Clinical trial NCT03418493
Conditions: Psoriasis
Sponsor: Eli Lilly and Company
Start date: 2018-01-30; Completion date: 2019-07-29
Enrollment: 63 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate how well LY3316531 is tolerated and what side effects may occur in healthy participants and participants with psoriasis. The study drug will be administered either subcutaneously (SC) (under the skin) or intravenously (IV) (into a vein in the arm).

This is a three-part study. Participants will enroll in only one part. Parts A and B are for healthy participants and Part C is for participants with psoriasis. Participation could last between 16 and 57 weeks.

Detailed description:

Arms: arm 1: Participants received single doses of 3 milligrams (mg), 15 mg, 75 mg, 300 mg, 900 mg, or 2000 mg LY3316531 administered Intravenously (IV), or 300 mg LY3316531 administered Subcutaneously (SC). arm 2: Placebo matching LY3316531 administered IV. arm 3: Participants received 3 doses of 2000 mg LY3316531 administered IV (1 dose every 4 weeks). arm 4: Placebo matching LY3316531 administered IV. arm 5: Participants with psoriasis received single doses of 300 mg LY3316531 administered IV.
Interventions: intervention 1: LY3316531 - IV intervention 2: LY3316531 - SC intervention 3: Placebo - IV
Intervention descriptions: intervention 1: Administered IV. intervention 2: Administered SC. intervention 3: Administered IV.

Protocol documents:
Prot_000.pdf: 
Protocol I9H-MC-FFAA(b) 
 
 
A Phase 1 Randomized, Placebo-Controlled Study of LY3316531 in Healthy Subjects and 
an Open-Label, Single-Dose Study in Patients with Psoriasis 
 
 
NCT03418493 
 
 
Approval Date: 17-Aug-2018 
 
 


I9H-MC-FFAA(b)Clinical Pharmacology Protocol
Page 1
LY3316531
Protocol I9H-MC-FFAA(b)
A Phase 1 Randomized, Placebo-ControlledStudyof 
LY3316531in Healthy Subjects and an Open-Label,
Single-Dose Study in Patients with Psoriasis
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 
LY3316531, 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 4and may not be reproduced or otherwise disseminated without the written 
approval of Eli Lilly and Company or its subsidiaries.
Approval Date: 17-Aug-2018 GMT
LY3316531
Eli Lilly and Company
Indianapolis, Indiana USA 46285
Clinical Pharmacology Protocol Electronically Signed and Approved by Lilly:
02November 2017
Amendment (a) Electronically Signed and Approved by Lilly: 
18January2018
Amendment (b) Electronically Signed and Approved by Lilly on date provided below.


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LY3316531
Table of Contents
A Phase 1 Randomized, Placebo-Controlled Study of 
LY3316531 in Healthy Subjects and an Open-Label,
Single-Dose Study in Patients with Psoriasis
Section
Page
Protocol I9H-MC-FFAA(b) A Phase 1 Randomized, Placebo-Controlled 
Study of LY3316531 in Healthy Subjects and an Open-Label, 
Single-Dose Study in Patients with Psoriasis.......................................................................1
Table of Contents........................................................................................................................2
1.
Protocol Synopsis................................................................................................................9
2.
Schedule of Activities .......................................................................................................12
2.1.
Part A (SAD in Healthy Subjects) ................................................................................13
2.2.
Part B (Multiple-Dose Study in Healthy Subjects)........................................................16
2.3.
Part C (Single-Dose Study in Patients with Psoriasis)...................................................20
3.
Introduction ......................................................................................................................24
3.1.
Study Rationale............................................................................................................24
3.2.
Background..................................................................................................................24
3.3.
Benefit/Risk Assessment..............................................................................................25
4.
Objectives and Endpoints..................................................................................................27
5.
Study Design.....................................................................................................................29
5.1.
Overall Design .............................................................................................................29
5.1.1.
Part A (SAD in Healthy Subjects) ........................................................................31
5.1.2.
Part B (Multiple-Dose Design in Healthy Subjects)..............................................31
5.1.3.
Part C (Single-Dose Design in Patients with Psoriasis).........................................32
5.2.
Number of Participants.................................................................................................32
5.2.1.
Part A (SAD Design in Healthy Subjects) ............................................................32
5.2.2.
Part B (Multiple-Dose Design in Healthy Subjects)..............................................33
5.2.3.
Part C (Single-Dose Design in Patients with Psoriasis).........................................33
5.3.
End of Study Definition ...............................................................................................33
5.4.
Scientific Rationale for Study Design...........................................................................33
5.5.
Justification for Dose ...................................................................................................34
6.
Study Population...............................................................................................................36
6.1.
Inclusion Criteria..........................................................................................................36
6.1.1.
For Healthy Subjects............................................................................................36
6.1.2.
For Patients with Psoriasis....................................................................................37
6.2.
Exclusion Criteria ........................................................................................................38


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LY3316531
6.2.1.
For Healthy Subjects and Patients with Psoriasis..................................................38
6.2.2.
For Healthy Subjects Only ...................................................................................41
6.2.3.
For Patients with Psoriasis Only...........................................................................41
6.3.
Lifestyle and/or Dietary Requirements .........................................................................43
6.3.1.
Meals and Dietary Restrictions.............................................................................43
6.3.2.
Caffeine, Alcohol, and Tobacco ...........................................................................43
6.3.2.1.
Caffeine..........................................................................................................43
6.3.2.2.
Alcohol...........................................................................................................43
6.3.2.3.
Smoking.........................................................................................................44
6.3.3.
Activity................................................................................................................44
6.3.4.
Contraception.......................................................................................................44
6.4.
Screen Failures.............................................................................................................45
7.
Treatment..........................................................................................................................47
7.1.
Treatment Administered...............................................................................................47
7.1.1.
Packaging and Labeling .......................................................................................47
7.2.
Method of Treatment Assignment ................................................................................48
7.2.1.
Selection and Timing of Doses.............................................................................48
7.3.
Blinding .......................................................................................................................48
7.4.
Dose Modification........................................................................................................49
7.4.1.
Dose Decision (Part C).........................................................................................49
7.4.2.
Dose Escalation (Parts A and B)...........................................................................49
7.4.3.
Special Treatment Considerations ........................................................................51
7.4.3.1.
Management of Infusion Reactions.................................................................51
7.5.
Preparation/Handling/Storage/Accountability...............................................................52
7.6.
Treatment Compliance .................................................................................................52
7.7.
Concomitant Therapy...................................................................................................53
7.8.
Treatment after the End of the Study............................................................................53
8.
Discontinuation Criteria ....................................................................................................54
8.1.
Discontinuation from Study Treatment.........................................................................54
8.1.1.
Discontinuation of Inadvertently Enrolled Patients/Subjects.................................54
8.2.
Discontinuation from the Study....................................................................................54
8.3.
Patients/Subjects Lost to Follow-up..............................................................................56
9.
Study Assessments and Procedures ...................................................................................57
9.1.
Efficacy Assessments...................................................................................................57
9.2.
Adverse Events ............................................................................................................57
9.2.1.
Serious Adverse Events........................................................................................58
9.2.1.1.
Suspected Unexpected Serious Adverse Reactions..........................................59
9.2.2.
Complaint Handling.............................................................................................59


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CCI
9.3. Treatment of Overdose.................................................................................................59
9.4. Safety...........................................................................................................................59
9.4.1.
Laboratory Tests..................................................................................................59
9.4.2.
Vital Signs...........................................................................................................59
9.4.3.
Electrocardiograms..............................................................................................60
9.4.4.
Safety Monitoring................................................................................................61
9.4.4.1.
Hepatic Safety................................................................................................61
9.4.4.3.
C-SSRS..........................................................................................................62
9.5. Pharmacokinetics.........................................................................................................62
9.5.1.
Bioanalysis...........................................................................................................63
9.6. Pharmacodynamics......................................................................................................63
9.6.1.
Pharmacodynamic Assessments...........................................................................63
9.6.1.1.
Exploratory Pharmacodynamic Samples for Patients with 
Psoriasis.........................................................................................................63
9.6.1.2.
Disease Activity Measures for Patients with Psoriasis.....................................63
9.6.2.
Immunogenicity Assessments..............................................................................64
9.7. Genetics.......................................................................................................................65
9.8. Biomarkers...................................................................................................................65
9.9.
Health Economics........................................................................................................66
10. Statistical Considerations and Data Analysis.....................................................................67
10.1. Sample Size Determination..........................................................................................67
10.2. Populations for Analyses..............................................................................................67
10.2.1. Study Participant Disposition...............................................................................67
10.2.2. Study Participant Characteristics..........................................................................67
10.3. Statistical Analyses......................................................................................................67
10.3.1. Safety Analyses....................................................................................................68
10.3.1.1. Clinical Evaluation of Safety..........................................................................68
10.3.1.2. Statistical Evaluation of Safety.......................................................................68
10.3.2. Pharmacokinetic Analyses....................................................................................68
10.3.2.1. Pharmacokinetic Analyses..............................................................................68
10.3.2.2. Pharmacokinetic Statistical Inference.............................................................69
10.3.3. Pharmacodynamic Analyses and Clinical Activity................................................69
10.3.3.1. Pharmacokinetic/Pharmacodynamic Analyses................................................69
10.3.3.2. Health Outcome Measures for Subjects with Psoriasis....................................69
10.3.4. Evaluation of Immunogenicity.............................................................................70


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10.3.5.
Data Review During the Study.............................................................................70
10.3.6.
Interim Analyses..................................................................................................70
11.
References ........................................................................................................................71


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List of Tables
Table
Page
Table FFAA.4.1.
Objectives and Endpoints .......................................................................27
Table FFAA.5.1.
Summary of Maximum Number of Patients/Subjects per Cohort ............30
Table FFAA.5.2.
Margin of Safety for Administration of LY3316531 Based on 
Administered Dose and Predicted Exposure............................................35
Table FFAA.7.1.
Permitted Medications for Treatment of Psoriasis...................................53


I9H-MC-FFAA(b) Clinical Pharmacology Protocol
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List of Figures
Figure
Page
Figure FFAA.5.1.
Illustration of study design for Protocol I9H-MC-FFAA.........................31


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List of Appendices
Appendix
Page
Appendix 1.
Abbreviations and Definitions ................................................................74
Appendix 2.
Clinical Laboratory Tests........................................................................79
Appendix 3.
Study Governance, Regulatory, and Ethical Considerations....................81
Appendix 4.
Hepatic Monitoring Tests for Treatment-Emergent Abnormality ............84
Appendix 5.
Blood Sampling Summary......................................................................85
Appendix 6.
Protocol FFAA PK, Immunogenicity, and ECG Sampling 
Schedule.................................................................................................88
Appendix 7.
Protocol Amendment I9H-MC-FFAA (b) Summary 
A Phase 1 Randomized, Placebo-Controlled Study of LY3316531 
in Healthy Subjects and an Open-Label, Single-Dose Study in 
Patients with Psoriasis ............................................................................96




I9H-MC-FFAA(b) Clinical Pharmacology Protocol
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Part A (Single-Ascending Dose [SAD] in Healthy Subjects):  After a screening period up to 28 days, eligible 
subjects will be randomized to receive a subcutaneous (SC) or intravenous (IV) dose of LY3316531 (3 mg IV, 15 
mg IV, 75 mg IV, 300 mg IV, 300 mg SC, 900 mg IV, or 2000 mg IV [planned dose]) or placebo (IV) on the 
morning of Day 1.  Subjects will remain in the CRU for 24 hours after study drug administration and attend 
scheduled visits at the CRU for 12 weeks to assess the measurements for safety, tolerability, and PK.  Sentinel 
dosing for the first 2 subjects of Cohorts 1 and 2 will be performed with 1 subject receiving LY3316531 and the 
other receiving placebo in a blinded manner.
Part B (Multiple-Dose in Healthy Subjects):  After a screening period up to 28 days, eligible subjects will be
randomized to receive a planned IV dose of LY3316531 (2000 mg [planned dose]) or placebo on the morning of 
Days 1, 29, and 57.  The planned dose of 2000 mg LY3316531 may be adjusted based on safety, PK, and target-
engagement data obtained in Part A of the study.  An optional SC or IV second multiple-dose cohort will be 
determined after reviewing the data from the first cohort.  
Subjects will be remain in the CRU for 24 hours after receiving each dose of study drug and attend scheduled visits 
at the CRU for 12 weeks following the final (third) dose of LY3316531 to assess the measurements for safety, 
tolerability, and PK.
Part C (Single-Dose in Patients with Psoriasis):  After a screening period up to 35 days, eligible patients with 
psoriasis will be enrolled to receive a single dose of LY3316531 on the morning of Day 1.  Patients will receive 300 
mg IV in Cohort 1 or, in the 2 optional cohorts, receive either a SC or IV dose (to be determined) not to exceed the 
maximum tolerated dose in Part A or the highest dose previously evaluated in healthy subjects.  Patients will remain 
in the CRU for 24 hours after study drug administration and attend scheduled visits at the CRU for 16 weeks 
following administration of the study drug to assess the measurements for safety, tolerability, PK, and PD.  Patients 
who respond to LY3316531 therapy will enter an extended follow-up period, which requires monthly visits up to 
Week 52.  Patients who enter the extended follow-up period should be discontinued from the study when additional 
therapy becomes necessary (as determined by the investigator and patient). 
Number of Patients/Subjects:
Part A: It is planned that up to 52 subjects may be enrolled in Part A of this study to obtain evaluable data from 46 
subjects.  The healthy subject SAD is planned to include 7 cohorts. Cohorts 1 and 2 are each planned to have 4 
subjects (3 LY3316531:1 placebo), whereas Cohorts 3, 4, 6, and 7 are each planned to have 8 subjects (6 
LY3316531:2 placebo).  Cohort 5 is planned to have 6 subjects, all receiving LY3316531.
Part B:  It is planned that up to 20 subjects may be enrolled in Part B of this study to obtain evaluable data from 16 
subjects (total number of subjects for planned and optional cohorts).  The healthy subject multiple-dose part of the 
study is planned to include up to 2 cohorts (2000 mg IV cohort with the option for 1 additional cohort) with 8 
subjects per cohort (6 LY3316531:2 placebo).
Part C:  It is planned that up to 30 patients may be enrolled in Part C of this study to obtain evaluable data from up 
to 24 patients (total number of patients for planned and optional cohorts).  The patients with psoriasis single-dose 
part of the study is planned to include up to 3 cohorts (300 mg IV cohort with the option for 2 additional cohorts)
with a minimum of 7 patients planned but up to 8 patients allowed per cohort (8 LY3316531).  The decision to 
initiate enrollment in the optional cohorts will be based on the clinical activity, safety, and tolerability of 
LY3316531 as observed in Cohort 1.  For example, a lower dose of LY3316531 may be investigated if the dose 
used in Cohort 1 is highly efficacious, based on the clinical activity measurement (Psoriasis Area and Severity Index


I9H-MC-FFAA(b) Clinical Pharmacology Protocol
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LY3316531
[PASI] scores), or if safety concerns arise.  Conversely, a higher dose may be explored in an optional cohort if it is 
determined that LY3316531 had minimal effect on PASI scores.
Statistical Analysis:
Safety:  All investigational products (IPs) and protocol procedure adverse events will be listed, and if the frequency 
of events allows, safety data will be summarized using descriptive methodology.  The incidence of 
treatment-emergent adverse events and serious adverse events will be presented by severity and by association with 
treatment as perceived by the investigator. Symptoms reported to occur prior to treatment with study drug will be 
distinguished from those reported as new or increased in severity during the trial. Safety parameters that will be 
assessed include laboratory tests, vital signs, electrocardiogram, body weight, immunogenicity, and injection-site 
reactions.
Pharmacokinetics: PK parameter estimates for LY3316531 will be calculated using standard noncompartmental 
methods of analysis.  Parameters for estimation will include absolute bioavailability following SC administration, 
maximum observed drug concentration (Cmax), time to reach Cmax, area under the concentration versus time curve 
(AUC) from time 0 to time of last measurable concentration (tlast), AUC from time zero to infinity (AUC0-∞), 
percentage extrapolated AUC from tlast to infinity, half-life, apparent clearance, and apparent volume of 
distribution.  The dose proportionality of selected LY3316531 PK parameters will be examined across the dose 
range using a power model approach.  Population PK analysis methods may be utilized if necessary.
Pharmacodynamics:  Relationships between LY3316531 exposure and CGRP target engagement may be explored 
using graphical- and model-based approaches for all parts of the study (Parts A, B, and C).  In patients with psoriasis
(Part C), PD data obtained will be documented in the study report by dose, plasma drug concentrations, and time 
from dose.  Figures showing values of potential PD markers versus time will be created for each dose, with a line for 
each patient.  Absolute percentage change from baseline for all will be summarized by providing the mean, standard 
deviation, median, minimum, and maximum for each cohort and overall for each sample day/time combination and 
maximum over the entire study.  Data may be log-transformed prior to summarizing if necessary.  The interpatient 
and intrapatient variability in human PD responses may also be assessed if appropriate.
Exposure–response relationships for clinical activity measures in psoriasis (such as PASI score, static Physician 
Global Assessment, and body surface area) and safety endpoints will be investigated initially using graphical 
methods.  Modeling approaches that relate exposure to the response at various time points or longitudinal models 
that relate the time course of exposure to the time course of response may be explored.
Statistical:  PK/PD analyses will be conducted on data from all patients/subjects who receive at least 1 dose of the 
IP and have evaluable PK. Placebo data from all cohorts will be pooled across all dose-escalation cohorts for the 
purpose of analysis.  Clinical activity and PD analyses will be conducted for all patients with psoriasis who receive 
the study drug (Part C only).  Pharmacodynamic parameters, and their change from baseline, will be summarized at 
each applicable visit using descriptive statistics (number of subjects, mean, standard deviation, median, minimum, 
and maximum for continuous variables and number of subjects, frequency, and percent for categorical variables).  
No statistical inferences will be made and no control for multiplicity is planned.  Additional analyses may be 
performed.


I9H-MC-FFAA(b) Clinical Pharmacology Protocol
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2. Schedule of Activities


I9H-MC-FFAA(b) Clinical Pharmacology Protocol
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LY3316531
2.1.
Part A (SAD in Healthy Subjects)
Study Schedule for Protocol I9H-MC-FFAA (Part A)
Screening
Baseline
Postdose
Visit No.
V1
V2
V3
V4
V5a
V6
V7
V8
V9
V10
V11
V12
ED
Study Day
-26 d from 
Day -2
-1
1
2
4 ± 
1 d
8 ± 
1 d
11 ± 
1 d
15 ± 
2 d
22 ± 
2 d
29 ± 
2 d
43 ± 
3 d
57 ±
3 d
71 ± 
3 d
85 
±3 d
Admission to CRU
X
Discharge from CRU
X
Informed consent
X
Review/confirm I/E 
criteria
X
X
Complete medical 
history 
X
Complete physical 
examination
X
X
X
Weight
X
X
X
Height
X
Symptom-directed 
physical examination
When needed
Concomitant 
medications
X
Xb
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs (pulse rate, 
blood pressure, and 
temperature)c,d
X
X
Predose, 
end of 
infusion, 
and 2, 6, 12
h after SC 
injection or 
start of 
infusion
24 h after
SC 
injection 
or start of 
infusion
X
X
X
X
X
X
X
X
X
X
X
Review preexisting 
conditions/AEs
X
Xb
X
X
X
X
X
X
X
X
X
X
X
X


I9H-MC-FFAA(b)Clinical Pharmacology Protocol
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LY3316531
Screening
Baseline
Postdose
Visit No.
V1 
V2
V3 
V4 
V5a
V6 
V7 
V8 
V9
V10 
V11 
V12
ED
Study Day
-26 d from 
Day -2
-1 
1 
2
4 ± 
1d
8 ± 
1d
11 ± 
1d
15 ± 
2d
22 ± 
2d
29 ± 
2d
43 ± 
3d
57 ±
3d
71 ± 
3d
85 
±3d
Injection-site 
assessment(including 
)
a,e
X 
X
X
X
ECGs
d,f
X
See ECG sampling schedule(Appendix 6)
LY3316531 or 
placeboadministration 
(IV or SC)
X
QuantiFERON®-TB
Gold testor TST
X
Read TST (if 
applicable)
Xg
HIV/HBV/HCV
X
FSH
h
X
Pregnancy test
h
X 
X
X
X
X 
X
Serum chemistry and 
hematology
X 
X
X 
X 
X
X 
X 
X 
X 
X 
X 
X 
X
Urinalysis
X 
X
X
X
X 
X
X 
X
Urine drug screen and 
ethanol test
X
X
Pharmacogenetics
(exploratory storage 
samples for DNA)
X
Immunogenicity
i
See immunogenicity sampling schedule (Appendix 6)
LY3316531 
concentration(PK)
i
See PK sampling schedule (Appendix 6)
Target engagement 
assay (total CGRP)
Xj
24 h 
after SC 
injection 
or start of 
infusion
X
X
X
X
X 
X
CCI


I9H-MC-FFAA(b)Clinical Pharmacology Protocol
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LY3316531
Screening
Baseline
Postdose
Visit No.
V1 
V2
V3 
V4 
V5a
V6 
V7 
V8 
V9
V10 
V11 
V12
ED
Study Day
-26 d from 
Day -2
-1 
1 
2
4 ± 
1d
8 ± 
1d
11 ± 
1d
15 ± 
2d
22 ± 
2d
29 ± 
2d
43 ± 
3d
57 ±
3d
71 ± 
3d
85 
±3d
Skin Biopsyk
Xl
Abbreviations:  AE = adverse event; CGRP = calcitonin gene-related peptide;CRU = clinical research unit; d = study day; DNA = deoxyribonucleic acid; ECG = 
electrocardiogram; ED = early discontinuation; FSH=follicle-stimulating hormone; h = hour(s); HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = 
human immunodeficiency virus; I/E = inclusion/exclusion; IV = intravenous; No.=number; PK=pharmacokinetic; SC=subcutaneous; 
; TB=tuberculosis; TST = tuberculin skin test; V = visit; 
.
a Required for subjects receiving SCdosing only.
b At the discretion of the CRU, the baseline measurement for this assessment can be collected at any time after the subject’sadmission to the CRU up until 
LY3316531 or placebo administration on Day 1.
c Additional vitalsign measurements may be obtainedwhenclinically indicated.  Vital signs should be taken following an approximate 5-minute rest in supine 
position.  Temperature measurement is required only atscreening andbaseline.
d ECG, vital sign, and PK sampling should occur at approximately the same time.  ECG recording and vital sign measurementsshould occur prior to the blood 
draw.
e Times are referenced to start of dosing. 0-hour assessments should be performedwithin 1minute after giving all SCinjections. Assessments should occur on 
Day 1 (0 min, 10 min, 0.5 h, 1 h, 3 h, and 6 h), Day 2 (24 h), Day 8 (168 h), and Day 15 (336 h) after SC injection of LY3316531.  Additional assessments 
may beperformed if deemed necessary by theinvestigator.
f Electrocardiograms should be taken following an approximate 5-minute rest in supine position.  Electrocardiograms arerequested to be taken at the specified 
time; however, aberrations to specified recording times will not be considered protocol deviations as long as the ECGsare taken and the actual recording time 
is documented.  Electrocardiograms will be collected in triplicateexcept at screening wherea singleECG will be collected(Section 9.4.3).
g Thefollow-up TSTreading should occur 2 to 3 days after V1.
h A serum pregnancy test will be conducted at screening only.  Urine pregnancy test will be used at all other time points.  For women who are considered to be 
postmenopausal, FSH shouldbe drawn to confirm postmenopausal status as defined in inclusion criterion [1b] and to be considered exempt for further 
pregnancy tests during the study.
i Refer to Appendix 6for specific PKand immunogenicitysampling schedule. Samples are requested to be taken at the specified time; however, aberrations to 
specified samplingtimes will not be considered protocol deviations as long as the samples are taken and the actual sampling time is recorded. It is essential 
that the actual timesof doses and samples are recorded accurately on the appropriate forms.
j This activity should be completed before LY3316531 or placebo administration (predose).
k Skin biopsies will be performed in the first 20 healthy subjects to volunteerfor this procedurein Parts A and B, collectively
.
l
CCI
After subject eligibility is confirmed, skin biopsies can be collected at any time prior todosing.
CCI


