Clinical trial NCT03158285
Conditions: Arthritis, Psoriatic
Sponsor: Janssen Research & Development, LLC
Start date: 2017-07-12; Completion date: 2020-11-10
Enrollment: 741 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary purpose of this study is to evaluate the efficacy of guselkumab treatment in participants with active psoriatic arthritis (PsA) by assessing the reduction in signs and symptoms of PsA.

Detailed description:
This is a study of guselkumab in participants with active PsA who are biologically naive and have had inadequate response to standard therapies. It will evaluate the clinical efficacy of guselkumab in the reduction of signs and symptoms, structural damage inhibition and the safety profile of guselkumab in the treatment of PsA. The study will consist of a screening phase (up to 6 weeks), a blinded treatment phase (approximately 100 weeks) including a placebo controlled period from Week 0 to Week 24 and an active treatment period from Week 24 to Week 100 and a safety follow-up phase of 12 weeks after the last administration of study agent. Efficacy, health economics, safety, pharmacokinetics, immunogenicity, biomarker and pharmacogenomics evaluations will be performed in the study at defined schedule.

Arms: arm 1: Participants will receive subcutaneous (SC) guselkumab 100 milligram (mg) once every 4 weeks (q4w) from Week 0 through Week 100. arm 2: Participants will receive SC guselkumab 100 mg at Weeks 0 and 4 then once every 8 weeks (q8w) (Weeks 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, and 100) and placebo injections at other visits (Weeks 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, and 96) to maintain the blind. arm 3: Participants will receive SC placebo q4w from Week 0 to Week 20 and will cross over at Week 24 to receive SC guselkumab 100 mg q4w from Week 24 through Week 100.
Interventions: intervention 1: Guselkumab intervention 2: Placebo
Intervention descriptions: intervention 1: Participants will receive 100 mg of guselkumab as a sterile liquid for SC injection. intervention 2: Participants will receive matching placebo as SC injection.

Protocol documents:
Prot_002.pdf: 
CONFIDENTIAL –FOIA Exemptions Apply in U.S.
1
Status: Approved,  Date:01 May 2020
Janssen Research & Development *
Clinical Protocol
COVID-19 Appendix
Protocol Title
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating
the Efficacy and Safety of Guselkumab Administered Subcutaneously in Subjects with
Active Psoriatic Arthritis
Discover2
ProtocolCNTO1959PSA3002; Phase 3
CNTO 1959  (guselkumab)
*Janssen Research & Development is a global organization that operates through different legal entities in
various countries. Therefore, the legal entity acting as the sponsor for Janssen Research & Development 
studies may vary, such as, but not limited toJanssen Biotech, Inc.; Janssen Products, LP; Janssen Biologics, 
BV; Janssen-Cilag International NV; Janssen, Inc; Janssen Pharmaceutica NV; Janssen SciencesIreland
UC; Janssen Biopharma Inc.;or Janssen Research & Development, LLC. The term “sponsor” is used 
throughout the protocol to represent these various legal entities; the sponsor is identified on the Contact 
Information page that accompanies the protocol.
United States (US)sites of this study will be conducted under US Food & Drug Administration
Investigational New Drug (IND)regulations (21 CFR Part 312).]
Status:
Approved  
Date:
01 May2020
Prepared by: Janssen Research & Development, LLC  
EDMS number:
EDMS-RIM-46730version 1.0
THIS APPENDIX APPLIES TO ALL CURRENT APPROVED VERSIONS OF PROTOCOL
CNTO1959PSA3002
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory 
requirements. 
Confidentiality Statement
NCT03158285
The information provided herein contains Company trade secrets, commercial or financial information that the Company 
customarily holds close and treats as confidential.  The information is being provided under the assurance that the recipient 
will maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or 
otherwise.


COVID-19 Appendix
CNTO 1959 (guselkumab)
Clinical ProtocolCNTO1959PSA3002
CONFIDENTIAL –FOIA Exemptions Apply in U.S.
2
Status: Approved,  Date:01 May 2020
COVID-19 APPENDIX
GUIDANCE ON STUDY CONDUCT DURING THECOVID-19 PANDEMIC
It is recognized that the Coronavirus Disease 2019 (COVID-19) pandemic may have an impact on 
the conduct of this clinical study due to, for example, self-isolation/quarantine by subjectsand 
study-site personnel; travel restrictions/limited access to public places, including hospitals; study 
site personnel being reassigned to critical tasks.
In alignment with recent health authority guidance, the sponsor is providing options for 
study-related subjectmanagement in the event of disruptionto the conduct of the study. This 
guidance does not supersede any local or government guidelines or requirements or the clinical 
judgement of the investigator to protect the health and well-being of subjectsand site staff. If, at 
any time, a subject’ssafety is considered to be at unacceptable risk, study agentwill be 
discontinued, and study follow-up will be conducted.
Scheduled visits that cannot be conducted in person at the study site will be performed to the extent 
possible remotely/virtually or delayed until such time that on-site visits can be resumed. At each 
contact, subjectswill be interviewed to collect safety data. Key efficacy endpoint assessments 
should be performed if required and as feasible. Subjectswill also be questioned regarding general 
health status to fulfill any physical examination requirement. 
Every effort should be made to adhere to protocol-specified assessments for subjectson study 
agent, including follow up. Modifications to protocol-required assessments may be permitted via 
COVID-19 Appendix after consultation between the subjectand investigator, and with the 
agreement of the sponsor (see below).
The sponsor will continue to monitor the conduct and progress of the clinical study, and any 
changes will be communicated to the sites and to the health authorities according to local guidance. 
If a subjecthas tested positive for COVID-19, theinvestigator should contact the sponsor’s 
responsible medical officer to discuss plans for study agentand follow-up. Modifications made to 
the study conduct as a result of the COVID-19 pandemic should be summarized in the clinical 
study report.


COVID-19 Appendix
CNTO 1959 (guselkumab)
Clinical ProtocolCNTO1959PSA3002
CONFIDENTIAL –FOIA Exemptions Apply in U.S.
3
Status: Approved,  Date:01 May 2020
ADDITIONAL ELEMENTS, WHERE APPLICABLE:
Certain protocol-mandated visits to the study site may not be possible during the COVID-19 
outbreak. Therefore, temporary measures may be implemented if considered appropriate by 
the sponsor and investigator to maintain continuity of subjectcare and studyintegrity. Certain 
measures, such as those listed below, may be necessary and should be instituted in accordance 
with applicable (including local) laws, regulations, guidelines, and procedures:
o remote (eg, by phone / telemedicine) or in-person, off-site (eg, in-home) interactions 
between site staff (or designees) and subjectsfor study procedures e.g. those related to 
safety monitoring / efficacy evaluation / study agentstorage and administration 
(including training where pertinent)
o procurement of study agentby subjects(or designee) or shipment of study agentfrom 
the study site directly to subjectsfor at home administration (including the potential for 
self-administration of study agent)
o laboratory assessments using a suitably accredited local laboratory; for selected 
measures (eg,urine pregnancy), home testing may be employed
o other procedures, eg, imaging, may be conducted at an appropriate facility
Missed assessments/visits will be captured in the clinical trial management system for 
protocol deviations.  Discontinuations of study agents and withdrawal fromthe study 
should be documented with the prefix “COVID-19-related” in the case report form (CRF).  
o other relevant study data elements impacted by the pandemic should also be 
documented / labeled as“COVID-19-related” in CRFs and / or other study systems, 
as directed by detailed sponsor guidance. These may include missed / delayed / 
modified study visits / assessments / dosing, and instances where temporary 
measures such as those above are implemented.  
The sponsor will evaluate the totality of impact of COVID-19 on collection of key study 
data and additional data analyses will be outlined in study SAP(s). 
Precaution: for those who may carry a higher risk for severe COVID-19 illness (eg,those 
aged over 65 years), follow guidance from local health authorities when weighing the 
potential benefits and risks during participation in the study. 


COVID-19 Appendix
CNTO 1959 (guselkumab)
Clinical ProtocolCNTO1959PSA3002
CONFIDENTIAL –FOIA Exemptions Apply in U.S.
4
Status: Approved,  Date:01 May 2020
INVESTIGATOR AGREEMENT


1
Status: Approved,  Date: 23 January 2018
Janssen Research & Development *
Clinical Protocol
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating 
the Efficacy and Safety of Guselkumab Administered Subcutaneously in Subjects with 
Active Psoriatic Arthritis
Discover 2
ProtocolCNTO1959PSA3002; Phase 3
AMENDMENT 1
CNTO 1959(guselkumab)
* Janssen Research &Development is a global organization that operates through different legal entities 
in various countries. Therefore, the legal entity acting as the Sponsor for Janssen Research & 
Development studies may vary, such as, but not limited to Janssen Biotech, Inc.; Janssen Products, LP; 
Janssen Biologics, BV; Janssen-Cilag International NV; Janssen, Inc; Janssen SciencesIrelandUC; or 
Janssen Research& Development, LLC. The term “Sponsor” is used throughout the protocol to 
represent these various legal entities; the Sponsor is identified on the Contact Information page that 
accompanies the protocol.
This study will be conducted under US Food & Drug Administration INDregulations (21 CFR 
Part 312)
EudraCT NUMBER:
2016-001224-63
Status:
Approved
Date:
23 January 2018
Prepared by: Janssen Research & Development, LLC  
EDMS number: EDMS-ERI-125132842:  3.0
GCP Compliance: This study will beconducted in compliance with Good Clinical Practice, and applicable regulatory 
requirements. 
Confidentiality Statement
NCT03158285
The information in this document contains trade secrets and commercial information that are privileged or confidential and may 
not be disclosed unless such disclosure is required by applicable law or regulations. In any event, persons to whom the 
information is disclosed must be informed that the information is privileged or confidential and may not be further disclosedby 
them. These restrictions on disclosure will apply equally to all future information supplied to you that is indicated as privileged or 
confidential.


