A Phase 3, Multicenter Study With a 36-Week Open-Label Period Followed by a Randomized Double-Blind Withdrawal Period From Week 36 to Week 104 to Evaluate the Long-Term Efficacy and Safety of Ixekizumab (LY2439821) 80 mg Every 2 Weeks in Biologic Disease-Modifying Antirheumatic Drug-Naive Patients With Active Psoriatic Arthritis
Phase: PHASE3
Conditions: Psoriatic Arthritis
Sponsor: Eli Lilly and Company

 
Protocol I1F-MC-RHBF(b) 
 
A Phase 3, Multicenter Study with a 36-Week Open-Label Period Followed by a Randomized 
Double-Blind Withdrawal Period from Week 36 to Week 104 to Evaluate the Long-Term 
Efficacy and Safety of Ixekizumab (LY2439821) 80 mg Every 2 Weeks in Biologic Disease-
Modifying Antirheumatic Drug–Naive Patients with Active Psoriatic Arthritis 
 
NCT02584855 
Approval Date: 21-Mar-2017 
 

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1.Protocol I1F-MC-RHBF(b)
A Phase 3, Multicenter Study with a 36-Week Open-Label 
Period Followed by a Randomized Double-Blind 
Withdrawal Period from Week 36 to Week 104 to Evaluate 
the Long-Term Efficacy and Safety of Ixekizumab 
(LY2439821) 80 mg Every 2 Weeks in Biologic 
Disease-Modifying Antirheumatic Drug–Naive Patients with 
Active Psoriatic Arthritis
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.  This document and its associated 
attachments are subject to United States Freedom of Information Act (FOIA) Exemption 4.
Ixekizumab (LY2439821)
Study I1F-MC-RHBF is a Phase 3, multicenter study with a 36-week initial open-label 
treatment periodexamining the effect of ixekizumab 80 mg every 2 weeks (Q2W)in 
patients with activepsoriatic arthritis(PsA)who are conventional disease-modifying 
antirheumatic drug (cDMARD) inadequate responders(IRs)and biological 
disease-modifying antirheumatic drug (bDMARD)naive followed by a randomized,
double-blind withdrawal period from Week 36 to Week 104examining the effect of 
ixekizumab 80mg Q2W compared to that of placebo.  
Approval Date: 21-Mar-2017 GMT
Eli Lilly and Company
Indianapolis, Indiana USA 46285
Protocol Electronically Signed andApproved by Lilly:  14 July 2015.
Amendment (a) Electronically Signed and Approved by Lilly:  10 February 2016
Amendment (b) Electronically Signed and Approved by Lilly
on approval date provided below. 

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2. Synopsis
Study Rationale
Ixekizumab (LY2439821) is an immunoglobulin G subclass 4 monoclonal antibody that binds 
with high affinity (<3 pM) and specificity to interleukin17A (IL-17A), a proinflammatory 
cytokine.  Ixekizumab does not bind to ligands IL-17B, IL-17C, IL-17D, IL-17E,or IL-17F.  
IL-17 has been shown to be elevated in peripheral blood, synovial fluid, and tissue of patients 
with psoriatic arthritis (PsA).  Specific inhibition of IL-17A represents a targeted approach to the 
management of PsA and a novel mechanism of action compared to other PsA therapies.  
Specifically targeting IL-17Awith ixekizumab is hypothesized to provide meaningful 
therapeutic benefit while reducing the risk of impacting host defenses, which may be inherent 
with some other biologic-based immunomodulatory treatments that targetmultiple immune 
components.  As such, it may provide a therapeutic option for patients who are candidates for 
initial systemic treatment as well as those patients who have lost response, failed to respond, or 
are intolerant to current marketed drugs; and may potentially offer a more favorable safety 
profile compared to currently marketed therapies. Because PsA is a chronic relapsing and 
remitting condition, it isimportant to understand the long-term effects of biologic treatment, 
including whether it is necessary to continue treatment for maintenance of effect.This study
 
fulfills global regulatory advicefrom the European Medicines Agencyfor establishing 
maintenance of treatment effect and assessing reintroduction of treatment upon relapse.

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Clinical Protocol Synopsis:  Study I1F-MC-RHBF
Name of Investigational Product:
ixekizumab (LY2439821)
Title of Study:  A Phase 3, Multicenter Study with a 36-Week Open-Label Period Followed by a Randomized 
Double-Blind Withdrawal Period from Week 36 to Week 104 to Evaluate the Long-Term Efficacy and Safety of 
Ixekizumab (LY2439821) 80 mg Every 2 Weeks in Biologic Disease-Modifying Antirheumatic Drug–Naive 
Patients with Active Psoriatic Arthritis 
Number of Planned Patients/Subjects:
   Entered:  560
   Enrolled/Randomized:  400
   Completed:  360
Phase of Development:  3
Length of Study:  3 years
Estimated first patient visit:  Nov 2015               Estimated last patient visit:  Dec2018
Objectives:  The primary objective of the study is to compare ixekizumab 80 mg every 2 weeks (Q2W) with 
placebo in maintenance of treatment response, as measured by the time to relapse during the randomized 
double-blind withdrawal periodin conventional disease-modifying antirheumatic drug(cDMARD)–inadequate 
responder(IR)and biological disease-modifying antirheumatic drug(bDMARD)–naive patients with active PsA 
who meet randomization criteria (Coates criteriafor minimal disease activity [MDA]for 3consecutive months 
over4consecutive visits).  
The secondary objectives of the study are:
to compare ixekizumab 80 mg Q2W with placebo in maintenance of treatment response, as measured by 
the proportion of patients who meet relapse criteria during the randomized double-blind withdrawal 
periodin cDMARD-IR and bDMARD-naive patients with active PsA who meet randomization criteria 
(Coates criteriafor MDA for 3consecutive months over 4 consecutive visits)
to evaluate the time to loss of response for each individual component of MDA in the randomized 
double-blind withdrawal period
to evaluate time to first meet Coates criteriafor MDA during the initial open-label treatment period
(Period 2)
to evaluate time to achieve Coates criteriafor MDA during the initial open-label treatment period
(Period2) (Coates criteriaforMDA for 3 consecutive months over 4 consecutive visits)
to assess the efficacy of ixekizumab 80 mg Q2W following disease relapse after randomization in the 
randomized double-blind treatment period
to assess the effect of treatment response as measured by the Health Assessment Questionnaire–Disability 
Index of ixekizumab 80 mg Q2W throughout the study
Study Design:  Study I1F-MC-RHBF is a Phase 3, multicenter study with a 36-week initial open-label treatment 
period examining the effect of ixekizumab 80 mg Q2W in patients with active PsA who are cDMARD-IRsand are 
bDMARDnaive followed by a randomized double-blind withdrawal period from Week 36 to Week 104 examining 
the effect of ixekizumab 80 mg Q2W compared with that of placebo.  Patients whodo not meet the randomized 
withdrawal criteria will continue on ixekizumab 80 mg Q2W uninterrupted during the randomized double-blind 
withdrawal period.  All randomized patients whono longer meet Coates criteriafor MDA at any visit after entering 
the randomized double-blind withdrawal period will receive ixekizumab 80 mg Q2W for the remainder of the 
study period.  In addition, efficacy and safety will be assessed for up to a total of 2 years for patientswho 
participate throughout the entire 2-year study.  
The study consists of 4periods:
Period 1:  screening period (Visits 1 and 1A) lasting from 4 to 30 days beforeWeek 0 (Visit 2)
Period 2:  initial open-label treatment period from Week 0 (baseline, Visit 2) up to Week 36 (Visit 12)
Period 3: randomized double-blind withdrawal period from Week 36 to Week 104 (Visit 29).  Patients 
who have been treated with ixekizumab 80 mg Q2W for at least 36 weeks and have achieved 
4consecutive visitsof meeting Coates criteriafor MDA from Week 36 up to Week 64 will be eligible for 
randomizationat the visit at which these criteria are met.  

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o Patients whomeet the eligibility criteria for randomizationany time from Week36 through 
Week 64 will be randomized in a 1:1 ratio to 1 of 2 treatment arms: ixekizumab 80 mg Q2W or 
placebo. Patients will be assessed for the Coates criteria for MDA at each visit during this study 
period and will remain on theirassigned treatmentsuntil they relapse (no longer meet the Coates 
criteriafor MDA), at which time they will be treated with ixekizumab 80 mg Q2Wuntil 
Week 104.  
o Patients whoare participating in the randomized double-blind withdrawal periodwhodo not 
meet randomization criteriawill continue on ixekizumab 80 mg Q2W until Week 104 and then 
move into the posttreatment follow-up period.
Period 4, theposttreatment follow-up period occurring from the early termination visitor the last 
scheduled visit for a minimum of 12 weeks after that visit, up to 24 weeks if the patient’s neutrophil count 
is low.  All patients withdrawing from the study after receiving even 1 dose of study treatment will 
proceed directly to Period 4.  
Diagnosis and Main Criteria for Inclusion and Exclusions:  The planned study population will include patients 
aged 18 years or older who havehada diagnosis of PsA for ≥6 months and currently meet Classification for 
Psoriatic Arthritis criteria, have at least 3 of 68 tender and 3 of 66 swollen joints, have had inadequate response or 
intolerance to treatment with 1 or more conventional DMARDs, have active psoriatic skin lesions (plaques) or a 
documented history of plaque psoriasis, and who are bDMARDnaive.
Investigational Product, Dosage, and Mode of Administrationor Intervention:  
Ixekizumab 80 mg Q2W = At Week 0, receive a starting dose of 160 mg (given as 2 subcutaneous injections of 
80mg)and at Week 2 begin a dosageof 80 mg Q2W.  
Reference Therapy, Dose, and Mode of Administration or Comparative Intervention:  Placebo maybe given 
during the randomized double-blind withdrawal period.
Planned Duration of Treatment:  Up to 2 years for investigational drug administration and up to 2 years 
24weeks for participation over all 4study periods:
Screening period:  4-30 days
Initial open-label treatment period:  Week 0 to Week 36
Randomized double-blind withdrawal period:  Week 36 to Week 104 
Posttreatment follow-up period:  Week 104 to Week 128.
Criteria for Evaluation:  
Efficacy:  
The following efficacy measures will be assessed in this study: American College of Rheumatology 
Responder Index, Coates criteria forMDA, Composite Psoriatic Disease Activity Index, Disease Activity Score 
(28 diarthrodial joint count) based on C-reactiveprotein, Physician’sGlobal Assessment of Disease Activity 
Visual Analog Scale (VAS), Patient’sGlobal Assessment of Disease Activity VAS, Patient’sAssessment of Pain 
VAS,Patient’s Assessment of Physical Function Health Assessment Questionnaire–Disability Index, TenderJoint 
Count (68 joints), Swollen Joint Count (66 joints), Leeds EnthesitisIndex,Spondyloarthritis Research Consortium 
of Canada enthesitis index, Leeds Dactylitis Index–Basic, Psoriasis Area and Severity Index, percentageof body 
surfaceareaaffected by psoriasis, staticPhysician
's Global Assessment of psoriasis, and Psoriatic Arthritis Disease 
Activity Score.
Safety:  The following safety measures will be assessed in this study:  adverse events (AEs), serious adverse 
events, suspected unexpected serious adverse reactions, AEsof special interest, sitting blood pressure and pulse
rate, electrocardiograms, physical examinations, chest radiographyand tuberculosis testing, urine pregnancy tests, 
and laboratory evaluations including, but not limited to, chemistry, hematology, and immunogenicity testing (anti-
drug antibodies).
Health Outcomes:  The following health outcome measures will be assessed in this study:  itch Numeric Rating 
Scale (NRS), fatigue severity NRS, Medical Outcomes Study 36-Item Short-Form Health Survey, Dermatology 
Life Quality Index, European Quality of Life–5 Dimensions 5 Level, Work Productivity and Activity Impairment–
Specific Health Problem, and Quick Inventory of Depressive Symptomatology–Self Report, (16 items).
Bioanalytical: Concentrations of immunoreactive ixekizumab in human serum as determined by a validated 
method.

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Pharmacokinetics:  For each immunogenicity sample, an aliquot of blood will be used to determine the serum 
concentration of ixekizumab.
Pharmacodynamics:  Efficacy endpoints such asAmerican College of Rheumatology 20% response rate(ACR20)
response rate and Psoriasis Area and Severity Indexand safety endpoints such as neutrophil counts.
Translational Medicine:A multifaceted approach will be employed to explore potential biomarkers in serum, 
plasma, and whole blood RNA and DNA.
Statistical Methods:  
Statistical:  Approximately 400 patients will enter the initial open-label treatment period.  It is expected that 
approximately 34% of the patients will meet the randomization criteria for the randomized double-blind 
withdrawal period.  Approximately 136patients will be randomized in a 1:1 ratio into ixekizumab 80 mg Q2W and 
placebo treatment groups (68patients per treatment group).  This assumption is based on the Study I1F-MC-RHAP 
Week 24 results and estimating the number of patients achieving Coates criteriafor MDA for 3consecutive 
months over 4consecutivevisits of meeting MDA.
It is assumed that approximately 60% and 20% of patients in the placebo and ixekizumab groups, respectively, 
who enter the randomized double-blind withdrawal periodwill relapse (nolonger meet Coates criteriafor MDA).  
According tothese assumptions, a total of 39 patients must meet relapse criteria in the combined treatment groups 
to achieve 95% power to test the superiority of ixekizumab 80 mg Q2W to placebo for time to relapse at a 2-sided 
0.05 significance level.  The dropoutrate beforerelapse for patients randomized in the randomized double-blind 
withdrawal periodis assumed to be 10%.  Sample size and power calculations were calculated using 
nQuery+nTerim 3.0.  Randomization and relapse rates will be monitored to assess whetherthe number of patients 
who enter the initial open-label treatment period should be increased in order to ensure sufficient sample size and 
power for the randomized withdrawal period.
Continuous data will be summarized in terms of the number of observations (n);mean;standard deviation and/or 
standard error of the mean, if applicable;median;minimum;and maximum.  
Categorical data will be summarized in terms of the number of observations (n), frequency count, and percentages.  
Investigator centers will be pooled by geographical region for statistical analysis purposes.
All tests of treatment effects will be conducted at a 2-sided level of 0.05 unless otherwise stated.
Efficacy, health outcomes, and safety data collected in Period 2will be summarized for ixekizumab 80 mg Q2W 
without inferential statistics.  For efficacy, health outcomes, and safety analyses, baseline is defined as the last 
available value before the first dose of study medication in Period 2and in most cases will be the value recorded at 
Week 0 (Visit 2).  
For analysis purposes, the endpoint for Period 2will be defined as the visit of randomization or Week 64 for 
patients who do not meet the randomization criteria.
Kaplan-Meir estimates will be used to estimate the survival curve for time-to variables.
For patients who are randomizedin Period 3, allefficacy, health outcomes, and safety data collected between 
randomization and either through relapse (no longer meetingCoates criteriafor MDA) or through the end of 
Period3will be compared between the ixekizumab 80 mg Q2W and placebo treatment groups.  For the efficacy 
analysis, baseline is defined as the last available value before the first dose of study medication in Period 2and in 
most cases will be the value recorded at Week 0 (Visit 2).  For the safety analysis,baseline is defined as the last 
available value before the first dose study treatment in Period 3.
The Kaplan-Meier product limit method will be used to estimate the survival curves for time-to variables for the 
patients who are randomized to the randomized double-blind withdrawal period.  Treatment comparisons will be 
performed using a log-rank test with treatment,geographic region, and cDMARD use (past use, current use), at the 
time of randomization in Period 3,in the model.
The primary analysis of the categorical efficacy and health outcome variables will use a logistic regression with 
treatment,geographic region, and cDMARD use (past use, current use), at the time of randomization in Period 3,in 
the model.  Secondary analysis of the categorical efficacy and health outcome variableswill be conducted using
the Fisher’sexact test.  
The analysis for all continuous efficacy and health outcome variables, change from baseline to endpoint analysis, 
will be made using analysis of covariance with treatment, baseline value, geographic region, and cDMARD use

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(past use, current use), at the time of randomization in Period 3,in the model.  Missing data will be imputed using 
last observation carried forward.  TypeIII sums of squares for the least-squaresmeans will be used for the 
statistical comparison; the 95% CI will also be reported.  
The Fisher
's exact test will be used for all AE, baseline, discontinuation, and other categorical data.  AEdata will 
be analyzed using exposure-adjusted incidence rates.  Continuous vital-sign and laboratoryvalues will be analyzed 
by an analysis of covariance model with treatment and baseline value as independent variables.  Other continuous 
variables will be analyzed by t-tests unless otherwise stated.
For patients who are randomizedand subsequentlyrelapse in Period 3, efficacy, health outcomes, and safety data 
collected between relapse and the end of Period 3will be summarized for ixekizumab 80 mg Q2W without 
inferential statistics.  For the efficacy and health outcomes analyses, baseline is defined as the last available value 
before the first dose of study medication in Period 2and in most cases will be the value recorded at Week 0 
(Visit2).  For the safety analysis,baseline is defined as the last available value before relapse in Period 3.
For patients who are randomizedin Period 3, efficacy, health outcomes, and safety data collected in Periods 2 and 
3 combined will be summarized for ixekizumab 80 mg Q2W without inferential statistics.  For efficacy, health 
outcomes, and safety analyses, baseline is defined as the last available value before the first dose of study 
medication in Period 2and in most cases will be the value recorded at Week 0 (Visit 2).  
For patients who are not randomizedin Period 3, efficacy, health outcomes, and safety data collected in Periods 2 
and 3 combined will be summarized for ixekizumab 80 mg Q2W without inferential statistics.  For efficacy, health 
outcomes, and safety analyses, baseline is defined as the last available value before the first dose of study 
medication in Period 2and in most cases will be the value recorded at Week 0 (Visit 2).
Safety:Safety will be assessed by summarizing and analyzing serious adverse events, AEs, AEsof special 
interest, vital signs, other measures of cardiovascular function,Columbia–Suicide Severity Rating Scale (C-SSRS),
and laboratory evaluations (including chemistry, calculated creatinine clearance, hematology [including white 
blood cell count and differential], urinalysis [dipstick and microscopic], thyroid-stimulating hormone and free T4, 
and immunogenicity testing [treatment-emergent anti-drug antibodies]).  
Pharmacokinetics/Pharmacodynamics:Observed ixekizumab serum concentrations will be summarized by visits 
and corresponding time when sampling occurred.  
As appropriate, exposure-response relationship will be investigated between ixekizumab exposure and clinically 
important efficacy and pharmacodynamic (PD)measures (for example, proportion of patients achieving Coates 
criteriafor MDA for 3 consecutive months over 4consecutive visits and the maintenance of treatment effects) 
specified in study objectives.  In addition, the relationship between the time course of ixekizumab exposure and the 
time course of the efficacy and PD measures may be explored using graphical methods and a modeling approach.  
Covariates such as body weight, disease duration, baseline value, and so on, will be investigated to assess their 
impact on the PD parameters.  Model evaluation will include using sensitivity analysis and visual predictive check.
Ifa trend or statistically significant difference between the ixekizumab cohort and the placebo cohortis noted in 
any safety endpoint, these endpoints will also be explored to investigate exposure-response relationships.
The potential impact of immunogenicity on ixekizumab exposure and/or PD responses will be evaluated, as 
appropriate, by graphical assessments to compare drug exposure or PD responses between 
immunogenicity-negative and immunogenicity-positive patients at correspondent visits or before and 
afterimmunogenicity development for patients whose immunogenicity was detected.  In addition, the effect 
ofimmunogenicity may be evaluated in the population pharmacokinetic/PD modeling analyses 
whereimmunogenicity will be evaluated as a covariate.

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3.Table of Contents
A Phase 3, Multicenter Study with a 36-Week Open-Label 
Period Followed by a Randomized Double-Blind Withdrawal 
Period from Week 36 to Week 104 to Evaluate the Long-Term 
Efficacy and Safety of Ixekizumab (LY2439821) 80 mg 
Every2Weeks in Biologic Disease-Modifying Antirheumatic 
Drug–Naive Patients with Active Psoriatic Arthritis
Section
Page
1.
Protocol I1F-MC-RHBF(b) A Phase 3, Multicenter Study with a 36-
Week Open-Label Period Followed by a Randomized Double-Blind 
Withdrawal Period from Week 36 to Week 104 to Evaluate the 
Long-Term Efficacy and Safety of Ixekizumab (LY2439821) 80 mg 
Every 2 Weeks in Biologic Disease-Modifying Antirheumatic Drug–
Naive Patients with Active Psoriatic Arthritis......................................................................1
2.
Synopsis.............................................................................................................................2
3.
Table of Contents................................................................................................................7
4.
Abbreviations andDefinitions...........................................................................................15
5.
Introduction......................................................................................................................21
6.
Objectives.........................................................................................................................25
6.1. Primary Objective........................................................................................................25
6.2. Secondary Objectives...................................................................................................25
6.3. Exploratory Objectives.................................................................................................25
7.
Investigational Plan...........................................................................................................27
7.1. Summary of Study Design............................................................................................27
7.1.1. Screening Period (Period 1)..................................................................................31
7.1.2. Initial Open-Label Treatment Period (Period 2)....................................................31
7.1.3. Randomized Double-Blind Withdrawal Period (Period 3)....................................31
7.1.4. Posttreatment Follow-Up Period (Period 4)..........................................................32
7.2. Discussion of Design and Control................................................................................33
8.
Study Population...............................................................................................................35
8.1. Inclusion Criteria..........................................................................................................35
8.2. Exclusion Criteria........................................................................................................36
8.2.1. Rationale for Exclusion of Certain Study Candidates...........................................41
8.3. Discontinuations..........................................................................................................
42
8.3.1. Discontinuation of Inadvertently Enrolled Patients...............................................42
8.3.1.1.
Discontinuation Criteria..................................................................................42

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8.3.2. Patients Lost to Follow-Up...................................................................................44
8.3.3. Discontinuation of Study Sites.............................................................................44
8.3.4. Discontinuation of the Study................................................................................45
9.
Treatment..........................................................................................................................46
9.1. Treatments Administered.............................................................................................46
9.1.1. Administration of Investigational Product............................................................46
9.2. Materials and Supplies.................................................................................................47
9.3. Method of Assignment to Treatment............................................................................48
9.4. Rationale for Selection of Doses in the Study...............................................................48
9.5. Selection and Timing of Doses.....................................................................................49
9.5.1. Special Treatment Considerations........................................................................49
9.5.2. Use of Study Drug Administration Log................................................................50
9.6. Continued Access to Investigational Product................................................................50
9.7. Blinding.......................................................................................................................51
9.8. Concomitant Therapy...................................................................................................51
9.9. Treatment Compliance.................................................................................................54
10. Efficacy, Health Outcome Measures, Safety Evaluations, Sample 
Collection and Testing, and Appropriateness of Measurements.........................................55
10.1. Efficacy Measures........................................................................................................55
10.1.1. Primary Efficacy Measures..................................................................................55
10.1.1.1. Coates Criteria for Minimal Disease Activity..................................................55
10.1.2. Secondary Efficacy Measures...............................................................................56
10.1.2.1. Tender and Swollen Joint Counts (68 and 66 Joints).......................................56
10.1.2.1.1. Tender Joint Count...................................................................................56
10.1.2.1.2. Swollen Joint Count..................................................................................57
10.1.2.2. Patient’s Assessment of Pain Visual Analog Scale..........................................57
10.1.2.3. Patient’s Global Assessment of Disease Activity Visual 
Analog Scale..................................................................................................57
10.1.2.4. Patient’s Assessment of Physical Function Health 
Assessment Questionnaire–Disability Index...................................................57
10.1.2.5. Psoriasis Area and Severity Index...................................................................58
10.1.2.6. Percentage of Body Surface Area...................................................................58
10.1.2.7. Static Physician
's Global Assessment..............................................................58
10.1.3. Exploratory Efficacy Measures............................................................................58
10.1.3.1. American College of Rheumatology Responder Index....................................58
10.1.3.2. Physician’s Global Assessment of Disease Activity 
Visual Analog Scale.......................................................................................59
10.1.3.3. Leeds Enthesitis Index....................................................................................59

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10.1.3.4. Spondyloarthritis Research Consortium of Canada 
Enthesitis Index..............................................................................................59
10.1.3.5. Leeds Dactylitis Index–Basic..........................................................................59
10.1.3.6. Disease Activity Score Based on C-Reactive Protein......................................60
10.1.3.7. Composite Psoriatic Disease Activity Index....................................................60
10.1.3.8. Psoriatic Arthritis Disease Activity Score.......................................................60
10.2. Health Outcome Measures............................................................................................61
10.2.1. Itch Numeric Rating Scale....................................................................................61
10.2.2. Fatigue Severity Numeric Rating Scale................................................................61
10.2.3. Dermatology Life Quality Index...........................................................................61
10.2.4. Medical Outcomes Study 36-Item Short-Form Health Survey..............................61
10.2.5. European Quality of Life–5 Dimensions 5 Level..................................................61
10.2.6. Work Productivity and Activity Impairment Questionnaire–
Specific Health Problem.......................................................................................62
10.2.7. Quick Inventory of Depressive Symptomatology–Self 
Report (16Items).................................................................................................62
10.3. Safety Evaluations........................................................................................................62
10.3.1. Adverse Events....................................................................................................63
10.3.1.1. Serious Adverse Events..................................................................................64
10.3.1.1.1. Suspected Unexpected Serious Adverse Reactions....................................64
10.3.1.1.2. Adverse Events of Special Interest............................................................65
10.3.2. Other Safety Measures.........................................................................................66
10.3.2.1. Physical Examination.....................................................................................66
10.3.2.2. Electrocardiograms.........................................................................................66
10.3.2.3. Chest Radiography and Tuberculosis Testing..................................................66
10.3.2.4. Vital Signs......................................................................................................68
10.3.2.5. Immunogenicity..............................................................................................68
10.3.2.6. Safety-Related Immune Markers.....................................................................68
10.3.2.7. Columbia–Suicide Severity Rating Scale........................................................68
10.3.3. Safety Monitoring................................................................................................69
10.3.3.1. Neutropenia....................................................................................................69
10.3.3.2. Hypertension..................................................................................................70
10.3.3.3. Hepatic Monitoring........................................................................................70
10.3.3.4. Hepatitis B Monitoring...................................................................................71
10.3.4. Complaint Handling.............................................................................................71
10.4. Sample Collection and Testing.....................................................................................72
10.4.1. Samples for Study Qualification and Health Monitoring.......................................72
10.4.2. Samples for Biomarker Research..........................................................................73
10.4.3. Samples for Immunogenicity Research.................................................................74

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10.4.4. Samples for Drug Concentration Measurements...................................................74
10.5. Appropriateness of Measurements................................................................................74
11. Data Quality Assurance.....................................................................................................75
11.1. Data Capture System....................................................................................................75
12. Sample Size and Statistical Methods.................................................................................77
12.1. Determination of Sample Size......................................................................................77
12.2. Statistical and Analytical Plans.....................................................................................77
12.2.1. General Considerations........................................................................................77
12.2.1.1. General Considerations for Analyses during Period 2 
(Initial Open-Label Treatment Period)............................................................78
12.2.1.2. General Considerations for Analyses during Period 3 
(Randomized Double-Blind Withdrawal Period).............................................78
12.2.1.3. General Considerations for Analyses during Periods 2 
and 3 Combined (Initial Open-Label Treatment and 
Randomized Double-Blind Withdrawal Periods)............................................79
12.2.1.4. Analysis Populations......................................................................................79
12.2.1.5. Missing Data Imputation................................................................................80
12.2.1.5.1. Nonresponder Imputation for Clinical Response.......................................80
12.2.1.5.2. Modified Baseline Observation Carried Forward......................................80
12.2.1.6. Adjustment for Multiple Comparisons............................................................80
12.2.2. Patient Disposition...............................................................................................80
12.2.3. Patient Characteristics..........................................................................................80
12.2.4. Concomitant Therapy...........................................................................................81
12.2.5. Treatment Compliance.........................................................................................81
12.2.6. Efficacy and Health Outcome Analyses................................................................81
12.2.6.1. Primary Analyses...........................................................................................81
12.2.6.2. Secondary Analyses........................................................................................81
12.2.6.2.1. Initial Open-Label Treatment Period (Period 2)........................................82
12.2.6.2.2. Randomized Double-Blind Withdrawal Period 
(Period 3)..................................................................................................82
12.2.6.2.3. Combined Initial Treatment and Randomized 
Double-Blind Withdrawal Periods (Periods 2 and 3).................................82
12.2.6.3. Exploratory Efficacy Analyses........................................................................82
12.2.7. Pharmacokinetic/Pharmacodynamic Analyses......................................................83
12.2.8. Safety Analyses....................................................................................................83
12.2.8.1. Adverse Events...............................................................................................83
12.2.8.2. Clinical Laboratory Tests................................................................................84
12.2.8.3. Vital Signs, Physical Findings, and Other Safety 
Evaluations.....................................................................................................84