I9H-MC-FFAA(b) Clinical Pharmacology Protocol
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LY3316531
2.2.
Part B (Multiple-Dose Study in Healthy Subjects)
Study Schedule for Protocol I9H-MC-FFAA (Part B)
Screening
Baseline
Postdose
Visit No.
V1
Dose Periods 1, 2, and 3
V20
V21
V22
ED
V2,8,14
V3,9,15
V4,10,16
V5,11,17a
V6,12,18
V7,13,19
Study Day(s)
-26 d from 
Day -2
-1
1
2
4 ± 1 d
8 ± 1 d
11 ± 1 d
15 ± 2 d
22 ± 2 d
85 
±3 d
113
±4 d
141 
±4 d
28
29
30
32 ± 1 d
36 ± 1 d
39 ± 1 d
43 ± 2 d
50 ± 2 d
56
57
58
60 ± 1 d
64 ± 1 d
67 ± 1 d
71 ± 2 d
78 ± 2 d
Week(s)
0,4,8
1,5,9
2,6,10
3,7,11
12
16
20
Admission to CRU
Xb
Discharge from CRU
Xc
Informed consent
X
Review/confirm I/E 
criteria
X
Xd
Complete medical 
history 
X
Complete physical 
examination
X
X
X
Weight
X
X
X
Height
X
Symptom-directed 
physical examination
When needed
Concomitant 
medications
X
Xe
X
X
X
X
X
X
X
X
X
X
Vital signs (heart rate, 
blood pressure, and 
temperature)
f,g
X
X
Predose, 
end of 
infusion, 
and 2, 6, 12 
h after SC 
injectionh or 
start of 
infusion
24 h after 
SC 
injectionh
or start of  
infusion
X
X
X
X
X
X
X
X
X
Review preexisting 
conditions/AEs
X
Xe
X
X
X
X
X
X
X
X
X
X




I9H-MC-FFAA(b) Clinical Pharmacology Protocol
Page 18
LY3316531
Screening
Baseline
Postdose
Visit No.
V1
Dose Periods 1, 2, and 3
V20
V21
V22
ED
V2,8,14
V3,9,15
V4,10,16
V5,11,17a
V6,12,18
V7,13,19
Study Day(s)
-26 d from 
Day -2
-1
1
2
4 ± 1 d
8 ± 1 d
11 ± 1 d
15 ± 2 d
22 ± 2 d
85 
±3 d
113
±4 d
141 
±4 d
28
29
30
32 ± 1 d
36 ± 1 d
39 ± 1 d
43 ± 2 d
50 ± 2 d
56
57
58
60 ± 1 d
64 ± 1 d
67 ± 1 d
71 ± 2 d
78 ± 2 d
Week(s)
0,4,8
1,5,9
2,6,10
3,7,11
12
16
20
assay (total CGRP)
SC 
injectionh
or start of  
infusion
Skin biopsyr
Xs


I9H-MC-FFAA(b)Clinical Pharmacology Protocol
Page 19
LY3316531
Abbreviations:  AE = adverse event; CGRP = calcitonin gene-related peptide; CRU = clinical research unit; C-SSRS = Columbia-Suicide Severity Rating Scale; 
d = study day; DNA = deoxyribonucleic acid; ECG = electrocardiogram; ED = early discontinuation; FSH=follicle-stimulating hormone; FU = follow-up; h 
= hour(s); HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus; I/E = inclusion/exclusion;IV =intravenous;
No.=number; PK=pharmacokinetic; SC=subcutaneous; 
; TB=tuberculosis; TST = tuberculin skin test; 
V = visit; 
a Visits 5, 11, and 17 (Days 11,39, and 67) are required for subjects receiving SC injectionsonly.
b Admission to the CRU occurs on Days -1, 28, and 56.
c Discharge from the CRU occurs on Days 2, 30, and 58.
d This activityshould occur on Day -1 only.
e At the discretion of the CRU, the baseline measurement for this assessment can be collected at any time after the subject’sadmission to the CRU up until 
LY3316531 or placebo administration on Day 1.
f Additional vital sign measurements may be obtained when clinically indicated.  Vital signs should be taken following an approximate 5-minute rest in supine 
position.  Temperature measurement is required only atscreening andbaseline.
g ECG, vital sign, and PK sampling should occur at approximately the same time.  ECG recording and vital sign measurementsshould occur prior to the blood 
draw.
h SC injection is only if an optionalSCcohort is added.
i Times are referenced to start of dosing. 0-hour assessments should be performed within 1minute after giving all SC injections.  Assessments should occur on 
Day 1 (0 min, 10 min, 0.5 h, 1 h, 3 h, and 6 h),Day 2 (24 h), Day 8 (168 h), and Day 15 (336 h)after SC injection of LY3316531.  Additional assessments 
may be performed if deemed necessary by the investigator.
j Required for subjects who will receive SC injections only.
k If the optional cohort uses SC dosing, then injection-site assessments will be performed.
l ECGs should be taken following an approximate 5-minute rest in supine position.  ECGs arerequested to be taken at the specified time; however, aberrations 
to specified recording times will not be considered protocol deviations as long as the ECGsare taken and the actual recording time is documented.  Single 
safety ECGs will becollected unless the ECG values for subjects in Part A show clinically significant changes(for example,increase in PR or QT interval). 
See Section 9.4.3for more details on ECGs. 
m The follow-up TST reading should occur 2 to 3 days after V1.
n A serum pregnancy test will be conducted at screening only.  Urine pregnancy test will be used at all other time points.  For women who are considered to be 
postmenopausal, FSH shouldbe drawn to confirm postmenopausal status as defined in Inclusion Criterion [1b] and to be considered exempt for further 
pregnancy tests during the study.
o Refer to Appendix 6for specific PKand immunogenicitysampling schedule. Samples are requested to be taken at the specified time; however, aberrations to 
specified samplingtimes will not be considered protocol deviations as long as the samples are taken and the actual sampling time is recorded. It is essential 
that the actual timesof doses and samples are recorded accurately on the appropriate forms.
p C-SSRS should be administered before subjects are discharged from the CRU on Day 2.
q This activity should be completed before LY3316531 or placebo administration (predose).
r Skin biopsies will be performed in the first 20 healthy subjects to volunteer for this procedure in Parts A and B, collectively.
s
CCI
After subject eligibility is confirmed, skin biopsies can be collected at any time prior to dosing.
CCI


I9H-MC-FFAA(b) Clinical Pharmacology Protocol
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LY3316531
2.3.
Part C (Single-Dose Study in Patients with Psoriasis)
Study Schedule for Protocol I9H-MC-FFAA (Part C)
Screening
Baseline
Postdose
Extended FU
Visit No.
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10
V11
V12
ED
FUa
ED
Study Day(s)
-33 d from 
Day -2
-1
1
2
4 ± 
1 d
8 ± 
1 d
15 ± 
2 d
22 ± 
2 d
29 ± 
2 d
43 ± 
3 d
57 ±
3 d
71 ± 
3 d
85 
±3 d
113
±4 d
Up to  
365 ± 5 d
Week(s)
0
1
2
3
4
6
8
10
12
16
Up to 52
Admission to CRU
X
Discharge from CRU
X
Informed consent
X
Review/confirm I/E 
criteria
X
X
Complete medical 
history 
X
Complete physical 
examination
X
X
Weight
X
X
X
X
X
X
Height
X
Symptom-directed 
physical examination
When needed
Chest x-ray
X
Concomitant 
medications
X
Xb
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs (heart 
rate, blood pressure, 
and temperature)
c,d
X
X
Predose, end of 
infusion, and 2, 
6, 12 h after SC 
injection
e or start 
of infusion
24 h after 
SC 
injection
e
or start of  
infusion
X
X
X
X
X
X
X
X
X
X
X
X
X
Review preexisting 
conditions/AEs
X
Xb
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ECGs
d,f
X
See ECG sampling schedule (Appendix 6)
LY3316531 
administration (IV or 
SC)
X


I9H-MC-FFAA(b)Clinical Pharmacology Protocol
Page 21
LY3316531
Screening
Baseline
Postdose
Extended FU
Visit No.
V1 
V2
V3 V4 V5 V6 V7 V8 V9
V10 V11 V12 ED
FUa
ED
Study Day(s)
-33d from 
Day -2
-1 
1
2
4 ± 
1d
8 ± 
1d
15 ± 
2d
22 ± 
2d
29 ± 
2d
43 ± 
3d
57 ±
3d
71 ± 
3d
85 
±3d
113
±4d
Up to  
365 ± 5d
Week(s)
0
1 
2 
3 
4 
6 
8 
10 
12 
16
Up to 52
QuantiFERON®-TB 
Gold test or TST
X
Read TST (if 
applicable)
Xg
HIV/HBV/HCV
X
FSH
h
X
Pregnancy test
h
X 
X
X 
X 
X 
X 
X 
X 
X
Serum chemistry and 
hematology
X 
X
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
Urinalysis
X 
X
X
X 
X
X
Urine drug screen 
and ethanol test
X 
X
Pharmacogenetics 
(exploratory storage 
samples for DNA)
X
Immunogenicity
d,i
See immunogenicity sampling schedule (Appendix 6)
LY3316531
concentration(PK)
d,i
See PK sampling schedule (Appendix 6)
C-SSRS/Self-Harm 
Supplement and FU
X 
X
Xj
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
Target engagement 
assay (total CGRP)
Xk
24 h after 
SC 
injection
e
or start of  
infusion
X 
X 
X 
X 
X 
X 
X 
X 
X
Patient’s Global 
Assessmentand PSS
l
Xk
X 
X 
X 
X 
X 
X 
X 
X 
X
PASI, sPGA, and 
BSA
X
Xk
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
HS-CRP
X
Xk
X 
X 
X 
X 
X
 Concentration
Xk
X 
X 
X 
X 
X
CCI


I9H-MC-FFAA(b) Clinical Pharmacology Protocol
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LY3316531
Screening
Baseline
Postdose
Extended FU
Visit No.
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10
V11
V12
ED
FUa
ED
Study Day(s)
-33 d from 
Day -2
-1
1
2
4 ± 
1 d
8 ± 
1 d
15 ± 
2 d
22 ± 
2 d
29 ± 
2 d
43 ± 
3 d
57 ±
3 d
71 ± 
3 d
85 
±3 d
113
±4 d
Up to  
365 ± 5 d
Week(s)
0
1
2
3
4
6
8
10
12
16
Up to 52
Exploratory storage 
samples (serum, 
plasma, RNA)
Xk
X
X
X
X
Skin biopsy
Xm
Xn


I9H-MC-FFAA(b) Clinical Pharmacology Protocol
Page 23
LY3316531
Abbreviations:  AE = adverse event; BSA = body surface area; CGRP = calcitonin gene-related peptide; CRU = clinical research unit; C-SSRS = Columbia-
Suicide Severity Rating Scale; d = study day; DNA = deoxyribonucleic acid; ECG = electrocardiogram; ED = early discontinuation; FSH = follicle-
stimulating hormone; FU = follow-up; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus; HS-CRP = high sensitivity-
C reactive protein; I/E = inclusion/exclusion; IL = interleukin; IV = intravenous; No. = number; PASI = Psoriasis Area and Severity Index; PK = 
pharmacokinetic; PSS = psoriasis symptom scale; RNA = ribonucleic acid; SC = subcutaneous; sPGA= static Physician Global Assessment; TB =
tuberculosis; TST = tuberculin skin test; V = visit.
a
Monthly follow-up visits will occur during this time period for patients who respond to treatment with LY3316531 after the initial 16-week follow-up period
(see Section 5.1.3 for more details).
b
At the discretion of the CRU, the baseline measurement for this assessment can be collected at any time after the patient’s admission to the CRU up until 
LY3316531 or placebo administration on Day 1.
c
Additional vital sign measurements may be obtained when clinically indicated.  Vital signs should be taken following an approximate 5-minute rest in supine
position.  Temperature measurement is required only at screening and baseline.
d
ECG, vital sign, and PK sampling should occur at approximately the same time.  ECG recording and vital sign measurement should occur prior to the blood 
draw.
e
SC injection is only if an optional subcutaneous-injection cohort is added.
f
ECGs should be taken following an approximate 5-minute rest in supine position. ECGs are requested to be taken at the specified time; however, aberrations 
to specified recording times will not be considered protocol deviations as long as the ECGs are taken and the actual recording time is documented.  Single 
safety ECGs will be collected unless the ECG values for subjects in Part A show clinically significant changes (for example, increase in PR or QT interval).  
See Section 9.4.3 for more details on ECGs.
g
The follow-up TST reading should occur 2 to 3 days after V1.
h
All female subjects of childbearing potential will have serum pregnancy test at screening only. Urine pregnancy test will be used at all other time points.  For 
women who are considered to be postmenopausal, FSH should be drawn to confirm postmenopausal status as defined in inclusion criterion [8b] and to be 
considered exempt for further pregnancy tests during the study.
i
Refer to Appendix 6 for specific PK and immunogenicity sampling schedule. Samples are requested to be taken at the specified time; however, aberrations to 
specified sampling times will not be considered protocol deviations as long as the samples are taken and the actual sampling time is recorded. It is essential 
that the actual times of doses and samples are recorded accurately on the appropriate forms.
j
C-SSRS should be administered before subjects are discharged from the CRU on Day 2.
k
This activity should be completed on Day -1 or Day 1 before LY3316531 or placebo administration (predose).
l
All patient-reported outcomes are to be collected from the subject prior to clinical assessment by the investigator.
m After patient eligibility is confirmed, baseline skin biopsies can be collected at any time starting on Day -7 up until dosing.
n
Postdose skin biopsies should be collected on Day 15 ± 2 days. 


I9H-MC-FFAA(b)Clinical Pharmacology Protocol
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LY3316531
3.Introduction
3.1. Study Rationale
LY3316531 is a humanized bispecific antibody that selectively binds to interleukin-23 (IL-23) 
and calcitonin gene-related peptide (CGRP).  This dual inhibitoris an innovative attempt to 
target pathways that affectthe pathologyassociated with auto-inflammatory conditions.
Study I9H-MC-FFAA (FFAA) is a Phase 1, first-in-human study toexplore the safety, 
tolerability, and pharmacokinetics (PK)of single and multiple doses of LY3316531 in healthy 
subjects andthe safety, tolerability, PK, and pharmacodynamics (PD)ofasingle doseof 
LY3316531in patients with psoriasis.  Theevaluation of LY3316531in patients with psoriasis 
will aid in thedetermination of a safe dose levelor range, characterize PK and PD, and explore 
clinical activity data for future studies.
Skinbiopsies will also be taken to observe the effects of LY3316531 on psoriatic skin lesions.  
 
 
While Study FFAA will evaluate LY3316531 in patients with psoriasis, atopic dermatitis and 
Crohn’s disease are also potential future indications.
3.2. Background
CCI
A typical organ-specific,T-cell-driven inflammatory disease, psoriasis had been considered a 
Thelper (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).  IL-23, a member of the IL-12 family of cytokines, is a 
heterodimeric protein comprised of 2 subunits; the p40 subunit, which it shares with IL-12, and 
the p19 subunit, believed to be specific to IL-23.  IL-23 is produced by antigen-presenting cells, 
such as dendritic cellsand macrophages, and plays an important role in maintenance and 
amplification of Th17 cells (Lee et al. 2004; Piskin et al. 2004).  In addition, Th17 cells and their 
downstream effector molecules, including IL-17A, IL-17F, IL-21, IL-22, and tumor necrosis 
factor alpha (TNF-α), are found at increased levels in human psoriatic skin lesions and 
circulation (Boniface et al. 2007; Lowes et al. 2008; Caruso et al. 2009; Kagami et al. 2010).
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).  
Agents specifically targeting the IL-23 p19 subunit have demonstrated clinical activity in 
psoriasis 
(Krueger et al. 2015; Papp et al. 
2015; Gordon et al. 2015; Koppet al. 2015; Sofen et al. 2014) and Crohn’s disease (Sands et al. 
2015).
CCI


I9H-MC-FFAA(b) Clinical Pharmacology Protocol
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LY3316531
Calcitonin gene-related peptide is a 37-amino acid neuropeptide member of a family of 
peptides that includes amylin, adrenomedullin, and calcitonin. The predominant form of CGRP 
is known as -CGRP, with a second isoform, -CGRP, being produced from a separate gene but 
having high sequence homology (Steenbergh et al. 1985).  Both isoforms have similar biological 
activities, but differ in their expression patterns; -CGRP is expressed mainly in the peripheral 
and central nervous system while -CGRP is expressed mostly in the enteric nervous system 
(Mulderry et al. 1988). Calcitonin gene-related peptide is a potent vasodilator (Brain et al. 
1985). While CGRP antagonists seem to restore normal tonus in CGRP-induced dilation of 
isolated arterial rings, the evidence to date suggests that CGRP antagonists do not alter basal 
vascular tone (Chaitman et al. 2012; Verheggen et al. 2002).  Calcitonin gene-related peptide has
a well-established role in neurogenic inflammation and nociception (Hirsch et al. 2013). It is 
able to facilitate the production and secretion of numerous pro-inflammatory mediators that lead 
to hyperemia, edema, and pain in inflamed tissues (Cady et al. 2011).  The CGRP pathway may
play a specific role in inflammatory skin disorders having direct effects on immune cells, 
cytokine production, and itch and pain pathologies in various dermatoses (Lotti et al. 2014; 
Kashem et al. 2015). Interestingly, CGRP regulates sensory neurons through the IL-23/IL-17 
axis as well (Riol-Blanco et al. 2014; Ding et al. 2016).  In addition to its involvement in 
inflammation and nociception, it is believed that CGRP can increase IL-23 production (Kashem 
et al. 2015).
Several nonclinical studies were performed to support the use of LY3316531 in humans.  
Weekly administration of LY3316531 to cynomolgus monkeys in a general toxicology study 
resulted in no adverse drug-related findings at doses of 20 or 60 mg/kg (subcutaneous [SC]), or 
200 mg/kg (intravenous [IV]) for 3 months.  The exposure multiple and dose multiple to the 
highest human dose, based on this monkey study, are 5× and 28×, respectively.  Additionally, a 
tissue cross-reactivity study was performed with LY3316531 in human and monkey tissues,
which produced no toxicologically important difference in tissue binding between the species.
3.3.
Benefit/Risk Assessment
The nonclinical safety information for LY3316531 supports the transition from preclinical status 
to a clinical, first-in-human study.  On the basis of the nonclinical data, LY3316531 is not 
considered to be a high-risk compound.  This protocol reflects the fact that LY3316531 has not 
been administered to humans previously, and to mitigate this risk, the study has been designed to 
be conducted in accordance with principles outlined in the Guideline on Strategies to Identify 
and Mitigate Risks for First-in-Human Clinical Trials with Investigational Medicinal Products.  
Any identified risks are considered to be monitorable and manageable at the planned dose range 
with starting dose of 3 mg up to a maximum dose not to exceed 2000 mg for LY3316531 in 
healthy subjects and patients with psoriasis.
There is no anticipated therapeutic benefit for the healthy subjects. There is a potential for 
patients with psoriasis to experience some level of therapeutic benefit during this study, as 
blockade of IL-23 is known to improve psoriasis.


I9H-MC-FFAA(b) Clinical Pharmacology Protocol
Page 26
LY3316531
More information about the known and expected benefits, risks, serious adverse events (SAEs) 
and reasonably anticipated adverse events (AEs) of LY3316531 are to be found in the 
Investigator’s Brochure (IB).


I9H-MC-FFAA(b) Clinical Pharmacology Protocol
Page 27
LY3316531
4. Objectives and Endpoints
Table FFAA.4.1 shows the objectives and endpoints of the study.
Table FFAA.4.1.
Objectives and Endpoints
Primary Objectives
Primary Endpoints
To explore the safety and tolerability of single and 
multiple doses of LY3316531 in healthy subjects
To explore the safety and tolerability of a single dose of 
LY3316531 in patients with psoriasis
Incidence of adverse events, TEAEs, and SAEs


I9H-MC-FFAA(b)Clinical Pharmacology Protocol
Page 28
LY3316531
Objectives and Endpoints
Secondary Objectives
Secondary Endpoints
To characterize the PK of LY3316531 following IV and 
SC administrationin healthy subjects
To characterize the PK of LY3316531 following IV 
administration inpatients with psoriasis
CmaxandAUC
Exploratory Objectives
Exploratory Endpoints
To evaluate the injection tolerance after SC 
administration of LY3316531
Pain scale scores and severity of ISR
To evaluate the formation of ADA to LY3316531 
Presence of ADA againstLY3316531
To evaluate the PD response (target engagement) of 
LY3316531 using total CGRP
Summary of total CGRP concentrations for each cohort 
and study time point
To evaluatepatient-reported outcomes, including 
measurement ofdisease activity of LY3316531in 
patients with psoriasis
Summary (mean, standard deviation, median, minimum, 
and maximum) of absolute percentage change from 
baseline for all of each cohort and overall for each 
sample day/time combination and maximum over the 
entire studyfor the patient’s global assessment
To evaluate relationships between LY3316531 exposure
andPD and clinical activity measuresand safety 
endpoints
Graphical and model-based summaries of relationships 
between LY3316531 exposure and total CGRP, 
, 
PASI, sPGA, ECGs, and safety endpoints of interest
CCI
Abbreviations:  ADA = antidrug antibody; AUC = area under the concentration versus time curve; CGRP = 
calcitonin gene-related peptide; Cmax= maximum observed drug concentration; ECG = electrocardiogram; IL = 
interleukin; ISR = injection-site reaction; IV = intravenous; PASI=Psoriasis Area and Severity Index; PD = 
pharmacodynamics; PK = pharmacokinetics;SAE = serious adverse event; SC = subcutaneous; sPGA = static 
Physician Global Assessment; TEAE = treatment-emergent adverse event.
CCI
CCI


I9H-MC-FFAA(b) Clinical Pharmacology Protocol
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LY3316531
5. Study Design
5.1.
Overall Design
Study FFAA is a 3-part Phase 1, multicenter, randomized, sponsor unblind, subject- and 
investigator-blind (investigator will be partially blinded for Cohorts 1 and 2 and unblind for 
Cohort 5 in Part A), placebo-controlled, parallel-dose group, single-ascending dose (SAD)
design (Part A), and multiple-dose design (Part B) in healthy subjects.  In addition, Part C of this 
study is an open-label, single-dose design in patients with psoriasis. There are 3 parts to this 
study to explore the safety, tolerability, PK, and PD of LY3316531:

Part A: SAD design in healthy subjects,

Part B: Multiple-dose design in healthy subjects,

Part C: Single-dose design in patients with psoriasis.
Table FFAA.5.1 provides a detailed description of subject/patient cohorts and planned doses for 
Parts A, B, and C.  Figure FFAA.5.1 demonstrates the relationship among Parts A, B, and C.  
Part A will begin first and will trigger the initiation of Parts B and C, which will run in parallel.
Patients/subjects will be admitted to the clinical research unit (CRU) on Day -1 (Days -1, 28, and 
56 in Part B) and fast overnight. Patients/subjects will receive a dose of study drug or placebo 
on Day 1 (Days 1, 29, and 57 in Part B) and will undergo the study assessments specified in the 
Schedule of Activities (Section 2). Patients/subjects may be discharged 24 hours after dose 
administration on Day 2 (Days 2, 30, and 58 in Part B).  In case of safety concerns,
patients/subjects will be required to stay in the CRU for a longer period at the discretion of the 
investigator. Patients/subjects will return to the CRU for outpatient visits for procedures 
specified in the Schedule of Activities (Section 2).
The decision to escalate to the next higher dose of LY3316531 will be based on safety data 
through Day 15 from at least 7 subjects (5 or 6 subjects will have received LY3316531 
determined by randomization) from the preceding dose cohort.  Exceptions will be for Cohorts 1 
and 2, and Cohort 5 if available at the time of decision in Part A, where safety data from all 
subjects through Day 15 will be required.  More detailed information about the safety reviews 
and dosing decisions may be found in Section 7.4.2.


