A Safety, Tolerability, and Pharmacokinetic Study of 1- and 2-mL Injections of LY3074828 Solution Using Investigational Pre-filled Syringes and Investigational Autoinjectors in Healthy Subjects
Phase: PHASE1
Conditions: Healthy
Sponsor: Eli Lilly and Company

 
 
Protocol I6T-MC-AMAQ (b) 
 
A Safety, Tolerability, and Pharmacokinetic Study of 1- and 2-mL Injections of LY3074828 
Solution Using Investigational Pre-filled Syringes and Investigational Autoinjectors in Healthy 
Subjects 
 
NCT02107703: NCT03456713 
 
Approval Date: 26-Jul-2018 

I6T-MC-AMAQ(b)Clinical Pharmacology Protocol
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LY3074828
ProtocolI6T-MC-AMAQ(b)
A Safety, Tolerability, and Pharmacokinetic Study of 1-and 
2-mL Injections of LY3074828 Solution Using
Investigational Pre-filled Syringes and Investigational
Autoinjectors in Healthy Subjects
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 subjectto 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: 26-Jul-2018 GMT
LY3074828
Eli Lilly and Company
Indianapolis, Indiana USA 46285
Clinical Pharmacology Protocol Electronically Signed and Approved by Lilly:  
13December2017
Amendment (b)Electronically Signed and Approved by Lilly on date provided below.

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Table of Contents
A Safety, Tolerability, and Pharmacokinetic Study of 1- and 
2-mL Injections of LY3074828 Solution Using Investigational 
Pre-filled Syringes and Investigational Autoinjectors in 
Healthy Subjects
Section
Page
Protocol I6T-MC-AMAQ(b) A Safety, Tolerability, and Pharmacokinetic Study 
of 1- and 2-mL Injections of LY3074828 Solution Using Investigational 
Pre-filled Syringes and Investigational Autoinjectors in Healthy Subjects ....................................... 1
Table of Contents .................................................................................................................................... 2
1.
Protocol Synopsis ........................................................................................................................... 7
2.
Schedule of Activities................................................................................................................... 10
3.
Introduction.................................................................................................................................. 17
3.1.
Study Rationale....................................................................................................................... 17
3.2.
Background............................................................................................................................. 17
3.3.
Benefit/Risk Assessment ......................................................................................................... 19
4.
Objectives and Endpoints.............................................................................................................. 20
5.
Study Design ................................................................................................................................ 21
5.1.
Overall Design ........................................................................................................................ 21
5.2.
Number of Participants............................................................................................................ 22
5.3.
End of Study Definition........................................................................................................... 22
5.4.
Scientific Rationale for Study Design ...................................................................................... 22
5.5.
Justification for Dose............................................................................................................... 23
6.
Study Population .......................................................................................................................... 24
6.1.
Inclusion Criteria..................................................................................................................... 24
6.2.
Exclusion Criteria.................................................................................................................... 26
6.3.
Lifestyle and/or Dietary Requirements..................................................................................... 29
6.3.1.
Meals and Dietary Restrictions ....................................................................................... 29
6.3.2.
Caffeine, Alcohol, and Tobacco...................................................................................... 29
6.3.3.
Activity .......................................................................................................................... 29
6.3.4.
Blood and Plasma Donation............................................................................................ 29
6.4.
Screen Failures........................................................................................................................ 29
7.
Dosing Regimens.......................................................................................................................... 30
7.1.
Dosing Regimens Administered............................................................................................... 30
7.1.1.
Packaging and Labeling.................................................................................................. 32
7.2.
Method of Treatment Assignment............................................................................................ 32
7.2.1.
Selection and Timing of Doses ....................................................................................... 32

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7.3.
Blinding .................................................................................................................................. 32
7.4.
Dose Modification................................................................................................................... 32
7.5.
Preparation/Handling/Storage/Accountability .......................................................................... 32
7.6.
Treatment Compliance ............................................................................................................ 33
7.7.
Concomitant Therapy.............................................................................................................. 33
7.8.
Treatment after the End of the Study........................................................................................ 33
8.
Discontinuation Criteria................................................................................................................ 34
8.1.
Discontinuation from Study Treatment .................................................................................... 34
8.1.1.
Discontinuation of Inadvertently Enrolled Subjects......................................................... 34
8.2.
Discontinuation from the Study ............................................................................................... 34
8.3.
Subjects Lost to Follow-up ...................................................................................................... 34
9.
Study Assessments and Procedures ............................................................................................... 35
9.1.
Efficacy Assessments .............................................................................................................. 35
9.2.
Adverse Events ....................................................................................................................... 35
9.2.1.
Serious Adverse Events .................................................................................................. 36
9.2.1.1.
Adverse Device Effects............................................................................................. 37
9.2.1.2.
Adverse Events of Special Interest............................................................................ 37
9.2.1.3.
Suspected Unexpected Serious Adverse Reactions.................................................... 37
9.2.1.4.
Adverse Event Monitoring with a Systematic Questionnaire ..................................... 37
9.2.2.
Complaint Handling........................................................................................................ 38
9.3.
Treatment of Overdose............................................................................................................ 38
9.4.
Safety...................................................................................................................................... 38
9.4.1.
Laboratory Tests............................................................................................................. 38
9.4.2.
Vital Signs...................................................................................................................... 39
9.4.3.
Electrocardiograms......................................................................................................... 39
9.4.4.
Other Tests..................................................................................................................... 39
9.4.4.1.
Tuberculosis Testing................................................................................................. 39
9.4.4.2.
Injection Instructions ................................................................................................ 40
9.4.4.3.
Injection Speed Assessments and Video Recording................................................... 40
9.4.4.4.
Injection-site Assessments ........................................................................................ 40
9.4.4.5.
Bleeding Assessment ................................................................................................ 40
9.4.4.6.
Injection-site Pain..................................................................................................... 40
9.4.4.6.1.
Short Form McGill Pain Questionnaire............................................................... 40
9.4.5.
Safety Monitoring........................................................................................................... 41
9.4.5.1.
Hepatic Safety .......................................................................................................... 41
9.4.5.2.
Monitoring of Hypersensitivity Reactions ................................................................. 41
9.5.
Pharmacokinetics .................................................................................................................... 42
9.5.1.
Bioanalysis..................................................................................................................... 42
9.6.
Pharmacodynamics.................................................................................................................. 42
9.6.1.
Immunogenicity Assessments ......................................................................................... 42

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9.7.
Genetics .................................................................................................................................. 43
9.8.
Biomarkers.............................................................................................................................. 44
9.9.
Health Economics ................................................................................................................... 44
10.
Statistical Considerations and Data Analysis................................................................................. 45
10.1.
Sample Size Determination...................................................................................................... 45
10.2.
Populations for Analyses ......................................................................................................... 45
10.2.1.
Study Participant Disposition.......................................................................................... 45
10.2.2.
Study Participant Characteristics..................................................................................... 45
10.3.
Statistical Analyses.................................................................................................................. 45
10.3.1.
Safety Analyses .............................................................................................................. 46
10.3.1.1.
Clinical Evaluation of Safety .................................................................................... 46
10.3.1.2.
Statistical Evaluation of Safety ................................................................................. 46
10.3.1.2.1.
Injection-site Pain............................................................................................... 46
10.3.1.2.2.
Duration of Injection .......................................................................................... 46
10.3.1.2.3.
Injection-site Assessments.................................................................................. 47
10.3.1.2.4.
Statistical Evaluation of Other Safety Parameters................................................ 47
10.3.2.
Pharmacokinetic Analyses .............................................................................................. 47
10.3.2.1.
Pharmacokinetic Parameter Estimation ..................................................................... 47
10.3.2.2.
Pharmacokinetic Statistical Inference........................................................................ 47
10.3.3.
Pharmacodynamic Analyses ........................................................................................... 47
10.3.4.
Pharmacokinetic/Pharmacodynamic Analyses................................................................. 47
10.3.5.
Evaluation of Immunogenicity........................................................................................ 48
10.3.6.
Data Review During the Study........................................................................................ 48
10.3.7.
Interim Analyses............................................................................................................. 48
11.
References.................................................................................................................................... 49

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List of Tables
Table
Page
Table AMAQ.1.
Objectives and Endpoints................................................................................. 20
Table AMAQ.2.
Dosing Regimens Administered – Part A ......................................................... 30
Table AMAQ.3.
Dosing Regimens Administered – Part B.......................................................... 31
Table AMAQ.4.
Amendment Summary for Protocol I6T-MC-AMAQ Amendment(b) ............... 60

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List of Appendices
Appendix
Page
Appendix 1.
Abbreviations and Definitions.......................................................................... 50
Appendix 2.
Clinical Laboratory Tests................................................................................. 54
Appendix 3.
Study Governance, Regulatory and Ethical Considerations............................... 55
Appendix 4.
Hepatic Monitoring Tests for Treatment-emergent Abnormality....................... 58
Appendix 5.
Blood Sampling Summary ............................................................................... 59
Appendix 6.
Protocol Amendment I6T-MC-AMAQ(b) Summary: A Safety, 
Tolerability, and Pharmacokinetic Study of 1- and 2-mL Injections of 
LY3074828 Solution Using Investigational Pre-filled Syringes and 
Investigational Autoinjectors in Healthy Subjects............................................. 60