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12.2.9. Subgroup Analyses..............................................................................................85
12.2.10. Interim Analyses..................................................................................................85
13. Informed Consent, Ethical Review, and Regulatory Considerations..................................86
13.1. Informed Consent.........................................................................................................86
13.2. Ethical Review.............................................................................................................86
13.3. Regulatory Considerations...........................................................................................86
13.3.1. Protocol Signatures..............................................................................................87
13.3.2. Final Report Signature.........................................................................................87
14. References........................................................................................................................88

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List of Tables
Table
Page
TableRHBF.1. Treatment Regimens......................................................................................46

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List of Figures
Figure
Page
FigureRHBF.1. Illustration of study design for Clinical Protocol I1F-MC-RHBF...................29

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List of Attachments
Attachment
Page
Attachment1.
Protocol RHBF Study Schedule.....................................................................95
Attachment2.
Protocol RHBF Clinical Laboratory Tests....................................................106
Attachment3.
Hepatic Monitoring Tests for Treatment-Emergent Abnormality..................109
Attachment4.
Protocol RHBF CASPAR Criteria...............................................................110
Attachment5.
Protocol RHBF Tender and Swollen Joint Count Assessment Form.............111
Attachment6.
Protocol Amendment I1F-MC-RHBF(b) Summary......................................113

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4.Abbreviations and Definitions
Term
Definition
ACR
American College of Rheumatology
ACR Responder
ACR20 Responder
A patient who has at least 20% improvement in both tender and swollen joint counts 
and at least 20% improvement in a minimum of 3 of the following 5 criteria:  patient’s 
assessment of arthritis pain, patient’s global assessment of disease activity, physician’s 
global assessment of disease activity, patient’s assessment of physical function (Health 
Assessment Questionnaire-Disability Index), and an acute-phase reactant value 
(C-reactive proteinor ESR).
ACR50 Responder
A patient who has at least 50% improvement in both tender and swollen joint counts 
and at least 50% improvement in a minimum of 3 of the following 5 criteria:  patient’s 
assessment of arthritis pain, patient’s global assessment of disease activity, physician’s 
global assessment of disease activity, patient’s assessment of physical function (Health 
Assessment Questionnaire-Disability Index), and an acute-phase reactant value 
(C-reactive proteinor ESR).
ACR70 Responder
A patient who has at least 70% improvement in both tender and swollen joint counts 
and at least 70% improvement in a minimum of 3 of the following 5criteria:  patient’s 
assessment of arthritis pain, patient’s global assessment of disease activity, physician’s 
global assessment of disease activity, patient’s assessment of physical function (Health 
Assessment Questionnaire-Disability Index), and an acute-phase reactant value 
(C-reactive proteinor ESR).
ACR-N Responder 
Index
A continuous measure of clinical, laboratory, and functional measure that characterizes 
the percentage of improvement from baseline in rheumatologicdisease activity.  This 
index is defined operationally as the lowest of either a) the percentagechange in tender 
joint count, b) the percentagechange in swollen joint count, or c) the median percentage
change of the remaining 5 ACR core criteria.  A patient with an ACR-N of X is a 
patient who has improvement of at least X% in both tender and swollen joint counts and 
a median improvement of at least X% in the following 5 criteria:  patient’s assessment 
of arthritis pain, patient’s global assessment of disease activity, physician’s global 
assessment of disease activity, patient’s assessment of physical function (Health 
Assessment Questionnaire-Disability Index), and an acute-phase reactant value 
(C-reactive proteinor ESR).
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 adverse event 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.
AESI
adverse event of special interest
ALP
alkaline phosphatase

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ALT
alanine aminotransferase
assent
agreement from a child or other individual who is not legally capable of providing 
consent, but who can understand the circumstances and risks involved in participating 
in a study (required by some institutional review boards [IRBs])
AST
aspartate aminotransferase
audit
asystematic 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, applicable 
standard operating procedures (SOPs), good clinical practice (GCP), and the applicable 
regulatory requirement(s)
BCG
Bacillus Calmette-Guérin
bDMARD
biological disease-modifying antirheumatic drug
blinding/masking
A procedure in which one or more parties to the trial are kept unaware of the treatment 
assignment(s).  Unless otherwise specified, blinding will remain in effect until final 
database lock.
A single-blind study is one in which the investigator and/or his/herstaff are aware of 
the treatment but the patientis not, or vice versa, or when the sponsor is aware of the 
treatment but the investigator and/or his/herstaff and the patientare not.  
A double-blind study is one in which neither the patientnor any of the investigator or 
sponsor staff who are involved in the treatment or clinical evaluation of the subjects are 
aware of the treatment received.
BP
blood pressure
BSA
body surface area
CASPAR
Classification for Psoriatic Arthritis
C-CASA
Columbia Classification Algorithm of Suicide Assessment
cDMARD
conventional disease-modifying antirheumatic drug
CEC
Clinical Events Committee
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.

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CPDAI
Composite Psoriatic Disease Activity Index
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.
C-SSRS
Columbia–Suicide Severity Rating Scale
DAS28
Disease Activity Score modified to include the28 diarthrodial joint count
DAS28-CRP
Disease Activity Score (28 diarthrodial joint count) based on C-reactive protein
DLQI
Dermatology Life Quality Index 
ECG
electrocardiogram
efficacy
Efficacy is the ability of a treatment to achieve a beneficial intended result under 
controlled conditions.
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 directly or 
through their legally acceptable representatives.
enthesitis
inflammation of tendons and ligaments that can manifest as localized pain and 
tenderness
EQ-5D 5L
European Quality of Life–5 Dimensions 5 Level
ERB/IRB
ethical review board/institutional review board:  a board or committee (institutional, 
regional, or national) composedof medical and nonmedical members whose 
responsibility is to verify that the safety, welfare, and human rights of the patients 
participating in a clinical study are protected
ETV
early termination visit
GCP
good clinical practice
HAQ-DI
Health Assessment Questionnaire–Disability Index
HBcAb+
positive for hepatitis B core antibody
HBsAb
hepatitis B surface antibody
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus

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IB
Investigator’s Brochure
ICF
informed consent form
ICH                                   International Conference on Harmonisation
IBD
Inflammatory bowel disease(e.g. Crohn’s disease and ulcerative colitis)
IL
Interleukin
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.  
interim analysis
An interim analysis is an analysis of clinical study data, separated into treatment groups, 
that is conducted before the final reporting database is created/locked.
investigational 
product
a pharmaceutical form of an active ingredient or placebo being tested or used as a 
reference in a clinical trial, including products already on the market when used or 
assembled (formulated or packaged) in a way different from the authorized form, or 
marketed products used for an unauthorized indication, or marketed products used to 
gain further information about the authorized form.
investigator
a person responsible for the conduct of the clinical study at a study site.  If a study is 
conducted by a team of individuals at a study site, the investigator is the responsible 
leader of the team and may be called the principal investigator.
IR
inadequate responder
ITT
intent-to-treat:  The principle that asserts that the effect of a treatment policy can be best 
assessed by evaluating on the basis of the intention to treat a patient (that is, the planned 
treatment regimen) rather than the actual treatment given.  It has the consequence that 
patients allocated to a treatment group should be followed up, assessed, and analyzed as 
members of that group irrespective of their compliance to the planned course of 
treatment.
IV
intravenous(ly)
IWRS
interactive web-response system
LDI-B
Leeds Dactylitis Index–Basic
legal representative
an individual, judicial, or other body authorized under applicable law to consent on 
behalf of a prospective patient to the patient’s participation in the clinical study
LEI
Leeds Enthesitis Index
LTBI
latent tuberculosis infection
LY2439821
ixekizumab
mBOCF
modified baseline observation carried forward

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MDA
minimal disease activity
MedDRA
Medical Dictionary for Regulatory Activities
MTX
methotrexate
NRI
nonresponder imputation
NRS
Numeric Rating Scale
NSAID
nonsteroidal anti-inflammatory drug
OMERACT
Outcome Measures in Rheumatology
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
PASDAS
Psoriatic Arthritis Disease Activity Score
PASI
Psoriasis Area and Severity Index
PASI 75
at least a 75% improvement from baseline in PASI score
PASI 90
at least a 90% improvement from baseline in PASI score
PASI 100
at least a 100% improvement from baseline in PASI score
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
PsA
psoriatic arthritis
Q2W
every 2 weeks
Q4W
every 4 weeks
QIDS-SR16
Quick Inventory of Depressive Symptomatology-self report 16 items
RA
rheumatoid arthritis
randomize
the process of assigning patients to an experimental group on a random basis
rescreen
to screen a patient who was previously declared a screen failure for the same study
SAE
serious adverse event
SAP
statistical analysis plan

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SC
subcutaneous(ly)
screen
the act of determining if an individual meets minimum requirements to become part of a 
pool of potential candidates for participation in a clinical study.  In this study, screening 
involves 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.
SF-36
36-Item Short Form Health Survey
SJC
swollen joint count
SPARCC
Spondyloarthritis Research Consortium of Canada 
sPGA
static Physician’s Global Assessment of psoriasis
SSZ
sulfasalazine
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 
TE-ADA
treatment-emergent anti-drug antibody
TEAE
treatment-emergent adverse event:  any untoward medical occurrence that either occurs 
or worsens at any time after treatment baseline and that does not necessarily have to 
have a causal relationship with this treatment
TJC
tender joint count
TNF
tumor necrosis factor
TPO
third-party organization
ULN
upper limit of normal
VAS
visual analog scale
WBC
white blood cell
WHO
World Health Organization

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A Phase 3, Multicenter Study with a 36-Week Open-Label 
Period Followed by a Randomized Double-Blind Withdrawal 
Period from Week 36 to Week 104 to Evaluate the Long-Term 
Efficacy and Safety of Ixekizumab (LY2439821) 80 mg 
Every2Weeks in Biologic Disease-Modifying Antirheumatic 
Drug–Naive Patients with Active Psoriatic Arthritis
5.Introduction
Psoriatic arthritis (PsA), an immune-mediated chronic inflammatory disorder commonly 
associated with psoriasis, is one of the most common rheumatic arthritides,occurring in 0.04% 
to 0.1% of the general population but in 6% to 42% of patients with psoriasis.  It is a progressive, 
destructive disease that results in deformities, impaired physical function, loss of quality of life, 
and increased mortality (Gladman et al. 1998; Leung et al. 2008).  PsA also has a considerable 
negative impact on multiple physical and emotional aspects of patients’ lives (Gladman et 
al.2005; Rosen et al. 2012).  Patients with PsA have reported poorer health-related quality of life 
thanthe general population and patients with psoriasis (Husted etal. 1997; Rosen et al. 2012) 
and suffer from a level of functional impairment similar to that of patients with rheumatoid 
arthritis (RA)(Husted et al. 2001).
The current standard of care for PsA includes nonsteroidal anti-inflammatory drugs (NSAIDs);
intra-articular and/or systemic glucocorticoids;conventional disease-modifying antirheumatic 
drugs (cDMARDs) such as methotrexate (MTX), sulfasalazine (SSZ), leflunomide, and 
cyclosporineA;and biologic agents such as tumor necrosis factor(TNF)inhibitors (Gossec et 
al. 2012; Smolen et al. 2014).  Although leflunomide has been shown to be effective in 
improving signs and symptoms of PsA as assessed by the Psoriatic Arthritis Response Criteria
and the American College of Rheumatology 20% response rate (ACR20), there is only weak 
evidence that other cDMARDs are effective, though limited controlled clinical trial data are 
available (Gossec et al. 2012; Mease and Armstrong 2014).  In a recent randomized controlled 
trial of patients with PsA treated with MTX, no significant improvement was demonstrated in 
peripheral arthritis (Kaltwasser et al.2004;Kingsley et al. 2012).  Additionally, cDMARDs have 
not demonstrated efficacy in treating axial involvement, enthesitis, or dactylitis, though limited 
data are available (Gossec et al. 2012; Mease and Armstrong 2014).  SSZhas been shown to be 
effective for axial manifestations in only 1 open-label trial but not effective for enthesitis or 
dactylitis (Dougadoset al. 1995).  Data on the effects of MTX on radiographic progression (joint 
damage) have not been conclusive and have been analyzed in only a small case-controlled study.  
Additionally,radiographic progression (joint damage) was not inhibited in a smallcase-
controlled study of 20SSZ-treated patients and 20matched controls(Ash et al. 2012).
Inpatients withPsA,TNF inhibitors are effective in treating signs and symptoms, inhibiting or 
slowing structural joint progression(mainly bone degradation), and improving skin lesions 
(Mease et al. 2000, 2004, 2005;Antoni et al. 2005a, 2005b; Kavanaugh etal. 2006, 2009).  
However, only between 30% and 40% ofpatients with PsA have a partial response, andothers 

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become resistant or intolerant to treatment with TNF inhibitors and continue to accrue disability 
(Nash and Clegg 2005; Rudwaleit et al. 2010).  In addition,infections, malignancies, blood 
dyscrasias, peripheral neuropathy, and central nervous system and spinal cord demyelination can 
occur in some patients treated with these agents (Singh etal. 2011; Ruderman 2012;Deepak et 
al. 2013).  Therefore, there is an unmet need for alternative effective medications with a different 
mechanism of action and an improved safety profile for patients with PsA.
Highernumbers of circulating Th17 cells have been found in the peripheral blood of patients 
with PsA (Jandus et al. 2008).  These cells secrete substantially more interleukin (IL)-17, have 
shown advanced differentiation, and are polyfunctional in T-cell receptor–driven cytokine 
production (Jandus et al. 2008).  Higher numbers of Th17 cells, evidenced by a higher Th17:Th1 
ratio, are observed in the PsA synovial fluid than inperipheral blood.  The higher numbers of 
Th17 cells are seen early in the disease course,suggesting a role of Th17 in induction of clinical 
disease activity in PsA (Leipe et al. 2010).  In addition, studies in the peripheral blood and 
synovial tissue and fluid in PsA have shown evidence of higher levels of IL-17 and other 
proinflammatory cytokines.  Furthermore, higher levels of IL-17 correlated with higher 
frequencies of Th17 cells, indicating that Th17 cells are amajor source of IL-17 in the 
production of local inflammation at the onset of disease (Fitzgerald and Winchester 2009; Leipe 
et al. 2010).  
Ixekizumab (LY2439821) is an immunoglobulin G subclass 4 monoclonal antibody that binds 
with high affinity (<3 pM) and specificity to IL-17A, a proinflammatory cytokine.  Ixekizumab 
does not bind to ligands IL-17B, IL-17C, IL-17D, IL-17E,or IL-17F.  IL-17 has been shown to 
be elevated in peripheral blood, synovial fluid, and tissue of patients with PsA.  Specific 
inhibition of IL-17A represents a targeted approach to the management of PsA and a novel 
mechanism of action compared to other PsA therapies.  Specifically targeting IL-17Awith 
ixekizumab is hypothesized to provide meaningful therapeutic benefit while reducing the risk of 
impacting host defenses, which may be inherent with some other biologic-based 
immunomodulatory treatments that target multiple immune components.  
To date, ixekizumab has been evaluated in the completedprimary treatment periods of one Phase 
2 and five Phase 3 clinical psoriasis studies; these studies are ongoing to collect longer-term data.  
In addition, Eli Lillyand Company (Lilly)has completed four Phase 1 studies (3 in patients with 
RA, 1 in patients with psoriasis) and has completed one Phase 2 study (patientswith RA).  
To evaluate ixekizumab’s efficacy and safety in PsA, Lilly has 2Phase 3 studies that are ongoing 
(Studies I1F-MC-RHAP [RHAP] and I1F-MC-RHBE [RHBE]).  Both Studies RHAP and RHBE 
are randomized, double-blind, placebo-controlled, 24-week studies with long-term open-label 
extensions.  These studies are designed to establish the efficacy and safetyprofiles of 
ixekizumab 80 mg every 2 weeks (Q2W)and 80 mg every 4 weeks (Q4W)compared with those 
of placebo.  
Because PsA is a chronic relapsing and remitting condition, it is also important to understand the 
long-term effects of biologic treatment, including whether it is necessary to continue treatment 
for maintenance of effect.  Once a treatment target is achieved and sustained on therapy, a 

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relevant question is whether treatment can bediscontinued to avoid unnecessaryexposure. 
There is a lack of large controlled trials with the current standard of care to assess withdrawal of 
treatmentin PsA,although several small studies suggest that many patients experience relapse 
upon standard of care (primarily TNF inhibitor) treatment withdrawal (Araujo et al. 2015; 
Moverly et al. 2015).The maintenance of effect forbiologics that target the IL-23/IL-17 
pathway has not been previously reported.
A further complication in the assessment of long-term outcomes in PsA is the lack of established 
definitions of remission, flare, and relapse.  Remission criteria and activity indices used in RA 
have sometimes beenapplied in PsA (Gladman et al. 2004; Kavanaugh and Cassell2005).  The 
Group for Research and Assessment of Psoriasis and Psoriatic Arthritis has recognized several 
domains in the treatment of PsA,including peripheral arthritis, skin and nail disease, axial 
disease, dactylitis,and enthesitis.  The American College of Rheumatology (ACR) Index and the 
Disease ActivityScore modified to include the 28diarthrodial joint count(DAS28) have 
historically been used for measuring disease activity in PsA clinical trials (vanderHeijde et al. 
1990; Felson et al. 1995).  However, these outcomes do not capture all of the domains of PsA 
disease activityand may lead to the misclassification of patient’s overall diseaseresponse or 
severity. The overall state of disease activity isa useful target of treatment by both the patient 
and the physician, given current treatment possibilities and limitations.Some newerindices 
have been specifically developed for PsAto measure disease activity:  Composite Psoriatic 
Disease Activity Index (CPDAI), Disease Activity Index for Psoriatic Arthritis, Psoriatic 
Arthritis Disease Activity Score (PASDAS), Arithmetic Mean of Desirability Function, and 
minimal disease activity (MDA) criteria in PsA (Coates et al. 2010; Schoels et al. 2010; Mumtaz 
etal. 2011; Helliwell et al. 2013).
While no remission criteria have been standardized for PsA, data from several clinical series and 
from the Swedish Early Psoriatic Arthritis Register reported a frequency of clinical remission 
(using different remission criteria) ranging from 17.6%to 68%;the highest rate was observed in 
patients treated with anti-TNFα agents (Cantini et al. 2008; Haddad et al.2015). Recent studies 
have suggested that stringent response/remission targets such as MDA may be appropriate 
treatment goals in PsA (Coateset al.2010).
The Coates criteria for MDA (described below)has been developed on the basis ofcurrent 
expert opinion and uses a composite of 7key outcome measures used in PsA to encompass the 
disease domains to measure the overall state of a patient’s disease (Coates et al. 2010; Coates 
and Helliwell 2010).  The criteria were developed specifically for PsA and have been validated 
in observational and interventional cohorts.  The specificMDA criteria are described belowand 
includeassessment ofjoints;enthesis;skin;and patient assessment of pain,overall disease,and 
functioning.TheCoates criteriaforMDA have evidence supporting their use within the 
Outcome Measures in Rheumatology (OMERACT)filter of truth, discrimination, and feasibility. 
In a retrospective analysis of infliximab treatment in patients with PsA, the Coates criteria for 
MDA were shown to be discriminative between drug and placebo,and there was a strong 
association between achieving MDA and achievement of the ACR outcomes, reductions in 
inflammatory markersand physician opinion of disease activity (Coates and Helliwell 2010).  

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Patients who maintainedthe Coates criteria forMDA for 38 Weeks or more have better 
long-term functional improvement, patient global assessment, and radiography outcomes after
5years (Kavanaugh et al. 2015).  In addition, the Coates criteria for MDA has been recently 
advocated as a feasible and clinically relevant treatment targetin clinical practice(Coates and 
Helliwell 2015) that is acceptable for patients and physicians (Coates et al. 2012).  The duration 
of treatment needed to achieve MDA is variable;as many as 52% patients meet the Coates 
criteria for MDA within 6 months of starting a TNF inhibitor,but even higher percentages meet 
the criteria at 1 year or more(Coates and Helliwell 2010; Haddad et al. 2015).
The Coates criteria for MDAare:
MDA-Psoriasis Area and Severity Index (PASI):  Patients are classified as achieving 
MDA if they fulfill 5 of 7 outcome measures:  
o tender joint count(TJC)≤1
o swollen joint count (SJC) ≤1,
o PASI total score ≤1 or body surface area(BSA)≤3
o patient pain visual analog scale (VAS) score of ≤15
o patient global disease activity VAS score of ≤20
o Health Assessment Questionnaire–Disability Index(HAQ-DI) score ≤0.5 
o tender entheseal points ≤1
On the basis ofthese previous data, MDA is considered a valid, clinically relevant, and 
implementable target for assessing long-termefficacy and maintenance ofeffect of an 
investigational compound. Study I1F-MC-RHBF (RHBF) is a Phase 3, multicenter study with a 
36-week initial open-label treatment periodexamining the effect of ixekizumab 80 mg Q2W in 
patients with active PsA who are cDMARD–inadequate responders(IRs)and arebiological 
disease-modifying antirheumatic drug (bDMARD)naive followed by a randomized double-blind 
withdrawal periodfrom Week 36 to Week 104. The primary objective of the study is to compare 
ixekizumab 80 mg Q2W and placebo in maintenance of treatment response, as measured by the 
time to relapse during the randomized double-blind withdrawal periodin cDMARD-IR and 
bDMARD-naive patients with active PsA who meet Coates criteria for MDAfor 3 consecutive 
months over 4 consecutive visits.  This study fulfills global regulatory advice for establishing 
maintenance of treatment effect andassessing reintroduction of treatment upon relapse.
More information about the known and expected benefits, risks, and reasonably anticipated 
adverse events (AEs) of ixekizumabmay be found in the Investigator’s Brochure (IB).  
Information on AEs expected to be related to the investigational product may be found in 
Section7 (Development Core Safety Information)of the IB.  Information on serious adverse 
events (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 sponsor, monitors, and investigators will perform this study in compliance with the protocol, 
good clinical practice (GCP),International Conference on Harmonisation (ICH) guidelines, and 
applicable local regulatory requirements.

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6.Objectives
6.1. Primary Objective
The primary objective of the study is to compare ixekizumab 80 mg Q2W with placebo in 
maintenance of treatment response,as measured by the time to relapse during the randomized 
double-blind withdrawal periodin cDMARD-IR and bDMARD-naive patients with active PsA 
who meet randomization criteria (Coates criteriafor MDA for 3consecutive months over 
4consecutive visits).
6.2. Secondary Objectives
The secondary objectives of the study are:
to compare ixekizumab 80 mg Q2W with placebo in maintenance of treatment response, 
as measured by the proportion of patients who meet relapse criteria during the 
randomized double-blind withdrawal periodin cDMARD-IR and bDMARD-naive 
patients with active PsAwho meet randomization criteria (Coates criteriafor MDA for 
3consecutive months over4consecutive visits)
to evaluate the time toloss of response for eachindividual component of MDA in the 
randomized double-blind withdrawal period
to evaluate time to first meetingCoates criteriafor MDAduring the initial open-label 
treatment period(Period 2)
to evaluate time to achievingCoates criteriafor MDA during the initial open-label 
treatment period(Period 2)(Coates criteriafor MDA for 3consecutive monthsover
4consecutive visits)
to assess the efficacy of ixekizumab 80 mg Q2W afterdisease relapse after 
randomization in the randomized double-blind treatment period
to assess the effect of treatment response as measured by the HAQ-DIof ixekizumab 
80mg Q2W throughout the study
6.3. Exploratory Objectives
The exploratory objectives of the study are:
to assess the clinical factors that predict Coates criteriafor MDA
to assess the time to achieve other composite measurements of low disease activity,such 
as DAS28based on C-reactive protein (DAS28-CRP), PASDAS, CPDAI, and others
during the initial open-label treatment period(Period 2)
to assess the changes in health utility (European Quality of Life–5 Dimensions 5 Level 
[EQ-5D 5L]),Work Productivity and Activity Impairment–Specific Health Problem, and 
Dermatology Life Quality Index (DLQI) throughout the study
to assess the changes inthehealth outcome endpoints fatigue severityNumeric Rating 
Scale(NRS) score, itchNRS score (in the subgroup of patients with psoriatic skin lesions 
involving ≥3% BSA at baseline), Quick Inventory of Depressive Symptomatology-self 
report 16items (QIDS-SR16) score, and Medical OutcomesStudy 36-Item Short Form 
Health Survey (SF-36) Physical Component Summary and Mental Component Summary 

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scores and the 8associated domains of SF-36(Physical Functioning, Role Physical, 
Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, and Mental 
Health) throughout the study
to explore biomarkers of disease or drug activity that may be contained in serum, plasma, 
whole-blood messenger RNAand DNA samples
to assess the pharmacokinetic (PK)/pharmacodynamic (PD) relationship and 
immunogenicity of ixekizumab throughout the study by:
o characterizing the PK of ixekizumab, determining the magnitude of within-and 
between-patient variability, and identifying the potential intrinsic and extrinsic 
factors that may have an effect on the PKof ixekizumab
o characterizing the exposure-response relationshipsforefficacy endpoints (for 
example, proportion of patients achieving Coates criteriafor MDA from Week 36 
throughWeek 64 and the maintenance of treatment effects), and identifying 
potential factors that may impact the efficacy endpoints
o evaluating the potential development of anti-ixekizumab antibodies and its impact 
on patient safety, efficacy, and PK of ixekizumab

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7.Investigational Plan
7.1. Summary of Study Design
Study I1F-MC-RHBF is a Phase 3, multicenter study with a 36-week initial open-label treatment 
periodexamining the effect of ixekizumab 80 mg Q2W in patients with active PsA who are 
cDMARD-IRsand are bDMARDnaive followed by a randomized double-blind withdrawal 
periodfrom Week 36 to Week 104 examining the effect of ixekizumab 80 mg Q2W compared 
with that of placebo.  Patients who do not meet the randomized withdrawalcriteriawill continue 
on ixekizumab 80 mg Q2W uninterrupted during the randomized double-blind withdrawal 
period.  Allrandomized patients who no longer meet Coates criteriafor MDA at any visit after 
entering the randomized double-blind withdrawal periodwill receive ixekizumab 80 mg Q2W
for the remainder of the study period.  In addition, efficacy and safety will be assessed for up to a 
total of 2 years for patients who participate throughout the entire 2-year study.  
The study consists of 4 periods:
Period 1(Section7.1.1):  screening period (Visits 1 and 1A) lasting from 4 to 30 days 
beforeWeek 0 (Visit 2)
Period 2(Section 7.1.2):  initial open-label treatment period from Week 0 (baseline, 
Visit2) upto Week 36 (Visit 12)
Period 3(Section 7.1.3):randomized double-blind withdrawal period from Week 36 to 
Week 104 (Visit 29).  Patients who have been treated with ixekizumab 80 mg Q2W for at 
least 36 weeks and have achieved4 consecutive visits of meetingCoates criteriafor
MDA from Week 36 up to Week 64 will be eligible for randomizationat the visit at 
which these criteria are met.
Period 4(Section 7.1.4):  posttreatment follow-up period occurring from the early 
termination visit(ETV) or the last scheduled visit for a minimum of 12 weeks afterthat 
visit, up to 24 weeks if the patient’s neutrophil count is low. All patients withdrawing 
from the study after receiving even 1 dose of study treatment will proceed directly to 
Period 4.  
FigureRHBF.1illustrates the study design.
All procedures to be conducted during the study, including timing of all procedures, are indicated 
in the study schedule (Attachment1).  Selected study procedures should be performed before
administration of the investigational product, as applicable, according to the study schedule.  
Section 10.4describes collection of laboratory samples; Attachment2lists the specific 
laboratory tests that will be performed for this study.  
Patients discontinuing from the study who have received at least 1 dose of investigational 
product should completethe ETV beforeproceeding to the posttreatment follow-up period 
(Period4).  For the management of patient safety, all patients should be monitored through the 
posttreatment follow-up period at least as frequently as indicated on the study schedule 
(Attachment1).  

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All treatment groups are described in Section 9.1.  Details of the administration of the 
investigational product are described in Section 9.1.1, special treatment considerations are 
outlined in Section 9.5.1, and the use of the study drug administration logis detailed in 
Section9.5.2.  
Excluded and restricted therapies are detailed in Section 9.8.  
PKsampling is detailed in Section 10.4.4.  

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See footnotes on the following page.
FigureRHBF.1. 
Illustration of study design for Clinical Protocol I1F-MC-RHBF.