I9H-MC-FFAA(b) Clinical Pharmacology Protocol
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LY3316531
Table FFAA.5.1.
Summary of Maximum Number of Patients/Subjects per Cohort
Cohort #
Planned Dose/
Administration Route
Number of
Planned Subjects
Total Number of 
Planned Subjects
LY
PBO
Part A
SAD Cohort 1a
3 mg/IV
3
1
4
SAD Cohort 2a
15 mg/IV
3
1
4
SAD Cohort 3
75 mg/IV
6
2
8
SAD Cohort 4
300 mg/IV
6
2
8
SAD Cohort 5
300 mg/SC
6
0
6
SAD Cohort 6
900 mg/IV
6
2
8
SAD Cohort 7
2000 mg/IV
6
2
8
Part B
Multiple-Dose Cohort 1
2000 mg/IV
6
2
8
Multiple-Dose Cohort 2b
Route and dose TBD 
6
2
8
Part C
Patient Cohort 1c
300 mg/IV
8
0
8
Patient Cohort 2b,c
Route and dose TBD 
8
0
8
Patient Cohort 3b,c
Route and dose TBD 
8
0
8
Abbreviations: IV = intravenous; LY = LY3316531; PBO = placebo; SAD = single-ascending dose; SC = 
subcutaneous; TBD = to be determined.
a
Sentinel dosing will be used in this cohort.
b
Optional subject or patient cohort.  Actual dose and route of administration will be determined based on 
cumulative data from previous cohorts, but will not exceed 2000 mg of LY3316531 administered IV.
c
A minimum of 7 patients are planned but up to 8 patients are allowed per cohort.
A follow-up visit will be performed according to the Schedule of Activities (Section 2).
Study governance considerations are described in detail in Appendix 3.
Figure FFAA.5.1 illustrates the study design.


I9H-MC-FFAA(b) Clinical Pharmacology Protocol
Page 31
LY3316531
Abbreviations:  IV = intravenous; LY = LY3316531; MD = multiple dose; PBO = 
placebo; PK = pharmacokinetic sampling; SAD = single-ascending dose; SC = 
subcutaneous; SR = safety review meeting; TBD = to be determined.
Figure FFAA.5.1.
Illustration of study design for Protocol I9H-MC-FFAA.
5.1.1. Part A (SAD in Healthy Subjects)
Seven planned dose-escalation cohorts will be enrolled to receive either IV or SC administration 
of LY3316531 (3, 15, 75, 300, 900, or an additional dose not to exceed 2000 mg) or placebo.
Sentinel dosing will be used in Cohorts 1 and 2 to minimize the risk to subjects receiving this 
novel antibody.  Initially, 2 subjects (1 receiving LY3316531 and 1 receiving placebo) will be 
dosed in a blinded manner (sentinel subjects) and these subjects will be followed for at least 
24 hours postdose before the remaining subjects in that cohort are dosed (subject blind only).  
The remaining subjects may then be dosed on the same day or subsequent days (but not 
necessarily consecutive days), as determined by the investigator.  Dose escalation to the next 
cohort can begin after a safety review of data from the preceding cohort (see Section 7.4.2 for a 
more detailed description).  All 6 subjects in Cohort 5 will receive 300 mg of LY3316531 SC.
All subjects who meet eligibility criteria will be followed for 12 weeks post-treatment 
administration.  A subject’s participation is considered as complete if he/she received the study 
drug and completes all activities up to and including at least Day 57.  Subjects may be replaced if
PK data are not collected up to and including Day 57.  
5.1.2. Part B (Multiple-Dose Design in Healthy Subjects)
One planned multiple-dose cohort will be enrolled to receive IV administration of LY3316531 
(2000 mg) or placebo.  The dose and route of administration (IV or SC) for an optional second 
multiple-dose cohort would be determined after reviewing the data from the first IV cohort.
It is planned that a review of the safety data from Cohort 7 (Part A) and the preliminary PK data
(maximum observed drug concentration [Cmax] and area under the concentration versus time 


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curve [AUC]) from Cohorts 1, 2, and 3 (through Day 29) in Part A will trigger enrollment to the 
first cohort in Part B.  Section 7.4.1 provides detailed information on how the dose level for the 
optional cohort will be determined and when the cohorts will begin enrollment procedures.
All subjects who meet eligibility criteria will receive 3 doses of LY3316531 (1 dose every 
4 weeks) and be followed for 12 weeks after the final treatment administration. A subject’s 
participation is considered as complete if he/she received the study drug and completes all 
activities up to and including at least Day 85.  Subjects may be replaced if PK data are not 
collected up to and including Day 85.
5.1.3. Part C (Single-Dose Design in Patients with Psoriasis)
One planned single-dose cohort will be enrolled to receive IV administration of LY3316531 with 
the option of 2 subsequent cohorts where the dose levels and route of administration (SC or IV) 
would be determined after reviewing the data from the first IV cohort.
The first cohort is planned to receive 300 mg of LY3316531 pending the analysis of available 
safety data from Part A.  The safety scenarios for AEs, SAEs, and adverse laboratory 
abnormalities described in Section 7.4.2 that would prevent dose escalation in Parts A and B are 
the same that would prevent initiation of Part C. The actual starting dose and expected exposure 
will not exceed the dose/exposure that is concurrently being evaluated in Part A.  Any available
preliminary PK data from Cohorts 1, 2, and 3 (through Day 29) in Part A will be considered in 
the decision to initiate Part C as well.  
Similarly, the dose for the optional cohorts will be determined based on cumulative data from 
previous cohorts, but will not exceed 2000 mg of LY3316531.  Section 7.4.1 provides detailed 
information on how dose levels for the 2 optional cohorts will be determined and when the 
cohorts will begin enrollment procedures.
All patients who respond to LY3316531 treatment by exhibiting at least 50% reduction from 
baseline Psoriasis Area and Severity Index (PASI) score at Week 12 (Visit 11; Day 85) can enter 
an extended follow-up period for up to 52 weeks post-treatment administration (see Section 2.3).  
Other subjects who do not meet the above criterion for PASI reduction should be considered for 
discontinuation from the study at Week 16 (Visit 12; Day 113). Exceptions could be considered 
after a discussion between the sponsor and investigator.
A patient’s participation is considered as complete if he/she received the study drug and 
completes all activities up to and including at least Day 85.  Patients may be replaced if PK or 
PD data are not collected up to and including Day 85.
5.2.
Number of Participants
5.2.1. Part A (SAD Design in Healthy Subjects)
Up to 52 subjects may be enrolled so that approximately 46 subjects complete Part A.  For 
purposes of this study, a subject completes Part A when he/she completes all scheduled 
procedures up to and including at least Day 57.  


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Refer to the Schedule of Activities (Section 2.1) for data to be collected at the time of 
discontinuation and follow-up.
5.2.2. Part B (Multiple-Dose Design in Healthy Subjects)
Up to 20 subjects may be enrolled so that approximately 16 subjects complete Part B (total 
number of subjects for planned Cohort 1 and the 1 optional cohort).  Subjects who drop out of 
the Part B prior to receiving the third dose will be replaced.  However, subjects who drop out 
following administration of the third dose, or withdraw from Part B due to safety reasons will not 
be replaced, unless more than half of the subjects in a given cohort have dropped out after the 
third dose.  For purposes of Part B, a subject completes the study when he/she completes all 
scheduled procedures up to and including at least Day 85.
Refer to the Schedule of Activities (Section 2.2) for data to be collected at the time of 
discontinuation and follow-up.
5.2.3. Part C (Single-Dose Design in Patients with Psoriasis)
Up to 30 patients may be enrolled so that up to 24 patients complete Part C (total number of 
patients planned for Cohort 1 and the 2 optional cohorts).  For purposes of Part C, a patient
completes the study when he/she completes all scheduled procedures up to and including at least 
Day 85.
Refer to the Schedule of Activities (Section 2.3) for data to be collected at the time of 
discontinuation and follow-up.
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 patient/subject.
5.4.
Scientific Rationale for Study Design
This study will be the first assessment of the safety and tolerability of single and multiple 
(monthly) doses of LY3316531 in humans.  A parallel-group design was selected based on the 
expected long half-life of the molecule in humans.  Although a crossover design could provide 
more robust data, the long washout period required for the anticipated 2- to 3-week half-life 
would make it impractical.  In addition, with an antibody such as LY3316531, there is the 
potential for developing antidrug antibodies (ADAs), which could confound analyses for 
subsequent doses.
Safety and tolerability assessments will be made over all dose levels.  Subjects (all cohorts) will 
remain in the CRU for at least 24 hours after each dose of LY3316531 or placebo, to provide 
adequate and close safety monitoring.  Sentinel dosing will be used in Cohorts 1 and 2 of Part A 
to minimize safety risks with this molecule.
For Part A, subjects are blinded and investigators are partially blinded to treatments to minimize 
bias during data collection (see Section 5.1.1).  As there is only a single cohort of subjects 
receiving LY3316531 via the SC route in Part A, it is not planned to include subjects receiving 


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SC placebo, as adequate controldata will be obtained from the IV cohort.A single-dose design 
is appropriate to assess the initial safety profile of the drug while minimizingsubject risk;it also 
provides an opportunity to explore safety and PK across a broad range of doses in an adequate 
number of subjects to determine a range of doses and regimens to be evaluated in later studies.
For Part B, subjects and investigators are blinded to treatments to minimize bias during data 
collection.  Intravenousplacebo controlsubjects are included to allow for a more robust 
interpretation of data.  Preliminary safety data from the SADportion in Part A will support the 
utilization of healthy subjects in the multiple-doseportion in Part B.  The multipledose is the 
next logical step for clinical evaluation of aninvestigational product(IP).
The starting dose in Parts B andC of the study will be administered via the IVroute.If 
additional cohorts are dosed, depending on the dose level chosen, the SC route may be used if 
feasible (maximum concentration ofLY3316531 is75mg/mL).  In addition, a wide dose range 
has been chosenin Part A as this study will support multiple indications, includinginflammatory 
bowel disease, which may require higher doses of LY3316531 to reach therapeutic levels as 
compared to psoriasis.
A population of healthy subjects wasselected to assess the PK, safety,and tolerability of 
LY3316531based upon the likelihood of less physiologic variability in the absence of disease 
states that may affect multiple organ systems.  Moreover, healthy subjects are usually devoidof 
other confounding factors such as concomitant medications.  The inclusion ofpatients with 
psoriasis will aid in thedetermination of safe dose levels,a characterization ofPK and PD, and 
the exploration ofclinical activity data for future studies.
5.5. Justification for Dose
The wide dose range selected for Part A of thestudy isbased on PK and efficacy data available 
from clinical studies with the IL-23 monoclonal antibody (mAb)( 
)and the CGRP 
mAb ( 
), coupled with preclinical PK information for LY3316531 in cynomolgus
monkeys and relative potency information collected in humanized IL-23 mouse PD model 
experiments.  The planned starting dose of 3mg IV is expected to have minimal biological 
activity and the maximum dose of 2000mg IV is expected to support the highest doses that may 
be evaluated in the multiple-doseand Phase 2 studies.  
 The starting and maximum 
doses are expected to produce AUCs that are 851and 5×lower, respectively,than the AUC 
observed at the NOAEL dose in toxicology studies in cynomolgus monkeys (Table FFAA.5.2
CCI
).
The dose(s)for Parts B and C will be selected based on available PK and safety data from Part A 
of the study.  The highest dose that may be evaluated in Part B will not exceed the maximum 
tolerated dose (MTD)in Part A.  In the event PK data from Part A indicate that significant drug 
accumulation is likely to occur with doses of 2000mg LY33165314 administered every 4weeks, 
the dose administered inPart B will be reduced. 
CCI
CCI




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6. Study Population
Eligibility of patients/subjects for the study will be based on the results of screening medical 
history, physical examination, vital signs, clinical laboratory tests, and an electrocardiogram 
(ECG). 
The nature of any conditions present at the time of the physical examination and any preexisting 
conditions will be documented.
Screening may occur up to 28 days (35 days for patients) prior to enrollment.  Subjects who are 
not enrolled within 28 days (35 days for patients) 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, is not permitted.
6.1.
Inclusion Criteria
Patients/subjects are eligible for inclusion in the study only if they meet all of the following 
criteria at screening and/or enrollment:
6.1.1. For Healthy Subjects
[1]
are overtly healthy males or females, as determined by medical history and 
physical examination.
[1a] male subjects:
agree to either remain abstinent (if this is their preferred and usual lifestyle)
or use condoms with spermicide as well as 1 additional highly effective
method of contraception or effective method of contraception during the 
study and for 5 months following the last dose.
[1b] female subjects:
must test negative for pregnancy at the time of screening and be of
non-childbearing potential, as defined by at least 1 of the following:

at least 6 weeks have elapsed after bilateral oophorectomy, tubal 
ligation, or hysterectomy

postmenopausal as defined in Section 6.3.4

female infertility due to other causes that have been discussed with, 
and accepted, by the sponsor.
[2]
are between 18 and 64 years of age, inclusive, at the time of screening.
[3]
have a body mass index of 18 to 32.0 kg/m2, inclusive, and a minimum body 
weight of 50 kg.


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[4]
have clinical laboratory test results within normal reference range for the 
population or investigative site, or results with acceptable deviations that are 
judged to be not clinically significant by the investigator.
[5]
have venous access sufficient to allow for blood sampling and administration 
of IP for IV administration as per the protocol.
[6]
are willing and able to undergo punch biopsies according to the Schedule of 
Activities (Section 2.2).
[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.
6.1.2. For Patients with Psoriasis
[9]
present with chronic plaque psoriasis based on an investigator-confirmed 
diagnosis of chronic psoriasis vulgaris for at least 6 months prior to baseline 
and meet the following criteria:

plaque psoriasis involving ≥5% body surface area (BSA) in affected skin 
other than the face and scalp at screening (Visit 1) and baseline (Day 1, 
Visit 2)

static Physician Global Assessment (sPGA) score of ≥2 at screening (Visit 
1) and baseline (Day 1, Visit 2)

are willing and able to undergo punch biopsies according to the Schedule 
of Activities (Section 2.3).
[9a] male patients:
agree to either remain abstinent (if this is their preferred and usual lifestyle)
or use condoms with spermicide as well as 1 additional highly effective
method of contraception or effective method of contraception during the 
study and for 5 months following the last dose of the IP.
[9b] female patients:
both childbearing and non-childbearing potential must test negative for 
pregnancy at the time of screening.
agree to use 2 effective methods of contraception during the study and for
5 months following the last dose of the IP unless they are not of child-
bearing potential, as defined by at least 1 of the following:

at least 6 weeks have elapsed after bilateral oophorectomy, tubal ligation, 
or hysterectomy

postmenopausal as defined in Section 6.3.4

female infertility due to other causes that have been discussed with, and 
accepted, by the sponsor.


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[10]are ≥18 years of age.
[11]have a minimum body weight of 50 kg.
[12]have adequate organ function, including:
• hematologic:  absolute neutrophil count ≥1.5×109/L (≥1.5×103/µL or ≥1.5 
GI/L), platelet count ≥100×109/L (≥100×103/µL or ≥100 GI/L), 
hemoglobin level ≥10.0 g/dL (≥100 g/L), lymphocyte count >500cells/µL 
(>0.50×103/µL or >0.50 GI/L), and total white blood cell count 
≥3.0×109/L (≥3.0×103/µL or ≥3.0 GI/L)
• chemistry:  
serum creatinine, alanine aminotransferase (ALT), and aspartate 
aminotransferase (AST) levels ≤2× upper limit of normal (ULN)
total bilirubin level (TBL) (subjectswith Gilbert’s syndrome must have 
serum direct bilirubin <1.5 mg/dL)and alkaline phosphatase (ALP) <1.5× 
ULN.
[13]have venous access sufficient to allow for blood sampling and administration 
of IPthroughIV (if applicable), as per the protocol.
[14]are reliable and willing to make themselves available for the duration of the 
study, and are able and willing to follow study procedures.
[15]have given written informed consent approved by Lilly and the ethicalreview 
board (ERB) governing the site.
6.2. Exclusion Criteria
Patients/subjects will be excluded from study enrollmentif they meet any of the following 
criteria at screening and/or enrollment:
6.2.1. For Healthy Subjects and Patients with Psoriasis
[16]are investigativesite personnel directly affiliated with this study and their 
immediate families.  Immediate family is defined as a spouse, biological or 
legalguardian, child,or sibling.
[17]are Lilly employees or are employees of a third-party organization involved 
with thestudy.
[18]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 studyor have received any non-biologic IP within 30 days or 5 half-lives 
(whichever is longer) of their initial screening visit.
CCI
[19]have previously completed a clinical trial investigating 
 (IL-23 
antibody) or 
(CGRP antibody) and have previously received 
either of these IPs.
CCI


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[20] a marked baseline prolongation of QT/corrected QT interval (QTc) (for 
example, repeated demonstration of a QTcB interval >470 ms);
A history of additional risk factors for Torsades de Pointes (for example, heart failure, 
persistent hypokalemia, family history of long QT syndrome); 
The use of concomitant medications that prolong the QT/QTc interval.
[21] have known or ongoing neuropsychiatric disorders.
[22] for Parts B and C only, patients who have answered ‘yes’ to either Question 4 
(Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) or 
Question 5 (Active Suicidal Ideation with Specific Plan and Intent) on the 
“Suicidal Ideation” portion of the Columbia-Suicide Severity Rating Scale
(C–SSRS), or answer “yes” to any of the suicide-related behaviors (actual 
attempt, interrupted attempt, aborted attempt, reparatory act or behavior) on 
the “Suicidal Behavior” portion of the C–SSRS; and the ideation or behavior 
occurred within the past month.
NOTE:  a patient does not necessarily have to be excluded if they have 
self-injurious behavior that would be classified as non-suicidal self-injurious 
behavior.  Of course, if this situation arises, it is likely the subject should be 
referred to a psychiatrist or appropriately trained professional.
[23] have evidence of clinically significant active infection, fever of 100.5°F 
(38°C) or above, at screening or baseline (Day 1).
[24] had any surgical procedure (except for minor surgery requiring local or no 
anesthesia and without any complications or sequelae) within 12 weeks prior 
to screening, or any planned surgical procedure scheduled to occur during the 
study.
[25] have received live vaccine(s) (including attenuated live vaccines) within 
28 days of screening or intend to receive during the study (non-live or 
inactivated vaccinations are allowed).
[26] have a history of multiple or severe allergies or has had an anaphylactic 
reaction to prescription or non-prescription drugs or food.
[27] have a history of allergy to mAbs or to the drug excipients, or have clinically 
significant multiple or severe drug allergies, intolerance to topical 
corticosteroids, or a history of severe post-treatment hypersensitivity reactions 
(including, but not limited to, erythema multiforme major, linear 
immunoglobulin A [IgA] dermatosis, toxic epidermal necrolysis, or 
exfoliative dermatitis).
[28] have had serious, opportunistic, or chronic/recurring infection within 6 
months prior to screening.  Examples include but are not limited to infections 
requiring IV antibiotics, hospitalization, or prolonged anti-infective treatment.


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[29] had any malignancy within the past 5 years except for basal cell or squamous 
epithelial carcinomas of the skin that have been resected with no subsequent 
evidence of recurrence for at least 3 years prior to screening and cervical 
carcinoma in situ with no evidence of recurrence within the 5 years prior to 
baseline.
[30] current smoker >10 cigarettes or other tobacco products per day.  Are 
unable/unwilling to stop smoking tobacco products while in the study unit.
Heavy smokers (as per judgment of the investigator) should be excluded from 
the study.  
[31] are regular users of known drugs of abuse and/or have positive findings on 
urinary drug tests at screening; OR an average weekly alcohol intake that 
exceeds 21 units per week (males) or 14 units per week (females), OR are 
unwilling to stop alcohol consumption during study visits/time in the research 
unit (1 unit of alcohol = 12 oz or 360 mL of beer; 5 oz or 150 mL of wine; 
1.5 oz or 45 mL of distilled spirits).
[32] have donated blood of more than 500 mL within the previous 30 days of study 
screening.
[33] show evidence of active or latent tuberculosis (TB), as documented through
medical history and examination, chest x-rays (posterior, anterior, and lateral)
for patients with psoriasis only (Part C), and TB testing: either a positive 
tuberculin skin test (TST; defined as a skin induration >5 mm at 48 to 
72 hours, regardless of Bacillus Calmette–Guérin or other vaccination history) 
or a positive (not indeterminate) QuantiFERON®-TB Gold test.  The choice to 
perform a TST or a QuantiFERON-TB Gold test will be made by the 
investigator according to local licensing and standard of care.  The 
QuantiFERON-TB Gold test can only be used in countries where it is 
licensed, and the use of this test is dependent on previous treatment(s).  This 
test may not be suitable if previous treatment(s) produce significant 
immunosuppression.
[34] have known hypogammaglobulinemia or a screening serum IgG <565 mg/dL, 
IgM <40 mg/dL, or IgA <70 mg/dL.
[35] are immunocompromised.
[36] have presence of significant uncontrolled cerebro-cardiovascular (for 
example, myocardial infarction, unstable angina, hypertension, moderate to 
severe [New York Heart Association Class III/IV] heart failure, or 
cerebrovascular accident), respiratory, hepatic, renal, gastrointestinal, 
endocrine, hematologic, neurologic or neuropsychiatric disorders or abnormal 
laboratory values at screening that, in the opinion of the investigator, pose an 
unacceptable risk to the subject if participating in the study or of interfering 
with the interpretation of data.
[37] in the opinion of the investigator or sponsor, are unsuitable for inclusion in the 
study.


