Clinical trial NCT04137380
Conditions: Healthy
Sponsor: Eli Lilly and Company
Start date: 2019-12-04; Completion date: 2020-12-11
Enrollment: 60 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The main purpose of this study is to evaluate the safety of the study drug known as mirikizumab. The study will investigate how the body processes the study drug. It will last up to about 4 months for each participant.

Detailed description:

Arms: arm 1: Participants received a single dose of 300 milligram (mg), 600 mg and 1200 mg mirikizumab administered IV using a forearm vein infused over at least 30 minutes, 60 minutes and 2 hours. arm 2: Participants received a single dose of placebo administered IV using a forearm vein. arm 3: Participants received a single dose of 200 mg, 400 mg mirikizumab administered SC as 2 injections, 1 into the skinfold of each lower abdominal wall quadrant (left and right). arm 4: Participants received a single dose of placebo administered SC as 2 injections, 1 into the skinfold of each lower abdominal wall quadrant (left and right).
Interventions: intervention 1: Mirikizumab - IV intervention 2: Mirikizumab - SC intervention 3: Placebo - IV intervention 4: Placebo - SC
Intervention descriptions: intervention 1: Administered IV intervention 2: Administered SC intervention 3: Administered IV intervention 4: Administered SC

Protocol documents:
Prot_000.pdf: 
Protocol I6T-MC-AMBD (c) 
 
A Single-Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of LY3074828 in  
 
Healthy Chinese Subjects 
 
 
NCT04137380 
 
Approval Date: 28-June-2020 
 
 


I6T-MC-AMBD(c) Clinical Pharmacology Protocol
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Protocol I6T-MC-AMBD(c)
A Single-Dose Study to Assess the Safety, Tolerability, and 
Pharmacokinetics of LY3074828 in Healthy Chinese 
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 subject to Freedom of Information Act (FOIA) 
Exemption 4 and may not be reproduced or otherwise disseminated without the written 
approval of Eli Lilly and Company or its subsidiaries.  
LY3074828
Eli Lilly and Company
Indianapolis, Indiana USA 46285
Clinical Pharmacology Protocol Electronically Signed and Approved by Lilly: 10 July 2018
Amendment (a) Electronically Signed and Approved by Lilly:  19-Sep-2018
Amendment (b) Electronically Signed and Approved by Lilly:  05-Sep-2019
Amendment (c) Electronically Signed and Approved by Lilly on date provided below.
Approval Date: 28-Jun-2020 GMT


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Table of Contents
A Single-Dose Study to Assess the Safety, Tolerability, and 
Pharmacokinetics of LY3074828 in Healthy Chinese Subjects
Section
Page
Protocol I6T-MC-AMBD(c) A Single-Dose Study to Assess the Safety, Tolerability, and 
Pharmacokinetics of LY3074828 in Healthy Chinese Subjects....................................................................... 1
Table of Contents................................................................................................................................................... 2
1.
Protocol Synopsis ......................................................................................................................................... 7
2.
Schedule of Activities................................................................................................................................. 10
3.
Introduction................................................................................................................................................ 15
3.1.
Study Rationale..................................................................................................................................... 15
3.2.
Background .......................................................................................................................................... 15
3.3.
Benefit/Risk Assessment....................................................................................................................... 17
4.
Objectives and Endpoints............................................................................................................................ 19
5.
Study Design .............................................................................................................................................. 20
5.1.
Overall Design...................................................................................................................................... 20
5.2.
Number of Participants.......................................................................................................................... 21
5.3.
End of Study Definition ........................................................................................................................ 21
5.4.
Scientific Rationale for Study Design .................................................................................................... 21
5.5.
Justification for Dose ............................................................................................................................ 21
6.
Study Population......................................................................................................................................... 22
6.1.
Inclusion Criteria .................................................................................................................................. 22
6.2.
Exclusion Criteria ................................................................................................................................. 24
6.3.
Lifestyle and/or Dietary Requirements................................................................................................... 25
6.3.1.
Meals and Dietary Restrictions .................................................................................................... 25
6.3.2.
Caffeine, Alcohol, and Tobacco................................................................................................... 26
6.3.3.
Activity....................................................................................................................................... 26
6.3.4.
Blood and Plasma Donation......................................................................................................... 26
6.4.
Screen Failures...................................................................................................................................... 26
7.
Treatment................................................................................................................................................... 27
7.1.
Treatment Administered........................................................................................................................ 27
7.1.1.
Packaging and Labeling............................................................................................................... 28
7.2.
Method of Treatment Assignment.......................................................................................................... 28
7.2.1.
Selection and Timing of Doses..................................................................................................... 28
7.3.
Blinding................................................................................................................................................ 28
7.4.
Dose Modification ................................................................................................................................ 28
7.5.
Preparation/Handling/Storage/Accountability........................................................................................ 28


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7.6.
Treatment Compliance.......................................................................................................................... 29
7.7.
Concomitant Therapy............................................................................................................................ 29
7.8.
Treatment After the End of the Study .................................................................................................... 29
8.
Discontinuation Criteria.............................................................................................................................. 30
8.1.
Discontinuation from Study Treatment.................................................................................................. 30
8.1.1.
Discontinuation of Inadvertently Enrolled Subjects ...................................................................... 30
8.2.
Discontinuation from the Study............................................................................................................. 30
8.3.
Subjects Lost to Follow-up.................................................................................................................... 30
9.
Study Assessments and Procedures ............................................................................................................. 31
9.1.
Efficacy Assessments............................................................................................................................ 31
9.2.
Adverse Events..................................................................................................................................... 31
9.2.1.
Serious Adverse Events ............................................................................................................... 31
9.2.1.1.
Adverse Device Effects......................................................................................................... 32
9.2.1.2.
Adverse Events of Special Interest......................................................................................... 33
9.2.1.3.
Suspected Unexpected Serious Adverse Reactions................................................................. 33
9.2.1.4.
Adverse Event Monitoring with a Systematic Questionnaire.................................................. 33
9.2.2.
Complaint Handling .................................................................................................................... 33
9.3.
Treatment of Overdose.......................................................................................................................... 34
9.4.
Safety ................................................................................................................................................... 34
9.4.1.
Laboratory Tests.......................................................................................................................... 34
9.4.2.
Vital Signs................................................................................................................................... 34
9.4.3.
Electrocardiograms...................................................................................................................... 34
9.4.4.
Other Tests.................................................................................................................................. 35
9.4.4.1.
Tuberculosis Testing............................................................................................................. 35
9.4.4.2.
Subcutaneous Injection-site Assessments............................................................................... 35
9.4.4.2.1.
Subcutaneous Injection-Site Reactions............................................................................ 35
9.4.4.2.2.
Subcutaneous Bleeding Assessment................................................................................ 35
9.4.4.2.3.
Subcutaneous Injection-site Pain Visual Analog Scale .................................................... 35
9.4.5.
Safety Monitoring........................................................................................................................ 35
9.4.5.1.
Hepatic Safety....................................................................................................................... 36
9.4.5.2.
Monitoring of Hypersensitivity Reactions.............................................................................. 36
9.5.
Pharmacokinetics.................................................................................................................................. 36
9.5.1.
Bioanalysis.................................................................................................................................. 37
9.6.
Pharmacodynamics ............................................................................................................................... 37
9.6.1.
Immunogenicity Assessments...................................................................................................... 37
9.7.
Biomarkers ........................................................................................................................................... 38
9.8.
Health Economics................................................................................................................................. 38
10.
Statistical Considerations and Data Analysis ............................................................................................... 39
10.1.
Sample Size Determination ................................................................................................................... 39
10.2.
Populations for Analyses....................................................................................................................... 39


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10.2.1.
Study Participant Disposition....................................................................................................... 39
10.2.2.
Study Participant Characteristics.................................................................................................. 39
10.3.
Statistical Analyses ............................................................................................................................... 39
10.3.1.
Safety Analyses........................................................................................................................... 39
10.3.1.1.
Clinical Evaluation of Safety................................................................................................. 39
10.3.1.2.
Statistical Evaluation of Safety.............................................................................................. 40
10.3.1.2.1.
Injection-site Pain .......................................................................................................... 40
10.3.1.2.2.
Injection-site Assessments.............................................................................................. 40
10.3.1.2.3.
Statistical Evaluation of Other Safety Parameters............................................................ 40
10.3.2.
Pharmacokinetic Analyses ........................................................................................................... 40
10.3.2.1.
Pharmacokinetic Parameter Estimation.................................................................................. 40
10.3.2.2.
Pharmacokinetic Statistical Inference .................................................................................... 40
10.3.3.
Pharmacodynamic Analyses ........................................................................................................ 40
10.3.4.
Pharmacokinetic/Pharmacodynamic Analyses.............................................................................. 40
10.3.5.
Evaluation of Immunogenicity..................................................................................................... 41
10.3.6.
Data Review During the Study..................................................................................................... 41
10.3.7.
Interim Analyses ......................................................................................................................... 41
11.
References.................................................................................................................................................. 42
12.
Appendices................................................................................................................................................. 43


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List of Tables
Table
Page
Table AMBD.1.
Objectives and Endpoints ............................................................................................ 19
Table AMBD.2.
Treatments Administered............................................................................................. 27


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List of Appendices
Appendix
Page
Appendix 1.
Abbreviations and Definitions...................................................................................... 44
Appendix 2.
Clinical Laboratory Tests............................................................................................. 48
Appendix 3.
Study Governance, Regulatory and Ethical Considerations........................................... 49
Appendix 4.
Hepatic Monitoring Tests for Treatment-Emergent Abnormality .................................. 52
Appendix 5.
Blood Sampling Summary........................................................................................... 53
Appendix 6.
Protocol Amendment I6T-MC-AMBD(c) Summary
A Single-Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of 
LY3074828 in Healthy Chinese Subjects ..................................................................... 54


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1. Protocol Synopsis
Title of Study:
A Single-Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of LY3074828 in Healthy Chinese 
Subjects
Rationale:  
Study I6T-MC-AMBD (AMBD) is a clinical evaluation of LY3074828 in Chinese subjects, and is being conducted 
to investigate the safety, tolerability, and pharmacokinetics (PK) of single-dose administration of LY3074828 in this 
population.  Data from completed preclinical and clinical studies support the administration to healthy Chinese 
subjects within the dose range planned for this study.  This study will support future Phase 3 clinical studies in 
Chinese patients.
Objectives/Endpoints:
Objectives
Endpoints
Primary

To assess the safety and tolerability of single 
LY3074828 IV doses (300, 600, and 
1200 mg) and single SC doses (200 and 
400 mg) in healthy Chinese subjects.