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1. Protocol Synopsis
Title of Study:
A Safety, Tolerability, and Pharmacokinetic Study of 1- and 2-mL Injections of LY3074828 Solution 
Using Investigational Pre-filled Syringes and Investigational Autoinjectors in Healthy Subjects
Rationale: 
Study I6T-MC-AMAQ (AMAQ) will assess the pharmacokinetics (PK), safety and tolerability of, and pain
associated with, a 250-mg subcutaneous (SC) dose of LY3074828 solution formulation administered as 1 x 2-mL 
125-mg/mL injection using an investigational manual pre-filled syringe (PFS; Test 1) and administered as 2 x 1-mL 
125-mg/mL injections using an investigational manual PFS (Reference).  The study will also compare safety and
tolerability of, and pain associated with, a 250-mg SC dose of LY3074828 solution formulation administered as 
1 x 2-mL 125-mg/mL injection using an investigational 2-mL autoinjector (AI) with slow (Test 2) and fast (Test 3) 
injection speeds, and a 125-mg dose administered as 1 x 1-mL 125-mg/mL injection using an investigational 1-mL 
AI with slow (Test 4) and fast (Test 5) injection speeds.  The study will bridge 2 different PFSs administering the 
same total volume, from 2 injections with the 1-mL PFS used to administer LY3074828 solution in 
Study I6T-MC-AMAE (AMAE) to 1 injection with a 2-mL investigational PFS.  Investigational 1- and 2-mL AI 
administrations are to be evaluated primarily for pain and injection site reactions. 
Objectives/Endpoints:
Objectives
Endpoints
Primary
Part A

To evaluate the PK of LY3074828 solution 
formulation after administration of 250-mg 
doses using 2 x 1-mL and 1 x 2-mL PFS 
injections in healthy subjects.

To assess the safety and tolerability of, and 
pain associated with, LY3074828 PFS 
administrations in healthy subjects.
Part A

The primary PK endpoints will be the Cmax, 
AUC(0-tlast), and AUC(0-∞) of LY3074828.

Incidence of TEAEs.

SF-MPQ, including VAS pain score.
Primary
Part B

To compare the safety and tolerability of, and 
pain associated with, LY3074828 solution 
formulation after administration of 125- and 
250-mg doses using 1-mL AI and 2-mL AI 
SC injections with different injection speeds 
(slow and fast) in healthy subjects.
Part B

Incidence of TEAEs.

SF-MPQ, including VAS pain score.
Abbreviations:  AI = autoinjector; AUC(0-∞) = area under the concentration versus time curve from time zero to 
infinity; AUC(0-tlast) = area under the concentration versus time curve from time zero to time t, where t is the 
last sample with a measurable concentration; Cmax = maximum observed drug concentration; PFS = pre-filled 
syringe; PK = pharmacokinetic; SC = subcutaneous; SF-MPQ = Short Form McGill Pain Questionnaire; 
TEAE = treatment-emergent adverse event; VAS = visual analog scale.

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Summary of Study Design:
Study I6T-MC-AMAQ (AMAQ) is a single-center, randomized, parallel-treatment, open-label, Phase 1 single-dose 
study of LY3074828 solution formulation in healthy subjects.  In Part A, PK, safety and tolerability of, and pain
associated with, SC doses administered using 1- and 2-mL PFS injections will be evaluated.  In Part B, safety and
tolerability of, and pain associated with, 1- and 2-mL AI injections administered with 2 different injection speeds
will be evaluated.
For Part A, 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 to either a 2 x 1-mL or a 1 x 2-mL 
125-mg/mL PFS dose regimen, study drug will be administered by investigative site staff by SC injection in the 
abdomen in the morning of Day 1 after an overnight fast.  Subjects will be followed for 12 weeks following dose 
administration.
For Part B, subjects will report to the CRU on Day -1 and will remain at the CRU until the scheduled procedures 
have been completed on Day 3.  Subjects will be randomized to receive, on Days 1 and 2, either a 1 x 1-mL or a
1 x 2-mL 125-mg/mL AI dose regimen.  The allocated AI dose regimen will be self-administered by slow and fast
SC injection(s) on consecutive days (sequence randomized) in the abdomen after an overnight fast.  Subjects will be 
followed for 12 weeks following dose administration.
Safety and tolerability will be explored by clinical laboratory tests, vital sign measurements, 12-lead 
electrocardiograms, recording of adverse events and product complaints, physical examinations/medical 
assessments, immunogenicity, and injection-site assessments.  Pain assessments will be made using the Short Form 
McGill Pain Questionnaire (SF-MPQ), which includes a subject-assessed injection-site pain visual analog scale 
(VAS).
Dosing Regimen Arms and Duration:  
Subjects will receive a 125- or 250-mg SC dose of LY3074828 and will be randomized to 1 of 2 dosing regimen 
arms within 1 study part:
Part A

Reference:  250 mg LY3074828 solution formulation, 2 x 1-mL 125-mg/mL PFS injections using an 
investigational PFS targeting 5- to 10-second injection time for each injection

Test 1:  250 mg LY3074828 solution formulation, 1 x 2-mL 125-mg/mL PFS injection using an 
investigational PFS targeting 5- to 15-second injection time
Part B

Tests 2 and 3: 250 mg LY3074828 solution formulation, 1 x 2-mL 125-mg/mL AI slow injection (Test 2; 
targeting approximately 13-second injection time) and fast injection (Test 3; targeting approximately
5-second injection time) using an investigational 2-mL AI

Tests 4 and 5:  125 mg LY3074828 solution formulation, 1 x 1-mL 125-mg/mL AI slow injection (Test 4; 
targeting approximately 7-second injection time) and fast injection (Test 5; targeting approximately
4.5-second injection time) using an investigational 1-mL AI

I6T-MC-AMAQ(b) Clinical Pharmacology Protocol
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Total duration of the study for each subject will be approximately 16 weeks (screening period ≤28 days, residential 
period of 2 or 3 days [depending on study part], and outpatient follow-up period of 12 weeks).
Number of Subjects:
A total of approximately 72 subjects (approximately 36 subjects per study Parts A and B) who fulfill the eligibility 
criteria will be randomized to 1 of 2 dosing regimen arms within their assigned study part, with 18 subjects 
randomized to each arm in order to ensure completion of 16 subjects in each.  A subject’s study participation is 
considered as complete if he/she receives the study drug as per the protocol requirements and completes all activities 
up to and including at least Day 57 for Part A or up to and including at least Day 15 for Part B.  A maximum of 
4 subjects per arm per study part may be replaced if multiple subjects do not complete the study.
Statistical Analysis:
For Part A, the area under the concentration versus time curve (AUC) from time zero to infinity (AUC[0-∞]), AUC
from time zero to time t, where t is the last sample with a measurable concentration (AUC[0-tlast]), and maximum 
observed drug concentration (Cmax) will be log-transformed and analyzed using a linear fixed-effects model.  The 
model will include dosing regimen arm as a fixed effect.  The dosing regimen differences between the Test 1 arm 
and the Reference arm will be back-transformed to present the ratios of geometric least squares (LS) means and the 
corresponding 90% confidence interval (CI).
The time to Cmax (tmax) of LY3074828 between the 2 x 1-mL PFS (Reference) and the 1 x 2-mL PFS (Test 1) will 
be analyzed using a Wilcoxon rank sum test for Part A.  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 for Part A if deemed appropriate. 
In Part A, a linear fixed-effects model will be used to analyze the 0-hour (post-injection) pain VAS score and 
SF-MPQ total score.  The model will include treatment (Reference or Test 1) as a fixed effect.  The LS means and 
differences in LS means (between Test 1 and Reference) will be presented along with the corresponding 90% CI.
A similar model will be used to analyze the 0-hour (post-injection) pain VAS score and SF-MPQ total score in 
Part B.
The following comparisons will be performed in Part B:

Test 2 versus Test 3 (slow versus fast injection for 2-mL AI)

Test 4 versus Test 5 (slow versus fast injection for 1-mL AI) 
For Parts A and B, safety parameters will be listed and summarized using standard descriptive statistics.
Additional safety and tolerability analyses will be performed if warranted upon review of the data.