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6.2.2. For Healthy Subjects Only
[38] intend to use herbal, over-the-counter, or prescription medication within 
14 days prior to dosing and during the study, other than estrogen/progesterone 
as a form of hormone replacement therapy.  Subjects taking these medications 
should be on stable doses for at least 28 days prior to screening.  Certain 
medications, for example vitamin supplements and local anesthetics, may be 
permitted at the discretion of the investigator.
[39] have received Ig-based biologic therapies (such as mAbs, including marketed 
or investigational biologic therapy) within the past 6 months, or at any time
received the compounds specified in criterion #19.
[40] have an abnormal blood pressure, pulse rate, and/or temperature as determined 
to be clinically significant by the investigator.
[41] have evidence of chronic viral infection:
[41a]
show evidence of hepatitis C and/or positive hepatitis C antibody with 
confirmed presence of hepatitis C virus (HCV) ribonucleic acid (RNA) at 
screening.
[41b]
show evidence of hepatitis B and/or positive hepatitis B surface antigen or 
are positive for hepatitis B core antibody (HBcAb) and negative for 
hepatitis B surface antibody (HBsAb) at screening.
[41c]
show evidence of human immunodeficiency virus (HIV) infection and/or 
positive for HIV antibodies at screening.
[41d]
have had symptomatic herpes zoster within 3 months (for patients in 
Part C) or 6 months (for healthy subjects in Parts A and B) prior to 
screening that constitutes (per investigator’s judgment) a risk to the 
subject when taking the study medication or that may interfere with the 
interpretation of study data.
[42] are not willing to receive multiple subcutaneous injections.
6.2.3. For Patients with Psoriasis Only
[43] have any other skin conditions (excluding chronic psoriasis vulgaris) that 
would affect interpretation of the results (including, but not limited to, 
scleroderma, eczema, drug-induced psoriasis, guttate psoriasis, pustular 
psoriasis, parapsoriasis, or cutaneous manifestations of other autoimmune 
diseases such as systemic lupus erythematosus).


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CCI
[44]have received systemic nonbiologic psoriasis therapy(including, but not 
limited to, oral psoralen plus ultraviolet A light therapy [PUVA]; 
cyclosporine; corticosteroids; methotrexate; oral retinoids; apremilast; 
tofacitinib; mycophenolate mofetil; thioguanine; hydroxyurea; sirolimus; 
tacrolimus; azathioprine; fumaric acid derivatives; or 1,25 dihydroxy vitamin 
D3 and analogs) or phototherapy (including either oral and topical PUVA, 
ultraviolet B,excimer laser,or self-treatment with tanning beds or therapeutic 
sunbathing)within 28 days prior to baseline.
[45]have received topical psoriasis treatment (including, but not limited to, 
corticosteroids[upper mid strength or lower potency topical steroids are 
permitted on the intertriginous areas and face], anthralin, calcipotriene, topical 
vitamin D derivatives, retinoids, tazarotene, pimecrolimus, tacrolimus, 
emollients,and other non-prescription topical products containing urea, >3% 
salicylic acid, alpha-or beta-hydroxyl acids, or medicated shampoos [for 
example,those that contain >3% salicylic acid, corticosteroids, coal tar, or 
vitamin D3 analogs])within 14 days prior to baseline.
[46]have received anti-TNF biologics and anti-IL-17 targeting biologics within 
8weeks prior to baseline.
[47]have previous exposure to any biologic therapy targeting IL-23 (including 
ustekinumab
)or CGRP(
), either 
licensed or investigational (previous briakinumab use is permitted)(see 
Exclusion #19).
[48]suffer chronic medical condition that are considered ‘unstable’ by the 
investigator. Subjects with well-controlled chronic conditions such as 
hypertension or hyperlipidemia may be permitted to participate, providedthe 
treatment regimen has been stable for at least 28 days prior to screening and 
both the investigator and the Lilly clinical pharmacologistagree that the 
subject may participate in the study.
[49]have evidence of chronic viral infection:
[49a] show evidence of hepatitis C and/or positive hepatitis C antibodywith 
confirmed presence of HCVRNA at screening.
Patients with a previous diagnosis of hepatitis Cwho have been treated 
with antiviral therapy and achieved a sustained virological responsemay 
be eligible for inclusion in the study, providedthey have no detectable 
HCV RNA on the screening test for this protocol. A sustained virological 
response is defined as an undetectable HCV RNA 12 weeks after 
completion of a full, documented course of an approved antiviral therapy 
for HCV.
Patients who have spontaneously cleared HCV infection, defined as: 
(i)a positive HCV antibody test and 
CCI


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(ii) a negative HCV RNA test, with no history of anti-HCV treatment, 
may be eligible for inclusion in the study, provided they have no 
detectable HCV RNA on screening for this study. 
Based on the judgment of the investigator, any patient exhibiting 
behaviors that would put them at risk for re-infection with HCV may be 
discontinued from the study.
Any patient with a history of HCV infection who develops elevated ALT 
>3× ULN during the study will be tested for HCV RNA in addition to a 
full liver evaluation as described in Section 9.4.4.1.
Anyone diagnosed with hepatitis C during the study will be discontinued 
from the study and should receive appropriate follow-up medical care.
[49b]
show evidence of hepatitis B and/or positive hepatitis B surface antigen or 
are positive for HBcAb and negative for HBsAb at screening.
[49c]
show evidence of HIV infection and/or positive for HIV antibodies at 
screening.
[49d]
have had symptomatic herpes zoster within 3 months (for patients in 
Part C) or 6 months (for healthy subjects in Parts A and B) prior to 
screening that constitutes (per investigator’s judgment) a risk to the 
subject when taking the study medication or that may interfere with the 
interpretation of study data.
[50] are unable or unwilling to avoid excessive sun exposure or use of tanning 
booths for at least 4 weeks prior to baseline and during the study.
6.3.
Lifestyle and/or Dietary Requirements
Throughout the study, patients/subjects may undergo medical assessments and review of 
compliance with requirements before continuing in the study.
6.3.1. Meals and Dietary Restrictions
Subjects should not eat after midnight during the night before study drug administration. Water 
is permitted. Subjects may eat breakfast approximately 2 hours postdose. A normal diet may be 
consumed at all other times during the study.
6.3.2. Caffeine, Alcohol, and Tobacco
6.3.2.1.
Caffeine
Subjects and patients should not consume caffeine from the start of each dosing day to 12 hours 
postdose.  Consumption of non-caffeinated beverages is permitted at any time during the study.
6.3.2.2.
Alcohol
Subjects should not consume alcohol for at least 24 hours prior to dosing.  During outpatient 
periods, all subjects should be advised to limit alcohol consumption to no more than 2 units per 
day.


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6.3.2.3.
Smoking
Subjects should be willing and able to abide by smoking restrictions at the study sites during 
both the in-house period and outpatient visits.
6.3.3. Activity
Subjects should avoid strenuous exercise and/or activity for at least 48 hours prior to dosing and
scheduled visits.
6.3.4. Contraception
Women of childbearing potential (WOCBP) are excluded from Parts A and B of the study.  For 
Part C, WOCBP 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. Otherwise, WOCBP must use 2 effective methods of contraception for the entirety of the 
study. Abstinence or contraception must continue following completion of study drug
administration for 5 half-lives or until plasma concentrations are equal to or below the 
pharmacologic effect level, whichever is longer.

The WOCBP must test negative for pregnancy prior to initiation of treatment as indicated 
by a negative urine pregnancy test at the screening visit followed by a negative serum 
pregnancy test within 24 hours prior to exposure to LY3316531 or placebo.

Two 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 (that is, condom with spermicide, 
diaphragm with spermicide, female condom with 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.
o
Of note, 1 of the 2 methods of contraception may be a highly effective (less than 
1% failure rate) method of contraception (such as combination oral 
contraceptives, implanted contraceptives, or intrauterine devices).
Women not of childbearing potential may participate and include those who are

infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal 
ligation), congenital anomaly such as mullerian agenesis; or

postmenopausal – defined as either
o
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


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
at least 6 months of spontaneous amenorrhea with a follicle-stimulating 
hormone >40 mIU/mL; or
o
A woman 55 years of age or older not on hormone therapy, who has had at least 
6 months of spontaneous amenorrhea; or
o
A woman at least 55 years of age with a diagnosis of menopause prior to starting 
hormone replacement therapy.
Men, regardless of their fertility status, with non-pregnant WOCBP partners must agree to either 
remain abstinent (if this is their preferred and usual lifestyle) or use condoms as well as 1 
additional highly effective (less than 1% failure rate) method of contraception (such as
combination oral contraceptives, implanted contraceptives, or intrauterine devices) or effective
method of contraception (such as diaphragms with spermicide or cervical sponges) for the
duration of the study and until their plasma concentrations are below the level that could result
in a relevant potential exposure to a possible fetus, predicted to be 5 months following the last 
dose of study drug.

Men and their partners may choose to use a double–barrier method of contraception.
(Barrier protection methods without concomitant use of a spermicide are not an effective 
or acceptable method of contraception. Thus, each barrier method must include use of a
spermicide. It should be noted, however, that the use of male and female condoms as a 
double-barrier method is not considered acceptable due to the high failure rate when these
barrier methods are combined).

Men with pregnant partners should use condoms during intercourse for the duration of the 
study and until the end of estimated relevant potential exposure in WOCBP (5 months 
following the last dose of study drug).

Men should refrain from sperm donation for the duration of the study and until their 
plasma concentrations are below the level that could result in a relevant potential 
exposure to a possible fetus, predicted to be 5 months following the last dose of study
drug.

Men who are in exclusively same sex relationships (as their preferred and usual lifestyle) 
are not required to use contraception.
6.4.
Screen Failures
Healthy subjects who do not meet the criteria for participation in this study (screen failure) may 
not be re-screened; however, re-assessment of laboratory parameters will be allowed once if 
handling issues, damaged samples, or hemolyzed samples may have confounded the 
measurement results.
Any patient with psoriasis who has a screening laboratory assessment that falls outside of the 
protocol-specified inclusion/exclusion parameters may (based on investigator judgment) undergo 
repeat laboratory testing 1 time without being considered a screen failure (this does not include 
TB testing).


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In addition, participants who were eligible for inclusion in previous cohorts, but were not 
randomized for nonmedical reasons, may be reassessed, following a discussion with the sponsor.
If rescreening is performed, the individual must sign a new informed consent form (ICF) each
time and will be assigned a new identification number.


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7.Treatment
7.1. Treatment Administered
The drug product LY3316531 is supplied for clinical trial use as solution formulation in glass 
vials.  Further dilution may be needed for SCand IV administration.  See Pharmacy Instructions 
for more information.
Placebo will be sterile saline (0.9% NaCl).  Placebo doses should be held in the pharmacy for an 
equivalent amount of time as is required to prepare doses of LY3316531.
The IPor placebo will be administered as SC injection(s)or a slow IV infusion over at least 
30minutes. Sites must have resuscitation equipment, emergency drugs, and appropriately 
trained staff available during the infusion and for at least 6hours after subjects have completed 
receiving their infusion.
Injection site selected for SC administration should be the abdominal region approximately5cm 
from the umbilicus and the treatment is administered throughthe needleapplied at 
approximately45°with pinching of the skin.Because subjects may receive multiple injections
per dose, each injection should be administered in a different abdominal quadrant (right upper 
quadrant, left upper quadrant, right lower quadrant, or left lower quadrant) and the quadrant used 
should be recorded at the time of the injection.  Subcutaneous administration of LY3316531 
should bedone by a limited number of individuals for consistency. The same type of syringe 
and needle(
) should be used for all subjects to ensure all injections are 
deliveredto a consistent depth target into the SC space.
All clinical trial materialsprovided to the investigator will be stored in a secure place, assigned 
using the interactive web response system,anddispensed by appropriately trained persons.The
dispensing of theIPs will be fully documented. Detailed records of the amounts of theIP
received, dispensed, and remaining at the end of the study will bemaintained.
The investigator or designee is responsiblefor
explaining the correct use of the IP(s) to the site personnel
verifying that instructions are followed properly
maintaining accurate records of IPdispensing and collection, and
returning all unused medicationsto Lilly or its designee at the end of the study.
Note:In some cases, sites may destroy the material if, during the investigativesite selection, the 
evaluator has verified and documented that the site has appropriate facilities and written 
procedures to dispose of clinical materials.
7.1.1. Packaging and Labeling
CCI
LY3316531 will be supplied to the investigative sites by Lilly.  Clinical trial materials will be 
labeled according to the country’s regulatory requirements.  All IPs will be stored, inventoried, 


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reconciled, and destroyed according to applicable regulations.  Clinical trial materials are 
manufactured in accordance with current good manufacturing practices.
LY3316531 is supplied for clinical trial use as solution in vial with study-specific labels.  The 
2-mL vial is manufactured to contain 150 mg of LY3316531 (75 mg/mL).  Vials will be supplied 
in cartons, with the appropriate quantity specific to the planned dispensing schedule of the IP. 
Placebo for all cohorts is 0.9% sodium chloride (sterile saline).
When prepared for dosing according to instructions, it will not be possible to distinguish between 
LY3316531 and placebo.
Detailed instructions for the preparation and handling of LY3316531 will be provided by the 
sponsor.
The IP must be prepared by an unblinded pharmacist who is not involved in any other 
study-related procedures.
7.2.
Method of Treatment Assignment
Randomization tables for allocation of LY3316531 or placebo will be prepared by the statistician or 
designee for the study and provided to the site pharmacists involved in dose preparation.  
The allocation and dispensation of the IP will be fully documented and verified by a second person.  
Detailed records of the amounts of the IP received, dispensed, and remained at the end of the study 
will be maintained by the site pharmacy.
7.2.1. Selection and Timing of Doses
The doses will be administered at approximately the same times on each day.  The actual time of 
all dose administrations will be recorded in the patient’s/subject’s electronic case report form 
(eCRF).
7.3.
Blinding
Parts A and B of Study FFAA are subject- and investigator-blind except for the non-sentinel 
subjects and the open-label SC administration cohort in Part A (Cohort 5).  Part C of Study FFAA is 
open-label.  As a result, all patients with psoriasis who enter the study will receive LY3316531.
Pharmacy staff who prepare and dispense study medication are required to be unblinded to 
treatment allocation.
Subject treatment assignments and drug accountability records will be held in a secure location 
accessible only by individuals involved with study drug preparation or dispensation.
Blinding will be maintained throughout the conduct of the study as described in the separate 
Blinding Plan.
If a subject’s study treatment assignment is unblinded, the subject must be discontinued from the 
study, unless the investigator obtains specific approval from a Lilly clinical pharmacologist or 
clinical research physician (CRP) for the study participant to continue in the study.


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In case of an emergency, the investigator has the sole responsibility for determining if unblinding 
of a subject’streatment assignment is warranted for medical management of the event. The 
subject’ssafety must always be the first consideration in making such a determination.  At the 
discretion of the investigator, if a subject’s treatment assignment is unblinded, as judged by the 
investigator,Lilly must be notifiedimmediately.It is the responsibility of the investigator to 
document the decision and rationale,promptly.
7.4. Dose Modification
7.4.1. Dose Decision (Part C)
The decision to initiate the first patient cohort in Part C will be based on the trial-level safety 
review for Cohort 3; however,any available preliminary PK data from Cohorts 1, 2, and 3 
(through Day 29) in Part Awill be considered as well.  Progression to the optional cohorts in 
Part C will occur when at least 4 weeks of clinical activity data (PASI scores) are available from 
at least 7 patients in the preceding cohort.  In addition to the PASI scores, any available PK and 
applicable safety data from Part A will be considered for determining the dose for the optional 
patient cohorts.  Dosing at the current level and further dose escalation will be discontinuedif 
any of the scenariosdescribed in Section 7.4.2occur.
 
 
 
 
7.4.2. Dose Escalation(Parts A and B)
By nature of being a dose-escalation study, data will be evaluated on an ongoing basis.The 
highest dose level that is tolerated will be designated as the MTD.
Safety datawill be the primary criteria for the dose escalation.  In addition, if available at the 
time of dose-escalation decision, PKresults (C
max
CCI
and AUC)will be used as supporting data for 
dose escalation, but such data are requiredonly for Cohort 1 in Part B.  No dose decision can 
occur without prior discussion and agreement between the investigator and theLilly clinical 
pharmacologist or CRP.
Prior todoseescalation, a safety review meeting will be undertaken by the sponsor (unblinded) 
andtheinvestigator (blinded) to evaluate thesafetydata and agree on the appropriate dose for 
the next cohort.  Emerging PK data (if available) may inform dose selection for the higher dose 
levels, based on planned PK preliminary analyses after SAD Cohort 3 (Part A).  If considered 
appropriate, previous dose levels may be repeated, or lower/intermediate dose levels may be 


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tested.  The magnitude of the dose escalation may be reduced after data review, but subsequent 
escalations cannot be increased by more than approximately 3-fold (a half-log increment).
For Cohorts 1 and 2 in Part A, the decision to escalate to the next cohort will occur when at least 
15 days have elapsed after all subjects in the preceding cohorts have been dosed.  In Cohorts 3, 
4, 6, and 7, the decision to dose the next cohort will occur when all subjects in the preceding 
cohorts have been dosed and data for a minimum of 15 days are available from at least 7 subjects 
in the preceding cohort.  If at the time of the trial level safety review for Cohort 4, data are also 
available from Cohort 5, all available data from Cohorts 4 and 5 will be considered in the review 
to dose the next cohort.
The decision to initiate the first multiple-dose cohort in Part B will occur when at least 15 days 
have elapsed after all subjects in the last cohort in Part A have been dosed (Cohort 7 unless 
safety concerns prevent escalation to this cohort).  The trial-level safety review for all previous 
cohorts and the preliminary analyses of PK data (planned to occur after the completion of Day 29 
for Cohort 3) will be considered in the decision to initiate Part B of the study.  Progression to the 
optional cohort in Part B will occur when all subjects have received the second dose of study 
drug and data for a minimum of 15 days (after the second dose) are available from at least 7 
subjects in Cohort 1 of Part B.
Throughout Part A and Part B, safety data up to and including Day 15 are required for 
dose-escalation decisions.  If any subjects withdraw before the Day 15 assessment, all available 
safety data for those subjects will be evaluated.
Safety data, in particular AEs, SAEs, and adverse laboratory abnormalities, will be 
independently assessed by the investigator, and will be considered related to the IP unless there 
is clear evidence that the event is not related.
After review of these data, an agreement on the appropriate dose will be made by the investigator 
and sponsor for the next cohort/dose level.  The magnitude of dose escalations may be reduced 
following data review, but subsequent escalations cannot be increased by more than 
approximately 3-fold (a half-log increment).
If any of the following scenarios occur, dosing at the current level and further dose escalation 
will be discontinued:
A single patient/subject experiences an SAE or clinically significant event that is 
related to LY3316531 administration
OR
Two or more patients/subjects develop AEs within 14 days of dosing that are considered 
to be related to study treatment and graded as at least moderate, clinically significant, and 
not responsive to supportive care
OR
One or more patients/subjects develop AEs within 14 days of dosing that are considered 
to be related to study treatment and graded as severe


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OR
Two or more subjects develop AEs that are graded as severe, unless there is an obvious 
explanation other than IP or study procedures for the event(s)
OR
After the introduction of premedication in accordance with the protocol, 2 or more 
patients/subjects develop (according to Common Terminology Criteria for Adverse 
Events) Grade 2 acute AEs related to the infusion, during or within 2 hours of 
completing the infusion that do not resolve with a reduced infusion rate and/or supportive 
care.
7.4.3. Special Treatment Considerations
Premedication for the infusions is not planned.  However, if an infusion reaction occurs, 
appropriate medication may be used as determined by the study investigator(s).  If infusion 
reactions are observed, but review of the data suggests that dose escalation may continue, 
acetaminophen 500 to 1000 mg and/or an antihistamine may be administered orally 30 to 
60 minutes prior to the start of infusion for subsequent patients/subjects.
The decision to implement premedication for infusions in subsequent cohorts will be made by 
the investigator and sponsor and recorded in the study documentation, along with the 
dose-escalation decision.
Any premedications given will be documented as a concomitant therapy (see Section 7.7).
7.4.3.1. Management of Infusion Reactions
There is a risk of infusion reaction with any biological agent; therefore, all patients/subjects
should be monitored closely.  Symptoms and signs that may occur as part of an infusion reaction 
include, but are not limited to fever, chills, nausea, headache, bronchospasm, hypotension, 
angioedema, throat irritation, rash, pruritus, myalgia, and dizziness.  In the event that a 
significant infusion reaction occurs, the following guidance should be followed:

The IP infusion should be slowed (for example, reduce infusion rate by 50% [for 
example, an infusion rate of 12 mL/h becomes 6 mL/h or slower]) or stopped, depending 
on the symptoms/signs present:
o
if slowed, the infusion should be completed at the slower rate, as tolerated
o
if determined by the investigator that the infusion should no longer continue, no 
further attempts to dose the patient/subject should be made

Supportive care should be employed in accordance with the symptoms/signs

If a patient/subject’s infusion reaction is sufficiently severe to discontinue the infusion, 
subsequent infusions may be administered with premedication at the discretion of the 
investigator following agreement with the Lilly CRP or clinical pharmacologist


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If a patient/subject’s infusion rate is reduced due to an infusion reaction, subsequent 
infusions may be administered at the discretion of the investigatorfollowing agreement 
with the Lilly CRP or clinical pharmacologist.  If further infusionsare administered, the 
infusion rate must not exceed the slowest rate used to complete the infusion whenthe 
infusion reaction occurred.  Premedication may be administered at the discretion of the 
investigator
If it is determined that the patient/subjectshould not receive further doses of IP, the 
patient/subjectshould complete AEand other follow-up procedures per Section 2of this 
protocol.
7.5. Preparation/Handling/Storage/Accountability
All clinical trial materialsprovided to the investigator will be stored in a secure place and 
allocated and dispensed by appropriately trained personnel.  The allocation and dispensationof 
the IPwill be fully documented and verified by a second person.  Detailed records of the 
amounts of theIPreceived, dispensed, and remainingat the end of the study will be maintained.
The investigator or designeemust confirm appropriate temperature conditions have been 
maintained, as communicated by the sponsor,during transit for all IPsreceived and any 
discrepancies are reported and resolved beforeuse of the study treatment.
Only participants enrolled in the study may receive IPsor study materials, and only authorized 
site staff may supply or administer IP.All IPs shouldbe stored in anenvironmentally controlled 
and monitored (manual or automated) area in accordance with the labeledstorage 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).
Investigational products will be supplied by Lilly or its representative, in accordance with current 
good manufacturing practices and will be supplied with lot numbers, expiry dates, and 
certificates of analysis, as applicable.
7.6. Treatment Compliance
CCI
The IPwill be administered at the clinical site, and documentation of treatment administration 
will occur at the site.


