A Multicenter, Randomized, Double-Blind Study Comparing the Efficacy and Safety of Ixekizumab Versus Placebo in Patients With Moderate-to-Severe Genital Psoriasis
Phase: PHASE3
Conditions: Genital Psoriasis, Psoriasis
Sponsor: Eli Lilly and Company

Protocol I1F-MC-RHBQ(a)
A Multicenter, Randomized, Double-Blind Study Comparing the Efficacy and Safety of Ixekizumab Versus 
Placebo in Patients with Moderate-to-Severe Genital Psoriasis
NCT02718898
Approval Date: 22-Jan-2016

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Protocol I1F-MC-RHBQ(a)
A Multicenter, Randomized, Double-Blind Study Comparing 
the Efficacy and Safety of Ixekizumab Versus Placebo in 
Patients with Moderate-to-Severe Genital Psoriasis
Confidential Information
The information contained in this document is confidential and is intended for the use of 
clinical investigators.  It is the property of Eli Lilly and Company or its subsidiaries and 
should not be copied by or distributed to persons not involved in the clinical investigation of 
ixekizumab (LY2439821), unless such persons are bound by a confidentiality agreement 
with Eli Lilly and Company or its subsidiaries.  
Note to Regulatory Authorities:  This document may contain protected personal data 
and/or commercially confidential information exempt from public disclosure.  Eli Lilly and 
Company requests consultation regarding release/redaction prior to any public release.  In 
the United States, this document is subject to Freedom of Information Act (FOIA) 
Exemption 4 and may not be reproduced or otherwise disseminated without the written 
approval of Eli Lilly and Company or its subsidiaries.
ixekizumab (LY2439821)
Study I1F-MC-RHBQ is a Phase 3, multicenter, randomized, double-blind, placebo-
controlled, parallel-group, outpatient study examining the efficacy and safety of ixekizumab 
80 mg Q2W (subcutaneous [SC]) as compared to placebo SC in patients with moderate-to-
severe genital psoriasis, during a double-blind, 12-week Blinded Treatment Period followed 
by a 40-week Open-Label Treatment Period.
Eli Lilly and Company
Indianapolis, Indiana USA 46285
Protocol Electronically Signed and Approved by Lilly:  14 Nov 2015
Amendment (a) Electronically Signed and Approved by Lilly on date provided below.
Approval Date: 22-Jan-2016 GMT

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Table of Contents
Section
Page
1.
Protocol Synopsis................................................................................................................9
2.
Introduction ......................................................................................................................12
2.1.
Background..................................................................................................................12
2.2.
Study Rationale............................................................................................................13
3.
Objectives and Endpoints..................................................................................................15
4.
Study Design.....................................................................................................................19
4.1.
Overview of Study Design ...........................................................................................19
4.2.
End of Trial Definition.................................................................................................22
4.3.
Scientific Rationale for Study Design...........................................................................22
4.4.
Justification for Dose ...................................................................................................22
4.5.
Benefit/Risk Assessment..............................................................................................23
5.
Study Population...............................................................................................................24
5.1.
Inclusion Criteria..........................................................................................................24
5.2.
Exclusion Criteria ........................................................................................................25
5.3.
Screen Failures.............................................................................................................30
5.4.
Lifestyle and/or Dietary Requirements .........................................................................30
6.
Treatment..........................................................................................................................31
6.1.
Treatments Administered .............................................................................................31
6.2.
Method of Treatment Assignment ................................................................................34
6.2.1.
Selection and Timing of Doses.............................................................................34
6.3.
Blinding .......................................................................................................................34
6.4.
Packaging and Labelling ..............................................................................................35
6.5.
Preparation/Handling/Storage.......................................................................................35
6.6.
Dose Modification........................................................................................................35
6.6.1.
Special Treatment Considerations ........................................................................35
6.7.
Treatment Compliance .................................................................................................37
6.8.
Concomitant Therapy...................................................................................................37
6.9.
Treatment after Study Completion................................................................................41
6.9.1.
Continued Access.................................................................................................41
7.
Discontinuation Criteria ....................................................................................................42
7.1.
Discontinuation from Study Treatment.........................................................................42
7.1.1.
Permanent Discontinuation from Study Treatment ...............................................42
7.1.2.
Discontinuation of Inadvertently Enrolled Patients...............................................44
7.1.3.
Permanent Discontinuation from the Study ..........................................................44

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7.1.4.
Patients Lost to Follow-Up...................................................................................45
8.
Study Assessments and Procedures ...................................................................................46
8.1.
Efficacy Assessments...................................................................................................46
8.1.1.
Primary Efficacy Assessments .............................................................................46
8.1.1.1.
Static Physician Global Assessment of Genitalia ............................................46
8.1.2.
Secondary Efficacy Assessments..........................................................................46
8.1.2.1.
Clinician Reported Assessments .....................................................................46
8.1.2.1.1.
Modified Genital Psoriasis Area and Severity Index .................................46
8.1.2.1.2.
(Overall) static Physician Global Assessment............................................47
8.1.2.2.
Patient Reported Assessments.........................................................................47
8.1.2.2.1.
Genital Psoriasis Symptoms Scale ............................................................47
8.1.2.2.2.
Genital Psoriasis Sexual Impact Scale.......................................................47
8.1.2.2.3.
Sexual Frequency Questionnaire...............................................................48
8.1.2.2.4.
Patient’s Global Assessment of Genital Psoriasis ......................................49
8.1.2.2.5.
Dermatology Life Quality Index ...............................................................49
8.1.2.2.6.
Medical Outcomes Study 36-Item Short-Form Health 
Survey ......................................................................................................49
8.1.3.
Exploratory Efficacy Assessments .......................................................................49
8.1.3.1.
Clinician Reported Assessments .....................................................................49
8.1.3.1.1.
(Overall) Psoriasis Area and Severity Index..............................................49
8.1.3.1.2.
Percentage of Body Surface Area..............................................................50
8.1.3.1.3.
Fitzpatrick Skin Type Assessment ............................................................50
8.1.3.1.4.
Binary Questions on Psoriasis Location ....................................................50
8.1.3.1.4.1.
Overall................................................................................................50
8.1.3.1.4.2.
Genital................................................................................................50
8.1.3.1.5.
Binary Questions on Characteristics..........................................................50
8.1.3.1.5.1.
Genital................................................................................................50
8.1.3.1.5.2.
Perianal/Gluteal Cleft..........................................................................51
8.1.3.2.
Combined Clinician/Patient Reported Assessment..........................................51
8.1.3.2.1.
Comprehensive Assessment of the Psoriasis Patient..................................51
8.1.3.3.
Patient Reported Assessment ..........................................................................51
8.1.3.3.1.
Touch Avoidance Numeric Rating Scale...................................................51
8.1.4.
Appropriateness of Assessments ..........................................................................51
8.1.4.1.
Static Physician Global Assessment of Genitalia ............................................51
8.1.4.2.
Modified Genital Psoriasis Area and Severity Index .......................................52
8.2.
Adverse Events ............................................................................................................52
8.2.1.
Serious Adverse Events........................................................................................53
8.2.2.
Adverse Events of Special Interest .......................................................................54

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8.2.2.1.
Suspected Unexpected Serious Adverse Reactions..........................................55
8.2.3.
Complaint Handling.............................................................................................55
8.3.
Treatment of Overdose.................................................................................................55
8.4.
Safety Assessments ......................................................................................................55
8.4.1.
Electrocardiograms ..............................................................................................55
8.4.2.
Vital Signs ...........................................................................................................55
8.4.3.
Laboratory Tests ..................................................................................................56
8.4.4.
Physical Examination...........................................................................................56
8.4.5.
Chest X-Ray and Tuberculosis Testing.................................................................56
8.4.6.
Immunogenicity...................................................................................................57
8.4.7.
Quick Inventory of Depressive Symptomatology—Self-
Report (16 Items) .................................................................................................57
8.4.8.
Columbia–Suicide Severity Rating Scale..............................................................58
8.4.9.
Safety Monitoring ................................................................................................58
8.4.9.1.
Neutropenia....................................................................................................58
8.4.9.2.
Hepatitis B Monitoring...................................................................................60
8.4.9.3.
Hypertension ..................................................................................................61
8.5.
Pharmacokinetics .........................................................................................................61
8.6.
Pharmacodynamics ......................................................................................................61
8.7.
Genetics .......................................................................................................................62
8.8.
Biomarkers...................................................................................................................62
8.8.1.
Samples for Immunogenicity Research.................................................................63
8.8.2.
Samples for Genital Candida Testing ...................................................................63
8.9.
Health Economics ........................................................................................................63
9.
Statistical Considerations and Data Analysis.....................................................................64
9.1.
Determination of Sample Size ......................................................................................64
9.2.
General Statistical Considerations ................................................................................64
9.3.
Analysis Population .....................................................................................................65
9.3.1.
Missing Data Imputation......................................................................................65
9.3.2.
Adjustment for Multiple Comparisons..................................................................66
9.4.
Treatment Group Comparability...................................................................................66
9.4.1.
Patient Disposition...............................................................................................66
9.4.2.
Patient Characteristics..........................................................................................66
9.4.3.
Concomitant Therapy...........................................................................................67
9.4.4.
Treatment Compliance .........................................................................................67
9.5.
Primary and Secondary Analyses .................................................................................67
9.5.1.
Primary Analyses.................................................................................................67
9.5.2.
Secondary Analyses .............................................................................................68

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9.5.3.
Exploratory Analyses...........................................................................................68
9.6.
Safety Analyses............................................................................................................68
9.6.1.
Adverse Events ....................................................................................................69
9.6.2.
Clinical Laboratory Tests .....................................................................................69
9.6.3.
Vital Signs, Physical Findings, and Other Safety Evaluations...............................70
9.7.
Pharmacokinetic/Pharmacodynamic Analyses..............................................................70
9.8.
Other Analyses.............................................................................................................70
9.8.1.
Subgroup Analyses ..............................................................................................70
9.8.2.
Immunogenicity Analyses....................................................................................71
9.9.
Interim Analyses ..........................................................................................................71
10.
Study Governance Considerations.....................................................................................72
10.1. Regulatory and Ethical Considerations, Including the Informed 
Consent Process ...........................................................................................................72
10.1.1.
Informed Consent.................................................................................................72
10.1.2.
Ethical Review.....................................................................................................72
10.1.3.
Regulatory Considerations ...................................................................................72
10.1.4.
Investigator Information.......................................................................................73
10.1.5.
Protocol Signatures ..............................................................................................73
10.1.6.
Final Report Signature .........................................................................................73
10.2. Data Quality Assurance................................................................................................73
10.2.1.
Data Capture System............................................................................................74
10.3. Study and Site Closure .................................................................................................74
10.3.1.
Discontinuation of Study Sites .............................................................................74
10.3.2.
Discontinuation of the Study................................................................................75
11.
References ........................................................................................................................76

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List of Tables
Table
Page
Table RHBQ.3.1.Objectives and Endpoints...............................................................................15
Table RHBQ.6.1.Treatment Regimens......................................................................................33
Table RHBQ.6.2.Concomitant Medication Permitted/Not Permitted in the Study .....................38

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List of Figures
Figure
Page
Figure RHBQ.4.1.
Illustration of study design for Clinical Protocol I1F-MC-RHBQ..............21

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List of Appendices
Appendix
Page
Appendix 1.
Abbreviations and Definitions........................................................................80
Appendix 2.
Schedule of Activities....................................................................................84
Appendix 3.
Clinical Laboratory Tests...............................................................................94
Appendix 4.
Hepatic Monitoring Tests for Treatment-Emergent Abnormality....................96
Appendix 5.
Protocol Amendment I1F-MC-RHBQ(a) Summary:  A Multicenter, 
Randomized, Double-Blind Study Comparing the Efficacy and Safety 
of Ixekizumab Versus Placebo in Patients with Moderate-to-Severe 
Genital Psoriasis............................................................................................97

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1.
Protocol Synopsis
Title of Study:
A Multicenter, Randomized, Double-Blind Study Comparing the Efficacy and Safety of Ixekizumab Versus Placebo 
in Patients with Moderate-to-Severe Genital Psoriasis
Rationale:  
Approximately 29% to 63% of patients with chronic plaque psoriasis are impacted by psoriatic lesions in the genital 
area at some point during the course of the disease (Fouéré et al. 2005; Meeuwis et al. 2010, 2011a; Ryan et al. 
2015). When compared to psoriasis patients without genital involvement, quality of life was found to be 
significantly worse in patients with genital lesions (Meeuwis et al. 2011b; Ryan et al. 2015). Itch and sexual 
impairment have been reported as key bothersome issues for patients with genital psoriasis (Meeuwis et al. 2015; 
Ryan et al. 2015). Despite the significant impact on quality of life and sexual health, genital psoriasis is neither 
frequently discussed by patients (AAD Work Group et al. 2011; Meeuwis et al. 2012; Andreassi and Bilenchi 2014) 
nor routinely questioned or examined by health care professionals (Farber and Nall 1992; AAD Work Group et al. 
2011).
Although genital psoriasis appears to be pathophysiologically identical to plaque psoriasis in other skin regions, the 
skin in this area is highly sensitive and at increased risk of adverse reactions to topical treatments (CDA 2009 
[WWW]; Meeuwis et al. 2011a; Guglielmetti et al. 2012). Specifically, available topical agents may not offer the 
optimal or even appropriate level of clinical improvement or tolerability, especially for patients with moderate-to-
severe genital psoriasis.
Currently, there are limited data from clinical trials, particularly well-controlled therapeutic interventional studies, 
which measure the efficacy of treatments for genital psoriasis. To date, the only published treatment studies of 
genital psoriasis include open-label studies of topical treatments (Jemec and Baadsgaard 1993; Rallis et al. 2005; 
Martín Ezquerra et al. 2006; Bissonnette et al. 2008), a recent open-label study of a stepwise treatment algorithm 
(Meeuwis et al. 2015), and scattered case reports. Based on the Phase 3 psoriasis clinical trial outcomes,
ixekizumab therapy in patients with moderate-to-severe genital psoriasis could address an unmet patient need and a
clinical research gap identified by the dermatology community and the American Academy of Dermatology Psoriasis 
Guidelines of Care Working Group (Ryan et al. 2014).
Objective(s)/Endpoints:
Objectives
Endpoints
Primary:  To assess whether 80 mg ixekizumab 
every 2 weeks (Q2W) is superior to placebo at Week 
12 in the treatment of patients with moderate-to-
severe genital psoriasis as measured by static 
Physician Global Assessment (sPGA) of Genitalia 
(0,1)
The proportion of patients achieving sPGA of Genitalia 
(0,1) at Week 12

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Objectives
Endpoints
Major Secondary:  To assess whether 80 mg 
ixekizumab Q2W is superior to placebo at Week 12 
in the treatment of patients with moderate-to-severe 
genital psoriasis as measured by change in itch, 
utilizing a modified genital psoriasis itch Numeric 
Rating Scale (NRS) item within the Genital Psoriasis 
Symptom Scale (GPSS)

Mean change from baseline in the genital psoriasis 
itch NRS item within the GPSS at Week 12
Summary of Study Design:  
Study I1F-MC-RHBQ is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group, 
outpatient study examining the efficacy and safety of ixekizumab 80 mg Q2W dosing as compared to placebo for 12 
weeks, followed by a 40-week Open-Label Treatment Period with 80 mg every 4 weeks (Q4W) dosing (with an 
option to step-up to 80 mg Q2W dosing) in patients with moderate-to-severe genital psoriasis.
Treatment Arms and Duration:  
There are 2 treatment groups in the Blinded Treatment Period, and patients will be randomized at Week 0 to 1 of the 
groups. The 2 groups are:  ixekizumab 80 mg Q2W subcutaneous (SC) dosing and placebo Q2W SC dosing.  There 
is 1 treatment group in the Open-Label Treatment Period:  ixekizumab 80 mg SC Q4W dosing with an option to 
step-up to Q2W dosing starting at Week 24 through Week 40. The study duration will be up to 1 year for 
ixekizumab administration, and up to 1 year and 4 months for study participation over 4 periods (Screening Period:  
7 to 30 days; Blinded Treatment Period:  12 weeks; Open-Label Treatment Period:  40 weeks; Post-Treatment 
Follow-Up:  at least 12 weeks after the date of the patient’s early termination visit [ETV] or last regularly scheduled 
visit).
Number of Patients:  
146 randomized
Statistical Analysis:
For the Blinded Treatment Period, analyses of efficacy and health outcomes will be conducted on the intent-to-treat
(ITT) population, and safety analyses will be conducted on the safety population.
The primary analysis method for treatment comparisons of categorical efficacy and health outcome variables will be
a logistic regression analysis with treatment and body surface area (BSA) category as factors, using the 
nonresponder imputation (NRI) method.
The primary analyses for the continuous efficacy and health outcome variables will be performed using
mixed-effects model for repeated measures (MMRM) analysis. The model will include treatment, baseline BSA 
category, baseline value, visit, treatment-by-visit interaction, and baseline-by-visit interaction as fixed factors.  
A sequential multiple testing procedure for the primary and the major secondary endpoint will be implemented to
control the family-wise type I error rate at a 2-sided α level of 0.05.

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Fisher’s exact test will be used for all adverse events (AE), baseline, discontinuation, and other categorical safety
data. Continuous vital sign and laboratory values will be analyzed by an analysis of covariance (ANCOVA) with
treatment and baseline value in the model.
Consistency of results among the 2 subpopulations determined by baseline BSA category (<10% versus ≥10% 
baseline BSA involvement) will be assessed by performing additional subgroup analyses on the primary endpoint.
The baseline BSA category by treatment interaction will be tested at the significance level of 0.10. Treatment group 
differences will be evaluated within each baseline BSA category using Fisher’s exact test, regardless of whether the 
interaction is statistically significant.

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2.
Introduction
2.1.
Background
Chronic plaque psoriasis is a common, lifelong, and life-shortening chronic inflammatory skin 
disease with an estimated prevalence in populations of approximately 3% which manifests as 
prototypic red, thick, and scaly plaques (Greaves and Weinstein 1995).  Psoriasis has been 
shown to have a significant impact on the overall health of patients with considerable effects on 
social functioning and quality of life.
Approximately 29% to 63% of patients with chronic plaque psoriasis are impacted by psoriatic 
lesions in the genital area at some point during the course of the disease (Fouéré et al. 2005; 
Meeuwis et al. 2010, 2011a; Ryan et al. 2015).  Due to moisture and maceration, genital psoriasis
can sometimes lack the characteristic scale present at other body sites (Buechner 2002; Weichert 
2004).  Both penile and vulvar psoriatic lesions generally appear as symmetrical, bright red thin
plaques with a well-defined edge (Buechner 2002; Welsh et al. 2003; ISSVD 2014 [WWW];
Meeuwis et al. 2015). Painful fissures and erosions can also be a problematic clinical feature of
genital psoriasis (Barchino-Ortiz et al. 2012; Guglielmetti et al. 2012; Meeuwis et al. 2015), and
severe pruritus may lead to scratching with significant excoriations and lichenification (Weichert
2004; Guglielmetti et al. 2012).
When compared to psoriasis patients without genital involvement, quality of life was found to be 
significantly worse in patients with genital lesions (Meeuwis et al. 2011b, Ryan et al. 2015).  
Overall DermatologyLife Quality Index (DLQI) score, all domain scores, and DLQI Question 9
(skin caused sexual difficulties) were significantly worse for those psoriasis patients with current 
genital involvement compared to those without genital lesions.  Itch and sexual impairment have 
been reported as key bothersome issues for patients with genital psoriasis (Meeuwis et al. 2015; 
Ryan et al. 2015).
Despite the significant impact on quality of life and sexual health, genital psoriasis is often not
discussed by patients (AAD Work Group et al. 2011; Meeuwis et al. 2012; Andreassi and 
Bilenchi 2014), and health care professionals do not routinely question or examine patients for 
its presence in clinical practice (Farber and Nall 1992; AAD Work Group et al. 2011).  While 
patients with genital psoriasis often do not discuss their symptoms with health care providers, 
many patients report actively treating their genital lesions (Meeuwis et al. 2012).  Therefore, this 
may indicate a risk of self-treatment in the genital area using medications that were originally 
prescribed for treatment of other body locations.  Inappropriate self-treatment has the potential to 
result in less than optimal or over-treatment (for example, with potent corticosteroids) and 
significant adverse reactions.  Although genital psoriasis appears to be pathophysiologically 
identical to plaque psoriasis in other skin regions, the skin in this area is highly sensitive and at 
increased risk of adverse reactions to topical treatments (CDA 2009 [WWW]; Meeuwis et al. 
2011a; Guglielmetti et al. 2012).  Moreover, currently available topical agents may not offer an
optimal or even appropriate level of clinical improvement or tolerability, especially for patients 
with moderate-to-severe genital psoriasis.  Weaker potency corticosteroids often have limited 
efficacy for use in maintenance treatment (Welsh et al. 2003), and the use of higher potency

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corticosteroids is limited due to the development of skin atrophy and striae (Linden and
Weinstein 1999). Irritation is commonly reported with vitamin D analogs (Scott et al. 2001;
Mason et al. 2013), and they may not be tolerated in the genital region (CDA 2009 [WWW]). 
Topical calcineurin inhibitors such as pimecrolimus and tacrolimus may improve genital 
psoriasis but can cause irritancy or a burning sensation, are not helpful in many patients (Menter
et al. 2009; Meeuwis et al. 2011[a]), and are not indicated for the treatment of psoriasis. Beyond
such topical therapies, there is rather limited evidence for viable therapeutic options to 
adequately manage genital psoriasis. For instance, psoralen and ultraviolet A (PUVA) and 
narrowband ultraviolet B (UVB) are not advised for use in the genital region due to potential 
carcinogenic adverse effects (Stern et al. 1990; Stern et al. 1994; Stern et al. 2002).
Currently, there are limited data from clinical trials, particularly well-controlled therapeutic 
interventional studies, which measure the efficacy of treatments for genital psoriasis.  To date, 
the only published treatment studies of genital psoriasis include open-label studies of topical 
treatments (Jemec and Baadsgaard 1993; Rallis et al. 2005; Martín Ezquerra et al. 2006; 
Bissonnette et al. 2008), a recent open-label study of a stepwise treatment algorithm (Meeuwis et 
al. 2015), and scattered case reports.  
2.2.
Study Rationale
Ixekizumab (LY2439821) is a humanized immunoglobulin G subclass 4 (IgG4) monoclonal
antibody designed and engineered to selectively inhibit interleukin-17A (IL-17A).  It binds with 
high affinity (<3 pM) and specificity to IL-17A, a proinflammatory cytokine. Neutralization of 
IL-17A by ixekizumab has been shown to reduce excess keratinocyte proliferation and activation
(Krueger et al. 2012). Ixekizumab does not bind to ligands IL-17B, IL-17C, IL-17D, IL-17E, or
IL-17F.  
Phase 3 clinical trials of ixekizumab therapy were completed in patients with moderate-to-severe 
plaque psoriasis with percentage of body surface area (BSA) ≥10%. Ixekizumab was highly 
efficacious in these trials as evidenced by over 80% of patients achieving at least a 75% 
reduction in their Psoriasis Area and Severity Index (PASI) from baseline (PASI 75) and over 
one-third having complete resolution of psoriatic plaques (PASI 100) by Week 12 using a dosing 
regimen of 80 mg every 2 weeks following a 160-mg starting dose (Griffiths et al. 2015).  In 
addition, patients with moderate-to-severe plaque psoriasis who were treated with ixekizumab in
these studies reported significant improvements as early as Week 2 in sexual difficulties 
compared to placebo as measured by Question 9 of the DLQI.  Thus, it is likely that ixekizumab 
is effective in the genital region in patients with a baseline BSA ≥10% and may lead to 
improvement in sexual function in these patients.  The most significant unmet medical need is in
patients with BSA <10% who have moderate-to-severe genital psoriasis and limited treatment 
options because of the limitations of topical and phototherapy treatments for genital psoriasis
described in Section 2.1.
Based on the Phase 3 psoriasis clinical trial outcomes, ixekizumab therapy in patients with
moderate-to-severe genital psoriasis could address an unmet patient need and a clinical research 
gap identified by the dermatology communityand the American Academy of Dermatology Psoriasis 

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Guidelines of Care Working Group (Ryan et al. 2014). One subcutaneous (SC) ixekizumab regimen 
will be explored:  a 160-mg starting dose followed by 80 mg every 2 weeks (Q2W) for 12 weeks, 
and then 80 mg every 4 weeks (Q4W) with the opportunity to step up to Q2W (Section 6.1).  The 
efficacy and safety profile of this ixekizumab dosing regimen was established in previous 
Phase 3 clinical studies of patients with moderate-to-severe plaque psoriasis.