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Abbreviations:  LV = date of last visit; LY = LY2439821 (ixekizumab); MDA = minimal disease activity; 
n=number of patients; Q2W = every 2 weeks; RW = randomized withdrawal; V = study visit; W = study week.
a The initial open-label treatment period(Period 2) encompasses Week 0 up to Week36.  During Period 2, all 
patients will receive open-label ixekizumab 80 mg Q2W.
b Between Weeks 36 and 64 (inclusive), patients who have been treated with ixekizumab 80 mg Q2W for at least 
36 weeks and have achieved 4consecutive visits of meeting Coatescriteriafor MDA will be eligible for
randomization at the visit at which these criteria are met.  Eligible patients will be randomized in a 1:1 ratio to 1 
of 2 treatment arms:  ixekizumab 80 mg Q2W or placebo Q2W.  Patients will remain in their RW treatment arms
until they no longer meet Coates criteriafor MDA, at which point they will receive ixekizumab 80mg Q2W.  
Patients who do not meet Coates criteriafor MDA at Week 52 are not eligible for randomization.
c Patients who do not meet the RW eligibility criteria by Week 64 will remain on ixekizumab 80 mg Q2W 
uninterrupted for the duration of Period 3.  
d Patients who no longer meet Coates criteriafor MDA during Period 3 (the RW period) will be switched to 
ixekizumab 80 mg Q2W.  Patients who continue to meet Coates criteriafor MDA during Period 3 (the RW 
period) will continue treatment until Week 104 and move to Period 4 (the posttreatment follow-up period).
Figure RHBF.1. 
Illustration of study design for Clinical Protocol I1F-MC-RHBF
(concluded).

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7.1.1. Screening Period (Period 1)
The duration of the screening periodis between 4 and 30 days,and the period consists of 1 or 
2screening visits (Visits 1 and 1A, where applicable) to assess patient eligibility.  The patient 
will sign the informed consent form (ICF) beforeany study assessments, examinations, or 
procedures are performed.
All inclusion and exclusion criteria are provided in Sections 8.1and 8.2, respectively.  Screening 
procedures will be performed according to the study schedule (Attachment1).  At Visit1, either 
a QuantiFERON
-TB Gold test or a T-SPOT.TBassay for tuberculosis (TB)will be performed 
or patients will be administered a purified protein derivative (PPD) test for TB 
(Section10.3.2.3).  For those patients administered a PPD test at Visit 1, thetest results will be 
read approximately 2to 3 days after test application, at Visit1A.  Subsequent visits denoted with 
the letter “A” (see study schedule, Attachment1) are for PPD reads, where applicable.
Patients who test positive for latent TB at screening may be rescreened afterappropriate 
treatment as described in Section 10.3.2.3.  Additionally, patients who do not qualify at 
screening under exclusion criterion[40] or [41] may be rescreened once, ≥4 weeks after 
documented resolution of symptoms.
7.1.2. Initial Open-Label Treatment Period (Period 2)
The initial open-label treatment period (Period 2) will occur from Week 0 (baseline, Visit 2) 
through Week36(Visit 12).  
At Week 0(baseline, Visit 2), routine safety assessments, blood draws for laboratory tests, and 
clinical efficacy assessments will be performed on eligible patients according to the study 
schedule(Attachment1).  
All patients will receive a starting dose ofopen-labelixekizumab160 mg followed by open-label 
ixekizumab 80 mg Q2W during the initial open-label treatment period.  
7.1.3. Randomized Double-Blind Withdrawal Period (Period 3)
The randomized double-blind withdrawal period(Period 3) will be a double-blind treatment 
period with ixekizumab 80 mg Q2W and placebo and will occur from Week 36 (Visit 12) to 
Week 104(Visit 29).  
In Period 3, safety and efficacy parameters in participating patients will continue to be evaluated 
according to the study schedule(Attachment1).  
Not all patients will be randomized in Period 3and the timing of randomization will be flexible 
for those patients who meet criteria for randomization.The criteria for randomization in 
Period3arehavingreceived ixekizumab 80 mg Q2W for at least 6 months and meeting Coates 
criteriafor MDA for3 consecutive months over 4consecutive visits.  
Patients who meet the randomization criteria at any time from Week 36 through Week64 will be 
randomized in a 1:1 ratio to 1 of 2 treatment arms: ixekizumab 80 mg Q2W orplacebo. Patients 
will be assessed for theCoates criteriaforMDA at each visit during this study period. Patients 

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who continue to meet Coates criteriafor MDA will continue in their assigned treatment arms
until Week 104. Patients who no longer meetthe Coates criteriafor MDA at any visit will be 
treated with ixekizumab 80 mg Q2W until Week 104. Patients receiving 80 mg ixekizumab 
Q2W who relapse will continue on 80 mg ixekizumab Q2W to maintain the study blind and to 
see if response can be regainedwith continued treatment. Patients who fail todemonstrate a 
20% improvement from baseline in both TJC and SJC at Week 24 or at anysubsequent visit will 
be discontinued (see Section 8.3.1).
Patients who do not meet the randomizationcriteria before or at Week 64will continue 
ixekizumab 80 mg Q2W throughout Period 3.  
Patients who complete Period 3will enter the posttreatment follow-up period.  Patients who 
discontinue the study treatment early during Period 3 will proceed to the ETV beforeentering the 
posttreatment follow-up period (Period4, Section 7.1.4).  
7.1.4. Posttreatment Follow-Up Period (Period 4)
All patients receiving at least 1 dose of investigational product will enter the posttreatment 
follow-up period (Period 4) for a minimum of 12 weeks after their last regularly scheduled visits
(or the date of their ETVs).  Required study visits should occur at 4 weeks after and at 12 weeks 
afterthe last regularly scheduled visit (or the date of the patient’s ETV)(Visits 801and 802, 
respectively), except for patients with concurrent infectionsthat require systemic anti-infective 
therapy (described below).  
If, at the last scheduled visit or ETV, a patient’s neutrophil count is <1500 cells/L 
(<1.50×103/µL or <1.50 GI/L)and less than the patient
's baseline neutrophil count, the 
following measures should be taken:
Patients with concurrent infection:  If there is a concurrent infection that requires 
systemic anti-infective therapy, the patient should receive appropriate medical care 
and a repeat test for neutrophil count should be performed at least Q4W (or sooner as 
appropriate) until resolution of infection.  Upon resolution of infection, the neutrophil 
count should be monitored using the required study visits in the posttreatment 
follow-up period (Period 4) design at Visits 801 (4 weeks after resolution of 
infection), 802 (8 weeks after Visit 801), and 803 (if necessary; 12weeks after 
Visit802); additional visits may be required depending on thedegree of neutropenia.
Patients without concurrent infection:  If there is no concurrent infection that requires 
systemic anti-infective therapy, the neutrophil count should be monitored using the 
required study visits in the posttreatment follow-up period (Period 4) design, 
Visits801 (4 weeks post ETV or last regularly scheduled visit), 802, and 803 (if 
necessary); additional visits may be required depending on the degree of neutropenia.
For Visit 801 and subsequent visits, the following monitoring applies:
o As long as a patient’s neutrophil count is <1000 cells/L (<1.00 × 103/µL or 
<1.00GI/L) at any follow-up visit, the patient should return for additional visits at 
least Q4W (unscheduled visitsmay be required).  

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o As long as a patient’s neutrophil count is ≥1000 cells/L and <1500 cells/L 
(≥1.00 × 103/µL and <1.50× 103/µL or ≥1.00 GI/L and <1.50 GI/L) at any 
follow-up visit, the patient should return for additional visit(s) at least every 4to 
8weeks (unscheduled visits may be required).  
o If at Visit 803 the patient’s neutrophil count remains <1500 cells/L 
(<1.50×103/µL or <1.50 GI/L) and less than the patient’s baseline neutrophil 
count or if the investigator deems additional follow-up may be necessary, the 
investigator in consultation with Lilly or qualified designee will determine the 
appropriate management of the patient and the appropriate timing of additional 
contact(s) or visit(s).
o If at Visit 802 or Visit 803 the patient’s neutrophil count is ≥1500 cells/L 
(≥1.50× 103/µL or ≥1.50× 103/µL) or greater than or equal to the patient’s 
baseline neutrophil count (whichever is lower), the patient’s participation in the 
study will be considered complete unless the investigator deems additional 
follow-up necessary.
For patients who completed or discontinued study treatment and have entered the posttreatment 
follow-up period (Period 4), PsA therapy with another agent is allowed, as determined 
appropriate by the investigator.
7.2. Discussion of Design and Control
Adosageregimen of ixekizumab 80 mg Q2W will be studied as detailed in Section 9.1, with the 
dose justification as outlined in Section 9.4.
TheWeek 36 to Week 64 randomization window will allow sufficient time for responding 
patients to reach randomization criteria.
The overall level of disease activity is a useful target of treatment for both the patient and the 
physician, given current available treatment options.  Recent studies have suggested that 
stringent response/remission targets such as MDA may be appropriate treatment goals in PsA 
(Coates et al. 2010).  The Coates criteriafor MDA has been developed on the basis ofcurrent 
expert opinion and uses a composite of 7key outcome measures(see Section 10.1.1.1)used in 
PsA to encompass domains of the disease to measure the overall state of a patient’s disease 
(Coates et al. 2010; Coates and Helliwell 2010).  The criteria were developed specificallyfor 
PsA and have been validated in observational and interventional cohorts.  The PsA Coates 
criteriafor MDA have evidence supporting their use within the OMERACT filter of truth, 
discrimination, and feasibility.  In a retrospective analysis of infliximab in PsA, the criteria were 
shown to be discriminative between drug and placebo,and there was a strong association 
between achieving MDA and achievement of the ACR outcomes, reductions in inflammatory 
markers,and physician opinion of disease activity (Coates and Helliwell 2010).  Patients who 
maintained the Coates Criteria forMDA for 38 Weeks or morehave better long-term functional 
improvement, patient global assessment, and radiography outcomes after 5 years (Kavanaugh et 
al. 2015). In addition, MDA has been recently advocated as a feasible and clinically relevant 
treatment target in clinical practice (Coates and Helliwell 2015) that is acceptable for patients 

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and physicians (Coates et al. 2012). Lossof MDA has also been used to define relapse upon 
withdrawal of treatment (Araujo et al. 2015; Haddad et al. 2015; Moverly et al. 2015).
On the basis ofthese previous data, MDA is a valid, clinically relevant, and implementable target 
for assessing long-termefficacy and maintenance of effect of an investigationalcompound. The 
duration of treatment needed to achieve MDA is variable;as many as 52% of patients meet the 
Coates criteria for MDA within 6 months of starting a TNF inhibitor,but even higher 
percentages meet the criteria at 1 year or more(Coates and Helliwell 2010; Haddad et al. 2015).
The flexible timing of randomization up to Week 64 will allow sufficient time for patients to 
meet Coates criteriafor MDAand ensure that patients’ response to treatment is stable by 
requiring 4consecutive visitsof MDAbeforepotential treatment withdrawal.
The studyblind is maintained as described in Section 9.7.  The placebo-controlled randomized 
double-blind withdrawal periodis blinded to minimize bias in the evaluation of ixekizumab 
treatment in patients with PsA.  Patients receiving placebo may still receive treatment in the form 
of the allowed concomitant therapies as described in the study exclusion criteria (Section 8.2)
and concomitant therapy (Section 9.8).  Patients receiving placebo who relapse will be re-treated 
with ixekizumab 80 mg Q2W at the first visit at which relapse (loss of MDA) occursto minimize 
the time patients may be off previously effective treatmentand to be able to assess whether 
responseupon retreatment is attained.Patients receiving 80 mg ixekizumab Q2W who relapse 
will continue on 80 mg ixekizumab Q2W tomaintain the study blind and to see if response can 
be regained with continued treatment.
Both the time to relapse (loss of MDA) and the number of patients who relapse in the 
ixekizumab and placebo groups after randomizationwill be compared. The time to relapse was 
chosen as the primary objective because it is a clinically relevant outcome and is not restricted to 
a single time pointandthusincorporates the time courseof response and relapse by individual 
patients.
The posttreatment follow-up period (Period 4) is for safety monitoring afterthe last treatment 
period and study visit.

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8.Study Population
This study will enroll patients aged 18 years or older who are cDMARD-IRsand are bDMARD
naive, have a diagnosis of PsA as defined by the Classification for Psoriatic Arthritis (CASPAR) 
criteria, have active psoriatic skin lesions or a documented history of psoriasis, and have at least 
3 tender and 3 swollen joints.
Individuals who do not meet the criteria for participation inthis study (screen failure) may be 
rescreened onlyin the following circumstances:  Patients who test positive for latent TB at 
screening may be rescreened afterappropriate treatment as described in Section10.3.2.3.  
Additionally, patients who do not qualify at screening under exclusion criterion [40] or [41] may 
be rescreened once, 4 or more weeks after documented resolution of symptoms.  When 
rescreening is performed, the individual must sign a new ICF and will be assigned a new 
identification number.
Study investigator(s) will review patient records and screening test results from Visit 1 (all 
criteria), Visit 1A (as applicable for PPD read), and Visit 2 (criteria [3], [35], [41], and [42]) to 
determine if the patient meets all inclusion and exclusion criteria to qualify for participation in 
the study.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, are not permitted.
8.1. Inclusion Criteria
Patients are eligible to be included 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 agree to use a reliable method of birth control during the 
study.
[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 12 weeks afterthe last dose of investigational product, whichever is 
longer.  Methods of contraception considered acceptable when used properly 
include oral contraceptives, contraceptive patch, injectable or implantable 
contraceptives, intrauterine device, vaginal ring, diaphragm with contraceptive 
gel, or condom with contraceptive foam.
-or-
are women of nonchildbearing potential, defined as:
women who have had surgical sterilization (hysterectomy, bilateral 
oophorectomy, or tubal ligation); 
-or-

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women who are≥60 years of age;
-or-
women ≥40 and <60 years of age who have had a cessation of menses for 
≥12months and a follicle-stimulating hormone test confirming 
nonchildbearing potential (≥40 mIU/mL).
[2] have had diagnosis of active PsA for at least 6 months (according toa detailed 
medical history provided by the patient, a physical examinationby the study 
investigator, and/or other evidence such as that provided by hand [wrist]and 
foot radiographsthat establishes a history consistent with a diagnosis of active 
PsA of at least 6 months duration) and currently meet the CASPAR criteria 
(Attachment4)
[3] have active PsA defined as the presence of at least 3of 68 tender and at least 3
of 66swollen joints as determined by the Tender and Swollen Joint Count 
Assessment Form at Visit 1 (screening) and Visit 2 (Week 0, baseline)
[4] have been treated with 1 or more cDMARDs (MTX, SSZ, leflunomide, 
hydroxychloroquine, or cyclosporine) and had adocumentedinadequate 
response(ina minimum of 12 weeks of therapy)or intolerance
[5] have active psoriatic skin lesions (plaque) or a documented history of plaque 
psoriasis
[6] have given written informed consent approved by Lilly or its designee and the 
institutional review board/ethicalreview board (IRB/ERB)governing the site
8.2. Exclusion Criteria
Patients will be excluded from study enrollmentif they meet any of the following criteria:
[7] have received any previous treatmentor arecurrently receiving treatment with 
any biologic or small-moleculetherapy for PsA or psoriasis, including 
investigational therapies (such as but not limited to TNF inhibitors, IL-1
receptor antagonists, IL-6 inhibitor, anti–IL-12/23p40, T-cell or B-cell 
targeted therapies, or Janus kinaseinhibitors).  Exception:  previous treatment 
of phosphodiesterase type 4 inhibitorswill bepermitted.Treatment with 
phosphodiesterase type 4 inhibitors must be discontinued at least 8 weeks
before baseline (Week 0, Visit 2).
[8] have previously completed or withdrawn from this study or any other study 
investigating ixekizumab or other IL-17 inhibitors, for example, anti–IL-17 or 
anti–IL-17 receptor monoclonal antibodies
[9] have history of drug-induced psoriasis
[10]have had, in the opinion of the investigator, inadequate response to treatment 
with ≥4cDMARDs or immune modifiers (such as MTX, leflunomide, 
azathioprine, cyclosporine, hydroxychloroquine, gold salts, or SSZ) 
prescribed alone or in combination for a minimum of 3 months

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[11]have used DMARDs other than MTX, leflunomide, SSZ, or 
hydroxychloroquine (for example, gold salts, cyclosporine, azathioprine, 
dapsone, 6mercaptopurine, mycophenolate mofetil, or any other 
immunosuppressive agents) in the 8 weeks beforebaseline (Week 0, Visit 2)
Have discontinued MTX or SSZ within the 8 weeks beforebaseline or 
hydroxychloroquine within 12 weeks beforebaseline
If taking MTX, leflunomide, SSZ, or hydroxychloroquine, must have been treated 
forat least 12 weeks beforebaseline and on stable dosagesfor at least 8 weeks 
beforebaseline as follows:  oral or parenteral MTX = upto 25 mg/wk, 
leflunomide=up to 20mg/d, SSZ= up to 3 g/d, or hydroxychloroquine = up to 400 
mg/d.  Local standard of care should be followed for concomitant administration of 
folic acid with MTX.
[12]are receiving treatment with more than 1 cDMARD (MTX, leflunomide, SSZ, 
hydroxychloroquine, or cyclosporine) at study entry.  Note:  Under no 
circumstances will simultaneous use of MTX and leflunomide be allowed at 
any time during the study for safety reasons.
[13]have discontinued leflunomide within 4 weeks beforebaseline or have 
received leflunomide from 4 to 12 weeks beforebaseline (Week 0, Visit 2) 
and have not undergone a drug elimination procedure
[14]use of oral corticosteroids at average daily doses of >10 mgof prednisone or 
its equivalent or use of variable dosages of any oral corticosteroids within 
4weeks beforebaseline (Week 0, Visit 2)
[15]have received any parenteral glucocorticoid administered by intraarticular, 
intramuscular, or intravenous (IV) injection within 6 weeks beforebaseline 
(Week 0, Visit 2) or anticipate a parenteral injection of glucocorticosteroids 
during the initial open-label treatment period(Period 2) of the study
[16]are using concomitant NSAIDs, including cyclooxygenase-2 inhibitors, unless 
the patient is on a stable dosagefor at least 2 weeks beforebaseline (Week 0, 
Visit2)
[17]within 6 weeks before baseline (Week 0, Visit 2) have usedany opiate 
analgesic at average daily doses of >30 mgof morphine or its equivalent or 
have used variable dosages of any opiate analgesic
[18]have received systemic nonbiologic psoriasis therapy other than DMARDs or 
corticosteroids as indicated above (including but not limited to oral psoralens 
and ultraviolet A light therapy, oral retinoids, thioguanine, hydroxyurea, 
fumaric acid derivatives, or topical 1,25dihydroxy vitamin D3 and analogues) 
or phototherapy (including either oral and topical psoralens and ultraviolet A, 
ultraviolet B,or self-treatment with tanning beds/boothsor therapeutic 
sunbathing) within 4 weeks beforebaseline (Week 0, Visit 2)

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OR had topical psoriasis treatment within 2 weeks beforebaseline (Week 0, Visit2).  
Exceptions:  weakpotency (World Health Organization [WHO]Group 1 
classification) topical steroids will be permitted.
[19]for those patients with plaque psoriasis,cannot avoid use of tanning 
beds/booths for at least 4weeks beforebaseline (Week 0, Visit 2) and during 
the study
[20]have a known allergy or hypersensitivity to any biologic therapy that would 
pose an unacceptable risk to the patient if participating in this study
[21]have ever received natalizumab or other agents that target -4-integrin
[22]had a live vaccination within 12 weeks beforebaseline (Week 0, Visit 2),
intend to have a live vaccination during the course of the study or within 
12weeks of completing treatment in this study, or have participated in a 
vaccine clinical study within 12 weeks beforebaseline.  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 beforetherapy.
Note:  Killed/inactive or subunitvaccines are expected to be safe; however, their 
efficacy with concomitant ixekizumab treatment is unknown.
[23]had a vaccination with Bacillus Calmette-Guérin (BCG) within 12 months 
beforebaseline (Week 0, Visit 2) or intend to have this vaccination with BCG 
during the course of the study or within 12 months of completing treatment in 
this study
[24]have a diagnosis of other inflammatory arthritic syndromes such as RA, 
ankylosing spondylitis, reactive arthritis,or enteropathic arthritis
[25]have active Crohn’s disease or active ulcerative colitis
[26]have a current diagnosis of fibromyalgia
[27]have a chronic pain condition that would confound evaluation of the patient
[28]have evidence of active vasculitis or uveitis
[29]have had surgical treatment of a joint within 8 weeks beforebaseline or will 
require such up to Week 24
[30]have had any major surgery that in the opinion of the investigator and in 
consultation with Lilly or its designee would pose an unacceptable risk to the 
patient within 8 weeks beforebaseline or will require such during the study
[31]have current lymphoproliferative diseaseor a history of it
[32]have diagnosis or history of malignant disease within 5 years beforebaseline 
(Week0, Visit 2). Note: Patients with successfully treated basal-cell 
carcinoma (no more than 3)orsquamous-cell carcinoma of the skin (no more 
than 2) within the 5 years beforebaseline may participate in the study

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[33]havesignificant uncontrolled cerebrocardiovascular, respiratory, hepatic, 
renal, gastrointestinal, endocrine, hematologic, neurologic,or 
neuropsychiatric disorders(for example, myocardial infarction, unstable 
angina, unstable arterial hypertension, moderate to severe [New York Heart 
Association class III/IV] heart failure, or cerebrovascular accident);abnormal 
laboratory values;or use of illicit drugs(including cannabinoids, whether 
legalized or not) at screening that in the opinion of the investigator pose an 
unacceptable risk to the patient if participating in the studyor of interfering 
with the interpretation of data
[34]have a history of uncompensated heart failure, fluid overload, or myocardial 
infarctionorhaveevidence of new-onset ischemic heart disease or other 
serious cardiac disease within 12 weeks beforebaseline (Week 0, Visit 2)
[35]have history of suicide attempt, have a score of 3 on Item 12 (Thoughts of 
Death or Suicide) on the QIDS-SR16 at screening (Visit 1) or at baseline 
(Week 0, Visit 2), or are clinically judged by the investigator to be at risk for 
suicide
[36]had a serious infection (for example, pneumonia, cellulitis), have been 
hospitalized, or have received IV antibiotics for an infection within 12 weeks 
beforebaseline (Week 0, Visit 2);had a serious bone or joint infection within 
24 weeks beforebaseline;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
[37]have or had an opportunistic infection characteristic of an 
immunocompromised host and/or that occurs with increased incidence in an 
immunocompromised host (including but not limited to Pneumocystis jiroveci
pneumonia, histoplasmosis, coccidioidomycosis, orcryptococcosis) or have a 
known immunodeficiency
[38]have or had a herpes zoster or any other clinically apparent varicella-zoster 
virus infection within 12 weeks of baseline (Week 0, Visit 2)
[39]haveevidence of or suspicion of active or latent TB (refer to Section10.3.2.3
for details on determining full TB exclusion criteria)
[40]within 4 weeks of baseline (Week 0, Visit 2), have any active or recent 
infection other than those mentioned above 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 once ≥4 weeks after documented 
resolution of symptoms
[41]have body temperature ≥38°C (100.5°F) at baseline (Week 0, Visit 2); these 
patients may be rescreened once ≥4 weeks after documented resolution of 
temperature≥38°C (100.5°F)

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[42]have uncontrolled arterial hypertension characterized by a sitting systolic 
blood pressure (BP)>160mmHg or diastolic BP >100 mm Hgat baseline 
(Week 0, Visit 2)
Note:  Determined by 2 consecutive readings.  If an initial sitting BP reading 
exceeds this limit, the BP may be repeated once after the patient has rested 
sitting for ≥10minutes.  If the repeat value is less than the criterion limits, the 
second value may be accepted.
[43]are positive for human immunodeficiency virus serology, that is, positive for 
human immunodeficiency virus antibody
[44]have evidence of or test positive for hepatitis B by any of the following 
criteria:  (1)positive for hepatitis B surface antigen (HBsAg+); (2) positive for 
anti–hepatitis B core antibody (HBcAb+) and negative for anti–hepatitis B 
surface antibody (HBsAb–); (3) positive for HBcAb+ and positive for anti–
hepatitis B surface antibody (HBsAb+) with concentration of HBsAb 
<200mIU/mL; or (4) HBcAb+, HBsAb+ (regardless of HBsAb level), and 
positive for serum hepatitis B virus (HBV) DNA
(Note: Patients who are negative for hepatitis B surface antigen (HBsAg–), 
HBcAb+, HBsAb+ with a concentration of HBsAb ≥200 mIU/mL, and
negative for serum HBV DNA may participate in the study. Patients who 
meet these criteria at screening must be monitored during the study as detailed 
in Section 10.3.3.4.
[45]have evidence of or test positive for hepatitis C virus (HCV).  A positive test 
result for HCV is defined as a result positive for hepatitis C antibody and 
positive via a confirmatory test for HCV (for example, HCV polymerase chain 
reaction)
[46]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:
[46a] 
neutrophil count <1500 cells/μL(<1.50 × 103/µLor <1.50 GI/L)
[46b] 
lymphocyte count <800 cells/μL(<0.80× 103/µL or <0.80 GI/L)
[46c] 
platelet count <100,000 cells/μL(<100× 103/µL or <100 GI/L)
[46d] 
aspartate aminotransferase (AST) or alanine aminotransferase 
(ALT)level>2.5times (x) the upper limit of normal (ULN).
(Note:  The AST and ALT tests may be repeated once within a week if the 
initial response exceeds this limit, and the repeat value may be accepted if 
it is within the limit).
[46e] 
total white blood cell (WBC) count <3000 cells/μL(<3.00× 
103/µL or <3.00GI/L)

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[46f] 
hemoglobin level <8.5 g/dL (85.0 g/L) for male patients and 
<8.0g/dL (80 g/L) for female patients
[46g] 
serum creatinine level >2.0 mg/dL (177μmol/L).
Note:  Laboratory tests should not be repeated unless there is a technical 
error or clinical reason to believe a result may be erroneous.
[47]have electrocardiogram (ECG) abnormalities that are considered clinically 
significant and would pose an unacceptable risk to the patient if participating 
in the study
[48]have, in the opinion of the investigator,any other condition that precludes the 
patient from following and completing the protocol
[49]have donated blood of more than 1 unit (approximately 500 mL)within the 
last 4weeks or intend to donate blood during the courseof the study
[50]are women who are lactating or breastfeeding
[51]are investigator site personnel directly affiliated with this study and/or their 
immediate families.Immediate family is defined as a spouse, parent, child, or 
sibling, whether biological or legally adopted.
[52]are employees of Lilly or its designee or are employees of third-party 
organizations (TPOs) involved in the study
[53]are currently enrolled in a clinical trial involving an investigational product or 
nonapproved use of a drug or device (other than the investigational product 
used in this study) or concurrently enrolled in any other type of medical 
research judged not to be scientifically or medically compatible with this 
study
[54]have been discontinued from a clinical trial involving an investigational 
product or nonapproved use of a drug or device within the last 4 weeks or a 
period of at least 5half-lives of the last administration of the drug, whichever 
is longer
8.2.1. Rationale for Exclusion of Certain Study Candidates
Exclusion criteria [7] through [49], [53], and [54] 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 [50] provides protection to 
offspring.  Exclusion criteria [51] and [52] reduce the potential bias that may be introduced at the 
study site.
The majority of the exclusion criteria are applied to reduce risks to patients by enrolling 
medically stable, relatively healthy (aside from the disease being studied) patients who are not 
receiving concomitant therapies that may impact their safety and/or confound effects when 
combined with the investigational product being studied.