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
2
Approved, Date: 23 January 2018
TABLE OF CONTENTS
TABLE OF CONTENTS...............................................................................................................................2
LIST OF ATTACHMENTS............................................................................................................................5
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................5
PROTOCOL AMENDMENTS.......................................................................................................................7
SYNOPSIS..................................................................................................................................................18
TIME AND EVENTS SCHEDULE..............................................................................................................29
ABBREVIATIONS......................................................................................................................................40
1.
INTRODUCTION................................................................................................................................43
1.1.
Background....................................................................................................................................43
1.1.1.
Disease Background...................................................................................................................43
1.1.2.
Treatment Options......................................................................................................................43
1.1.3.
Clinical Studies...........................................................................................................................44
1.1.3.1.
Phase 2 Study in Psoriatic Arthritis (CNTO1959PSA2001)....................................................45
1.1.3.2.
Phase 2 Study in Psoriasis (CNTO1959PSO2001, X-PLORE)..............................................47
1.1.3.3.
Phase 3 Studies in Psoriasis (CNTO1959PSO3001, CNTO1959PSO3002, and 
CNTO1959PSO3003)..............................................................................................................49
1.1.3.3.1.
Efficacy.................................................................................................................................49
1.1.3.3.2.
Safety...................................................................................................................................49
1.1.3.4.
Phase 2 Study in Rheumatoid Arthritis (CNTO1275ARA2001)..............................................49
1.2.
Overall Rationale for the Study......................................................................................................50
1.2.1.
Role of Interleukin-23 and TH17 Pathways in the Treatment of Psoriatic Arthritis....................50
1.2.2.
Study Rationale..........................................................................................................................51
1.2.3.
Dose Rationale...........................................................................................................................51
1.2.3.1.
Rationale for Guselkumab 100 mg at Weeks 0 and 4 then Every 8Weeks Dose 
Regimen..................................................................................................................................51
1.2.3.2.
Rationale for Guselkumab 100 mg Every 4 Weeks Dose Regimen........................................52
2.
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS...........................................................................53
2.1.
Objectives and Endpoints..............................................................................................................53
2.1.1.
Objectives...................................................................................................................................53
2.1.2.
Endpoints....................................................................................................................................53
2.2.
Hypothesis.....................................................................................................................................58
3.
STUDY DESIGN AND RATIONALE.................................................................................................58
3.1.
Overview of Study Design..............................................................................................................58
3.2.
Study Design Rationale..................................................................................................................60
3.2.1.
Study Population.........................................................................................................................60
3.2.2.
Study Control, Randomization, and Blinding..............................................................................60
3.2.3.
Study Phases and Duration of Treatment..................................................................................61
3.2.4.
Study Evaluations.......................................................................................................................61
4.
SUBJECT POPULATION..................................................................................................................62
4.1.
Inclusion Criteria............................................................................................................................62
4.2.
Exclusion Criteria...........................................................................................................................67
4.3.
Prohibitions and Restrictions.........................................................................................................70
5.
TREATMENT ALLOCATIONAND BLINDING.................................................................................
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CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
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Approved, Date: 23 January 2018
6.
DOSAGE AND ADMINISTRATION..................................................................................................72
7.
TREATMENT COMPLIANCE............................................................................................................73
8.
PRESTUDY AND CONCOMITANT THERAPY................................................................................74
8.1.
Non-biologic DMARDs...................................................................................................................75
8.1.1.
Permitted Non-biologic DMARDs...............................................................................................75
8.1.2.
Prohibited Non-biologic DMARDs and Apremilast.....................................................................78
8.1.3.
Systemic Immunosuppressive Drugs.........................................................................................78
8.2.
Corticosteroids...............................................................................................................................78
8.2.1.
Oral Corticosteroids....................................................................................................................78
8.2.2.
Corticosteroids –Intravenous,Intramuscular, or Epidural Administration.................................78
8.2.3.
Corticosteroids –Intra-articular Injection....................................................................................79
8.2.4.
Corticosteroids –Other Routes of Administration......................................................................79
8.3.
Nonsteroidal Anti-inflammatory Drugs and Other Analgesics........................................................79
8.4.
Biologic Agents, Cytotoxic Drugs, JAK Inhibitors, or Investigational Agents.................................79
8.5.
Complementary Therapies.............................................................................................................80
8.6.
Topical Therapy and Ultraviolet B Light.........................................................................................80
8.7.
Systemic Therapy for Psoriasis.....................................................................................................80
9.
STUDY EVALUATIONS....................................................................................................................80
9.1.
Study Procedures...........................................................................................................................80
9.1.1.
Overview.....................................................................................................................................80
9.1.2.
Blood Sample Collection.............................................................................................................81
9.1.3.
Screening Phase........................................................................................................................81
9.1.4.
Treatment Phase........................................................................................................................84
9.1.5.
Post Treatment Phase (Follow-Up)............................................................................................85
9.2.
Efficacy Evaluations.......................................................................................................................86
9.2.1.
Psoriatic Arthritis Response Evaluations....................................................................................86
9.2.1.1.
Joint Assessment....................................................................................................................86
9.2.1.2.
Nonevaluable Joints................................................................................................................87
9.2.1.3.
American College of Rheumatology Response.......................................................................87
9.2.1.4.
Dactylitis Assessment..............................................................................................................88
9.2.1.5.
Enthesitis Assessment............................................................................................................88
9.2.1.6.
Imaging Evaluation..................................................................................................................88
9.2.1.7.
Disability Index of the Health Assessment Questionnaire.......................................................89
9.2.1.8.
Minimal Disease Activity..........................................................................................................90
9.2.1.9.
Psoriatic Arthritis Disease Activity Score.................................................................................90
9.2.1.10.
Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAppa) 
Composite Score (GRACE).....................................................................................................90
9.2.1.11.
Disease Activity Index Score 28..............................................................................................91
9.2.1.12.
Modified Composite Psoriatic Disease Activity Index.............................................................92
9.2.1.13.
Disease Activity Index for Psoriatic Arthritis............................................................................92
9.2.1.14.
Modified Psoriatic Arthritis Responder Criteria........................................................................92
9.2.1.15.
Bath Anky
losing Spondylitis Disease Activity Index................................................................92
9.2.2.
Psoriasis Response Evaluations................................................................................................93
9.2.2.1.
Investigator’s Global Assessment of Psoriasis........................................................................93
9.2.2.2.
Psoriasis Area and Severity Index..........................................................................................93
9.2.2.3.
Dermatology Life Quality Index...............................................................................................93
9.2.3.
Other Patient Reported Outcomes.............................................................................................94
9.2.3.1.
36-Item Short-form Health Survey...........................................................................................94
9.2.3.2.
EQ-5D Questionnaire..............................................................................................................94
9.2.3.3.
Functional Assessment of Chronic Illness Therapy -Fatigue.................................................95
9.3.
Health Economics..........................................................................................................................95
9.4.
Pharmacokinetics and Immunogenicity.........................................................................................95
9.4.1.
Serum Collection and Handling..................................................................................................
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CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
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Approved, Date: 23 January 2018
9.4.2.
Analytical Procedures.................................................................................................................96
9.4.3.
Pharmacokinetic Parameters.....................................................................................................96
9.4.4.
Immunogenicity Assessments....................................................................................................96
9.5.
Biomarkers.....................................................................................................................................96
9.6.
Pharmacogenomics (DNA) Evaluations.........................................................................................97
9.7.
Safety Evaluations.........................................................................................................................97
9.7.1.
Evaluations of Safety and Tolerability........................................................................................97
9.7.2.
Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS)..............................................100
9.7.3.
Anticipated Events....................................................................................................................102
9.8.
Sample Collection and Handling..................................................................................................103
10. SUBJECT COMPLETION/DISCONTINUATION OF STUDY TREATMENT/WITHDRAWAL 
FROM THE STUDY.........................................................................................................................103
10.1.
Completion...................................................................................................................................103
10.2.
Discontinuation of Study Treatment.............................................................................................103
10.3.
Withdrawal From the Study..........................................................................................................105
10.4.
Withdrawal From the Use of Research Samples.........................................................................106
11. STATISTICAL METHODS...............................................................................................................106
11.1.
Subject Information......................................................................................................................107
11.2.
Sample Size Determination.........................................................................................................107
11.3.
Efficacy Analyses.........................................................................................................................109
11.3.1.
Primary Endpoint Analyses......................................................................................................109
11.3.2.
Major Secondary Analyses.......................................................................................................111
11.3.3.
Other Planned Secondary Analyses.........................................................................................111
11.4.
Pharmacokinetic Analyses...........................................................................................................111
11.5.
Immunogenicity Analyses............................................................................................................111
11.6.
Biomarkers Analyses...................................................................................................................111
11.7.
Pharmacokinetic/Pharmacodynamic Analyses............................................................................111
11.8.
Pharmacogenomic Analyses.......................................................................................................112
11.9.
Health Economics Analysis..........................................................................................................112
11.10. Safety Analyses...........................................................................................................................112
11.11. Interim Analysis............................................................................................................................112
11.12. Data Monitoring Committee.........................................................................................................112
12. ADVERSE EVENT REPORTING....................................................................................................113
12.1.
Definitions....................................................................................................................................113
12.1.1.
Adverse Event Definitions and Classifications.........................................................................113
12.1.2.
Attribution Definitions................................................................................................................115
12.1.3.
Severity Criteria........................................................................................................................115
12.2.
Special Reporting Situations........................................................................................................116
12.3.
Procedures...................................................................................................................................116
12.3.1.
All Adverse Events....................................................................................................................116
12.3.2.
Serious Adverse Events...........................................................................................................117
12.3.3.
Pregnancy.................................................................................................................................118
12.3.4.
Events of Special Interest.........................................................................................................118
12.4.
Contacting Sponsor Regarding Safety.........................................................................................118
13. PRODUCT QUALITY COMPLAINT HANDLING............................................................................118
13.1.
Procedures...................................................................................................................................119
13.2.
Contacting Sponsor Regarding Product Quality..........................................................................119
14. STUDY AGENT INFORMATION.....................................................................................................119
14.1.
Physical Description of Study Agents..........................................................................................119
14.2.
Packaging....................................................................................................................................119
14.3.
Labeling........................................................................................................................................120
14.4.
Preparation, Handling, and Storage.............................................................................................
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CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
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Approved, Date: 23 January 2018
14.5.
Drug Accountability......................................................................................................................120
15. STUDY-SPECIFIC MATERIALS.....................................................................................................121
16. ETHICAL ASPECTS.......................................................................................................................121
16.1.
Study-Specific Design Considerations.........................................................................................121
16.2.
Regulatory Ethics Compliance.....................................................................................................122
16.2.1.
Investigator Responsibilities.....................................................................................................122
16.2.2.
Independent Ethics Committee or Institutional Review Board.................................................122
16.2.3.
Informed Consent.....................................................................................................................123
16.2.4.
Privacy of Personal Data..........................................................................................................124
16.2.5.
Long-Term Retention of Samples for Additional Future Research..........................................125
16.2.6.
Country Selection.....................................................................................................................125
17. ADMINISTRATIVE REQUIREMENTS............................................................................................126
17.1.
Protocol Amendments..................................................................................................................126
17.2.
Regulatory Documentation..........................................................................................................126
17.2.1.
Regulatory Approval/Notification..............................................................................................126
17.2.2.
Required Prestudy Documentation...........................................................................................126
17.3.
Subject Identification, Enrollment, and Screening Logs..............................................................127
17.4.
Source Documentation.................................................................................................................127
17.5.
Case Report Form Completion....................................................................................................128
17.6.
Data Quality Assurance/Quality Control......................................................................................129
17.7.
Record Retention.........................................................................................................................129
17.8.
Monitoring....................................................................................................................................130
17.9.
Study Completion/Termination.....................................................................................................131
17.9.1.
Study Completion/End of Study................................................................................................131
17.9.2.
Study Termination.....................................................................................................................131
17.10. On-Site Audits..............................................................................................................................131
17.11. Use of Information and Publication..............................................................................................131
REFERENCES..........................................................................................................................................134
INVESTIGATOR AGREEMENT...............................................................................................................143
LIST OF ATTACHMENTS
Attachment 1:
The CASPAR Criteria...............................................................................................137
Attachment 2:
QuantiFERON® TB Gold Testing.............................................................................138
Attachment 3:
Tuberculin Skin Testing............................................................................................140
Attachment 4:
Hepatitis B Virus (HBV) Screening with HBV DNA..................................................141
Attachment 5:
Anticipated Events....................................................................................................142
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1:
TIME AND EVENTS SCHEDULE FROM SCREENING THROUGH WEEK 24......................29
Table 2:
TIME AND EVENTS SCHEDULE FROM WEEK 28 THROUGH WEEK 112..........................35
Table 3:
Summary of Efficacy Results at Week 24 (CNTO1959PSA2001)...........................................46
Table4:
Permitted Concomitant Medications for PsA and the Maximum Allowed Doses During 
the Study...................................................................................................................................75
Table5:
Protocol Requirements of the Permitted Non-biologic DMARDs.............................................77
Table 6:
DAS Response.........................................................................................................................91
Table 7:
Statistical Power for Treatment Difference in ACR 20 Response at Week 24.......................108
Table 8:
Statistical Power for Treatment Difference in vdH-S Change from Baseline at Week 24......
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CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
6
Approved, Date: 23 January 2018
FIGURES
Figure 1: Schematic Overview of the Study Through End of Study.........................................................
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CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
7
Approved, Date: 23 January 2018
PROTOCOL AMENDMENTS
Protocol Version
Issue Date
Original Protocol
16 March 2017
Amendment 1
23January 2018
Amendments below are listed beginning with the most recent amendment.
Amendment 1(23January 2018)
This amendment is considered to be substantialbased on the criteria set forth in Article 10(a) of Directive 
2001/20/EC of the European Parliament and the Council ofthe European Union.  
The overall reason for the amendment:The overall reason for the amendment is due to FDAfeedbackand 
correction of errors.
Applicable Section(s) Description of Change(s)
Rationale:Toupdate the footnotes in Table 1 tocorrect minor errorsand provide clarification.
Table 1, Time and 
Events Schedule from 
screening through 
Week 24
Footnote ‘b’ was modified to have a visitwindow of ±4 days instead of 7 and text was 
clarified: Through Week 24, study visitswill have a visit window of ±4days.
Footnote ‘p’ language was revised for clarification(deleted text is striked-through):“All 
patient questionnaires should be completed before any other tests, procedures, or 
evaluations on the day of the visit for baseline and post-baseline visits.  The questionnaires 
and site assessments will be completed/recordedon the tablet.”
Footnotes‘q’ and ‘r’: “will/must” was changed to “should”.
Footnote ‘v’ was citedto the following rows: Hepatitis B and C Serologies, HIV Antibody 
Test, C-reactive Protein, Rheumatoid factor, and Follicle Stimulating Hormone.
Rationale:To update the footnotes in Table 1 to provide clarification.
Table 1, Time and 
Events Schedule from 
screening through 
Week 24
Footnote ‘x’ was modified as follows:
Original text:
Prior to randomization, FSH is required for selected female subjects to determine 
childbearing potential.  This test is only required for a female subject of any age with 
amenorrhea for at least 6 months. This test should NOT be done for any female subject of 
childbearing potential or female subjects >45 years of age with amenorrhea for at least 12 
months. Refer to Inclusion Criterion 10 for details.
Modified text (deleted text is striked-through and new text in bold and underlined): 
Prior to randomization, FSH isonlyrequired for selected female subjects with 
amenorrhea for less than 12 monthsto determine childbearing potential.  This test is only 
required for a female subject of any age with amenorrhea for at least 6 months.Two FSH 
measurements are needed to confirm amenorrhea in these subjects. This test should 
NOT be done for any female subject of childbearing potential or female subjects >45 years 
of agewith amenorrhea for at least 12 months. Refer to Inclusion Criterion 10 for details.
Rationale:To updateTable 1 footnote and study procedures to state that the eC-SSRS will be completed at 
screening after the Independent Joint Assessor has completed the Joint Count assessment so that the site user can 
determine subject’s eligibility prior to the subject completing the PRO assessment.  Also, to clarify that the 
eC-SSRS will be performed firstof the PRO assessmentsat baseline and all post-baseline visits.
NCT03158285


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
8
Approved, Date: 23 January 2018
Applicable Section(s) Description of Change(s)
Table 1, Time and 
Events Schedule from 
screening through 
Week 24, footnote i;
Sections9.1.3 
Screening Phase; and 
9.7.2 eC-SSRS
Original text:
The eC-SSRS will be performed first at the screening visit (after signing informed consent)
if the screening visit is a single visit. If the screening visit is divided into more than 1 visit, 
the eC-SSRS will be performed first at the second screening visit (after the subject is 
determined to be eligible by the central laboratory test results).  The eC-SSRS will be 
performed first at Week 0/baseline, before study agent administration. At all post baseline 
visits, the eC-SSRS will be the first assessment/questionnaire that the subject must 
complete.
Modified text (deleted text is striked-through and newtext in bold and underlined): 
The eC-SSRS shouldwillbe performed firstafter the joint assessmentat the screening 
visit (after signing informed consent)if the screening visit is a single visit. If the screening 
visit is divided into more than 1 visit, the eC-SSRS will be performed first at the second 
screening visit (after the subject is determined to be eligible by the central laboratory test 
results).  At Week 0/baseline and at all post-baseline visits, the eC-SSRS willshouldbe 
the first assessment/questionnaire that the subject mustcompletesprior to study agent 
administration (see Section 9.7.2 for details).
Rationale:To correct minor errors.
Table 1,footnotes l 
and u; Table 2,
footnote j; Exclusion 
criterion 30; and 
Section 9.1.3 
Screening phase
Reference to Inclusion Criterion 13 was changed to Criterion 14.
Rationale:To update the footnotesin Table 2 to correct minor errors.
Table 2, Time and 
Events Schedulefrom 
Week 28 through 
Week 112
Footnote ‘a’ was clarified and now reads (new text in bold and underlined): Through 
Week 100, study visits will have a visit window of ±7 days; Week 112 visit or thefinal
safety visit (12 weeks after the last dosein subjects who discontinued study 
treatment)will have a visit window of ±14 days.
Footnote ‘n’ language was clarified and now reads(deleted text is striked-through):All 
patient questionnaires should be performed before any other tests, procedures, or
evaluations on the day of the visit.  The patient questionnaires and site assessments will be 
completed/recorded on the tablet.
Footnote ‘o’:the word“must” was changed to “should”.
Footnote ‘q’ was added to C-reactive Protein.
NCT03158285


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
9
Approved, Date: 23 January 2018
Applicable Section(s) Description of Change(s)
Rationale:To delete redundancies.
Section 1.2.3.2 
Rationale for 
Guselkumab 100mg 
Every 4weeks Dose 
Regimen
Deleted text: 
Although subjects who had higher systemic exposure of guselkumab (serum guselkumab 
concentrations at the fourth quartile level) had 12-13% higher rates of infections when 
compared with subjects who had serum guselkumab concentrations in the lower 3 
quartiles, a pattern of increasing rates of these events with higher exposure was not present 
across the first, second, and third quartile levels. Moreover, the clinical relevance of this 
finding appears to be limited, given that the vast majority of infections were non-serious 
and mild to moderate in intensity and that the frequency of the infections requiring 
treatment was generally similar across all 4 exposure quartiles.
Rationale:To correct error noted in hemoglobin level.
Section 4.1 
Inclusion criteria 
Original text in inclusion criterion 17 from:
a. Hemoglobin
≥8.5 g/dL
(SI: ≥100 g/L)
Modified text (deleted text is striked-through and newtext in bold and underlined): 
a. Hemoglobin
≥8.5 g/dL
(SI: ≥85100g/L)
Rationale: To correct error noted in visit windows.
Section 7 Treatment 
Compliance 
Original text:
All post-baseline visits will have a visit window of ±7 days counting from Week 0 as 
Day1. The safety follow-up visit at 12 weeks after the last dose will have a visit window 
of ±14 days.  
Modified text (deleted text is striked-through and new text in bold and underlined): 
All post-baseline visitsthrough Week 100up to and including Week 24will have a visit 
window of ±74days counting from Week 0 as Day 1. After Week 24, all visits will have 
a visit window of ±7 days.The Week 112 visit orthefinalsafetyfollow-upvisit at (12 
weeks after the last dose in subjects who discontinued study treatment) will have a visit 
window of ±14 days.    
Rationale: To revise for clarification.
Sections4.2 
Exclusion Criteria
#13; 9.1.3 Screening 
Phase; 9.1.4 
Treatment Phase; 
9.7.2 eC-SSRS; 10.2 
Discontinuation of 
Study Treatment
The eC-SSRS ideation level language was revised for better clarity.
The Baseline/Screeningversion name was changed to Lifetimeversion.
The Since Last Visitversion was changed to Since Last Contactversion
Clarified that the eC-SSRS measures five possible levels of suicidal ideation and four 
possible suicidal behaviors.
Rationale:To allow for a reduction in steroid dose after Week 24,as it may be medically appropriate.
Section 8.2.1 Oral 
Corticosteroids
The following text regarding reduction of steroid dose after Week 24 has been added: 
After Week 24 and through Week 52, a one-time dose decrease in oral corticosteroids
is allowed.
NCT03158285


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
10
Approved, Date: 23 January 2018
Applicable Section(s) Description of Change(s)
Rationale: To clarify requirements for hand and footradiographs at screening.
Sections9.1.1 
Overview; 9.1.3 
Screening; 9.2.1.6 
Imaging Evaluation
The requirement for hand and footradiographs at screening was changed to: 
All eligible subjects should have radiographs taken approximately 2 weeks but not greater 
than 4 weeks prior to randomization.  
The word “will” was changed to “should”.
For posterior-anterior view chest radiograph, the text “as per country regulations where 
applicable” was deleted.
Rationale: To revise for clarification.
Section 9.1.3
Screening Phase
Original text:
The electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) (Baseline/Screening 
version) will be the first assessment performed at the screening visit (after signing 
informed consent) if the screening visit is a single visit. If the screening visit is divided 
into more than 1 visit, the eC-SSRS will be performed as the first assessment at the visit 
that occurs after the subject is determined to be eligible by the central laboratory test 
results.  
Modified text (deleted text is striked-through and new text in bold and underlined): 
If the screening is a single visit, tThe electronic Columbia-Suicide Severity Rating Scale 
(eC SSRS) (LifetimeBaseline/Screening version) shouldwillbe performedafter the 
joint assessment the first assessment performed at the screening visit(after signing 
informed consent) if the screening visit is a single visit. If the screening visit is divided 
into more than 1 visit, the eC-SSRS shouldwillbe performed after the joint assessment 
andas the first assessment at the visit that occurs afterthe subject is determined to be 
eligible by the central laboratory test results.  
Rationale:To revise for clarification.
Section 9.2.1.10 
Group for Research 
and Assessment of 
Psoriasis and 
Psoriatic Arthritis 
(GRAPPA) 
Composite Score 
(GRACE)
Original text:
9.2.1.10. Arithmetic Mean of the Desirability Function and Group for Research and 
Assessment of Psoriasis and Psoriatic Arthritis (GRAppa) Composite Score 
(GRACE) Index
The Arithmetic Mean of the Desirability Function is calculated by transforming the 
following variables, using predefinedalgorithms and expressing the total score as a mean 
with a score range of 0–1, where 1 indicates a better state than 0:23,22
• Tender joint count (0-68)
• Swollen joint count (0-66)
• HAQ (0-3)
• Patient’s global assessment of disease activity by VAS (arthritis and psoriasis, 0-
100mm)
• Patient’s assessment of skin disease activity by VAS (0-100 mm)
• Patient’s global assessment of disease activity (arthritis) by VAS (0-100 mm)
• PASI (0-72)
• Psoriatic arthritis Quality of Life Index (PsAQoL) which is determined from a 
transformation algorithm in which:
      - PsAQoL = 25.355 + (2.367 × HAQ) –(0.234 × PCS) –(0.244 × MCS)
     - GRACE index = (1-AMDF) ×1024
NCT03158285