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2. Schedule of Activities

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Study Schedule Protocol I6T-MC-AMAQ – Part A
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
Randomization
X
Subjects randomized to 1 x 2-mL or 2 x 1-mL 
PFS arm.
LY3074828 injection
X
Doses administered by investigative site staff.
Stopwatch recording
X
Stopwatch is the source for injection duration 
capture.
Medical history
X
Weight, height, and BMI
X
Vital signs:  blood pressure, 
pulse rate, temperature (hour)
X
X
0, 6
24
X
X X
X
X
X
X
X
Times with respect to start of dosing.  Single 
ECGs to be collected.  Zero-hour collection 
within 30 minutes before dosing.  Time 
allowance for 6- and 24-hour time points:  
±30 and ±90 minutes, respectively.  For vital 
sign assessments, temperature need only be 
included at predose and when clinically 
indicated.
12-lead ECG (hour)
X
0
24
X
Physical examination / 
medical assessment
X
X
X
X
X
Full physical examination/medical 
assessment at screening.  Symptom-directed 
physical examination/medical assessment at 
all other time points, 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. Product 
complaints and device-related AEs collected 
as appropriate.
QuantiFERON®-TB Gold 
test 
X

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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
Serology
X
See Appendix 2 for test details.
Ethanol test and urine drug 
screen
X
X
May be repeated at the discretion of the 
investigator.  Ethanol test may be either
breath or urine testing.  See Appendix 2 for 
test details.
FSH / serum pregnancy test
X
X
X
X
X
Serum pregnancy tests for all female subjects
at screening and on Day -1, and only for 
women of childbearing potential on Days 29, 
57, and 85/ED.  For all women who are 
considered to be postmenopausal, FSH should 
be drawn at screening to confirm 
postmenopausal status as defined in inclusion 
criterion [1b]; women with confirmed 
postmenopausal status can be exempted from
further pregnancy tests during the study.  See 
Appendix 2 for test details.
Clinical chemistry, 
hematology, and urinalysis
X
X
X
X
X
X
See Appendix 2 for test details.
Creatine phosphokinase
X
X
X
Injection-site assessment for 
erythema, induration, 
categorical pain, pruritus, 
edema, and visible bleeding
(hour)
0, 0.25 
X
X
X
Times with respect to start of dosing.  
Zero-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.
Pain assessment (SF-MPQ, 
including pain VAS)
X
Immediately after the start of injection (t = 0) 
(within approximately 5 minutes) and at 15 
(±5), 30 (±5), 60 (±5), 120 (±10), and 240 
(±10) minutes post injection. For 1-mL PFS, 
assessments to be completed on the first of 
the 2 injections only.
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.  
Zero-hour collection immediately (within 
15 minutes) before dosing. Time allowance 
for 2-, 6-, and 24-hour time points:  ±15, ±30, 

I6T-MC-AMAQ(b) Clinical Pharmacology Protocol
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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
and ±90 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; PFS = pre-filled syringe; SF-MPQ = Short Form McGill Pain Questionnaire; 
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, pain assessment, injection-site assessment, immunogenicity sample, stored 
sample, such that pharmacokinetic 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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Study Schedule Protocol I6T-MC-AMAQ – Part B
Screening
Days
Comments
Procedure
≤28 days
-1
1
2
3
15
±2d
43
±2d
86/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
Randomization
X
Subjects randomized to 1-mL or 2-mL AI arm, and then 
further randomized within the arm in respect to 
sequence of injection speed on Days 1 and 2 (slow/fast 
or fast/slow).
Injection training
X
LY3074828 injection
X
X
Doses self-administered.
Stopwatch and video recording
X
X
Stopwatch is the source for injection duration capture. 
Video recording for device functionality.
AI Use Assessment 
Questionnaire
X
X
Clinical staff who observe the subject’s self-injection 
with the AI will fill out the AI Use Assessment 
Questionnaire
Medical history
X
Weight, height, and BMI
X
Vital signs:  blood pressure, 
pulse rate, temperature (hour)
X
X
0, 6
0, 6
24
X
X
X
Times with respect to start of dosing.  Single ECGs to 
be collected.  Zero-hour collection within 30 minutes 
before dosing.  Time allowance for 6- and 24-hour time
points:  ±30 and ±90 minutes, respectively.  For vital 
sign assessments, temperature need only be included at 
predose and when clinically indicated.
12-lead ECG (hour)
X
0
0
24
X
Physical examination / medical 
assessment
X
X
X
X
Full physical examination/medical assessment at 
screening.  Symptom-directed physical 
examination/medical assessment at all other time points, 
and as deemed necessary by the investigator.

I6T-MC-AMAQ(b) Clinical Pharmacology Protocol
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Screening
Days
Comments
Procedure
≤28 days
-1
1
2
3
15
±2d
43
±2d
86/ED
±3d
AE review
X
X
X
X
X
X
X
X
AE only after signing ICF. Product complaints and 
device-related AEs collected as appropriate.
QuantiFERON®-TB Gold test 
X
Serology
X
See Appendix 2 for test details.
Ethanol test and urine drug 
screen
X
X
May be repeated at the discretion of the investigator.  
Ethanol test may be either breath or urine testing.  See 
Appendix 2 for test details.
FSH / serum pregnancy test
X
X
X
X
X
Serum pregnancy tests for all female subjects at 
screening and on Day -1, and only for women of 
childbearing potential on Days 15, 43, and 86/ED.  For 
all women who are considered to be postmenopausal, 
FSH should be drawn at screening to confirm 
postmenopausal status as defined in inclusion criterion 
[1b]; women with confirmed postmenopausal status can 
be exempted from further pregnancy tests during the 
study.  See Appendix 2 for test details.
Clinical chemistry, 
hematology, and urinalysis
X
X
X
X
X
See Appendix 2 for test details.
Creatine phosphokinase
X
X
X
Injection-site assessment (Day 
1 injection) for erythema, 
induration, categorical pain, 
pruritus, edema, and visible 
bleeding (hour)
0, 0.25 
24
X
Times with respect to start of dosing.  Zero-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 assessment (Day 
2 injection) for erythema, 
induration, categorical pain, 
pruritus, edema, and visible 
bleeding (hour)
0, 0.25
24
X
Times with respect to start of dosing.  Zero-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.  
Pain assessment (SF-MPQ, 
including pain VAS)
X
X
Immediately after the start of each injection (t = 0) 
(within approximately 5 minutes) and at 15 (±5), 30 
(±5), 60 (±5), 120 (±10), and 240 (±10) minutes post 
injection. 
LY3074828 pharmacokinetic 
X
X
X
Samples collected to match immunogenicity collections.

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Screening
Days
Comments
Procedure
≤28 days
-1
1
2
3
15
±2d
43
±2d
86/ED
±3d
sampling
Predose
Samples will be stored and will only be sent for 
bioanalysis at a later date based on immunogenicity or 
safety results from Part B of the study.
Immunogenicity sample
Predose
X
X
X
LY3074828 antibody sample.
Pharmacogenetics sample
X
Abbreviations:  AE = adverse event; AI = autoinjector; BMI = body mass index; CRU = clinical research unit; d = day; ECG = electrocardiogram; ED = early 
discontinuation; FSH = follicle-stimulating hormone; ICF = informed consent form; SF-MPQ = Short Form McGill Pain Questionnaire; 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:  ECG, vital signs, clinical laboratory tests, pain assessment, injection-site assessment, immunogenicity and pharmacokinetic samples, stored 
sample.  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-AMAQ (AMAQ) will assess the pharmacokinetics (PK), safety and tolerability
of, and pain associated with, a 250-mg subcutaneous (SC) dose of LY3074828 solution
formulation administered as 1 x 2-mL 125-mg/mL injection using an investigational manual 
pre-filled syringe (PFS; Test 1) and administered as 2 x 1-mL 125-mg/mL injections using an 
investigational manual PFS (Reference).  The study will also compare safety and tolerability of, 
and pain associated with, a 250-mg SC dose of LY3074828 solution formulation administered as 
1 x 2-mL 125-mg/mL injection using an investigational 2-mL autoinjector (AI) with slow 
(Test 2) and fast (Test 3) injection speeds and a 125-mg dose administered as a 1 x 1-mL 
125-mg/mL injection using an investigational 1-mL AI with slow (Test 4) and fast (Test 5) 
injection speeds.  The study will bridge 2 different PFSs administering the same total volume,
from 2 injections with the 1-mL PFS used to administer LY3074828 solution in 
Study I6T-MC-AMAE (AMAE) to 1 injection with a 2-mL investigational PFS.  Investigational 
1- and 2-mL AI administrations are to be evaluated primarily for pain and injection-site 
reactions.
3.2.
Background
LY3074828 is a humanized immunoglobulin G4-variant monoclonal antibody that is directed 
against the p19 subunit of interleukin-23 (IL-23) and does not bind interleukin-12.  LY3074828 
is being developed for the treatment of autoimmune diseases in which the 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). 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 subjects (single 120-mg SC doses) and in 
33 subjects with plaque psoriasis (single ascending intravenous [IV] doses of 5, 20, 60, 120, 200, 
350, or 600 mg) in Study I6T-MC-AMAA (AMAA).  Furthermore, 43 healthy Japanese and 
Caucasian subjects were administered single IV doses of 60, 200, 600, or 1200 mg LY3074828, 
or placebo, or single SC doses of 200 mg LY3074828, or placebo, in Study I6T-MC-AMAD
(AMAD).
No serious adverse events (SAEs) were reported in either study.  There were no drug-related 
treatment-emergent adverse events (TEAEs) of National Cancer Institute Common Terminology 
Criteria for Adverse Events Grade 2 or higher reported in Study AMAA, and no infusion 
reactions, injection-site reactions, or adverse events (AEs) considered related to study drug were 
reported in Study AMAD.  There were no dose-dependent trends in AEs, or clinically important 
changes in vital signs, electrocardiograms (ECGs), or clinical laboratory results across both 
studies that were considered to be related to the study drug.  Pharmacokinetic results obtained 