Incidence of TEAEs.

VAS pain score.
Secondary

To evaluate the PK of single LY3074828 IV
doses (300, 600, and 1200 mg) and single 
SC doses (200 and 400 mg) in healthy 
Chinese subjects.

Including Cmax, AUC(0-tlast), AUC(0-∞), and 
tmax of LY3074828.
Abbreviations:  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; IV = intravenous; 
PK = pharmacokinetic; SC = subcutaneous; TEAE = treatment-emergent adverse event; tmax = time to 
maximum observed drug concentration; VAS = visual analog scale.
Summary of Study Design:
Study I6T-MC-AMBD (AMBD) is a subject- and investigator-blinded, randomized, parallel-group, 
placebo-controlled, Phase 1 single-dose study of LY3074828 in healthy Chinese subjects.  Native Chinese subjects 
born in China, with all 4 grandparents and both parents of Chinese origin will be enrolled.  The study will consist of 
5 planned dose cohorts:  3 intravenous (IV) dose cohorts (300 mg, 600 mg, and 1200 mg) and 2 subcutaneous (SC)
dose cohorts (200 mg and 400 mg).  Subjects will be randomized within each cohort to receive LY3074828 
(10 subjects) or placebo (2 subjects).
Subjects will report to the clinical research unit (CRU) on Day -1.  After randomization, study drug will be 
administered by investigative site staff by either IV administration using a forearm vein or SC injection in the 
abdomen using pre-filled syringes in the morning of Day 1 after an overnight fast.  Subjects will remain at the CRU 
until the scheduled procedures have been completed on Day 2, and will then be discharged.  Subjects will be 
followed for approximately 12 weeks following dose administration.


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Safety and tolerability will be explored by clinical laboratory tests, vital sign measurements, 12-lead 
electrocardiograms, recording of adverse events, physical examinations/medical assessments, immunogenicity, and 
injection-site assessments.  Pain assessments will be made using a subject-assessed injection-site pain visual analog 
scale.
Dosing Regimen Arms and Duration:  
Subjects will be randomized within each cohort to receive study drug or placebo:

Cohort 1:  a single dose of LY3074828 300 mg or placebo IV infused over at least 30 minutes (n=12; 
10 LY3074828, 2 placebo)

Cohort 2:  a single dose of LY3074828 600 mg or placebo IV infused over at least 60 minutes (n=12; 
10 LY3074828, 2 placebo)

Cohort 3:  a single dose of LY3074828 1200 mg or placebo IV infused over at least 2 hours (n=12; 
10 LY3074828, 2 placebo)

Cohort 4:  a single dose of LY3074828 200 mg or placebo SC (n=12; 10 LY3074828, 2 placebo)

Cohort 5:  a single dose of LY3074828 400 mg or placebo SC (n=12; 10 LY3074828, 2 placebo)
Dosing of cohorts may be conducted in parallel or sequentially at the discretion of the investigator.  Total duration 
of the study for each subject will be up to approximately 16 weeks (screening period ≤28 days, residential period of 
3 days/2 nights, and outpatient follow-up period of approximately 12 weeks).
Number of Subjects:
Sixty subjects who fulfill the eligibility criteria may be enrolled into the study to try to ensure that approximately 
50 subjects complete (10 subjects per cohort are required in order to provide the necessary safety and PK data). 
Furthermore, every effort should be made to enroll subjects so that at least 4 subjects per cohort are female. Each 
subject will participate in 1 of the 5 cohorts.  Subjects who withdraw from the study will not be replaced.  For 
analytical purposes, 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.
Statistical Analysis:
Safety parameters will be listed and summarized using standard descriptive statistics, as applicable.
Additional safety and tolerability analyses will be performed if warranted upon review of the data.
The frequency of formation of antibodies to LY3074828 will be listed.  If a neutralization assay is performed, the 
frequency of neutralizing antibodies will be listed.
Pharmacokinetic parameter estimates for LY3074828 will be calculated by standard noncompartmental methods of 
analysis.  The primary parameters for PK analysis will be 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).  The secondary parameter for 
analysis will be the time to maximum observed drug concentration (tmax) of LY3074828.  Other noncompartmental 
parameters, such as bioavailability following SC administration, half-life, clearance, and volume of distribution 
(apparent clearance and apparent volume of distribution for SC administration), may be reported.


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No formal statistical analysis will be performed for this study.  The PK parameters will be summarized by treatment 
and listed.  Additional PK analyses may be conducted if deemed appropriate.  


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2. Schedule of Activities


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Study Schedule Protocol I6T-MC-AMBD
Screen-
ing
Days
Comments
Procedure
≤28 
days
-1
1
2
4
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
Subject admission to CRU
X
Subject discharge from 
CRU
X
Outpatient visit
X
X
X
X
(SC 
only)
X
X
X
X
X
X
X
Randomization
X
Subjects randomized to 1 cohort (dose 
level and administration) and to 
LY3074828 or placebo within each 
cohort.
LY3074828 or placebo 
administration
X
Intravenous or subcutaneous doses 
administered by investigative site staff.  
The maximum IV infusion rate is 10 mg 
per minute; thus, the 300-mg dose must 
be given over at least 30 minutes, 600 
mg over at least 1 hour, and 1200 mg 
over at least 2 hours.
Medical history
X
Weight, height, and BMI
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.


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Screen-
ing
Days
Comments
Procedure
≤28 
days
-1
1
2
4
8
±1d
11
±1d
15
±2d
22
±2d
29
±2d
43
±2d
57
±3d
71
±3d
85/ED
±3d
Vital signs (supine):  blood 
pressure, pulse rate, 
temperature (hour)
X
X
0, 6 24 X
X
X
(SC 
only)
X
X
X
X
X
X
X
Times with respect to start of dosing.  
Single ECGs to be collected.  ECGs, 
blood pressure, and pulse rate after 
5 minutes supine.  Zero-hour collection 
within 2 hours before dosing.  Time 
allowances (minutes):  6-hour (±30), 
24-hour (90).  For vital sign 
assessments, temperature need only be 
included at predose and when clinically 
indicated.  
12-lead ECG (hour)
X
0, 6 24
X
AE review
X
X
X
X
X
X
X
(SC 
only)
X
X
X
X
X
X
X
AE only after signing ICF.  
Device-related AEs collected as 
appropriate.
Chest X-ray
X
Posterior / anterior and lateral.  Not 
required if chest X-ray was performed
within the last 1 year, found to be
normal, and report is available.
QuantiFERON®-TB Gold 
test or TB T-Spot test
X
See Section 9.4.4.1 for further details.  
regarding retest
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.  See Appendix 2  for test 
details.


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Screen-
ing
Days
Comments
Procedure
≤28 
days
-1
1
2
4
8
±1d
11
±1d
15
±2d
22
±2d
29
±2d
43
±2d
57
±3d
71
±3d
85/ED
±3d
FSH / serum pregnancy test
X
X
X
X
X
Serum pregnancy tests for all female 
subjects.  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
X
See Appendix 2 for test details.
Subcutaneous injection-site 
assessment for erythema, 
induration, categorical 
pain, pruritus, edema, 
visible bleeding, and 
bruising (hour)
0, 
0.25 X
X
X
For Cohorts 4 and 5 only. Times with 
respect to the time of first injection.  
Time allowances (minutes):  0-hour 
(within 5 minutes following first 
injection), 0.25-hour (±5).  Additional 
assessments performed if deemed 
necessary by the investigator.
Injection-site pain 
assessment (VAS) (hour)
0, 
0.25, 
0.5, 
1, 2, 
4
For Cohorts 4 and 5 only.  Times with 
respect to the time of first injection.  
Time allowances (minutes):  0-hour 
(within approximately 1 minute after 
start of first injection), 0.25-hour (±5), 
0.5-hour (±5), 1-hour (±5), 2-hour (±10) 
and 4-hour (±10) post first injection.




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3. Introduction
3.1.
Study Rationale
Study I6T-MC-AMBD (AMBD) is a clinical evaluation of LY3074828 in Chinese subjects, and is being conducted 
to investigate the safety, tolerability, and pharmacokinetics (PK) of single-dose administration of LY3074828 in this 
population.  Data from completed preclinical and clinical studies support the administration to healthy Chinese 
subjects within the dose range planned for this study.  This study will support future Phase 3 clinical studies in 
Chinese patients.
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).  
Psoriasis is one of the most common immune-mediated chronic inflammatory skin diseases, affecting about 2% to 
3% of the world's population (Nestle et al. 2009; Perera et al. 2012).  A typical organ-specific T-cell-driven 
inflammatory disease, psoriasis had been considered a T helper (Th) 1-type skin disease for decades until a new Th 
population, Th17, was identified (Lew et al. 2004; Steinman 2007; Weaver et al. 2007). However, substantial 
clinical and basic research observations now suggest that the IL-23/Th17 axis is essential in the pathogenesis of 
psoriasis (Di Cesare et al. 2009).  Treatment of psoriasis with biologic therapy, particularly with those agents 
targeting the IL-23/Th17 axis, has demonstrated clinical activity in patients with psoriasis (Crow 2012).
As of the Investigator’s Brochure (IB) cutoff date, there were approximately 819 participants in studies of 
LY3074828.  These included 245 patients with psoriasis, 248 patients with ulcerative colitis, 85 patients with 
Crohn’s disease (CD), and 241 healthy subjects who were exposed to either placebo or LY3074828 at single doses 
ranging from 5 to 1200 mg and multiple doses up to a maximum of 1000 mg intravenous (IV) and 300 mg 
subcutaneous (SC).  
Data from the clinical pharmacology development program are available for 1 completed Phase 1 study and 4 
ongoing Phase 1 studies, as follows.  
Completed Phase 1 study:

Study I6T-MC-AMAA (AMAA):  LY3074828 has been evaluated in 5 healthy subjects (single 120-mg 
SC doses) and in a total of 33 subjects with plaque psoriasis (single ascending IV doses of 5, 20, 60, 120, 
200, 350, or 600 mg).  
Ongoing Phase 1 studies:


I6T-MC-AMBD(c) Clinical Pharmacology Protocol
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LY3074828

Study I6T-JE-AMAD (AMAD):  A total of 43 healthy Japanese and Caucasian subjects were administered 
single IV doses of 60, 200, 600, 1200, or 2400 mg LY3074828 (or placebo), or single SC doses of 200 mg 
LY3074828 (or placebo).