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
11
Approved, Date: 23 January 2018
Applicable Section(s) Description of Change(s)
Modified text (deleted text is striked-through and new text in bold and underlined): 
9.2.1.10. Arithmetic Mean of the Desirability Function and Group for Research and 
Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Composite Score 
(GRACE) Index
The GRAPPA Composite score (GRACE) is a composite score of Group for Research 
and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), derived as GRACE 
Index = (1 -AMDF) x 10, where, AMDF is the Arithmetic Mean of the Desirability 
Function (AMDF).22-24
The Arithmetic Mean of the Desirability Function AMDFis calculated by transforming 
the following variables, using predefined algorithms and expressing the total score as a 
mean with a score range of 0–1, where 1 indicates a better state than 0:22, 23
• Tender joint count (0-68)
• Swollen joint count (0-66)
• HAQ-DI score(0-3)
• Patient’s global assessment of disease activity by VAS (arthritis and psoriasis, 0-
100mmVAS)
• Patient’s assessment of skin disease activity by VAS(0-100 mmVAS)
• Patient’s global assessment of disease activity (arthritis) by VAS (0-100 mm)
• PASI score(0-72)
• Psoriatic arthritis Quality of Life Index (PsAQoL)which is derived as follows:which 
is determined from a transformation algorithm in which:
      - PsAQoL = 25.355+ (2.367 × HAQ-DI) –(0.234 × SF-PCS) –(0.244 × SF-MCS), 
where,
o
HAQ-DI: HAQ-DI score (0-3)
o
SF-PCS: PCS score of SF-36 Health Survey
o SF-MCS: MCS score of SF-36 Health Survey
     - GRACE index = (1-AMDF) ×1024
Rationale:To revise for clarification.
Section 9.7.1 
Evaluation of Safety
Original text:
• FSH is optional.  It is only needed for determining childbearing potential of a female 
subject of any age with amenorrhea for at least 6 months.A female subject of any age with 
amenorrhea for at least 6 months who also has FSH >40 IU/L is considered not of 
childbearing potential. FSH is not needed for female subjects >45 years of age with 
amenorrhea for at least 12 months or any female subject of childbearing potential. Refer to 
Inclusion Criterion 10 fordetail.
Modified text (deleted text is striked-through and new text in bold and underlined): 
• FSH is optional.  It is only needed for determining childbearing potential of a female 
subject of any age with amenorrhea for at least 6 monthsless than 12 months..In the 
absence of 12 months of amenorrhea, 2 FSH measurements are needed. A female 
subject of any age with amenorrhea for at least 6 months who also has FSH >40 IU/L is 
considered not of childbearing potential.FSH is not needed for female subjects>45 years 
of agewith amenorrhea for at least 12 months or any female subject of childbearing 
potential. Refer to Inclusion Criterion 10 for detail.
NCT03158285


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
12
Approved, Date: 23 January 2018
Applicable Section(s) Description of Change(s)
Rationale:To revise to allow for telephone system.
Section 9.7.2 
eC-SSRS
Original text:
Subjects will complete the eC-SSRS questionnaire using the Sponsor-provided electronic 
tablets. Study site personnel will train the subjects on how to use the electronic device. The 
eC-SSRS will be provided in the local languages in accordance with local guidelines.
TheeC-SSRS will be performed during each evaluation visit according to the Time and 
Events schedule. During a visit, subjects will be directed to a private, quiet place with the 
electronic device to complete the assessment. 
Modified text (deleted text is striked-through and new text in bold and underlined): 
Subjects will complete the eC-SSRS questionnaire using the Sponsor-provided electronic 
tablets (or through an Interactive Voice Response System [IVRS], if available ). Study 
site personnel will train the subjects on how to use the electronic device and/or a 
telephone system. The eC-SSRS will be provided in the local languages in accordance 
with local guidelines.
The eC-SSRS will be performed during each evaluation visit according to the Time and 
Events schedule. During a visit, subjects will be directed to a private, quiet place with the 
electronic device and/or a telephoneto complete the assessment. 
Rationale:Treatment failure criteria was amended to include study termination for any reason.  Treatment failure 
criteria amended to remove early escape criteria met at Week 16 and initiated or increased the dose of one of the 
permitted concomitant medications.Additional sensitivity/supplemental analyses as well as tipping point analysis 
will be defined in the SAP.
Synopsis; 
Section11.3.1 
Primary Endpoint 
Analyses
Original text:
The primary endpoint to be analyzed for the primary analysis is proportion of subjects who 
achieved an ACR 20 response at Week 24 and who had not met the following treatment 
failure criteria prior to Week 24.  Subjects who met the following treatment failure prior to 
Week 24 will be considered as ACR 20 non-responder at Week 24 regardless of the 
observed ACR 20 response status.   Subjects who meet the following treatment failure 
criteria include subjects who:
1. Discontinued study agent injections due to lack of efficacy.
2. Initiated or increased the dose of non-biologic DMARDs (MTX, SSZ, HCQ, LEF) or 
oral corticosteroids over baseline for PsA.
3. Initiated protocol prohibitedmedications/therapies for PsA.
4. Met early escape criteria at Week 16 and initiated or increased the dose of one of the 
permitted concomitant medications.
The treatment effect of each guselkumab group versus placebo will be tested using a CMH 
test stratified by baseline non-biologic DMARD (MTX, SSZ, HCQ, LEF) use (yes/no) and 
the most recent available CRP value prior to randomization (<2.0 mg/dL or ≥2.0 mg/dL).  
The magnitude of the effect will be estimated by the difference in ACR 20 response rates 
between the guselkumab and placebo groups with the 95% confidence interval calculated 
based on Wald statistics.
In the primary efficacy analysis, data from all randomized subjects who received at least 1 
administration of study treatment (full analysis set) will be analyzed according to their 
assigned treatment group regardless of their actual treatment received. In general, subjects 
with missing data for ACR 20 at Week 24 will be considered non-responders at Week 24. 
NCT03158285


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
13
Approved, Date: 23 January 2018
Applicable Section(s) Description of Change(s)
[…]
Sensitivity Analysis
To evaluate the robustness of the primary analysis results, sensitivity analyses will be 
performed., including, but not limited to, the following: 
1. A similar analysis, however, if subjects meet treatment failure rules, ACR 20 response 
will be assumed tobe missing. Subjects with missing ACR 20 response will be imputed by 
Multiple-Imputation (MI) method under the assumption of Missing At-Random. 
2. A similar analysis, however, ACR 20 response using all observed data regardless of 
meeting treatment failure criteria.  Subjects with missing ACR 20 response will be 
imputed by Multiple-Imputation (MI) method under the assumption of Missing At-
Random.  And 2-dimensional tipping point analyses based on MI will be included to assess 
the robustness of the assumption regarding the missing data mechanism.
Additional sensitivity analyses may be specified in the SAP to further address the 
robustness of the primary analysis. 
Modified text (deleted text is striked-through and new text in bold and underlined): 
The primary endpoint to be analyzed for the primary analysis is proportion of subjects who 
achieved an ACR 20 response at Week 24 and who had not met the following treatment 
failure criteria prior to Week 24.  Subjects who met the following treatment failure prior to 
Week 24 will be considered as ACR 20 non-responder at Week 24 regardless of the 
observed ACR 20 response status.   Note that the intercurrent event of Treatment 
Failure prior to Week 24 (defined below) will be treated as non-response for the 
primary analysis, regardless of the observed ACR 20 response status.
Treatment Failure Criteria
Subjects who meet the following treatment failure criteria include subjects who:
1. Discontinued study agent injections due to lack of efficacy.
2. Terminate study participation for any reason.
3.2.  Initiated or increased the dose of non-biologic DMARDs (MTX, SSZ, HCQ, LEF) or 
oral corticosteroids over baseline for PsA.
4.3.
Initiated protocol prohibited medications/therapies for PsA.
4. Met early escape criteria at Week 16 and initiated or increased the dose of one of the 
permitted concomitant medications.
Subjects with missing data at Week 24 will be considered non-responders.
The treatment effect of each guselkumab group versus placebo will be tested usinga CMH 
test stratified by baseline non-biologic DMARD (MTX, SSZ, HCQ, LEF) use (yes/no) and 
the most recent available CRP value prior to randomization (<2.0 mg/dL or ≥2.0 mg/dL).  
The magnitude of the effect will be estimated by the difference in ACR 20 response rates 
between the guselkumab and placebo groups with the 95% confidence interval calculated 
based on Wald statistics.
In the primary efficacy analysis, data from all randomized subjects who received at least 1 
administration of study treatment (fullanalysis set) will be analyzed according to their 
assigned treatment group regardless of their actual treatment received. In general, subjects 
with missing data for ACR 20 at Week 24 will be considered non-responders at Week 24. 
NCT03158285


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
14
Approved, Date: 23 January 2018
Applicable Section(s) Description of Change(s)
[…]
Sensitivity Analysis
To evaluate the robustness of the primary endpoint analysis results, the exhaustive 
scenario tipping pointsensitivity analyses will be performedby varying the amount of 
non-responder imputation for missing data. including, but not limited to, the following:
Additional supplemental estimand and sensitivity analyses which vary how 
intercurrent events (eg, treatment failures) are handled, how observed data are used, 
and how missing data are treatedwill be specified in the SAP to further address the 
robustness of treatment effect of ACR20 at Week 24for the primary and alternative 
estimands (which will also be defined in the SAP).
Rationale:Subjects must sign the ICF independently and be able toread and write to participate in this study.
Sections 16.2.3 
Informed Consent; 
16.2.4 Privacy of 
Personal Data
Original text:
Each subject (or a legally acceptable representative) must give written consent according 
to local requirements after the natureof the study has been fully explained. The ICF(s) 
must be signed before performance of any study-related activity. The ICF(s) that is/are 
used must be approved by both the Sponsor and by the reviewing IEC/IRB and be in a 
language that the subject can readand understand. The informed consent should be in 
accordance with principles that originated in the Declaration of Helsinki, current ICH and 
GCP guidelines, applicable regulatory requirements, and Sponsor policy.
Before enrollment in the study, the investigator or an authorized member of the study-site 
personnel must explain to potential subjects or their legally acceptable representatives the 
aims, methods, reasonably anticipated benefits, and potential hazards of the study, and any 
discomfort participation in the study may entail. Subjects will be informed that their 
participation is voluntary and that they may withdraw consent to participate at any time. 
They will be informed that choosing not to participate will not affect the care the subject 
will receive for the treatment of his or her disease. Subjects will be told that alternative 
treatments are available if they refuse to take part and that such refusal will not prejudice 
future treatment. Finally, they will be told that the investigator will maintain a subject 
identification register for the purposes of long-term follow up if needed and that their 
records may be accessed by health authorities and authorized Sponsor personnel without 
violating the confidentiality of the subject, to the extent permitted by the applicable law(s) 
or regulations. By signing the ICF the subject or legally acceptable representative is 
authorizing such access. 
The subject or legally acceptable representative will be given sufficient time to read the 
ICF and the opportunity to ask questions. After this explanation and before entry into the 
study, consent should be appropriately recorded by means of either the subject
's or his or 
her legally acceptable representative
's personally dated signature. After having obtained 
the consent, a copy of the ICF must be given to the subject.
NCT03158285


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
15
Approved, Date: 23 January 2018
Applicable Section(s) Description of Change(s)
Subjects will be asked for consent to provide optional samples for research (where local 
regulations permit). After informed consent for the study is appropriately obtained, the 
subject or his or her legally acceptable representative will be asked to sign and personally 
date a separate ICF indicating agreement to participate in the optional research component. 
Refusal to participate in the optional research will not result in ineligibility for the study. A 
copy of this signed ICF will be given to the subject.
If the subject or legally acceptable representative is unable to read or write, an impartial 
witness should be present for the entire informed consent process (which includes reading 
and explaining all written information) and should personally date and sign the ICF after 
the oral consent of the subject or legally acceptable representative is obtained.
A limited number of study sites may be asked by the Sponsor to obtain informed consent 
usinga validated electronic system instead of a paper-based process. If both parties 
(Sponsor and the study site) agree, and if participation is allowed by local regulations and 
IEC/IRB requirements, the means to facilitate such a process will be provided to the sites 
by Sponsor. The actual mechanism of consenting will be facilitated by the use of an 
eTablet device (eg, iPad®), but overall the consent process will remain the same, as 
described in this section. At these study sites, subjects will still be required to review the 
entire informed consent as a written document on the eTablet and then to apply their 
handwritten signature electronically by the use of a stylus directly onto the eTablet. 
Modified text (deleted text is striked-through, new text in boldand underlined):
Each subject (or a legally acceptable representative)must give written consent according 
to local requirements after the nature of the study has been fully explained. The ICF(s) 
must be signed before performance of any study-related activity. The ICF(s) that is/are 
used must be approved by both the Sponsor and by the reviewing IEC/IRB and be in a 
language that the subject can read and understand. The informed consent should be in 
accordance with principles that originated in the Declaration of Helsinki, current ICH and 
GCP guidelines, applicable regulatory requirements, and Sponsor policy.
Before enrollment in the study, the investigator or an authorized member of the study-site 
personnel must explain to potential subjects or their legally acceptable representativesthe 
aims, methods, reasonably anticipated benefits, and potential hazards of the study, and any 
discomfort participation in the study may entail. Subjects will be informed that their 
participation is voluntary and that they maywithdraw consent to participate at any time. 
They will be informed that choosing not to participate will not affect the care the subject 
will receive for the treatment of his or her disease. Subjects will be told that alternative 
treatments are available if they refuse to take part and that such refusal will not prejudice 
future treatment. Finally, they will be told that the investigator will maintain a subject 
identification register for the purposes of long-term follow up if needed and that their 
recordsmay be accessed by health authorities and authorized Sponsor personnel without 
violating the confidentiality of the subject, to the extent permitted by the applicable law(s) 
or regulations. By signing the ICF the subject or legally acceptable representative is 
authorizing such access.
The subject or legally acceptable representativewill be given sufficient time to read the 
ICF and the opportunity to ask questions. After this explanation and before entry into the 
study, consent should be appropriately recorded by means of eitherthe subject
's or his or 
her legally acceptable representative
'spersonally dated signature. After having obtained 
the consent, a copy of the ICF must be given to the subject.
NCT03158285


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
16
Approved, Date: 23 January 2018
Applicable Section(s) Description of Change(s)
Subjects will be asked for consent to provide optional samples for research (where local 
regulations permit). After informed consent for the study is appropriately obtained, the 
subject or his or her legally acceptable representativewill be asked to sign and personally 
date a separate ICF indicating agreement to participate in the optional research component. 
Refusal to participate in the optional research will not result in ineligibility for the study. A 
copy of this signed ICF will be given to the subject.
If the subject or legally acceptable representative is unable to read or write, an impartial 
witness should be present for the entire informed consent process (which includes reading 
and explaining all written information) and should personally date and sign the ICF after 
the oral consent of the subject or legally acceptable representative is obtained
The subject must be able to read and write and should personally sign the ICF. An 
impartial witness or legally acceptable representative should not sign the ICF on the 
subject’s behalf. 
A limited number of study sites may be asked by the Sponsor to obtain informed consent 
using a validated electronic system instead of a paper-based process. If both parties 
(Sponsor and the study site) agree, and if participation is allowed by local regulations and 
IEC/IRB requirements, the means to facilitate such a process will be provided to the sites 
by Sponsor. The actual mechanism of consenting will be facilitated by the use of an 
eTablet device (eg, iPad®), but overall the consent process will remainthe same, as 
described in this section. At these study sites, subjects will still be required to review the 
entire informed consent as a written document on the eTablet and then to apply their 
handwritten signature electronically by the use of a stylus directly onto the eTablet. 
Alternately, the site will also have the option to print the electronic version of the ICF 
and apply a handwritten signature .
Section 16.2.4
Original text:
The informed consent obtained from the subject (or his or her legally acceptable 
representative) includes explicit consent for the processing of personal data and for the 
investigator/institution to allow direct access to his or her original medical records (source 
data/documents) for study-related monitoring, audit, IEC/IRB review, and regulatory 
inspection. This consent also addresses the transfer of the data to other entities and to other 
countries.
Modified text (deleted text is striked-through, new text in bold and underlined):
The informed consent obtained from the subject (or his or her legally acceptable 
representative) includes explicit consent for the processing of personal data and for the 
investigator/institution to allow direct access to his or her original medical records (source 
data/documents) for study-related monitoring, audit, IEC/IRB review, and regulatory 
inspection. This consent also addresses the transfer of the data to other entities and to other 
countries.
NCT03158285


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
17
Approved, Date: 23 January 2018
Applicable Section(s) Description of Change(s)
Rationale: To clarify the sample storage period.
Section 16.2.5 Long-
Term Retention of 
Samples
Original text:
Samples collected in this study may be stored for up to 15 years.
Modified text (deleted text is striked-through, new text in bold and underlined):
Samples collected in this study may be stored for up to 15 years, starting from last 
patient, last visit.
Rationale: To revise for clarification.
Section 17.4 Source 
Documentation
Revised language to clarify eC-SSRS questionnaires can be completed through IVRS as an 
alternative method.
Clarified that the at-home administrations occur at Weeks 56, 60, 64, 72, 80, 88, 92, and 
96.  
Rationale:Minor errors were noted.
Throughout the 
protocol
Minor grammatical, formatting, or spelling changes were made.
NCT03158285


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
18
Approved, Date: 23 January 2018
SYNOPSIS
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the 
Efficacy and Safety of Guselkumab Administered Subcutaneously in Subjects with Active Psoriatic 
Arthritis
CNTO 1959 (guselkumab) is a fully human immunoglobulin G1 lambda monoclonal antibody that binds 
to the p19 protein subunit of human interleukin 23 (IL‑23) with high specificity and affinity.  The binding 
of guselkumab to the IL-23p19 subunit blocks the binding of extracellular IL-23 to the cell surface IL-23 
receptor, inhibiting IL-23 specific intracellular signaling and subsequent activation and cytokine 
production. In this manner, guselkumab inhibits the biological activity of IL-23 in all in vitro assays 
examined.
EudraCT NUMBER: 2016-001224-63
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS
Primary Objective
The primary objective of this study is to evaluate the efficacy of guselkumab treatment in subjects with 
active psoriatic arthritis (PsA) by assessing the reduction in signs and symptoms of PsA.
Secondary Objectives
The secondary objectives are to assess the following for guselkumab treatment:

Efficacy in improving psoriatic skin lesions

Improvement in physical function 

Inhibition of progression of structural damage

Efficacy in improving general and disease specific health-related quality of life and patient-reported 
health outcomes 

Safety 

Pharmacokinetics, pharmacodynamics, and immunogenicity 
Primary Endpoint
The primary endpoint is the proportion of subjects who achieve an American College of Rheumatology 
(ACR)20 response at Week 24. 
Major Secondary Endpoints
NCT03158285
1. Change from baseline inDisability Index of the Health Assessment Questionnaire(HAQ-DI)score 
at Week 24.
2. Proportion of subjects who achieve an ACR 50 response at Week 24.
3. Proportion of subjects with a psoriasis response of an Investigator’sGlobal Assessment (IGA) (ie, an 
IGA psoriasis score of 0 [cleared] or 1 [minimal] AND ≥2-grade reduction from baseline) at 
Week 24 among the subjects with ≥3% body surface area (BSA) psoriatic involvement and an IGA 
score of ≥2 (mild) at baseline.
4. Proportion of subjects who achieve an ACR 20 response at Week 16.


