A Multicenter, Long-Term Extension to Evaluate the Long-term Safety and Maintenance of Treatment Effect of LY3074828 in Patients With Moderate-to-Severe Plaque Psoriasis OASIS-3
Phase: PHASE3
Conditions: Psoriasis
Sponsor: Eli Lilly and Company

Protocol I6T-MC-AMAH(a) 
 
 
A Multicenter, Long-Term Extension to Evaluate the Long-Term Safety and Maintenance of 
Treatment Effect of Mirikizumab in Patients with Moderate-to-Severe Plaque Psoriasis 
(OASIS-3) 
 
NCT03556202  
 
Approval Date: 15-Nov-2018 
 
 

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Protocol I6T-MC-AMAH(a)
A Multicenter, Long-Term Extension to Evaluate the 
Long-Term Safety and Maintenance of Treatment Effect of 
Mirikizumab in Patients with Moderate-to-Severe 
Plaque Psoriasis
OASIS-3
EUDRA: 2017-003299-30
Confidential Information
The information contained in this document is confidential and is intended for the use of 
clinical investigators.  It is the property of Eli Lilly and Company or its subsidiaries and 
should not be copied by or distributed to persons not involved in the clinical investigation of 
mirikizumab (LY3074828), unless such persons are bound by a confidentiality agreement 
with Eli Lilly and Company or its subsidiaries.  
Note to Regulatory Authorities:  This document may contain protected personal data 
and/or commercially confidential information exempt from public disclosure. Eli Lilly and 
Company requests consultation regarding release/redaction prior to any public release. In 
the United States, this document is subject to Freedom of Information Act (FOIA) 
Exemption 4 and may not be reproduced or otherwise disseminated without the written 
approval of Eli Lilly and Company or its subsidiaries.
Mirikizumab (LY3074828)
Eli Lilly and Company
Indianapolis, Indiana USA 46285
Protocol Electronically Signed and Approved by Lilly:  30 March 2018.
Amendment (a) Electronically Signed and Approved by Lilly on approval 
date provided below.
Approval Date: 15-Nov-2018 GMT

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Table of Contents
Section
Page
Protocol I6T-MC-AMAH(a) A Multicenter, Long-Term Extension to 
Evaluate the Long-Term Safety and Maintenance of Treatment Effect 
of Mirikizumab in Patients with Moderate-to-Severe Plaque Psoriasis  
OASIS-3.............................................................................................................................1
Table of Contents........................................................................................................................2
1.
Synopsis .............................................................................................................................9
2.
Schedule of Activities .......................................................................................................13
3.
Introduction ......................................................................................................................20
3.1.
Study Rationale............................................................................................................20
3.2.
Background..................................................................................................................20
3.3.
Benefit/Risk Assessment..............................................................................................21
4.
Objectives and Endpoints..................................................................................................23
5.
Study Design.....................................................................................................................25
5.1.
Overall Design .............................................................................................................25
5.1.1.
Qualifying Period.................................................................................................25
5.1.2.
Treatment Period..................................................................................................25
5.1.3.
Post-Treatment Follow-Up Period (12 Weeks) .....................................................26
5.2.
Number of Participants.................................................................................................27
5.3.
End of Study Definition ...............................................................................................27
5.4.
Scientific Rationale for Study Design...........................................................................27
5.5.
Justification for Dose ...................................................................................................28
6.
Study Population...............................................................................................................30
6.1.
Inclusion Criteria..........................................................................................................30
6.2.
Exclusion Criteria ........................................................................................................32
6.2.1.
Rationale for Exclusion of Certain Study Candidates ...........................................33
6.3.
Lifestyle Restrictions....................................................................................................33
6.4.
Screen Failures.............................................................................................................33
7.
Treatments........................................................................................................................34
7.1.
Treatments Administered .............................................................................................34
7.1.1.
Packaging and Labeling .......................................................................................35
7.2.
Method of Treatment Assignment ................................................................................36
7.2.1.
Selection and Timing of Doses.............................................................................36
7.3.
Blinding .......................................................................................................................36
7.4.
Dosage Modification....................................................................................................37

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7.5.
Preparation/Handling/Storage/Accountability...............................................................37
7.6.
Treatment Compliance .................................................................................................38
7.7.
Concomitant Therapy...................................................................................................38
7.8.
Treatment after the End of the Study............................................................................40
7.8.1.
Treatment after Study Completion........................................................................40
7.8.2.
Special Treatment Considerations ........................................................................41
7.8.2.1.
Management of Hypersensitivity Events, Including 
Injection Site Events.......................................................................................41
8.
Discontinuation Criteria ....................................................................................................42
8.1.
Discontinuation from Study Treatment.........................................................................42
8.1.1.
Permanent Discontinuation from Study Treatment ...............................................42
8.1.2.
Temporary Interruption (Withholding) of Study Treatment ..................................42
8.1.3.
Discontinuation of Inadvertently Enrolled Patients...............................................43
8.2.
Discontinuation from the Study....................................................................................43
8.3.
Lost to Follow-Up........................................................................................................45
9.
Study Assessments and Procedures ...................................................................................46
9.1.
Efficacy Assessments...................................................................................................46
9.1.1.
Primary Efficacy Assessments .............................................................................46
9.1.1.1.
Static Physician’s Global Assessment.............................................................46
9.1.1.2.
Psoriasis Area and Severity Index...................................................................46
9.1.2.
Secondary Efficacy Assessments..........................................................................46
9.1.2.1.
Static Physician’s Global Assessment.............................................................46
9.1.2.2.
Psoriasis Area and Severity Index...................................................................47
9.1.2.3.
Body Surface Area .........................................................................................47
9.1.2.4.
Nail Psoriasis Severity Index ..........................................................................47
9.1.2.5.
Psoriasis Scalp Severity Index ........................................................................47
9.1.2.6.
Palmoplantar Psoriasis Severity Index ............................................................47
9.1.2.7.
Health Outcomes Assessments........................................................................47
9.1.2.7.1.
Dermatology Life Quality Index ...............................................................48
9.1.2.7.2.
Psoriasis Symptoms Scale.........................................................................48
9.1.2.7.3.
16-Item Quick Inventory of Depressive 
Symptomatology-Self Report....................................................................48
9.1.3.
Appropriateness of Assessments ..........................................................................49
9.2.
Adverse Events ............................................................................................................49
9.2.1.
Serious Adverse Events........................................................................................50
9.2.1.1.
Suspected Unexpected Serious Adverse Reactions..........................................51
9.2.2.
Adverse Event Monitoring with a Systematic Questionnaire ................................51
9.2.3.
Adverse Events of Special Interest .......................................................................52

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9.2.4.
Complaint Handling.............................................................................................53
9.3.
Treatment of Overdose.................................................................................................53
9.4.
Safety...........................................................................................................................53
9.4.1.
Electrocardiograms ..............................................................................................53
9.4.2.
Vital Signs ...........................................................................................................54
9.4.2.1.
Hypertension ..................................................................................................54
9.4.3.
Laboratory Tests ..................................................................................................54
9.4.3.1.
Pregnancy Testing ..........................................................................................54
9.4.4.
Immunogenicity Assessments ..............................................................................55
9.4.5.
Other Tests...........................................................................................................55
9.4.5.1.
Physical Examination .....................................................................................55
9.4.5.2.
Tuberculosis...................................................................................................56
9.4.5.3.
Hepatitis B Monitoring...................................................................................56
9.4.5.4.
Hepatitis C Monitoring...................................................................................57
9.4.6.
Safety Monitoring ................................................................................................57
9.4.6.1.
Hepatic Safety Monitoring..............................................................................57
9.5.
Pharmacokinetics .........................................................................................................58
9.6.
Pharmacodynamics ......................................................................................................58
9.7.
Pharmacogenomics OR Genetics..................................................................................58
9.7.1.
Whole Blood and/or Saliva Sample for Pharmacogenetic 
Research ..............................................................................................................58
9.8.
Biomarkers...................................................................................................................58
9.9.
Medical Resource Utilization and Health Economics ...................................................58
10.
Statistical Considerations ..................................................................................................59
10.1. Sample Size Determination ..........................................................................................59
10.2. Populations for Analyses..............................................................................................59
10.3. Statistical Analyses ......................................................................................................59
10.3.1.
General Statistical Considerations ........................................................................59
10.3.1.1.
Missing Data Imputation ................................................................................60
10.3.1.2.
Multiple Comparisons/Multiplicity.................................................................61
10.3.2.
Treatment Group Comparability...........................................................................61
10.3.2.1.
Patient Disposition..........................................................................................61
10.3.2.2.
Patient Characteristics ....................................................................................61
10.3.2.3.
Concomitant ...................................................................................................61
10.3.2.4.
Treatment Compliance....................................................................................61
10.3.3.
Efficacy Analyses ................................................................................................62
10.3.3.1.
Primary Analyses ...........................................................................................62
10.3.3.2.
Secondary Analyses........................................................................................62

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10.3.3.3.
Tertiary/Exploratory Analyses ........................................................................62
10.3.4.
Safety Analyses....................................................................................................62
10.3.5.
Pharmacokinetic/Pharmacodynamic Analyses......................................................62
10.3.6.
Evaluation of Immunogenicity .............................................................................63
10.3.7.
Other Analyses.....................................................................................................63
10.3.7.1.
Subgroup Analyses.........................................................................................63
10.3.8.
Interim Analyses..................................................................................................63
11.
References ........................................................................................................................65
12.
Appendices .......................................................................................................................69

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List of Tables
Table
Page
Table AMAH.1. Schedule of Activities....................................................................................14
Table AMAH.2. Objectives and Endpoints...............................................................................23
Table AMAH.3. Treatment Regimens......................................................................................34
Table AMAH.4. Excluded Classes of Concomitant Medications or Classes with 
Restricted Use ...............................................................................................39

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List of Figures
Figure
Page
Figure AMAH.1. Illustration of study design for Clinical Protocol I6T-MC-AMAH. ................27

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List of Appendices
Appendix
Page
Appendix 1.
Abbreviations and Definitions........................................................................70
Appendix 2.
Clinical Laboratory Tests...............................................................................75
Appendix 3.
Study Governance Considerations..................................................................77
Appendix 4.
Examples of Infections that May Be Considered Opportunistic in the 
Setting of Biologic Therapy...........................................................................82
Appendix 5.
Risk Factors for Latent Tuberculosis Infection...............................................84
Appendix 6.
Hepatic Monitoring Tests for Treatment-Emergent Abnormality....................87
Appendix 7.
Protocol Amendment I6T-MC-AMAH(a) Summary (A Multicenter, 
Long-Term Extension to Evaluate the Long-Term Safety and 
Maintenance of Treatment Effect of Mirikizumab in Patients with 
Moderate-to-Severe Plaque Psoriasis [OASIS-3])..........................................88