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3.
Objectives and Endpoints
Table RHBQ.3.1 shows the objectives and endpoints of the study.
Table RHBQ.3.1.
Objectives and Endpoints
Objectives
Endpoints
Primary Objective
Primary Endpoint

To assess whether 80 mg ixekizumab Q2W is 
superior to placebo at Week 12 in the treatment of 
patients with moderate-to-severe genital psoriasis as 
measured by sPGA of Genitalia (0,1)

The proportion of patients achieving sPGA of 
Genitalia (0,1) at Week 12
Major Secondary Objective
Major Secondary Endpoint

To assess whether 80 mg ixekizumab Q2W is 
superior to placebo at Week 12 in the treatment of 
patients with moderate-to-severe genital psoriasis as 
measured by change in itch, utilizing a modified 
genital psoriasis itch NRS item within the GPSS

Mean change from baseline in the genital 
psoriasis itch NRS item within the GPSS at Week 
12
Other Secondary Objectives
Other Secondary Endpoints

To assess whether 80 mg ixekizumab Q2W is 
superior to placebo at Week 12 in the treatment of 
patients with moderate-to-severe genital psoriasis as 
measured by change in impact of genital psoriasis 
on sexual activity, utilizing the GPSIS, Sexual 
Activity Avoidance Subscale

The proportion of patients with at least a 2-point 
improvement from baseline to Week 12 in the 
GPSIS, Sexual Activity Avoidance Subscale

To assess whether 80 mg ixekizumab Q2W is 
superior to placebo at Week 12 in the treatment of 
patients with moderate-to-severe genital psoriasis as 
measured by change in frequency of sexual activity 
due to genital psoriasis, utilizing the SFQ item 2

The proportion of patients with at least a 2-point 
improvement from baseline to Week 12 in the 
SFQ item 2

To assess whether 80 mg ixekizumab Q2W is 
superior to placebo at Week 12 in the treatment of 
patients with moderate-to-severe genital psoriasis as 
measured by change in mGPASI 

Mean change from baseline in mGPASI at 
Week 12

To assess whether 80 mg ixekizumab Q2W is 
superior to placebo at Week 12 in the treatment of 
patients with moderate-to-severe genital psoriasis as 
measured by overall sPGA (0,1)

The proportion of patients achieving overall 
sPGA (0,1) at Week 12

To assess whether 80 mg ixekizumab Q2W is 
superior to placebo at Week 12 in the treatment of 
patients with moderate to severe genital psoriasis as 
measured by the following health outcomes 
measures:
o
PatGA-Genital
o
The proportion of patients with at least a 2-point 
improvement from baseline to Week 12 in 
PatGA-Genital

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Objectives
Endpoints
o
DLQI

Total score

Item 9

DLQI (0,1)

Mean change from baseline in DLQI total 
score at Week 12

Mean change from baseline in DLQI Item 
9 score at Week 12

The proportions of patients achieving 
DLQI (0,1)
o
SF-36
o
Mean change from baseline on the SF-36 PCS 
and MCS at Week 12
o
GPSS 

Total score

Individual items other than itch
o
Mean change from baseline to Week 12 in

GPSS total score and 

individual items (other than itch)

Evaluate the incidence of anti-ixekizumab 
antibodies and its relationship to patient efficacy of 
ixekizumab at Week 12

The proportion of patients achieving sPGA of 
Genitalia (0,1) at Week 12 by TE-ADA status and 
by NAb status

Time course of response to treatment as measured 
by sPGA of Genitalia (0,1)

The proportion of patients who achieve sPGA of 
Genitalia (0,1) over time through Week 52

Time course of response to treatment as measured 
by mGPASI

Mean change in mGPASI over time through
Week 52
Exploratory Objectives
Exploratory Endpoints

To assess whether 80 mg ixekizumab Q2W is 
superior to placebo at Week 12 in the treatment of 
genital psoriasis patients with baseline BSA ≥10%
as measured by overall PASI

Mean change from baseline in overall PASI at 
Week 12

To assess whether 80 mg ixekizumab Q2W is 
superior to placebo at Week 12 in genital psoriasis 
patients with baseline BSA ≥10% as measured by 
overall PASI 75/90/100

The proportion of patients achieving overall 
PASI 75/90/100 at Week 12 

To assess whether 80 mg ixekizumab Q2W is 
superior to placebo at Week 12 in patients with 
moderate-to-severe genital psoriasis as measured 
by:
o
sPGA of Genitalia (0)
o
overall sPGA (0)

The proportion of patients achieving 
o sPGA of Genitalia (0) at Week 12
o overall sPGA (0) at Week 12

To explore whether there is any impact of 
Fitzpatrick Skin Type on improvement measured by 
sPGA of Genitalia (0,1) response at Week 12

Association between Fitzpatrick Skin Type 
(reported at baseline) and sPGA of Genitalia (0,1)
response at Week 12

To assess whether 80 mg ixekizumab Q2W is 
superior to placebo at Week 12 in the treatment of 
patients with moderate to severe genital psoriasis as 
measured by:

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Objectives
Endpoints
o
GPSIS, Impact of Sexual Activity on Genital 
Psoriasis Symptoms Subscale for patients 
who reported being sexually active at 
baseline (score of “0” on GPSIS Question 1)
o The proportion of patients with at least a 
2-point improvement from baseline to Week 12
in the GPSIS, Impact of Sexual Activity on 
Genital Psoriasis Symptoms Subscale for 
patients who reported a score of “0” on GPSIS 
Question 1 at baseline.
o
SFQ item 1
o The proportion of patients at each level of SFQ 
item 1
o
CAPP Genital subindex
o Mean change from baseline in the total CAPP 
Genital subindex score
o
Touch Avoidance NRS
o Mean change from baseline in the Touch 
Avoidance NRS

To explore the impact of ixekizumab versus 
placebo at Week 12 on the change in presence or 
absence of fissure, ulcer, and/or erosion in the 
genital area and its association with measures of 
quality of life

The proportion of patients with presence or 
absence of genital fissure, ulcer, and/or erosion
and the association of absence/presence with 
measures of quality of life (SF-36 MCS, DLQI, 
GPSIS Subscales, and SFQ items) in the subgroup 
of patients with fissure, ulcer, and/or erosion

To explore the impact of ixekizumab versus 
placebo at Week 12 on the change in presence or 
absence of psoriasis in perianal/gluteal cleft area (as 
indicated by the investigator in the case report 
form) and its association with measures of quality 
of life

The proportion of patients with presence or 
absence of perianal/gluteal cleft psoriasis and the 
association of absence/presence with measures of 
quality of life (SF-36 MCS, DLQI, GPSIS 
Subscales, and SFQ items) in the subgroup of 
patients with psoriasis located in perianal area 

To explore the impact of ixekizumab versus 
placebo at Week 12 on the change in presence or 
absence of psoriasis on the face and its association 
with measures of quality of life

The proportion of patients with presence or 
absence of facial psoriasis and the association of 
absence/presence with measures of quality of life 
(SF-36 MCS, DLQI, and SFQ items) in the 
subgroup of patients with psoriasis located on the
face

To explore long-term impact of ixekizumab on 
symptoms and quality of life through Week 52

The change over time through Week 52 in DLQI, 
SF-36 MCS, GPSS items, GPSIS Subscales, and 
SFQ items

To assess the psychometric properties (including 
reliability, validity, and responsiveness) of the 
GPSS, GPSIS, SFQ, and sPGA of Genitalia

Test-retest reliability, construct validity, and 
responsiveness will be assessed by ICCs, Pearson 
correlation/Spearman rank-based correlation 
coefficient, and correlations of calculated changes 
in scores, respectively, or as deemed appropriate

To measure ixekizumab exposure and assess the 
relationship between exposure and efficacy, and 
exposure and immunogenicity

Serum trough concentrations of ixekizumab

Model parameters for the exposure-response 
relationship between ixekizumab serum trough 
concentrations and efficacy endpoints

Ixekizumab serum trough concentrations 
associated with ADA titer subgroups

To explore biomarkers that are predictive of 
response to ixekizumab treatment that may be 
contained in DNA, RNA, serum, or plasma samples

Association between biomarker and ixekizumab 
response

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Abbreviations:  ADA = anti-drug antibodies; BSA = body surface area; CAPP = Comprehensive Assessment of the 
Psoriasis Patient; DLQI = Dermatology Life Quality Index; DLQI (0,1) = DLQI total score of 0 and 1;
DNA = deoxyribonucleic acid; GPSIS = Genital Psoriasis Sexual Impact Scale; GPSS = Genital Psoriasis 
Symptom Scale; ICC = intraclass correlation coefficients; MCS = mental component summary;
mGPASI = modified Genital PASI; NAb = neutralizing anti-drug antibody; NRS = Numeric Rating Scale; 
PASI = Psoriasis Area and Severity Index; PASI 75/90/100 = 75/90/100% improvement from baseline in the 
PASI; PatGA-Genital = Patient’s Global Assessment of Genital Psoriasis; PCS = physical component summary; 
Q2W = every 2 weeks; SF-36 = 36-Item Short-Form Health Survey; SFQ = Sexual Frequency Questionnaire; 
RNA = ribonucleic acid; sPGA of Genitalia = static Physician Global Assessment of Genitalia; 
TE-ADA = treatment-emergent anti-drug antibody.

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4.
Study Design
4.1.
Overview of Study Design
Study I1F-MC-RHBQ (RHBQ) is a Phase 3, multicenter, randomized, double-blind, 
placebo-controlled, parallel-group, outpatient study examining the efficacy and safety of
ixekizumab as compared to placebo in patients with moderate-to-severe genital psoriasis.  The 
study consists of 4 periods:

Period 1: Screening Period (Visit 1 and Visit 1A) will assess patient eligibility and start 
e-diary data collection, occurring approximately 7 to 30 days prior to Period 2 (baseline; 
Week 0; Visit 2).

Period 2: Blinded Treatment Period will occur from Week 0 (Visit 2) up to Week 12 
(Visit 7).  Patients will be randomized to ixekizumab or placebo in a 1:1 ratio.  
Two injections of ixekizumab 80 mg SC (total dose of 160 mg) or 2 injections of placebo 
SC, respectively, will be given at Week 0 (Visit 2).  From Week 2 through Week 10 
patients will receive ixekizumab 80 mg Q2W SC or placebo Q2W SC (Section 6.1).

Period 3: Open-Label Treatment Period will occur from Week 12 (Visit 7) up to
Week 52 (Visit 12).  At Week 12 (Visit 7) 1 injection of ixekizumab 80 mg SC and 1 
injection of placebo SC (total dose of ixekizumab 80 mg) will be given to patients who 
were randomized to ixekizumab in Period 2; and 2 injections of ixekizumab 80 mg SC
(total dose of ixekizumab 160 mg) will be given to patients who were randomized to 
placebo in Period 2.  During the remainder of Period 3, patients will receive ixekizumab 
80 mg Q4W dosing with an option to step-up to Q2W dosing starting at Week 24 through 
Week 40 (at Visit 9 [Week 24], Visit 10 [Week 28], or Visit 11 [Week 40]) (Section 6.1).  
This open-label period will allow evaluation of long-term efficacy and safety of 
ixekizumab through 1 year (52 weeks).

Period 4: Post-Treatment Follow-Up (Visit 801 through Visit 803) is for safety 
monitoring after treatment discontinuation for any patient receiving at least 1 dose of 
investigational product.  Once patients complete study treatment or discontinue study 
treatment early, patients will complete the Post-Treatment Follow-Up (Period 4). This 
period occurs from the last treatment period visit or early termination visit (ETV) up to a 
minimum of 12 weeks following that visit.
Figure RHBQ.4.1 illustrates the study design, and all treatment groups and administration of the 
investigational product are described in Section 6.1. The study drug administration log (SDAL) 
is described in Section 6.2.1. 
All procedures to be conducted during the study, including timing of all procedures, are indicated 
in the Schedule of Activities (Appendix 2).  Selected study procedures should be performed prior 
to administration of the investigational product, as applicable.  Appendix 3 lists 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 will continue to the ETV prior to 
proceeding to the Post-Treatment Follow-Up Period (Period 4).  For the management of patient 

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safety, all patients should be monitored through the Post-Treatment Follow-Up Period at least as 
frequently as indicated on the Schedule of Activities (Appendix 2).
Excluded and restricted therapies are detailed in Section 6.8.
Pharmacokinetic (PK) sampling is detailed in Section 8.5.
Section 9.9 outlines the information regarding the interim analyses including the primary 
database lock at Week 12.
Figure RHBQ.4.1 illustrates the study design.

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Abbreviations:  inj = injection; LV = date of last visit; LY = LY2439821(ixekizumab); n = number of patients; pt = patient; PBO = 
placebo; Q2W = every 2 weeks; Q4W = every 4 weeks; SC = subcutaneous; V = visit; W = study week.
a  Patients who discontinue the study for any reason and who have received at least 1 dose of investigational product will continue 
to Early Termination Visit before entering the Post-Treatment Follow-Up Period.
b  All patients who increase dosing from 80 mg Q4W to 80 mg Q2W will remain on Q2W until completion of the study (W52 or 
early discontinuation) (Section 6.1).
Figure RHBQ.4.1.
Illustration of study design for Clinical Protocol I1F-MC-RHBQ.

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4.2.
End of Trial Definition
End of the trial is the date of the last visit or last scheduled procedure shown in the Schedule of 
Activities (Appendix 2) for the last patient.
4.3.
Scientific Rationale for Study Design
Study RHBQ includes a blinded treatment period (Period 2) and an open-label treatment period 
(Period 3) to determine the efficacy and safety of ixekizumab.  During the 12-week blinded 
treatment period, ixekizumab Q2W is compared to placebo Q2W, while during the 40-week 
open-label treatment period, patients are treated with ixekizumab Q4W.  These period durations 
were chosen based on Phase 3 pivotal clinical studies in moderate-to-severe plaque psoriasis.  
The 12-week blinded treatment period will allow for the assessment of the response of moderate-
to-severe genital psoriasis to treatment with ixekizumab while limiting exposure to placebo 
treatment.
The efficacy of ixekizumab will be primarily assessed at Week 12, using the static Physician 
Global Assessment (sPGA) of Genitalia.  In addition, efficacy at Week 12 will be assessed using 
outcome measures such as the modified Genital PASI (mGPASI) as well as the e-diary to assess 
symptoms and impact of genital psoriasis using the Genital Psoriasis Symptom Scale (GPSS), 
Genital Psoriasis Sexual Impact Scale (GPSIS), and Sexual Frequency Questionnaire (SFQ).
All patients will begin ixekizumab 80 mg Q4W at Week 12 to assess the efficacy and safety of 
ixekizumab treatment over the total 52-week period.  During the Open-Label Treatment Period 
(Period 3), patients may ‘step-up’ in dosing frequency from ixekizumab 80 mg Q4W to Q2W in 
order to achieve or maintain a sufficient level of efficacy (Section 6.1).  
4.4.
Justification for Dose 
The ixekizumab dosing regimen of ixekizumab 80 mg Q2W for 12 weeks (starting dose 160 mg) 
and ixekizumab 80 mg Q4W for 40 weeks was chosen based on results from the pivotal Phase 3 
studies which provided safety and efficacy data for Q2W/Q4W dosing and Q4W/Q4W dosing 
following an initial dose of 160 mg.  These studies did not evaluate Q2W dosing beyond 
12 weeks; however, continuous Q2W dosing is being evaluated in an ongoing study,
I1F-MC-RHBP. 
As no treatment to date has been demonstrated to be effective and safe for the treatment of 
moderate-to-severe genital psoriasis in a controlled trial, placebo will be included as the 
comparator.
Study RHBQ is designed to assess the efficacy and safety profile of the Q2W regimen in the first 
12 weeks (Blinded Treatment Period, Period 2) in patients with genital psoriasis.  In addition, the 
study will collect long-term safety data for patients taking Q4W in the Open-Label Treatment 
Period (Period 3), as well as for those initially taking Q4W who increase dose frequency to Q2W 
of ixekizumab during the Open-Label Treatment Period (Period 3) if they do not achieve or 
maintain satisfactory disease control (Section 6.1).  

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4.5.
Benefit/Risk Assessment
More information about the known and expected benefits, risks, serious adverse events (SAEs) 
and reasonably anticipated adverse events (AEs) of ixekizumab are to be found in the 
Investigator’s Brochure (IB).  

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5.
Study Population
The study population will include patients with moderate-to-severe genital psoriasis who have 
given written informed consent approved by Eli Lilly and Company (Lilly), or its designee, and 
the ethical review board (ERB)/institutional review board (IRB) governing the site.
Study investigator(s) will review patient records and screening test results from Visit 1, Visit 1A 
(as applicable for purified protein derivative [PPD] read), and Visit 2 to determine if the patient 
meets all inclusion and exclusion criteria to qualify for participation in the study as noted in 
Section 5.1and Section 5.2, respectively.  All screening activities must be completed and 
reviewed before the patient is randomized.  Individuals who do not meet study entry criteria 
(screen failure) may be rescreened as described in Section 5.3.
Study participants should be instructed not to donate blood or blood products during the study.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, are not permitted.
5.1.
Inclusion Criteria
Patients are eligible to be included in the study only if they meet all of the following criteria prior 
to randomization as indicated below:
Type of Patient and Disease Characteristics
[1]
Present with chronic plaque psoriasis based on a diagnosis of chronic plaque 
psoriasis for at least 6 months before baseline (Week 0; Visit 2), as 
determined by the investigator
[2]
Are candidates for phototherapy and/or systemic therapy
[3]
Have an overall sPGA ≥3 at screening (Visit 1) and at baseline (Week 0, 
Visit 2)
[4]
Have sPGA of Genitalia ≥3 at screening (Visit 1) and at baseline (Week 0, 
Visit 2)
[5]
Have BSA involvement of ≥1% at screening (Visit1) and at baseline (Week 0, 
Visit 2)
(Note:  The majority of patients will be required to have BSA involvement 
≥10% and up to approximately 40% of patients will be allowed to have BSA 
involvement of 1 to <10%.  Enrollment will be closely monitored, and 
enrollment in this lower BSA subpopulation will be stopped if a maximum of 
40% is reached.)
[6]
Have confirmation of plaque psoriasis in a nongenital area at screening 
(Visit1) and baseline (Week 0, Visit 2)

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[7]
Have failed to respond to, or are intolerant of, at least 1 topical therapy
(corticosteroids, calcineurin inhibitors and/or vitamin D analogs) used for 
treatment of psoriasis affecting the genital area
Patient Characteristics 
[8]
Are male or female patients of 18 years or older
[9]
Must agree to use reliable method of birth control:

If a male patient, agree to use a reliable method of birth control during the
study and for at least 12 weeks following the last dose of investigational 
product.  Examples of reliable methods include abstinence, vasectomy, and 
male condom with spermicide.
OR

If a female patient of childbearing potential, must test negative for pregnancy 
and agree to use a reliable method of birth control during the study and for at 
least 12 weeks following the last dose of investigational product.  Methods of 
contraception considered acceptable include abstinence, oral contraceptives, 
contraceptive patch, intrauterine device, vaginal ring, diaphragm with 
contraceptive gel, or condom with contraceptive gel.
OR

For nonchildbearing potential female patients, patients must be:  
Women who have had surgical sterilization (hysterectomy, bilateral 
oophorectomy, or tubal ligation)
OR
Women who are ≥60 years of age
OR
Women who are ≥40 and <60 years of age who have had a cessation of 
menses for ≥12 months and a follicle-stimulating hormone (FSH) test 
confirming nonchildbearing potential (≥40 mIU/mL)
Informed Consent
[10] Are able and have given written informed consent approved by Lilly, or its 
designee, and the IRB/ ERB governing the site
5.2.
Exclusion Criteria
Patients will be excluded from study enrollment if they meet any of the following criteria prior to 
randomization as indicated below:

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Medical Conditions
[11] Have predominant pattern of pustular, erythrodermic, and/or guttate forms of 
psoriasis
[12] Have pustules or vesicles in the genital area
[13] Have a history of drug-induced psoriasis
Prior/Concomitant Therapy
[14] Have received systemic nonbiologic psoriasis therapy or phototherapy within 
4 weeks of baseline (Week 0, Visit 2), or have had topical psoriasis treatment 
within 2 weeks of baseline (Week 0, Visit 2) as specified in Table RHBQ.6.2.
Exceptions (see Table RHBQ.6.2):

mild corticosteroids will be permitted for use limited to the face and/or 
axilla
[15] Cannot avoid excessive sun exposure or use of tanning booths for at least 
4 weeks prior to baseline (Week 0, Visit 2) and during the study, per 
investigator assessment
[16] Concurrent or recent use of any biologic agent within the following periods 
prior to baseline (Week 0, Visit 2): etanercept <28 days; infliximab or 
adalimumab <60 days; golimumab <90 days; ustekinumab <8 months; 
rituximab <12 months; or any other biologic agent <5 half-lives
[17] Have ever received natalizumab or other agents that target alpha-4 integrin
[18] Have ever received treatment with IL-17 antagonists such as ixekizumab, 
secukinumab, or brodalumab
Vaccinations
[19] Had a live vaccination within 12 weeks prior to baseline (Week 0, Visit 2), 
intend to have a live vaccination during the course of the study or within 
12 weeks of completing treatment in this study, or have participated in a 
vaccine clinical study within 12 weeks prior to baseline. Investigators should 
review the vaccination status of their patients and follow the local guidelines 
for adult vaccination with nonlive vaccines intended to prevent infectious 
disease prior to therapy.
(Note:  Killed/inactive or subunit vaccines are expected to be safe; however, 
their efficacy with concomitant ixekizumab treatment is unknown.)
[20] Had a vaccination with Bacillus Calmette-Guérin (BCG) within 12 months 
prior to baseline (Week 0, Visit 2) or intend to have vaccination with BCG 
during the course of the study or within 12 months of completing treatment in 
this study

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Medical Status and Medical History
[21] Have a known allergy or hypersensitivity to any biologic therapy that would, 
in the opinion of the investigator, pose an unacceptable risk to the patient if 
participating in this study
[22] Have current or a history of lymphoproliferative disease or signs or symptoms 
of lymphoproliferative disease within 5 years prior to baseline (Week 0; Visit 
2); or have active or history of malignant disease within 5 years prior to 
baseline (Week 0; Visit 2)  
(Note:  Patients with history of malignancy with no evidence of recurrence or 
active disease within the 5 years prior to baseline may participate in the 
study.)
[23] Had any major surgery within 8 weeks prior to baseline (Week 0, Visit 2) or 
will require such during the study that, in the opinion of the investigator in 
consultation with Lilly or its designee, would pose an unacceptable risk to the 
patient
[24] Presence of significant uncontrolled respiratory, hepatic, renal, gastrointestinal
(including Crohn’s disease or ulcerative colitis), endocrine, hematologic
(including a history of bleeding disorder), neurologic, or neuropsychiatric 
disorders that would, in the opinion of the investigator, pose an unacceptable 
risk to the patient if participating in the study or of interfering with the 
interpretation of data
[25] Presence of significant uncontrolled cerebrocardiovascular (for example, 
myocardial infarction [MI], unstable angina, unstable arterial hypertension, 
moderate to severe [New York Heart Association (NYHA) class III/IV] heart 
failure, or cerebrovascular accident [CVA]) that would, in the opinion of the 
investigator, pose an unacceptable risk to the patient if participating in the 
study or of interfering with the interpretation of data
[26] Have electrocardiogram (ECG) abnormalities that are considered clinically 
significant and would pose an unacceptable risk to the patient if participating 
in the study, in the opinion of the investigator
[27] Have uncontrolled arterial hypertension characterized by a systolic blood 
pressure (BP) >160 mm Hg or diastolic BP >100 mm Hg at screening 
(Visit 1) or at baseline randomization (Week 0, Visit 2)
(Note:  If an initial BP reading exceeds this limit, the BP may be repeated 
once after the patient has rested sitting for ≥10 minutes.  If the repeat value is 
less than the criterion limits, the second value may be accepted.)
[28] Have had fluid overload, MI, or new onset ischemic heart disease (for 
example, unstable angina), uncompensated heart failure, or in the opinion of 
the investigator other serious cardiac disease within 12 weeks prior to baseline 
(Week 0; Visit 2)

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[29] Recent history of a suicide attempt (≤30 days), have a score of 3 on Item 12 
(Thoughts of Death or Suicide) of the Quick Inventory of Depressive 
Symptomatology–Self Report (16 items) (QIDS-SR16) at screening (Visit 1) 
or baseline (Week 0; Visit 2), or are clinically judged by the investigator to be 
at risk for suicide
[30] Have evidence or suspicion of active or latent tuberculosis (TB) (refer to 
Section 8.4.5 for details on determining full TB exclusion criteria)
[31] Are positive for human immunodeficiency virus serology (HIV; positive for 
human immunodeficiency virus antibody [HIVAb])
[32] Have evidence of or test positive for hepatitis B virus (HBV) by testing:  1)
positive for hepatitis B surface antigen (HBsAg+) OR 2) positive for 
anti-hepatitis B core antibody (HBcAb+) and are HBV DNA positive
(Note: Patients who are HBcAb+ and HBV DNA negative may be enrolled in 
the study. Patients who meet these criteria at screening will be identified by 
the central laboratory and monitored during the study as detailed in
Section 8.4.9.2.)
[33] Have evidence of or test positive for hepatitis C virus (HCV).  A positive test 
for HCV is defined as:  1) positive for hepatitis C antibody (anti-HCVAb) and 
2) positive via a confirmatory test for HCV (for example, HCV polymerase 
chain reaction).
[34] Have a body temperature ≥38°C (100.5°F) at baseline (Week 0; Visit 2); these 
patients may be rescreened (1 time) ≥4 weeks after documented resolution of 
elevated temperature.  Body temperature will be determined via tympanic or 
oral methods.
Infections
[35] Had a serious infection (for example, pneumonia, cellulitis), have been 
hospitalized, or have received intravenous (IV) antibiotics for an infection 
within 12 weeks prior to baseline (Week 0, Visit 2); or had a serious bone or 
joint infection within 24 weeks prior to baseline; or 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
[36] Have or had an infection typical of an immunocompromised host and/or that 
occurs with increased incidence in an immunocompromised host (including, 
but not limited to, Pneumocystis jirovecii pneumonia, histoplasmosis, or 
coccidioidomycosis) or have a known immunodeficiency
[37] Have or had a herpes zoster or any other clinically apparent varicella-zoster 
virus infection within 12 weeks of baseline (Week 0, Visit 2)

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[38] Have any other active or recent infection within 4 weeks of baseline (Week 0, 
Visit 2) that, in the opinion of the investigator, would pose an unacceptable 
risk to the patient if participating in the study; these patients may be 
rescreened (1 time) ≥4 weeks after documented resolution of symptoms.
[39] Have, or currently receiving treatment for, active candidiasis or tinea in the 
genital area.  Patients with active candidiasis or tinea in the genital area may 
be treated and rescreened (1 time) ≥4 weeks after documented resolution of 
symptoms.
(Note: Investigator may clinically assess for active infection as needed using 
potassium hydroxide [KOH] preparation tests or other methodology per local 
procedures.)
Prior/Concurrent Clinical Trial Experience
[40] Are currently enrolled in any other clinical trial involving an investigational 
product or any other type of medical research judged not to be scientifically or 
medically compatible with this study
[41] Have previously completed or withdrawn from this study or participated in 
any other study with ixekizumab, or have participated in any study 
investigating other IL-17 antagonists
[42] Are currently enrolled in, have participated, or discontinued from a clinical 
trial involving an investigational product or nonapproved use of a drug or 
device within the last 30 days or a period of at least 5 half-lives of the last 
administration of the drug, whichever is longer, or concurrently enrolled in 
any other type of medical research judged not to be scientifically or medically 
compatible with this study (eg, observational study requiring blood draws, 
biopsies, and/or other interventional monitoring procedures)
Diagnostics Assessments
Laboratory tests should not be repeated unless there is a technical error or clinical 
reasons to believe a result may be erroneous (except for exclusion criteria 
[46]).
[43] At screening, have a neutrophil count <1500 cells/μL (<1.50x103/µL or 
<1.50 GI/L)  
[44] At screening, have a lymphocyte count <800 cells/μL (<0.80x103/µL or 
<0.80 GI/L)  
[45] At screening, have a platelet count <100,000 cells/μL (<100x103/µL or 
<100 GI/L)  
[46] At screening, have aspartate aminotransferase (AST) or alanine 
aminotransferase (ALT) >2.5 times the upper limit of normal (ULN)

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(Note:  The AST and ALT may be repeated once within a week if the initial 
response exceeds this limit, and the repeat value may be accepted if it meets 
this criterion.)
[47] At screening, have a total white blood cell (WBC) count <3000 cells/μL 
(<3.00x103/µL or <3.00 GI/L) 
[48] At screening, have hemoglobin <8.5 g/dL (85.0 g/L) for male patients and 
<8.0 g/dL (80 g/L) for female patients 
[49] Have other clinical laboratory test results at screening that are outside the 
normal reference range for the population and are considered clinically 
significant, per investigator assessment 
Other Exclusions
[50] Have donated more than 1 unit (approximately 450 mL) of blood within the 
last 4 weeks prior to screening (Visit 1) or intend to donate blood during the 
course of the study.  These patients may be rescreened (1 time) to allow the 
required 4-week minimum time since donation of more than 1 unit of blood.
[51] Are women who are lactating or breast feeding
[52] Have any other condition that precludes the patient from following and 
completing the protocol, in the opinion of the investigator
[53] 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.
[54] Are Lilly employees or its designee or are employees of third-party 
organizations (TPOs) involved in the study
[55] Are unwilling or unable to comply with the use of a data collection device to 
directly record data from the subject
5.3.
Screen Failures
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened in the following circumstances: Patients who test positive for latent TB at screening 
may be rescreened following appropriate treatment as described in Section 8.4.5; patients who do 
not qualify at screening under exclusion criteria [34], [38], or [39] may be rescreened once, 4 or 
more weeks after documented resolution of symptoms.  Patients who do not qualify at screening 
under exclusion criterion [50] may be rescreened once to allow the required 4-week minimum 
time since donation of more than 1 unit of blood.  When rescreening is performed, the individual 
must sign a new informed consent form (ICF) and will be assigned a new identification number.  
Additionally, all screening procedures must be conducted to ensure all eligibility criteria are met.
5.4.
Lifestyle and/or Dietary Requirements
See inclusion criterion [9] in Section 5.1 for birth control requirements.

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6.
Treatment
6.1.
Treatments Administered
The Blinded Treatment Period (Period 2) involves a comparison of ixekizumab 80 mg Q2W 
(starting dose of 160 mg) and placebo Q2W. All doses are administered via SC injection. 
All patients assigned to ixekizumab 80 mg Q2W regimen will receive a starting dose of 160 mg 
ixekizumab as 2 SC injections.  The placebo group will receive 2 SC injections of placebo at this 
visit as well, to maintain the blind.
For training purposes, the starting dose of 160 mg (two 80-mg SC injections) will be 
administered at the clinic at Week 0 (Visit 2).  The first injection will be administered by clinical 
staff, and the second injection will be administered by the patient or the patient’s caregiver while 
under supervision of clinical staff.  Subsequent injections of investigational product will be 
administered by the patient or the patient’s caregiver unsupervised by the clinical staff, 
regardless of whether there is a study visit scheduled except at Visit 7 (Week 12). At Visit 7 
(Week 12), the 2 injections will be administered by the patient or the patient’s caregiver 
supervised by the clinical staff to allow for vital sign monitoring (Section 8.4.2).  It is 
recommended that all subsequent injections be administered outside the trial site, preferably at 
the patient’s home.
A dose of investigational product will consist of 1 SC injection of ixekizumab or placebo.  
Possible injection sites include the abdomen (upper left, upper right, lower left, or lower right 
quadrant [with the umbilicus being the center]), left or right thigh, and left or right upper arm.  If 
the upper arm is utilized as the injection site, the injection must be administered by a caregiver.  
The injection site should not be in a psoriatic lesion.  On days when multiple injections will be 
administered, the injection sites should be in different areas (note the abdomen has 4 possible 
injection areas).
At Week 12, during the Open-Label Treatment Period (Period 3), all patients will be reassigned 
to ixekizumab 80 mg Q4W.  Patients originally assigned to placebo will receive a blinded
ixekizumab starting dose of 160 mg as 2 SC injections.  To maintain blinding, patients originally 
assigned to ixekizumab 80 mg Q2W will receive a blinded ixekizumab 80-mg dose and a 
placebo dose at Week 12.  Dosing may be increased in the Open-Label Treatment Period
(Period 3) to ixekizumab 80 mg Q2W, starting at Week 24 through Week 40 (at Visit 9 
[Week 24], Visit 10 [Week 28], or Visit 11 [Week 40]), if the patient is eligible to receive 
additional investigational product (that is, if it is determined by the patient and the investigator 
that the patient needs additional ixekizumab in order to achieve or maintain satisfactory disease 
control).  All patients who increase dosing to 80 mg Q2W will remain on this dose until 
completion of the treatment period or early discontinuation.  Table RHBQ.6.1 shows the 
treatment regimens.  If patients remain on ixekizumab 80 mg Q4W, their last dose will occur at 
Week 48.  If patients step up to ixekizumab 80 mg Q2W, their last dose will occur at Week 50.
Treatment received during the Blinded Treatment Period (Period 2) will remain blinded to 
investigators, study site personnel, and patients until all patients have completed Week 52

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(Visit 12) or have discontinued from the study (moved into Post-Treatment Follow-Up 
[Period 4]).
The investigator or his/her designee is responsible for the following:

explaining the correct use of the investigational product to the patient/patient caregiver

verifying that instructions are followed properly

maintaining accurate records of investigational product dispensing, collection, and 
administration

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 he or she has a 
complaint or problem with the investigational product so that the situation can be assessed.
Further instructions and special considerations for the administration of the investigational 
product are provided in Sections 6.2.1 and 6.6.1.

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Table RHBQ.6.1.
Treatment Regimens
Randomized Treatment 
Arm
Dose
Week 0 (Day 1)
Dose
Week 2 to Week 10 
Dose
Week 12
Dose
Week 16 to Week 50a
Blinded Dosing
Open-Label Dosing
Ixekizumab
80 mg 
2 ixekizumab 80-mg 
injections
1 ixekizumab 80-mg 
injection Q2W 
1 ixekizumab 80-mg 
injection
1 placebo injection 
1 ixekizumab 80-mg injection 
Q4W with Q2W step-up as 
neededb
Placebo 
2 placebo injections
1 placebo injection Q2W
2 ixekizumab 80-mg 
injections 
1 ixekizumab 80-mg injection 
Q4W with Q2W step-up as 
neededb
Abbreviations:  Q2W = every 2 weeks; Q4W = every 4 weeks.
a
If patients remain on ixekizumab 80 mg Q4W, their last dose will occur at Week 48.  If patients step up to ixekizumab 80 mg Q2W, their last dose will occur 
at Week 50 (Section 6.1).
b
Dosing may be increased to ixekizumab 80 mg Q2W starting at Week 24 through Week 40 (at Visit 9 [Week 24], Visit 10 [Week 28], or Visit 11 [Week 40]).  
Once a step-up from Q4W to Q2W occurs, the dose is maintained at Q2W for the remainder of the treatment period (Section 6.1).

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6.2.
Method of Treatment Assignment
Patients who meet all criteria for enrollment will be randomized to blinded treatment at Visit 2
(Week 0) in a 1:1 ratio to ixekizumab 80 mg Q2W or placebo.  Assignment to treatment groups 
will be 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.
To achieve between-group comparability for BSA, the randomization will be stratified by 
BSA (1% to <10% versus ≥10%).
6.2.1. Selection and Timing of Doses
Patients are randomized to dosing regimens and will receive their assigned investigational 
product as outlined in Section 6.2 and Section 6.1, respectively.  
Investigational product should be administered at approximately the same time of day each time, 
as much as possible.  For injections that are missed and not administered on the scheduled day of 
the week, the missed dose should be administered within 5 days of the originally scheduled day.
Dates of subsequent study visits should not be modified according to the delay of the injection of 
the missed scheduled dose.
Throughout their participation in the study, randomized patients and/or site personnel will record
information in a Study Drug Administration Log, including 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.
6.3.
Blinding
This is a double-blind study.  To preserve the blinding of the study, a minimum number of Lilly 
personnel will see the randomization table and treatment assignments before the study is 
complete.
Emergency unblinding for AEs may be performed through the IWRS, which may supplement or 
take the place of emergency codes generated by a computer drug-labeling system.  This option 
may be used ONLY if the patient’s well-being requires knowledge of the patient’s treatment 
assignment.  All actions resulting in an unblinding event are recorded and reported by the IWRS.
If an investigator, site personnel performing assessments, or patient is unblinded, the patient
must be discontinued from the study treatment.  All patients should continue to be followed for 
safety (Period 4).  In cases where there are ethical reasons to have the patient remain on study
treatment, the investigator must obtain specific approval from a Lilly clinical research physician 
(CRP) for the patient to continue study treatment.  
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 

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consideration in making such a determination.  If the investigator decides that unblinding is 
warranted, the investigator should make every effort to contact the Lilly CRP prior to unblinding 
a patient’s treatment assignment.  If a patient’s treatment assignment is unblinded, Lilly must be 
notified immediately by telephone, email, or fax.  Including this unblinding information in the 
SAE report is not sufficient for notification purposes.
6.4.
Packaging and Labelling
The investigational products will be supplied by the sponsor or its designee in accordance with 
current Good Manufacturing Practices (cGMP).  
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. 
Ixekizumab and placebo to match (excipients only) will be supplied as an injectable solution in 
1-mL, single-dose, prefilled, disposable manual syringes with study specific labels.  Each syringe 
of ixekizumab is designed to deliver ixekizumab 80 mg.  The syringes (and contents) containing 
either ixekizumab or placebo will be visibly indistinguishable from each other.  Syringes will be 
supplied in cartons; each carton will contain the appropriate quantity of syringes specific to the 
planned dispensing schedule of the investigational product.
6.5.
Preparation/Handling/Storage
Investigational products will be supplied by Lilly or its representative, in accordance with 
cGMP, and will be supplied with lot numbers, expiry dates, and certificates of analysis, as 
applicable.
The investigational product should be stored at 2°C to 8°C (36°F to 46°F) in its original carton to 
protect from light.  Investigational product should not be frozen.  Sites will be required to
monitor temperature of the on-site storage conditions of the investigational product.
6.6.
Dose Modification
Dose adjustments are not permitted for the Q2W dosing regimen during the Blinded Treatment 
Period (Period 2).  During the Open-Label Treatment Period (Period 3), patients will receive 
continuous Q4W dosing from Week 12 through Week 20.  Patients may step-up the Q4W dosing 
regimen to Q2W starting at Week 24 through Week 40 as outlined in Section 6.1.  Once a 
step-up to Q2W occurs, the dose is maintained at Q2W for the remainder of the Open-Label 
Treatment Period (Period 3).
6.6.1.Special Treatment Considerations 
Patients will be screened for eligibility in the study as described in Section 5.1 and Section 5.2
and will be informed of the study-specific restrictions and requirements of the study.  Patients 
who are not willing to comply with the study restrictions and requirements of the study will not 
be eligible for enrollment.

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Patients should be instructed not to donate blood or blood products during participation in the 
study.  
All biological agents carry the risk of systemic allergic/hypersensitivity reactions.  Clinical 
manifestations of these reactions may include, but are not limited to:

skin rash

pruritus (itching)

urticaria (hives)

angioedema (for example, swelling of the lips and/or tongue)

anaphylactic reaction
Sometimes, these reactions can be life-threatening.  Proteins may also cause redness, itching, 
swelling, or pain locally at the injection site.  Therefore, all patients should be closely monitored 
for signs or symptoms that could result from such reactions, educated on the signs or symptoms 
of these types of reactions, and instructed to contact the study site immediately if any of the 
symptoms are experienced following an injection.  If a patient experiences an acute 
allergic/hypersensitivity reaction after an injection of investigational product, he or she should be 
managed appropriately and given instruction to receive relevant supportive care.  Additionally, 
for an event judged by the investigator to be a potential systemic allergic/hypersensitivity 
reaction, a blood sample should be drawn as soon as possible. These samples may be tested for 
anti-drug antibodies (ADAs), other laboratory tests needed to elucidate the cause of the 
allergic/hypersensitivity reaction, and/or ixekizumab serum concentration.  These results will not 
be provided to the investigator for patient care decisions but are intended to assist the sponsor in 
accurately characterizing the reaction.
For patients who experience a potential allergic/hypersensitivity reaction, consideration for any 
premedication for future injections will be agreed upon between the investigator and sponsor 
and/or its designee.  Examples of potential allergic/hypersensitivity reactions that might merit 
premedication include mild-to-moderate skin rashes, mild-to-moderate generalized pruritus 
and/or urticaria, and mild-to-moderate injection-site reactions (for example, injection-site 
erythema, injection-site pruritus).  Patients who develop clinically significant systemic 
allergic/hypersensitivity reactions following administration of investigational product and who 
do not respond to symptomatic medication or who experience clinical sequelae (for example, 
hospitalization) should be discontinued from study treatment and should not receive further 
doses of investigational product, with or without premedication (see Section 7.1).  Medications 
considered appropriate for premedication include but are not restricted to 
acetaminophen/paracetamol up to 1000 mg and antihistamines (for example, oral 
diphenhydramine, 50 mg), given 30 to 60 minutes prior to investigational product injection.  
Patients may self-premedicate at home prior to administration of investigational product, as 
directed by the investigator.  All such premedications will be recorded as concomitant therapy.  
Corticosteroids are not permitted as agents for premedication.

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6.7.
Treatment Compliance
Every attempt will be made to select patients who have the ability to understand and comply with 
instructions.  To ensure high treatment compliance, the investigator is responsible for discussing 
methods with the patient before randomization.
Patient compliance with the investigational product (Section 9.4.4) will be assessed at each study 
visit during the Blinded Treatment and Open-Label Treatment Periods (Periods 2 and 3) by 
review of the SDAL (Section 6.2.1), return of empty investigational product packaging, and/or 
direct questioning.  Deviation(s) from the prescribed dosage regimen should be documented.
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
(see Section 7.1.3).
6.8.
Concomitant Therapy
All concomitant medication taken during the study must be recorded on the Concomitant 
Medication case report form (eCRF) at the study visits indicated in the Schedule of Activities 
(Appendix 2).  Treatment with concomitant psoriasis therapies during the study will be permitted 
only as outlined in the exclusion criteria (Sections 5.2) and as described in the table below.  
Patients taking permitted medications should be on stable doses at the baseline visit (Week 0,
Visit 2) as specified in Section 5.2.  Table RHBQ.6.2 summarizes concomitant medications that 
are or are not permitted for use during the study and related comments and conditions for use.

