Relative Bioavailability of LY3074828 Solution Formulation in Pre-Filled Syringes Compared to Lyophilized Formulation After Single Subcutaneous Administration
Phase: PHASE1
Conditions: Healthy
Sponsor: Eli Lilly and Company

Protocol I6T-MC-AMAE 
 
 
Relative Bioavailability of LY3074828 Solution Formulation in Pre-Filled Syringes Compared to 
Lyophilized Formulation After Single Subcutaneous Administration 
 
NCT03188510 
 
Approval Date: 05-Apr-2017 
 
 
 

I6T-MC-AMAE Clinical Pharmacology Protocol
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LY3074828
Protocol I6T-MC-AMAE
Relative Bioavailability of LY3074828 Solution Formulation 
in Pre-Filled SyringesCompared to Lyophilized
FormulationAfter Single Subcutaneous Administration
Confidential Information
The information contained in this protocol 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 
LY3074828, unless such persons are bound by a confidentiality agreement with Eli Lilly 
and Company or its subsidiaries.
Note to Regulatory Authorities:  This document may contain protected personal data 
and/or commercially confidential information exempt from public disclosure.  Eli Lilly and 
Company requests consultation regarding release/redaction prior to any public release.  In 
the United States, this document is subject to Freedom of Information Act (FOIA) 
Exemption 4 and may not be reproduced or otherwise disseminated without the written 
approval of Eli Lilly and Company or its subsidiaries.
Approval Date: 05-Apr-2017 GMT
LY3074828
Eli Lilly and Company
Indianapolis, Indiana USA 46285
Clinical Pharmacology Protocol Electronically Signed and Approved by Lilly on date 
provided below.

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LY3074828
Table of Contents
Relative Bioavailability of LY3074828 Solution Formulation in 
Pre-Filled Syringes Compared to Lyophilized Formulation
After Single Subcutaneous Administration
Section
Page
Protocol I6T-MC-AMAE Relative Bioavailability of LY3074828 Solution 
Formulation in Pre-Filled Syringes Compared to Lyophilized 
Formulation After Single Subcutaneous Administration......................................................1
Table of Contents........................................................................................................................2
1.
Protocol Synopsis................................................................................................................7
2.
Schedule of Activities .........................................................................................................9
3.
Introduction ......................................................................................................................13
3.1.
Study Rationale............................................................................................................13
3.2.
Background..................................................................................................................13
3.3.
Benefit/Risk Assessment..............................................................................................14
4.
Objectives and Endpoints..................................................................................................16
5.
Study Design.....................................................................................................................17
5.1.
Overall Design .............................................................................................................17
5.2.
Number of Participants.................................................................................................17
5.3.
End of Study Definition ...............................................................................................17
5.4.
Scientific Rationale for Study Design...........................................................................17
5.5.
Justification for Dose ...................................................................................................18
6.
Study Population...............................................................................................................19
6.1.
Inclusion Criteria..........................................................................................................19
6.2.
Exclusion Criteria ........................................................................................................21
6.3.
Lifestyle and/or Dietary Requirements .........................................................................23
6.3.1.
Meals and Dietary Restrictions.............................................................................23
6.3.2.
Caffeine, Alcohol, and Tobacco ...........................................................................23
6.3.3.
Activity................................................................................................................23
6.4.
Screen Failures.............................................................................................................23
7.
Treatment..........................................................................................................................24
7.1.
Treatment Administered...............................................................................................24
7.1.1.
Packaging and Labeling .......................................................................................25
7.2.
Method of Treatment Assignment ................................................................................26
7.2.1.
Selection and Timing of Doses.............................................................................26
7.3.
Blinding .......................................................................................................................26

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7.4.
Dose Modification........................................................................................................26
7.5.
Preparation/Handling/Storage/Accountability...............................................................26
7.6.
Treatment Compliance .................................................................................................27
7.7.
Concomitant Therapy...................................................................................................27
7.8.
Treatment After the End of the Study...........................................................................27
8.
Discontinuation Criteria ....................................................................................................28
8.1.
Discontinuation from Study Treatment.........................................................................28
8.1.1.
Discontinuation of Inadvertently Enrolled Subjects..............................................28
8.2.
Discontinuation from the Study....................................................................................28
8.3.
Subjects Lost to Follow-up...........................................................................................28
9.
Study Assessments and Procedures ...................................................................................29
9.1.
Efficacy Assessments...................................................................................................29
9.2.
Adverse Events ............................................................................................................29
9.2.1.
Serious Adverse Events........................................................................................30
9.2.1.1.
Suspected Unexpected Serious Adverse Reactions..........................................31
9.2.2.
Complaint Handling.............................................................................................31
9.3.
Treatment of Overdose.................................................................................................31
9.4.
Safety...........................................................................................................................31
9.4.1.
Laboratory Tests ..................................................................................................31
9.4.2.
Vital Signs ...........................................................................................................31
9.4.3.
Electrocardiograms ..............................................................................................32
9.4.4.
Tuberculosis Testing ............................................................................................32
9.4.5.
Safety Monitoring ................................................................................................32
9.4.5.1.
Hepatic Safety................................................................................................33
9.4.5.2.
Monitoring of Hypersensitivity Reactions.......................................................33
9.4.6.
Injection-Site Assessments...................................................................................34
9.5.
Pharmacokinetics .........................................................................................................34
9.5.1.
Bioanalysis...........................................................................................................34
9.6.
Pharmacodynamics ......................................................................................................35
9.6.1.
Immunogenicity Assessments ..............................................................................35
9.7.
Genetics .......................................................................................................................36
9.8.
Biomarkers...................................................................................................................36
9.9.
Health Economics ........................................................................................................36
10.
Statistical Considerations and Data Analysis.....................................................................37
10.1. Sample Size Determination ..........................................................................................37
10.2. Populations for Analyses..............................................................................................37
10.2.1.
Study Participant Disposition ...............................................................................37
10.2.2.
Study Participant Characteristics ..........................................................................37

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10.3. Statistical Analyses ......................................................................................................37
10.3.1.
Safety Analyses....................................................................................................38
10.3.1.1.
Clinical Evaluation of Safety..........................................................................38
10.3.1.2.
Statistical Evaluation of Safety.......................................................................38
10.3.2.
Pharmacokinetic Analyses....................................................................................38
10.3.2.1.
Pharmacokinetic Parameter Estimation...........................................................38
10.3.2.2.
Pharmacokinetic Statistical Inference .............................................................38
10.3.3.
Pharmacodynamic Analyses.................................................................................39
10.3.4.
Pharmacokinetic/Pharmacodynamic Analyses......................................................39
10.3.5.
Evaluation of Immunogenicity .............................................................................39
10.3.6.
Exploratory Analysis............................................................................................39
10.3.7.
Data Review During the Study.............................................................................39
10.3.8.
Interim Analyses..................................................................................................40
11.
References ........................................................................................................................41

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List of Tables
Table
Page
Table AMAE.1.
Objectives and Endpoints .......................................................................16
Table AMAE.2.
Treatments Administered........................................................................24

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List of Appendices
Appendix
Page
Appendix 1.
Abbreviations and Definitions ................................................................42
Appendix 2.
Clinical Laboratory Tests........................................................................46
Appendix 3.
Study Governance, Regulatory and Ethical Considerations.....................47
Appendix 4.
Hepatic Monitoring Tests for Treatment-Emergent Abnormality ............50
Appendix 5.
Blood Sampling Summary......................................................................51

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1.Protocol Synopsis
Title of Study:
Relative Bioavailability of LY3074828 Solution Formulation in Pre-FilledSyringes Compared to Lyophilized 
Formulation After Single Subcutaneous Administration
Rationale:  
Study I6T-MC-AMAE (AMAE) is a Phase 1 study conducted in healthy subjects to determine the relative 
bioavailability ofLY3074828 solution formulationssupplied in pre-filled syringes(PFSs)compared tolyophilized 
formulation supplied in a vial, after single subcutaneous administration.  The lyophilized formulation was used in 
completed and ongoing Phase 1 and 2 clinical trials.  The solution formulation supplied in PFSsis being developed 
as the commercial formulation of LY3074828 for the treatment of autoimmune and inflammatory diseases to offer a 
more convenient method of administration.
Objectives/Endpoints:  
Objectives
Endpoints
Primary
To evaluate the relative bioavailability ofLY3074828
solution formulation in PFSsand lyophilized
formulation.
The ratio of geometric least square means between the 
 LY3074828 solution formulation supplied in the 
PFSs and the 
 LY3074828lyophilized 
formulation forarea under the concentration-time curve 
from time 0 extrapolated to infinity (AUC[0-∞]), and 
area under the concentration-time curve from time 0 to 
the time of last measurable concentration(AUC[0-t
last]).  
Secondary
To evaluate the relative bioavailability of  
 and 
 LY3074828 solution formulations, and 
 
LY3074828 solution formulations in PFSs and 
 
LY3074828 lyophilizedformulation.
To assess the tolerability of LY3074828 in healthy 
subjects.
The ratio of geometric least square means between the 
 and  
 LY3074828 solution formulations
supplied in PFSs, and between the 
 LY3074828 
solutions formulation supplied in PFSs and the 
 