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
19
Approved, Date: 23 January 2018
5. Change from baseline in modified van der Heijde-Sharp (vdH-S) score at Week24.
6. Proportion of subjects withresolution of enthesitis at Week 24 among the subjects with enthesitis at 
baseline.
7. Proportion of subjects with resolution of dactylitis at Week 24 among the subjects with dactylitis at 
baseline.
8. Change from baseline in enthesitis score (based on Leeds Enthesitis Index [LEI]) at Week 24 among 
the subjects with enthesitis at baseline. 
9. Change from baseline in dactylitis scoreat Week 24 among the subjects with dactylitis at baseline. 
10. Change from baseline in 36-item Short Form Health Survey Physical Component Summary (SF-36 
PCS)at Week 24.
11. Change from baseline in Disease Activity Score 28 (DAS28) C-reactive protein (CRP) at Week 24.
12. Change from baseline in SF-36 Mental Component Summary (MCS)at Week 24. 
13. Proportion of subjects who achieve anACR 50 response at Week 16.
14. Proportion of subjects who achieve an ACR 70 response at Week 24.
Other Secondary Endpoints
Endpoints Related to Reduction of Signs and Symptoms and Physical Function
NCT03158285
1. Proportions of subjects who achieve an ACR 20, ACR 50, and ACR 70 responses by visit over time 
through Week 100.
2. Percent change from baseline in ACR components by visit over time through Week 100.
3. Change from baseline in HAQ-DI score by visit over time through Week 100.  
4. Proportion of subjects who achieve a clinically meaningful improvement (a ≥0.35 improvement 
from baseline) in HAQ-DI score by visit over time through Week 100 among those subjects with 
HAQ-DI score ≥ 0.35 at baseline.  
5. Proportion of subjects who achieve a DAS28 (CRP) response by visit over time through Week100.
6. Proportion of subjects who achieve a DAS28 (CRP) remission by visit over time through Week100.
7. Change from baseline in DAS28 (CRP) by visit over time through Week 100.
8. Proportion of subjects who achieve a response based on modified Psoriatic ArthritisResponse 
Criteria (PsARC) by visit over time through Week 100.
9. Proportion of subjects with resolution of enthesitis by visit by visit over time through Week 100 
among the subjects with enthesitis at baseline.
10. Proportion of subjects with resolution of dactylitis by visit by visit over time through Week 100 
among the subjects with dactylitis at baseline.
11. Change from baseline in enthesitis score (based on LEI) by visit over time through Week 100 among 
the subjectswith enthesitis at baseline.


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
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Approved, Date: 23 January 2018
12. Change from baseline in dactylitis score by visit over time through Week 100 among the subjects 
with dactylitis at baseline.
13. Change from baseline in Psoriatic ArthritiS Disease Activity Score (PASDAS) by visit over time 
through Week 100.
14. Change from baseline in Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 
GRAppa Composite ScoreIndex by visit over time through Week 100.
15. Change from baseline in Work Productivity and Activity Impairment Questionnairescores by visit 
over time through Week 100.
16. Change from baseline in modified Composite Psoriatic Disease Activity Index (mCPDAI) score by 
visit over time through Week 100.
17. Change from baseline in Disease Activity Index for Psoriatic Arthritis score by visit over time 
through Week 100.
18. Proportion of subjects who maintain an ACR 20 response at Week 52 and Week 100 among the 
subjects who achieved an ACR 20 response at Week 24.  
19. Proportion of subjects who maintain an ACR 50 response at Week 52 and Week 100 among the 
subjects who achieved an ACR 50 response at Week 24.  
20. Proportion of subjects who maintain an ACR 70 response at Week 52 and Week 100 among the 
subjects who achieved an ACR 70 response at Week 24.  
21. Proportion of subjects who maintainaHAQ-DI response (ie, ≥0.35 improvement from baseline in 
HAQ-DI score) at Week 52 and Week 100 among the subjects who achieved a HAQ-DI response at 
Week 24.  
22. Proportion of subjects who achieve minimal disease activity by visit over time through Week 100.
23. Proportions of subjects who achieve a ≥20%, ≥50%, ≥70%, and ≥90% improvement from baseline in 
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score by visit over time through 
Week 100 among the subjects with spondylitis and peripheral joint involvement as their primary 
arthritic presentation of PsA.
Endpoints Related to Skin Disease
NCT03158285
1. Proportions of subjects who achieve ≥ 75%, ≥ 90%, and 100% improvement in Psoriatic Area and 
Severity Index (PASI) score from baseline by visit over time through Week 100 among the subjects 
with ≥3% BSA psoriatic involvement and an IGA score of ≥2 (mild) at baseline.
2. Proportion of subjects withanIGA score of 0 (cleared) by visit over time through Week 100 among 
the subjects with ≥3% BSA psoriatic involvement and anIGA score of ≥2 (mild) at baseline.
3. Change from baseline in PASI score by visit over time through Week 100 among the subjects with 
≥3% BSA psoriatic involvement and an IGA score of ≥2 (mild) at baseline.
4. Proportion of subjects who achieve a Dermatology Life Quality Index (DLQI) score of 0 or 1 by 
visit over time through Week 100 among the subjects with baseline DLQI score >1 and with ≥ 3% 
BSA psoriatic involvement and an IGA score of ≥2 (mild) at baseline.


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
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Approved, Date: 23 January 2018
5. Proportion of subjects who achieve ≥ 5-point improvement from baseline in DLQI score by visit 
over time through Week 100 among the subjects with baseline DLQI score ≥ 5 and with ≥ 3% BSA 
psoriatic involvement and an IGA score of ≥2 (mild) at baseline.
6. Change from baseline in DLQI score by visit over time through Week 100 among the subjects with 
≥ 3% BSA psoriatic involvement and an IGA score of ≥2 (mild) at baseline.
7. Proportion of subjects who achieve both PASI 75 and ACR 20 responses by visit over time through 
Week 100 among the subjects with ≥3% BSA psoriatic involvement and an IGA score of ≥2 (mild) 
at baseline.
8. Proportion of subjects who achieve both PASI 75 and modified PsARC response by visit over time 
through Week 100 among the subjects with ≥3% BSA psoriatic involvement and an IGA score of ≥2 
(mild) at baseline.
Endpoints Related to Joint Structural Damage
NCT03158285
1. Change from baseline in modified vdH-S score by visit over time through Week 100. 
2. Change in total modified vdH-S score from Week 24 to Week 52, from Week 24 to Week 100, and 
from Week 52 to Week 100.
3. Change from baseline in modified vdH-S erosion score by visit over time through Week 100.
4. Change in modified vdH-S erosion score from Week 24 to Week 52, from Week 24 to Week 100, 
and from Week 52 to Week 100.
5. Change from baseline in modified vdH-Sjoint space narrowing (JSN) score by visit over time 
through Week 100.
6. Change in modified vdH-S JSN score from Week 24 to Week 52, from Week 24 to Week 100, and 
from Week 52 to Week 100.
7. Change from baseline in modified vdH-S score by region and type of damage (ie, hand erosion, hand 
JSN, foot erosion, foot JSN subscores) by visit over time through Week 100.
8. Proportion of subjects with a change of ≤0 from baseline and proportion of subjects with a change of 
≤ 0.5 from baseline in modified vdH-S score by visit over time through Week 100.
9. Proportion of subjects with a change of ≤0 from baseline and proportion of subjects with a change of 
≤ 0.5 from baseline in modified vdH-S erosion score at by visit over time through Week 100.  
10. Proportion of subjects with achange of ≤0 from baseline and proportion of subjects with a change of 
≤ 0.5 from baseline in modified vdH-S JSN score by visit over time through Week 100.  
11. Proportion of subjects with radiographic progression (based on the smallest detectable change 
[SDC]) from baseline by visit over time through Week 100.
12. Proportion of subjects with radiographic joint erosion progression (based on SDC) from baseline by 
visit over time through Week 100.
13. Proportion of subjects with radiographic JSN progression (based on the SDC) from baseline by visit 
over time through Week 100.
14. Proportion of subjects with pencil in cup or gross osteolysis deformities by visit over time through 
Week 100.


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
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Approved, Date: 23 January 2018
Endpoints Related to Health Related Quality of Life
1. Change from baseline in PCS score of the SF-36 by visit over time through Week 100.
2. Change from baseline in MCS score of the SF-36 by visit over time through Week 100.
3. Change from baseline in domain scales scores of SF-36 by visit over time through Week 100.
4. Proportion of subjects who achieve ≥ 5-point improvement from baseline in SF-36 MCS score by 
visit over time through Week 100.
5. Proportion of subjects who achieve ≥ 5-point improvement from baseline in SF-36 PCS score by 
visit over time through Week 100.
6. Change from baseline in Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-
Fatigue)by visit over time through Week 100.
7. Proportion of subjects who achieve ≥ 4-point improvement from baseline in FACIT-Fatigue score 
improvement by visit over time through Week 100.
8. Change from baseline in EuroQol five-dimension questionnaire (EQ-5D) Visual Analogue Scale and 
in EQ-5D index scores by visit over time through Week 100.
Hypothesis
The primary hypothesis is the guselkumab 100 mg every 4 weeks (q4w)treatment group is superior to
placebo as assessed by the proportion of subjects achieving an ACR 20 response at Week24.
OVERVIEW OF STUDY DESIGN
This is a Phase 3randomized, double-blind, placebo-controlled, multicenter, 3-arm study of guselkumab 
in subjects with active PsA who are biologic naïve* and have had inadequate response to standard 
therapies (eg, non-biologic disease-modifying antirheumatic drugs[DMARDs], apremilast, nonsteroidal 
anti inflammatory drugs [NSAIDs]).
*
Subjects may not have previously received any biologic treatment including, but not limited to, 
guselkumab, ustekinumab, secukinumab (AIN457), anti-tumor necrosis factor alpha (TNFα)agents 
(such as adalimumab, etanercept, infliximab, golimumab subcutaneous [SC]or intravenous [IV], 
certolizumab pegol, or their respective biosimilars), tildrakizumab (MK3222), ixekizumab 
(LY2439821), brodalumab (AMG827), risankizumab (BI-655066), or other investigative biologic 
treatment for PsA or psoriasis.
Stable doses (as defined below) of concomitant NSAIDs, oral corticosteroids, and selected non-biologic 
DMARDs(limited to methotrexate[MTX], sulfasalazine[SSZ], hydroxychloroquine[HCQ], leflunomide
LEF) will be allowed but are not required:

NSAIDsand other analgesics:  the marketed dose approved in the country where the study is being 
conducted 

Oral Corticosteroids:
equivalent to ≤10 mg/day of prednisone

Selected Non-biologic DMARDs:

MTX:≤25 mg/week

NCT03158285
SSZ: ≤3 g/day


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
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Approved, Date: 23 January 2018

HCQ:≤400 mg/day

LEF:≤20 mg/day
The study will include approximately 684 subjects.  
Subjects who satisfy all inclusion and exclusion criteria will be randomly assigned to one of the following 
3 treatment groups in a 1:1:1 ratio using permuted block randomization stratified by baseline non-biologic 
DMARD (MTX, SSZ, HCQ, LEF) use (yes/no) and the most recent available CRP value prior to 
randomization (<2.0mg/dL vs ≥2.0 mg/dL):

Group I(n=228):  Subjects will receive SC guselkumab 100 mg q4w from Week 0 through 
Week 100.

Group II(n=228):  Subjects will receive SC guselkumab 100 mg at Weeks 0and 4then every 
8weeks (q8w) (Weeks 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, and 100) and placebo injections at 
other visits (Weeks 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, and 96) to maintain the blind.

Group III(n=228):  Subjects will receive SC placebo q4w from Week 0 to Week 20and will cross 
over at Week 24 to receive SC guselkumab 100 mg q4w from Week 24 through Week 100.
At Week 16, all subjects in Groups I, II and III with <5% improvement from baseline in both tender and 
swollen joint counts will be considered as meeting early escape criteria. These subjects will remain on the 
dosing regimen they were to randomized at Week 0. At Week 16, subjects who meet early escape criteria 
will be allowed to initiate or increase the dose of one of the permitted concomitant medications up to the 
maximum allowed dose as specified above, as selected by the investigator.  Titration to a stable dose of 
the medication should be completed for subjects qualifying for early escape by the Week 24 visit.
At Week 24, all subjects in the placebo group (Group III) will cross over to receive guselkumab 100 mg 
SC q4w through Week 100; this will allow for collection of additional safety data for the 100 mg SC q4w 
dose.  Subjects in the guselkumab groups (Groups I and II) will remain on the dosing regimen they were 
randomized to at Week 0, through Week100.
Subjects will be followed for adverse events and serious adverse events up to 12 weeks following the last 
study agent administration.  The end of the study is defined as the time the last subject completes the last 
study visit. For subjects who complete the Week 100 visit, the last study visit is the Week 112 visit.  For 
subjects who discontinue study agent prior toWeek 100, the last study visit is the final safety visit.
An independent Data Monitoring Committeewill be established to monitor unblinded data on an ongoing 
basis through at least the Week 24 DBL to ensure the continuing safety of the subjects enrolled in this 
study.
Samples for the analysis of pharmacodynamic biomarkers will be collected from all subjects. 
A pharmacogenomic blood sample will be collected from subjects who consent separately to this 
component of the study where local regulations permit.  Subject participation in pharmacogenomic 
research is optional.
Three DBLs are scheduledat Weeks 24, 52, and 112.
SUBJECT POPULATION
NCT03158285
The target study population is subjects with active PsA who are biologic naïve (see above) and have had 
inadequate response to standard therapies (eg, non-biologic DMARDs, apremilast, and/or NSAIDs). This 
population is considered appropriate to provide relevant efficacy and safety information for the intended 
use of guselkumab in PsA.   Additionally, a biologic naïve population with a CRP ≥0.6 mg/dL is required 


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
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Approved, Date: 23 January 2018
to enrich the population for radiographic progression and increase the power for detection of treatment 
effect on radiographic endpoints.
Subjects must also meet all inclusion and exclusion criteria.
DOSAGE AND ADMINISTRATION
Guselkumab 100 mg and matching liquid placebo for guselkumab will be provided in a single-use 
prefilled syringe (PFS) assembled with the UltraSafe PLUS
TMPassive Needle Guard (PFS-U).
Study agent will be administered at the site by a health care professional until the subject (or caregiver) is 
trained for self-administration. Study agent will be administered by site personnel at Weeks 0 and 
4. Beginning at Week 8, at the discretion of the investigator and subject, and after appropriate and 
documented training, subjects will self-administer study agent at the investigative site under the 
supervision of a health care professional.  The option to begin self-administration of study agent at home 
will begin afterWeek 52.Subjects unable to have injection(s)administered away from study site will be 
required to return to the site for administration of study agent injection(s) by a health care professional.  
After Week 52, subjects will have study visits and assessments at Weeks 68, 76, 84, 100, and 112.
Safety and efficacy assessments, including blood samples for clinical laboratory and 
pharmacokinetics/immunogenicity, should be performed before study agent administration.
The three dose groups(Groups I, II, and III) are described above.
EFFICACY EVALUATIONS
Psoriatic Arthritis Response Evaluations

Joint Assessment

Nonevaluable Joints

American College of Rheumatology Response(ACR)

Dactylitis Assessment

Enthesitis Assessment

Imaging Evaluation

Disability Index of the Health Assessment Questionnaire

Minimal Disease Activity

PsoriaticArthritis Disease Activity Score

Group for Research and Assessment of Psoriasis and Psoriatic Arthritis Composite Score(GRACE)

DiseaseActivity Index Score 28

ModifiedComposite Psoriatic Disease Activity Index

DiseaseActivity Index for Psoriatic Arthritis

ModifiedPsoriatic Arthritis Responder Criteria

NCT03158285
BathAnkylosing Spondylitis Disease Activity Index


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
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Approved, Date: 23 January 2018
Psoriasis Response Evaluations

Investigator’sGlobal Assessment of Psoriasis

PsoriasisArea and Severity Index

DermatologyLife Quality Index
Other Patient Reported Outcomes

36-Item Short-form Health Survey

EQ-5D Questionnaire

Functional Assessment of Chronic Illness Therapy –Fatigue(FACIT)
HEALTH ECONOMICS EVALUATIONS
The Work Productivity and Activity Impairment Questionnaire - Specific Health Problem 
(WPAI-SHP):PsAwill be used to study the impact of PsA on work and other daily activities during the 
past 7 days.
PHARMACOKINETIC AND IMMUNOGENICITYEVALUATIONS
Serum samples will be used to evaluate the PK of guselkumab as well as the immunogenicity of 
guselkumab.  Serum collected for PK and immunogenicity analyses may additionally be used to evaluate 
safety or efficacy aspects that address concerns arising during or after the study period.
BIOMARKERS

Samples for the analysis of pharmacodynamic biomarkers will be collected from all subjects. The 
samples will be used to better understand the biology of PsA, to provide a biological assessment of 
the response of patients to treatment with guselkumab, to analyze differences between responders 
and non-responders, and to determine if the markers can be used to classify patients as potential
responders prior to treatment.
RNA from whole blood samples will be used for gene expression analysis to determine the 
molecular profile of PsA and to assess changes in gene expression post guselkumab treatment.

