Conditions: Psoriasis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 32
Healthy volunteers: no

Brief summary:
The purpose of the study is to research how much ixekizumab enters the bloodstream and how long the body takes to get rid of the drug and the safety of ixekizumab and any side effects that might be associated with it. The study has two parts: A single-dose part and multiple-dose part. The single dose part of this study will last up to 24 weeks, including the screening period. The multiple dose part of this study will last up to 32 weeks including the screening period.

Detailed description:

Arms:
arm 1: Participants received single dose of 80mg Ixekizumab by subcutaneous injection. arm 2: Participants received multiple doses of Ixekizumab starting with 160mg initial dose followed by 80mg every two weeks (Q2W) by subcutaneous injection. arm 3: Participants received multiple doses of 80mg Ixekizumab starting with 160mg initial dose followed by 80mg every four weeks (Q4W) by subcutaneous injection.

Interventions: intervention 1: Ixekizumab
Intervention descriptions: intervention 1: Administered as subcutaneous (SC) injection

Protocol document:
Prot_000.pdf: 
 
I1F-MC-RHBN(c) Protocol 
 
 
A Phase 1, Single- and Multiple-Dose Study to Assess the Safety and Pharmacokinetics of 
Ixekizumab (LY2439821) (Anti–IL-17 Humanized Antibody) in Chinese Patients with Psoriasis 
Vulgaris 
 
NCT03073213 
 
Approval Date: 20-Jun-2017 
 
 


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1. Protocol I1F-MC-RHBN(c)
A Phase 1, Single- and Multiple-Dose Study to Assess the 
Safety and Pharmacokinetics of Ixekizumab (LY2439821) 
(Anti–IL-17 Humanized Antibody) in
Chinese Patients with Psoriasis Vulgaris
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 
ixekizumab (LY2439821), unless such persons are bound by a confidentiality agreement 
with Eli Lilly and Company or its subsidiaries.  
Note to Regulatory Authorities:  This document may contain protected personal data 
and/or commercially confidential information exempt from public disclosure.  Eli Lilly and 
Company requests consultation regarding release/redaction prior to any public release.  In 
the United States, this document is subject to Freedom of Information Act (FOIA) 
Exemption 4 and may not be reproduced or otherwise disseminated without the written 
approval of Eli Lilly and Company or its subsidiaries.
Ixekizumab (LY2439821)
A Phase 1, multicenter, open-label, single- and multiple-dose study of ixekizumab in 
approximately 45 patients with moderate to severe psoriasis vulgaris. Patients in the 
single-dose phase will receive ixekizumab 80 mg subcutaneously (SC) followed by a 
20-week observation period.  Patients in the multiple-dose phase will receive a starting 
dose of ixekizumab 160 mg SC and will then be randomized to 2 treatment arms (80 mg 
SC every 2 weeks [Q2W] or every 4 weeks [Q4W]) for an 8-week treatment period,
followed by an additional 20-week observation period.  
Eli Lilly and Company
Indianapolis, Indiana USA 46285
Clinical Pharmacology Protocol Electronically Signed and Approved by Lilly:
10 May 2016
Amendment (a) Electronically Signed and Approved by Lilly: 22 July 2016
Amendment (b) Electronically Signed and Approved by Lilly:  23 November 2016
Amendment (c) Electronically Signed and Approved by Lilly on approval date provided 
below.
Approval Date: 20-Jun-2017 GMT


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2. Synopsis
Clinical Pharmacology Protocol Synopsis:  Study I1F-MC-RHBN
Name of Investigational Product:  Ixekizumab (LY2439821)
Title of Study:  A Phase 1, Single- and Multiple-Dose Study to Assess the Safety and Pharmacokinetics of 
Ixekizumab (LY2439821) (Anti–IL-17 Humanized Antibody) in Chinese Patients with Psoriasis Vulgaris
Number of Planned Patients:  
Single-dose phase:  
Enrolled:  up to 15 patients
Planned to complete:  8 patients
Multiple-dose phase:
Enrolled:  up to 30 patients
Planned to complete:  every 2 weeks (Q2W) = 10 patients; every 4 weeks 
(Q4W) = 10 patients
Phase of Development:  1
Length of Study:  single-dose phase = 20 weeks; multiple-dose phase = 28 weeks
Objectives:  The primary objective of this study is to assess the pharmacokinetics (PK) of ixekizumab after single 
and multiple subcutaneous (SC) doses in Chinese patients with psoriasis.
The secondary objective of this study is as follows:
•
to assess the safety, tolerability, and immunogenicity of ixekizumab in Chinese patients with psoriasis.
The exploratory objective of this study is as follows:
•
to assess the efficacy endpoints of Psoriasis Area and Severity Index (PASI) and static Physician’s Global 
Assessment (sPGA) of ixekizumab after single and multiple SC doses in Chinese patients with psoriasis.
Study Design:  Study RHBN is an open-label, multiple-site study.  
Diagnosis and Main Criteria for Inclusion and Exclusion:  This study will enroll male or female patients aged 
18 years or older who have chronic plaque psoriasis based on a confirmed diagnosis of moderate to severe chronic 
psoriasis vulgaris for at least 6 months before baseline, are candidates for phototherapy and/or systemic therapy, 
and have 10% body surface area (BSA) involvement, an sPGA score 3, and a PASI score 12 at screening and 
baseline.
Dosage and Mode of Administration:   
Single-dose phase:  80 mg SC
Multiple-dose phase:  160 mg SC starting dose for all patients.  Patients will then be randomized to receive either 
80 mg SC Q2W or 80 mg SC Q4W.  
Planned Duration of Treatment:  Single-dose phase: 1 80 mg SC
Multiple-dose phase:  160 mg SC starting dose followed by 80 mg SC Q2W or 80 mg SC Q4W for 8 weeks.
Criteria for Evaluation:  
Safety:  Safety endpoints will include adverse events (AEs), clinical laboratory testing (eg, hematology, clinical 
chemistry, and urinalysis), electrocardiogram (ECG) monitoring, and physical examinations.
Bioanalytical: Serum will be collected at selected visits to determine concentration of ixekizumab.
Pharmacokinetic: Ixekizumab concentration versus time profile.
Pharmacodynamic: PASI, sPGA.
Immunogenicity: Anti-ixekizumab antibodies will be assessed at selected visits.  
Evaluation Methods:  
Safety:  Descriptive statistical methods will be employed to analyze clinical safety parameters.
Bioanalytical: Serum concentrations of ixekizumab will be assayed using validated enzyme-linked immunosorbent 
assay.
Pharmacokinetic: Pharmacokinetic parameter estimates for ixekizumab will be calculated by standard 
noncompartmental methods of analysis.  The PK parameters for estimation will include maximum observed drug 
concentration (Cmax), time to Cmax, area under the concentration versus time curve (AUC), terminal half-life, 
apparent clearance, and apparent volume of distribution.
Pharmacodynamic:  Descriptive statistics of pharmacodynamic (PD) parameters will be presented at each 
scheduled time point.


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3. Table of Contents
Protocol I1F-MC-RHBN 
A Phase 1, Single- and Multiple-Dose Study to Assess the 
Safety and Pharmacokinetics of Ixekizumab (LY2439821) 
(Anti–IL-17 Humanized Antibody) in 
Chinese Patients with Psoriasis Vulgaris
Section
Page
1.
Protocol I1F-MC-RHBN(c) A Phase 1, Single- and Multiple-Dose 
Study to Assess the Safety and Pharmacokinetics of Ixekizumab 
(LY2439821) (Anti–IL-17 Humanized Antibody) in Chinese Patients 
with Psoriasis Vulgaris........................................................................................................1
2.
Synopsis .............................................................................................................................2
3.
Table of Contents................................................................................................................3
4.
Abbreviations and Definitions.............................................................................................9
5.
Introduction ......................................................................................................................13
5.1.
General Introduction ....................................................................................................13
5.2.
Rationale and Justification for the Study ......................................................................14
6.
Objectives.........................................................................................................................15
6.1.
Primary Objective ........................................................................................................15
6.2.
Secondary Objective ....................................................................................................15
6.3.
Exploratory Objective ..................................................................................................15
7.
Investigational Plan...........................................................................................................16
7.1.
Summary of Study Design............................................................................................16
7.2.
Discussion of Design and Control ................................................................................16
7.3.
End of Study ................................................................................................................17
8.
Study Population...............................................................................................................18
8.1.
Criteria for Enrollment .................................................................................................18
8.1.1.
Inclusion Criteria .................................................................................................18
8.1.2.
Exclusion Criteria ................................................................................................19
8.1.3.
Rationale for Exclusion of Certain Study Candidates ...........................................24
8.2.
Discontinuation............................................................................................................24
8.2.1.
Discontinuation of Patients...................................................................................24
8.2.1.1.
Patients Inadvertently Enrolled .......................................................................24
8.2.1.2.
Discontinuations from Investigational Product or from 
the Study ........................................................................................................25


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8.2.2.
Discontinuation of Study Sites .............................................................................26
8.2.3.
Discontinuation of the Study................................................................................26
9.
Treatment..........................................................................................................................27
9.1.
Treatment Materials and Supplies.................................................................................27
9.1.1.
Packaging, Preparation, Labeling, and Storage.....................................................27
9.2.
Treatment Administration ............................................................................................27
9.3.
Rationale for Selection of Dose....................................................................................28
9.4.
Specific Restrictions/Requirements ..............................................................................29
9.4.1.
Special Treatment Considerations ........................................................................30
9.5.
Blinding .......................................................................................................................30
9.6.
Concomitant Therapy...................................................................................................31
10.
Sample Collection and Safety Data Collection ..................................................................33
10.1. Laboratory Samples .....................................................................................................33
10.2. Samples for Pharmacokinetic and Pharmacodynamic Evaluations................................33
10.2.1.
Pharmacokinetic Samples.....................................................................................33
10.2.2.
Bioanalysis...........................................................................................................33
10.2.3.
Pharmacodynamic Clinical Outcome Measures....................................................34
10.3. Samples for Immunogenicity Research.........................................................................34
10.4. Safety Evaluations........................................................................................................34
10.4.1.
Adverse Events ....................................................................................................35
10.4.2.
Serious Adverse Events........................................................................................35
10.4.2.1.
Suspected Unexpected Serious Adverse Reactions..........................................36
10.4.3.
Other Safety Measures .........................................................................................37
10.4.3.1.
Physical Examination .....................................................................................37
10.4.3.2.
Vital Signs......................................................................................................37
10.4.3.3.
Body Weight ..................................................................................................37
10.4.3.4.
Electrocardiograms.........................................................................................37
10.4.3.5.
Chest X-Ray and Tuberculosis Testing ...........................................................37
10.4.3.6.
Quick Inventory of Depressive Symptomatology–Self 
Report, 16 item...............................................................................................38
10.4.3.7.
Columbia-Suicide Severity Rating Scale.........................................................38
10.4.4.
Safety Monitoring ................................................................................................39
10.4.5.
Complaint Handling.............................................................................................39
10.5. Appropriateness and Consistency of Measurements......................................................40
10.6. Compliance..................................................................................................................40
11.
Sample Size and Analyses Methods ..................................................................................41
11.1. Determination of Sample Size ......................................................................................41
11.2. Data Analysis Plans......................................................................................................41


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11.2.1.
General Considerations ........................................................................................41
11.2.2.
Study Participant Disposition ...............................................................................41
11.2.3.
Study Participant Characteristics ..........................................................................41
11.2.4.
Pharmacokinetic Analyses....................................................................................42
11.2.5.
Pharmacodynamic Analyses.................................................................................42
11.2.5.1.
Pharmacodynamic Parameter Estimation ........................................................42
11.2.5.2.
Pharmacodynamic Statistical Inference...........................................................42
11.2.6.
Pharmacokinetic/Pharmacodynamic Analyses......................................................42
11.2.7.
Safety Analyses....................................................................................................42
11.2.7.1.
Clinical Evaluation of Safety..........................................................................42
11.2.7.2.
Statistical Evaluation of Safety.......................................................................43
11.2.7.3.
Evaluation of Immunogenicity........................................................................43
11.3. Interim Analyses ..........................................................................................................43
12.
Data Management Methods...............................................................................................44
12.1. Data Quality Assurance................................................................................................44
12.2. Data Capture Systems ..................................................................................................44
12.2.1.
Source Data and Case Report Form......................................................................44
12.2.2.
Ancillary Data......................................................................................................45
13.
Informed Consent, Ethical Review, and Regulatory Considerations ..................................46
13.1. Informed Consent.........................................................................................................46
13.2. Ethical Review.............................................................................................................46
13.3. Regulatory Considerations ...........................................................................................46
13.3.1.
Investigator Information.......................................................................................47
13.3.2.
Protocol Signatures ..............................................................................................47
13.3.3.
Final Report Signature .........................................................................................47
14.
References ........................................................................................................................48


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List of Tables
Table
Page
Table RHBN.1.
Margin of Safety for Administration of Ixekizumab to Humans 
Based on Exposure at the NOAEL and LOAEL in Monkeys ..................29


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List of Figures
Figure
Page
Figure RHBN.1.
Study design for the single-dose phase of Study I1F-MC-RHBN............17
Figure RHBN.2.
Study design for multiple-dose phase of Study I1F-MC-RHBN. .............17


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List of Attachments
Attachment
Page
Attachment 1.
Protocol RHBN Study Schedule—
Single-Dose Phase..................................................................................50
Attachment 2.
Protocol RHBN Study Schedule—
Multiple-Dose Phase ..............................................................................53
Attachment 3.
Protocol RHBN Clinical Laboratory Tests..............................................57
Attachment 4.
Protocol RHBN Blood Sampling Summary ............................................59
Attachment 5.
Protocol Amendment I1F-MC-RHBN(c) Summary 
A Phase 1, Single- and Multiple-Dose Study to Assess the Safety 
and Pharmacokinetics of Ixekizumab (LY2439821) (Anti–IL-17 
Humanized Antibody) in
Chinese Patients with Psoriasis Vulgaris.................................................60


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4. Abbreviations and Definitions
Term
Definition
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.
ALT
alanine aminotransferase
AST
aspartate aminotransferase
AUC
area under the concentration versus time curve
audit
A systematic and independent examination of the trial-related activities and documents to 
determine whether the evaluated trial-related activities were conducted, and the data were
recorded, analyzed, and accurately reported according to the protocol, sponsor’s standard 
operating procedures (SOPs), good clinical practice (GCP), and the applicable regulatory 
requirement(s).
BCG
Bacillus Calmette-Guérin
BMI
body mass index
BP
blood pressure
BSA
body surface area
Cmax
maximum observed drug concentration
complaint
A complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, purity, durability, reliability, safety or effectiveness, or 
performance of a drug or drug delivery system.
compliance
Adherence to all the trial-related requirements, good clinical practice (GCP) requirements, 
and the applicable regulatory requirements.
confirmation
A process used to confirm that laboratory test results meet the quality requirements defined 
by the laboratory generating the data and that Lilly is confident that results are accurate.  
Confirmation will either occur immediately after initial testing or will require that samples 
be held to be retested at some defined time point, depending on the steps required to obtain 
confirmed results.
CRF/eCRF
case report form/electronic case report form:  Sometimes referred to as clinical report form.  
A printed or electronic form for recording study participants’ data during a clinical study, as 
required by the protocol.
CRP/CRS
clinical research physician/clinical research scientist:  Individual responsible for the medical 
conduct of the study.  Responsibilities of the CRP may be performed by a physician, CRS, 
global safety physician, or other medical officer.


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CSE
clinically significant event:  A moderate to severe adverse event (AE), abnormal clinical 
sign, or clinical laboratory finding that may pose a risk to the well-being of the subject.
C-SSRS
Columbia-Suicide Severity Rating Scale
CTCAE
Common Terminology Criteria for Adverse Events
ECG
electrocardiogram
EMA
European Medicines Agency
end of trial (study)
End of trial is the date of the last visit or last scheduled procedure shown in the study 
schedule for the last patient.
enroll
The act of assigning a patient to a treatment.  Patients who are enrolled in the trial are those 
who have been assigned to a treatment.
enter
Patients entered into a trial are those who sign the informed consent form (ICF) directly or 
through their legally acceptable representatives.
ERB/IRB
ethical review board/institutional review board:  A board or committee (institutional, 
regional, or national) composed of medical professionals and nonmedical members whose 
responsibility is to verify that the safety, welfare, and human rights of the patients
participating in a clinical trial are protected.
FSH
follicle-stimulating hormone
GCP
good clinical practice:  A standard for the design, conduct, performance, monitoring, 
auditing, recording, analyses, and reporting of clinical trials that provides assurance that the 
data and reported results are credible and accurate, and that the rights, integrity, and 
confidentiality of trial subjects are protected.
HCV
hepatitis C virus
HIV
human immunodeficiency virus
IB
Investigator’s Brochure:  A compilation of the clinical and nonclinical data on the 
investigational product(s) which is relevant to the study of the investigational product(s) in 
human subjects.
ICF
informed consent form
ICH
International Conference on Harmonisation
informed consent
A process by which a patient voluntarily confirms his or her willingness to participate in a 
particular trial, after having been informed of all aspects of the trial that are relevant to the 
patient’s decision to participate. Informed consent is documented by means of a written, 
signed, and dated informed consent form (ICF).  
investigational 
product
A pharmaceutical form of an active ingredient or placebo being tested or used as a reference 
in a clinical trial.