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1. Synopsis
Title of Study:
A Multicenter, Long-Term Extension to Evaluate the Long-Term Safety and Maintenance of 
Treatment Effect of Mirikizumab in Patients with Moderate-to-Severe Plaque Psoriasis
Rationale: 
LY3074828 (mirikizumab) is a humanized immunoglobulin G4 (IgG4)–variant monoclonal 
antibody that binds to the p19 subunit of IL-23 and does not bind IL-12. Mirikizumab is being 
developed for the treatment of immune-mediated or inflammatory diseases in which the IL-23 
pathway is thought to have a pathogenic role. Study I6T-MC-AMAH (AMAH) is a 
confirmatory study testing mirikizumab as a treatment for plaque psoriasis and is intended to 
support registration of this indication.  This Phase 3 trial is designed to contribute to the 
evaluation of the safety, and to evaluate the long-term efficacy as measured by improvement in 
disease severity and key patient-reported outcomes following long-term treatment with 
mirikizumab.
Objective(s)/Endpoints:
Objectives
Endpoints
Primary

To evaluate the long-term maintenance of 
efficacy of mirikizumab in patients with 
moderate-to-severe plaque psoriasis 
Over the duration of the study:

Proportion of patients with an sPGA (0,1) 
among those who entered Study AMAH with 
sPGA (0,1)

Proportion of patients who maintained a 
≥90% improvement in PASI (PASI 90) 
among those who entered Study AMAH with 
a PASI 90 response
Abbreviations:  PASI = Psoriasis Area and Severity Index; PASI 90 = ≥90% improvement in PASI from baseline;
sPGA = static Physician’s Global Assessment

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Summary of Study Design:
Study AMAH is a long-term study in which patients completing one of four originator studies 
(16T-MC-AMAF [AMAF], 16T-MC-AMAJ [AMAJ], 16T-MC-AMAK [AMAK], or 
16T-MC-AMBK [AMBK]) will receive mirikizumab for an extended period of time 
(approximately 4 years or until commercial availability of mirikizumab), and then enter a 
12-week Post-Treatment Follow-Up period (Figure AMAH.1).  Patients who qualify for Study 
AMAH may enter directly into the study upon the final visit of a qualifying study period of the 
originator study.  The qualifying study periods of the originator studies are as follows:

AMAJ, AMAK, AMAF: Blinded Maintenance Period

AMBK: Treatment Period
Most patients will enter Study AMAH at the last visit of a qualifying study period of the 
originator studies. All patients must enter Study AMAH within 12 weeks of their final visit in 
these periods or they will become ineligible.  Patients in the secukinumab treatment group of 
Study AMAJ will be eligible to enter Study AMAH; such patients will receive mirikizumab for 
the first time in Study AMAH.
Treatment Period:
All patients participating in Study AMAH will receive subcutaneous (SC) administration of
mirikizumab every 8 weeks (Q8W).  The dose used in Study AMAH will depend on the 
treatment that the patients were receiving during the qualifying period of the originator study.  
For all treatment groups in Study AMAH, dosing begins at Visit 1 and continues to Week 208.

Patients entering from Study AMAJ or Study AMAK who received mirikizumab
during the qualifying period will continue to receive the dose they were receiving
(either 250 mg mirikizumab Q8W SC or 125 mg mirikizumab Q8W SC).  Patients 
entering from Study AMAJ or Study AMAK who were receiving secukinumab or
placebo, respectively, during the qualifying period will receive 250 mg mirikizumab
Q8W SC.

Patients entering from Study AMBK will receive 250 mg mirikizumab Q8W SC.

Patients entering from Study AMAF whose last treatment was 300 mg mirikizumab, on 
either the fixed Q8W dosing regimen or on the as-needed (PRN) regimen, will start 
250 mg mirikizumab Q8W SC in Study AMAH.  Patients entering from Study AMAF 
whose last treatment was either 30 mg or 100 mg mirikizumab on a PRN regimen will 
start 125 mg mirikizumab Q8W SC in Study AMAH.

After Study AMAH dosing is no longer blinded, patients who in the opinion of the 
investigator have experienced significant clinically meaningful loss of efficacy during 
study participation may be increased from 125 mg mirikizumab Q8W to 250 mg 
mirikizumab Q8W if it is determined by the patient and the investigator that the patient 
might benefit from additional study drug in order to maintain satisfactory disease 

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control. All patients who increase dosing to 250 mg mirikizumab Q8W will remain on 
this dose until completion of the study or early discontinuation.
Post-Treatment Follow-up Period (12 weeks):
All patients, whether they discontinue early for any reason or else complete study treatment, will 
enter the 12-week Post-Treatment Follow-Up Period.
Number of Patients:
Approximately 1600-2000 participants are expected to enroll in Study AMAH from the 
originator studies. 
Statistical Analysis:
The sample size for Study AMAH will be determined by the number of patients who continue 
into Study AMAH from the originator studies.
The analysis will be focused on point estimates and confidence intervals.  Thus, no hypothesis 
testing will be performed, and multiple testing will not need to be accounted for.
Efficacy and safety summaries will be reported by the following 3 cohorts: 
(1) Patients assigned to 250 mg mirikizumab Q8W SC in Study AMAH, excluding patients 
who received secukinumab during the qualifying period of their originating study.
(2) Patients assigned to 125 mg mirikizumab Q8W SC in Study AMAH
(3) Patients who received secukinumab during the qualifying period of their originating 
study.
For assessment of the primary endpoints and other categorical efficacy endpoints, proportions 
and 95% confidence intervals will be reported using the simple asymptotic method, without 
continuity correction (that is, normal approximation to the binomial distribution). For the primary 
endpoint, missing data will be handled in at least 2 different ways: (1) proportions, calculated using 
only observed data, and (2) non-responder imputation (NRI).  For the NRI method, all patients who 
do not meet the clinical response criteria or have missing clinical response data at the analysis time 
point will be defined as nonresponders. 
For continuous efficacy and health outcome variables with multiple post-baseline measurements,
the mean response over time will be estimated using the mixed-effects model for repeated 
measures (MMRM). For continuous efficacy and health outcome variables with a single post-
baseline time point, the mean response will be estimated using analysis of covariance 
(ANCOVA).
Continuous safety data, including vital sign and laboratory values, will be analyzed by 
ANCOVA with treatment and baseline value in the model, unless otherwise specified.  Also,

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laboratory analytes will be presented as mean changes from baseline and as incidence of shift 
between normal and abnormal states.
A single Data Monitoring Committee consisting of members external to Eli Lilly and Company 
will be established for interim safety monitoring across all Phase 3 trials in patients with 
psoriasis.

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2. Schedule of Activities

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Table AMAH.1.
Schedule of Activities
Procedurea
Treatment Period (Visits 1-14, every-8-week visits)
Visit Number
V1b
V2
V3
V4
V5
V6
V7
V8
V9
V10
V11
V12
V13
V14
Week Relative to Study Drug 
Initiation
0
8
16
24
32
40
48
56
64
72
80
88
96
104
Day Relative to Study Drug 
Initiation, with Visit Tolerance 
Interval
1 
5
57 
5
113 
5
169 
5
225 
5
281 
5
337 
5
393 
5
449 
5
505 ± 
5 
561 
5
617 
5 
673 
5
729 
5
Informed consent
X
Demographics
X
Physical examinationc
X
Weight 
X
Review and confirm 
inclusion/exclusion criteria
X
Complete medical/surgical history 
and habits
X
Concomitant medications
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
Vital signs (BP, temperature, and 
heart rate)d
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PPD/QuantiFERON-TB Gold/
T-SPOT.TB®
(per local guidelines)e
TB testing required only 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.
ECGf
C-SSRS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Self-Harm Supplement Formg
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Self-Harm Follow-up Form
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
X
X
X
X
X
X
X
IP dosed
X
X
X
X
X
X
X
X
X
X
X
X
X
IP dispensed
Xh

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Procedurea
Treatment Period (Visits 1-14, every-8-week visits)
Visit Number
V1b
V2
V3
V4
V5
V6
V7
V8
V9
V10
V11
V12
V13
V14
Week Relative to Study Drug 
Initiation
0
8
16
24
32
40
48
56
64
72
80
88
96
104
Day Relative to Study Drug 
Initiation, with Visit Tolerance 
Interval
1 
5
57 
5
113 
5
169 
5
225 
5
281 
5
337 
5
393 
5
449 
5
505 ± 
5 
561 
5
617 
5 
673 
5
729 
5
Investigator-Completed Clinical 
Efficacy Scales
PASI
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
sPGA
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PSSIi
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
PPASIi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Patient-Completed Health 
Outcomes Scalesj
PSS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
DLQI
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Laboratory Tests
Hematologyk
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Clinical serum chemistryk
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urinalysis
X
hsCRP
X
X
X
X
X
X
X
X
X
X
X
X
X
X
HBV DNA testingl
X
X
X
X
X
X
X
HCV RNA testing
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Immunogenicity for 
mirikizumabn
Xo
X
X
X
X
X
X
Serum for mirikizumab 
concentrations (PK)p
Xo
X
X
X
X
X
X
Urine pregnancy testq (local; 
WCBP only)
X
X
X
X
X
X
X
X
X
X
X
X
X
X

I6T-MC-AMAH(a) Clinical Protocol
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Procedurea
Treatment Period (Visits 15-21, every-16-week visits)
ETVr
Follow-up Period (Visits 801 
and 802)
Visit Number
V15
V16
V17
V18
V19
V20
V21
V801
V802
Week Relative to Study Drug 
Initiation
120
136
152
168
184
200
208
LV +4W
LV
+12W
Day Relative to Study Drug Initiation, 
with Visit Tolerance Interval
841 
5
953 
5
1065 
5
1177 
5
1289 
5
1401 
5
1457 
5
29
± 5
85
± 5
Physical examinationc
X
X
Weight
X
X
Concomitant medications
X
X
X
X
X
X
X
X
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X
Vital signs (BP, temperature, and heart 
rate)d
X
X
X
X
X
X
X
X
X
X
PPD/QuantiFERON-TB Gold/
T-SPOT.TB®
(per local guidelines)e
TB testing required only 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.
ECGf
X
X
C-SSRS
X
X
X
X
X
X
X
X
X
X
Self-Harm Supplement Formg
X
X
X
X
X
X
X
X
X
X
Self-Harm Follow-up Form
X
X
X
X
X
X
X
X
X
X
QIDS-SR16 (patient completed)
X
X
X
X
X
X
X
X
X
IP dispensed
X
X
X
X
X
X
X
IP returned
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
BSA
X
X
X
X
X
X
X
X
X
X
sPGA
X
X
X
X
X
X
X
X
X
X
PSSIi
X
X
X
X
X
X
X
X
X
X
NAPSIi
X
X
X
X
X
X
X
X
X
X