Pharmacogenomics testing is optional.  For subjects who provide consent, awhole blood sample will 
be utilized for pharmacogenomics evaluation.  The analysis may include complete genome-wide 
testing and/or targeted sequencing.  The testing will be done to search for links of specific genes to 
disease or response to drug.
SAFETY EVALUATIONS
The safety and tolerability of study agent(guselkumab and placebo) will be monitored by collecting 
information on adverse events (including injection site and allergic reactions), clinical laboratory tests, 
physical examinations, vital signs, suicidal ideation or behavior (usingthe electronic Columbia-Suicide 
NCT03158285
Severity Rating Scale questionnaires), concomitant medication review, and early detection of 
tuberculosis.
Serum and/or plasma samples collected for pharmacokinetic or pharmacodynamicanalyses may also be 
used to evaluate safety concerns that may arise during or after the study period.
Safety will be monitored through Week 112.


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
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Approved, Date: 23 January 2018
STATISTICAL METHODS
Simple descriptive summary statistics, such as n, mean, standard deviation, median, inter quantile range, 
minimum, and maximum for continuous variables, and counts and percentages for discrete variables will 
be used to summarize most data.
Sample Size Determination
The sample size selection was determined based on the primary endpoint of proportion of subjects who 
achieve ACR 20 response at Week 24 and the major secondary endpointof change from baseline in 
vdH-S score at Week 24.
The table below provides the statistical power under various assumptions using a 2-sided chi-square test.  
For this study, the sample size was also evaluated based on the following assumptions:  

20% to 25% ACR 20 response rates at Week 24 in subjects treated with placebo 

40% to 50% ACR 20 response rates at Week 24 in subjects treated with guselkumab 
Statistical Power for Treatment Difference in ACR 20 Response at Week 24
Sample size per arm
ACR 20 Response Rate
Power
Placebo Group
Guselkumab Group
Difference (Δ) 
228
20%
40%
20%
>99%
228
20%
45%
25%
>99%
228
25%
45%
20%
99%
228
25%
50%
25%
>99%
228
30%
50%
20%
99%
The table below provides the statistical power under various assumptions.  The statistical power was 
estimated based on 10000simulations with treatment comparison performed at each simulation using an 
ANOVA test on the van der Waerden normal score.  
For this study, the sample size was determined based on the following assumptions:

The overall mean difference in change from baseline in vdH-S score at Week 24 between the 
placebo group and a guselkumab group ranges from 0.6 to 0.8.

40% –50% subjects in eachtreatment group have a change score of 0 from baseline in vdH-S 
score at Week 24 (ie, the subpopulation with a change score of 0). 

NCT03158285
For the other subjects (those from the normal distributions), the SD of the normal distributions 
is 2.5 for all treatment groups and the mean of the normal distribution is 1.80 for the placebo 
group. 
If the SD of the normal distributions is 3.0, the power will go down to as low as approximately 80%. 


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
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Approved, Date: 23 January 2018
Statistical Power for Treatment Difference in vdH-S Change from Baseline atWeek 24
Placebo Group
Guselkumab Group
Overall
Mean 
Difference 
Power
%subjects 
without change
Rest of 
subjects
Overall
mean
%subjects
without change
Rest of 
subjects
Overall
mean
Mean
SD
Mean
SD
45%
1.80
2.5
1.00
45%
0.71
2.5
0.40 
0.60
89.0%
45%
1.80
2.5
1.00
45%
0.35
2.5
0.20 
0.80
98.9%
50%
1.80
2.5
0.90
50%
0.60
2.5
0.30 
0.60
91.7%
50%
1.80
2.5
0.90
50%
0.20
2.5
0.10 
0.80
99.4%
50%
1.80
2.5
0.90
45%
0.55
2.5
0.30 
0.60 
91.1%
50%
1.80
2.5
0.90
45%
0.18
2.5
0.10 
0.80
99.2%
Primary Endpoint Analysis
The primary endpoint to be analyzed for the primary analysis is the proportion of subjects who achieved 
an ACR 20 response at Week 24.  Note that the intercurrent event of Treatment Failure prior to Week 24 
(defined below) will be treated as non-response for the primary analysis, regardless of the observed 
ACR20 response status.
Treatment Failure Criteria
NCT03158285
Subjects who meet the followingtreatment failure criteria include subjects who:
1. Discontinued study agent injections due to lack of efficacy.
2. Terminate study participation for any reason
3. Initiated or increased the dose of non-biologic DMARDs (MTX, SSZ, HCQ, LEF) or oral 
corticosteroids over baseline for PsA.
4. Initiated protocol prohibited medications/therapies for PsA. 
Subjects with missing data at Week 24 will be considered non-responders.
The treatment effect of each guselkumab group versus placebo will be tested using a Cochran-Mantel-
Haenszel test stratified by baseline non-biologic DMARD (MTX, SSZ, HCQ, LEF) use (yes/no) and the 
most recent available CRP value prior to randomization (<2.0 mg/dL or ≥2.0mg/dL).  The magnitude of 
the effect will be estimated by the difference in ACR 20 response rates betweenthe guselkumab and 
placebo groups with the 95% confidence interval calculated based on Wald statistics.
In order to control the overall Type 1 error rate, the primary analysis will be tested in a fixed sequence.
1. Guselkumab 100 mg q4w versus placebo in ACR 20 response at Week 24
2. Guselkumab 100 mg at Weeks 0, 4, and then q8w versus placebo in ACR 20 response at Week 24
With the above specified order, each of the hypotheses will be tested at a 2-sided α-level of 0.05 provided 
that significance is achieved for the preceding hypothesis in the specified order. If a given comparison is 
not significant at the 2-sided α-level of 0.05, the remaining treatment group comparisons will be 
considered as supportive analysis.


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Approved, Date: 23 January 2018
Major Secondary Analyses
The major secondary endpoints are listed above.  The methods of analysis and the approach to control the 
TypeI error for multiplicity, as well as the data-handling rules for the major secondary endpoints will be 
specified in the Statistical Analysis Plan.  
Safety Analysis
Routine safety evaluations will be performed.  Adverse events, serious adverse events, and infectionswill 
be summarized by treatment group.  The following analyses will also be usedto assessthe safety of 
subjects in the study:  incidence and type of adverse events, incidence and type ofserious adverse events, 
incidence and type of infections, and incidence and type of injection site reactions.
Laboratory parameters, change from baseline in selected laboratory parameters(hematologyand 
chemistry) and incidence of laboratory parameters that meet the criteria for Common Terminology 
Criteria for Adverse Events Grade 3 or Grade 4 will be summarized by treatment group.
All safety analyses will be based on the population of subjects who received at least 1 injection of study 
agent.  Subjects will be summarized by the treatment they actually received
Interim Analysis
NCT03158285
No interim analysis is planned for this study.


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
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Approved, Date: 23 January 2018
TIMEAND EVENTS SCHEDULE 
Table 1:
TIME AND EVENTS SCHEDULE FROM SCREENING THROUGH WEEK 24
Phase
Screeninga
Placebo-controlled Treatment
b
Week
0c
2
4
8
12 
16 
20 
24
Study Proceduresd
Screening/Administrative
Informed Consent(ICF/eICF
e)
X
Pharmacogenomics (DNA) (optional)
f
ICF/eICF
e
X
Review of Inclusion/Exclusion Criteria
X
X
Demography/Medical History 
X
Pre-planned Surgery/Procedure(s)
X
Pre-study Therapy Review for Eligibility
X
X
Study Agent Administrationg
Randomization
X
Study Agent Administration
X
X 
X
X
X
X 
X
Early Escape
Early Escape 
Xh
Safety Assessments
Physical Examination (including skin)
X
X
eC-SSRSi
X
X 
X 
X 
X
X
X
X 
X
Vital Signs
j
X
X 
X 
X 
X
X
X
X 
X
Height
X
Weight
X
X
Local 12-lead ECG
Xk
Tuberculosis Evaluationl
X
X 
X 
X 
X
X
X
X 
X
Chest Radiograph
m
X
Pregnancy Test
n
X
X
X 
X
X
X
X 
X
Injection Site Reaction Evaluation
X
X 
X
X
X
X 
X
NCT03158285


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
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Approved, Date: 23 January 2018
Table 1:
TIME AND EVENTS SCHEDULE FROM SCREENING THROUGH WEEK 24
Phase
Screeninga
Placebo-controlled Treatment
b
Week
0c
2
4
8
12 
16 
20 
24
Efficacy Assessments
PsA Evaluations for Arthritis
o
X
X 
X 
X 
X
X
X
X 
X
HAQ-DIp
X 
X 
X 
X
X
X
X 
X
Patient’s Global Assessment of Disease 
Activity (Arthritis and Psoriasis)
p
X
X
X
X
Patient’s Assessment of Skin Disease 
Activity (Skin VAS)p
X
X
X
X
Dactylitis assessments
X 
X 
X 
X
X
X
Enthesitis assessments (LEI)
X 
X 
X 
X
X
X
Radiographs of Hands and Feetq,r
X
X
BASDAIp,s
X
X
X
X
Pelvicx-ray
t
X
SF-36p
X
X
X
X
DLQIp
X
X
X
X
FACIT-fatigue
p
X
X
X
X
WPAI:PsAp
X
X
X
EQ-5Dp
X
X
X
BSA %Involvement of Psoriasis
X
IGA-Psoriasis
X
X
X
PASI
X
X
X
NCT03158285


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
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Approved, Date: 23 January 2018
Table 1:
TIME AND EVENTS SCHEDULE FROM SCREENING THROUGH WEEK 24
Phase
Screeninga
Placebo-controlled Treatment
b
Week
0c
2
4
8
12 
16 
20 
24
Clinical Laboratory Assessments
QuantiFERON-TB testu
X
Hepatitis B and C Serologiesv
X
HIV Antibody Test
v
X
Hematology
v
X
X
X 
X
X
X
X 
X
Chemistryv
X
X
X 
X
X
X
X 
X
Lipid Panel
v
X
C-reactive Protein
v
X
X 
X 
X 
X
X
X
X 
X
Rheumatoid Factor
v,w
X
Follicle Stimulating Hormonev,x
X
Pharmacokinetics/Immunogenicityy
Serum GuselkumabConcentration
X 
X 
X 
X
X
X
X 
X
Population PK
Xz
Antibodies to Study Agent
X
X
X
X
Pharmacogenomics (DNA)
DNA Collection (Whole Blood in EDTA)
f
X
X
X
Other Biomarkers
Serum Biomarkers
X
X
X
Whole Blood (RNA)
X
X
X
Ongoing Subject Review
Concomitant Therapy
X--------------------------------------------------------------------------------------------------------------------------------------------------X
Adverse Events
X--------------------------------------------------------------------------------------------------------------------------------------------------X
NCT03158285


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
32
Approved, Date: 23 January 2018
Table 1:
TIME AND EVENTS SCHEDULE FROM SCREENING THROUGH WEEK 24
a:The screening visit is to occur within 6 weeks before administration of study agent at Week 0. The screening visit may be completed in a single visit or may be divided 
into more than 1 visit. It is recommended that after obtaining informed consent, the investigator complete all laboratory tests at the first visit. The subject may then return 
for theremainder of the screening procedures only if the subject is eligible for the study as determined by the central laboratory test results. 
b: Through Week 24,study visits will have a visit window of ±4days.
c:Subjects must fast (ie, no food or beverages [except water]) for at least 8 hours before blood is drawn forthelipid panel(Week 0). All other visits can be nonfasting.
d:If a subject permanently discontinues study agent administration at Week 24, the final efficacy visitshould occur at the time of discontinuation or as soon as possible and 
all assessments under the Week 100/final efficacyshould be performed, including radiographs of hands and feet(see footnote “r” below), with the exception of study 
agent administration.  Fasting is not required for the final efficacy visit. The subject should also return for a final safety visit approximately 12 weeks after the last study 
agent administration.   
e:An eICF will be used at a limited number of sites to obtain informed consentto participate in the study, and to obtain informed consent to participate in the optional 
DNA research component of the study, asapplicable.
f:To participate in the optional DNA research component of this study, subjects must sign the DNA research ICF (or eICF) indicating willingness to participate.  Blood 
samples for pharmacogenomic and epigenetic research will be collected only from subjects who give informed consent for DNA research. 
g:Study agent will be administered SC at the site by a health care professional during visits to the site until the subject (or caregiver) is trained for 
self-administration.Study agent will be administered bysite personnel at Weeks 0 and 4.Beginning at Week 8, at the discretion of the investigator and subject, and
after appropriate and documented training, subjects mayself-administer study agent at the investigative site under the supervision of a health care professional.  A 
caregiver may also be trained to administer study agent. Safety and efficacy assessments, including blood samples for clinical laboratory and 
pharmacokinetics/immunogenicity, should be performed before study agent administration.  
h: At Week 16, all subjects who qualify for early escape will continue on the dosing regimen they were randomized to and will be allowed to initiate or increase the dose of 
one of the permitted concomitant medication interventions up to the maximum dose as specified in Table4, at the discretion of the investigator.  Titration to a stable 
dose of themedicationshould be completed for subjects qualifying for early escape by the Week 24 visit.
i:The eC-SSRS shouldbe performed after the joint assessmentat the screening visit (after signing informed consent). At Week 0/baseline and at all post-baseline visits,
the eC-SSRS shouldbe the first assessment/questionnaire that the subject completesprior to study agent administration(see Section 9.7.2for details). 
j:Vital signs include blood pressure and heart rate.
k:12-lead ECG mustbe done prior to administration of study agent.
l:Subjects (as outlined inInclusion Criterion14) must undergo testing for TB (Attachment 2or Attachment 3) and their medical history assessment must include specific 
questions about a history of TB or known occupational or other personal exposure to individuals with active TB.  
m:The chest radiograph may be taken within 3 months prior to the first administration of study agent.
n:Females of childbearing potential must have a negative serum pregnancy test prior to randomization and a negative urine pregnancy test at all dosing visits prior to 
administration of study agent.
NCT03158285