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from Study AMAA indicated that serum exposure of LY3074828 increases in a 
dose-proportional manner, and that the mean half-life associated with the terminal rate constant 
(t1/2) was 10.5 days, which did not appear to be dependent on dose.  Maximum concentrations 
were observed 3 days postdose following SC administration and, based on the area under the 
concentration versus time curve (AUC), the SC bioavailability was 40%.
Treatment-emergent anti-drug antibodies (TE-ADAs) developed in 3 of 33 subjects after 
administration of single IV doses of LY3074828 in Study AMAA; however, there was no 
correlation between TE-ADA titers and the doses of LY3074828.  The earliest time point at 
which TE-ADAs were detected was Day 22, which was the first postdose time point at which 
immunogenicity was assessed. The highest anti-drug antibody (ADA) titer observed was 1:320.  
None of the healthy subjects (n=5) who received 120 mg SC LY3074828 developed TE ADA. 
Treatment-emergent ADAs developed in 2 of 6 subjects following single SC doses of 200 mg 
LY3074828 in Study AMAD; however, titers were ≤1:160.
LY3074828 is currently being evaluated in three Phase 2 studies:

Study I6T-MC-AMAC is being conducted in approximately 240 subjects with ulcerative 
colitis.  Three IV doses of 50, 200, or 600 mg LY3074828 (or placebo) are administered 
every 4 weeks (Q4W) during the induction period.  Subjects with a clinical response are 
subsequently administered SC doses of 200 mg LY3074828 (or placebo) Q4W or 200 mg 
LY3074828 every 12 weeks during the 92-week maintenance period.  Subjects with no 
clinical response in the induction period may be administered 3 further 1000 mg 
LY3074828 IV doses Q4W, followed by 200 mg LY3074828 SC Q4W for 80 weeks. 

Study I6T-MC-AMAF is being conducted in approximately 200 subjects with plaque 
psoriasis.  Two SC doses of 30, 100, or 300 mg LY3074828 (or placebo) are 
administered every 8 weeks (Q8W) during the induction period, followed by 30, 100, or 
300 mg Q8W or as required during the 88-week maintenance period.

Study I6T-MC-AMAG is to be conducted in approximately 180 subjects with Crohn’s 
disease (CD).  Three IV doses of 200, 600, or 1000 mg LY3074828 (or placebo) will be 
administered Q4W.  LY3074828-treated subjects with an improvement in CD score will 
either continue with this dose regimen, or will be administered 300 mg LY3074828 SC 
Q4W, over a period of 40 weeks.  Subjects who receive placebo or who did not have a 
clinical improvement in CD score will receive 1000 mg LY3074828 IV Q4W.  Subjects 
with clinical benefit may continue with 300 mg LY3074828 SC Q4W for an additional 
52 weeks.
LY3074828 is currently being evaluated in 2 bioavailability studies:

Study I6T-MC-AMAL is being conducted in approximately 72 healthy subjects.  The 
relative bioavailability, absolute bioavailability, and tolerability of LY3074828 
lyophilized and solution formulations will be assessed.  Dosing using the IV route will 
allow the absolute bioavailability of LY3074828 to be determined.

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LY3074828

Study I6T-MC-AMAE is being conducted in approximately 54 healthy subjects.  The 
study will assess relative bioavailability of LY3074828 solution formulation in pre-filled 
1-mL syringes compared to lyophilized formulation (250 mg). Doses of 250 (2 x 1-mL
syringes) and 500 mg (4 x 1-mL syringes) of LY3074828 are included in the assessment.
3.3.
Benefit/Risk Assessment
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 infection or may exacerbate an existing serious infection.  These may include 
opportunistic infections and reactivation of latent infections, such as tuberculosis (TB) and 
hepatitis B.  Subjects will therefore be screened for hepatitis B/C, human immunodeficiency 
virus (HIV), and TB.  
Treatment-emergent ADAs have been observed in 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 (single 1200-mg IV doses).  
Healthy subjects are not expected to derive any benefit from participating in studies of 
LY3074828.  
Possible device-based risks include local effects such as pain at the injection site from either the 
needle or the solution entry into the SC tissue, swelling, erythema, bleeding, and bruising.  
Systemic effects may include sweating, feeling faint, or fever, as a sign of infection.  These risks 
are mitigated by sterile filling of the semi-finished syringes (SFSs), assembly of devices that 
meet regulatory standards, training of investigative site staff and subjects on proper injection 
techniques, and monitoring of the subjects to ensure injections are performed properly.
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).
More information about the known and expected benefits, risks, SAEs, and reasonably 
anticipated AEs of the AI is found in the device IB.

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4. Objectives and Endpoints
Table AMAQ.1 shows the objectives and endpoints of the study.
Table AMAQ.1.
Objectives and Endpoints
Objectives
Endpoints
Primary
Part A

To evaluate the PK of LY3074828 solution 
formulation after administration of 250-mg 
doses using 2 x 1-mL and 1 x 2-mL PFS 
injections in healthy subjects.

To assess the safety and tolerability of, and 
pain associated with, LY3074828 PFS 
administrations in healthy subjects.
Part A

The primary PK endpoints will be the Cmax, 
AUC(0-tlast), and AUC(0-∞) of LY3074828.

Incidence of TEAEs.

SF-MPQ, including VAS pain score.
Part B

To compare the safety and tolerability of, and 
pain associated with, LY3074828 solution 
formulation after administration of 125- and 
250-mg doses using 1-mL AI and 2-mL AI 
SC injections with different injection speeds 
(slow and fast) in healthy subjects.
Part B

Incidence of TEAEs.

SF-MPQ, including VAS pain score.
Abbreviations:  AI = autoinjector; AUC(0-∞) = area under the concentration versus time curve from time zero to 
infinity; AUC(0-tlast) = area under the concentration versus time curve from time zero to time t, where t is the 
last sample with a measurable concentration; Cmax = maximum observed drug concentration; PFS = pre-filled 
syringe; PK = pharmacokinetic; SC = subcutaneous; SF-MPQ = Short Form McGill Pain Questionnaire; 
TEAE = treatment-emergent adverse event; VAS = visual analog scale.

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5. Study Design
5.1.
Overall Design
Study I6T-MC-AMAQ (AMAQ) is a single-center, randomized, parallel-treatment, open-label, 
Phase 1 single-dose study of LY3074828 solution formulation in healthy subjects.  In Part A, 
PK, safety and tolerability of, and pain associated with, SC doses administered using 1- and 
2-mL PFS injections will be evaluated.  In Part B, safety and tolerability of, and pain associated 
with, single AI injections of 1- and 2-mL that will be administered with 2 different injection 
speeds will be evaluated.
Screening Period (≤28 days):  Subjects will be evaluated for study eligibility ≤28 days prior to 
enrollment.
Residential Period (2 days [Part A] or 3 days [Part B]):  A total of approximately 72 subjects 
(approximately 36 subjects per study Parts A and B) who fulfill the eligibility criteria will be 
randomized to 1 of 2 dosing regimen arms within their assigned study part, with 18 subjects 
randomized to each arm in order to ensure completion of 16 subjects in each:
Part A

Reference:  250 mg LY3074828 solution formulation, 2 x 1-mL 125-mg/mL PFS 
injections using an investigational PFS targeting 5- to 10-second injection time for 
each injection

Test 1:  250 mg LY3074828 solution formulation, 1 x 2-mL 125-mg/mL PFS 
injection using an investigational PFS targeting 5- to 15-second injection time
Part B

Tests 2 and 3:  250 mg LY3074828 solution formulation, 1 x 2-mL 125-mg/mL AI 
slow injection (Test 2; targeting approximately 13-second injection time) and fast 
injection (Test 3; targeting approximately 5-second injection time) using an 
investigational 2-mL AI

Tests 4 and 5:  125 mg LY3074828 solution formulation, 1 x 1-mL 125 mg/mL AI 
slow injection (Test 4; targeting approximately 7-second injection time) and fast 
injection (Test 5; targeting approximately 4.5-second injection time) using an 
investigational 1-mL AI
For Part A, 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 to 
either a 2 x 1-mL or a 1 x 2-mL 125-mg/mL PFS dose regimen, study drug will be administered 
by investigative site staff by SC injection in the abdomen in the morning of Day 1 after an 
overnight fast.
For Part B, subjects will report to the CRU on Day -1 and will remain at the CRU until the 
scheduled procedures have been completed on Day 3.  Subjects will be randomized to receive, 
on Days 1 and 2, either a 1 x 1-mL or a 1 x 2-mL 125-mg/mL AI dose regimen.  The allocated 

