A 24-Week Multicenter, Open-label, Single-arm, Phase 4 Study to Evaluate the Safety of Ixekizumab in Patients With Moderate-to-Severe Plaque Psoriasis or Active Psoriatic Arthritis in India
Phase: PHASE4
Conditions: Plaque Psoriasis, Psoriatic Arthritis
Sponsor: Eli Lilly and Company

Protocol: I1F-IN-RHCZ (a) 
 
 
A 24-Week Multicenter, Open-Label, Single-Arm, Phase 4 Study to Evaluate the Safety of 
Ixekizumab in Patients with Moderate-to-Severe Plaque Psoriasis and/or Active Psoriatic 
Arthritis in India 
 
 
NCT05855967 
 
 
Approval Date: 14-Feb-2023 
 
 

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Protocol I1F-IN-RHCZ (a) 
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Title Page  
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. 
Protocol Title: A 24-Week Multicenter, Open-Label, Single-Arm, Phase 4 Study to Evaluate the 
Safety of Ixekizumab in Patients with Moderate-to-Severe Plaque Psoriasis 
and/or Active Psoriatic Arthritis in India 
Protocol Number: I1F-IN-RHCZ 
Amendment Number: RHCZ(a) 
Compound: Ixekizumab (LY2439821) 
Brief Title: A study to investigate the safety of ixekizumab in participants aged ≥18 years with 
moderate-to-severe plaque psoriasis and/or active psoriatic arthritis in India 
Study Phase:  4 
Sponsor Name: Eli Lilly and Company (India) Pvt. Ltd. 
Legal Registered Address:  
Eli Lilly and Company (India) Pvt. Ltd. 
 
 
 
Plot no. 92, Sector 32, Gurugram, Haryana-122001, India 
Regulatory Agency Identifier Number(s): 
 
 
CDSCO Permission Reference Number: IMP/BIO/22/000012 
 
Approval Date: Protocol Amendment (a) Electronically Signed and Approved by Lilly on date 
provided below. 
 
Document ID: VV-CLIN-075015 
 
 
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Protocol I1F-IN-RHCZ (a) 
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Medical Monitor Name and Contact Information will be provided separately.  
 
 
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Protocol I1F-IN-RHCZ (a) 
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Protocol Amendment Summary of Changes Table  
 
DOCUMENT HISTORY 
Document 
Date 
Original Protocol 
05 May 2022 
Overall Rationale for the Amendment: 
Protocol I1F-IN-RHCZ, a 24-Week Multicenter, Open-Label, Single-Arm, Phase 4 Study to 
Evaluate the Safety of Ixekizumab in Patients with Moderate-to-Severe Plaque Psoriasis and/or 
Active Psoriatic Arthritis in India, 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 following are the overall rationale for the changes made to this protocol: 
 To comply with Subject Expert Committee (SEC; Ministry of Health [MoH]) 
recommendations, and  
 To provide more clarity regarding the assessments to be collected and analyzed for the 
PsA participants who have active plaque psoriasis. 
Other minor corrections (spelling errors, grammar corrections, formatting, and so on) and 
clarifications or semantic changes not affecting content have also been made in the document. 
The following table presents the overall changes and rationale for the changes made to this 
protocol: 
Section # and Name 
Description of Change 
Brief Rationale 
Section 1.1 Protocol 
Synopsis and 
Section 3 Objectives and 
Endpoints 
Added a note for Other 
Efficacy Endpoints (PASI 
75, 90, 100, PASI change 
from baseline, sPGA [0, 1] 
and sPGA [0], and BSA 
change from baseline) - “For 
PsA participants with 3% or 
more body surface area 
(BSA) of PsO, both PsA and 
PsO efficacy outcomes will 
be collected.” 
To provide more clarity regarding 
the assessments to be collected and 
analyzed for the PsA participants 
who have active plaque psoriasis. 
Section 1.1 Protocol 
Synopsis, 
Section 1.2 Schema and 
Section 4.1 Overall 
Design 
Updated a statement related 
to study treatment. 
To provide clarity that treatment 
regimen for PsA participants with 
moderate-to-severe PsO is same as 
that for participants with PsO. 
Section 1.1 Protocol 
Synopsis, 
Updated text regarding PsA 
participants with 
moderate-to-severe PsO is 
To provide clarity that treatment 
regimen for PsA participants with 
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Protocol I1F-IN-RHCZ (a) 
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Section # and Name 
Description of Change 
Brief Rationale 
Section 4.2 Scientific 
Rationale for Study 
Design, and 
Section 6.1 Study 
Intervention(s) 
administered 
same as that for participants 
with PsO in synopsis and 
Section 6.1. 
 
Also, updated Tables 
RHCZ.6.1 and RHCZ.6.2 in 
Section 6.1. 
moderate-to-severe PsO is same as 
that for participants with PsO. 
Section 1.3 Schedule of 
Activities 
Added a row for “Substance 
use (alcohol, caffeine, 
tobacco use).” 
To collect additional participant 
history information. 
Section 1.3 Schedule of 
Activities 
Added “Evaluation for 
Disease Relapse” and 
footnote annotation b. 
To comply with Subject Expert 
Committee (SEC; Ministry of 
Health [MoH]) recommendations, 
Disease Relapse Evaluation has 
been included at screening visit. 
Section 1.3 Schedule of 
Activities 
Added a footnote annotation 
“i” to update a note 
describing requirement of 
assessments for participants 
with psoriatic arthritis 
(PsA).  
To provide clarity on what 
assessments are to be administered 
to which participants. 
Section 1.3 Schedule of 
Activities 
Removed baseline 
assessment of “Collect, 
review, and enter data from 
Study Intervention 
Administration Log.” 
Rectified original protocol typo 
error. 
Section 1.3 Schedule of 
Activities 
Included Week 24 
evaluation of active 
tuberculosis (TB) in patients 
by QuantiFERON 
Tuberculosis TB Gold test 
and chest x-ray. 
To comply with SEC (MoH) 
recommendations, Week 24 
evaluation has been included for 
active tuberculosis by 
QuantiFERON TB Gold test and 
chest x-ray at Week 24 of the 
treatment. 
Section 1.3 Schedule of 
Activities 
Modified a general table 
note at the end of schedule 
of activities (SoA) table 
footnote. 
To provide more clarity regarding 
the assessments to be collected and 
analyzed for the PsA participants 
who have active plaque psoriasis. 
Section 2.1 Study 
Rationale 
Added definition of 
moderate-to-severe plaque 
psoriasis. 
To clarify original content. 
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Section # and Name 
Description of Change 
Brief Rationale 
Section 4.1.4 Post-
Treatment Follow-Up 
Period (Period 4) 
Timing of follow-up visit, 
Visit 802 is updated to 8 
weeks after Visit 801. 
To clarify original content. 
Section 8.1 Efficacy 
Assessment 
Updated a statement to 
mention that PsO outcome 
will be collected among all 
the PsA participants with 
3% or more BSA of PsO. 
Added Table RHCZ.8.1 to 
present clinician and patient 
assessments for different 
participants. 
To provide clarity on what 
assessments are to be administered 
to which participants. 
Section 8.1.2 American 
College of Rheumatology 
20, 50, and 70 Responder 
Index 
Included a statement in 
subsection Patient’s 
Assessment of Pain Visual 
Analog Scale – “Patient’s 
Assessment of Pain VAS 
will be administered only to 
PsA participants. The 
question related to pain 
assessment will be included 
in HAQ-DI assessment.” 
To clarify original content. 
Section 8.1.3 Patient 
Global Assessment of 
Disease Activity VAS  
 
Section 8.1.4 Physician’s 
Global Assessment of 
Disease Activity Visual 
Analog Scale 
Added separate scales for 
PsO and PsA participants. 
To clarify original content. 
Section 8.2.4 Evaluation 
of Disease Relapse 
Added details for Evaluation 
of Disease Relapse. 
To comply with SEC (MoH) 
recommendations, Disease 
Relapse Evaluation has been 
included at screening visit. 
Section 9.2 Analyses 
Populations. 
Updated the definition 
details of analysis 
population, 
Updated the analysis populations 
to include PsO with no active PsA 
population and active PsA 
population; text was defined 
accordingly. 
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Section # and Name 
Description of Change 
Brief Rationale 
Sections 9.5.3 Secondary 
Endpoint(s) Analysis and 
9.5.5 Safety Analyses 
Updated the secondary and 
safety analysis details for 
each indication and 
subgroup. 
To provide clarity on the analysis 
of the PsO and PsA endpoints 
based on the groups or subgroups 
and corresponding populations as 
per the data collection. 
 
Updated to provide clarity on the 
stratification for Safety Analyses. 
 
 
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Table of Contents  
1. 
Protocol Summary ........................................................................................................11 
1.1. 
Synopsis ..........................................................................................................................11 
1.2. 
Schema ............................................................................................................................16 
1.3. 
Schedule of Activities (SoA) ..........................................................................................17 
2. 
Introduction ...................................................................................................................21 
2.1. 
Study Rationale ...............................................................................................................21 
2.2. 
Background .....................................................................................................................21 
2.3. 
Benefit/Risk Assessment ................................................................................................23 
3. 
Objectives and Endpoints ............................................................................................24 
4. 
Study Design ..................................................................................................................26 
4.1. 
Overall Design ................................................................................................................26 
4.1.1. 
Screening Period (Period 1) ............................................................................................27 
4.1.2. 
Induction Dosing Period (Period 2) ................................................................................27 
4.1.3. 
Maintenance Period (Period 3) .......................................................................................27 
4.1.4. 
Post-Treatment Follow-Up Period (Period 4) .................................................................28 
4.2. 
Scientific Rationale for Study Design ............................................................................29 
4.3. 
Justification for Dose ......................................................................................................29 
4.4. 
End of Study Definition ..................................................................................................29 
5. 
Study Population ...........................................................................................................30 
5.1. 
Inclusion Criteria ............................................................................................................30 
5.2. 
Exclusion Criteria ...........................................................................................................32 
5.3. 
Lifestyle Considerations .................................................................................................38 
5.4. 
Screen Failures ................................................................................................................38 
5.5. 
Criteria for Temporarily Delaying Enrollment/Administration of 
Study Intervention of a Participant .................................................................................38 
6. 
Study Intervention(s) and Concomitant Therapy .....................................................39 
6.1. 
Study Intervention(s) Administered................................................................................39 
6.2. 
Preparation, Handling, Storage, and Accountability ......................................................41 
6.3. 
Measures to Minimize Bias ............................................................................................41 
6.4. 
Study Intervention Compliance ......................................................................................41 
6.5. 
Dose Modification ..........................................................................................................42 
6.6. 
Continued Access to Study Intervention after the End of the 
Study ...............................................................................................................................42 
6.7. 
Treatment of Overdose ...................................................................................................42 
6.8. 
Concomitant Therapy .....................................................................................................42 
7. 
Discontinuation of Study Intervention and Participant 
Discontinuation/ Withdrawal.......................................................................................46 
7.1. 
Discontinuation of Study Intervention ............................................................................46 
7.1.1. 
Permanent Discontinuation from Study Intervention .....................................................46 
7.1.2. 
Liver Chemistry Stopping Criteria ..................................................................................48 
7.1.3. 
Temporary Discontinuation ............................................................................................48 
7.2. 
Participant Discontinuation/Withdrawal from the Study ................................................49 
7.2.1. 
Discontinuation of Inadvertently Enrolled Participants ..................................................49 
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7.3. 
Lost to Follow up ............................................................................................................49 
8. 
Study Assessments and Procedures.............................................................................51 
8.1. 
Efficacy Assessments .....................................................................................................51 
8.1.1. 
Efficacy Assessments......................................................................................................53 
8.1.2. 
American College of Rheumatology 20, 50, and 70 Responder 
Index ...............................................................................................................................53 
8.1.3. 
Patient Global Assessment of Disease Activity VAS .....................................................56 
8.1.4. 
Physician’s Global Assessment of Disease Activity Visual 
Analog Scale ...................................................................................................................56 
8.2. 
Safety Assessments .........................................................................................................56 
8.2.1. 
Physical Examinations ....................................................................................................56 
8.2.2. 
Vital Signs .......................................................................................................................56 
8.2.3. 
Electrocardiograms .........................................................................................................57 
8.2.4. 
Evaluation of Disease Relapse ........................................................................................57 
8.2.5. 
Clinical Safety Laboratory Tests ....................................................................................58 
8.2.6. 
Pregnancy Testing ...........................................................................................................59 
8.2.7. 
Chest X-Ray and Tuberculosis Testing ..........................................................................59 
8.2.8. 
Safety Monitoring ...........................................................................................................61 
8.3. 
Adverse Events, Serious Adverse Events, and Product 
Complaints ......................................................................................................................63 
8.3.1. 
Timing and Mechanism for Collecting Events ...............................................................64 
8.3.2. 
Pregnancy ........................................................................................................................65 
8.3.3. 
Adverse Events of Special Interest .................................................................................66 
8.4. 
Pharmacokinetics ............................................................................................................66 
8.5. 
Pharmacodynamics .........................................................................................................66 
8.6. 
Genetics ..........................................................................................................................66 
8.7. 
Biomarkers ......................................................................................................................66 
8.8. 
Health Economics or Medical Resource Utilization and Health 
Economics] .....................................................................................................................66 
9. 
Statistical Considerations .............................................................................................67 
9.1. 
Statistical Hypotheses .....................................................................................................67 
9.2. 
Analyses Populations ......................................................................................................67 
9.3 
Missing Data Imputation ................................................................................................67 
9.3.1 
General Nonresponder Imputation for Clinical Response ..............................................67 
9.4 
Study Participant Disposition and Characteristics ..........................................................68 
9.4.1 
Study Participant Disposition .........................................................................................68 
9.4.2 
Study Participant Characteristics ....................................................................................68 
9.4.3 
Concomitant Therapy......................................................................................................68 
9.4.4 
Treatment Compliance ....................................................................................................68 
9.5 
Statistical Analyses .........................................................................................................68 
9.5.1. 
General Considerations ...................................................................................................68 
9.5.2 
Primary Endpoint Analysis .............................................................................................69 
9.5.3 
Secondary Endpoint(s) Analysis .....................................................................................69 
 
 
9.5.5 
Safety Analyses ...............................................................................................................70 
9.6 
Interim Analysis ..............................................................................................................71 
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9.7 
Sample Size Determination ............................................................................................72 
10 
Supporting Documentation and Operational Considerations ..................................73 
10.1 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ................................................................................................................73 
10.1.1 
Regulatory and Ethical Considerations ...........................................................................73 
10.1.2 
Financial Disclosure........................................................................................................73 
10.1.3 
Informed Consent Process ..............................................................................................74 
10.1.4 
Data Protection................................................................................................................74 
10.1.5 
Data Quality Assurance ..................................................................................................74 
10.1.6 
Source Documents ..........................................................................................................76 
10.1.7 
Study and Site Start and Closure ....................................................................................76 
10.1.8 
Publication Policy ...........................................................................................................77 
10.1.9 
Investigator Information .................................................................................................77 
10.2 
Appendix 2: Clinical Laboratory Tests ...........................................................................78 
10.3 
Appendix 3: Adverse Events and Serious Adverse Events: 
Definitions and Procedures for Recording, Evaluating, Follow-
up, and Reporting ............................................................................................................80 
10.3.1 
Definition of AE .............................................................................................................80 
10.3.2 
Definition of SAE ...........................................................................................................81 
10.3.3 
Definition of Product Complaints ...................................................................................82 
10.3.4 
Recording and Follow-Up of AE and/or SAE and Product 
Complaints ......................................................................................................................83 
10.3.5 
Reporting of SAEs ..........................................................................................................85 
10.3.6 
Regulatory Reporting Requirements ...............................................................................85 
10.4 
Appendix 4: Contraceptive and Barrier Guidance ..........................................................86 
10.4.1 
Definitions.......................................................................................................................86 
10.4.2 
Contraception Guidance..................................................................................................87 
10.5 
Appendix 5: Liver Safety: Suggested Actions and Follow-Up 
Assessments ....................................................................................................................88 
10.6 
Appendix 6: Protocol RHCZ CASPAR Criteria ............................................................90 
10.7 
Appendix 7: Protocol RHCZ Tender and Swollen Joint Count 
Assessment Form ............................................................................................................91 
10.8 
Appendix 8: Protocol Amendment History ....................................................................93 
10.9 
Appendix 9: Abbreviations and Definitions .................................................................118 
11 
References ....................................................................................................................124 
 
 
 
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Table of Contents 
Table 
Page 
Table RHCZ.1.1. 
Schedule of Activities ................................................................................. 17 
Table RHCZ.6.1. 
Treatment Regimens ................................................................................... 39 
Table RHCZ.6.2.  
Dosing Summary for the Induction and Maintenance Periods .................. 40 
Table RHCZ.6.3. 
Concomitant Medications Permitted/Not Permitted in the Study and 
Conditions for Use  ..................................................................................................................... 43 
Table RHCZ.8.1. 
Efficacy Assessments .................................................................................. 52 
 
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1. 
Protocol Summary  
1.1. 
Synopsis  
Protocol Title: A 24-Week Multicenter, Open-Label, Single-Arm, Phase 4 Study to Evaluate the 
Safety of Ixekizumab in Patients with Moderate-to-Severe Plaque Psoriasis and/or Active 
Psoriatic Arthritis in India 
Brief Title: A study to investigate the safety of ixekizumab in participants aged ≥18 years with 
moderate-to-severe plaque psoriasis and/or active psoriatic arthritis in India 
Rationale: 
The rationale for this post-approval Phase 4 study is to evaluate the safety and tolerability when 
ixekizumab is administered to participants in India with moderate-to-severe plaque psoriasis 
(PsO) and/or active psoriatic arthritis (PsA). This Phase 4 safety study is being performed as per 
conditional marketing approval from the Central Drugs Standard Control Organization 
(CDSCO), India. As per permission reference, Lilly has committed to conduct a Phase 4 study 
with ixekizumab in India. In addition to the established safety profile for adult PsO, and PsA, the 
safety and tolerability data in Indian population from this study are intended to: 
 further support the known safety profile for ixekizumab in adult participants with PsO 
and PsA, and  
 establish a better understanding of the benefit-risk relationship for ixekizumab in 
participants with PsO and PsA. 
 
 
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Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
 
 To assess the type of adverse event 
(AE) and the proportion of Indian 
participants with PsO and 
participants with PsA reporting AEs 
and serious adverse events (SAEs) 
occurring within the duration of the 
study (24 weeks) after being started 
on ixekizumab 
 AEs, including SAEs, treatment-
emergent adverse events (TEAEs), and 
adverse events of special interest 
(AESIs) during the treatment period 
(Week 0 to Week 24) 
 
Secondary 
 
Specific to Psoriasis Group 
 
 To evaluate percentage of 
participants achieving a ≥75% 
improvement in Psoriasis Area and 
Severity Index (PASI) 
 Proportion of participants who achieve 
the following PASI scores:  PASI 75 
(defined as 75% improvement from 
baseline in PASI) at Week 12 
 To evaluate percentage of 
participants with a Static Physician 
Global Assessment (sPGA) (0,1) 
 Proportion of participants with an sPGA 
psoriasis score of 0 or 1 (0, 1) at 
Week 12 
Specific to Psoriatic Arthritis Group 
 
 To evaluate percentage of 
participants achieving a 20% 
improvement in American College 
of Rheumatology response criteria 
(ACR20) 
 Proportion of PsA participants 
achieving ACR20 at Week 24 
 
 
 
 
 
 
 
 
 
 
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Objectives 
Endpoints 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
Overall Design: 
Study RHCZ is a prospective, multicenter, open-label, single-arm, Phase 4 study with 4 study 
periods assessing outcomes in terms of AEs and SAEs with ixekizumab when used in 
participants aged ≥18 years for PsO and PsA in an Indian population. 
Brief Summary: 
The study will consist of 4 periods. The study duration for the 4 study periods are: 
 Screening Period (Period 1; 5 to 28 days),  
 Induction Dosing Period (Period 2; 12 weeks),  
 Maintenance Period (Period 3; 12 weeks), and 
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 Post-Treatment Follow-Up Period (Period 4; at least 4 weeks after the date of 
participants’ early termination visit [ETV] or last regularly scheduled visit at Week 24). 
The following treatment will be assessed in this study for PsO participants with no active PsA 
and PsA participants who meet criteria for moderate-to-severe PsO (participants with 
moderate-to-severe plaque psoriasis are defined as those with PASI ≥12, sPGA ≥3, and BSA 
≥10%): 
 Ixekizumab: 80-mg subcutaneous (SC) injection 
o At Week 0, 160-mg starting dose (two 80-mg injections), followed by 80 mg 
every 2 weeks (Q2W) from Weeks 2 through 12, and then followed by 80 mg 
every 4 weeks (Q4W) thereafter (i.e., at Weeks 16 and 20). 
The following treatment will be assessed in this study for PsA participants who do not meet 
criteria of moderate-to-severe PsO: 
 Ixekizumab:  80-mg SC injection   
o At Week 0, 160-mg starting dose (two 80-mg injections), followed by 80 mg 
Q4W (i.e., at Weeks 4, 8, 12, 16 and 20). 
Statistical Analysis: 
Adverse events and treatment-emergent adverse events will be summarized and analyzed for the 
safety population for the combined Period 2 (Induction Dosing Period) and Period 3 
(Maintenance Period), including the number and percentage of participants who reported 
TEAEs, TEAEs by maximum severity, death, SAEs, TEAEs related to study treatment, AEs 
leading to treatment discontinuation, and TEAEs of special interest.  
Efficacy analyses in the secondary objectives specific to PsO and PsA will be conducted on the 
PsO with no active PsA and active PsA participants with at least 1 dose of study intervention and 
will be summarized with number of responders, response rate and its corresponding 95% 
confidence intervals (CIs) using normal approximation.  
Number of Participants: 
Approximately 250 participants (PsO: 150 participants; PsA: 100 participants) are planned to be 
enrolled into this study and, assuming discontinuations of approximately 10%, approximately 
225 participants should complete the 24-week period of treatment. 
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Intervention Groups and Duration: 
Treatment Group 
Starting Dose 
W0 
Dose 
W2-W10 
Dosea 
W12-W20 
Ixekizumab for  
 
PsO participants with 
no active PsA, and 
 
PsA participants who 
meet criteria for 
moderate-to-severe 
PsO. 
Ixekizumab 80 mg 2 × SC 
(total of 160 mg) 
Ixekizumab 80 mg SC Q2W 
at W2, 4, 6, 8, and 10 
Ixekizumab 80 mg SC Q4W 
at W12, 16, and 20 
Ixekizumab for PsA 
participants who do not 
meet criteria for moderate-
to-severe PsO 
Ixekizumab 80 mg 2 × SC 
(total of 160 mg) 
Ixekizumab 80 mg SC Q4W 
at W4, 8, 12, 16, and 20. 
Abbreviations: PsA = psoriatic arthritis; PsO = psoriasis; Q2W = every 2 weeks; Q4W = every 4 weeks; 
SC = subcutaneous injection; W = week. 
a 
No dose is given at W24; therefore, W24 is not included in this table. 
Note: When the dosing is scheduled at home (for PsO participants with no active PsA and PsA participants who 
meet criteria for moderate-to severe PsO: W2, W6, W10, W16, and W20; for PsA participants who do not meet 
criteria of moderate-to-severe PsO: W16 and W20), the participants or care givers will administer the provided 
ixekizumab prefilled syringes. 
 