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7.7.
Concomitant Therapy
In general, concomitant medication should be avoided. Use of chronic, stable doses of 
Thyroxine or hormone replacement therapy (estrogens/progesterones) is allowed in both healthy 
subjects and patients with psoriasis.
Acetaminophen (1 g, maximum 2 g/24 hours) may be administered at the discretion of the 
investigator for treatment of headache, etc.  If the need for concomitant medication (other than
acetaminophen) arises, inclusion or continuation of the patient/subject may be at the discretion of 
the investigator after consultation with a Lilly clinical pharmacologist or CRP.  Any medication 
used during the course of the study must be documented.
Uses of nonlive (inactivated) vaccinations are allowed for all subjects.  Use of live, attenuated 
vaccines is prohibited.
Patients in Part C who are on stable concomitant medication at the time of study entry should 
continue their regular, unchanged dose throughout the study and the extended follow-up period 
(up to Week 52).  Concomitant therapies for treatment of psoriasis during the study are permitted 
only as outlined in Table FFAA.7.1.
Table FFAA.7.1.
Permitted Medications for Treatment of Psoriasis
Drug Class
As Needed Chronic Use
Conditions for Use
Topical steroids
Yes
Yes
Topical steroids Class 6 [mild] or 7 [least potent] will be permitted 
for use limited to the face, axilla, and/or genitalia, as needed. These 
topical medications should not be used within approximately
24 hours prior to study visits.
Topical medications 
for psoriasis
Noa
No
a
Exceptions:  topical steroids will be permitted for use limited to the face, axilla, and/or genitalia.
Topical moisturizers/emollients may be used on nontarget lesions (that is, plaque psoriasis 
lesions that have not been or will not be biopsied) following the Day 1 visit. 
7.8.
Treatment after the End of the Study
Not Applicable.


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8. Discontinuation Criteria
Patients/subjects discontinuing from the study prematurely for any reason must complete AE and 
follow-up procedures per Section 2 of this protocol.
8.1.
Discontinuation from Study Treatment
Discontinuation of the IP for abnormal liver tests should be considered by the investigator when 
a patient/subject meets 1 of the following conditions after consultation with the Lilly-designated 
medical monitor:

ALT or AST >5× ULN for healthy subjects, 8× ULN for patients

ALT or AST >3× ULN for healthy subjects, 5× ULN for patients sustained for more than 
2 weeks or

ALT or AST >3× ULN and TBL >2× ULN or international normalized ratio >1.5 or

ALT or AST >3× ULN with the appearance of fatigue, nausea, vomiting, right 
upper-quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%)

ALP >3× ULN

ALP >2.5× ULN and TBL >2× ULN

ALP >2.5× ULN with the appearance of fatigue, nausea, vomiting, right-quadrant pain or 
tenderness, fever, rash, and/or eosinophilia (>5%).
8.1.1. Discontinuation of Inadvertently Enrolled Patients/Subjects
If the sponsor or investigator identifies a patient who did not meet enrollment criteria and was 
inadvertently enrolled, a discussion must occur between the Lilly clinical pharmacologist or CRP
and the investigator to determine if the patient may continue in the study.  If both agree it is 
medically appropriate to continue, the investigator must obtain documented approval from the 
Lilly clinical pharmacologist or CRP to allow the inadvertently enrolled patient to continue in the 
study with or without continued treatment with IP.
8.2.
Discontinuation from the Study
Patients/subjects will be discontinued under 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 (GCP)

Investigator Decision
o
the investigator decides that the patient/subject should be discontinued from the 
study


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o
if the patient/subject, for any reason, requires treatment with another therapeutic 
agent that has been demonstrated to be effective for treatment of the study 
indication, discontinuation from the study occurs prior to introduction of the new 
agent

Subject Decision
o
the patient/subject, or legal representative, requests to be withdrawn from the 
study.

Sponsor Decision
o
Lilly stops the study or stops the subject’s participation in the study for medical, 
safety, regulatory, or other reasons consistent with applicable laws, regulations, 
and GCP

Suicidal Ideation and/or Behavior
o
When a subject discontinues from a study due to suicidal ideation and/or 
behavior, the same follow-up procedures can be used as would be done for 
discontinuation due to any other AEs leading to discontinuation.  It is not 
necessary to collect additional information (except what is already requested on 
the C-SSRS, the Self-Harm Supplement Form, and the Self-Harm Follow-up 
Form).  
o
Investigators are responsible for monitoring the safety of patients/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 patient/subject.
o
The investigator is responsible for the appropriate medical care of 
patients/subjects during the study.
o
The investigator remains responsible for following, through an appropriate health 
care option, AEs that are serious or that caused the patient/subject to discontinue 
before completing the study.  The patient/subject should be followed up until the 
event is resolved or explained.  Frequency of follow-up evaluation is left to the 
discretion of the investigator

Adverse event 
o
if a clinically significant event (CSE) occurs, the IP has to be discontinued and 
appropriate measures taken.  Lilly or its designee should be alerted immediately.  
A CSE will be defined as a moderate to severe AE, abnormal clinical sign, or 
clinical laboratory finding that may pose a risk to the wellbeing of the subject.  
Refer to Safety Section (Section 9.4).
o
A clinically significant systemic hypersensitivity reaction occurs following 
administration of the IP (for example, drug-related symptomatic bronchospasm, 


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allergy-related edema/angioedema, or hypotension) that requires parenteral 
medication, does not respond to symptomatic medication, or results in clinical 
sequelae or an anaphylactic reaction.
Following the investigator’s determination that CSE criteria have been met and the investigator’s 
judgment of relatedness to the IP is documented, a decision will be made between the 
investigator and Lilly or its designee regarding subject discontinuation.
The nature of any conditions, clinical signs or symptoms, or abnormal laboratory values present 
at the time of discontinuation and any applicable follow-up procedures will be documented.  
Refer to the Schedule of Activities (Section 2) for data to be collected at the time of 
discontinuation and follow-up.
8.3.
Patients/Subjects Lost to Follow-up
A patient/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 patients/subjects who fail to return for a scheduled visit or were 
otherwise unable to be followed up by the site.


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9. Study Assessments and Procedures
Section 2 lists the Schedule of Activities, detailing the study procedures and their timing 
(including tolerance limits for timing).
Appendix 2 lists the laboratory tests that will be performed for this study.
Appendix 5 provides a summary of the maximum number and volume of invasive samples, for
all sampling, during the study.
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 patients/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 patient/subject.
The investigator is responsible for the appropriate medical care of patients/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 patient/subject to discontinue the IP before completing the study.  The 
patient/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 ICF is signed, study site personnel will record, via electronic data entry/designated data 
transmission methods, the occurrence and nature of each patient/subject’s preexisting conditions, 
including clinically significant signs and symptoms of the disease under treatment in the study.  
Additionally, site personnel will record any change in the condition(s) and the occurrence and 
nature of any AEs.
The investigator will interpret and document whether or not an AE has a reasonable possibility 
of being related to study treatment, or a study procedure, taking into account the disease, 
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.


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Planned surgeries and nonsurgical interventions should not be reported as AEs unless the 
underlying medical condition has worsened during the course of the study.
If a patient’s/subject’s IP is discontinued as a result of an AE, study site personnel must report 
this to Lilly or its designee via electronic data entry/designated data transmission methods.
9.2.1. Serious Adverse Events
An SAE is any AE from this study that results in 1 of the following:

death

initial or prolonged inpatient hospitalization

a life-threatening experience (that is, immediate risk of dying)

persistent or significant disability/incapacity

congenital anomaly/birth defect

important medical events that may not be immediately life-threatening or result in death 
or hospitalization but may jeopardize the patient or may require intervention to prevent 1
of the other outcomes listed in the definition above

when a condition related to the injection syringe or IV 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/clinical pharmacologist, or its designee, of any 
SAE as soon as practically possible.
Additionally, study site personnel must alert Lilly Global Patient Safety, or its designee, of any 
SAE within 24 hours of investigator awareness of the event via a sponsor-approved method.  If 
alerts are issued via telephone, they are to be immediately followed with official notification on 
study-specific SAE forms.  This 24-hour notification requirement refers to the initial SAE 
information and all follow-up SAE information.
Although all AEs are recorded in the electronic data entry/designated data transmission methods
after signing informed consent, SAE reporting to the sponsor begins after the patient/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 patient/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.


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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.
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.
9.2.2. Complaint Handling
Lilly collects product complaints 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.
Patients/subjects should be instructed to contact the investigator as soon as possible if he or she 
has a complaint or problem with the IP so that the situation can be assessed.
9.3.
Treatment of Overdose
For the purposes of this study, an overdose of LY3316531 is considered any dose higher than the 
dose assigned through randomization.  There is no specific antidote to LY3316531 and in the 
case of overdose, subjects should be observed and treated with the appropriate supportive care.
Refer to the IB for LY3316531.
9.4.
Safety
9.4.1. Laboratory Tests
For each patient/subject, 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 central 
vendor, if a central vendor is used for the study.
9.4.2. Vital Signs
For each patient/subject, vital sign measurements should be conducted according to the Schedule 
of Activities (Section 2) and as clinically indicated.  Vital sign measurements may be repeated at 
the discretion of the investigator.
Blood pressure and pulse rate should be measured after at least 5 minutes supine (or semi-
recumbent if subject is unable to lie supine).
If orthostatic measurements are required, patients/subjects should be supine for at least 5 minutes 
and stand for at least 3 minutes.


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If the patient/subject feels unable to stand, supine vital signs only will be recorded. 
Unscheduled orthostatic vital signs should be assessed, if possible, during any AE of dizziness or 
posture-induced symptoms.  Additional vital signs may be measured during each study period if 
warranted.
Body temperature will be measured as specified in the Schedule of Activities (Section 2) and as 
clinically indicated.
Body weight will be recorded as specified in the Schedule of Activities (Section 2) and as 
clinically indicated.
9.4.3. Electrocardiograms
For each subject in Part A, a centralized 12-lead digital ECG will be collected as triplicates 
according to the Schedule of Activities (Section 2), except at screening where a single ECG will 
be collected.
For each patient/subject in Parts B and C, a single ECG will be collected locally and stored at the 
investigator’s site unless the ECG values for subjects in Part A show clinically significant 
changes (for example, increase in PR or QT interval).  In this situation, the ECGs for 
patients/subjects in Parts B and/or C will be collected as in Part A of the study.
Electrocardiograms should be recorded up to 5 minutes before collecting any blood for safety or 
PK tests.  Consecutive triplicate ECGs will be obtained at approximately 1-minute intervals.  
Patients/subjects should be supine for approximately 5 minutes before ECG collection and 
remain supine, but awake, during ECG collection.  Electrocardiograms may be obtained at 
additional times, when deemed clinically necessary.  Collection of additional ECGs at a 
particular time point is allowed to ensure high-quality records.
Electrocardiograms will be interpreted by a qualified physician (the investigator or qualified 
designee) at the site as soon after the time of ECG collection as possible, and ideally while the 
subject is still present, to determine whether the patient/subject meets entry criteria at the 
relevant visit(s) and for immediate patient/subject management should any clinically relevant 
findings be identified.
If a clinically significant quantitative or qualitative change from baseline is identified after 
enrollment, the investigator will assess the patient/subject for symptoms (for example, 
palpitations, near syncope, syncope) to determine whether the patient/subject can continue in the 
study.  The investigator or qualified designee is responsible for determining if any change in 
patient/subject management is needed and must document his/her review of the ECG printed at 
the time of evaluation from at least 1 of the triplicate ECGs from each time point.
Digital ECGs will be electronically transmitted to a central ECG laboratory designated by Lilly.  
The central ECG laboratory will perform a basic quality control check (for example, 
demographics and study details) then store the ECGs in a database.  At a future time, the stored 
ECG data may be overread at the central ECG laboratory for further evaluation of machine-read 
measurements or to meet regulatory requirements.


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The machine-read ECG intervals and heart rate may be used for data analysis and report writing 
purposes unless a cardiologist overread of the ECGs is conducted prior to completion of the final 
study report (in which case the overread data would be used).
9.4.4. Safety Monitoring
The Lilly clinical pharmacologist or CRP/scientist will monitor safety data throughout the course 
of the study.
Lilly will review SAEs within time frames mandated by company procedures.  The Lilly clinical 
pharmacologist or CRPwill periodically review the following data:
trends in safety data
laboratory analytes
adverse eventsincluding monitoring of incidence and nature of any infections, infusion 
reactions,and injection-site reactions.
When appropriate, the Lilly clinical pharmacologist or CRPwill consult with the functionally 
independent Global Patient Safety therapeutic area physician or clinical research scientist.
9.4.4.1. Hepatic Safety
If a study patient/subject experiences elevated ALT ≥3×ULN, ALP ≥2×ULN, or elevated TBL
≥2×ULN, liver tests (Appendix 4) should be repeated within 3 to5 days including ALT, AST, 
ALP, TBL, direct bilirubin, gamma-glutamyl transferase,and creatinine kinaseto confirm the 
abnormality and to determine if it is increasing or decreasing.  If the abnormality persists or 
worsens, clinical and laboratory monitoring should be initiated by the investigator based on 
consultation with the Lilly clinical pharmacologist or CRP.  Monitoring should continue until 
levels normalize and/or are returningto approximate baseline levels. 
Additional safety data should be collected if 1or more of the following conditions occur: 
elevation of serum ALT to ≥5×ULN on 2or more consecutive blood tests
elevation ofserum TBL to ≥2×ULN (except for cases of known Gilbert’s 
syndrome)
elevation of serum ALP to ≥2×ULN on 2or more consecutive blood tests 
patient/subject discontinued from treatment due to a hepatic event or abnormality 
of liver tests

CCI
hepatic event considered to be anSAE.


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9.4.4.3. C-SSRS
The Columbia-SuicideSeverity Rating Scale(C-SSRS)captures the occurrence, severity,and 
frequency of suicidal ideation and/or behaviorduring the assessment period(Posner et al. 2011; 
Columbia University Medical Center [WWW]).  The scale includes suggestedquestions to 
solicit the type of information needed to determine if suicidal ideation and/or behavioroccurred.  
The C-SSRS is administered by an appropriately trained healthcare professional with at least 1 
year of patient care/clinical experience.  Thetool was developed by the National Institute of 
Mental Healthtrial group for the purpose of being a counterpart to the Columbia Classification 
Algorithm of Suicide Assessmentcategorization of suicidal events.  
The nonleading AE collection should occurprior to the collection of the C-SSRS.If a 
suicide-related event is discovered during the C-SSRSbut was not captured during the 
nonleading AE collection, sites should not change the AE form.If an event is serious or leads to 
discontinuation, this is an exception where the SAE and/or AE leading to discontinuation should 
be included on the AE form and the process for reporting SAEs should be followed.
9.5. Pharmacokinetics
At the visits and times specified in the Scheduleof Activities(Section 2
CCI
), venous blood samples 
of approximately 5mL each will be collected to determine the serum concentrations of 
LY3316531.  A maximum of 2samples may be collected at additional time points during the 
study if warranted and agreed upon between both the investigator and sponsor.  Instructions for 
the collection and handling of blood samples will be provided by the sponsor.  The actual date 
and time (24-hour clock time) of each sampling will be recorded.
Drug concentration information thatmayunblind the study will not be reported to investigative 
sites or blinded personnel until the study has been unblinded.


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9.5.1. Bioanalysis
Samples will be analyzed at a laboratory approved by the sponsor and stored at a facility 
designated by the sponsor.
Serum concentrations of LY3316531 will be assayed using validated enzyme-linked
immunosorbent assay methods. Analyses of samples collected from subjects who received 
placebo arenot planned.
Bioanalytical samples collected to measure study drugconcentrations will be retained for a 
maximum of1 year following last subject visit for the study. During this time, samples 
remaining after thebioanalyses may be used for exploratory metabolism studies or exploratory 
analyses such as bioanalytical assay validation or cross-validation exercises.
9.6. Pharmacodynamics
Measurements of total CGRP concentrations will be used to evaluate target engagementin Part 
A of the study. Samples collected in Parts B and Cof the study will be analyzed based on the 
concentrations of total CGRPobserved in Part A.  Samples for CGRP measurements will be 
analyzed in a validated assay at a laboratory approved by the sponsor and stored at a facility 
designated by the sponsor.
The sample(s) will be stored for upto a maximum of 15yearsafter the lastpatient/subjectvisit 
for the study at a facility selected by the sponsor.
9.6.1. Pharmacodynamic Assessments
9.6.1.2. Disease Activity Measures for Patients with Psoriasis
The disease activity measures described below will be collected at the times shown in the 
Scheduleof Activities(Section 2.3).
The PASI scores the severity of disease on a scale from 0 to 72 (where a score of 72 
indicates extreme disease severity) by combining assessments of the extent of body
surface involvement in the head, trunk, arms, and legs together with the severity of 
desquamation, erythema, and plaque induration.
Percent BSA will be evaluated as the percent involvement of psoriasis on each patient’s 
BSA on a continuous scale from 0% (no involvement) to 100% (full involvement), where 
1% corresponds to the size of the patient’s hand (including the palm, fingers, and thumb) 
(National Psoriasis Foundation 2009).

CCI
The sPGA provides the physician’s determination of the patient’s psoriasis lesions 
overall at a given time point.  Overall lesions are graded for induration, erythema, and 


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scaling, and the sum of the 3 scores is divided by 3 to obtain a final sPGA score (range 0 
to 5).  For the analysis of responder rates, the sPGA scores are rounded to the nearest 
whole number, and the patient’s psoriasis is assessed as clear (0), minimal (1), mild (2), 
moderate (3), severe (4), or very severe (5).

In the Patient’s Global Assessment of Disease Severity, patients are asked to rank on a 
0 to 5 numeric rating scale the severity of their psoriasis “today” from 0 (clear; no 
psoriasis) to 5 (severe; worst their psoriasis has ever been).

The Psoriasis Symptom Scale (PSS) is a patient-reported assessment of 8 symptoms:  itch, 
pain, discomfort, stinging, burning, redness, scaling, and cracking.  Respondents are 
asked to answer the questions based on their psoriasis symptoms.  Numeric rating scales 
are used to assess the self-reported overall severity of each of the 8 symptoms 
individually on an 11-point horizontal scale anchored at 0 (no) and 10 (worst imaginable).  
The overall severity for each individual symptom from psoriasis is indicated by selecting 
the number from 0 to 10 that best describes the worst level of each symptom in the 
preceding 24 hours.  The instructions for completion are embedded within the PSS 
questionnaire for subjects to read before responding to the items.  The symptom severity 
scores, ranging from 0 to 10, are the values of the selected numbers indicated by the 
subject on the instrument’s horizontal scale.  Each of the 8 individual items will receive a 
score of 0 to 10 and will be reported as item scores for itch, pain, discomfort, stinging, 
burning, redness, scaling, and cracking.  In addition, a total score ranging from 0 (no 
psoriasis symptoms) to 80 (worst imaginable psoriasis symptoms) will be reported.
9.6.2. Immunogenicity Assessments 
At the visits and times specified in the Schedule of Activities (Section 2), venous blood samples 
will be collected to determine antibody production against the LY3316531.  To interpret the 
results of immunogenicity, a PK sample will be collected at the same time points. All samples 
for immunogenicity should be taken predose when applicable. In the event of drug 
hypersensitivity reactions (immediate or non-immediate), additional samples will be collected as 
close to the onset of the event as possible, at the resolution of the event, and 30 days following 
the event.  Instructions for the collection and handling of blood samples will be provided by the 
sponsor.  The actual date and time (24-hour clock time) of each sampling will be recorded.
Immunogenicity will be assessed by a validated assay designed to detect ADAs in the presence 
of LY3316531 at a laboratory approved by the sponsor.  Antibodies may be further characterized 
and/or evaluated for their ability to neutralize the activity of LY3316531.  Patients/subjects who 
are treatment-emergent (TE) ADA positive at the end of the study or early discontinuation will 
be followed up with samples taken approximately every 3 months, until they return to 2-fold titer 
of baseline or for a maximum of 1 year. Treatment-emergent ADAs are defined in 
Section 10.3.4.
Samples will be retained for a maximum of 15 years after the last patient/subject visit, or for a 
shorter period if local regulations and ERBs allow, at a facility selected by the sponsor.  The 


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duration allows the sponsor to respond to future regulatory requests related to LY3316531.  Any 
samples remaining after 15 years will be destroyed.
9.7. Genetics
A blood sample will be collected for pharmacogenetic analysis as specified in the Schedule of 
Activities(Section 2), where local regulations allow.
Samples willnotbeused toconduct unspecified disease or population genetic research either 
now or in the future.  Samples will be used to investigate variable exposure or response to 
LY3316531and to investigate genetic variants thought to play a role in psoriasis.  Assessment of 
variable response may include evaluation of AEsor differences in efficacy.
CCI
All samples will be coded with the patient/subject number.  These samples and any data 
generated can be linked back to the patient/subject only by the investigativesite personnel.
Samples will be retained for a maximum of 15 years after the last patient visit, or for a shorter 
period iflocal regulationsand/or ERBsimpose shorter time limits, for the study at a facility 
selected byLilly or its designee.This retention period enables use of new technologies, response 
to regulatory questions, and investigation of variable response that may not be observed until 
later in the development of LY3316531or after LY3316531is commercially available.
Molecular technologies are expected to improve during the 15-year storage period and therefore 
cannot be specifically named.  However, existing approaches include whole genome or exome 
sequencing, genome-wide association studies, multiplex assays, and candidate gene studies.  
Regardless of technology utilized, data generated will be used only for the specific research 
scope described in this section.


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9.9. Health Economics
CCI
Thissection is not applicable for this study.


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10.
Statistical Considerations and Data Analysis
10.1. Sample Size Determination
The sample size for each cohort is customary for the first-in-human study in which formal power 
analyses is not necessary to address the objectives associated with safety, tolerability, PK, and/or 
PD assessments. Approximately 86 patients/subjects are planned for enrollment; however, up to 
102 subjects may be enrolled to allow for replacement of subjects and any additional dose 
cohorts (Parts A, B, and C).
Subjects/patients who withdraw from the study before completing the Day 57 (Part A) or Day 85 
(Parts B and C) assessment may be replaced if necessary to have the planned number of 
subjects/patients complete a dose cohort.  A replacement subject/patient will be assigned the 
same treatment as the subject/patient he or she replaces (Parts A, B, and C).
10.2. Populations for Analyses
10.2.1. Study Participant Disposition
A detailed description of patient/subject disposition will be provided at the end of the study.
All subjects who discontinue from the study will be identified, and the extent of their 
participation in the study will be reported.  If known, a reason for their discontinuation will be 
given.  A disposition table for all enrolled subjects will be provided.
10.2.2. Study Participant Characteristics
The subject’s/patient’s age, sex, weight, height, racial designation, or other demographic and 
study disease characteristics will be recorded and summarized.
10.3. Statistical Analyses
Statistical analysis of this study will be the responsibility of Eli Lilly and Company or its 
designee.
Pharmacokinetic/PD analyses (CGRP target engagement) will be conducted on data from all 
patients/subjects who receive at least 1 dose of the IP and have evaluable PK.
Clinical activity and PD analyses will be conducted for all patients with psoriasis who receive 
the study drug (Part C only).
Safety analyses will be conducted for all enrolled patients/subjects, whether or not they 
completed all protocol requirements.
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 prior to 
database lock and unblinding.  Details of subject assignment to the analysis populations will be 
listed.