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LY3074828
AI dose regimen will be self-administered by slow and fast SC injection(s) on consecutive days 
(sequence randomized) in the abdomen after an overnight fast.  
Outpatient Follow-up Period (12 weeks):  The follow-up period will include outpatient visits 
for a total of 12 weeks (Days 4, 8, 11, 15, 22, 29, 43, 57, 71, and 85 for Part A; Days 15, 43, and 
86 for Part B) following dose administration on Day 1 to assess the PK, safety, and tolerability
of, and pain associated with, LY3074828 PFS administrations for Part A, and to assess the safety
and tolerability of, and pain associated with, LY3074828 investigational AI administrations for 
Part B.
Safety and tolerability will be explored by clinical laboratory tests, vital sign measurements, 
12-lead ECGs, recording of AEs and product complaints, physical examinations/medical 
assessments, immunogenicity, and injection-site assessments.  Pain assessments will be made 
using the Short Form McGill Pain Questionnaire (SF-MPQ), which includes a subject-assessed 
injection-site pain visual analog scale (VAS).
5.2.
Number of Participants
A total of approximately 72 subjects (approximately 36 subjects per study Parts A and B) who 
fulfill the eligibility criteria will be randomized to 1 of 2 dosing regimen arms within their 
assigned study part, with 18 subjects randomized to each arm in order to ensure completion of 
16 subjects in each.  A subject’s study participation is considered as complete if he/she receives 
the study drug as per the protocol requirements and completes all activities up to and including at 
least Day 57 for Part A or up to and including at least Day 15 for Part B.  A maximum of 
4 subjects per arm per study part may be replaced if multiple subjects do not complete the study.
5.3.
End of Study Definition
End of the study is 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
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.
For Part A, single doses of LY3074828 and the PK sampling time points have been selected to 
generate PK profiles sufficient to fulfill the study objectives.  As the primary endpoints for 
Part A of this study are PK-related and are not subject to bias, it is not considered necessary for 
this study to be blinded.  Subjects and site staff will be aware of the administration route and 
treatment.
For Part B, only an evaluation of safety and tolerability of, and pain associated with, the 
investigational AI administrations is intended.  Pharmacokinetic samples are collected only in 
conjunction with immunogenicity samples to provide concentrations of LY3074828 to aid in the 
interpretation of ADA data if needed.

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LY3074828
For Part A, aparallel-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.
For Part B, a crossover design was chosen as PK analysis is not an endpointand a relatively 
short time between injections will allow a more accurate comparison of injection-site pain by 
subjects
Monoclonal antibody therapy has been associated with hypersensitivity reactions, including 
injection-sitereactions.  Follow-up details on injection-sitereactions 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
CCI
Doses up to 1200mg were found to be well toleratedwhen administered by IV infusion in 
healthy subjects in the single-dose Study AMAD.  Subcutaneous bioavailability was 
approximately 40% in StudyAMAA.

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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 ECG.  
The nature of any conditions present at the time of the physical examination and any preexisting 
conditions will be documented.
Screening will 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 male or female subjects, as determined by medical history 
and physical examination
[1a] male subjects:

Men, regardless of their fertility status, with non-pregnant women of 
childbearing potential partners must agree to either remain abstinent (if this 
is their preferred and usual lifestyle) or use condoms as well as one 
additional highly effective (less than 1% failure rate) method of 
contraception (such as combination oral contraceptives, implanted 
contraceptives, or intrauterine devices) or effective method of contraception 
(such as diaphragms with spermicide or cervical sponges) for the duration 
of the study and for 24 weeks following dosing with the study drug
o
Men and their partners may choose to use a double-barrier method 
of contraception. (Barrier protection methods without concomitant 
use of a spermicide are not an effective or acceptable method of 
contraception. Thus, each barrier method must include use of a 
spermicide. It should be noted, however, that the use of male and 
female condoms as a double-barrier method is not considered 
acceptable due to the high failure rate when these barrier methods 
are combined)
o
Periodic abstinence (e.g., calendar, ovulation, symptothermal, 
post-ovulation methods), declaration of abstinence just for the 
duration of a trial, and withdrawal are not acceptable methods of 
contraception

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LY3074828

Men with pregnant partners should use condoms during intercourse for the 
duration of the study and for 24 weeks following dosing with the study drug

Men should refrain from sperm donation for the duration of the study and 
for 24 weeks following dosing with the study drug

Men who are in exclusively same-sex relationships (as their preferred and 
usual lifestyle) are not required to use contraception
[1b] female subjects:

All female subjects must test negative for pregnancy prior to initiation of 
treatment as indicated by a negative serum pregnancy test at the screening 
visit followed by a negative serum pregnancy test within 24 hours prior to 
exposure

Women of childbearing potential who are abstinent (if this is complete 
abstinence, as their preferred and usual lifestyle) or in a same-sex 
relationship (as part of their preferred and usual lifestyle) must agree to 
either remain abstinent or stay in a same-sex relationship without sexual 
relationships with males. Periodic abstinence (e.g., calendar, ovulation, 
symptothermal, post-ovulation methods), declaration of abstinence just for 
the duration of a trial, and withdrawal are not acceptable methods of 
contraception

Otherwise, women of childbearing potential participating must agree to use 
one highly effective method (less than 1% failure rate) of contraception, or 
a combination of 2 effective methods of contraception (for 12 weeks
following dosing with the study drug)
o
Either one highly effective method of contraception (such as 
combination oral contraceptives, implanted contraceptives, or 
intrauterine device) or a combination of 2 effective methods of 
contraception (such as male or female condoms with spermicide, 
diaphragms with spermicide, or cervical sponges) will be used. The 
subject may choose to use a double-barrier method of contraception. 
Barrier protection methods without concomitant use of a spermicide 
are not a reliable or acceptable method. Thus, each barrier method 
must include use of a spermicide. It should be noted that the use of 
male and female condoms as a double-barrier method is not 
considered acceptable due to the high failure rate when these 
methods are combined

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LY3074828

Women not of childbearing potential may participate and include those who 
are: 
o
infertile due to surgical sterilization (hysterectomy, bilateral 
oophorectomy, or tubal ligation) or congenital anomaly such as 
mullerian agenesis; or 
o
postmenopausal – defined as either:

A woman at least 50 years of age with an intact uterus, not 
on hormone therapy, who has had either:

cessation of menses for at least 1 year; or 

at least 6 months of spontaneous amenorrhea with a 
follicle-stimulating hormone >40 mIU/mL; or 

A woman 55 or older not on hormone therapy, who has had 
at least 6 months of spontaneous amenorrhea; or 

A woman at least 55 years of age with a diagnosis of 
menopause prior to starting hormone-replacement therapy
[2]
are between 18 and 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
[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

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LY3074828
[10] are currently enrolled in a clinical study involving an investigational product 
(IP) 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 IP 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 IP
[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, or neurological disorders capable 
of significantly altering the absorption, metabolism, or elimination of drugs; 
of constituting a risk when taking the IP; or of interfering with the 
interpretation of data
[17] have known or ongoing psychiatric disorders deemed clinically significant by 
the investigator
[18] regularly use known drugs of abuse and/or show positive findings on drug 
screening
[19] show evidence of HIV infection and/or positive 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 1 month prior to screening 

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[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.  Subjects with any history of active TB are excluded from the 
study, regardless of previous or current TB treatments
[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 
[34] have clinically significant multiple or severe drug allergies, or intolerance to 
topical corticosteroids, or severe posttreatment hypersensitivity reactions 
(including, but not limited to, erythema multiforme major, linear 
immunoglobulin A dermatosis, toxic epidermal necrolysis, or exfoliative 
dermatitis)
[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] have excessive tattoos over the abdomen that would interfere with 
injection-site assessments

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[38] in the opinion of the investigator, 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 will 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 will not consume caffeinated beverages (decaffeinated beverages are permitted) 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 strenuous activity from 24 hours prior to each visit and 48 hours prior 
to any visit where creatine phosphokinase testing will occur (Day -1, Day 8, and Day 29 in 
Part A, and Day -1, Day 15, and Day 43 in Part B).  While certain study procedures are in 
progress at the site, subjects may be required to remain recumbent or sitting.
6.3.4. Blood and Plasma Donation
Subjects will not donate blood or plasma for 12 weeks following dosing with the study drug.
6.4.
Screen Failures
Individuals who do not meet the criteria for participation in this study (screen failure) may not be 
re-screened.

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7. Dosing Regimens
7.1.
Dosing Regimens Administered
This study evaluates the PK, safety, and tolerability of, and pain associated with, LY3074828 
solution formulation SC dose administered by investigational site staff using 2 x 1-mL and 
1 x 2-mL PFS injections (Part A); and compares the safety and tolerability of, and pain 
associated with, 1 x 1-mL and 1 x 2-mL AI injections self-administered with 2 different injection 
speeds (Part B).
Using the investigational 2-mL AI, the targeted injection duration will be approximately 
13 seconds for slow injection rate and approximately 5 seconds for fast injection rate.  Using the
investigational 1-mL AI, the targeted injection duration will be approximately 7 seconds for slow 
injection rate and approximately 4.5 seconds for fast injection rate.  Manual injections using the 
investigational PFS should target an injection duration of about 5 to 10 seconds for 1-mL PFS for 
each injection and about 5 to 15 seconds for 2-mL PFS, to approximate the injection time range 
for AIs.  Approximate injection durations for AIs and PFSs will be obtained using a calibrated 
stopwatch and recorded in the electronic case report form (eCRF).  
Drug and device accountability records will be maintained by the site pharmacy.
Table AMAQ.2 and Table AMAQ.3 show the dosing regimens for Part A and Part B, 
respectively.
Table AMAQ.2.
Dosing Regimens Administered – Part A
Dosing Regimen
PFS
(250 mg)
PFS
(250 mg)
Reference/test
Reference
Test 1
Product
LY3074828
LY3074828
Dose
250 mg
250 mg
Concentration
125 mg/mL
125 mg/mL
Injection volumes
2 × 1 mL
(2 mL total)
1 × 2 mL
(2 mL total)
Number of injections
2
1
Injection rate
5 to 10 seconds
5 to 15 seconds
Formulation and presentation
Solution in a PFS
Solution in a PFS
Abbreviations:  PFS = pre-filled syringe.