Data Monitoring Committee: No. 
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1.2. 
Schema  
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1.3. 
Schedule of Activities (SoA)  
Table RHCZ.1.1. 
Schedule of Activities  
 
Screening 
(Period 1) 
Induction Dosing  
(Period 2) 
Maintenance 
(Period 3) 
Post Treatment 
Follow-Up (Period 4) 
 
 
Baseline 
 
 
 
As Needed 
CRF Visit Number 
V1 
V2 
V3 
V4 
V5 
V6 
ETV 
V801 
V802 
Study Week 
 
W0 
W4 
W8 
W12 
W24 
 
LV + W4 
LV + W8 
Study Days 
-28 to -5 d 
0 d 
28 ± 3 d 
56 ± 3 d 
84 ± 3d 
168 ± 5 d 
 
± 4 d 
± 4 d 
Informed consent 
X 
 
 
 
 
 
 
 
 
Complete medical history 
X 
 
 
 
 
 
 
 
 
Demographicsa 
X 
 
 
 
 
 
 
 
 
Substance use (alcohol, caffeine, tobacco use) 
X 
 
 
 
 
 
 
 
 
Electrocardiogram 
X 
 
 
 
 
 
 
 
 
Evaluation for disease relapseb 
X 
 
 
 
 
 
 
 
 
Physical examinationc 
X 
 
 
 
 
 
 
 
 
Weight 
X 
X 
 
 
X 
X 
X 
 
 
Height 
 
X 
 
 
 
 
 
 
 
Body mass index 
 
X 
 
 
 
 
 
 
 
Inclusion/exclusion criteriad 
X 
X 
 
 
 
 
 
 
 
Vital signs 
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 
Administer study interventione 
 
X 
X 
X 
X 
 
 
 
 
Dispense study drug 
 
X 
X 
X 
X 
 
 
 
 
Study drug compliancef 
 
X 
X 
X 
X 
 
 
 
 
Dispense Study Intervention Administration Log 
 
X 
X 
X 
X 
 
 
 
 
Collect, review, and enter data from Study 
Intervention Administration Log 
 
 
X 
X 
X 
X 
X 
 
 
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Schedule of Activities 
 
Screening 
(Period 1) 
Induction Dosing  
(Period 2) 
Maintenance 
(Period 3) 
Post Treatment 
Follow-Up (Period 4) 
 
 
Baseline 
 
 
 
As 
Needed 
CRF Visit Number 
V1 
V2 
V3 
V4 
V5 
V6 
ETV 
V801 
V802 
Study Week 
 
W0 
W4 
W8 
W12 
W24 
 
LV + W4 
LV + W8 
Study Days 
-28 to -5 d 
0 d 
28 ± 3 d 
56 ± 3 d 
84 ± 3d 
168 ± 5 d 
 
± 4 d 
± 4 d 
Efficacy Measures 
Clinician-Rated or -Administered Assessments 
PASIg 
X 
X 
X 
X 
X 
X 
X 
 
 
BSAg 
X 
X 
X 
X 
X 
X 
X 
 
 
sPGAg 
X 
X 
X 
X 
X 
X 
X 
 
 
TJC/SJC (68/66 joints)h  
X 
X 
X 
X 
X 
X 
X 
 
 
PGA Disease Activity VASh 
 
X 
X 
X 
X 
X 
X 
 
 
Patient-Rated Assessments 
Patient Assessment of Pain VASi 
 
X 
X 
X 
X 
X 
X 
 
 
Patient Global Assessment Disease Activity VAS 
 
X 
X 
X 
X 
X 
X 
 
 
HAQ-DIi 
 
X 
X 
X 
X 
X 
X 
 
 
Laboratory Tests 
Chest x-ray (local)j 
X 
 
 
 
 
X 
X 
 
 
Administer Mantoux TB test/QuantiFERON®-TB 
Goldk 
X 
 
 
 
 
X 
X 
 
 
HIV/HCV  
X 
 
 
 
 
 
 
 
 
HBVl 
X 
X 
 
 
X 
X 
X 
 
X 
Serum pregnancy testm 
X 
 
 
 
 
 
 
 
 
Urine pregnancy testn 
 
X 
X 
X 
X 
X 
X 
 
 
Serum chemistry 
X 
X 
 
 
X 
X 
X 
 
 
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Protocol I1F-IN-RHCZ (a) 
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Schedule of Activities 
 
Screening 
(Period 1) 
Induction Dosing  
(Period 2) 
Maintenance 
(Period 3) 
Post Treatment 
Follow-Up (Period 4) 
 
 
Baseline 
 
 
 
As 
needed 
CRF Visit Number 
V1 
V2 
V3 
V4 
V5 
V6 
ETV 
V801 
V802 
Study Week 
 
W0 
W4 
W8 
W12 
W24 
 
LV + W4 
LV + W8 
Study Days 
-28 to -5 d 
0 d 
28 ± 3 d 
56 ± 3 d 
84 ± 3d 
168 ± 5 d 
 
± 4 d 
± 4 d 
Laboratory Tests 
 
 
 
 
 
 
 
 
 
Hematology 
X 
X 
X 
 
X 
X 
X 
X 
X 
hs-CRP 
 
X 
X 
X 
X 
X 
X 
 
 
Urinalysis 
X 
X 
 
 
 
X 
X 
 
 
Abbreviations:  AE = adverse event; BSA = body surface area; CRF = case report form; d = day; ETV = early termination visit; HAQ-DI = Health Assessment 
Questionnaire – Disability Index; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus; hs-CRP = high-sensitivity 
C-reactive protein; LV = last visit; PGA = Physician Global Assessment; PASI = Psoriasis Area and Severity Index; PsA = psoriatic arthritis; SJC = swollen 
joint count; sPGA = static Physician’s Global Assessment; TB = tuberculosis; TJC = tender joint count, V = visit; VAS = visual analog scale; W = week. 
a Includes year of birth, gender, and ethnicity. 
b Subjects will be evaluated for past and present disease relapse by the physician (Section 8.2.4).  
c 
Complete physical at screening (excluding pelvic, rectal, and breast examinations). Physicals should include symptom-directed physical, as well as an 
examination of heart, lungs, and abdomen, and visual examination of the skin. 
d Participants who test positive for latent TB at screening may be re-screened following appropriate treatment.  
e See Table RHCZ.6.1. When the dosing is scheduled at home, the participants/care givers will administer the provided ixekizumab prefilled syringes. All 
participants should remain under observation for at least 1 hour after study intervention administration to monitor safety at Week 0. 
f Designated site personnel will be responsible for handling and dispensing of study intervention (ixekizumab). 
g Administered to PsA participants only at the baseline (W0) visit. For PsO participants with 3% or more BSA of PsO, administered at all study visits.  
h Administered to PsO participants only at the baseline (W0) visit. For PsA participants, administered at all study visits. 
i 
Administered only to PsA participants. The question related to pain assessment will be included in HAQ-DI assessment. 
j 
To be performed if not done in the prior 6 months to rule out pulmonary TB provided the x-ray and/or report are available for review. 
k Participants who test positive for latent TB at screening may be re-screened. QuantiFERON® may be performed by a Lilly-designated or local laboratory. See 
Section 8.2.7 for detailed description of QuantiFERON®-TB Gold . In case of Mantoux TB   test, participants will have to come back to the site after 2 days 
for reading the results. 
l 
All participants will be tested for HBV at screening. Participant who meet criteria for HBV monitoring (see Section 8.2.8.1) will be identified by the central 
laboratory at baseline and monitored according to the study schedule. 
m To be performed for females of childbearing potential only. Additional urine pregnancy testing can be performed at the investigator’s decision. Participants 
determined to be pregnant will be discontinued from treatment and will no longer be administered study intervention. 
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Protocol I1F-IN-RHCZ (a) 
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n To be performed for females of childbearing potential only. Participants determined to be pregnant will be discontinued from treatment and will no longer be 
administered study intervention. 
Note:  For PsO participants with no active PsA, only PsO efficacy outcomes will be collected. For PsA participants with 3% or more BSA of PsO, both PsA and 
PsO efficacy outcomes will be collected. For PsA participants with less than 3% BSA of PsO, only PsA efficacy outcomes will be collected. (Table RHCZ.8.1).   
 
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2. 
Introduction  
2.1. 
Study Rationale  
The rationale for this post-approval Phase 4 ixekizumab study is to evaluate the safety and 
tolerability when ixekizumab is administered to participants in India with moderate-to-severe 
plaque psoriasis (PsO) and/or active psoriatic arthritis (PsA). Participants with 
moderate-to-severe plaque psoriasis are defined as those with PASI ≥12, sPGA ≥3, and BSA 
≥10%. This Phase 4 safety study is being performed as per conditional marketing approval from 
the Central Drugs Standard Control Organization (CDSCO), India. Per permission reference, 
Lilly has committed to conduct a Phase 4 study with ixekizumab in India. In addition to the 
established safety profile for adult PsO, and PsA, the safety and tolerability data in Indian 
population from this study are intended to: 
 further support the known safety profile for ixekizumab in adult participants with PsO 
and PsA, and  
 establish a better understanding of the benefit-risk relationship for ixekizumab in 
participants with PsO and PsA. 
2.2. 
Background  
Psoriasis is a common, lifelong and life-shortening, chronic inflammatory skin disease 
manifested by prototypic red, thick, and scaly plaques. PsO is the most common form and has 
been shown to have a significant impact on the overall health of participants. Along with an 
association with inflammatory arthritis in the form of PsA, PsO is associated with increased risk 
for multiple comorbid conditions, including myocardial infarction (MI) and stroke, metabolic 
syndrome, diabetes mellitus, chronic renal insufficiency, and liver abnormalities (Yeung et al. 
2013). The lifespan of participants with moderate-to-severe PsO may be shortened by as many as 
5 years, partly due to association with comorbidities (Gelfand et al. 2006; Ryan and Kirby 2015). 
The worldwide prevalence of PsO is 2% to 3% (Christophers 2001; IFPA 2017; NPF 2018) 
while in India the incidence is 0.44% to 2.2%, and the prevalence is 0.8% to 2.3% (Dogra and 
Yadav 2010). Almost one-third of participants with PsO in the United States (US) suffer from 
moderate-to-severe disease (Dubin et al. 2003). Certain symptoms, such as itching, can 
especially impact the quality of life and is detrimental to work productivity and sleep (Zimolag 
et al. 2009; Gowda et al. 2010; Janowski et al. 2014; Lebwohl et al. 2014). 
Early treatments for PsO obtained 50% to 75% improvement in skin clearance; however, 
expectations for treatment goals of efficacy are expected to be higher as new and more 
efficacious therapies have emerged. Recent studies of biologics which block the interleukin-17 
(IL-17) or interleukin-23 (IL-23) pathways, both central to PsO pathogenesis (Leonardi et al. 
2012; Langley et al. 2014; Sofen et al. 2014; Gordon et al. 2015; Griffiths et al. 2015; Krueger et 
al. 2015; Lebwohl et al. 2015; Papp et al. 2015), have demonstrated substantial efficacy. 
Complete skin clearance and improved long-term efficacy have increasingly become the desired 
treatment outcomes (Gniadecki et al. 2015; Bartos et al. 2016). Some studies have suggested that 
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Protocol I1F-IN-RHCZ (a) 
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increased levels of clearance resulted in greater improvement in quality of life (Takeshita et al. 
2014; Feldman et al. 2016; Fairchild et al. 2017). 
Ixekizumab (LY2439821) is a humanized immunoglobulin G (IgG) subclass 4 monoclonal 
antibody (MAb) designed and engineered to selectively inhibit 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 the other members of the IL-17 family (IL-17B, 
IL-17C, IL-17D, IL-17E, or IL-17F). 
Ixekizumab has demonstrated efficacy at both short- and long-term time points, with a favorable 
safety profile (Griffiths et al. 2015, Gordon et al. 2016, Strober et al. 2017). In all 3 pivotal Phase 
3 studies (the UNCOVER studies), ixekizumab was superior to placebo with respect to all 
primary and major secondary endpoints. In I1F-MC-RHAJ study, the primary objective was met, 
as the percentage of participants who achieved Psoriasis Area and Severity Index (PASI) 75 at 
Week 12 (Visit 8) was superior to placebo in all ixekizumab dose groups, including statistically 
significant improvements (p<0.001) compared with placebo for the 25-mg, 75-mg, and 150-mg 
ixekizumab dose groups. The time course of the PASI 75 response by dose groups demonstrated 
increasing rapidity of onset of effect with increasing doses.  
In the UNCOVER studies, 32% to 42% of participants who received treatment with ixekizumab 
had complete resolution (PASI 100 or static Physician Global Assessment [sPGA] score of 0; 
versus none in the placebo group) of their PsO at Week 12; high levels of clinical response were 
maintained with continued exposure to ixekizumab 80 mg every 4 weeks (Q4W) through 
Week 60 with at least 50% of participants maintaining or attaining PASI 100 (Gordon et al. 
2016). In the UNCOVER-2 and UNCOVER-3 studies, ixekizumab had greater efficacy than 
etanercept, a tumor necrosis factor inhibitor (TNFi); 40.5% of participants treated with 
ixekizumab 80 mg every 2 weeks (Q2W), compared with 5.3% of etanercept‐treated participants, 
achieved PASI 100 after 12 weeks (Griffiths et al. 2015, Gordon et al. 2016). In a Phase 3 
head-to-head study (IXORA-S), ixekizumab demonstrated superiority over the IL-12/23 
antagonist ustekinumab in participants with moderate-to-severe PsO at Week 12; this trend was 
maintained through Week 52. The majority (76.5%) of ixekizumab-treated participants sustained 
a PASI 90 response through 1 year, and more than one-half of ixekizumab-treated participants 
(52.2%) had completely clear skin at Week 52. The corresponding rates for the 
ustekinumab-treated participants were 59.0% and 35.5%, respectively.  
Studies of ixekizumab suggest ability to achieve PASI 90 (as shown in the VOYAGE studies). 
Ixekizumab also demonstrated a high percentage of participants achieving PASI 100, and a rapid 
onset of skin improvement after administration of ixekizumab (UNCOVER). Long-term 
evaluation of ixekizumab in a study, in which safety is tested, will provide important information 
to clinicians trying to determine long-term safety of drug class is the best for a given participant. 
The purpose of this study is to evaluate efficacy and safety, as well as rapidness of efficacy, of 
ixekizumab. 
In both UNCOVER-2 and UNCOVER-3 studies combined, the most common (≥2% of all 
participants given ixekizumab) were nasopharyngitis, upper respiratory tract infection, 
injection-site reaction, injection-site erythema, injection-site pain, pruritus, headache, and 
arthralgia. Most treatment-emergent adverse events (TEAEs) were mild or moderate in severity. 
Serious adverse events (SAEs) were reported by ≤2% of participants in each treatment group 
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Protocol I1F-IN-RHCZ (a) 
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across both studies. No deaths were recorded in either study. Rates of SAEs and discontinuations 
due to adverse events (AEs) were comparable across study groups in both studies. 
During the extension period of Phase 3 SPIRIT-P1 study in participants with active PsA, 
ixekizumab Q4W or Q2W treatment demonstrated sustained efficacy in key PsA domains with a 
safety profile consistent with other studies investigating ixekizumab. Phase 3 SPIRIT-P1 study in 
participants with active PsA showed that both the 2-week and 4-week ixekizumab dosing 
regimens improved the signs and symptoms of participants with active PsA and who had 
previously inadequate response to TNFIs, with a safety profile consistent with previous studies 
investigating ixekizumab. 
The purpose of RHCZ Phase 4 safety study is to evaluate safety and tolerability of ixekizumab in 
Indian participants with PsO or PsA. 
More information about the known and expected benefits, risks, and reasonably anticipated AEs 
of ixekizumab may be found in the Copellor® package insert. Information on AEs expected to be 
related to the investigational product may be found in Section 6.2 (Development Core Safety 
Information [DCSI]) of the Investigator’s Brochure (IB). Information on SAEs that are expected 
in the study population (independent of drug exposure) and that will be assessed by the Sponsor 
in aggregate, periodically during the course of the study, may be found in Section 5 (Effects in 
Humans) of the IB. 
2.3. 
Benefit/Risk Assessment  
Ixekizumab has been demonstrated to be safe and effective for the treatment of participants with 
moderate-to-severe chronic PsO and/or active PsA. The risk profile for participants within this 
study is anticipated to be consistent with the known safety experience for ixekizumab. 
More information about the known and expected benefits, risks, SAEs, and reasonably 
anticipated AEs of ixekizumab are found in the IB. Information on AEs expected to be related to 
the study intervention may be found in Section 6.2 (DCSI) of the IB. Information on SAEs that 
are expected in the study population independent of drug exposure and that will be assessed by 
the Sponsor in aggregate periodically during the course of the study, may be found in Section 5 
(Effects in Humans) of the IB. 
Taking into account the measures taken to minimize risk to participants participating in this 
study, the potential risks identified in association with ixekizumab are justified by the anticipated 
benefits that may be afforded to participants with PsO or PsA. 
 
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3. 
Objectives and Endpoints  
Objectives 
Endpoints 
Primary 
 
 To assess the type of adverse event 
(AE) and the proportion of Indian 
participants with plaque psoriasis 
(PsO) and participants with psoriatic 
arthritis (PsA) reporting AEs and 
serious adverse events (SAEs) 
occurring within the duration of the 
study (24 weeks) after being started 
on ixekizumab. 
 AEs including SAEs, treatment-
emergent adverse events (TEAEs), and 
adverse events of special interest 
(AESIs) during the treatment periods 
(Week 0 to Week 24) 
Secondary 
 
Specific to Psoriasis Group 
 
 To evaluate percentage of participants 
Achieving a ≥75% Improvement in 
Psoriasis Area and Severity Index 
(PASI) 
 Proportion of participants who achieve 
the following PASI scores: PASI 75 
(defined as 75% improvement from 
baseline in PASI) at Week 12 
 To evaluate percentage of participants 
with a Static Physician Global 
Assessment (sPGA) (0,1) 
 Proportion of participants with an 
sPGA score of 0 or 1 (0, 1) at Week 12 
Specific to Psoriatic Arthritis Group 
 
 To evaluate percentage of participants 
achieving a 20% in American College 
of Rheumatology improvement 
criteria (ACR20) 
Proportion of PsA participants 
achieving ACR20 at Week 24 
 
 
 
 
 
 
 
 
 
 
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Objectives 
Endpoints 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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4. 
Study Design  
4.1. 
Overall Design  
Study RHCZ is a prospective, multicenter, open-label, single-arm, Phase 4 study with 4 study 
periods assessing outcomes in terms of AEs and SAEs with ixekizumab when used in 
participants aged ≥18 years for PsO and PsA in Indian population (Section 1.2). 
The following treatment will be assessed in this study for PsO participants with no active PsA 
and PsA participants who meet criteria for moderate-to-severe PsO: 
 Ixekizumab: 80-mg subcutaneous (SC) injection. 
o At Week 0, 160-mg starting dose (two 80-mg injections), followed by 80 mg 
Q2W from Weeks 2 through 12, and then followed by 80 mg Q4W thereafter 
(i.e., at Weeks 16 and 20). 
The following treatment will be assessed in this study for PsA participants who do not meet 
criteria of moderate-to-severe PsO: 
 Ixekizumab: 80-mg SC injection.   
o At Week 0, 160-mg starting dose (two 80-mg injections), followed by 80 mg 
Q4W (i.e., at Weeks 4, 8, 12, 16 and 20). 
The study will consist of 4 periods: 
 Period 1 (Section 4.1.1): Screening Period (Visit 1) will assess participant eligibility 
and occurs approximately 5 to 28 days prior to Period 2 (baseline; Week 0 [Visit 2]). 
 Period 2 (Section 4.1.2): Induction Dosing Period occurring from Week 0 (baseline; 
Visit 2) to Week 12 (Visit 5). 
 Period 3 (Section 4.1.3): Maintenance Period occurring after Week 12 (Visit 5) to 
Week 24 (Visit 6). 
 Period 4 (Section 4.1.4): Post-Treatment Follow-Up Period (PTFU) occurring from 
last treatment period Week 24 (Visit 6) or early termination visit (ETV), for a minimum 
of 4 weeks following that visit. 
All procedures to be conducted during the study, including timing and sequence (as necessary), 
are indicated in the Schedule of Activities (SoA; Section 1.3). Appendix 10.2 lists the specific 
laboratory tests that will be performed for this study. 
Participants discontinuing from the study intervention who have received at least 1 dose of study 
intervention will continue to the ETV prior to entering to the PTFU period (Period 4) (see 
Section 7). For the management of participant safety, all participants should be monitored 
through Period 4 at least as frequently as indicated on the SoA (Section 1.3). 
Treatment group is described in Section 6.1, Table RHCZ.6.1, and administration of the study 
intervention is described in Section 6.1, Table RHCZ.6.2. 
Excluded and restricted therapies are detailed in Section 6.8. 
Section 9.6 outlines the information regarding interim analyses, including the primary database 
lock at Week 12. 
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4.1.1. Screening Period (Period 1)  
The duration of the Screening Period will be 5 to 28 days before the Induction Dosing Period 
(Period 2) and consists of 1 screening visit (Visit 1) to assess participant eligibility. The 
participant will sign the informed consent form (ICF) before any study assessments, 
examinations, or procedures are performed. 
All inclusion and exclusion criteria are provided in Sections 5.1 and 5.2, respectively. Screening 
procedures (including complete medical history, demographics, and substance use) will be 
performed according to the SoA (Section 1.3). At Visit 1, a QuantiFERON®-TB Gold test assay 
may be performed by a Lilly-designated or local laboratory (Section 8.2.7).  
Participants who test positive for latent tuberculosis (TB) at screening may be re-screened once 
following appropriate treatment, as described in Section 8.2.7. 
4.1.2. Induction Dosing Period (Period 2)  
The Induction Dosing Period (Period 2) will occur from Week 0 (baseline; Visit 2) to Week 12 
(Visit 5). 
At Week 0 (baseline, Visit 2), routine safety assessments, laboratory tests, and clinical efficacy 
assessments will be performed on eligible participants, according to the SoA (Section 1.3).  
At Week 4 (Visit 3) and Week 8 (Visit 4), safety and efficacy parameters in study participants 
will be performed according to the SoA (Section 1.3). The investigator or his/her designee is 
responsible for explaining the correct method for dose administration to the participant or 
participant’s caregiver, and verifying those instructions are followed properly (Section 6.2). 
During study visits, the investigator or his/her designee will administer the ixekizumab prefilled 
syringes to the participant and explain the correct method for dose administration to the 
participant or the participant’s caregiver.  
When the dosing is scheduled at home (Week 2, Week 6, Week 10), the participants or care 
givers will administer the provided ixekizumab prefilled syringes.  
Please refer to Section 6.1, Table RHCZ.6.1, and Table RHCZ.6.2 for a full description of 
treatment groups and dosing during Period 2. Participants who discontinue from study 
intervention for any reason during Period 2 will continue to the ETV before entering the 
Post-Treatment Follow-Up Period (Period 4; Section 4.1.4). 
4.1.3. Maintenance Period (Period 3)  
The Maintenance Period (Period 3) will occur from Week 12 (Visit 5) up to Week 24 (Visit 6). 
During Period 3, safety and efficacy parameters in participating participants will continue to be 
evaluated according to the SoA (Section 1.3). 
At Week 12 (Visit 5), the investigator or his/her designee will administer the ixekizumab 
prefilled syringes to the participant and explain the correct method for dose administration to the 
participant or the participant’s caregiver.  
When the dosing is scheduled at home (Week 16 and Week 20), the participants or care givers 
will administer the provided ixekizumab prefilled syringes. 
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Please refer to Section 6.1, Table RHCZ.6.1, and Table RHCZ.6.2 for a full description of 
treatment groups and dosing during Period 3. 
Participants who discontinue from study intervention for any reason during Period 3 will continue 
to the ETV before entering the Post-Treatment Follow-Up Period (Period 4; Section 4.1.4). 
4.1.4. Post-Treatment Follow-Up Period (Period 4)  
All participants receiving at least 1 dose of study intervention will enter the Post-Treatment 
Follow-Up Period (Period 4) for a minimum of 4 weeks, beginning after their last regularly 
scheduled visit at Week 24 (or the date of their ETV).   
Required study visits should occur at 4 weeks (Visit 801) after the last regularly scheduled visit 
at Week 24 (or the date of the participant’s ETV), except for participants with a concurrent 
infection that requires systemic anti-infective therapy (described below). 
If, at Visit 801, a participant’s neutrophil count is ≥1500 cells/L or greater than or equal to the 
participant’s baseline neutrophil count, the participant’s participation in the study will be 
considered complete unless the investigator determines additional follow-up may be necessary. 
An additional study visit (Visit 802) 8 weeks after Visit 801 may be required for appropriate 
participant management (described below). 
If, at the last scheduled visit or ETV, a participant’s neutrophil count is <1500 cells/L 
(<1.50 × 103/µL or <1.50 GI/L) and less than the participant’s baseline neutrophil count, the 
following measures should be taken: 
 Participants with concurrent infection: If there is a concurrent infection that requires 
systemic anti-infective therapy, the participant 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 after resolution 
of infection) and 802 (8 weeks after Visit 801); additional visits may be required 
depending on the degree of neutropenia. 
 Participants 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 at Week 24) 
and 802 (if necessary); additional visits may be required depending on the degree of 
neutropenia. 
 For Visit 801 and subsequent visits, the following monitoring applies: 
o As long as a participant’s neutrophil count is <1000 cells/L (<1.00 × 103/µL or 
<1.00 GI/L) at any follow-up visit, the participant should return for additional 
visits at least Q4W (unscheduled visits may be required).   
o As long as a participant’s neutrophil count is ≥1000 cells/L and <1500 cells/L 
(≥1.00 × 103/µL and <1.50 × 103/µL or ≥1.00 GI/L and <1.50 GI/L) at any 
follow-up visit, the participant should return for additional visit(s) at least every 
4 to 8 weeks (unscheduled visits may be required).   
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o If at Visit 802 the participant’s neutrophil count remains <1500 cells/L 
(<1.50 × 103/µL or <1.50 GI/L) and less than the participant’s baseline neutrophil 
count or if the investigator deems additional follow-up may be necessary, the 
investigator in consultation with Eli Lilly and Company (Lilly) or qualified 
designee will determine the appropriate management of the participant and the 
appropriate timing of additional contact(s) or visit(s). 
o If at Visit 802 the participant’s neutrophil count is ≥1500 cells/L (≥1.50 × 103/µL 
or ≥1.50 GI/L) or greater than or equal to the participant’s baseline neutrophil 
count (whichever is lower), the participant’s participation in the study will be 
considered complete unless the investigator deems additional follow-up 
necessary. 
For participants who have entered Period 4, PsO and PsA therapy is allowed, as determined 
appropriate by the investigator.  
Note: Eli Lilly and company will provide study medication only until Week 20. Eli Lilly and 
company will not provide the post-trial/compassionate use for study intervention as it will be 
commercially available in India. 
4.2. 
Scientific Rationale for Study Design  
This study will examine the effect of ixekizumab on participants with moderate-to-severe PsO 
and/or PsA. 
During the Induction Dosing Period (Period 2), participant’s safety and efficacy will be assessed 
at 80 mg Q2W dose for the participants with PsO and PsA participants who meet criteria for 
moderate-to-severe PsO. In PsA participants who do not meet criteria of moderate-to-severe 
PsO, participant’s safety and efficacy will be assessed at 80 mg Q4W dose. During the 
maintenance Period (Period 3), ixekizumab 80 mg Q4W will be studied. 
Safety endpoints are in alignment with the safety endpoints for currently approved PsO and PsA 
therapies, as well as regulatory guidance (EMA 2004). 
The Maintenance Period (Period 3) will permit collection of data for the assessment of safety and 
efficacy of ixekizumab. 
The Post-Treatment Follow-Up Period (Period 4) is for safety monitoring following the last 
treatment period and last study visit. 
4.3. 
Justification for Dose  
Ixekizumab will be studied at the approved dosing regimen for treatment of adults with 
moderate-to-severe -PsO and PsA participants. 
4.4. 
End of Study Definition  
The end of the study is defined as the date of the last visit or last scheduled procedure shown in 
the SoA (Section 1.3). 
A participant is considered to have completed the study if the participant has completed all periods 
of the study including the last visit or the last scheduled procedure shown in the SoA (Section 1.3). 
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5. 
Study Population  
This study will include participants who have presence of moderate to- -severe PsO 
(moderate -to -severe PsO is defined as BSA ≥10, sPGA ≥3, PASI ≥12) and/or active PsA 
(active PsA defined as the presence of at least 
 tender and at least 
 
swollen joints) for at least 6 months, treated in outpatient settings of India, who have given 
written informed consent approved by Lilly, or its designee, and the ethics review board (ERB) 
governing the site. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
re-screened only once in the following circumstances:  participants who test positive for latent 
TB at screening may be re-screened following appropriate treatment, as described in 
Section 8.2.7. When re-screening is performed, the individual must sign a new ICF and will be 
assigned a new identification number. 
Study investigator(s) will review patient records and/or patient history and screening test 
results/measurements to determine if the patient meets all inclusion and exclusion criteria to 
qualify for participation in the study.   
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
5.1. Inclusion Criteria  
Participants are eligible to be included in the study only if all of the following criteria apply: 
[1] 
Are male or female patients 18 years or older and are of ≥50.0 kg weight. 
[2] 
Male or nonpregnant, nonbreastfeeding female participants. 
Participants of child-bearing potential who are abstinent (if this is 
complete abstinence, as their preferred and usual lifestyle). 
Total abstinence is defined as refraining from intercourse during the 
entirety of the study and for at least 12 weeks following the last dose of 
ixekizumab. Periodic abstinence such as calendar, ovulation, 
symptothermal, post-ovulation methods, and withdrawal are not 
acceptable methods of contraception. 
Otherwise, participants and their partners of childbearing potential must 
agree to use 2 effective methods of contraception, where at least 1 form is 
highly effective for the entirety of the study and for at least 12 weeks 
following the last dose of ixekizumab. 
The following contraception methods are considered acceptable (the 
participant, and their partner, should choose 2, and 1 must be highly 
effective [defined as <1% failure rate per year when used consistently and 
correctly]): 
 Highly effective birth control methods: 
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o Combined (estrogen- and progestogen-containing) hormonal 
contraception associated with inhibition of ovulation: oral, intravaginal, 
or transdermal; 
o Progestogen-only hormonal contraception associated with inhibition of 
ovulation: oral, intravaginal, or implantable; 
o Intrauterine device/intrauterine hormone releasing system; 
o Vasectomized partner (with appropriate post-vasectomy documentation 
of the absence of sperm in the ejaculate). 
 Effective birth control methods: 
o Male or female condom with spermicide (it should be noted that the use 
of male and female condoms as a double barrier method is not 
considered acceptable due to the high failure rate when these methods 
are combined). 
o Diaphragm with spermicide. 
o Cervical sponge. 
o Cervical cap with spermicide. 
Note: When local guidelines concerning highly effective or effective 
methods of birth control differ from the above, the local guidelines must 
be followed. 
Adolescent females who have started menses (even 1 cycle and any 
amount of spotting) are considered to be of childbearing potential. 
Women of nonchildbearing potential are not required to use birth control 
and they are defined as: 
 