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8.3. Discontinuations
8.3.1. Discontinuation of Inadvertently Enrolled Patients
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 sponsor clinical research physician 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 Lilly clinical research 
physician agreeswith the investigator that it is medically appropriate for that patient.  The patient 
may not continue in the study with or without investigational product if the Lilly clinical 
research physician 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 research physician to allow the inadvertently enrolled patient to continue in the 
study with or without investigational product.
For any patient discontinued from the study
 and who has received at least 1 dose of
investigational product, the investigational product will be withheld, and the patient will 
complete the ETV and the posttreatment follow-up period (Period 4) as shown in the study 
schedule (Attachment1).
Patients who meet any of the criteria in Section 8.3.1.1will be discontinued from the study as 
indicated.
8.3.1.1. Discontinuation Criteria
Discontinuation of the investigational productfor abnormal liver tests should be 
considered by the investigator when a patient meets 1 of the following conditions after 
consultation with the Lilly-designated medical monitor:
o ALT or AST level >8× ULN
o ALT or AST level >5× ULN for more than 2 weeks 
o ALT or AST level >3× ULN and total bilirubin level >2× ULN or prothrombin time 
>1.5 × ULN
o ALT or AST level >3× ULN with fatigue, nausea, vomiting, abdominal right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%)
o alkaline phosphatase (ALP) level >3× ULN
o ALP level >2.5× ULN and total bilirubin >2× ULN
ALP level >2.5× ULN with fatigue, nausea, vomiting, abdominal right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%)
neutrophil (segmented) counts (see safety monitoring for neutropenia in 
Section10.3.3.1):
o <500 cells/µL(<0.50×103/µL or <0.50 GI/L)

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o ≥500 and <1000 cells/µL(≥0.50×103/µLand <1.00×103/µLor ≥0.50 GI/L and 
<1.00GI/L)(from2 test results; the second test must be performed within 1week 
from knowledge of the initial result)
o ≥1000 and <1500 cells/µL (≥1.00×103/µLand <1.50×103/µLor ≥1.00 GI/L and 
<1.50 GI/L)(from 3 test results as specified in Section10.3.3.1) andan infection that 
is not fully resolved
total WBC count <2000 cells/µL(<2.00×103/µL or <2.00GI/L)
lymphocyte count <500 cells/μL(<0.50×103/µL or <0.50 GI/L)
platelet count <50,000 cells/μL(<50×103/µL or <50 GI/L)
changes in BP defined as sitting systolic BP at ≥160 mm Hg plus ≥20 mm Hg increase 
from baseline (Week 0, Visit 2) and/or diastolic BP at ≥100 mm Hg plus ≥10 mm Hg 
increase from baseline that do not respond aftermaximal allowed intervention 
(Section10.3.3.2)
If the investigator decides that the patient should be withdrawn because of anSAE or a 
clinically significant laboratory value, the investigational product is to be discontinued 
and appropriate measures are to be taken.  Lilly or its designee is to be alerted 
immediately.  Refer to Safety Evaluations, Section 10.2.7).
clinically significant systemic hypersensitivity reaction aftersubcutaneous (SC)
administration of investigational product
the patient becomes pregnant
The patient develops a malignancy.  Note:  Patients may be allowed to continue if they 
develop no more than 2 nonmelanoma skin cancers over any 12-month period during the 
study.
Any positive TB test that indicates TB test conversion since prior testing (based on 
patient medical history or Visit1 screening test), AND the patient does not receive 
appropriate treatment for latent TB; or there is evidence of active TB infection at any 
time(see Section 10.3.2.3)
the patient develops symptoms suggestive of a lupus-like syndrome or is positive for 
antibodies against double-stranded DNA
If the patient for any reason requires treatment with another therapeutic agent that has 
been demonstrated to be effective for the treatment of PsA or psoriasisbeforethe 
posttreatment follow-up period, discontinuation from the study must occur before
introduction of the new agent.  For patients who completed or discontinued study 
treatment and have entered the posttreatment follow-up period (Period 4), PsA therapy 
with another agent is allowed, as determined appropriate by
 the investigator.
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
If the patient scores a 3 for Item 12 (Thoughts of Death or Suicide) on the QIDS-SR16 at 
any time in the study,
-OR-

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if the patient develops active suicidal ideation with some intent to act with or without a 
specific plan (yes to Question 4 or 5 on the “Suicidal Ideation” portion of the 
Columbia-Suicide Severity Rating Scale [C-SSRS]),
-OR-
if the patient develops suicide-related behaviors as recorded on the C-SSRS,
then it is recommended that the patient be assessed by a psychiatrist or appropriately 
trained professional to assist in deciding whether the subject is to be discontinued from 
the study.
failure to demonstrate at least a 20% improvement from baseline in both TJC and SJC at 
Week 24orat any subsequent visitthrough Week 104 except from the point of 
randomization until the visit afterrelapse for those patients who are randomized in 
Period3
the investigator decides that the patient should be withdrawn from the study
the patient requests to be withdrawn from the study
Lilly or its designee stops the patient’s participation in the study or Lilly stopsthe study 
for medical, safety, regulatory, or other reasons consistent with applicable laws, 
regulations, andGCP
The patient becomes HBV DNA positive.  The patient should be referred to a specialist 
physician. Discussion of discontinuation from study treatment and from the study is 
provided in Section 10.3.3.4.
If a patient is noncompliant with study procedures and/or study drug administration (see
Section12.2.5), the investigator should assess the patient to determine the reason for 
noncompliance and educate and/or manage the patient as appropriate to improve compliance.  If 
in consultation with Lilly or its designee the noncompliance is deemed to be significant or if 
further noncompliance occurs, the patient should be discontinued from the study.
Any patient who discontinues the study for any reason will stop treatment and continue to the 
ETV beforeentering the posttreatment follow-up period (Period 4).
8.3.2. Patients Lost to Follow-Up
A patient willbe considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site.  Site personnel are expected to make 
diligent attempts to contact patients who fail to return for a scheduled visit or were otherwise 
unable to be followed up by the site.
8.3.3. Discontinuation of Study Sites
Study site participation may be discontinued if Lilly or its designee, the investigator, or the 
IRB/ERB of the study site judges it necessary for medical, safety, regulatory, or other reasons 
consistent with applicable laws, regulations, and GCP.

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

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9.Treatment
9.1. Treatments Administered
During the initial open-label treatment period(Period 2), all patients will receive ixekizumab 
80mg Q2W(TableRHBF.1).  The randomized double-blind withdrawal period(Period 3) 
involves a comparison of ixekizumab 80mg Q2Wwith placebofor those patients who meet 
randomization criteriabased on Coates Criteriafor MDA. Patients who do not meet
randomization criteria will receive ixekizumab 80 mg Q2W for the duration ofPeriod 3
(TableRHBF.1).  All doses are administered as SC injections.  
TableRHBF.1. 
Treatment Regimens
Treatment Group
Description
Initial Open-Label Treatment Period (Period 2)
80 mg ixekizumab Q2W
Starting dose of 160 mg of ixekizumab will be given as2 SC 
injections at Week 0followed by 80 mg given as 1 SC injection 
Q2W from Week 2 to Week36 
Randomized Double-Blind Withdrawal Period (Period 3)
80 mg ixekizumabQ2W 
80 mg given as 1 SC injectionQ2Wany time fromWeek 36 to 
Week 104
Placebo
Placebo given as 1 SC injection Q2W any time from Week 36 to 
Week 104
Abbreviations:  Q2W = every 2 weeks; SC = subcutaneous.
The investigator or his/her designee is responsible for 
explaining the correct use of the investigational agent(s) to the patient and/or patient’s 
caregiver, 
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.
Patients will be instructed to contact the investigator as soon as possible if they havecomplaints
or problemswith the investigational product so that the situation can be assessed.
Further instructions regarding administration of the investigational products are provided in 
Section9.5.1and 9.5.2.
9.1.1. Administration of Investigational Product
Injections will be administered SC by the patient or caregiver after training by the clinical staff.
Training:  At Week 0 (baseline, Visit 2) each patient is scheduled to receive 2 injections of 
ixekizumab 80 mg.  For training purposes, the proper procedures for administration of the initial 
injection will be performed by clinical staff and the second injection of investigational product at 
that visit will be administered by the patientor caregiverunder the supervision of clinical staff.  

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If additional training is necessary, an injection may be administered by the patientor caregiver
under the supervision of clinical staff at Week 2 (Visit 3).
Administration:  If the patient is unable to perform the injection, a caregiver, who will also be 
trained under supervision of site staff, may administer the investigational product.  All 
subsequent injections will be administered by the patient or caregiver and should be administered 
unsupervised by the clinical staff.  It is recommended that for these subsequent injections, the 
patientor caregiver administer the investigational product outside the trial site, preferably at the 
patient’s home.  If the patient or caregiver is not able to administer the second injection of the 
starting dose, or any dose through the study, study site personnel may administer that injection.
Refer to the appropriate Manual Syringe Directions for Useprovided by the sponsor for the 
investigational product.  Note that injections should not be given in the same arm from which 
immunogenicitysamples are being drawn at relevant visits.
Study drug administration logs will be dispensed to each patient as needed for recording 
pertinent data about each injection; details of the use of these logs is provided in Section9.5.2.
Observation:  Patients should remain under observation for at least 1 hour after dosing at 
Week 0 (baseline, Visit 2) for safety monitoring because patients will be receiving ixekizumab 
for the first time at thisvisit.  This allowsfor observation for any AEs and collection of 
postinjection sitting BP and pulse measurements approximately 1 hour after administration of the 
investigational product (Section10.3.2.4and Attachment1).  
9.2. Materials and Supplies
The investigational products will be supplied by the sponsor or its designee in accordance with 
current good manufacturing practices and will be supplied with lot numbers, expiry dates, and 
certificates of analysis, as applicable.
Ixekizumab and Placebo to Match (excipients only) will be supplied as injectable solutionsin 
1-mL, single-dose, disposable manual,prefilled syringes with study-specific labels.  Each 
syringe of ixekizumab is designed to deliver ixekizumab 80 mg.  The syringes (and contents) 
containing either ixekizumab or matching placebo will be visibly indistinguishable from each 
other.  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 the country’s regulatory requirements.  All 
investigational products 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) and in its original 
carton to protect it from light.  Sites will be required to monitor temperature of the on-site 
storage conditions of the syringes.  
Study drug administration logs will be dispensed to each patient as needed for recording 
pertinent data about each injection; details of the useof these logs are provided in Section9.5.2.

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9.3. Method of Assignment to Treatment
Patients who meet the eligibility criteria for randomizationany time fromWeek 36 through 
Week 64 will be randomized to double-blind treatment groups as determined by a 
computer-generated random sequence using an interactive web-response system (IWRS).  The 
IWRS will be used to assign double-blind investigational product to each patient.  Site personnel 
will confirm that they have located the correct assigned investigational product package by 
entering a confirmation number found on the package into the IWRS.  Patients will be stratified 
by geographic region and cDMARD useat the time of randomization in Period 3.
9.4. Rationale for Selection of Doses in the Study
Rationale for the 80-mg Q2W Dose Regimen:  The 80-mg Q2W dose regimen has been 
selected for evaluation in Study RHBF.  In Study RHAK, the Phase 2 dose-ranging study in 
patients with RA, a dose-response relationship was detected for ACR20 at the Week 12 primary 
endpoint across the dose range tested (3-, 10-, 30-, 80-, and 180-mg ixekizumab Q2W) in the 
bDMARD-naive population.  In that study, 80-and 180-mg ixekizumab Q2W doses 
demonstrated significantly better ACR20 responses compared to placebo in the TNF-IR 
population.  Similar to ACR20 responses, a dose-related reduction in the mean change from 
baseline in DAS28-CRP was observed with increasing doses of ixekizumab at Week 12 in both 
patient populations.  Numerically higher ACR20 and DAS28-CRP responses were observed at 
the 180-mg Q2W dose level compared to all other doses across most time points in the 12-week 
time course in both patient populations.  This was evident from the ACR20 and DAS28-CRP 
responses observed within the first week of the study as well as the consistency in clinical 
efficacy compared to other doses, which was maintained up to the Week 12 time point.  The 
ACR20 and DAS28-CRP response rates for the 80-mg Q2W dose begin to approximate the 
responses for the 180-mg Q2W dose around Week 12.  Results for the mean ACR-N responses 
in both populations were consistent with those observed for the ACR20 and DAS28-CRP 
responses.  Given that the 80-mg Q2W and 180-mg Q2W dose regimens appear to demonstrate 
similar ACR20 and DAS28-CRP response rates around Week 12 in both bDMARD-naive and 
TNF-IR patient populations, Lilly believes that evaluating an 80-mg Q2W dose in Phase 3 
studies in patients with PsA may provide close to maximal efficacious response while reducing 
the overall exposure to ixekizumab.
Rationale for the 160-mg Starting Dose:  A starting dose of 160 mg ixekizumab will be used to 
achieve steady state concentrations earlier and allow a rapid onset of responses.  
According to PK analyses conducted with pooled data from clinical trials in psoriasis patients, 
over 80% of the steady state drug exposure of 80 mg Q2W regimen was achieved after the 
160-mg starting dose.  
In StudyRHAK, the 180-mg dose demonstrated the greatest magnitude of ACR20 and 
DAS28-CRP responses at Week 1 in both the bDMARD-naive and TNF-IR populations.  
Similarly,in Study I1F-MC-RHAJ(RHAJ), the 150-mg dose demonstrated the greatest 
magnitude of PASI responses at Week2 in patients with psoriasis.  This early onset of efficacy
 is 
hypothesized to be related to the increased IL-17 neutralization at higher doses of ixekizumab.  

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Therefore, 160-mg ixekizumab used as a starting dose at Week 0 should provide an early onset 
of clinical responses in PsA similar to the ACR20 and DAS28-CRP responses observed with the 
first dose of 180-mg ixekizumab in Study RHAK and of PASI response similar to that observed 
with the first 150-mg dose in Study RHAJ.
9.5. Selection and Timing of Doses
Patients are assigned to treatment (Section 9.3) and will receive their assigned treatmentsas 
outlined in Sections 9.1and 9.1.1.
Investigational product should be administered at approximately the sametime each day as much 
as possible.  For injections not administered on the scheduled day of the week, the missed dose 
should be administered within 4 days of the scheduled day or as close as possible to the 
scheduled day and within the visit window as allowed according to the study schedule 
(Attachment1).  Dates of subsequent study visits should not be modified because of this delay.
Study drug administration logs will be dispensed to each patient as needed for recording 
pertinent data about each injection; details of the use of these logs are provided in Section9.5.2.
9.5.1. Special Treatment Considerations
Patients will be screened for eligibility in the study as described in Sections8.1and 8.2and will 
be informed of the study-specific restrictions and requirements of the study.  Patients who are not 
willing to comply with the study requirements and restrictions of the study will not be eligible 
for enrollment.
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
Proteins may also cause redness, itching, swelling, or pain locally at the injection site.  
Sometimes these reactions can be life-threatening.  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 afteran injection.  If a patient experiences an acute allergicor 
hypersensitivity reactionafter 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 allergicor hypersensitivity 
reaction, a blood sample should be drawn to test for anti-drug antibodies as soon as feasible.  

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For patients who experience a potential allergicor hypersensitivity reaction, consideration for 
any premedication for future injections will be agreed upon between the investigator and 
sponsor.  Examples of potential allergicor hypersensitivity reactions that might merit 
premedication include mildtomoderate skin rashes, mildtomoderate generalized pruritus 
and/or urticaria, and mildtomoderate injection-site reactions (for example, injection-site 
erythema, injection-site pruritus).  Patients who develop clinically significant systemic allergicor 
hypersensitivity reactions afteradministration of investigational product (for example, a reaction 
that causes hospitalization) should be discontinued from the study and not receive further doses 
of investigational product, with or without premedication (see Section8.3.1.1).  Medications 
considered appropriate for premedication include but are not restricted to acetaminophenor 
paracetamol up to 1000 mg and antihistamines (for example, oral diphenhydramine 50 mg); 
premedications should begivenafter allefficacy assessments have been completed for a given 
visit and30 to 60 minutes beforeinvestigational product SC injectionfor visits where injections 
are administered at the clinic.  For all other injections, patients may self-premedicate at home 
beforeadministration 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.
9.5.2. Use of Study Drug Administration Log
A study drug administration log will be completed for each injection throughout all patients’ 
participation in the study per the study schedule (Attachment1).
The study drug administration log collects information on the date, time, and anatomical location 
of administration (for treatment compliance); syringe number; the person who administered the 
investigational product (patient, study staff, or caregiver); andwhether the investigational 
product was fully administered and, if not, the appropriate reason(s) from the list provided:
1)study drug leaked from syringe/device
2)study drug leaked from injection site
3) hard to hold
4)syringe/device jammed during injection
5)studydrug administration instructions difficult to understand
6) other
Patients will be instructed to contact their study sitesin the event of an injection problem.  In 
addition, site personnel will review all study drug administration logs at each visit to identify any 
product complaints, and they will complete a product complaint form for each operation failure 
reported on a study drug administration log(see Section 10.3.4for additional instructions 
regarding complaint handling).
9.6. Continued Access to Investigational Product
Investigational productwill not be made available after conclusion of the study to patients.

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9.7. Blinding
In the randomized double-blind withdrawal period(Period 3),patientsand study site personnel
will be blinded to study treatment assignment (ixekizumab 80 mg Q2W or placebo).To preserve 
the blinding of the study, a minimum number of sponsor personnel not in direct contact with 
study sites will see the randomization table and treatment assignments before the study is 
unblinded.  Section9.1provides the dosing details pertinent to maintenance of the study blind.
In case of an emergency, the investigator has the sole responsibility for determining if unblinding 
of a patient’s treatment assignment is warranted.  Patient safety must always be the first 
consideration in making such a determination.  If the investigator decides that unblinding is 
warranted, the investigator should make every effort to contact the Lilly clinical research 
physician beforeunblinding a patient’s treatment assignment.  If a patient’s treatment assignment 
is unblinded, Lilly must be notified immediately.
If an investigator, site personnel performing assessments, or patient is prematurely unblinded, the 
patient must be discontinued from the investigational product and should continue in the 
posttreatment follow-up period (Period 4).  In cases where there are ethical reasons to have the 
patient remain on the investigational product, the investigator must obtain specific approval from 
a Lilly clinical research physician or representativefor the patient to continue in the study.
Unblinding will be performed through the IWRS.  All transactions resulting in an unblinding 
event are recorded and reported by the IWRS.
9.8. Concomitant Therapy
All concomitant medication taken during the study must be recorded on the concomitant 
medication case report form (CRF).  Treatment with concomitant PsA and coexisting psoriasis
therapies during the study is permitted only as outlined in the exclusion criteria (Section8.2) and 
as described in the paragraphs below.  Patients taking permitted medications should be on 
chronic stable dosages at baseline(Week 0, Visit 2) as specified in Section8.2.
The following therapies will notbe permitted during the course of the study:
PsA and coexisting psoriasistherapies that are excluded as described in the exclusion 
criteria (Section 8.2)
any therapy within the washout periods specified in exclusion criteria (Section8.2)
live vaccines (including BCG)
phototherapy
The following medications willbe permitted during the course of the study (but note 
restrictions):
NSAIDs and analgesics:  NSAIDs, including cyclooxygenase-2inhibitors, will be allowed up to 
the maximum recommended dosages for pain.  Nonopioid analgesics (for example, 
acetaminophenor paracetamol) up to the maximum recommended dosages for pain may be 
administered on an as-needed basis during the studybut should be withheld within 24 hours of a 
visit.  Aspirin (dosagenot exceeding 350mg/d) may be taken to manage cardiovascular risk.

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During the initial open-label treatment period(Period 2), any dosageadjustment, change of 
NSAIDs, and/or introduction of a new NSAID may be made.For patients who are not 
randomizedduring the randomized double-blind withdrawal period(Period 3), any dosage
adjustment, change of NSAIDs, and/or introduction of a new NSAID may continue to be made
throughout Period 3.  For patients who are randomized during Period 3, dosage adjustment, 
change of NSAIDs, and/or introduction of a new NSAID may notbe made untilthe point of 
relapse (if relapse occurs).  Any changes must be recorded on the concomitant medication CRF.
During study Periods2 and3, the use of variable doses of opiate analgesics is allowed but may 
not exceed an average daily dose of 30mg morphine or its equivalent.  Any changes must be 
recorded on the concomitant medication CRF.
Conventional DMARDs:  During the initial open-label treatment period(Period 2), alteration of 
cDMARD dosageand/or introduction of a new cDMARD arepermitted.  For patients who are 
not randomizedduring the randomized double-blind withdrawal period(Period 3), alteration of 
cDMARD dosageand/or introduction of a new cDMARDmay continue to be made throughout 
Period 3. For patients who are randomized during Period 3,alteration of cDMARD dosage 
and/or introduction of a new cDMARDmay not be made untilthe point of relapse (if relapse 
occurs).  If, at any time, the investigator believes that side effects or laboratory abnormalities 
may be attributable to the cDMARD, the cDMARD dosageshould be lowered or the medication
should bestopped.  In this case, reintroduction of the cDMARD may occur when the investigator 
deems clinically appropriate.  Not more than 1adjustment of cDMARDs within 12 weeks is 
recommended.  Any changes must be recorded on the concomitant medication CRF.
The maximum allowed dosageduring the study is 25 mg/wk for MTX, 400 mg/dfor 
hydroxychloroquine, 20 mg/dfor leflunomide, and 3 g/dfor SSZ.  The local standard of care 
should be followed for concomitant administration of folic acid if MTX is taken and for 
administration of other cDMARDs.  Under no circumstances will simultaneous use of MTX and 
leflunomide be allowed at anytime during the study for safety reasons.
Topical steroids:  Topical steroids of weak potency (WHO Group 1 classification) will be 
permitted for use as needed during the study.  More-potent topical steroids may be used, as 
needed, for an individual patient except from the point of randomization to the point of relapse 
(if relapse occurs).  These topical medications should not be used within approximately 24 hours 
beforestudy visits requiring static Physician’s Global Assessment of psoriasis (sPGA)and PASI 
measures.
Other topical therapies:  The following will be allowed as needed:  shampoos that do not 
contain >3% salicylic acid, corticosteroids, coal tar, or vitamin D3 analogues; topical 
moisturizersor emollients and other nonprescription topical products that do not contain urea, 
>3% salicylic acid, -or -hydroxyl acids, corticosteroids, or vitamin D3 analogues; bath oils 
and oatmeal bath preparations.  These topical therapies are not to be used within 12 hours before
a study visit.  Shampoos that contain >3% salicylic acid, corticosteroids, coal tar, or vitamin D3 
analogues may be used, as needed,for an individual patient except from the point of 
randomization to the point of relapse (if relapse occurs).

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Oral corticosteroids:  During the initial open-label treatment period(Period 2), adjustments of 
oral corticosteroids (for example, dose change, introduction) are allowed.  The maximum dosage
is not to exceed 10 mg/d of prednisone or its equivalent at any time during this period.
During the randomized double-blind withdrawal period(Period 3), adjustments of oral 
corticosteroids are allowed for an individual patient but are strongly discouragedfrom the point 
of randomization to the point of relapse (if relapse occurs).  The maximum dosageis not to 
exceed 10mg/dof prednisone or its equivalent at any time during these periods.
IV, intramuscular, soft tissue (bursa, tendons, and ligaments) and intra-articular 
corticosteroids:  Treatment with any parenteral corticosteroids is not permitted within 6weeks 
beforebaselineor during the study.
However, except from the point of randomization to the point of relapse (if relapse occurs), 
intra-articular injection of a corticosteroid may be allowed on a limited basis:  it is recommended 
that there be no more than 1injection within any 1-year period (1 injection = 1large joint or up 
to 5 small joints or 1soft tissue).  The joint(s) injected must be designated along with the 
medication taken on the concomitant medications CRF and must be recorded as unevaluable on 
the TJC/SJC assessment CRF.
Inhaled steroids:  Regular use of inhaled steroids for asthma or nasal corticosteroids for 
allergies will be permitted during the study.
Additional guidance: Patients requiring surgery at any time during the study should interrupt 
administration of the investigational product beginning 8weeks prior to the surgery, or as early 
as possible within 8weeks of surgery, and resume administration of the Investigational product 
only after complete wound healing.
Additional drugs are to be avoided during the study unless required to treat an AE or for the 
treatment of an ongoing medical problem.  If the need for concomitant medication arises, the 
investigator should base decisions on the patient and clinical factors.  Any additional medication, 
whether prescription or over-the-counter, used at baseline (Week0,Visit2) and/or during the 
course of the study must be documented with the start and stop dates on the concomitant 
medications CRF.
Patients will maintain their usual medication regimen for other concomitant diseases throughout 
the study unless specifically excluded in the protocol.  Patients taking allowed concomitant 
medications should be on stable doses at the time of baseline (Week0,Visit2) and should 
remain at a stabledose throughout the study, unless changes need to be made for an AEor for 
appropriate medical management.  Additional systemic drugs are to be avoided during the study, 
unless required to treat an AE.  Other medications may be allowed, if approved by the sponsor or 
its designee.
Any changes in medications not addressed above shouldbe discussed with the investigator.  
Unless urgent medication is indicated by the patient’s medical condition, patientsshould be 
instructed to consult the investigatoror other appropriate study personnel at the site before taking 
any new medications or supplements.

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9.9. Treatment Compliance
Every attempt will be made to select patients who have the ability to understand and comply with 
study instructions.  The investigator is responsible for discussing methods to ensure high 
treatment compliance with the patient before randomization.
Patients will record the date and time of administration of investigational product in a study drug 
administration logthroughout their participation in the study (see also Section9.5.2).  The data 
from the study drug administration logmust be transcribed into the electronic case report form 
(eCRF)by site personnel.  Patient compliance with the investigational product will be assessed at 
each study visit by review of the study drug administration log, return ofempty investigational 
product packaging, and/or direct questioning.  Deviation(s) from the prescribed dosage regimen 
should be documented in the CRF.
If a patient is noncompliant with study procedures and/or study drug administration (see 
Section12.2.5), the investigator should assess the patient to determine the reason for 
noncompliance and educate and/or manage the patient as appropriate to improve compliance.  If, 
in consultation with Lilly or its designee, the noncompliance is deemed to be significant or if 
further noncompliance occurs, the patient should be discontinued from the study.

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10. Efficacy, Health Outcome Measures, Safety Evaluations, 
Sample Collection and Testing, and Appropriateness of 
Measurements
Study procedures and their timing (including tolerance limits for timing) are summarized in the 
study schedule(Attachment1).  Additionally, a list of the specific planned laboratory tests to be 
performed for this study is provided in Attachment2.
10.1.Efficacy Measures
10.1.1.Primary Efficacy Measures
The primary objective is to compare ixekizumab 80 mg Q2W with placebo in maintenance of 
treatment outcome, as measured by the time to relapse during the randomized double-blind 
withdrawal periodin cDMARD-IR and bDMARD-naive patients with active PsA who met 
Coates criteriafor MDA.
10.1.1.1.Coates Criteria for Minimal Disease Activity
The Coates criteriafor MDA (described below)has been developed on the basis ofcurrent 
expert opinion and uses a composite of 7key outcome measures used in PsA to encompass all of 
the domains of the disease to measure the overall state of a patient’s disease (Coates et al. 2010; 
Coates and Helliwell 2010).  The criteria were developed specifically for PsA and have been 
validated in observational and interventional cohorts.  TheCoatescriteriaforMDA have 
evidence supporting their use within the OMERACT filter of truth, discrimination, and 
feasibility.  In a retrospective analysis of infliximab in PsA, the criteria were shown to be 
discriminative between drug and placebo and there was a strong association between achieving 
MDA and achievement of the ACR outcomes, reductions in inflammatory markers,and 
physician opinion of disease activity (Coates and Helliwell 2010). Patients who maintain Coates 
Criteria for MDA for 38 Weeks or more have better long-term functional improvement, patient 
global assessment, and radiography outcomes after 5 years (Kavanaugh et al. 2015). In addition, 
MDA has been recently advocated as a feasible and clinically relevant treatment target in clinical 
practice (Coates and Helliwell 2015) that is acceptable for patients and physicians (Coates et 
al.2012). The duration of treatment needed to achieve MDA isvariable;as many as 52% of 
patients meet the Coates criteria for MDA within 6 months of starting a TNF inhibitor,but even 
higher percentages meet the criteria at 1 year or more (Coates and Helliwell 2010; Haddad et 
al.2015).  

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Two version of the MDA have been defined. The Coates criteriaforMDA will be used to 
determine randomization eligiblyand for the primary analysis. Modified Coates criteriafor 
MDAthat use thesPGA in place of the PASI will be used as a secondary analysis. The criteria 
are:
Coates criteriafor MDA:  Patients are classified as achieving MDA if they fulfill 5 of 
7outcome measures:  
o TJC≤1
o SJC≤1 
o PASI total score ≤1 or BSA ≤3
o patient pain VAS score of ≤15
o patient global disease activity VAS score of ≤20
o HAQ-DI score ≤0.5 
o tender entheseal points ≤1
modified Coates criteriafor MDA:  For the modifiedcriteria for MDA, sPGA “skin 
clear” or “skin almost clear” (as MDA-sPGA[0,1])is substituted for PASI ≤1 (Mease et 
al.2013).
10.1.2.Secondary Efficacy Measures
10.1.2.1.Tenderand Swollen Joint Counts(68and 66 Joints)
10.1.2.1.1.Tender Joint Count
For ACR measures, the number of tender and painful joints will be determined by examination 
of 68 joints (34 joints on each side of the patient’s body).  The 68joints to be assessed and 
classified as tender or not tender are detailed in Attachment5.  Any joints that require 
intra-articular injections during the study (according to Section 9.8) should be excluded from 
evaluation from the time of the injection to the conclusion of the study.
Joints will be assessed for tenderness by pressure and jointmanipulation on physical 
examination.  The patient will be asked for pain sensations on these manipulations and watched 
for spontaneous pain reactions.  Any positive response on pressure, movement, or both will then 
be translated into a single tender-versus–not tender dichotomy.  
Joint assessments will be performed by an independent, blinded assessor to minimize bias.  The 
same assessor should perform the TJC and SJC for a given patient if possible, particularly during 
the initial open-label treatment period(Period 2) to minimize interobserver variation.  The 
blinded joint assessor will not be involved in patient care and is asked not to discuss disease 
activity or treatment with patients or principal investigator.
Missing, replaced, ankylosed, or arthrodesed joints will be identified by the investigator at the 
screening visit and will be excluded from evaluation during the trial.  