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Table RHBQ.6.2.
Concomitant Medication Permitted/Not Permitted in the Study 
Drug Class
Use During Study
Comments/Conditions
SYSTEMIC THERAPIES
Biologic agent other than 
investigational product as part of 
this protocol
Not permitted
Minimum required time since last biologic agent dose 
prior to baseline (Week 0, Visit 2):  

etanercept – at least 28 days

infliximab, adalimumab – at least 60 days

golimumab- at least 90 days

ustekinumab – at least 8 months

rituximab– at least 12 months

any other biologic agent – at least 5 half-lives
IL-17 antagonists, other than investigational product as 
part of this protocol:  

Must never have received, or participated in any 
study investigating, IL-17 antagonists

Examples include:  ixekizumab, secukinumab, 
brodalumab
Natalizumab, or other agents 
targeting α 4 integrin
Not permitted

Must have never received
Systemic nonbiologic psoriasis 
therapy
Not permitted

Must not have received within 4 weeks prior to
baseline (Week 0, Visit 2)

Examples include: oral PUVA light therapy, 
cyclosporine, corticosteroids, MTX, apremilast, 
tofacitinib, oral retinoids, mycophenolate mofetil, 
thioguanine, hydroxyurea, sirolimus, 
azathioprine, fumaric acid derivatives, 1, 25 
dihydroxy vitamin D3 and analogs
PHOTOTHERAPY
Phototherapy
Not permitted

Must not have received within 4 weeks prior to 
baseline (Week 0, Visit 2)

Examples include: either oral and topical PUVA 
light therapy, UVB, self-treatment with tanning 
beds or therapeutic sunbathing

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Drug Class
Use During Study
Comments/Conditions
TOPICAL THERAPIES
Bath oils and oatmeal bath 
preparations
Permitted with conditions

Not to be used within 12 hours prior to a study 
visit
Shampoos NOT containing 
salicylic acid, corticosteroids, coal 
tar, or vitamin D analogs
Permitted with conditions

Not to be used within 12 hours prior to a study 
visit
Shampoos and Scalp Treatments
containing salicylic acid, 
corticosteroids, coal tar, or vitamin 
D analogs
Not permitted

Must not be used within 2 weeks prior to baseline 
(Week 0, Visit 2).  
Topical moisturizers/emollients 
and other nonprescription topical 
products NOT containing urea, 
salicylic acid, alpha- or beta-
hydroxyl acids, corticosteroids, or 
vitamin D analogs
Permitted with conditions

Not to be used within 12 hours prior to a study 
visit
Topical moisturizers/emollients 
and other nonprescription topical 
products containing urea, salicylic 
acid, alpha- or beta-hydroxyl acids, 
corticosteroids, or vitamin D 
analogs
Not permitted

Must not be used within 2 weeks prior to baseline 
(Week 0, Visit 2). 
Topical corticosteroids, more 
potent than mild
Not permitted

Must not be used within 2 weeks prior to baseline 
(Week 0, Visit 2).

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Drug Class
Use During Study
Comments/Conditions
Topical corticosteroids, low to 
mild potency
Permitted with conditions

Must not be used within 2 weeks prior to baseline 
(Week 0, Visit 2).  

Study Periods 1 and 2:  Not permitted for use 
except to face and/or axilla.  If used for face 
and/or axilla, may not be used within 
approximately 24 hours prior to study visits 
requiring sPGA and PASI measures 

Study Periods 3 and 4:  Permitted for use, as 
needed, after Week 12 assessments are complete 
but not for the genital area.  May not be used 
within approximately 24 hours prior to study 
visits requiring sPGA and PASI measures.

Examples include:  desonide, hydrocortisone
Other prescription topical 
products
Not permitted

Must not be used within 2 weeks prior to baseline 
(Week 0, Visit 2) 

Examples include: calcineurin inhibitors, 
anthralin, vitamin D analogs, and retinoids
VACCINES
Vaccine, Bacillus Calmette-
Guérin (BCG)
Not permitted

Must not have received within 12 months prior to 
baseline (Week 0, Visit 2)

Should not receive within 12 months of 
completed treatment in this study
Vaccines, live 
Not permitted

Must not have received within 12 weeks prior to 
baseline (Week 0, Visit 2)  

Should not receive within 12 weeks of completed 
treatment in this study
Vaccines, nonlive seasonal and/or 
emergency
Permitted with conditions

Killed/inactive or subunit vaccines are expected 
to be safe; however, their efficacy with 
concomitant ixekizumab treatment is unknown
OTHER
NSAIDs, aspirin, or 
acetaminophen/paracetamol
Permitted

Allowed as needed
Abbreviations:  IL = interleukin; MTX = methotrexate; NSAID = nonsteroidal anti-inflammatory drug; PASI = Psoriasis Area and Severity Index; 
PUVA = psoralen and ultraviolet A; sPGA = static Physician Global Assessment; UVB = ultraviolet B.

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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 for an 
AE or for appropriate medical management (including the limited use of therapeutic agents 
which, if used under treatment regimens other than for treating an AE or for appropriate medical 
management, might be considered psoriasis therapies), the investigator should base decisions on 
the patient and clinical factors.  Any additional medication, whether prescription or over-
the-counter, used at baseline (Week 0, Visit 2) and/or during the course of the study must be 
documented with the start and stop dates on the Concomitant Medications eCRF.
Patients will maintain their usual medication regimen for other concomitant diseases throughout 
the study unless those medications are specifically excluded in the protocol.  Patients taking 
concomitant medications should be on stable doses at the time of baseline (Week 0, Visit 2) and 
should remain at a stable dose throughout the study, unless changes need to be made for an AE 
or for appropriate medical management.  Other medications may be allowed if approved by the 
sponsor or its designee.
6.9.
Treatment after Study Completion
6.9.1. Continued Access
Investigational product will not be made available to patients after conclusion of the study.

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7.
Discontinuation Criteria
7.1.
Discontinuation from Study Treatment
The reason for and date of discontinuation from study treatment (investigational product) and
reason for and date of discontinuation from study participation will be collected for all
randomized patients.
For any patient discontinuing from study treatment, the investigational product will be withheld,
and the patient will complete the ETV and the Post-Treatment Follow-Up Period (Period 4), as
shown in the Schedule of Activities (Appendix 2).
Missing data may compromise the integrity of the study. Complete information from each 
patient is critical to achieving the fullest understanding of the potential benefits and risks of 
ixekizumab. All efforts should be made to keep patients in the study, to attend scheduled visits 
and procedures, and to take investigational product as medically appropriate.
Patients who meet any of the criteria described in Section 7.1.1 will be discontinued from the 
study treatment.
7.1.1. Permanent Discontinuation from Study Treatment
Patients may be permanently discontinued from study treatment in the following situations:
[1]
Discontinuation of the investigational product for 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:

ALT or AST >8X ULN

ALT or AST >5X ULN for more than 2 weeks

ALT or AST >3X ULN and total bilirubin level (TBL) >2X ULN or 
prothrombin time >1.5X ULN

ALT or AST >3X ULN with the appearance of fatigue, nausea, vomiting, 
right upper-quadrant pain or tenderness, fever, rash, and/or eosinophilia 
(>5% of total leukocytes)

ALP >2.5X ULN and TBL >2X ULN

ALP >2.5 ULN with the appearance of fatigue, nausea, vomiting, right 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%)
In addition, patients will be discontinued from the investigational product in the following 
circumstances:
[2]
Laboratory results:

Neutrophil (segmented) counts (see safety monitoring for neutropenia in 
Section 8.4.9.1);
o
<500 cells/L (<0.50x103/µL or <0.50 GI/L)

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o
≥500 and <1000 cells/L (≥0.50x103/µL and <1.00x103/µL or 
≥0.50 GI/L and <1.00 GI/L) (based on 2 test results; the second test 
performed within 1 week from knowledge of the initial result) 
o
≥1000 and <1500 cells/L (≥1.00x103/µL and <1.50x103/µL or ≥1.00 GI/L 
and <1.50 GI/L) (based on 3 test results as specified in Section 8.4.9.1)
- AND - a concurrent infection

Total WBC count <2000 cells/L (<2.00x103/µL or <2.00 GI/L)

Lymphocyte count <500 cells/μL (<0.50x103/µL or <0.50 GI/L)

Platelet count <50,000 cells/μL (<50x103/µL or <50 GI/L)
[3]
Changes in BP (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 following 
intervention (Section 8.4.9.3)
[4]
The patient experiences a severe AE, an SAE, or a clinically significant 
change in a laboratory value occurs that, in the opinion of the investigator, 
merits the discontinuation of the investigational product and appropriate 
measures being taken.  In this case, Lilly or its designee is to be notified 
immediately.  Refer to Adverse Events, Section 8.2.
[5]
Clinically significant systemic hypersensitivity reaction following SC 
administration of investigational product that does not respond to 
symptomatic medication or results in clinical sequelae
[6]
The patient becomes pregnant.  Patients will undergo urine pregnancy self-testing at 
home on a monthly basis during periods between scheduled visits until Week 52.  
During these intervisit periods, the site must call the patient each month to obtain her 
pregnancy test results.  Additional urine pregnancy testing can be performed at the 
investigator’s discretion. Patients that are determined to be pregnant will be 
discontinued from treatment and will no longer be administered investigational 
product.
[7]
The patient develops a malignancy.
(Note:  Patients may be allowed to continue if they develop no more than 
2 nonmelanoma skin cancers during the study.)  
[8]
Any patient who has a change in disease phenotype at any time (for example, 
a change to pustular psoriasis)
[9]
If the patient requires long-term treatment with a therapeutic regimen that has 
been demonstrated to be effective for the treatment of psoriasis  
[10] 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

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[11] 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-
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 patient is 
to be discontinued from the study. 
[12] The investigator or attending physician decides that the patient should be 
withdrawn from study treatment.
[13] The patient requests to be withdrawn from study treatment.
[14] The investigator or Lilly stops the patient’s participation in the study.
[15] The patient becomes HBV DNA positive.  The patient should be referred to a 
specialist physician.  Discussion of the timing of discontinuation from the 
study and study treatment is provided in Section 8.4.9.2.
If a patient is noncompliant with study procedures and/or investigational product administration, 
the investigator should assess the patient to determine the reason for noncompliance and educate 
and/or manage the patient as appropriate to improve compliance (Section 6.7).
Patients who discontinue the investigational product early will have an ETV and end-of-therapy 
procedures performed as shown in the Schedule of Activities (Appendix 2) and will continue into 
the Post-Treatment Follow-Up Period.
7.1.2. Discontinuation of Inadvertently Enrolled Patients
The criteria for enrollment must be followed explicitly.  If the sponsor or investigator identify a 
patient who did not meet enrollment criteria and was inadvertently enrolled, a discussion must 
occur between the sponsor CRP and the investigator to determine if the patient may continue in 
the study treatment.  If both agree it is medically appropriate to continue, the investigator must 
obtain documented approval from the sponsor CRP to allow the inadvertently enrolled patient to 
continue in the study with or without treatment with investigational product.
7.1.3. Permanent Discontinuation from the Study
Some possible reasons that may lead to permanent discontinuation include:

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
Participation in the study needs to be stopped for medical, safety, regulatory, or other 
reasons consistent with applicable laws, regulations, and good clinical practice (GCP)

Subject Decision
o
the patient requests to be withdrawn from the study
7.1.4. Patients Lost to Follow-Up
A patient will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site.  Site personnel are expected to make 
diligent attempts to contact patients who fail to return for a scheduled visit or were otherwise 
unable to be followed up by the site.

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8.
Study Assessments and Procedures
Appendix 2 lists the Schedule of Activities, with the study procedures and their timing (including 
tolerance limits for timing).  Appendix 3 lists the laboratory tests that will be performed for this 
study.
Unless otherwise stated in the subsections below, all samples collected for specified laboratory 
tests will be destroyed within 60 days of receipt of confirmed test results.  Certain samples may 
be retained for a longer period, if necessary, to comply with applicable laws, regulations, or 
laboratory certification standards.
8.1.
Efficacy Assessments
8.1.1. Primary Efficacy Assessments 
8.1.1.1.
Static Physician Global Assessment of Genitalia
The sPGA of Genitalia is the clinician’s determination of the patient’s psoriasis lesions’ overall 
severity in the genital area (labia majora, labia minora, and perineum in females; penis, scrotum, 
and perineum in males) at a given time point.  Overall, lesions are categorized by descriptions for 
elevation, erythema, and scaling.  It is not necessary that all 3 criteria be fulfilled.  The sPGA of 
Genitalia score is based on a combination of erythema and the secondary features (plaque 
elevation and/or scale).  Since erythema is the most robust finding, it should be the dominant 
feature influencing the sPGA of Genitalia rating in the majority of cases.  For the analysis of 
responses, the patient’s psoriasis is assessed as clear (0), minimal (1), mild (2), moderate (3), 
severe (4), or very severe (5).
8.1.2.
Secondary Efficacy Assessments 
8.1.2.1.
Clinician Reported Assessments
8.1.2.1.1. Modified Genital Psoriasis Area and Severity Index
The mGPASI was adapted from the standard PASI by Bissonnette et al. (2008) and Ryan et al. 
(2015) for use in male and female genital psoriasis patients.  The measure is the clinician’s 
determination of the patient’s psoriasis severity in the genital region (labia majora, labia minora, 
and perineum in females; penis, scrotum, and perineum in males) at a given time point yielding 
an overall score of 0 for no psoriasis to 72 for the most severe disease.  The scoring index 
incorporates the degree of erythema, induration, and scaling of the genital plaques as well as 
erosion, fissure, and/or ulcer as a product of the genital area involved.  Severity is rated for each 
characteristic on a 0 to 4 scale (0 for no involvement up to 4 for severe involvement including 
erosion, fissure, and/or ulcer).  The area of involvement for the entire genital area, excluding the 
inguinal area, is graded on a 0 to 6 scale (0 for no involvement; up to 6 for 90% to 100% 
involvement).

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8.1.2.1.2. (Overall) static Physician Global Assessment
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 assess efficacy in the treatment of 
psoriasis (EMA 2004).  Overall, lesions are categorized by descriptions for induration, erythema, 
and scaling.  For the analysis of responses, the patient’s psoriasis is assessed as clear (0), 
minimal (1), mild (2), moderate (3), severe (4), or very severe (5).
8.1.2.2.
Patient Reported Assessments
The patient-reported questionnaires will be administered according to the Schedule of Activities
(Appendix 2) in countries where the questionnaires have been translated into the native language 
of the region and linguistically validated.
8.1.2.2.1. Genital Psoriasis Symptoms Scale
The GPSS is a patient-administered assessment of 8 symptoms:  itch, pain, discomfort, stinging, 
burning, redness, scaling, and cracking.  Respondents are asked to answer the questions based on 
their psoriasis symptoms in the genital area.  Genital area is defined as the labia majora (outer 
lip), labia minora (inner lip), and perineum (area between vagina and anus) for females; penis, 
scrotum, and perineum (area between the penis and anus) for males. 
Numeric rating scales (NRS) are used to assess the self-reported overall severity of each of the 
8 symptoms individually in the genital area on an 11-point horizontal scale anchored at 0 (no)
and 10 (worst imaginable). The overall severity for each individual symptom from patient's 
genital psoriasis is indicated by selecting the number from 0 to 10 that best describes the worst 
level of each symptom in the genital area in the past 24 hours.  An e-diary will be used to collect 
these patient rated assessments during the first 12 weeks; thereafter, patients will answer these 
questions only at scheduled study visits using the same recall period as used for the e-diary. The 
GPSS can be completed within 1 minute by patients. It will be completed before the patient’s 
clinical examination; before the patient receives any text or test results; and before the patient’s 
health, health data, or emotions are discussed. The instructions for completion are embedded 
within the GPSS questionnaire for patients to read before responding to the items. The symptom 
severity scores, ranging from 0 to 10, are the values of the selected numbers indicated by the
patient on the instrument’s horizontal scale.  Each of the 8 individual items will receive a score 
of 0 to 10 and will be reported as item scores for itch, pain, discomfort, stinging, burning, 
redness, scaling, and cracking.  In addition, a total score ranging from 0 (no genital psoriasis 
symptoms) to 80 (worst imaginable genital psoriasis symptoms) will be reported.
8.1.2.2.2. Genital Psoriasis Sexual Impact Scale
The GPSIS is a patient reported outcome measure to evaluate the impact of genital psoriasis 
symptoms on sexual activity.  Respondents are asked to answer the questions based on their 
psoriasis symptoms in the genital area.  Genital area is defined as the labia majora (outer lip), 
labia minora (inner lip), and perineum (area between vagina and anus) for females; penis, 
scrotum, and perineum (area between the penis and anus) for males.  The definition of sexual 
activity is not limited to intercourse and includes activities such as masturbation.  The 
instructions for completion are embedded within the GPSIS questionnaire for patients to read 
before responding to the items.  

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The GPSIS consists of 3 items that include 2 subscales on avoidance of sexual activity (Sexual 
Activity Avoidance Subscale) as well as the worsening of genital psoriasis symptoms during or 
following sexual activity (Impact of Sexual Activity on Genital Psoriasis Symptoms Subscale). 
The Sexual Activity Avoidance Subscale includes items 1 and 2.  Item 1 asks whether the patient
has been sexually active in the past week.  If a patient selects “no due to reasons other than my 
genital psoriasis,” they do not answer any additional questions on the scale and do not receive a 
score on the Sexual Activity Avoidance Subscale.  If a patient responds “no due to my genital 
psoriasis” on GPSIS item 1, this receives a score of “5” (equivalent to always avoid sexual 
activity due to genital psoriasis on item 2, which asks how often the patient avoided sexual 
activity in the past week due to genital psoriasis symptoms) on the Sexual Activity Avoidance 
Subscale.  For patients who are sexually active, a response of never, rarely, sometimes, and often 
on item 2 receive a score of 1, 2, 3, and 4, respectively, on the Sexual Activity Avoidance 
Subscale.  The Sexual Activity Avoidance Subscale ranges from 1 (never) to 5 (always) avoid 
sexual activity.  
The Impact of Sexual Activity on Genital Psoriasis Symptoms Subscale score includes only the 
score for GPSIS item 3.  Those patients who report as being sexually active on the GPSIS item 1 
are given the opportunity to respond to item 3.  Item 3 asks the patient to select a response of 
very low or not at all (1) to very high (5) to reflect the level (degree) of worsening of genital 
psoriasis symptoms following sexual activity.  
No total score is calculated for the GPSIS.
During the first 12 weeks, patients will use an e-diary, using a recall period of 1 week, and the 
response for each item uses a Likert scale.  Thereafter, study participants will answer these 
questions only at scheduled study visits using the same 1-week recall period as used for the 
e-diary.
8.1.2.2.3. Sexual Frequency Questionnaire
The SFQ is a patient reported outcome measure to evaluate the impact of genital psoriasis 
symptoms on sexual frequency.  It consists of 2 items that assess the impact of genital psoriasis 
symptoms on the frequency of sexual activity.  Respondents are asked to answer the questions 
based on their psoriasis symptoms in the genital area.  Genital area is defined as the labia majora 
(outer lip), labia minora (inner lip), and perineum (area between vagina and anus) for females; 
penis, scrotum, and perineum (area between the penis and anus) for males.  The definition of 
sexual activity is not limited to intercourse and includes activities such as masturbation.  
Item 1 asks how many times the patient engaged in sexual activity in the past week with 
response options of none/zero (2), once (1), and two or more (0).  
Item 2 assesses how often genital psoriasis symptoms limited the frequency of sexual activity 
with response options ranging from 0 (never) to 4 (always).  
The individual item scores of the SFQ are reported separately.  No total score is calculated for 
the SFQ. 

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The instructions for completion are embedded within the SFQ questionnaire for patients to read 
before responding to the items.  During the first 12 weeks, patients will use an e-diary, using a 
recall period of 1 week, and the response for each item uses a Likert scale.  Thereafter, study 
participants will answer these questions only at scheduled study visits using the same 1-week 
recall period as used for the e-diary.
8.1.2.2.4. Patient’s Global Assessment of Genital Psoriasis
The Patient’s Global Assessment of Genital Psoriasis (PatGA-Genital) is a patient-administered, 
single-item scale on which patients are asked to rank, by circling a number on a 0 to 5 NRS, the 
severity of their genital psoriasis “today” from 0 (clear), no genital psoriasis; to 5 (severe).
8.1.2.2.5. Dermatology Life Quality Index
The DLQI is a simple, patient-administered, 10 question, validated, quality-of-life questionnaire 
that covers 6 domains:  symptoms and feelings, daily activities, leisure, work and school, 
personal relationships, and treatment.  Response categories include “not at all,” “a little,” “a lot,” 
and “very much,” with corresponding scores of 0, 1, 2, and 3, respectively, and “not relevant” 
responses scored as “0”.  Totals range from 0 to 30 (less to more impairment). A DLQI total 
score of 0 to 1 is considered as having no effect on a patient’s HRQoL, and a 5-point change 
from baseline is considered clinically relevant (Basra et al. 2008).
8.1.2.2.6. Medical Outcomes Study 36-Item Short-Form Health Survey 
The Short-Form Health Survey (SF-36) is a 36-item, patient-completed 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 summary (MCS) scores and physical component summary (PCS), respectively.  The 
summary scores range from 0 to 100, with higher scores indicating better levels of function 
and/or better health.  Items are answered on Likert scales of varying lengths.  The SF-36 acute 
version will be used, which has a 1-week recall period (SF-36 Health Survey Update [WWW]).
8.1.3. Exploratory Efficacy Assessments
8.1.3.1.
Clinician Reported Assessments
8.1.3.1.1. (Overall) Psoriasis Area and Severity Index
The PASI is an accepted primary efficacy measurement for this phase of development of 
psoriasis treatments (EMA 2004).  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 (scaling), erythema, and plaque induration/infiltration (thickness) in each region, 
yielding an overall score from 0 for no psoriasis up to 72 for the most severe disease 
(Fredriksson and Pettersson 1978).  The PASI has been the most frequently used endpoint and 
measure of psoriasis severity in clinical trials (EMA 2004; Menter et al. 2008).  A clinically 
meaningful response is a PASI 75, which represents at least a 75% decrease (improvement) from 
the baseline PASI score.  Higher levels of clearance (PASI 90), as well as complete resolution of 
psoriasis (PASI 100), have become additional endpoints because of the increasing recognition of 

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the association of higher clearance with greater health-related quality of life (HRQoL) (Puig 
2015).
8.1.3.1.2. Percentage of Body Surface Area
The investigator will evaluate the percentage involvement of psoriasis on each patient’s BSA on 
a continuous scale from 0% (no involvement) to 100% (full involvement), in which 1% 
corresponds to the size of the patient’s hand (including the palm, fingers, and thumb) (Van 
Voorhees et al. 2009).
8.1.3.1.3. Fitzpatrick Skin Type Assessment
The Fitzpatrick Skin Type is a skin classification system that classifies the typical response of 
different types of skin to ultraviolet light.  Types range from the very fair (Type I) to the very 
dark (Type VI).
8.1.3.1.4. Binary Questions on Psoriasis Location
8.1.3.1.4.1.
Overall
Studying psoriasis involvement in the face, pubis, inguinal creases, gluteal cleft, and perianal 
area is of considerable interest for patients.  These are locations that bear high potential for 
stigmatization and negative impact on quality of life.  In addition, it is important to confirm that 
association of psoriasis on nails, scalp, axillae, and inframammary folds that have been 
correlated with genital involvement in past studies (Ryan et al. 2015).  To this end, binary
responses (yes/no) will be noted at baseline (Week 0), Week 4, 12, 24, 52, or ETV (footnote j of 
Schedule of Activities; Appendix 2) whether the patient currently has visible psoriasis on face, 
inframammary fold, axilla, scalp, nail, pubis, perianal region, gluteal cleft and inguinal creases.
8.1.3.1.4.2.
Genital
The specific location of psoriasis in the genital area may differentially impact patients in terms of 
sexual avoidance and frequency as well as physical discomfort and pain.  To this end, binary 
questions (yes/no) will be asked at each study visit (footnote h of Schedule of Activities;
Appendix 2) whether the patient current has visible psoriasis in women on labia minora, labia 
majora, and/or perineum and in men on the penis (glans and/or shaft), scrotum, and/or perineum.
8.1.3.1.5. Binary Questions on Characteristics
8.1.3.1.5.1.
Genital
Publications related to genital psoriasis note that fissure, erosion, and ulcers may be present in 
the genital area.  These characteristics may increase the pain and discomfort of genital psoriasis 
and also significantly impact sexual function and quality of life.  Fissure, erosion, and ulcer are 
assessed collectively on the mGPASI but are not identified individually on the scale.  To better
understand which specific characteristics impact patients with psoriasis, information on presence 
of these characteristics will be recorded on the eCRF.  Binary questions (yes/no) will be asked at 
each study visit (footnote i of Schedule of Activities; Appendix 2) regarding presence of fissure, 
erosion, and ulcer in the genital area (labia minora, labia majora, and perineum in female patients 
and penis, scrotum, and perineum in male patients).