Women who are infertile due to surgical sterilization 
(hysterectomy, bilateral oophorectomy, or tubal ligation) and 
congenital anomaly such as Müllerian agenesis. 
[3] 
Have given written informed consent approved by Lilly, or its designee, 
and the Investigational Review Board (IRB)/ERB governing the site. 
[4] 
Willing to self-administer study intervention. 
For PsO Participants 
[5] 
Present with chronic PsO based on a confirmed diagnosis of chronic PsO 
vulgaris for at least 6 months prior to baseline (Week 0; Visit 2). 
[6] 
Have ≥10% BSA of psoriasis at screening (Visit 1) and baseline (Week 0; 
Visit 2). 
[7] 
Have both an sPGA score of ≥3 and PASI score ≥12 at screening (Visit 1) 
and baseline (Week 0; Visit 2). 
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[8] 
Are a candidate for phototherapy and/or systemic therapy. 
For PsA Participants  
[9] 
Have a diagnosis of active PsA for at least 6 months (based on a detailed 
medical history provided by the patient, and a physical exam by the Study 
Investigator, and/or other evidence such as that provided by joint x-rays, 
that establishes a history consistent with a diagnosis of active PsA of at 
least 6 months’ duration) and currently meet the Classification for PsA 
(CASPAR) criteria (Section 10.6). 
[10] Have active PsA defined as the presence of at least 3/68 tender and at least 
3/66 swollen joints, as determined by the Tender and Swollen Joint Count 
Assessment Form (Section 10.7) at Visit 1 (Screening) and Visit 2 
(Week 0, baseline). 
[11] Presence of active PsO or a documented history of psoriasis.  
5.2. Exclusion Criteria  
Participants are excluded from the study if any of the following criteria apply: 
[12] Have previously completed or withdrawn from this study, participated in 
any other study with ixekizumab, or have participated in any study 
investigating other IL-17 antagonists. 
[13] Have a history of drug-induced PsO. 
[14] Concurrent or recent use of any biologic agent within the following 
washout periods:  etanercept <28 days; infliximab, adalimumab, or 
alefacept <60 days; golimumab <90 days; ustekinumab <8 months; 
rituximab or efalizumab <12 months; or any other biologic agent 
<5 half-lives prior to baseline (Week 0 Visit 2).  
[15] Cannot avoid excessive sun exposure or use of tanning booths for at least 
4 weeks prior to baseline (Week 0; Visit 2) and during the study. 
[16] Have a known allergy or hypersensitivity to any biologic therapy that 
would pose an unacceptable risk to the patient if participating in this 
study.   
[17] Have ever received natalizumab or other agents that target alpha-4-integrin. 
[18] Had a live vaccination within 12 weeks prior to baseline (Week 0; Visit 2), 
or intend to have a live vaccination during the course of the study, or 
within 12 months of completing treatment in this study, or have 
participated in a vaccine clinical study within 12 weeks prior to baseline 
(investigators should review the vaccination status of their patients and 
follow the local guidelines for adult vaccination with non-live vaccines 
intended to prevent infectious disease prior to therapy).   
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Note:  Killed/Inactive or subunit vaccines are expected to be safe; 
however, their efficacy with concomitant ixekizumab treatment is 
unknown.   
[19] Had a vaccination with Bacillus Calmette-Guérin (BCG) within 12 months 
prior to baseline (Week 0; Visit 2), or intend to have this vaccination with 
BCG during the course of the study, or within 12 months of completing 
treatment in this study. 
[20] 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. 
[21] Have current or a history of lymphoproliferative disease; or signs or 
symptoms of lymphoproliferative disease; or have active or history of 
malignant disease. 
[22] Have diagnosis or history of malignant disease within the 5 years prior to 
baseline (Week 0, Visit 2).  
Note: Patients with successfully treated basal-cell carcinoma (no more than 
3), squamous-cell carcinoma of the skin, or cervical carcinoma in situ, 
with no evidence of recurrence within the 5 years prior to baseline 
(Week 0; Visit 2) may participate in the study. 
[23] Presence of significant uncontrolled cerebrocardiovascular (e.g., MI, 
unstable angina, unstable arterial hypertension, moderate-to-severe [New 
York Heart Association (NYHA) class III/IV] heart failure, or 
cerebrovascular accident [CVA]), respiratory, hepatic, renal, 
gastrointestinal, endocrine, hematologic, neurologic or neuropsychiatric 
disorders, or abnormal laboratory values at screening that, in the opinion 
of the investigator, pose an unacceptable risk to the patient if participating 
in the study or of interfering with the interpretation of data.   
[24] Have had fluid overload, MI or new onset ischemic heart disease (e.g., 
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).   
[25] Have a current or recent acute, active infection (for at least 30 days before 
screening (Visit 1), participants must have no symptoms or signs of 
confirmed or suspected infection and must have completed any 
appropriate anti-infective treatment). 
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Note: Participants who have an upper respiratory infection, a vaginal 
candida infection, or an oral candida infection and who are being treated 
only symptomatically and not requiring systemic anti-infectives may be 
considered for enrollment if other study eligibility criteria are met. 
Enrollment of participants with other uncomplicated local infections 
should be discussed with the Sponsor’s designated medical monitor. 
[26] Have had any of the following types of infection within 3 months prior to 
the screening visit (Visit 1): 
 Serious (requiring hospitalization, or intravenous or equivalent oral 
antibiotic treatment, or both). 
 Opportunistic (as defined in Winthrop et al. 2015). 
Note: Herpes zoster is considered active and ongoing until all vesicles 
are dry and crusted over. 
 Chronic (duration of symptoms, signs, and/or treatment of 6 weeks or 
longer). 
 Recurring (including, but not limited to, herpes simplex, herpes zoster, 
recurring cellulitis, chronic osteomyelitis). 
Note: Participants with only recurrent mild and uncomplicated 
orolabial herpes, or genital herpes, or both may be discussed with the 
Sponsor’s designated medical monitor and considered for enrollment if 
other study eligibility criteria are met. 
[27] Have active TB (refer to Section 8.2.7 for details on determining full TB 
exclusion criteria). 
[28] 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 or more weeks after documented resolution of symptoms. 
[29] 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. 
[30] Have uncontrolled arterial hypertension characterized by a systolic blood pressure 
(SBP) >160 mm Hg or diastolic blood pressure (DBP) >100 mmHg. 
Note:  Determined by 2 consecutive elevated readings. If an initial blood 
pressure (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. 
[31] Are positive for human immunodeficiency virus (HIV) serology (positive 
for human immunodeficiency virus antibody [HIVAb]). 
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[32] Have evidence of or test positive for hepatitis B by any of the following criteria:  
1) positive for hepatitis B surface antigen (HBsAg+); 2) positive for anti-hepatitis 
B core antibody (HBcAb+) and negative for anti-hepatitis B surface antibody 
(HBsAb–); 3) positive for anti-hepatitis B core antibody (HBcAb+) and positive 
for anti-hepatitis B surface antibody (HBsAb+) with a concentration of HBsAb 
<200 mIU/mL; or 4) HBcAb+, HBsAb+ (regardless of HBsAb level), and 
positive for serum hepatitis B virus (HBV) DNA. 
Note:  Patients who are negative for hepatitis B surface antigen (HBsAg-), 
HBcAb+, HBsAb+ with a concentration of HBsAb >200 mIU/mL, and 
negative for serum HBV DNA may participate in the study. Patients who 
meet these criteria at screening will be identified by the central laboratory 
and monitored during the study as detailed in Section 8.2.8.1. 
[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 (e.g., HCV 
polymerase chain reaction [PCR]). 
[34] Have clinical laboratory test results at screening that are outside the 
normal reference range for the population and are considered clinically 
significant, and/or have any of the following specific abnormalities:   
[34a] Neutrophil count <1500 cells/L  
[34b] Lymphocyte count <500 cells/L   
[34c] Platelet count <100,000 cells/L   
[34d] Aspartate aminotransferase (AST) or alanine aminotransferase 
(ALT) >2.5 times the upper limit of normal (ULN) 
[34e] Total white blood cell (WBC) count <3000 cells/L   
[34f] Hemoglobin <8.5 g/dL (85.0 g/L) for male patients and <8.0 g/dL 
(80 g/L) for female patients   
[34g] Serum creatinine >2.0 mg/dL 
Note:  The AST and ALT may be repeated once within a week if the initial 
response exceeds this limit, and the repeat value may be accepted if it meets 
this criterion. Other laboratory tests should not be repeated unless there is a 
technical error or clinical reasons to believe a result may be erroneous. 
[35] Have electrocardiogram (ECG) abnormalities that are considered 
clinically significant and would pose an unacceptable risk to the patient if 
participating in the study. 
[36] Have any other condition that precludes the patient from following and 
completing the protocol, in the opinion of the investigator. 
[37] Have donated blood of >500 mL within the last 4 weeks, or intend to 
donate blood during the course of the study. 
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[38] Are women who are lactating or breastfeeding. 
[39] 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. 
[40] Are Lilly employees or its designee or are employees of third-party 
organizations (TPOs) involved in the study. 
[41] Are currently enrolled in, or discontinued from a clinical trial involving an 
investigational product or nonapproved use of a drug or device within the 
last 4 weeks or a period of at least of 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. 
PsO Participants 
[42] Have received systemic non-biologic PsO therapy (including, but not 
limited to, oral psoralens and ultraviolet A [PUVA] light therapy; 
cyclosporine; corticosteroids; methotrexate [MTX]; oral retinoids; 
mycophenolate mofetil; thioguanine; hydroxyurea; sirolimus; 
azathioprine; fumaric acid derivatives; or 1,25 dihydroxy vitamin D3 and 
analogues) or phototherapy (including either oral and topical PUVA light 
therapy, ultraviolet B [UVB] or self-treatment with tanning beds or 
therapeutic sunbathing) within 4 weeks prior to baseline (Week 0; Visit 2);  
or had topical PsO treatment (including, but not limited to, corticosteroids, 
anthralin, calcipotriene, topical vitamin D derivatives, retinoids, 
tazarotene, emollients and other non-prescription topical products 
containing urea, >3% salicylic acid, or alpha- or beta-hydroxyl acids, and 
medicated shampoos [e.g., those that contain >3% salicylic acid, 
corticosteroids, coal tar, or vitamin D3 analogues]) within the previous 
2 weeks prior to baseline (Week 0; Visit 2).  
Exceptions:  class 6 (mild, such as desonide) or class 7 (least potent, such 
as hydrocortisone) topical steroids will be permitted for use limited to the 
face, axilla, and/or genitalia.   
[43] Have pustular, erythrodermic, and/or guttate forms of PsO. 
[44] Had a clinically significant flare of PsO during the 12 weeks prior to 
baseline (Week 0; Visit 2).     
[45] Have allergy to rubber or latex. 
PsA Participants 
[46] Have used conventional synthetic disease-modifying antirheumatic drug 
(csDMARDs) other than MTX, leflunomide, sulfasalazine, or 
cyclosporine in the 8 weeks prior to baseline (Week 0; Visit 2). 
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Have discontinued MTX, sulfasalazine, or cyclosporine within 12 weeks prior to 
baseline (Week 0; Visit 2). 
If taking MTX, leflunomide, sulfasalazine, or cyclosporine, must have 
been treated for at least 12 weeks prior to baseline and on a stable dose for 
at least 8 weeks prior to baseline, as follows:  oral or parenteral MTX = 10 
to 25 mg/week; leflunomide = 20 mg/day; sulfasalazine = up to 3 g/day; or 
cyclosporine up to 5 mg/kg/day. The dose of these allowed concomitant 
medications must remain unchanged during the study periods of the unless 
changes are required for safety issues. Local standard of care should be 
followed for concomitant administration of folic acid with MTX.   
[47] Are currently receiving treatment with any biologic or small molecule therapy 
for PsA or PsO, including investigational therapies (such as, but not limited 
to, a TNFi, IL-1 receptor antagonists, IL-6 inhibitor, anti-IL-12/23p40, T cell 
or B cell targeted therapies, phosphodiesterase [PDE] 4 inhibitors, or Janus 
kinase [JAK] inhibitors), or have received denosumab. 
[48] Have received treatment with IL-17 or IL12/23 targeted Mab therapy. 
[49] Have used disease-modifying antirheumatic drug (DMARDs) other than 
MTX, leflunomide, sulfasalazine, or hydroxychloroquine (e.g., gold salts, 
cyclosporine, azathioprine, dapsone, 6-mercaptopurine, mycophenolate 
mofetil, or any other immunosuppressive agents) in the 8 weeks prior to 
baseline (Week 0, Visit 2). 
Have discontinued MTX or sulfasalazine within the 8 weeks prior to 
baseline, or hydroxychloroquine within 12 weeks prior to baseline. 
If taking MTX, leflunomide, sulfasalazine, or hydroxychloroquine must 
have been treated for at least 12 weeks prior to baseline and on a stable dose 
for at least 8 weeks prior to baseline, as follows:  oral or parenteral MTX = 
10 to 25 mg/week; leflunomide = 20 mg/day; sulfasalazine = up to 3 g/day; 
or hydroxychloroquine = up to 400 mg/day. The dose of these allowed 
concomitant medications must remain unchanged until W12 of the study, 
unless changes are required for safety issues. Local standard of care should 
be followed for concomitant administration of folic acid with MTX. 
[50] Are receiving treatment with more than 1 conventional DMARD (MTX, 
leflunomide, sulfasalazine, or hydroxychloroquine) at study entry.   
Note:  Under no circumstances will simultaneous use of MTX and 
leflunomide be allowed at any time during the study for safety reasons. 
[51] Have discontinued leflunomide within 4 weeks prior to baseline or have 
received leflunomide from 4 to 12 weeks prior to baseline (Week 0, 
Visit 2) and have not undergone a drug elimination procedure. 
[52] Use of oral corticosteroids at average daily doses of >10 mg/day of 
prednisone or its equivalent, or use of variable doses of any oral 
corticosteroids, within 4 weeks prior to baseline (Week 0, Visit 2). 
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[53] Have received any parenteral glucocorticoid administered by 
intraarticular, intramuscular, or intravenous (IV) injection within 6 weeks 
prior to baseline (Week 0, Visit 2), or for whom a parenteral injection of 
glucocorticosteroids is anticipated until W12 of the study. 
[54] Concomitant use of nonsteroidal anti-inflammatory drug (NSAIDs), 
including cyclooxygenase-2 (COX-2) inhibitors, unless the patient is on a 
stable dose for at least 2 weeks prior to baseline (Week 0, Visit 2). 
[55] Use of any opiate analgesic at average daily doses of >30 mg/day of 
morphine or its equivalent or use of variable doses of any opiate analgesic 
within 6 weeks prior to baseline (Week 0, Visit 2). 
[56] Have a diagnosis of other inflammatory arthritic syndromes such as 
rheumatoid arthritis (RA), ankylosing spondylitis, reactive arthritis, or 
enteropathic arthritis. 
[57] Have active Crohn’s disease or active ulcerative colitis. 
[58] Have diagnosis of fibromyalgia. 
[59] Have a chronic pain condition that would confound evaluation of the patient. 
[60] Have evidence of active vasculitis or uveitis. 
[61] Have had surgical treatment of a joint within 8 weeks prior to baseline or 
will require such up to Week 24. 
5.3. 
Lifestyle Considerations  
See inclusion criteria [2] in Section 5.1 for birth control requirements. 
5.4. 
Screen Failures  
A screen failure occurs when a participant who consents to participate in the clinical study is not 
subsequently enrolled in the study. A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure participants to meet the Consolidated Standards of Reporting 
Trials (CONSORT) publishing requirements and to respond to queries from regulatory authorities. 
Minimal information includes demography, screen failure details, eligibility criteria, and any SAE. 
Individuals may be re-screened only once in the following circumstances: 
 Patients who test positive for latent TB at screening and have undergone documented 
subsequent treatment for at least 4 weeks (more details in Section 8.2.7). 
 Other reasons for rescreening must be discussed, approved and documented by the Lilly 
Medical Team (clinical research scientist [CRS]/clinical research physician [CRP]). 
5.5. 
Criteria for Temporarily Delaying Enrollment/Administration of 
Study Intervention of a Participant  
Dates of subsequent study visits should not be modified according to the delay of the injection of 
the missed scheduled dose.  
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6. 
Study Intervention(s) and Concomitant Therapy  
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to/used by a study participant 
according to the study protocol. 
6.1. 
Study Intervention(s) Administered  
Table RHCZ.6.1. 
Treatment Regimens  
Treatment Group 
Starting Dose 
W0 
Dose 
W2-W10 
Dosea 
W12-W20 
Ixekizumab for  
 
PsO participants with 
no active PsA  
 
PsA participants who 
meet criteria for 
moderate-to-severe 
PsO 
Ixekizumab 80 mg × 2 SC 
(total of 160 mg) 
Ixekizumab 80 mg SC Q2W 
at W2, 4, 6, 8, and 10 
Ixekizumab 80 mg SC Q4W 
at W12, 16, and 20 
Ixekizumab for PsA 
participants who do not 
meet criteria for 
moderate-to-severe PsO 
Ixekizumab 80 mg × 2 SC 
(total of 160 mg) 
Ixekizumab 80 mg SC Q4W 
at W4, 8, 12, 16, and 20 
Abbreviations: PsA = psoriatic arthritis; PsO = psoriasis; Q2W = every 2 weeks; Q4W = every 4 weeks; 
SC = subcutaneous injection; W = week. 
a No dose is given at W24; therefore, W24 is not included in this table. 
Note: When the dosing is scheduled at home (for PsO participants with no active PsA and PsA participants who 
meet criteria for moderate-to-severe PsO: W2, W6, W10, W16, and W20; for PsA participants who do not meet 
criteria for moderate-to-severe PsO: W16 and W20), the participants or care givers will administer the provided 
ixekizumab prefilled syringes. 
 
The investigator or his/her designee is responsible for the following: 
 explaining the correct method of dose administration to the participant or participant’s 
caregiver; 
 explaining the correct use of the investigational agent(s) to site personnel/legal 
representative; 
 verifying those instructions are followed properly; 
 maintaining accurate records of study intervention dispensing and collection; and 
 returning all unused medication to Lilly or its designee at the end of the study 
During study visits, the investigator or his/her designee will administer the ixekizumab prefilled 
syringes to the participant. When the dosing is scheduled at home, the participants or care givers 
will administer the provided ixekizumab prefilled syringes.  
Note: In some cases, sites may destroy clinical trial material if during the investigator site 
selection, the evaluator has verified and documented that the site has appropriate facilities and 
written procedures for disposing of clinical trial materials. 
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Induction Dosing Period (Period 2) (Table RHCZ.6.2) 
 At Week 0, a 160-mg starting dose of ixekizumab (two 80-mg injections), followed by 
ixekizumab 80 mg Q2W from Weeks 2 through 12 for PsO participants with no active 
PsA and PsA participants who meet criteria for moderate-to-severe PsO.  
 At Week 0, a 160-mg starting dose of ixekizumab (two 80-mg injections), followed by 
ixekizumab 80 mg Q4W from Weeks 4 through 12 for PsA participants who do not meet 
the criteria for moderate-to-severe PsO participants. 
Maintenance Period (Period 3) (Table RHCZ.6.2) 
 Ixekizumab 80 mg Q4W (i.e., at Weeks 16 and 20). 
Table RHCZ.6.2 presents the number of injections administered at each study week, for each 
dosing period. 
Table RHCZ.6.2.  
Dosing Summary for the Induction and Maintenance Periods  
 
 
Ixekizumab Treatment Groupa 
Dosing Period 
Study Week 
Ixekizumab (80 mg) 
PsO Participants with 
no active PsA and PsA 
Participants Who Meet 
Criteria for Moderate-
to-Severe PsO b 
PsA Participants Who 
Do Not Meet Criteria for 
Moderate-to-Severe PsOc 
Induction Dosing Period 2 
0 
2a 
2a 
 
2 
1 
- 
 
4 
1 
1 
 
6 
1 
- 
 
8 
1 
1 
 
10 
1 
- 
 
12 
1 
1 
Maintenance Period 3 
16 
1 
1 
20 
1 
1 
24 
- 
- 
Abbreviations: PsA = psoriatic arthritis; PsO = psoriasis; Q2W = every 2 weeks; Q4W = every 4 weeks; 
Q8W = every 8 weeks; SC = subcutaneous. 
a A starting dose of 160 mg (Week 0) of ixekizumab will be given as 2 SC injections at Week 0. 
b For PsO participants with no active PsA and PsA participants who meet criteria for moderate-to-severe PsO, 
during the Induction Dosing Period, ixekizumab (80 mg) will be given as 1 SC injection Q2W (i.e., Weeks 2, 4, 
6, 8, 10, and 12). During the Maintenance Period, ixekizumab (80 mg) will be given as 1 SC injection Q4W 
(i.e., Weeks 16 and 20).  
c For PsA participants who do not meet criteria for moderate to severe PsO, ixekizumab (80 mg) will be given as 
1 SC injection Q4W (i.e., Weeks 4, 8, 12, 16, and 20). 
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6.2. Preparation, Handling, Storage, and Accountability  
The Pharmacy Manual provides information about the handling and storage of the study 
intervention, as well as the site responsibility and accountability for the administered products.  
Additional information about the study intervention administration is provided in other documents. 
Site responsibilities and accountability 
1. The investigator or designee must confirm appropriate storage conditions have been 
maintained during transit for all study intervention received and any discrepancies are 
reported and resolved before use of the study intervention. 
2. Only participants enrolled in the study may receive study intervention. Only authorized 
study personnel may supply, prepare, or administer study intervention. All study 
intervention must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area in accordance with the labeled storage conditions with access 
limited to the investigator and authorized study personnel. 
3. The investigator or authorized study personnel are responsible for study intervention 
accountability, reconciliation, and record maintenance (i.e., receipt, reconciliation, and 
final disposition records). 
4. Further guidance and information for the final disposition of unused study interventions 
are provided in the Pharmacy Manual. 
In addition, the investigator or his/her designee is responsible for the following (see also 
Section 6.3): 
 explaining the correct use of the investigational agent to the participant or participant’s 
caregiver; and 
 verifying those instructions are followed properly. 
6.3. Measures to Minimize Bias  
This is an open-label study. The site will record the intervention assignment on the applicable 
case report form (CRF).  
6.4. Study Intervention Compliance  
Every attempt will be made to select participants who have the ability to understand and comply 
with instructions. The investigator is responsible for discussing methods with the participants 
and caregiver before study entry to ensure high treatment compliance. 
Throughout the study, site personnel, the participant, or the caregiver will record information 
about injections in the Study Intervention Administration Logs, including:  
 the date, time, and anatomical location of administration of ixekizumab (for treatment 
compliance); 
 syringe number; 
 who prepared (if applicable) and administered ixekizumab; and 
 the reason, if ixekizumab was not fully administered or missed. 
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As indicated in the SoA (Section 1.3), the Study Intervention Administration Log will be 
dispensed to all participants or their caregivers. Either the participant or the caregiver will 
compete the Log with the information about injections and bring it to the site at each regular 
study visit. 
Participants’ compliance with ixekizumab will be assessed at each regular visit. Compliance will 
be assessed by the number of injections needed versus the number of injections administered to 
the participants. Deviation(s) from the prescribed dosage regimen should be recorded in the 
electronic case report form (eCRF). 
6.5. 
Dose Modification  
Not applicable. 
6.6. 
Continued Access to Study Intervention after the End of the Study  
Ixekizumab will not be made available to participants at the conclusion of the study. Lilly will 
provide Ixekizumab from Week 0 to Week 20. Last study dose is scheduled at Week 20. 
6.7. 
Treatment of Overdose  
Refer to the IB for ixekizumab. 
6.8. 
Concomitant Therapy  
All concomitant medication taken during the study must be recorded on the Concomitant 
Medication CRF at the study visits indicated in the SoA (Section 1.3). Treatment with 
concomitant PsO and PsA therapies during the study will be permitted only as outlined in the 
inclusion and exclusion criteria (Sections 5.1 and 5.2, respectively) and as described in the 
paragraphs below. Participants taking permitted medications need to be documented to be in 
stable control. After trial enrollment, significant dose escalation of a concomitant medication 
should be discussed with Lilly medical before allowing participant to receive study intervention. 
Table RHCZ.6.3 summarizes concomitant medications that are and are not permitted and their 
conditions for use during the study. 
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Table RHCZ.6.3. 
Concomitant Medications Permitted/Not Permitted in the Study and Conditions for Use  
Drug Class 
Permitted/Not 
Permitted 
during the Trial 
Conditions for Use 
Bath oils and oatmeal bath preparations 
Permitted 
Not to be used within 12 hours of a study visit. 
NSAIDs, acetaminophen, or aspirin 
Permitted 
Allowed as needed. 
Shampoos 
Permitted 
May not contain >3% salicylic acid, corticosteroids, coal tar, or vitamin D3 
analogues. 
Not to be used within 12 hours of a study visit. 
Topical moisturizers/emollients and other 
non-prescription topical products 
Permitted 
Do not contain urea, >3% salicylic acid, alpha- or beta-hydroxyl acids, 
corticosteroids, or vitamin D3 analogues. Not to be used within 12 hours of a 
study visit. 
Topical steroids 
 
 
Mild (such as hydrocortisone) 
Permitted 
Permitted for use limited to the face, axilla, groin, and/or genitalia, as needed. 
These topical medications should not be used within approximately 24 hours 
before study visits requiring sPGA and PASI measures. More widespread use on 
large surfaces is not permitted. 
Strong (such as mometasone), very strong 
(betamethasone)a, and halogenated steroids 
(clobetasone) 
Not permitted 
 
Biologic agents other than study intervention as part 
of this protocol  
Not Permitted 
Washout periods before baseline (Week 0, Visit 2); at least 5 half-lives 
IL-17, IL-23p19 antagonists, other than the 
2 products used as part of this protocol. 
Not permitted 
Must have never received ixekizumab or IL-23p19 antagonists; or participated in 
any study investigating IL-23p19 antagonists. Participant with previous exposure 
to another IL-17 antagonist(s) will be limited to approximately 15% of the total 
participant population. 
Natalizumab or other agents targeting α 4 integrin 
Not permitted 
Must have never received. 
Phototherapy (including either oral and topical 
PUVA light therapy, UVB, or self-treatment with 
tanning beds or therapeutic sunbathing) 
Not permitted 
Must not have received within 4 weeks of baseline (Week 0, Visit 2). 
 