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Procedurea
Treatment Period (Visits 15-21, every-16-week visits)
ETVr
Follow-up Period (Visits 801 
and 802)
Visit Number
V15
V16
V17
V18
V19
V20
V21
V801
V802
Week Relative to Study Drug 
Initiation
120
136
152
168
184
200
208
LV +4W
LV
+12W
Day Relative to Study Drug Initiation, 
with Visit Tolerance Interval
841 
5
953 
5
1065 
5
1177 
5
1289 
5
1401 
5
1457 
5
29
± 5
85
± 5
PPASIi
X
X
X
X
X
X
X
X
X
X
Patient-Completed Health Outcomes 
Scalesj
PSS
X
X
X
X
X
X
X
X
X
DLQI
X
X
X
X
X
X
X
X
X
Laboratory Tests
Hematologyk
X
X
X
X
X
X
X
X
X
X
Clinical Serum chemistryk
X
X
X
X
X
X
X
X
X
X
Urinalysis
Xs
X
HsCRP
X
X
X
X
X
X
X
X
X
X
HBV DNA testingl
X
X
X
X
X
X
X
X
X
X
HCV RNA testing
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Xm
Immunogenicity for mirikizumabn
X
X
X
X
X
Serum for mirikizumab concentrations 
(PK)p
X
X
X
X
X
Urine pregnancy testq
(local; WCBP only)
X
X
X
X
X
X
X
X
X
Abbreviations:  ALT = alanine aminotransferase; BP = blood pressure; BSA = body surface area; C-SSRS = Columbia–Suicide Severity Rating Scale; DLQI = 
Dermatology Life Quality Index; DNA = deoxyribonucleic acid; ECG = electrocardiogram; ETV = early termination visit; HBcAb+ = positive for hepatitis B 
core antibody; HBV = hepatitis B virus; HCV = hepatitis C virus; hsCRP = high-sensitivity C-reactive protein; IP = investigational product; LV = last study 
visit; LVTP = last visit of a qualifying study treatment period; NAPSI = Nail Psoriasis Severity Index; PASI = Psoriasis Area and Severity Index; 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; sPGA = static Physician’s 
Global Assessment; TB = tuberculosis; ULN = upper limit of normal; V = visit; W = weeks; WCBP = women of child-bearing potential.
a
All activities should be completed prior to any study dose administration, unless otherwise stated.

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b
For most patients, the final visit of the originating study will coincide with Visit 1 (Week 0) of Study AMAH. In these cases, any assessments/procedures 
(including laboratory tests) conducted during the patient’s final visit in the originating study should not be repeated for Visit 1 (Week 0) of Study AMAH.  In 
cases where entry into Study AMAH is delayed beyond the LVTP of the originating study, assessments/procedures (including laboratory tests) indicated for 
Visit 1 (Week 0) of Study AMAH that are not conducted during the patient’s last visit of the originating study will be performed as indicated in the Schedule 
of Activities.  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 Visit 1. 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) (see Section 9.4.5.1.)  Physical examination does not need to be performed again if Visit 1 occurs on the same date as 
the last visit of the originator study and if physical examination was performed at the last visit of the originator study.
d
When multiple assessments are scheduled for the same time point, the preferred order of completion should be as follows:  vital signs and then blood 
sampling.
e
Tuberculosis testing will be conducted based on clinical assessment of TB risk (symptoms/signs/known or suspected TB exposure; risk factors detailed in 
Appendix 5), determined by the principal investigator, and according to local regulations and/or local standard of care (Section 9.4.6).  Tuberculosis 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 the 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 Section 9.4.5.2.
f
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.
g
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).
h
Patients will self administer injections starting at Visit 14.  Sites will train patients on how to self inject the drug at Visit 14 and will provide a log for patients 
to track their at home dosing.
i
The PSSI, NAPSI, and PPASI assessments are applicable only if symptoms are present at baseline.
j
These assessments should be completed before administration of IP; 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
Unscheduled blood chemistry and hematology panels may be performed at the discretion of the investigator. See Appendix 2, for details.

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l
Any enrolled patient who is HBcAb+ in the originator trial will undergo monitoring of HBV DNA with HBV DNA testing (see Section 9.4.5.3).  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.
m Any enrolled patient with a history of HCV infection (tested positive for HCV antibody in the originator study) who develops elevated ALT >3xULN will be 
tested for HCV RNA (see Section 9.4.5.4). 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.
n
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).
o
Sample from last vist of originator study should be used.  If no sample <4 weeks old is available, then a baseline sample should be collected in this study.
p
Scheduled pharmacokinetic samples are taken as an aliquot from the immunogenicity sample.  Unscheduled pharmacokinetic 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.q
To be performed only on 
women of child-bearing potential.  Between visits, urine pregnancy tests are to be performed monthly at home.
r
If a patient discontinues IP early, the patient will complete the ETV and then enter the Post-Treatment Follow-up Period (Visit 801 and Visit 802).
s
Urinalysis assessed only for early termination due to an adverse event for which urinalysis is clinically indicated.

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3. Introduction
3.1.
Study Rationale
Mirikizumab (LY3074828) is a humanized immunoglobulin G4 (IgG4)–variant monoclonal 
antibody being developed for the treatment of immune-mediated or inflammatory diseases in 
which the IL-23 pathway is thought to have a 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-AMAH (AMAH) is a long-term extension study of 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 long-term efficacy and safety of mirikizumab in 
patients with moderate-to-severe plaque psoriasis, who wish to continue treatment following 
completion of Studies 16T-MC-AMAF (AMAF), 16T-MC-AMBK (AMBK), 16T-MC-AMAK
(AMAK), or 16T-MC-AMAJ (AMAJ).
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).  Interleukin-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.  Interleukin-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 Food and Drug 
Administration (FDA)-approved monoclonal antibody for the treatment of psoriasis, psoriatic 
arthritis, and Crohn’s disease (Stelara® package insert 2017) and is being evaluated in a Phase 3 
trial for the treatment of ulcerative colitis (NCT02407236).  Ustekinumab binds the p40 subunit 

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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 (TremfyaTM package insert 2017) 
and the European Medicines Agency (EMA) (Tremfya Summary of Product Characteristics 
2017).  Other similar agents, including mirikizumab in Studies I6T-MC-AMAA (AMAA) and 
AMAF, have demonstrated clinical activity in plaque psoriasis (Krueger et al. 2015; Papp et al. 
2015, 2017; Reich et al. 2017).
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. 2017).
The doses and regimens planned for Studies AMAJ, AMAK, and AMAH 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, 
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 

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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 of 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 AMAH 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).

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4.
Objectives and Endpoints
Table AMAH.2 shows the objectives and endpoints of the study.
Table AMAH.2.
Objectives and Endpoints
Objectives
Endpoints
Primary

To evaluate the long-term maintenance of 
efficacy of mirikizumab in patients with 
moderate-to-severe plaque psoriasis
Over the duration of the study:

Proportion of patients with an sPGA (0,1) 
among those who entered Study AMAH with 
sPGA (0,1)

Proportion of patients who maintained a 
≥90% improvement in PASI (PASI 90)
among those who entered Study AMAH with 
a PASI 90 response
Secondary

To evaluate the long-term efficacy and patient 
reported outcomes with mirikizumab
treatment in patients with moderate-to-severe 
plaque psoriasis
Over the duration of the study:

Proportion of patients achieving sPGA (0,1)

Proportion of patients achieving PASI 90

Proportion of patients achieving a 100% 
improvement in PASI (PASI 100)

Proportion of patients with a PSS symptom 
score of 0 (free of itch, pain, stinging, and 
burning) in those with a PSS symptoms 
score ≥1 at baseline.

Proportion of patients achieving Dermatology 
Life Quality Index (DLQI) score of 0,1 with 
baseline score >1

Percent change in Palmoplantar Psoriasis 
Severity Index (PPASI) total score in patients 
with palmoplantar involvement at baseline

Percent change in Psoriasis Scalp Severity 
Index (PSSI) total score in patients with scalp 
involvement at baseline

Percent change in Nail Psoriasis Severity 
Index (NAPSI) total score in patients with 
fingernail involvement at baseline

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Exploratory
To evaluate the potential development of 
anti-mirikizumab antibodies and their potential 
relationship with efficacy, TEAEs, and 
mirikizumab exposure 
Over the course of the 208 week study, by 
treatment-emergent anti-drug antibody (TE-ADA) 
status and by neutralizing anti-drug antibody (NAb) 
status:

Relationship between ADA and efficacy (sPGA 
and PASI)

Relationship between ADA and TEAEs

Relationship between TE-ADA and mirikizumab 
pharmacokinetics
Abbreviations:  ADA= antidrug antibodies; DLQI = Dermatology Life Quality Index; Nab = neutralizing anti-drug 
antibody; NAPSI = Nail Psoriasis Severity Index; PASI = Psoriasis Area and Severity Index; PPASI = 
Palmoplantar Psoriasis Severity Index; PSS = Psoriasis Symptoms Scale; PSSI = Psoriasis Scalp Severity Index; 
sPGA = static Physician’s Global Assessment; TE-ADA = treatment-emergent anti-drug antibody; TEAEs = 
treatment-emergent adverse events.