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10.1.2.1.2.Swollen Joint Count
For ACR measures, the number of swollen joints will be determined by examination of 66 joints 
(33 joints on each side of the patient’s body).  The 66 joints to be assessed and classified as 
swollen or not swollen are detailed in Attachment5.  Any joints that require intra-articular 
injections during the study (according to Section 9.8) should be excluded from evaluation from 
the time of the injection to the conclusion of the study.
Joints will be classified as either swollen or not swollen.  Swelling is defined as palpable 
fluctuating synovitis of the joint.  Swelling secondary
 to osteoarthritis will be assessed as not 
swollen unless there is unmistakable fluctuation.  Dactylitis should be counted as 1 joint.
Missing, replaced, ankylosed, or arthrodesed joints will be identified by the investigator at the 
screening visit and will be excluded from evaluation during the trial.  
Joint assessments will be performed by an independent, blinded assessor to minimize bias.  The 
same assessor should perform the TJC and SJC for a given patient if possible, particularly during 
the initial open-label treatment period(Period 2) to minimize interobserver variation.  The 
blinded joint assessor will not be involved in patient care and is asked not to discuss disease 
activity or treatment with patients or principal investigator.
10.1.2.2.Patient’sAssessment of Pain Visual Analog Scale
The patient will be asked to assess his or her current level of joint pain by marking a vertical tick 
on a 100-mm horizontal VAS where the left end represents no joint pain and the right end 
represents worst possible joint pain.  The Patient’s Assessment of Pain VAS should be 
administered beforethe TJC and SJC examinations.  
Results will be expressed in millimeters measured between the left end of the scale and the 
crossing point of the vertical line of the tick; this procedure is applicable for all VAS used in the 
trial.
10.1.2.3.Patient’sGlobal Assessment of Disease ActivityVisual Analog Scale
The patient’s overall assessment of his or her PsA activity will be recorded using the 100-mm 
horizontal VAS where the left end represents no disease activity and the right end represents 
extremely active disease activity.  
10.1.2.4.Patient’s Assessment of Physical Function Health Assessment 
Questionnaire–Disability Index
The HAQ-DI is a patient-reported standardized questionnaire that is commonly used in PsA to 
measure disease-associated disability (assessment of physical function).  It consists of 
24questions referring to 8 domains:  dressing/grooming, arising, eating, walking, hygiene, reach, 
grip, and other daily activities (Fries et al. 1980; Fries et al. 1982).  
The disability section of the questionnaire scores the patient’s self-perception on the degree of 
difficulty (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 
3=unable to do), covering the 8 domains.  The reported use of special aids or devices and/or the 
need for assistance of another person to perform these activities is also assessed.  The scores for 
each of the functional domains will be averaged to calculate the functional disability index.  

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Aminimally clinical important difference minimally clinical important differenceis a clinically 
relevant change in a patient’s status.  The HAQ-DI minimally clinical important difference has 
been estimated to be about 0.35 for patients with PsA (Mease et al. 2011). Details of scoring and 
calculations are presented in the statistical analysis plan (SAP).
10.1.2.5.Psoriasis Area and Severity Index 
If the patient has plaque psoriasis, the PASI will be administered by sitepersonnel.  The PASI 
combines assessments of the extent of body-surface 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 the most severe disease (Fredriksson and Pettersson 1978).  Patients achieving PASI 75, 
PASI 90, or PASI 100 are defined as having an improvement of at least 75%, 90%, or 100%, 
respectively, in PASI score from baseline.  
10.1.2.6.Percentage of Body Surface Area
The investigator will evaluate the percentageofinvolvement of psoriasis on each patient’s BSA 
on a continuous scale from 0% = no involvement to 100% = full involvement, where 1% 
corresponds to the size of thepatient’s handprint including the palm, fingers, and thumb 
(National Psoriasis Foundation 2009).  
10.1.2.7.Static Physician's Global Assessment
If the patient has plaque psoriasis, the sPGA will be administered by site personnel.  The sPGA
is the physician’s determination of the patient’s psoriasis lesions overall at a given time point.  
The sPGA is recommended as an endpoint to use to assess efficacy in the treatment of psoriasis 
(EMEA 2004).  Overall lesions are categorized by descriptions for induration, erythema, and 
scaling.  For the analysis of responses, the patient’s psoriasis is assessed at a given time point on 
a 6-point scale in which 0 = cleared, 1 = minimal, 2 = mild, 3 = moderate; 4 = severe, and 
5=very severe.
10.1.3.Exploratory Efficacy Measures
10.1.3.1.AmericanCollege of Rheumatology Responder Index
Relief of signs and symptoms will be assessed using the ACR Responder Index, a composite of 
clinical, laboratory, and functional measures in PsA. ACR responses are presented as the 
minimal numeric percentageimprovement from baseline in multiple disease assessment criteria.
ACR20and American College of Rheumatology 50% (ACR50) and 70% (ACR70) response 
ratesare exploratoryefficacy measures for which a patient must have:
≥20%, ≥50%, and ≥70% improvements, respectively,in both TJC and SJC
≥20%, ≥50%, and ≥70% improvements, respectively,in at least 3 of the following 5ACR 
Core Set criteria:
1. Patient’s Assessment of Pain VAS
2. Patient’s Global Assessment of Disease Activity VAS
3. Physician’s Global Assessment of Disease Activity VAS

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4. patient’s assessment of physical function as measured by the HAQ-DI
5. acute phase reactant as measured by C-reactive protein
10.1.3.2.Physician’sGlobal Assessment of Disease Activity Visual Analog Scale 
The investigator will be asked to give an overall assessment of the severity of the patient’s 
current PsA activity using a 100-mm horizontal VAS, where 0 represents no disease activity and 
100 represents extremely active disease.  The investigator making the assessment must be a 
rheumatologist or medically qualified physician.  The same assessor should perform the 
Physician’s Global Assessment of Disease Activity VAS for a given patientif possible,to 
minimize interobserver variation.  
10.1.3.3.Leeds Enthesitis Index
If the patient has enthesitis, an assessment of 18 entheseal points will be performed by site 
personnel,and from this assessment the Leeds Enthesitis Index (LEI)will be evaluated.  The LEI 
has been developed specifically for use in PsA.  The LEI measures enthesitis at 6sites (lateral 
epicondyle[left and right],medial femoral condyle[left and right],and Achilles tendon insertion
[left and right]) (Healy and Helliwell 2008).  Each site is assigned a score of 0 (absent) or 
1(present); the results from each site are then added to produce a total score (range:  0 to 6).
The LEI will be administered by an independent assessor to minimize bias.  The assessor will not 
be involved in patient care and is asked not to discuss disease activity or treatment with patients 
or principal investigator.
10.1.3.4.Spondyloarthritis Research Consortium of CanadaEnthesitis Index
If the patient has enthesitis, an assessment of 18 entheseal points will be performed by site 
personnel,and from this assessment the Spondyloarthritis Research Consortium of Canada
(SPARCC)enthesitis index will be evaluated.  The SPARCC enthesitis index evaluates 
tenderness in a total of 16 enthesitis sites:  the greater trochanter (rightand left), quadriceps 
tendon insertion into the patella (right and left), patellar ligament insertion into the patella and 
tibial tuberosity (right and left), Achilles tendon insertion (right and left), plantar fascia insertion 
(right and left), medial and lateral epicondyles (right and left), and the supraspinatus insertion 
(right and left) (Mease 2011). Tenderness at each site is quantified on a dichotomous basis:
0=nontender and 1 = tender.  The results from each site are then added to produce a total score 
(range,0 to 16).
The SPARCC enthesitis index will be administered by an independent assessor to minimize bias.  
The assessor will not be involved in patient care and is asked not to discuss disease activity or 
treatment with patients or principal investigator.
10.1.3.5.Leeds Dactylitis Index–Basic
If the patient has dactylitis, the Leeds Dactylitis Index–Basic (LDI-B)will be administered by 
site personnel.  The LDI-B has been developed to measure the severity of dactylitis.  Once the 
presence of dactylitis is established in each digit, the ratio of the circumference of the affected 
digit to the circumference of the same digit on the patient’s other hand or foot is measured 
(Helliwell et al. 2005).  Each dactylitic digit is defined by a minimum increase of 10% in 
circumference over the contralateral digit.  If the same digits on both handsor feet are thought to 

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be involved, the clinician will refer to a table of normative values (provided to investigative 
sites) for a value that will be used to provide the comparison.  The calculated ratio is then 
multiplied by a tenderness score of 0 (not tender) or 1(tender).  Tenderness is assessed in the 
area between the joints.  The results of each digit are then added to produce a total score (range:  
0 to 20) (Healy and Helliwell 2007).
The LDI-B will be administered by an independent assessor to minimize bias.  The assessor will 
not be involved in patient care and is asked not to discuss disease activity or treatment with 
patients or principal investigator.
10.1.3.6.Disease Activity ScoreBased on C-Reactive Protein
The DAS28-CRP is a measure of disease activity in 28 joints that consists of a composite 
numerical score using the following variables:  TJC, SJC, C-reactive protein (measured in mg/L), 
and Patient’s Global Assessment of Disease Activity recorded by patients on a 100-mm VAS.  
For DAS28-CRP, the 28 joints to be examined and assessed as tender or not tender for TJC and 
as swollen or not swollen for SJC are a subset of those assessed for the TJC and SJC and include 
14joints on each side of the patient’s body:  the 2 shoulders, the 2 elbows, the 2 wrists, the 
10metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8proximal 
interphalangeal joints, and the 2 knees (Smolen et al. 1995).  The following equation will be used 
to calculate the DAS28 (Vander Cruyssen et al. 2005):  
 
 
 

 

 
 


96
.
0
014
.
0
1
ln
36
.
0
28
28
.
0
28
56
.
0
28







VAS
CRP
SJC
TJC
CRP
DAS
10.1.3.7.Composite Psoriatic Disease Activity Index
The CPDAI is a validated instrument intended to assess composite psoriatic disease activity and 
response to therapy (Mumtaz et al. 2011).  This instrument assesses individual domains involved 
as well as the global effect of disease in all dimensions by which each patient may be affected.  
Domains include peripheral arthritis as assessed by the number of tender and swollen joints and 
the HAQ-DI, skin as assessed by the PASI and the DLQI, enthesitis as assessed by the number of 
sites with enthesitis and the HAQ-DI, and dactylitis as assessed by the number of digits affected 
and the HAQ-DI.  A modified version that does not include the axial domain is beingused in this 
study.  Scores range from 0 to 12;a higher score indicates higher disease activity.
10.1.3.8.Psoriatic Arthritis Disease Activity Score
The PASDAS is a weighted index comprising assessments of joints, function, acute-phase 
response, quality of life, and patient and physicianglobal assessment of disease by VAS.  All 
VAS scores are 0mm to 100mm. The TJCis 68 joints, and the SJC is66. The score range of 
the PASDAS is 0to 10;worse disease activity is represented by higher scores (Helliwell et 
al.2013).

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10.2.Health Outcome Measures
10.2.1.Itch Numeric Rating Scale
The itch NRS is a patient-administered, 11-point horizontal scale anchored at 0 and 10, on which 
0 represents “no itch” and 10 represents “worst itch imaginable.”  Overall severity of a patient’s 
itching from psoriasisis indicated by circling the number that best describes the worst level of 
itching in the past 24 hours.
10.2.2.Fatigue Severity Numeric Rating Scale
The fatigue severity NRS is a patient-administered single-item 11-point horizontal scale 
anchored at 0 and 10, on which 0represents “no fatigue” and 10 represents “as bad as you can 
imagine.”  Patientsrate their fatigue (feeling tired or worn out) by circling the single number that 
describes their worst level of fatigue during the past 24hours.  
10.2.3.Dermatology Life Quality Index
The DLQI is a simple, patient-administered, 10-question, validated, quality-of-life questionnaire 
that covers 6 domains including symptoms and feelings, daily activities, leisure, work and 
school, personal relationships, and treatment.  Response categories include “not at all,”“a lot,” 
and “very much,” with corresponding scores of 1, 2, and 3,respectively,and unanswered (“not 
relevant”) responsesarescored as 0.  The recall period is “over the last week,” and totals range 
from 0 to 30 (less to more impairment);a 5-point change from baseline is considered clinically 
relevant (Basra et al. 2008).
10.2.4.Medical Outcomes Study 36-Item Short-Form Health Survey
The SF-36 is a 36-item patient-administered measure designed to be a short, multipurpose 
assessment of health in the areas of physical functioning, role—physical, role—emotional, 
bodily pain, vitality, social functioning, mental health, and general health.  The 2 overarching 
domains of mental well-being and physical well-being are captured by the Mental Component 
Summaryand Physical Component Summaryscores.  The summary scores range from 0to 100;
higher scores indicate better levels of function and/or better health.  Items are answered on Likert 
scales of varying lengths.  The SF-36version 2(acute version)will be used,which has a 1-week 
recall period (Brazier et al. 1992; Ware and Sherbourne 1992).
10.2.5.European Quality of Life–5 Dimensions 5 Level
The EQ-5D 5L is a standardized measure of health status thatprovidesa simple, generic measure 
of health for clinical and economic appraisal.  The EQ-5D 5L consists of 2 components:  a 
descriptive system of the respondent’s health and a rating of his/her current health state using a 
100-mm VAS.  The descriptive system comprises the following 5 dimensions:  mobility, 
self-care, usual activities, pain/discomfort, and anxiety/depression.  Each dimension has 5 levels:  
no problems, slight problems, moderate problems, severe problems, and extreme problems.  The 
respondent is asked to indicate his/her health state by ticking (or placing across) in the box 
associated with the most appropriate statement in each of the 5 dimensions.  It should be noted 

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that the numerals 1 to 5 have no arithmetic properties and should not be used as an ordinal score.  
The VAS records the respondent’s self-rated health on a vertical VAS where the endpoints are 
labeled “best imaginable health state” and “worst imaginable health state.”  This information can 
be used as a quantitative measure of health outcome.  The EQ-5D 5L health states, defined by 
the EQ-5D 5L descriptive system, may be converted into a single summary index by applying a 
formula that essentially attaches values (also called weights) to each of the levels in each 
dimension (Brooks 1996; Herdman et al. 2011; EuroQol Group [WWW]2013).
10.2.6.Work Productivity and Activity Impairment Questionnaire–
Specific Health Problem
The Work Productivity and Activity Impairment–Specific Health Problemconsists of 
6questions to determine employment status, hours missed from work because ofPsA, hours 
missed from work for other reasons, hours actually worked, the degree to which PsA affected 
work productivity while at work, and the degree to which PsA affected activities outside of 
work.  Four scores are derived:  percentage of absenteeism, percentage of presenteeism (reduced 
productivity while at work), an overall work impairment score that combines absenteeism and 
presenteeism, and percentage of impairment in activities performed outside of work.  Greater 
scores indicate greater impairment (Reilly et al. 1993; Reilly Associates Health Outcomes 
Research [WWW]).
10.2.7.Quick Inventory of Depressive Symptomatology–Self Report 
(16Items)
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 (APA 1994). A patient is 
asked to consider each statement as it relates to the way he/she hasfelt 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;higher scores denote greater 
symptom severity. The domains assessed by the instrument are(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 (Rush et al. 2003; Trivedi et al. 
2004; University of Pittsburgh Epidemiology Data Center [WWW]).
10.3.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.

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The investigator remains responsible for following, through an appropriate health care option, 
AEs that are serious, considered related to the studytreatment 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.
10.3.1.Adverse Events
Lilly has standards for reporting AEs that are to be followed regardless of applicable regulatory 
requirements that may be less stringent.  
Lack of drug effect is not an AE in clinical studies because the purpose of the clinical study is to 
establish drug effect.
Cases of pregnancy that occur during maternal or paternal exposures to investigational product 
should be reported.  Data on fetal outcome and breast-feeding are collected for regulatory 
reporting and drug safety evaluation.
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.
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.
In addition, all AEs occurring after the patient receives the first dose of investigational product 
must be reported to Lilly or its designee via the eCRF.
Any clinically significant findings from ECGs, laboratory tests, vital sign measurements, or other 
proceduresthat result in a diagnosis should be reported 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,investigational product, and/or drug delivery 
systemvia eCRF.
The investigator will decide whether he or she interprets the observed AEs as reasonably 
possibly related to disease, the study medication, study procedure, or other concomitant 
treatment or pathologies.  To assess the relationship of the AEs, the following is defined:
Reasonably Possibly Related:  Reasonable possibility that there is a cause and effect 
relationship between the investigational product, study device, and/or study procedure 
and the AE.
The investigator answers yes/no when making this assessment.
If a patient’s dosage is reduced or treatment is discontinued as a result of an AE, study site 
personnel must clearly report to Lilly or its designee via eCRF the circumstances and data 
leading to any such dosage reduction or discontinuation of treatment.

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10.3.1.1.Serious Adverse Events
SAEcollection begins after the patient has signed informed consent and has received 
investigational product.  If a patient has an SAE after signing informed consent but before
receiving investigational product, the event will NOT be reported as serious unless the 
investigator feels the event may have been caused by a protocol procedure.
Plannedsurgeries should not be reported as SAEs unless the underlying medical condition has 
worsened during the course of the study.
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 1 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 serious adverse drug events 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.
SAEsoccurring up to and including thepatient’s last study visitwill be collected,regardless of 
the investigator’s opinion of causation, in the clinical data collection database and the 
pharmacovigilance system at the sponsor.
The investigator does not need to actively monitor patients for AEs once the trial has ended 
unless provided otherwise in the protocol.  However, 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 the SAEs 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 SAEsthat areexpected 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.  
10.3.1.1.1.Suspected Unexpected Serious Adverse Reactions
Suspected unexpected serious adverse reactions (SUSARs) are serious events that are not listed 
in the IB and that the investigator identifies as related to investigational product or procedure.  
United States 21 CFR 312.32 and European Union Clinical Trial Directive 2001/20/EC and the 
associated detailed guidancesor national regulatory requirements in participating countries 

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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.
10.3.1.1.2.Adverse Events of Special Interest
The following adverse events of special interest (AESIs) will be evaluated in particular to 
determine the safety and tolerability of ixekizumab over the range of doses selected for this 
clinical study.  
AESIsfor ixekizumab are:  
cytopenias (leukopenia, neutropenia, and thrombocytopenia)
liver function test result changes/high enzyme levels (ALT, AST, bilirubin, andALP)
infection
injection-site reactions
allergic reactionsor hypersensitivities
cerebrocardiovascular events
malignancies
depression
Crohn’s disease and ulcerative colitis(inflammatory bowel disease[IBD])
Pneumocystispneumonia and interstitial lung disease
If infections, injection-site reactions, allergicor hypersensitivity reactions, or IBDare reported, 
sites will provide details on these events as instructed on the eCRF.  Investigators will also 
educate patients and/or caregivers about the symptoms of allergicor hypersensitivity reactions 
and will provide instructions on dealing with these reactions (see also Section 9.5.1).  A blood 
sample will be collected when possible for any patient whoexperiences an AE of allergicor 
hypersensitivity reaction during the study.
Data on cerebrocardiovascular events (defined as death,cardiac ischemic event including 
myocardial infarction and hospitalization for unstable angina, hospitalization for heart failure, 
serious arrhythmia, resuscitated sudden death, cardiogenic shock, coronary revascularization 
procedure, stroke/transient ischemic attack, peripheral revascularization procedure, peripheral 
arterial event,and hospitalization for hypertension)will be collected,and the events will be 
adjudicated by an external Clinical Events Committee (CEC) made up of a chairperson, 
2cardiologists, and a neurologist.  The role of the CEC is to adjudicate these defined clinical 
events in a blinded, consistent, and unbiased manner throughout the course of a study.  The 
purpose of the CEC is to ensure that all events that have been reported are evaluateduniformly 
by a single group(the CEC).
Data on suspected IBD, as identified by events possibly indicative of ulcerative colitis and/or
Crohn’s disease, will be collected and the events will be adjudicated by an external CEC made 
up of gastroenterologists with expertise in IBD.  The role of the CEC will beto adjudicate 
defined clinical events, in a blinded, consistent, and unbiased manner throughout the course of a 
study. The importance of the CEC is to ensure that all events that have been reported are 
evaluated uniformly by a single group.

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10.3.2.Other Safety Measures
10.3.2.1.PhysicalExamination
One complete physical examination (excluding pelvic, rectal, and breast examinations) will be 
performed at screening (Visit 1).  This examination will determine whether the patient meets the 
criteria required to participate in the study and will also serve as a monitor for preexisting 
conditions and as a baseline for treatment-emergent adverse event (TEAE) assessment.  All 
remaining physical examinations throughout the study should include a symptom-directed 
physical evaluation as well as an examination of the heart, lungs, and abdomen and a visual 
examination of the skin.  
10.3.2.2.Electrocardiograms
For each patient, a single 12-lead ECG will be obtained according to the study schedule
(Attachment1). The patient must be supine for approximately 5 to 10 minutes before ECG 
collection and remain supine but awake during ECG collection. ECGs must be recorded before 
collecting any blood forsafety or PK tests. ECGs may be obtained at additional times when 
deemed clinically necessary. All ECGs recorded should be stored at the investigational site.
ECGs will be locally (machine) read and interpreted by a qualified physician (the investigatoror 
qualified designee) at the site as soon after the time of ECG collection as possible and ideally 
while the patient is still present to determine whether the patient meets entry criteria and for 
immediate patient management should any clinically relevant findings be identified.
After enrollment, if a clinically significant finding is identified (including but not limited to 
changes in QT/corrected QT interval from baseline), the investigator will determine if the patient 
can continue in the study. The investigator or qualified designee is responsible for determining 
whether 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 
anAE.
10.3.2.3.Chest Radiographyand Tuberculosis Testing
Eligibility Assessments and Testing for TB
Radiography:  At Visit 1, posterior-anterior view chest radiographywill be obtained locally 
unless the radiographsor results from chest radiographyobtained within6 months beforethe 
study are available.  Chest radiographsor results will be reviewed by the investigator or 
designee to exclude patients with active TB infection.
TB testing:  Patient history of TB test results should be assessed beforescreening (Visit 1).
Patients with no TB test results on file:  These patients will be tested at screening 
(Visit1).  A PPD skin test response of ≥5-mm induration, between approximately 2 and 
3days after test application, regardless of BCG vaccination history, will be considered a 
positive result.  In countries where the QuantiFERON-TB Gold test or T-SPOT.TB 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, thosetests may be used instead of the PPD 

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test.  If the QuantiFERON-TB Gold test or the T-SPOT.TB test is indeterminate, 1 retest 
is allowed.  If the retest is indeterminate, the patient is excluded from the study.
Patients with positive results from a TB testperformed at screening (Visit 1) but no other 
evidence of active TB may be rescreened once and enrolled on the basis ofthe following 
requirements:

after receiving at least 4 weeks of appropriate latent tuberculosis infection (LTBI)
therapy,

no evidence of hepatotoxicity (ALTand AST levels must remain ≤2× ULN) upon 
retesting of serum ALTand AST beforerandomization.  Such patients must 
complete appropriate LTBI therapy during the course of the study toremain eligible, 
and

meet all other inclusion/exclusion criteria for participation.
Patients with negative TB test results on file:  Patients with documentation of a 
negative TB test result within 3 months beforebaseline (Week 0, Visit 2) should not be 
administered a TB test at Visit1.  Documentation of PPD test results must include a 
record of the size of the induration response; if it does not, a retest at screening (Visit 1) 
will be required to determine patient eligibility.
Patients with positive TB test results on file:  Patients with history of a positive TB test 
should not be administered a TB test at Visit 1. Documentation of this history and of at 
least 4 weeks of appropriate LTBItreatment beforebaseline (Week 0, Visit 2) is required 
for study eligibility.  Patients who have a documented historyof completing an 
appropriate TB treatment regimen with no history of re-exposure since their treatment 
was completed and no evidence of active TB are eligible to participate in the study.
TB Testing and Assessment for Patients during the Study:
Tuberculosis testing during the study will be conducted based on clinical assessment of TB risk 
(symptoms/signs/known or suspected TB exposure), and as required by local regulations and/or 
local standard of care.
.
Patients testing positive for TB at any time during the study must immediately discontinue 
administration of investigational product.  The patient must be evaluated for latent or active 
infection.  Patients with active infection must be discontinued from the study and should receive 
appropriate follow-up medical care and TB treatment according to local guidelines; patients with 
latent infection must receive a full course of LTBI treatment but may resume administration of 
investigational product after receiving 4weeks of LTBI treatmentwith no evidence of 
hepatotoxicity (ALT and AST levels must remain ≤2× ULN) upon retesting of serum ALT and 
AST before resumption of investigational product.  Such patients must complete appropriate 
LTBI therapy during the course of the study to remain eligible to continue the study treatment.