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
33
Approved, Date: 23 January 2018
Table 1:
TIME AND EVENTS SCHEDULE FROM SCREENING THROUGH WEEK 24
o:PsA evaluations for arthritis include joint assessments (swollen and tender joint counts), patient’s assessment of pain, patient’s global assessment of disease activity 
(arthritis), and physician’s global assessment of disease activity on VAS. These procedures should be performed prior to study agent administration at each visit, as 
applicable.
p:All patient questionnairesshould be completed before any other tests, procedures, or evaluations on the day of the visit for baseline and post-baseline visits.
q: To minimize unnecessary x-rays, it is recommended that subjects have the baseline radiographs of hands and feet taken after the inclusion and exclusioncriteria have 
been checked and the subject appears eligible to enter the study.  All eligible subjects shouldhave radiographs taken approximately 2 weeks but not greater than 4 weeks 
prior to randomization.
r: Week 24 radiographs shouldbe taken within ±2 weeks of the Week 24 visit.  For subjects who discontinue study agent prior to Week 24, radiographs ofthe hands and 
feet should be performed at the time of study agent discontinuation. If discontinuation occurs prior toor atWeek 16, the subject should also have radiographs performed 
at the Week 24 visit. If discontinuation occursafter Week 16, the radiographs do not need to be repeated at Week 24.  For subjects who also discontinue study 
participationat any time during the study, radiographs should be performed at the time of study discontinuationunlessanother set of radiographshas been obtained 
within the past 6 weeks.
s:The BASDAI will be completed only in subjects with spondylitis with peripheral arthritis as their primary arthritic presentation of PsA.
t:For patients with spondylitis, confirmation of sacroiliitis should be performed at the screening visit byalocally performedpelvic x-ray (single anterior-posterior view) 
unless a pelvic or SI joint x-ray or pelvic MRIhas been previously performed.  Results must be documented.    
u:A tuberculin skin test is additionally required if the QuantiFERON®-TB Gold test is not approved/registered in the country in which this study is being conducted, with 
the exception noted in Inclusion Criterion14.
v:Laboratory tests are listed in Section 9.7.1.
w:This test is optional.  It can be done if needed to confirm whether CASPAR criteria are met. 
x:Prior to randomization, FSH is only required for female subjects with amenorrhea for less than 12 months. Two FSH measurements are needed to confirm amenorrhea in 
these subjects. This testshould NOT be done for any female subject of childbearing potential or female subjects with amenorrhea for at least 12 months. Refer to 
Inclusion Criterion 10for details.
y:All blood samples must be collected before study agent administration at visitswhen a study agent administration is scheduled. Blood collected from one venipuncture 
will be divided into multiple aliquots of serum for the measurement of guselkumab concentration, antibodies to guselkumab, and a back-up sample. Details will be 
provided in the Laboratory Manual.
NCT03158285


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
34
Approved, Date: 23 January 2018
Table 1:
TIME AND EVENTS SCHEDULE FROM SCREENING THROUGH WEEK 24
z:An additional study visit, at which a venous blood sample (approximately 4 mL) for population PK analysis will be collected from all subjects, must occur on a random 
day between Week 4 to Week 12, but not on the same days of the scheduled Weeks 4, 8 or 12 visits. Additionally, this blood sample must be collected at least 24 hours 
prior to or after the actual time of study agent administration at Weeks 4, 8, or 12 (ie, itcannot be collected within 24 hours before or after study agent administration).  
The serum sample for population PK will be split into 2 aliquots (1 aliquot for serum guselkumab concentration and 1 aliquot as a back-up sample).
Abbreviations: BASDAI = Bath Ankylosing Spondylitis Disease Activity Index; BSA = body surface area; CASPAR = ClASsification criteria for Psoriatic Arthritis;
DLQI = Dermatology Life Quality Index; DNA = deoxyribonucleic acid; ECG = electrocardiogram;eC-SSRS= electronic Columbia-Suicide Severity 
Rating Scale; EDTA = ethylenediaminetetraacetic acid; eICF=electronic informed consent form; EQ-5D = EuroQol five dimensions questionnaire; 
FACIT = Functional Assessment of Chronic Illness Therapy; FSH = follicle stimulating hormone; HAQ-DI = Disability Index of the Health Assessment 
Questionnaire; HIV = human immunodeficiency virus; ICF=informed consent form; IGA = Investigator’s Global Assessment; LEI = Leeds Enthesitis 
Index; MRI = magnetic resonance imaging; PASI= Psoriatic Area and Severity Index; PsA = psoriatic arthritis; RNA = ribonucleic acid; SF-36 = 36-item 
Short Form Health Survey; SI =TB = tuberculosis;VAS = visual analog scale; WPAI = Work Productivity and Activity Impairment Questionnaire.
NCT03158285


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
35
Approved, Date: 23 January 2018
Table 2:
TIME AND EVENTS SCHEDULE FROM WEEK 28 THROUGH WEEK 112
Phase
Active Treatmenta
Safety 
Follow-up
Weekb
28 
32 
36 
40 
44 
48 
52 
56 
60 
64 
68 
72 
76 
80 
84 
88 
92 
96
Final 
Efficacy
Visit
c/ 
100
Final 
Safety 
Visita/112
Study Proceduresd
Study Agent Administratione
Study Agent 
Administration
X 
X 
X 
X 
X 
X 
X 
Xf
Xf
Xf
Xg
Xf
Xg
Xf
Xg
Xf
Xf
Xf
X
Safety Assessments
Physical 
Examination 
(including skin)
X
X
eC-SSRSh
X 
X 
X 
X 
X 
X 
X
X
X
X
X 
X
Vital Signsi
X
X
X 
X
X 
X
Weight
X
X
X
Tuberculosis 
Evaluationj
X 
X 
X 
X 
X 
X 
X
X
X
X
X 
X
Pregnancy Testk
X 
X 
X 
X 
X 
X 
X
Xl
Xl
Xl
X 
X
Injection Site 
Reaction 
Evaluation
X 
X 
X 
X 
X 
X 
X
Xl
Xl
Xl
X
NCT03158285


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
36
Approved, Date: 23 January 2018
Table 2:
TIME AND EVENTS SCHEDULE FROM WEEK 28 THROUGH WEEK 112
Phase
Active Treatmenta
Safety 
Follow-up
Weekb
28 
32 
36 
40 
44 
48 
52 
56 
60 
64 
68 
72 
76 
80 
84 
88 
92 
96
Final 
Efficacy
Visit
c/ 
100
Final 
Safety 
Visita/112
Efficacy Assessments
PsA Evaluations 
for Arthritism
X
X
X
X
X
X
X
X
HAQ-DIn
X
X
X
X
X
X
X
X
Patient’s Global 
Assessment of 
Disease Activity
(arthritis and 
psoriasis)n
X
X
X
Patient’s 
Assessment of 
Skin Disease 
Activity (Skin 
VAS)n
X
X
X
Dactylitis 
Assessments
X
X
X
Enthesitis 
Assessments 
(LEI)
X
X
X
Radiographs of 
Hands and Feet
o
X
X
BASDAIn,p
X
X
X
SF-36n
X
X
X
DLQIn
X
X
X
FACIT-fatigue
n
X
X
X
WPAI:PSAn
X
X
X
EQ-5Dn
X
X
X
IGA-Psoriasis
X
X
X
PASI
X
X
X
NCT03158285


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
37
Approved, Date: 23 January 2018
Table 2:
TIME AND EVENTS SCHEDULE FROM WEEK 28 THROUGH WEEK 112
Phase
Active Treatmenta
Safety 
Follow-up
Weekb
28 
32 
36 
40 
44 
48 
52 
56 
60 
64 
68 
72 
76 
80 
84 
88 
92 
96
Final 
Efficacy
Visit
c/ 
100
Final 
Safety 
Visita/112
Clinical Laboratory Assessments
Hematologyq
X 
X 
X
X
X
X
X
X
X 
X
Chemistryq
X 
X 
X
X
X
X
X
X
X 
X
CRPq
X
X
X
X
X
X
X
X
Pharmacokinetics/Immunogenicityr
Serum 
Guselkumab 
Concentration
X
X
X
X
X
X 
X
Antibodies to 
Study Agent
X
X
X
X 
X
Pharmacogenomics (DNA)
DNA Collection 
(Whole Blood in 
EDTA)s
X
X
Biomarkers
Serum 
Biomarkers
X
X
Whole Blood 
(RNA)
X
X
Ongoing Subject Review
Concomitant 
Therapy
X-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------X
Adverse Events
X-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------X
NCT03158285


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
38
Approved, Date: 23 January 2018
Table 2:
TIME AND EVENTS SCHEDULE FROM WEEK 28 THROUGH WEEK 112
a:Through Week 100, study visits willhave a visit window of ±7 days; Week 112 visit or the final safety visit (12 weeks after the last dosein subjects who discontinued study 
treatment) will have a visit window of ±14 days.
b:All visits can be nonfasting.
c:With the exception of study agent administration, all assessments performed at Week 100 will also be performed at the final efficacy visit.
d:If a subject discontinues study agent at or after Week 24, the final efficacy visitassessments should occur at the time of discontinuation or as soon as possible and all assessments 
under the final efficacy/Week 100 visit should be performed, including radiographs of hands and feet, with the exception of study agent administration.  Thesubject should also 
return for a final safety visit approximately 12 weeks after the last study agent administration.   
e: At the discretion of the investigator and subject, and after appropriate and documented training, subjects will continue to self-administer study agent at the investigative site under the 
supervision of a health care professional.  Safety and efficacy assessments, including blood samples for clinical laboratory and pharmacokinetics/immunogenicity, should be 
performed before study agent administration.
f:The option to begin self-administration of study agent at home will begin at Week 56; subjects will record study agent administration on a diary card.  Subjects who self-administer 
are not required to visit the study site at Weeks 56,60, 64, 72, 80, 88, 92, and 96.  Subjects unable to have injection(s)administered away from the study site will be required to 
return to the site at these study weeks for administration of study agent injection(s). An injection site evaluation and AE review will be done at the study site at the time of injection.
g:Dosing for all clinic visits (ie, Weeks 28, 32, 36, 40, 44, 48, 52, 68, 76, 84, and 100)should occur after all procedures at the clinic visit.
h:At all post-baseline visits, the eC-SSRS willbe the first assessment/questionnaire that the subject must complete.
i:Vital signs include blood pressure and heart rate.
j:Subjects (as outlined in Inclusion Criterion14) must undergo testing for TB (Attachment 2or Attachment 3) and their medical history assessment must include specific questions 
about a history of TB or known occupational or other personal exposure to individuals with active TB.  
k:Females of childbearing potential who are dosed at the clinicmust have a negative urine pregnancy test at all dosing visits prior to administration of study agent.  For subjects not 
dosed at the clinic (see footnote “f”above), a urine pregnancy test is not required prior to administration of study agent.
l:Only performed for subjects who are dosed at the site.
m:PsA evaluations for arthritis include joint assessments(swollen and tender joint counts), patient’s assessment of pain, patient’s global assessment of disease activity (arthritis),and 
physician’s global assessment of disease activity on VAS. These assessments should be performed prior to study agent administration at each visit, as applicable.
n:All patient questionnaires should be performed before any other tests, procedures, or evaluations on the day of the visit.
NCT03158285


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
39
Approved, Date: 23 January 2018
Table 2:
TIME AND EVENTS SCHEDULE FROM WEEK 28 THROUGH WEEK 112
o:Single radiographs ofthe hands (posteroanterior) and feet (anteroposterior) shouldbe performedwithin ±2 weeks of the Week 52 and Week 100 visits.  For subjects who 
permanently discontinue study agent after Week 24 but prior to Week 100, radiographs of hands and feet should be performed atthe time of discontinuation of study agent or as soon 
as possible unless another set of radiographs has been obtained within the past 6 weeks.
p:The BASDAI will be completed only in subjects with spondylitiswith peripheral arthritis as their primary arthritic presentation of PsA.  
q:Laboratory tests are listed in Section 9.7.1.
r:All blood samples must be collected before study agent administration at visits when a study agent administration is scheduled.Blood collected from one venipuncture will be 
divided into multiple aliquots of serum for the measurement of guselkumab concentration, antibodies to guselkumab and a back-up sample. Details will be provided in the 
Laboratory Manual.
s:Blood samples for pharmacogenomic and epigenetic research will be collected only from subjects who give informed consent for DNA research. 
Abbreviations:
BASDAI = Bath Ankylosing Spondylitis Disease Activity Index; CRP =C-reactive protein; DLQI = Dermatology Life Quality Index; DNA = deoxyribonucleic acid; 
eC-SSRS = electronic Columbia-Suicide Severity Rating Scale; EDTA = ethylenediaminetetraacetic acid; EQ-5D = EuroQol five dimensions questionnaire; FACIT = 
Functional Assessment of Chronic Illness Therapy; HAQ-DI = Disability Index of the Health Assessment Questionnaire; IGA = Investigator’s Global Assessment; LEI 
= Leeds Enthesitis Index; PASI = Psoriatic Area and Severity Index; PsA = psoriatic arthritis; RNA = ribonucleic acid; SF-36 = 36-item Short Form Health Survey; 
VAS = visual analog scale; WPAI = Work Productivity and Activity Impairment Questionnaire
NCT03158285


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
40
Approved, Date: 23 January 2018
ABBREVIATIONS
ACR
American College of Rheumatology
AMDF
Arithmetic Mean of the Desirability Function
AE
adverse event
ALT
alanine aminotransferase
ANOVA
analysis of variance
ARC
Anticipated Event Review Committee
AST
aspartate aminotransferase
BASDAI
Bath Ankylosing Spondylitis Disease Activity Index
BCG
bacillusCalmette-Guérin
BQL
below the lowest quantifiable sample concentration of the assay
BSA
body surface area
CASPAR
ClASsification criteria for Psoriatic Arthritis
CRF
case report form(s) (paper or electronic as appropriate for this study)
CRP
C-reactive protein
DAS28
Disease Activity Score 28 
DBL
database lock
DLQI
Dermatology Life Quality Index
DMARDs
disease-modifying antirheumatic drugs
DMC
Data Monitoring Committee
DNA
deoxyribonucleic acid
ECG
electrocardiogram
eC-SSRS
electronic Columbia-Suicide Severity Rating Scale
eDC
electronic data capture
EDTA
ethylenediaminetetraacetic acid
NCT03158285
EQ-5D
EuroQol five dimensions questionnaire
FACIT
Functional Assessment of Chronic Illness Therapy
FAS
Full Analysis Set
FSH
follicle stimulating hormone
GCP
Good Clinical Practice
GRACE 
GRAppa Composite score
GRAppa
Group for Research and Assessment of Psoriasis and Psoriatic Arthritis
HAQ
Health Assessment Questionnaire
HAQ-DI
Disability Index of the Health Assessment Questionnaire
HBV
hepatitis B virus
HCP
healthcare professional
HCQ
Hydroxychloroquine


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
41
Approved, Date: 23 January 2018
HCV
hepatitis C virus
HIV
human immunodeficiency virus
ICF
informed consent form
ICH
International Conference on Harmonisation
IEC
Independent Ethics Committee
IGA
Investigator’s Global Assessment
IJA
independent joint assessor
IL
interleukin
IRB
Institutional Review Board
IV
intravenous
IWRS
interactive web response system
JAK
Janus kinase
JSN
joint space narrowing
LEF
leflunomide
LEI
Leeds Enthesitis Index
mAb
monoclonal antibody
MCP
metacarpophalangeal 
mCPDAI
modified Composite Psoriatic Disease Activity Index
MCS
Mental Component Summary
MDA
minimal disease activity
MI
multiple imputation
MRI
magnetic resonance imaging
MTX
methotrexate
NAb
neutralizing antibody
NSAID
nonsteroidal anti-inflammatory drug
PASDAS
Psoriatic ArthritiS Disease Activity Score
PASI
Psoriatic Area and Severity Index
PCS
Physical Component Summary
PD
pharmacodynamic(s)
PFS
prefilled syringe
PFS-U
prefilled syringe with an UltraSafe PLUS
TM
NCT03158285
PassiveNeedle Guard
PGA
Physician’s Global Assessment
PIP
proximal interphalangeal
PK
pharmacokinetic(s)
PQC
Product Quality Complaint
PRO
patient-reported outcome(s) (paper or electronic as appropriate for this study)
PsA
psoriatic arthritis
PsARC
Psoriatic ArthritisResponse Criteria


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
42
NCT03158285
Approved, Date: 23 January 2018
q4w
every 4weeks
q8w
every 8 weeks
RA
rheumatoid arthritis
RNA
ribonucleic acid
SAE
serious adverse event
SAP
Statistical Analysis Plan
SC
subcutaneous
SD
standard deviation
SDC
smallest detectable change
SF-36
36-item Short Form Health Survey
SSZ
sulfasalazine
SUSAR
suspected unexpected serious adverse reaction
TB
tuberculosis
Th17
T helper 17
TNFα
tumor necrosis factor alpha
UV
ultraviolet
VAS
Visual Analogue Scale
vdH-S
van der Heijde-Sharp (score)
WPAI
Work Productivity and Activity Impairment Questionnaire


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
43
Approved, Date: 23 January 2018
1.
INTRODUCTION
CNTO 1959 (guselkumab) is a fully human immunoglobulin G1 lambda monoclonal antibody 
(mAb) that binds to the p19 protein subunit of human interleukin 23 (IL‑23) with high 
specificity and affinity.  The binding of guselkumab to the IL-23p19 subunit blocks the binding 
of extracellular IL-23 to the cell surface IL-23 receptor, inhibiting IL-23 specific intracellular 
signaling and subsequent activation and cytokine production. In this manner, guselkumab 
inhibits the biological activity of IL-23 in all in vitro assays examined.
Guselkumab has been extensively studied in 3 large Phase 3 studies in psoriasis. For the most
comprehensive nonclinical and clinical information regarding guselkumab, refer to the latest 
version of the Investigator
's Brochurefor guselkumab.
The term "Sponsor" used throughout this document refers to the entities listed in the Contact 
Information page(s), which will be provided as a separate document.
1.1.
Background
1.1.1.
Disease Background
Psoriaticarthritis (PsA) is a chronic inflammatory arthropathy of the peripheral and axial joints 
associated with psoriasis.46The estimated prevalence of PsA in the general population varies 
from 0.02% to 1.0% across the world.15,46  In patients with psoriasis, the prevalence of PsA 
ranges from 6% to 42%.15  Psoriatic arthritis is a multi-faceted disease that impacts the joints, soft 
tissues, and skin, all of which affect quality of life.18,45  The burden of disease can be severe, with 
some patients developing destructive arthritis leading to bony erosion and loss of joint 
architecture; some patients even require surgical intervention to alleviate pain and restore 
function of severely damaged joints.
57  Psoriatic arthritis not only results in functional disability 
and impaired quality of life, but patients with this disease have increased mortality.
16,47,49,56
1.1.2.
Treatment Options
NCT03158285
Current treatment options for PsA include conventional therapies such as nonsteroidal 
anti-inflammatory drugs (NSAIDs), intra-articular corticosteroid injections, low-dose systemic 
steroids, oral disease-modifying antirheumatic drugs (DMARDs; eg, methotrexate [MTX], 
sulfasalazine [SSZ], and leflunomide [LEF]), and immunosuppressive drugs (eg, cyclosporine A, 
tacrolimus).  The addition of biologic treatments for PsA, including tumor necrosis factor alpha 
(TNFα) inhibitors (etanercept, infliximab, adalimumab, golimumab, certolizumab), ustekinumab, 
an IL-12/IL-23 inhibitor, and secukinumab (an IL-17inhibitor) significantly improved skin and 
joint responses in patients when used on top of conventional DMARDS or alone.  Apremilast, a 
new oral phosphodiesterase 4 inhibitor, is also available for the treatment of PsA; however, its 
use is associated with less degree of skin and joint improvements compared with biologic 
treatments.