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5. Study Design
5.1.
Overall Design
Study AMAH is a long-term study in which patients completing 1 of the 4 originator studies 
(AMAF, AMAJ, AMAK, or AMBK) will receive 250 mg or 125 mg mirikizumab Q8W,
administered SC, for an extended period of time (approximately 4 years or until commercial 
availability of mirikizumab) and then enter a 12-week Post-Treatment Follow-Up period.
Study governance considerations are described in detail in Appendix 3.
5.1.1. Qualifying Period
Patients who qualify for Study AMAH may enter directly into the study upon the last visit of a 
qualifying study treatment period (LVTP) of the originator study.  For most patients, Week 52 of 
the originating study (AMAJ and AMAK) will be the LVTP and will coincide with Week 0 
(Visit 1) for Study AMAH. Similar alignment will occur for other originator studies, that is, 
Visit 1 of Study AMAH to coincide with the LVTP in AMAF or AMBK.  The qualifying study 
treatment periods of the originator studies are as follows:

AMAJ, AMAK, AMAF:  Blinded Maintenance Period

AMBK: Treatment Period
Study investigator(s) will review patient data from the LVTP in the respective originating study 
to determine if the patient meets all inclusion and none of the exclusion criteria to qualify for 
participation in Study AMAH.
If, at LVTP of the originating study, a patient is not able to enter Study AMAH (for example, 
due to unresolved safety concerns), the patient will be evaluated in the originating study for up to 
12 weeks beyond the LVTP (that is, in a post-treatment follow up period) to determine whether 
treatment with investigational product can resume in Study AMAH.  If, in the opinion of the 
investigator, starting or restarting treatment with mirikizumab does not pose an unacceptable 
risk, the patient can begin participation in Study AMAH, that is, have Visit 1 in Study AMAH. 
Eligible patients must enter Study AMAH within 12 weeks of the LVTP of originating study or 
they will become ineligible.
5.1.2. Treatment Period
All patients participating in Study AMAH will receive mirikizumab every 8 weeks (Q8W) SC.  
The dose used in Study AMAH will depend on the treatment patients were receiving during the 
qualifying period of the originator study.  For all treatment groups in Study AMAH, dosing 
begins at Visit 1 and continues to Week 208.

Patients entering from Study AMAJ or Study AMAK who received mirikizumab
during the qualifying period, will continue to receive the dose they were using (either 
250 mg mirikizumab Q8W SC or 125 mg mirikizumab Q8W SC).  Patients entering 

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from Study AMAJ or Study AMAK who were receiving secukinumab or placebo, 
respectively, during the qualifying period will receive 250 mg mirikizumab Q8W SC.

Patients entering from Study AMBK will receive 250 mg mirikizumab Q8W SC.

Patients entering from Study AMAF whose last treatment was 300 mg mirikizumab
Q8W, on either the fixed dosing regimen or in the as needed (PRN) regimen, will start 
250 mg mirikizumab Q8W SC in Study AMAH.  Patients entering from Study AMAF 
whose last treatment was either 30 mg or 100 mg mirikizumab on a PRN regimen will 
start 125 mg mirikizumab Q8W SC in Study AMAH.

After Study AMAH dosing is no longer blinded, patients who in the opinion of the 
investigator have experienced significant clinically meaningful loss of efficacy during 
study participation may be increased from 125 mg mirikizumab Q8W to 250 mg 
mirikizumab Q8W if it is determined by the patient and the investigator that the patient 
might benefit from additional study drug in order to maintain satisfactory disease 
control. All patients who increase dosing to 250 mg mirikizumab Q8W will remain on 
this dose until completion of the study or early discontinuation.
5.1.3. Post-Treatment Follow-Up Period (12 Weeks)
All patients, whether they discontinue early for any reason or complete study treatment, will 
enter the 12-week Post-Treatment Follow-Up Period (Visit 801 and Visit 802) of Study AMAH.
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 AMAH.1 illustrates the study design.  

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Abbreviations: LV = last study visit; miri = mirikizumab given as subcutaneous 
injection (SC); PRN=as needed; pts = patients; Q8W =every 8 weeks; V = visit; 
W or w = week.
aPatients will remain blinded to treatment until the last patient completes the last 
originator study. 
bPatients receiving 125 mg Q8W may be eligible to escalate to 250 mg Q8W; see
Section 7.4
Figure AMAH.1.
Illustration of study design for Clinical Protocol I6T-MC-AMAH.
5.2.
Number of Participants
Approximately 1600-2000 participants are expected to enroll in Study AMAH from the 
originator studies. 
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.
5.4.
Scientific Rationale for Study Design
Mirikizumab (LY3074828) is a humanized immunoglobulin G4 (IgG4)–variant monoclonal 
antibody that binds to the p19 subunit of IL-23 and does not bind IL-12. Mirikizumab is being 
developed for the treatment of immune-mediated or inflammatory diseases in which the IL-23 
pathway is thought to have a pathogenic role.  Study AMAH is a confirmatory study testing 
mirikizumab as a treatment for plaque psoriasis and is intended to support registration of this 
indication. This Phase 3 trial is designed to evaluate the safety and efficacy of mirikizumab 
Entry from
originator study: 
AMAF
W0
V1
Pts previously on 300 mg miri, fixed 
Q8W or PRN: 250 mg miri Q8W
Pts previously on 30 mg or 100 mg 
miri PRN: 125 mg miri Q8Wb
W104
V14
Extension Treatment Perioda
Visits every 16 weeks
LV+4w
V801
LV+12w
V802
Post-Treatment 
Follow-Up Period
All Pts: 250 mg miri Q8W
W208
V21
Visits every 8 weeks 
Entry from
originator study: 
AMAJ, AMAK
Pts previously on miri: Continue dose 
most recently used in originator study 
(250 mg miri Q8W or 125 mg miri Q8Wb)
Pts previously on placebo or 
secukinumab: 250 mg miri Q8W
Entry from
originator study: 
AMBK

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following long-term administration, as determined by the evaluation of safety laboratory results 
and analysis of AE parameters and by improvement in disease severity and key patient-reported 
outcomes.
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
Single doses of up to 600 mg IV were evaluated in Study AMAA (healthy patients and patients
with psoriasis), and up to 1200 mg IV were evaluated in Study I6T-JE-AMAD (healthy patients); 
no dose-related safety or tolerability issues were observed in either study.  Evaluation of the 
safety data available to date in the ongoing Phase 2 studies in patients with ulcerative colitis 
(Study I6T-MC-AMAC) and in patients with Crohn’s disease (Study I6T-MC-AMAG) that are 
evaluating higher and more frequent dosing regimens of up to 1000 mg IV every 4 weeks for up 
to 52 weeks has not revealed any difference in the safety profile resulting from these higher 
exposures.
The MOS for the highest dosing regimen of 250 mg Q8W SC proposed for this study relative to 
the NOAEL level in the 6-month nonclinical toxicology study in cynomolgus monkeys is 44, 
based on area under the plasma concentration versus time curve.
Efficacy Considerations
A dosing regimen of 250 mg mirikizumab Q8W SC is the highest dosing regimen being 
evaluated during the maintenance periods of Studies AMAJ and AMAK.  This dosing regimen is 
expected to maintain or further enhance the efficacy achieved at the end of the Induction Period
in those studies.  A second maintenance dosing regimen of 125 mg Q8W SC is also being 
evaluated during maintenance in those studies to determine whether efficacy could be maintained 
with a lower dosing regimen.  This second dosing regimen is expected to result in mirikizumab 
concentrations that have, in individual patients, minimal overlap with the concentrations 
produced with the 250 mg mirikizumab Q8W SC regimen.
Formulation Considerations
A 125 mg/mL concentration was selected to provide the maximum amount of mirikizumab that 
could be delivered as a single SC injection (that is, 2 mL).  Therefore, a 2 mL dose of 
mirikizumab (delivered either as two 1 mL injections or a single 2 mL injection) would deliver 
250 mg of mirikizumab, which is comparable to the 300 mg dose that was evaluated in the 
Phase 2 Study, AMAF.  The 125 mg dose will be delivered as a single 1 mL SC injection; this 
dose is comparable to the 100 mg dose evaluated in Study AMAF.

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Therefore, based on all the available clinical and non-clinical data, the dosing regimens planned 
for this study are expected to provide an acceptable safety profile while providing maximum 
clinical response in patients with plaque psoriasis.

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6.
Study Population
The study population for Study AMAH will include patients who have completed participation 
in qualifying study periods of 1 of the originating studies (Study AMAF, AMAJ, AMAK, or 
AMBK) and meet eligibility criteria for Study AMAH, and will therefore include adult patients 
with moderate-to-severe plaque psoriasis at the time of entry into the originating study.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, are not permitted.
Patients in the secukinumab treatment group of Study AMAJ will be eligible to enter 
Study AMAH; such patients will receive mirikizumab for the first time in Study AMAH.  
Approximately 1600-2000 patients are planned to be enrolled in Study AMAH.
6.1.
Inclusion Criteria
Patients are eligible to be included in the study only if they meet the following criteria before the 
start of treatment in Study AMAH, unless otherwise specifically defined:
Type of Patient
[1]
Have completed the last visit of an eligible study period of 1 of the originator
studies (Study AMAF, AMAJ, AMAK, or AMBK).  
Patient Characteristics
[2a] Male patients
No male contraception required except in compliance with specific local 
government study requirements. 
[2b] Female Patients
Women not of child-bearing 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 of at least 50 years of age with an intact 
uterus, not on hormone therapy, who has had either:

Cessation of menses for at least 1 year,
OR

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
At least 6 months (or longer if required by 
local regulatory requirements) of spontaneous 
amenorrhea with a follicle stimulating hormone 
level of >40 mIU/mL
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 child-bearing potential:
A. Must test negative for pregnancy prior to first dose in 
Study AMAH as indicated 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, or 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.

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ii.
Of note, 1 of the 2 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.
[3]
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
[4]
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, unless 
otherwise specified:
[5]
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 that 
developed during the originating mirikizumab study (Studies AMAF, AMAJ, 
AMAK, or AMBK) that, in the opinion of the investigator, would potentially 
affect patient safety within the study or would interfere with the interpretation 
of data.
[6]
Have a known hypersensitivity to mirikizumab or any component of this 
investigational product.
[7]
Have had investigational product permanently discontinued during a previous 
mirikizumab study.
[8]
Have had temporary investigational product interruption at any time during or 
at the final study visit of a previous mirikizumab study and, in the opinion of 
the investigator, restarting mirikizumab would pose an unacceptable risk for 
the patient’s participation in the study.
[9]
Have any other condition that, in the opinion of the investigator, renders the 
patient unable to understand the nature, scope, and possible consequences of 
the study or precludes the patient from following and completing the protocol.
[10] 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.

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Other Exclusions
[11] 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.
6.2.1. Rationale for Exclusion of Certain Study Candidates
Patients who were not suitable candidates to receive mirikizumab treatments at the end of the 
originator study treatment period will be excluded from this study, which is intended to evaluate
the safety and efficacy of long-term mirikizumab treatment.
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
Screen failures are not applicable as study participation is dependent on completion of the 
originator studies and not the screening process. 