LY3074828 lyophilizedformulation,for AUC(0-∞) and 
AUC(0-t
last).
Incidence of treatment-emergent adverse events 
(TEAEs).
Incidence of treatment-emergent anti-drug antibodies 
(TE-ADAs).
Summary of Study Design:  
CCI
Study AMAE is a single-center, randomized, parallel-treatment, open-label, Phase1 single-dose study evaluating 
LY3074828 in healthy subjects. 
Subjects will report to the clinical research unit (CRU) on Day -1 and will remain at the CRU until the scheduled 
procedures have been completed on Day 2.  After randomization, study drug will be administered by subcutaneous 
(SC)injection in the morning of Day 1 after an overnight fast.  Subjects will be followed for 12 weeks following 
dose administration to assess the tolerability andpharmacokinetics(PK)of LY3074828.
CCI
CCI
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CCI
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Safety and tolerability will be explored by clinical laboratory tests, vital sign measurements, 12-lead 
electrocardiograms (ECGs), recording of adverse events (AEs), physical examinations/medical assessments, 
immunogenicity,and injection-site assessments.
Treatment Arms and Duration:  
Subjects will each receive a single SC dose of LY3074828 and will be randomized to 1 of 3 treatment arms:
Reference:  
 LY3074828 lyophilized formulation, as three SC injections
Test 1:  
 LY3074828 solution formulation in two PFSs, as SC injections
Test 2:  
 LY3074828 solution formulation in four PFSs, as SC injections
Number of Subjects:  
Approximately 54 subjects(18 per treatment arm)may be enrolled in this study to allow evaluable data from 16 
subjects per treatment arm to be obtained.  A subject’s study participation is considered as complete if he/she 
received the study drug and completes all activities up to and including at least Day 57.  A maximum of 6 subjects 
may be replaced if pharmacokinetic (PK)and anti-drug antibody (ADA) samplesare not collected up to and 
including Day 57.
Statistical Analysis:
Pharmacokinetic parameter estimates will be evaluated to delineate effects of formulation.  Log-transformed 
dose-normalized (DN)-AUC(0-∞
CCI
), DN-AUC(0-tlast),and DN-maximum drug concentration (Cmax) will be 
evaluated in a linear fixed-effects model with a fixed effect for formulation.  For the primary endpoint, a model 
comparing the differences between the 
 LY3074828 solution formulation and the  
 LY3074828 
lyophilized formulationwill be used.  For the secondary endpoints, amodelcomparing the differences between the 
 LY3074828 solution formulation and the  
 LY3074828 lyophilized formulation, and between the 
 and  
 LY3074828 solution formations will be used.  Differenceswill be back-transformed to present 
the ratios of geometric least squares means and the corresponding 90%confidence interval (CI).  If leakage occurs 
frequently, whether injection-siteleakage occurred (yes/no) may also be included as a covariate in the model.  
Furthermore, if leakage is found to be significant, the amount of leakage will also be added to the model.
Time of Cmax(tmax) will be analyzed using a Wilcoxon rank sum test.  Estimates of the median difference, 90% 
CIs,and p-values from the Wilcoxon rank sum test will be calculated.
AdditionalPKanalyses may be conducted if deemed appropriate.
Safety parameters will be listed,and summarized using standard descriptive statistics.The 0 hour (post-injection) 
pain score will be evaluated in a linear fixed-effects model with a fixed effect for treatment.  The distribution of the 
data will be explored prior to analysis to determine whether data transformation is required.  The differences 
between the  
 and 
 injections for the lyophilized formulation will be back-transformed (if applicable) to 
present the ratios of geometric least squares means and the corresponding 90% CI.
Additional safety and tolerability analyseswill be performed if warranted upon review of the data.
CCI
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2. Schedule of Activities

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Study Schedule Protocol I6T-MC-AMAE
Screening
Days
Comments
Procedure
≤ 28 days
-1
1
2
4
±1d
8
±1d
11
±1d
15
±2d
22
±2d
29
±2d
43
±2d
57
±3d
71
±3d
85/ED
±3d
Informed consent
X
Review / confirm 
inclusion/exclusion criteria
X
X
Any time prior to dosing.
Subject admission to CRU
X
Subject discharge from CRU
X
Outpatient visit
X
X
X
X
X
X
X
X
X
X
X
LY3074828 dose
X
Medical history
X
Weight, height, and BMI
X
Vital signs:  blood pressure, 
pulse rate, temperature (hour)
X
X
Predose,
2, 6
24
72
168 240
336
504
672 1008 1344
X
Times with respect to start of dosing.  Single 
ECGs to be collected. Time allowance for 2, 
6, and 24 hour timepoints:  ±15, ±30, and 
±90 minutes, respectively.  
12-lead ECG (hour)
X
Predose,
2, 6
24
72
168
336
672
1344
X
Physical examination / medical 
assessment
X
X
X
X
Full physical examination/medical assessment
at Day -1 and ED.  Symptom directed
physical examination/ medical assessment at 
all other timepoints, and as deemed necessary 
by the investigator.
AE review
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE only after signing ICF.
QuantiFERON®-TB Gold test 
X
Serology
X
Ethanol test and urine drug 
screen
X
X
May be repeated at the discretion of the 
investigator.
FSH / Serum pregnancy test
X
X
X
X
X
Serum pregnancy tests for female subjects of 
childbearing potential only.  For women who 
are considered to be postmenopausal, FSH
should be drawn at screening to confirm 
postmenopausal status as defined in inclusion 

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Screening
Days
Comments
Procedure
≤ 28 days
-1
1
2
4
±1d
8
±1d
11
±1d
15
±2d
22
±2d
29
±2d
43
±2d
57
±3d
71
±3d
85/ED
±3d
criterion [1b]; women with confirmed 
postmenopausal status can be exempted from
further pregnancy tests during the study.
Clinical chemistry, 
hematology, and urinalysis
X
X
X
X
X
X
Injection-site assessment for 
erythema, induration, 
categorical pain, pruritus, and 
edema (hour)
0, 0.25 
24
168
336
Times with respect to start of dosing.  0 hour
assessments within 5 minutes following 
injection.  Time allowance for 0.25-hour 
assessment is ±5 minutes.  Additional 
assessments performed if deemed necessary 
by the investigator.
Injection-site pain based on 
VAS (hour) 
0, 0.5, 
1, 3, 6
24
Performed for both injections of lyophilized 
formulation into the lower quadrants (ie, first 
2 injections), and for the first injection of 
solution formulation (administered to a lower 
quadrant).  0 hour assessments to be 
performed within 1 minute following 
injection.  Time allowance for 0.5 and 1 hour 
will be ±5 minutes and all other time 
allowances will be ±15 minutes.
Injection-site leakage and 
bleeding assessment (hour)
0
Performed for both injections of lyophilized 
formulation into the lower quadrants (ie, first 
2 injections), and for the first injection of 
solution formulation (administered to a lower 
quadrant).  0 hour assessments to be 
performed within 1 minute following 
injection.
LY3074828 pharmacokinetic 
sampling (hour)
0, 2, 6
24
72
168
240 336
504
672 1008 1344 1680
2016
Times with respect to start of dosing.  0 hour
collection immediately (within 15 minutes) 
before dosing.  Time allowance for 2, 6, and 
24 hour timepoints:  ±15, ±30, and ±90 

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Screening
Days
Comments
Procedure
≤ 28 days
-1
1
2
4
±1d
8
±1d
11
±1d
15
±2d
22
±2d
29
±2d
43
±2d
57
±3d
71
±3d
85/ED
±3d
minutes respectively.
Immunogenicity sample
Predose
X
X
X
X
LY3074828 antibody sample.
Pharmacogenetics sample
X
Abbreviations:  AE = adverse event; BMI = body mass index; CRU = clinical research unit; d = day; ECG = electrocardiogram; ED = early discontinuation; FSH = follicle-
stimulating hormone; ICF = informed consent form; TB = tuberculosis; VAS = visual analog scale.
Site should schedule activities as appropriate.  In cases where several study procedures are scheduled at the same time, follow this order of priority for procedures:  
pharmacokinetic samples, ECG, vital signs, clinical laboratory tests, VAS, injection-site leakage assessment, injection-site assessment, immunogenicity sample, stored sample, 
such that PK sample collection occurs as close to the nominal collection time as possible.  Procedures specified as predose may be performed within 2 hours from planned dosing.  
.

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3.Introduction
3.1. Study Rationale
Study I6T-MC-AMAE (AMAE) is a Phase 1 study conducted in healthy subjects to determine 
the relative bioavailability ofLY3074828solution formulations suppliedin pre-filled syringes 
(PFSs) compared to lyophilizedformulationsupplied in a vial,after single subcutaneous (SC) 
administration.  The lyophilized formulation was used incompleted and ongoing Phase 1 and 2 
clinical trials.  The solution formulation supplied in PFSsis being developed as the commercial 
formulation of LY3074828 for the treatment of autoimmune and inflammatory diseases to offer a 
more convenient method of administration.
3.2. Background
CCI
LY3074828 is a humanized immunoglobulin G4-variant monoclonal antibody that is directed 
against the p19subunit of interleukin-23 (IL-23)and does not bind interleukin-12 (IL-12).  
LY3074828 is being developed for the treatment of autoimmune diseases in whichthe IL-23 
pathway is thought to have a significant pathogenic role.  Neutralization of IL-23 with an 
anti-mouse IL-23 surrogate antibody (directed against the p19 subunit) significantly reduced the 
development of arthritis and inhibited ileal inflammation in a mouse model of 
spondyloarthropathy with bowel inflammation(Ruutu et al. 2012), and additionally,
neutralization of IL-23 significantly reduced the disease score in the relapsing-remitting 
experimental autoimmune encephalomyelitis (multiple sclerosis-like) model in mice.  Anti-IL-23 
antibody also demonstrated some efficacy in preclinical arthritis models, depending on the 
timing of intervention (Cornelissen et al. 2013).  
LY3074828 has been evaluated in 5 healthy volunteers(single  
 SC doses)and in 
33subjects with plaque psoriasis(single ascending IV doses of 
or 
mg) in StudyI6T-MC-AMAA(AMAA).  Furthermore, 43healthy Japanese and Caucasian 
subjects were administered single intravenous (IV)doses of 
 or  
 mg 
LY3074828,or placebo,or single SC doses of  
mg LY3074828, or placebo, in 
StudyI6T-MC-AMAD(AMAD). 
No serious adverse events (SAEs)were reported in either study.There were no drug-related 
treatment-emergent adverse events (TEAEs)of Grade 2 or higher reported in Study AMAA, and 
no infusion reactions or injection-site reactions, orAEs considered related to study drug, were 
reportedin Study AMAD.There were no dose-dependent trends in adverse events (AEs), or
clinically important changes in vital signs, electrocardiograms (ECGs), or clinical laboratory 
resultsacross both studies that were considered to be related to the study drug. 
 
