diagnosis of hepatitis C who have been treated with antiviral therapy 
and achieved a sustained anti-virologic response may be eligible for inclusion in the study, 
provided they have no detectable RNA on the screening HCV RNA test for this protocol.  A 
sustained virologic response is defined as an undetectable HCV RNA level, 12 weeks after 
completion of a full, documented course of an approved antiviral therapy for HCV.
Patients who have spontaneously cleared HCV infection, defined as (i) a positive HCV antibody 
test and (ii) a negative HCV RNA test, with no history of anti-HCV treatment, may be eligible 

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for inclusion in the study, provided they have no detectable HCV RNA on screening for this 
study and no detectable HCV RNA on the screening HCV RNA test for this protocol.
Appendix 2.  Clinical Laboratory Tests
Clinical Laboratory Tests
Clinical (Serum) Chemistrya
Other
Serum Concentrations of:
Gamma-glutamyl transferase (GGT)
PPD or QuantiFERON-TB Gold test or T-
SPOT.TB testb,d
Tryptasea
Complement panel (C3 and C4)a
Cytokine panela
Abbreviations:  DNA = deoxyribonucleic acid; HBV = hepatitis B virus; HCV = hepatitis C virus; 
PK = pharmacokinetic(s); PPD = purified protein derivative (skin test); RBC = red blood cells; 
RNA = ribonucleic acid; TB = tuberculosis; WBC = white blood cells.
a
Unscheduled hematology or blood chemistry panels may be performed at the discretion of the investigator.  An 
immunogenicity sample may be obtained at unscheduled visits iIf a patient develops an acute hypersensitivity 
event after administration of IP, blood samples will be collected for pharmacokinetic, immunogenicity, and 
exploratory hypersensitivity analyses.
b
Performed at screening only.
c
Following screening, patients will not undergo monitoring for Hepatitis C unless liver enzymes are elevated.  
Hepatitis B monitoring will be performed at protocol-specified intervals in patients who test positive for 
anti-hepatitis B core antibody.
d
TB testing may will be performed locally using an interferon-release assay (IGRA, for example
QuantiFERON®-TB Gold or T-SPOT.TB) or a PPD tuberculin skin test.  If PPD test is performed, patients will 
return 2 to 3 days afterwards Visit 1 to have their PPD test read.
Appendix 4.  Examples of Infections That May Be Considered Opportunistic in the Setting 
of Biologic Therapy
Winthrop et al. (2015) consider tuberculosis (TB) and non-TB mycobacterial disease to be opportunistic infections 
in the context of biologic therapy.  See Section 9.4.5.2 for the approach to screening for latent TB infection
within the study.  Patients with any history of active TB are excluded from the study, regardless of previous or 
current TB treatments.

PPD
Leo Document ID = af579d13-7262-4f43-94a7-afa8ea6c690f
Approver: 
Approval Date & Time: 12-Dec-2018 00:50:00 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 12-Dec-2018 15:44:57 GMT
Signature meaning: Approved
PPD