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7. Treatments
7.1.
Treatments Administered
This study involves an evaluation of long-term maintenance of response to mirikizumab 250 mg 
or 125 mg administered SC for up to 208 weeks of dosing.  Table AMAH.3 shows the treatment 
regimens.
Table AMAH.3.
Treatment Regimens
Originator Study
Treatment at End of Originating 
Study
Treatment in Study AMAH (Q8W)
AMBK
250 mg miri Q4W
250 mg miri
(2 x 1-mL miri PFS)
AMAF
300 mg miri, Q8W fixed or PRN
250 mg miri
(2 x 1-mL miri PFS)
30 mg or 100 mg miri PRN
125 mg miria
(1 x 1-mL miri PFS plus 
1 x 1-mL placebo PFSb)
AMAJ
250 mg miri Q8W or secukinumab
250 mg miri
(2 x 1-mL miri PFS)
125 mg miri Q8W
125 mg miria
(1 x 1-mL miri PFS plus 
1 x 1-mL placebo PFSb)
AMAK
250 mg miri Q8W or placebo
250 mg miri
(2 x 1-mL miri PFS)
125 mg miri Q8W
125 mg miria
(1 x 1-mL miri PFS plus 
1 x 1-mL placebo PFSb)
Abbreviations:  miri = mirikizumab; PFS = prefilled syringe; PRN = as needed; Q4W = every 4 weeks; 
Q8W = every 8 weeks.
a
Patients receiving 125 mg Q8W may be eligible to escalate to 250 mg Q8W (see Section 7.4)
b
Placebo will be administered only until study treatments are unblinded (see Section 7.3 describing how long 
treatments are blinded).
Administration:
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 until Visit 14, at 
which time site staff will train patients on self-injection and will provide them with a log to track 
their doses at home.

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Following Visit 14, injections will be self-administered SC by the patient or caregiver. It is
recommended that these injections be administered away from the investigational site. If the
patient or caregiver is not able to administer any dose throughout the study, study site staff may
administer that injection.
Refer to the appropriate Manual Syringe Directions for Use provided by the sponsor for the
investigational product. Note that in the case a study drug injection is performed in an arm, it is
not to be given in the same arm from which patient blood samples, including PK samples, are
drawn at relevant visits.
Study Drug Administration Logs will be dispensed to each patient for recording pertinent data
about each injection; details of the use of these logs are provided in Section 7.2.1.  Possible 
injection sites are identified in the Manual Syringe Directions for Use. The injection site may be 
rotated to another area for subsequent doses.
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,

At the end of the study returning all unused medication to Eli Lilly and 
Company (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
At the time of unblinding, patients, site personnel and the Sponsor will become unblinded so that 
patients on the 125 mg miri can stop receiving a 1 x 1-mL placebo PFS (see Table AMAH.3).
7.1.1. Packaging and Labeling
Mirikizumab and 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, and returned or destroyed according to applicable 
regulations.  Clinical trial materials are manufactured in accordance with current Good 
Manufacturing Practices (GMP).
Investigational product will be supplied as single-use solution in prefilled syringes containing 
mirikizumab or placebo.  The 1-mL syringe of mirikizumab is manufactured to contain 125 mg
of the drug.  
Mirikizumab cannot be distinguished visually from placebo.

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Investigational product will 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 assigned to double-blind treatment at Visit 1
based on the ending treatment regimen of the originating study (see Table AMAH.3). The
interactive web-response system (IWRS) will be used to assign prefilled syringes containing 
investigational product to each patient. Investigational product will be dispensed according to 
the Schedule of Activities (Section 2). Site personnel will confirm that they have located the 
correct prefilled syringes by entering a confirmation number found on the prefilled syringes into 
the IWRS.
7.2.1. Selection and Timing of Doses
Study visits at which the investigational product is administered are preferred, if possible, to 
occur on the same day of the week.  In any case, the study visits should occur within the visit 
window specified on the 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). Study drug 
will be administered by site personal at Visits 1-13. Starting with Visit 14 patients should self-
administer study drug on the day of the visit, and then every 8 weeks thereafter, preferably on the 
same day of the week.
7.3.
Blinding
This is a double-blind study until the originating studies AMAJ and AMAK have had database 
lock and dosing for those studies is no longer blinded. The blinding applies to patients, site 
personnel, and Sponsor personnel.
Personnel in the originator Studies AMAF and AMAJ performing unblinded tasks (e.g., study 
drug dosing/dispensing) will by default know the treatment assignments of individual patients in 
Study AMAH by the protocol design. If these unblinded site personnel in the originator Studies
AMAF and AMAJ also have a role in Study AMAH, they must assume the same responsibilities 
taken in the originator study for these patients and must not be involved in any patient 
assessment activities, seek any information related to these patients beyond their allowed 
activities, discuss the treatment assignment with the patient or with the blinded personnel.  
Principal Investigators will need to ensure that the blinded conditions of the originating studies 
are maintained during Study AMAH until database lock has occurred and dosing for those 
studies is no longer blinded.
Emergency unblinding for AEs may be performed through the IWRS, which may supplement or 
take the place of emergency codes generated by a computer drug-labeling system.  This option 
may be used ONLY if the patient’s well-being requires knowledge of the patient’s treatment 
assignment.  All actions resulting in an unblinding event are recorded and reported by the IWRS.

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If an investigator, site personnel performing assessments, or patient is unblinded before the study 
dosing is no longer blinded, the patient may continue the study, unless there are safety or 
benefit/risk reasons for the patient not to continue the study as determined by the principal 
investigator or Sponsor.  
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’s 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
After Study AMAH dosing is no longer blinded, patients who in the opinion of the investigator 
have experienced significant clinically meaningful loss of efficacy during study 
participation may be increased from 125 mg mirikizumab Q8W to 250 mg mirikizumab Q8W if 
it is determined by the patient and the investigator that the patient might benefit from additional 
study drug in order to maintain satisfactory disease control. All patients who increase dosing to 
250 mg mirikizumab Q8W will remain on this dose until completion of the study or early 
discontinuation. No other dose adjustments are permitted in Study AMAH.
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 the investigator and 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 of
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 destroyed 
according to applicable regulations.

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Mirikizumab, placebo, and secukinumab should be transported and stored in refrigerated 
conditions at 2°C to 8°C (36°F to 46°F).
7.6.
Treatment Compliance
Deviations from the prescribed dosage regimen should be recorded in the eCRF.
Every attempt will be made to select patients who have the ability to understand and comply with 
the study instructions.  The investigator is responsible for discussing methods to ensure high 
treatment compliance with the patient.  
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.  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.  
Patients 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 AMAH.4 below (also see the section Exclusion Criteria 
[Section 6.2]).

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Table AMAH.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 
(including, but not limited to, 
corticosteroids, 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)
N
N
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
.

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Drug Class
Allowed for 
Chronic Use
Allowed with 
Restrictions
Conditions for Allowed Use
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. 
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 AMAH or complete Study AMAH.

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7.8.2. Special Treatment Considerations 
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)

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 the 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 (assess immune complex formation), and 

have a cytokine panel performed.
See also Section 9.4.4.  
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 
5.1.3 (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, the following:

Development of:
o
Serious or opportunistic infections, as described in Section 9.2.3).
o
Hypertension (see Section 9.4.2.1).
o
Latent tuberculosis (TB) infection (LTBI) (see Section 9.4.5.2).
o
Positive hepatitis B virus (HBV) deoxyribonucleic acid (DNA) results that are 
below the level of quantification (see Section 9.4.5.3).
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 
alanine aminotransferase (ALT), alkaline phosphatase (ALP) or total bilirubin 
level (TBL) include one of the following (Section 9.4.6.1):

ALT ≥3xupper limit of normal (ULN) and TBL <2xULN

ALP ≥2xULN and TBL <2xULN

TBL ≥2xULN without increase from baseline in ALT/aspartate 
aminotransferase (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 the 
study treatment.  If the investigator and the Sponsor-designated medical monitor agree that it is 
medically appropriate to continue, the investigator must obtain documented approval from the 
Sponsor-designated 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 this 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:

Patient Decision
o
The patient requests to be either discontinued from 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 >8xULN

ALT or AST >5xULN for more than 2 weeks

ALT or AST >3xULN and TBL >2xULN or international normalized ratio 
(INR) >1.5 

ALT or AST >3xULN, with the appearance of fatigue, nausea, vomiting, 
right upper-quadrant pain or tenderness, fever, rash, and/or eosinophilia 
(>5%)

ALP >3xULN

ALP >2.5xULN and TBL >2xULN

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
ALP >2.5xULN, 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 count <2000 cells/L (<2.00x103/µL or 
<2.00 GI/L).

Lymphocyte count <500 cells/μL (<0.50x103/µL or <0.50 GI/L).

Platelet count <50,000 cells/μL (<50x103/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 of this protocol).

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 a 12-month period).

Any patient who has a change in disease phenotype at any time (for 
example, a change to pustular psoriasis).

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 if:
1. 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 
2. The patient 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 Columbia-Suicide Severity 
Rating Scale [C-SSRS]) 
OR 

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3. The patient 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 positive or hepatitis C virus (HCV)
ribonucleic acid (RNA) positive.  The patient should be referred to a 
specialist physician (see Sections 8.1.2 and 9.4.5.3 for HBV, and Section 
9.4.5.4 for HCV).

Patients will also be permanently discontinued from study drug, complete the 
Post-Treatment Follow-up, and then permanently discontinue from the study in the 
following circumstances:

Enrollment in any other clinical study involving an investigational product 
or enrollment in any other type of medical research judged not to be 
scientifically or medically compatible with this study

Participation in the study needs to be stopped for medical, safety, 
regulatory, or other reasons consistent with applicable laws, regulations, 
and Good Clinical Practice (GCP)

Investigator decision
o
The investigator decides that the patient should be discontinued
from the study
o
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 the 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 5.1.3 (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 to assess the proportion of patients maintaining efficacy achieved 
in the originator studies are as follows:
9.1.1.1.
Static Physician’s Global Assessment
The static Physician’s Global Assessment (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).
9.1.1.2.
Psoriasis Area and Severity Index
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 the 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:
9.1.2.1.
Static Physician’s Global Assessment
Both sPGA (0) and sPGA (0,1) will be assessed at various time points up to 4 years.  For 
assessment description, see Section 9.1.1.1.

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9.1.2.2.
Psoriasis Area and Severity Index
PASI 75, PASI 90, and PASI 100 will be assessed at various time points up to 4 years.  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.
9.1.2.3.
Body Surface Area
Percent body surface area (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).
9.1.2.4.
Nail Psoriasis Severity Index
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).
9.1.2.5.
Psoriasis Scalp Severity Index
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).
9.1.2.6.
Palmoplantar Psoriasis Severity Index
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).
9.1.2.7.
Health Outcomes Assessments
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.

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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 
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 threshold (Khilji et al. 2002; Hongbo et al. 2005).
9.1.2.7.2. 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 from 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.
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.  
9.1.2.7.3. 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).