Study I6T-MC-AMAL (AMAL):  A total of 67 healthy subjects were administered single IV or SC doses 
of 250 mg LY3074828.  

Study I6T-MC-AMAE (AMAE):  A total of 54 healthy subjects were administered single SC doses of 250 
mg or 500 mg LY3074828; the study is evaluating relative bioavailability of solution compared to 
lyophilized formulations.  

Study I9O-MC-AABA (AABA):  A total of 72 healthy subjects were administered single IV doses of 1200 
mg LY3074828, or single SC doses of 250, 1000, or 2400 mg LY3074828 (SC doses coadministered with 
LY9999QS).
No deaths, serious adverse events (SAEs), or discontinuations due to an adverse event (AE) were reported in any of 
the Phase 1 studies, as of the IB cutoff date.
In the completed Study AMAA, a total of 82 treatment-emergent adverse events (TEAEs) were reported by 
37 subjects.  The most commonly reported TEAEs in this study were nasopharyngitis and headache.  There were no 
drug-related TEAEs of National Cancer Institute Common Terminology Criteria for Adverse Events Grade 2 or 
higher reported in Study AMAA.  
There were no obvious trends in the pattern of AEs across studies apart from injection-site reactions.  Injection-site 
pain, of short duration (usually hours), has been reported in both the completed and ongoing clinical pharmacology 
studies.  In Study AMAA, injection-site pain (related to study drug) was reported in 3 out of 5 healthy subjects 
receiving 120 mg LY3074828 via SC administration; however, no infusion reactions were reported.  Preliminary 
data from Studies AMAE and AMAL showed that most injection-site reactions were mild or moderate in severity, 
with severe injection-site pain reported in 2% of injection-site reactions in the 250-mg SC test formulation group.  
 
 
 
 
 
  
 
 
 
 
  
LY3074828 is currently being evaluated in 3 ongoing Phase 2 studies, as follows:
Study I6T-MC-AMAC (AMAC) is being conducted in approximately 250 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 
CCI


I6T-MC-AMBD(c) Clinical Pharmacology Protocol
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LY3074828
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. During the open-label extension portion of this study in 
which IV infusions of 1000 mg of LY3074828 were administered, a patient experienced an acute anaphylactic 
reaction.  As a result of this SAE, LY3074828 was discontinued for this patient.

Study I6T-MC-AMAF (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 (AMAG) is being conducted in subjects with CD (85 subjects randomized, 
approximately 180 subjects planned).  Three IV doses of 200, 600, or 1000 mg LY3074828 (or placebo) 
are administered Q4W.  LY3074828-treated subjects with an improvement in CD score either continue 
with this dose regimen (with SC placebo to maintain blind), or are administered 300 mg LY3074828 SC 
(with IV placebo) Q4W, through Week 48.  Subjects who receive placebo or who did not have a clinical 
improvement in CD score receive 1000 mg LY3074828 IV (with SC placebo) Q4W through Week 48.  
Subjects with clinical benefit may continue with 300 mg LY3074828 SC Q4W for an additional 52 weeks
(open-label).  Two events of anaphylaxis were reported in this study, with 1 occurring during an infusion of 
LY3074828. The other event also occurred during an intravenous infusion, but the study team remained
blinded to study treatment.  In both cases, the infusions of study medication were stopped and patients were 
treated with antihistamines, which resulted in resolution of the patients’ symptoms.  Both patients were 
discontinued from the study.
To date, evaluation of the unblinded safety data from Studies AMAF and AMAC have not revealed any dose-related 
safety or tolerability issues.  
Pharmacokinetic results obtained 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%.
A lyophilized SC formulation was used in Studies AMAA and AMAD and is currently being used in the Phase 2 
Studies AMAC, AMAF, and AMAG.  Data from Study AMAL indicate that the PK of LY3074828 following SC 
administration is similar in subjects receiving the lyophilized formulation versus the solution formulation that will 
be used in Phase 3 studies.  Preliminary data from Study AMAE also indicate that SC administration of the solution 
formulation using a pre-filled syringe (PFS) provides comparable LY3074828 exposure as the lyophilized SC 
formulation used in Phase 1 and 2 studies.
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 


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LY3074828
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.  Immunomodulatory therapies may increase the risk of malignancies; however, due to only single doses of 
LY3074828 being administered in this study, it is not considered necessary to monitor for such effects.  
 
 
No clinically significant safety or tolerability concerns have been identified in patients or healthy subjects to date for 
LY3074828 up to the highest doses given (single 1200-mg IV doses and 2400-mg SC doses).  
Healthy subjects are not expected to derive any benefit from participating in studies with administration of
LY3074828.  
As this study will use PFS, device-based risks will be evaluated.  Possible device-based risks include local effects 
such as pain at the injection sites from either the needle or the solution entry into the SC tissue, swelling, erythema, 
bleeding, and bruising.  These risks are mitigated by training of investigative site staff on proper injection 
techniques. Systemic effects may include sweating, feeling faint, or fever, as a sign of infection.  
More information about the known and expected benefits, risks, SAEs, and reasonably anticipated AEs of 
LY3074828 are to be found in the IB.
CCI




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5. Study Design
5.1.
Overall Design
Study I6T-MC-AMBD (AMBD) is a subject- and investigator-blinded, randomized, placebo-controlled, parallel-
group, Phase 1 single-dose study of LY3074828 in healthy Chinese subjects.  Safety, tolerability, and PK of 
LY3074828 will be evaluated.
Native Chinese subjects born in China will be enrolled; all 4 biological grandparents and both biological parents 
must be of Chinese origin.  Every effort should be made to enroll subjects so that at least 4 subjects in each cohort 
will be female.  However, if the desired number of female subjects is not achieved, this will not constitute a protocol 
deviation.
Screening Period (≤28 days):  Subjects will be evaluated for study eligibility ≤28 days prior to enrollment.
Residential Period (3 days/2 nights):  A total of approximately 60 subjects (12 subjects per cohort) who fulfill the 
eligibility criteria will be enrolled into the study.  Subjects will be randomized within each cohort to receive study 
drug or placebo:

Cohort 1:  a single dose of LY3074828 300 mg or placebo IV infused over at least 30 minutes (10 
LY3074828, 2 placebo)

Cohort 2:  a single dose of LY3074828 600 mg or placebo IV infused over at least 60 minutes (10 
LY3074828, 2 placebo)

Cohort 3:  a single dose of LY3074828 1200 mg or placebo IV infused over at least 2 hours (10 
LY3074828, 2 placebo)

Cohort 4:  a single dose of LY3074828 200 mg or placebo SC (10 LY3074828, 2 placebo)

Cohort 5:  a single dose of LY3074828 400 mg or placebo SC (10 LY3074828, 2 placebo)
Dosing of cohorts may be conducted in parallel or sequentially at the discretion of the investigator.  Subjects will 
report to the clinical research unit (CRU) on Day -1.  After randomization, study drug will be administered by 
investigative site staff by IV administration using a forearm vein or SC injection in the abdomen using PFSs in the 
morning of Day 1 after an overnight fast.  Subjects will remain at the CRU until the scheduled procedures have been 
completed on Day 2, and will then be discharged.
Outpatient Follow-up Period (12 weeks):  The follow-up period will include outpatient visits for a total of 
approximately 12 weeks (Days 4, 8, 11 [SC only], 15, 22, 29, 43, 57, 71, and 85) following dose administration on 
Day 1 to assess the safety, tolerability, and PK of LY3074828 in healthy Chinese subjects.
Safety and tolerability will be explored by clinical laboratory tests, vital sign measurements, 12-lead 
electrocardiograms (ECGs), recording of AEs, physical examinations/medical assessments, immunogenicity, and 
injection-site assessments.  Pain assessments will be made using a subject-assessed injection-site pain visual analog 
scale (VAS).


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5.2.
Number of Participants
Sixty subjects may be enrolled into the study to try to ensure that approximately 50 subjects complete (10 subjects 
per cohort are required in order to provide the necessary safety and PK data).  Furthermore, every effort should be 
made to enroll subjects so that at least 4 subjects per cohort are female.  Each subject will participate in 1 of the 5
cohorts.  Subjects who withdraw from the study will not be replaced. For analytical purposes, 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.
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
A subject- and investigator-blinded, randomized, and placebo-controlled design is being used to minimize bias on 
safety and tolerability assessments.
The parallel group design has been chosen due to the long half-life of LY3074828 and to determine the incidence of 
ADA formation.
It is not considered necessary to conduct safety data reviews of previous cohorts (lower dose levels) prior to dosing.  
This is because sufficient safety cover has already been obtained from previous studies to dose the highest IV and 
SC doses planned in this study (see Section 5.5).  Although sequential dosing of cohorts is not considered necessary 
from a safety perspective, it is anticipated that it may be preferred for logistical reasons.  The relative dosing of 
cohorts (parallel or sequential) will therefore be at the discretion of the investigator.  
A single dose on Day 1 will be given in order to evaluate the safety, tolerability, and PK profile of LY3074828 in 
healthy Chinese subjects.
Monoclonal antibody therapy has been associated with hypersensitivity reactions, including injection-site reactions.  
Follow-up details on injection-site reactions will be collected by the investigative site regarding the severity, 
duration, type, and timing of the start of the event in relation to the start of study drug administration in order to 
further characterize these events.
 