 
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LY3074828
Treatment-emergent anti-drug antibodies (TE-ADAs) developed in 3subjects after 
administration of single IV doses of LY3074828in Study AMAA; however, there was no 
correlation between TE-ADA titers and the doses of LY3074828.  The earliest timepoint at 
which TE-ADAs were detected was Day 22, which was the first postdose timepoint at which 
immunogenicity was assessed.  Treatment-emergent ADAs developed in 2 subjects following 
single SC doses of   mg LY3074828 in Study AMAD; however, titers were ≤1:160.
LY3074828 is currently being evaluated in threePhase 2 studies:
Study I6T-MC-AMAC is being conducted in approximately 240 subjects with ulcerative 
colitis.  Three IV doses of , 
,or 
 mg LY3074828(or placebo)are administered 
every 4weeks (Q4W) during theinduction period.  Subjects with a clinical response are 
subsequently administered SC doses of 
mg LY3074828 (or placebo) 
or
mg 
LY3074828 
 during the 92-week maintenance period.  
 
 
Study I6T-MC-AMAF is being conducted in approximately 200 subjects with plaque 
psoriasis.  Two SC doses of ,  , or   mg LY3074828 (or placebo) are 
administered 
 during the induction period, followed by 
 
 during the 88-week maintenance period.
Study I6T-MC-AMAGis to be conducted in approximately 180 subjects with Crohn’s 
disease(CD).  
 
 LY3074828 treated subjects with an improvement in CD score will 
eithercontinue with this dose regimen,
 
 
3.3. Benefit/Risk Assessment
CCI
Based on LY3074828 nonclinical and preliminary clinical data, there are no anticipated risks 
requiring monitoring beyond those for a typical humanized monoclonal antibody in human 
studies.  As with other immunomodulatory therapies, LY3074828 may increase the risk of 
developing an infectionor may exacerbate an existingseriousinfection. These may include 
opportunistic infections and reactivation of latent infections, such astuberculosis(TB) and
hepatitis B.  Subjectswill therefore be screened for hepatitis B/C, human immunodeficiency 
virus (HIV),and TB. 
Treatment-emergent ADAshave been observedin 2 of the 11 healthy subjects that have been 
administered SC doses of LY3074828; however, titers were ≤1:160.No clinically significant 
safety or tolerability concerns have been identified in patients or subjects to date for LY3074828 
up to the highest dose given 
 
CCI CCI
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LY3074828
Healthy subjects are not expected to derive any benefit from participating in studies of 
LY3074828.  
More information about the known and expected benefits, risks, SAEs and reasonably 
anticipated AEs of LY3074828 are to be found in the Investigator’s Brochure (IB). 

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LY3074828
4.Objectivesand Endpoints
TableAMAE.1shows the objectives and endpoints of the study.
TableAMAE.1.
Objectives and Endpoints
Objectives
Endpoints
Primary
To evaluate the relative bioavailability ofLY3074828
solution formulation in PFSsand lyophilized
formulation.
The ratio of geometric least square means between the 
 LY3074828 solution formulation supplied in the 
PFSs and the  
 LY3074828 lyophilized 
formulation forarea under the concentration-time curve 
from time 0 extrapolated to infinity (AUC[0-∞]), and 
area under the concentration-time curve from time 0 to 
the time of last measurable concentration(AUC[0-t
last]).
Secondary
To evaluate the relative bioavailability of  
 and 
 LY3074828 solution formulations, and 
 
LY3074828 solution formulation in PFSs and 
 
LY3074828 lyophilizedformulation.
To assess the tolerability of LY3074828 in healthy 
subjects.
The ratio of geometric least square means between the 
 and  
 LY3074828 solution formulations
supplied in PFSs, and between the 
 LY3074828 
solutions formulation supplied in PFSs and the 
 
LY3074828 lyophilizedformulation, for AUC(0-∞) and 
AUC(0-t
last).
Incidence of treatment-emergent adverse events 
(TEAEs).
Incidence of treatment-emergent anti-drug antibodies 
(TE-ADAs).
Exploratory 
To assess local tolerabilityand leakage ofa 
LY3074828 lyophilized formulationand solution 
formulations supplied in PFSsat injection-sites.
Assessments of pain (using avisual analog scale).
Incidence of erythema, induration, categoricalpain, 
pruritus, edema, and leakage at injection-sites.
CCI
CCI
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LY3074828
5.Study Design
5.1. OverallDesign
Study AMAE is a single-center, randomized, parallel-treatment, open-label, Phase1 single-dose 
study evaluating LY3074828healthy subjects. 
Screening Period (≤28 days):  Subjects shouldbe evaluated for study eligibility ≤28 days prior 
to enrollment.
Residential Period (2 days): Fifty-foursubjects who fulfill the eligibility criteria will be 
randomized to 1 of 3treatmentarms, with 18subjects randomized to eacharm:
Reference:  
 LY3074828 lyophilized formulation,as three SC injections
Test 1: 
 LY3074828 solution formulation in twoPFSs,as SC injections
Test 2:  
 LY3074828 solution formulation in four PFSs, as SC injections
Subjects will report to the clinical research unit (CRU) on Day -1 and will remain at the CRU 
until the scheduled procedures have been completed on Day 2, as defined in the Schedule of 
Activities (Section 2).  After randomization, study drug will be administered bySCinjectionin 
the morning of Day1 afteran overnight fast.  Subjects within the same enrollment group may be 
dosed across several days if required by the site for logistical or other purposes.  
Outpatient Follow-up Period (12weeks):  The follow-up period will include outpatient visits 
for a total of 12 weeks following dose administration on Day 1 to assess tolerability and PK of 
LY3074828.  
5.2. Number of Participants
Approximately 54 subjects(18 per treatment arm)may be enrolled in this study to allow 
evaluable data from 16 subjects from each treatment armto be obtained.  A subject’s study 
participation is considered as complete if he/she received the study drug and completes all 
activities up to and including at least Day 57.  A maximum of 6 subjects may be replaced ifPK 
and anti-drug antibody (ADA)samplesare not collected up to and including Day 57.
5.3. End of Study Definition
End of the studyis the date of the last visit or last scheduled procedure shown in the Schedule of 
Activities(Section 2) for the last subject.
5.4. Scientific Rationale for Study Design
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Conducting the study in healthy subjects mitigates the potential confounding effects of the 
disease state and concomitant medications in patients.  Healthy subjects are frequently used in 
the assessment of bioavailability of both small and large molecules.
Single doses of LY3074828 and the PK sampling timepoints have been selected to generate PK 
profiles sufficient to fulfill the study objectives.  As the primary endpoints of this study are 
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PK-related and are not subject tobias, it is not considered necessary for this study to be blinded.  
Subjects and site staff will be aware of the administration route.
A parallel-group design was chosen because a crossover design is impractical for compounds 
that have long half-lives, such as monoclonal antibodies.  Additionally, a crossover study design 
could confound PK data if subjects develop neutralizing ADAs.
Monoclonal antibody therapy has been associated with hypersensitivity reactions, including
injection-sitereactions.  Follow-up details on injection-site reactions will be collected by the 
investigative site regarding the severity, duration, type, and timing of the start of the event in 
relation to the start of study drug administration in order to further characterize these events.
5.5. Justification for Dose
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6. Study Population
Eligibility of subjects for study enrollment will be based on the results of medical history, 
physical examination, vital signs, clinical laboratory tests, and electrocardiogram (ECG).  
The nature of any conditions present at the time of the physical examination and any pre-existing 
conditions will be documented.
Screening should occur up to 28 days prior to enrollment.  Subjects who are not enrolled within 
28 days of screening may be subjected to an additional medical assessment and/or clinical 
measurements to confirm their eligibility.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, are not permitted.
6.1.
Inclusion Criteria
Subjects are eligible for inclusion in the study only if they meet all of the following criteria at 
screening and/or enrollment:
[1] are overtly healthy males or female subjects, as determined by medical history 
and physical examination.  
[1a] male subjects:
a) male subjects with non-pregnant partners of childbearing potential must 
use a male condom with spermicide, or agree that a sponge with 
spermicide will be used by the female partner, for the duration of the 
study, and for 24 weeks following dosing with the study drug.  Barrier 
protection methods without concomitant use of spermicide are not an 
effective or acceptable method of contraception.  The combined use of 
male and female condoms as a method of contraception is not acceptable
b) male subjects with pregnant partners must use condoms during intercourse 
for the duration of the study, and for 24 weeks following dosing with the 
study drug
c) for male subjects with female partners of non-childbearing potential, 
contraceptive requirements do not apply
d) for male subjects who are exclusively in same sex relationships, as their 
preferred and usual lifestyle, contraceptive requirements do not apply
e) male subjects should refrain from sperm donation for the duration of the 
study, and for 24 weeks following dosing with the study drug
[1b] female subjects:
women of non-childbearing potential may participate, and include those who 
are:

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a) infertile due to surgical sterilization (at least 6 weeks following 
hysterectomy, bilateral oophorectomy) with verbal confirmation of 
surgical success, or congenital anomaly such as mullerian agenesis
b) postmenopausal, defined as:
a.
a women at least 50 years of age, not on hormone therapy, with an 
intact uterus, and who has had:
cessation of menses for at least 1 year, or
at least 6 months of spontaneous amenorrhea, without an 
alternative medical cause, and confirmed with a 
follicle-stimulating hormone >40 mIU/mL, or
b. a woman of at least 55 years of age, not on hormone therapy, who 
has had at least 6 months of spontaneous amenorrhea, without an 
alternative medical cause, or
c.
a woman of at least 55 years of age, with a diagnosis of menopause 
prior to starting hormone-replacement therapy
women of childbearing potential may participate, and must agree to use a 
highly effective method of contraception (ie, a contraceptive measure with a 
failure rate of <1% per year), in addition to the use of a male condom with 
spermicide by the male partner, for the duration of the study, and for 12 weeks 
following dosing with the study drug
Highly effective methods of contraception include:

placement of a hormonal or non-hormonal intrauterine device, or

established use of oral, injected, or implanted hormonal 
contraception associated with inhibition of ovulation, or

male partner sterilized, with verbal confirmation of surgical 
success (the vasectomized male partner must be the sole partner of 
that subject), or

bilateral tubal ligation
Additionally:
a) women of childbearing potential must test negative for pregnancy prior to 
initiation of treatment based on a serum pregnancy test at the screening 
visit and on Day -1
b) for female subjects who are exclusively in same sex relationships, as their 
preferred and usual lifestyle, contraceptive requirements do not apply
[2]
are 18 to 65 years of age, inclusive, at time of screening
[3]
have a body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive, at time of 
screening