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Table AMAQ.3.
Dosing Regimens Administered – Part B
Dosing Regimen
2-mL AI
(250 mg)
1-mL AI
(125 mg)
Reference/test
Test 2 and Test 3
Test 4 and Test 5
Product
LY3074828
LY3074828
Dose
250 mg
125 mg
Concentration
125 mg/mL
125 mg/mL
Injection volumes
1 × 2 mL
(2 mL total)
1 × 1 mL
(1 mL total)
Number of injections
1
1
Injection rate
Approximately 13 seconds (Test 2)
Approximately 5 seconds (Test 3)
Approximately 7 seconds (Test 4)
Approximately 4.5 seconds (Test 5)
Formulation and presentation
Solution in an AI
Solution in an AI
Abbreviations:  AI = autoinjector.
Investigational AIs will be assembled at the site by Lilly Delivery and Device Research and 
Development engineers.  Device Development Quality Assurance will inspect the assembled 
investigational devices on site to ensure basic good manufacturing practice (GMP) guidelines are
met, and that assembly is performed as per GMP procedures, prior to use in the clinical trial.  
The investigational PFSs containing LY3074828 will be supplied by Lilly fully assembled.
Adjustments to the device (such as changing the spring) will be based on injection duration and 
tolerability/AEs (pain, bleeding, bruising, leakage, induration, swelling, pruritus, and 
erythema/redness), and will be performed on site.  Device issues that result in AEs will be 
reported as product quality complaints (PCs).
All injections, whether administered by PFS or AI, will be given into the lower quadrant of the 
abdomen, with site staff or subject selecting left or right quadrant when a single injection is 
being given. For administrations requiring 2 injections, injections will be given into separate 
lower quadrants (right and left). Investigational product administered using PFS will be 
administered to subjects on-site by designated trained clinical site personnel.  Investigational 
product administered using AI will be self-administered by subjects on-site after receiving 
instruction from trained clinical site personnel.
Further information regarding SC administration will be included in the device Instructions for 
Use (IFU) for the PFS and in the device IB (which contains IFU) for the AI.
In some cases, the site may destroy the material if, during the investigative site selection, the 
evaluator has verified and documented that the site has appropriate facilities and written 
procedures to dispose of clinical trial materials.  

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7.1.1. Packaging and Labeling
LY3074828 will be supplied by the sponsor or its designee in accordance with current GMP, and 
labeled according to the country’s regulatory requirements. The following products will be 
supplied by Lilly:

pre-assembled investigational LY3074828 PFSs, 1-mL and 2-mL

LY3074828 (solution for injection) SFS 
Each SFS will be supplied as a 1- or 2-mL single-use syringe designed to deliver LY3074828 
125 mg/mL.  Members of Lilly Delivery and Device Research and Development will attend the 
study site and assemble the SFS and appropriate device components, to form the investigational 
AIs. 
Each investigational device will be individually identified and labeled according to US 
regulatory requirements for investigational devices.
7.2.
Method of Treatment Assignment
Subjects will be randomized within 1 study part (Part A or Part B) to 1 of 2 dosing regimen arms 
(Table AMAQ.2 and Table AMAQ.3).  In addition, the sequence of injections on Days 1 and 2
(fast/slow versus slow/fast) for subjects participating in Part B will be randomized. 
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 eCRF.
7.3.
Blinding
This is an open-label study; however, subjects in Part B will not be informed as to whether the
AI is fast or slow injection speed.
7.4.
Dose Modification
Dose adjustments are not permitted in this study.
7.5.
Preparation/Handling/Storage/Accountability
The IPs for this study will be:

LY3074828 in an investigational PFS

LY3074828 in an SFS incorporated into an investigational AI
Investigational product will be stored refrigerated at 2°C to 8°C (36°F to 46°F) in its original 
carton to protect from light.  Investigational product should not be frozen or shaken.  Sites will 
be required to monitor temperature of the on-site storage conditions of the IP.  The investigator 
or designee must confirm appropriate temperature conditions have been maintained, as 
communicated by the sponsor, during transit for all IP received and ensure any discrepancies are 
reported and resolved before use of the study treatment.

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The SFSs assembled into AIs containing LY3074828 and the PFSs containing LY3074828 
should be allowed to warm to room temperature for at least 30 minutes before use. 
Parts to be used for the assembly of AIs may be stored at room temperature.
Only participants enrolled in the study may receive IP or study materials, and only authorized 
site staff may supply IP.  All IP should be stored in an environmentally-controlled and monitored 
(manual or automated) area in accordance with the labeled storage conditions with access limited 
to the investigator and authorized site staff.
The investigator is responsible for study treatment accountability, reconciliation, and record 
maintenance (such as receipt, reconciliation, and final disposition records).
7.6.
Treatment Compliance
The IP 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 medications, 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 (CP) or 
clinical research physician (CRP).  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 
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 CP or CRP and the investigator 
to determine if the subject may continue in the study.  If a subject is inadvertently enrolled into 
Part B and this is discovered prior to the scheduled administration of the second dose, the second
dose would not be administered.  Any subjects that are inadvertently enrolled subjects will be 
followed for safety.
8.2.
Discontinuation from the Study
Subjects will be discontinued in the following circumstances:

Enrollment in any other clinical study involving an IP 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

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 clinical 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 emerging 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 IP or the study, 
or that caused the subject to discontinue the IP 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 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, study device, 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 IP, 
study device, 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

when a condition related to the investigational device (PFS or AI) necessitates medical or 
surgical intervention to preclude either permanent impairment of a body function or 
permanent damage to a body structure, the serious outcome of “required intervention” 
will be assigned
Study site personnel must alert the Lilly CRP/CP, 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 IP.  However, if 
an SAE occurs after signing informed consent, but prior to receiving IP AND is considered 
reasonably possibly related to a study procedure then it MUST be reported.

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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 
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 IP) 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.
Adverse Device Effects
Any AE believed to be related to an issue with the investigational device (AI) or to the use of the 
study device (PFS) is considered an adverse device event.  These events must be clearly 
indicated as such in the eCRF, and reported to the sponsor.  A PC should also be reported.
For the purpose of this protocol, “unanticipated” adverse device effect means any serious adverse 
event alleged to be associated or related to the device, and which has been confirmed as such by 
the sponsor.  The SAE relatedness must be clearly indicated as such in the eCRF, and reported to 
the sponsor within 24 hours of site knowledge of the event.  A PC should also be reported.
9.2.1.2.
Adverse Events of Special Interest
The following AEs of special interest will be used to determine the safety and tolerability of 
LY3074828 injections administered by either investigational PFS or investigational AI in this 
clinical study.
Adverse events of special interest for LY3074828 are:

infection

injection-site reactions

allergic/hypersensitivity reactions
If infections, injection-site reactions, or allergic/hypersensitivity reactions are reported, sites will 
provide details on these events as instructed on the eCRF. Investigators will also educate 
subjects about the symptoms of allergic/hypersensitivity reactions and will provide instructions 
on dealing with these reactions. A blood sample will be collected when possible for any subject 
who experiences an AE of allergic/hypersensitivity reaction during the study.
9.2.1.3.
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 IP 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.
9.2.1.4.
Adverse Event Monitoring with a Systematic Questionnaire
Before administering the SF-MPQ, study site personnel will question the subject about any 
change in the preexisting condition(s) and the occurrence and nature of any AEs.

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Injection-site assessment at the scheduled protocol time points will not be double reported in the 
AE form, but will be captured in the eCRF.
Only serious AEs elicited through the SF-MPQ are to be recorded as AEs via electronic data 
entry and reported to Lilly or its designee within 24 hours as SAEs.
Unsolicited AEs (e.g., headache, redness reported by subjects during the follow-up period) will 
be reported in the AE form.
9.2.2. Complaint Handling
Lilly collects PCs on IPs 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 IP or drug delivery system so that the situation can be assessed.  
A PFS or AI that is associated with a product quality issue or complaint must be returned to 
Lilly.
The investigator or his/her designee is responsible for handling the following aspects of the PC
process in accordance with the instructions provided for this study:

recording a complete description of the PC reported and any associated AEs using the 
study-specific complaint forms provided for this purpose,

faxing the completed Product Complaint Form within 24 hours to Lilly or its designee.
If the investigator is asked to return the product for investigation, he/she will return a copy of the 
Product Complaint Form with the product.
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 study drug 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.