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8.1.3.1.5.2.
Perianal/Gluteal Cleft
Little information is available regarding perianal characteristics in patients with psoriasis, and 
better understanding is needed.  Fissures, abscess, ulcer, and skin tags may be present in the 
perianal area/gluteal cleft but have not been well studied in patients with psoriasis.  However, 
perianal disease may significantly impact quality of life and add to discomfort/pain related to the 
disease.  To this end, binary questions (yes/no) will be asked periodically at study visits, 
according to the Schedule of Activities (Appendix 2, row for “Perianal/gluteal cleft 
characteristics examination”), regarding presence in the perianal area of fissure, abscess, ulcer, 
and skin tags and in the gluteal cleft of fissure.
8.1.3.2.
Combined Clinician/Patient Reported Assessment
The patient-reported portion of the questionnaire will be administered according to the Schedule 
of Activities (Appendix 2) in countries where this portion of the questionnaire has been 
translated into the native language of the region and linguistically validated.
8.1.3.2.1. Comprehensive Assessment of the Psoriasis Patient
An assessment of psoriasis severity, combining both clinician (exam) and patient-evaluation 
(patient reported outcome [PRO]; visual analog scale) to determine severity of overall plaque 
psoriasis as well as several subindices (scalp, nail, palmar-plantar, inverse, and genital).  Each 
area is scored as 0 to 20 (0 to 10 for clinician assessment plus 0 to 10 for the higher of the 
2 PROs).  For this study, we will assess only the genital severity index.  The genital severity 
score will range from 0 (clear/no impact) to 20 (severe genital psoriasis/worst imaginable pain 
and/or unable to be intimate at all).
8.1.3.3.
Patient Reported Assessment
The patient-reported questionnaire will be administered according to the Schedule of Activities
(Appendix 2) in countries where the questionnaire has been translated into the native language of 
the region and linguistically validated.
8.1.3.3.1. Touch Avoidance Numeric Rating Scale
The Touch Avoidance Numeric Rating Scale is a self-administered, single item scale that 
assesses touch avoidance over the past 2 weeks due to the look or feel of the patient’s skin.  The 
item is rated on scale of 0 (not at all) to 10 (very much).
8.1.4. Appropriateness of Assessments
8.1.4.1.
Static Physician Global Assessment of Genitalia
The sPGA of Genitalia is a version of the sPGA scale used in Lilly’s Phase 3 ixekizumab clinical 
trials that has been modified for the assessment of genital involvement as noted above
(Section 8.1.2.1.2).  The instruction set directs clinicians to specifically evaluate plaque lesion 
severity in the genital area rather than the entire body.  Instrument scoring is based on the 
identical categories and similar category descriptions of the sPGA scale but has been revised to 
reflect the importance of erythema in the presentation of genital psoriasis.  The modifications to 
the scale were established with input from an Expert Consensus Development panel as well as
clinical experts in genital psoriasis from 3 countries.

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8.1.4.2.
Modified Genital Psoriasis Area and Severity Index
The mGPASI was adapted from the standard PASI by Bissonnette et al. (2008) for use in male 
patients with genital psoriasis and later by Ryan et al. (2015) for use in male and female genital 
psoriasis patients.  The PASI was modified to include erosion, fissure, and ulcer as part of the 
clinical assessment in order to capture some of the additional symptoms that may be present in 
genital psoriasis as described above.  The mGPASI has been used to measure treatment effect in 
an open-label treatment study of male patients with genital psoriasis (Bissonnette et al. 2008), as 
well as to measure severity of genital involvement in a recent cross-sectional study of male and 
female patients with genital psoriasis (Ryan et al. 2015).  Ryan et al. (2015) found that patients 
with increased severity of genital disease, as measured quantitatively by the mGPASI, had more 
significant impairment of quality of life, independent of overall disease severity for all subjective 
patient reported quality of life assessments, including the Relationship and Sexuality Scale 
(RLSS), Center for Epidemiologic Studies Depression Scale (CED-S), and DLQI and was the 
only objective psoriasis measure which showed a significant correlation to all of these PROs.  
These studies demonstrated the utility of the mGPASI in quantifying the objective severity of
genital psoriasis for use in future studies.
8.2.
Adverse Events
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.
Investigators must document their review of each laboratory safety report.
The investigator remains responsible for following, through an appropriate health care option, 
AEs that are serious or otherwise medically important, considered related to the investigational 
product or the study, or that caused the patient to discontinue the investigational product before 
completing the study.  The patient should be followed until the event resolves, stabilizes with 
appropriate diagnostic evaluation, or is reasonably explained.  The frequency of follow-up 
evaluations of the AE is left to the discretion of the investigator.
An AE is defined as any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product that does not necessarily have a causal 
relationship with this treatment.  An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally associated with the 
use of a medicinal (investigational) product, whether or not related to the medicinal 
(investigational) product.  Lack of drug effect is not an AE in clinical studies, because the 
purpose of the clinical study is to establish treatment effect.
After the ICF is signed, study site personnel will record via electronic data entry (eCRF) the 
occurrence and nature of each patient’s preexisting conditions, including clinically significant 
signs and symptoms of the disease under treatment in the study.  In addition, site personnel will 
record via eCRF any change in the condition(s) and any new conditions as AEs. Investigators 

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should record their assessment of the potential relatedness of each AE to protocol procedure, 
investigational product, via eCRF.
The investigator decides whether he or she interprets the observed AEs as reasonably possibly 
related to the investigational product, study device, study procedure, to disease, 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.
Planned surgeries and nonsurgical interventions should not be reported as AEs unless the 
underlying medical condition has worsened during the course of the study.
If a patient’s investigational product is discontinued as a result of an AE, study site personnel 
must report this to Lilly or its designee via eCRF, clarifying if possible, the circumstances 
leading to any dosage modifications, or discontinuations of treatment. 
8.2.1. Serious Adverse Events
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

important medical events that may not be immediately life-threatening or result in death 
or hospitalization but may jeopardize the patient or may require intervention to prevent 
one of the other outcomes listed in the definition above.
If an SAE occurs after signing the ICF, but prior to receiving investigational product, it needs to 
be reported ONLY if it is considered reasonably possibly related to study procedure.
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.
Pregnancy (during maternal or paternal exposure to investigational product) does not meet the 
definition of an AE.  However, to fulfill regulatory requirements any pregnancy should be 
reported following the SAE process to collect data on the outcome for both mother and fetus.

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Investigators are not obligated to actively seek AEs or SAEs in subjects once they have 
discontinued and/or completed the study (the patient summary eCRF has been completed).  
However, if the investigator learns of any SAE, including a death, at any time after a subject has 
been discharged from the study, and he/she considers the event reasonably possibly related to the 
study treatment or study participation, the investigator must promptly notify Lilly.
8.2.2. Adverse Events of Special Interest
The following adverse events of special interest (AESIs) will be used to determine the safety and
tolerability of ixekizumab over the range of doses selected for this clinical study.
AESIs for ixekizumab are:

cytopenias (leukopenia, neutropenia, and thrombocytopenia)

liver function test changes/enzyme elevations (ALT, AST, bilirubin, and alkaline 
phosphatase)

infections

injection-site reactions

allergic reactions/hypersensitivities

cerebrocardiovascular events

malignancies

inflammatory bowel disease 

depression 
Sites will provide details on AEs as instructed on the eCRF.  Investigators will also educate 
patients and/or caregivers about the symptoms of systemic allergic/hypersensitivity reactions and 
will provide instructions on the management and reporting of these reactions.  Blood samples
will be collected as soon as possible for any patient who experiences an AE of a potential 
systemic allergic/hypersensitivity reaction during the study as judged by the investigator.  These 
samples may be tested for ADAs, other laboratory tests needed to elucidate the cause of the
allergic/hypersensitivity reaction, and/or ixekizumab serum concentration.
Data on preferred terms associated with cerebrocardiovascular events (defined as death, cardiac 
ischemic event including MI 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 
these events and any deaths will be adjudicated by an external Clinical Events Committee (CEC) 
made up of a chairperson, 2 cardiologists, 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 evaluated uniformly by a single group (the CEC).

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8.2.2.1.
Suspected Unexpected Serious Adverse Reactions
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.
8.2.3. Complaint Handling
Lilly collects product complaints on investigational products and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and to 
facilitate process and product improvements.
Patients will be instructed to contact the investigator as soon as possible if he or she has a 
complaint or problem with the investigational product so that the situation can be assessed.
8.3.
Treatment of Overdose
Refer to the IB.
8.4.
Safety Assessments
8.4.1. Electrocardiograms
For each patient, a 12-lead digital ECG will be collected locally at screening according to the 
Schedule of Activities (Appendix 2).  Patients must be supine for approximately 5 to 10 minutes 
before ECG collection and remain supine but awake during ECG collection.
Electrocardiograms will be interpreted locally by a qualified physician 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.  The qualified physician must document his/her review of the ECG at the
time of evaluation. Any clinically significant findings from ECGs that result in a diagnosis and 
that occur after the patient receives the first dose of the investigational treatment should be 
reported to Lilly or its designee as an AE via eCRF.
The ECGs will be maintained at the site and made available to the sponsor as requested.
8.4.2. Vital Signs
Vital signs (BP and pulse) and body temperature will be measured (sitting) after resting for a
minimum of 10 minutes at visits indicated in the Schedule of Activities (Appendix 2).  At 
baseline (Week 0) and Visit 7 (Week 12), BP and pulse should be measured prior to 
administration of the investigational product and again approximately 1 hour 
post-administration.  
Any clinically significant findings from vital signs measurement that result in a diagnosis and 
that occur after the patient receives the first dose of study treatment should be reported to Lilly or 
its designee as an AE via eCRF. Additional measurements of vital signs may be performed at 
the discretion of the investigator.

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8.4.3. Laboratory Tests
For each patient, laboratory tests detailed in (Appendix 3) should be conducted according to the 
Schedule of Activities (Appendix 2). 
Any clinically significant findings from laboratory tests that result in a diagnosis and that occur 
after the patient receives the first dose of investigational product should be reported to Lilly or its 
designee as an AE via eCRF.
8.4.4. Physical Examination
For each patient, one complete physical examination (excluding pelvic, rectal, and breast 
examinations) will be performed at screening.  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 physical examinations throughout the study are indicated in the Schedule of 
Activities (Appendix 2) and 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.
Any clinically significant findings from a complete physical examination that result in a 
diagnosis and that occur after the patient receives the first dose of study treatment should be 
reported to Lilly or its designee as an AE via eCRF.
8.4.5. Chest X-Ray and Tuberculosis Testing
A posterior-anterior view chest x-ray will be obtained, unless the x-ray or results from a chest 
x-ray obtained within 6 months prior to the study are available.  The chest x-ray or results will be 
reviewed by the investigator or designee to exclude patients with active TB infection.  
In addition, patients will be tested at screening as indicated on the Schedule of Activities
(Appendix 2) for evidence of active or latent TB indicated by a positive tuberculin PPD skin test 
response (≥5 mm induration, between approximately 2 and 3 days after test application, 
regardless of BCG vaccination history).  In countries where an Interferon-Gamma Release Assay
(QuantiFERON®-TB Gold test, and/or T-SPOT®) is available and in the judgment of the 
investigator preferred as an alternative to the PPD skin test for the evaluation of TB infection, it 
may be used instead of the PPD test (positive tests excluded) and may be read locally.  If the 
QuantiFERON®-TB Gold test is indeterminate, or the T-SPOT® is invalid or borderline, 1 retest 
is allowed.  If the retest for the QuantiFERON®-TB Gold test is indeterminate, or the retest for 
the T-SPOT® is invalid or borderline, then the patient is excluded from enrollment in the study.
Patients with documentation of a negative test result within 3 months prior to baseline (Week 0; 
Visit 2) do not need a TB screen at Visit 1.  Documentation of this test result must include a 
record of the size of the induration response (<5 mm induration).  A PPD test recorded as 
negative without documenting the size of induration will result in a retest.
However, patients with a PPD skin test ≥5 mm induration or a positive QuantiFERON®-TB 
Gold or positive T-SPOT® test at screening, but no other evidence of active TB may be 

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rescreened 1 time and may be enrolled without repeating a PPD or QuantiFERON®-TB Gold test 
or T-SPOT® if the following conditions are met:

after receiving at least 4 weeks of appropriate latent TB infection (LTBI) 
therapy, with commitment by the patient and the investigator for the patient to 
complete a full course of prophylaxis for TB

with no evidence of hepatotoxicity (ALT/AST must remain ≤2 times ULN) 
upon retesting of serum ALT/AST prior to randomization.  Such patients must 
complete appropriate LTBI therapy during the course of the study in order to 
remain eligible

meet all other inclusion/exclusion criteria for participation  
If rescreening occurs within 6 months of the screening chest x-ray, there is no necessity for 
repeat of chest x-ray for considering enrollment.  
Patients with positive TB test results on file:  Patients with prior history of a positive TB test 
should not have a TB test performed at Visit 1.  Documentation of this history and of at least 4 
weeks of appropriate latent TB treatment prior to baseline (Week 0, Visit 2) is required for study 
eligibility.  Patients who have a documented history of completing an appropriate TB treatment 
regimen with no history of re-exposure to TB since their treatment was completed and no 
evidence of active TB are eligible to participate in the study.  Patients who have had household 
contact with a person with active TB are excluded, unless an appropriate and documented course 
of prophylaxis for TB was completed.
Any clinically significant findings from chest x-rays and/or tuberculosis testings that result in a 
diagnosis and that occur after the patient receives the first dose of study treatment should be
reported to Lilly or its designee as an AE via eCRF.
8.4.6. Immunogenicity
Samples for immunogenicity testing, including samples that may be analyzed for ixekizumab 
concentration, will be collected at time points indicated in the Schedule of Activities (Appendix 
2). Additionally, blood samples for potential immunogenicity testing will be collected, as soon 
as possible, for any patient who experiences a potential systemic allergic/hypersensitivity 
reaction during the study as judged by the investigator.  These samples may be tested for ADAs, 
ixekizumab serum concentration, and/or other laboratory tests needed to elucidate the cause of 
the allergic/hypersensitivity reaction.
8.4.7. Quick Inventory of Depressive Symptomatology—Self-Report 
(16 Items)
QIDS-SR16 is a self-administered, 16-item instrument intended to assess the existence and 
severity of symptoms of depression as listed in the American Psychiatric Association’s 
Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) (APA 1994).  A 
patient is asked to consider each statement as it relates to the way they have felt for the past 
7 days.  There is a 4-point scale for each item ranging from 0 to 3.  The 16 items corresponding 

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to 9 depression domains are summed to give a single score ranging from 0 to 27, with higher 
scores denoting greater symptom severity.  The domains assessed by the instrument include:  (1) 
sad mood, (2) concentration, (3) self-criticism, (4) suicidal ideation, (5) interest, 
(6) energy/fatigue, (7) sleep disturbance (initial, middle, and late insomnia or hypersomnia), 
(8) decrease/increase in appetite/weight, and (9) psychomotor agitation/retardation.  Additional 
information and the QIDS-SR16 questions may be found at the University of Pittsburgh 
IDS/QIDS internet page [WWW].  A QIDS-SR16 assessment will be taken at times indicated in 
the Schedule of Activities (Appendix 2).
8.4.8. 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 
during the 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 
Classification Algorithm of Suicide Assessment (C-CASA) categorization of suicidal events.  
Patients will be assessed according to the Schedule of Activities (Appendix 2).
The Self-Harm Supplement Form is a one-question form that asks for the number of suicidal or 
nonsuicidal self-injurious behaviors the patient has experienced 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 to be completed. This information is 
then documented in the eCRF.  The Self-Harm Supplement Form will be completed according to 
the Schedule of Activities (Appendix 2).
8.4.9. Safety Monitoring
Lilly will periodically review evolving aggregate safety data within the study by appropriate 
methods.
If a study patient/subject experiences elevated ALT ≥3X ULN, ALP ≥2X ULN, or elevated TBL 
≥2X 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 CRP regarding collection of specific recommended 
clinical information and follow-up laboratory tests.  See Appendix 4.
8.4.9.1.
Neutropenia
During treatment with investigational product, patients with neutrophil counts <1500 cells/L 
(<1.50x103/µL or <1.50 GI/L) should be managed for neutropenia as follows:

<500 cells/L (<0.50x103/µL or <0.50 GI/L), see Discontinuation Criteria 
(Section 7.1)

≥500 cells/L and <1000 cells/L (≥0.50x103/µL and <1.00x103/µL or 
≥0.50 GI/L and <1.00 GI/L), see Discontinuation Criteria (Section 7.1)

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
≥1000 cells/L and <1500 cells/L (≥1.00x103/µL and <1.50x103/µL or 
≥1.00 GI/L and <1.50 GI/L), and the patient has a concurrent infection that 
requires systemic anti-infective therapy (for example, 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 (≥1.50x103/µL or 
≥1.50x103/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 
(≥1.00x103/µL and <1.50x103/µL or ≥1.00 GI/L and <1.50 GI/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 
tests, the neutrophil count still remains ≥1000 cells/L and <1500 cells/L 
(≥1.00x103/µL and <1.50x103/µL or ≥1.00 GI/L and <1.50 GI/L), and:

the infection has not fully resolved, the patient will be discontinued from 
the study treatment and continue safety follow up.

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 treatment and continue safety follow up.

≥1000 cells/L and <1500 cells/L (≥1.00x103/µL and <1.50x103/µL or ≥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 
8 weeks 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 ≥1500 cells/L (≥1.50x103/µL or 
≥1.50 GI/L).  If the patient has 3 or more postbaseline neutrophil counts of 
≥1000 cells/L (≥1.00x103/µL or ≥1.00 GI/L) and <1500 cells/L 
(<1.50x103/µL or <1.50 GI/L), no value of <1000 cells/L (<1.00 x103/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 be managed as indicated above for patients with 
concurrent infection.  

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If, at the last scheduled visit or ETV, the patient’s neutrophil count is <1500 cells/L 
(<1.50x103/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 
Post-Treatment Follow-Up Period (Period 4) design at Visits 801 (4 weeks 
post-resolution of infection), 802 (8 weeks after Visit 801), and 803 (if necessary; 
12 weeks after Visit 802); additional visits may be required depending on the 
degree 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 Post-Treatment Follow-Up Period (Period 4) 
design, Visits 801 (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:

As long as a patient’s neutrophil count is <1000 cells/L (<1.00x103/µL or 
<1.00 GI/L) at any follow up visit, the patient should return for visits at least 
Q4W (may require unscheduled visits).  

As long as a patient’s neutrophil count is ≥1000 cells/L and <1500 cells/L 
(≥1.00x103/µL and <1.50x103/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 4 to 8 weeks 
(may require unscheduled visits).  