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
44
Approved, Date: 23 January 2018
Despite these recent advances in treatment options for PsA, there remains an unmet medicalneed 
for novel therapeutic agents that address the heterogeneous clinical manifestations of PsA and 
offer an improved benefit/risk profile for the individual patient. 
1.1.3.
Clinical Studies
Guselkumab is being developed as a potential treatment for psoriasis, PsA, and other 
immune-mediated diseases.  As of 31 August 2016, 15clinical studies with guselkumab have 
been completed or are ongoing.
Seven clinical studies have been completed:

CNTO1959PSO1001, a Phase 1 study with 2 parts; Part 1 enrolled healthy subjects and 
Part2 enrolled subjects with moderate to severe plaque psoriasis.
CNTO1959PSO1002, a Phase 1 study of guselkumab in Japanese subjects with moderate to 
severe plaque psoriasis.
CNTO1959PSO2001, a Phase 2, randomized, placebo-and active-comparator-controlled, 
parallel group, multicenter, dose-ranging study of guselkumab in subjects with moderate to 
severe plaque psoriasis.

CNTO1275ARA2001, a Phase 2 study of guselkumab and ustekinumab (STELARA®) in 
subjects with activerheumatoid arthritis (RA)despite concomitant MTX therapy. Further 
development of guselkumab in the RA indication hasbeen discontinued by the Sponsor.
CNTO1959PPP2001, a Phase 2 study to assess the efficacy, safety, and tolerability of 
guselkumab following subcutaneous (SC) administration in Japanese subjects with 
palmoplantar pustulosis.

CNTO1959NAP1001, a Phase 1 study to assess pharmacokinetic (PK)comparability of 2 
formulations and to evaluate the PK comparability of guselkumab delivered by 2 different 
devices in healthy subjects.
CNTO1959NAP1002, a Phase 1 study to characterize the elimination of guselkumab 
glycoform variants in healthy subjects.
Eight studies are ongoing:
CNTO1959PSO1003, a Phase 1 study to assess the drug-drug interaction potential of 
guselkumab treatment in subjects with moderate to severe plaque psoriasis.
CNTO1959PSA2001, a Phase 2 study to evaluate the efficacy and safety of guselkumab in 
subjects with active PsA.
CNTO1959PSO3001, a Phase 3 study to evaluate the efficacy and safety of guselkumab in 
subjects with moderate to severe plaque psoriasis.

NCT03158285
CNTO1959PSO3002, a Phase 3 study to evaluate the efficacy and safety of guselkumab in 
subjects with moderate to severe plaque psoriasis with randomized withdrawal and 
retreatment.


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
45
Approved, Date: 23 January 2018
CNTO1959PSO3003, a Phase 3 study to evaluate the efficacy and safety of guselkumab in 
subjects with moderate to severe plaque psoriasis and an inadequate response to 
ustekinumab.
CNTO1959PSO3004, a Phase 3 study to evaluate the efficacy and safety of guselkumab in 
subjects with moderate to severe plaque psoriasis in Japan. 
CNTO1959PSO3005, a Phase 3 study to evaluate the efficacy and safety of guselkumab in 
subjects with generalized pustular psoriasis or erythrodermic psoriasis in Japan.
CNTO1959PPP3001, a Phase 3 study to evaluate the efficacy and safety of guselkumab in 
subjects with palmoplantar pustulosis in Japan.
Preliminary efficacy and safety results for the ongoing Phase 2 PsA study (CNTO1959PSA2001)
arepresented in Section 1.1.3.1.  Preliminary efficacy and safety results for the 5 ongoing studies 
in psoriasis are presented in Section 1.1.3.2(Phase 2 study) and Section 1.1.3.3(Phase 3 studies).
In RA, 1 Phase 2 dose-ranging study has been completed; see Section 1.1.3.4.
Further detailsare provided in the guselkumab Investigator’s Brochure.
1.1.3.1. 
Phase 2 Study in Psoriatic Arthritis (CNTO1959PSA2001)
Study Design
CNTO1959PSA2001 isa Phase 2a, multicenter, randomized, double-blind, placebo-controlled, 
study evaluating the efficacy and safety of guselkumab in subjects with active PsAand ≥3% 
body surface area (BSA) of plaque psoriasis despite current or previous treatment with 
standard-of-care therapies, including those previously exposed to anti-TNFαagents. In this 
study, 149 subjects with active PsA were randomized in a 1:2 ratio to receive either placebo or 
guselkumab 100 mg SC at Weeks 0, 4,then every 8 weeks (q8w) through Week 44. At 
Week 16,subjects in both treatment groups who had<5% improvement from baseline in both 
tender and swollen joint countsqualifiedfor early escape andswitched to open-label therapy 
with ustekinumab.  At Week 24, subjects remaining in the placebo group crossedover to receive
guselkumab 100 mg at Week 24, 28, then q8w through Week 44. All subjects will have a final 
safety visit at Week 56.
Preliminary efficacy, safety and PK results through Week 24 are summarized below:
EfficacyResults
The study met its primary and all secondary endpoints. The primary endpoint was the proportion 
of subjects who achieved an American College of Rheumatology (ACR)20 response at 
Week 24, and was significantly higher in the guselkumab group (58.0%) compared with the 
placebo group (18.4%, p<0.001).
In addition, significantly more guselkumab subjects achieved ACR 50 and ACR 70 responses, 
and PASI 50, PASI 75, and PASI 90 responses at Week 24 compared with the placebo group 
(Table 3
NCT03158285
).Significant treatment effect on ACR 20 response was observed as early as Week 4 
(21% vs 0, p<0.001), and the effect increased over time reaching the maximum by Week 16 


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(60.0% vs. 16.3%, p<0.001) vs. placebo. Other secondary efficacy endpoints are summarized in 
Table 3.These results demonstrated that treatment with guselkumab significantly improved joint 
symptoms, physical function, psoriasis, enthesitis, dactylitis,and quality of life in this 
population.
Table 3:
Summary of Efficacy Results at Week 24 (CNTO1959PSA2001)
Efficacy Endpoints
Placebo
Guselkumab
p-value
ACR 20
18.4%
58.0%
p<0.001
ACR 50
10.2%
34.0%
P=0.002
ACR 70
2.0%
14.0%
p=0.023
(post hoc)
PASI 75
12.5%
78.6%
p<0.001
PASI 90
6.3%
66.3%
p<0.001
PASI 100
6.3%
39.8%
P<0.001
Mean (SD) change from baseline in HAQ-DI score
-0.06 (0.530)
-0.42 (0.512)
p<0.001
Median percent change from baseline in Leeds 
EnthesitisIndex (LEI)
a
-33.33%
-100.00%
p=0.009
% of patients with unresolved enthesitisa
71.0%
43.4%
p=0.012
Median percent change from baseline in dactylitisb
-33.33%
-100.00%
p<0.001
% of patients with unresolved dactylitisb
82.6%
44.8%
p=0.001
Mean (SD) change from baseline in SF-36 physical 
component summary (PCS) score
0.46 (6.51) 
6.59 (7.47)
p<0.001
Mean (SD) change from baseline in SF-36 mental 
component summary (MCS) score
0.42(6.74)
4.95 (9.06)
p=0.002
% of patients achieving Minimal Disease Activity 
(MDA)
2.0%
23.0%
p=0.001
a Among the patients with enthesitis at baseline (Placebo: N=31; Guselkumab: N=76)
b Among the patients with dactylitis at baseline (Placebo: N=23; Guselkumab: N=58)
ACR = American College of Rheumatology; HAQ-DI = Disability Index of the Health Assessment 
Questionnaire; PASI = Psoriatic Area and Severity Index; SD = standard deviation
Safety Results
NCT03158285
Treatment with guselkumab was generally well-tolerated through Week 24. 
Through Week 24, the proportions of subjects with 1 or more adverse events (AEs)were 
comparable between placebo (32.7%) and guselkumab (36.0%) groups. The proportions of 
subjects with 1 or more AEs were similar in subjects with or without MTX at baseline. The most 
common AE in both treatment groups was nasopharyngitis, which wasreported in 5 (10.2%) 
subjects in the placebo groupand 6 (6.0%) subjects in the guselkumab group. No injection site 
reactions were reported in the guselkumab group. Two serious adverse events (SAEs)were 


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Approved, Date: 23 January 2018
reported, one (2.0%) in the placebo group (joint injury) and one (1.0%) in guselkumab group 
(myocardial infarction). One (1.0%) subject in guselkumab group had AEs of leukopenia and 
neutropenia (both of mild severity) that subsequently resulted in discontinuation of study agent 
administration after the Week 24visit. No deaths, malignancies, anaphylactic or serum sickness-
like reactions were reported in the study through Week 24.
Infections (as assessed by the investigators) were comparable between the placebo (20.4%) and 
guselkumab (16.0%) groups. Infections reported by >1 subject in the guselkumab group included 
nasopharyngitis (6 [6.0%]), gingivitis (2 [2.0%]) and urinary tract infection (2 [2.0%]). No 
serious infections, tuberculosis (TB) or opportunistic infections were reported through Week 24. 
The proportions of subjects with 1 or more infections requiringoral or parenteral antimicrobial 
treatment were similar between the placebo (14.3%) and guselkumab (10.0%) groups.
Overall, there were no clinically important findings for hematology or chemistry laboratory 
parameters.    
Pharmacokinetics and Immunogenicity Results
Steady state of serum guselkumab concentration was achieved by approximately Week 20 
followingSC administrations of 100 mg guselkumab at Week 0 and 4, and q8w thereafter. The 
median steady-state trough serum guselkumab concentration at Week 20 was 0.93 µg/mL, which 
is similar to those observed in Phase 3 studies in subjects with psoriasis.Only one subject (1%, 
1/100) was positive for antibodies to guselkumab through Week 24 with low antibody titers 
(1:20).
Conclusions
In subjects with active PsA who had ≥3% BSA involvement of psoriasis, guselkumab 
demonstratedrobust efficacy across all efficacy endpoints on joint signs and symptoms, physical 
function, skin disease, enthesitis, dactylitis, andhealth-related quality of life.
Efficacy was generally demonstrated both in subjects receiving MTX and in subjects not 
receivingMTX.  Similarly, guselkumab 100 mg was well tolerated in the PsA population 
through Week 24 with no unexpected safety findings.  
1.1.3.2. 
Phase 2 Study in Psoriasis (CNTO1959PSO2001, X-PLORE)
Study Design
In the X-PLORE study, 293 subjects with moderate to severe plaque-type psoriasis were 
randomized to receive 1 of 5 guselkumab SCdose regimens (5 mg at Weeks 0, 4, and then every 
12 weeks [q12w], 15 mg q8w, 50 mg at Weeks 0, 4, and then q12w, 100 mg q8w, or 200 mg at 
Weeks 0, 4, and then q12w), placebo, or adalimumab (HUMIRA®
NCT03158285
) 80 mg at Week 0, 40 mg at 
Week 1, and then 40 mg every 2 weeks (q2w). 


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Efficacy Results
The proportions of subjects who achieved a Physician’s Global Assessment (PGA) score of 
cleared (0) or minimal (1) were significantly higher at Week 16 in all guselkumab treatment 
groups compared with the placebo group. In addition, higher proportions of subjects in the 
guselkumab 50 mg q12w, 100 mg q8w, and 200 mg q12w groups achieved a PGA score of 
cleared (0) or minimal (1) compared with the adalimumab group at Week 16. A dose-response in 
efficacy was observed up to 100 mg q8w; the proportions of subjects who achieved aPGA of 0 
or 1 were similar in the 100 mg q8w and 200 mg q12w dose groups. Results for improvements in 
Psoriasis Area and Severity Index (PASI) scores were generally similar to those observed for 
PGA.
Safety Results
Treatment with guselkumab was generally well-tolerated through Week 52. The proportions of 
subjects with 1 or more AEs were comparable across the combined guselkumab, placebo, and the 
adalimumab groups through Week 16, with no evidence of a dose-response in the occurrence of 
AEs across the guselkumab groups. Through Week 16, the proportion of subjects with 1 or more 
SAEs was low across all treatment groups. Two serious infections (appendicitis and lung abscess 
in the guselkumab 50 mg group), no malignancies, and no major cardiovascular events were 
reported.  Similar patterns of AEs were observed through Week 52. Events of interest through 
Week 52 included the 2 serious infections noted through Week 16, 1malignancy (cervical 
dysplasia, including carcinoma in situ) in the 200 mg q12w group, and 3 major cardiovascular 
events (1 fatal myocardial infarction in the 5 mg q12w group and 1 nonfatal myocardial 
infarction and 1 stroke, each in the 100 mg q8w group).
Pharmacokinetics and Immunogenicity Results
NCT03158285
Approximate dose-proportionality in serum guselkumab concentrations through Week 52 was 
observed after multiple SC administrations at dose levels ranging from 15 mg to 200 mg. Steady 
state serum guselkumab concentrations were achieved by approximately Week 16 for both the 
q8w and q12w regimens. In each treatment group, mean or median trough serum guselkumab 
concentrations were maintained at steady state through Week 40 (q8w groups) or Week 52 
(q12w groups). There was no evidence of accumulation in serum guselkumab concentrations 
over time with SC q8w or q12w administrations. Serum guselkumab concentrations appeared to 
be affected by subject body weight; higher-weight subjects (>90 kg) had lower mean steady-state 
trough serum guselkumab concentrations compared with lower-weight subjects (≤90 kg).
The overall incidence of antibodies to guselkumab across all guselkumab treatment groups 
through Week 52 was 3.8%, with generally low titers. None of the subjects who were positive 
for antibodies to guselkumab had antibodies that were able to neutralize the bioactivity of 
guselkumab in vitro. No consistent impact of antibodies to guselkumab on serum guselkumab 
concentrations was observed across the guselkumab treatment groups.


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Conclusions
Treatment with guselkumabwas well tolerated across a wide range of doses andled to 
substantial, clinically meaningful improvements in psoriasis, with several dose regimens yielding 
superior outcomes to those observed with adalimumab.
1.1.3.3.
Phase 3 Studies in Psoriasis (CNTO1959PSO3001, 
CNTO1959PSO3002, and CNTO1959PSO3003)
1.1.3.3.1.
Efficacy
A large global Phase 3 program consisting of 3 studies (CNTO1959PSO3001, 
CNTO1959PSO3002, and CNTO1959PSO3003) is ongoing to investigate the efficacy and safety 
of SC guselkumab in subjects with moderate to severe plaque psoriasis. Guselkumab treatment 
was compared with adalimumab treatment in both CNTO1959PSO3001 and 
CNTO1959PSO3002. Study CNTOPSO3003 was conducted in subjects with an inadequate 
response to ustekinumab.
Guselkumab administered as a 100 mg SC injection at Weeks 0and 4then q8w:  

Provided a rapid, substantial, and clinically meaningful improvement in skin disease as well 
as difficult to treat regional psoriasis resulting in improvements in patient-reported outcomes 
compared with placebo over 16 weeks and adalimumab up to 48 weeks. The superior 
efficacy of guselkumab was evident across all endpoints and thresholds assessed including 
measures of complete clearance of psoriasis as defined by an Investigator’s Global 
Assessment (IGA)0 or a PASI 100 response.
Continuous q8w guselkumab maintenance treatment was significantly more effective at 
maintaining a high level skin response than withdrawal of treatment in study PSO3002.