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9.4.2. Vital Signs
For each subject, vital sign measurements (blood pressure, pulse rate, and temperature) should be 
conducted according to the Schedule of Activities (Section 2).  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.
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 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 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 clinically significant findings from ECGs that result in a diagnosis and that occur after the 
subject receives the first dose of the IP should be reported to Lilly, or its designee, as an AE via 
eCRF.
9.4.4. Other Tests
9.4.4.1.
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 completed.
Subjects with any history of active TB are excluded from the study, regardless of previous or 
current TB treatments.

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9.4.4.2.
Injection Instructions
Prior to the PFS or AI injection, the investigator or his/her designee will prepare the subject’s 
skin.  The injections will be given according to the instructions provided by the sponsor.  
Pre-filled syringe injections into the abdomen will be administered by investigative site staff.  
All subjects will receive training on how to use the AI to self-administer into the abdomen.  The 
investigator or his/her designee will answer any questions the subject may have and will 
demonstrate the steps required for injection according to the IFU.  Subjects will be monitored 
while using the AI to ensure successful self-injections.  Investigative site staff who observe the 
subject’s self-injection with the AI will fill out the AI Use Assessment Questionnaire.  All study 
injection sites will be marked using a template for size and with a surgical marker in order to 
identify study injection sites for later assessments.
9.4.4.3.
Injection Speed Assessments and Video Recording
Injection duration will be measured by a calibrated stopwatch by qualified trained study staff.  
For Part A, the duration of injection for the PFSs will be defined as the time between when the 
plunger rod is pressed down and when all of the LY3074828 solution is injected.  For Part B, the 
duration of injection for the AIs will be defined as the time between the first audible click after 
the injection button is pressed and the last audible click, which indicates that the needle has 
retracted and the injection is complete.  
For Part B, a video recorder will be used to record the AI injection site and the device as it is 
being used. The video recordings may be examined to explore device functionality. The 
subject’s face, voice, or identifiable markings will not be video recorded. The video recording 
will be identified by the subject number. The video data will be managed by the sponsor and 
securely stored electronically in the sponsor’s network. Further analysis of the video recordings 
may be performed by qualified sponsor personnel after completion of the study.
9.4.4.4.
Injection-site Assessments
While the SF-MPQ will be administered to capture data for pain on injection, other injection-site 
reactions will be captured in the subjects’ eCRF as AEs (including erythema, induration, 
categorical pain, pruritus, and edema).  
9.4.4.5.
Bleeding Assessment
All injection sites will be observed at the times indicated in the Schedule of Activities (Section 2) 
by the investigator or designee, and the presence of visible bleeding will be recorded on the 
eCRF.  A bandage may be placed on the injection site after assessment.
9.4.4.6.
Injection-site Pain
9.4.4.6.1. Short Form McGill Pain Questionnaire
Acute pain from SC injection will be assessed using the 15-item short form of the SF-MPQ 
(Melzack 1987) modified to meet the purpose of the study at times specified in the Schedule of 
Activities (Section 2).
As part of the SF-MPQ, pain measurements will be quantified using the 100-mm validated VAS 
for all subjects, whether or not they report injection pain.  The VAS is a well-validated tool
(Williamson and Hoggart 2005) to assess injection-site pain; it is presented as a 100-mm line 

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anchored by verbal descriptors, usually “no pain” and “worst possible pain.”  The subject will be 
asked to rate any pain on a scale of 0 to 100 mm on the line immediately (approximately within 
5 minutes) following the start of the injection and at the time points listed in the Schedule of 
Activities (Section 2).
For 1-mL PFS, assessments are to be completed on the first of the 2 injections only.
9.4.5. Safety Monitoring
The Lilly CP or CRP/scientist will monitor safety data throughout the course of the study.
Lilly will review SAEs within time frames mandated by company procedures.  The Lilly CP or 
CRP will periodically review the following data:

trends in safety data

laboratory analytes

AEs, including monitoring of incidence of any nature of any infections, and injection-site 
reactions

PCs
When appropriate, the Lilly CP or CRP will consult with the functionally independent Global 
Patient Safety (GPS) therapeutic area physician, GPS device physician, or GPS 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, ALP, TBL, direct bilirubin, gamma-glutamyl transferase, and 
creatine phosphokinase 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 CP or CRP.  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 an 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 

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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 CRP based on accepted criteria (Sampson et 
al. 2006). 
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 for Parts A and B.  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.
Pharmacokinetic samples will be collected in both Part A and Part B; however, PK statistical 
analyses will only be performed for Part A.  Samples from Part B will be stored and will only be 
sent for bioanalysis at a later date based on immunogenicity or safety results from Part B of the 
study.
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 IP concentrations will be retained for a maximum of 
1 year following last subject visit for the study.  
9.6.
Pharmacodynamics
9.6.1. Immunogenicity Assessments
Blood samples for immunogenicity testing will be collected to determine antibody production 
against LY3074828, as specified in the Schedule of Activities (Section 2) for Parts A and B.  
Additional samples may be collected if there is a possibility that an AE is immunologically 
mediated. If additional immunogenicity testing samples are taken, matching PK sample 
collections will also be required. Immunogenicity will be assessed by a validated assay designed 
to detect ADAs in the presence of the IP.  Antibodies may be further characterized and/or 
evaluated for their ability to neutralize the activity of the IP.  
A risk-based approach will be used to monitor subjects who develop TE-ADAs during and 
following treatment with LY3074828.  Treatment-emergent ADAs are defined as either a 2-fold 

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increase in titer (i.e., 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 in Part A, and only 2 doses 
over an approximately 24-hour period in Part B, any ADA response is anticipated to peak and 
then diminish due to lack of additional exposures.  Subjects will have ADA sampling at baseline 
(predose) and Days 15, 29, 57, and 85 in Part A, and at baseline (predose) and Days 15, 43, and 
86 in Part B.  Subjects that are observed to have a titer greater than 1:1000, or 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 IPs.  Any samples remaining after 15 years will be destroyed.
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.  

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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
A total of approximately 72 subjects (approximately 36 subjects per study Parts A and B) who 
fulfill the eligibility criteria will be randomized to 1 of 2 dosing regimen arms within their 
assigned study part, with 18 subjects randomized to each arm in order to ensure completion of 
16 subjects in each.  The estimated total variability (coefficient of variation) in AUC from time 
zero to infinity AUC(0-∞), AUC from time zero to time t, where t is the last sample with a 
measurable concentration (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 dosing regimen arms.  A sample size of 64 subjects will provide a precision, in 
log scale, of approximately 0.28 for the geometric means ratio in AUC(0-∞), AUC(0-tlast), and 
Cmax of 1- to 2-mL solution formulation injection.  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 0.28.  Subjects who are randomized but not administered treatment, or subjects that 
are administered treatment but do not have PK and ADA samples collected up to and including 
Day 57, may be replaced (maximum of 4 per arm per study part) to ensure that approximately 
16 subjects from each dosing regimen arm 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 dosing regimen 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 in Part A.  
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 IP and protocol procedure AEs and PCs 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 IP 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 IP- and device-related SAEs and any related PCs will be reported.
10.3.1.2. Statistical Evaluation of Safety
10.3.1.2.1.Injection-site Pain
For Parts A and B, the intensity of pain at each injection site immediately (approximately within 
5 minutes) following the start of the injection will be evaluated, as reported by the subject and 
measured according to the 0 to 100 mm VAS that forms part of the SF-MPQ.  Assessments will 
also be performed at 15, 30, 60, 120, and 240 minutes post injection; however, the primary 
endpoint will be the 0-hour assessment. 
Descriptive statistics will be used to summarize the intensity and type of pain at each time point
as captured by the SF-MPQ.
In Part A, a linear fixed-effects model will be used to analyze the 0-hour (post-injection) pain 
VAS score and SF-MPQ total score.  The model will include treatment (Reference or Test 1) as a 
fixed effect.  The least squares (LS) means and differences in LS means (between Test 1 and 
Reference) will be presented along with the corresponding 90% CI.  The distribution of the data 
will be explored prior to analysis to determine whether data transformation is required.  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.
A similar model will be used to analyze the 0-hour (post-injection) pain VAS score and SF-MPQ 
total score in Part B.  
The following comparisons will be performed in Part B:

Test 2 versus Test 3 (slow versus fast injection for 2-mL AI)

Test 4 versus Test 5 (slow versus fast injection for 1-mL AI) 
10.3.1.2.2.Duration of Injection
The duration of the injection (measured in seconds) will be summarized for each drug delivery 
device for each dosing regimen.