 
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Concomitant Medications Permitted/Not Permitted in the Study and Conditions for Use 
Abbreviations:  CRS/CRP = clinical research scientist/clinical research physician; csDMARD = conventional synthetic disease-modifying antirheumatic drug; 
IL = interleukin; MTX = methotrexate; NSAID = nonsteroidal anti-inflammatory drug; PASI = Psoriasis Area and Severity Index; PsA = psoriatic arthritis; 
PsO = plaque psoriasis; PUVA = psoralen and ultraviolet A; RNA = ribonucleic acid; sPGA = static Physician Global Assessment; UVB = ultraviolet B. 
a Mason et al. 2002. 
 
Drug Class 
Permitted/Not 
Permitted 
Conditions for Use 
Systemic nonbiologic psoriasis therapy (e.g., oral 
PUVA light therapy, cyclosporine, corticosteroids, 
MTX, oral retinoids, mycophenolate mofetil, 
thioguanine, hydroxyurea, sirolimus, azathioprine, 
fumaric acid derivatives, apremilast, and 
1,25 dihydroxy vitamin D3 and analogues) 
Not permitted 
(for PsO 
participants)  
 
Permitted (for 
PsO participants 
who met PsA 
criteria and PsA 
participants) 
with conditions 
Must not have received within 4 weeks of baseline (Week 0, Visit 2). 
 
 
 
Stable dose allowed. Stable doses with no dose adjustments, changes, and/or 
introduction of a new csDMARD 
Allowed doses: 
 
Oral or parenteral MTX; 10 to 25 mg/week 
 
Leflunomide:  up to 20 mg/day 
 
Sulfasalazine:  up to 3 g/day 
 
Cyclosporine:  up to 5 mg/kg/day 
Vaccine, Bacillus Calmette-Guérin 
Not permitted 
Must not have received within 12 months of 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 of baseline (Week 0, Visit 2). 
Should not receive within 15 weeks of completed treatment in this study. 
Vaccines, non-live seasonal and/or emergency 
Permitted with 
conditions 
Killed/inactive, RNA vaccine, or subunit vaccines are expected to be safe; 
however, their efficacy with concomitant ixekizumab treatments is unknown. 
Check with Lilly Medical Team (CRS/CRP) before administration. 
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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, the 
investigator should base decisions on the participant and clinical factors. Any additional 
medication (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 PsO/PsA therapies) 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 CRF. 
Participants will maintain their usual medication regimen for other concomitant diseases 
throughout the study unless those medications are specifically excluded in the protocol. 
Participants 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. 
Participants should be instructed to consult the investigator or other appropriate study personnel 
at the site before taking any new medications or supplements. Any changes in medications not 
addressed above should be discussed by the investigator with the Sponsor. 
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7. 
Discontinuation of Study Intervention and Participant Discontinuation/ 
Withdrawal  
Discontinuation of specific sites or of the study as a whole are handled as part of Section 10.1, 
Section 10.1.7. 
7.1. Discontinuation of Study Intervention  
Study intervention may be temporarily withheld or permanently discontinued during the study. 
Participants who permanently discontinue study intervention early will undergo early termination 
procedures, which include:  
 an ETV, and 
 PTFU visits (V801 and V802). 
The investigator will complete any AE reporting and follow-up (Section 8.3). 
7.1.1. Permanent Discontinuation from Study Intervention  
In rare instances, it may be necessary for a participant to permanently discontinue (definitive 
discontinuation) study intervention. If study intervention is definitively discontinued, the 
participant will remain in the study to have ETV and PTFU visits. See the SoA (Section 1.3) for 
data to be collected at the time of discontinuation of study intervention and follow-up and for any 
further evaluations that need to be completed. 
Possible reasons leading to permanent discontinuation of study intervention: 
 Participant decision: 
o the participant or the participant’s designee, e.g., parents or legal guardian, 
requests to discontinue the study intervention. 
Participants will be discontinued from the study intervention under the following 
circumstances: 
 Neutrophil (segmented) counts: 
o <500 cells/L 
o ≥500 and <1000 cells/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 (based on 3 test results) and an infection that is not 
fully resolved 
o WBC count <1000 cells/L (1.00 × 103/L or 1.00 billion/L)  
o absolute neutrophil count (ANC) <500 cells/L (0.50 × 103/L or 0.50 billion/L) 
o lymphocyte count <200 cells/L (0.20 × 103/L or 0.20 billion/L) 
o hemoglobin <6.5 g/dL (<65.0 g/L) 
o platelet count <50,000 cells/μL. 
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Note: Temporary interruption rules (see Section 7.1.3) must be followed, where 
applicable. For laboratory values that meet permanent discontinuation thresholds, the 
study intervention should be discontinued. However, if in the opinion of the investigator 
the laboratory abnormality is due to intercurrent illness such as cholelithiasis or another 
identified factor, laboratory tests may be repeated. Only when the laboratory value meets 
resumption thresholds following the resolution of the intercurrent illness or other 
identified factor may the investigator restart the study intervention after consultation with 
the Sponsor-designated medical monitor. 
In addition, participants will be discontinued from the study intervention in the following 
circumstances: 
 The participant experiences a severe AE or SAE or has a clinically significant change 
in a laboratory value that, in the opinion of the investigator, merits discontinuation of 
the study intervention and appropriate measures being taken. This includes evidence 
of active viral hepatitis or active tuberculosis (TB). In such cases, the Sponsor or its 
designee is to be notified immediately. 
 Clinically significant systemic hypersensitivity reaction following SC administration 
of study intervention that does not respond to symptomatic medication or results in 
clinical sequelae 
 The participant becomes pregnant 
 The participant develops a malignancy (Note:  participants may be allowed to 
continue if they develop no more than 2 non-melanoma skin cancers during the study) 
 The participant has a positive TB test using QuantiFERON®-TB Gold or T-Spot or 
purified protein derivative (PPD and is assessed as having latent TB infection (see 
Section 8.2.7), and/or develops symptoms or signs of tuberculosis. 
 if the participant develops active suicidal ideation with some intent to act with or 
without a specific plan, 
 
-OR- 
 
if the participant develops suicide-related behaviors,  
  
 then it is recommended that the participant be assessed by a psychiatrist or 
appropriately trained professional to assist in deciding whether the participant is to be 
discontinued from the study. 
 
Participants discontinuing from the study intervention prematurely for any reason should 
complete AE and other follow-up procedures per the SoA (Section 1.3), Safety Assessments 
(Section 8.2), and Adverse Events and Serious Adverse Events (Section 8.3) of this protocol . 
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7.1.2. Liver Chemistry Stopping Criteria  
The study intervention should be interrupted or discontinued if one or more of these conditions 
occur:  
Elevation 
Exception 
ALT or AST >5 × ULN  
 
ALT or AST >3 × ULN and either TBL >2 × ULN or INR >1.5  
In participants with Gilbert’s syndrome, 
doubling of direct bilirubin should be used 
for drug interruption/ discontinuation 
decisions rather than TBL>2 × ULN. 
ALT or AST >3 × ULN with the appearance of fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness, fever, rash, 
and/or eosinophilia (>5%) 
 
ALP >3 × ULN, when the source of increased ALP is the liver 
 
ALP >2.5 × ULN and TBL > 2 × ULN  
In participants with Gilbert’s syndrome, 
doubling of direct bilirubin should be used 
for drug interruption/ discontinuation 
decisions rather than TBL>2 × ULN. 
ALP >2.5 × ULN with the appearance of fatigue, nausea, vomiting, 
right upper quadrant pain or tenderness, fever, rash, and/or 
eosinophilia (>5%) 
 
Abbreviations:  ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; 
FDA = Food and Drug Administration; INR = international normalized ratio; TBL = total bilirubin level; 
ULN = upper limit of normal. 
Source: FDA 2009. 
 
Resumption of the study intervention can be considered only in consultation with the 
Lilly-designated medical monitor and only if the liver test results return to baseline and if a 
self-limited non-drug etiology is identified.   
7.1.3. Temporary Discontinuation  
In some circumstances, participants may need to temporarily interrupt treatment as a result of 
AEs or abnormal laboratory values that may have an unclear relationship to the study 
intervention. See Section 8.2.7 for details regarding managing participants who test positive for 
TB at any time during the study. 
The abnormal laboratory values as reason for temporary discontinuation of study intervention 
may include HBV DNA results that are reported as positive, or as detecting HBV DNA, but 
HBV DNA is below the level of quantification. The Sponsor’s designated medical monitor 
should be contacted regarding study status of the participant. HBV DNA testing is to be repeated 
as soon as is feasible. If HBV DNA is confirmed as positive, the participant must be permanently 
discontinued from study intervention (Section 7.1.1). 
Participants requiring surgery at any time during the study should interrupt administration of the 
study intervention beginning 8 weeks before the surgery, or as early as possible, and resume 
administration of the study intervention only after complete wound healing. 
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7.2. Participant Discontinuation/Withdrawal from the Study  
A participant may withdraw from the study: 
 at any time at the participant’s own request; 
 at the request of the participant’s designee (e.g., parents or legal guardian); 
 at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons; 
 if enrolled in any other clinical study involving an investigational product, or 
enrolled in any other type of medical research judged not to be scientifically or 
medically compatible with this study;  
 if 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) or 
 if the participant, for any reason, requires treatment with a therapeutic agent that 
is prohibited by the protocol and has been demonstrated to be effective for 
treatment of the study indication. In this case, discontinuation from the study 
occurs prior to introduction of the new agent. 
Discontinuation is expected to be uncommon. 
At the time of discontinuing from the study, if possible, an ETV should be conducted, as shown 
in the SoA (Section 1.3). See the SoA for data to be collected at the time of study discontinuation 
and follow-up and for any further evaluations that need to be completed. The participant will be 
permanently discontinued both from the study intervention and from the study at that time. 
If the participant withdraws consent for disclosure of future information, the Sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. If a participant 
withdraws from the study, the participant may request destruction of any samples taken and not 
tested, and the investigator must document this in the site study records. 
7.2.1. Discontinuation of Inadvertently Enrolled Participants  
If the Sponsor or investigator identifies a subject who did not meet enrollment criteria and was 
inadvertently enrolled, a discussion must occur between the Lilly clinical pharmacologist and the 
investigator to determine if the participant may continue in the study. If both agree that it is 
medically appropriate to continue, the investigator must obtain documented approval from the 
Sponsor to allow the inadvertently enrolled participant to continue in the study with or without 
continued treatment with ixekizumab.  Safety follow-up should be performed as outlined in the 
SoA (Section 1.3), Safety Assessments (Section 8.2), and Adverse Events and Serious Adverse 
Events (Section 8.3) of the protocol. 
7.3. Lost to Follow up  
A participant will be considered lost to follow-up if he/she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. Site personnel or designee are 
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expected to make diligent attempts to contact participants who fail to return for a scheduled visit 
or were, otherwise, unable to be followed up by the site. 
Site personnel, or an independent third party, will attempt to collect the vital status of the 
participant within legal and ethical boundaries for all participants enrolled, including those who 
did not get investigational product. Public sources may be searched for vital status information. 
If vital status is determined to be deceased, this will be documented, and the participant will not 
be considered lost to follow-up.  
The Sponsor personnel will not be involved in any attempts to collect vital status information. 
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8. 
Study Assessments and Procedures  
Study procedures and their timing are summarized in the SoA (Section 1.3).  
Immediate safety concerns should be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue 
study intervention.  
Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct.  
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
The joint assessor (or designee) should be a rheumatologist, trained dermatologist or skilled joint 
assessor and will be responsible for completing the joint counts for swelling, tenderness, and 
limited range of motion. Additionally, the assessor will perform the following assessments: 
Physician’s Global Assessment of Disease Activity, PASI, BSA.  
To ensure consistent skin and/or joint evaluation throughout the study, individual participants 
should be evaluated by the same assessor for all study visits whenever possible.  
Investigators or relevant clinical staff will provide age-appropriate explanations to all study 
participants prior to any assessment or procedure. 
8.1. Efficacy Assessments  
The secondary endpoints for PsO group are: 
 Proportion of participants who achieve the following PASI scores:  PASI 75 (defined as 
75% improvement from baseline in PASI) at Week 12 
 Proportion of participants with an sPGA score of 0 or 1 (0, 1) at Week 12. 
The secondary endpoints for PsA group are: 
 Proportion of PsA participants achieving ACR20 at Week 24. 
Exploratory endpoints include, but not limited to, DAS-28-CRP and ACR individual components. 
For PsO participant who also meet active PsA definition, both PsA and PsO outcomes will be 
collected for that participant. Likewise, to fulfill the study objective, PsO outcomes will be 
collected among all the PsA participants with 3% or more BSA of PsO (Table RHCZ.8.1). 
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Table RHCZ.8.1. 
Efficacy Assessments  
Assessments 
PsO Participants with No Active 
PsA 
PsA Participants with 
≥3% BSA of PsO 
<3% BSA of PsO 
Clinician assessments 
 
PASI 
 
Percentage of BSA - Psoriasis 
 
sPGA 
 
PGA Disease Activity VAS 
 
TJC/SJC (68/66 joints) 
 
PGA of Disease Activity VAS -Psoriasis  
 
PGA of Disease Activity VAS - PsA 
 
PASI 
 
Percentage of BSA - Psoriasis 
 
sPGA 
 
DAS28 - CRPa  
 
ACR20/50/70a 
 
TJC/SJC (68/66 joints) 
 
PGA of Disease Activity VAS - PsA 
 
DAS28 - CRPa 
 
ACR20/50/70a 
Patient assessments 
 
Patient’s Global Assessment of 
disease activity VAS - Psoriasis 
 
HAQ-DI  
 
PsA Pain assessment question included in 
HAQ-DI 
 
Patient’s Global Assessment of Disease 
Activity VAS - PsA 
 
Patient’s Global Assessment of Disease 
Activity VAS - Psoriasis 
 
HAQ-DI  
 
PsA Pain assessment question 
included in HAQ-DI 
 
Patient’s Global Assessment of 
Disease Activity VAS - PsA 
Abbreviations: ACR20/50/70 = 20%/50%/70% improvement in American College of Rheumatology response criteria; BSA = body surface area; 
CRP = C-reactive protein; DAS28 = Disease Activity Score-28; HAQ-DI = Health Assessment Questionnaire – Disability Index; PASI = Psoriasis Area and 
Severity Index; hs-CRP = high-sensitivity C-reactive protein; PGA = Physician’s Global Assessment; PsA  =  psoriatic arthritis; PsO = plaque psoriasis; 
SJC = swollen joint count; sPGA = static Physician’s Global Assessment; TJC = tender joint count, V  = visit; VAS = visual analog scale. 
a Assessments are derived by calculations using PsA assessments and hs-CRP assay. 
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8.1.1. Efficacy Assessments   
8.1.1.1.Psoriasis Area and Severity Index (PASI 75, PASI 90, PASI 100)  
The PASI will be used to assess PsO and PsA. 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. As minimum treatment response, the European and German guidelines mention a 
PASI 50 response. 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 
the association of higher clearance with greater health-related quality of life (Puig 2015).   
Participants achieving PASI 75, 90, or 100 are defined as having an improvement of at least 
75%, 90%, or 100%, respectively, in the PASI, compared to baseline. 
8.1.1.2.Static Physician Global Assessment   
The sPGA is the physician’s determination of the participant’s psoriatic lesions, overall, at a 
given time point. The sPGA is recommended as an endpoint to assess efficacy in the treatment of 
PsO/PsA (EMA 2004). Overall, lesions are categorized by descriptions for induration, erythema, 
and scaling. For the analysis of responses, the participant’s PsO/PsA is assessed as clear (0), 
minimal (1), mild (2), moderate (3), severe (4), or very severe (5). 
8.1.1.3.Percentage of Body Surface Area  
The investigator will evaluate the percentage involvement of PsO/PsA on each participant’s BSA 
on a continuous scale from 0% (no involvement) to 100% (full involvement), in which 1% 
corresponds to the size of the participant’s palm of the hand, including the palm, fingers, and 
thumb (NPF 2018). 
8.1.2. American College of Rheumatology 20, 50, and 70 Responder Index  
ACR20, ACR50, and ACR70 responses are efficacy measures which for which a participants 
must satisfy the following: 
1) ≥20%, ≥50%, and ≥70% improvement from baseline in tender joint count (TJC); and 
2) ≥20%, ≥50%, and ≥70% improvement from baseline in swollen joint count (SJC); and 
3) ≥20%, ≥50%, and ≥70% improvement from baseline in at least 3 of the following 5 ACR 
Core Set criteria: 
a. Patient’s Assessment of Pain Visual Analog Scale (VAS) 
b. Patient Global Assessment of Disease Activity VAS 
c. Physician Global Assessment of Disease Activity VAS 
d. Patient’s assessment of physical function as measured by the Health Assessment 
Questionnaire – Disability Index (HAQ-DI) 
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e. Acute-phase reactant as measured by high-sensitivity C-reactive protein (hs-CRP) 
assay 
ACR20, ACR50 and ACR70 responses will be assessed over Week 24 (Visit 6). 
American College of Rheumatology Core Set   
Tender Joint Count 
For ACR measures, the number of tender and painful joints will be determined by examination 
of 68 joints (34 joints on each side of the participant’s body). The 68 joints to be assessed and 
classified as tender or not tender are detailed in Section 10.7. Any joints that require 
intra-articular injections during the study (according to Section 6.8 should be excluded from 
evaluation from the time of the injection to the conclusion of the study. 
Joints will be assessed for tenderness by pressure and joint manipulation on physical 
examination. The participant will be asked for pain sensations on these manipulations and 
watched for spontaneous pain reactions. Any positive response on pressure, movement, or both 
will then be translated into a single tender-versus-nontender dichotomy. 
Joint assessments will be performed by an independent, blinded assessor to minimize bias. The 
same assessor should preferably perform the TJC and SJC for a given participant particularly 
during the Induction Dosing Period (Period 2) to minimize interobserver variation. The blinded 
joint assessor will not be involved in participant care and is asked not to discuss disease activity 
or treatment with participants or principal investigator. 
Missing, replaced, ankylosed, or arthrodesed joints will be identified by the investigator at the 
Screening Visit and will be excluded from evaluation during the trial. 
Swollen Joint Count 
For ACR measures, the number of swollen joints will be determined by examination of 66 joints 
(33 joints on each side of the participant’s body). The 66 joints to be assessed and classified as 
swollen or not swollen are detailed in Section 10.7. Any joints that require intra-articular 
injections during the study (according to Section 6.8) should be excluded from evaluation from 
the time of the injection to the conclusion of the study. 
Joints will be classified as either swollen or not swollen. Swelling is defined as palpable 
fluctuating synovitis of the joint. Swelling secondary to osteoarthritis will be assessed as not 
swollen, unless there is unmistakable fluctuation. Dactylitis should be counted as 1 joint. 
Missing, replaced, ankylosed, or arthrodesed joints will be identified by the Investigator at the 
Screening Visit and will be excluded from evaluation during the trial. 
Joint assessments will be performed by an independent, blinded assessor to minimize bias. The 
same assessor should preferably perform the TJC and SJC for a given participant particularly 
during the Induction Dosing Period (Period 2) to minimize interobserver variation. The blinded 
joint assessor will not be involved in participant care and will be instructed not to discuss disease 
activity or treatment with participants or principal investigator. 
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Patient’s Assessment of Pain Visual Analog Scale 
Patient’s Assessment of Pain VAS will be administered only to PsA participants. The question 
related to pain assessment will be included in HAQ-DI assessment. 
The participant will be asked to assess his/her current level of joint pain by marking a vertical 
tick on a 100-mm horizontal VAS where the left end represents no joint pain and the right end 
represents worst possible joint pain. The Patient’s Assessment of Pain VAS should be 
administered prior to the TJC and SJC examinations. 
Results will be expressed in millimeters, measured between the left end of the scale and the crossing 
point of the vertical line of the tick; this procedure is applicable for all VAS used in the trial. 
Patient’s Global Assessment of Disease Activity Visual Analog Scale 
The participant’s overall assessment of his/her PsA activity will be recorded using the 100 mm 
horizontal VAS where the left end represents no disease activity, and the right end represents 
extreme disease activity. 
Physician’s Global Assessment of Disease Activity Visual Analog Scale 
The Investigator will be asked to give an overall assessment of the severity of the participant’s 
current PsA activity using a 100 mm horizontal VAS, where 0 represents no disease activity and 
100 represents extremely active disease. The investigator making the assessment must be a 
rheumatologist or medically qualified physician. The same assessor should preferably perform 
the Physician’s Global Assessment of Disease Activity VAS for a given participant particularly 
during the Induction Dosing Period (Period 2) to minimize interobserver variation. 
Patient’s Assessment of Physical Function as Assessed by the Health Assessment 
Questionnaire-Disability Index 
The HAQ-DI is a patient-reported standardized questionnaire that is commonly used in PsA to 
measure disease-associated disability (assessment of physical function). It consists of 
24 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, 
grip, and other daily activities (Fries et al. 1980; Fries et al. 1982). 
The disability section of the questionnaire scores the participant’s self-perception on the degree 
of difficulty (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 
3 = unable to do), covering the 8 domains. The reported use of special aids or devices and/or the 
need for assistance of another person to perform these activities is also assessed. The scores for 
each of the functional domains will be averaged to calculate the functional disability index. 
Details of scoring and calculations are presented in the statistical analysis plan (SAP). 
C-Reactive Protein 
CRP will be the ACR Core Set measure of acute phase reactant. It will be measured with a high 
sensitivity assay at the central laboratory to help assess the effect of ixekizumab on the 
participant’s PsA.   
Disease Activity Score based on C-Reactive Protein  
The DAS28-CRP is a measure of disease activity in 28 joints that consists of a composite 
numerical score utilizing the following variables: TJC, SJC, hs-CRP (measured in mg/L), and 
Patient’s General Assessment recorded by participants on a 0 to 100 mm VAS. 
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For DAS28-CRP, the 28 joints to be examined and assessed as tender or not tender for TJC and 
as swollen or not swollen for SJC are a subset of those assessed for the TJC and SJC, and include 
14 joints on each side of the participant’s body: the 2 shoulders, the 2 elbows, the 2 wrists, the 
10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal 
interphalangeal joints, and the 2 knees (Smolen et al. 1995). The following equation will be used 
to calculate the DAS28-CRP (Vander Cruyssen et al. 2005): 
 