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investigator
A person responsible for the conduct of the clinical trial at a trial site.  If a trial is conducted 
by a team of individuals at a trial site, the investigator is the responsible leader of the team 
and may be called the principal investigator.
IL
interleukin
IV
intravenous
LTBI
latent tuberculosis infection
MAb
monoclonal antibody
MI
myocardial infarction
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
patient
A study participant who has the disease or condition for which the investigational product is 
targeted.
PD
pharmacodynamic(s)
PK
pharmacokinetic(s)
PPD
purified protein derivative
PUVA
psoralens and ultraviolet A
Q2W
every 2 weeks
Q4W
every 4 weeks
QIDS-SR16
Quick Inventory of Depressive Symptomatology–Self Report, 16 item
QTF
QuantiFERON®-TB Gold test
randomize
The process of assigning subjects to an experimental group according to the randomization 
schedule for the trial.
rescreen
To screen a subject who was previously declared a screen failure for the same study.
SAE
serious adverse event:  Any untoward medical occurrence that at any dose results in death, 
is life threatening, requires inpatient hospitalization or prolongation of existing 
hospitalization, results in persistent or significant disability/incapacity, or is a congenital 
anomaly/birth defect.
SC
subcutaneous


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screen
The act of determining if an individual meets minimum requirements to become part of a 
pool of potential candidates for participation in a clinical trial.  In this study, screening 
involves invasive or diagnostic procedures and/or tests (for example, blood draws).  For this 
type of screening, informed consent for these screening procedures and/or tests shall be 
obtained; this consent may be separate from obtaining consent for the study.
sPGA
static Physician’s Global Assessment
subject
An individual who is or becomes a participant in clinical research, either as a recipient of 
the investigational product(s) or as a control.  A subject may be either a healthy human or a 
patient.
SUSAR
suspected unexpected serious adverse reaction
TB
tuberculosis
TEAE
treatment-emergent adverse event
TPO
third-party organization
T-SPOT
T-SPOT®.TB test 
ULN
upper limit of normal
US-FDA
United States Food and Drug Administration
WBC
white blood cell


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Protocol I1F-MC-RHBN:  A Phase 1, Single- and Multiple-
Dose Study to Assess the Safety and Pharmacokinetics of 
Ixekizumab (LY2439821) (Anti–IL-17 Humanized Antibody) in 
Chinese Patients with Psoriasis Vulgaris
5. Introduction
5.1.
General Introduction
Psoriasis is a common, lifelong, and life-shortening chronic inflammatory skin disease 
manifested by prototypic red, thick, and scaly plaques.  Psoriasis vulgaris or plaque psoriasis 
(hereafter psoriasis) is the most common form and has been shown to have a significant impact 
on the overall health of patients, including an association with inflammatory arthritis in the form 
of psoriatic arthritis.  Psoriasis is associated with increased risk for multiple comorbid 
conditions, including myocardial infarction (MI) and stroke, metabolic syndrome, diabetes 
mellitus, chronic renal insufficiency, and liver abnormalities (Yeung et al. 2013).  
The worldwide prevalence of psoriasis is 2% to 3% (Christophers 2001; International Federation 
of Psoriasis Associations [IFPA] 2014 [WWW]), with rates varying across ethnic groups and 
geographic regions (Chandran and Raychaudhuri 2010; Parisi et al. 2013). A recent population-
based and dermatologist-confirmed study showed that the prevalence of psoriasis in China is 
0.47%, higher than the incidence of 0.12% observed in a 1987 study, which may mean it is 
increasing (Ding et al. 2012). 
Ixekizumab (LY2439821) was approved in March 2016 for the treatment of moderate-to-severe 
psoriasis in adults by the United States Food and Drug Administration (US-FDA).  Ixekizumab 
(LY2439821) is a humanized immunoglobulin G subclass 4 (IgG4) monoclonal antibody (MAb)
designed and engineered to selectively inhibit interleukin-17A (IL-17A). Psoriasis is an IL-17A-
driven disease (Clark 2015).  Ixekizumab binds with high affinity (≤3 pM) and specificity to 
IL-17A, a proinflammatory cytokine.  Neutralization of IL-17A by ixekizumab has been shown 
to reduce excess keratinocyte proliferation and activation (Krueger et al. 2012).  Ixekizumab 
does not bind to ligands IL-17B, IL-17C, IL-17D, IL-17E, or IL-17F. 
The global clinical development program for ixekizumab for treatment of psoriasis included one 
Phase 1 study I1F-MC-RHAG [RHAG]; one Phase 2 study I1F-MC-RHAJ [RHAJ]; and three 
pivotal Phase 3 studies (I1F-MC-RHAZ [RHAZ], I1F-MC-RHBA [RHBA], and I1F-MC-RHBC 
[RHBC]).  A Phase 3, randomized, open-label, pharmacokinetics (PK) study (I1F-MC-RHBL; 
[RHBL]) compared the PK of ixekizumab administered via prefilled syringe and auto-injector
device.  Additionally, for the purposes of registration in Japan, in addition to participation in the 
global Phase 3 trial RHAZ, one Phase 3 open-label study (1IF-JE-RHAT; [RHAT]) determined 
the efficacy and safety of ixekizumab in Japanese patients diagnosed with plaque psoriasis or the 
more severe psoriasis subtype of erythrodermic and pustular psoriasis.  Additional details on 
each of these studies are located in the Investigator’s Brochure (IB).


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Results of a population PK analysis of data in patients with psoriasis from global studies show 
that ixekizumab exhibits linear PK over a dose range of 5 to 160 mg.  The mean elimination half-
life of ixekizumab after subcutaneous (SC) administration was approximately 13 days, and the 
time of maximum observed serum drug concentration (Cmax) occurred at approximately 4 to 
7 days.  These values are typical for MAbs in humans. Based on PK, efficacy, and safety 
evaluations, no dose adjustment of ixekizumab is recommended based on body weight, age, sex, 
and ethnic origin.
From global clinical trials, individual treatment-emergent adverse events (TEAEs) (preferred 
terms) that were reported at a significantly greater frequency in the total ixekizumab group than 
in the placebo group were injection site reaction, injection site erythema, nausea, and 
oropharyngeal pain.  Most TEAEs were mild or moderate in severity.  Overall, severe TEAEs 
were similar across the ixekizumab treatment groups compared with those of the placebo group.  
For the percentage of patients with at least 1 serious adverse event (SAE), there were no 
significant differences between the ixekizumab treatment groups and the placebo group.  
Approximately 2% of ixekizumab-treated patients discontinued because of adverse events (AEs), 
whereas approximately 1% of placebo-treated patients discontinued because of AEs.
More information about the known and expected benefits, risks, and reasonably anticipated AEs
may be found in the IB.  Information on AEs expected to be related to the investigational product
may be found in Section 7 (Development Core Safety Information) of the IB.  Information on 
SAEs expected in the study population independent of drug exposure and that will be assessed 
by the sponsor in aggregate periodically during the course of the study may be found in Section 6 
(Effects in Humans) of the IB.
The proposed study, Study I1F-MC-RHBN (RHBN), is a Phase 1, multicenter, single- and 
multiple-dose, open-label study in Chinese patients with moderate to severe psoriasis.  This 
study will assess the PK and safety of ixekizumab for the future development of ixekizumab in 
China.  The sponsor, monitor, and investigators will perform this study in compliance with the 
protocol, good clinical practice (GCP), International Conference on Harmonisation (ICH) 
guidelines, and applicable regulatory requirements.
5.2.
Rationale and Justification for the Study
The purpose of this study is to assess the PK and safety of ixekizumab in Chinese patients with 
moderate to severe psoriasis to enable the future development of ixekizumab in China. The PK
of ixekizumab in Chinese patients will be compared to the PK observed in non-Chinese patients 
from global studies.


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6. Objectives
6.1.
Primary Objective
The primary objective of this study is to assess the PK of ixekizumab after single and multiple 
SC doses in Chinese patients with psoriasis.
6.2.
Secondary Objective
The secondary objective of this study is as follows:

to assess the safety, tolerability, and immunogenicity of ixekizumab in 
Chinese patients with psoriasis.
6.3.
Exploratory Objective
The exploratory objective of this study is as follows:

to assess the efficacy endpoints of Psoriasis Area and Severity Index (PASI)
and static Physician’s Global Assessment (sPGA) of ixekizumab after single 
and multiple SC doses in Chinese patients with psoriasis.


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7. Investigational Plan
7.1.
Summary of Study Design
Study RHBN is a Phase 1, multicenter, open-label, single- and multiple-dose outpatient study in 
up to 45 patients with psoriasis.  This study will assess the safety, tolerability, and PK profile of 
ixekizumab 80 mg SC in Chinese patients since 80 mg SC is the maintenance dose used in 
Phase 3 global studies and is the planned dose for Phase 3 studies in China.  Ixekizumab was
evaluated as a 160 mg SC starting dose and as an 80 mg SC maintenance dose every 2 weeks 
(Q2W) or every 4 weeks (Q4W) in global Phase 3 studies for the treatment of psoriasis;
therefore, these dose regimens will be used for the multiple-dose phase in Study RHBN.  
For the single-dose phase, patients will receive a single dose of ixekizumab 80 mg SC on Day 1 
and will be assessed at regular visits for 20 weeks.  Patients completing the single-dose phase
have the option of enrolling in the multiple-dose phase after completing the final visit in the 
single-dose phase.  Patients will remain at the site for a minimum of 4 hours postdose.  
The multiple-dose phase can be initiated once 6 patients have completed the Week 6 (Day 43) 
visit in the single-dose phase and safety data collected through 6 weeks postdosing from these
patients have been reviewed.  After review of these safety data, an agreement on initiation of the 
multiple-dose phase will be made by the investigator and sponsor.
In the multiple-dose phase, patients will be administered a starting dose of ixekizumab 160 mg 
SC on Day 1 and will then be randomized into 1 of 2 dosing regimens for the 8-week treatment 
period:  (1) 80 mg SC Q2W or (2) 80 mg SC Q4W.  Patients will be assessed at regular visits for 
an additional 20 weeks. Patients will remain at the site for a minimum of 4 hours after the first 
dose and for 2 hours after subsequent doses.
Figure RHBN.1 and Figure RHBN.2 illustrate the study design for the single-dose phase and 
multiple-dose phase, respectively. The rationale for dose selection is described in Section 9.3.  
The Study Schedules (Attachment 1 and Attachment 2) detail the procedures and tests occurring 
at specific times throughout the study.  
7.2.
Discussion of Design and Control
The primary endpoint is the evaluation of PK of ixekizumab in Chinese patients with moderate 
to severe psoriasis; therefore, an open-label study design is considered appropriate.  The 
psoriasis population for this study will be patients with a minimum body surface area (BSA) 
involvement of 10%, a total PASI score of at least 12, and an sPGA score of 3, representative 
of the population likely to receive a biologic therapy. Additional patients may be added to a 
group if several patients discontinue treatment for reasons other than AEs possibly related to 
study drug. Safety and outcome measures during the follow-up period will allow detection and 
assessment of delayed effects, if any, that could result from treatment with ixekizumab.


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Abbreviations:  D = day; SC = subcutaneous; V = visit; W = week.
Note:  Patients who complete Visit 14 of the single-dose phase are eligible for 
participation in the multiple-dose phase.
Figure RHBN.1.
Study design for the single-dose phase of Study I1F-MC-RHBN.
Abbreviations:  D = day; Q2W = every 2 weeks; Q4W = every 4 weeks; SC = 
subcutaneous; V = visit; W = week.
Figure RHBN.2.
Study design for multiple-dose phase of Study I1F-MC-RHBN.  
7.3.
End of Study 
The end of the study is the date of the last visit or last scheduled procedure shown in the Study 
Schedule (Attachment 2) for the last patient.  


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8. Study Population
8.1.
Criteria for Enrollment
Eligibility of patients for study enrollment will be based on the results of a screening medical 
history, physical examination, vital signs, clinical laboratory tests, and electrocardiogram (ECG).  
The nature of any conditions present at the time of the physical examination and any preexisting 
conditions will be documented.
Screening may occur from 28 days up to 3 days prior to enrollment.  Patients who are not 
enrolled within 28 days of screening may be subjected to an additional medical assessment 
and/or clinical measurements to confirm their eligibility.
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened.  Individuals may be rescreened once.  The interval between rescreening should be at 
least 2 weeks.  If rescreening is performed, the individual must sign a new informed consent 
form (ICF) and will be assigned a new identification number.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, are not permitted.
8.1.1. Inclusion Criteria
Patients are eligible for enrollment in the study only if they meet all of the following criteria:
[1]
are male or female patients 18 years or older.
[1a] male patients:
will agree to use a reliable method of birth control and will not donate 
sperm during the study and for at least 3 months following the last dose 
of ixekizumab, whichever is longer.
Examples of reliable methods of birth control are condoms with 
spermicide, oral contraceptives, intrauterine device, and male 
sterilization.  
[1b] female patients:
are women of childbearing potential who test negative for pregnancy 
and agree to use a reliable method of birth control or remain abstinent 
during the study and for at least 3 months following the last dose of 
ixekizumab, whichever is longer.  Methods of contraception considered 
acceptable include oral contraceptives, contraceptive patch, intrauterine 
device, vaginal ring, diaphragm with contraceptive gel, or condom with 
contraceptive gel.
-or-
are women of nonchildbearing potential, defined as:


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women who have had surgical sterilization (hysterectomy, bilateral 
oophorectomy, or tubal ligation); 
-or-
women who are 60 years of age;
-or-
women 40 and <60 years of age who have had a cessation of 
menses for 12 months and a follicle-stimulating hormone (FSH) 
test confirming nonchildbearing potential (40 mIU/mL).
[2]
have a body mass index (BMI) between 18 and 35, inclusive.
[3]
present with chronic plaque psoriasis based on a confirmed diagnosis of 
chronic psoriasis vulgaris for at least 6 months before baseline (Week 0; 
Visit 2).
[4]
have 10% BSA involvement at screening (Visit 1) and baseline (Week 0; 
Visit 2).
[5]
have both an sPGA score of 3 and PASI score 12 at screening (Visit 1) and 
baseline (Week 0; Visit 2).
[6]
are candidates for phototherapy and/or systemic therapy at the discretion of 
the investigator.
[7]
have given written informed consent approved by Lilly or its designee and by 
the ethical review board (ERB)/institutional review board (IRB) governing the 
site.
8.1.2. Exclusion Criteria
Patients will be excluded from study enrollment if they meet any of the following criteria:
[8]
are investigator site personnel directly affiliated with this study and their 
immediate families.  Immediate family is defined as a spouse, parent, child, or 
sibling, whether biological or legally adopted.
[9]
are Lilly employees.
[10] are currently enrolled in a clinical trial involving an investigational product or 
off-label use of a drug or device, or are concurrently enrolled in any other type 
of medical research judged not to be scientifically or medically compatible 
with this study.
[11] have pustular, erythrodermic, and/or guttate forms of psoriasis.
[12] have a history of drug-induced psoriasis.
[13] had a clinically significant flare of psoriasis during the 12 weeks before 
baseline (Week 0; Visit 2).