If, at Visit 802 or Visit 803, the patient’s neutrophil count is ≥1500 cells/L 
(≥1.50x103/L or ≥1.50 GI/L) 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 may 
be necessary.  
If, at Visit 803, the patient’s neutrophil count remains <1500 cells/L (<1.50x103/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).
8.4.9.2.
Hepatitis B Monitoring
Patients that are HBcAb+ at screening, regardless of other hepatitis B testing results, will have a 
serum HBV DNA specimen obtained to be analyzed by the central laboratory.  Such patients that 

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are determined to be HBV DNA negative (undetectable) may be enrolled into the study with 
required HBV DNA monitoring every 3 to 4 months during treatment and 12 weeks after the last 
dose of ixekizumab.  Patients that are found to be HBV DNA positive (detectable) at screening 
will be excluded from the trial.  
If the result of any subsequent HBV DNA testing is positive, the patient must be discontinued 
from the study treatment, should continue safety follow up, and should receive appropriate 
follow-up medical care, including consideration for antiviral therapy. A specialist physician in 
the care of patients with hepatitis (for example, infectious disease or hepatologist subspecialists) 
should be consulted and potentially start antiviral therapy prior to discontinuation of any 
immunosuppressant or immunomodulatory therapy (including investigational drug). Timing of 
discontinuation from the study and of any immunosuppressant/immunomodulatory therapy 
(including investigational product) needs to be based on the recommendations of the consulting 
specialist physician in conjunction with the investigator and medical guidelines/standard of care.
8.4.9.3.
Hypertension
Patients who experience changes in BP (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) on 2 consecutive visits should receive intervention for the management of 
hypertension.  See Section 7.1 for the discontinuation criterion related to hypertension.
8.5.
Pharmacokinetics
At the visits and times specified in the Schedule of Activities (Appendix 2), blood samples of 
approximately 4 mL each will be collected to determine the serum concentrations of ixekizumab.  
These blood samples for PK analysis are matched to the timing of samples for the assessment of 
immunogenicity.  These samples are designed to be taken at trough, that is, immediately prior to 
dosing at visits where dosing is scheduled. It is expected that these PK samples will allow 
sufficient description of ixekizumab PK profiles at steady state throughout the study.
Instructions for the collection and handling of blood samples will be provided by the sponsor.  
The actual date and time (24-hour clock time) of each sampling will be recorded.
Drug concentration information that may unblind the study will not be reported to investigative 
sites or blinded personnel until the study has been unblinded.
Samples collected for PK analysis will be tested at a laboratory approved by Lilly or its designee. 
Concentrations of immunoreactive ixekizumab in human serum will be determined by a 
validated method.
Bioanalytical samples collected to measure investigational product concentration will be retained 
for a maximum of 1 year following last patient visit for the study.
8.6.
Pharmacodynamics
Not applicable

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8.7.
Genetics
A blood sample will be collected for pharmacogenetic analysis as specified in the Schedule of 
Activities (Appendix 2) where local regulations and ERBs allow.  These samples are not being 
collected to create a biobank for conducting unspecified disease or population genetic research 
either now or in the future.
Samples will not be used to conduct unspecified disease or population genetic research either 
now or in the future.  Samples will be used to investigate variable response to ixekizumab and to 
investigate genetic variants thought to play a role in psoriasis and/or associated autoimmune 
conditions.  Assessment of variable response may include evaluation of AEs or differences in 
efficacy.  These studies may include but are not limited to the IL-17 and IL-23 family and 
receptor and signaling pathways, to evaluate their association with observed response to 
ixekizumab.
All pharmacogenetic samples will be coded with the patient number.  These samples and any 
data generated can be linked back to the patient only by the investigator site personnel.  Samples 
will be destroyed according to a process consistent with local regulations.
Samples will be retained for a maximum of 15 years after the last patient visit for the study, or 
for a shorter period if local regulations and/or ERBs impose shorter time limits, at a facility 
selected by the sponsor.  This retention period enables use of new technologies, response to 
regulatory questions, and investigation of variable response that may not be observed until later 
in drug development or when the drug is commercially available.
Molecular technologies are expected to improve during the 15-year storage period and therefore 
cannot be specifically named.  However, existing approaches include whole genome or exome 
sequencing, genome wide association studies, candidate gene studies, and epigenetic analyses.  
Regardless of technology utilized genotyping data generated will be used only for the specific 
research scope described here. 
8.8.
Biomarkers
Serum, plasma, and mRNA samples for nongenetic biomarker research will be collected at the 
times specified in the Schedule of Activities (Appendix 2) where local regulations and ERBs 
allow.
Samples will be used for research on the drug target, disease process, pathways associated with 
psoriasis and/or associated autoimmune conditions, mechanism of action of ixekizumab, and/or 
research method or in validating diagnostic tools or assay(s) related to psoriasis and/or associated 
autoimmune conditions. Proteomic, gene-expression, genomic, epigenetic, or metabolomic 
analysis may be performed on these samples.
All biomarker samples will be coded with the patient number.  These samples and any data 
generated can be linked back to the patient only by the investigator site personnel.  Samples will 
be destroyed according to a process consistent with local regulations.

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Samples will be retained for a maximum 15 years after the last patient visit for the study, or for a 
shorter period if local regulations and ERBs impose shorter time limits, at a facility selected by 
the sponsor.  This retention period enables use of new technologies, response to regulatory 
questions, and investigation of variable response that may not be observed until later in drug 
development or when the drug is commercially available.
8.8.1. Samples for Immunogenicity Research
Where local regulations and ERBs allow, blood samples for immunogenicity testing will be 
collected to determine antibody production against ixekizumab as specified in the Schedule of 
Activities (Appendix 2). The actual date of each sampling will be recorded at the study 
site. 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.
Samples will be retained for a maximum of 15 years after the last patient visit for the study, or 
for a shorter period if regulations and ERBs impose shorter time limits, at a facility selected by 
the sponsor.  The duration allows the sponsor to respond to future regulatory requests related to 
ixekizumab.
8.8.2. Samples for Genital Candida Testing 
Where local regulations and ERBs allow, genital skin swab samples for Candida testing will be 
collected and may be used to determine presence of Candida at baseline. Swabs will be 
collected from labia majora in women and glans penis in men.
Deficiency or inhibition of IL-17 has been linked to mucocutaneous candidiasis (Puel et al. 2011; 
Cosentyx package insert, 2015). In the Phase 3 trials of ixekizumab in the treatment of psoriasis, 
Candida infections were observed in approximately 3% of patients who received ixekizumab, 
some of which involved the genital area. None of the Candida infections were SAEs or led to 
discontinuation of study treatment. None of the vulvovaginal candidiasis cases were considered 
severe, and none were considered related to investigational product by investigators.  
Candida skin swabs will be tested at baseline for exploratory purposes to better understand 
colonization with Candida spp. of the genitalia of patients with psoriasis that involves the genital 
area.  In general, these test results are not clinically informative without a clinical diagnosis of 
candidiasis, and the results will not be shared with investigators.  If an investigator believes it is 
clinically indicated for patient management (per the local standard of care), then he/she may 
choose to take an additional skin swab to be evaluated per local procedures.
8.9.
Health Economics
Not applicable

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9. Statistical Considerations and Data Analysis
9.1.
Determination of Sample Size
The total sample size for the study will be approximately 146 patients randomized at 1:1 ratio in 
the Blinded Treatment Period to ixekizumab Q2W and placebo (73 patients per treatment group). 
No prior sPGA of Genitalia (primary outcome measure) data was available at the time of 
planning this study to guide sample size and power calculations because no biologic drug has 
been evaluated in a well-controlled clinical trial to date in patients with genital psoriasis.  
Therefore, based on the relevance and impact of sexual impairment in genital psoriasis, data 
from the assessment of DLQI Item 9 (How much has your skin caused any sexual difficulties?) 
outcomes in the ixekizumab Phase 2 and Phase 3 studies were used to calculate the sample size.  
Sample size was calculated assuming sexual impairment rates of 2% and 20% in the ixekizumab
Q2W and placebo treatment groups, respectively. With these assumed rates, a sample size of 
146 (73 per treatment group) is likely to achieve 94% power, based on a 2-sided Fisher's exact 
test at 0.05 level of significance.
9.2.
General Statistical Considerations
Statistical analysis of this study will be the responsibility of Eli Lilly and Company.
Categorical data for baseline variables will be summarized as frequency counts and percentages.  
Continuous data for baseline variables will be summarized in using the mean, standard deviation, 
minimum, maximum, median, and number of observations.
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 (CSR).  Additional exploratory analyses of the data will be conducted 
as deemed appropriate.
Complete details of the planned analyses will be documented in the statistical analysis plan 
(SAP).
General Considerations for Analyses during Period 2 (Blinded Treatment Period)
Comparisons of ixekizumab Q2W dosing versus placebo will be performed for all outcome 
variables in Period 2.  Baseline will be defined as the last available value before the first 
injection of the investigational product for both efficacy and safety analyses.  In most cases, this 
will be the measurement recorded at Week 0 (Visit 2).  For efficacy measures, if the patient does 
not take any injection, the last available value on or prior to randomization date will be used.  
Change from baseline at a particular visit will be calculated as the value at that visit minus the 
baseline value.  For safety analyses using a baseline period, the baseline period is defined as the 
time from Visit 1 to the date/time of the first injection.
For outcome measures that are not collected at each postbaseline visit, data may exist at visits 
where the outcome measure was not scheduled to be collected, due to ETVs.  In these situations, 

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data from the ETVs that does not correspond to the planned collection schedule will be excluded 
from any mixed-effects models for repeated measures (MMRM) analysis.  However, the data 
will still be used in other analyses, including shift analyses, change from baseline analyses using
last observation carried forward (LOCF) imputation method, and other categorical analyses.
9.3.
Analysis Population
Intent-to Treat Population:  The intent-to-treat (ITT) population consists of all randomized 
patients.  Even if the patients are not administered the assigned treatment, do not receive the 
correct treatment, or otherwise do not follow the protocol, they will be analyzed according to the 
treatment group to which they were assigned. 
Safety Population:  The safety population is defined as all randomized patients who received at 
least 1 dose of study treatment. Patients will be analyzed according to the dosing regimen to 
which they were assigned.
Open-Label Treatment Population:  The open-label treatment population consists of all 
randomized patients who received at least 1 dose of study treatment during Period 3 and have 
entered the Open-Label Treatment Period.  Patients will be analyzed according to the treatment 
group to which they were assigned in Period 2.  All analyses for Period 3 (Open-Label Treatment 
Period) will be conducted on this analysis population.  
Post-Treatment Follow-Up Population:  The post-treatment follow up population consists of
all randomized patients who received at least 1 dose of study treatment during Period 2 and have 
entered the Post-Treatment Follow-Up Period.  Patient data will be summarized according to the 
treatment group to which they were assigned in Period 2.  Safety analyses for Period 4 
(Post-Treatment Follow-Up Period) will be conducted on this analysis population.
9.3.1. Missing Data Imputation
The methods for imputation of missing data to be used in this study are described below.
Nonresponder Imputation (NRI)
Analysis of categorical efficacy and health outcome variables will be performed using NRI
method.  Patients will be considered nonresponders if they do not meet the clinical response 
criteria or have missing clinical response data at the time point of analysis.  Randomized patients 
without at least 1 postbaseline observation will also be defined as nonresponders for the NRI 
analysis.
Last Observation Carried Forward (LOCF)
LOCF method will be used to impute missing data for only the major secondary continuous 
outcome variable.  For patients having missing data at a visit, the last nonmissing postbaseline 
observation before the missing data will be carried forward to the corresponding time point of 
evaluation.  Randomized patients without at least 1 postbaseline observation will not be included 
in LOCF analyses.

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Modified Baseline Observation Carried Forward (mBOCF) 
An mBOCF analysis will be performed on all continuous efficacy and health outcome variables.
For patients discontinuing investigational product due to an AE, the baseline observation will be 
carried forward to the corresponding primary endpoint for evaluation.  For patients discontinuing 
investigational product for any other reason, the last nonmissing postbaseline observation before 
discontinuation will be carried forward to the corresponding time point of evaluation.
Randomized patients without at least 1 postbaseline observation will not be included for 
evaluation with the exception of patients discontinuing study treatment due to an AE.
In addition to NRI, mBOCF, and LOCF, other imputation methods may be used as deemed 
appropriate.
9.3.2. Adjustment for Multiple Comparisons
A multiple testing strategy for the primary and the major secondary endpoint will be 
implemented to control the family-wise type I error rate at a 2-sided α level of 0.05. The 
following primary and major secondary endpoint will be sequentially tested in the following 
order to compare ixekizumab Q2W versus placebo, using the primary analysis method.

Primary – Proportion of patients achieving sPGA of Genitalia (0,1) at Week 12

Major Secondary – Mean change from baseline in the genital psoriasis itch NRS item 
within the GPSS at Week 12
The primary endpoint will be tested at 2-sided α = 0.05. If the test for primary endpoint is 
significant, then the test for the major secondary endpoint will be performed. Otherwise the 
testing will stop. 
There will be no adjustment for multiple comparisons for any other analyses.
9.4.
Treatment Group Comparability
9.4.1. Patient Disposition
A detailed description of patient disposition will be provided at the end of the study.  All patients 
who discontinue from the study treatment and the study will be identified, and the extent of their 
participation in the study will be reported.  Patient disposition will be summarized for each 
treatment period and will include reasons for discontinuation.  The reasons for discontinuation 
during Blinded Treatment Period (Period 2) will be compared between treatment groups using 
Fisher’s exact test.
9.4.2. Patient Characteristics
Baseline characteristics, clinical, and health outcome measurements will be summarized for each
population – ITT and Open-Label Treatment.  Baseline characteristics will include gender, age, 
age category, weight, race, geographic region, baseline disease severity, duration of disease, 
previous nonbiologic systemic therapy, and previous biologic therapy.  Baseline clinical and 
PRO measurements will include sPGA of Genitalia score, mGPASI total score, overall sPGA,  

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overall PASI, BSA, GPSS total and item scores (including Genital Psoriasis Itch NRS), DLQI 
total score, GPSIS subscales, SFQ items, PatGA-Genital, Touch avoidance NRS, SF-36, QIDS-
SR16, and CAPP.
Treatment group comparisons will be conducted using Fisher’s exact test for categorical data and 
an analysis of variance (ANOVA) model with treatment as a factor for continuous data.
9.4.3. Concomitant Therapy
Previous and concomitant medications (including concomitant topical products such as 
emollients and other nonprescription topical products) will be summarized for patients who enter 
each treatment period and will be presented by World Health Organization Anatomic 
Therapeutic Class (WHOATC) Level 4 and WHO preferred term.  Treatment group comparisons 
in Period 2 will be conducted using Fisher’s exact test.
9.4.4. Treatment Compliance
Treatment compliance with investigational product will be summarized for patients who enter 
Period 2.  A patient will be considered compliant overall for each study period if he/she misses 
no more than 20% of the expected doses, does not miss 2 consecutive doses, and does not over-
dose (that is, take more injections at the same time point than specified in the protocol).  
Proportions of patients compliant overall will be compared between treatment groups during 
Period 2 using Fisher’s exact test.
9.5.
Primary and Secondary Analyses
9.5.1. Primary Analyses

Categorical
o
Treatment comparisons of categorical efficacy and health outcome variables will 
be performed using a logistic regression model with treatment and BSA category 
as factors, using NRI method. 

Continuous
o
The primary analyses for all continuous efficacy and health outcome variables 
will be performed using MMRM.  The model will include treatment, baseline 
BSA category, baseline value, visit, treatment-by-visit interaction, and 
baseline-by-visit interaction as fixed factors.  The covariance structure to model 
the within-patient errors will be unstructured.  If the unstructured covariance 
matrix results in a lack of convergence, the heterogeneous Toeplitz covariance 
structure, followed by the heterogeneous autoregressive covariance structure will 
be used. The Kenward-Roger method will be used to estimate the denominator 
degrees of freedom. Type III tests for the least-square (LS) means will be used 
for the statistical comparison; the 95% confidence interval (CI) will also be 
reported. Treatment group comparisons at all visits up to Week 12 will be tested.  
If the unstructured covariance matrix results in a lack of convergence, the 
heterogeneous Toeplitz covariance structure, followed by the heterogeneous 

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autoregressive covariance structure, followed by the compound symmetry will be 
used. This order is specified according to a decreasing number of covariance 
parameters in the structure.
9.5.2. Secondary Analyses

Categorical
o
Secondary analysis on the categorical efficacy variables will be conducted using a 
Fisher’s exact test.  
o
A categorical, pseudo-likelihood-based MMRM for categorical repeated measures 
analysis may also be performed for the primary endpoint of sPGA of 
Genitalia (0, 1).  The details of the analysis model will be presented in the SAP.

Continuous
o
Secondary analyses for treatment comparisons on continuous outcome variables 
will be conducted using an analysis of covariance (ANCOVA) model and LOCF 
or mBOCF imputation methods. The ANCOVA model will include treatment, 
baseline BSA category, and baseline value.  Type III sums of squares for the LS 
means will be used for the statistical comparison; the 95% CI will be reported.
9.5.3. Exploratory Analyses
The exploratory outcome measures will be analyzed using similar analysis methods described 
above. Complete details will be documented in the SAP.
9.6.
Safety Analyses
Safety will be assessed by summarizing and analyzing AEs including adjudicated
cerebrocardiovascular events, QIDS-SR16, C-SSRS, laboratory analytes including neutrophil 
counts and immunogenicity, vital signs, and concomitant medications. The duration of exposure 
will also be summarized.
The primary safety analyses will focus on comparisons of ixekizumab Q2W versus placebo in 
Period 2.  Treatment comparisons of categorical safety outcome variables will be performed
using Fisher’s exact test. Treatment comparisons of continuous safety outcome variables will be 
performed using ANCOVA with treatment and baseline value in the model.  
Summaries of safety data collected during the Open-Label Treatment Period and Post-Treatment 
Follow-Up Period will be presented separately. The categorical safety measures will be 
summarized with incidence rates. The mean change of the continuous safety measures will be 
summarized by visits. 
Unless otherwise specified, the baseline for safety analyses in the Open-Label Treatment Period
is defined as the last nonmissing assessment on or prior to Week 12 (Visit 7). Unless otherwise 
specified, the Post-Treatment Follow-Up Period Baseline is defined as the last nonmissing 
assessment on or prior to Week 52 (Visit 12) or ETV.

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9.6.1. Adverse Events
Adverse events are classified based upon the Medical Dictionary for Regulatory Activities 
(MedDRA). A TEAE is defined as an event that first occurred or worsened in severity after the 
first dose of study treatment and on or prior to the date of the last visit within the treatment 
period. Both the date/time of the event and the date/time of the dose (ie, injection) are 
considered when determining TEAEs.  For each TEAE, the severity is recorded according to the 
patient’s or physician’s perceived severity of the event (mild, moderate, or severe). A follow-up
emergent adverse event (FEAE) is defined as an event that first occurred or worsened in severity 
after the date of Week 52 (Visit 15) or the ETV. For events that are gender specific, the 
denominator and computation of the percentage will only include patients from the given gender.
An overall summary of AEs will be provided for each treatment period.  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 MedDRA system organ class 
(SOC) and preferred term (PT). TEAEs will also be summarized by PT sorted by decreasing 
frequency within SOC for all TEAEs, TEAEs by maximum severity, and TEAEs considered 
possibly related to investigational product.
FEAEs (all, by maximum severity, and FEAEs possibly related to investigational product by the 
investigator), SAEs including deaths, AEs that lead to study discontinuation will be summarized 
by MedDRA SOC and PT or by PT for the Post-Treatment Follow-Up Period (Period 4).
In addition to general safety parameters, safety information on specific topics of special interest 
will also be presented. Potential AESIs will be identified by a standardized MedDRA query 
(SMQ) or a Lilly defined MedDRA PT listing.
9.6.2. Clinical Laboratory Tests
Laboratory assessments will be presented as mean changes from baseline and as incidence of 
treatment-emergent abnormal, high, or low laboratory values.  Shift tables will be presented for 
selected parameters.

For categorical lab tests:  
o
Treatment-emergent abnormal value = a change from normal at all baseline visits 
to abnormal at any time postbaseline.

For continuous lab tests:  
o
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.
o
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.

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9.6.3. Vital Signs, Physical Findings, and Other Safety Evaluations
Vital signs will be presented as mean changes from baseline and as incidence of abnormal values 
and will be summarized for both predose and postdose at Week 0 (Visit 2) and Week 12 
(Visit 7), as applicable.
The maximum postbaseline QIDS-SR16 total score will be summarized by treatment, and shift 
table will be produced for the change from baseline in QIDS-SR16 total score category.
Suicide-related thoughts and behaviors and self-injurious behavior with no suicidal intent, based 
on the C-SSRS, will be listed by patient.
Other covariate data, including body weight, will be descriptively summarized by treatment 
groups.  Further analyses may be performed comparing the treatment groups.
9.7.
Pharmacokinetic/Pharmacodynamic Analyses
Observed ixekizumab serum concentrations will be summarized by visits and corresponding time 
when sampling occurred.
As appropriate, the PK and the exposure-response relationship between ixekizumab exposure 
and clinically important efficacy measures (for example, sPGA or mGPASI) may be explored 
using graphical methods and/or a modeling approach. If a modeling approach is taken, data may 
be combined with data from other ixekizumab studies if appropriate. 
The potential impact of immunogenicity on ixekizumab exposure and/or efficacy responses may
be evaluated by graphical assessments, as appropriate, to compare drug exposure or efficacy
responses between ADA negative and ADA positive patients at corresponding visits, or before
and after ADA development for patients who developed ADA.  Both treatment-emergent only
and all ADA positive/negative patients may be explored.  A similar approach may be taken if
patients become neutralizing anti-drug antibody (NAb) positive.
Additional analyses may be performed upon receipt of the data.  Data from this study may be
combined with data from previous efficacy studies for additional population PK and/or exposure
efficacy modelling if deemed appropriate.
9.8.
Other Analyses
9.8.1. Subgroup Analyses
To assess consistency of results among the 2 subpopulations determined by baseline BSA 
category (<10% versus ≥10% baseline BSA involvement), subgroup analysis will be conducted 
on sPGA of Genitalia (0,1) using the ITT population.
Other subgroups that may be evaluated include gender, age, weight, race, and geographic region. 
Detailed description of the subgroup variables will be provided in the SAP.
A logistic regression model with treatment, subgroup, and the interaction of subgroup by 
treatment included as factors will be used. The subgroup-by-treatment interaction will be tested 
at the significance level of 0.10. Treatment group differences will be evaluated within each 

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category of the subgroup using Fisher’s exact test, regardless of whether the interaction is 
statistically significant. Missing data will be imputed using NRI.  If any group within the 
subgroup is less than 10% of the total population, only summaries of the efficacy data will be 
provided (that is no inferential testing will be performed).  
Additional subgroup analyses on efficacy or safety may be performed as deemed appropriate.
9.8.2. Immunogenicity Analyses
The analyses of ADA effects will be conducted on all evaluable patients within the defined 
safety population.  Evaluable patients will be defined as either a) patients with an evaluable 
baseline sample and at least 1 evaluable postbaseline sample (that is, sample after administration
of investigational product); or b) patients with no evaluable baseline sample whose evaluable 
postbaseline samples were all ADA negative.  A treatment-emergent positive anti-drug antibody 
(TE-ADA+) patient will be defined as any occurrence of a greater than or equal to 4-fold or 
2 dilution increase in immunogenicity titer over the baseline titer.  This is equivalent to an 
increase in titer to ≥1:10, in the case of a negative result at baseline.  
The frequency and percentage (incidence) of patients with positive, negative, or inconclusive 
ADA at baseline and patients with positive, negative, or inconclusive TE-ADA postbaseline will 
be summarized by treatment group.  Additional summarizations for patients who are TE-ADA+
will be done for patients who are TE-ADA persistent or transient positive; patients who are NAb 
positive, negative, or inconclusive; and for ADA titers.
Assessment of immunogenicity with respect to safety will include comparison of patients who 
experience TEAEs of systemic allergy/hypersensitivity and of injection-site reactions and also 
develop treatment-emergent ADA positive status with patients who experience the same types of 
TEAEs but who remain treatment-emergent ADA negative.  ADA titers will also be evaluated in 
patients who experience these events.
9.9.
Interim Analyses
An interim database lock and the unblinding of the sponsor will occur, and the analysis will be 
performed at the time (that is, a cut-off date) the last patient completes Visit 7 (Week 12), 
completes ETV, or discontinues from the Blinded Treatment Period (Period 2).  This interim 
database lock will include all data collected by the cut-off date including data from the 
Open-Label Treatment Period and follow-up data from patients who have begun Post-Treatment 
Follow-Up Period (Period 4).  Because the study will still be ongoing for the Open-Label 
Treatment Period and the Post-Treatment Follow-Up Period at the time of this database lock, the 
analysis will be referred to as an interim analysis.  This interim analysis includes the final 
analysis for the Blinded Treatment Period (Period 2) of the study; therefore, there is no alpha 
adjustment due to this interim analysis.  There will be no data monitoring committee.
A final database lock will occur after the Post-Treatment Follow-Up Period is completed.  
Site-level unblinding will occur after final database lock is complete.
Unblinding details will be specified in a separate unblinding plan document.