 
8.1.3. Patient Global Assessment of Disease Activity VAS  
The participant’s overall assessment of his/her PsO and PsA activity will be recorded using the 
100 mm horizontal VAS where the left end represents no disease activity, and the right end 
represents extreme disease activity. 
8.1.4. Physician’s Global Assessment of Disease Activity Visual Analog Scale  
The Investigator will be asked to give an overall assessment of the severity of the participant’s 
current PsO and PsA activity using a 100 mm horizontal VAS, where 0 represents no disease 
activity and 100 represents extremely active disease. The investigator making the assessment 
must be a rheumatologist or medically qualified physician. The same assessor should preferably 
perform the Physician’s Global Assessment of Disease Activity VAS for a given participant 
particularly during the Induction Dosing Period (Period 2) to minimize interobserver variation. 
8.2. Safety Assessments  
Any clinically significant findings from physical examination, vital signs measurements, or 
laboratory measurements that result in a diagnosis and that occur after the participant receives 
the first dose of the study intervention should be reported to the Sponsor or its designee as an AE 
via eCRF. 
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
8.2.1. Physical Examinations  
The complete physical examination (excluding pelvic, rectal, and breast examinations) will be 
performed according to the SoA (Section 1.3). This examination will determine whether the 
participant meets the criteria required to participate in the study and will also serve as a monitor 
for preexisting conditions and as a baseline for TEAE assessment. All physical examinations 
throughout the study should include an examination of the heart, lungs, and abdomen and a 
visual examination of the skin. 
8.2.2. Vital Signs  
For each participant, vital signs measurements should be conducted according to the SoA 
(Section 1.3). 
Vital signs (sitting BP and pulse) and body temperature will be measured after resting for a 
minimum of 10 minutes at times indicated in the study schedule. At baseline (Week 0, Visit 2), 
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Week 12 (Visit 5), and Week 24 (Visit 6), sitting BP and pulse should be measured prior to 
administration of the investigational product and again approximately 1 hour after 
administration.   
Any clinically significant findings from vital signs measurement that result in a diagnosis and 
that occur after the participant receives the first dose of the study intervention should be reported 
to the Sponsor or its designee as an AE via electronic data entry. Additional measurements of 
vital signs may be performed at the discretion of the investigator. 
8.2.3. Electrocardiograms  
For each participant, a 12-lead digital ECG will be collected locally only at screening visit 
according to the Study Schedule (Section 1.3). Participants must be supine for approximately 5 
to 10 minutes before ECG collection and remain supine, but awake, during ECG collection. 
Electrocardiograms will be interpreted by a qualified physician as soon after the time of ECG 
collection as possible, and ideally while the participant is still present, to determine whether the 
participant meets entry criteria and for immediate participant management, should any clinically 
relevant findings be identified. The qualified physician must document his/her review of the 
ECG at the time of evaluation.   
The ECG will be maintained at the site and made available to the Sponsor as requested. 
8.2.4. Evaluation of Disease Relapse  
Patients will be assessed for the presence or absence of relapse at screening based on the 
following definitions: 
a. Assessment of relapse for psoriasis participants:  
Relapse is defined as worsening of psoriasis from the previous routine medical visit by 50% 
PASI or 1% BSA or sPGA ≥3 (Tian and Lai 2016). 
If PASI, BSA, or sPGA are not available in medical report, relapse of psoriasis is defined as 
any worsening of psoriatic lesions that would, if persistent, in most cases require initiation or 
change of systemic therapy for psoriasis. 
During the study period, relapse with ixekizumab would be defined as worsening of psoriasis 
from the previous visit by 50% PASI or 1% BSA or sPGA ≥3. 
Relapse present based on the above definition: Yes/No 
Following details will be collected in addition in all PsO participants: 
 Duration of the psoriasis since diagnosis: 
 Duration of the psoriatic arthritis since diagnosis: 
 Prior systemic medications used for psoriasis:  
o Name of the drug and dose 
o Start date 
o End date 
 Prior systemic medications used for psoriatic arthritis:  
o Name of the drug and dose 
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o Start date 
o End date 
b. Assessment of relapse for psoriatic arthritis participants:  
Relapse is defined as an increase in PsA disease activity from the previous routine medical 
records  
 either DAS28 (erythrocyte sedimentation rate [ESR]) >2.6 and DAS28 (ESR) 
increase >0.6 or  
 DAS28 (ESR) increase ≥1.2, irrespective of absolute DAS28(ESR) (Emery et al. 
2020; Helliwell et al. 2021). 
If DAS-28 ESR is not available in medical records, relapse of PsA is defined as any increase 
in disease activity that would, if persistent, in most cases require initiation or change of 
systemic therapy for PsA.  
Relapse present based on the above definition: Yes/No 
Additionally, the following details will be collected in all PsA participants: 
 Duration of the psoriasis since diagnosis: 
 Duration of the psoriatic arthritis since diagnosis: 
 Prior systemic medications used for psoriasis:  
o Name of the drug and dose 
o Start date 
o End date 
 Prior systemic medications used for psoriatic arthritis:  
o Name of the drug and dose 
o Start Date 
o End date 
8.2.5. Clinical Safety Laboratory Tests  
See Appendix 10.2 for the list of clinical laboratory tests to be performed by a Lilly-designated 
or local laboratory and the SoA (Section 1.3) for the timing and frequency. 
The investigator must review the laboratory results, document this review, and report any 
clinically relevant changes occurring during the study as an AE. The laboratory results must be 
retained with source documents unless a Source Document Agreement or comparable document 
cites an electronic location that accommodates the expected retention duration. Clinically 
significant abnormal laboratory findings are those which are not associated with the underlying 
disease, unless judged by the investigator to be more severe than expected for the participant’s 
condition. 
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study or within a time period equivalent to the maximum 5 half-lives of active 
interventions after the last dose of study intervention should be repeated until the values return to 
normal or baseline or are no longer considered clinically significant by the investigator or 
medical monitor. 
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 If such values do not return to normal/baseline within a period of time judged 
reasonable by the investigator, the etiology should be identified, and the Sponsor 
notified. 
 All protocol-required laboratory assessments, as defined in Appendix 10.2, must 
be conducted in accordance with the SoA (Section 1.3), standard collection 
requirements, and applicable study laboratory manual. 
If laboratory values from non-protocol specified laboratory assessments performed at an 
investigator-designated local laboratory require a change in participant management or are 
considered clinically significant by the investigator (e.g., SAE or AE or dose modification), then 
report the information as an AE.  
8.2.6. Pregnancy Testing  
See the SoA (Section 1.3) for frequency of pregnancy testing and Appendix 10.2 for additional 
details about these tests. 
At screening 
Serum pregnancy tests will be given prior to the first dose of the study intervention for females 
≥10 years of age (<10 years at investigator discretion) if menarche has been reached or if there is 
reason to believe the participant is sexually active. Pregnancy test results at screening must be 
known prior to first dose of the study intervention. 
During the induction dosing and maintenance period 
Female participants of childbearing potential (age 10 and older if menarche has been reached or 
if there is reason to believe the participant is sexually active, or younger participants per 
investigator assessment of sexual maturity) will undergo a urine pregnancy test at the clinic on a 
quarterly basis during scheduled regular visits through Week 156 or the ETV. Additional urine 
pregnancy testing may be performed at the investigator’s discretion. Participants determined to 
be pregnant will be discontinued from treatment and will no longer be administered study 
intervention (see Section 7.1.1). 
During the post-treatment follow-up period 
As indicated in the SoA (Section 1.3), urine pregnancy tests will be collected during each of the 
post-treatment follow-up visits. 
8.2.7. Chest X-Ray and Tuberculosis Testing  
An anterior-posterior view chest x-ray will be obtained, unless the x-ray or results from a chest 
x-ray obtained within 6 months before the study are available. The chest x-ray or results will be 
reviewed by the investigator or designee to exclude participants with active TB infection prior to 
enrollment. 
Tuberculosis testing will be conducted based on clinical assessment of TB risk (symptoms, signs, 
and known or suspected TB exposure), and as required by local regulations and/or local standard 
of care. Participants with a positive TB test and/or other evidence of active TB should be 
discontinued (Section 7.1.1). 
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Tuberculosis testing – QuantiFERON® TB Gold will be the preferred testing option for TB. The 
QuantiFERON® TB Gold test may be performed locally or centrally. If the QuantiFERON®-TB 
Gold test is indeterminate (not negative), 1 retest is allowed. If the retest for the 
QuantiFERON®-TB Gold test is indeterminate (not negative), the participant is excluded from 
enrollment in the study. 
In countries where the QuantiFERON®-TB Gold test is not available or due to investigator’s 
judgement (e.g., need to reduce the volume of blood collected), the T-Spot or PPD test may be 
used. In the case of selecting the PPD test, the participant must return within 48 to 72 hours to 
read the skin test.  
A positive PPD skin test response for this study is defined as ≥5-mm induration between 48 and 
72 hours after PPD application, regardless of BCG vaccination history.  
Participants with a PPD skin test ≥5 mm induration or a positive QuantiFERON®-TB Gold or 
T-Spot test but no evidence of active TB, and participants who have a documented history of a 
positive TB test but no documented history of completion of a full, appropriate latent TB 
treatment course, who are assessed as having latent TB infection may be re-screened 1 time and 
may be enrolled without repeating a QuantiFERON®-TB Gold, T-Spot or PPD test if the 
following conditions are met: 
 after receiving at least 4 weeks of appropriate latent TB infection therapy with no 
evidence of hepatotoxicity (ALT/AST must remain ≤2 × ULN) upon retesting of serum 
ALT/AST prior to enrolment, 
 commitment by the participant and the caregiver for the participant to complete a full 
course of standard prophylaxis for TB, and 
 meet all other inclusion/exclusion criteria for participation. 
Such participants must complete appropriate latent TB infection therapy to remain eligible for 
continued study participation. If rescreening occurs within 6 months of the screening chest x-ray, 
a repeat of chest x-ray for considering enrollment is not required. 
If a participant with a positive QuantiFERON®-TB Gold or T-Spot or PPD is fully assessed by 
the investigator and the investigator determines that the participant has no risk factors for and no 
symptoms or signs of Mycobacterium tuberculosis infection, the investigator may contact the 
Sponsor’s medical monitor to discuss the possibility of a false-positive test result. 
Participants with positive TB test results on file: Participants with a documented prior history 
of a positive TB test and participants who have a documented history of completion of an 
appropriate TB treatment regimen for latent or active TB should not have a TB test performed at 
Visit 1. Such participants 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. Participants 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. 
Participants are to be monitored on a regular basis for any symptoms or signs of active TB and 
for any new risk factors for TB infection, with full medical evaluation including TB testing when 
medically indicated. Participants that exhibit symptoms of active TB should be referred to a 
specialist in the care of participants with TB.  
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Any clinically significant findings from TB testing that result in a diagnosis and that occur after 
the participant signs the ICF should be reported to the Sponsor or its designee as an AE via 
eCRF. 
8.2.8. Safety Monitoring  
The Sponsor will periodically review evolving aggregate safety data within the study by 
appropriate methods. 
8.2.8.1. 
Hepatic Safety Monitoring  
Close hepatic monitoring 
Laboratory tests (Appendix 10.5), including ALT, AST, alkaline phosphatase (ALP), total 
bilirubin (TBL), direct bilirubin, gamma-glutamyltransferase (GGT), and creatine kinase (CK), 
should be repeated within 48 to 72 hours to confirm the abnormality and to determine if it is 
increasing or decreasing, if one or more of these conditions occur: 
If a participant with baseline results of ...  
develops the following elevations: 
ALT or AST <1.5 × ULN 
ALT or AST ≥3 × ULN 
ALP <1.5 × ULN 
ALP ≥2 × ULN 
TBL <1.5 × ULN 
TBL ≥2 × ULN (except for participants with Gilbert’s 
syndrome) 
ALT or AST ≥1.5 × ULN 
ALT or AST ≥2 × baseline 
ALP ≥1.5 × ULN 
ALP ≥2 × baseline 
TBL ≥1.5 × ULN 
TBL ≥2 × baseline (except for participants with Gilbert’s 
syndrome) 
 
If the abnormality persists or worsens, clinical and laboratory monitoring, and evaluation for 
possible causes of abnormal liver tests should be initiated by the investigator in consultation with 
the Lilly-designated medical monitor. At a minimum, this evaluation should include physical 
examination and a thorough medical history, including symptoms, recent illnesses (e.g., heart 
failure, systemic infection, hypotension, or seizures), recent travel, history of concomitant 
medications (including over-the-counter), herbal and dietary supplements, and a history of 
alcohol drinking and other substance abuse.  
Initially, monitoring of symptoms and hepatic biochemical tests should be done at a frequency of 
1 to 3 times weekly, based on the participant’s clinical condition and hepatic biochemical tests. 
Subsequently, the frequency of monitoring may be decreased to once every 1 to 2 weeks, if the 
participant’s clinical condition and laboratory results stabilize. Monitoring of ALT, AST, ALP, 
and TBL should continue until levels normalize or return to approximate baseline levels. 
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Comprehensive hepatic evaluation  
A comprehensive evaluation should be performed to search for possible causes of liver injury if 
one or more of these conditions occur: 
If a participant with baseline 
results of...  
develops the following elevations: 
ALT or AST <1.5 × ULN 
ALT or AST ≥3 × ULN with hepatic signs/symptoms*, or  
ALT or AST ≥5 × ULN 
ALP <1.5 × ULN 
ALP ≥3 × ULN 
TBL <1.5 × ULN 
TBL ≥2 × ULN (except for participants with Gilbert’s syndrome) 
ALT or AST ≥1.5 × ULN 
ALT or AST ≥2 × baseline with hepatic signs/symptoms,* or 
ALT or AST ≥3 × baseline 
ALP ≥1.5 × ULN 
ALP ≥2 × baseline 
TBL ≥1.5 × ULN 
TBL ≥1.5 × baseline (except for participants with Gilbert’s 
syndrome)  
* Hepatic signs/symptoms are severe fatigue, nausea, vomiting, right upper quadrant abdominal pain, fever, rash, 
and/or eosinophilia >5%. 
At a minimum, this evaluation should include physical examination and a thorough medical 
history, as outlined above, as well as tests for prothrombin time - international normalized ratio 
(PT-INR); tests for viral hepatitis A, B, C, or E; tests for autoimmune hepatitis; and an abdominal 
imaging study (e.g., ultrasound or CT scan).  
Based on the participant’s history and initial results, further testing should be considered in 
consultation with the Lilly-designated medical monitor, including tests for hepatitis D virus 
(HDV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), acetaminophen levels, 
acetaminophen protein adducts, urine toxicology screen, Wilson’s disease, blood alcohol levels, 
urinary ethyl glucuronide, and serum phosphatidylethanol. Based on the circumstances and the 
investigator’s assessment of the participant’s clinical condition, the investigator should consider 
referring the participant for a hepatologist or gastroenterologist consultation, magnetic resonance 
cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), 
cardiac echocardiogram, or a liver biopsy.  
8.2.8.1.1. Additional Hepatic Data Collection in Participants Who Have Abnormal Liver 
Tests During the Study  
Additional hepatic safety data collection in hepatic safety eCRFs should be performed in study 
participants who meet 1 or more of the following 5 conditions: 
 Elevation of serum ALT to ≥5 × ULN on 2 or more consecutive blood tests (if baseline 
ALT <1.5 × ULN): 
o In participants with baseline ALT ≥1.5 × ULN, the threshold is ALT ≥3 × baseline 
on 2 or more consecutive tests; 
 Elevated TBL to ≥2 × ULN (if baseline TBL <1.5 × ULN) (except for cases of known 
Gilbert’s syndrome): 
o In participants with baseline TBL ≥1.5 × ULN, the threshold should be 
TBL ≥2 × baseline; 
 Elevation of serum ALP to ≥2 × ULN on 2 or more consecutive blood tests (if baseline 
ALP <1.5 × ULN): 
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o In participants with baseline ALP ≥1.5 × ULN, the threshold is ALP ≥2 × baseline 
on 2 or more consecutive blood tests; 
 Hepatic event considered to be an SAE; 
 Discontinuation of study intervention due to a hepatic event.  
Note: the interval between the 2 consecutive blood tests should be at least 2 days. 
8.2.8.2.Hepatitis C Testing and Monitoring  
Initial testing for HCV infection includes testing for antibodies to HCV: 
 
If anti-HCV is positive, a serum test for circulating HCV RNA is required. 
 
If HCV RNA test is negative, the participant is not excluded. 
 
If HCV RNA test is positive, the participant is excluded. 
Participants who have had HCV infection and been successfully treated, defined as a sustained 
virologic response (HCV RNA by PCR-negative for at least 24 weeks following treatment 
completion) are not excluded on the basis of HCV as long as HCV RNA test is negative at 
screening. 
If HCV RNA is detected during the study, the study intervention will be discontinued (see 
Section 7.1.1), and the participant should receive appropriate follow-up medical care. 
8.2.8.3.Hepatitis B Testing and Monitoring  
Initial testing for hepatitis B virus (HBV) infection includes hepatitis B surface antigen (HBsAg) 
and antibody to hepatitis B core antigen (anti-HBc): 
 
If HBsAg is positive, the participant is excluded; 
 
If HBsAg is negative and anti-HBc is negative, the participant is not excluded; 
 
If HBsAg is negative and anti-HBc is positive, further testing for HBV DNA is required: 
o If the screening HBV DNA is positive, the participant is excluded; 
o If the screening HBV DNA is negative, the participant is not excluded. Repeat 
testing for HBV DNA is required at least every 3 months during the study (see 
the SoA [Section 1.3]), with temporary withholding or permanent discontinuation 
of study intervention if HBV DNA is positive, as described in Section 7.1.1. 
Management of enrolled participants with detectable HBV DNA during the study 
If HBV DNA is detected during the study, the study intervention will be temporarily withheld or 
permanently discontinued, and participants should receive appropriate follow-up medical care as 
described in Section 7. 
8.3. Adverse Events, Serious Adverse Events, and Product Complaints  
The definitions of the following events can be found in Appendix 10.3: 
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 Adverse events (AEs) 
 Serious adverse events (SAEs) 
 Product complaints (PCs) 
These events will be reported by the participant (or, when appropriate, by a caregiver, surrogate, 
or the participant’s legally authorized representative). 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet these definitions and remain responsible for following up events that 
are serious, considered related to the study intervention or study procedures, or that caused the 
participant to discontinue the study (see Section 7). 
After the initial report, the investigator is required to proactively follow each participant at 
subsequent visits/contacts. All SAEs and AEs of special interest (as defined in Section 8.3.3) will 
be followed until resolution, stabilization, the event is otherwise explained, or the participant is 
lost to follow-up (as defined in Section 7.3). For PCs, the investigator is responsible for ensuring 
that follow-up includes any supplemental investigations as indicated to elucidate the nature 
and/or causality. Further information on follow-up procedures is provided in Appendix 10.3. 
8.3.1. Timing and Mechanism for Collecting Events  
All SAEs will be collected from the signing of the ICF until the follow-up visit at the time points 
specified in the SoA (Section 1.3). 
All AEs will be collected from the signing of the ICF until participation in the study has ended. 
Adverse events that begin before the start of study intervention but after signing of the ICF will 
be recorded on the Adverse Event eCRF. 
Although all AEs after signing the ICF and Assent Form (as applicable) are recorded by the site 
in the eCRF/electronic data entry, SAE reporting to the Sponsor begins after the participant has 
signed the ICF and has received study intervention. However, if an SAE occurs after signing the 
ICF, but prior to receiving ixekizumab, it needs to be reported ONLY if it is considered 
reasonably possibly related to study procedures. 
All SAEs will be recorded and reported to the Sponsor or designee immediately and under no 
circumstance should this exceed 24 hours, as indicated in Appendix 10.3. The investigator will 
submit any updated SAE data to the Sponsor within 24 hours of it being available. Participants 
with a serious hepatic AE should have additional data collected using the electronic data entry. 
Investigators are not obligated to actively seek AEs or SAEs after conclusion of the study 
participation. However, if the investigator learns of any SAE, including a death, at any time after 
a participant has been discharged from the study, and he/she considers the event to be reasonably 
related to the study intervention or study participation, the investigator must promptly notify the 
Sponsor. 
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8.3.2. Pregnancy  
Collection of pregnancy information  
Male participants with partners who become pregnant 
 The investigator will attempt to collect pregnancy information on any male participant’s 
female partner who becomes pregnant while the male participant is in this study. This 
applies only to male participants who receive intervention. 
 After learning of a pregnancy in the female partner of a study participant, the investigator 
will: 
o obtain a consent to release information from the pregnant female partner directly; 
and  
o within 24 hours after obtaining this consent, will record pregnancy information on 
the appropriate form and submit it to the Sponsor.  
The female partner will also be followed to determine the outcome of the pregnancy. Information 
on the status of the mother and child will be forwarded to the Sponsor. Generally, the follow-up 
will be no longer than 6 to 8 weeks following the estimated delivery date. Any termination of the 
pregnancy will be reported regardless of gestational age, fetal status (presence or absence of 
anomalies), or indication for the procedure. 
Female participants who become pregnant 
The investigator will collect pregnancy information on any female participant who becomes pregnant 
while participating in this study. The initial information will be recorded on the appropriate form and 
submitted to the Sponsor within 24 hours of learning of a participant’s pregnancy. 
 The participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on the participant and the neonate and the 
information will be forwarded to the Sponsor. Generally, follow-up will not be required 
for longer than 6 to 8 weeks beyond the estimated delivery date. Any termination of 
pregnancy will be reported, regardless of gestational age, fetal status (presence or absence 
of anomalies) or indication for the procedure. 
 While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be reported 
as an AE or SAE. 
 A spontaneous abortion (occurring at <20 weeks gestational age) or still birth (occurring at 
≥20 weeks gestational age) is always considered to be an SAE and will be reported as such. 
 Any post-study pregnancy-related SAE considered reasonably related to the study 
intervention by the investigator will be reported to the Sponsor as described in protocol 
Section 8.3.1. While the investigator is not obligated to actively seek this information in 
former study participants, he/she may learn of an SAE through spontaneous reporting. 
 Any female participant who becomes pregnant while participating in the study will 
discontinue study intervention. If the participant is discontinued from the study, follow 
the standard discontinuation process and continue directly to the follow-up phase. The 
follow-up on the pregnancy outcome should continue independent of intervention or 
study discontinuation. 
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8.3.3. 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. 
Adverse events of special interests for ixekizumab are the following: 
 cytopenias (leukopenia, neutropenia, and thrombocytopenia), 
 liver function test changes/enzyme elevations (ALT, AST, bilirubin, and ALP), 
 infections, 
 injection-site reactions, 
 allergic reactions/hypersensitivities, 
 cerebro-cardiovascular events, 
 malignancies, 
 inflammatory bowel disease (IBD), and 
 depression.  
Sites will provide details on AEs as instructed on the eCRF. Investigators will also educate 
participants 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 participant 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 antidrug antibodies (ADAs), other laboratory tests needed to elucidate 
the cause of the allergic/hypersensitivity reaction, and/or ixekizumab serum concentration. 
8.4. Pharmacokinetics  
Pharmacokinetics parameters are not evaluated in this study.  
8.5. Pharmacodynamics  
Pharmacodynamic parameters are not evaluated in this study. 
8.6. Genetics  
Genetics are not evaluated in this study. 
8.7. Biomarkers  
Biomarkers are not evaluated in this study. 
8.8. Health Economics or Medical Resource Utilization and Health 
Economics]  
Health economics or medical resource utilization and health economics parameters are not 
evaluated in this study 
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9. 
Statistical Considerations  
The SAP will include a more technical and detailed description of the statistical analyses 
described in this section. This section is a summary of the planned statistical analyses of the most 
important endpoints, including primary and key secondary endpoints. 
9.1. Statistical Hypotheses  
No statistical hypotheses testing is planned for this study.  
9.2. Analyses Populations  
The following analysis populations will be used; additional analysis populations will be specified 
in the SAP: 
Analysis Population 
Description 
PsO with No Active PsA – 
Modified Intent-to-Treat 
(mITT) Population 
Unless otherwise specified, efficacy and health outcomes analyses specific to 
psoriasis will be conducted on the PsO with No Active PsA - mITT 
population, defined as all enrolled participants with a psoriasis indication, who 
do not qualify for Active PsA and receive at least 1 dose of study treatment, 
even if the participant does not receive the correct treatment, or otherwise 
does not follow the protocol.   
Active PsA – mITT 
Population 
Unless otherwise specified, efficacy and health outcomes analyses specific to 
PsA will be conducted on the Active PsA mITT population, defined as all 
enrolled participants with an Active PsA indication who receive at least 1 dose 
of study treatment, even if the participant does not receive the correct 
treatment, or otherwise does not follow the protocol.  
Safety Population 
Safety analyses will be conducted on the safety population, defined as all 
enrolled participants who receive at least 1 dose of study treatment. 
Participants will be analyzed according to the treatment to which they are 
assigned.   
9.3 
Missing Data Imputation  
The following methods for imputation of missing data will be used:   
9.3.1 
General Nonresponder Imputation for Clinical Response  
Analysis of categorical efficacy and health outcomes variables will be assessed using a 
nonresponder imputation (NRI) method. Participants will be considered a nonresponder for the 
NRI analysis if they: 
 do not meet the clinical response criteria (e.g., ACR20, PASI75, PASI90, PASI100, 
sPGA [0,1]);  
 have missing clinical response data at a timepoint of interest (e.g., Week 12, Week 24);  
 discontinue study treatment at any time prior to a timepoint of interest for any reason; or 
 have no postbaseline observation.  
The NRI may be applied at any time point specified for analysis.   
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9.4 
Study Participant Disposition and Characteristics  
9.4.1 Study Participant Disposition  
All participants who prematurely discontinue from the study treatment and/or from 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 with reasons for 
discontinuation.   
9.4.2 Study Participant Characteristics  
Participant demographic characteristics and baseline clinical measures will be summarized 
overall. Baseline characteristics will include sex, age, age category, weight, body mass index, 
race, and other demographic characteristics as per the SoA (Section 1.3).   
9.4.3 Concomitant Therapy  
Previous and concomitant medications will be summarized for participants who enter treatment 
and will be presented by the World Health Organization (WHO) Anatomic Therapeutic Class 
(ATC) Level 4 and WHO preferred term (PT).   
9.4.4 Treatment Compliance  
Treatment compliance with investigational product will be summarized for participants who 
enter the treatment. A participant will be considered overall compliant for treatment if he/she is 
missing no more than 20% of the expected doses, does not miss 2 consecutive doses, and does 
not over-dose (i.e., take more injections at the same time point than specified in the protocol).   
Proportions of participants compliant by visit and overall will be reported. 
9.5 
 Statistical Analyses   
9.5.1. General Considerations  
Statistical analysis of this study will be the responsibility of Lilly. 
Unless otherwise specified, continuous data will be summarized in terms of the mean, standard 
deviation, minimum, maximum, median, and number of observations. Categorical data will be 
summarized as frequency counts and percentages. 
Baseline will be defined as the last non missing assessment recorded on or prior to the date of 
first injection for efficacy and health outcomes. In most cases, this will be the measure recorded 
at Week 0 (Visit 2). Change from baseline will be calculated as the visit value of interest 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. 
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. 
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Complete details of the planned analyses will be documented in the SAP.   
9.5.2 
Primary Endpoint Analysis  
The primary analysis, the number and percentage of participants in the safety population 
experiencing:  
 TEAEs,  
 TEAE by maximum severity,  
 Death,  
 SAEs,  
 TEAE related to study treatment,  
 AEs leading to treatment discontinuation, and  
 TEAEs of special interest (hepatic, cytopenias, infections, allergic 
reactions/hypersensitivities, injection-site reactions, cerebrocardiovascular events, major 
adverse cerebrocardiovascular events [MACE], malignancies, depression, IBD, 
interstitial lung disease [ILD]). 
These AEs, occurring within the duration of the study (24 weeks) after being started on 
Ixekizumab, will be summarized. For events that are gender-specific (as defined by the Medical 
Dictionary for Regulatory Activities [MedDRA]), the denominator and computation of 
percentage will include only participants from the given gender.  
Refer to Section 9.5.5.1 for further details. 
9.5.3 
Secondary Endpoint(s) Analysis  
Endpoints Specific to Psoriasis (PsO) and Psoriatic Arthritis (PsA) Participants with 3% or 
More BSA of PsO 
As a part of the secondary analyses, the following endpoints will be summarized (i) for the PsO 
indication and will be based on the PsO with no active PsA– mITT population, and (ii) for the 
active PsA indication and will be based on the active PsA – mITT population with BSA of PsO 
≥3% at baseline, unless otherwise specified: 
Proportion of Participants with sPGA (0 or 1)  
The proportion of participants achieving sPGA response of 0 or 1 at Week 12 will be 
summarized and the associated 95% confidence interval (CI) will be provided using normal 
approximation. Missing data will be imputed using the NRI method as defined in Section 9.3.1. 
Further details will be provided in SAP. 
Proportion of Participants with PASI 75  
The proportion of participants achieving a PASI 75 response at Week 12 will be summarized and 
the associated 95% CI will be provided using normal approximation. Missing data will be 
imputed using the NRI method as defined in Section 9.3.1. Further details will be provided in 
SAP.  
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Endpoints Specific to Psoriatic Arthritis (PsA) 
As a part of the secondary analyses, the following endpoint will be summarized for the PsA 
indication and will be based on the active PsA-mITT population: 
Percentage of Participants Achieving ACR20  
The proportion of participants achieving a response of ACR20 at Week 24 (Visit 15) will be 
summarized and 95% CI will be provided using normal approximation. Further details will be 
provided in SAP. 
9.5.5 
Safety Analyses  
Safety will be assessed by summarizing AEs, laboratory analytes and vital signs. Abnormal 
physical examinations and concomitant medications will be listed. The overall duration of 
treatment exposure will also be summarized.   
Safety data collected after study treatment discontinuation will be summarized separately. 
The categorical safety measures will be summarized with incidence rates. The absolute and mean 
change from baseline of the continuous safety measures will be summarized by visits.   
All safety analyses will be based on the safety population and will be summarized overall and by 
dosing regimen (Q2W/Q4W and Q4W/Q4W) as specified in Table RHCZ.6.1. 
Further details will be described in the SAP.   
9.5.5.1.Adverse Events  
Adverse events are classified based upon MedDRA. A TEAE is defined as an event that first 
occurred or worsened in severity after baseline 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 injection are 
considered when determining TEAEs. TEAEs will be assigned to the treatment period in which 
they first occurred or worsened. A follow-up emergent adverse event (FEAE) is defined as an 
event that first occurred or worsened in severity after the date of Week 24 (Visit 6) or the ETV. 
For events that are gender specific, the denominator and computation of the percentage will 
include only participants from the given gender.   
A summary of AEs will be provided overall and by dosing regimen, including the number and 
percentage of participants who reported TEAEs, TEAEs by maximum severity, death, SAEs, 
TEAEs related to study intervention, discontinuations from the treatment due to an AE, and 
treatment-emergent AESIs: cytopenias, infections, injection-site reactions (ISRs), allergic 
reactions/hypersensitivities, cerebrocardiovascular events, MACE, malignancies, depression, 
IBD, ILD. TEAEs (all, by maximum severity, and possibly related to study intervention by the 
investigator), SAEs including deaths, AEs that lead to treatment discontinuation will be 
summarized by MedDRA system organ class (SOC) and PT.   
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In addition to general safety parameters, safety information on specific topics of AESIs will also 
be presented. Potential AESIs will be identified by a standardized MedDRA query (SMQ) or a 
Lilly defined MedDRA PT listing.   
FEAEs, SAEs (including deaths), and AEs that lead to study discontinuation will be summarized.    
9.5.5.2.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 (see below). Shift tables will be 
presented for selected parameters.   
 For categorical laboratory tests:  
o Treatment-emergent abnormal value = a change from normal at all baseline 
visits to abnormal at any time post baseline;  
 For continuous laboratory 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; and 
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. 
9.5.5.3.Vital Signs  
Vital signs will be presented as mean changes from baseline and as incidence of treatment-
emergent high or low values (see below) and will be summarized both pre- and post dose at 
Week 0 (Visit 2) and postbaseline visits, as applicable.   
 For treatment-emergent high and low:   
o A treatment-emergent high result is defined as a change from a value less than 
or equal to the high limit at baseline to a value greater than the high limit at 
any time that meets the specified change criteria during the treatment period; 
o 
A treatment-emergent low result is defined as a change from a value 
greater than or equal to the low limit at baseline to a value less than the low 
limit at any time that meets the specified change criteria during the treatment 
period. 
9.6 
Interim Analysis  
No interim analysis planned. 
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9.7 
Sample Size Determination  
No formal sample size calculation was done for this study. 
Approximately, 250 participants (PsO: 150 participants and PsA: 100 participants) are planned to 
be enrolled into this study, and assuming discontinuations of approximately 10%, approximately 
225 participants will be able to complete the 24-week period of treatment. 
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10 Supporting Documentation and Operational Considerations  
10.1 Appendix 1: Regulatory, Ethical, and Study Oversight Considerations  
10.1.1 Regulatory and Ethical Considerations  
● This study will be conducted in accordance with the protocol and with the following: 
○ Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
○ Applicable International Council for Harmonisation (ICH) Good Clinical 
Practice (GCP) Guidelines 
○ Applicable laws and regulations 
● The protocol, protocol amendments, ICF, IB, and other relevant documents (e.g., 
advertisements) must be submitted to an ERB by the investigator and reviewed and 
approved by the IRB/IEC before the study is initiated. 
● Any amendments to the protocol will require IRB/IEC approval before 
implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to study participants. 
● Protocols and any substantial amendments to the protocol will require health 
authority approval prior to initiation except for changes necessary to eliminate an 
immediate hazard to study participants. 
● The investigator will be responsible for the following: 
○ Providing written summaries of the status of the study to the IRB/IEC 
annually or more frequently in accordance with the requirements, policies, 
and procedures established by the IRB/IEC 
○ Notifying the IRB/IEC of SAEs or other significant safety findings as 
required by IRB/IEC procedures 
○ Providing oversight of study conduct for participants under their responsibility 
and adherence to requirements of 21 Code of Federal Regulations (CFR), ICH 
guidelines, the IRB/IEC, European regulation 536/2014 for clinical studies (if 
applicable), and all other applicable local regulations 
● Investigator sites are compensated for participation in the study as detailed in the 
clinical trial agreement. 
10.1.2 Financial Disclosure  
Investigators and sub investigators will provide the Sponsor with sufficient, accurate financial 
information as requested to allow the Sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study. 
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10.1.3 Informed Consent Process  
● The investigator or his/her representative will explain the nature of the study, including 
the risks and benefits, to the participant or his/her legally authorized representative and 
answer all questions regarding the study. 
● Participants must be informed that their participation is voluntary.  
● Participants or their legally authorized representative will be required to sign a statement 
of informed consent that meets the requirements of 21 Code of Federal Regulations 
(CFR) 50, local regulations, ICH guidelines, Health Insurance Portability and 
Accountability Act (HIPAA) requirements, where applicable, and the IRB/IEC or study 
center. 
● The medical record must include a statement that written informed consent was obtained 
before the participant was entered in the study and the date the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICF. 
● Participants must be re-consented to the most current version of the ICF(s) during their 
participation in the study. 
● If a participant reaches the age of legal consent during the study, an ICF must be obtained 
from the participant for his or her continued participation in the study. 
● A copy of the ICF(s) must be provided to the participant or the participant’s legally 
authorized representative and is kept on file. 
10.1.4 Data Protection  
● Participants will be assigned a unique identifier by the Sponsor. Any participant records, 
datasets, or tissue samples that are transferred to the Sponsor will contain the identifier 
only; participant names or any information which would make the participant identifiable 
will not be transferred. 
● The participant must be informed that the participant’s personal study-related data will be 
used by the Sponsor in accordance with local data protection law. The level of disclosure 
must also be explained to the participant who will be required to give consent for their 
data to be used as described in the informed consent.  
● The participant must be informed that their medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the Sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
● The Sponsor has processes in place to ensure data protection, information security and 
data integrity. These processes include appropriate contingency plan(s) for appropriate 
and timely response in the event of a data security breach. 
10.1.5 Data Quality Assurance  
● All participant data relating to the study will be recorded on electronic CRFs unless 
transmitted to the Sponsor or designee electronically (e.g., laboratory data). The 
investigator is responsible for verifying that data entries are accurate and correct by 
electronically signing the CRF. 
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● The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
● The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents. 
● Monitoring details describing strategy (e.g., risk-based initiatives in operations and 
quality such as risk management and mitigation strategies and analytical risk-based 
monitoring), methods, responsibilities and requirements, including handling of 
noncompliance issues and monitoring techniques are provided in the Monitoring Plan. 
● The Sponsor or designee is responsible for the data management of this study including 
quality checking of the data. 
● The Sponsor assumes accountability for actions delegated to other individuals (e.g., 
contract research organizations). 
● Study monitors will perform ongoing source data verification to confirm that data 
transcribed into the CRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of participants are being 
protected; and that the study is being conducted in accordance with the currently 
approved protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements. 
● Records and documents, including signed ICFs, pertaining to the conduct of this study 
must be retained by the investigator for the time period outlined in the Clinical Trial 
Agreement (CTA) unless local regulations or institutional policies require a longer 
retention period. No records may be destroyed during the retention period without the 
written approval of the Sponsor. No records may be transferred to another location or 
party without written notification to the Sponsor. 
● In addition, Sponsor or its representatives will periodically check a sample of the 
participant data recorded against source documents at the study site. The study may be 
audited by Sponsor or its representatives, and/or regulatory agencies at any time. 
Investigators will be given notice before an audit occurs. 
Data Capture System 
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness 
of the data reported to the Sponsor. 
An electronic data capture system (EDC) will be used in this study for the collection of CRF 
data. The investigator maintains a separate source for the data entered by the investigator or 
designee into the Sponsor-provided EDC system. The investigator is responsible for the 
identification of any data to be considered source and for the confirmation that data reported are 
accurate and complete by signing the CRF. 
Data collected via the Sponsor-provided data capture systems will be stored at third parties. The 
investigator will have continuous access to the data during the study and until decommissioning 
of the EDC systems. Prior to decommissioning, the investigator will receive an archival copy of 
pertinent data for retention. 
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Data managed by a central vendor, such as laboratory test data, will be stored electronically in 
the central vendor’s database system and reports/electronic transfers will be provided to the 
investigator for review and retention. Data will subsequently be transferred from the central 
vendor to the Sponsor’s data warehouse. 
Data from complaint forms submitted to the Sponsor will be encoded and stored in the global 
product complaint management system. 
10.1.6 Source Documents  
● Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site. 
● Data reported on or entered in the CRF and are transcribed from source documents must 
be consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending 
on the study. Also, current medical records must be available. 
● Definition of what constitutes source data can be found in Section 10.1.5. 
10.1.7 Study and Site Start and Closure  
First Act of Recruitment 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
The first act of recruitment is the opening of the first site and will be the study start date. 
Study or Site Termination 
The Sponsor or Sponsor’s designee reserves the right to close the study site or terminate the 
study at any time for any reason at the sole discretion of the Sponsor. Study sites will be closed 
upon study completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or investigator may include but are 
not limited to: 
For study termination: 
● Discontinuation of further study intervention development; 
For site termination: 
● Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the Sponsor’s procedures, or GCP guidelines; 
● Inadequate recruitment (evaluated after a reasonable amount of time) of 
participants by the investigator 
● Total number of participants included earlier than expected. 
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If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up. 
10.1.8 Publication Policy  
In accordance with the Sponsor’s publication policy the results of this study will be submitted for 
publication by a peer-reviewed journal. 
10.1.9 Investigator Information  
Physicians with experience in the diagnosis and treatment of PsO and PsA will participate as 
investigators in this clinical trial. 
 