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[14] have received systemic nonbiologic psoriasis therapy (including but not 
limited to oral psoralens and ultraviolet A [PUVA] light therapy,
cyclosporine, corticosteroids, methotrexate, oral retinoids, mycophenolate 
mofetil, thioguanine, hydroxyurea, sirolimus, azathioprine, fumaric acid 
derivatives, or 1, 25 dihydroxy vitamin D3 and analogues) or phototherapy 
(including either oral or topical PUVA light therapy, ultraviolet B, self-
treatment with tanning beds, or therapeutic sunbathing) within 4 weeks prior 
to baseline (Week 0; Visit 2) or have had topical psoriasis treatment 
(including but not limited to corticosteroids, anthralin, calcipotriene, topical 
vitamin D derivatives, retinoids, tazarotene, emollients, and other 
nonprescription topical products containing urea, >3% salicylic acid, or - or 
-hydroxyl acids), or medicated shampoos [for example those that contain 
>3% salicylic acid, corticosteroids, coal tar, or vitamin D3 analogues]) within 
the previous 2 weeks prior to baseline (Week 0; Visit 2).
Exceptions:  mild (for example, desonide) or least potent (for example, 
hydrocortisone) topical steroids will be permitted for use, limited to the face, 
axilla, and/or genitalia.  
[15] cannot avoid excessive sun exposure or use of tanning booths for at least 
4 weeks prior to baseline (Week 0; Visit 2) and during the study.
[16] current or recent use of any biologic agent within the following washout 
periods:  etanercept <28 days; infliximab, adalimumab, or alefacept <60 days; 
golimumab <90 days; ustekinumab <8 months; rituximab or efalizumab 
<12 months; or any other biologic agent <5 half-lives prior to baseline 
(Week 0; Visit 2).  
[17] have ever received natalizumab or other agents that target -4-integrin.
[18] have previously completed or withdrawn from this study, participated in any 
other study with ixekizumab, or have participated in any study investigating 
other IL-17 antagonists.
[19] have a known allergy or hypersensitivity to any biologic therapy that would 
pose an unacceptable risk to the patient if participating in this study.
[20] have had a live vaccination within 12 weeks prior to baseline (Week 0; 
Visit 2), intend to have a live vaccination during the study or within 
12 months of completing treatment in this study, or have participated in a 
vaccine clinical study within 12 weeks prior to baseline.  Investigators should 
review the vaccination status of their patients and follow the local guidelines
for adult vaccination with nonlive vaccines intended to prevent infectious 
disease prior to therapy.  
(Note:  Killed/inactive vaccines are expected to be safe.)  


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[21] had a vaccination with Bacillus Calmette-Guérin (BCG) within 12 months 
prior to baseline (Week 0; Visit 2) or intend to have this vaccination with 
BCG during the study or within 12 months of completing treatment in this 
study.
[22] had any major surgery within 8 weeks prior to baseline (Week 0; Visit 2) or 
will require such during the study that, in the opinion of the investigator in 
consultation with Lilly or its designee, would pose an unacceptable risk to the 
patient.  
[23] have current or a history of lymphoproliferative disease; or signs or symptoms 
of lymphoproliferative disease; or have active or history of malignant disease.  
(Note:  Patients with successfully treated basal cell carcinoma [no more 
than 3 treatments for removal of basal cell carcinoma], squamous cell 
carcinoma of the skin, or cervical carcinoma in situ, with no evidence of 
recurrence within the 5 years prior to baseline [Week 0; Visit 2] may 
participate in the study.)
[24] have the presence of significant uncontrolled cerebrocardiovascular disorder 
(for example, MI, unstable angina, unstable arterial 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 disorder; or abnormal 
laboratory values at screening that, in the opinion of the investigator, pose an 
unacceptable risk to the patient if participating in the study or risk of 
interfering with the interpretation of data.
[25] have had fluid overload, MI, or new-onset ischemic heart disease (for 
example, unstable angina), uncompensated heart failure or, in the opinion of 
the investigator, other serious cardiac disease within 12 weeks prior to 
baseline (Week 0; Visit 2).  
[26] have the presence of significant uncontrolled neuropsychiatric disorder, have 
history of a suicide attempt, have a score of 3 on Item 12 (Thoughts of Death 
or Suicide) of the 16-item Quick Inventory of Depressive Symptomatology–
Self Report (QIDS-SR16) at screening (Visit 1), or are clinically judged by the 
investigator to be at risk for suicide.
[27] had a serious infection (for example, pneumonia, cellulitis), have been 
hospitalized, or have received intravenous (IV) antibiotics for an infection 
within 12 weeks prior to baseline (Week 0; Visit 2); had a serious bone or 
joint infection within 24 weeks prior to baseline; have ever had an infection of 
an artificial joint; or are immunocompromised to an extent such that 
participation in the study would pose an unacceptable risk to the patient.
[28] have or have had an infection that is typical of an immunocompromised host
and/or that occurs with increased incidence in an immunocompromised host 
(including, but not limited to, Pneumocystis jirovecii pneumonia, 
histoplasmosis, or coccidioidomycosis) or have a known immunodeficiency.


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[29] have a herpes zoster or any other clinically apparent varicella-zoster virus 
infection or had such within 12 weeks of baseline (Week 0; Visit 2).
[30] have any other active or recent infection within 4 weeks of baseline (Week 0; 
Visit 2) that, in the opinion of the investigator, would pose an unacceptable 
risk to the patient if participating in the study; these patients may be 
rescreened (1 time) 4 weeks after documented resolution of symptoms.
[31] have a body temperature 38C (100.5F) at baseline (Week 0; Visit 2); these 
patients may be rescreened (1 time) 4 weeks after documented resolution of 
elevated temperature.
[32] have clinical evidence or suspicion of active TB or have previously had 
evidence of active TB and did not receive appropriate and documented 
treatment.  (Refer to Section 10.4.3.5 for additional details on determining full 
TB exclusion criteria.)
a
Evidence of active TB is documented by a positive purified protein 
derivative (PPD) test (≥5-mm induration) which is to be read between 
48 and 72 hours after placement, regardless of vaccination history, 
medical history, clinical symptoms, and abnormal chest x-ray at 
screening.
b
If either the QuantiFERON®-TB Gold test (QTF) or T-SPOT® TB test 
(T-SPOT) is available, it may be used as an alternative instead of the 
PPD test, per principal investigator preference or judgment, and may 
be read locally.  Locally read results must be documented in the eCRF.
have evidence of latent TB (as documented by a positive QTF or T-SPOT or 
PPD [≥5-mm induration] with no clinical symptoms or signs consistent with 
active TB, and a normal chest x-ray at screening) unless patients complete at 
least 4 weeks of appropriate treatment prior to randomization and agree to 
complete the remainder of treatment while in the trial (see Section 10.4.3.5 for 
additional requirements).
a
If the QTF or T-SPOT test is indeterminate, the test may be repeated 
once within approximately 2 weeks of the initial value.  If the repeat 
test is indeterminate, the patient will be excluded from the study.  If 
the retest is positive with no clinical evidence of TB, the patient will 
be considered to have latent TB. 
b
If the PPD test is performed and positive (≥5-mm induration) and the 
patient has no medical history or chest x-ray findings consistent with 
active TB, a retest can be performed using a QTF or T-SPOT test. 
Note:  If retest is done with QTF or T-SPOT, this result will be used to 
determine eligibility in place of the PPD result.  Indeterminate results 
of either test are to be handled as directed above.
c
Exceptions include patients with a history of active or latent TB who 
have documented evidence of appropriate treatment.


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[33] have uncontrolled arterial hypertension characterized by a systolic blood 
pressure (BP) >160 mm Hg or diastolic BP >100 mm Hg.
(Note:  This will be determined by 2 consecutive elevated readings.  If an 
initial BP reading exceeds this limit, the BP may be repeated once after the 
patient has rested sitting for 10 minutes.  If the repeat value is less than the 
criterion limits, the second value may be accepted.)
[34] are positive for human immunodeficiency virus (HIV) serology (positive for 
HIV antibody).
[35] have evidence of active hepatitis B virus (positive for hepatitis B surface 
antigen) OR are positive for hepatitis B core antibody and negative for 
hepatitis B surface antibody.
[36] have evidence of or test positive for hepatitis C virus (HCV).  A positive test 
for HCV is defined as:  (1) positive for hepatitis C antibody and (2) positive 
via a confirmatory test for HCV (for example, HCV polymerase chain 
reaction).
[37] have clinical laboratory test results at screening that are outside the normal 
reference range for the population and are considered clinically significant 
and/or have any of the following specific abnormalities:  
[37a]
neutrophil count <1500 cells/L (<1.50×103 cells/μL or <1.50 GI/L)
[37b]
lymphocyte count <500 cells/L (<0.50×103 cells/μL or <0.50 GI/L)
[37c]
platelet count <100,000 cells/L (<100×103 cells/μL or <100 GI/L)
[37d]
aspartate aminotransferase (AST) or alanine aminotransferase (ALT) 
>2.5 times the upper limit of normal (>2.5xULN)  
[37e]
total white blood cell (WBC) count <3000 cells/L 
(<3.00×103 cells/μL or <3.00 GI/L)
[37f]
hemoglobin <8.5 g/dL (85.0 g/L) for male patients and <8.0 g/dL 
(80 g/L) for female patients  
[37g]
serum creatinine >2.0 mg/dL.
(Note:  The AST and ALT may be repeated once within a week if the initial 
response exceeds this limit, and the repeat value may be accepted if it meets 
this criterion.  Other laboratory tests should not be repeated unless there is a 
technical error or clinical reasons to believe a result may be erroneous.)
[38] have ECG abnormalities that are considered clinically significant and would 
pose an unacceptable risk to the patient if participating in the study.
[39] have any other condition that precludes the patient from following and 
completing the protocol, in the opinion of the investigator.


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[40] have donated blood >400 mL within the last 4 weeks prior to baseline or 
intend to donate blood during the course of the study.
[41] are women who are lactating or breastfeeding.
[42] are unwilling to abstain from alcohol beverage intake 24 hours prior to any 
scheduled visits until the completion of all study visit procedures.
[43] have used any traditional Chinese treatments within 14 days prior to study 
enrollment or intend to use any traditional Chinese treatment during the study.
[44] Have allergy to rubber or latex.
8.1.3. Rationale for Exclusion of Certain Study Candidates
Exclusion Criteria [8] and [9] reduce the potential bias that may be introduced at the study site.  
Exclusion Criteria [14] through [18] exclude patients who are taking concomitant medications or 
receiving treatment or phototherapy that could have a negative safety impact on the patients 
enrolled or confound the results of the study.  Exclusion Criteria [19] through [38] exclude 
patients who would be at a greater safety risk, including patients at increased risk of infective 
complications or immunosuppression, if administered investigational product or whose data 
could confound the results of the study in the analysis of ixekizumab and/or patients.  Exclusion 
Criterion [41] provides protection to offspring.  
8.2.
Discontinuation
The reason for and date of discontinuation will be collected for all patients.  All patients who 
discontinue, regardless of whether or not they received investigational product, will have 
procedures performed as shown in the Study Schedule (Attachment 1).
8.2.1. Discontinuation of Patients
8.2.1.1.
Patients Inadvertently Enrolled
The criteria for enrollment must be followed explicitly.  If the investigator site identifies a patient
who did not meet enrollment criteria and who was inadvertently enrolled, the sponsor must be 
notified.  If the sponsor identifies a patient who did not meet enrollment criteria and who was 
inadvertently enrolled, the investigator site will be notified.  A discussion must occur between 
the Lilly clinical pharmacologist or clinical research physician (CRP) and the investigator to 
determine whether the patient may continue in the study, with or without investigational product.  
Inadvertently enrolled patients may be maintained in the study and on investigational product 
when the investigator and Lilly clinical pharmacologist or CRP agree it is medically appropriate 
for that patient. 
The patient may not continue in the study with or without investigational product if the Lilly 
clinical pharmacologist or CRP does not agree with the investigator’s determination that it is 
medically appropriate for the subject 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 investigational product.


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8.2.1.2.
Discontinuations from Investigational Product or from the Study
In addition, patients will be discontinued from the investigational product or from the study in
the following circumstances:

Enrollment in any other clinical trial involving an investigational product or enrollment in 
any other type of medical research judged not to be scientifically or medically compatible 
with this study.

Investigator decision:
o
The investigator decides that the patient should be discontinued from the study.
o
If the patient, for any reason, requires treatment with another therapeutic agent 
that has been demonstrated to be effective for treatment of the study indication, 
discontinuation from the study occurs prior to introduction of the other agent.

Subject decision:
o
The patient requests to be discontinued from the study.

Sponsor decision:
o
Lilly stops the study or stops the patient’s participation in the study for medical, 
safety, regulatory, or other reasons consistent with applicable laws, regulations, 
and GCP.

AE:
o
If a clinically significant event (CSE) occurs, the investigational product is 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 
well-being of the subject.  Refer to Section 10.4, Safety Evaluations.
o
A clinically significant systemic hypersensitivity reaction occurs following 
administration of the investigational product (for example, drug-related 
symptomatic bronchospasm, allergy-related edema/angioedema, or hypotension) 
and requires parenteral medication, does not respond to symptomatic medication, 
or results in clinical sequelae or an anaphylactic reaction.
After the investigator’s determination that CSE criteria have been met and the investigator’s 
judgment of relatedness to the investigational product 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.  
Discontinuation procedures are outlined in the Study Schedules (Attachment 1 and Attachment 
2).


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8.2.2. Discontinuation of Study Sites
Study site participation may be discontinued if Lilly, the investigator, or the ERB of the study 
site judges it necessary for any reason consistent with applicable laws, regulations, and GCP.
8.2.3. Discontinuation of the Study
The study will be discontinued if Lilly judges it necessary for medical, safety, regulatory, or 
other reasons consistent with applicable laws, regulations, and GCP.


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9. Treatment
9.1.
Treatment Materials and Supplies
All patients will be administered ixekizumab via prefilled syringe.
9.1.1. Packaging, Preparation, Labeling, and Storage
The ixekizumab solution for injection will be supplied by the sponsor or its designee in 
accordance with current Good Manufacturing Practices.  Ixekizumab will be supplied as an 
injectable solution in a 1-mL, single-dose, disposable manual syringe.  Each syringe of 
ixekizumab is designed to deliver 80 mg of ixekizumab.  Syringes will be supplied in cartons, 
with the appropriate quantity of syringes specific to the planned dispensing schedule of the 
investigational product.  
Clinical trial materials will be labeled according to China’s regulatory requirements.  All 
investigational products will be supplied with lot numbers, expiry dates, and certificates of 
analysis and will be stored, inventoried, reconciled, and destroyed according to applicable 
regulations.  
The investigational product should be stored at 2C to 8C (36F to 46F) in its original carton to 
protect from light.  Investigational product should not be frozen or shaken.  Sites will be required 
to monitor temperature of the on-site storage conditions of the syringes.
9.2.
Treatment Administration
This study involves an evaluation of ixekizumab 80 mg administered by prefilled syringe during 
the treatment period.  For the single-dose phase, all patients will receive a single dose of 80 mg 
given as one 80 mg SC injection at Week 0 (Visit 2) and will then be observed for a 20-week
period.  For the multiple-dose phase, all patients will receive a 160 mg SC starting dose 
(2 injections) and will then be randomized at a 1:1 ratio to 1 of 2 dose groups via a computer-
generated random sequence using an interactive web-response system (IWRS):  one group will 
receive 80 mg SC Q2W starting on Day 15, and the other group will receive 80 mg SC Q4W 
starting on Day 29 for the duration of the 8-week treatment period.  All patients in the multiple-
dose phase will be followed for an additional 20-week observation period after the treatment 
period completes.  
Injections will be administered at the site by the clinical staff.  
Administration:  A dose of investigational product will consist of SC injection(s) of 
investigational product.  Possible injection sites include the abdomen, thigh, and upper arm.  The 
injection site should not be in a psoriatic lesion and should be rotated to another area for 
subsequent doses.  
Allow the prefilled syringe containing the drug product to equilibrate to room temperature for 
approximately 30 minutes.  Do not return syringe to the refrigerator.  
The investigator or designee is responsible for:


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
explaining the correct use of the investigational agent to the site personnel,

verifying that instructions are followed properly,

maintaining accurate records of investigational product dispensing and collection,

and returning all unused medication to Lilly or its designee at the end of the study.
Note: In some cases, sites may destroy the material if, during the investigator site selection, the 
evaluator has verified and documented that the site has appropriate facilities and written 
procedures to dispose clinical trial materials.  
Patients will be instructed to contact the investigator as soon as possible if he or she has a 
complaint or problem with the investigational product so that the situation can be assessed.  See 
Section 10.4.5 for more details.
All clinical trial material provided to the investigator will be stored in a secure place and 
allocated and dispensed by appropriately trained persons.  The allocation and dispensing of the 
investigational products will be fully documented and verified by a second person.  Detailed 
records of the amounts of investigational product received, dispensed, and remaining at the end 
of the study will be maintained.
The doses will be administered at approximately the same times on each planned dosing day, and 
each patient should have doses administered by the same member of the staff as far as possible.
The actual time of all dose administrations will be recorded in the subject’s case report form 
(CRF).
9.3.
Rationale for Selection of Dose
Ixekizumab has been administered to patients with rheumatoid arthritis, psoriatic arthritis, and 
psoriasis.  A 160 mg SC starting dose (Week 0) followed by an 80 mg SC dose Q2W or Q4W 
was evaluated as an induction dosing regimen over 12 weeks of treatment in global pivotal Phase 
3 studies in patients with psoriasis (Studies RHAZ, RHBA, and RHBC). In this study, the PK 
profile and safety/tolerability of ixekizumab 80 mg will be assessed initially in the single-dose 
phase.  Thereafter, the induction dosing regimens evaluated in the pivotal Phase 3 studies will be 
evaluated in the multiple-dose phase for this Phase 1 study in China.  The doses planned for this 
study are justified by adequate margins of safety from toxicology studies in cynomolgus 
monkeys (Table RHBN.1) and the safety and tolerability data from single- and multiple-dose 
studies in patients with psoriasis.  