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10.3.2.4.Vital Signs
Vital signs (sitting BP and pulserate) and body temperature will be measured after the patient 
has been resting for a minimum of 10 minutes at times indicated in the study schedule 
(Attachment1).  At baseline (Week 0, Visit 2),sitting BP and pulserateshould be measured 
beforeadministration of the investigational product and again approximately 1hour after 
administration.  Any clinically significant findings that result in a diagnosis should be captured 
on the eCRF.  Additional measurements of vital signs may be performed at the discretion of the 
investigator.
10.3.2.5.Immunogenicity
Samples for immunogenicity testing will be collected at time points indicated in the study 
schedule (Attachment1) and for each event judged by the investigator to be a potential systemic 
allergic/hypersensitivity reaction, when possible (Section 9.5.1).  Venous blood samples 
(approximately 10 mLeach) will be collected into tubes and used to determine antibody 
production against ixekizumab.  The actual date of each sampling will be recorded on the 
laboratory requisition.
Immunogenicity will be assessed by a validated assay designed to perform in the presence of 
ixekizumab.  Antibodies may be further characterized and/or evaluated for their ability to 
neutralize the activity of ixekizumab.  Treatment-emergent immunogenicity is defined as any 
occurrence of a 4-fold or 2-dilution increase in titer over the pretreatment baseline titer.  In the 
case of a negative result at baseline, treatment-emergent immunogenicity is defined as an 
increase in titer to ≥1:10.  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 afterlast 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 the investigational product.
10.3.2.6.Safety-Related Immune Markers
IL-17 is believed to play a role in neutrophil homeostasis and in neutrophil-dependent host 
defense against extracellular infections (Happel et al. 2003; Huang et al. 2004; Milner et 
al.2008).  Neutrophil counts will therefore serve as a safety marker in the current investigation.
Ixekizumabis not expected to affect the numbers of B, T, and natural killer (NK)lymphocytes or 
serum immunoglobulinclasses A, G, and M(IgA, IgG, and IgM, respectively) in peripheral 
blood.  However, since this is a novel immunomodulatory drug, these parameters will be 
measuredin patients.
10.3.2.7.Columbia–Suicide Severity Rating Scale
The C-SSRS (Posner et al. 2007; Columbia University Medical Center[WWW])is a scale that 
captures the occurrence, severity, and frequency of suicide-related ideations and behaviors 
duringthe assessment period.  The C-SSRS must be administered by appropriately trained site 
personnel.  The tool was developed by the National Institute of Mental Health Treatment of 
Adolescent Suicide Attempters trial group for the purpose of being a counterpart to the Columbia 

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Classification Algorithm of Suicide Assessment (C-CASA) categorization of suicidal events.  
Patients will be assessed according to the Study Schedule (Attachment1).
The Self-Harm Supplement Form is a one-questionformthat asksfor the number of suicidal or 
nonsuicidal self-injurious behaviors the patienthasexperienced since the last assessment. For 
each unique event identified,a questionnaire (Self-Harm Follow-Up Form) which collects 
supplemental information on the self-injurious behavior is tobe completed.  The Self-Harm 
Supplement Form will be completed according to the Study Schedule (Attachment1).
10.3.3.Safety Monitoring
The Lilly clinical research physician/scientist will monitor safety data throughout the course of 
the study andwill, as appropriate, consult with the functionally independent Global Patient 
Safety therapeutic area physician or clinical research scientist.  
Lilly will review SAEs within time frames mandated by company procedures.  The Lilly clinical 
research physician/scientistwill, as is appropriate, consult with the functionally independent 
Global Patient Safety therapeutic area physician or clinical scientist and periodically review 
trends in safety data, laboratory analytes, and AEs.  
See Section 8.3.1.1for discontinuation criteria and Sections 10.3.3.1, 10.3.3.2, 10.3.3.3, and 
10.3.3.4for the monitoring of neutropenia, hypertension, hepatic monitoring, and hepatitis B 
monitoring, respectively.
Vitals signs will be monitored beforeandafter dosing as indicated in the study schedule 
(Attachment1).
10.3.3.1.Neutropenia
Patients with neutrophil counts <1500 cells/L should be managed for neutropenia as follows:
<500 cells/L(<0.50×103/µL or <0.50 GI/L), see discontinuation criteria 
(Section8.3.1.1)
≥500 cells/L and <1000 cells/L(≥0.50×103/µLand <1.00×103/µLor ≥0.50GI/L 
and <1.00 GI/L), see discontinuation criteria (Section8.3.1.1)
≥1000 cells/L and <1500 cells/L (≥1.00×103/µLand <1.50×103/µLor ≥1.00GI/L 
and <1.50 GI/L)and the patient has a concurrent infection that requires systemic 
anti-infective therapy (forexample, antibiotic, antifungal agent, antiviral agent):  
o The dose of investigational product should be withheld, the patient should receive 
appropriate medical care, and a repeat test for neutrophil count should be performed 
within 4 weeks from knowledge of the initial report.  If the repeat neutrophil count 
has returned to ≥1500 cells/L (≥1.50×103/µLor ≥1.50×103/µL)and the infection 
has resolved or is resolving, the patient may resume dosing of investigational product 
and evaluation at scheduled visits.  If the neutrophil count remains ≥1000 cells/L 
and <1500 cells/L(≥1.00×103/µLand <1.50×103/µLor ≥1.00 GI/L and 
<1.50GI/L), investigational product should continue to be withheld and a repeat 
neutrophil count should again be performed within another 4 weeks.  If, after 2 repeat 

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tests, the neutrophil count still remains ≥1000cells/L and <1500cells/L 
(≥1.00×103/µLand <1.50×103/µLor ≥1.00 GI/L and <1.50GI/L)and:
a. the infection has not fully resolved, the patient will be discontinued from the 
study.
b. the infection has resolved, the patient may resume dosing and evaluation at 
scheduled visits.  However, if resumption of dosing is not deemed appropriate by 
the investigator, the patient will be discontinued from the study.
≥1000 cells/L and <1500 cells/L(≥1.00×103/µLand <1.50×103/µLor ≥1.00 GI/L 
and <1.50 GI/L), and the patient has no concurrent infection that requires systemic 
anti-infective therapy (for example, antibiotic, antifungal agent, antiviral agent):  
o Dosing may continue, and a repeat neutrophil count should be performed 4 to 
8weeks from knowledge of the initial report.  Testing may be at a regularly 
scheduled visit or at an unscheduled visit, as necessary.
Repeat testing should be performed at 4-to 8-week intervals until the neutrophil 
count has returned to ≥1500cells/L(≥1.50×103/µL or ≥1.50GI/L).  If the patient 
has 3 or more postbaseline neutrophil counts of ≥1000cells/L(≥1.00×103/µL or 
≥1.00 GI/L)and <1500cells/L(<1.50×103/µL or <1.50 GI/L), no value of 
<1000cells/L(<1.00×103/µL or <1.00 GI/L), and no postbaseline infection 
requiring systemic anti-infective therapy, the patient may continue or resume further 
evaluation at scheduled visits, as deemed appropriate by the investigator.
If a patient without initial concurrent infection develops an infection that requires systemic 
anti-infective therapy, then the patient should bemanaged as indicated above for patients with 
concurrent infection.  Management of neutropenia during Period 4is described in Section7.1.4.
10.3.3.2.Hypertension
Patients who have changes in sitting BP—defined as systolic BP at ≥160 mm Hg plus 
≥20mmHg increase from baseline (Week 0, Visit 2) and/or diastolic BP at ≥100 mm Hg plus 
≥10 mm Hg increase from baseline (Week 0, Visit 2)—on 2consecutive visits should receive 
intervention for the management of hypertension.  Intervention could include the maximal 
intervention of withholding the dose of investigational product and/or the introduction of an 
anti-hypertensive agent.  See Section8.3.1.1for criteria for patient discontinuation related to 
hypertension.
10.3.3.3.Hepatic Monitoring
If astudy patient/subject experiences elevated ALT ≥3× ULN, ALP ≥2×ULN, or elevated total 
bilirubin >2× ULN, clinical and laboratory monitoring should be initiated by the investigator.  
Details for hepatic monitoring depend upon the severity and persistence of observed laboratory 
test abnormalities.  To ensure patient/subject safety and comply with regulatory guidance, the 
investigator is to consult with the Lilly designated medical monitor regarding collection of 
specific recommended clinical information and follow-up laboratory tests.  See Attachment3.

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10.3.3.4.Hepatitis B Monitoring
For any patient who is HBsAg–, HBcAb+, and HBsAb+ at screening, a quantitative HBsAb level 
and anHBV DNA test will be performed by the central laboratory.  A patient with an HBsAb 
level ≥200 mIU/mL and a negative serum HBV DNA test result may be enrolled in the study.  
However periodic monitoring of the patient’s HBsAb level must be performed as indicated in the 
study schedule (Attachment1).  If the patient’s HBsAb level decreases to <200mIU/mL, then a 
HBV DNA test will also be performed by the central laboratory.  If the HBV DNA test is 
negative, then the patient may remainin the study.  However, repeat testing of the patient’s 
HBsAb level and HBV DNA must be performed at 4-to 8-week intervals, as long as the HBsAb 
level is <200 mIU/mL.  If the HBsAb level increases to ≥200 mIU/mL, the site may resume 
periodic monitoring of the patient’s HBsAb as indicated in the study schedule (Attachment1).  
For any enrolled patient who is HBcAb+, regardless of HBsAb status or level, and who has ALT 
or AST levels >3 × ULN, an HBV DNA test will be performed by the central laboratory
.  The 
investigator should consult with the Lilly medical monitor regarding further management of the 
patient.  
Any enrolled patient with a positiveHBV DNA testresult at any timemust be discontinued from 
the study and should receive appropriate follow-up medical care, including consideration for 
antiviral therapy.
Study investigators should consult with a specialist physician in the care of patients with 
hepatitis (for example, infectious disease or hepatologist subspecialists) on whether to continue 
any immunosuppressanttherapy including investigational product for a period of time while 
antiviral therapy is being initiated.  Timing of withdrawal from investigational product should be 
based on recommendation of the consulting specialist physician in conjunctionwith the 
investigator andlocalor regional medical guidelines or standards of care.
Upon discontinuation from investigational product, the patient should be discontinued from the 
study.  Any patient who discontinued the study for any reason will complete the ETV before
entering the posttreatment follow-up period (Period 4).
10.3.4.Complaint Handling
Lilly collects product complaints on investigational products and drug delivery systems used in 
clinical studies toensure the safety of study participants, monitor quality, and to facilitate 
process and product improvements.
Complaints related to unblindedconcomitant drugsare reported directly to the manufacturers of 
those drugsor devices in accordance with the package insert.
For blinded studies, all product complaints associated with material packaged, labeled, and 
released by Lilly or delegate will be reported.
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:
reviewing all study drug administration logs to identify any product complaints

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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.
10.4.Sample Collection and Testing
Attachment1lists the schedule for sample collections in this study.
Attachment2lists the laboratory tests that will be performed for this study.  
10.4.1.Samples for Study Qualification and Health Monitoring 
As applicable, blood and urine samples will be collected at the time points specified in the study 
schedule (Attachment1) and after ECG, vital-sign, and clinical efficacy measurements.  
Clinical laboratory tests will be analyzed by a central laboratory unless otherwise specified.  
Protocol RHBF Clinical Laboratory Tests (Attachment2)lists the specific tests that will be 
performed for this study.
Blood will be drawn at the visits specified in the study schedule (Attachment1)for routine safety 
laboratories including clinical chemistry, hematology, TSH, T4, coagulation panel, and lipid 
panel in amounts ranging from 5 mL to 50 mL, depending on the visit.  Additional blood 
samples may be drawn if needed for safety purposes and/or if warranted and agreed upon 
between the investigator and Lilly or its designee.  An additional 10 mL (approximate) of blood 
may be drawn at screening for viral serologies.
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.

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10.4.2.Samples for Biomarker Research
Pharmacogenetic Evaluations:
There is growing evidence that genetic variation may affect a patient’s response to therapy.  
Variable response to therapy may be caused bygenetic determinants that affect drug absorption, 
distribution, metabolism, and excretion;the mechanism of action of the drug;the disease 
etiology;and/or the molecular subtype of the disease being treated.  Therefore, where local 
regulations and ERBs allow, blood samples (approximately 10mL) will be collected for 
pharmacogenetic and epigenetic analyses, as noted in the study schedule (Attachment1).  
Samples will be stored,and DNA and RNA analyses may be performed on genetic variants 
thought to play a role in PsA including but not limited to HLA-C, IL-2, IL-21, IL-12B, IL-13,
TNFAIP3, TNIP1, TRAF3IP2, NFKB1A, LCE3 locus, NOS2, and FBXL19; the IL-17 and 
IL-23 family, receptors,and signaling pathways; MTX metabolizing genes such as methylene 
tetrahydrofolate reductase;and other folate reductases to evaluate their association with observed 
response to ixekizumab.
In the event of an unexpected AE or the observation of unusual response, the pharmacogenetic 
samples may be genotyped and analyses may be performed to evaluate a genetic association with 
response to ixekizumab.  These investigations may be limited to a focused candidate gene study 
or, if appropriate, genome-wide analysismay be performed to identify regions of the genome 
associated with the variability observed in drug response.  The pharmacogenetic samples will be 
used for only investigations related to disease and drug or class of drugs under study in the 
context of this clinical program.  They will not be used for broad exploratory unspecified disease 
or population genetic analyses.
The samples will be coded with the patient number and stored for up to a maximum 15years 
after the last patient visit for the study at a facility selected by the sponsor.  The samples and any 
data generated from them can only be linked back to thepatient by investigator site personnel.  
The duration allows the sponsor to respond to regulatory requests related to the investigational 
product.
Samples will be destroyed according to a process consistent with local regulation.
Nonpharmacogenetic/Biomarker Evaluation:
Samples will be collected for potential nonpharmacogenetic biomarker research where local
regulations allow.  Serum, plasma, and whole blood RNA samples will be collected at thetimes 
specified in the study schedule(Attachment1).
It is increasingly recognized that in addition to the ability of germline DNA sequence to
influence disease susceptibility, so called epigenetic modification of DNA may also have
influence on disease susceptibility and disease phenotype. These modifications include DNA
methylation, histone modification, and other modifications of less defined significance. To be
able to investigate the potential of epigenetic changes on drug response, we plan to collect
1DNA sample at baseline and 1 additional DNA sample aftertreatment with ixekizumab.  

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Therefore, to be able to test for epigenetic changes, 2 DNA samples will be collected during this
study.
Samples may be used for research on the drug target, disease process, pathways associated with
PsA, mechanism of action of ixekizumab, and/or research method or in validating diagnostic
tools or assay(s) related to PsA.
Samples will be identified by the patient number (coded) and stored for up to a maximum of
15years after the last patient visit for the study at a facility selected by the sponsor.
Samples will be destroyed according to a process consistent with local regulations.
10.4.3.Samples for Immunogenicity Research
Blood samples for immunogenicity testing will be collected to determine antibody production 
against the investigational product.See Section 10.3.2.5for further details.
10.4.4.Samples for Drug Concentration Measurements
As described in Section 10.3.2.5, an aliquot for every immunogenicity sample will be used to 
determine ixekizumab serum concentrationby a validated enzyme-linked immunosorbent assay. 
It is expected that the obtained PK samples will allow sufficient description of ixekizumab PK 
profiles at steady state through the study. The actual date and exact timing (24-hour clocktime) 
of each sample collected will be recorded on the laboratory
 requisition.
Bioanalytical samples collected to measure investigational product concentration will be retained 
for a maximum of 1 year afterlast patient visit for the study.  
10.5.Appropriateness of Measurements
In general, the clinical and safety assessments in this study are standard, widely used, and 
generally recognized as reliable, accurate, and relevant.  Blood inflammatory/immunologic 
molecules will provide information on safety and PD.

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11. 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 use standard computer edits to detect errors in data 
collection
conduct a quality review of the database
In addition, Lilly or its representatives willperiodically check a sample of the patient data 
recorded against source documents at the study site.  The study may be audited by Lilly or its 
representatives and/or regulatory agencies at any time.  Investigators will be given notice before 
an audit occurs.
To ensure the safety of participants in the study, and to ensure accurate, complete, and reliable 
data, the investigator will keep records of laboratory tests, clinical notes, andpatient medical 
records in thepatient files as original source documents for the study.  If requested, the 
investigator will provide the sponsor, applicable regulatory agencies, and applicable ERBs with 
direct access to original source documents.
11.1.Data Capture System
All data entry and data management processes and procedures for this study will be documented 
within a Data Management Plan.
An electronic data capture system will be used in this study.  The site maintains a separate source 
for the data entered by the site personnelinto the sponsor-provided or designee-provided 
electronic data capture system.
Any data for which paper documentation provided by the patient will serve as the source 
document will be identified and documented by each site in that site’s study file.  Paper 
documentation provided by the patient may include, for example, a paper study drug 
administration logto collect the date, time, and anatomical location of administration of 
investigational product (for treatment compliance), syringe number, who administered the 
investigational product, and the reason if investigational product was not fully administered.  
These data will also be entered electronically by study site personnel.
Data managed by a central vendor, such as laboratory test data, will be stored electronically in 
the central vendor’s database system.  Data will subsequently be transferred from the central 
vendor to the Lilly generic labs system.

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Case report form data collected by the TPO will be encoded by the TPO and stored electronically 
in the TPO’s database system.  Validated data will subsequently be transferred to Lilly’s data 
warehouse, using standard Lilly file-transfer processes.  Electronic patient-reported outcome
measures (for example, a rating scale) or other data reported directly by the subject (for example, 
VAS, health outcome questionnaires) are entered into an ePRO instrument (a hand-held tablet)at 
the time that the information is obtained.  In these instances for which there is no prior written or 
electronic source data at the site, the ePRO instrument record will serve as the source.
If ePRO records are stored at a third-partysite, investigator sites will have continuous access to 
the source documents during the study and will receive an archival copy at the end of the study 
for retention.
Any data for which the ePRO instrument record will serve to collect source data will be 
identified and documented by each site in that site’s study file.
Data from complaint forms submitted to Lilly will be encoded and stored in the global product 
complaint management system.

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12. Sample Size and Statistical Methods
12.1.Determination of Sample Size
Approximately 400 patients will enter the initial open-label treatment period.  It is expected that 
approximately 34% of the patients will meet the randomization criteria for the randomized 
double-blind withdrawal period. Approximately 136patients will be randomized in a 1:1 ratio 
into ixekizumab 80 mg Q2W and placebo treatment groups (68patients per treatment group).  
This assumption is based on the Study RHAPWeek 24 results and estimating the number of 
patients achieving Coates criteriafor MDA for 3consecutivemonths over 4consecutivevisits of 
meeting MDA.  
It is assumedthat approximately 60% and 20% of patientsin the placebo and ixekizumab groups, 
respectively,who enter the randomized double-blind withdrawal period will relapse (nolonger 
meet Coates criteriafor MDA). According tothese assumptions, a total of 39 patients must meet 
relapse criteria in the combined treatment groups to achieve 95% power to test the superiority of 
ixekizumab 80 mg Q2Wto placebo for time to relapseat a 2-sided 0.05 significance level. 
The dropoutrate beforerelapse for patients randomized in the randomized double-blind 
withdrawal periodis assumed to be 10%.  Sample size and power calculationswere calculated 
using nQuery+nTerim 3.0.
Randomization and relapse rates will be monitored to assess whetherthe number of patients who 
enter the initial open-label treatment period should be increasedto ensure sufficient sample size 
and power for the randomized withdrawal period.
12.2.Statistical and Analytical Plans
12.2.1.General Considerations
Statistical analysis of this study will be the responsibility of Lilly or its designee.
Continuous data will be summarized in terms of the number of observations (n); mean; standard 
deviation and/or standard error of the mean, if applicable; median; minimum; and maximum.
Categorical data will be summarized in terms of the number of observations (n), frequency 
count, and percentages. 
Investigatorcenters will be pooled by geographical region for statistical analysis purposes.
All tests of treatment effectswill be conducted at a2-sided level of 0.05unless otherwise 
stated.
Any change to the data analysis methods described in the protocol will require an amendment 
ONLY if it changes a principal feature of the protocol.  Any other change to the data analysis 
methods described in the protocol, and the justification for making the change, will be described 
in the clinical study report.  Additional exploratory analyses of the data will be conducted as 
deemed appropriate.  Complete details of the planned analyses will be documented in the SAP.

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12.2.1.1.General Considerations for Analyses during Period 2(Initial Open-Label 
Treatment Period)
Efficacy, health outcomes, and safety data collected in Period 2will be summarized for 
ixekizumab 80 mg Q2W without inferential statistics.  For efficacy, health outcomes,and safety 
analyses, baseline is defined as the last available value before the first dose of study medication 
in Period 2and in most cases will be the value recorded at Week 0 (Visit 2). For analysis 
purposes, the endpoint for Period 2will be defined as the visit of randomization or Week 64 for 
patients who do not meet the randomization criteria.
Kaplan-Meir estimates will be used to estimate the survival curve for time-to variables.  
12.2.1.2.General Considerations for Analyses during Period 3(Randomized 
Double-Blind Withdrawal Period)
For patients who are randomizedin Period 3, all efficacy, health outcomes,and safety data 
collectedbetween randomizationand either through relapse (no longermeetingCoates criteria
for MDA) or through the end of Period 3will be compared between the ixekizumab 80 mg Q2W 
and placebo treatment groups.  For the efficacy analysis, baseline is defined as the last available 
value before the first dose of study medication in Period 2and in most cases will be the value 
recorded at Week 0 (Visit 2). For the safety analysis,baseline is defined as the last available 
value beforethefirst dose of study treatmentin Period 3.
The Kaplan-Meier product limit method will be used to estimate the survival curves for time-to 
variablesfor the patients who are randomized to the randomized double-blind withdrawal period. 
Treatment comparisons will be performed using a log-rank test with treatment,geographic 
region, and cDMARD use (past use, current use), at the time of randomization in Period 3,in the 
model.
The primary analysis ofthe categorical efficacy and health outcome variables will usea logistic 
regression with treatment,geographic region, and cDMARD use (past use, current use), at the 
time of randomization in Period 3,in the model.  Secondary analysis ofthe categorical efficacy 
and health outcome variables will be conducted using the Fisher’s exact test.  
The analysis for all continuous efficacy and health outcome variables, change from baseline to 
endpoint analysis,will be made using analysis of covariance with treatment, baseline value, 
geographic region, and cDMARD use(past use, current use), at the time of randomization in 
Period 3,in the model.  Missing data will be imputed using modified baseline observation 
carried forward (mBOCF).  Type III sums of squares for the least-squares means will be used for 
the statistical comparison; the 95% CI will also be reported.
The Fisher
's exact test will be used for all AE, baseline, discontinuation, and other categorical 
data.  AEdata will be analyzed using exposure-adjusted incidence rates.  Continuous vital sign 
and laboratory values will be analyzed by an analysis of covariance model with treatment and 
baseline value as independent variables.  Other continuous variableswill be analyzed by t-tests 
unless otherwise stated.
For patients who randomize and subsequentlyrelapse in Period 3, efficacy, health outcomes, and 
safety data collected between relapse and the end of Period 3will be summarized for ixekizumab 

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80 mg Q2W without inferential statistics.  For the efficacy and health outcomes analyses, 
baseline is defined as the last available value before the first dose of study medication in Period 2
and in most cases will be the value recorded at Week 0 (Visit 2).  For the safety analysis,
baseline is defined as the last available value before relapse in Period 3.
12.2.1.3.General Considerations for Analyses during Periods 2 and 3 Combined 
(Initial Open-Label Treatment and Randomized Double-Blind Withdrawal 
Periods)
For patients who are randomizedin Period 3, efficacy, health outcomes, and safety data collected 
in Periods 2 and 3 combined will be summarized for ixekizumab 80 mg Q2W without inferential 
statistics.  For efficacy, health outcomes,and safety analyses, baseline is defined as the last 
available value before the first dose of study medication in Period 2and in most cases will be the 
value recorded at Week 0 (Visit 2).  
For patients who arenot randomizedin Period 3, efficacy, health outcomes,and safety data 
collected in Periods 2 and 3 combined will be summarized for ixekizumab 80 mg Q2W without 
inferential statistics.  For efficacy, health outcomes,and safety analyses, baseline is defined as 
the last available value before the firstdose of study medication in Period 2and in most cases 
will be the value recorded at Week 0 (Visit 2).  
12.2.1.4.Analysis Populations
Unless otherwise specified, efficacy, health outcomes, and safety summariesfor Period 2(initial 
open-label treatment period) will be conducted on the initial open-label treatment period
population, defined as all patientswho receive at least 1 dose ofixekizumab 80 mg Q2Win 
Period 2.
Efficacyand health outcomes analyses for Period 3(randomized double-blind withdrawal 
period) will be conducted ontherandomized withdrawalintent-to-treat (ITT) population, 
defined as all randomized patients, even if the patient does not receive the correct treatment or 
otherwise does not follow the protocol.  Patients will be analyzed according to the treatment to 
which they were assigned.
Safety analyses for Period 3will be conducted on therandomized withdrawal safety 
population, defined as all randomized patients who received at least 1 dose of study treatment 
after randomization.  Patients will be analyzed according to the treatment to which they were 
assigned.
Efficacy, health outcomes, and safety summaries for combined Periods 2 and3 will be conducted 
on the nonrandomized population, defined as all patients who were not randomizedand who 
receivedat least 1 dose of ixekizumab 80 mg Q2W.
Efficacy, health outcomes, and safety summaries will be conducted on the relapse population, 
defined as all randomized patients who relapsed(no longer met Coates criteriafor MDA) after 
randomization and who received at least 1 dose of ixekizumab 80 mg Q2W after relapse.
Safety analyses for Period 4(posttreatment follow-up period)will be conducted on the follow-up 
period population, defined as all patients who receive at least 1dose of study treatment at any 

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time during Periods2and 3and have entered the posttreatment follow-up period. Patients will 
be analyzed according to the treatment they were taking beforeentering Period 4.
12.2.1.5.Missing Data Imputation
12.2.1.5.1.Nonresponder Imputation for Clinical Response 
Patients will be considered a nonresponder for the nonresponder imputation (NRI) analysis if 
they do not meet the clinical response criteria atany specified analysis time point. All 
nonrespondersat anyspecified time point as well as all patients who discontinue study treatment 
beforethe specified analysis time point,for any reason, will be defined as a nonresponder for the 
NRI analysis. Patients without at least 1 observation on study treatment will also be defined as a 
nonresponder for theNRI analysis.
12.2.1.5.2.Modified Baseline Observation Carried Forward
AnmBOCF analysis will be performed on all continuous efficacy and health outcome variables.  
In this approach,the baseline observation will be carried forward to the corresponding endpoint 
for evaluation for patients who discontinuestudy treatment due to an AE.  Thelast nonmissing 
observation before discontinuation of study treatment will be carried forward to the 
corresponding primary endpoint for evaluationfor patients who discontinue studytreatment for 
any reason other than due to an AE.  Patients without at least 1postbaseline observation will not 
be included for evaluation,with the exception of patients who discontinue study treatment due to 
an AE.
12.2.1.6.Adjustment for Multiple Comparisons
There will be no adjustment for multiple comparisons in this study.
12.2.2.Patient 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.
Patient disposition will be summarized for each treatment period.  Reasons for discontinuation 
from the study will be summarized.  The reasons for discontinuation during Period 3will be 
tested between treatment groups using Fisher’s exacttestfor the randomized withdrawalITT 
population.
12.2.3.Patient Characteristics
Patient characteristics and baseline clinical measureswill be summarized for each treatment 
period.  Baseline characteristics will include gender, age, age category, weight, race, geographic 
region, baseline disease severity, duration of disease, disease diagnosis, previous cDMARDs, 
and subtypes of PsA.  Baseline clinical measurements may include Coates criteriafor MDA 
components, ACR components, sPGA score, PASI total score, BSA, Psoriatic Arthritis Response 
Criteria, DAS28-CRP, Joint Pain VAS, Physician’s or Patient’sGlobal Assessment of Disease 
Activity VAS, HAQ-DI, SPARCC, CPDAI, Itch NRS score, DLQI total score, LDI-B, SF-36, 
Fatigue Severity NRS.

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Treatment group comparisons between ixekizumab 80 mg Q2Wand placebo in Period 3will be 
conducted using Fisher’s exact test for categorical data and a 1-way analysis of variance for 
continuous datafor the randomized withdrawal ITT population.
12.2.4.Concomitant Therapy
Previous and concomitant medications will be summarized for patients who enter each treatment 
period and presented by WHO Anatomic Therapeutic Class Level1 and generic name.  
Treatment group comparisons between ixekizumab 80 mg Q2Wand placebo in Period 3will be 
conducted using Fisher’s exact testfor the randomized withdrawalITT population.
12.2.5.Treatment Compliance
Treatment compliance with investigational product will be summarized for each treatment 
period.  Patient compliance with investigational product will be assessed at each visit.  A patient 
will be considered overall compliant for each study period if he/sheis missing no more than 20% 
of the expected doses and not missing 2consecutive doses.  Proportions of patients compliant by 
visit and overall compliance will be compared between treatment groups for Period 3using 
Fisher’s exact testfor the randomized withdrawal ITT population.  
12.2.6.Efficacy and Health Outcome Analyses
12.2.6.1.Primary Analyses
The primary analysis is the time-torelapse (no longer meetingCoates criteria for MDA) for the 
randomized withdrawal ITT population.  Time-torelapse will be calculated in weeksasfollows:
(
 
 
 
 
− 
 
 
 
 
 
 
 
 
 
 
  
 
 3)+1
7
If the date of first dose is missing, the date of randomization will be used.  Patients completing 
Period 3will be censored at the date of completion (that is, the date of the last scheduled visit in 
the period).  Patients without a date of completion or discontinuation for Period 3will be 
censored at the latest nonmissing date out of the following dates:date of last dose and date of 
last attended visit in Period 3(scheduledor unscheduled).  
Treatment comparison between ixekizumab 80mg Q2W and placebo in time-torelapse for the 
randomized withdrawal ITTpopulation will be analyzed using a log-rank test with treatment,
geographic region, and cDMARD use (past use, current use), at the time of randomization in 
Period 3,in the model. The Kaplan-Meier product limit method will be used to estimate the 
survival curves for time-to relapse.Time-torelapse will also be summarized graphically by 
treatment group using Kaplan-Meier techniques.
12.2.6.2.Secondary Analyses
The secondary efficacy and health outcomes analyses for Period 2will be based on the initial 
open-label treatment periodpopulation.  The secondary efficacy and health outcomes analyses 
for Period 3will be based on either the randomized withdrawal ITTpopulation or the relapse 
population, as specified below.  Additional efficacy and health outcome analyses for combined 

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Periods2 and 3 analyseswill be based on both the randomized withdrawal ITT population and 
the nonrandomized population.
12.2.6.2.1.Initial Open-Label Treatment Period (Period 2)
Time to achieve Coates criteriafor MDA and time to achieve Coates criteriafor MDA for 
3consecutive months over 4consecutive visitsduring the initial open-label treatment period
(Period 2) will be summarized.  The summarizationswill include Kaplan-Meier estimates for the 
probabilityof achieving Coates criteriafor MDA and achieving Coatescriteriafor MDA for 
3consecutive months over 4consecutive visits. The Kaplan-Meier product limit method will be 
used to estimate the survival curve for time-to to achieve Coates criteriafor MDA for 
3consecutive months over 4consecutive visits.
12.2.6.2.2.RandomizedDouble-BlindWithdrawal Period (Period 3)
Treatment comparisonsbetween ixekizumab 80mg Q2W and placebo in proportion of patients 
who relapse will be analyzed using a logistic regression with treatment, geographic region, and 
cDMARD usein the modeland a Fisher’s exact testfor the randomized withdrawal ITT 
population.  Missing data will be imputed using the NRI method.
Time to loss of responsefor each of the belowindividual components (in weeks) of the Coates 
criteriafor MDA will be calculated and treatment comparisons will be conducted using the same 
methods as described for the primary analysis (see Section 12.2.6.1)for randomized withdrawal 
ITT populationpatients who meet the individual component criteria at the time of 
randomization:  
TJC≤1
SJC≤1
PASI total score ≤1 or BSA ≤3
sPGA (0,1) or BSA ≤3
pain VAS score of ≤15
global disease activity scale VAS score ≤20
HAQ-DI score ≤0.5
tender entheseal points ≤1
12.2.6.2.3.Combined Initial Treatment and Randomized Double-Blind Withdrawal 
Periods (Periods 2 and 3)
The HAQ-DI score will be summarized for the ixekizumab 80 mg Q2W treatment group at each 
visit and endpoint (mBOCF)during the combined Periods2 and 3 forthe randomized 
withdrawal ITT and the nonrandomized withdrawal populations.  Summarizations will include 
observed scores, change from baseline, percentageimprovement, and response rates≥0.35.
12.2.6.3.ExploratoryEfficacy Analyses
Analyses will be conducted for the exploratory efficacy objectives as defined in Section 6.3.  
Complete details will be described in the SAP.