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10. Study Governance Considerations
10.1. Regulatory and Ethical Considerations, Including the Informed 
Consent Process
10.1.1. Informed Consent
The investigator is responsible for ensuring:

that the patient understands the potential risks and benefits of participating in the 
study

that informed consent is given by each patient or legal representative.  This 
includes obtaining the appropriate signatures and dates on the ICF prior to the 
performance of any protocol procedures and prior to the administration of 
investigational product.

answering any questions the patient may have throughout the study and sharing in 
a timely manner any new information that may be relevant to the patient’s
willingness to continue his or her participation in the trial
10.1.2. Ethical Review
The investigator must give assurance that the ERB was properly constituted and convened as 
required by International Conference on Harmonisation (ICH) guidelines and other applicable 
laws and regulations.
Documentation of ERB approval of the protocol and the ICF must be provided to Lilly before the 
study may begin at the investigative site(s).  Lilly or its representatives must approve the ICF, 
including any changes made by the ERBs, before it is used at the investigative site(s).  All ICFs 
must be compliant with the ICH guideline on GCP.
The study site’s ERB(s) should be provided with the following:

the current IB and updates during the course of the study

ICF

relevant curricula vitae
10.1.3. Regulatory Considerations
This study will be conducted in accordance with:

consensus ethics principles derived from international ethics guidelines, including 
the Declaration of Helsinki and Council for International Organizations of
Medical Sciences (CIOMS) International Ethical Guidelines

applicable ICH GCP Guidelines

applicable laws and regulations
Some of the obligations of the sponsor will be assigned to a third-party.

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10.1.4. Investigator Information
Physicians with a specialty in dermatology or other specialties with appropriate experience 
(private practice, university, psoriasis research centers) will participate as investigators in this 
clinical trial.
10.1.5. Protocol Signatures
The sponsor’s responsible medical officer will approve the protocol, confirming that, to the best 
of his or her knowledge, the protocol accurately describes the planned design and conduct of the 
study.
After reading the protocol, each principal investigator will sign the protocol signature page and 
send a copy of the signed page to a Lilly representative.
10.1.6. Final Report Signature
The CSR coordinating investigator will sign the final CSR 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 CSR 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 CSR
coordinating investigator.
The sponsor’s responsible medical officer and statistician will approve the final CSR for this 
study, confirming that, to the best of his or her knowledge, the report accurately describes the 
conduct and results of the study.
10.2. 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 eCRFs, and 
study procedures.

make periodic visits to the study site

be available for consultation and stay in contact with the study site personnel by 
mail, telephone, and/or fax

review and evaluate eCRF data and use standard computer edits to detect errors in 
data collection

conduct a quality review of the database
In addition, Lilly or its representatives will periodically check a sample of the patient data 
recorded against source documents at the study site.  The study may be audited by Lilly or its 

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representatives, and/or regulatory agencies at any time.  Investigators will be given notice before 
an audit occurs.
The investigator will keep records of all original source data.  This might include laboratory 
tests, medical records, and clinical notes.  If requested, the investigator will provide the sponsor, 
applicable regulatory agencies, and applicable ERBs with direct access to original source 
documents.
10.2.1. Data Capture System
An electronic data capture system and an electronic source system will be used in this study.  
The site maintains a separate source for the data entered by the site into the sponsor-provided 
electronic data capture system.  Some or all of a patient’s data will be directly entered into the 
eCRF at the time that the information is obtained.  In instances where direct data entry is not 
used, the site will maintain source documentation in the trial files, and the patient’s data will be 
transcribed into the eCRF.  Paper documentation provided by the patient will serve as the source 
document, including a SDAL, that will be identified and documented by each site in that site’s 
study file.  
In this study, patient-rated scales/questionnaires will be collected at office visits (and at home) 
directly via an electronic patient-reported outcome (ePRO) tablet device as part of an 
ePRO/Clinical Outcome Assessment (COA) system.  Data entered into the ePRO/COA system 
will serve as the source data.
ePRO records are stored at a third party site.  Investigator sites will have continuous access to the 
source data during the study and will receive an archival copy at the end of the study for 
retention.
Any data collected within the ePRO instrument will serve as the source data and will be 
identified and documented by each site in that site’s study file.
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.
Data from complaint forms submitted to Lilly will be encoded and stored in the global product 
complaint management system.
10.3. Study and Site Closure
10.3.1. Discontinuation of Study Sites
Study site participation may be discontinued if Lilly, the investigator, or the ERB of the study 
site judges it necessary for medical, safety, regulatory, or other reasons consistent with 
applicable laws, regulations, and GCP.

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

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Appendix 1.
Abbreviations and Definitions
Term
Definition
ADA
anti-drug antibody
AE
adverse event:  Any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product that does not necessarily have a causal 
relationship with this treatment.  An 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
ALT
alanine aminotransferase
ANCOVA
analysis of covariance
AST
aspartate aminotransferase
BCG
Bacillus Calmette-Guérin
BP
blood pressure
BSA
body surface area
blinding/masking
A procedure in which one or more parties to the trial are kept unaware of the treatment 
assignment(s).  Unless otherwise specified, site level blinding will remain in effect until 
final database lock is complete.
A double-blind study is one in which neither the patient nor any of the investigator or 
sponsor staff who are involved in the treatment or clinical evaluation of the subjects are 
aware of the treatment received.
C-CASA
Columbia Classification Algorithm of Suicide Assessment
CEC
Clinical Events Committee
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
cGMP
current Good Manufacturing Practices
COA
Clinical Outcome Assessment
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.

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C-SSRS 
Columbia–Suicide Severity Rating Scale
eCRF
electronic case report form:  printed or electronic form for recording study participants’ 
data during a clinical study, as required by the protocol 
CRP
clinical research physician:  Individual responsible for the medical conduct of the study.  
Responsibilities of the CRP may be performed by a physician, clinical research 
scientist, global safety physician or other medical officer.
CSR
clinical study report
DLQI
Dermatology Life Quality Index
ECG
electrocardiogram
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.
ERB
ethical review board
ETV
early termination visit
FEAE
follow-up emergent adverse event
GCP
good clinical practice
GPSIS
Genital Psoriasis Sexual Impact Scale
GPSS
Genital Psoriasis Symptom Scale
HBcAb+
anti-hepatitis B core antibody
HBV
hepatitis B virus
HCV
hepatitis C virus
HRQoL
health-related quality of life
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Conference on Harmonisation
IL-17A
interleukin-17A 
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.

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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.
IRB
institutional review board
ITT
intention 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.
IWRS
interactive web-response system
LTBI
latent tuberculosis infection
LOCF
last observation carried forward
LS
least-square
mBOCF
modified baseline observation carried forward
MedDRA
Medical Dictionary for Regulatory Activities
mGPASI
modified Genital PASI
MI
myocardial infarction
MMRM
mixed-effects model for repeated measures
NAb
neutralizing anti-drug antibody
NRI
nonresponder imputation
NRS
numeric rating scale
PASI
Psoriasis Area and Severity Index
PASI 75
75% reduction in PASI from baseline
PK
pharmacokinetics
PPD
purified protein derivative
PPS
per-protocol set:  The set of data generated by the subset of patients who sufficiently 
complied with the protocol to ensure that these data would be likely to exhibit the 
effects of treatment, according to the underlying scientific model.
PRO/ePRO
patient-reported outcome/electronic patient-reported outcome
PT
preferred term

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PUVA
psoralen and ultraviolet A
Q2W
every 2 weeks
Q4W
every 4 weeks
QIDS-SR16
Quick Inventory of Depressive Symptomatology–Self Report (16 items)
QTc
corrected QT interval
SAE
serious adverse event
SAP
statistical analysis plan
SC
subcutaneous
screen
the act of determining if an individual meets minimum requirements to become part of a 
pool of potential candidates for participation in a clinical study
SDAL
study drug administration log
SF-36
36-Item Short Form Health Survey
SFQ
Sexual Frequency Questionnaire
SOC
system organ class
sPGA
static Physician Global Assessment
SUSARs
suspected unexpected serious adverse reactions
TB
tuberculosis
TBL
total bilirubin level
TE-ADA+
treatment-emergent positive 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.
ULN
upper limit of normal
UVB
ultraviolet B
WBC
white blood cell

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Appendix 2.
Schedule of Activities

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Schedule of Activities, Protocol I1F-MC-RHBQ
Screening
Baseline 
Randomization
Blinded Treatment Period 
(Period 2)
CRF Visit (V) Number
V1
V2
V3
V4
V5
V6
V7
Weeks since Randomization
W0
W1
W2
W4
W8
W12
Study Days
-30 to -7 d
V1A: 2-3 d 
post-V1
1
7 ± 2d
14 ± 2d
28 ± 2d
56 ± 2d
84 ± 4d
Informed consent
X
Complete medical history 
X
Demographicsa
X
Sociodemographicsb
X
X
Physical examinationc
X
X
X
Perianal/gluteal cleft
characteristics examination
X
X
X
Inclusion/exclusion criteriad
X
X
Body temperature 
X
Height
X
Weight
X
X
Waist circumference
X
Vital signs (BP and pulse)
X
Xe
X
X
X
X
Xe
Consumption habitsf
X
Concomitant medications
X
X
X
X
X
X
X
Review preexisting 
conditions/AEs
X
X
X
X
X
X
Randomization
X
Administer IP on site
X
X

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Screening
Baseline 
Randomization
Blinded Treatment Dosing Period 
(Period 2)
CRF Visit (V) Number
V1
V2
V3
V4
V5
V6
V7
Weeks since Randomization
W0
W1
W2
W4
W8
W12
Study Days
-30 to -7 d
V1A: 2-3 d 
post-V1
1
7 ± 2d
14 ± 2d
28 ± 2d
56 ± 2d
84 ± 4d
Dispense IP
X
X
X
X
X
Provide SDALg
X
X
X
X
X
Collect, review, and enter data 
from SDAL
X
X
X
X
X
Review e-diary
X
X
X
X
X
Dispense e-diary (includes GPSS, 
GPSIS, and SFQ)
X
Collect e-diary
X
Clinical Efficacy/Health Outcomes
sPGA (overall)
X
X
X
X
X
X
X
sPGA of Genitaliah
X
X
X
X
X
X
X
PASI (overall)
X
X
X
X
X
X
X
mGPASIi
X
X
X
X
X
X
X
BSA 
X
Xj
X
X
Xj
X
Xj
Fitzpatrick skin type
X
GPSSk
Daily from Screening (V1) to Week 12 (V7)
X
GPSISk
Weekly from Screening (V1) to Week 12 (V7)
X
SFQk
Weekly from Screening (V1) to Week 12 (V7)
X
PatGA-Genital
X
X
X
X
X
X
Touch avoidance NRS
X
X
X
X
X

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Screening
Baseline 
Randomization
Blinded Treatment Dosing Period 
(Period 2)
CRF Visit (V) Number
V1
V2
V3
V4
V5
V6
V7
Weeks since Randomization
W0
W1
W2
W4
W8
W12
Study Days
-30 to -7 d
V1A: 2-3 d 
post-V1
1
7 ± 2d
14 ± 2d
28 ± 2d
56 ± 2d
84 ± 4d
SF-36
X
X
DLQI
X
X
X
X
X
QIDS-SR16
X
X
X
C-SSRS§
X
X
X
X
X
X
Self-Harm Supplement Form§
X
X
X
X
X
X
CAPP (genital subindex)
X
X
Laboratory Tests
Administer PPD/QuantiFERON®-
TB Gold/T-SPOT®l
X
Read PPD
X
Chest x-raym
X
ECG
X
HIV/HCV
X
HBVn
X
X
X
FSHo
X
Serum pregnancy testp
X
Urine pregnancy testq
X
X
X
X
Serum chemistry
X
X
X
X
Lipid panelr
X
X
X
Hematology
X
X
X
X
TSH and free T4
X

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Screening
Baseline 
Randomization
Blinded Treatment Dosing Period 
(Period 2)
CRF Visit (V) Number
V1
V2
V3
V4
V5
V6
V7
Weeks since Randomization
W0
W1
W2
W4
W8
W12
Study Days
-30 to -7 d
V1A: 2-3 d 
post-V1
1
7 ± 2d
14 ± 2d
28 ± 2d
56 ± 2d
84 ± 4d
Genetic biomarker exploratory 
storage samples (DNA)s
Xt
Nonpharmacogenetic biomarker 
exploratory storage samples 
(serum, plasma, mRNA)s
X
X
X
X
Immunogenicity testings,u
X
X
X
X
PK sample (trough)s,v
X
X
X
X
Candida skin swabw
X

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Open-Label Treatment
(Period 3)
ETV
Post-Treatment Follow-Up
(Period 4)x
Required Follow-Up 
Visits
As-Needed 
Follow-Up 
Visits
CRF Visit (V) Number
V8
V9
V10
V11
V12
ETVy
V801
V802
V803z and 
onward
Weeks since Randomization
W16
W24
W28
W40
W52
LV + 4W
LV + 12W
LV + 24W
Study Days
112 ± 
7d
168 ± 
7d
196 ± 
7d
280 ± 
7d
364 ± 
7d
Sociodemographicsb
X
X
Physical examinationc
X
X
X
X
Perianal/gluteal cleft
characteristics examination
X
X
X
Weight
X
X
Waist circumference
X
X
Vital signs (BP and pulse)
X
X
X
X
X
X
X
X
X
Concomitant medications
X
X
X
X
X
X
X
X
X
Review preexisting conditions 
/AEs
X
X
X
X
X
X
X
X
X
Dispense IP
X
X
X
X
Provide SDALg
X
X
X
X
Collect, review, and enter data 
from SDAL
X
X
X
X
X
X

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Open-Label Treatment
(Period 3)
ETV
Post-Treatment Follow-Up
(Period 4)x
Required Follow-Up 
Visits
As-Needed 
Follow-Up 
Visits
CRF Visit (V) Number
V8
V9
V10
V11
V12
ETVy
V801
V802
V803z and 
onward
Weeks since Randomization
W16
W24
W28
W40
W52
LV + 4W
LV + 12W
LV + 24W
Study Days
112 ± 
7d
168 ± 
7d
196 ± 
7d
280 ± 
7d
364 ± 
7d
Review e-diary
X
Collect e-diary
X
Clinical Efficacy/Health Outcomes
sPGA (overall)
X
X
X
X
X
X
sPGA of Genitaliah
X
X
X
X
X
X
PASI (overall)
X
X
X
X
X
X
mGPASIi
X
X
X
X
X
X
BSA
X
Xj
X
X
Xj
Xj
GPSSk
X
X
X
X
X
X
GPSISk
X
X
X
X
X
X
SFQk
X
X
X
X
X
X
Touch avoidance NRS
X
X
X
X
X
X
SF-36
X
X
PatGA-Genital
X
X
X
X
X
X

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Open-Label Treatment
(Period 3)
ETV
Post-Treatment Follow-Up
(Period 4)x
Required Follow-Up 
Visits
As-Needed 
Follow-Up 
Visits
CRF Visit (V) Number
V8
V9
V10
V11
V12
ETVy
V801
V802
V803z and 
onward
Weeks since Randomization
W16
W24
W28
W40
W52
LV + 4W
LV + 12W
LV + 24W
Study Days
112 ± 
7d
168 ± 
7d
196 ± 
7d
280 ± 
7d
364 ± 
7d
DLQI
X
X
X
X
X
X
QIDS-SR16
X
X
X
X
C-SSRS§
X
X
X
X
X
X
X
X
X
Self-Harm Supplement Form§
X
X
X
X
X
X
X
X
X
CAPP (genital subindex)
X
X
Laboratory Tests
HBVn
X
X
X
X
Urine pregnancy testq
X
X
X
X
X
X
Serum chemistry
X
X
X
X
X
X
X
X
Hematology
X
X
X
X
X
X
X
X
Lipid panelr
X
X
X
X
Nonpharmacogenetic biomarker 
exploratory storage samples 
(serum, plasma, mRNA)s
X
X
Immunogenicity testings,u
X
X
X
X
X
PK sample (trough)s,v
X
X
X
X
X

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Abbreviations:  AE = adverse event; BP = blood pressure; BSA = body surface area; CAPP = Comprehensive Assessment of the Psoriasis Patient; CRF = case 
report form; C-SSRS = Columbia–Suicide Severity Rating Scale; d = days; DLQI = Dermatology Life Quality Index; DNA = deoxyribonucleic acid; ECG = 
electrocardiogram; ETV = early termination visit; FSH = follicle-stimulating hormone; GPSS = Genital Psoriasis Symptoms Scale; GPSIS = Genital 
Psoriasis Sexual Impact Scale; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus; IP = investigational product; LV= 
last visit; mRNA = messenger ribonucleic acid; mGPASI = modified Genital PASI; NRS = numeric rating scale; PASI = Psoriasis Area and Severity Index; 
PatGA-Genital = Patient’s Global Assessment of Genital Psoriasis; PK = pharmacokinetic; PPD = purified protein derivative; QIDS-SR16 = Quick Inventory 
of Depressive Symptomatology–Self Report (16 items); SDAL = Study Drug Administration Log; SFQ = Sexual Function Questionnaire; sPGA = static 
Physician’s Global Assessment; T4 = thyroxine; TB = tuberculosis; TSH = thyroid stimulating hormone; V = study visit; W = study week.
a
Demographics includes recording of year of birth, gender, ethnicity, and race.
b
Sociodemographics includes recording information on marital and sexual partner status.
c
One complete physical examination (excluding pelvic, rectal, and breast examinations) will be performed at screening.  All physical examinations throughout 
the study should include a symptom directed physical as well as examination of heart, lungs, abdomen, and visual examination of the skin. 
d
Patients who test positive for latent TB at screening may be rescreened (Section 8.4.5).  Additionally, patients who do not qualify at screening under exclusion 
criteria [34, 38, 39, 50] may be rescreened (1 time) as described in Section 5.3.
e
At baseline (Week 0) and Visit 7 (Week 12), BP and pulse should be measured prior to administration of the investigational product and again approximately 
1 hour post-administration.
f
Habits include recording of caffeine, alcohol, and tobacco consumption.
g
Patients will record information including the date, time, and 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 in the SDAL.
h
As part of sPGA of Genitalia, the investigator will record on the eCRF (yes/no) whether psoriasis is present in women on labia minora, labia majora, and/or 
perineum and in men on penis (glans and/or shaft), scrotum, and/or perineum.
i
As part of mGPASI, the investigator will record on the eCRF (yes/no) if fissure, erosion, and/or ulcer are present in the genital area (defined as labia minora, 
labia majora, perineum for female patients and on the penis, scrotum, perineum for male patients).
j
As part of BSA, the investigator will record if psoriasis is present on the face, inframammary fold, axilla, scalp, nail, pubis, perianal region, gluteal cleft, and 
inguinal creases in the eCRF (yes/no) at baseline (Week 0), Week 4, 12, 24, 52, or ETV.
k
Patients should complete the scales in the following order:  1. GPSS, 2. GPSIS, and 3. SFQ.  An e-diary will be used to collect these PROs up to and including 
Week 12 (V7); thereafter, patients will answer these questions only at scheduled study visits.  At Week 12 (V7), patients will complete these scales on site 
before completion of any other assessments.
l
See Section 8.4.5 for detailed description of QuantiFERON®-TB Gold, T-SPOT®, and PPD testing.
m A chest x-ray will be taken at screening unless one has been obtained within the past 6 months (provided the x-ray and/or report are available for review).
n
All patients will be tested for HBV at screening.  Patients who are HBsAg+ at screening are excluded.  Patients who are HBcAb+ at screening, regardless of 
other HBsAb status, will have serum HBV DNA obtained to be analyzed by the central laboratory.  Patients that are found to be HBV DNA positive 
(detectable) at screening will be excluded from the trial.  Patients that are HBcAb+ at screening and HBV DNA negative (undetectable) may be enrolled into 
the study with required HBV DNA monitoring every 3 to 4 months as outlined above in the Schedule of Activities during treatment and 12 weeks after the 
last dose of ixekizumab.  If the result of the HBV DNA testing is positive, the patient must be discontinued from the study treatment, should continue safety 
follow up, and should receive appropriate follow-up medical care (refer to Section 8.4.9.2 for further information regarding the timing of discontinuation).

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o
FSH test performed for women ≥40 and <60 years of age who have had a cessation of menses for at least 12 months to confirm nonchildbearing potential 
(≥40 mIU/mL).  FSH test will be performed centrally.
p
To be performed for females of childbearing potential only.  Serum pregnancy test will be done at Visit 1 only and will be performed centrally.  
q
To be performed for females of childbearing potential only.  Patients will undergo urine pregnancy self-testing at home on a monthly basis during periods 
between scheduled visits through Week 52. During these intervisit periods, the site must call the patient each month to obtain her pregnancy test results.  
Additional urine pregnancy testing can be performed at the investigator’s discretion.  Patients determined to be pregnant will be discontinued from treatment 
and will no longer be administered investigational product (see Section 7.1).
r
For the fasting lipid profile patients should not eat or drink anything except water for 12 hours prior to test. (For ETV:  [1] If ETV is planned, then fasting 
lipid profile should be performed, and [2] if ETV is not planned and patient is not fasting, the lipid profile should not be performed.)
s
Samples will be collected as allowed by local regulations.
t
If the DNA sample is not collected at Visit 2 (Week 0), it can be collected at Visit 3 (Week 4).
u
Immunogenicity samples may also be analyzed for ixekizumab serum concentration to facilitate in the interpretation of the immunogenicity data.  In addition, 
a blood sample will be collected, when possible, for any patient who experiences a potential systemic allergic/hypersensitivity reaction during the study as 
judged by the investigator (Section 8.4.6).
v
At visits where dosing is scheduled, PK samples will be collected prior to administration of investigational product (Section 8.5).
w Swab from labia majora for women and glans penis for men.
x
All patients receiving investigational product must enter into Period 4 and complete through Visit 802.  Patients may be followed beyond Visit 802 for 
continued monitoring of their neutrophil counts or for other safety reasons.
y
If a patient discontinues study treatment early, the patient will complete the ETV and then enter the Post-Treatment Follow-Up Period.
z
This visit will only occur if a patient’s neutrophil counts have not returned to the criteria defined in Section 8.4.9.1 or for other safety reasons.
§ 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.