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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 of 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 them 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 informed consent form (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 
investigational product, via eCRF.
The investigator will interpret and document whether or not an AE has a reasonable possibility 
of being related to study treatment, study device, or a study procedure, taking into account the 
disease, concomitant treatment or pathologies.
A “reasonable possibility” means that there is a cause and effect relationship between the 
investigational product, study device and/or study procedure and the AE.
The investigator answers yes/no when making this assessment.
Planned surgeries and nonsurgical interventions should not be reported as AEs unless the 
underlying medical condition has worsened during the course of the study.

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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 any 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 the investigational product.  However, if an SAE occurs after signing the ICF, but prior 
to receiving the 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’s
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 subjects once they have 
discontinued and/or completed the study (the patient disposition case report form has been 
completed).  However, if the investigator learns of any SAE, including a death, at any time after 
a subject 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.
9.2.1.1.
Suspected Unexpected Serious Adverse Reactions
Suspected unexpected serious adverse reactions (SUSARs) are serious events that are not listed 
in the IB and that the investigator identifies as related to investigational product or procedure.  
United States 21 CFR 312.32 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 suicide ideations 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 9.1.2.7.3) 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.  
•
Retain the investigational product 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.
•
Follow the instructions outlined in the Product Complaint Form 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, electrocardiograms (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.
9.4.2.1.
Hypertension
Patients who experience changes in BP (systolic BP at ≥160 mm Hg plus ≥20 mm Hg increase 
from baseline [Week 0; Visit 1 of AMAH]; 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.
9.4.3.1.
Pregnancy Testing
Pregnancy testing is to be performed only on women of child-bearing potential.
Patients determined to be pregnant will be discontinued from the study.
Patients will undergo urine pregnancy testing at the clinic during designated scheduled visits (see 
Section 2), which will be performed locally.  Between visits, urine pregnancy tests are to be 
performed monthly at home.
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.

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Urine pregnancy testing may be performed at additional time points during the treatment period 
and/or the follow-up period, at the discretion of the investigator or if this is required by local 
regulations.
If a urine pregnancy test is not available, a serum pregnancy test is an acceptable alternative.
9.4.4. Immunogenicity Assessments
At the visits and times specified in the Schedule of Activities (Section 2), venous blood samples 
will be collected to determine antibody production against mirikizumab.  To interpret the results 
of immunogenicity, a blood sample for PK analysis will be collected at the same time points.  All 
samples for immunogenicity should be taken predose when applicable.  With reports of 
hypersensitivity events (immediate or non-immediate), additional samples will be collected as 
close to the onset of the event as possible, at the resolution of the event, and 30 days following 
resolution of the event.  Samples will be evaluated for PK, ADA, and additional exploratory 
markers of hypersensitivity (see Section 7.8.2.1).  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.  
Immunogenicity will be assessed by a validated assay designed to detect ADAs in the presence 
of mirikizumab at a laboratory approved by the Sponsor. Patient samples will be analyzed using 
a 4-tiered approach.  All samples will be assessed in Tier 1 (screening).  Samples above the 
disease state screening assay cut point factor (Tier 1) will be assessed in Tier 2 (confirmation).  
Any samples confirmed as positive for anti-mirikizumab antibodies in Tier 2 will be reported as 
“detected.”  All samples below the screening assay cut point factor in Tier 1 or not confirmed in 
Tier 2 will be reported as “not detected.”  Any “detected” sample in Tier 2 will be assessed in 
Tier 3 (titer assessment; values reported) and Tier 4 (neutralizing ADA assay).  Any samples 
above the disease state Tier 4 cut point will be reported as “detected” for neutralizing antibodies;
samples below the disease state Tier 4 cut point will be reported as “not detected” for 
neutralizing antibodies.  
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)
require.  The duration allows the Sponsor to respond to future regulatory requests related to 
mirikizumab.  Any samples remaining after 15 years will be destroyed. 
9.4.5. Other Tests 
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 

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heart, lungs, peripheral lymph nodes, and abdomen and visual examination of all skin areas 
(including genitalia and breast areas).
9.4.5.2.
Tuberculosis
Diagnosis of LTBI During Study
Tuberculosis testing in Study AMAH 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.
Patients diagnosed with LTBI, based on a positive interferon-release assay test result or a 
positive purified protein derivative response ≥5 mm of induration, and no evidence of active TB,
during the study will temporarily discontinue investigational product and be offered treatment, if 
clinically appropriate. These patients can be considered for resumption of investigational 
product after completing the first 4 weeks of appropriate ongoing prophylactic therapy for LTBI
based on national or international guidelines, for example, United States Centers for Disease 
Control and Prevention (CDC [WWW]); or the World Health Organization (WHOa [WWW]), 
and no evidence of treatment hepatotoxicity (ALT and AST levels must remain ≤2xULN).  
These patients must continue with and complete a full course of treatment for latent TB in order 
to continue on investigational product. Noncompliance with LTBI treatment during the study is 
a reason for permanent discontinuation from study drug.  
Active TB
Patients diagnosed with active TB during the study will be discontinued and should be referred 
for appropriate treatment.
9.4.5.3.
Hepatitis B Monitoring
Any enrolled patient who tested positive for hepatitis B core antibody (HBcAb+) in the 
originator study will undergo periodic monitoring of HBV DNA as per the Schedule of Activities 
(Section 2).  
In addition to the above, any enrolled patient who tested HBcAb+ in the originator study and 
who experiences an elevated ALT or AST level >3xULN 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 

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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.  
9.4.5.4.
Hepatitis C Monitoring
Any enrolled patient with a history of HCV infection (tested positive for HCV antibody in the 
originator study) who develops elevated ALT level >3xULN, will be tested for HCV RNA.
Any patient diagnosed with hepatitis C, as demonstrated by a positive HCV RNA test during the 
study, will be discontinued from the study and should receive appropriate follow-up medical care. 
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.
Data from Study AMAH may be included in a psoriasis program level DMC if this data is 
available at the time DMC meets.
9.4.6.1.
Hepatic Safety Monitoring
If a study patient experiences elevated ALT level ≥3xULN, ALP level ≥2xULN, or elevated 
TBL ≥2xULN, 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 levels 
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 level to ≥5xULN on 2 or more consecutive blood 
tests

Elevated serum TBL to ≥ 2xULN (except for cases of known Gilbert’s 
syndrome)

Elevation of serum ALP level to ≥2xULN on 2 or more consecutive blood 
tests

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
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.
9.6.
Pharmacodynamics
Not applicable.
9.7.
Pharmacogenomics OR Genetics
9.7.1. Whole Blood and/or Saliva Sample for Pharmacogenetic 
Research
Not applicable.
9.8.
Biomarkers
Not applicable.
9.9.
Medical Resource Utilization and Health Economics
Health Economics and Medical Resource Utilization parameters will not be evaluated in this 
study.

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10. Statistical Considerations
10.1. Sample Size Determination
The samples size for Study AMAH will be determined by the number of patients who continue 
into Study AMAH from the originator studies. Approximate planned sample sizes for Studies 
AMAF, AMAJ, AMAK, and AMBK are respectively 205, 1440, 500, and 300. Based on the 
assumption that 80% to 90% of patients complete the originator studies and 80% to 90% of the 
completers continue on into Study AMAH, Lilly anticipates that approximately 1600 to 2000
patients will enter Study AMAH.
10.2. Populations for Analyses
For all safety, efficacy and healthy outcomes analysis, the intent-to-treat (ITT) population will be 
used unless otherwise stated. The ITT population includes all enrolled patients who are assigned 
to receive treatment, 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. Additional populations for further analysis may be 
defined in the SAP.
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.  Additional exploratory analyses of the data will be conducted as 
deemed appropriate.
For all safety, efficacy and health outcomes analysis, the ITT population will be used unless 
otherwise stated. 
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. The analysis will be focused on point estimates and 
confidence intervals. Thus, no hypothesis testing will be performed, and control for multiplicity
is not applicable. Efficacy and safety summaries will be provided by the following 3 cohorts: 
(1) Patients assigned to 250 mg mirikizumab Q8W SC in Study AMAH, excluding patients 
who received secukinumab during the qualifying period of their originating study.
(2) Patients assigned to 125 mg mirikizumab Q8W SC in Study AMAH
(3) Patients who received secukinumab during the qualifying period of their originating 
study.

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Additional cohorts for further analysis may be defined in the SAP and summarized. Sensitivity 
analyses may be done by excluding from Cohort (1) patients who were receiving placebo during 
the qualifying period of their originator study.
Unless otherwise specified, all references to baseline for efficacy and health outcomes related 
endpoints in this study protocol refer to baseline values of the originating study. Detailed 
definitions of baseline for safety, vital sign, laboratory, and immunogenicity related analyses will 
be described in the SAP prior to first unblinded analysis. 
For assessment of categorical efficacy endpoints, proportions and 95% confidence intervals will 
be reported using the simple asymptotic method, without continuity correction (that is, normal 
approximation to the binomial distribution).
For continuous efficacy and health outcome variables with multiple post-baseline measurements,
the mean response over time will be estimated using mixed-effects model for repeated measures 
(MMRM). When MMRM is used, the model includes cohort (defined above), baseline value, 
visit, the interaction of cohort-by-visit as fixed factors, originating study, previous exposure to 
biologic therapy (yes/no), body weight (<100 kg or 100 kg), and geographic region (North 
America, Europe, or Other).  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. Least squares (LS) means for each cohort will be reported 
along with the 95% confidence intervals.
For continuous efficacy and health outcome variables with a single post-baseline time point, the 
mean response will be estimated using analysis of covariance (ANCOVA) with the following in 
the model: cohort (defined above), baseline value and previous exposure to originating study, 
biologic therapy (yes/no), body weight (<100 kg or 100 kg), and geographic region (North 
America, Europe, or Other).  Type III tests for LS means will be used for statistical comparison 
between treatment groups.  The LS means for each cohort will be reported along with the 95% 
confidence intervals. Missing data imputation method for the ANCOVA model will be specified 
in the SAP.
Continuous safety data, including vital sign and laboratory values, will be analyzed by 
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.
10.3.1.1. Missing Data Imputation
The following methods for imputation of missing data will be used:

Non-Responder Imputation (NRI) for Binary Clinical Responses:  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.  This is the 
primary analysis method for all binary efficacy endpoints.