 
 
 
 
 
 
  
CCI
CCI


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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:  

No male contraception required, except in compliance with specific local government study 
requirements

Men should refrain from sperm donation for the duration of the study and for 12 weeks 
following dosing with the study drug
[1b] female subjects:

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
Women of childbearing potential participating 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 of study drug


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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

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 years 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]
native Chinese (all 4 biological grandparents and both biological parents to be of Chinese 
origin)
[3]
are between 18 and 65 years of age, inclusive, at time of screening
[4]
have a body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive, at time of screening
[5]
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
[6]
have venous access sufficient to allow for blood sampling and administration of 
investigational product (IP) or placebo as per the protocol
[7]
are reliable and willing to make themselves available for the duration of the study and are 
willing to follow study procedures
[8]
are able and willing to give signed informed consent


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6.2.
Exclusion Criteria
Subjects will be excluded from study enrollment if they meet any of the following criteria at screening and/or 
enrollment:
[9]
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
[10]
are Lilly employees or are employees of the third-party organizations involved with the study
[11]
are currently enrolled in a clinical study involving an IP or any other type of medical research 
judged not to be scientifically or medically compatible with this study
[12]
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
[13]
have previously completed or withdrawn from this study or any other study investigating
LY3074828, and have previously received the IP
[14]
have known allergies to LY3074828, humanized monoclonal antibodies, related compounds
or any components of the formulation, or history of significant atopy
[15]
have an abnormality in the 12-lead ECG that, in the opinion of the investigator, increases the 
risks associated with participating in the study
[16]
have an abnormal blood pressure as determined by the investigator
[17]
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
[18]
have known or ongoing psychiatric disorders deemed clinically significant by the investigator
[19]
regularly use known drugs of abuse and/or show positive findings on drug screening
[20]
show evidence of HIV infection and/or positive human HIV antibodies
[21]
show evidence of hepatitis C and/or positive hepatitis C antibody
[22]
show evidence of hepatitis B and/or positive hepatitis B surface antigen or positive hepatitis B 
core antibody
[23]
are women who are lactating
[24]
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 (estrogen and thyroid) are permitted, at 
the discretion of the investigator
[25]
have donated blood of more than 400 mL within 1 month prior to screening


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[26]
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)
[27]
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 
measurement during the study, or who are unwilling to abide by the CRU smoking guidelines 
described in Section 6.3.2
[28]
have had symptomatic herpes zoster within 3 months of screening
[29]
show evidence of active or latent TB, as documented by medical history, examination, chest 
X-rays (posterior/anterior and lateral), and TB testing (positive or indeterminate for 
QuantiFERON® -TB Gold test or TB T-Spot test; 1 retest permitted following indeterminate 
result); 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.  See Section 9.4.4.1
for further details. 
[30]
have received live vaccine(s), including attenuated live vaccines and those administered 
intranasally, within 8 weeks of screening, or intend to during the study
[31]
are immunocompromised
[32]
have clinically significant multiple or severe drug allergies, or intolerance to topical 
corticosteroids, or severe post treatment hypersensitivity reactions (including, but not limited 
to, erythema multiforme major, linear immunoglobulin A dermatosis, toxic epidermal 
necrolysis, or exfoliative dermatitis)
[33]
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
[34]
have had breast cancer within the past 10 years
[35]
have excessive tattoos over the abdomen that would interfere with injection-site assessments
[36]
in the opinion of the investigator or Sponsor, are unsuitable for inclusion in the study
6.3.
Lifestyle and/or Dietary Requirements
Throughout the study, subjects may undergo medical assessments and review of compliance with requirements
before continuing in the study.  
6.3.1. Meals and Dietary Restrictions
Subjects will fast overnight for at least 8 hours before dosing and 2 hours postdose (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.


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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
during the outpatient period, 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 
measurement, and to abide by the CRU smoking guidelines.
6.3.3. Activity
Subjects will be advised to maintain their regular levels of physical activity/exercise during the study, but to refrain 
from vigorous exercise.  Strenuous activity should be avoided from 24 hours prior to admission until discharge from 
the CRU.  While certain study procedures are in progress at the site, subjects may be required to remain recumbent 
or sitting.
6.3.4. 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. Treatment
7.1.
Treatment Administered
The LY3074828 solution formulation (20 mg/mL) for IV infusion will be supplied by Lilly to the investigative site 
in a sterile vial manufactured to deliver 300 mg of LY3074828.  Placebo for IV infusion will be the identical sterile 
solution without LY3074828, and will be supplied by Lilly to the investigative site in a vial designed to deliver
15 mL.
A 100-mg/mL LY3074828 solution formulation for SC injection will be supplied by Lilly to the investigative site in
a PFS designed to deliver 1 mL.  Further information regarding SC administration will be included in the device 
Instructions for Use for the PFS.  Placebo for SC injection will be the identical sterile solution without LY3074828, 
and will be supplied by Lilly to the investigative site in a PFS designed to deliver 1 mL.
Table AMBD.2 shows the treatment regimens.
Table AMBD.2.
Treatments Administered
Cohort
Cohort 1
Cohort 2
Cohort 3
Cohort 4
Cohort 5
Regimen
300 mg IV
600 mg IV
1200 mg IV
200 mg SC
400 mg SC
LY3074828 
concentration (or 
placebo)
20 mg/mL
20 mg/mL
20 mg/mL
100 mg/mL
100 mg/mL
Volume per dose
15 mL
30 mL
60 mL
2 mL
4 mL
Infusion duration 
(minutes)
≥30
≥60
≥120
NA
NA
Abbreviations:  IV = intravenous; NA = not applicable; SC = subcutaneous.
LY3074828 will be administered using a forearm vein as a slow IV infusion at an infusion rate of no greater than 10 
mg per minute. The duration of the placebo infusions will match those of the LY3074828 infusions to maintain 
subject and investigator blinding to study treatment.  Subcutaneous administration of the 200-mg dose of 
LY3074828 or placebo will be given by investigative site staff as 2 x 1-mL injections, with 1 injection into the 
skinfold of the left lower abdominal wall and the other into the skinfold of the right lower abdominal wall.  The SC 
administration of the 400-mg dose of LY3074828 will be given by investigative site staff as 4 x 1-mL injections, 
with the first 2 injections given into separate lower abdominal quadrants, and the final 2 injections given into 
separate upper abdominal quadrants.
The actual date and time of all dose preparation and administration will be documented, and drug accountability 
records will be maintained by the site pharmacy.
The investigator or designee is responsible for returning all unused medication to Lilly or its designee at the end of 
the study.
The site may destroy used syringes if, during the investigative site selection, the evaluator has verified and 
documented that the site has appropriate facilities and written procedures to dispose of clinical materials.  


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7.1.1. Packaging and Labeling
LY3074828 and placebo will be supplied to the investigator by Lilly or its designee.  Clinical trial materials will be 
labeled according to the country’s regulatory requirements.  All IPs will be stored, inventoried, reconciled, and 
destroyed according to applicable regulations.  Clinical trial materials are manufactured in accordance with current 
good manufacturing practices.
Study drug will be supplied as a single-use solution vial or a single-use PFS containing LY3074828 or placebo with 
study-specific labels.  The 15-mL vial of LY3074828 is manufactured to deliver 300 mg (20 mg/mL).  The 1-mL 
PFS is manufactured to deliver 100 mg (100 mg/mL).  LY3074828 cannot be distinguished visually from placebo.  
Vials and PFSs will be supplied in cartons, with the appropriate quantity specific to the planned dispensing schedule 
of the IP.  
7.2.
Method of Treatment Assignment
Subjects will be randomized to LY3074828 or placebo within each cohort.
Randomization will be performed using a randomization table.
7.2.1. Selection and Timing of Doses
The actual time of all dose administrations will be recorded in the subject’s electronic case report form (eCRF).
7.3.
Blinding
This is a subject- and investigator-blinded study. The Sponsor and site pharmacists will be unblinded.  Blinding will 
be maintained throughout the conduct of the study.
Emergency codes will be available to the investigator.  A code, which reveals the treatment for a specific study 
subject, may be opened during the study only if the subject’s well-being requires knowledge of the subject’s 
treatment assignment.
In case of an emergency, the investigator has the sole responsibility for determining if unblinding of a subject’s
treatment assignment is warranted for medical management of the event.  The subject’s safety must always be the 
first consideration in making such a determination.  If the investigator decides that unblinding is warranted, it is the 
responsibility of the investigator to promptly document the decision and rationale and notify Lilly as soon as 
possible.
Upon completion of the study, all codes must be returned to Lilly or its designee.
7.4.
Dose Modification
Dose adjustments are not permitted in this study.
7.5.
Preparation/Handling/Storage/Accountability
The investigator or designee must confirm appropriate temperature conditions have been maintained, as 
communicated by Sponsor, during transit for all IP received and any discrepancies are reported and resolved before
use of the study treatment.


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Only participants enrolled in the study may receive IP or study materials, and only authorized site staff may supply 
or administer 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, institution, or the head of the medical institution (where applicable) is responsible for study 
treatment accountability, reconciliation, and record maintenance (such as receipt, reconciliation, and final 
disposition records).
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, until the subject’s last visit.  However, stable doses of oral contraceptive or 
hormone-replacement therapy (estrogen and thyroid) 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 procedures 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, discussion must occur between the Lilly CP or CRP and the investigator to determine if the subject may 
continue in the study.  If both agree it is medically appropriate to continue, the investigator must obtain documented 
approval from the Lilly CP or CRP to allow the inadvertently enrolled subject to continue in the study.  
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

Investigator Decision
o
the investigator decides that the subject should be discontinued from the study

Subject Decision
o
the subject, or legal representative, requests to be withdrawn from the study.
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.
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.
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.
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, concomitant treatment, or pathologies.  
A “reasonable possibility” means that there is a potential 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


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
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 (for example, drug delivery system) 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.
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 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 product 
complaint (PC) should also be reported.
For the purpose of this protocol, “unanticipated” adverse device effect means any SAE alleged to be associated with 
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.