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12.2.7.Pharmacokinetic/Pharmacodynamic Analyses 
Observed ixekizumab serum concentrations will be summarized by visits and corresponding time 
when sampling occurred.
As appropriate, exposure-response relationship will be investigated between ixekizumab 
exposure and clinically important efficacy and PD measures (for example, proportion of patients 
achieving Coates criteriafor MDAfor 4 consecutive visitsand the maintenance of treatment 
effects) specified in study objectives. In addition, the relationship between the time course of 
ixekizumab exposure and the time course of the efficacy and PD measures may be explored 
using graphical methods and a modeling approach. Covariates such as body weight, disease 
duration, baseline value, and so on, will be investigated to assess their impact on the PD 
parameters.  Model evaluation will include using sensitivity analysis and visual predictive check.  
Ifa trend or statistically significant difference between the ixekizumab cohort and the placebo 
cohortis noted in any safety endpoint, thisendpoint will also be explored to investigate 
exposure-response relationships.
The potential impact of immunogenicity on ixekizumab exposure and/or PD responses will be 
evaluated, as appropriate, by graphical assessments to compare drug exposure or PD responses 
between immunogenicity-negative and immunogenicity-positive patients at correspondent visits 
or before and after immunogenicitydevelopment for patients whose immunogenicity was 
detected. In addition, the effect of immunogenicity may be evaluated in the population PK/PD 
modeling analyses where immunogenicity will be evaluated as a covariate. 
12.2.8.Safety Analyses
Safety will be assessed by summarizing and analyzing SAEs, AEs, AESIs, vital signs, other 
measures of cardiovascular function, C-SSRS, laboratory evaluations (including chemistry, 
calculated creatinine clearance, hematology [including WBC count and differential], urinalysis 
[dipstick and microscopic], thyroid-stimulating hormoneand free T4, and immunogenicity 
testing [treatment-emergent antidrug antibodies (TE-ADAs)]). Primary safety analyses will 
focus on comparison of ixekizumab 80 mg Q2W to placebo for the randomized withdrawal 
safetypopulation in Period 3.  Treatment group comparisons will be analyzed using the methods 
described in Section 12.2.1.2.
For thePeriod 2and the combined Periods 2 and 3, the same safety variables as in Period 3will 
be summarized as described in Sections 12.2.1.1and 12.2.1.3,respectively.
Summaries of safety data collected during the Period 4(posttreatment follow-up period)will be 
presented separately.  
12.2.8.1.Adverse Events
AEsare considered TEAEs if they first occur or worsen afterthe start of treatment during a study 
period. In the case of a missing onset date for an AE, an AE with a start date equal to or greater 
than the dosing date will be considered a TEAE. For each TEAE, the severity is recorded 

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according to the patient’s or physician’s perceived severity of the event (mild, moderate, or 
severe).
TEAEs, SAEs including deaths, AEs that led to investigational product discontinuation, and AEs 
by maximum severity and relationship to investigational product will be summarized by the 
Medical Dictionary for Regulatory Activities(MedDRA) system organ class and preferred term.
TEAEs will also be summarized by preferred termsorted by decreasing frequency within system 
organ classfor all TEAEs, TEAEs by maximum severity, and TEAEs considered possibly 
related to study drug. For events that are gender specific, the denominator and computation of 
the percentage will include only patients from the given gender. MedDRA groupings of 
preferred termswill be used to investigate AESIs.
AESIs will also be presented by severity. AESIswill include cytopenias, liver function test 
changes/enzyme elevations, infections, injection-site reactions, allergic/hypersensitivity 
reactions, cerebrocardiovascular events, malignancies, depression, Crohn’s disease and 
ulcerative colitis, and Pneumocystis pneumoniaand interstitial lung disease.  
12.2.8.2.Clinical Laboratory Tests
Laboratory assessments will be presented as mean changes from baseline, change from baseline 
to minimum postbaseline value, change from baseline to maximum postbaseline value and as 
incidence of treatment-emergent abnormal, high, or low laboratory values.Shift tables will be 
presented for selected parameters.
Treatment-emergent abnormal value = a change from normal at all baseline visits to 
abnormal at any time postbaseline
Treatment-emergent high value = a change from a value less than or equal to the high 
limit at all baseline visits to a value greater than the high limit at any time postbaseline
Treatment-emergent low value = a change from a value greater than or equal to the low 
limit at all baseline visits to a value less than the low limit at any time postbaseline
12.2.8.3.Vital Signs,Physical Findings, and Other Safety Evaluations
Vital signs will be presented as mean changes from baseline and as incidence of abnormal values 
(as defined in the SAP) and will be summarized both beforeand after dosing, as applicable.
The analyses of TE-ADA effects will be conducted on all evaluable patients within the defined 
safety population. Evaluable patients will be identified as positive, negative, or inconclusive for 
TE-ADA (as defined in the SAP). The frequency and percentage (incidence) of patients with 
positive, negative, or inconclusive TE-ADA and neutralizing anti-drug antibodyat baseline and 
postbaseline will be summarized by treatment group. Patients who are TE-ADA positive 
(persistent positive or transient positive), TE-ADA persistent positive, and TE-ADA transient 
positive will also be summarized.
Suicide-related thoughts and behaviors and self-injurious behavior with no suicidal intent, based 
on the C-SSRS, will be listed by patient.
Other data, including body weight,will be descriptively summarized by treatment groups. 
Further analyses may be performed comparing the treatment groups.

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12.2.9.Subgroup Analyses
Subgroup analyses will be conducted for time to relapse and the proportion of patients who 
relapse for the randomized withdrawal ITT population.
Subgroups to be evaluated may include variables such as gender, age category, race, geographic 
region, and cDMARDstherapyat the time of randomization in Period 3.  Additional subgroups 
may be described in theSAP.
The Kaplan-Meier product limit method will be used to estimate the survival curves for time to 
relapse.  Analyses will be performed using a log-rank test with treatment, subgroup, and the 
interaction of treatment-by-subgroup included as factors in the model.  
Forthe proportion of patients who relapse, a logistic regression model with treatment, subgroup, 
and the interaction of treatment-by-subgroup included as factors will be used.  Missing data will 
be imputed using NRI as described in Section12.2.1.5.1.  
The subgroup-by-treatment interactionswill be tested at the significance level of 0.10.  
Treatment group differences will be evaluated within each category of the subgroup, regardless 
of whether the interaction is statistically significant.  
Detailed description of the subgroup variables and detailed analysis methodology will be defined 
in the SAP.  Additional subgroup analyses may be performed as deemed necessary.
12.2.10. 
Interim Analyses
The study will have approximately 2 interim and 1 final database locks. The first interim
database lock mayoccur once all patients completeor discontinue inthe initial open-label 
treatment period; only data from the initial open-label treatment periodwill be summarized. For 
analysis purposes, the end of the initial open-label treatment period will be defined as the visit of 
randomization or Week64 for patients who do not meet the randomization criteria.The second 
interimdatabase lockmayoccur when all patients complete Week104or discontinue study 
treatment prior to the end of the randomized double-blind withdrawal period.The final database 
lock will occur when all patientscomplete or discontinue the study.  However, the second 
interim may not be performed depending upon the timing of the final database lock once all 
patients complete the post-treatment follow up period.  Analysesfor these interim analyses will 
be specified in the SAP along with the unblinding plan.Additional analyses andsnapshots of 
study data may be performed to fulfill the need for regulatory interaction or publication purposes.
Information that may unblind the study during the analyses will not be reported to study sites or 
the blinded study team until the study has been unblinded.  All investigators and patients will 
remain blinded to treatment assignments until the last patient completes the randomized 
double-blind withdrawal periodand the finaldatabaselock occurs.

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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 anyquestions thepatient 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 risksand 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 risks and benefits of participating in the 
study and desires to participate in the study.
The investigator is responsible for ensuring that informed consent is given by each patient or 
legal representative.  This includes obtaining the appropriate signatures and dates on the ICF 
beforethe performance of any protocol procedures and beforethe administration of 
investigational product.
As used in this protocol, the term “informed consent” includes all consent and assent given by 
patients or their legal representatives.
13.2.Ethical Review
Lilly or its representatives must approveall ICFsbefore theyare submitted to the ERB andare 
used at investigative sites.  All ICFs must be compliant with theICH guideline on GCP.
The investigator must give assurance that the ERB was properly constituted and convened as 
required by ICH guidelines and other applicable laws and regulations.
Documentation of ERB approval of the protocol and the ICF must be provided to Lillybefore the 
study may begin at the investigative sites.  The ERBs will review the protocol as required.
The study site’s ERBs should be provided with the following:
the current IBand 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 CouncilforInternationalOrganizationsofMedicalSciences
International Ethical Guidelines
2) the ICH GCP Guideline [E6]
3) applicable laws and regulations

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The investigator or designee will promptly submit the protocol to applicable ERBs.
All investigators are expected to comply with GCP and all applicable local clinical trial 
regulations.
Some of the obligations of the sponsor will be assigned to a TPO.
Anidentification code assigned by the investigator 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.Protocol Signatures
The sponsor’s responsible medical officerwill 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 pageand 
send a copy of the signed page to a Lilly representative.
13.3.2.Final Report Signature
The clinical study report coordinating investigator will sign the final 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 clinical study report coordinating investigator will be selected by the sponsor.  If this 
investigator is unable to fulfill this function, another investigator will be chosen by Lilly to serve 
as the clinical study report coordinating investigator.
The sponsor’s responsible medical officerand statistician will 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
Antoni C, Krueger GG, de Vlam K, Birbara C, Beutler A, Guzzo C, Zhou B, Dooley LT, 
Kavanaugh A. IMPACT 2 Investigators. Infliximab improves signs and symptoms of psoriatic 
arthritis: results of the IMPACT 2 trial. Ann Rheum Dis.2005a;64(8):1150–1157.
Antoni CE, Kavanaugh A, Kirkham B Tutuncu Z, Burmester GR, Schneider U, Furst DE, 
Molitor J, Keystone E, Gladman D, Manger B, Wassenberg S, Weier R, Wallace DJ, Weisman 
MH, Kalden JR, Smolen J. Sustained benefits of infliximab therapy for dermatologic and 
articular manifestations of psoriatic arthritis: results from the Infliximab Multinational 
Psoriatic Arthritis Controlled Trial (IMPACT). Arthritis Rheum. 2005b;52(4):1227-1236.
[APA] American Psychiatry Association. Diagnostic and Statistical Manual of Mental
Disorders. 4th ed. Washington DC:APA;1994.
Araujo EG, Finzel S, Englbrecht M, Schreiber DA, Faustini F, Hueber A, Nas K, Rech J, 
SchettG. High incidence of disease recurrence after discontinuation of disease-modifying 
antirheumatic drug treatment in patients with psoriatic arthritis in remission. Ann Rheum Dis.
2015;74(4):655-660.
Ash Z, Gaujoux-Viala C, Gossec L, Hensor EM, FitzGerald O, Winthrop K, van der Heijde D, 
Emery P, Smolen JS, Marzo-Ortega H. A systematic literature review of drug therapies forthe 
treatment of psoriatic arthritis: current evidence and meta-analysis informing the EULAR 
recommendations for the management of psoriatic arthritis. Ann Rheum Dis. 
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Attachment1. Protocol RHBFStudySchedule

I1F-MC-RHBF(b)Clinical Protocol
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Study Schedule, Protocol I1F-MC-RHBF
Screening
(Period 1) Baseline
Initial Open-Label Treatment Perioda
Visit No.(V)
V1 
V1A 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11
Study Week (W)
W0 
W2 
W4 
W8 
W12 
W16 
W20 
W24 
W28 
W32
Study Days 
-30 to-4 2-3d 
post V1
0 
14 ± 2d 28 ± 2d 56± 4d 84 ± 4d112 ± 4d140± 4d168 ± 4d196± 4d224 ± 4d
Informed consent
X
Complete medical history 
X
Review preexisting conditions
X
Age, gender, ethnicity
X
Physical examinationb
X
X
X
PsA diagnosis 
(CASPAR criteria)
X
Inclusion/exclusion criteria
X
X
Body temperature
X
Height
X
Weight
X
X
X
X
X
Sitting blood pressure and pulse
X
Xc
X  
X  
X  
X  
X  
X  
X  
X  
X
Habits (tobacco, alcohol, caffeine use)
X
X
TB risk factors
X
Concomitant medications
X
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Review adverse events
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Administer IPd
Xd
Open-label IP Q2W
Dispense IP
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Dispense study drug administration log 
Completestudy drug administration logimmediately after each IP administration.
IP compliance
e
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
TJC/SJC entry to IWRS
f
X
X  
X  
X
MDA entry to IWRS
X  
X  
X
Patient Global Assmt Disease Activity VAS
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Physician Global Assmt Disease Activity 
VAS
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Patient’s Assessment of Pain VAS
X  
X  
X  
X  
X  
X  
X  
X  
X  
X

I1F-MC-RHBF(b)Clinical Protocol
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Screening
(Period 1) Baseline
Initial Open-Label Treatment Perioda
Visit No.(V)
V1 
V1A 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11
Study Week (W)
W0 
W2 
W4 
W8 
W12 
W16 
W20 
W24 
W28 
W32
Study Days 
-30 to-4 2-3d 
post V1
0 
14 ± 2d 28 ± 2d 56± 4d 84 ± 4d112 ± 4d140± 4d168 ± 4d196± 4d224 ± 4d
TJC/SJC (68/66joints)
X
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
HAQ-DI
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Enthesitis assessment (SPARCC and LEI)
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
LDI-B
X
X  
X
X  
X  
X
PASI
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
% BSA
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
sPGA
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Itch NRS
X
X  
X  
X  
X  
X  
X  
X  
X  
X
Fatigue Severity NRS
X  
X  
X  
X  
X  
X  
X  
X  
X
SF-36 v2 acute
X
X
X  
X
X  
X
QIDS-SR16
X
X
X
X
X
EQ-5D 5L
X
X  
X  
X  
X
X  
X
WPAI-SHP 
X
X
X  
X
X  
X
DLQI
X  
X  
X
X  
X
X
C-SSRSr
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Self-Harm Supplement Formr
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Administer TB test
X
Read PPD (if applicable)g
X
Chest radiography
Xh
ECGi
X
FSH
Xj
HIV/HCV
X
HBVk,l
X
X
Serum pregnancy test
m
X
Urine pregnancy test
m
X
X  
X  
X  
X  
X  
X  
X  
X
Serum chemistry
X
X
X
X
X
Lipase/total amylase
X

I1F-MC-RHBF(b)Clinical Protocol
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Screening
(Period 1) Baseline
Initial Open-Label Treatment Perioda
Visit No.(V)
V1 
V1A 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11
Study Week (W)
W0 
W2 
W4 
W8 
W12 
W16 
W20 
W24 
W28 
W32
Study Days 
-30 to-4 2-3d 
post V1
0 
14 ± 2d 28 ± 2d 56± 4d 84 ± 4d112 ± 4d140± 4d168 ± 4d196± 4d224 ± 4d
Lipid panel (fasting)
X
X
X
X
X
Advanced lipid profile
X
X
Hematology
X
X
X
X
X
PTT and PT
X
TSH and free T4
X
Urinalysis
X
X
X
X
IgA, IgG, IgM
X
X
X
X
RF
X
anti-CCP Ab(ACPA)
X
hs-CRP
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Lymphocyte subset (B, T, CD4+ T, CD8+ 
T, and NK)
X
X
X
X
X
Exploratory storage samples (serum, plasma 
and RNA)
X
X
X
X
Exploratory storage samples (DNAfor 
pharmacogenetics)
X
Exploratory storage samples (DNA for 
epigenetics)
X
X
Immunogenicity testing
n
X
X
X
X
PKo
X
X
X
X

I1F-MC-RHBF(b)Clinical Protocol
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LY2439821
RandomizedDouble-Blind Withdrawal Perioda
Visit No.(V)
V12 
V13 
V14 
V15 
V16 
V17 
V18 
V19 
V20 
V21 
V22
Study Week (W)
W36 
W40 
W44 
W48 
W52 
W56 
W60 
W64 
W68 
W72 
W76
Study Days 
252 ± 4d 280 ± 4d 308 ± 4d 336 ± 4d 364 ± 4d 392 ± 4d 420 ± 4d 448 ± 4d 476 ± 4d 504 ± 4d 532 ± 4d
Physical examinationb
X
X
Weight
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Sitting blood pressure and 
pulse
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Habits (tobacco, alcohol, 
caffeine use)
X
Concomitant medications 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Review adverse events 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Administer IPd
Blinded IP Q2W per randomization schedule
Dispense IP
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
Dispense study drug 
administration log
Complete study drug administration log immediately after each IP administration.
IP compliancee
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
TJC/SJC entry to IWRSf
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
MDA entry to IWRS
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Patient Global Assmt Disease 
Activity VAS
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Physician Global Assmt 
Disease Activity VAS
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Patient’s Assessment of Pain 
VAS
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
TJC/SJC (68/66joints) 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
HAQ-DI
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Enthesitis assessment 
(SPARCC and LEI)
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
LDI-B
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
PASI
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
%BSA
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X

I1F-MC-RHBF(b)Clinical Protocol
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LY2439821
RandomizedDouble-Blind Withdrawal Perioda
Visit No.(V)
V12 
V13 
V14 
V15 
V16 
V17 
V18 
V19 
V20 
V21 
V22
Study Week (W)
W36 
W40 
W44 
W48 
W52 
W56 
W60 
W64 
W68 
W72 
W76
Study Days 
252 ± 4d 280 ± 4d 308 ± 4d 336 ± 4d 364 ± 4d 392 ± 4d 420 ± 4d 448 ± 4d 476 ± 4d 504 ± 4d 532 ± 4d
sPGA
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Itch NRS
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Fatigue Severity NRS
X
X
X
X
X
X
SF-36 v2 acute
X
X
X
X
X
X
QIDS-SR16
X
X
X
X
EQ-5D 5L
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
WPAI-SHP
X
X
X
X
X
X
DLQI
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
C-SSRSp
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Self-Harm Supplement 
Formp
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
HBVk,l
X
Urine pregnancy test
m
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Serum chemistry
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Lipid panel (fasting)
X
X
Advanced lipid profile
X
X
Hematology
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Urinalysis
X
X
IgA, IgG, IgM
X
X
hs-CRP
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Lymphocyte subset (B, T, 
CD4+ T, CD8+ T, and NK) 
X
X
Exploratory storage samples 
(serum, plasma, RNA)
X
X
Immunogenicity testing
n
X
X
X
PKo
X
X
X

I1F-MC-RHBF(b)Clinical Protocol
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Randomized Double-Blind Withdrawal Perioda
Early
Termination
Posttreatment 
Follow-Up Period 
(Period4)q
Visit No.(V)
V23
V24
V25 
V26
V27 V28 
V29 
ET 
V801 V802 V803
Study Week (W)
W80
W84
W88 
W92 W96 W100 
W104
LV + 
4W
V801 
+ 
8W
V802 
+ 
12W
Study Days 
560 ± 
4d
588± 4d 
616 ± 
4d
644 
± 4d
672 
± 4d
700 ± 
4d
728 ± 4d
± 4d ± 4d
± 4d
Physical examinationb
X  
X
Weight
X
X
X  
X  
X  
X  
X  
X  
X  
X  
X
Sitting blood pressure and pulse 
X
X
X  
X  
X  
X  
X  
X  
X  
X  
X
Habits (tobacco, alcohol, caffeine 
use)
X  
X
Concomitant medications
X
X
X  
X  
X  
X  
X  
X  
X  
X  
X
Review adverse events
X
X
X  
X  
X  
X  
X  
X  
X  
X  
X
Administer IPd
Blinded IP Q2W per randomization schedule
Dispense IP 
X
X
X  
X  
X  
X
Dispense study drug administration 
log
Complete study drug administration log immediately after each IP administration.
IP compliancee
X
X
X  
X  
X  
X  
X  
X
TJC/SJC entry to IWRSf
X
X
X  
X  
X  
X  
X
MDA entry to IWRS
X
X
X  
X  
X  
X
Patient Global Assmt Disease 
Activity VAS
X
X
X  
X  
X  
X  
X  
X
Physician Global Assmt Disease 
Activity VAS
X
x
X  
X  
X  
X  
X  
X
Patient’s Assessment of Pain VAS 
X
X
X  
X  
X  
X  
X  
X
TJC/SJC (68/66joints)
X
X
X  
X  
X  
X  
X  
X
HAQ-DI
X
X
X  
X  
X  
X  
X  
X
Enthesitis assessment (SPARCC and 
LEI)
X
X
X  
X  
X  
X  
X  
X

I1F-MC-RHBF(b)Clinical Protocol
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Randomized Double-Blind Withdrawal Perioda
Early
Termination
Posttreatment 
Follow-Up Period 
(Period4)q
Visit No.(V)
V23
V24
V25 
V26
V27 V28 
V29 
ET 
V801 V802 V803
Study Week (W)
W80
W84
W88 
W92 W96 W100 
W104
LV + 
4W
V801 
+ 
8W
V802 
+ 
12W
Study Days 
560 ± 
4d
588± 4d 
616 ± 
4d
644 
± 4d
672 
± 4d
700 ± 
4d
728 ± 4d
± 4d ± 4d
± 4d
LDI-B
X
X
X  
X  
X  
X  
X  
X
PASI
X
X
X  
X  
X  
X  
X  
X
%BSA
X
X
X  
X  
X  
X  
X  
X
sPGA
X
X
X  
X  
X  
X  
X  
X
Itch NRS
X
X
X  
X  
X  
X  
X  
X
Fatigue Severity NRS
X
X
X  
X  
X  
X  
X  
X
SF-36 v2 acute
X
X
X  
X
QIDS-SR16
X
X
EQ-5D 5L
X
X
X  
X  
X  
X  
X  
X
WPAI-SHP
X
X
X  
X
DLQI
X
X
X  
X  
X  
X  
X  
X
C-SSRSp
X
X
X  
X  
X  
X  
X  
X  
X  
X  
X
Self-Harm Supplement Formp
X
X
X  
X  
X  
X  
X  
X  
X  
X  
X
ECG
X
HBVk,l
X  
X
X
Urine pregnancy test
m
X
X
X  
X  
X  
X  
X  
X
Serum chemistry
X
X
X  
X  
X  
X  
X  
X  
X  
X  
X
Lipid panel (fasting)
X  
X
Advanced lipid profile
X  
X
Hematology
X
X
X  
X  
X  
X  
X  
X  
X  
X  
X
Urinalysis
X  
X
IgA, IgG, IgM
X
X
hs-CRP
X
X
X  
X  
X  
X  
X  
X

I1F-MC-RHBF(b)Clinical Protocol
Page 103
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Randomized Double-Blind Withdrawal Perioda
Early
Termination
Posttreatment 
Follow-Up Period 
(Period4)q
Visit No.(V)
V23
V24
V25 
V26
V27 V28 
V29 
ET 
V801 V802 V803
Study Week (W)
W80
W84
W88 
W92 W96 W100 
W104
LV + 
4W
V801 
+ 
8W
V802 
+ 
12W
Study Days 
560 ± 
4d
588± 4d 
616 ± 
4d
644 
± 4d
672 
± 4d
700 ± 
4d
728 ± 4d
± 4d ± 4d
± 4d
Lymphocyte subset (B, T, CD4+ T, 
CD8+ T, and NK)
X  
X
X
Exploratory storage samples (serum, 
plasma, RNA)
X  
X
X
Immunogenicity testing
on
X
X  
X  
X
PKpo
X
X

I1F-MC-RHBF(b)Clinical Protocol
Page 104
LY2439821
Study Schedule, Protocol I1F-MC-RHBF
Abbreviations:  anti-CCP Ab = anti-cyclic citrullinated peptide antibodies, also known as ACPA (anti-citrullinated protein antibodies); ALT = alanine 
aminotransferase; Assmt = assessment; AST = aspartate aminotransferase; BSA = body surface area; CASPAR = Classification of Psoriatic Arthritis;
C-SSRS=Columbia–Suicide Severity Rating Scale;d=days; DLQI = Dermatology Life Quality Index; ECG = electrocardiogram; EQ-5D 5L = European 
Quality of Life–5 Dimensions 5 Level; ET = Early Termination; ETV = early termination visit; FSH=follicle-stimulating hormone; HAQ-DI = Health 
Assessment Questionnaire–Disability Index; HBcAb+=positive for anti-hepatitis B core antibody; HBsAb = anti-hepatitis B surface antibody; HBsAg–= 
negative for hepatitis B surface antigen; HBV=hepatitis B virus; HCV = hepatitis C virus; HIV= human immunodeficiency virus; hs-CRP = high-sensitivity 
(assay) C-reactive protein; IgA=immunoglobulin A; IgG = immunoglobulin G; IgM=immunoglobulin M; IP = investigational product; IWRS = interactive 
web-response system; LDI-B=Leeds Dactylitis Index–Basic; LEI = Leeds Enthesitis Index; LV = date of last visit; MDA = minimal disease activity; NK = 
natural killer; No.=number; NRS = Numeric Rating Scale; PASI = Psoriasis Area and Severity Index; PK = pharmacokinetic; PPD = purified protein 
derivative; PsA=psoriatic arthritis; PT = prothrombin time; PTT=partial thromboplastin time; Q2W = every 2 weeks; QIDS-SR16 = Quick Inventory of 
Depressive Symptomatology-self report (16 items); RF = rheumatoid factor; RNA = ribonucleic acid; SF-36 V2 = Medical OutcomesStudy 36-Item Short 
Form Health Survey, Version 2; SJC = swollen joint count; SPARCC = Spondyloarthritis Research Consortium of Canada; sPGA=Static Physician Global 
Assessment of Psoriasis; T4 = thyroxine; TB = tuberculosis; TJC = tender joint count; TSH = thyroid-stimulating hormone; ULN = upper limit of normal; V = 
study visit; VAS = visual analog scale; W = study week; WPAI-SHP = Work Productivity and Activity Impairment–Specific Health Problem.
a If a patient discontinues the IPearly, the patient will complete the ETV and then enter the posttreatment follow-up period of the protocol.
b One complete physical examination (excluding pelvic,rectal, and breastexaminations) will be performed at Visit 1 (Screening).  All remaining physical 
examinations throughout the study should include a symptom-directed physical evaluation as well as an examination of the heart, lungs, and abdomen and a 
visual examination of the skin.
c Sitting blood pressure and pulse will be recorded before IP dosing and 1 hour postdosing at baseline (Week0, Visit 2) (Section 10.3.2.4).
d At Week 0 (baseline, Visit 2), initial injection will be performed by clinical staff and the second injection of IPat that visit will be administered by the patient 
or caregiver under the supervision of clinical staff (as described in Section 9.1.1).  If additional training is necessary, an injection may be administered by the 
patient or caregiver under the supervision of clinical staff at Week 2 (Visit 3).  Thereafter, IPwill be administered by the patient or caregiver and should be 
administered unsupervised by the clinical staff.  It is recommended that for these subsequent injections, the patient/caregiver administer the IPoutside the trial 
site, preferably at the patient’s home.
e IPcompliance assessment begins with site personnel collecting, reviewing, and entering data from the patient’s study drug administration log(s).
f Failure to demonstrate at least a 20% improvement from baseline in both TJC and SJC at Week 24 and at any subsequent visit through Week 104 will require 
treatment discontinuationexcept from the point of randomization until the visit afterrelapse for those patients who are randomized in Period 3.
g PPD results will be read approximately 2to 3 days after test application.
h Chest radiographywill be performed at screening (Visit 1) and assessed at site unless chest radiographyhas been obtained within past 6months and the 
radiographsand/or report are available for review.
i ECGs may be obtained at additional times when deemed clinically necessary.
Study Schedule, Protocol I1F-MC-RHBF

I1F-MC-RHBF(b)Clinical Protocol
Page 105
LY2439821
j For female patients ≥40 and <60 years of age who have had a cessation of menses for at least 12 months, an FSH test will be performed to confirm 
nonchildbearing potential (FSH ≥40 mIU/mL).  
k For any patient who is HBsAg–, HBcAb+, and HBsAb+ at screening, a quantitative HBsAb level, and a HBV DNA test will be performed by the central 
laboratory.  A patient with an HBsAb level ≥200 mIU/mL and a negative serum HBV DNA test result may be enrolled in the study.  However periodic 
monitoring of the patient’s HBsAb level must be performed, as indicated in the study schedule.  If the patient’s HBsAb level decreases to <200 mIU/mL, then 
a HBV DNA test will also be performed by the centrallaboratory.  If the HBV DNA test is negative, then the patient may remain in the study.  However, 
repeat testing of the patient’s HBsAb level and HBV DNA must be performed, at 4-to 8-week intervals, as long as the HBsAb level is <200 mIU/mL.  If the 
HBsAb level increases to ≥200 mIU/mL, then the site may resume periodic monitoring of the patient’s HBsAb, as indicated in the study schedule.  See 
Section10.3.3.4for additional details.
l Any enrolled patient who is HBcAb+, regardless of HBsAb status or level, and w
ho has an ALT or AST level >3xULN must undergo HBV DNA testing (see 
Section 10.3.3.4).
m Only for females of childbearing potential.
n Immunogenicity samples may also be analyzed for ixekizumab serum concentration to facilitate in theinterpretation of immunogenicity data.  An additional 
blood sample will be collected, when possible, for any patient who experiences a potential systemic allergic/hypersensitivityreaction during the study as 
judged by the investigator.
o PK samples will be froman aliquot ofthe immunogenicity samples.
p A Self-Harm Follow-Up Form is to be completed for each discrete self-harm event identified on the C-SSRS and the Self-Harm Supplement Form.
q Patients receiving investigational product who discontinue at any time prior to the end of the study or who complete the study (Week 104) will have safety 
Follow-Up Visits 801 and 802 at 4 weeks and 12 weeks, respectively,after the date of their last regularly scheduled visit.  Visit 803 will only occur if a 
patient’s neutrophil counts have not returned to the criteria defined in Section 7.1.4.