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[4]
have clinical laboratory test results within normal reference range for the 
investigative site, or results with acceptable deviations that are judged to be 
not clinically significant by the investigator
[5]
have venous access sufficient to allow for blood sampling as per the protocol
[6]
are reliable and willing to make themselves available for the duration of the 
study and are willing to follow study procedures
[7]
are able and willing to give signed informed consent
6.2.
Exclusion Criteria
Subjects will be excluded from study enrollment if they meet any of the following criteria at 
screening and/or enrollment:
[8] are investigative site personnel directly affiliated with this study and their 
immediate families.  Immediate family is defined as a spouse, biological or 
legal guardian, child, or sibling.
[9] are Lilly employees or employees of Covance
[10] are currently enrolled in a clinical study involving an investigational product 
or any other type of medical research judged not to be scientifically or 
medically compatible with this study  
[11] have participated in a clinical trial involving an investigational product within 
30 days or 5 half-lives (whichever is longer) prior to screening.  If the clinical 
trial involved treatment with biologic agents (such as monoclonal antibodies, 
including marketed drugs), at least 3 months or 5 half-lives (whichever is 
longer) should have elapsed prior to Day 1
[12]
have previously completed or withdrawn from this study or any other study 
investigating LY3074828, and have previously received the investigational 
product 
[13]
have known allergies to LY3074828, related compounds or any components 
of the formulation, or history of significant atopy
[14]
have an abnormality in the 12-lead ECG that, in the opinion of the 
investigator, increases the risks associated with participating in the study
[15]
have an abnormal blood pressure as determined by the investigator
[16]
have a history or presence of cardiovascular, respiratory, hepatic, renal, 
gastrointestinal, endocrine, hematological (including thalassemia and serious 
glucose-6-phosphate dehydrogenase deficiency), or neurological disorders 
capable of significantly altering the absorption, metabolism, or elimination of 
drugs; of constituting a risk when taking the investigational product; or of 
interfering with the interpretation of data
[17]
have known or ongoing psychiatric disorders deemed clinically significant by 
the investigator

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[18]
regularly use known drugs of abuse and/or show positive findings on drug 
screening
[19]
show evidence of HIV infection and/or positive human HIV antibodies
[20]
show evidence of hepatitis C and/or positive hepatitis C antibody
[21]
show evidence of hepatitis B, and/or positive hepatitis B surface antigen, 
and/or hepatitis B core antibody
[22]
are women who are lactating
[23]
have used or intend to use over-the-counter or prescription medications, 
including herbal medications, within 14 days prior to dosing and for the 
duration of the study.  Stable doses of oral contraceptive or hormone-
replacement therapy are permitted, at the discretion of the investigator
[24]
have donated blood of more than 500 mL within the month prior to screening 
[25]
have an average weekly alcohol intake that exceeds 21 units per week (males) 
and 14 units per week (females), have a positive test for ethanol, or are 
unwilling to abide by the alcohol restrictions described in Section 6.3.2 (1 unit 
= 12 oz or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of 
distilled spirits)
[26]
have a tobacco consumption of more than 10 cigarettes per day (or 
equivalent), are unwilling to refrain from smoking for approximately 1 hour 
prior to each ECG and vital sign measurements during the study, or who are 
unwilling to abide by the CRU smoking guidelines described in Section 6.3.2
[27]
have had symptomatic herpes zoster within 3 months of screening
[28]
show evidence of active or latent TB, as documented by medical history, 
examination, and TB testing (negative [not indeterminate] QuantiFERON®-
TB Gold test); or have had household contact with a person with active TB, 
unless appropriate and documented prophylaxis treatment has been given
[29]
have received live vaccine(s), including attenuated live vaccines, and those 
administered intranasally, within 8 weeks of screening, or intend to during the 
study
[30]
have been treated with steroids within 1 month of screening, or intend to 
during the study
[31]
are immunocompromised
[32]
have received treatment with biologic agents (such as monoclonal antibodies) 
for a medical condition within 3 months or 5 half-lives (whichever is longer) 
prior to Day 1
[33]
have significant allergies to humanized monoclonal antibodies 

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[34]
have clinically significant multiple or severe drug allergies, or intolerance to 
topical corticosteroids, or severe post treatment hypersensitivity reactions 
(including, but not limited to, erythema multiforme major, linear 
immunoglobulin A dermatosis, toxic epidermal necrolysis, or exfoliative 
dermatitis)
[35]
have had lymphoma, leukemia, or any malignancy within the past 5 years 
except for basal cell or squamous epithelial carcinomas of the skin that have 
been resected with no evidence of metastatic disease for 3 years
[36]
have had breast cancer within the past 10 years
[37]
in the opinion of the investigator or sponsor, are unsuitable for inclusion in the 
study
6.3.
Lifestyle and/or Dietary Requirements
Throughout the study, subjects may undergo medical assessments and review of compliance with 
requirements before continuing in the study.  
6.3.1. Meals and Dietary Restrictions
Subjects should fast overnight for at least 8 hours before dosing (water is permitted).  Standard 
meals will be provided at all other times while subjects are resident at the CRU, as per the 
CRU’s policy.
6.3.2. Caffeine, Alcohol, and Tobacco
Subjects should not consume caffeine while at the CRU, and for 12 hours prior to admission to 
the CRU. At other times during the outpatient period, subjects will be allowed to maintain their 
regular caffeine consumption.
Alcohol consumption is not permitted while at the CRU, and for 12 hours prior to each study 
visit.  At other times, alcohol consumption should be limited to 2 units per day (1 unit = 12 oz or 
360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits).
Subjects who smoke will be advised to not increase their consumption of tobacco products 
during the study.  Subjects will be asked to refrain from smoking for approximately 1 hour prior 
to each ECG and vital sign measurements, and to abide by the CRU smoking guidelines.
6.3.3. Activity
Subjects will be advised to maintain their regular levels of physical activity/exercise during the 
study, but to refrain from vigorous exercise.  Strenuous activity should be avoided from 24 hours
prior to admission until discharge from the CRU.  While certain study procedures are in progress 
at the site, subjects may be required to remain recumbent or sitting.
6.4.
Screen Failures
Individuals who do not meet the criteria for participation in this study (screen failure) may not be 
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7.Treatment
7.1. TreatmentAdministered
The LY3074828 lyophilized formulation will be supplied in a sterile vial to be reconstituted prior 
to injection as detailed in the pharmacy instructions.  
TheLY3074828solution formulationswill be supplied in
containing  
 
LY3074828.  The 
dose will comprise two
 and the 
 
The actual date and time of all dose preparation and administration will be documented,and drug 
accountability records will be maintained by the site pharmacy.
This study involves a comparison of 
 SC doses of LY3074828that will be prepared from 
a lyophilized product with 
 and 
 SC doses of LY3074828 that willsupplied as a 
solution in PFSs.TableAMAE.2shows the treatment regimens.
TableAMAE.2.
TreatmentsAdministered
Treatment arm
Lyophilized formulation 
Pre-filledsyringes
Pre-filledsyringes
Reference/test
Reference
Test 1
Test 2
Product
LY3074828
LY3074828
LY3074828
Dose
Concentration
Injection volumes
Number of injections
3
2
4
Formulation and 
presentation
Lyophilized powder for 
reconstitution
Solution in a PFS
Solution in a PFS
Abbreviations:  PFS = pre-filled syringe.
a Theoretical total dose = 252 mg
CCI
Injection-sites selected for SC administration should be in the abdominal region approximately 
5cm from the umbilicus, and treatment should be administered with the needle applied at 
approximately 45 degrees with pinching the skin.  Subcutaneousadministration of LY3074828
should be given by a limited number of individuals for consistency.  The same type of syringe 
and needle(27-gauge, half-inch needle) should be used for all subjects to ensure all injections are 
deliveredto a consistent depth target into the SC space.  Subsequent injection(s) should be given 
immediately following the previousinjection. 
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For the lyophilizedformulation(Reference),the 
 injection and the firstof the 
injections will be given into lower quadrantsof the abdomen.  Theremaining
 injection 
will be administered into an upper quadrant. The order and location of the first 2 injections will 
be randomized (see Section 7.2).
For administration of the 
 solution formulation in PFSs(Test 1), injections will be given 
intoseparate lower quadrants of the abdomen.For administration of the 
 solution 
formulation in PFSs(Test 2), the first 2injections will be given into separate lowerquadrants of 
the abdomen, and the final 2 injections will be given into separate upper quadrants of the 
abdomen.
Further information around SC administration will be inpharmacy handling instructions.
Investigational products will be prepared at the site by pharmacists or other trained personnel.  
Investigational products will only be administered to subjects on-site by nurses or other 
appropriately trained personnel.
The investigator or designee is responsible for:
explaining the correct use of the investigational productsto the site personnel 
verifying that instructions are followed properly
maintaining accurate records of investigational product dispensing and collection
returning all unused medication to Lilly or its designee at the end of the study
Note: In some cases, the sitemay destroy the material if, during the investigativesite selection, 
the evaluator has verified and documented that the site has appropriate facilities and written 
procedures to dispose of clinical trial materials.  
7.1.1. Packaging and Labeling
CCI
LY3074828 lyophilized formulation andsolution formulation inPFSswill be supplied to the 
investigator by Lilly.  Clinical trial materials are manufactured in accordance with good 
manufacturingpractices.  All investigational products will be stored, inventoried, reconciled, and 
destroyed according to applicable regulations.
LY3074828 lyophilized formulation will be supplied for clinical trial use as a powder in a glass 
vial and should be storedrefrigerated (2°C to 8°C).  Each vial is manufactured to deliver 
LY3074828 and will be reconstituted with sterile water to a concentration of 
  