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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 PFS 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.
Although an increased risk of malignancy may be associated with immunomodulatory therapies, such effects will 
not be monitored in this study as subjects will only receive a single dose of LY3074828 or placebo.
Depression and suicidality may be increased with certain autoimmune disorders.  For this program of work, and 
where consistent with the study protocols, patients should be monitored for signs and symptoms of such behavior.  
Specific monitoring (e.g. Columbia Suicide Severity Rating Scale, Hamilton Depression Rating Scale) is not 
considered necessary for this study as the study population is healthy subjects (i.e. do not have autoimmune 
disorders such as ulcerative colitis or CD) and only single doses will be administered.  
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 reports 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 the self-assessed pain VAS is conducted (see Section 9.4.4.2.3), study site personnel will question the subject 
about any change in the preexisting condition(s) (first assessment time point only) and the occurrence and nature of 
any AEs.  
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 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:


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
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).
With the exception of safety laboratory test results that may unblind the study, Lilly or its designee will provide the 
investigator with the results of laboratory tests analyzed by a local laboratory used for the study.
9.4.2. Vital Signs
For each subject, vital sign measurements 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.  


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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 
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 
which includes a QuantiFERON-TB Gold test or TB T-Spot 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.
9.4.4.2.
Subcutaneous Injection-site Assessments
9.4.4.2.1.
Subcutaneous Injection-Site Reactions
Injection-site reactions will be evaluated through the collection of pain assessments and specific site assessments for 
local tolerability which will evaluate erythema, induration, categorical pain, pruritus, edema, and bruising as
indicated in the Schedule of Activities (Section 2).  Data from injection site evaluations (including pain VAS 
[9.4.4.2.3]) which are recorded as a result of specific questionnaires will not be reported as AEs.  Any spontaneous 
reports by the subject will be reported as AEs.  Additionally, if during the assessment of the injection sites, a 
clinically significant reaction (including pain) is observed by site staff, an AE will be reported at the discretion of 
the Investigator.  For injection site reactions reported as an AE, additional characterization of the event will be 
documented using the injection site eCRF form.  
9.4.4.2.2.
Subcutaneous 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.  Injection site bleeding may be recorded as AE at the discretion of the investigator.
9.4.4.2.3.
Subcutaneous Injection-site Pain Visual Analog Scale
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 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 first injection and at the time points listed in the Schedule of Activities (Section 2).
9.4.5. Safety Monitoring
The Lilly CP or CRP/scientist will monitor safety data throughout the course of the study.


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Lilly will review SAEs within time frames mandated by company procedures.  The Lilly CP or CRP will review the 
following data:

trends in safety data

laboratory analytes

AEs, including monitoring of incidence of any nature of any infections, injection-site reactions, and 
allergic/hypersensitivity 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 creatinine kinase to confirm the abnormality and to determine if it is increasing or decreasing.  If the 
abnormality persists or worsens, clinical and laboratory monitoring should be initiated by the investigator based on 
consultation with the Lilly 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 immunogenic response with any biological agent, including hypersensitivity reactions
(including non-immediate hypersensitivities), anaphylactic reactions, and infusion-related reactions.  Symptoms and 
signs that may occur as part of such a response include, but are not limited to, fever, chills, weakness of limbs, rash, 
itching, urticaria, dizziness, headache, tightening of throat, and wheezing.  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.  Any potential hypersensitivity events will be evaluated, during the trial level safety review and/or the 
preparation of the study report, 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.  A maximum of 3 samples may 


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be collected at additional time points during the study if warranted and agreed upon between 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.
Drug concentration information that may unblind the study will not be reported to investigative site or blinded 
personnel until the study has been unblinded.
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.  Analyses of 
samples collected from placebo-treated subjects are not planned.
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
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
  
 
  
 
 
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9.7.
Biomarkers
This section is not applicable for this study.
9.8.
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
Sixty subjects who fulfill the eligibility criteria may be enrolled into the study to try to ensure that approximately 50 
subjects (10 subjects per cohort) complete.  The number of subjects in Study AMBD is not sufficient for any formal 
ethnic comparison, but the safety, tolerability, and PK data will be assessed in Chinese subjects and will be used to 
support the inclusion of Chinese subjects in future studies involving LY3074828.  
The sample size is customary for Phase 1 studies evaluating safety and PK, and is not powered on the basis of 
statistical hypothesis testing.
Subjects who withdraw from the study will not be replaced.  For analytical purposes, 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.
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, 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 data from all subjects who receive IP and have evaluable PK. Safety 
analyses will be conducted for all enrolled subjects, whether or not they completed all protocol requirements.
Analysis will be according to the treatment the subjects actually received.  
Additional exploratory analyses of the data will be conducted as deemed appropriate.  
 
 
  
No adjustments for multiple comparisons will be made.
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 
CCI


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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
The intensity of pain at the injection sites immediately (approximately within 1 minute after start of first injection, 
designated as “0-hour assessment”) following the start of the first injection will be evaluated, as reported by the 
subject and measured according to the 0 to 100 mm VAS. Assessments will also be performed at 0.25, 0.5, 1, 2, and 
4 hours post first injection; however, the 0-hour assessment will be considered the primary endpoint for 
injection-site pain assessment.
Descriptive statistics will be used to summarize the intensity of pain at each time point as captured by the VAS.
10.3.1.2.2.Injection-site Assessments
Incidence of erythema, induration, categorical pain, pruritus, edema, bleeding, and bruising will be listed.
10.3.1.2.3.Statistical Evaluation of Other Safety Parameters
Other safety parameters that will be assessed include clinical laboratory parameters and vital signs.  The parameters, 
and changes from baseline (predose) where appropriate, will be listed and summarized using standard descriptive 
statistics.  Additional analysis will be performed if warranted upon review of the data.
10.3.2. Pharmacokinetic Analyses
10.3.2.1. Pharmacokinetic Parameter Estimation
Pharmacokinetic parameter estimates for LY3074828 will be calculated by standard noncompartmental methods of 
analysis.
The primary parameters for analysis will be AUC 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) for LY3074828.  The secondary parameter for analysis will be the time to maximum observed 
drug concentration (tmax) of LY3074828.  Other PK parameters, such as bioavailability following SC 
administration, t1/2, clearance, and volume of distribution (apparent clearance and apparent volume of distribution 
for SC administration), may be reported.
10.3.2.2. Pharmacokinetic Statistical Inference
No formal statistical analysis will be performed for this study.  The PK parameters will be summarized by treatment 
and listed.  Additional analyses may be conducted as 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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10.3.6. 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.  
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.
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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.
Crow JM. Therapeutics: silencing psoriasis. Nature. 2012;492(7429):S58-S59.
Di Cesare A, Di Meglio P, Nestle FO. The IL-23/Th17 axis in the immunopathogenesis of psoriasis. J Invest 
Dermatol. 2009;129(6):1339–1350.
Lew W, Bowcock AM, Krueger JG. Psoriasis vulgaris: cutaneous lymphoid tissue supports T-cell activation and 
“Type 1” inflammatory gene expression. Trends Immunol. 2004;25(6):295-305.
Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med. 2009;361(5):496–509.
Perera GK, Di Meglio P, Nestle FO. Psoriasis. Annu Rev Pathol. 2012;7:385–422.
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.
Steinman L. A brief history of T(H)17, the first major revision in the T(H)1/T(H)2 hypothesis of T cell-mediated 
tissue damage. Nat Med. 2007;13(2):139–145.
Weaver CT, Hatton RD, Mangan PR, Harrington LE. IL-17 family cytokines and the expanding diversity of effector 
T cell lineages. Annu Rev Immunol. 2007;25:821–852.
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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12.
Appendices


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Appendix 1.
Abbreviations and Definitions


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Term
Definition
ADA
anti-drug antibody
AE
adverse event:  Any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product that does not necessarily have a causal 
relationship with this treatment.  An AE can therefore be any unfavorable and unintended 
sign (including an abnormal laboratory finding), symptom, or disease temporally associated 
with the use of a medicinal (investigational) product, whether or not related to the medicinal 
(investigational) product.
ALP
alkaline phosphatase
ALT
alanine aminotransferase
AUC
area under the concentration versus time curve
AUC(0-∞)
area under the concentration versus time curve from time zero to infinity
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
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 study-related requirements, good clinical practice (GCP) 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
CRP
clinical research physician:  Individual responsible for the medical conduct of the study.  
Responsibilities of the CRP may be performed by a physician, clinical research scientist, 
global safety physician or other medical officer.
CRU
clinical research unit
ECG
electrocardiogram
eCRF
electronic case report form


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enroll
The act of assigning a subject to a treatment.  Subjects who are enrolled in the study are 
those who have been assigned to a treatment.
enter
Subjects entered into a study are those who sign the informed consent form directly or 
through their legally acceptable representatives.
ERB
ethical review board
GCP
good clinical practice
GPS
Global Patient Safety
HIV
human immunodeficiency virus
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonisation
IL-23
interleukin-23
informed consent
A process by which a subject voluntarily confirms his or her willingness to participate in a 
particular study, after having been informed of all aspects of the study that are relevant to 
the subject’s decision to participate.  Informed consent is documented by means of a 
written, signed and dated informed consent form.  
investigational 
product (IP)
A pharmaceutical form of an active ingredient or placebo being tested or used as a reference 
in a clinical study, including products already on the market when used or assembled 
(formulated or packaged) in a way different from the authorized form, or marketed products 
used for an unauthorized indication, or marketed products used to gain further information 
about the authorized form.
investigator
A person responsible for the conduct of the clinical study at a study site.  If a study is 
conducted by a team of individuals at a study site, the investigator is the responsible leader 
of the team and may be called the principal investigator.
IV
intravenous(ly)
PC
product complaint
PFS
pre-filled syringe
PK
pharmacokinetic(s)
Q4W
every 4 weeks
Q8W
every 8 weeks
randomize
The process of assigning subjects to an experimental group on a random basis.
SAE
serious adverse event
SC
subcutaneous(ly)