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Table RHBN.1.
Margin of Safety for Administration of Ixekizumab to Humans 
Based on Exposure at the NOAEL and LOAEL in Monkeys
SC Dose
AUC0-168hr (mg•hr/mL)
Margin of Safety Based 
on AUC in Phase 3
Human 
Dose regimen producing 
highest exposure in Phase 3 
studies 
80 mg Q2W 
following 160 mg 
starting dose
2.366a
-
Monkey
NOAEL
5 mg/kg Q1W
15.3b
6.5x
LOAEL
50 mg/kg Q1W
144c
61x
Abbreviations:  AUC = area under the concentration versus time curve; AUC0-168hr = AUC from time 0 to 
168 hours after dosing; LOAEL = lowest-observed-adverse-effect level; NOAEL = no-observed-adverse-effect 
level; Q1W = once weekly; Q2W = every 2 weeks; SC = subcutaneous.
a
Predicted mean steady-state AUC0-168hr following 80 mg Q2W dosing, using simulations from the integrated 
population pharmacokinetic model.  The model-predicted AUC0-168hr value for the starting dose of 160 mg was 
1.987 mg•hr/mL, and for the proposed maintenance dose of 80 mg every 4 weeks was 1.560 mg•hr/mL.
b
Estimated mean male and female AUC0-168hr after 39 weekly SC doses of 5 mg/kg in Study 7608-478; Day 1 
AUC was multiplied by 2.5, which was the extent of accumulation observed at 50 mg/kg.
c
Mean male and female AUC0-168hr after 39 weekly SC doses of 50 mg/kg in Study 7608-478.
9.4.
Specific Restrictions/Requirements
Prior to beginning the study, the patients will complete informed consent and baseline tests.  
Patients will be screened for eligibility in the study as described in Sections 8.1 and 8.2 and will 
be informed of the study-specific restrictions and requirements of the study.  Patients who are not 
willing to comply with the study restrictions and requirements will not be eligible to be enrolled.  
Patients will reside in the clinical research unit during the infusion visits until completion of all 
procedures associated with that visit.  Patients will adhere to the following study restrictions 
and/or requirements:  

It is unlikely that there are significant reproductive risks, including risks of harm to the 
fetus or infant, with ixekizumab treatment.  This is based on results from reproductive 
and developmental toxicity studies in monkeys. However, male patients should use 
barrier method contraception during intercourse with female partners of childbearing 
potential during the study and for at least 3 months after the last dose of ixekizumab, 
whichever is longer. Female patients must use a reliable method of birth control or 
remain abstinent during the study and for at least 3 months after the last dose of 
ixekizumab, whichever is longer (additional details are provided in the Inclusion Criteria 
[Section 8.1.1]).

Patients must abstain from alcoholic beverages intake for 24 hours prior to any scheduled 
visit and until completion of the study procedures associated with that visit.  

Patients must refrain from smoking for 30 minutes prior to any study procedure and until 
completion of that procedure.  


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9.4.1. Special Treatment Considerations
Patients should be instructed not to donate blood or blood products during participation in the 
study.  All biological agents carry the risk of systemic allergic/hypersensitivity reactions.  
Clinical manifestations of these reactions may include but are not limited to:

skin rash

pruritus (itching) 

urticaria (hives) 

angioedema (for example, swelling of the lips and/or tongue) 

anaphylactic reaction.
Sometimes, these reactions can be life threatening.  Proteins may also cause redness, itching, 
swelling, or pain locally at the injection site; therefore, all patients should be closely monitored 
for signs or symptoms that could result from such reactions, educated on the signs or symptoms 
of these types of reactions, and instructed to contact the study site immediately if any of the 
symptoms are experienced following an injection.  If a patient experiences an acute 
allergic/hypersensitivity reaction after an injection of investigational product, he or she should be 
managed appropriately and given instruction to receive relevant supportive care.  Additionally, 
for an event judged by the investigator to be a potential systemic allergic/hypersensitivity 
reaction, a blood sample should be drawn to test for antidrug antibodies.  
For patients who experience a potential allergic or hypersensitivity reaction, consideration for 
any premedication for future injections will be agreed upon between the investigator and the 
sponsor and/or its designee.  Examples of potential allergic or hypersensitivity reactions that 
might merit premedication include mild to moderate skin rashes, mild to moderate generalized 
pruritus and/or urticaria, and mild to moderate injection site reactions (for example, injection site 
erythema or injection site pruritus).  Patients who develop clinically significant systemic allergic
or hypersensitivity reactions after administration of investigational product who do not respond 
to symptomatic medication or have clinical sequelae (for example, hospitalization) should be 
discontinued from the study and should not receive further doses of investigational product, with 
or without premedication (see Section 8.2).  Medications considered appropriate for 
premedication include but are not restricted to acetaminophen/paracetamol up to 1000 mg and 
antihistamines (for example, oral diphenhydramine 50 mg), given 30 to 60 minutes prior to 
investigational product injection.  Patients may self-premedicate at home prior to administration 
of investigational product as directed by the investigator.  All such premedications will be 
recorded as concomitant therapy.  Corticosteroids are not permitted as agents for premedication.
9.5.
Blinding
This study is an open-label study.


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9.6.
Concomitant Therapy
Patients will maintain their usual medication regimen for other concomitant diseases throughout 
the study unless that regimen is specifically excluded in the protocol.  Patients taking 
concomitant medications should be on stable doses at the time of baseline and should remain at 
stable doses throughout the study unless changes need to be made for an AE.  Additional 
systemic drugs are to be avoided during the study unless they are required to treat an AE.  Other 
medications may be allowed if approved by the sponsor or its designee.
If the need for concomitant medication arises, inclusion or continuation of the patient may be at 
the discretion of the investigator after consultation with a Lilly clinical pharmacologist or CRP.  
Any additional medication used during the course of the study must be documented.
All concomitant medication taken during the study must be recorded on the concomitant 
medication page of the CRF.  Treatment with concomitant psoriasis therapies during the study is 
permitted only as outlined in the Exclusion Criteria (Section 8.1.2) and as described in the 
following paragraphs.  Patients taking permitted medications should be on chronic stable doses at 
the baseline visit (Week 0; Visit 2) as specified in Section 8.1.2.
The following therapies will not be permitted during the course of the study:  

psoriasis therapy as described in the Inclusion and Exclusion Criteria (Sections 8.1.1 and 
8.1.2), except as described in the following paragraphs for topical agents.

concomitant medications as described in the Inclusion and Exclusion Criteria 
(Sections 8.1.1 and 8.1.2)

live vaccines

phototherapy.
Topical Psoriasis Treatment: Topical psoriasis treatment as indicated below will be permitted 
after completion of Week 4 (Visit 9) and prior to Week 18 (Day 127) during the single-dose 
phase and after completion of the Week 12 visit during the multiple-dose phase.

Topical treatments including, but not limited to corticosteroids, vitamin D analogues, 
tarzarotene, and tacrolimus are permitted. Only steroids of mild potency (for 
example, desonide, fluocinolone acetonide, and alclometasone) or low potency (that 
is, hydrocortisone) are recommended for the face, axilla, and/or genitalia.  These 
topical medications should not be used within approximately 24 hours prior to study 
visits requiring sPGA and PASI measures.

Medicated shampoos and other nonsteroidal topical therapies: Medicated 
shampoos, topical moisturizers/emollients, and other nonprescription topical products 
are permitted. These topical medications should not be used within approximately 
12 hours prior to study visits requiring sPGA and PASI measures.


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Vaccines:  Use of nonlive seasonal vaccinations and/or emergency vaccination (such as rabies or 
tetanus vaccinations) is allowed.
Other Concomitant Therapies:  Acetaminophen or aspirin will also be allowed as needed.
Traditional Chinese Medicine:  Patients must stop any traditional Chinese treatments at least 
14 days prior to study enrollment and must not resume treatment until after last study visit.  


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10.
Sample Collection and Safety Data Collection
Attachment 1 and Attachment 2 list the schedules for sample collection in this study.
Attachment 3 lists the clinical laboratory tests that will be performed for this study.
Attachment 4 summarizes the blood volumes for all blood sampling during the study.  
10.1. Laboratory Samples
Blood and urine samples will be collected to determine whether patients meet 
inclusion/exclusion criteria and to monitor patient health.  Routine clinical laboratory tests will 
be analyzed by a central laboratory selected by Lilly.  
Investigators must document their review of each laboratory safety report.
Samples collected for specified laboratory tests will be destroyed within 60 days of receipt of 
confirmed test results.  Tests are run and confirmed promptly whenever scientifically 
appropriate.  When scientific circumstances warrant, however, it is acceptable to retain samples 
to batch the tests run or to retain the samples until the end of the study to confirm that the results 
are valid.  Certain samples may be retained for a longer period, if necessary, to comply with 
applicable laws, regulations, or laboratory certification standards.
10.2. Samples for Pharmacokinetic and Pharmacodynamic 
Evaluations
10.2.1. Pharmacokinetic Samples
Samples for the measurement of serum ixekizumab concentrations will be collected from 
patients enrolled in the study at the time points specified in the PK sampling times in the Study 
Schedules (Attachment 1 and Attachment 2).  An intensive sampling scheme is being 
implemented to capture the entire ixekizumab concentration profile after single-dose 
administration and at steady state during a dosing interval.  
Venous blood samples (approximately 4 mL) will be collected into tubes, and serum ixekizumab
concentrations will be determined.  Instructions for collection and handling of blood samples will 
be provided by Lilly or its designee.  The actual date and time (24-hour clock time) of each 
sampling will be recorded.
10.2.2. Bioanalysis
Samples will be analyzed at a laboratory approved by the sponsor and stored at a facility 
designated by the sponsor.
Concentrations of ixekizumab will be assayed using a validated enzyme-linked immunosorbent 
assay.  
Bioanalytical samples collected to measure investigational product concentrations will be 
retained for a maximum of 1 year following last patient visit for the study.  


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10.2.3. Pharmacodynamic Clinical Outcome Measures 
The clinical outcome measures, PASI and sPGA, are considered the pharmacodynamic (PD) 
measures in this study.  
The PASI is the most commonly used primary endpoint and measure of psoriasis severity in 
clinical trials (European Medicines Agency [EMA] 2004 WWW; Menter et al. 2008).  The PASI 
combines assessments of the extent of BSA involvement in 4 anatomical regions (head, trunk, 
arms, and legs) and the severity of desquamation, erythema, and plaque induration/infiltration 
(thickness) in each region, yielding an overall score of 0 for no psoriasis to 72 for severe disease 
(Fredriksson and Pettersson 1978).  
The static Physician Global Assessment (sPGA) is the physician’s global assessment of the 
patient’s psoriasis (Ps) lesions evaluated at a given time point (European Medicines Agency 
[EMA] 2004 [WWW]).  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). 
Data will be collected at the times shown in the Study Schedules (Attachment 1 and Attachment 
2).
10.3. Samples for Immunogenicity Research 
Blood samples for immunogenicity testing will be collected to determine antibody production 
against ixekizumab.  Immunogenicity will be assessed by a validated assay designed to detect 
antidrug antibodies in the presence of ixekizumab.  Antibodies may be further characterized 
and/or evaluated for their ability to neutralize the activity of ixekizumab.  Immunogenicity 
samples may also be analyzed for ixekizumab serum concentration to facilitate in the 
interpretation of the immunogenicity data.
Samples may be stored for a maximum of 15 years following last patient visit for the trial at a 
facility selected by the sponsor to enable further analysis of immune responses to ixekizumab.  
The duration allows the sponsor to respond to regulatory requests related to ixekizumab.
10.4. Safety Evaluations
Investigators are responsible for monitoring the safety of patients 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.
The investigator is responsible for the appropriate medical care of patients during the study.  
Planned safety assessments and measures are detailed in Section 10.4.3, but additional 
assessments and safety tests may be performed at the investigator’s discretion.
The investigator remains responsible for following, through an appropriate health care option, 
AEs that are serious, considered related to study treatment or the study, or that caused the patient
to discontinue before completing the study.  The patient should be followed until the event is 
resolved or explained.  Frequency of follow-up evaluation is left to the discretion of the 
investigator.


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In addition to records of observations made at specific times, unexpected signs and symptoms 
and concomitant medications will be recorded in the clinical trial records throughout the study.
10.4.1. Adverse Events
Lilly has standards for reporting AEs that are to be followed regardless of applicable regulatory 
requirements that may be less stringent.
Study site personnel will record the occurrence and nature of each patient’s preexisting 
conditions, including clinically significant signs and symptoms of the disease under treatment in 
the study.
Cases of pregnancy that occur during maternal or paternal exposures to the investigational 
product should be reported.  Data on fetal outcome and breastfeeding are collected for regulatory 
reporting and drug safety evaluation.
After the ICF is signed, site personnel will record any change in the condition(s) and the 
occurrence and nature of any AEs.  All AEs related to protocol procedures are reported to Lilly 
or designee.
Any clinically significant findings from ECGs, laboratory test results, vital sign measurements, 
other procedures, and so on should be reported as AEs to Lilly or its designee.
Investigators will be instructed to report to Lilly or its designee their assessment of the potential 
relatedness of each AE to protocol procedure, studied disease state, or investigational product via
CRF, electronic data entry, or designated data transmission methods.
The investigator decides whether he or she interprets the observed AEs as related to disease, 
study medication, study procedure, or other concomitant treatment or pathologies.  To assess the 
relationship of the AE to the investigational product, the following terminologies are defined:

Related:  A direct cause and effect relationship between the study treatment and the AE 
is likely.

Possibly related:  A cause and effect relationship between the study treatment and the 
AE has not been demonstrated at this time and is not probable, but is also not impossible.

Unrelated:  Without question, the AE is definitely not associated with the study 
treatment.
Per Lilly’s standard operating procedures, all “related” and “possibly related” AEs and SAEs 
will be defined as related to the investigational product.
10.4.2. Serious Adverse Events
Serious adverse event collection and reporting will commence after the ICF is signed.  
Planned surgeries should not be reported as SAEs unless the underlying medical condition has 
worsened during the course of the study.


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Study site personnel must alert Lilly 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.  
An SAE is any AE from this study that results in one of the following outcomes:

death

initial or prolonged inpatient hospitalization

a life-threatening experience (that is, immediate risk of dying)

persistent or significant disability/incapacity

congenital anomaly/birth defect

considered significant by the investigator for any other reason.
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered SAEs when, based upon appropriate medical judgment, they 
may jeopardize the patient and may require medical or surgical intervention to prevent one of the 
outcomes listed in this definition.
Serious adverse events occurring up to and including the patient’s last study visit will be 
collected, regardless of the investigator’s opinion of causation, in the clinical data collection 
database and the pharmacovigilance system at the sponsor.
If an investigator becomes aware of SAEs occurring to a patient after the patient’s participation 
in the trial has ended, the investigator should report them to the sponsor, regardless of the 
investigator’s opinion of causation, and the SAEs will be entered in the pharmacovigilance 
system at the sponsor.
Information on SAEs expected in the study population independent of drug exposure and that 
will be assessed by the sponsor in aggregate periodically during the course of the trial may be 
found in the IB.  
10.4.2.1. Suspected Unexpected Serious Adverse Reactions 
Suspected unexpected serious adverse reactions (SUSARs) are serious events that are not listed 
in the IB and that the investigator identifies as related to investigational product or procedure.  
United States 21 Code of Federal Regulations (CFR) 312.32 and European Union Clinical 
Trial Directive 2001/20/EC, and the associated detailed guidances or national regulatory 
requirements in participating countries, require the reporting of SUSARs.  Lilly has procedures 
that will be followed for the recording and expedited reporting of SUSARs that are consistent 
with global regulations and the associated detailed guidances.