Contents from multiple vials will be pooled for each injection, as required.
LY3074828 solutionformulationwill be supplied as an injectable solution in a 1-mL, 
single-dose, disposable manual syringe.  Each syringe of LY3074828 will be designed to deliver 
LY3074828and therefore twoorfourPFSs will berequired to administer dosesof 
LY3074828 or
LY3074828, respectively.  The PFSsshould be stored 
refrigerated, and should be removed from refrigerated storage and allowed to equilibrate to room 
temperature for approximately 30 minutes prior to dose administration.  
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Clinical trial materials will be labeled according to the country’s regulatory requirements.
7.2. Method of Treatment Assignment
Subjects will be randomized to 1 of 3 treatment arms (
LY3074828 lyophilized
formulation[Reference], 
 LY3074828 solution formulation[Test 1], or 500 mg 
LY3074828solution formulation[Test 2]).  Those that are randomized to receive the lyophilized
formulationwill be further randomized to 1 of 4treatment sequences:
Sequence
First Injection
Second Injection
1
 administered intoleft lower quadrant
 administered intoright lower quadrant
2
 administered intoright lower quadrant
 administered intoleft lower quadrant
3
 administered intoleft lower quadrant
 administered intoright lower quadrant
4
 administered intoright lower quadrant
 administered intoleft lower quadrant
For all sequences, the third injection will comprise a 1.0mL injection administered into an upper quadrant.
Randomization will be performed using a computer-generated randomization schedule.
7.2.1. Selection and Timing of Doses
The actual time of all dose administrations will be recorded in the subject’s electronic case report 
form (eCRF).
7.3. Blinding
This is an open-label study.
7.4. Dose Modification
Dose adjustments are not permitted in this study.
7.5. Preparation/Handling/Storage/Accountability
The investigator or designeemust confirm appropriate temperature conditions have been 
maintained, as communicated by the sponsor,during transit for all investigational product
received and any discrepancies are reported and resolved beforeuse of the study treatment.
Only participants enrolled in the study may receive investigational productsand only authorized 
site staff may supply or administer study treatment.  All study treatments shouldbe stored in an
environmentally controlled and monitored (manual or automated) area in accordance with the 
labeledstorage conditions(see Section 7.1.1)
CCI
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 records).
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7.6.
Treatment Compliance
The investigational product will be administered at the clinical site, and documentation of 
treatment administration will occur at the site.
7.7.
Concomitant Therapy
Over-the-counter or prescription medication, including herbal medication, are not permitted 
within 14 days prior to dosing and throughout the study.  However, stable doses of oral 
contraceptive or hormone-replacement therapy are permitted at the discretion of the investigator.
Paracetamol/acetaminophen (up to 2 g/day) is permitted at the discretion of the investigator.  
Additional drugs are to be avoided during the study, unless required to treat an AE.
If the need for concomitant medication arises, inclusion or continuation of the subject may be at 
the discretion of the investigator after consultation with a Lilly clinical pharmacologist or clinical 
research physician.  Any additional medication used during the course of the study must be 
documented.
7.8.
Treatment After the End of the Study
This section is not applicable for this study.

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8. Discontinuation Criteria
8.1.
Discontinuation from Study Treatment
Randomized subjects who discontinue the study prematurely for any reason should complete the 
AE and early discontinuation (ED) procedures performed as shown in the Schedule of Activities
(Section 2).  The reason for, and the date of discontinuation, will be collected for all subjects.
8.1.1. Discontinuation of Inadvertently Enrolled Subjects
If the sponsor or investigator identifies a subject who did not meet enrollment criteria and was 
inadvertently enrolled, a discussion must occur between the Lilly clinical pharmacologist or 
clinical research physician and the investigator to determine if the subject may continue in the 
study.  If both agree it is medically appropriate to continue, the investigator must obtain 
documented approval from the Lilly clinical pharmacologist or clinical research physician to 
allow the inadvertently enrolled subject to continue in the study without continued treatment 
with investigational product.
8.2.
Discontinuation from the Study
Subjects will be discontinued 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)

The investigator decides that the subject should be discontinued from the study

The subject requests to be withdrawn from the study
Subjects who discontinue the study early will have ED procedures performed as shown in the 
Schedule of Activities (Section 2).
8.3.
Subjects Lost to Follow-up
A subject 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 subjects 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, detailing the study procedures and their timing 
(including tolerance limits for timing).
Appendix 2 lists the laboratory tests that will be performed for this study.
Appendix 5 provides a summary of the maximum number and volume of invasive samples, for
all sampling, during the study.
The specifications in this protocol for the timings of safety and sample collection are given as 
targets to be achieved within reasonable limits.  Modifications may be made to the time points 
based upon merging clinical information.  The scheduled time points may be subject to minor 
alterations; however, the actual time must be correctly recorded in the eCRF.  Late collection 
outside the stipulated time allowances or failure to obtain samples due to clinical issues, such as 
problems with equipment, venous access, or subject defaulting on a scheduled procedure, will 
not be considered as protocol deviations but the site will still be required to notify the sponsor in 
writing via a file-note.
Unless otherwise stated in subsections below, all samples collected for specified laboratory tests 
will be destroyed within 60 days of receipt of confirmed test results.  Certain samples may be 
retained for a longer period, if necessary, to comply with applicable laws, regulations, or 
laboratory certification standards.
Investigators must document their review of each laboratory safety report.
9.1.
Efficacy Assessments
This section is not applicable for this study.
9.2.
Adverse Events
Investigators are responsible for monitoring the safety of subjects who have entered this study 
and for alerting Lilly or its designee to any event that seems unusual, even if this event may be 
considered an unanticipated benefit to the subject.
The investigator is responsible for the appropriate medical care of subjects during the study.
Investigators must document their review of each laboratory safety report.
The investigator remains responsible for following, through an appropriate health care option, 
AEs that are serious or otherwise medically important, considered related to the investigational 
product or the study, or that caused the subject to discontinue the investigational product before 
completing the study.  The subject 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.

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After the informed consent form (ICF) is signed, study site personnel will record, via eCRF, the 
occurrence and nature of each subject’s preexisting conditions.  Additionally, site personnel will 
record any change in the condition(s) and the occurrence and nature of any AEs.  
The investigator will interpret and document whether or not an AE has a reasonable possibility 
of being related to study treatment, or a study procedure, taking into account concomitant 
treatment or pathologies.  
A “reasonable possibility” means that there is a cause and effect relationship between the 
investigational product and/or study procedure and the AE.
Planned surgeries should not be reported as AEs unless the underlying medical condition has 
worsened during the course of the study.
9.2.1. Serious Adverse Events
An SAE is any AE from this study that results in one of the following:

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 subject or may require intervention to prevent 
one of the other outcomes listed in the definition above
Study site personnel must alert the Lilly clinical research physician/clinical pharmacologist, or 
its designee, of any SAE as soon as practically possible.
Additionally, study site personnel must alert Lilly Global Patient Safety, or its designee, of any 
SAE within 24 hours of investigator awareness of the event via a sponsor-approved method.  If 
alerts are issued via telephone, they are to be immediately followed with official notification on 
study-specific SAE forms.  This 24-hour notification requirement refers to the initial SAE 
information and all follow-up SAE information.  
Although all AEs are recorded in the eCRF after signing informed consent, SAE reporting to the 
sponsor begins after the subject has signed informed consent and has received investigational 
product.  However, if an SAE occurs after signing informed consent, but prior to receiving 
investigational product, AND is considered reasonably possibly related to a study procedure then 
it MUST be reported.
Investigators are not obligated to actively seek AEs or SAEs in subjects once they have 
discontinued from and/or completed the study (the subject summary eCRF has been completed).  
However, if the investigator learns of any SAE, including a death, at any time after a subject has 

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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.  
Pregnancy (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.
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.  
Lilly has procedures that will be followed for the recording and expedited reporting of SUSARs 
that are consistent with global regulations and the associated detailed guidances.
9.2.2. Complaint Handling
Lilly collects product complaints on investigational products and drug delivery systems used in 
clinical trials in order to ensure the safety of study participants, monitor quality, and to facilitate 
process and product improvements.
Subjects should be instructed to contact the investigator as soon as possible if he or she has a 
complaint or problem with the investigational product so that the situation can be assessed.
9.3.
Treatment of Overdose
For the purposes of this study, an overdose of LY3074828 is considered any dose higher than the 
dose assigned through randomization.
There is no specific antidote for LY3074828.  In the event of an overdose, the subject should 
receive appropriate supportive care and any AEs should be documented.
Refer to the IB for further details.
9.4.
Safety
9.4.1. Laboratory Tests
For each subject, clinical laboratory tests detailed in Appendix 2 should be conducted according 
to the Schedule of Activities (Section 2).
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 study.
9.4.2. Vital Signs
For each subject, vital signs measurements (blood pressure, pulse rate, and temperature) should 
be conducted according to the Schedule of Activities (Section 2) and following the study-specific 
recommendations included in the Manual of Operations for the study.  Additional vital signs may 
be measured during the study if warranted.
Blood pressure and pulse rate should be measured after at least 5 minutes supine.