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The placebo data from all cohorts will be pooled across all dose-escalation cohorts for the 
purpose of analysis.
Additional exploratory analyses of the data will be conducted as deemed appropriate.  Study 
results may be pooled with the results of other studies for population PKanalysis purposes to 
avoid issues with posthoc analyses and incomplete disclosures of analyses.  
10.3.1.Safety Analyses
10.3.1.1.Clinical Evaluation of Safety
All IPsand protocol procedure AEs will be listed, and if the frequency of events allows, safety 
data will be summarized using descriptive methodology.
The incidence of symptoms for each treatment will be presented by severity and by association 
with IPas perceived by the investigator.  Symptoms reported to occur prior to treatment with 
study drugwill be distinguished from those reported as new or increased in severity during the 
study.  Each symptom will be classified by the most suitable term from the Medical Dictionary
for RegulatoryActivities.
Safety analyses will include summaries of the following:
AEs and SAEs, including severity and possible relationship to study drug
laboratory measures
The number of IP-related SAEs will be reported and summarized by preferred term.
Suicidal ideation and/or behavior and self-injurious behavior with no suicidal intent, based on the 
C-SSRS, will be listed by patient/subject(Parts B and C).
10.3.1.2.Statistical Evaluation of Safety
Safety parameters that will be assessed include safety laboratoryparameters, vital signs, and 
ECG parameters.  The parameters will be listed, and summarized using standard descriptive 
statistics.  Additional analysis will be performed if warranted upon review of the data.
Baseline for safety parameters will be defined as the last evaluable value before the first dose.
10.3.2.Pharmacokinetic Analyses
10.3.2.1.Pharmacokinetic Analyses
Pharmacokinetic parameter estimates for LY3316531will be calculated usingstandard 
noncompartmental methods of analysis.
The primary parameters for analysis will be C
max
CCI
and AUC of LY3316531.  Other 
noncompartmental parameters, such as half-life, apparent clearance, absolute bioavailability,and 
apparent volume of distribution may be reported.  Mean and individual plasma concentration 


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versus time profiles and individual and summary statistics of PK parameter estimates by 
treatment group will be generated.
Population-based methods of analyses may also be performed, to understand factors that 
influence the PK, characterize the inter- and intra-subject variability in PK and support 
simulations of multiple dose administration.
10.3.2.2. Pharmacokinetic Statistical Inference
The dose proportionality of selected LY3316531 PK parameters following IV administration in 
Part A of the study, including logarithm of Cmax and relevant AUC values, will be examined 
across the entire dose range using a power-model approach (Smith et al. 2000).  Other analyses 
of PK parameters may be performed as deemed appropriate.
10.3.3. Pharmacodynamic Analyses and Clinical Activity
Clinical activity and PD data obtained will be documented in the study report by dose, plasma 
drug concentrations, and time from dose.  However, the data collected at the visits leading up to 
and including the Week 4 visit will be the data used for evaluation of changes in clinical activity 
and PD measures.  Figures showing values of potential PD markers versus time will be created 
for each dose, with a line for each patient.  Absolute percentage change from baseline for all will 
be summarized by providing the mean, standard deviation, median, minimum, and maximum for 
each cohort and overall for each sample day/time combination and maximum over the entire 
study.  Data may be log-transformed prior to summarizing if necessary.  The interpatient and 
intrapatient variability in human PD responses may also be assessed if appropriate. 
10.3.3.1. Pharmacokinetic/Pharmacodynamic Analyses
Analyses of the relationship between LY3316531 exposure and efficacy endpoints collected in 
Part C (such as PASI score, sPGA, and BSA) will be investigated initially using graphical 
methods.  Modeling approaches that use a simple direct response relationship (using AUC) or
longitudinal models that link the time course of LY3316531 concentrations to the time course of 
response may be explored.  
Analyses of the relationship between LY3316531 exposure and total CGRP serum 
concentrations will also be conducted using graphical- and model-based approaches. Additional 
PD endpoints and safety endpoints may be explored for exposure-response relationships if 
warranted upon review of the data.
10.3.3.2. Health Outcome Measures for Subjects with Psoriasis
The Patient’s Global Assessment of Disease Severity will be reported and summarized at each 
applicable visit using standard descriptive statistics including number of subjects, mean, standard 
deviation, median, minimum, and maximum for continuous variables and number of subjects, 
frequency, and percentages for categorical variables.  Comparisons between each active 
treatment and pooled placebo group will be made.  Results from statistical analyses will be 
provided for descriptive purposes only; therefore, no statistical inferences will be made, and no 
control for multiplicity is planned.


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10.3.4. Evaluation of Immunogenicity
The frequency and percentage of patients/subjects with baseline ADA, with ADA anytime
postbaseline, and/or with TE ADA to LY3316531 will be tabulated. For patients/subjects who 
are ADA negative at baseline, TE ADAs are defined as those with a titer 2-fold (1 dilution) 
greater than the minimum required dilution of the assay.  For patients/subjects who are ADA 
positive at baseline, TE ADAs are defined as those with a 4-fold (2 dilutions) increase in titer 
compared to baseline. For the patients with TE ADA, the distribution of maximum titers will be 
described.  The frequency and percentage of patients with neutralizing antibodies may also be
tabulated for patients with TE ADA.
The relationship between the presence of antibodies and the PK parameters and PD response
including safety to LY3316531 may be assessed.
10.3.5. Data Review During the Study
Access to safety data is scheduled to occur after every dosing session.  The purpose of these 
reviews is to guide dose selection for the next dosing session, and/or to inform the design of 
subsequent studies.  The investigator and the Lilly sponsor team will make the determination 
regarding dose escalation, based upon their review of the data.  The investigator will remain 
blinded, and the Lilly sponsor team will be unblinded during these reviews.
In addition, data snapshots for preliminary analyses of PK data are planned to occur after Day 29 
of Cohort 3 (Part A) prior to the initiation of the multiple-dose cohorts (Part B).  The evaluation 
of these data will aid in determining the dose, margin of safety, and adjustment of PK sampling 
schedule.  Data snapshots are also planned to occur after Day 29 of Cohort 6 in Part A and Day 
57 of Cohort 1 in Part B.  Additional data snapshots may be conducted as required.  These 
snapshots and analyses will be conducted while the trial is ongoing, but no changes to the study 
design are planned.
10.3.6. Interim Analyses
An interim analysis will occur when all patients/subjects in Parts A, B, and C have completed all 
requirements stated in the Schedule of Activities (Section 2; up to Day 85 for Part A, up to Day 
141 for Part B, and up to Day 113 for Part C) or discontinued early from the study. Lilly 
employees and employees of any third-party organization involved in the interpretation of data 
collected during the study are authorized to evaluate unblinded data for the interim analyses.  
This interim analysis will include all planned analyses of available data.  The data will be used 
for the development of a clinical study report (CSR). Results that are not available at the time a
CSR is developed can be provided in a separate report or CSR addendum.


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National Psoriasis Foundation. The Psoriasis and Psoriatic Arthritis Pocket Guide. Portland, OR.
2009.
Mulderry PK, Ghatei MA, Spokks RA, Jonhs PM, Pierson AM, Hamid QA, Kanse S, Amara SG, 
Burrin JM, Legon S, Polak JM, Bloom SR. Differential expression of α-CGRP and β-CGRP 
by primary sensory neurons and enteric autonomic neurons of the rat. Neuroscience. 
1988;25(1):195-205.
Papp K, Thaci D, Reich K, Riedl E, Langley RG, Krueger JG, Gottlieb AB, Nakagawa H, 
Bowman EP, Mehta A, Li Q, Zhou Y, Shames R. Tildrakizumab (MK-3222) an anti-
interleukin-23 p19 monoclonal antibody, improves psoriasis in a phase IIb randomized 
placebo-controlled trial. Br J Dermatol. 2015;173(4):930-939.


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Posner K, Brown G, Stanley B, Brent DA, Yershova KV, Oquendo MA, Currier GW, Melvin 
GA, Greenhill L, Shen S, Mann JJ. The Columbia-Suicide Severity Rating Scale: initial 
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Riol-Blanco L, Ordovas-Montanes J, Perro M, Naval E, Thiriot A, Alvarez D, Paust S, Wood 
JN, von Andrian UH. Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform 
skin inflammation. Nature. 2014;510(7503):157-161.
Sandborn WJ, Gasink C, Gao LL, Blank MA, Johanns J, Guzzo C, Sands BE, Hanauer SB,
Targan S, Rutgeerts P, Ghosh S, de Villiers WJ, Panaccione R, Greenberg G, Schreiber S,
Lichtiger S, Feagan BG; CERTIFI Study Group. Ustekinumab induction and maintenance
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Appendix 1.
Abbreviations and Definitions


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Term
Definition
ADA
antidrug 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
assent
Agreement from a child or other individual who is not legally capable of providing consent, 
but who can understand the circumstances and potential risks involved in participating in a 
study (required by some institutional review boards [IRBs]/ethical review boards [ERBs]). 
AST
aspartate aminotransferase
blinding
A procedure in which 1 or more parties to the study are kept unaware of the treatment 
assignment(s).  Unless otherwise specified, blinding will remain in effect until final 
database lock.
A single-blind study is one in which the investigator and/or his staff are aware of the 
treatment but the patient/subject is not, or vice versa, or when the sponsor is aware of the 
treatment but the investigator and/his staff and the patient/subject are not.  A double-blind 
study is one in which neither the patient/subject nor any of the investigator or sponsor staff 
who are involved in the treatment or clinical evaluation of the subjects are aware of the 
treatment received
CGRP
calcitonin gene-related peptide
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 re-tested at some defined time point, depending on the steps required to obtain 
confirmed results.
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
CSE
clinically significant event


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CSR
clinical study report
C–SSRS
Columbia-Suicide Severity Rating Scale
ECG
electrocardiogram
eCRF
electronic case report form
enroll
The act of assigning a patient/subject to a treatment.  Patients/subjects who are enrolled in 
the study are those who have been assigned to a treatment.
enter
Patients/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
HBcAb
hepatitis B core antibody
HBsAb
hepatitis B surface antibody
HIV
human immunodeficiency virus
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonisation
Ig
immunoglobulin
IL
interleukin
informed consent
A process by which a patient/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 patient’s/subject’s decision to participate. Informed consent is 
documented by means of a written, signed, and dated informed consent form.  
interim analysis
An interim analysis is an analysis of clinical study data, separated into treatment groups, 
that is conducted before the final reporting database is created/locked.
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


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legal 
representative
An individual or judicial or other body authorized under applicable law to consent, on 
behalf of a prospective patient/subject, to the patient’s/subject’s participation in the clinical 
study.
mAb
monoclonal antibody
MTD
maximum tolerated dose
open-label
A study in which there are no restrictions on knowledge of treatment allocation, therefore 
the investigator and the study participant are aware of the drug therapy received during the 
study.
PASI
Psoriasis Area and Severity Index
PD
pharmacodynamic(s)
PK
pharmacokinetic(s)
PSS
Psoriasis Symptom Scale
PUVA
psoralen plus ultraviolet A light therapy
QTc
QT interval
randomize
The process of assigning subjects/patients to an experimental group on a random basis.
RNA
ribonucleic acid
SAD
single-ascending dose;
SAE
serious adverse event
SC
subcutaneous
screen
The act of determining if an individual meets minimum requirements to become part of a 
pool of potential candidates for participation in a clinical study.  
SUSAR
suspected unexpected serious adverse reaction
TB
tuberculosis
TBL
total bilirubin level
TE
treatment emergent
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
TNF
tumor necrosis factor


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TST
tuberculin skin test
ULN
upper limit of normal
WOCBP
women of childbearing potential
CCI


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Appendix 2. Clinical Laboratory Tests
Safety Laboratory Tests
Hematology
Clinical Chemistry
Hematocrit
Sodium
Hemoglobin
Potassium
Erythrocyte count (RBC)
Glucose, random
Mean cell volume
Blood urea nitrogen (BUN)
Mean cell hemoglobin
Uric acid
Mean cell hemoglobin concentration
Total cholesterol
Leukocytes (WBC)
Total protein
Platelets
Albumin
Total bilirubin
Absolute Counts of:
Alkaline phosphatase (ALP)
Neutrophils
Aspartate aminotransferase (AST/SGOT)
Lymphocytes
Alanine aminotransferase (ALT/SGPT)
Monocytes
Creatinine
Eosinophils
Gamma-glutamyl transferase (GGT)
Basophils
Immunoglobulins (IgA, IgM and IgG)
a
Serology
Hepatitis B surface antigena
Urinalysis
Hepatitis B core antibodya
Specific gravity
Hepatitis B surface antibodya
pH
Hepatitis C antibodya,c
Protein
Hepatitis C virus (HCV) ribonucleic acid (RNA)
c
Glucose
HIVa
Ketones
Bilirubin
Other
Urobilinogen
Urine ethanoltest
d
Blood
Urine drug screen
d
Leukocyte esterase or nitrite
QuantiFERON®-TB Gold test or TSTa
Microscopic examination of sedimentf
Pregnancy teste(serum
aand urine)
FSHa,e
HS-C-reactive protein
b
Serum concentration of LY3316531 (PK)
Target engagement assay (CGRP)
Pharmacogenetics (exploratory storage samples for DNA)
Exploratory storage samples (serum, plasma, RNA)
b
Immunogenicity (anti-LY3316531 antibodies)
CCI


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Abbreviations:  CGRP = calcitonin gene-related peptide; DNA = deoxyribonucleic acid; FSH = follicle-stimulating 
hormone; HIV = human immunodeficiency virus; HS = high sensitivity; IL = interleukin; PK = pharmacokinetic; 
RBC = red blood cell; RNA = ribonucleic acid; SGOT = serum glutamic oxaloacetic transaminase; SGPT = 
serum glutamic pyruvic transaminase; TB = tuberculosis; TST = tuberculin skin test; WBC = white blood cell.
a
Performed at screening only.
b
Performed in patients with psoriasis only.
c
A positive hepatitis C antibody laboratory assessment will be confirmed with a test for hepatitis C virus (HCV) 
ribonucleic acid (RNA).
d
Urine drug screen and ethanol test will be performed at screening and repeated prior to admission to the clinical 
research unit (Day -1), and when clinically indicated.
e
For female patients/subjects only.
f
Will only be performed if urine dipstick evaluation shows abnormality.


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


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Regulatory Considerations
This study will be conducted in accordance with the protocol and with
1) consensus ethics principles derived from international ethics guidelines, 
including the Declaration of Helsinki and Council for International 
Organizations of Medical Sciences International Ethical Guidelines 
2) applicable ICH GCP guidelines 
3) applicable laws and regulations
Some of the obligations of the sponsor will be assigned to a third-party organization.
Protocol Signatures
The sponsor’s responsible medical officer will approve the protocol, confirming that, to the best 
of his or her knowledge, the protocol accurately describes the planned design and conduct of the 
study.
After reading the protocol, each principal investigator will sign the protocol signature page and 
send a copy of the signed page to a Lilly representative.
Final Report Signature
The investigator or designee will sign the clinical study report for this study, indicating 
agreement with the analyses, results, and conclusions of the report.
The investigator with the most enrolled patients/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 CRFs, 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 CRF data and/or use standard computer edits to detect errors in data 
collection.


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
conduct a quality review of the database.
In addition, Lilly or its representatives will periodically check a sample of the patient/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 ERBs with direct access to the original source 
documents.
Data Collection Tools/Source Data
An electronic data capture system will be used in this study.  The site must define and retain all 
source records and must maintain a record of any data where source data are directly entered into 
the data capture system.
Data Protection
Data systems used for the study will have controls and requirements in accordance with local 
data protection law.  
The purpose and use of subject/patient personal information collected will be provided in a 
written document to the subject/patient 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 TE hepatic abnormality and may be required in 
follow-up with patients in consultation with Lilly or its designee CRP.
Hepatic Monitoring Tests
Hepatic Hematologya
Haptoglobina
Hemoglobin
Hematocrit
Hepatic Coagulationa
RBC
Prothrombin time
WBC
Prothrombin time, INR
Neutrophils
Lymphocytes
Hepatic Serologiesa,b
Monocytes
Hepatitis A antibody, total
Eosinophils
Hepatitis A antibody, IgM
Basophils
Hepatitis B surface antigen
Platelets
Hepatitis B surface antibody
Hepatitis B core antibody
Hepatic Chemistrya
Hepatitis C antibody
Total bilirubin
Hepatitis E antibody, IgG
Conjugated bilirubin
Hepatitis E antibody, IgM
Alkaline phosphatase
ALT
Anti-nuclear Antibodya
AST
Alkaline Phosphatase Isoenzymesa
GGT
CPK 
Anti-smooth Muscle Antibody (or Anti-actin 
Antibody)a
Abbreviations:  ALT = alanine aminotransferase; AST = aspartate aminotransferase; CPK = creatinine 
phosphokinase; GGT = gamma-glutamyl transferase; Ig = immunoglobulin; INR = international normalized
ratio; RBC = red blood cell; WBC = white blood cell.
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
APP. 5.1.
Part A (SAD in Healthy Subjects)
This table summarizes the approximate number of venipunctures and blood volumes for all 
blood sampling (screening, safety laboratories, and bioanalytical assays) during Part A.  
Protocol I9H-MC-FFAA Sampling Summary (Part A)
Purpose
Blood Volume per Sample 
(mL)
Number of Blood 
Samples
Total Volume (mL)
Screening testsa
45
1
45
Clinical laboratory testsa
12
13
156
Pharmacokineticsb
5
18
90
Blood discard for cannula patency
1
4
4
Pharmacodynamics (total CGRP)
2
8
16
Immunogenicityb
7.5
7
52.5
Pharmacogenetics
6
1
6
Total
369.5
Total for clinical purposes
370
Abbreviation: CGRP = calcitonin gene-related peptide.
a
Additional samples may be drawn if needed for safety purposes.
b
Includes 3 additional samples to be drawn if needed to aid in the assessment of anti-drug hypersensitivity 
reactions.


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APP.5.2.
Part B (Multiple-Dose in Healthy Subjects)
This table summarizes the approximate number of venipunctures and blood volumes for all 
blood sampling (screening, safety laboratories, and bioanalytical assays) during Part B.  
Protocol I9H-MC-FFAA Sampling Summary (Part B)
Purpose
Blood Volume per Sample 
(mL)
Number of Blood 
Samples
Total Volume (mL)
Screening testsa
45
1
45
Clinical laboratory testsa
12
9
108
Pharmacokineticsb
5
30
150
Blood discard for cannula patency
1
4
4
Pharmacodynamics (total CGRP)
2
9
18
Immunogenicityb
7.5
11
82.5
Pharmacogenetics
6
1
6
Total
413.5
Total for clinical purposes 
420
Abbreviation: CGRP = calcitonin gene-related peptide.
a
Additional samples may be drawn if needed for safety purposes.
b
Includes 3 additional samples to be drawn if needed to aid in the assessment of anti-drug hypersensitivity 
reactions.


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APP.5.3.
Part C (Single Dose in Patients with Psoriasis)
This table summarizes the approximatenumber of venipunctures and blood volumes forall 
blood sampling (screening, safety laboratories,and bioanalytical assays) during Part C.  
Protocol I9H-MC-FFAA Sampling Summary
Purpose
Blood Volume per Sample 
(mL)
Number of Blood 
Samples
Total Volume (mL)
Screening testsa,b
45
1
45
Clinical laboratory testsa,b
12
15
180
Pharmacokineticsc
5
21
105
Blood discard for cannula patency
1
4
4
Pharmacodynamics (total CGRP)
2
11
22
Pharmacodynamics (
2.5
6
15
Immunogenicity
c
7.5
10
75
Pharmacogenetics
6
1
6
Exploratory samples (serum, plasma,
RNA)
15
5
75
Total
527
Total for clinical purposes 
530
Abbreviations:CGRP = calcitonin gene-related peptide; IL = interleukin; RNA = ribonucleic acid.
a Additional samples may be drawn if needed for safety purposes.
b The screening and clinical laboratory tests will include a hsCRP sample draw when indicated in the Schedule of 
Activities (Section 2.3).
c
CCI
Includes 3 additional samples tobe drawn if needed to aid in the assessment of anti-drug hypersensitivity 
reactions.


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Appendix 6.
Protocol FFAA PK, Immunogenicity, and ECG 
Sampling Schedule
APP.6.1.
Part A (SAD in Healthy Subjects)


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Visit
Week
Day 
Relative to 
LY/PL
Treatment
PK Sampling 
Time IV Dosinga
PK Sampling 
Time 
SC Dosinga
Immunogenicity 
Samplinga
ECGb
2
0
1
Predose
Predose
Predose
Predose
2
0
1
End of infusionc
NA
NA
End of infusionc
2
0
1
2 h after start of 
infusion
NA
NA
NA
2
0
1
6 h after start of 
infusion
6 h post-injection 
NA
6 h after SC 
injection or start 
of infusion
2
0
1
NA
NA
NA
12 h after start of 
infusion
2
0
2
24 h after start of 
infusion
24 h post-
injection
NA
24 h after SC 
injection or start 
of  infusion
3
0
4 ± 1 day
Any time during 
day
Any time during 
day
NA
NA
4
1
8 ± 1 day
Any time during 
day
Any time during 
day
NA
Any time during 
day
5
1
11 ± 1 day
NA
Any time during 
day
NA
NA
6
2
15 ± 2 days
Any time during 
day
Any time during 
day
Any time during 
day
Any time during 
day
7
3
22 ± 2 days
Any time during 
day
Any time during 
day
NA
NA
8
4
29 ± 2 days
Any time during 
day
Any time during 
day
Any time during 
day
NA
9
6
43 ± 3 days
Any time during 
day
Any time during 
day
NA
Any time during 
day
10
8
57 ± 3 days
Any time during 
day
Any time during 
day
NA
NA
11
10
71 ± 3 day
Any time during 
day
Any time during 
day
NA
NA
12
12
85 ± 3 days
Any time during 
day
Any time during 
day
Any time during 
dayd
Any time during 
day
ED
ED
Any time during 
day
Any time during 
day
Any time during 
dayd
Any time during 
day
Abbreviations:  ADA = antidrug antibody; ECG = electrocardiogram; ED = early discontinuation; h = hour(s); IV = 
intravenous; LY = LY3316531; PL = Placebo; NA = not applicable (no sampling needed at this time point); 
PK = pharmacokinetic; SC = subcutaneous; TE = treatment emergent.
a
In the event of drug hypersensitivity reactions (immediate or non-immediate), up to 3 additional samples will be 
collected each for pharmacokinetics and immunogenicity as close to the onset of the reaction event as possible, at 
the resolution of the event, and 30 days following the event.


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b
ECG measurement should occur prior to the blood draw.
c
Required for subjects receiving intravenous dosing only.  ECGs (and vital signs) should be measured within 5 
minutes prior to the end of infusion and PK samples as soon as possible after the infusion is completed
d
Subjects who are TE ADA positive at the end of the study or early discontinuation will be followed with samples
for ADA and PK being taken approximately every 3 months, until they return to 2-fold titer of baseline or for a 
maximum of 1 year.
Note:  Samples that are requested to be taken predose through Day 2 should be collected as close to the sampling 
time as possible.  Aberrations to the specified sampling times will not be considered protocol deviations as long 
as the samples are taken and the actual sampling time is recorded.