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10.4.3. Other Safety Measures
10.4.3.1. Physical Examination
Physical examinations and routine medical assessments will be conducted as specified in the 
Study Schedules (Attachment 1 and Attachment 2) and as clinically indicated.
10.4.3.2. Vital Signs
Vital signs (BP, respiratory rate, pulse rate, and body temperature) will be measured in a sitting 
posture.  Any clinically significant findings that result in a diagnosis should be captured on the 
CRF.  Additional measurements of vital signs may be performed at the discretion of the 
investigator.  
10.4.3.3. Body Weight
Body weight will be recorded as specified in the Study Schedules (Attachment 1 and Attachment 
2) and as clinically indicated.
10.4.3.4. Electrocardiograms
For each patient, a single 12-lead digital ECG will be collected according to the Study Schedules
(Attachment 1 and Attachment 2).  Electrocardiograms must be recorded before collecting any 
blood for safety or PK tests.  Patients must be supine for approximately 5 to 10 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. All ECGs recorded 
should be stored at the investigational site.
Electrocardiograms will be interpreted by a qualified physician (the investigator or qualified 
designee) at the site as soon after the time of ECG collection as possible, ideally while the patient
is still present, to determine whether the patient meets entry criteria at the relevant visit(s) and 
for immediate patient management, should any clinically relevant findings be identified.  
If a clinically significant finding is identified (including, but not limited to changes in QT/QTc 
interval from baseline) after enrollment, the investigator will determine if the patient can 
continue in the study.  The investigator or qualified designee is responsible for determining if 
any change in patient management is needed and must document his/her review of the ECG 
printed at the time of collection.  Any new clinically relevant finding should be reported as an 
AE.
10.4.3.5. Chest X-Ray and Tuberculosis Testing
A posterior-anterior view chest x-ray will be obtained, unless the x-ray or results from a chest x-
ray obtained within 6 months prior to the study are available.  The chest x-ray or results will be 
reviewed by the investigator or designee to exclude patients with active TB infection.
In addition, patients will be tested at screening as indicated in the Study Schedules (Attachment 1
and Attachment 2) for evidence of active or latent TB (positive PPD [≥5-mm induration] or 
positive QTF or T-SPOT at screening but no other evidence of active TB).  In sites where the 
QTF or T-SPOT test is available and, in the judgment of the investigator, preferred as an 
alternative to the PPD skin test for the evaluation of TB infection, it may be used instead of the 


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PPD test (positive test excluded) and may be read locally. If the QTF or T-SPOT test is 
indeterminate, 1 retest is allowed. If the retest is indeterminate, the patient will be excluded from 
the study.  If the retest is positive but without clinical evidence of TB, the patient will be 
considered as latent TB for study purposes. 
Patients with documentation of a negative test result within 3 months prior to baseline (Week 0;
Visit 2) do not need a TB screen at Visit 1.  Documentation of this test result must include a 
record of the size of the induration response.  A PPD test recorded as negative without 
documenting the size of induration will result in a retest.
However, patients with a positive QTF or T-SPOT at screening, but no other evidence of active 
TB, may be rescreened 1 time and may be enrolled without repeating the test if the following 
conditions are met:

after receiving at least 4 weeks of appropriate latent TB infection (LTBI) therapy, and

no evidence of hepatotoxicity (ALT/AST must remain ≤2xULN) upon retesting of serum 
ALT/AST prior to randomization (such patients must complete appropriate LTBI therapy 
during the course of the study in order to remain eligible), and 

meet all other inclusion and exclusion criteria for participation.
If rescreening occurs within 6 months of the screening chest x-ray, there is no necessity for 
repeat of chest x-ray for considering enrollment. Patients who have a documented history of 
completing an appropriate TB treatment regimen with no history of re-exposure to TB since their 
treatment was completed and no evidence of active TB are eligible to participate in the 
study. Patients who have had household contact with a person with active TB are excluded, 
unless appropriate and documented prophylaxis for TB was given.
10.4.3.6. Quick Inventory of Depressive Symptomatology–Self Report, 16 item
The QIDS-SR16 is a self-administered, 16-item instrument intended to assess the existence and 
severity of symptoms of depression as listed in the American Psychiatric Association’s 
Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) (APA 1994). A 
patient is asked to consider each statement as it relates to the way they have felt for the past 
7 days. There is a 4-point scale for each item ranging from 0 to 3. The 16 items corresponding 
to 9 depression domains are summed to give a single score ranging from 0 to 27, with higher 
scores denoting greater symptom severity. The domains assessed by the instrument 
include: (1) sad mood, (2) concentration, (3) self-criticism, (4) suicidal ideation, (5) interest, 
(6) energy/fatigue, (7) sleep disturbance (initial, middle, and late insomnia or hypersomnia), 
(8) decrease/increase in appetite/weight, and (9) psychomotor agitation/retardation. Additional 
information and the QIDS-SR16 questions can be found at the University of Pittsburgh 
IDS/QIDS internet page (http://www.ids-qids.org).
10.4.3.7. Columbia-Suicide Severity Rating Scale
Consistent with the United States Food and Drug Administration (US-FDA) regulatory guidance 
(FDA 2012), any occurrence of suicide-related thoughts and behaviors will be assessed as 
indicated in the Study Schedules (Attachment 1 and Attachment 2) using the Columbia-Suicide 
Severity Rating Scale (C-SSRS), a scale that captures the occurrence, severity, and frequency of 


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suicide-related thoughts and behaviors during the corresponding assessment period.  The scale 
includes suggested questions to elicit the type of information needed to determine if a suicide-
related thought or behavior occurred. 
Terms captured by the use of the C-SSRS can be mapped to Columbia Classification Algorithm 
for Suicide Assessment (Posner et al. 2007) to facilitate future pooling of data. 
The first time the scale is administered in this study, the C-SSRS “Baseline” version will be 
used, and the findings will constitute the baseline assessment.  The C-SSRS “Since Last Visit”
scale will be used for all subsequent assessments.  If a suicide-related thought or behavior is 
identified at any time during the study, a thorough evaluation will be performed by a study 
physician, and appropriate medical care will be provided.  The Lilly Self-Harm Supplement 
should be completed every time the C-SSRS is administered.  If, based on administration of the 
C-SSRS, it is determined that suicide-related behaviors have occurred, then the Lilly Self-Harm 
Follow-Up form will be used to collect additional information to allow for a more complete 
assessment of these behaviors.
10.4.4. Safety Monitoring
The Lilly clinical pharmacologist or CRP 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 research physician will consult with the functionally independent Global 
Patient Safety therapeutic area physician or clinical research scientist (CRS) when appropriate, 
and periodically review:

trends in safety data

laboratory analytes

AEs including monitoring of infection.
10.4.5. Complaint Handling
Lilly collects product complaints on investigational products and drug delivery systems used in 
clinical trials in order to ensure the safety of study participants, monitor quality, and facilitate 
process and product improvements.
The investigator or his/her designee is responsible for handling the following aspects of the 
product complaint process in accordance with the instructions provided for this study:

recording a complete description of the product complaint reported and any associated 
AEs using the study-specific complaint forms provided for this purpose

faxing the completed product complaint form within 24 hours to Lilly or its designee.
If the investigator is asked to return the product for investigation, he/she will return a copy of the 
product complaint form with the product.


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10.5. Appropriateness and Consistency of Measurements
Pharmacokinetic measurements are appropriate for the proposed study design which consists of 
both single- and multiple-dose treatment groups.  Safety measures used in this trial are all well 
established.  The PASI and sPGA, rating measures specific for psoriasis, are well-recognized 
tools for assessing efficacy in this disease.  
10.6. Compliance
Every attempt will be made to select patients who have the ability to understand and comply with 
instructions.  Noncompliant patients may be discontinued from the study.  The time and day of 
drug administration will be recorded.  Drug accountability records will be maintained by the 
study site.
The specifications in this protocol for the timings of safety, PK, and PD sampling are given as 
targets, to be achieved within reasonable limits.  Modifications may be made to the time points 
based upon the safety information obtained.  The scheduled time points may be subject to minor 
alterations; however, the actual time must be correctly recorded in the CRF.
Any major modifications that might affect the conduct of the study, patient safety, and/or data 
integrity will be detailed in a protocol amendment.


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11.
Sample Size and Analyses Methods
11.1. Determination of Sample Size
Up to 45 patients (15 patients for the single-dose phase and 30 patients for the multiple-dose 
phase) will be enrolled to target that 8 patients complete the single-dose phase and 20 patients 
(10 for each dosing regimen) complete the multiple-dose phase.
This study has been designed to meet the primary objective of assessing the PK of a single dose 
and multiple doses of ixekizumab in Chinese patients with psoriasis.  The sample size was 
chosen to meet Chinese regulatory requirements and to provide sufficient data to evaluate the 
objectives and is not intended to achieve any prior statistical requirements.  
11.2. Data Analysis Plans
11.2.1. General Considerations
Statistical analysis of this study will be the responsibility of Eli Lilly and Company or its 
designee.
PK and PD analyses will be conducted on the full analysis set.  This set includes all data from all 
patients receiving at least 1 dose of the investigational product, and for PK analyses, it includes 
patients with sufficient PK samples to enable a PK assessment.  Safety analyses will be 
conducted for all enrolled patients, whether or not they completed all protocol requirements.
Additional exploratory analyses of the data will be conducted as deemed appropriate.  Analyses 
will be fully detailed in the statistical analysis plan. Study results may be pooled with the results 
of other studies for population PK analysis to avoid issues with post-hoc analyses and incomplete 
disclosures of analyses.  
Data will be presented using summary tables and patient data listings.  
11.2.2. Study Participant Disposition
All patients 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.
11.2.3. Study Participant Characteristics
The patient’s age, sex, weight, BMI, height, race, and ethnicity, or other demographic 
characteristics (such as geographic region, baseline disease severity, duration of disease, 
previous systemic therapy, and previous biologic therapy) will be summarized.
Baseline clinical measures (such as sPGA score, PASI total score, and BSA) will be 
summarized.


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11.2.4. Pharmacokinetic Analyses
Pharmacokinetic parameter estimates for ixekizumab will be calculated by standard 
noncompartmental methods of analysis.  The PK parameters for estimation after the single dose 
will include Cmax, time to Cmax (tmax), and area under the concentration versus time curve
(AUC).  Other parameters such as terminal half-life, apparent clearance, and apparent volume of 
distribution may be determined.  The PK parameters for estimation after the last dose of the 
8- week treatment will include Cmax, tmax, and AUC.  Other parameters such as terminal half-
life, apparent clearance, and apparent volume of distribution may be determined.
Descriptive statistics of PK parameters will be presented for each dose regimen (single dose, 
Q2W multiple dose, and Q4W multiple dose).  Data may also be analyzed by population PK 
methods alone or in combination with other studies as deemed appropriate.  
11.2.5. Pharmacodynamic Analyses
11.2.5.1. Pharmacodynamic Parameter Estimation 
Clinical outcome measures PASI and sPGA are considered the PD measures in this study (see
Section 10.2.3).
11.2.5.2. Pharmacodynamic Statistical Inference
Descriptive statistics will be presented for PASI scores and sPGA scores (for both the single-
dose and multiple-dose phases of the study) by dose regimen and study day. Mean percentage 
change in PASI scores from baseline will be calculated and summarized.
Additional analyses may be conducted as deemed appropriate.
11.2.6. Pharmacokinetic/Pharmacodynamic Analyses
Exploratory exposure-response relationship analyses for PASI scores and sPGA scores may be 
conducted, if deemed appropriate.
11.2.7. Safety Analyses
11.2.7.1. Clinical Evaluation of Safety
All investigational product and protocol procedure AEs will be listed, and if the frequency of 
events allows, safety data will be summarized using descriptive methodology.
The incidence of symptoms for each treatment will be presented by severity and by association 
with investigational product as perceived by the investigator.  Symptoms reported to occur prior 
to study enrollment will be distinguished from those reported as new or increased in severity 
during the study.  Each symptom will be classified by the most suitable term from the medical 
regulatory dictionary.
The number of SAEs related to the investigational product will be reported.


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11.2.7.2. Statistical Evaluation of Safety
Safety parameters that will be assessed include the C-SSRS, safety laboratory test parameters,
and vital signs.  The parameters will be listed and summarized using standard descriptive 
statistics.  Additional analysis will be performed if warranted upon review of the data.
11.2.7.3. Evaluation of Immunogenicity
The frequency of antibody formation to ixekizumab will be determined.  If a neutralization assay 
is performed, the frequency of neutralizing antibodies will be determined.  The relationship 
between the presence (or absence) of antibodies and clinical parameters (for example, AEs and
PD measures) will be assessed, as will the relationship between the presence of antibodies and 
the PK parameters of ixekizumab.  
11.3. Interim Analyses
No interim analyses are planned for this study in order to support the primary or secondary 
objectives.  If an unplanned interim analysis is deemed necessary, the Lilly clinical 
pharmacologist, CRP or investigator, or designee will consult with the appropriate medical 
director or designee to determine if it is necessary to amend the protocol.
However, interim access to data may be conducted to support comparisons of PK data from 
Chinese patients in this study to PK data observed in non-Chinese patients from global studies, to
enable planning for future studies.  No changes to this study design are planned based on these 
PK analyses. Additionally, interim access to safety data may occur if deemed necessary or 
appropriate.  


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12.
Data Management Methods
12.1. Data Quality Assurance
To ensure accurate, complete, and reliable data, Lilly or its representatives will do the following:

provide instructional material to the study sites, as appropriate.

sponsor start-up training to instruct the investigators and study coordinators.  This 
training will give instruction on the protocol, the completion of the 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.

conduct a quality review of the database.
In addition, Lilly or its representatives will periodically check a sample of the patient data 
recorded against source documents at the study site.  The study may be audited by Lilly 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.
12.2. Data Capture Systems
12.2.1. Source Data and Case Report Form
A source document is the first record of data.  These can be paper (for example, ECG tracing or 
patient diary), a paper CRF on which the data is initially recorded, or data captured directly on an 
investigator site electronic system (for example, Holter monitor record data files or electronic 
health records).  The site must retain all source records and must maintain a record of any data 
where source data are directly entered into the paper CRF.
Data may then be entered into either an electronic (eCRF) or paper CRF, and the process will be 
documented and communicated by the sponsor to the investigator site before first patient visit.
Some investigator site data may be collected directly in the paper CRF, whereas other data that is 
collected by the site on paper or electronic records may be transferred to the paper CRF.
Lilly does not allow direct source data entry into Lilly computer systems, with the exception of 
the investigator site systems at the Lilly clinical research unit.


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For data handled by a data management third-party organization (TPO), CRF data and some or 
all data that are related will be managed and stored electronically in the TPO system.  
Subsequent to the final database lock, validated data will be transferred to the sponsor.
For data handled internally, CRF data and some or all data that are related will be managed by 
the sponsor and stored electronically in the sponsor’s system.
12.2.2. Ancillary Data
Data managed by a central vendor will be stored electronically in the central laboratory’s 
database system.  Data will subsequently be transferred from the central vendor to the Lilly data 
warehouse and the TPO’s system.
Bioanalytical data will be stored electronically in the bioanalytical laboratory’s database.  Data 
will subsequently be transferred from the bioanalytical laboratory to the Lilly data warehouse 
and the TPO’s system.
Data from complaint forms submitted to Lilly will be encoded and stored in the global product 
complaint management system.


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13.
Informed Consent, Ethical Review, and Regulatory
Considerations
13.1. Informed Consent
The investigator is responsible for ensuring that the patient understands the potential risks and 
benefits of participating in the study, including answering any questions the patient may have 
throughout the study and sharing in a timely manner any new information that may be relevant to 
the patient’s willingness to continue his or her participation in the trial.
The ICF will be used to explain the potential risks and benefits of study participation to the 
patient in simple terms before the patient is entered into the study and to document that the 
patient is satisfied with his or her understanding of the potential risks and benefits of 
participating in the study and desires to participate in the study.
The investigator is ultimately responsible for ensuring that informed consent is given by each 
patient before the study is started.  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 
the investigational product.
13.2. Ethical Review
Lilly or its representatives must approve all ICFs before they are used at investigative sites.  All 
ICFs must be compliant with the ICH guideline on GCP.  
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).  The ERB(s) will review the protocol as required.
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.
13.3. Regulatory Considerations
This study will be conducted in accordance with:
1) consensus ethics principles derived from international ethics guidelines, including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences
(CIOMS) International Ethical Guidelines 
2) the ICH GCP Guideline [E6]
3) applicable laws and regulations.
The investigator or designee will promptly submit the protocol to applicable ERB(s).
Some of the obligations of the sponsor will be assigned to a TPO.