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screen
The act of determining if an individual meets minimum requirements to become part of a 
pool of potential candidates for participation in a clinical study.  
SUSAR
suspected unexpected serious adverse reaction
t1/2
half-life associated with the terminal rate constant
TB
tuberculosis
TBL
total bilirubin
TEAE
treatment-emergent adverse event:  Any untoward medical occurrence that emerges during 
a defined treatment period, having been absent pretreatment, or worsens relative to the 
pretreatment state, and does not necessarily have to have a causal relationship with this 
treatment.
Th
T helper
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
Urinalysisa
Ethanol testingd
Specific gravity
Urine drug screend
pH
QuantiFERON-TB Gold test or TB T-Spot test
a,e
Protein
Glucose
Serologye,f
Ketones
Hepatitis B surface antigen
Bilirubin
Hepatitis B core antibody
Urobilinogen
Hepatitis C antibody
Blood
HIV antibodies
Nitrite
Microscopic examination of sedimentb
Serum Pregnancy testg,h
Hormone Panel
Follicle-stimulating hormonee,i
Abbreviations:  HIV = human immunodeficiency virus; RBC = red blood cells; TB = tuberculosis; WBC = white 
blood cells.
a
Performed by local laboratory. 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, conjugated (direct) bilirubin and unconjugated (indirect) bilirubin may be measured.
d
Urine drug screen and ethanol level will be performed locally at screening and on Day -1 during admission to the 
clinical research unit.  May be repeated at the discretion of the investigator. 
e
Performed at screening only.
f
Performed by local laboratory at screening.
g
Serum pregnancy tests for all female subjects; women with confirmed postmenopausal status at Screening can be 
exempted from further pregnancy tests during the study.  
h
Refer to Section 2 for specific sampling timing.
i
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.  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 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 ethical review board (ERB) was properly constituted and convened as 
required by International Council for Harmonisation (ICH) guidelines and other applicable laws and regulations.
Documentation of ERB approval of the protocol and the ICF must be provided to Lilly before the study may begin 
at the investigative site.  Lilly or its representatives must approve the ICF before it is used at the investigative site.  
All ICFs must be compliant with the ICH guideline on good clinical practice (GCP).
The study site’s ERB should be provided with the following:

the current Investigator’s Brochure and updates during the course of the study

ICF

relevant curricula vitae
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 


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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.
If the study is conducted at more than 1 site, the investigator with the most enrolled subjects will serve as the final 
report coordinating investigator.  If this investigator is unable to fulfill this function, another investigator will be 
chosen by Lilly to serve as the final report coordinating investigator.
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.

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 ERB with direct access to the original source documents.


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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 ERB of the study site
judges it necessary for medical, safety, regulatory, or other reasons consistent with applicable laws, regulations, and 
GCP.
Discontinuation of the Study
The study will be discontinued if Lilly or its designee judges it necessary for medical, safety, regulatory, or other 
reasons consistent with applicable laws, regulations, and GCP.


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Appendix 4.
Hepatic Monitoring Tests for Treatment-
Emergent Abnormality
Selected tests may be obtained in the event of a treatment-emergent hepatic abnormality and may be required in 
follow-up with subjects in consultation with Lilly or its designee clinical research physician.
Hepatic Monitoring Tests
Hepatic Hematologya
Haptoglobina
Hemoglobin
Hematocrit
Hepatic Coagulationa
RBC
Prothrombin Time
WBC
Prothrombin Time, INR
Neutrophils
Lymphocytes
Hepatic Serologiesa,b
Monocytes
Hepatitis A antibody, total
Eosinophils
Hepatitis A antibody, IgM
Basophils
Hepatitis B surface antigen
Platelets
Hepatitis B surface antibody
Hepatitis B Core antibody
Hepatic Chemistrya
Hepatitis C antibody
Total bilirubin
Hepatitis E antibody, IgG
Conjugated (direct) 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 = creatinine 
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 table summarizes the approximate number of venipunctures and blood volumes for all blood 
sampling (screening, safety laboratories, and bioanalytical assays) during the study.  Fewer venipunctures and blood 
draws may actually occur, but this will not require a protocol amendment.  
Protocol I6T-MC-AMBD Sampling Summary
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
6
75
Pharmacokineticsb
2
16
32
Immunogenicitya
10
4
40
Pregnancy tests
3.5
4
14
Total
180.5
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).


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Appendix 6.
Protocol Amendment I6T-MC-AMBD(c) 
Summary
A Single-Dose Study to Assess the Safety, Tolerability, and 
Pharmacokinetics of LY3074828 in Healthy Chinese 
Subjects 
Overview
Protocol I6T-MC-AMBD, “A Single-Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of 
LY3074828 in Healthy Chinese Subjects”, has been amended.  The new protocol is indicated by Amendment (c) 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 as follows:

The statement that this is a single-site study has been removed throughout in order to allow flexibility in the 
number of sites at which the study may be conducted.    

A description of how the final report coordinating investigator will be identified if the study is conducted at 
more than 1 site has been added.  
Revised Protocol Sections
Note:
All deletions have been identified by strikethroughs.
All additions have been identified by the use of underscore.


I6T-MC-AMBD(c) Clinical Pharmacology Protocol
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1. Protocol Synopsis
Summary of Study Design:
Study I6T-MC-AMBD (AMBD) is a single center, subject- and investigator-blinded, randomized, parallel-group, 
placebo-controlled, Phase 1 single-dose study of LY3074828 in healthy Chinese subjects.  Native Chinese subjects 
born in China, with all 4 grandparents and both parents of Chinese origin will be enrolled.  The study will consist of 
5 planned dose cohorts:  3 intravenous (IV) dose cohorts (300 mg, 600 mg, and 1200 mg) and 2 subcutaneous (SC)
dose cohorts (200 mg and 400 mg).  Subjects will be randomized within each cohort to receive LY3074828 
(10 subjects) or placebo (2 subjects).
5.1
Overall Design
Study I6T-MC-AMBD (AMBD) is a single center, subject- and investigator-blinded, randomized, placebo-
controlled, parallel-group, Phase 1 single-dose study of LY3074828 in healthy Chinese subjects.  Safety, tolerability, 
and PK of LY3074828 will be evaluated.


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12. Appendices


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Appendix 3.
Study Governance, Regulatory and Ethical 
Considerations
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 
studywith the analyses, results, and conclusions of the report.
If the study is conducted at more than 1 site, the investigator with the most enrolled subjects will serve as the final 
report coordinating investigator.  If this investigator is unable to fulfill this function, another investigator will be 
chosen by Lilly to serve as the final report coordinating investigator.
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.


Leo Document ID = 89e992c5-8742-49f1-ba82-64c2be7103e9
Approver: 
Approval Date & Time: 28-Jun-2020 00:50:29 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 28-Jun-2020 23:43:51 GMT
Signature meaning: Approved
PPD
PPD

SAP_001.pdf: 
Statistical Analysis Plan I6T-MC-AMBD 
 
A Single-Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of LY3074828 in  
 
Healthy Chinese Subjects 
 
 
NCT04137380 
 
Approval Date: 05-Dec-2018 
 
 
 


Final, 23 Nov 2018
             Page 1 of 17
STATISTICAL ANALYSIS PLAN
A Single-Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of 
LY3074828 in Healthy Chinese Subjects
Statistical Analysis Plan Status: Final
Statistical Analysis Plan Date: 23-November-2018
Study Drug: LY3074828
Sponsor Reference: I6T-MC-AMBD
Covance CRU Study: 1001215-8379301
Clinical Phase I
Approval Date: 05-Dec-2018 GMT


Final, 23 Nov 2018
             Page 2 of 17
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1001215-8379301
Sponsor Reference I6T-MC-AMBD
1. TABLE OF CONTENTS
1.
TABLE OF CONTENTS ............................................................................................... 2
2.
ABBREVIATIONS........................................................................................................ 4
3.
INTRODUCTION ......................................................................................................... 6
4.
STUDY OBJECTIVE .................................................................................................... 6
4.1
Primary Objective.................................................................................................... 6
4.2
Secondary Objective................................................................................................ 6
4.3
Exploratory Objective.............................................................................................. 6
5.
STUDY DESIGN........................................................................................................... 7
6.
TREATMENTS............................................................................................................. 7
7.
SAMPLE SIZE JUSTIFICATION ................................................................................. 8
8.
DEFINITION OF ANALYSIS POPULATIONS............................................................ 8
9.
STATISTICAL METHODOLOGY ............................................................................... 8
9.1
General.................................................................................................................... 8
9.2
Demographics and Subject Disposition.................................................................... 9
9.3
Pharmacokinetic Assessment................................................................................... 9
9.3.1
Pharmacokinetic Analysis............................................................................... 9
9.3.2
Pharmacokinetic Statistical Methodology ..................................................... 14
9.4
Safety and Tolerability Assessments...................................................................... 14
9.4.1
Adverse events ............................................................................................. 14
9.4.2
Concomitant medication............................................................................... 14
9.4.3
Clinical laboratory parameters...................................................................... 14
9.4.4
Vital signs .................................................................................................... 14
9.4.5
Electrocardiogram (ECG)............................................................................. 15
9.4.6
Subcutaneous Injection-site Reaction............................................................ 15
9.4.7
Subcutaneous Injection-site Pain .................................................................. 15
9.4.8
Subcutaneous Injection-Procedure Evaluation .............................................. 15
9.4.9
Immunogenicity ........................................................................................... 15
9.4.10
Hepatic Monitoring ...................................................................................... 15
9.4.11
Hypersensitivity Reactions ........................................................................... 16
9.4.12
Safety and Tolerability Statistical Methodology............................................ 16


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Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1001215-8379301
Sponsor Reference I6T-MC-AMBD
10. INTERIM ANALYSES ............................................................................................... 16
11. CHANGES FROM THE PROTOCOL SPECIFIED STATISTICAL ANALYSES ...... 16
12. REFERENCES ............................................................................................................ 16
13. DATA PRESENTATION ............................................................................................ 16
13.1 Derived Parameters ............................................................................................... 16
13.2 Missing Data ......................................................................................................... 17
13.3 Insufficient Data for Presentation .......................................................................... 17


Final, 23 Nov 2018
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Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1001215-8379301
Sponsor Reference I6T-MC-AMBD
2. ABBREVIATIONS
Abbreviations pertain to the Statistical Analysis Plan (SAP) only (not the tables, figures and 
listings [TFLs]).
AE
Adverse event
ADA
Anti-drug antibody
ALP
Alkaline phosphatase
ALT
Alanine aminotransferase
AUC
Area under the concentration versus time curve
AUC(0-tlast)
Area under the concentration versus time curve from time zero to 
time t, where t is the last time point with a measurable concentration
AUC(0-∞)
Area under the concentration versus time curve from time zero to 
infinity
%AUC(tlast-)     Percentage of AUC(0-∞) extrapolated
BMI
Body mass index
BQL
Below the lower limit of quantification
Clast
Last quantifiable drug concentration
Cmax
Maximum observed drug concentration
CI
Confidence interval
CL/F
Apparent total body clearance of drug calculated after extra-vascular
administration
CRF
Case Report Form
CRU
Clinical Research Unit
CSR
Clinical Study Report
CV
Coefficient of variation
EC
Early Clinical 
ECG
Electrocardiogram
e.g.
For example (Latin: exempli gratia)
F
Fraction of extravascular dose reaching the general circulation 
compared to an IV administration
ICH
International Conference on Harmonisation
IV
Intravenous
LLOQ
Lower limit of quantification
MedDRA
Medical Dictionary for Regulatory Activities