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
Mixed Model Repeated Measures (MMRM) for Continuous Outcomes:  This analysis will 
be the primary analysis method for longitudinal continuous measurements.  It assumes
that the data is missing at random and that the bias caused by missing data can be 
attenuated by modeling random effects using the within-patient error correlation structure.
In addition, estimation based on observed data only will be used. Additional methods for the 
primary endpoints will be discussed in the SAP.
10.3.1.2. Multiple Comparisons/Multiplicity
The analysis will be focused on point estimates and confidence intervals. Thus, no hypothesis 
testing will be performed, and multiple testing will not need to be accounted for.
10.3.2. Treatment Group Comparability
10.3.2.1. Patient Disposition
A detailed description of patient disposition will be provided at the end of the study. Reasons for 
discontinuation from the study will be summarized by cohort.
10.3.2.2. Patient Characteristics
Patient characteristics and baseline clinical measures will be summarized for both the baseline of 
the originating study and the baseline of Study AMAH by the cohorts described in 
Section 10.3.1.  Baseline characteristics will include gender, age, age category, weight, race, 
geographic region (US/Non-US), 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 total score, BSA, PSSI, PSS 
symptom and sign total scores, DLQI total score, Short Form 36-item Health Survey (SF-36)
(physical component summary), and SF-36 (mental component summary).
10.3.2.3. Concomitant
Previous and concomitant medications will be summarized for patients who enter Study AMAH
by the cohorts described in Section 10.3.1. Summaries will be presented using the latest version 
of the World Health Organization drug dictionary. 
10.3.2.4. Treatment Compliance 
Treatment compliance with investigational product will be summarized for patients who enter 
Study AMAH by the cohorts described in Section 10.3.1.  A patient will be considered as having 
missed the visit if he or she fails to attend for administration of 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 and 
not missing 2 consecutive doses.  

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10.3.3. Efficacy Analyses
10.3.3.1. Primary Analyses
For assessment of the primary endpoints and other categorical efficacy endpoints, proportions 
and 95% confidence intervals will be reported. Further details to be provided in the SAP. For the 
primary endpoint, missing data will be handled in at least 2 different ways: (1) proportions, 
calculated using only observed data, and (2) non-responder imputation (NRI). For the NRI 
method, all patients who do not meet the clinical response criteria or have missing clinical 
response data at the analysis time point will be defined as nonresponders. 
10.3.3.2. Secondary Analyses
The secondary efficacy and health outcome endpoints of the trial are presented in 
Table AMAH.2.  Details of the analysis methods that will be utilized are provided in 
Section 10.3.1. Additional analyses of the secondary efficacy and health outcome endpoints may 
be considered and will be fully detailed in the SAP.
10.3.3.3. Tertiary/Exploratory Analyses
The exploratory efficacy and health outcome endpoints of the trial are presented in 
Table AMAH.2.  Details of the analysis methods that will be utilized are provided in Section 
10.3.1. Additional analyses of the secondary efficacy and health outcome endpoints may be 
considered and will be fully detailed in the SAP.
10.3.4. Safety Analyses
Safety assessments will include AEs, laboratory analytes, vital signs, ECGs, and C-SSRS.
Safety data assessments will be summarized for the cohorts described in Section 10.3.1
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities 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 study 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 table of 
TEAEs.  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 plan for analyzing AESIs 
will be described in the Program Safety Analysis Plan and SAP.
10.3.5. Pharmacokinetic/Pharmacodynamic Analyses
No PK/pharmacodynamics (PD) analyses are planned.

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Serum drug level sampling will support the assessment of immunogenicity (simultaneous 
sampling with immunogenicity sampling). Serum drug level samples are taken as an aliquot 
from the immunogenicity sample.
10.3.6. Evaluation of Immunogenicity
Immunogenicity will be evaluated cumulatively, using data both from the patient’s originating
study and from the present study.  Baseline for ADA assessment will be the baseline ADA 
assessment from the originating study, and postbaseline will be time after initiation of 
mirikizumab.  The frequency and percentage of patients with preexisting (baseline) ADA and 
with treatment-emergent ADA to mirikizumab will be tabulated.  For patients with treatment-
emergent ADA, the frequency of neutralizing antibodies will also be tabulated.
The relationship between the presence of antibodies and the PK parameters and PD response,
including safety and efficacy to mirikizumab, will be assessed.
10.3.7. Other Analyses
10.3.7.1. Subgroup Analyses
The primary analysis will focus on the cohorts described in Section 10.3.1. Additional 
subgroups for further analysis may be defined in the SAP.
10.3.8. Interim Analyses
As previously mentioned, Study AMAH is a double-blind study until the originating studies 
AMAJ and AMAK have had database lock and dosing for those studies is no longer blinded.  
After Study AMAH treatment is unblinded, multiple interim analyses will be performed as 
described in the SAP. To protect the study integrity during the blinded period, 1 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 an 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 members of the SAC will be internal to 
Lilly, but external to the study team. The study team will not have access to the 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. Study sites will receive 
information about interim assessments ONLY if they need to know for the safety of their patients. 
The DMC 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 will be done prior to the first unblinded assessment. 

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An unblinded interim analysis may be performed to support a regulatory submission when the 
originator studies have completed.  Additional yearly interim analysis may be performed along 
with the 4-month safety update.

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11.
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12.
Appendices

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Appendix 1.
Abbreviations and Definitions
Term
Definition
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 events 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.
BP
blood pressure
BSA
body surface area
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
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.
ERB
Ethical Review Board
GCP
Good Clinical Practice
GMP
Good Manufacturing Practices
HBcAb
hepatitis B core antibody
HBV
hepatitis B virus
HCV
hepatitis C virus
HRQoL
health-related quality of life
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonisation

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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
intent-to-treat:  The principle that asserts that the effect of a treatment policy can be best 
assessed by evaluating on the basis of the intention to treat a 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
LS
least squares
LTBI
latent tuberculosis infection
LVTF
last visit of a qualifying study treatment period
MMRM
mixed-effects model for repeated measures
MOS
margin of safety
NAPSI
Nail Psoriasis Severity Index
NOAEL
no-observed-adverse-effect-level
NRI
non-responder imputation

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PASI
Psoriasis Area and Severity Index
PD
Pharmacodynamic(s)
PK
pharmacokinetic(s)
PPASI
Palmoplantar Psoriasis Severity Index
PRN
as needed
PSS
Psoriasis Symptoms Scale
PSSI
Psoriasis Scalp Severity Index
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
SAP
statistical analysis plan
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
Short Form 36-item Health Survey
Spga
static Physician’s Global Assessment
study drug
See "investigational product"
SUSARs
suspected unexpected serious adverse reactions
TB
Tuberculosis
TBL
total bilirubin level

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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
ULN
upper limit of normal

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Appendix 2.
Clinical Laboratory Tests 
Clinical Laboratory Tests 
Hematologya
Clinical Chemistrya
Hemoglobin
Serum Concentrations of:
Hematocrit
Sodium
Erythrocyte count (RBC)
Potassium
Mean cell volume 
Total bilirubin
Mean cell hemoglobin
Total protein
Mean cell hemoglobin concentration 
Direct bilirubin
Leukocytes (WBC)
Alkaline phosphatase (ALP)
Cell morphology
Alanine aminotransferase (ALT)
Absolute Counts and Percentage of:
Aspartate aminotransferase (AST)
 Neutrophils, segmented
Gamma-glutamyl transferase (GGT)
 Lymphocytes
Blood urea nitrogen (BUN)
 Monocytes
Creatinine
 Eosinophils
Uric acid
 Basophils
Calcium
Absolute Counts and Percentage of:
Glucose
 Platelets
Albumin
Cholesterol (total)
Urinalysis:
Low-density lipoprotein (LDL)
Specific gravity
High-density lipoprotein (HDL)
Ph
Triglycerides
Protein
Creatine kinase (CK)
Glucose
Ketones
Other:
Bilirubin
HBV DNA testb
Urobilinogen
HCV RNA testb
Blood
Urine pregnancy test (females only; assayed locally by 
clinical study site)
Nitrite
PPD or QuantiFERON®-TB Gold test or T-SPOT®.TB 
testc
Urine leukocyte esterase
Anti-mirikizumab antibodies (immunogenicity)a
Microscopic examination of sediment
Serum mirikizumab concentration (PK)a
Tryptasea

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Complement panel (C3 and C4)a
Cytokine panela
High-sensitivity C-reactive protein (hsCRP)
Abbreviations:  DNA = deoxyribonucleic acid; HBV = hepatitis B virus; HCV = hepatitis C virus; IP = 
investigational product; PK = pharmacokinetic; PPD = purified protein derivative (skin test); RBC = red blood 
cell; RNA  =ribonucleic acid; TB = tuberculosis; WBC = white blood cell.
Note:  Tuberculosis testing will be conducted based on clinical assessment of TB risk (symptoms/signs/known or 
suspected TB exposure), and as required by local regulations and/or local standard of care.
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
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.
c
Tuberculosis 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 the following:

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
Eli Lilly and Company (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 Investigator’s
Brochure (IB) and updates during the course of the study

ICF

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 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 with 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 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.  The 
CRF 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 or electrocardiogram 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-AMAH 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

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Congo
Myanmar
Ukraine
Democratic Republic of the Congo
Namibia
Uzbekistan
Ethiopia
Nigeria
Vietnam
Ghana
Pakistan
Zambia
Guinea-Bissau
Papua New Guinea
Zimbabwe
Source:  WHOb [WWW]

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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-AMAH(a) 
Summary (A Multicenter, Long-Term Extension to 
Evaluate the Long-Term Safety and Maintenance of 
Treatment Effect of Mirikizumab in Patients with 
Moderate-to-Severe Plaque Psoriasis [OASIS-3])
Overview
Protocol I6T-MC-AMAH (A Multicenter, Long-Term Extension to Evaluate the Long-Term
Safety and Maintenance of Treatment Effect of Mirikizumab in Patients with 
Moderate-to-Severe Plaque Psoriasis [OASIS-3]) 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:

Text has been added to Section 7.3 (Blinding).  This text clarifies the roles and 
responsibilities of site personnel who know the treatment assignments of patients in 
Study AMAH, through their work in an originating study

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-AMAH Amendment (a)
Section # and Name
Description of Change
Brief Rationale
Global
Various typos fixed and clarifications made
Section 2.  Schedule of Activities
1.
Added “temperature” to Vital Signs
2.
Added immunogenicity and associated PK 
sample to V1, for patients with no sample 
within prior 4 weeks
1.
Regulatory request from US FDA
2.
Ensures continuity of immunogenisity 
sampling
Section 5.1.3.  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 6.1.  Inclusion Criteria
Added that local contraception guidelines must be 
followed
Allow sites to meet local regulatory requirements
Section 7.3.  Blinding
Added text to clarify the roles and responsibilities 
of site personnel who know the treatment 
assignments of patients in Study AMAH, through 
their work in an originating study
Original protocol assumed all personnel start the 
study blinded, which is not necessarily true as 
patients continue from an originator study into this 
one with the same site personnel.
Section 7.8.2.1.  Management of Hypersensitivity 
Events, Inlcuding 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
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 rest of the protocol.  
2.
Alignment with commitment to US FDA