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10.3.1.2.3.Injection-site Assessments
Incidence of erythema, induration, categorical pain, pruritus, edema, and bleeding will be listed 
and summarized by dosing regimen.  
10.3.1.2.4.Statistical Evaluation of Other Safety Parameters
Other safety parameters that will be assessed include clinical laboratory parameters, vital signs, 
and ECG parameters.  The parameters, and changes from baseline (predose) where appropriate, 
will be listed and summarized using standard descriptive statistics.  Additional analyses will be 
performed if warranted upon review of the data.
10.3.2. Pharmacokinetic Analyses
10.3.2.1. Pharmacokinetic Parameter Estimation
For Part A, PK parameter estimates for LY3074828 will be calculated by standard 
noncompartmental methods of analysis.
The primary parameters for analysis will be AUC(0-∞), AUC(0-tlast), and Cmax for LY3074828.  
The secondary parameter for analysis will be the time to maximum observed drug concentration
(tmax) of LY3074828.  Other noncompartmental parameters, such as t1/2, apparent total body 
clearance of drug calculated after extra-vascular administration (CL/F), and apparent volume of 
distribution during the terminal phase after extra-vascular administration (Vz/F), may be 
reported.
For Part B, no PK parameters will be evaluated.  Pharmacokinetic samples are collected only in 
conjunction with immunogenicity samples to provide serum concentrations of LY3074828 to aid 
in the interpretation of ADA data if needed.  Samples will be stored and will only be sent for 
bioanalysis at a later date based on immunogenicity or safety results from Part B of the study.
10.3.2.2. Pharmacokinetic Statistical Inference
For Part A, the AUC(0-∞), AUC(0-tlast), and Cmax will be log-transformed and analyzed using 
linear fixed-effects model.  The model will include dosing regimen arm as a fixed effect.  The 
dosing regimen differences between the Test 1 arm and the Reference arm will be 
back-transformed to present the ratios of geometric LS means and the corresponding 90% CI.
The tmax of LY3074828 between the 2 x 1-mL PFS (Reference) and the 1 x 2-mL PFS (Test 1) 
will be analyzed using a Wilcoxon rank sum test for Part A.  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 for Part A 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.

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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 or greater 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 or concentrations of LY3074828 may be assessed if deemed 
appropriate.  
10.3.6. 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.
For Parts A and B of the study, available safety data will be reviewed at approximately Day 30 in 
order to review emerging safety and tolerability data.
For Part A of the study, data review is scheduled to occur when safety and PK data through 
approximately Day 57 (8 weeks postdose) become available for at least 12 subjects from each 
dosing regimen arm.  The 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.
10.3.7. Interim Analyses
An exploratory interim analysis is planned for this study. This will be for internal purposes only.  

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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.
Melzack R. The short-form McGill Pain Questionnaire. Pain. 1987;30(2):191-197.
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):391-397.
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.
AI
autoinjector
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
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
CL/F
apparent total body clearance of drug calculated after extra-vascular administration
Cmax
maximum observed drug concentration
complaint
A complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, purity, durability, reliability, safety or effectiveness, or 
performance of a drug or drug delivery system.
compliance
Adherence to all 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.
CP
clinical pharmacologist
CPK
creatine phosphokinase
CRP
clinical research physician
CRU
clinical research unit

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ECG
electrocardiogram
eCRF
electronic case report form
ED
early discontinuation
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
GMP
good manufacturing practice
GPS
Global Patient Safety
HIV
human immunodeficiency virus
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonisation
IFU
Instructions for Use
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.
IP
investigational product
IRB
institutional review board
IV
intravenous(ly)
LS
least squares
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.

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PC
product quality complaint
PFS
pre-filled syringe
PK
pharmacokinetic(s)
Q4W
every 4 weeks
Q8W
every 8 weeks
SAE
serious adverse event
SC
subcutaneous(ly)
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.  
SF-MPQ
Short Form McGill Pain Questionnaire
SFS
semi-finished syringe
SUSAR
suspected unexpected serious adverse reaction 
t1/2
half-life associated with the terminal rate constant
TB
tuberculosis
TBL
total bilirubin
TE-ADA
treatment-emergent anti-drug antibody
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. 
tmax
time to maximum observed drug concentration
ULN
upper limit of normal
VAS
visual analog scale
Vz/F
apparent volume of distribution during the terminal phase after extra-vascular 
administration

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Appendix 2.
Clinical Laboratory Tests
Safety 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
Creatine phosphokinase (CPK)
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
Microscopic examination of sedimentb
Serum Pregnancy testf,g
Hormone Panel
Follicle-stimulating hormone e,h
Abbreviations:  HIV = human immunodeficiency virus; RBC = red blood cells; TB = tuberculosis; 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 (determined via breath or urine testing) 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
For all females at screening and on Day -1, and only for women of childbearing potential at sampling time points 
thereafter.
g
Refer to Section 2 for specific sampling timing.
h
To be done for women 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, the 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 informed consent form 
(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 study.

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 institutional review board (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 good clinical practice (GCP).
The study site’s IRB(s) should be provided with the following:

the current Investigator’s Brochure and updates during the course of the study

ICF

relevant curricula vitae

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Regulatory Considerations
This study will be conducted in accordance with the protocol and with:
1) consensus ethics principles derived from international ethics guidelines, 
including the Declaration of Helsinki and Council for International 
Organizations of Medical Sciences 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 final report coordinating investigator or designee will sign the clinical study report for this 
study, indicating agreement that, to the best of his or her knowledge, the report accurately 
describes the conduct and results of the study.
The 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 electronic case report forms 
(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.

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
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, 
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/scientist.
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
Conjugated bilirubin
Hepatitis E antibody, IgM
Alkaline phosphatase
ALT
Anti-nuclear antibodya
AST
Alkaline phosphatase isoenzymesa
GGT
CPK 
Anti-smooth muscle antibody (or anti-actin 
antibody)a
Abbreviations:  ALT = alanine aminotransferase; AST = aspartate aminotransferase; CPK = creatine phosphokinase; 
GGT = gamma-glutamyl transferase; 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
The following tables summarize 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-AMAQ Sampling Summary – Part A
Purpose
Maximum Blood Volume 
per Sample (mL)
Maximum Number 
of Blood Samples
Maximum Total 
Volume (mL)
Screening testsa
19.5
1
19.5
Clinical laboratory testsa
12.5
5
62.5
Pharmacokineticsb
2
17
34
Immunogenicitya
10
5
50
Pregnancy tests
3.5
4
14
Pharmacogenetics
10
1
10
Total
190
Total for clinical purposes [rounded up to nearest 10 mL]
190
a
Additional samples may be drawn if needed for safety purposes.
b
Includes a potential 3 additional samples to be matched to additional immunogenicity samples (see 
Section 9.6.1).
Protocol I6T-MC-AMAQ Sampling Summary – Part B
Purpose
Maximum Blood Volume 
per Sample (mL)
Maximum Number 
of Blood Samples
Maximum Total 
Volume (mL)
Screening testsa
19.5
1
19.5
Clinical laboratory testsa
12.5
4
50
Pharmacokineticsb
2
7
14
Immunogenicitya
10
4
40
Pregnancy tests
3.5
4
14
Pharmacogenetics
10
1
10
Total
147.5
Total for clinical purposes [rounded up to nearest 10 mL]
150
a
Additional samples may be drawn if needed for safety purposes.
b
Includes a potential 3 additional samples.

I6T-MC-AMAQ(b) Clinical Pharmacology Protocol
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LY3074828
Appendix 6.
Protocol Amendment I6T-MC-AMAQ(b)
Summary: A Safety, Tolerability, and Pharmacokinetic 
Study of 1- and 2-mL Injections of LY3074828 Solution 
Using Investigational Pre-filled Syringes and 
Investigational Autoinjectors in Healthy Subjects
Overview
Protocol I6T-MC-AMAQ, A Safety, Tolerability, and Pharmacokinetic Study of 1- and 2-mL Injections 
of LY3074828 Solution Using Investigational Pre-filled Syringes and Investigational Autoinjectors in 
Healthy Subjects, has been amended.  The new protocol is indicated by Amendment (b) and will be used 
to conduct the study in place of any preceding version of the protocol.
The overall changes and rationale for the changes made to this protocol are described in the following 
table:
Table AMAQ.4.
Amendment Summary for Protocol I6T-MC-AMAQ Amendment(b)
Section # and Name
Description of Change
Brief Rationale
Section 10.3.7. Interim Analysis
An update has been made to 
introduce an exploratory interim 
analysis to this study.
An exploratory interim analysis is 
planned for this study.

I6T-MC-AMAQ(b) Clinical Pharmacology Protocol
Page 61
LY3074828
Revised Protocol Sections
Note:
All deletions have been identified by strikethroughs.
All additions have been identified by the use of underscore.
10.3.7. Interim Analyses
No interim analyses are planned for this study.  If an unplanned interim analysis is deemed 
necessary, the Lilly CP, CRP/investigator, or designee will consult with the appropriate medical 
director or designee to determine if it is necessary to amend the protocol. An exploratory interim 
analysis is planned for this study. This will be for internal purposes only. 

PPD
Leo Document ID = 80a780ee-b11a-4f91-bf13-92570501d634
Approver: 
Approval Date & Time: 26-Jul-2018 19:03:41 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 26-Jul-2018 19:03:41 GMT
Signature meaning: Approved
PPD