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Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1001215-8379301
Sponsor Reference I6T-MC-AMBD
MRE
Magnetic resonance elastography
PK
Pharmacokinetic
SAP
Statistical Analysis Plan
SC
Subcutaneous
SD
Standard deviation 
SOP
Standard Operating Procedure
t1/2
Half-life associated with the terminal rate constant (λz) in 
non-compartmental analysis
TBL
Total bilirubin
TEAE
Treatment-emergent adverse event
TFLs
Tables, Figures, and Listings
tmax
Time of maximum observed drug concentration
ULN
Upper limit of normal
Vss
Volume of distribution at steady state after intravenous 
administration
Vss/F
Apparent volume of distribution at steady state after extra-vascular 
administration
Vz
Volume of distribution during the terminal phase after IV 
administration
Vz/F
Apparent volume of distribution during the terminal phase after 
extra-vascular administration
WHO
World Health Organization
CCI




Final, 23 Nov 2018
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Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1001215-8379301
Sponsor Reference I6T-MC-AMBD
5. STUDY DESIGN
Study I6T-MC-AMBD is a single-center, subject- and investigator-blinded, randomized, parallel-
group, placebo-controlled, Phase 1 single-dose study of LY3074828 in healthy Chinese subjects. 
Safety, tolerability, and PK of LY3074828 will be evaluated.
Native Chinese subjects born in China will be enrolled; all 4 biological grandparents and both 
biological parents must be of Chinese origin. Every effort should be made to enroll subjects so 
that at least 4 subjects in each cohort will be female. However, if the desired number of female 
subjects is not achieved, this will not constitute a protocol deviation.
Screening Period (≤28 days): Subjects will be evaluated for study eligibility ≤28 days prior to 
enrolment.
Residential Period (3 days/2 nights): A total of approximately 60 subjects (12 subjects per 
cohort) who fulfil the eligibility criteria will be enrolled into the study. Subjects will be 
randomized within each cohort to receive study drug or placebo:

Cohort 1: a single dose of LY3074828 300 mg or placebo IV infused over at least 
30 minutes (10 LY3074828, 2 placebo)

Cohort 2: a single dose of LY3074828 600 mg or placebo IV infused over at least
60 minutes (10 LY3074828, 2 placebo)

Cohort 3: a single dose of LY3074828 1200 mg or placebo IV infused over at least
2 hours (10 LY3074828, 2 placebo)

Cohort 4: a single dose of LY3074828 200 mg or placebo SC (10 LY3074828, 2 placebo)

Cohort 5: a single dose of LY3074828 400 mg or placebo SC (10 LY3074828, 2 placebo)
Dosing of cohorts may be conducted in parallel or sequentially at the discretion of the 
investigator. Subjects will report to the clinical research unit (CRU) on Day -1. After 
randomization, study drug will be administered by investigative site staff by IV administration 
using a forearm vein or SC injection in the abdomen using pre-filled syringes (PFSs) in the 
morning of Day 1 after an overnight fast. Subjects will remain at the CRU until the scheduled 
procedures have been completed on Day 2, and will then be discharged.
Outpatient Follow-up Period (12 weeks): The follow-up period will include outpatient visits
for a total of approximately 12 weeks (Days 4, 8, 11 [SC only], 15, 22, 29, 43, 57, 71, and 85)
following dose administration on Day 1 to assess the safety, tolerability, and PK of LY3074828
in healthy Chinese subjects.
6. TREATMENTS
The following is a list of the study treatment abbreviations that will be used in the TFLs. Placebo 
IV and Placebo SC data may be pooled in the TFLs, as appropriate.


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Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1001215-8379301
Sponsor Reference I6T-MC-AMBD
Study Treatment Name
Treatment order in TFL
Placebo IV
1
300 mg LY3074828 IV
2
600 mg LY3074828 IV
3
1200 mg LY3074828 IV
4
Placebo SC
5
200 mg LY3074828 SC
6
400 mg LY3074828 SC
7
7. SAMPLE SIZE JUSTIFICATION
Sixty subjects who fulfil the eligibility criteria may be enrolled into the study to try to ensure that 
approximately 50 subjects (10 subjects per cohort) complete. The number of subjects in Study 
AMBD is not sufficient for any formal ethnic comparison, but the safety, tolerability, and PK 
data will be assessed in Chinese subjects and will be used to support the inclusion of Chinese
subjects in future studies involving LY3074828.
The sample size is customary for Phase 1 studies evaluating safety and PK, and is not powered
on the basis of statistical hypothesis testing.
Subjects who withdraw from the study will not be replaced. For analytical purposes, 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.
8. DEFINITION OF ANALYSIS POPULATIONS
The “Safety” population will consist of all enrolled subjects who received LY3074828 or 
placebo, and have at least one postdose safety assessment.
The “Pharmacokinetic” population will consist of all subjects who received at least one dose of 
LY3074828 and have evaluable PK data. 
All protocol deviations that occur during the study will be considered for their severity/impact 
and will be taken into consideration when subjects are assigned to analysis populations.
9. STATISTICAL METHODOLOGY
9.1
General
Data listings will be provided for all data that is databased. Summary statistics and statistical 
analysis will only be presented for data where detailed in this SAP. For continuous data, 
summary statistics will include the arithmetic mean, arithmetic standard deviation (SD), median, 
min, max and N; for log-normal data (e.g. the PK parameters: area under the concentration time 
curve [AUC] and maximum observed drug concentration [Cmax]) the geometric mean and 
geometric coefficient of variation (CV%) will also be presented. For categorical data, frequency 


Final, 23 Nov 2018
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Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1001215-8379301
Sponsor Reference I6T-MC-AMBD
count and percentages will be presented. Data listings will be provided for all subjects up to the 
point of withdrawal, with any subjects excluded from the relevant population highlighted. 
Summary statistics and statistical analyses will generally only be performed for subjects included 
in the relevant analysis population. For the calculation of summary statistics and statistical 
analysis, unrounded data will be used. 
Mean change from baseline is the mean of all individual subjects’ change from baseline values. 
Each individual change from baseline will be calculated by subtracting the individual subject’s 
baseline value from the value at the time point. The individual subject’s change from baseline 
values will be used to calculate the mean change from baseline using a SAS procedure such as 
Proc Univariate.
No adjustments for multiple comparisons will be made.
Data analysis will be performed using SAS® Version 9.4 or greater.
9.2
Demographics and Subject Disposition
Subject disposition will be listed. The demographic variables age, sex, race, ethnicity, country of 
enrolment, site ID, body weight, height and body mass index (BMI) will be summarized and 
listed. All other demographic variables, including associated person demographics, will be listed 
only.
9.3
Pharmacokinetic Assessment
9.3.1
Pharmacokinetic Analysis
The PK parameter estimates will be determined for LY3074828 using non-compartmental 
procedures with a validated software program 
 
Serum concentrations of LY3074828 will be used to determine the following PK parameters, 
when possible: 
CCI


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Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1001215-8379301
Sponsor Reference I6T-MC-AMBD
Parameter
Units
Definition
AUC(0-tlast)
day*µg/mL
area under the concentration versus time curve from time zero to 
time t, where t is the last time point with a measurable 
concentration
AUC(0-∞)
day*µg/mL
area under the concentration versus time curve from time zero to 
infinity
%AUC(tlast-)
%
percentage of AUC(0-∞) extrapolated
Cmax
µg/mL
maximum observed drug concentration
tmax
day
time of maximum observed drug concentration
t1/2
day
half-life associated with the terminal rate constant (λz) in 
non-compartmental analysis
CL
L/day
total body clearance of drug calculated after extra-vascular
administration
CL/F
L/day
apparent total body clearance of drug calculated after IV
administration
Vz
L
volume of distribution during the terminal phase after IV
administration
Vz/F
L
apparent volume of distribution during the terminal phase after 
extra-vascular administration
Vss
L
volume of distribution at steady state after IV administration
Vss/F
L
apparent volume of distribution at steady state after extra-vascular
administration
F
%
absolute bioavailabilty
F (pooled)
%
absolute bioavailability of pooled 200 mg and 400 mg SC 
treatments
Additional PK parameters may be calculated, as appropriate. The software and version used for 
the final analyses will be specified in the clinical study report. Any exceptions or special 
handling of data will be clearly documented within the final study report.
Estimates of absolute bioavailability will be made as follows:
F = .
Geo Mean AUC(0 −∞) D
⁄
(200 mg or 400 mg SC)
Geo Mean AUC(0 −∞) D (pooled 300 mg, 600 mg & 1200 mg IV)
⁄
× 100
and
F (pooled) =
Geo Mean AUC(0 −∞) D
⁄
(pooled 200 mg & 400 mg SC)
Geo Mean AUC(0 −∞) D (pooled 300 mg, 600 mg & 1200 mg IV)
⁄
× 100
where AUC(0-∞)/D = AUC(0-∞) divided by dose.
 
CCI


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Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1001215-8379301
Sponsor Reference I6T-MC-AMBD
General PK Parameter Rules

Actual sampling times will be used in the final analyses of individual PK parameters, 
except for non-bolus pre-dose sampling times which will be set to zero.

Cmax and tmax will be reported from observed values. If Cmax occurs at more than one time 
point, tmax will be assigned to the first occurrence of Cmax. 

AUC parameters will be calculated using a combination of the linear and logarithmic 
trapezoidal methods (linear-log trapezoidal rule). The linear trapezoidal method will be 
applied up to tmax and then the logarithmic trapezoidal method will be used after tmax. The 
minimum requirement for the calculation of AUC will be the inclusion of at least three 
consecutive concentrations above the lower limit of quantification (LLOQ), with at least 
one of these concentrations following Cmax.