I1F-MC-RHBF(b)Clinical Protocol
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Attachment2.Protocol RHBFClinical Laboratory Tests

I1F-MC-RHBF(b)Clinical Protocol
Page 107
LY2439821
Clinical Laboratory Tests
Hematologya
Serum Chemistrya
Hemoglobin
Sodium
Hematocrit
Potassium
Erythrocyte count (RBC)
Bicarbonate
Mean cell volume
Chloride
Mean cell hemoglobin concentration
Phosphorus
Leukocytes (WBC)
Total bilirubin
Platelets
Direct bilirubin
Alkaline phosphatase
Absolute counts of:
Alanine aminotransferase (ALT/SGPT)
Neutrophils, segmented
Aspartate aminotransferase (AST/SGOT)
Neutrophils, juvenile (bands)
Blood urea nitrogen
Lymphocytes
Uric acid
Monocytes
Creatinine
Eosinophils
Calcium
Basophils
Glucose, random
Lymphocyte subset (B cells, T cells, CD4+ T cells,  
Albumin
CD8+ T cells, NK cells) (absolute and percentage) 
Cholesterol (total)
Total protein
Urinalysis (dipstick)a:
Calculated creatinine clearanceb
Color
Creatine phosphokinase
Specific gravity
Triglycerides
pH
Gamma-glutamyl transferase
Protein
Lipase
Glucose
Total amylase
Ketones
Lipid panel (fasting)c
Bilirubin
   LDL
Urobilinogen
   HDL
Blood
   Very low density lipoprotein (VLDL)
Nitrite
Advanced lipid profile 
Urine creatinine
   Oxidized LDL
Leukocyte esterase
   Apolipoprotein A1
   Apolipoprotein B
Other Tests
Serum immunoglobulins (IgA, IgG, and IgM)
HIV antibodyd
Pregnancy test (serum)e
Hepatitis B surface antigen (HBsAg)
d
Urine pregnancy test (assayed by clinical study site)
Hepatitis B surface antibody (HBsAb)
d
Follicle-stimulating hormone (FSH)f
Hepatitis B core antibody (HBcAb)d
Thyroid-stimulating hormone (TSH) and free T4
HBV DNAd
Ixekizumab serum concentration
Double-stranded DNA antibody
g
Partial thromboplastin time
Hepatitis C antibodyh
Prothrombin time
HCV RNA PCRi
Rheumatoid factor
PPD, QuantiFERON-TB Gold, T-SPOT.TBj
High-sensitivity C-reactive protein
anti-cyclic citrullinated peptide antibodies(also known as 
ACPA, anti-citrullinated protein antibodies)
Immunogenicity testing (anti-ixekizumab Ab)
Exploratory storage samples (serum, plasma, urine, 
DNA, and RNA)

I1F-MC-RHBF(b)Clinical Protocol
Page 108
LY2439821
Clinical Laboratory Tests
Abbreviations:  Ab = antibody; FSH = follicle-stimulating hormone;HBcAb+ = positive for anti-hepatitis B core 
antibody; HBsAb+= positive foranti-hepatitis B surface antibody; HBsAg-= negative for hepatitis B surface 
antigen;HBV = hepatitis B virus; HDL = high low-density lipoprotein; HIV = human immunodeficiency virus; 
HCV = hepatitis C virus; IgA = immunoglobulin A; IgG = immunoglobulin G; IgM = immunoglobulin M; 
LDL=low-density lipoprotein; NK = natural killer; PCR = polymerase chain reaction; PPD = purified protein 
derivative; RBC = red blood cell; RNA=ribonucleic acid; SGOT = serum glutamic oxaloacetic transaminase; 
SGPT = serum glutamic pyruvic transaminase; T4=thyroxine; TB = tuberculosis; WBC = white blood cell.
a Unscheduled blood chemistry, hematology, and urinalysis panels may be performed at the discretion of the 
investigator. 
b Cockcroft-Gault calculation is used for the calculated creatinine clearance.
c For the fasting lipid profile,patients should not eat or drink anything exceptwater for 12 hours beforetest. 
d Test required at Visit 1 only to determine eligibility of patient for the study.  Quantitative HBsAband HBV DNA 
testing will be done in those patients who are HBsAg–, HBcAb+, and HBsAb+ at screening.
e Serum pregnancy test for all women <60 years of age who are still of childbearing potential; urine pregnancy test 
(performed locally) for all women of childbearing potential.
f Women ≥40 and <60 years of age who have had a cessation of menses for ≥12 months will have an FSH test 
confirming nonchildbearing potential (≥40 mIU/mL).
g Double-stranded DNA antibody is not a part of routine screening for this study; however, it may be required 
during the study for follow-up.
h See exclusion criterion[45](Section 8.2) specific to hepatitis C antibody.
i Confirmatory test for anti–hepatitis C antibody.
j See Section 10.3.2.3:  In countries where the QuantiFERON-TB Gold test or T-SPOT.TB test is available, it may 
be used instead of the PPD TB test.  

I1F-MC-RHBF(b)Clinical Protocol
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Attachment3.Hepatic Monitoring Tests for 
Treatment-Emergent Abnormality
Hepatic Monitoring Tests
Hepatic Hematologya
Haptoglobina
Hemoglobin
Hematocrit
Hepatic Coagulationa
RBC
Prothrombin time
WBC
Prothrombin time, INR
Neutrophils, segmented
Lymphocytes
Hepatic Serologiesa,b
Monocytes
Hepatitis A antibody, total
Eosinophils
Hepatitis A antibody, IgM
Basophils
Hepatitis B surface antigen
Platelets
Hepatitis B surface antibody
Hepatitis B core antibody
Hepatic Chemistrya
Hepatitis C antibody
Total bilirubin
Hepatitis E antibody, IgG
Direct bilirubin
HepatitisE antibody, IgM
Alkaline phosphatase
ALT
Anti-nuclear antibodya
AST
GGT
Anti-smooth muscle antibodya
CPK
Abbreviations:  ALT = alanine aminotransferase; AST = aspirate aminotransferase; CPK = creatinine 
phosphokinase; GGT = gamma-glutamyl transferase; IgG = immunoglobulin G; IgM = immunoglobulin M; 
INR=international normalizedratio; RBC = red blood cell; WBC = white blood cell.
a Assayed by Lilly-designated or local laboratory.
b Reflex/confirmation dependent on regulatory requirements and/or testing availability.

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Attachment4.Protocol RHBF CASPAR Criteria
The CASPAR criteria for psoriatic arthritis (PsA) consist of inflammatory articular disease (joint, 
spine, or entheseal) with ≥3 pointsfrom the following 5 categories.  
• Evidence of current psoriasis, a personal history of psoriasis, or a family 
history of psoriasis (2 points)
o Current psoriasis is defined as psoriatic skin or scalp disease present 
today as judged by a rheumatologist or dermatologist.
†
o A personal history of psoriasis is defined as a history of psoriasis that 
may be obtained from a patient, family physician, dermatologist, 
rheumatologist, or other qualified health care provider.  
o A family history of psoriasis is defined as a history of psoriasis in a 
first-or second-degree relative according to patient report.
• Typical psoriatic nail dystrophy including onycholysis, pitting, and 
hyperkeratosis observed on current physical examination (1 point)
• A negative test result for the presence of rheumatoid factor by any method 
except latex (1point)
• Either current dactylitis, defined as swelling of an entire digit, or a history of 
dactylitis recorded by a rheumatologist (1 point)
• Radiographic evidence of juxta-articular new bone formation appearing as ill-
defined ossification near joint margins (but excluding osteophyte formation) 
on plain radiographs of the hand or foot (1 point)
†Current psoriasis is assigned a score of 2; all other features are assigned a score of 1.
Taylor, W, Gladman, D, Helliwell, P, Marchesoni, A, Mease, P, Mielants, H, CASPAR Study 
Group. Classification criteria for psoriatic arthritis: development of new criteria from a large 
international study. Arthritis Rheum.2006;54(8):2665–2673.

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Attachment5.Protocol RHBFTender and Swollen Joint 
Count Assessment Form
68/66 JOINT EVALUATION
Patient Right
Patient Left
Pain/
Tenderness 
Swelling 
Pain/Tenderness 
Swelling
JOINT*
(Circle Correct Answer)
0 = Absent
1 = Present
9 = N/A*
0 = Absent
1 = Present
9 = N/A*
0 = Absent
1 = Present
9 = N/A*
0 = Absent
1 = Present
9 = N/A*
1.  Temporomandibular 
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
2.  Sternoclavicular
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
3.  Acromioclavicular 
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
4.  Shoulder
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
5.  Elbow
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
6.  Wrist
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
7.  Metacarpophalangeal I 
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
8.  Metacarpophalangeal II 
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
9.  Metacarpophalangeal III 
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
10.  Metacarpophalangeal IV 
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
11.  Metacarpophalangeal V 
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
12.  Thumb interphalangeal 
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
13.  Proximal interphalangeal II 0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
14.  Proximal interphalangeal III 0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
15.  Proximal interphalangeal IV 0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
16.  Proximal interphalangeal V 0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
17.  Distal interphalangeal II 
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
18.  Distal interphalangeal III 
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
19.  Distal interphalangeal IV 
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
20.  Distal interphalangeal V 
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
21.  Hip
0 1 
9 
N/A  
0 
1  9 
N/A
22.  Knee
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
23.  Ankle
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
24.  Tarsus
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
25.  Metatarsophalangeal I 
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
26.  Metatarsophalangeal II 
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
27.  Metatarsophalangeal III 
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
28.  Metatarsophalangeal IV 
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
29.  Metatarsophalangeal V 
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
30.  Great toe
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
31.  Interphalangeal II 
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9

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68/66 JOINT EVALUATION
Patient Right
Patient Left
Pain/
Tenderness 
Swelling 
Pain/Tenderness 
Swelling
JOINT*
(Circle Correct Answer)
0 = Absent
1 = Present
9 = N/A*
0 = Absent
1 = Present
9 = N/A*
0 = Absent
1 = Present
9 = N/A*
0 = Absent
1 = Present
9 = N/A*
32.  Interphalangeal III 
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
33.  Interphalangeal IV 
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
34.  Interphalangeal V 
0 1 
9 
0 
1 
9 
0 
1  9  0 
1 
9
*For replaced, ankylosed, or arthrodesed joints, please record as 9 (not applicable) and record details of replaced, 
ankylosed, or arthrodesed joints.
Abbreviation:  N/A = not applicable.

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Attachment6. ProtocolAmendment I1F-MC-RHBF(b)
Summary
Overview
Protocol I1F-MC-RHBF,A Phase 3, Multicenter Study with a 36-Week Open-Label Period 
Followed by a Randomized Double-Blind Withdrawal Period from Week 36 to Week 104 to 
Evaluate the Long-Term Efficacy and Safety of Ixekizumab (LY2439821) 80 mg Every 2 Weeks 
in Biologic Disease-Modifying Antirheumatic Drug–Naive Patients with Active Psoriatic 
Arthritis,has been amended.  The new protocol is indicated by amendment (b) and will be used 
to conduct the study in place of any preceding version of the protocol.
The overall changes and rationale for the changes made to this protocol are as follows:
Change the 2nd interim analysis (which includes the primary outcome) from when 39 
patients relapse or when all patients complete Week 104, whichever comes firstto when 
all patients complete Week 104. 
Remove annual TB testing consistent with compound level decision.
Add IBD adjudication consistent with compound level decision.
Adjust the language for the first Interim DBL for more clarity.
Add in language clarifying withholding study treatment for surgery and the use of 
concomitant medicationfor AEs.

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Revised Protocol Sections
Note: 
Deletions have been identified by strikethroughs.
Additions have been identified by the use of underscore.
4.  Abbreviations and Definitions
Term
Definition
IBD
Inflammatory bowel disease (e.g. Crohn’s disease and ulcerative colitis)
LOCF
last observation carried forward
mBOCF
modified baseline observation carried forward
8.3.1.1  Discontinuation Criteria
Any positive TB test that indicates TB test conversion since prior testing (based on 
patient medical history or Visit1 screening test), AND the patient does not receive 
appropriate treatment for latent TB; or there is evidence of active TB infection at any 
timethe result of the TB test is positive at Week 52 (Visit 16) or later AND the patient is 
diagnosed with active infection(see Section 10.3.2.3).
9.8.  Concomitant Therapy
Additional guidance: Patients requiring surgery at any time during the study should interrupt 
administration of the investigational product beginning 8weeks prior to the surgery, or as early 
as possible within 8weeks of surgery, and resume administration of the Investigational product 
only after complete wound healing.
Additional drugs are to be avoided during the study unless required to treat an AE or for the 
treatment of an ongoing medical problem.  If the need for concomitant medication arises, the 
investigator should base decisions on the patient and clinical factors.  Any additional medication, 
whether prescription or over-the-counter, used at baseline (Week0, Visit2) and/or during the 
course of the study must be documented with the start and stop dates on the concomitant 
medications CRF.
Patients will maintain their usual medication regimen for other concomitant diseases throughout 
the study unless specifically excluded in the protocol.  Patients taking allowed concomitant 
medications should be on stable doses at the time of baseline (Week0, Visit2) and should 
remain at a stable dose throughout the study, unless changes need to be made for an AE or for 
appropriate medical management.  Additional systemic drugs are to be avoided during the study, 
unless required to treat an AE.  Other medications may be allowed, if approved by the sponsor or 
its designee.

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Any changes in medications not addressed above should be discussed with the investigator.  
Unless urgent medication is indicated by the patient’s medical condition,patients should be 
instructed to consult the investigator or other appropriate study personnel atthe site before taking 
any new medications or supplements.
10.3.1.1.2.  Adverse Events of Special Interest
Data on suspected IBD, as identified by events possibly indicative of ulcerative colitis and/or
Crohn’s disease, will be collected and the events will be adjudicated by an external CEC made 
up of gastroenterologists with expertise in IBD.  The role of the CEC will be to adjudicate 
defined clinical events, in a blinded, consistent, and unbiased manner throughout the course of a 
study. The importance of the CEC is to ensure that all events that have been reported are 
evaluated uniformly by a single group.
10.3.2.3.  Chest Radiography and Tuberculosis Testing
TB testing:  Patient history of TB test results should be assessed before screening (Visit 1).
Patients with no TB test results on file:  These patients will be tested at screening 
(Visit1).  A PPD skin test response of ≥5-mm induration, between approximately 2 and 
3days after test application, regardless of BCG vaccination history, will be considered a 
positive result.  In countries where the QuantiFERON-TB Gold test or T-SPOT.TB 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, those tests may be used instead of the PPD 
test.  If the QuantiFERON-TB Gold test or the T-SPOT.TB test is indeterminate, 1 retest 
is allowed.  If the retest is indeterminate, the patient is excluded from the study.
Patients with positive results from a TB test performed at screening(Visit 1) but no other 
evidence of active TB may be rescreened once and enrolled on the basis of the following 
requirements:

after receiving at least 4 weeks of appropriate latent tuberculosis infection (LTBI) 
therapy,

no evidence of hepatotoxicity (ALT and AST levels must remain ≤2× ULN) upon 
retesting of serum ALT and AST before randomization.  Such patients must 
complete appropriate LTBI therapy during the course of the study to remain eligible, 
and

meet all other inclusion/exclusion criteria for participation.
The same TB test method used for determining eligibility should be used for all TB 
testing throughout the study for a given patient.
TB Testing and Assessment for Patients during the Study:
Eligible patients with negative TB test results at screening (Visit 1) or on file are required to 
have annual TB tests as per the study schedule (Attachment1).

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Eligible patients with positive TB test results at screening (Visit 1) or on file are not required to 
have annual TB tests.
Patients who develop positive TB test results during the study and are eligible to continue the 
study are not required to have subsequent annual TB tests.
Tuberculosis testing during the study will be conducted based on clinical assessment of TB risk 
(symptoms/signs/known or suspected TB exposure), and as required by local regulations and/or 
local standard of care.
Patients testing positive for TB at any time during the study must immediately discontinue 
administration of investigational product.  The patient must be evaluated for latent or active 
infection.  Patients with active infection must be discontinued from the study and should receive 
appropriate follow-up medical care and TB treatment according to local guidelines; patients with 
latent infection must receive a full course of LTBI treatment but may resume administration of 
investigational product after receiving 4 weeks of LTBI treatmentwith no evidence of 
hepatotoxicity (ALT and AST levels must remain ≤2× ULN) upon retesting of serum ALT and 
AST before resumption of investigational product.  Such patients must complete appropriate 
LTBI therapy during the course of the study to remain eligibleto continue the study treatment.
12.2.1.2.  General Considerations for Analyses during Period 3 (Randomized 
Double-Blind Withdrawal Period)
For patients who are randomized in Period 3, all efficacy, health outcomes, and safety data 
collected between randomization and either through relapse (no longer meeting Coates criteria 
for MDA) or through the end of Period 3 will be compared between the ixekizumab 80 mg Q2W 
and placebo treatment groups.  For the efficacy analysis, baseline is defined as the last available 
value before the first dose of study medication in Period 2and in most cases will be the value 
recorded at Week 0 (Visit 2). For the safety analysis, baseline is defined as the last available 
value before the first dose of study treatment in Period 3.
The Kaplan-Meier product limit method will be used to estimate the survival curves for time-to 
variables for the patients who are randomized to the randomized double-blind withdrawal period.  
Treatment comparisons will be performed using a log-rank test with treatment,geographic 
region, and cDMARD use (past use, current use), at the time of randomization in Period 3,in the 
model.
The primary analysis of the categorical efficacy
 and health outcome variables will use a logistic 
regression with treatment,geographic region, and cDMARD use (past use, current use), at the 
time of randomization in Period 3,in the model.  Secondary analysis of the categorical efficacy 
and health outcome variables will be conducted using the Fisher’s exact test.  
The analysis for all continuous efficacy and health outcome variables, change from baseline to 
endpoint analysis, will be made using analysis of covariance with treatment, baseline value, 
geographic region, and cDMARD use(past use, current use), at the time of randomization in 
Period 3,in the model.  Missing data will be imputed using modified baselinelastobservation 

I1F-MC-RHBF(b)Clinical Protocol
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carried forward (mBLOCF).  Type III sums of squares for the least-squares means will be used 
for the statistical comparison; the 95% CI will also be reported.
The Fisher
's exact test will be used for all AE, baseline, discontinuation, and other categorical 
data.  AE data will be analyzed using exposure-adjusted incidence rates.  Continuous vital sign 
and laboratory values will be analyzed by an analysis of covariance model with treatment and 
baseline value as independent variables.  Other continuous variables will be analyzed by t-tests 
unless otherwise stated.
For patients who randomize and subsequently relapse in Period 3, efficacy, health outcomes, and 
safety data collected between relapse and the end of Period 3 will be summarized for ixekizumab 
80 mg Q2W without inferential statistics.  For the efficacy and health outcomes analyses, 
baseline is defined as the last available value before the first dose of study medication in Period 2
and in most cases will be the value recorded at Week 0 (Visit 2).  For the safety analysis, 
baseline is defined as the last available value before relapse in Period 3.
12.2.1.5.2.  Modified BaselineLastObservation Carried Forward
AnmBOCF analysis will be performed on all continuous efficacy and health outcome variables.  
In this approach,the baseline observation will be carried forward to the corresponding endpoint 
for evaluation for patients who discontinue study treatment due to an AE.  The last nonmissing 
observation before discontinuation of study treatment will be carried forward to the 
corresponding primary endpoint for evaluation for patients who discontinue study treatment for 
any reason other than due to an AE.  Patients without at least 1postbaseline observation will not 
be included for evaluation,with the exception of patients who discontinue study treatment due to 
an AE.
A LOCF analysis will be performed on all continuous efficacy and health outcome variables.  In 
this approach the last nonmissing postbaseline observation before study treatment 
discontinuation will be carried forward tothe corresponding endpoint for evaluation.  Patients 
without at least 1 postbaseline observation will not be included for evaluation.
12.2.6.2.3.  Combined Initial Treatment and Randomized Double-Blind Withdrawal Periods 
(Periods 2 and 3)
The HAQ-DI scorewill be summarized for the ixekizumab 80 mg Q2W treatment group at each 
visit and endpoint (mBLOCF) during the combined Periods 2 and 3 for the randomized 
withdrawal ITT and the nonrandomized withdrawal populations.  Summarizations will include 
observed scores, change from baseline, percentage improvement, and response rates ≥0.35.
12.2.10.  Interim Analysis
The study will have approximately 2 interim and 1 final database locks.  The first interim 
database lockmaywilloccur once all patients complete or discontinue inthe initial open-label 
treatment period; only data from the initial open-label treatment period will be summarized. For 
analysis purposes, the end of the initialopen-label treatment period will be defined as the visit of 
randomization or Week 64 for patients who do not meet the randomization criteria.The second 

I1F-MC-RHBF(b)Clinical Protocol
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LY2439821
interim database lock maywilloccur when 39 patients meet relapse criteria orwhen all patients 
complete Week104or discontinue study treatment prior to the end of the randomized 
double-blind withdrawal period, whichever comes first.  The final database lock will occur when 
all patients complete or discontinue the study.  The study will not be terminated early
 on the 
basis of efficacy after the second interim database lock.  However, the second interim may not be 
performed depending upon the timing of the final database lock once all patients complete the 
post-treatment follow up period.  Analyses for these interim analyses will be specified in the 
SAP along with the unblinding plan.Additional analyses and snapshots of study data may be 
performed to fulfill the need for regulatory interaction or publication purposes.Analyses for 
these interim analyses will be specified in the SAP along with the unblinding plan.
Information that may unblind the study during the analyses will not be reported to study sites or 
the blinded study team until the study has been unblinded.  All investigators and patients will 
remain blinded to treatment assignments until the last patient completes the randomized 
double-blind withdrawal period and the final database lock occurs.

I1F-MC-RHBF(b)Clinical Protocol
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Attachment 1.  Protocol RHBF Study Schedule
Study Schedule, Protocol I1F-MC-RHBF(changes/additions)
Screening
(Period 1) Baseline
Initial Open-Label Treatment Perioda
Visit No. (V)
V1 
V1A 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11
Study Week (W)
W0 
W2 
W4 
W8 
W12 
W16 
W20 
W24 
W28 
W32
Study Days 
-30 to -4 2-3d 
post V1
0 
14 ± 2d 28 ± 2d 56 ± 4d 84 ± 4d112 ± 4d140 ± 4d168 ± 4d196 ± 4d224 ± 4d
Read PPD (if applicable)g
Xh
Chest radiography
Xih
ECGji
X
FSH
Xkj
HBVlk,ml
X
X
Serum pregnancy testnm
X
Urine pregnancy test
nm
X
X  
X  
X  
X  
X  
X  
X  
X
Immunogenicity testing
on
X
X
X
X
PKpo
X
X
X
X

I1F-MC-RHBF(b)Clinical Protocol
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LY2439821
Randomized Double-Blind Withdrawal Perioda
Visit No. (V)
V12 
V13 
V14 
V15 
V16 
V17 
V18 
V19 
V20 
V21 
V22
Study Week (W)
W36 
W40 
W44 
W48 
W52 
W56 
W60 
W64 
W68 
W72 
W76
Study Days 
252 ± 4d 280 ± 4d 308 ± 4d 336 ± 4d 364 ± 4d 392 ± 4d 420 ± 4d 448 ± 4d 476 ± 4d 504 ± 4d 532 ± 4d
TB risk factors
X
C-SSRSr
p
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Self-Harm Supplement 
Formr
p
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Administer TB test
X
Read PPD (if applicable)g
X
HBVl
k,ml
X
Urine pregnancy test
nm
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X
Immunogenicity testing
on
X
X
X
PKpo
X
X
X

I1F-MC-RHBF(b)Clinical Protocol
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LY2439821
Study Schedule, Protocol I1F-MC-RHBF(changes/additions -concluded)
Randomized Double-Blind Withdrawal Perioda
Early 
Termination
Posttreatment 
Follow-Up Period 
(Period4)
q
Visit No. (V)
V23
V24
V25 
V26
V27 V28 
V29 
ET 
V801 V802 V803
Study Week (W)
W80
W84
W88 
W92 W96 W100 
W104
LV + 
4W
V801 
+ 
8W
V802 
+ 
12W
Study Days 
560 ± 
4d
588 ± 4d 
616 ± 
4d
644 
± 4d
672 
± 4d
700 ±
4d
728 ± 4d
± 4d ± 4d
± 4d
TB risk factors
X
C-SSRSr
p
X
X
X  
X  
X  
X  
X  
X  
X  
X  
X
Self-Harm Supplement Formr
p
X
X
X  
X  
X  
X  
X  
X  
X  
X  
X
Administer TB test
X
Read PPD (if applicable)g
X
HBVl
k,ml
X  
X
X
Urine pregnancy test
nm
X
X
X  
X  
X  
X  
X  
X
Immunogenicity testing
on
X
X  
X  
X
PKpo
X
X

I1F-MC-RHBF(b)Clinical Protocol
Page 122
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Study Schedule, Protocol I1F-MC-RHBF
h Patients with a PPD TB skin test ≥5-mm induration or a positive QuantiFERON-TB Gold test at Screening (Period 1), or who have a documented treatment 
history as defined in Section 10.3.2.3, should not undergo the TB test at Week 52 (Visit 16) or the yearly testing.
ihChest radiography will be performed at screening (Visit 1) and assessed at site unless chest radiography has been obtained within past 6months and the 
radiographs and/or report are available for review.
ji ECGs may be obtained at additional times when deemed clinically necessary.
kj For female patients ≥40 and <60 years of age who have had a cessation of menses for at least 12 months, an FSH test will be performed to confirm 
nonchildbearing potential (FSH ≥40 mIU/mL).  
lkFor any patient whois HBsAg–, HBcAb+, and HBsAb+ at screening, a quantitative HBsAb level, and a HBV DNA test will be performed by the central 
laboratory.  A patient with an HBsAb level ≥200 mIU/mL and a negative serum HBV DNA test result may be enrolled in the study.  However periodic 
monitoring of the patient’s HBsAb level must be performed, as indicated in the study schedule.  If the patient’s HBsAb level decreases to <200 mIU/mL, then 
a HBV DNA test will also be performed by the central laboratory.  If the HBV DNA test is negative, then the patient may remain in the study.  However, 
repeat testing of the patient’s HBsAb level and HBV DNA must be performed, at 4-to 8-week intervals, as long as the HBsAb level is <200 mIU/mL.  If the 
HBsAb level increases to ≥200 mIU/mL, then the site may resume periodic monitoring of the patient’s HBsAb, as indicated in the study schedule.  See 
Section10.3.3.4for additional details.
ml Any enrolled patient who is HBcAb+, regardless of HBsAb status or level, and w
ho has an ALT or AST level >3xULN must undergo HBV DNA testing (see 
Section 10.3.3.4).
nmOnly for females of childbearing potential.
onImmunogenicity samples may also be analyzed for ixekizumab serum concentration to facilitate in the interpretation of immunogenicity data.  An additional 
blood sample will be collected, when possible, for any patient who experiences a potential systemic allergic/hypersensitivityreaction during the study as 
judged by the investigator.
poPK samples will be from an aliquot of the immunogenicity samples.
rpA Self-Harm Follow-Up Form is to be completed for each discrete self-harm event identified on the C-SSRS and the Self-Harm Supplement Form.

PPD
Leo Document ID = 35ea2526-d905-4ee0-81c4-b3967ba0d623
Approver: 
Approval Date & Time: 21-Mar-2017 12:57:43 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 21-Mar-2017 22:10:02 GMT
Signature meaning: Approved
PPD