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An identification code assigned to each patient will be used in lieu of the patient’s name to 
protect the patient’s identity when reporting AEs and/or other trial-related data.
13.3.1. Investigator Information
Site-specific contact information may be provided in a separate document.
13.3.2. 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.
13.3.3. Final Report Signature
The final report coordinating investigator or designee will sign the clinical study report for this 
study, indicating agreement that, to the best of his or her knowledge, the report accurately 
describes the conduct and results of the study.
The investigator with the most enrolled patients 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.


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14.
References
[APA] American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 
4th ed. (DSM-IV). Washington, DC: APA; 1994.  
Chandran V, Raychaudhuri SP. Geoepidemiology and environmental factors of psoriasis and 
psoriatic arthritis. J Autoimmun. 2010;34(3):J314-J321.
Christophers E. Psoriasis—epidemiology and clinical spectrum. Clin Exp Dermatol. 
2001;26(4):314-320.
Clark RA. Resident memory T cells in human health and disease. Sci Transl Med. 
2015;7(269):269rv1.
Ding X, Wang T, Shen Y, Wang X, Zhou C, Tian S, Liu Y, Peng G, Zhou J, Xue S, Wang R, 
Tang Y, Meng X, Pei G, Bai Y, Liu Q, Li H, Zhang J. Prevalence of psoriasis in China: a 
population-based study in six cities. Eur J Dermatol. 2012;22(5):663-667.
[EMA] European Medicines Agency. Committee for medicinal products for human use (CHMP). 
Guideline on clinical investigation of medicinal products indicated for the treatment of 
psoriasis. 2004;CHMP/EWP/2454/02 corr. Available at: 
http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC50
0003329.pdf. Accessed 08 April 2016.
[FDA] Food and Drug Administration. Guidance for industry: Suicidal ideation and behavior: 
prospective assessment of occurrence in clinical trials [draft]. 2012. Available at: 
http://www.fda.gov/drugs/guidancecomplianceregulatoryinformation/guidances/ucm315156.ht
m. Accessed 21 July 2016.
Fredriksson T, Pettersson U. Severe psoriasis—oral therapy with a new retinoid. Dermatologica. 
1978;157(4):238-244.
[IFPA] International Federation of Psoriasis Associations. Profile of psoriasis. 2016. Available 
at: http://www.ifpa-pso.org/web/page.aspx?refid=42. Accessed 28 April 2016.
Krueger JG, Fretzin S, Suárez-Fariñas M, Haslett PA, Phipps KM, Cameron GS, McColm J, 
Katcherian A, Cueto I, White T, Banerjee S, Hoffman RW. IL-17A is essential for cell 
activation and inflammatory gene circuits in subjects with psoriasis. J Allergy Clin Immunol. 
2012;130(1):145-154.
Menter A, Gottlieb A, Feldman SR, VanVoorhees AS, Leonardi CL, Gordon KB, Lebwohl M, 
Koo JYM, Elmets CA, Korman NJ, Beutner KR, Bhushan R. Guidelines of care for the 
management of psoriasis and psoriatic arthritis: section 1. Overview of psoriasis and 
guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. 
2008;58(5):826-850.
Parisi R, Symmons DPM, Griffiths CEM, Ashcroft DM. Identification and Management of 
Psoriasis and Associated ComorbidiTy (IMPACT) project team. Global epidemiology of 
psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol.
2013;133(2):377-385.


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Posner K, Oquendo MA, Gould M, Stanley B, Davies M. Columbia Classification Algorithm of 
Suicide Assessment (C-CASA): classification of suicidal events in the FDA’s pediatric 
suicidal risk analysis of antidepressants. Am J Psychiatry. 2007;164(7):1035-1043.
Yeung H, Takeshita J, Mehta NN, Kimmel SE, Ogdie A, Margolis DJ, Shin DB, Attor R, Troxel 
AB, Gelfand JM. Psoriasis severity and the prevalence of major medical comorbidity: a 
population-based study. JAMA Dermatol. 2013;149(10):1173-1179.


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Attachment 1.Protocol RHBN Study Schedule—
Single-Dose Phase


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Study Schedule Protocol I1F-MC-RHBN—Single-Dose Phase 
Period
Procedure
Screening
Dosing
Observation Period
Visit Number
V1a
V2
V3
V4
V5
V6
V7
V8
V9
V10
V11
V12
V13
V14
Day Relative to Start of Study Drug
-28 to -3
1 
3
5
8
11
15
22
29
43
57
85
113
141
Week Relative to Start of Study Drug
0
1
2
3
4
6
8
12
16
20
Visit Tolerance Interval (Days)
0
0
0
0
0
1
2
2
2
2
2
7
7
Informed consent (before procedures/ tests)
X
Demographics, height, weightb
X
Inclusion/exclusion review
X
PreD
History and/or physical examination
X
PreD
X
X
X
Concomitant medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Preexisting conditions/adverse events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital signsc
X
PreD, 1h, 
3 h
X
X
X
X
X
Body temperature
X
PreD
X
Chest x-ray and PPD/QTF or T-SPOT
testing for TBd,e
X
ECGf,g
X
PreD
X
X
X
X
Study drug dosed 
X
Serum ixekizumab PK sampleh
PreD
X
X
X
X
X
X
X
X
X
X
X
X
QIDS-SR16
X
C-SSRS
PreD
X
X
X
X
X
X
X
X
X
X
X
X
PASI
X
PreD
X
X
X
X
X
sPGA
X
PreD
X
X
X
X
X
Clinical chemistry, electrolytes, 
hematologyi
X
PreD
X
X
X
X
X
High-sensitivity C-reactive protein
PreD
X
X
X
Urinalysis
X
PreD
X
X
X
Serum for anti-ixekizumab antibody
PreD
X
X
X
X
X
Urine pregnancy testj
X
PreD
X
X


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Study Schedule Protocol I1F-MC-RHBN—Single-Dose Phase 
Abbreviations: C-SSRS = Columbia-Suicide Severity Rating Scale; ECG = electrocardiogram; h = hour(s); PASI = Psoriasis Area and Severity Index; PK = 
pharmacokinetics; PPD = purified protein derivative; PreD = prior to dose; QIDS-SR16 = Quick Inventory of Depressive Symptomatology–Self Report, 
16 item; QTF = QuantiFERON®-TB Gold test; sPGA = static Physician’s Global Assessment; TB = tuberculosis; T-SPOT = T-SPOT®.TB test; V = visit.  
Notes:  Patients who withdraw from the treatment phase will have an early treatment discontinuation visit with procedures performed as shown for Visit 14.
Each blood draw should be collected at approximately the same time of day as the dose administration at Week 0 (Visit 2). 
a
Visit 1 procedures may be conducted over more than 1 day as long as all tasks are completed within the allowable visit tolerance (at least 3 days should be 
allowed for receipt of laboratory test results).
b
Weight may be recorded at other visits as clinically indicated.
c
Sitting blood pressure, respiratory rate, and pulse rate are to be obtained at approximately the same time as ECG measurements or plasma ixekizumab blood 
sampling.  When multiple assessments are scheduled for the same time point, the order of completion should be ECG, vital signs, and then blood sampling.
d
Patients with documentation of a negative test result within 3 months prior to baseline (Week 0; Visit 2) do not need a TB screen at Visit 1.
e
See Section 10.4.3.5 for detailed description of PPD/QTF or T-SPOT testing.
f
To account for diurnal variations, ECGs should be performed at approximately the same time of day as the Visit 2 predose ECG (2 hours).  
g
Additional ECGs may be performed as clinically indicated. 
h
Each blood draw should be collected at approximately the same time of day as the initial sample taken prior to dose administration at Week 0 (Visit 2).  
i
Unscheduled blood chemistry and hematology panels may be performed at the discretion of the investigator.
j
Required for all women.


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Attachment 2.Protocol RHBN Study Schedule—
Multiple-Dose Phase 


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Study Schedule Protocol I1F-MC-RHBN—Multiple-Dose Phase 
Period
Procedure
Screening
Treatment Period
Observation Period
Visit Number
V1a
V2
Randomize
V3 V4 V5 V6 V7 V8 V9 V10 V11 V11A V11B V11C V11D V11E V11F V12 V12A V13 V14 V15V16
Day Relative to Start of 
Study Drug
-28 to 
-3
1 
3
5
8
11 15
22
29
43
57
59
61
64
67
71
78
85
99
113 141 169 197
Week Relative to Start of 
Study Drug
0
1
2
3
4
6
8
8
8
9
9
10
11
12
14
16
20
24
28
Visit Tolerance Interval 
(Days)
0
0
0
0
0
1 2
2
2
2
1
1
1
1
1
2
2
7
7
7
7
7
Informed consent (before 
procedures/tests)
X
Demographics, height, 
weightb
X
Inclusion/exclusion review
X
PreD
History and/or physical 
examination
X
PreD
X
X
X
Concomitant medications
X
X
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
Preexisting 
conditions/adverse events
X
X
X X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital signsc
X
PreD, 1h, 
3 h
X
X
X
X
X
X
X
Body temperature
X
PreD
X
X
X
d
X
X
Chest x-ray and PPD/QTF 
or T-SPOT testing for TBe,f
X
ECGg,h
X
PreD 
X X
X
X
X
X
Study drug dosed 
   Q2W group
X
X
X
X
X
   Q4W group
X
X
X
Serum ixekizumab PK 
samplei,j
PreD
X X
X
X
X
X
X
Xk
X
X
X
X
X
X
X
X
X
X
X
X
X
QIDS-SR16
X
C-SSRS
PreD
X X
X
X
X
X
X
X
X
X
X
X
X
X
PASI
X
PreD
X
X
X
X
X
X
X
X


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Study Schedule Protocol I1F-MC-RHBN—Multiple-Dose Phase 
Period
Procedure
Entry
Treatment Period
Observation Period
Visit Number
V1a
V2
Randomize
V3 V4 V5 V6 V7 V8 V9 V10 V11 V11A V11B V11C V11D V11E V11F V12 V12A V13 V14 V15 V16
Day Relative to Start of 
Study Drug
-28 to 
-3
1 
3
5
8
11 15 22
29
43
57
59
61
64
67
71
78
85
99
113 141 169 197
Week Relative to Start of 
Study Drug
1
2
3
4
5
7
9
9
9
10
10
11
12
13
15
17
21
25
29
Visit Tolerance Interval 
(Days)
0
0
0
0
0
1 2
2
2
2
1
1
1
1
1
2
2
7
7
7
7
7
sPGA
X
PreD
X
X
X
X
X
X
X
X
Clinical chemistry, 
electrolytes, hematologyl
X
PreD
X
X
X
X
X
X
High-sensitivity C-reactive 
protein
PreD
X
X
X
X
Urinalysis
X
PreD
X
X
X
X
Serum for anti-ixekizumab 
antibody
PreD
X
X
X
X
X
X
Urine pregnancy testm
X
PreD
X
X
X
Abbreviations: C-SSRS = Columbia-Suicide Severity Rating Scale; ECG = electrocardiogram; h = hour(s); PASI = Psoriasis Area and Severity Index; PK = 
pharmacokinetics; PPD = purified protein derivative; PreD = prior to dose; Q2W = every 2 weeks; Q4W = every 4 weeks; QIDS-SR16 = Quick Inventory of 
Depressive Symptomatology–Self Report,16 item; QTF = QuantiFERON®-TB Gold test; sPGA = static Physician’s Global Assessment; TB = tuberculosis; 
T-SPOT = T-SPOT®.TB test; V = visit.  
Notes:  Patients who withdraw from the treatment phase will have an early treatment discontinuation visit with procedures performed as shown for Visit 16. 
Visits denoted by a letter after the visit number are visits at which the patient will visit the study site for serum ixekizumab sampling only.  No other tests will be 
performed at these visits. 
a
Visit 1 procedures may be conducted over more than 1 day as long as all tasks are completed within the allowable visit tolerance (at least 3 days should be 
allowed for receipt of laboratory test results).
b
Weight may be recorded at other visits as clinically indicated.
c
Sitting blood pressure, respiratory rate, and pulse rate are to be obtained at approximately the same time as ECG measurements or plasma ixekizumab blood 
sampling.  When multiple assessments are scheduled for the same time point, the order of completion should be ECG, vital signs, and then blood sampling.
d
Body temperature should be taken only for patients in the Q2W group at this visit because patients in the Q4W group do not receive study drug at this visit.
e
Patients with documentation of a negative test result within 3 months prior to baseline (Week 0; Visit 2) do not need a TB screen at Visit 1.
f
See Section 10.4.3.5 for detailed description of PPD/QTF or T-SPOT testing.
g
To account for diurnal variations, ECGs should be performed at approximately the same time of day as the Visit 2 predose ECG (2 hours).
h
Additional ECGs may be performed as clinically indicated. 
i
Each blood draw should be collected at approximately the same time of day as the initial sample taken prior to dose administration at Week 0 (Visit 2).  


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j
When PK samples are scheduled at the same visits as dose administrations, then the PK sample should be taken pre-dose. 
k
Only for the Q2W dosing regimen.
l
Unscheduled blood chemistry and hematology panels may be performed at the discretion of the investigator.
m Required for all women.


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Attachment 3.Protocol RHBN Clinical Laboratory Tests


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Laboratory Tests
Hematologya,b
Clinical Chemistrya,b
Hemoglobin
Serum Concentrations of:
Hematocrit
Sodium
Erythrocyte count (RBC)
Potassium
Mean cell volume (MCV)
Total bilirubin
Mean cell hemoglobin concentration (MCHC)
Direct bilirubin
Leukocytes (WBC)
Alkaline phosphatase
Neutrophils, segmented
Alanine aminotransferase (ALT/SGPT)
Lymphocytes
Aspartate aminotransferase (AST/SGOT)
Monocytes
Blood urea nitrogen (BUN)
Eosinophils
Creatinine
Basophils
Calcium
Platelets
Glucose, nonfasting
Total protein
Albumin
Cholesterol 
High-sensitivity C-reactive protein  (see Study Schedule 
for sampling time points)
Urinalysisa
Specific gravity
pH
Other Tests
Protein
Follicle-stimulating hormone (FSH)a,d
Glucose
Hepatitis B core antibody, Hepatitis B surface antibody, 
and Hepatitis B surface antigena,e
Ketones
Hepatitis C antibodya,e
Blood
Human immunodeficiency virus (HIV)a,e
Leukocyte esterase  
Purified protein derivative (PPD) skin testc,f
Urine drug screen (at screening only)
Immunogenicity testing (anti-ixekizumab antibody)
Urine Pregnancy Testc,d
a
Assayed by Lilly-designated laboratory.
b
Unscheduled blood chemistry and hematology panels may be performed at the discretion of the investigator.  
c
Performed and read by investigator or investigator’s designee.  
d
Required for all women of childbearing potential.  Also required at Visit 1 for women 40 and <60 years of age 
who have had a cessation of menses for 12 months and an FSH test confirming nonchildbearing potential 
(40 mIU/mL).
e
Test required only at Visit 1 to determine eligibility of subject for the study.  Test may be waived if results are 
available from a test obtained within the last 6 months.
f
The QuantiFERON-TB Gold test or T-SPOT.TB test may be used instead of the PPD test at Visit 1 to 
determine eligibility of a subject for the study.  Test may be waived if documented negative results are available 
from a test obtained within the last 3 months and no history of exposure to a case of active tuberculosis (TB) or 
visit to a TB endemic area since the time of the test.