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APP.6.2.
Part B (Multiple-Dose in Healthy Subjects) 


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Visit
Week
Day 
Relative to 
First Dose 
LY/PL 
Treatment
PK Sampling 
Time IV Dosinga
PK Sampling 
Time 
SC Dosinga,b
Immunogenicity 
Samplinga
ECGc
2
0
1
Predose
Predose
Predose
Predose
2
0
1
End of infusion
NA
NA
End of infusiond
2
0
1
2 h after start of 
infusion
NA
NA
NA
2
0
1
6 h after start of 
infusion
6 h post-injection 
NA
6 h after SC 
injection or start 
of  infusion
2
0
2
24 h after start of 
infusion
24 h post-
injection
NA
24 h after SC 
injection or start 
of  infusion
3
0
4 ± 1 day
Any time during 
day
Any time during 
day
NA
NA
4
1
8 ± 1 day
Any time during 
day
Any time during 
day
NA
Any time during 
day
5
1
11 ± 1 day
NA
Any time during 
day
NA
NA
6
2
15 ± 2 days
Any time during 
day
Any time during 
day
Any time during 
day
Any time during 
day
7
3
22 ± 2 days
Any time during 
day
Any time during 
day
NA
NA
8
4
29
Predose
Predose
Predose
Predose
8
4
29
End of infusion
NA
NA
End of infusionc
8
4
30
24 h after start of 
infusion
24 h post-
injection
NA
24 h after SC 
injection or start 
of  infusion
9
4
32 ± 1 days
Any time during 
day
Any time during 
day
NA
NA
10
5
36 ± 1 days
Any time during 
day
Any time during 
day
NA
NA
11
5
39 ± 1 day
NA
Any time during 
day
NA
NA
12
6
43 ± 2 days
Any time during 
day
Any time during 
day
NA
NA
13
7
50 ± 2 days
Any time during 
day
Any time during 
day
NA
NA
14
8
57
Predose
Predose
Predose
Predose
14
8
57
End of infusion
NA
NA
End of infusiond
14
8
58
24 h after start of 
infusion
24 h post-
injection
NA
24 h after SC 
injection or start 
of  infusion
15
8
60 ± 1 day
Any time during 
day
Any time during 
day
NA
NA
16
9
64 ± 1 day
Any time during 
day
Any time during 
day
NA
Any time during 
day


I9H-MC-FFAA(b) Clinical Pharmacology Protocol
Page 93
LY3316531
17
9
67 ± 1 day
NA
Any time during 
day
NA
NA
18
10
71 ± 2 days
Any time during 
day
Any time during 
day
NA
Any time during 
day
19
11
78 ± 2 days
Any time during 
day
Any time during 
day
NA
NA
20
12
85 ± 3 days
Any time during 
day
Any time during 
day
Any time during 
day
Any time during 
day
21
16
113 ± 4 
days
Any time during 
day
Any time during 
day
NA
NA
22
20
141 ± 4 
days
Any time during 
day
Any time during 
day
Any time during 
daye
Any time during 
day
ED
ED
Any time during 
day
Any time during 
day
Any time during 
daye
Any time during 
day
Abbreviations:  ADA = antidrug antibody; ECG = electrocardiogram; ED = early discontinuation; h = hour(s); IV = 
intravenous; LY = LY3316531; PL = Placebo; NA = not applicable (no sampling needed at this time point); 
PK = pharmacokinetic; SC = subcutaneous; TE = treatment emergent.
a
In the event of drug hypersensitivity reactions (immediate or non-immediate), up to 3 additional samples will be 
collected each for pharmacokinetics and immunogenicity as close to the onset of the reaction event as possible, at 
the resolution of the event, and 30 days following the event.
b
Use this sampling schedule if SC dosing is utilized in the optional cohort.
c
ECG measurement should occur prior to the blood draw.
d
Required for subjects receiving intravenous dosing only.
e
Subjects who are TE ADA positive at the end of the study or early discontinuation will be followed with samples 
for ADA and PK being taken approximately every 3 months, until they return to 2-fold titer of baseline or for a 
maximum of 1 year.
Note:  Samples that are requested to be taken predose through Day 2 should be collected as close to the sampling 
time as possible.  Aberrations to the specified sampling times will not be considered protocol deviations as long 
as the samples are taken and the actual sampling time is recorded.


I9H-MC-FFAA(b) Clinical Pharmacology Protocol
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LY3316531
APP.6.3.
Part C (Single Dose in Patients with Psoriasis)
Visit
Week
Day 
Relative to 
LY 
Treatment
PK Sampling 
Time IV Dosinga
PK Sampling 
Time 
SC Dosinga,b
Immunogenicity 
Samplinga
ECGc
2
0
1
Predose
Predose
Predose
Predose
2
0
1
End of infusion
NA
NA
End of infusion
2
0
1
2 h after start of 
infusion
NA
NA
NA
2
0
1
6 h after start of 
infusion
6 h post-injection
NA
6 h after SC 
injection or start 
of  infusion
2
0
2
24 h after start of 
infusion
24 h post-
injection
NA
24 h after SC 
injection or start 
of  infusion
3
0
4 ± 1 day
Any time during 
day
Any time during 
day
NA
NA
4
1
8 ± 1 day
Any time during 
day
Any time during 
day
NA
Any time during 
day
5
2
15 ± 2 days
Any time during 
day
Any time during 
day
Any time during 
day
Any time during 
day
6
3
22 ± 2 days
Any time during 
day
Any time during 
day
NA
NA
7
4
29 ± 2 days
Any time during 
day
Any time during 
day
Any time during 
day
NA
8
6
43 ± 3 days
Any time during 
day
Any time during 
day
NA
Any time during 
day
9
8
57 ± 3 days
Any time during 
day
Any time during 
day
NA
NA
10
10
71 ± 3 days
Any time during 
day
Any time during 
day
NA
NA
11
12
85 ± 3 days
Any time during 
day
Any time during 
day
Any time during 
day
Any time during 
day
12
16
113 ± 4 days
Any time during 
day
Any time during 
day
Any time during 
dayd
Any time during 
day
ED
ED
Any time during 
day
Any time during 
day
Any time during 
dayd
Any time during 
day
Up to 
20e
Up to 
52e
Up to 365e
Any time during 
dayf
Any time during 
dayf
Any time during 
dayg
Any time during 
day
ED
ED
Any time during 
day
Any time during 
day
Any time during 
day
Any time during 
day
Abbreviations:  ADA = antidrug antibody; ECG = electrocardiogram; ED = early discontinuation; h = hour(s); IV = 
intravenous; LY = LY3316531; NA = not applicable (no sampling needed at this time point); 
PK = pharmacokinetic; TE = treatment emergent.
a
In the event of drug hypersensitivity reactions (immediate or non-immediate), up to 3 additional samples will be 
collected each for pharmacokinetics and immunogenicity as close to the onset of the reaction event as possible, at 
the resolution of the event, and 30 days following the event.
b
Use this sampling schedule if SC dosing is utilized in an optional cohort.


I9H-MC-FFAA(b) Clinical Pharmacology Protocol
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LY3316531
c
ECG measurement should occur prior to the blood draw.
d
Patients who are TE ADA positive at the end of the study or early discontinuation will be followed with samples
for ADA and PK being taken approximately every 3 months, until they return to 2-fold titer of baseline or for a 
maximum of 1 year.
e
An extended follow-up period that requires monthly follow-up visits for patients who respond to treatment with 
LY3316531 after the initial 16-week follow-up period (see Section 5.1.3 for more details).
f
PK sampling will be conducted at each monthly visit during the extended follow-up period for patients who 
responded to LY3316531 treatment.
g
Patients should be assessed for ADAs during Weeks 26 (Day 183 ± 7 days) and 52 (Day 365 ± 7 days) of the 
extended follow-up period.
Note:  Samples that are requested to be taken predose through Day 2 should be collected as close 
to the sampling time as possible.  Aberrations to the specified sampling times will not be 
considered protocol deviations as long as the samples are taken and the actual sampling time is 
recorded.


I9H-MC-FFAA(b) Clinical Pharmacology Protocol
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LY3316531
Appendix 7.
Protocol Amendment I9H-MC-FFAA (b) 
Summary 
A Phase 1 Randomized, Placebo-Controlled Study of 
LY3316531 in Healthy Subjects and an Open-Label, 
Single-Dose Study in Patients with Psoriasis
Overview
Protocol I9H-MC-FFAA, A Phase 1 Randomized, Placebo-Controlled Study of LY3316531 in 
Healthy Subjects and an Open-Label, Single-Dose Study in Patients with Psoriasis has been 
amended.  The new protocol is indicated by Amendment (b) and will be used to conduct the 
study in place of any preceding version of the protocol.
The overall changes and rationale for the changes made to this protocol are as follows:
The number of patients to be enrolled in the planned and 2 optional cohorts of Part C was 
decreased from 8 patients to a minimum of 7 patients.  A minimum of 7 patients are required to 
complete a cohort but up to 8 patients would still be allowed if 8 eligible patients can be 
identified in a timely manner.    The reduced minimum required sample size was deemed 
sufficient to assess if there is evidence of clinical activity of LY3316531 based on PASI scores at 
4 weeks, and is adequate for assessment of safety, tolerability and PK of the compound in the 
patient population at this stage of development.
Decreasing the cohort size to 7 patients will facilitate analysis of PASI scores for the purpose of 
determining if an optional cohort is needed to proceed once 4 weeks of data have been collected 
from 7 patients in a preceding cohort, thus preventing delay if 8 eligible patients cannot be 
identified in a timely manner.  This overall decrease in cohort size from 8 patients to 7 patients 
has resulted in the specific changes outlined below.  The rationale described for the overall 
change applies to these specific changes.

Section 1 Protocol Synopsis
o
Number of Patients/Subjects

Part C:  The number of patients from which evaluable data will be 
obtained was changed from 24 patients to up to 24 patients (total number 
of patients for planned and optional cohorts).

Part C:  The number of patients per cohort was changed from 8 patients to 
a minimum of 7 patients planned but up to 8 patients allowed per cohort.

Section 5 Study Design
o
5.1 Overall Study Design


I9H-MC-FFAA(b) Clinical Pharmacology Protocol
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LY3316531

Table FFAA.5.1.  Title was changed from “Summary of Patient/Subject 
Cohorts” to “Summary of Maximum Number of Patients/Subjects per 
Cohort” to reflect the planned number of subjects are the maximum 
number per cohort

Table FFAA.5.1.1 Summary of Maximum Number of Patients/Subjects 
per Cohort Part C:  Footnote c was added to Patient Cohorts 1, 2, and 3 to 
explain that a minimum 7 patients are planned but up to 8 patients are
allowed per cohort.

Figure FFAA.5.1. Study Design:    Footnote d was added to Patient 
Cohorts 1, 2, and 3 to explain that a minimum 7 patients are planned but 
up to 8 patients are allowed per cohort.
o
5.2 Number of Participants

5.2.3. Part C (Single-Dose Design in Patients with Psoriasis):  The number 
of patients to complete was changed from approximately24 patients to up 
to 24 patients.

Section 7 Treatment
o
7.4. Dose Modification

7.4.1. Dose Decision (Part C):  The number of patients from which 
4 weeks of clinical activity data are needed in order to progress to the 
optional cohorts in Part C was changed from all patients (which in prior to 
amendment b is 8 patients) to at least 7 patients.


I9H-MC-FFAA(b) Clinical Pharmacology Protocol
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LY3316531
Revised Protocol Sections
Note:
All deletions have been identified by strikethroughs.
All additions have been identified by the use of underscore.
1.  Protocol Synopsis
Part C:  It is planned that up to 30 patients may be enrolled in Part C of this study to obtain evaluable data 
from up to 24 patients (total number of patients for planned and optional cohorts).  The patients with 
psoriasis single-dose part of the study is planned to include up to 3 cohorts (300 mg IV cohort with the 
option for 2 additional cohorts) with a minimum of 7 patients planned but up to 8 patients allowed per 
cohort (8 LY3316531).
5.1.  Overall Design
Table FFAA.5.1.
Summary of Maximum Number of Patients/Subjects per Cohorts
Cohort #
Planned Dose/
Administration Route
Number of Planned
Subjects
Total Number of 
Planned Subjects
LY
PBO
Part A
SAD Cohort 1a
3 mg/IV
3
1
4
SAD Cohort 2a
15 mg/IV
3
1
4
SAD Cohort 3
75 mg/IV
6
2
8
SAD Cohort 4
300 mg/IV
6
2
8
SAD Cohort 5
300 mg/SC
6
0
6
SAD Cohort 6
900 mg/IV
6
2
8
SAD Cohort 7
2000 mg/IV
6
2
8
Part B
Multiple-Dose Cohort 1
2000 mg/IV
6
2
8
Multiple-Dose Cohort 2b
Route and dose TBD 
6
2
8
Part C
Patient Cohort 1c
300 mg/IV
8
0
8
Patient Cohort 2b,c
Route and dose TBD 
8
0
8
Patient Cohort 3b,c
Route and dose TBD 
8
0
8
Abbreviations:  IV = intravenous; LY = LY3316531; PBO = placebo; SAD = single-ascending dose; SC = 
subcutaneous; TBD = to be determined.
a
Sentinel dosing will be used in this cohort.
b
Optional subject or patient cohort.  Actual dose and route of administration will be determined based on 
cumulative data from previous cohorts, but will not exceed 2000 mg of LY3316531 administered IV.
c
A minimum of 7 patients are planned but up to 8 patients are allowed per cohort.


I9H-MC-FFAA(b) Clinical Pharmacology Protocol
Page 99
LY3316531
Figure FFAA.5.2.
Illustration of study design for Protocol I9H-MC-FFAA.
5.2.3.  Part C (Single-Dose Design in Patients with Psoriasis)
Up to 30 patients may be enrolled so that up to approximately 24 patients complete Part C (total 
number of patients planned for Cohort 1 and the 2 optional cohorts).  For purposes of Part C, a 
patient completes the study when he/she completes all scheduled procedures up to and including 
at least Day 85.
7.4.1.  Dose Decision (Part C)
The decision to initiate the first patient cohort in Part C will be based on the trial-level 
safety review for Cohort 3; however, any available preliminary PK data from Cohorts 1, 
2, and 3 (through Day 29) in Part A will be considered as well.  Progression to the 
optional cohorts in Part C will occur when at least 4 weeks of clinical activity data (PASI 
scores) are available from all at least 7 patients in the preceding cohort.  In addition to the 
PASI scores, any available PK and applicable safety data from Part A will be considered 
for determining the dose for the optional patient cohorts.  Dosing at the current level and 
further dose escalation will be discontinued if any of the scenarios described in 
Section 7.4.2 occur.


PPD
Leo Document ID = cb0ed918-d8dd-4aa3-83cf-466c1dd988b0
Approver: 
Approval Date & Time: 17-Aug-2018 19:38:54 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 17-Aug-2018 19:38:54 GMT
Signature meaning: Approved
PPD

SAP_001.pdf: 
Statistical Analysis Plan I9H-MC-FFAA 
 
 
A Phase 1 Randomized, Placebo-Controlled Study of LY3316531 in Healthy Subjects and 
an Open-Label, Single-Dose Study in Patients with Psoriasis 
 
 
NCT03418493 
 
 
Approval Date: 31-Jan-2018 
 
 


Final, 30 Jan 2018
             Page 1of 20
STATISTICAL ANALYSIS PLAN
A Phase 1 Randomized, Placebo-Controlled Study ofLY3316531 in Healthy Subjects and 
an Open-Label, Single-Dose Study in Patients with Psoriasis
Approval Date: 31-Jan-2018 GMT
Statistical Analysis Plan Status:  Final
Statistical Analysis Plan Date:  30-January-2018
Study Drug:  LY3316531
Sponsor Reference:  I9H-MC-FFAA
Covance CRU Study: 1000071-8371710
Clinical Phase I


Final, 30 Jan 2018
             Page 2of 20
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8371710
Sponsor Reference I9H-MC-FFAA
1.TABLE OF CONTENTS
1. TABLE OF CONTENTS.....................................................................................................2
2. ABBREVIATIONS..............................................................................................................4
3. INTRODUCTION...............................................................................................................6
4. STUDY OBJECTIVES........................................................................................................6
4.1 Primary objectives.........................................................................................................6
5. STUDY DESIGN.................................................................................................................7
5.1 Part A (SAD in Healthy Subjects)..................................................................................8
5.2 Part B (Multiple-Dose Design in Healthy Subjects).......................................................9
5.3 Part C (Single-Dose Design in Patients with Psoriasis)..................................................9
6. TREATMENTS.................................................................................................................10
7. SAMPLE SIZE JUSTIFICATION.....................................................................................10
8. DEFINITION OF ANALYSIS POPULATIONS................................................................10
9.
CCI
STATISTICAL METHODOLOGY...................................................................................11
9.1 General........................................................................................................................11
9.2 Demographicsand Subject Disposition........................................................................11
9.3 Pharmacokinetic Assessment.......................................................................................12
9.3.1
Pharmacokinetic Analysis...................................................................................12
9.4 Pharmacodynamic Assessment....................................................................................12
9.4.1
Pharmacodynamic Analysis................................................................................12
9.4.1.1Static Physicians Global Assessment (sPGA).....................................................15
9.4.1.2Psoriasis Area Severity Index (PASI).................................................................15
9.4.1.3Percentage of Body Surface Area (%BSA) Assessment......................................15
9.4.1.4Target Engagement Assay (Total Calcitonin Gene-Related Peptide [CGRP]).....15
9.4.1.5High Sensitivity-C Reactive Protein (HS-CRP)..................................................16
9.4.1.6Exploratory biomarkers......................................................................................16
9.4.2
Pharmacodynamic Statistical Methodology........................................................16
9.5 Safety and Tolerability Assessments............................................................................16
9.5.1
Adverse events...................................................................................................16
9.5.2
Concomitant medication.....................................................................................16
9.5.3
Clinical laboratory parameters............................................................................17
9.5.4
Vital signs..........................................................................................................17
9.5.5
Electrocardiogram (ECG)...................................................................................17
9.5.9
Immunogenicity.................................................................................................18
9.5.10 Hepatic Monitoring............................................................................................18


Final, 30 Jan 2018
             Page 3 of 20
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8371710
Sponsor Reference I9H-MC-FFAA
9.5.11
Columbia Suicide Severity Rating Scale (C-SSRS).............................................18
9.5.12
Patient's Global Assessment of Psoriasis (PatGA) 
and Psoriasis Symptom Scale .............................................................................18
9.5.13
Biopsy Assessment.............................................................................................18
9.5.14
Other assessments...............................................................................................19
9.5.15
Safety and Tolerability Statistical Methodology..................................................19
10. INTERIM ANALYSES .....................................................................................................19
11. CHANGES FROM THE PROTOCOL SPECIFIED STATISTICAL ANALYSES ............19
12. REFERENCES ..................................................................................................................19
13. DATA PRESENTATION ..................................................................................................19
13.1 Derived Parameters .....................................................................................................19
13.2 Missing Data ...............................................................................................................19
13.3 Insufficient Data for Presentation ................................................................................20


Final, 30 Jan 2018
             Page 4 of 20
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8371710
Sponsor Reference I9H-MC-FFAA
2. ABBREVIATIONS
Abbreviations pertain to the Statistical Analysis Plan (SAP) only (not the tables, figures and 
listings [TFLs]).
ADA
Antidrug antibody
AE
Adverse event
ALP
Alkaline phosphatase
ALT
Alanine aminotransferase
AUC
Area under the concentration versus time curve
BSA
Body surface area
CGRP
Calcitonin gene-related peptide
Cmax
Maximum observed drug concentration
CRF
Case Report Form
CRU
Clinical Research Unit
CSR
Clinical Study Report
C-SSRS
Columbia Suicide Severity Rating Scale
CV
Coefficient of variation
EC
Early Clinical 
ECG
Electrocardiogram
e.g.
For example (Latin: exempli gratia)
HS-CRP
High Sensitivity-C Reactive Protein
ICH
International Council for Harmonisation
IP
Investigational product
IV
Intravenous
LY
LY3316531
MD
Multiple dose
MedDRA
Medical Dictionary for Regulatory Activities
MRE
Magnetic resonance elastography
PASI
Psoriasis Area and Severity Index
PatGA
Patient's Global Assessment of Psoriasis
PBO
Placebo
PD
Pharmacodynamic
PK
Pharmacokinetic


Final, 30 Jan 2018
             Page 5of 20
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8371710
Sponsor Reference I9H-MC-FFAA
Ps
Psoriasis
SAD
Single ascending dose
SAP
Statistical Analysis Plan
SC
Subcutaneous
SD
Standard deviation 
sPGA
Static Physician Global Assessment
SR
Safety review meeting
TBD
To be determined
TBL
Total bilirubin level
TFLs
Tables, Figures, and Listings
t
max
CCI
Time ofmaximum observed drugconcentration
ULN
Upper limit of normal
WHO
World Health Organization
CCI


Final, 30 Jan 2018
             Page 6 of 20
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8371710
Sponsor Reference I9H-MC-FFAA
3. INTRODUCTION
This SAP has been developed after review of the Clinical Study Protocol (final version dated
02 November 2017) and Protocol Amendment (a) (final version dated 18 January 2018).
This SAP describes the planned analysis of the safety, tolerability, pharmacokinetic (PK) and 
pharmacodynamic (PD) data from this study. A detailed description of the planned TFLs to be 
presented in the clinical study report (CSR) is provided in the accompanying TFL shell 
document.
The intent of this document is to provide guidance for the statistical, PK and PD analyses of data. 
In general, the analyses are based on information from the protocol, unless they have been 
modified by agreement between Eli Lilly and Company and Covance Early Clinical (EC)
Biometrics. A limited amount of information concerning this study (e.g., objectives, study 
design) is given to help the reader’s interpretation. This SAP must be signed off prior to first 
subject administration for this study. When the SAP and TFL shells are agreed upon and 
finalized, they will serve as the template for this study’s CSR.
This SAP supersedes the statistical considerations identified in the protocol; where 
considerations are substantially different, they will be so identified. If additional analyses are 
required to supplement the planned analyses described in this SAP, they may be performed and 
will be identified in the CSR. Any substantial deviations from this SAP will be agreed upon 
between Eli Lilly and Company and Covance EC Biometrics and identified in the CSR. Any 
minor deviations from the TFLs may not be documented in the CSR.
This SAP is written with consideration of the recommendations outlined in the International 
Council on Harmonisation (ICH) E9 Guideline entitled Guidance for Industry: Statistical 
Principles for Clinical Trials1 and the ICH E3 Guideline entitled Guidance for Industry:  
Structure and Content of Clinical Study Reports2.
4. STUDY OBJECTIVES
4.1
Primary objectives
The primary objectives of this study are:

To explore the safety and tolerability of single and multiple doses of LY3316531 in 
healthy subjects

To explore the safety and tolerability of a single dose of LY3316531 in patients with 
psoriasis
The secondary objectives of this study are:

To characterize the PK of LY3316531 following intravenous (IV) and subcutaneous (SC)
administration in healthy subjects

To characterize the PK of LY3316531 following IV administration in patients with 
psoriasis


Final, 30 Jan 2018
             Page 7of 20
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8371710
Sponsor Reference I9H-MC-FFAA
The exploratory objectives of this studyare:
To evaluate the injection tolerance after SC administration of LY3316531
To evaluate the formation of antidrug antibodies(ADA)to LY3316531
To evaluate the PD response (target engagement) of LY3316531 using total calcitonin 
gene-related peptide(CGRP)
To evaluate patient-reported outcomes, including measurement of disease activity of 
LY3316531 in patients with psoriasis
To evaluate relationships between LY3316531 exposure and PD and clinical activity 
measures and safety endpoints
5.STUDY DESIGN
Study FFAA is a 3-part Phase 1, multicenter, randomized,sponsor unblind, subject-and 
investigator-blind (investigator will be partially blind for Cohorts 1 and 2 and unblind for 
Cohort5 in Part A), placebo-controlled, parallel-dose group, single-ascending dose (SAD) 
design (Part A), and multiple-dose design (Part B)in healthy subjects. In addition, Part C of this 
study is an open-label, singledosedesignin patients with psoriasis. There are 3 parts to this 
study to explore the safety,tolerability, PK, and PD of LY3316531:
Part A: SADdesignin healthy subjects,
Part B: Multiple-dose design in healthy subjects,

CCI
Part C: Single-dose design in patients with psoriasis.
Table1 provides a detailed description of subject/patient cohorts and planned doses forParts A, 
B, and C. Figure1 demonstrates the relationship among Parts A, B, and C.  Part A will begin 
first and will trigger the initiation of Parts B and C, which will run in parallel.  
Patients/subjects will be admitted to the clinical research unit (CRU) on Day -1 (Days -1, 28, and
56 in Part B) and fast overnight. Patients/subjects will receive a dose of study drug or placebo
on Day 1 (Days 1, 29, and 57 in Part B) and will undergo the study assessments specified in the
Schedule of Activities (Section 2of the protocol). Patients/subjects may be discharged 24 hours 
after doseadministration on Day 2 (Days 2, 30, and 58 in Part B).In case of safety concerns,
patients/subjects will be required to stay in the CRU for a longer period at the discretion of the
investigator.Patients/subjects will return to the CRU for outpatient visits for procedures
specified in the Schedule of Activities (Section 2of the protocol).
The decision to escalate to the next higher dose of LY3316531 will be based on safety data
through Day 15 from at least 7 subjects (5 or 6 subjects will have received LY3316531
determined by randomization) from the preceding dose cohort.  Exceptions will befor Cohorts 1 
and2, and Cohort 5 inif available at the time of decision in Part A, where safety data from all 
subjects through Day 15will be required.