 
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10.2 Appendix 2: Clinical Laboratory Tests  
The tests detailed in the table below will be performed by the central laboratory or by the 
local laboratory as specified in the table. 
Protocol-specific requirements for inclusion or exclusion of participants are detailed in 
Section 5 of the protocol. 
Additional tests may be performed at any time during the study as determined necessary 
by the investigator or required by local regulations. 
Pregnancy testing is described in the SoA (Section 1.3) and in the table below. 
Investigators must document their review of each laboratory safety report. 
Due to blood volume restrictions, some laboratory tests may not be collected. Laboratory 
samples are recommended to be collected as described in the Sponsor provided weight-based 
prioritization chart. 
 
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 
 
Indirect bilirubin 
Absolute counts of: 
Alkaline phosphatase 
Neutrophils, segmented 
Alanine aminotransferase (ALT/SGPT) 
Neutrophils, juvenile (bands) 
Aspartate aminotransferase (AST/SGOT) 
Lymphocytes 
Blood urea nitrogen (BUN) 
Monocytes 
Uric acid 
Eosinophils 
Creatinine 
Basophils 
Calcium 
 
Glucoseg 
Urinalysisa,b 
Albumin 
Color 
Cholesterol (total) 
Specific gravity 
Total protein 
pH 
CPK  
Protein 
Triglycerides 
Glucoseg 
Gamma-Glutamyl Transferase (GGT) 
Ketones 
 
Bilirubin 
 
Urobilinogen 
 
Blood 
 
Nitrite 
Urine creatinine 
 
Leukocyte esterase 
Urinalysis (microscopic): 
 
Sediment, cells, casts  
 
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Other Testsa 
 
Human immunodeficiency virus antibody (HIV)c,d 
Pregnancy Test (serum and urine)e 
Hepatitis B Surface antigen (HBsAg)c,d 
Follicle stimulating hormone (FSH)d,f 
Anti-Hepatitis B Core antibody (HBcAb)c,d 
 
Anti-Hepatitis B Surface antibody (HBsAb)d  
 
Anti-Hepatitis C d 
 
HBV DNAc,d 
 
 
 
Tuberculosisd 
 
 
 
Abbreviations:  CPK = creatine phosphokinase; DNA = deoxyribonucleic acid; HBV =  hepatitis B virus; 
RBC = red blood cells; SGOT = serum glutamic oxaloacetic transaminase; SGPT = serum glutamic pyruvic 
transaminase; WBC = white blood cells. 
a 
Assayed by Sponsor-designated laboratory. 
b 
Unscheduled blood chemistry, urinalysis, 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 participant for the study (with the exception of those 
participants who require further HBV monitoring [Section 8.2.8.3]).  
e 
Serum pregnancy test (women <60 years of age who are still of childbearing potential) and urine pregnancy test 
(women of childbearing potential). Participants will undergo urine pregnancy self-testing at home on a monthly 
basis during periods between scheduled visits until Week 24. During these intervisit periods, the site must call 
the participant each month to obtain her pregnancy test results. Additional urine pregnancy testing can be 
performed at the investigator’s discretion. Participants determined to be pregnant will be discontinued from 
treatment and will no longer be administered study intervention (see Section 7.1.1). 
f 
Women ≥40 and <60 years of age who have had a cessation of menses for ≥12 months will have an FSH test 
confirming nonchildbearing potential (≥40 mIU/mL). The FSH test will be performed centrally. 
g 
Non-fasting glucose. 
 
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10.3 Appendix 3: Adverse Events and Serious Adverse Events: Definitions 
and Procedures for Recording, Evaluating, Follow-up, and Reporting  
10.3.1 Definition of AE  
AE Definition 
An AE is any untoward medical occurrence in a participant or clinical study participant, 
temporally associated with the use of study intervention, whether or not considered related to 
the study intervention. 
 NOTE: An AE can therefore be any unfavourable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study intervention. 
 
Events Meeting the AE Definition 
 Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g., ECG, radiological scans, vital signs measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator (i.e., not related to progression of 
underlying disease). 
 Exacerbation of a chronic or intermittent preexisting condition including either an 
increase in frequency and/or intensity of the condition. 
 New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study. 
 Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
 Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent. Such overdose should be reported regardless of sequelae. 
 “Lack of efficacy” or “failure of expected pharmacological action,” per se, will not be 
reported as an AE or SAE. Such instances will be captured in the efficacy assessments. 
However, the signs, symptoms, and/or clinical sequelae resulting from lack of efficacy 
will be reported as AE or SAE if they fulfill the definition of an AE or SAE. 
 
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Events NOT Meeting the AE Definition 
 Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
 The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition. 
 Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that leads to 
the procedure is the AE. 
 Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
 Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present or 
detected at the start of the study that do not worsen. 
10.3.2 Definition of SAE  
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (e.g., hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease). 
 
An SAE is defined as any untoward medical occurrence that, at any dose, meets one or 
more of the criteria listed: 
a. Results in death 
b. Is life-threatening 
The term life-threatening in the definition of serious refers to an event in which the participant 
was at risk of death at the time of the event. It does not refer to an event, which hypothetically 
might have caused death, if it were more severe. 
c. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
 In general, hospitalization signifies that the participant has been admitted to hospital or 
emergency ward (usually involving at least an overnight stay) for observation and/or 
treatment that would not have been appropriate in the physician’s office or outpatient 
setting. Complications that occur during hospitalization are AEs. If a complication 
prolongs hospitalization or fulfills any other serious criteria, the event is serious. When 
in doubt as to whether hospitalization occurred or was necessary, the AE should be 
considered serious. 
 Hospitalization for elective treatment of a preexisting condition that did not worsen 
from baseline is not considered an AE. 
 
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d. Results in persistent disability/incapacity 
 The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
 This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, 
and accidental trauma (e.g., sprained ankle) which may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption. 
e. 
Is a congenital anomaly/birth defect 
 Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs. 
f. 
Other situations: 
 Medical or scientific judgment should be exercised by the investigator in deciding 
whether SAE reporting is appropriate in other situations such as important medical 
events that may not be immediately life-threatening or result in death or hospitalization 
but may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events should 
usually be considered serious. 
 
Examples of such events include invasive or malignant cancers, intensive treatment in 
an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency or 
drug abuse.  
10.3.3 Definition of Product Complaints  
Product Complaint 
 A PC is any written, electronic, or oral communication that alleges deficiencies related 
to the identity, quality, durability, reliability, safety, effectiveness or performance of a 
study intervention. When the ability to use the study intervention safely is impacted, 
the following are also PCs: 
o Deficiencies in labeling information, and 
o Use errors for device or drug-device combination products due to ergonomic 
design elements of the product. 
 Product complaints related to study interventions used in clinical trials are collected in 
order to ensure the safety of participants, monitor quality, and to facilitate process and 
product improvements. 
 Investigators will instruct participants to contact the site as soon as possible if he/she 
has a PC or problem with the study intervention so that the situation can be assessed. 
 An event may meet the definition of both a PC and an AE/SAE. In such cases, it 
should be reported as both a PC and as an AE/SAE. 
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10.3.4 Recording and Follow-Up of AE and/or SAE and Product Complaints  
AE, SAE, and Product Complaint Recording 
 When an AE/SAE/PC occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory reports, and diagnostics 
reports) related to the event. 
 The investigator will then record all relevant AE/SAE/PC information in the 
participant’s medical records, in accordance with the investigator’s normal clinical 
practice. AE/SAE information is reported on the appropriate CRF page and PC 
information is reported on the Product Complaint Form. 
Note: An event may meet the definition of both a PC and an AE/SAE. In such cases, it 
should be reported as both a PC and as an AE/SAE. 
 It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to Sponsor or designee in lieu of completion of the CRF page for AE/SAE and 
the Product Complaint Form for PCs. 
 There may be instances when copies of medical records for certain cases are requested 
by Sponsor or designee. In this case, all participant identifiers, with the exception of 
the participant number, will be redacted on the copies of the medical records before 
submission to Sponsor or designee. 
 The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported during 
the study and assign it to one of the following categories:  
 Mild: A type of AE that is usually transient and may require only minimal treatment or 
therapeutic intervention. The event does not generally interfere with usual activities of 
daily living. 
 Moderate: A type of AE that is usually alleviated with additional specific therapeutic 
intervention. The event interferes with usual activities of daily living, causing 
discomfort but poses no significant or permanent risk of harm to the research 
participant. 
 Severe: A type of AE that interrupts usual activities of daily living, or significantly 
affects clinical status, or may require intensive therapeutic intervention. An AE that is 
assessed as severe should not be confused with an SAE. Severe is a category utilized 
for rating the intensity of an event; and both AEs and SAEs can be assessed as severe. 
An event is defined as “serious” when it meets at least one of the predefined outcomes 
as described in the definition of an SAE, NOT when it is rated as severe. 
 
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Assessment of Causality 
 The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE. The investigator will use clinical judgment to 
determine the relationship. 
 A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out. 
 Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 
 The investigator will also consult the IB in his/her assessment. 
 For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
 There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to Sponsor or designee. However, it 
is very important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to Sponsor or designee. 
 The investigator may change their opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment. 
 The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
Follow-up of AEs and SAEs 
 The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by Sponsor or 
designee to elucidate the nature and/or causality of the AE or SAE as fully as possible. 
This may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other healthcare professionals. 
 If a participant dies during participation in the study or during a recognized follow-up 
period, the investigator will provide Sponsor or designee with a copy of any 
postmortem findings including histopathology. 
 New or updated information will be recorded in the originally completed eCRF. 
 The investigator will submit any updated SAE data to the Sponsor or designee within 
24 hours of receipt of the information. 
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10.3.5 Reporting of SAEs  
SAE Reporting via an Electronic Data Collection Tool 
 The primary mechanism for reporting an SAE will be the electronic data collection 
tool. 
 If the electronic system is unavailable or if a pregnancy is reported, then the site will 
use the paper SAE or pregnancy data collection tool (see next section) to report the 
event within 24 hours. 
 The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
 After the study is completed at a given site, the electronic data collection tool will be 
taken offline to prevent the entry of new data or changes to existing data. 
 If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken offline, then the site can report this information on a paper SAE form (see next 
section) or to the Sponsor or designee by telephone. 
 Contacts for SAE reporting can be found in the site training documents. 
SAE Reporting via Paper Form 
 In the event the electronic system is unavailable, facsimile transmission of the SAE 
paper CRF is the preferred method to transmit this information to the Sponsor. 
 Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE CRF pages within the designated reporting time frames. 
 Contacts for SAE reporting can be found in the site training documents 
10.3.6 Regulatory Reporting Requirements  
SAE Regulatory Reporting 
 Prompt notification by the investigator to the Sponsor of an SAE is essential so that 
legal obligations and ethical responsibilities towards the safety of participants and the 
safety of a study intervention under clinical investigation are met. 
● The Sponsor has a legal responsibility to notify both the local regulatory 
authority and other regulatory agencies about the safety of a study intervention 
under clinical investigation. The Sponsor will comply with country-specific 
regulatory requirements relating to safety reporting to the regulatory authority, 
IRB/IEC, and investigators. 
● An investigator who receives an investigator safety report describing an SAE or 
other specific safety information (e.g., summary or listing of SAEs) from the 
Sponsor will review and then file it along with the Investigator’s Brochure and 
will notify the IRB/IEC, if appropriate, according to local requirements. 
 
 
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10.4 Appendix 4: Contraceptive and Barrier Guidance  
10.4.1 Definitions  
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile (see below). 
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study intervention, additional evaluation should be considered. 
Women in the following categories are not considered WOCBP: 
 Premenarchal 
 Premenopausal female with 1 of the following: 
o Documented hysterectomy 
o Documented bilateral salpingectomy 
o Documented bilateral oophorectomy 
 
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (e.g., Mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study entry. 
 
Note: Documentation can come from the site personnel’s: review of the participant’s medical 
records, medical examination, or medical history interview. 
A postmenopausal female is defined as women with: 
o At least 6 weeks post-surgical bilateral oophorectomy with or without 
hysterectomy, confirmed by operative note. 
OR 
o With spontaneous amenorrhea for at least 12 months, not induced by a medical 
condition such as anorexia nervosa and not taking medications during the 
amenorrhea (e.g., oral contraceptives, hormones, gonadotropin releasing 
hormone, anti-estrogens, selective estrogen receptor modulators (SERMs), or 
chemotherapy that induced the amenorrhea. And if age ≤50, has an FSH of 
≥40 mIU/mL and estradiol of ≤ 30 pg/mL. 
Contraception guidance for women of childbearing potential (WOCBP): 
See Section 5.1, inclusion criterion [1b]. 
Contraception guidance for men: 
See Section 5.1, inclusion criterion [1a]. 
 
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10.4.2 Contraception Guidance  
Male participants with partners who become pregnant 
The investigator will attempt to collect pregnancy information on a male participant’s female 
partner who becomes pregnant while the male participant is in this study.  
After obtaining the necessary signed informed consent and/or assent from the pregnant female 
partner directly, the investigator will record pregnancy information on the appropriate form and 
submit it to the Sponsor within 24 hours of learning of the partner’s pregnancy. The female 
partner will also be followed up to determine the outcome of the pregnancy. Information on the 
status of the mother and child will be forwarded to the Sponsor. Generally, the follow-up will be 
no longer than 6 to 8 weeks following the estimated delivery date. Any termination of the 
pregnancy will be reported, including fetal status (presence or absence of anomalies) or 
indication for the procedure. 
Female participants who become pregnant 
The investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study. The initial information will be recorded on the 
appropriate form and submitted to the Sponsor within 24 hours of learning of a participant’s 
pregnancy. 
The participant will be followed up to determine the outcome of the pregnancy. The investigator 
will collect follow-up information on the participant and the neonate, and the information will be 
forwarded to the Sponsor. Generally, follow-up will not be required for longer than 6 to 8 weeks 
beyond the estimated delivery date. Any termination of pregnancy will be reported, including 
fetal status (presence or absence of anomalies) or indication for the procedure. 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be reported as an AE or SAE. 
A spontaneous abortion (occurring at <20 weeks gestational age) or still birth (occurring at 
≥20 weeks gestational age) is always considered to be an SAE and will be reported as such. 
Any post-study pregnancy-related SAE considered reasonably related to the study intervention 
by the investigator will be reported to the Sponsor. While the investigator is not obligated to 
actively seek this information in former study participants, the investigator may learn of an SAE 
through spontaneous reporting. 
Any female participant who becomes pregnant while participating in the study will permanently 
discontinue the study intervention (see Section 7.1.1). 
 
 
 
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10.5 Appendix 5: Liver Safety: Suggested Actions and Follow-Up 
Assessments  
See Section 8.2.8.1 for guidance on appropriate test selection. 
The Lilly-designated central laboratory must complete the analysis of all selected testing except 
for microbiology testing. 
Local testing may be performed in addition to central testing when necessary for immediate 
participant management. 
Results will be reported if a validated test or calculation is available. 
Hematology 
Clinical Chemistry 
Hemoglobin 
Total bilirubin 
Hematocrit 
Direct bilirubin 
Erythrocytes (RBCs – red blood cells) 
Alkaline phosphatase (ALP) 
Leukocytes (WBCs – white blood cells) 
Alanine aminotransferase (ALT) 
Differential: 
Aspartate aminotransferase (AST) 
Neutrophils, segmented 
Gamma-glutamyl transferase (GGT) 
Lymphocytes 
Creatine kinase (CK) 
Monocytes 
Other Chemistry 
Basophils 
Acetaminophen 
Eosinophils 
Acetaminophen protein adducts 
Platelets 
Alkaline phosphatase isoenzymes 
Cell morphology (RBC and WBC) 
Ceruloplasmin 
Coagulation 
Copper 
Ethyl alcohol (EtOH) 
Prothrombin time, INR (PT-INR) 
Haptoglobin 
Serology 
Immunoglobulin A (IgA, quantitative) 
Hepatitis A virus (HAV) testing: 
Immunoglobulin G (IgG, quantitative) 
HAV total antibody 
Immunoglobulin M (IgM, quantitative) 
HAV IgM antibody 
Phosphatidylethanol (Peth) 
Hepatitis B virus (HBV) testing: 
Urine Chemistry 
Hepatitis B surface antigen (HBsAg) 
Drug screen 
Hepatitis B surface antibody (anti-HBs) 
Ethyl glucuronide (EtG) 
Hepatitis B core total antibody (anti-HBc) 
Other Serology 
Hepatitis B core IgM antibody 
Anti-nuclear antibody (ANA) 
Hepatitis B core IgG antibody 
Anti-smooth muscle antibody (ASMA)a 
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Hematology 
Clinical Chemistry 
HBV DNAd 
Anti-actin antibodyb 
Hepatitis C virus (HCV) testing: 
Epstein-Barr virus (EBV) testing: 
HCV antibody 
EBV antibody 
HCV RNAd 
EBV DNAd 
Hepatitis D virus (HDV) testing: 
Cytomegalovirus (CMV) testing: 
HDV antibody 
CMV antibody 
Hepatitis E virus (HEV) testing: 
CMV DNAd 
HEV IgG antibody 
Herpes simplex virus (HSV) testing: 
HEV IgM antibody 
HSV (Type 1 and 2) antibody  
HEV RNAd 
HSV (Type 1 and 2) DNAd 
Microbiologyc 
Liver kidney microsomal type 1 (LKM-1) antibody 
Culture: 
Blood 
Urine 
 
a Not required if anti-actin antibody is tested. 
b Not required if anti-smooth muscle antibody (ASMA) is tested. 
c Assayed ONLY by investigator-designated local laboratory; no central testing available. 
d Reflex/confirmation dependent on regulatory requirements, testing availability, or both. 
 