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Attachment 4.Protocol RHBN Blood Sampling Summary
This table summarizes the approximate number of venipunctures and blood volumes for all 
blood sampling (screening, safety laboratories, and bioanalytical assays) during the study.  Fewer 
venipunctures and blood draws may actually occur, but this will not require a protocol 
amendment.
Protocol I1F-MC-RHBN Sampling Summary—Single-Dose Phase
Purpose
Maximum Blood Volume 
per Sample (mL)
Maximum Number 
of Blood Samples
Maximum Total 
Volume (mL)
Screening testsa
45
1
45
Blood chemistry and hematologya
12
6
72
High-sensitivity C-reactive protein
2.5
4
10
Anti-ixekizumab antibody
7.5
6
45
Serum ixekizumab PK sampleb
4
13
52
Total for clinical purposes (rounded up to the nearest 10 mL)
230
a
Additional samples may be drawn if needed for safety purposes.
b
With the exception of Visit 12, blood samples that may be analyzed for ixekizumab serum concentration will be 
collected at the same time as the immunogenicity samples.  These results may be used to facilitate the 
interpretation of the immunogenicity data.  
Protocol I1F-MC-RHBN Sampling Summary—Multiple-Dose Phase
Purpose
Maximum Blood Volume 
per Sample (mL)
Maximum Number 
of Blood Samples
Maximum Total 
Volume (mL)
Screening testsa
45
1
45
Blood chemistry and hematologya
12
7
84
High-sensitivity C-reactive protein
2.5
5
12.5
Anti-ixekizumab antibody
7.5
7
52.5
Serum ixekizumab PK sampleb
4
22
88
Total for clinical purposes (rounded up to the nearest 10 mL)
290
a
Additional samples may be drawn if needed for safety purposes.
b
With the exception of Visit 12, blood samples that may be analyzed for ixekizumab serum concentration will be 
collected at the same time as the immunogenicity samples.  These results may be used to facilitate the 
interpretation of the immunogenicity data. 


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Attachment 5.Protocol Amendment I1F-MC-RHBN(c) 
Summary
A Phase 1, Single- and Multiple-Dose Study to Assess the 
Safety and Pharmacokinetics of Ixekizumab (LY2439821) 
(Anti–IL-17 Humanized Antibody) in
Chinese Patients with Psoriasis Vulgaris
Overview
Protocol I1F-MC-RHBN(b), A Phase 1, Single- and Multiple-Dose Study to Assess the Safety 
and Pharmacokinetics of Ixekizumab (LY2439821) (Anti–IL-17 Humanized Antibody) in 
Chinese Patients with Psoriasis Vulgaris, has been amended.  The new protocol is indicated by 
Amendment (c) and will be used to conduct the study in place of any preceding version of the 
protocol.
The overall changes and rationale for the changes made to this protocol are as follows:

Section 9.2 has been amended to allow for warming of the syringes for approximately 30 
minutes as opposed to strictly 30 minutes.  This will allow more flexibility and ease of 
operation for the site.

Section 9.6 has been amended to ensure alignment with exclusion criterion [14] and to 
include additional topical therapies for patient’s use during the study since they will not 
impact the primary and secondary objectives.


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Revised Protocol Sections
Note:
All deletions have been identified by strikethroughs.
All additions have been identified by the use of underscore.
Section 9.2
Treatment Administration
Allow the prefilled syringe containing the drug product to equilibrate to room temperature for 
approximately 30 minutes.  Do not return syringe to the refrigerator. The prefilled syringes 
should be taken from the refrigerator and allowed to warm up to room temperature for 30 
minutes prior to use.  
Section 9.6
Concomitant Therapy
The following therapies will not be permitted during the course of the study:  

psoriasis therapy as described in the Inclusion and Exclusion Criteria (Sections 8.1.1 and 
8.1.2), except as described in the following paragraphs for topical agents.

concomitant medications as described in the Inclusion and Exclusion Criteria 
(Sections 8.1.1 and 8.1.2)

live vaccines

phototherapy.
Topical Psoriasis Treatment: Topical psoriasis treatment as indicated below will be permitted 
after completion of Week 4 (Visit 9) and prior to Week 18 (Day 127) during the single-dose 
phase and after completion of the Week 12 visit during the multiple-dose phase.

Steroids: Topical treatments including, but not limited to corticosteroids, vitamin D 
analogues, tarzarotene, and tacrolimus are permitted. SteroidsOnly steroids of mild 
potency (for example, desonide, fluocinolone acetonide, and alclometasone) or low 
potency (that is, hydrocortisone) will be permitted for use limited to are 
recommended for the face, axilla, and/or genitalia as needed.  These topical 
medications should not be used within approximately 24 hours prior to study visits 
requiring sPGA and PASI measures.  More potent topical steroids may be used as 
needed after last study visit.

Medicated shampoos and other nonsteroidal topical therapies: Medicated 
shampoos, topical moisturizers/emollients, and other nonprescription topical products 
are permitted. These topical medications should not be used within approximately 
12 hours prior to study visits requiring sPGA and PASI measures.


I1F-MC-RHBN(c) Protocol
Page 62
LY2439821
Other Concomitant Therapies:  The following will be allowed as needed:  shampoos that do 
not contain <3% salicylic acid, corticosteroids, coal tar, or vitamin D3 analogues; topical 
moisturizers/emollients and other nonprescription topical products that do not contain urea, 
>3% salicylic acid, - or -hydroxyl acids, corticosteroids, or vitamin D3 analogues; and bath 
oils and oatmeal bath preparations. (These topical therapies are not to be used within 12 hours 
prior to a study visit.)  Shampoos that contain >3% salicylic acid, corticosteroids, coal tar, or 
vitamin D3 analogues may be used as needed after end-of-study assessments are complete.  
Acetaminophen or aspirin will also be allowed as needed.


Leo Document ID = 0858ddad-8548-4a3f-b56b-8a7517d78796
Approver: 
Approval Date & Time: 20-Jun-2017 14:36:57 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 20-Jun-2017 16:05:15 GMT
Signature meaning: Approved
PPD
PPD

SAP_001.pdf: 
Statistical Analysis Plan Version 2 
 
 
A Phase 1, Single- and Multiple-Dose Study to Assess the Safety and Pharmacokinetics of 
Ixekizumab (LY2439821) (Anti–IL-17 Humanized Antibody) in Chinese Patients with Psoriasis 
Vulgaris 
 
NCT03073213 
 
Approval Date: 28-Sep-2018 
 


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STATISTICAL ANALYSIS PLAN
A Phase 1, Single-and Multiple-Dose Study to Assess theSafety and Pharmacokinetics of 
Ixekizumab (LY2439821)(Anti–IL-17 Humanized Antibody) inChinese Patients with 
Psoriasis Vulgaris
Statistical Analysis Plan Status:Version 2
Statistical Analysis Plan Date:28-September-2018
Study Drug: Ixekizumab (LY2439821)
Sponsor Reference:  I1F-MC-RHBN
Covance CRU Study: 1001215-8346599
Clinical Phase I
Statistical Analysis Plan Version 1 electronically signed and approved by Lilly:
28 Feburary 2017
Statistical Analysis Plan Version 2 electronically signed and approved by Lilly on the data 
provided below.


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1.TABLE OF CONTENTS
1. TABLE OF CONTENTS...................................................................................................2
2. ABBREVIATIONS............................................................................................................4
3. INTRODUCTION.............................................................................................................6
4. STUDY OBJECTIVES......................................................................................................6
4.1 Primary Objective........................................................................................................6
4.2 Secondary Objective....................................................................................................6
4.3 Exploratory Objective..................................................................................................6
5. STUDY DESIGN...............................................................................................................7
6. TREATMENTS.................................................................................................................8
7. SAMPLE SIZE JUSTIFICATION.....................................................................................9
8. DEFINITION OF ANALYSIS POPULATIONS................................................................9
9. STATISTICAL METHODOLOGY...................................................................................9
9.1 General........................................................................................................................9
9.2 Demographics and Patient Disposition.......................................................................10
9.3 Pharmacokinetic Assessment.....................................................................................10
9.3.1
Pharmacokinetic Analysis.................................................................................10
9.3.2
Pharmacokinetic Statistical Methodology.........................................................15
9.4 Pharmacodynamic Assessment..................................................................................15
9.4.1
Pharmacodynamic Analysis..............................................................................15
9.4.2
Pharmacodynamic Statistical Methodology......................................................15
9.5 Pharmacokinetic/Pharmacodynamic Analyses...........................................................18
9.6 Safety and Tolerability Assessments..........................................................................18
9.6.1
Adverse events.................................................................................................18
9.6.2
Concomitant medication...................................................................................19
9.6.3
Clinical laboratory parameters..........................................................................19
9.6.4
Vital signs........................................................................................................19
9.6.5
Immunogenicity...............................................................................................19
9.6.6
Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR16).....20
9.6.7
Columbia-Suicide Severity Rating Scale (C-SSRS)..........................................20
9.6.8
Other assessments.............................................................................................20
9.6.9
Safety and Tolerability Statistical Methodology................................................20


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10.INTERIM ANALYSES...................................................................................................20
11.CHANGES FROM THE PROTOCOL SPECIFIED STATISTICAL ANALYSES..........20
12.REFERENCES................................................................................................................20
13.DATA PRESENTATION................................................................................................20
13.1Derived Parameters...................................................................................................20
13.2Missing Data.............................................................................................................21
13.3Insufficient Data for Presentation..............................................................................21


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2.ABBREVIATIONS
Abbreviations pertain to the Statistical Analysis Plan (SAP)only (not thetables, figures and 
listings[TFLs]).
AE
Adverse event
AUC
Area under the concentration versus time curve
AUC(0-t
last)  
Area under the concentration versus time curve from time zero to 
time t, where t isthe last time point with a measurable concentration
AUC(0-∞) 
Area under the concentration versus time curve from zero to infinity
%AUC(tlast-)
Percentage of AUC(0-∞) extrapolated
AUCτ
Area under the concentration versus time curve during one dosing 
interval
BSA
Body surface area
BQL
Below the quantifiable lower limit of the assay
Clast
Last predicted concentration
Cmax
Maximum observed drug concentration
CL/F
Apparent total body clearance of drug calculated after extra-vascular
administration
CRF
Case Report Form
CSR
Clinical Study Report
C-SSRS 
Columbia-Suicide Severity Rating Scale
CRU
Clinical Research Unit
CV
Coefficient of variation
EC
Early Clinical 
e.g.
For example (Latin: exempli gratia)
ICH
International Conference on Harmonisation
LLOQ 
Lower limit of quantification
MedDRA 
Medical Dictionary for Regulatory Activities
PASI 
Psoriasis Area and Severity Index
PD
Pharmacodynamic
PK
Pharmacokinetic
PSAP 
Program Safety Analysis Pllan
QIDS-SR16 
Quick Inventory of Depressive Symptomatology-Self Report


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Q2W
Every 2 weeks
Q4W
Every 4 weeks
QTcB 
QT interval corrected using Bazett’s formula
QTcF 
QT interval corrected using Fridericia’s formula
SAP
Statistical Analysis Plan
sPGA 
Static Physician’sGlobal Assessment
SC
Subcutaneous
SD
Standard deviation 
SDP
Single-dose phase
MDP
Multiple-dose phase
TFLs
Tables, Figures, and Listings
t
1/2
Half-life associated with the terminal rate constant (λ
z) in non-
compartmentalanalysis
TE-ADA 
treatment-emergent antidrug antibody
t
max
Time ofmaximum observed drug concentration
t
last
Time of last observed drug concentration
Vss/F 
Apparent volume of distribution at steady state after extra vascular 
administration.
Vz/F
Apparent volume of distribution during the terminal phase after 
extra-vascularadministration
WHO
World Health Organization


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3.INTRODUCTION
This SAP has been developed after review of the Clinical Study Protocol (final version dated 
10May 2016),Protocol Amendment (a) (final version dated 22 July 2016), Protocol Amendment
(b) (final version dated23 November 2016), and Protocol Amendment(c) (final version dated20 
June 2017).
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, PDand PK 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 limitedamount 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 
patientadministrationfor 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 supersedesthe 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 ECBiometricsand 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 
Conferenceon Harmonisation (ICH) E9 Guideline entitled Guidance for Industry: Statistical 
Principles for Clinical Trials1and the ICH E3 Guideline entitled Guidance for Industry: 
Structure and Content of Clinical Study Reports
2.
4.STUDY OBJECTIVES
4.1Primary Objective
The primary objective of this study is to assess the PK of ixekizumab after single and multiple
subcutaneous (SC)doses in Chinese patients with psoriasis.
4.2Secondary Objective
The secondary objective of this study is as follows:
to assess the safety, tolerability, and immunogenicity of ixekizumab inChinese patients 
with psoriasis.
4.3Exploratory Objective
The exploratory objective of this study is as follows:


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to assess the efficacy endpoints of Psoriasis Area and Severity Index (PASI)and static 
Physician’s Global Assessment (sPGA) of ixekizumab after singleand multiple SC doses 
in Chinese patients with psoriasis.
5.STUDY DESIGN
Study RHBN is a Phase 1, multicenter, open-label, single-and multiple-dose outpatient study in
up to 45 patients with psoriasis.  A 160 mg SC starting dose (Week 0) followed by an 80 mg SC 
dose Q2W or Q4Wwas evaluated as an induction dosing regimen over 12 weeks of treatment in 
global pivotal Phase3 studies in patients with psoriasis (Studies RHAZ, RHBA, and RHBC). In 
this study, the PK profile and safety/tolerability of ixekizumab 80 mg will be assessed initially in 
the single-dosephase. Thereafter, the induction dosing regimens evaluated in the pivotal Phase 3 
studies will beevaluated in the multiple-dose phase for this Phase 1 study in China.
For the single-dose phase, patients will receive a single dose of ixekizumab 80 mg SC on Day 1
and will be assessed at regular visits for 20 weeks. Patients completing the single-dose phase
have the option of enrolling in the multiple-dose phase after completing the final visit in the
single-dose phase. Patients will remain at the site for a minimum of 4 hours postdose.
The multiple-dose phase can be initiated once 6 patients have completed the Week 6 (Day 43)
visit in the single-dose phase and safety data collected through 6 weeks postdosing from these
patients have been reviewed. After review of these safety data, an agreement on initiation of the
multiple-dose phase will be made by the investigator and sponsor.
In the multiple-dose phase, patients will be administered a starting dose of ixekizumab 160 mg
SC on Day 1 and will then be randomized into 1 of 2 dosing regimens for the 8-week treatment
period: (1) 80 mg SC Q2W(at Weeks 2, 4, 6 and 8)or (2) 80 mg SC Q4W(at Weeks 4 and 8). 
After Week 8, patients will be assessed at regular visits foran additional 20 weeks. Patients will 
remain at the site for a minimum of 4 hours after the firstdose and for 2 hours after subsequent 
doses.
Figure 1 and Figure 2 illustrate the study design for the single-dose phase andmultiple-dose 
phase, respectively. 