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Unscheduled orthostatic vital signs should be assessed where considered appropriate by the 
investigator.  If orthostatic measurements are required, subjects should be supine for at least 
5 minutes and stand for at least 3 minutes.  If the subject feels unable to stand, supine vital signs 
only will be recorded.  
9.4.3. Electrocardiograms
For each subject, a single 12-lead digital ECG will be collected according to the Schedule of 
Activities (Section 2).  Electrocardiograms must be recorded before collecting any blood for 
safety or PK tests.  Subjects must be supine for at least 5 minutes before ECG collection and 
remain supine but awake during ECG collection.  Electrocardiograms may be obtained at 
additional times, when deemed clinically necessary by the investigator.  All ECGs recorded 
should be stored at the investigational site.
Electrocardiograms will be interpreted by a qualified physician (the investigator or qualified 
designee) at the site as soon after the time of ECG collection as possible, and ideally while the 
subject is still present, to determine whether the subject meets entry criteria at the relevant 
visit(s) and for immediate subject management, should any clinically relevant findings be 
identified.  
If a clinically significant finding is identified (including, but not limited to, changes in 
QT/corrected QT [QTc] interval from baseline) after enrollment, the investigator will determine 
if the subject can continue in the study.  The investigator, or qualified designee, is responsible for 
determining if any change in subject management is needed, and must document his/her review 
of the ECG printed at the time of collection.  Any new clinically relevant finding should be 
reported as an AE.
Any clinically significant findings from ECGs that result in a diagnosis and that occur after the 
subject receives the first dose of the investigational product, should be reported to Lilly, or its 
designee, as an AE via eCRF.
9.4.4. Tuberculosis Testing
Subjects will be tested as indicated in the Schedule of Activities (Section 2) for evidence of 
active or latent TB using the QuantiFERON-TB Gold test.  If the test is indeterminate, 1 retest is 
allowed.  If the retest is indeterminate, the subject will be excluded from the study.
Subjects who have had household contact with a person with active TB must be excluded unless 
appropriate and documented prophylaxis treatment for TB has been given.
Subjects with any history of active TB are excluded from the study, regardless of previous or 
current TB treatments.
9.4.5. Safety Monitoring
The Lilly clinical pharmacologist or clinical research physician/scientist will monitor safety data 
throughout the course of the study.

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Lilly will review SAEs within time frames mandated by company procedures.  The Lilly clinical 
pharmacologist or clinical research physician will periodically review the following data:

trends in safety data

laboratory analytes

AEs including monitoring of incidence of any nature of any infections, and injection-site 
reactions
When appropriate, the Lilly clinical pharmacologist or clinical research physician will consult 
with the functionally independent Global Patient Safety therapeutic area physician or clinical 
research scientist.
9.4.5.1.
Hepatic Safety
If a study subject experiences elevated alanine aminotransferase (ALT) ≥3× upper limit of 
normal (ULN), alkaline phosphatase (ALP) ≥2× ULN, or elevated total bilirubin (TBL)
≥2× ULN, liver tests (Appendix 4) should be repeated within 3 to 5 days including ALT,
aspartate aminotransferase (AST), ALP, TBL, direct bilirubin, gamma-glutamyl transferase, and 
creatinine 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 based on consultation with the Lilly clinical pharmacologist or clinical research 
physician.  Monitoring should continue until levels normalize and/or are returning to 
approximate baseline levels. 
Additional safety data should be collected if 1 or more of the following conditions occur:  

elevation of serum ALT to ≥5× ULN on 2 or more consecutive blood tests

elevated serum TBL to ≥2× ULN (except for cases of known Gilbert’s syndrome)

elevation of serum ALP to ≥2× ULN on 2 or more consecutive blood tests 

hepatic event considered to be a SAE.
9.4.5.2.
Monitoring of Hypersensitivity Reactions
There is a risk of systemic hypersensitivity reactions with any biological agent, including acute 
anaphylaxis and delayed hypersensitivities to LY3074828.  Symptoms and signs that may occur 
as part of these hypersensitivity reactions include, but are not limited to:  fever, chills, joint and 
muscle pain, rash, itching, urticaria, dizziness, headache, throat irritation, and shortness of 
breath.  Less commonly, life-threatening anaphylactic reactions may occur, which may include 
vascular collapse and/or respiratory compromise.
All subjects will be closely monitored for signs and symptoms of hypersensitivity reactions 
following administration of the study drug, and appropriate medical care should be provided. 
Hypersensitivity reactions will be evaluated by examination of TEAEs and SAEs, and through 
the use of a follow-up form which will be completed by the investigator.  Potential 
hypersensitivity events will be evaluated by a Lilly clinical research physician based on accepted 
criteria (Sampson et al. 2006). 

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9.4.6. Injection-Site Assessments
Injection-site reactions will be evaluated through the collection and review of TEAEs and 
through the use of an Injection-Site Reaction Follow-up Form completed by the investigator. 
Local tolerability at the injection-sites will be examined by evaluation of erythema, induration, 
categorical pain, pruritus, and edema as indicated in Section 2.  For each event, the severity, 
duration, and timing of the event in relation to the administration of study drug will be recorded.  
If one or more symptom(s) of an injection-site reaction is reported during the assessment, a 
single AE for injection-site reaction will be recorded on the AE page of the eCRF.
Pain assessments will help to determine if injection volume (1.0 mL versus 1.5 mL) is a 
contributing factor.  For the lyophilized formulation, injection-site assessments of pain and 
leakage will be performed for the 2 injections in the lower quadrants of the abdomen (1.0 mL 
and 1.5 mL injections).  For both dose levels of solution formulation in PFSs, injection-site 
assessments of pain and leakage will be performed for the first injection, which will be 
administered into a lower quadrant of the abdomen. 
Pain measurements will be quantified using a 100-mm validated visual analog scale (VAS).  The 
VAS is a well-validated tool (Williamson and Hoggart 2005) for the assessment of injection-site 
pain, and is presented as a 10-cm (100-mm) line, anchored by verbal descriptors, usually “no 
pain” and “worst imaginable pain.” The subject will be asked to rate any pain on a scale of 0 to 
100 mm on the line immediately (within 1 minute) following the start of the injection and at time 
points according to the Schedule of Activities (Section 2).
Injection-site leakage will be assessed using pre-weighed filter paper, blotting the injection-site 
immediately after the injection to absorb any post-injection leakage and placing the filter paper 
back on the tared analytical balance in a similar manner as previously described (Ignaut and Fu 
2012). The amount of leakage will be calculated by subtracting the pre-weighed filter paper 
measurement from the post-injection-site blot filter paper measurement.  Any bleeding from the 
injection-site will also be documented.  
9.5.
Pharmacokinetics
At the visits and times specified in the Schedule of Activities (Section 2), venous blood samples 
of approximately 2 mL each will be collected to determine the serum concentrations of 
LY3074828.  A maximum of 3 samples may be collected at additional time points during the 
study if warranted and agreed upon between both the investigator and sponsor.  Instructions for 
the collection and handling of blood samples will be provided by the sponsor.  The actual date 
and time (24-hour clock time) of each sampling will be recorded.
9.5.1. Bioanalysis
Samples will be analyzed at a laboratory approved by the sponsor and stored at a facility 
designated by the sponsor.  Concentrations of LY3074828 will be assayed using a validated 
enzyme-linked immunosorbent assay.  
Bioanalytical samples collected to measure investigational product concentrations will be 
retained for a maximum of 1 year following last subject visit for the study.  

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9.6.
Pharmacodynamics
9.6.1. Immunogenicity Assessments
Blood samples for immunogenicity testing will be collected to determine antibody production 
against the investigational products, as specified in the Schedule of Activities (Section 2).  
Additional samples may be collected if there is a possibility that an AE is immunologically 
mediated.  Immunogenicity will be assessed by a validated assay designed to detect ADAs in the 
presence of the investigational products.  Antibodies may be further characterized and/or 
evaluated for their ability to neutralize the activity of the investigational product(s).  
A risk-based approach will be used to monitor subjects who develop TE-ADAs during and 
following treatment with LY3074828.  TE-ADAs are defined as either 2-fold increase in titer 
(ie, 1:20) above the minimum required dilution (1:10) if no ADAs were detected at baseline
(predose), or a 4-fold or greater increase in titer over baseline for subjects that are ADA-positive 
at baseline.  LY3074828 is a monoclonal antibody that binds to p19 of IL-23, and there is no 
unique/non-redundant endogenous protein counterpart, greatly minimizing the risk of 
cross-reactive ADA.  Any potential risks of ADA development following this single-dose trial 
would be dependent on LY3074828 exposure outside of this clinical trial.  The largest potential 
risk would be reaction upon subsequent drug exposure that could range in severity from mild 
local injection-site reactions to systemic anaphylaxis and/or systemic immune complex disease 
(Arthus-reaction).  These potential risks would likely be associated with higher serum 
concentrations of ADA.  
Given that the subjects have only a single exposure to LY3074828, any ADA response is 
anticipated to peak and then diminish due to lack of additional exposures.  Subjects will have 
ADA sampling at baseline (predose), Day 15, Day 29, Day 57, and Day 85.  Subjects that are 
observed to have significant (ie, greater than 1:1000 titer) and non-decreasing titers that meet the 
definition of TE-ADA, will be requested to return every 3 months after the last sample to have 
follow-up ADA samples tested until the titer has returned to within 1 titer of their baseline or is 
clearly trending back to the baseline titer.  The rationale for the definitions of both TE-ADA and 
return to baseline is based on the premise that a 1-titer change may result from expected assay 
variability. 
Subjects followed for at least 1 year since last dose who have not returned to baseline, as defined 
above, will be assessed for safety concerns and, if no clinical sequelae are recognized by the 
clinical team, no further follow-up will be required.  Subjects who have clinical sequelae that are 
considered potentially related to the presence of TE-ADA may also be asked to return for 
additional follow-up testing.  
Samples will be retained for a maximum of 15 years after the last subject visit, or for a shorter 
period if local regulations and the institutional review board (IRB) allow, at a facility selected by 
the sponsor.  The duration allows the sponsor to respond to future regulatory requests related to 
the investigational products.  Any samples remaining after 15 years will be destroyed.