AUC(0-) values where the percentage of the total area extrapolated is more than 20% 
will be flagged. Any AUC(0-) value excluded from summary statistics will be noted in 
the footnote of the summary table.

Half-life (t½) will be calculated, when appropriate, based on the apparent terminal 
log-linear portion of the concentration-time curve. The start of the terminal elimination 
phase for each subject will be defined by visual inspection and generally will be the first 
point at which there is no systematic deviation from the log-linear decline in serum 
concentrations. Half-life will only be calculated when a reliable estimate for this 
parameter can be obtained comprising of at least 3 data points. If t½ is estimated over a 
time window of less than 2 half-lives, the values will be flagged in the data listings. Any 
t½ value excluded from summary statistics will be documented in the footnote of the 
summary table. 

A uniform weighting scheme will be used in the regression analysis of the terminal 
log-linear portion of the concentration-time curve.

The parameters based on the observed last quantifiable drug concentration (Clast) will be 
reported.
Individual PK Parameter Rules

Only quantifiable concentrations will be used to calculate PK parameters with the 
exception of special handling of certain concentrations reported below the lower limit of 
quantification (BQL). Serum concentrations reported as BQL will be set to a value of
zero when all of the following conditions are met:
o
The compound is non-endogenous.
o
The samples are from the initial dose period for a subject or from a 
subsequent dose period following a suitable wash-out period.


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Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1001215-8379301
Sponsor Reference I6T-MC-AMBD
o
The time points occur before the first quantifiable concentration.

All other BQL concentrations that do not meet the above criteria will be set to missing.

Also, where two or more consecutive concentrations are BQL towards the end of a 
profile, the profile will be deemed to have terminated and therefore any further 
quantifiable concentrations will be set to missing for the calculation of the PK parameters 
unless it is considered to be a true characteristic of the profile of the drug.
Individual Concentration vs. Time Profiles

Individual concentrations will be plotted utilizing actual sampling times.

The terminal point selections will be indicated on a semi-logarithmic plot.
Average Concentration vs. Time Profiles

The average concentration profiles will be graphed using scheduled (nominal) sampling 
times.

The average concentration profiles will be graphed using arithmetic average 
concentrations.

The pre-dose average concentration for single-dose data from non-endogenous 
compounds will be set to zero. Otherwise, only quantifiable concentrations will be used 
to calculate average concentrations.

Concentrations at a sampling time exceeding the sampling time window specified in the 
protocol, or ± 10%, will be excluded from the average concentration profiles.

Concentrations excluded from the mean calculation will be documented in the final study 
report.

A concentration average will be plotted for a given sampling time only if 2/3 of the 
individual data at the time point have quantifiable measurements that are within the 
sampling time window specified in the protocol or ± 10%. An average concentration 
estimated with less than 2/3 but more than 3 data points may be displayed on the mean 
concentration plot if determined to be appropriate and will be documented within the 
final study report.
Treatment of Outliers during Pharmacokinetic Analysis
Application of this procedure to all PK analyses is not a requirement. Rather, this procedure 
provides justification for exclusion of data when scientifically appropriate. This procedure 
describes the methodology for identifying an individual value as an outlier for potential 


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Covance Clinical Study No. 1001215-8379301
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exclusion, but does not require that the value be excluded from analysis. The following 
methodology will not be used to exclude complete profiles from analysis.
Data within an Individual Profile
A value within an individual profile may be excluded from analysis if any of the following 
criteria are met:

For PK profiles during single dosing of non-endogenous compounds, the concentration in 
a pre-dose sample is quantifiable.

For any questionable datum that does not satisfy the above criteria, the profile will be 
evaluated and results reported with and without the suspected datum.
Data between Individual Profiles
1.
If n<6, then the dataset is too small to conduct a reliable range test. Data will be analyzed 
with and without the atypical value, and both sets of results will be reported. 
2.
If n6, then an objective outlier test will be used to compare the atypical value to other 
values included in that calculation:
a.
Transform all values in the calculation to the logarithmic domain.
b. Find the most extreme value from the arithmetic mean of the log transformed
values and exclude that value from the dataset.
c.
Calculate the lower and upper bounds of the range defined by the arithmetic 
mean ±3*SD of the remaining log-transformed values.
d. If the extreme value is within the range of arithmetic mean ±3*SD, then it is 
not an outlier and will be retained in the dataset.
e.
If the extreme value is outside the range of arithmetic mean ±3*SD, then it is 
an outlier and will be excluded from analysis.
If the remaining dataset contains another atypical datum suspected to be an outlier and n ≥ 6 
following the exclusion, then repeat step 2 above. This evaluation may be repeated as many 
times as necessary, excluding only one suspected outlier in each iteration, until all data 
remaining in the dataset fall within the range of arithmetic mean ±3*SD of the log-transformed 
values.
Reporting of Excluded Values
Individual values excluded as outliers will be documented in the final report. Approval of the 
final report will connote approval of the exclusion.


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Statistical Analysis Plan 
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Covance Clinical Study No. 1001215-8379301
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9.3.2
Pharmacokinetic Statistical Methodology
No formal statistical analysis will be performed for this study. The PK parameters will be
summarized by treatment and listed.
9.4
Safety and Tolerability Assessments
9.4.1
Adverse events
Where changes in severity are recorded in the Case Report Form (CRF), each separate severity 
of the adverse event (AE) will be reported in the listings, only the most severe will be used in the 
summary tables. A pre-existing condition is defined as an AE that starts before the subject has 
provided written informed consent and is ongoing at consent. A non-treatment emergent AE is 
defined as an AE which starts after informed consent but prior to dosing. A treatment-emergent 
AE (TEAE) is defined as an AE which occurs postdose or which is present prior to dosing and 
becomes more severe postdose. 
All AEs and product complaints will be listed. TEAEs will be summarized by treatment, severity 
and relationship to the study drug. The frequency (the number of AEs, the number of subjects 
experiencing an AE and the percentage of subjects experiencing an AE) of TEAEs will be 
summarized by treatment, Medical Dictionary for Regulatory Activities (MedDRA) version 21.0
system organ class and preferred term. The summary and frequency AE tables will be presented 
for all causalities and those considered related to the study drug. Any serious AEs will be listed. 
9.4.2
Concomitant medication
Concomitant medication will be coded using the World Health organization (WHO) drug 
dictionary (Version March 2018). Concomitant medication will be listed.
9.4.3
Clinical laboratory parameters
All clinical chemistry and hematology data will be summarized by parameter and treatment, and 
listed. Urinalysis data will be listed. Changes from baseline (Day -1) will also be presented.
Additionally clinical chemistry, hematology and urinalysis data outside the reference ranges will 
be listed.
Values for any clinical chemistry, hematology and urinalysis values outside the reference ranges 
will be flagged on the individual subject data listings.
9.4.4
Vital signs
Vital signs data will be summarized by treatment together with changes from baseline, where 
baseline is defined as Day 1 predose. Figures of mean vital signs and mean changes from 
baseline profiles will be presented by treatment.
Furthermore, values for individual subjects will be listed.




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Statistical Analysis Plan 
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Covance Clinical Study No. 1001215-8379301
Sponsor Reference I6T-MC-AMBD
The subjects’ liver disease history and associated person liver disease history data will be listed. 
Any concomitant medication of acetaminophen/paracetamol will be listed. Results from any 
hepatic monitoring procedures, such as a magnetic resonance elastography (MRE) scan, and a 
biopsy assessment will be listed, if performed.
Hepatic risk factor assessment data will be listed. Liver related signs and symptoms data will be 
summarized by treatment and listed. Alcohol and recreational drug use data will also be listed.
All hepatic chemistry, hematology, coagulation, and serology data will be listed. Values outside 
the reference ranges will be flagged on the individual subject data listings.
9.4.11
Hypersensitivity Reactions
Hypersensitivity reactions will be evaluated by examination of TEAEs and serious AEs, and 
through the use of a follow-up form which will be completed by the investigator. Data from the 
follow-up form will be listed. Furthermore, the subjects’ medical history and associated person 
medical history data for drug hypersensitivity and infusion related reactions will be listed.
9.4.12
Safety and Tolerability Statistical Methodology
No inferential statistical analyses are planned.
10.
INTERIM ANALYSES
No interim statistical analyses are planned. 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.
11.
CHANGES FROM THE PROTOCOL SPECIFIED STATISTICAL ANALYSES
There were no changes from the protocol specified statistical analyses.
12.
REFERENCES
1. International Conference on Harmonization of Technical Requirements for Registration of 
Pharmaceuticals for Human Use, ICH Harmonized Tripartite Guideline, Statistical Principles 
for Clinical Trials (E9), 5 February 1998.
2. International Conference on Harmonization of Technical Requirements for Registration of 
Pharmaceuticals for Human Use, ICH Harmonized Tripartite Guideline, Structure and 
Content of Clinical Study Reports (E3), 30 November 1995.
13.
DATA PRESENTATION
13.1
Derived Parameters
Individual derived parameters (e.g. PK parameters) and appropriate summary statistics will be 
reported to three significant figures. Observed concentration data, e.g. Cmax, should be reported 
as received. Observed time data, e.g. tmax, should be reported as received. N and percentage 


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Statistical Analysis Plan 
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Covance Clinical Study No. 1001215-8379301
Sponsor Reference I6T-MC-AMBD
values should be reported as whole numbers. Median values should be treated as an observed 
parameter and reported to the same number of decimal places as minimum and maximum values.
13.2
Missing Data
Missing data will not be displayed in listings. No imputation of data will be applied unless 
otherwise stated.
13.3
Insufficient Data for Presentation
Some of the TFLs may not have sufficient numbers of subjects or data for presentation. If this 
occurs, the blank TFL shell will be presented with a message printed in the centre of the table, 
such as, “No serious adverse events occurred for this study.”


Leo Document ID = 6f2ad1c7-6c47-46f0-9847-11b960ad234d
Approver: 
Approval Date & Time: 27-Nov-2018 23:27:31 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 03-Dec-2018 10:15:58 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 03-Dec-2018 10:36:29 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 05-Dec-2018 13:15:34 GMT
Signature meaning: Approved
PPD
PPD
PPD
PPD