 
 
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10.6 Appendix 6: 
Protocol RHCZ CASPAR Criteria  
CASPAR Criteria 
The CASPAR criteria for psoriatic arthritis consist of inflammatory articular disease (joint, 
spine, or entheseal) with ≥3 points from the following 5 categories.  
 Evidence of current psoriasis, a personal history of psoriasis, or a family history of 
psoriasis (2 points)  
o Current psoriasis is defined as psoriatic skin or scalp disease present today as 
judged by a rheumatologist or dermatologist.†  
o A personal history of psoriasis is defined as a history of psoriasis that may be 
obtained from a participant, family physician, dermatologist, rheumatologist, or 
other qualified healthcare provider.  
o A family history of psoriasis is defined as a history of psoriasis in a first- or 
second-degree relative according to participant report. 
 Typical psoriatic nail dystrophy including onycholysis, pitting, and hyperkeratosis 
observed on current physical examination (1 point)  
 A negative test result for the presence of rheumatoid factor by any method except latex 
(1 point)  
 Either current dactylitis, defined as swelling of an entire digit, or a history of dactylitis 
recorded by a rheumatologist (1 point)  
 Radiographic evidence of juxta-articular new bone formation appearing as ill-defined 
ossification near joint margins (but excluding osteophyte formation) on plain radiographs 
of the hand or foot (1 point)  
† Current psoriasis is assigned a score of 2; all other features are assigned a score of 1.  
Taylor, W, Gladman, D, Helliwell, P, et al.; CASPAR Study Group. Classification criteria for 
psoriatic arthritis: development of new criteria from a large international study. Arthritis 
Rheum. 2006;54(8):2665–2673. 
 
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10.7 Appendix 7: 
Protocol RHCZ Tender and Swollen Joint Count 
Assessment Form  
68/66 JOINT EVALUATION 
 
Patient Right 
Patient Left 
 
Pain/Tenderness 
Swelling 
Pain/Tenderness 
Swelling 
JOINT* 
(Circle Correct Answer) 
0 = Absent 
1 = Present 
9 = Not 
applicable* 
0 = Absent 
1 = Present 
9 = Not 
applicable* 
0 = Absent 
1 = Present 
9 = Not 
applicable* 
0 = Absent 
1 = Present 
9 = Not 
applicable* 
1. Temporomandibular 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
2. Sternoclavicular 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
3. Acromioclavicular 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
4. Shoulder 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
5. Elbow 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
6. Wrist 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
7. Metacarpophalangeal I 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
8. Metacarpophalangeal II 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
9. Metacarpophalangeal III 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
10. Metacarpophalangeal IV 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
11. Metacarpophalangeal V 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
12. Thumb Interphalangeal 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
13. Proximal Interphalangeal II 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
14. Proximal Interphalangeal III 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
15. Proximal Interphalangeal IV 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
16. Proximal Interphalangeal V 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
17. Distal Interphalangeal II 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
18. Distal Interphalangeal III 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
19. Distal Interphalangeal IV 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
20. Distal Interphalangeal V 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
21. Hip 
0 
1 
9 
N/A 
0 
1 
9 
N/A 
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68/66 JOINT EVALUATION 
 
Patient Right 
Patient Left 
 
Pain/Tenderness 
Swelling 
Pain/Tenderness 
Swelling 
JOINT* 
(Circle Correct Answer) 
0 = Absent 
1 = Present 
9 = Not 
applicable* 
0 = Absent 
1 = Present 
9 = Not 
applicable* 
0 = Absent 
1 = Present 
9 = Not 
applicable* 
0 = Absent 
1 = Present 
9 = Not 
applicable* 
22. Knee 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
23. Ankle 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
24. Tarsus 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
25. Metatarsophalangeal I 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
26. Metatarsophalangeal II 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
27. Metatarsophalangeal III 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
28. Metatarsophalangeal IV 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
29. Metatarsophalangeal V 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
30. Great Toe 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
31. Interphalangeal II 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
32. Interphalangeal III 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
33. Interphalangeal IV 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
34. Interphalangeal V 
0 
1 
9 
0 
1 
9 
0 
1 
9 
0 
1 
9 
Abbreviation:  N/A = not applicable. 
* For replaced, ankylosed, or arthrodesed joints, please record as 9 (not applicable) and record details of replaced, 
ankylosed, arthrodesed joints. 
 
 
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Protocol I1F-IN-RHCZ (a) 
Page 93 
10.8 Appendix 8: Protocol Amendment History  
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents (TOC). 
Amendment [a]: 03 February 2023 
Overall Rationale for the Amendment 
Protocol I1F-IN-RHCZ, a 24-Week Multicenter, Open-Label, Single-Arm, Phase 4 Study to 
Evaluate the Safety of Ixekizumab in Patients with Moderate-to-Severe Plaque Psoriasis and/or 
Active Psoriatic Arthritis in India, 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 following are the overall rationale for the changes made to this protocol: 
 To comply with Subject Expert Committee (SEC; Ministry of Health [MoH]) 
recommendations, and  
 To provide more clarity regarding the assessments to be collected and analyzed for the 
PsA participants who have active plaque psoriasis. 
Other minor corrections (spelling errors, grammar corrections, formatting, and so on) and 
clarifications or semantic changes not affecting content have also been made in the document. 
The overall changes and rationale for the changes made to this protocol are provided in below 
table: 
Section # and Name 
Description of Change 
Brief Rationale 
Section 1.1 Protocol 
Synopsis and 
Section 3 Objectives and 
Endpoints 
Added a note for Other 
Efficacy Endpoints (PASI 
75, 90, 100, PASI change 
from baseline, sPGA [0, 1] 
and sPGA [0], and BSA 
change from baseline) - “For 
PsA participants with 3% or 
more body surface area 
(BSA) of PsO, both PsA and 
PsO efficacy outcomes will 
be collected.” 
To provide more clarity regarding 
the assessments to be collected and 
analyzed for the PsA participants 
who have active plaque psoriasis. 
Section 1.1 Protocol 
Synopsis, 
Section 1.2 Schema and 
Section 4.1 Overall 
Design 
Updated a statement related 
to study treatment. 
To provide clarity that treatment 
regimen for PsA participants with 
moderate-to-severe PsO is same as 
that for participants with PsO. 
Section 1.1 Protocol 
Synopsis, 
Updated text regarding PsA 
participants with 
moderate-to-severe PsO is 
To provide clarity that treatment 
regimen for PsA participants with 
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Protocol I1F-IN-RHCZ (a) 
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Section # and Name 
Description of Change 
Brief Rationale 
Section 4.2 Scientific 
Rationale for Study 
Design, and 
Section 6.1 Study 
Intervention(s) 
administered 
same as that for participants 
with PsO in synopsis and 
Section 6.1. 
 
Also, updated Tables 
RHCZ.6.1 and RHCZ.6.2 in 
Section 6.1. 
moderate-to-severe PsO is same as 
that for participants with PsO. 
Section 1.3 Schedule of 
Activities 
Added a row for “Substance 
use (alcohol, caffeine, 
tobacco use).” 
To collect additional participant 
history information. 
Section 1.3 Schedule of 
Activities 
Added “Evaluation for 
Disease Relapse” and 
footnote annotation b. 
To comply with Subject Expert 
Committee (SEC; Ministry of 
Health [MoH]) recommendations, 
Disease Relapse Evaluation has 
been included at screening visit. 
Section 1.3 Schedule of 
Activities 
Added a footnote annotation 
“i” to update a note 
describing requirement of 
assessments for participants 
with psoriatic arthritis 
(PsA).  
To provide clarity on what 
assessments are to be administered 
to which participants. 
Section 1.3 Schedule of 
Activities 
Removed baseline 
assessment of “Collect, 
review, and enter data from 
Study Intervention 
Administration Log.” 
Rectified original protocol typo 
error. 
Section 1.3 Schedule of 
Activities 
Included Week 24 
evaluation of active 
tuberculosis (TB) in patients 
by QuantiFERON 
Tuberculosis TB Gold test 
and chest x-ray. 
To comply with SEC (MoH) 
recommendations, Week 24 
evaluation has been included for 
active tuberculosis by 
QuantiFERON TB Gold test and 
chest x-ray at Week 24 of the 
treatment. 
Section 1.3 Schedule of 
Activities 
Modified a general table 
note at the end of schedule 
of activities (SoA) table 
footnote. 
To provide more clarity regarding 
the assessments to be collected and 
analyzed for the PsA participants 
who have active plaque psoriasis. 
Section 2.1 Study 
Rationale 
Added definition of 
moderate-to-severe plaque 
psoriasis. 
To clarify original content. 
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Protocol I1F-IN-RHCZ (a) 
Page 95 
Section # and Name 
Description of Change 
Brief Rationale 
Section 4.1.4 Post-
Treatment Follow-Up 
Period (Period 4) 
Timing of follow-up visit, 
Visit 802 is updated to 8 
weeks after Visit 801. 
To clarify original content. 
Section 8.1 Efficacy 
Assessment 
Updated a statement to 
mention that PsO outcome 
will be collected among all 
the PsA participants with 
3% or more BSA of PsO. 
Added Table RHCZ.8.1 to 
present clinician and patient 
assessments for different 
participants. 
To provide clarity on what 
assessments are to be administered 
to which participants. 
Section 8.1.2 American 
College of Rheumatology 
20, 50, and 70 Responder 
Index 
Included a statement in 
subsection Patient’s 
Assessment of Pain Visual 
Analog Scale – “Patient’s 
Assessment of Pain VAS 
will be administered only to 
PsA participants. The 
question related to pain 
assessment will be included 
in HAQ-DI assessment.” 
To clarify original content. 
Section 8.1.3 Patient 
Global Assessment of 
Disease Activity VAS  
 
Section 8.1.4 Physician’s 
Global Assessment of 
Disease Activity Visual 
Analog Scale 
Added separate scales for 
PsO and PsA participants. 
To clarify original content. 
Section 8.2.4 Evaluation 
of Disease Relapse 
Added details for Evaluation 
of Disease Relapse. 
To comply with SEC (MoH) 
recommendations, Disease 
Relapse Evaluation has been 
included at screening visit. 
Section 9.2 Analyses 
Populations. 
Updated the definition 
details of analysis 
population, 
Updated the analysis populations 
to include PsO with no active PsA 
population and active PsA 
population; text was defined 
accordingly. 
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Protocol I1F-IN-RHCZ (a) 
Page 96 
Section # and Name 
Description of Change 
Brief Rationale 
Sections 9.5.3 Secondary 
Endpoint(s) Analysis and 
9.5.5 Safety Analyses 
Updated the secondary and 
safety analysis details for 
each indication and 
subgroup. 
To provide clarity on the analysis 
of the PsO and PsA endpoints 
based on the groups or subgroups 
and corresponding populations as 
per the data collection. 
 
Updated to provide clarity on the 
stratification for Safety Analyses. 
 
 
 
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Protocol I1F-IN-RHCZ (a) 
Page 97 
Revised Protocol Sections 
Note: 
Deletions have been identified by strikethroughs. 
Additions have been identified by the use of underscore.  
 
1.1. Synopsis  
Protocol Title: A 24-Week Multicenter, Open-lLabel, Single-aArm, Phase 4 Study to Evaluate 
the Safety of Ixekizumab in Patients with Moderate-to-Severe Plaque Psoriasis and/or Active 
Psoriatic Arthritis in India 
Brief Title: A study to investigate the safety of ixekizumab in participants aged ≥18 years with 
moderate-to-severe plaque psoriasis and/or active psoriatic arthritis in India 
Rationale: 
The rationale for this post-approval Phase 4 study is to evaluate the safety and tolerability when 
ixekizumab is administered to participants in India with moderate-to-severe plaque psoriasis 
(PsO) and/or active psoriatic arthritis (PsA). 
… 
 
Objectives and Endpoints: 
… 
Objectives 
Endpoints 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Protocol I1F-IN-RHCZ (a) 
Page 98 
Objectives 
Endpoints 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
Brief Summary: 
The study will consist of 4 periods. The study duration for the 4 study periods are:   
 Screening Period (Period 1; 5 to 28 days),  
 Induction Dosing Period (Period 2; 12 weeks),  
 Maintenance Period (Period 3; 12 weeks), and 
 Post-Treatment Follow-Up Period (Period 4; at least 4 weeks after the date of 
participants’ early termination visit [ETV] or last regularly scheduled visit at Week 24). 
The following treatment will be assessed in this study for PsO participants with no active PsA 
and PsA participants who meet criteria for moderate-to-severe PsO (participants with moderate-
to-severe plaque psoriasis are defined as those with PASI ≥12, sPGA ≥3, and BSA ≥10%): 
 Ixekizumab: 80-mg subcutaneous (SC) injection 
o At Week 0, 160-mg starting dose (two 80-mg injections), followed by 80 mg 
every 2 weeks (Q2W) from Weeks 2 through 12, and then followed by 80 mg 
every 4 weeks (Q4W) thereafter (i.e., at Weeks 16 and 20). 
… 
Statistical Analysis: 
… 
Efficacy analyses in the secondary objectives specific to PsO and PsA will be conducted on the 
PsO with no active PsA and active PsA participants with at least 1 dose of study intervention and 
will be summarized with number of responders, response rate and its corresponding 95% 
confidence intervals (CIs) using normal approximation. 
 
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Intervention Groups and Duration: 
Treatment Group 
Starting Dose 
W0 
Dose 
W2-W10 
Dosea 
W12-W20 
Ixekizumab for  
 
PsO participants with 
no active PsA, and 
 
PsA participants who 
meet criteria for 
moderate-to-severe 
PsO. 
Ixekizumab 80 mg 2 × SC 
(total of 160 mg) 
Ixekizumab 80 mg SC Q2W 
at W2, 4, 6, 8, and 10 
Ixekizumab 80 mg SC Q4W 
at W12, W16 and 20 
Ixekizumab for PsA 
participants who do not 
meet criteria of for 
moderate-to-severe PsO 
Ixekizumab 80 mg 2 × SC 
(total of 160 mg) 
Ixekizumab 80 mg SC Q4W 
at W4, 8, 12, 16 and 20. 
Abbreviations: PsA = psoriatic arthritis; PsO = psoriasis; Q2W = every 2 weeks; Q4W = every 4 weeks; 
SC = subcutaneous injection; W = week. 
a 
No dose is given at W24; therefore, W24 is not included in this table. 
Note: When the dosing is scheduled at home (for PsO group participants with no active PsA and PsA participants 
who meet criteria for moderate-to severe PsO: W2, W6, W10, W16, and W20; for PsA participants who do not meet 
criteria of moderate-to-severe PsO: W16 and W20), the participants or care givers will self-administer the provided 
ixekizumab prefilled syringes. 
 
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1.2 Schema 
 
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1.3 Schedule of Activities (SoA) 
Table RHCZ.1.1. 
Schedule of Activities 
 
Screening 
(Period 1) 
Induction Dosing  
(Period 2) 
Maintenance 
(Period 3) 
Post Treatment 
Follow-Up (Period 4) 
 
 
Baseline 
 
 
 
As Needed 
CRF Visit Number 
V1 
V2 
V3 
V4 
V5 
V6 
ETV 
V801 
V802 
Study Week 
 
W0 
W4 
W8 
W12 
W24 
 
LV + W4 
LV + 
W812 
Study Days 
-28 to -5 d 
0 d 
28 ± 3 d 
56 ± 3 d 
84 ± 3d 
168 ± 5 d 
 
± 4 d 
± 4 d 
Informed consent 
X 
 
 
 
 
 
 
 
 
Complete medical history 
X 
 
 
 
 
 
 
 
 
Demographicsa 
X 
 
 
 
 
 
 
 
 
Substance use (alcohol, caffeine, tobacco use) 
X 
 
 
 
 
 
 
 
 
Electrocardiogram 
X 
 
 
 
 
 
 
 
 
Evaluation for Disease relapseb 
X 
 
 
 
 
 
 
 
 
Physical examinationcb 
X 
 
 
 
 
 
 
 
 
Weight 
X 
X 
 
 
X 
X 
X 
 
 
Height 
 
X 
 
 
 
 
 
 
 
Body mass index 
 
X 
 
 
 
 
 
 
 
Inclusion/exclusion criteriad 
X 
X 
 
 
 
 
 
 
 
Vital signs 
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 
Administer study interventione 
 
X 
X 
X 
X 
 
 
 
 
Dispense study drug 
 
X 
X 
X 
X 
 
 
 
 
Study drug compliancef 
 
X 
X 
X 
X 
 
 
 
 
Dispense Study Intervention Administration Log 
 
X 
X 
X 
X 
 
 
 
 
Collect, review, and enter data from Study 
Intervention Administration Log 
 
X 
X 
X 
X 
X 
X 
 
 
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Schedule of Activities 
 
Screening 
(Period 1) 
Induction Dosing  
(Period 2) 
Maintenance 
(Period 3) 
Post Treatment 
Follow-Up (Period 4) 
 
 
Baseline 
 
 
 
As 
Needed 
CRF Visit Number 
V1 
V2 
V3 
V4 
V5 
V6 
ETV 
V801 
V802 
Study Week 
 
W0 
W4 
W8 
W12 
W24 
 
LV + W4 
LV + 
W812 
Study Days 
-28 to -5 d 
0 d 
28 ± 3 d 
56 ± 3 d 
84 ± 3d 
168 ± 5 d 
 
± 4 d 
± 4 d 
Efficacy Measures 
Clinician-Rated or -Administered Assessments 
PASIg 
X 
X 
X 
X 
X 
X 
X 
 
 
BSAg 
X 
X 
X 
X 
X 
X 
X 
 
 
sPGAg 
X 
X 
X 
X 
X 
X 
X 
 
 
TJC/SJC (68/66 joints)gh  
X 
X 
X 
X 
X 
X 
X 
 
 
PGA Disease Activity VASgh 
 
X 
X 
X 
X 
X 
X 
 
 
Patient-Rated Assessments 
Patient Assessment of Pain VASi 
 
X 
X 
X 
X 
X 
X 
 
 
Patient Global Assessment Disease Activity VAS 
 
X 
X 
X 
X 
X 
X 
 
 
HAQ-DIi 
 
X 
X 
X 
X 
X 
X 
 
 
Laboratory Tests 
Chest x-ray (local)cj 
X 
 
 
 
 
X 
X 
 
 
Administer Mantoux TB test/QuantiFERON®-TB 
Goldhk 
X 
 
 
 
 
X 
X 
 
 
HIV/HCV 
X 
 
 
 
 
 
 
 
 
HBVil 
X 
X 
 
 
X 
X 
X 
 
X 
Serum pregnancy testjm 
X 
 
 
 
 
 
 
 
 
Urine pregnancy testkn 
 
X 
X 
X 
X 
X 
X 
 
 
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Screening 
(Period 1) 
Induction Dosing  
(Period 2) 
Maintenance 
(Period 3) 
Post Treatment 
Follow-Up (Period 4) 
 
 
Baseline 
 
 
 
As 
Needed 
CRF Visit Number 
V1 
V2 
V3 
V4 
V5 
V6 
ETV 
V801 
V802 
Study Week 
 
W0 
W4 
W8 
W12 
W24 
 
LV + W4 
LV + 
W812 
Study Days 
-28 to -5 d 
0 d 
28 ± 3 d 
56 ± 3 d 
84 ± 3d 
168 ± 5 d 
 
± 4 d 
± 4 d 
Serum chemistry 
X 
X 
 
 
X 
X 
X 
 
 
Hematology 
X 
X 
X 
 
X 
X 
X 
X 
X 
hs-CRP 
 
X 
X 
X 
X 
X 
X 
 
 
Urinalysis 
X 
X 
 
 
 
X 
X 
 
 
Abbreviations: AE = adverse event; BSA = body surface area; CRF = case report form; d = day; ETV = early termination visit; HAQ-DI = Health Assessment 
Questionnaire – Disability Index; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus; hs-CRP = high-sensitivity 
C-reactive protein; LV = last visit; PGA = Physician Global Assessment; PASI = Psoriasis Area and Severity Index; PsA = psoriatic arthritis; SJC = swollen 
joint count; sPGA = static Physician’s Global Assessment; TB = tuberculosis; TJC = tender joint count, V = visit; VAS = visual analog scale; W = week. 
a Includes year of birth, gender, and ethnicity. 
b Subjects will be evaluated for past and present disease relapse by the physician (Section 8.2.4).  
c 
Complete physical at screening (excluding pelvic, rectal, and breast examinations). Physicals should include symptom-directed physical, as well as an 
examination of heart, lungs, and abdomen, and visual examination of the skin. 
c To be performed if not done in the prior 6 months to rule out pulmonary TB. 
d Participants who test positive for latent TB at screening may be re-screened following appropriate treatment.  
e See Table RHCZ.6.1. When the dosing is scheduled at home, the participants or care givers will self-administer the provided ixekizumab prefilled syringes. 
All participants should remain under observation for at least 1 hour after study intervention administration to monitor safety at Week 0. 
f Designated site personnel will be responsible for handling and dispensing of study intervention (ixekizumab). 
g Administered to PsA participants only at the baseline (W0) visit. For PsO participants with 3% or more BSA of PsO, administered at all study visits. 
gh Administered only to PsO participants with PsO only at the baseline (W0) visit. For PsA participants, administered at all study visits.  
hi Administered only to PsA participants. The question related to pain assessment will be included in HAQ-DI assessment. 
cj To be performed if not done in the prior 6 months to rule out pulmonary TB, provided the x-ray and/or report are available for review. 
hk Participants who test positive for latent TB at screening may be re-screened. QuantiFERON® may be performed by a Lilly-designated or local laboratory. See 
Section 8.2.67 for detailed description of QuantiFERON®-TB Gold . In case of Mantoux TB   test, participants will have to come back to the site after 2 days 
for reading the results. 
il All participants will be tested for HBV at screening. Participant who meet criteria for HBV monitoring (see Section 8.2.78.1) will be identified by the central 
laboratory at baseline and monitored according to the study schedule. 
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jm To be performed for females of childbearing potential only. Additional urine pregnancy testing can be performed at the investigator’s decision. Participants 
determined to be pregnant will be discontinued from treatment and will no longer be administered study intervention. 
kn To be performed for females of childbearing potential only. Participants determined to be pregnant will be discontinued from treatment and will no longer be 
administered study intervention. 
Note: For PsO participants with no active PsA, only PsO efficacy outcomes PASI, sPGA scores and patient related assessment will be collected. For PsA 
participants with 3% or more BSA of PsO, both PsA and PsO efficacy outcomes will be collected. For PsA participants with less than 3% BSA of PsO, only PsA 
efficacy outcomes will be collected. (Table RHCZ.8.1). For PsO participant who also meet active PsA definition, both PsA and PsO outcomes will be collected 
for that participant. For PsO only participants, PASI, sPGA scores and patient rated assessments will be collected. 
 
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2.1 
Study Rationale 
The rationale for this post-approval Phase 4 ixekizumab study is to evaluate the safety and 
tolerability when ixekizumab is administered to participants in India with moderate-to-severe 
plaque psoriasis (PsO) and/or active psoriatic arthritis (PsA). Participants with 
moderate-to-severe plaque psoriasis are defined as those with PASI ≥12, sPGA ≥3, and BSA 
≥10%. … 
 
2.2. 
Background 
… 
More information about the known and expected benefits, risks, and reasonably anticipated AEs 
of ixekizumab may be found in the Copellor® package insert. Information on AEs expected to be 
related to the investigational product may be found in Section 6.27 (Development Core Safety 
Information [DCSI]) of the Investigator’s Brochure (IB). Information on SAEs that are expected 
in the study population (independent of drug exposure) and that will be assessed by the Sponsor 
in aggregate, periodically during the course of the study, may be found in Section 56 (Effects in 
Humans) of the Copellor package insertIB. 
 
2.3. 
Benefit/Risk Assessment 
Ixekizumab has been demonstrated to be safe and effective for the treatment of participants with 
moderate-to-severe chronic PsO and/or active PsA. The risk profile for participants within this 
study is anticipated to be consistent with the known safety experience for ixekizumab. 
 
3. 
Objectives and Endpoints 
…. 
Objectives 
Endpoints 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Objectives 
Endpoints 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4.1. 
Overall Design 
Study RHCZ is a prospective, multicenter, open-label, single-arm, Phase 4 study with 4 study 
periods assessing outcomes in terms of AEs and SAEs with ixekizumab when used in 
participants aged ≥18 years for PsO and PsA in Indian population (Section 1.2). 
The following treatment will be assessed in this study for PsO participants with no active PsA 
and PsA participants who meet criteria for moderate-to-severe PsO: 
 Ixekizumab: 80-mg subcutaneous (SC) injection. 
o At Week 0, 160-mg starting dose (two 80-mg injections), followed by 80 mg 
Q2W from Weeks 2 through 12, and then followed by 80 mg Q4W thereafter 
(i.e., at Weeks 16 and 20). 
… 
 
4.1.1. 
Screening Period (Period 1) 
… 
All inclusion and exclusion criteria are provided in Sections 5.1 and 5.2, respectively. Screening 
procedures (including complete medical history, and demographics, and substance use) will be 
performed according to the SoA (Section 1.3). At Visit 1, a QuantiFERON®-TB Gold test assay 
may be performed by a Lilly-designated or local laboratory (Section 8.2.78.2.6). 
Participants who test positive for latent tuberculosis (TB) at screening may be re-screened once 
following appropriate treatment, as described in Section 8.2.78.2.6. 
 