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9.7.
Genetics
A blood sample will be collected for pharmacogenetic analysis as specified in the Schedule of 
Activities (Section 2), where local regulations allow.  
Samples will not be used to conduct unspecified disease or population genetic research either 
now or in the future.  Samples will be used to investigate variable exposure or response to 
LY3074828 and to investigate genetic variants thought to play a role in autoimmune and 
inflammatory diseases.  Assessment of variable response may include evaluation of AEs or 
differences in efficacy.  
All samples will be coded with the subject number.  These samples and any data generated can 
be linked back to the subject only by the investigative site personnel.  
Samples will be retained for a maximum of 15 years after the last subject visit, or for a shorter 
period if local regulations and/or IRB impose shorter time limits, for the study at a facility 
selected by Lilly or its designee.  This retention period enables use of new technologies, response 
to regulatory questions, and investigation of variable response that may not be observed until 
later in the development of LY3074828 or after LY3074828 is commercially available.  
Molecular technologies are expected to improve during the 15 year storage period and therefore 
cannot be specifically named.  However, existing approaches include whole genome or exome 
sequencing, genome wide association studies, multiplex assays, and candidate gene studies.  
Regardless of technology utilized, data generated will be used only for the specific research 
scope described in this section. 
9.8.
Biomarkers
This section is not applicable for this study.
9.9.
Health Economics
This section is not applicable for this study.

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10.
Statistical Considerations and Data Analysis
10.1. Sample Size Determination
Approximately 54 subjects (18 per treatment arm) may be enrolled to allow evaluable data from 
16 subjects from each treatment arm to be obtained. The estimated total variability (coefficient 
of variation) in AUC(0-∞), AUC(0-tlast), and maximum observed drug concentration (Cmax) 
was 49%, 49%, and 23%, respectively, in Study AMAA following a single SC dose of 120 mg 
LY3074828. The coefficient of variation of 49% was used for precision estimates and is 
assumed for all treatment arms.  A sample size of 48 subjects will provide a precision, in log 
scale, of approximately 0.32 for the geometric means ratio in AUC(0-∞), AUC(0-tlast), and
Cmax of lyophilized to solution formulation in log scale. That is, there is a 90% probability that 
the half-length of the 90% confidence interval (CI) of the geometric means ratio in log scale is 
not larger than 0.32. Subjects who are randomized but not administered treatment, or subjects
(maximum of 6) that are administered treatment but do not have PK and ADA samples collected 
up to and including Day 57, may be replaced to ensure that approximately 16 subjects from each 
treatment arm may complete the study.
10.2. Populations for Analyses
10.2.1. Study Participant Disposition
A detailed description of subject disposition will be provided at the end of the study. 
10.2.2. Study Participant Characteristics
The subject’s age, sex, weight, BMI, height, race/subrace, and other demographic data will be 
summarized by treatment and overall.
10.3. Statistical Analyses
Statistical analysis of this study will be the responsibility of Eli Lilly and Company or its 
designee.
Pharmacokinetic analyses will be conducted on the full analysis set.  This set includes all data 
from all randomized subjects receiving the dose of LY3074828 with evaluable PK data, 
according to the treatment the subjects actually received.  Safety analyses will be conducted for 
all subjects receiving a dose of LY3074828, whether or not they completed all protocol 
requirements.
Additional exploratory analyses of the data will be conducted as deemed appropriate.  Study 
results may be pooled with the results of other studies for population PK analysis purposes to 
avoid issues with post-hoc analyses and incomplete disclosures of analyses.  
No adjustments for multiple comparisons will be made.

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10.3.1.Safety Analyses
10.3.1.1.Clinical Evaluation of Safety
All investigational product and protocol procedure AEs will be listed, and if the frequency of 
events allows, safety data will be summarized using descriptive methodology.
The incidence of symptoms for each treatment will be presented by severity and by association 
with investigational product as perceived by the investigator.  Symptoms reported to occur prior 
to study entry will be distinguished from those reported as new or increased in severity during 
the study.  Each symptom will be classified by the most suitable term from the medical 
regulatory dictionary.
The number of investigational product-related SAEs will be reported.
10.3.1.2.Statistical Evaluation of Safety
Safety parameters that will be assessed include clinicallaboratoryparameters, vital signs, and 
ECG parameters.  The parameters, and changes from baseline (predose) where appropriate,will 
be listed, and summarized using standard descriptive statistics.  Additional analysis will be 
performed if warranted upon review of the data.
10.3.2.Pharmacokinetic Analyses
10.3.2.1.Pharmacokinetic Parameter Estimation
Pharmacokinetic parameter estimates for LY3074828 will be calculated by standard 
noncompartmental methods of analysis.
The primary parameters for analysis will be AUC(0-∞)and AUC(0-tlast) forLY3074828.  The 
secondary parameters for analysis will be C
maxand time of Cmax(tmax) of LY3074828.  
Dose-normalized (DN)-AUC(0-∞), DN-AUC(0-tlast),and DN-C
maxwill be calculated.  Other
noncompartmental parameters, such as t
1/2, apparent total body clearance of drug calculated after 
extra-vascular administration (CL/F), and apparent volume of distributionduring the terminal 
phaseafter extra-vascular administration (VZ/F)may be reported.
10.3.2.2.Pharmacokinetic Statistical Inference
Pharmacokinetic parameter estimates will be evaluated to delineate effects of formulation.  
Log-transformed DN-AUC(0-∞), DN-AUC(0-tlast),and DN-C
max
CCI
will be evaluated in a linear 
fixed-effects model with a fixed effect for formulation.  For the primary endpoint, a model 
comparing the differences betweenthe 
 LY3074828solution formulation and the 
 
LY3074828 lyophilized formulationwill be used. For the secondary endpoints,a model 
comparing the differences between the  
 LY3074828 solution formulation and the  
 
LY3074828 lyophilized formulation,and between the  
 and  
 LY3074828 solution 
formulationswill be used.Differences will be back-transformed to present the ratios of 
geometric least squares means and the corresponding 90% CI. If leakage occurs frequently, 
whether injection-siteleakage occurred (yes/no) may also be included as a covariate in the 
model.  Furthermore, if leakage is found to be significant, the amount of leakage will also be 
added to the model.
CCI
CCI
CCI
CCI
CCI

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The tmax will be analyzed using a Wilcoxon rank sum test.  Estimates of the median difference, 
90% CIs, and p-values from the Wilcoxon rank sum test will be calculated.
Additional PK analyses may be conducted if deemed appropriate.
10.3.3. Pharmacodynamic Analyses
This section is not applicable for this study.
10.3.4. Pharmacokinetic/Pharmacodynamic Analyses
This section is not applicable for this study.
10.3.5. Evaluation of Immunogenicity
The frequency of formation of antibodies to LY3074828 will be determined.  
Treatment-emergent ADAs are those that are induced or boosted by exposure to study drug, with 
a 4-fold increase in titer compared to baseline if ADAs were detected at baseline, or a titer 2-fold 
greater than the minimum required dilution (1:10) if no ADAs were detected at baseline.
If a neutralization assay is performed, the frequency of neutralizing antibodies will be 
determined.  The relationship between the presence (or absence) of antibodies and clinical 
parameters (AEs) will be assessed.  Likewise, the relationship between the presence of 
antibodies and the PK parameters to LY3074828 will be assessed.  
10.3.6. Exploratory Analysis
Incidence of erythema, induration, categorical pain, pruritus and edema will be listed and 
summarized by treatment.
The 0 hour (post-injection) pain score will be evaluated in a linear fixed-effects model with a 
fixed effect for treatment. The distribution of the data will be explored prior to analysis to
determine whether data transformation is required. The differences between the 1.5 mL and 
1.0 mL injections for the lyophilized formulation will be back-transformed (if applicable) to 
present the ratios of geometric least squares means and the corresponding 90% CI.  It is possible 
that the pain scores will be 0 so if the distribution of the data implies that a log-transformation is 
required then the score may be updated to log(VAS+1) to allow for the inclusion of the 0 values 
in the analysis.
Leakage data will be summarized by treatment using descriptive statistics and may be used as a 
covariate in the PK analyses.
10.3.7. Data Review During the Study
Data may be accessed and analyzed while the trial is ongoing, but no changes to the study design 
are planned.  An assessment committee will not be formed.
Data review is scheduled to occur when safety and PK data through approximately Day 57
(8 weeks postdose) become available from at least 12 subjects from each treatment group. The 

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purpose of the data review is to trigger Chemistry, Manufacturing, and Control processes with 
respect to LY3074828 formulation, and to inform dose selection for Phase 3 first registration.
10.3.8. Interim Analyses
No formal interim analyses are planned for this study.  If an unplanned interim analysis is 
deemed necessary, the Lilly clinical pharmacologist, clinical research physician/investigator, or 
designee will consult with the appropriate medical director or designee to determine if it is 
necessary to amend the protocol.

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11.
References
Cornelissen F, Asmawidjaja PS, Mus AM, Corneth O, Kikly K, Lubberts E. IL-23 dependent and 
independent stages of experimental arthritis: no clinical effect of therapeutic IL-23p19 
inhibition in collagen-induced arthritis. PLoS One. 2013;8(2):e57553.
Ignaut DA, Fu H. Comparison of insulin diluent leakage postinjection using two different needle 
lengths and injection volumes in obese patients with type 1 or type 2 diabetes mellitus. J 
Diabetes Sci Technol. 2012 Mar 1;6(2):389-93.
Ruutu M, Thomas G, Steck R, Degli-Esposti MA, Zinkernagel MS, Alexander K, Velasco J, 
Strutton G, Tran A, Benham H, Rehaume L, Wilson RJ, Kikly K, Davies J, Pettit AR, Brown 
MA, McGuckin MA, Thomas R. β-glucan triggers spondylarthritis and Crohn's disease-like 
ileitis in SKG mice. Arthritis Rheum. 2012;64(7):2211-2222.
Sampson HA, Muñoz-Furlong A, Campbell RL, Adkinson NF Jr, Bock SA, Branum A, Brown 
SG, Camargo CA Jr, Cydulka R, Galli SJ, Gidudu J, Gruchalla RS, Harlor AD Jr, Hepner DL, 
Lewis LM, Lieberman PL, Metcalfe DD, O'Connor R, Muraro A, Rudman A, Schmitt C, 
Scherrer D, Simons FE, Thomas S, Wood JP, Decker WW. Second symposium on the 
definition and management of anaphylaxis: summary report - Second National Institute of 
Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy 
Clin Immunol. 2006;117(2):391-7.
Williamson A, Hoggart B. Pain: a review of three commonly used pain rating scales. J Clin 
Nurs. 2005;14(7):798-804.