Final, 30 Jan 2018
             Page 8 of 20
Statistical Analysis Plan 
CONFIDENTIAL
Covance Clinical Study No. 1000071-8371710
Sponsor Reference I9H-MC-FFAA
Table 1
Summary of Patient/Subject Cohorts
Cohort #
Planned Dose/ 
Administration Route
Number of Planned 
Subjects
Total Number of 
Planned Subjects
LY
PBO
Part A
SAD Cohort 1a
3 mg/IV
3
1
4
SAD Cohort 2a
15 mg/IV
3
1
4
SAD Cohort 3
75 mg/IV
6
2
8
SAD Cohort 4
300 mg/IV
6
2
8
SAD Cohort 5
300 mg/SC
6
0
6
SAD Cohort 6
900 mg/IV
6
2
8
SAD Cohort 7
2000 mg/IV
6
2
8
Part B
Multiple-Dose Cohort 1
2000 mg/IV
6
2
8
Multiple-Dose Cohort 2b
Route and dose TBD
6
2
8
Part C
Patient Cohort 1
300 mg/IV
8
0
8
Patient Cohort 2b
Route and dose TBD
8
0
8
Patient Cohort 3b
Route and dose TBD
8
0
8
Abbreviations: IV = intravenous; LY = LY3316531; PBO = placebo; SAD = single-ascending dose; 
SC = subcutaneous; TBD = to be determined.
a Sentinel dosing will be used in this cohort.
b Optional subject or patient cohort. Actual dose and route of administration will be determined based on
cumulative data from previous cohorts, but will not exceed 2000 mg of LY3316531 administered IV.
Figure 1
Illustration of study design
Abbreviations:  IV = intravenous; LY = LY3316531; MD = multiple dose; PBO = placebo; PK = pharmacokinetic 
sampling; SAD = single-ascending dose; SC = subcutaneous; SR = safety review meeting; TBD = to be determined
5.1
Part A (SAD in Healthy Subjects)
Seven planned dose-escalation cohorts will be enrolled to receive either IV or SC administration 
of LY3316531 (3, 15, 75, 300, 900, or an additional dose not to exceed 2000 mg) or placebo. 
Sentinel dosing will be used in Cohorts 1 and 2 to minimize the risk to subjects receiving this 
novel antibody.  Initially, 2 subjects (1 receiving LY3316531 and 1 receiving placebo) will be 
dosed in a blinded manner (sentinel subjects) and these subjects will be followed for at least 
24 hours postdose before the remaining subjects in that cohort are dosed (subject blind only).


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The remaining subjects may then be dosed on the same day or subsequent days (but not 
necessarily consecutive days), as determined by the investigator. Dose escalation to the next 
cohort can begin after a safety review of data from the preceding cohort.  All 6 subjects in 
Cohort 5 will receive 300 mg of LY3316531 SC.
All subjects who meet eligibility criteria will be followed for 12 weeks post-treatment 
administration. A subject’s participation is considered as complete if he/she received the study 
drug and completes all activities up to and including at least Day 57. Subjects may be replaced if
PK data are not collected up to and including Day 57.
5.2
Part B (Multiple-Dose Design in Healthy Subjects)
One planned multiple-dose cohort will be enrolled to receive IV administration of LY3316531 
(2000 mg) or placebo.  The dose and route of administration (IV or SC) for an optional second 
multiple-dose cohort would be determined after reviewing the data from the first IV cohort.
It is planned that a review of the safety data from Cohort 7 (Part A) and the preliminary PK data 
(maximum observed drug concentration [Cmax] and area under the concentration versus time 
curve [AUC]) from Cohorts 1, 2, and 3 (through Day 29) in Part A will trigger enrollment to the 
first cohort in Part B.
All subjects who meet eligibility criteria will receive 3 doses of LY3316531 (1 dose every 
4 weeks) and be followed for 12 weeks after the final treatment administration.  A subject’s 
participation is considered as complete if he/she received the study drug and completes all 
activities up to and including at least Day 85.  Subjects may be replaced if PK data are not
collected up to and including Day 85.
5.3
Part C (Single-Dose Design in Patients with Psoriasis)
One planned single-dose cohort will be enrolled to receive IV administration of LY3316531 with 
the option of 2 subsequent cohorts where the dose levels and route of administration (SC or IV) 
would be determined after reviewing the data from the first IV cohort.
The first cohort is planned to receive 300 mg of LY3316531 pending the analysis of available 
safety data from Part A.  The actual starting dose and expected exposure will not exceed the 
dose/exposure that is concurrently being evaluated in Part A.  Any available preliminary PK data 
from Cohorts 1, 2, and 3 (through Day 29) in Part A will be considered in the decision to initiate 
Part C as well.  Similarly, the dose for the optional cohorts will be determined based on 
cumulative data from previous cohorts, but will not exceed 2000 mg of LY3316531.
All patients who respond to LY3316531 treatment by exhibiting at least 50% reduction from
baseline Psoriasis Area and Severity Index (PASI) score at Week 12 (Visit 11; Day 85) can enter 
an extended follow-up period for up to 52 weeks post-treatment administration.  Other subjects 
who do not meet the above criterion for PASI reduction should be considered for discontinuation 
from the study at Week 16 (Visit 12; Day 113).  Exceptions could be considered after a 
discussion between the sponsor and investigator.


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A patient’s participation is considered as complete if he/she received the study drug and 
completes all activities up to and including at least Day 85.  Patients may be replaced if PK or 
PD data are not collected up to and including Day 85.
6. TREATMENTS
The following is a list of the study treatment abbreviations that will be used in the TFLs.
Part
Cohort
Study Treatment Name
Treatment order in TFL
A
*
Pooled Placebo IV
1
1
3 mg LY3316531 IV
2
2
15 mg LY3316531 IV
3
3
75 mg LY3316531 IV
4
4
300 mg LY3316531 IV
5
5
300 mg LY3316531 SC
6
6
900 mg LY3316531 IV
7
7
2000 mg LY3316531 IV
8
B
*
Pooled Placebo IV
9
1
2000 mg LY3316531 IV
10
2
XXX mg LY3316531 TBD
11
C
1
300 mg LY3316531 IV
12
2
XXX mg LY3316531 TBD
13
3
XXX mg LY3316531 TBD
14
* Placebo IV data will be pooled across all cohorts within each part
7. SAMPLE SIZE JUSTIFICATION
The sample size for each cohort is customary for first-in-human studies in which formal power 
analyses are not necessary to address the objectives associated with safety, tolerability, PK, 
and/or PD assessments.  Approximately 86 patients/subjects are planned for enrollment; 
however, up to 102 subjects may be enrolled to allow for replacement of subjects and any 
additional dose cohorts (Parts A, B, and C).
Subjects/patients who withdraw from the study before completing the Day 57 (Part A) or Day 85 
(Parts B and C) assessment may be replaced if necessary to have the planned number of 
subjects/patients complete a dose cohort.  A replacement subject/patient will be assigned the 
same treatment as the subject/patient he or she replaces (Parts A, B, and C).
8. DEFINITION OF ANALYSIS POPULATIONS
Safety analyses will be conducted for all enrolled patients/subjects, whether or not they 
completed all protocol requirements.


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PK/PD analyses (CGRP target engagement) will be conducted on data from all patients/subjects 
who receive at least 1 dose of the study drug and have evaluable data.
Clinical activity and PD analyses will be conducted for all patients with psoriasis who receive 
the study drug (Part C only).
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 prior to 
database lock and unblinding.  Details of subject assignment to the analysis populations will be 
listed.
9. STATISTICAL METHODOLOGY
9.1
General
Data listings will be provided for all data in the database. 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, 
minimum, maximum, and number of data points (N). For log-normal data, the geometric mean 
and geometric coefficient of variation (CV%) will also be presented. For categorical data, 
frequency counts 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 timepoint. 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.
Data analysis will be performed using SAS® Version 9.4 or greater.
9.2
Demographics and Subject Disposition
Subject/patient disposition will be listed. The demographic variables age, sex, race, ethnicity,
country of enrolment, site ID, body weight, height and body mass index will be summarized and 
listed.  
Furthermore, baseline disease characteristics (Psoriasis Area and Severity Index [PASI] score, 
static Physician Global Assessment [sPGA], and the percent total body surface area [BSA] of 
psoriasis) for  patients in Part C will also be summarized and listed.


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9.3
Pharmacokinetic Assessment
9.3.1 Pharmacokinetic Analysis
The PK analysis and any associated TFLs will be the responsibility of Eli Lilly and Company.  
Pharmacokinetic parameter estimates for LY3316531 will be calculated using standard 
noncompartmental methods, and the primary parameters will be Cmax and AUC of LY3316531.  
Refer to Section 10.3.2.1 of the protocol for additional details. 
9.4
Pharmacodynamic Assessment
9.4.1
Pharmacodynamic Analysis
The sPGA, PASI, and percent BSA are considered PD (efficacy) measures of disease activity in 
this study.  Table 2 includes the description and derivation of the efficacy outcomes.


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Table 2
Description and Derivation of Efficacy Outcomes (PD measures)
Measure
Description
Variable
Derivation / Comment
Imputation 
Approach if 
with Missing 
Components
sPGA
Static Physician Global 
Assessment (sPGA): the 
physician’s global 
assessment of the 
patient’s psoriasis (Ps) 
lesions at a given time 
point (European 
Medicines Agency 
[EMA] 2004).  Plaques 
are assessed for 
induration, erythema, 
and scaling, and an 
overall rating of
psoriasis severity is 
given using the anchors 
of clear (0), minimal (1), 
mild (2), moderate (3), 
severe (4), or very 
severe (5).  
sPGA (0) 
Score is clear (0)
Single item, 
missing if 
missing
sPGA (0,1)
Score is clear or minimal (0 or 1)
Single item, 
missing if 
missing
PASI
Psoriasis Area and 
Severity Index (PASI): 
combines assessments 
of the extent of body-
surface involvement in 4 
anatomical regions 
(head and neck, trunk, 
arms, and legs) and the 
severity of scaling (S), 
redness (R), and plaque 
induration/infiltration 
(thickness, T) in each 
region, yielding an 
overall score of 0 for no
psoriasis to 72 for the 
PASI 75
A clinically meaningful response; at least 
a 75% improvement in PASI score from 
baseline
Missing if 
baseline or 
observed 
value is 
missing
PASI 90
Higher level of clearance; at least a 90% 
improvement in PASI score from 
baseline
Missing if 
baseline or 
observed 
value is 
missing
PASI 100
Complete resolution of plaque Ps; a 
100% improvement in PASI score from 
baseline
Missing if 
baseline or 
observed 
value is 
missing


 
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Measure 
Description 
Variable 
Derivation / Comment 
Imputation 
Approach if 
with Missing 
Components 
most severe disease 
(Fredriksson and 
Pettersson 1978).   
Severity is rated for 
each index (R, S, T) on 
a 0-4 scale (0 for no 
involvement up to 4 for 
very severe 
involvement): 
0 = none 
1 = slight 
2 = moderate 
3 = severe 
4 = very severe 
The body is divided into 
four anatomical regions 
comprising the head (h), 
upper limb (u), trunk (t), 
and lower limb (l).  In 
each of these areas, the 
fraction of total body 
surface area affected is 
graded on a 0-6 scale (0 
for no involvement; up 
to 6 for 90% - 100% 
involvement):   
0 = 0% (clear) 
1 = >0% to <10% 
2 = 10% to <30% 
3 = 30% to <50% 
4 = 50% to <70% 
5 = 70% to <90% 
6 = 90% to 100% 
 
The various body 
regions are weighted to 
reflect their respective 
proportion of body 
surface area.   
PASI total 
score 
Sum the 3 scores for each body region to 
give a lesion score sum. 
Multiply the lesion score sum by the area 
score, for each body region to give 4 
individual subtotals. 
Multiply each of the subtotals by amount 
of body surface area represented by that 
region, i.e., x 0.1 for head, x 0.2 for 
upper body, x 0.3 for trunk, and x 0.4 for 
lower limbs. 
Add together each of the scores for each 
body region to give the final PASI score. 
Missing if 
baseline or 
observed 
value is 
missing 
PASI change 
from baseline 
Calculated as:  observed PASI – baseline 
PASI 
Missing if 
baseline or 
observed 
value is 
missing 
PASI percent 
improvement 
from baseline 
Calculated as:   
ܲ݁ݎܿ݁݊ݐ݅݉݌ݎ݋ݒ݁݉݁݊ݐ݂ݎ݋݉ ܾܽݏ݈݁݅݊݁ 
ൌ  
100 ൈ
஻௔௦௘௟௜௡௘ ௉஺ௌூିை௕௦௘௥௩௘ௗ ௉஺ௌூ
஻௔௦௘௟௜௡௘ ௉஺ௌூ
   
 
If a patient has experienced an 
improvement, this measure will be 
positive.  If a patient has experienced a 
worsening in the condition, this measure 
will be negative.   
Missing if 
baseline or 
observed 
value is 
missing 
BSA 
 
Percentage of Body 
Surface Area (BSA):  
The investigator will 
BSA 
Collected as a single scale as part of 
PASI electronic case report form (eCRF) 
page.  Range from 0% to 100%. 
Single item, 
missing if 
missing 


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Measure
Description
Variable
Derivation / Comment
Imputation 
Approach if 
with Missing 
Components
evaluate the percentage 
involvement of psoriasis 
on each patient’s BSA 
on a continuous scale 
from 0% (no 
involvement) to 100% 
(full involvement), in 
which 1% corresponds 
to the size of the 
patient’s hand 
(including the palm, 
fingers, and thumb) 
(National Psoriasis 
Foundation [NPF] 
2009).
BSA change 
from baseline
Calculated as:  observed BSA – baseline 
BSA 
Missing if 
baseline or 
observed 
value is 
missing
9.4.1.1
Static Physicians Global Assessment (sPGA)
The proportion of patients who achieve sPGA (0,1) and sPGA (0) will be summarized over time 
using descriptive statistics.  A by-patient listing of sPGA scores and response rates will be 
provided.  The listing will include patient number, treatment, timepoint, sPGA score and the 
sPGA response.    
9.4.1.2
Psoriasis Area Severity Index (PASI)
The proportion of patients who achieve PASI 75 (at least a 75% improvement from baseline in 
PASI score), PASI 90 (at least a 90% improvement from baseline in PASI score) and PASI 100 
(a 100% improvement from baseline in PASI score) will be summarized over time using 
descriptive statistics.  In addition, the change from baseline and percent improvement from 
baseline will be summarized over time using descriptive statistics.  A by-patient listing of PASI 
will be provided.  The listing will include patient number, treatment, timepoint, PASI total score, 
change from baseline, percent improvement and the PASI response.  
9.4.1.3
Percentage of Body Surface Area (%BSA) Assessment
The change from baseline in the %BSA will be summarized over time using descriptive 
statistics.  A by-patient listing of %BSA will be provided.  The listing will include patient 
number, treatment, timepoint, %BSA and change from baseline in the %BSA.   
9.4.1.4
Target Engagement Assay (Total Calcitonin Gene-Related Peptide [CGRP])
Total CGRP data and its change from baseline (Day 1 predose) will be summarized by treatment 
and listed.


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9.4.1.5
High Sensitivity-C Reactive Protein(HS-CRP)
HS-CRP data and its change from baseline(Day 1 predose)will be summarized by treatment and 
listed.
9.4.2
Pharmacodynamic Statistical Methodology
The PD biomarkers will be summarized by treatment and timepoint, and listed.  The changes 
from baseline, and absolute percentage change from baseline, will also be summarized.  Figures 
of mean valuesand mean changes from baseline will be presented by treatment.  Individual 
profiles will also be plotted over time.
Analyses of PK-PD relationships will be the responsibility of Eli Lilly and Company.  Refer to 
Section 10.3.3.1 of the protocol for additional details.  
9.5
Safety and Tolerability Assessments
9.5.1Adverse 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 consentand is ongoing at consent. A non-treatment emergent AE is 
defined as an AE which startsafter informed consent but prior to dosing. A treatment-emergent
AE is defined as an AE which occurs postdose or which is present prior to dosing and becomes 
more severe postdose. AEsby day of onset will be presentedfor Part B.
All AEs will be listed.  Treatment-emergentAEs will be summarized by treatment, severity and 
relationship to the study drug. The frequency (the number of AEs, the number of subjects 
experiencing an AEand the percentage of subjects experiencing an AE) of treatment-emergent 
AEswill be summarized by treatment, Medical Dictionary for Regulatory Activities (MedDRA)
version 20.0system organ class and preferred term. The summary and frequency AEtables will 
be presented for all causalities and those considered related to the study drug.Any serious AEs
will be tabulated.
9.5.2Concomitant medication
CCI
Concomitant medication will be coded using the WHO drug dictionary (Version March 2017).
Concomitant medication will be listed.


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9.5.3Clinical laboratory parameters
Allclinical chemistry andhematologydatawill be summarizedby parameter and treatment, and 
listed.Urinalysis data will be listed.Additionally clinical chemistry, hematologyand 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.
9.5.4Vital 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 by treatment will be presented by treatment. 
Furthermore, values for individual subjects will be listed.
9.5.5Electrocardiogram (ECG)
The ECG data will be obtained directly from the 12-lead ECG traces.  These data include the PR, 
QT, QTcB intervals, QRS duration and heart rate, where QTcB is the QT interval corrected using 
Bazett’s formula. In addition, QTcF (the QT interval corrected using Fridericia’s formula) will 
be calculated as follows:
 

3 60HR
QT
QTcF
CCI
The ECG data will be summarized by treatment together with changes from baseline, where 
baseline is defined as Day 1 predose. Figures of mean ECG data and mean changes from 
baselinewill be presented by treatment. The frequency of subjects with a maximum increase 
from baseline in QTcB and QTcF interval will be summarized for each treatment according to 
the following categories: >30ms and >60ms. In addition, the frequency of subjects with QTcB 
and QTcF postdose values, according to the following categories: >450 ms, >480 ms and >500 
ms, will be summarized by treatment.
A plasma LY3316531concentration-QT analysis will be performed to assess the changes from
baseline (Day 1 predose) QTcF interval relative to plasma LY3316531concentrations across all
active treatments. The change from baseline adjustment will be based on individual subject’s
Day 1 predose value. The analysis will be performed by plotting change from baseline QTcF
against LY3316531concentrations, including all post Day 1 dosing timepoints.The plot will be
produced separately forpartsA, B, and C of the study. Eachplot will include a simple linear 
regression.


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9.5.9
Immunogenicity 
Immunogenicity data will be listed and frequency tables will be presented.  The frequency of 
treatment-emergent ADAs will also be calculated. Treatment-emergent ADAs are those that are 
induced or boosted by exposure to study drug, with a 4-fold increase in titer compared to 
baseline if ADAs were detected at baseline or a titer 2-fold greater thanthe minimum required 
dilution (1:40) if no ADAs were detected at baseline.
To show the association of treatment-emergent ADAs with AEs, the frequency of 
treatment-emergent ADAs will be presented by MedDRA preferred term.  Relationship between 
the presence of antibodies and the PK parameters of LY3316531may be assessed graphically.
9.5.10
Hepatic Monitoring
If a 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 will be performed to confirm the abnormality.  
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 a 
magnetic resonance elastography (MRE) scan and biopsy assessment will be listed, if performed.
Hepatic risk factor assessment data will be listed.  Liver related signs and symptomsdata will be 
summarizedby treatment and listed. 
9.5.11
Columbia Suicide Severity Rating Scale(C-SSRS)
The C-SSRS data will be listed.
9.5.12
Patient's Global Assessment of Psoriasis (PatGA)and Psoriasis Symptom Scale
The data will be listed and summarized by treatment.
9.5.13
Biopsy Assessment
CCI
The biopsy assessment data will be listed.


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9.5.14
Other assessments
All other safety assessments not detailed in this section will be listed but not summarized or 
statistically analysed.
9.5.15
Safety and Tolerability Statistical Methodology
No inferential statistical analyses are planned.
10.
INTERIM ANALYSES
An interim analysis will occur when all patients/subjects in Parts A, B, and C have completed all 
requirements stated in the Schedule of Activities (Section 2; up to Day 85 for Part A, up to Day 
141 for Part B, and up to Day 113 for Part C) or discontinued early from the study. Lilly 
employees and employees of any third-party organization involved in the interpretation of data 
collected during the study are authorized to evaluate unblinded data for the interim analyses. 
This interim analysis will include all planned analyses of available data. The data will be used 
for the development of a CSR. Results that are not available at the time the CSR is developed 
can be provided in a separate report or CSR addendum. 
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 
values should be reported as whole numbers. Median values should be treated as observed 
quantities 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.


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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.”


PPD
Leo Document ID = 862516ca-17c0-465d-b0f5-863b5011ba9d
Approver: 
Approval Date & Time: 31-Jan-2018 10:10:31 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 31-Jan-2018 11:44:42 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 31-Jan-2018 23:33:53 GMT
Signature meaning: Approved
PPD
PPD