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Figure 1. Study design for the single-dose phase of Study I1F-MC-RHBN
Figure 2. Study design for multiple-dose phase of Study I1F-MC-RHBN
6.TREATMENTS
The following is a list of the study treatment abbreviations that will be used in the TFLs.
Study Treatment Name
Treatment order in TFL
Ixekizumab80 mg Single Dose
1
Ixekizumab160 mgStarting Dose /80 mg Q2W
2
Ixekizumab160 mgStarting Dose/80 mg Q4W
3


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7.SAMPLE SIZE JUSTIFICATION
Up to 45 patients (15 patients for the single-dose phase and 30 patients for the multiple-dose
phase) will be enrolled to target that 8 patients complete the single-dose phase and 20 patients
(10 for each dosing regimen) complete the multiple-dose phase.
This study has been designed to meet the primary
 objective of assessing the PK of a single dose
and multiple doses of ixekizumab in Chinese patients with psoriasis. The sample size was
chosen to meet Chinese regulatory requirements and to provide sufficient data to evaluate the
objectives and is not intended to achieve any prior statistical requirements.
8. DEFINITION OF ANALYSIS POPULATIONS
For the single-dose phase the “Safety” population will consist of all enrolled patientswho 
received at least one dose of study drugduring the single-dose phase,whether or not they 
completed all protocol requirements.For the multiple-dose phase, this population will consist of 
all enrolled patients who receivedat least one dose of study drug during the multiple-dose phase.
For the single-dose phase the “Pharmacokinetic” population will consist of all patientswho 
received at least one dose of study drugduring the single-dose phaseand have evaluable PK
data.For the multiple-dose phase, this population will consist of all enrolled patients who 
received at least one dose of study drug during the multiple-dose phase and have evaluable PK 
data.  
For the single-dose phase the “Pharmacodynamic” population will consist of all patientswho 
received at least one dose of study drugduring the single-dose phase and haveat least one 
postbaseline measurement.For the multiple-dose phase, this population will consist of all 
enrolled patients who received at least one dose of study drug during the multiple-dose phaseand 
have at least one postbaseline measurement.
All protocol deviations that occur during the study will be considered for their severity/impact 
and will be taken into consideration when patientsare assigned to analysis populations.
9.STATISTICAL METHODOLOGY
9.1General
Data listings will be provided for all datathat isdatabased. Summary statistics and statistical 
analysis will only be presented for data where detailed in this SAP. For continuous data, 
including PASI, sPGA, and % body surface area (BSA), summary statistics will include the
arithmetic mean, arithmetic standard deviation (SD), median, min, max and N; for log-normal 
data (e.g. the PK parameters: area under the concentration versus time curve[AUCs]and 
maximum observed drug concentration[C
max]) the geometric mean and geometric coefficient of 
variation (CV%) will also be presented.The minimum and maximum will be reported to the 
same number of decimal places as the raw data recorded in the database.  The mean and median 
will be reported to 1 more decimal place than the raw data recorded in the database.  The SD will 


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be reported to 2 more decimal places than the raw data recorded in the database.  In general, the 
maximum number of decimal places reported shall be 4 for any summary statistic.For 
categorical data, frequency count and percentages will be presented. Percentages will be 
presented to 1 decimal place.  Percentages will not be presented for zero counts.  Data listings 
will be provided for all patientsup to the point of withdrawal, with any patientsexcluded from 
the relevant population highlighted. Summary statistics and statistical analyses will generally 
only be performed for patientsincluded 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 patients’change from baseline values. 
Each individual change from baseline will be calculated by subtracting the individual patient’s
baseline value from the value at the timepoint. The individual patient’schange 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 9.3or greater.
9.2 Demographics and PatientDisposition
Patientdisposition will be listed. The demographic variables age, sex, race, ethnicity,country of 
enrolment, site ID,body weight, height and body mass index at baselinewill be summarized and 
listed.If a patient only participates in thesingle-dose phase (SDP) ormultiple-dose phase 
(MDP), baseline is defined as the screening visit; if a patient participates in both SDP and MDP, 
the baseline for SDP and MDP willbe the screening visit in SDP.
Baseline clinical measures such as sPGA score, PASI total score and body surface areaat 
baseline (Day 1, predose)will be summarizedand listed.  If a patient participates in both the 
single-dose and multiple-dose phase of the study, the baseline for SDPwill be the baseline visit
(Day 1, predose)fromSDP, and the baseline for MDP will be the baseline visit (Day 1, predose) 
from MDP.If the baseline Day 1, predose value is missing, the screening value may be used.
9.3 Pharmacokinetic Assessment
9.3.1Pharmacokinetic Analysis
Noncompartmental methods will be applied usinga validated software program (Phoenix 
WinNonlin Version6.4 or later)to analyze the serum concentrations of ixekizumab and 
determine the PK parametersof ixekizumab.  
Single-Dose Phase
Following the 80 mg in the single dose phase, the following PK parameters will be determined, 
when possible:


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Parameter 
Units 
Definition
AUC(0-t
last) 
µg.day/mL 
area under the concentration versus time curve from time zero to 
time t, where t is the last time point with a measurable 
concentration
AUC(0-∞) 
µg.day/mL 
area under the concentration versus time curve from zero to 
infinity
%AUC(tlast-)
%
percentage of AUC(0-∞) extrapolated
Cmax
µg/mL 
maximum observed drug concentration
t
max
day
time of maximum observed drug concentration
t
last
day
time of last observed drug concentration
t
1/2
day
half-life associated with the terminal rate constant (λz) in non-
compartmental analysis
CL/F
L/h
apparent total body clearance of drug calculated after 
extra-vascular administration
Vz/F
L
apparent volume of distribution during the terminal phase after 
extra-vascular administration
Vss/F 
L
apparent volume of distribution at steady state after extra-vascular 
administration
Multiple-Dose Phase
Serum concentrations of ixekizumab following single dosing of 160 mg on Day 1 (i.e. up to 14 
days post the first dose and prior to the second ixekizumab dose), will be used to determine the 
single dose PK parametersand will be a subset of the parameters listed above that can be 
calculated based on only 14 days worth of sampling. Serum concentrations of ixekizumab from 
Week 8 following the last dose of repeated dosing of ixekizuamb will be used to determine the 
following multiple-dose PK parameters, when possible:  
Parameter 
Units 
Definition
AUCτ 
µg.day/mL
area under the concentration versus time curve during one dosing 
interval
Cmax
µg/mL 
maximum observed drug concentration
t
max
day 
time of maximum observed drug concentration
t
1/2
day 
half-life associated with the terminal rate constant (λz) in non-
compartmental analysis
CL/F
L/h 
apparent total body clearance of drug calculated after 
extra-vascular administration
Vz/F
L 
apparent volume of distribution during the terminal phase after 
extra-vascular administration
Vss/F
L 
apparent volume of distribution at steady state after extra-vascular 
administration


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Additional PK parameters may be calculated, as appropriate.  The software and version used for 
the final analyses will be specified in the CSR. Any exceptions or special handling of data will 
be clearly documented within thefinal study report.
Formatting of tables, figures and abbreviations will follow the Eli Lilly Global PK/PD/TS Tool:  
NON-COMPARTMENTAL PHARMACOKINETIC STYLE GUIDE. The version of the tool
effective at the time of PK analysis will be followed.
General PK Parameter Rules
Actual sampling times will be used in the final analyses of individual PK parameters, 
except for non-bolus pre-dose sampling times which will be set to zero. For non-bolus, 
multiple dose profiles, the pre-dose time will be set to zero unless a time deviation falls 
outside of the protocol blood collection time window which is considered to impact PK 
parameter derivation.  
Cmaxand t
maxwill be reported from observed values.  If Cmaxoccurs at more than onetime 
point, tmaxwill be assigned to the first occurrence of C
max. 
AUC parameters will be calculated using a combination of the linear and logarithmic 
trapezoidal methods (linear-log trapezoidal rule).  The linear trapezoidal method will be 
applied up to t
maxand then the logarithmic trapezoidal method will be used after t
max. The 
minimum requirement for the calculation of AUC will be the inclusion of at least three 
consecutive serum concentrations above the lower limit of quantification (LLOQ), with 
at least one of these concentrations following Cmax. 
Half-life (t
½) will be calculated, when appropriate, based on the apparent terminal 
log-linear portion of the concentration-time curve. The start of the terminal elimination 
phase for each patientwill be defined by visual inspection and generally will be the first 
point at which there is no systematic deviation from the log-linear decline in serum 
concentrations.  Half-life will only be calculated when a reliable estimate for this 
parameter can beobtained comprising of at least 3data points.  If t½is estimated over a 
time window of less than 2half-lives, the values will be flagged in the data listings. Any 
t
½ value excluded from summary statistics will be documented in the footnote of the 
summary table. 
A uniform weighting scheme will be used in the regression analysis of the terminal log-
linear portion of the concentration-time curve.
The parameters based on last predicted concentration (Clast) will be reported.
Individual PK Parameter Rules
Only quantifiable concentrations will be used to calculate PK Parameters with the 
exception of special handling of certain concentrations reported below the lower limit of 
quantification (BQL).  Serum concentrations reported as BQL will be set to a value of 
zero when all of the following conditions are met: 


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o The compound is non-endogenous.
o The samples are from the initial dose period for a patientor from a 
subsequent dose period following a suitable wash-out period.
o For patients who participate in the single-dose phase and move to the 
multiple-dose phase a review of the data for measurable predose.
o The time points occur before the first quantifiable concentration.
All other BQL concentrations that do not meet the above criteria will be set to missing. 
Also, where two or more consecutive concentrations are BQL towards the end of a 
profile, the profile will be deemed to have terminated and therefore any further 
quantifiable concentrations will be set to missing for the calculation of the PK parameters 
unless it is considered to be a true characteristic of the profile of the drug.
Quantifiable predose concentrationsobserved on Day 1 of the multiple dose phase will be 
evaluatedfor impact on derived PK parameters.If this occurs, the method of dealing with 
it will be documented in the study report. 
  
Individual Concentration vs. Time Profiles
Individual concentrations will be plotted utilizing actual sampling times.
The terminal point selections will be indicatedon a semi-logarithmic plot.
Average Concentration vs. Time Profiles
The average concentration profiles will be graphed using scheduled (nominal) 
sampling times. 
The average concentration profiles will be graphed using arithmetic average 
concentrations.
The pre-dose averageconcentration for single-dose data from non-endogenous 
compounds will be set to zero.  Otherwise, only quantifiable concentrations will 
be used to calculate average concentrations.
Concentrations at a sampling time exceeding the sampling time window specified 
in the protocol, or ±10%, will be excluded from the average concentration 
profiles.
Concentrations excluded from the mean calculation will be documented in the 
final study report.


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A concentration average will be plotted for a givensampling time only if 2/3 of 
the individual data at the time point have quantifiable measurements that are 
within the sampling time window specified in the protocol or ±10%. An average 
concentration estimated with less than 2/3 but more than 3data points may be 
displayed on the mean concentration plot if determined to be appropriate and will 
be documented within the final study report.
Treatment of Outliers during Pharmacokinetic Analysis
Application of this procedure to all PKanalyses is not a requirement. Rather, this procedure 
provides justification for exclusion of data when scientifically appropriate. This procedure 
describes the methodology for identifying an individual value as an outlier for potential 
exclusion, but does not require that the value be excluded from analysis.  The following 
methodology will not be used to exclude complete profiles from analysis.
Data within an Individual Profile
A value within an individual profile may be excluded from analysis if any ofthe following 
criteria are met:
For PKprofiles during multiple dosing, the concentration of the pre-dose sample exceeds 
all measured concentrations for that individual in the subsequent post-dose samples.
For PKprofiles during single dosing of non-endogenous compounds, the concentration in 
a pre-dose sample is quantifiable.
For any questionable datum that does not satisfy the above criteria, the profile will be 
evaluated and results reported with and without the suspected datum. 
Data between Individual Profiles
1. If n<6, then the dataset is too small to conduct a reliable range test.  Data will be 
analyzed with and without the atypical value, and both sets of results will be reported.  
2. If n6, then an objective outlier test will be used to compare the atypical value to other 
values included in that calculation:
a. Transform all values in the calculation to the logarithmic domain.
b. Find the most extreme value from the arithmetic mean of the log transformed 
values and exclude that value from the dataset.
c. Calculate the lower and upper bounds of the range defined by the arithmetic 
mean ±3*SD of the remaining log-transformed values.
d. If the extreme value is within the range of arithmetic mean ±3*SD, then it is 
not an outlier and will be retained in the dataset.


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e. If the extreme value is outside the range of arithmetic mean ±3*SD, then it is 
an outlier and will be excluded from analysis.
If the remaining dataset contains another atypical datum suspected to be an outlier and n ≥ 6 
following the exclusion, then repeat step 2 above. This evaluation may be repeated as many 
times as necessary, excluding only one suspected outlier in each iteration, until all data 
remaining in the dataset fall within the range of arithmetic mean ±3*SD of the log-transformed 
values.
Reportingof Excluded Values
Individual values excluded as outliers will be documented in the final report.  Approval of the 
final report will connote approval of the exclusion.
9.3.2Pharmacokinetic Statistical Methodology
Descriptive statistics of PK parameterswill be presentedfor each dose regimen (single-dose, 
Q2W multiple-dose, and Q4W multiple-dose)separately.
9.4 Pharmacodynamic Assessment
9.4.1Pharmacodynamic Analysis
Clinical outcome measure PASI and sPGA are considered the PD measures in this study.
9.4.2Pharmacodynamic Statistical Methodology
The sPGAandPASIare considered PD (efficacy) measures of disease activity in this study.  
TableRHBN9.1 includes the description and derivation of the efficacy outcomes.
Descriptive statistics will be presented foroverallPASI scores and sPGA scores (for both the 
single-dose and multiple-dose phases of the study) by dose regimen and study day. 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 will be provided.  The listing 
will include patient number, treatment, timepoint, sPGA score and the sPGA response.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 percent change in PASI scores 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, percent change 
from baseline and the PASI response.    
Additional analyses may be conducted as deemed appropriate.


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Table RHBU.9.1.
Description and Derivationof 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 [WWW]).  
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.
Multiple 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 bodysurface 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:  
 
 
=
100×
 
  
If a patient has experienced an 
improvement, this measure will be 
positive.  If a patient has experienceda 
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
PASIelectronic 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 ofpsoriasis 
on each patient’s BSA 
on acontinuous 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
9.5 Pharmacokinetic/Pharmacodynamic Analyses
Exploratory exposure-response relationship analyses for PASI scores and sPGA scores may be 
conducted, if deemed appropriate.
9.6 Safety and Tolerability Assessments
9.6.1Adverse 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 patienthas 
provided the first 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 within the defined phase, or which is 
present prior to the first dosing and becomes more severe postdosewithin the defined phase.
Treatment-emergent AEs will be assigned to the phaseto which it’s considered treatment-
emergent.Note that for patients who participate inboth phases,(i)if AEs start and end during 
the gap(afterthe end of SDP and before the start of MDP), or if AEs start during the gapand 
continue to the multiple-dose phase without worseningin severity, suchAEs will not be
considered as treatment-emergentor be analyzed, but may be noted in CSR; (ii)if AEs start in 
SDP and continue to MDP without worsening in severity, it will beconsidered as treatment-
emergent in SDP, but not treatment-emergent in MDP. AEsby weekof onset will be presented.
All AEs will be listed. Treatment-emergentAEs will be summarized by phase, dose regimen, 
severity and relationship to the study drug.The frequency (the number of AEs, the number of 
patientsexperiencing an AEand the percentage of patientsexperiencing an AE) of 


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treatment-emergent AEswill be summarized bydose regimen, Medical Dictionary for 
Regulatory Activities (MedDRA)version 19.1(use the latest version of MedDRA whenan 
updated version becomes available)system 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 AEswill be tabulated.
9.6.2Concomitant medication
Concomitant medication will be coded using the World Health Organization(WHO)drug 
dictionary (Version September 2016[use the latest version if an updated version becomes 
available]).Concomitant medication will be listed.If a patient participates in both single-dose 
phase and multiple-dose phase, the concomitant medication startingafter the end of SDP and 
before the start of MDP, will be listed separately and may be noted in CSR.  
9.6.3Clinical laboratory parameters
Allclinical chemistry andhematologydatawill be summarizedby dose regimen and parameter,
and listed.Urinalysis datawill 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 patientdata listings.
9.6.4Vital signs
Vital signs data will be summarized by dose regimentogether with changes from baseline, where 
baseline is defined as Day 1 predose.If a patient participates in both single-dose phase and 
multiple-dose phase, the baseline for the single-dose phaseis defined as Day 1 predose in the 
single-dose phase, and the baseline for the multiple-dose phase is definded as Day 1 predose in 
the multiple-dose phase.Figures of mean vital signs and mean changes from baseline profiles by
treatment will be presented by dose regimen. Furthermore, values for individual patientswill be 
listed.
9.6.5Immunogenicity
A by-patient listing of immunogenicity data will be provided, to include patient, treatment, visit, 
treatment-emergent antidrug antibody (TE-ADA)status, NAb (neutralizing antibody)  status, 
titer and PK concentration.  A by-patient listing of AEsfor patients who are TE-ADA positive 
will be provided along with their immunogenicity data. Definitions are documented in a separate 
ixekizumab program safety analysis plan (PSAP).
By-patient figures will also be provided, which will include immunogenicity results, PK 
concentration and efficacy endpoints.
Additional analyses of immunogenicity data will be conducted as deemed appropriate.


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9.6.6Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR16)
Data from the QIDS-SR16 questionnaire will be listed for individual patients.
9.6.7Columbia-Suicide Severity Rating Scale (C-SSRS)
Data from the C-SSRS will be listed for individual patients.
9.6.8
Other assessments
All other safety assessments not detailed in this section will be listed but not summarized or 
statistically analyzed. 
9.6.9
Safety and Tolerability Statistical Methodology
No inferential statistical analyses are planned.
10. INTERIM ANALYSES
Interim access to data may be conducted to support comparisons of PK data from Chinese 
patients in this study to PK data observed in non-Chinese patients from global studies, to enable 
planning for future studies.  No changes to this study design are planned based on these PK 
analyses.  Additionally, interim access to safety data may occur if deemed necessary or 
appropriate.
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. Observedtime data, e.g. tmax, should be reported as received. N and percentage 
valuesshould be reported as whole numbers.Median values should be treated as an observed 
parameter and reported to the same number of decimal places as minimum and maximum values.


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13.2 
Missing Data
Missing data will not be displayed in listings.
13.3 
Insufficient Data for Presentation
Some of the TFLs maynot have sufficient numbers of patientsor data for presentation. If this 
occurs, the blank TFL shell will be presented with a message printed in the centre ofthe table, 
such as, “No serious adverse events occurred for this study.”