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Appendix 1.
Abbreviations and Definitions

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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 AE 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.
ALP
alkaline phosphatase
ALT
alanine aminotransferase
AUC
area under the concentration versus time curve
AUC(0-∞)
area under the concentration versus time curve from time zero to infinity
AUC0-168
area under the concentration versus time curve during the dosing interval
AUC(0-tlast)
area under the concentration versus time curve from time zero to time t, where t is the last 
sample with a measurable concentration
BMI
body mass index
CD
Crohn’s disease
CI
confidence interval
Cmax
maximum observed drug concentration
complaint
A complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, purity, durability, reliability, safety or effectiveness, or 
performance of a drug or drug delivery system.
compliance
Adherence to all the trial-related requirements, good clinical practice requirements, and the 
applicable regulatory requirements.
confirmation
A process used to confirm that laboratory test results meet the quality requirements defined 
by the laboratory generating the data and that Lilly is confident that results are accurate.  
Confirmation will either occur immediately after initial testing or will require that samples 
be held to be retested at some defined time point, depending on the steps required to obtain 
confirmed results.
CRU
clinical research unit
DN
dose normalized
ECG
electrocardiogram
eCRF
electronic case report form
ED
early discontinuation

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enroll
The act of assigning a subject to a treatment.  Subjects who are enrolled in the trial are those 
who have been assigned to a treatment.
enter
Subjects entered into a trial are those who sign the informed consent form directly or 
through their legally acceptable representatives.
GCP
good clinical practice
HIV
human immunodeficiency virus
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonisation
IL-12
interleukin-12
IL-23
interleukin-23
informed consent
A process by which a subject voluntarily confirms his or her willingness to participate in a 
particular trial, after having been informed of all aspects of the trial that are relevant to the 
subject’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 trial data, separated into treatment groups, that 
is conducted before the final reporting database is created/locked.
investigator
A person responsible for the conduct of the clinical trial at a trial site.  If a trial is conducted 
by a team of individuals at a trial site, the investigator is the responsible leader of the team 
and may be called the principal investigator.
IRB
institutional review board
IV
intravenous
open-label
A study in which there are no restrictions on knowledge of treatment allocation, therefore 
the investigator and the study participant are aware of the drug therapy received during the 
study.
PFS
pre-filled syringe
PK
pharmacokinetic(s)
Q1W
once every week
QTc
corrected QT
SAE
serious adverse event

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SC
subcutaneous
screen
The act of determining if an individual meets minimum requirements to become part of a 
pool of potential candidates for participation in a clinical trial.  
SUSARs
suspected unexpected serious adverse reactions
t1/2
half-life associated with the terminal rate constant
TB
tuberculosis
TBL
total bilirubin
TEAE
treatment-emergent adverse event:  Any 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.
TE-ADA
treatment-emergent anti-drug antibody
tmax
time to maximum observed drug concentration
ULN
upper limit of normal
VAS
visual analog scale

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Appendix 2.
Clinical Laboratory Tests
Laboratory Tests
Hematologya
Clinical Chemistrya
Hematocrit
Sodium
Hemoglobin
Potassium
Erythrocyte count (RBC)
Calcium
Mean cell volume 
Phosphorus
Mean cell hemoglobin 
Glucose (random)
Mean cell hemoglobin concentration 
Blood urea nitrogen (BUN)
Leukocytes (WBC)
Uric acid
Cell Morphology
Total cholesterol
Absolute counts of:
Total protein
Neutrophils
Albumin
Lymphocytes
Total bilirubinc
Monocytes
Alkaline phosphatase (ALP)
Eosinophils
Aspartate aminotransferase (AST)
Basophils
Alanine aminotransferase (ALT)
Platelets
Creatinine
Urinalysisa
Ethanol testingd
Specific gravity
Urine drug screend
pH
QuantiFERON-TB Gold testa,e
Protein
Glucose
Serologye
Ketones
Hepatitis B surface antigen
Bilirubin
Hepatitis B core antibody
Urobilinogen
Hepatitis C antibody
Blood
HIV antibodies
Nitrite
Serum Pregnancy testf,g
Microscopic examination of sedimentb
Hormone Panel
Follicle-stimulating hormone e,h
Abbreviations:  HIV = human immunodeficiency virus; RBC = red blood cells; WBC = white blood cells.
a
Results will be validated by the local laboratory at the time of initial testing.
b
If clinically indicated, per investigator’s discretion.
c
If total bilirubin is elevated, direct bilirubin and indirect bilirubin may be measured.
d
Urine drug screen and ethanol level will be performed locally at screening and on Day -1 during admission to the 
clinical research unit.  May be repeated at the discretion of the investigator.
e
Performed at screening only.
f
Women of childbearing potential only.
g
Refer to Section 2 for specific sampling timing.
h
To be done for women only when needed to confirm postmenopausal status. 

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Appendix 3.
Study Governance, Regulatory and Ethical 
Considerations
Informed Consent
The investigator is responsible for:

ensuring that the subject understands the nature of the study, potential risks and benefits 
of participating in the study, and that their participation is voluntary.

ensuring that informed consent is given by each subject or legal representative.  This 
includes obtaining the appropriate signatures and dates on the ICF prior to the 
performance of any protocol procedures and prior to the administration of investigational 
product.

answering any questions the subject may have throughout the study and sharing in a 
timely manner any new information that may be relevant to the subject’s willingness to 
continue his or her participation in the trial.

providing a copy of the ICF to the participant or the participant’s legal representative and 
retaining a copy on file.
Recruitment
Lilly, or its designee, is responsible for the central recruitment strategy for subjects.  Individual 
investigators may have additional local requirements or processes.  Study-specific recruitment 
material should be approved by Lilly.
Ethical Review
The investigator must give assurance that the IRB was properly constituted and convened as 
required by International Council for Harmonisation (ICH) guidelines and other applicable laws 
and regulations.
Documentation of IRB 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 
before it is used at the investigative site(s).  All ICFs must be compliant with the ICH guideline 
on GCP.
The study site’s IRB should be provided with the following:

the current IB and updates during the course of the study

ICF

relevant curricula vitae
Regulatory Considerations
This study will be conducted in accordance with:

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1) consensus ethics principles derived from international ethics guidelines, 
including the Declaration of Helsinki and Council for International
Organizations of Medical Sciences (CIOMS) International Ethical Guidelines 
2) applicable ICH GCP Guidelines 
3) applicable laws and regulations
Some of the obligations of the sponsor will be assigned to a third party organization.
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.
Final Report Signature
The investigator or designee will sign the clinical study report for this study, indicating 
agreement with the analyses, results, and conclusions of the report.
The sponsor’s responsible medical officer and statistician will sign/approve the final clinical 
study report for this study, confirming that, to the best of his or her knowledge, the report 
accurately describes the conduct and results of the study.
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.

provide training to instruct the investigators and study coordinators.  This training will 
give instruction on the protocol, the completion of the eCRFs, and study procedures.

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 eCRF data and/or 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 subject data 
recorded against source documents at the study site.  The study may be audited by Lilly 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, 

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applicable regulatory agencies, and applicable IRBs with direct access to the original source 
documents.
Data Collection Tools/Source Data
An electronic data capture system will be used in this study.  The site must define and retain all 
source records and must maintain a record of any data where source data are directly entered into 
the data capture system.
Data Protection
Data systems used for the study will have controls and requirements in accordance with local 
data protection law.  
The purpose and use of subject personal information collected will be provided in a written 
document to the subject by the sponsor.
Study and Site Closure
Discontinuation of Study Sites
Study site participation may be discontinued if Lilly or its designee, the investigator, or the IRB
of the study site judges it necessary for medical, safety, regulatory, or other reasons consistent 
with applicable laws, regulations, and GCP.
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.

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Appendix 4.
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 subjects in consultation with Lilly or its designee clinical research 
physician.
Hepatic Monitoring Tests
Hepatic Hematologya
Haptoglobina
Hemoglobin
Hematocrit
Hepatic Coagulationa
RBC
Prothrombin Time
WBC
Prothrombin Time, INR
Neutrophils
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
Alanine aminotransferase (ALT)
Anti-nuclear antibodya
Aspartate aminotransferase (AST)
Alkaline Phosphatase Isoenzymesa
Gamma-glutamyl transferase (GGT)
Creatinine kinase (CPK)
Anti-smooth muscle antibody (or anti-actin 
antibody)a
Abbreviations:  Ig = immunoglobulin; INR = international normalized ratio; RBC = red blood cells; WBC = white 
blood cells.
a
Assayed by Lilly-designated or local laboratory.
b
Reflex/confirmation dependent on regulatory requirements and/or testing availability.

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Appendix 5.
Blood Sampling Summary
This table summarizes the approximate number of venipunctures and blood volumes for all 
blood sampling (screening, safety laboratories, and bioanalytical assays) during the study.  Fewer 
venipunctures and blood draws may actually occur, but this will not require a protocol 
amendment.
Protocol I6T-MC-AMAE Sampling Summary
Purpose
Maximum Blood Volume 
per Sample (mL)
Maximum Number 
of Blood Samples
Maximum Total 
Volume (mL)
Screening testsa
14
1
14
Clinical laboratory testsa
7.5
5
37.5
Pharmacokineticsb
2
17
34
Immunogenicitya
10
5
50
Pregnancy tests
3.5
4
14
Pharmacogenetics
10
1
10
Total
159.5
Total for clinical purposes [rounded up to nearest 10 mL]
160
a
Additional samples may be drawn if needed for safety purposes.
b
Includes a potential 3 additional sample.

PPD
Leo Document ID = f2710a55-46cb-479f-ac8c-02791f209472
Approver: 
Approval Date & Time: 04-Apr-2017 20:30:35 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 05-Apr-2017 14:28:47 GMT
Signature meaning: Approved
PPD