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Section 8.2 Discontinuation from the Study (sixth 
subbullet of third bullet point)
“Clinically significant systemic hypersensitivity 
event following administration of investigational 
product that does not respond to symptomatic 
medication or results in clinical sequelae.”
Alignment with commitment to US FDA
Section 9.4.4.  Immunogenicity Assessments
Added that immunogenicity samples will be 
evaluated for PK, ADA, and additional exploratory 
markers of hypersensitivity.
To provide information in the event of a 
hypersensitivity event
Section 9.4.5.1.  Physical Examination and 
Section 2.  Schedule of Activities
Added peripheral lymph nodes to list for symptom-
directed evaluation
New safety guideline
Section 9.4.5.2.  Tuberculosis
Added expectation on timing of clinical 
assessments of TB risk
Clarification
Appendix 2.  Clinical Laboratory Tests
1.
Added “Gamma-glutamyl transferase (GGT)”
to list of clinical chemistry.
2.
Exploratory hypersensitivity biomarkers added
1.
Regulatory request from US FDA
2.
To provide information in the event of a 
hypersensitivity event
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 2.  Schedule of Activities (overleaf)

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Table AMAH.1.
Schedule of Activities (Table Truncated)
Procedurea
Treatment Period (Visits 1-14, every-8-week visits)
Visit Number
V1b
V2
V3
V4
V5
V6
V7
V8
V9
V10
V11
V12
V13
V14
Week Relative to Study Drug 
Initiation
0
8
16
24
32
40
48
56
64
72
80
88
96
104
Day Relative to Study Drug 
Initiation, with Visit Tolerance 
Interval
1 
5
57 
5
113 
5
169 
5
225 
5
281 
5
337 
5
393 
5
449 
5
505 ± 
5 
561 
5
617 
5 
673 
5
729 
5
Vital signs (BP, temperature, and 
heart rate)d
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Immunogenicity for 
mirikizumabn
Xo
X
X
X
X
X
X
Serum for mirikizumab 
concentrations (PK)p
Xo
X
X
X
X
X
X
Procedurea
Treatment Period (Visits 15-21, every-16-week visits)
ETVr
Follow-up Period (Visits 
801 and 802)
Visit Number
V15
V16
V17
V18
V19
V20
V21
V801
V802
Week Relative to Study Drug Initiation
120
136
152
168
184
200
208
LV +4W
LV
+12W
Day Relative to Study Drug Initiation, with 
Visit Tolerance Interval
841 
5
953 
5
1065 
5
1177 
5
1289 5
1401 
5
1457 
5
29
± 5
11285
± 5
Vital signs (BP, temperature, and heart rate)d
X
X
X
X
X
X
X
X
X
X
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 Visit 1.  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) (see Section 9.4.5.1.)  Physical examination does not need to be performed again if Visit 1 occurs on the same date as 
the last visit of the originator study and if physical examination was performed at the last visit of the originator study.
e
Tuberculosis testing will be conducted based on clinical assessment of TB risk (symptoms/signs/known or suspected TB exposure; risk factors detailed in 
Appendix 5), determined by the principal investigator, and according to local regulations and/or local standard of care (Section 9.4.6).  Tuberculosis 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 the 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 Section 9.4.5.2.

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f
The preferred order of completion is Supine supine ECGs should be completed prior to vital signs, blood sampling, or any other study proceduresstudy dose 
administration.  For additional details on ECG collection, see Section 9.4.1. An ECG should be performed at the ETV and Visit 802, only if there is early 
termination due to a cardiovascular event.
o
Sample from last vist of originator study should be used.  If no sample <4 weeks old is available, then a baseline sample should be collected in this study.
p
Scheduled Ppharmacokinetic samples are taken as an aliquot from the immunogenicity sample.  Unscheduled pharmacokinetic 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.

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Section 5.1.3.  Post-Treatment Follow-Up Period (12 Weeks)
All patients, whether they discontinue early for any reason or complete study treatment, will 
enter the 12-week Post-Treatment Follow-Up Period (Visit 801 and Visit 802) of Study AMAH.
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 AMAH.1.
Illustration of study design for Clinical Protocol I6T-MC-AMAH.
Section 6.1.  Inclusion Criteria
Patient Characteristics
[2b] Female Patients
Women of child-bearing potential:
Entry from
originator study: 
AMAF
W0
V1
Pts previously on 300 mg miri, fixed 
Q8W or PRN: 250 mg miri Q8W
Pts previously on 30 mg or 100 mg 
miri PRN: 125 mg miri Q8Wb
W104
V14
Extension Treatment Perioda
Visits every 16 weeks
LV+48w
V801
LV+12w
V802
Post-Treatment 
Follow-Up Period
All Pts: 250 mg miri Q8W
W208
V21
Visits every 8 weeks 
aPatients will remain blinded to treatment until the last patient completes the last originator study. 
bPatients receiving 125 mg Q8W may be eligible to escalate to 250 mg Q8W, see section 7.4
Entry from
originator study: 
AMAJ, AMAK
Pts previously on miri: Continue dose 
most recently used in originator study 
(250 mg miri Q8W or 125 mg miri Q8Wb)
Pts previously on placebo or 
secukinumab: 250 mg miri Q8W
Entry from
originator study: 
AMBK

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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, or 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, 1 of the 2 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.

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Section 7.1.  Treatments Administered
Table AMAH.3.
Treatment Regimens
Originator Study
Treatment at End of Originating 
Study
Treatment in Study AMAH (Q8W)*
AMBK
250 mg miri Q4W
250 mg miri
(2 x 1-ml mL miri PFS)
AMAF
300 mg miri, Q8W fixed or PRN
250 mg miri
(2 x 1-ml mL miri PFS)
30 mg or 100 mg miri PRN
125 mg miria
(1 x 1-ml mL miri PFS plus 
1 x 1-mL placebo PFSb)
AMAJ
250 mg miri Q8W or secukinumab
250 mg miri
(2 x 1-ml mL miri PFS)
125 mg miri Q8W
125 mg miria
(1 x 1-ml mL miri PFS plus 
1 x 1-mL placebo PFSb)
AMAK
250 mg miri Q8W or placebo
250 mg miri
(2 x 1-ml mL miri PFS)
125 mg miri Q8W
125 mg miria
(1 x 1-ml mL miri PFS plus 
1 x 1-mL placebo PFSb)
…At the time of unblinding, patients, site personnel and the Sponsor will become unblinded so 
that patients on the 125 mg miri can stop receivingrecieving a 1 x 1-mL placebo PFS (see
Table AMAH.3).
Section 7.3.  Blinding
This is a double-blind study until the originating studies AMAJ and AMAK have had database 
lock and dosing for those studies is no longer blinded.  The blinding applies to patients, site 
personnel, and Sponsor personnel.
Personnel in the originator Studies AMAF and AMAJ performing unblinded tasks (e.g., study 
drug dosing/dispensing) will by default know the treatment assignments of individual patients in 
Study AMAH by the protocol design.  If these unblinded site personnel in the originator Studies
AMAF and AMAJ also have a role in Study AMAH, they must assume the same responsibilities 
taken in the originator study for these patients and must not be involved in any patient 
assessment activities, seek any information related to these patients beyond their allowed 
activities, discuss the treatment assignment with the patient or with the blinded personnel.  

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Principal Investigators will need to ensure that the blinded conditions of the originating studies 
are maintained during Study AMAH until database lock has occurred and dosing for those 
studies is no longer blinded.
Section 7.7.  Concomitant Therapy
Table AMAH.4.
Excluded Classes of Concomitant Medications or Classes with 
Restricted Use (Table Truncated)
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, 
certolizuamab)
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 months or 12 weeks, respectively, after 
discontinuation of study drug).
N
N
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)

Urticaria (hives)

Angioedema (for example, swelling of the lips and/or tongue) 

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
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 the 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 (assess 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.
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 

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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:

Opportunistic Infections, including opportunistic 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, electrocardiograms (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.

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Section 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.
Section 9.4.4.  Immunogenicity Assessments
At the visits and times specified in the Schedule of Activities (Section 2), venous blood samples 
will be collected to determine antibody production against mirikizumab.  To interpret the results 
of immunogenicity, a blood sample for PK analysis will be collected at the same time points.  All 
samples for immunogenicity should be taken predose when applicable.  With reports of 
hypersensitivity events (immediate or non-immediate), additional samples will be collected as 
close to the onset of the event as possible, at the resolution of the event, and 30 days following 
resolution of the event.  Samples will be evaluated for PK, ADA, and additional exploratory 
markers of hypersensitivity (see Section 7.8.2.1).  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.  
Immunogenicity will be assessed by a validated assay designed to detect ADAs in the presence 
of mirikizumab at a laboratory approved by the Sponsor. Patient samples will be analyzed using 
a 4-tiered approach.  All samples will be assessed in Tier 1 (screening).  Samples above the 
disease state screening assay cut point factor (Tier 1) will be assessed in Tier 2 (confirmation).  
Any samples confirmed as positive for anti-mirikizumab antibodies in Tier 2 will be reported as 
“detected.”  All samples below the screening assay cut point factor in Tier 1 or not confirmed in 
Tier 2 will be reported as “not detected.”  Any “detected” sample in Tier 2 will be assessed in 
Tier 3 (titer assessment; values reported) and Tier 4 (neutralizing ADA assay).  Any samples 
above the disease state Tier 4 cut point will be reported as “detected” for neutralizing antibodies;
samples below the disease state Tier 4 cut point will be reported as “not detected” for 
neutralizing antibodies.  
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)
require.  The duration allows the Sponsor to respond to future regulatory requests related to 
mirikizumab.  Any samples remaining after 15 years will be destroyed. 

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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
Diagnosis of LTBI During Study
Tuberculosis testing in Study AMAH 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.
Appendix 2.  Clinical Laboratory Tests
Clinical Laboratory Tests (Table Truncated)
Clinical Chemistrya
Serum Concentrations of:
Gamma-glutamyl transferase (GGT)
Other
Tryptasea
Complement panel (C3 and C4)a
Cytokine panela
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.
c
Tuberculosis 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 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.

Leo Document ID = 1aa133d6-0689-4275-822c-c0dcb7ebad8a
Approver: 
Approval Date & Time: 15-Nov-2018 22:30:40 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 15-Nov-2018 22:36:40 GMT
Signature meaning: Approved
PPD
PPD