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Appendix 3.
Clinical Laboratory Tests 
Hematologya,b
Serum Chemistrya,b
Hemoglobin
Sodium
Hematocrit
Potassium
Erythrocyte count (RBC)
Bicarbonate
Mean cell volume (MCV)
Chloride
Mean cell hemoglobin concentration (MCHC)
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 (BUN)
Lymphocytes
Uric acid
Monocytes
Creatinine
Eosinophils
Calcium
Basophils
Glucose
Albumin
Other Testsa
Cholesterol (total)
Human immunodeficiency virus antibody (HIV)c
Total protein
Hepatitis B Surface antigen (HBsAg)d,e
Anti-Hepatitis B Surface antibody (HBsAb)d,e
Triglycerides
Anti-Hepatitis B Core antibody (HBcAb)d,e
Gamma-Glutamyl Transferase (GGT)
Anti-Hepatitis C antibodyc,d
HBV DNAc,f
Lipid Panela,h
Thyroid-stimulating hormone (TSH) and Free T4
   Low Density Lipoprotein (LDL-C)
Ixekizumab serum concentration
   High Density Lipoprotein (HDL)
Exploratory storage samples (serum, plasma, DNA, & 
mRNA)
   Very Low Density Lipoprotein (VLDL)
Pregnancy Test (serum and urine)i
Purified Protein Derivative (PPD)g
Follicle-stimulating hormone (FSH)j

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Clinical Safety Laboratory Tests
Abbreviations:  Ab = antibody; DNA = deoxyribonucleic acid; HBcAb = anti-hepatitis B core antibody; HBsAb = 
anti-hepatitis B surface antibody; HBsAb+ = positive for anti-hepatitis B surface antibody; HBsAg- = negative 
for hepatitis B surface antigen; HBV = hepatitis B virus; LDL-C = low density lipoprotein calculated; mRNA = 
messenger ribonucleic acid; RBC = red blood cells; SGOT = serum glutamic oxaloacetic transaminase; SGPT = 
serum glutamic pyruvic transaminase; T4 = thyroxine; TB = tuberculosis; WBC = white blood cells.
a
Assayed by sponsor-designated laboratory.
b
Unscheduled blood chemistry and hematology panels may be performed at the discretion of the investigator.  
c
See exclusion criteria (Section 5.2).
d
Test required at Visit 1 only to determine eligibility of patient for the study.  
e
Quantitative HBsAb testing will be done in those patients who are HBsAg–, HBcAb+, and HBsAb+ at screening.  
f
Refer to hepatitis B monitoring (Section 8.4.9.2).
g
In countries where the QuantiFERON®-TB Gold test or T-SPOT® is available, it may be used instead of the PPD 
TB test and may be performed locally.
h
For the fasting lipid profile patients should not eat or drink anything except water for 12 hours prior to test.
i
Serum pregnancy test (women <60 years of age who are still of childbearing potential) and urine pregnancy test 
(women of childbearing potential).  Patients will undergo urine pregnancy self-testing at home on a monthly 
basis during periods between scheduled visits until Week 52.  During these intervisit periods, the site must call 
the patient each month to obtain her pregnancy test results.  Additional urine pregnancy testing can be performed 
at the investigator’s discretion.  Patients determined to be pregnant will be discontinued from treatment and will 
no longer be administered investigational product (see Section 7.1).
j
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).  FSH test will be performed centrally.

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Appendix 4.
Hepatic Monitoring Tests for 
Treatment-Emergent Abnormality
Selected tests may be obtained in the event of a treatment-emergent hepatic abnormality and may 
be required in follow-up with patients in consultation with the Lilly, or its designee, clinical 
research physician.
Hepatic Monitoring Tests
Hepatic Hematologya
Haptoglobina
Hemoglobin
Hematocrit
Hepatic Coagulationa
RBC
Prothrombin Time
WBC
Prothrombin Time, INR
Neutrophils, 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
Hepatitis E antibody, IgM
Alkaline phosphatase
ALT
Anti-nuclear antibodya
AST
GGT
Alkaline Phosphatase Isoenzymesa
CPK
Anti-smooth muscle antibody (or anti-actin 
antibody)a
Abbreviations:  ALT = alanine aminotransferase; AST = aspartate aminotransferase; GGT = gamma-glutamyl 
transferase; CPK = creatine phosphokinase; IgG = immunoglobulin G; IgM = immunoglobulin M; INR = 
international normalized ratio; RBC = erythrocyte count; WBC = leukocytes.  
a
Assayed by Lilly-designated or local laboratory.
b
Reflex/confirmation dependent on regulatory requirements and/or testing availability.

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Appendix 5.
Protocol Amendment I1F-MC-RHBQ(a) 
Summary: A Multicenter, Randomized, Double-Blind 
Study Comparing the Efficacy and Safety of Ixekizumab 
Versus Placebo in Patients with Moderate-to-Severe 
Genital Psoriasis
Overview
Protocol I1F-MC-RHBQ, A Multicenter, Randomized, Double-Blind Study Comparing the 
Efficacy and Safety of Ixekizumab Versus Placebo in Patients with Moderate-to-Severe Genital 
Psoriasis, has been amended.  The new protocol is indicated by amendment (a) and will be used 
to conduct the study in place of any preceding version of the protocol.  The overall changes and 
rationale for the changes made to this protocol are described below:

Added Columbia–Suicide Severity Rating Scale (C-SSRS) and Self-Harm Supplement 
Form to Schedule of Activities and C-SSRS to Discontinuation Criteria (Section 7.1.1, 
[11]), based on the following:
Patients with psoriasis are known to be at increased risk for depression and 
suicide-related behavior (including suicidal ideation), with psoriasis as a possible 
independent factor (Kurd et al. 2010; Dowlatshahi et al. 2014).  Psoriasis may
share etiological risks and pathophysiological mechanisms with depression, 
including a central inflammatory process common to both conditions (Serafini et 
al. 2013).  Thus, in Phase 3 studies of ixekizumab for treatment of psoriasis, the 
Quick Inventory of Depressive Symptomatology–Self Report (16 items) (QIDS-
SR16) scale, a reliable and validated tool, was used to ensure enrollment of 
appropriate patients for a trial of an investigational compound and was used to 
assess the potential impact of treatment on new onset or changes in depression, 
thoughts of death, and/or suicidal ideation severity during the conduct of the 
studies.  In addition to the QIDS-SR16 scale, analyses of adverse event (AE) data
related to depression and suicide-related behavior were also completed.
The C-SSRS is a tool used for prospective assessment of suicidal ideation and 
behavior.  The C-SSRS has become increasingly recognized by some clinical 
experts and regulatory bodies as the accepted standard for assessing such events 
in psoriasis clinical trials. Given this recognition, the clinical importance of 
suicide-related behavior, and the need for its continued assessment, Lilly plans to
add the C-SSRS in this clinical study to help further assess potential risk for such 
events.  The evaluation of QIDS-SR16 and AE data across all ixekizumab clinical 
trials to date do not indicate an increased risk of depression and/or suicide-related 
behaviors associated with ixekizumab treatment.

Added assessment of pharmacokinetics (PK) and immunogenicity at early termination 
visit (ETV) to improve the completeness of the dataset for patients who have an ETV.

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
Added collection of vital signs, review of concomitant medications, and review of 
preexisting conditions and AEs at visits in the Post-Treatment Follow-Up Period to 
facilitate safety monitoring in this study period.

Removed references to DermatologyLife Quality Index 0 (DLQI 0) in the interest of 
simplicity.  After approval of the original protocol, assessment of DLQI (0,1) was 
determined to be adequate for the purpose of this study.  

Removed general references to a Manual of Operations with regard to certain procedures 
(electrocardiograms [ECGs], vital signs, and physical examinations) and replaced with 
more detailed information for the convenience and understanding of readers.

Revised the note below inclusion criterion [5] to improve clarity.  

Corrected verb tenses and typographic errors, such as units of measure which should have 
been superscripted in the original text, to improve accuracy.  

Added cross references to Appendix 2 to improve clarity.
References cited in this appendix:
Dowlatshahi EA, Wakkee M, Arends LR, Nijsten T. The prevalence and odds of depressive 
symptoms and clinical depression in psoriasis patients: a systematic review and meta-analysis. 
J Invest Dermatol. 2014;134(6):1542-1551.
Kurd SK, Troxel AB, Crits-Christoph P, Gelfand JM. The risk of depression, anxiety, and 
suicidality in patients with psoriasis: a population-based cohort study. Arch Dermatol.
2010;146(8):891-895.
Serafini G, Pompili M, Elena Seretti M, Stefani H, Palermo M, Coryell W, Girardi P. The role of 
inflammatory cytokines in suicidal behavior: a systematic review. 
Eur Neuropsychopharmacol. 2013;23(12):1672-1686.

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Revised Protocol Sections
Note:
Deletions have been identified by strikethroughs.
Additions have been identified by the use of underscore.
Minor changes, such as for correction of punctuation or spelling errors, are not displayed.
3.
Objectives and Endpoints
Table RHBQ.3.1.
Objectives and Endpoints
Objectives
Endpoints
o
DLQI

Total score

Item 9

DLQI (0,1) and DLQI 0

Mean change from baseline in DLQI total score at 
Week 12

Mean change from baseline in DLQI total score 
and Item 9 score at Week 12

The proportions of patients achieving DLQI (0,1)
or DLQI 0, respectively
5.1.
Inclusion Criteria
Type of Patient and Disease Characteristics
[5]
Have BSA involvement of ≥1% at screening (Visit1) and at baseline (Week 0, 
Visit 2)
(Note:  Approximately 60%The majority of patients will be required to have 
BSA involvement ≥10% and up to approximately 40% of patients will be 
allowed to have BSA involvement of 1 to <10%.  Enrollment will be closely 
monitored, and enrollment in this lower BSA subpopulation will be stopped if a 
maximum of 40% is reached.)
7.1.1. Permanent Discontinuation from Study Treatment
Patients will may be permanently discontinued from study treatment in the following situations:
[11]
If Tthe patient scores a 3 for Item 12 (Thoughts of Death or Suicide) on the 
QIDS-SR16 at any time in the study.,
-OR-
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-

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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 patient is to 
be discontinued from the study. The patient should be evaluated on-site for risk 
of suicide and/or referred to a mental health provider for assessment.
8.1.2.2.2.
Genital Psoriasis Sexual Impact Scale
The Sexual Activity Avoidance Subscale includes items 1 and 2.  Item 1 asks whether the patient 
has been sexually active in the past week.  If a patient selects “no due to reasons other than my 
genital psoriasis,” they do not answer any additional questions on the scale and do not receive a 
score on the Sexual Activity Avoidance Subscale.  If a patient responds “no due to my genital 
psoriasis” on GPSIS item 1, this receives a score of “5” (equivalent to always avoid sexual 
activity due to genital psoriasis on item 2, which asks how often the patient avoided sexual 
activity in the past week due to genital psoriasis symptoms) on the Sexual Activity Avoidance 
Subscale.  For patients who are sexually active, a response of never, rarely, sometimes, and often 
on item 2 receive a score of 1, 2, 3, and 4, respectively, on the Sexual Activity Avoidance 
Subscale.  The Sexual Activity Avoidance Subscale ranges from 1 (never) to 5 (always) avoid 
sexual activity.  
8.1.3.1.4.
Binary Questions on Psoriasis Location
8.1.3.1.4.1.
Overall
Studying psoriasis involvement in the face, pubis, inguinal creases, gluteal cleft, and perianal 
area is of considerable interest for patients.  These are locations that bear high potential for 
stigmatization and negative impact on quality of life.  In addition, it is important to confirm that 
association of psoriasis on nails, scalp, axillae, and inframammary folds that have been 
correlated with genital involvement in past studies (Ryan et al. 2015).  To this end, binary
responses (yes/no) will be noted at baseline (Week 0), Week 4, 12, 24, 52, or ETV (footnote j of 
Schedule of Activities; Appendix 2) whether the patient currently has visible psoriasis on face, 
inframammary fold, axilla, scalp, nail, pubis, perianal region, gluteal cleft and inguinal creases.
8.1.3.1.4.2.
Genital
The specific location of psoriasis in the genital area may differentially impact patients in terms of 
sexual avoidance and frequency as well as physical discomfort and pain.  To this end, binary 
questions (yes/no) will be asked at each study visit (footnote h of Schedule of Activities;
Appendix 2) whether the patient current has visible psoriasis in women on labia minora, labia 
majora, and/or perineum and in men on the penis (glans and/or shaft), scrotum, and/or perineum.

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8.1.3.1.5.
Binary Questions on Characteristics
8.1.3.1.5.1.
Genital
Publications related to genital psoriasis note that fissure, erosion, and ulcers may be present in 
the genital area.  These characteristics may increase the pain and discomfort of genital psoriasis 
and also significantly impact sexual function and quality of life.  Fissure, erosion, and ulcer are 
assessed collectively on the mGPASI but are not identified individually on the scale.  To better 
understand which specific characteristics impact patients with psoriasis, information on presence 
of these characteristics will be recorded on the eCRF.  Binary questions (yes/no) will be asked at 
each study visit (footnote i of Schedule of Activities; Appendix 2) regarding presence of fissure, 
erosion, and ulcer in the genital area (labia minora, labia majora, and perineum in female patients 
and penis, scrotum, and perineum in male patients).
8.1.3.1.5.2.
Perianal/Gluteal Cleft
Little information is available regarding perianal characteristics in patients with psoriasis, and 
better understanding is needed.  Fissures, abscess, ulcer, and skin tags may be present in the 
perianal area/gluteal cleft but have not been well studied in patients with psoriasis.  However, 
perianal disease may significantly impact quality of life and add to discomfort/pain related to the 
disease.  To this end, binary questions (yes/no) will be asked periodically at study visits, 
according to the Schedule of Activities (Appendix 2, row for “Perianal/gluteal cleft 
characteristics examination”), regarding presence in the perianal area of fissure, abscess, ulcer, 
and skin tags and in the gluteal cleft of fissure.
8.4.
Safety Assessment
8.4.1. Electrocardiograms
For each patient, ECGs should a 12-lead digital ECG will be collected locally at screening 
according to the Schedule of Activities (Appendix 2).  Patients must be supine for approximately 
5 to 10 minutes before ECG collection and remain supine but awake during ECG 
collection.Electrocardiograms should be recorded according to the study specific 
recommendations included in the Manual of Operations for the study. 
Electrocardiograms will be interpreted locally by a qualified physician 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.  The qualified physician must document his/her review of the ECG at the 
time of evaluation.  Any clinically significant findings from ECGs that result in a diagnosis and 
that occur after the patient receives the first dose of the investigational treatment should be 
reported to Lilly or its designee as an AE via eCRF.
The ECGs will be maintained at the site and made available to the sponsor as requested.

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8.4.2. Vital Signs
Vital signs (BP and pulse) and body temperature will be measured (sitting) after resting for a 
minimum of 10 minutes at visits indicated in For each patient, vital signs measurements should 
be conducted according to the Schedule of Activities (Appendix 2) and following the study 
specific recommendations included in the Manual of Operations for the study.  At baseline 
(Week 0) and Visit 7 (Week 12), BP and pulse should be measured prior to administration of the 
investigational product and again approximately 1 hour post-administration.  
Any clinically significant findings from vital signs measurement that result in a diagnosis and 
that occur after the patient receives the first dose of study treatment should be reported to Lilly or 
its designee as an AE via eCRF.  Additional measurements of vital signs may be performed at 
the discretion of the investigator.
8.4.4. Physical Examination
For each patient, aone complete physical examination (excluding pelvic, rectal, and breast
examinations) will be performed at screeningshould be conducted according to the Schedule of 
Activities (Appendix 2) and following the study specific recommendations included in the 
Manual of Operations for the study.  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 
physical examinations throughout the study are indicated in the Schedule of Activities (Appendix 
2) and 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.
8.4.8. 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 
during the 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 
Classification Algorithm of Suicide Assessment (C-CASA) categorization of suicidal events.  
Patients will be assessed according to the Schedule of Activities (Appendix 2).
The Self-Harm Supplement Form is a one-question form that asks for the number of suicidal or 
nonsuicidal self-injurious behaviors the patient has experienced 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 to be completed. This information is 
then documented in the eCRF.  The Self-Harm Supplement Form will be completed according to 
the Schedule of Activities (Appendix 2).

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8.4.9. 8.4.8.  Safety Monitoring
8.4.9.1. 8.4.8.1.  Neutropenia
8.4.9.2. 8.4.8.2.  Hepatitis B Monitoring
8.4.9.3. 8.4.8.3.  Hypertension
8.5.
Pharmacokinetics
At the visits and times specified in the Schedule of Activities (Appendix 2), blood samples of 
approximately 4 mL each will be collected to determine the serum concentrations of ixekizumab.  
These blood samples for PK analysis are matched to the timing of samples for the assessment of 
immunogenicity.  These samples are designed to be taken at trough, that is, immediately prior to 
dosing at visits where dosing is scheduled.  It is expected that these PK samples will allow 
sufficient description of ixekizumab PK profiles at steady state throughout the study.
9.6.
Safety Analyses
Safety will be assessed by summarizing and analyzing AEs including adjudicated
cerebrocardiovascular events, QIDS-SR16, C-SSRS, laboratory analytes including neutrophil 
counts and immunogenicity, vital signs, and concomitant medications.  The duration of exposure 
will also be summarized.
9.6.3. Vital Signs, Physical Findings, and Other Safety Evaluations
Vital signs will be presented as mean changes from baseline and as incidence of abnormal values 
and will be summarized for both predose and postdose at Week 0 (Visit 2) and Week 12 
(Visit 7), as applicable.
The maximum postbaseline QIDS-SR16 total score will be summarized by treatment, and shift 
table will be produced for the change from baseline in QIDS-SR16 total score category.
Suicide-related thoughts and behaviors and self-injurious behavior with no suicidal intent, based 
on the C-SSRS, will be listed by patient.
Other covariate data, including body weight, will be descriptively summarized by treatment 
groups.  Further analyses may be performed comparing the treatment groups.

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11.
References
Columbia University Medical Center. Columbia–Suicide Severity Rating Scale (C-SSRS) web 
site. Available at: http://www.cssrs.columbia.edu. Accessed April 21, 2011.
Dowlatshahi EA, Wakkee M, Arends LR, Nijsten T. The prevalence and odds of depressive 
symptoms and clinical depression in psoriasis patients: a systematic review and meta-analysis. 
J Invest Dermatol. 2014;134(6):1542-1551.
Kurd SK, Troxel AB, Crits-Christoph P, Gelfand JM. The risk of depression, anxiety, and 
suicidality in patients with psoriasis: a population-based cohort study. Arch Dermatol. 
2010;146(8):891-895.
Posner K, Oquendo MA, Gould M, Stanley B, Davies M. Columbia Classification Algorithm of 
Suicide Assessment (C-CASA): classification of suicidal events in the FDA’s pediatric 
suicidal risk analysis of antidepressants. Am J Pyschiatry. 2007;164(7):1035-1043.
Serafini G, Pompili M, Elena Seretti M, Stefani H, Palermo M, Coryell W, Girardi P. The role of 
inflammatory cytokines in suicidal behavior: a systematic review. 
Eur Neuropsychopharmacol. 2013;23(12):1672-1686.
Appendix 1.
Abbreviations and Definitions
Term
Definition
C-CASA
Columbia Classification Algorithm of Suicide Assessment
C-SSRS 
Columbia–Suicide Severity Rating Scale

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Appendix 2.
Schedule of Activities
Schedule of Activities, Protocol I1F-MC-RHBQ (additions)
Screening
Baseline 
Randomization
Blinded Treatment Dosing Period 
(Period 2)
CRF Visit (V) Number
V1
V2
V3
V4
V5
V6
V7
Weeks since Randomization
W0
W1
W2
W4
W8
W12
Study Days
-30 to -7 d
V1A: 2-3 d 
post-V1
1
7 ± 2d
14 ± 2d
28 ± 2d
56 ± 2d
84 ± 4d
C-SSRS§
X
X
X
X
X
X
Self-Harm Supplement Form§
X
X
X
X
X
X

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Schedule of Activities, Protocol I1F-MC-RHBQ (additions - concluded)
Open-Label Treatment
(Period 3)
ETV
Post-Treatment Follow-Up
(Period 4)x
Required Follow-Up 
Visits
As-Needed 
Follow-Up 
Visits
CRF Visit (V) Number
V8
V9
V10
V11
V12
ETVy
V801
V802
V803z and 
onward
Weeks since Randomization
W16
W24
W28
W40
W52
LV + 4W
LV + 12W
LV + 24W
Study Days
112 ± 
7d
168 ± 
7d
196 ± 
7d
280 ± 
7d
364 ± 
7d
Vital signs (BP and pulse)
X
X
X
X
X
X
X
X
X
Concomitant medications
X
X
X
X
X
X
X
X
X
Review preexisting conditions 
/AEs
X
X
X
X
X
X
X
X
X
Clinical Efficacy/Health Outcomes
C-SSRS§
X
X
X
X
X
X
X
X
X
Self-Harm Supplement Form§
X
X
X
X
X
X
X
X
X
Laboratory Tests
Immunogenicity testings,u
X
X
X
X
X
PK sample (trough)s,v
X
X
X
X
X
Abbreviations:  C-SSRS = Columbia–Suicide Severity Rating Scale;
v
At visits where dosing is scheduled, PK samples will be collected prior to administration of investigational product (Section 8.5).
§ 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.

Leo Document ID = 4db7f1f5-9467-41d2-b99e-65a2cd765327
Approver: 
Approval Date & Time: 22-Jan-2016 15:37:16 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 22-Jan-2016 17:49:44 GMT
Signature meaning: Approved
PPD
PPD