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4.1.2. 
Induction Dosing Period (Period 2) 
… 
When the dosing is scheduled at home (Week 2, Week 6, Week 10), the participants or care 
givers will self-administer the provided ixekizumab prefilled syringes. 
… 
 
4.1.3. 
Maintenance Period (Period 3) 
… 
When the dosing is scheduled at home (Week 16 and Week 20), the participants or care givers 
will self-administer the provided ixekizumab prefilled syringes. 
… 
 
4.1.4. 
Post-Treatment Follow-Up Period (Period 4) 
… 
If, at Visit 801, a participant’s neutrophil count is ≥1500 cells/L or greater than or equal to the 
participant’s baseline neutrophil count, the participant’s participation in the study will be 
considered complete unless the investigator determines additional follow-up may be necessary. 
An additional study visit (Visit 802) 4 8 weeks after Visit 801 may be required for appropriate 
participant management (described below). 
… 
 Participants with concurrent infection: If there is a concurrent infection that requires 
systemic anti-infective therapy, the participant 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 after resolution 
of infection) and 802 (4 8 weeks after Visit 801); additional visits may be required 
depending on the degree of neutropenia. 
… 
 
4.2. 
Scientific Rationale for Study Design 
This study will examine the effect of ixekizumab on participants with moderate-to-severe PsO 
and/or PsA. 
During the Induction Dosing Period (Period 2), participant’s safety and efficacy will be assessed 
at 80 mg Q2W dose for the participants with PsO and PsA participants who meet criteria for 
moderate-to-severe PsO. In PsA participants who do not meet criteria of moderate-to-severe 
PsO, participant’s safety and efficacy will be assessed at 80 mg Q4W dose. During the 
maintenance Period (Period 3), ixekizumab 80 mg Q4W will be studied. 
… 
 
4.3. 
Justification for Dose  
Ixekizumab will be studied at the approved dosing regimen for treatment of adults with 
moderate-to-severe PsO and PsA participants who do not meet criteria of moderate-to-severe 
PsO. 
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5. 
Study Population 
This study will include participants who have presence of moderate-to-severe PsO 
(moderate-to-severe PsO is defined as BSA ≥10, sPGA ≥3, PASI ≥12) and/or active PsA (active 
PsA defined as the presence of at least 3 (out of 68) tender and at least 3 [out of 66] swollen 
joints) for at least 6 months, treated in outpatient settings of India, who have given written 
informed consent approved by Lilly, or its designee, and the ethics review board (ERB) 
governing the site. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
re-screened only once in the following circumstances:  participants who test positive for latent 
TB at screening may be re-screened following appropriate treatment, as described in 
Section 8.2.78.2.6. When re-screening is performed, the individual must sign a new ICF and will 
be assigned a new identification number. 
… 
 
5.2. 
Exclusion criteria  
… 
[27] 
Have active TB (refer to Section 8.2.78.2.6 for details on determining full TB 
exclusion criteria). 
… 
[32] 
… 
Note:  Patients who are negative for hepatitis B surface antigen (HBsAg-), 
HBcAb+, HBsAb+ with a concentration of HBsAb >200 mIU/mL, and 
negative for serum HBV DNA may participate in the study. Patients who meet 
these criteria at screening will be identified by the central laboratory and 
monitored during the study as detailed in Section 8.2.8.18.2.7.1. 
 
5.4. 
Screen Failures 
… 
 Patients who test positive for latent TB at screening and have undergone documented 
subsequent treatment for at least 4 weeks (more details in Section 8.2.67). 
… 
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6.1. 
Study Intervention(s) Administered  
Table RHCZ.6.1. 
Treatment Regimens 
Treatment Group 
Starting Dose 
W0 
Dose 
W2-W10 
Dosea 
W12-W20 
Ixekizumab for  
 
PsO participants with 
no active PsA and  
 
PsA participants who 
meet criteria for 
moderate-to-severe 
PsO 
Ixekizumab 80 mg × 2 SC 
(total of 160 mg) 
Ixekizumab 80 mg SC Q2W 
at W2, 4, 6, 8, and 10 
Ixekizumab 80 mg SC Q4W 
at W12, W16 and 20 
Ixekizumab for PsA 
participants who do not 
meet criteria of for 
moderate-to-severe PsO 
Ixekizumab 80 mg × 2 SC 
(total of 160 mg) 
Ixekizumab 80 mg SC Q4W 
at W4, 8, 12, 16 and 20. 
Abbreviations: PsA = psoriatic arthritis; PsO = psoriasis; Q2W = every 2 weeks; Q4W = every 4 weeks; 
SC = subcutaneous injection; W = week. 
a 
No dose is given at W24; therefore, W24 is not included in this table. 
Note: When the dosing is scheduled at home (for PsO participants with no active PsA and PsA participants who 
meet criteria for moderate-to-severe PsOgroup: W2, W6, W10, W16, and W20; for PsA participants who do not 
meet criteria of for moderate-to-severe PsO: W16 and W20), the participants or care givers will self-administer 
the provided ixekizumab prefilled syringes. 
… 
During study visits, the investigator or his/her designee will administer the ixekizumab prefilled 
syringes to the participant. When the dosing is scheduled at home, the participants or care givers 
will self-administer the provided ixekizumab prefilled syringes. 
… 
Induction Dosing Period (Period 2) (Table RHCZ.6.2) 
 At Week 0, a 160-mg starting dose of ixekizumab (two 80-mg injections), followed by 
ixekizumab 80 mg Q2W from Weeks 2 through 12 for PsO participants with no active 
PsA and PsA participants who meet criteria for moderate-to-severe PsO. 
 At Week 0, a 160-mg starting dose of ixekizumab (two 80-mg injections), followed by 
ixekizumab 80 mg Q4W from Weeks 4 through 12 for PsA participants who do not meet 
the criteria for moderate-to-severe without PsO participants. 
… 
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Table RHCZ.6.2. 
Dosing Summary for the Induction and Maintenance Periods
  
 
Ixekizumab Treatment Groupa 
Dosing Period 
Study Week 
Ixekizumab (80 mg) 
PsO Participants 
with no active PsA 
and PsA Participants 
Who Meet Criteria 
for Moderate-to-
Severe PsO with or 
without PsA 
Participantsb 
PsA Participants Who 
Do Not Meet Criteria for 
Moderate-to-Severe PsO 
PsA without PsO 
Participantsc 
Induction Dosing Period 2 
0 
2a 
2a 
 
2 
1 
- 
 
4 
1 
1 
 
6 
1 
- 
 
8 
1 
1 
 
10 
1 
- 
 
12 
1 
1 
Maintenance Period 3 
16 
1 
1 
20 
1 
1 
24 
- 
- 
Abbreviations: PsA = psoriatic arthritis; PsO = psoriasis; Q2W = every 2 weeks; Q4W = every 4 weeks; 
Q8W = every 8 weeks; SC = subcutaneous. 
a 
A starting dose of 160 mg (Week 0) of ixekizumab will be given as 2 SC injections at Week 0. 
b 
For PsO participants with no active PsA and PsA participants who meet criteria for moderate-to-severe PsO, 
during the Induction Dosing Period, ixekizumab (80 mg) will be given as 1 SC injection Q2W (i.e., Weeks 2, 4, 
6, 8, 10, and 12). During the Maintenance Period, ixekizumab (80 mg) will be given as 1 SC injection Q4W 
(i.e., Weeks 16 and 20).  
c 
For PsA participants who do not meet criteria of for moderate to severe PsO, ixekizumab (80 mg) will be given 
as 1 SC injection Q4W (i.e., Weeks 4, 8, 12, 16, and 20). 
 
6.8. 
Concomitant Therapy 
All concomitant medication taken during the study must be recorded on the Concomitant 
Medication CRF at the study visits indicated in the SoA (Section 1.3). Treatment with 
concomitant PsO and PsA therapies during the study will be permitted only as outlined in the 
inclusion and exclusion criteria (Sections 5.1 and 5.2, respectively) and as described in the 
paragraphs below. Participants taking permitted medications need to be documented to be in 
stable control. After trial enrollment, significant dose escalation of a concomitant medication 
should be discussed with Lilly medical before allowing participant to receive study intervention. 
… 
 
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7.1.1. 
Permanent Discontinuation from Study Intervention 
… 
 The participant has a positive TB test using QuantiFERON®-TB Gold or T-Spot or 
purified protein derivative (PPD and is assessed as having latent TB infection (see 
Section 8.2.78.2.6), and/or develops symptoms or signs of tuberculosis. 
... 
 
7.1.3. 
Temporary Discontinuation 
In some circumstances, participants may need to temporarily interrupt treatment as a result of 
AEs or abnormal laboratory values that may have an unclear relationship to the study 
intervention. See Section 8.2.78.2.6 for details regarding managing participants who test positive 
for TB at any time during the study. 
… 
 
8.1. 
Efficacy Assessments 
… 
For PsO participant who also meet active PsA definition, both PsA and PsO outcomes will be 
collected for that participant. Likewise, to fulfill the study objective, PsO outcomes will be 
collected among all the PsA participants with 3% or more BSA of PsO (Table RHCZ.8.1). 
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Table RHCZ.8.1. 
Efficacy Assessments 
Assessments 
PsO pParticipants with No Active PsA 
PsA Participants Wwith 
≥3% BSA of PsO 
<3% BSA of PsO 
Clinician 
assessments 
 
PASI  
 
Percentage of BSA - Psoriasis 
 
sPGA  
 
PGA Disease Activity VAS 
 
TJC/SJC (68/66 joints) 
 
PGA of Disease Activity VAS - 
Psoriasis and PsA 
 
PASI 
 
Percentage of BSA 
 
sPGA 
 
DAS28 - CRPa  
 
ACR20/50/70a 
 
TJC/SJC (68/66 joints) 
 
PGA of Disease Activity VAS - PsA  
 
DAS28 - CRPa 
 
ACR20/50/70a 
Patient 
assessments 
 
Patient’s Global Assessment of 
Disease Activity VAS - Psoriasis 
 
HAQ-DI  
 
PsA Pain assessment question included 
in HAQ-DI 
 
Patient’s Global Assessment of Disease 
Activity VAS - PsA 
 
Patient’s Global Assessment of Disease 
Activity VAS - Psoriasis 
 
HAQ-DI.  
 
PsA Pain assessment question included 
in HAQ-DI 
 
Patient’s Global Assessment of Disease 
Activity VAS – PsA 
Abbreviations: ACR20/50/70 = 20%/50%/70% improvement in American College of Rheumatology response criteria; BSA = body surface area; 
CRP = C-reactive protein; DAS28 = Disease Activity Score-28; HAQ-DI = Health Assessment Questionnaire – Disability Index; PASI = Psoriasis Area and 
Severity Index; hs-CRP = high-sensitivity C-reactive protein; PGA = Physician’s Global Assessment; PsA = psoriatic arthritis; PsO = plaque psoriasis; 
SJC  = swollen joint count; sPGA = static Physician’s Global Assessment; TJC = tender joint count, V = visit; VAS = visual analog scale. 
a Assessments are derived by calculations using PsA assessments and hs-CRP assay.
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8.1.1. 
Efficacy Assessments for Plaque Psoriasis and Psoriatic Arthritis Participants 
with 3% of more BSA of PsO 
… 
 
8.1.2. 
Efficacy Assessments Specific to Psoriatic Arthritis Participants 
8.1.2.1. 
American College of Rheumatology 20, 50, and 70 Responder Index   
… 
Patient’s Assessment of Pain Visual Analog Scale 
Patient’s Assessment of Pain VAS will be administered only to PsA participants. The question 
related to pain assessment will be included in HAQ-DI assessment. 
… 
Patient’s Global Assessment of Disease Activity Visual Analog Scale 
The participant’s overall assessment of his/her PsO and PsA activity will be recorded using the 
100mm horizontal VAS where the left end represents no disease activity, and the right end 
represents extreme disease activity. 
Physician’s Global Assessment of Disease Activity Visual Analog Scale 
The Investigator will be asked to give an overall assessment of the severity of the participant’s 
current PsO and PsA activity using a 100mm horizontal VAS, where 0 represents no disease 
activity and 100 represents extremely active disease. The investigator making the assessment 
must be a rheumatologist or medically qualified physician. The same assessor should preferably 
perform the Physician’s Global Assessment of Disease Activity VAS for a given participant 
particularly during the Induction Dosing Period (Period 2) to minimize interobserver variation. 
… 
Disease Activity Score based on C-Reactive Protein  
The DAS28-CRP is a measure of disease activity in 28 joints that consists of a composite 
numerical score utilizing the following variables: TJC, SJC, hs-CRP (measured in mg/L), and 
Patient’s General Assessment recorded by participants on a 0 to 100 mm VAS. 
For DAS28-CRP, the 28 joints to be examined and assessed as tender or not tender for TJC and 
as swollen or not swollen for SJC are a subset of those assessed for the TJC and SJC, and include 
14 joints on each side of the participant’s body: the 2 shoulders, the 2 elbows, the 2 wrists, the 
10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal 
interphalangeal joints, and the 2 knees (Smolen et al. 1995). The following equation will be used 
to calculate the DAS28-CRP (Vander Cruyssen et al. 2005): 
 
 
8.1.3. 
Patient Global Assessment of Disease Activity VAS  
The participant’s overall assessment of his/her PsO and PsA activity will be recorded using the 
100 mm horizontal VAS where the left end represents no disease activity, and the right end 
represents extreme disease activity. 
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8.1.4. 
Physician’s Global Assessment of Disease Activity Visual Analog Scale 
The Investigator will be asked to give an overall assessment of the severity of the participant’s 
current PsO and PsA activity using a 100 mm horizontal VAS, where 0 represents no disease 
activity and 100 represents extremely active disease. The investigator making the assessment 
must be a rheumatologist or medically qualified physician. The same assessor should preferably 
perform the Physician’s Global Assessment of Disease Activity VAS for a given participant 
particularly during the Induction Dosing Period (Period 2) to minimize interobserver variation. 
 
8.2.4. 
Evaluation of Disease Relapse 
Patients will be assessed for the presence or absence of relapse at screening based on the 
following definitions: 
a. Assessment of relapse for psoriasis participants:  
Relapse is defined as worsening of psoriasis from the previous routine medical visit by 50% 
PASI or 1% BSA (in each case if sPGA ≥3) (Tian and Lai 2016). 
If PASI, BSA, or sPGA are not available in medical charts, relapse of psoriasis is defined as 
any worsening of psoriatic lesions that would, if persistent, in most cases require initiation or 
change of systemic therapy for psoriasis. 
During the study period, relapse with ixekizumab would be defined as worsening of psoriasis 
from the previous visit by 50% PASI or 1% BSA or sPGA ≥3. 
Relapse present based on the above definition: Yes/No 
Following details will be collected in addition in all PsO participants: 
 Duration of the psoriasis since diagnosis: 
 Duration of the psoriatic arthritis since diagnosis: 
 Prior systemic medications used for psoriasis:  
o Name of the drug and dose 
o Start date 
o End date 
 Prior systemic medications used for psoriatic arthritis:  
o Name of the drug and dose 
o Start date 
o End date 
b. Assessment of relapse for psoriatic arthritis participants:  
Relapse is defined as an increase in PsA disease activity from the previous routine medical 
either DAS28(ESR) >2.6 and DAS28(ESR) increase >0.6 or DAS28(ESR) increase ≥1.2, 
irrespective of absolute DAS28(ESR) (Emery et al. 2020; Helliwell et al. 2021). 
If DAS-28 CRP is not available in medical charts, relapse of PsA is defined as any increase 
in disease activity that would, if persistent, in most cases require initiation or change of 
systemic therapy for PsA.  
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Relapse present based on the above definition: Yes/No 
Additionally, the following details will be collected in all PsA participants: 
 Duration of the psoriasis since diagnosis: 
 Duration of the psoriatic arthritis since diagnosis: 
 Prior systemic medications used for psoriasis:  
o Name of the drug and dose 
o Start date 
o End date 
 Prior systemic medications used for psoriatic arthritis:  
o Name of the drug and dose 
o Start date 
o End date 
 
8.2.4.5. 
Clinical Safety Laboratory Tests 
… 
 
8.2.5.6. 
Pregnancy Testing 
… 
 
8.2.6.7. 
Chest X-Ray and Tuberculosis Testing 
… 
 
8.2.7.8. 
Safety Monitoring 
… 
 
8.2.7.1.8.1. 
Hepatic Safety Monitoring 
… 
 
8.2.7.1.8.1.1 
Additional Hepatic Data Collection in Participants Who Have 
Abnormal Liver Tests During the Study 
… 
 
8.2.7.2.8.2Hepatitis C Testing and Monitoring 
… 
 
8.2.7.3.8.3Hepatitis B Testing and Monitoring 
… 
 
9.2. 
Analyses Populations 
The following analysis populations will be used; additional analysis populations will be specified 
in the SAP: 
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Analysis Population 
Description 
PsO with No Active PsA– 
Modified Intent-to-Treat 
(mITT) Population 
Unless otherwise specified, efficacy and health outcomes analyses specific to 
psoriasis will be conducted on the PsO with No Active PsA- PsO mITT 
population, defined as all enrolled participants with a psoriasis indication, who 
do not qualify for Active PsA and who receives at least 1 dose of study 
treatment, even if the participant does not receive the correct treatment, or 
otherwise does not follow the protocol.   
Active PsA – mITT 
Population 
Unless otherwise specified, efficacy and health outcomes analyses specific to 
PsA will be conducted on the Active PsA mITT population, defined as all 
enrolled participants with an Active PsA indication who receives at least 1 
dose of study treatment, even if the participant does not receive the correct 
treatment, or otherwise does not follow the protocol.  
Safety Population 
Safety analyses will be conducted on the safety population, defined as all 
enrolled participants who receive at least 1 dose of study treatment. 
Participants will be analyzed according to the treatment to which they are 
assigned.   
 
9.5.2 
Primary Endpoint Analysis 
… 
Refer to Section 9.5.5.18.2 for further details. 
 
9.5.3 
Secondary Endpoint(s) Analysis 
Endpoints Specific to Psoriasis Group (PsO) and Psoriatic Arthritis (PsA) Participants 
with 3% or More BSA of PsO 
As a part of the secondary analyses, the following endpoints will be summarized (i) for the PsO 
indication and will be based on the PsO with no active PsA – mITT population, and (ii) for the 
Active PsA indication and will be based on the active PsA – mITT population with BSA of PsO 
≥ 3% at baseline, unless otherwise specified: 
… 
Endpoints Specific to Psoriatic Arthritis Group (PsA) 
As a part of the secondary analyses, the following endpoint will be summarized for the PsA 
indication and will be based on the active PsA-mITT population: 
… 
 
9.5.5 
Safety Analyses 
… 
All safety analyses will be based on the safety population and will be summarized overall and by 
dosing regimen (Q2W/Q4W and Q4W/Q4W) as specified in Table RHCZ.6.1indications (PsO 
and PsA). 
Further details will be described in the SAP. 
 
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9.5.5.1. 
Adverse Events 
… 
A summary of AEs will be provided overall and by dosing regimen, indications, including the 
number and percentage of participants who reported TEAEs, TEAEs by maximum severity, 
death, SAEs, TEAEs related to study intervention, discontinuations from the treatment due to an 
AE, and treatment-emergent AESIs: cytopenias, infections, injection-site reactions (ISRs), 
allergic reactions/hypersensitivities, cerebrocardiovascular events, MACE, malignancies, 
depression, IBD, ILD. TEAEs (all, by maximum severity, and possibly related to study 
intervention by the investigator), SAEs including deaths, AEs that lead to treatment 
discontinuation will be summarized by MedDRA system organ class (SOC) and PT. 
… 
 
10.2 
Appendix 2: Clinical Laboratory Tests 
… 
d Test required at Visit 1 only to determine eligibility of participant for the study (with the 
exception of those participants who require further HBV monitoring [Section 8.2.8.38.2.7.3]). 
… 
 
10.5 
Appendix 5: Liver Safety: Suggested Actions and Follow-Up Assessments  
See Section 8.2.8.18.2.7.1 for guidance on appropriate test selection. 
… 
 
11 
References 
… 
Emery P, Burmester GR, Naredo E, et al. Adalimumab dose tapering in patients with rheumatoid 
arthritis who are in long-standing clinical remission: results of the phase IV PREDICTRA study. 
Ann. Rheum. Dis. 2020;79(8):1023-30.  
… 
Helliwell PS, Tillett W, Waxman R, et al. Evaluation and validation of a patient-completed 
psoriatic arthritis flare questionnaire. J. Rheumatol. 2021;48(8):1268-71. 
… 
Tian D, Lai Y. The relapse of psoriasis: mechanisms and mysteries. JID Innovations. 
2022;2(3):100116. 
… 
 
 
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10.9 Appendix 9: Abbreviations and Definitions  
Term 
Definition 
ACR 
American College of Rheumatology 
ACR20/50/70 
20%/50%/70% Improvement in ACR criteria 
ADA 
antidrug antibodies 
AE 
adverse event 
AESI 
adverse events of special interest 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
AST 
aspartate aminotransferase 
ATC 
Anatomic Therapeutic Class 
BCG 
Bacillus Calmette-Guérin 
BP 
blood pressure 
BSA 
body surface area 
CASPAR 
ClASsification criteria for Psoriatic ARthritis 
CDISC 
Clinical Data Interchange Standards Consortium 
CDSCO 
Central Drugs Standard Control Organization 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CIOMS 
Council for International Organizations of Medical Sciences 
CK 
creatine kinase 
CMV 
cytomegalovirus 
companion diagnostic  An in vitro diagnostic device (assay or test) that provides information that is essential 
for the safe and effective use of a corresponding therapeutic product 
complaint 
A complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, purity, durability, reliability, safety or effectiveness, or 
performance of a drug or drug delivery system. 
compliance 
Adherence to all study-related, good clinical practice (GCP), and applicable regulatory 
requirements. 
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Term 
Definition 
CONSORT 
Consolidated Standards of Reporting Trials 
COX-2 
Cyclooxygenase-2 
CRF 
Case report form; a printed, optical, or electronic document designed to record all of 
the protocol-required information to be reported to the Sponsor for each trial 
participant. 
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. 
CRS 
clinical research scientist 
csDMARDs 
Conventional synthetic disease-modifying antirheumatic drug 
CSR 
clinical study report 
CTA 
clinical trial agreement 
CVA 
cerebrovascular accident 
DAS-28 
Disease Activity Score-28 
DBP 
Diastolic blood pressure 
device deficiencies 
equivalent to product complaint 
DMARD 
disease-modifying antirheumatic drug 
EBV 
Epstein-Barr virus 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture system 
EMA 
European Medicines Agency 
enroll 
The act of assigning a participant to a treatment. Participants who are enrolled in the 
study are those who have been assigned to a treatment. 
enter 
Participants entered into a study are those who sign the informed consent form directly 
or through their legally acceptable representatives. 
ERB 
Ethical review board: a board or committee (institutional, regional, or national) 
composed of medical and nonmedical members whose responsibility is to verify that 
the safety, welfare, and human rights of the patients participating in a clinical study are 
protected. 
ERCP 
endoscopic retrograde cholangiopancreatography 
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Term 
Definition 
ESR 
erythrocyte sedimentation rate 
ETV 
early termination visit 
FEAE 
follow-up emergent adverse event 
GCP 
Good Clinical Practice 
GGT 
gamma-glutamyltransferase 
HAQ-DI 
Health Assessment Questionnaire – Disability Index 
HBcAb 
hepatitis B core antibodies 
HBsAb 
hepatitis B surface antibodies 
HBsAg 
hepatitis B surface antigens 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HCVAb 
hepatitis C virus antibodies 
HDV 
hepatitis D virus 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
human immunodeficiency virus 
HIVAb 
human immunodeficiency virus antibodies 
hs-CRP 
high-sensitivity C-reactive protein 
IB 
investigator’s brochure 
IBD 
inflammatory bowel disease 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IgG 
immunoglobulin G 
IL-17 
interleukin-17 
IL-23 
interleukin-23 
ILD 
interstitial lung disease 
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Term 
Definition 
informed consent 
A process by which a participant voluntarily confirms their willingness to participate 
in a particular study, after having been informed of all aspects of the study that are 
relevant to the participant’s decision to participate. Informed consent is documented by 
means of a written, signed and dated informed consent form. 
interim analysis 
An interim analysis is an analysis of clinical study data, separated into treatment 
groups, that is conducted before the final reporting database is created/locked. 
investigational 
product 
A pharmaceutical form of an active ingredient or placebo being tested or used as a 
reference in a clinical trial, including products already on the market when used or 
assembled (formulated or packaged) in a way different from the authorized form, or 
marketed products used for an unauthorized indication, or marketed products used to 
gain further information about the authorized form. 
IRB 
Institutional review board: a board or committee (institutional, regional, or national) 
composed of medical and nonmedical members whose responsibility is to verify that 
the safety, welfare, and human rights of the patients participating in a clinical study are 
protected. 
ISR 
injection-site reaction 
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 participant (i.e., the 
planned treatment regimen) rather than the actual treatment given. It has the 
consequence that participant allocated to a treatment group should be followed up, 
assessed, and analyzed as members of that group irrespective of their compliance to 
the planned course of treatment. 
IV 
intravenous 
JAK 
Janus kinase 
LV 
last visit 
MAb 
monoclonal antibodies 
MACE 
major adverse cerebrocardiovascular events 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
myocardial infarction 
mITT 
modified intent-to-treat 
MoH 
Ministry of Health 
MRCP 
magnetic resonance cholangiopancreatography 
MTX 
methotrexate 
NRI 
nonresponder imputation 
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Term 
Definition 
NSAID 
nonsteroidal anti-inflammatory drug 
NYHA 
New York Heart Association 
participant 
Equivalent to CDISC term “subject”: an individual who participates in a clinical trial, 
either as recipient of an investigational medicinal product or as a control 
PASI 
Psoriasis Area and Severity Index 
PASI 75/90/100 
75%/90%/100% Improvement in the PASI criteria 
PC 
product complaint 
PCR 
polymerase chain reaction 
PDE4 
phosphodiesterase 4 
PsA 
psoriatic arthritis 
PsO 
plaque psoriasis 
PT 
preferred term 
PTFU 
post-treatment follow-up  
PT-INR 
prothrombin time - international normalized ratio 
PUVA 
psoralens and ultraviolet a light therapy 
Q2W 
every 2 weeks 
Q4W 
every 4 weeks 
RA 
rheumatoid arthritis 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SBP 
systolic blood pressure 
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.  
SEC 
Subject Expert Committee  
SERM 
selective estrogen receptor modulators 
SJC 
swollen joint count 
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Term 
Definition 
SMQ 
Standardized MedDRA Query 
SoA 
Schedule of Activities 
SOC 
system organ class 
sPGA 
Static Physician Global Assessment of Disease 
TB 
tuberculosis 
TBL 
total bilirubin 
TEAE 
Treatment-emergent adverse event:  An untoward medical occurrence that emerges 
during a defined treatment period, having been absent pretreatment, or worsens 
relative to the pretreatment state, and does not necessarily have to have a causal 
relationship with this treatment. 
TJC 
tender joint count 
TNFi 
tumor necrosis factor inhibitor 
TPO 
third-party organization 
ULN 
upper limit of normal 
UVB 
Ultraviolet B light 
VAS 
visual analogue scale 
WBC 
white blood cell 
WHO 
World Health Organization 
WOCBP 
woman of childbearing potential 
 
 
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