Guselkumab therapy provided a high level clinical response and treatment benefits among 
adalimumab PASI 90 non-responders in study PSO3002 and ustekinumab inadequate 
responders (IGA≥2) in study PSO3003.
1.1.3.3.2.
Safety
In the Phase 3 pooled safety analysis set (subjects from CNTO1959PSO3002 and 
CNTO1959PSO3003), guselkumab at the dose regimen of 100 mg, administered SC at Weeks 0, 
4 and then q8w, demonstrated a favorable safety profile consistent with that seen in the overall 
population from studies CNTO1959PSO3001 and CNTO1959PSO3002 and was well tolerated 
in adult patients with moderate to severe plaque psoriasis.
1.1.3.4. 
Phase 2 Study in Rheumatoid Arthritis (CNTO1275ARA2001)
Study Design
NCT03158285
CNTO1275ARA2001 was a randomized, double-blind, multicenter, placebo-controlled, 
parallel-group study to evaluate the efficacy and safety of ustekinumab and guselkumab 
administered SC in subjects with active RA despite MTX treatment. In this study, 274 subjects 
with active RA who were on a stable dose of MTX were randomized to receive 1 of 5 treatments: 


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Approved, Date: 23 January 2018
placebo, ustekinumab 90 mg q8w, ustekinumab 90 mg q12w, guselkumab 50mg q8w, or 
guselkumab 200 mg q8w through Week 28 with induction doses at Weeks 0 and 4. After the last 
study agentadministration at Week 28, subjects were followed for safety through Week48.
Conclusions
The primary efficacy endpoint (ACR 20 response at Week 28) was not met in the guselkumab
groupsand no significant improvements were observed in any of the major secondary endpoints 
for the combined guselkumab group. Further development of guselkumab for this indication has 
been discontinued.
Guselkumab was generally well tolerated.
1.2.
Overall Rationale for the Study
1.2.1.
Role of Interleukin-23 and TH17 Pathways in the Treatment of
Psoriatic Arthritis
Interleukin (IL)-23 is a member of the IL-12 family of heterodimeric cytokines. IL-23 shares the 
p40 subunit with IL-12. However, in contrast to IL-12, which is formed from p40/p35 
heterodimers, the p40 subunit is paired with a p19 subunit to form IL-23.
39  IL-23, alone or in 
combination with other cytokines (transforming growth factor-β and IL-6 or IL-1β), drives the 
expansion and/or maintenance of mouse and human CD4+ IL-17 producing T helper 17 (Th17) 
cells. Th17 cells produce downstreampro-inflammatory cytokines, IL-17A, IL-17F, IL-22, IL-6, 
and TNFα.
5,29,50
Inhibition of upstream signaling by IL-23 blockade is expected to interrupt Th17 pathways that 
contribute to the chronic inflammationunderlying the pathophysiology of many immune 
mediated diseases41,48including PsA, psoriasis, multiple sclerosis, inflammatory bowel disease, 
and axial spondyloarthritis.  In addition, susceptibility to psoriasis, PsA, and inflammatory bowel 
disease has been shown to be associated with genetic polymorphisms in IL-23/IL-23R receptor 
(R) components.
2,7,30,38,40
In addition to the robust efficacy demonstrated in the treatment of psoriasis, biologic treatments 
targeting Th17 pathways, including ustekinumab, secukinumab, and ixekizumab, have been 
shownto induce rapid and significant improvement of arthritis and psoriasis in subjects with 
active PsA. The efficacy and safety of ustekinumab, a fully human IgG1κ mAb that binds with 
high affinity and specificity to the shared p40 subunit of both human IL-12 and IL-23, in subjects 
with active PsA have been demonstrated in 3 adequate, placebo-controlled studies (1Phase2 
study, C0743T1020; and 2 Phase 3 studies, CNTO1275PSA3001 [PSUMMIT1]26,31 and 
CNTO1275PSA3002 [PSUMMIT2]
44).  In the Phase 3 PsA studies FUTURE 1,
32  FUTURE 2,36
and SPIRIT-P1,
33 both secukinumab and ixekizumab, the 2 anti-IL17 agents, demonstrated 
significant reduction on signs and symptoms of PsA, improvement of physical function and 
inhibition of structural damage.  The robust efficacy of the treatments targeting Th17 pathways
observed in both psoriasis and PsA, including that demonstrated by guselkumab across all 
efficacy endpointsin the Phase 2 PsA study (CNTO1959PSA2001)(see Section 1.1.3.1
NCT03158285
), 


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highlightsthe central role that IL-23/IL-17 axis has in the pathogenesis of both psoriasis and 
PsA.  
1.2.2.
Study Rationale
Psoriatic arthritisis a multi-faceted disease that impacts the joints, soft tissues, and skin, all of 
which affect quality of life. Up to 42% of patients with moderate to severe psoriasis have PsA. 
There is often a medical need to have a single therapeutic agent to control both skin and joint 
psoriatic symptoms, as well as to control enthesitis, dactylitis, and to prevent joint damage.
Investigation of guselkumab in the current Phase 3 PsA clinical study is supported by the 
following:

Robust efficacy results and a favorable safety profile from a Phase 2 study of guselkumab in 
PsA (Section 1.1.3.1), in whichthe primary and all secondary endpoints were met.
Efficacyand safety results of guselkumab observed in Phase 2 and Phase 3 studies in 
psoriasis (Sections1.1.3.2and 1.1.3.3, respectively).
The purpose of this study is to further define the clinical efficacy of guselkumabin the reduction
of signs and symptoms, and structural damage inhibition and to evaluate the safety profile of 
guselkumab in the treatment of PsA.
1.2.3.
Dose Rationale
Based upon guselkumabclinical efficacy, safety, pharmacokinetics data,and exposure-response 
modeling analysis using data from the Phase 2 study (CNTO1959PSA2001) in subjects with 
PsA, 2dose regimens have been chosen for evaluation in the guselkumab Phase 3 PsA program: 
100mg at Weeks0and 4then every 8 weeks (q8w)
100mg every 4 weeks (q4w)
The rationalefor these dose regimens of guselkumab is presented below in Section 1.2.3.1
(100mg at Weeks 0 and 4 then q8w) and Section 1.2.3.2(100 mg q4w).
1.2.3.1.
Rationale forGuselkumab 100 mg at Weeks 0 and 4 then Every 
8Weeks Dose Regimen
This dose regimenwas evaluated in the Phase 2 PsA study (CNTO1959PSA2001) and in the
3 global Phase 3 studies in psoriasis. In the CNTO1959PSA2001study, robust efficacy and 
clinically meaningful improvement was observed with this dose regimen in all important 
domains of PsA including jointsigns and symptoms, physical function, psoriasis, enthesitis, 
dactylitis, and quality of life in patients with active PsA and ≥3% BSA of psoriasis 
(Section1.1.3.1). Additionally, significant benefit was also observed with this dose regimen 
on plaquepsoriasis in patients with moderate-to-severe psoriasis in the Phase 3 psoriasis
studies (Section 1.1.3.3
NCT03158285
).  


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PsA is a chronic inflammatory arthropathy which can result in irreversible structural damage 
of joints, therefore, rapid control of the disease is desired.  An additional dose is being 
included at Week 4 to ensure that trough guselkumab levels do not fall below those obtained 
at steady-state levels.  This additional Week 4 dose results in a slightly higher Cmax and 
Ctroughin the first 12 weeks than those at steady state (~21% and ~18%, respectively) and 
may result in a more rapid onset of response. However, this dosing regimen is not expected 
to result in substantially higher levels of efficacy at Week 24 than would be achieved by 
q8w dosing during maintenance, ie, from Week 24 and onwards.
The safety of this dosing regimen has been established in a large psoriasis development 
program.Furthermore, the safety profile in the Phase 2 studies in patients with PsA and RA 
is consistent with that seen in the psoriasis program.  

In summary, the efficacy and safety data in both the PsA and psoriasisstudies support 
further evaluation of this dose regimen in the Phase 3 PsA studies, including evaluation of 
its effect on the inhibition ofstructural damage.
1.2.3.2.
Rationale for Guselkumab 100 mg Every4 WeeksDose Regimen
A dose regimen of 100 mg q4w is being included in this study in order to determine ifmore 
frequent dosing may achieve higher efficacy in PsA, including the inhibition of structural 
damage.
Modeling analyses based on data from CNTO1959PSA2001 suggest that a higher or more 
frequent dose regimen may achieve better efficacy in PsA:

Based on population pharmacokinetic modelingand simulation, the 100mg q4w dose 
regimen was predicted to result in an approximately 4-fold higher median steady-state 
trough concentration (3.95 µg/mL) compared to 100 mg q8w (0.99 µg/mL), and higher 
trough concentrations, may provide an opportunity to maximize efficacy, including 
inhibition of structural damage, in PsA.
An exposure-response modeling and simulation analysis based on the data from 
CNTO1959PSA2001 predicted that the 100 mg q4w dose regimen could achieve higher 
efficacy (ie, ACR responses) in PsA patients at Week 16 compared with the q8w dose 
regimen. Conversely, this analysis showed that a lower dose regimen (50 mg q8w) 
could result in lower efficacy (ie, ACR responses).
Treatment with the 100 mg q4w dose regimen is expected to result in acceptable safety 
based on the exposure-safetyanalysis in thePhase 3psoriasisprogram:
No consistent pattern suggesting an association between systemic guselkumab exposure 
quartiles and the rates of occurrence of SAEs or AEs leading to discontinuation was 
evident, with a possible exception of non-serious infections. Moreover, the clinical 
relevance of this finding appears to be limited, given that the vast majority of these 
non-serious infections were mild to moderate in intensity and that the frequency of the 
infections requiring treatment was generally similar across all 4 exposure quartiles.

NCT03158285
Guselkumab has been shown to have an acceptable safety profile in multiple patient 
populations, including with a higher dose regimen thatwas studied in a Phase 2 RA study 
(200mg q8w).  Therefore, guselkumab 100 mg q4w is expectedto be well tolerated in the 
Phase 3 PsA population. 


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Approved, Date: 23 January 2018
Overall, the two dose regimens of guselkumab (100 mg Weeks 0 and 4 then q8wand 100 mg 
q4w) selected for the Phase 3PsAprogramwill allow for an adequate assessment of theoptimal 
benefit/risk profile of guselkumabin PsA.
2.
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS
2.1.
Objectivesand Endpoints
2.1.1.
Objectives
PrimaryObjective
The primary objective of this study is to evaluate the efficacy of guselkumab treatment in 
subjects with active PsA by assessing the reduction in signs and symptoms of PsA.
Secondary Objectives
The secondary objectives are to assess the following for guselkumab treatment:
Efficacy in improving psoriatic skin lesions

Improvement in physical function
Inhibition of progression of structural damage
Efficacy in improving general and disease specific health-related quality of life and patient-
reported health outcomes 

Safety 
Pharmacokinetics, pharmacodynamics (PD), and immunogenicity 
2.1.2.
Endpoints
Note:  Refer to Section 9for evaluations related to endpoints.
Primary Endpoint
The primary endpoint is proportion of subjects who achieve an ACR 20 response at Week 24. 
Major Secondary Endpoints
NCT03158285
1. Change from baseline in HAQ-DI score at Week 24.
2. Proportion of subjects who achieve an ACR 50 response at Week 24.
3. Proportion of subjects with a psoriasis response of an IGA(ie, an IGA psoriasis score of 0 
[cleared] or 1 [minimal] AND ≥2-grade reduction from baseline) at Week 24 among the 
subjects with ≥3% BSApsoriatic involvement and an IGA score of ≥2 (mild) at baseline.
4. Proportion of subjects who achieve an ACR 20 response at Week 16.
5. Change from baseline in modified van der Heijde-Sharp (vdH-S) score at Week24.


CNTO 1959  (guselkumab)
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6. Proportion of subjects with resolution of enthesitis at Week 24 among the subjects with 
enthesitis at baseline.
7. Proportion of subjects with resolution of dactylitis at Week 24 among the subjects with 
dactylitis at baseline.
8. Change from baseline in enthesitis score (based on Leeds Enthesitis Index [LEI]) at 
Week 24 among the subjects with enthesitis at baseline. 
9. Change from baseline in dactylitis score at Week 24 among the subjects with dactylitis at 
baseline. 
10.Change from baseline in 36-item Short Form Health Survey(SF-36) Physical Component 
Summary (PCS)at Week 24.
11.Change from baseline in Disease Activity Score 28 (DAS28) C-reactive protein(CRP) at 
Week 24.
12. Change from baseline in SF-36 Mental Component Summary (MCS)at Week 24. 
13.Proportion of subjects who achieve an ACR 50 response at Week 16.
14.Proportion of subjects who achieve an ACR 70 response at Week 24.
Other SecondaryEndpoints
Endpoints Related to Reduction of Signs and Symptoms and Physical Function
NCT03158285
1. Proportions of subjects who achieve an ACR 20, ACR 50, and ACR 70 responses by visit 
over time through Week 100.
2. Percent change from baseline in ACR components by visit over time through Week 100.
3. Change from baseline in HAQ-DI score by visit over time through Week 100.  
4. Proportion of subjects who achieve a clinically meaningful improvement (a ≥0.35 
improvement from baseline) in HAQ-DI score by visit over time through Week 100 among 
those subjects with HAQ-DI score ≥ 0.35 at baseline.  
5. Proportion of subjects who achieve a DAS28 (CRP) response by visit over time through 
Week 100.
6. Proportion of subjects who achieve a DAS28 (CRP) remission by visit over time through 
Week 100.
7. Change from baseline in DAS28 (CRP) by visit over time through Week 100.
8. Proportion of subjects who achieve a response based on modified Psoriatic 
ArthritisResponse Criteria (PsARC) by visit over time through Week 100.


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NCT03158285
9. Proportion of subjects with resolution of enthesitis by visit by visit over time through 
Week 100 among the subjects with enthesitis at baseline.
10.Proportion of subjects with resolution of dactylitis by visit by visit over time through 
Week 100 among the subjects withdactylitis at baseline.
11.Change from baseline in enthesitis score (based on LEI) by visit over time through 
Week 100 among the subjects with enthesitis at baseline.
12.Change from baseline in dactylitis score by visit over time through Week 100 among the 
subjects with dactylitis at baseline.
13.Change from baseline in Psoriatic ArthritiS Disease Activity Score (PASDAS) by visit over 
time through Week 100.
14.Change from baseline in Group for Research and Assessment of Psoriasis and Psoriatic 
Arthritis(GRAppa) Composite score (GRACE) Index by visit over time through Week 100.
15.Change from baseline in Work Productivity and Activity Impairment Questionnaire(WPAI) 
scores by visit over time through Week 100.
16.Change from baseline in modified Composite Psoriatic Disease Activity Index (mCPDAI) 
score by visit over time through Week 100.
17.Change from baseline in Disease Activity Index for Psoriatic Arthritis score by visit over 
time through Week 100.
18.Proportion of subjects who maintainan ACR 20 response at Week 52 and Week 100 among 
the subjects who achieved an ACR 20 response at Week 24.  
19.Proportion of subjects who maintainan ACR 50 response at Week 52 and Week 100 among 
the subjects who achieved an ACR 50 response at Week 24.  
20.Proportion of subjects who maintainanACR 70 response at Week 52 and Week 100 among 
the subjects who achieved an ACR 70 response at Week 24.  
21.Proportion of subjects who maintain aHAQ-DI response (ie, ≥0.35 improvement from 
baseline in HAQ-DI score) at Week 52 and Week 100 among the subjectswho achieved a 
HAQ-DI response at Week 24.  
22.Proportion of subjects who achieve minimal disease activity (MDA) by visit over time 
through Week 100.
23.Proportions of subjects who achieve a ≥20%, ≥50%, ≥70%, and ≥90% improvement from 
baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score by visit 
over time through Week 100 among the subjects with spondylitis and peripheral joint 
involvement as their primary arthritic presentation of PsA.


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Endpoints Related to Skin Disease
1. Proportions of subjects who achieve ≥75%, ≥90%, and 100% improvement in Psoriatic Area 
and Severity Index (PASI) score from baseline by visit over time through Week 100 among 
the subjects with ≥3% BSA psoriatic involvement and an IGA score of ≥2 (mild) at baseline.
2. Proportion of subjects with an IGA scoreof 0 (cleared) by visit over time through Week 100 
among the subjects with ≥3% BSA psoriatic involvement and an IGA score of ≥2 (mild) at 
baseline.
3. Change from baseline in PASI score by visit over time through Week 100 among the 
subjects with ≥3% BSA psoriatic involvement and an IGA score of ≥2 (mild) at baseline.
4. Proportion of subjects who achieve a Dermatology Life Quality Index (DLQI) score of 0 or 
1 by visit over time through Week 100 among the subjects with baseline DLQI score >1 and 
with ≥ 3% BSA psoriatic involvement and an IGA score of ≥2 (mild) at baseline.
5. Proportion of subjects who achieve ≥ 5-point improvement from baseline in DLQI score by 
visit over time through Week 100 among the subjects with baseline DLQI score ≥ 5 and 
with ≥ 3% BSA psoriatic involvement and an IGA score of ≥2 (mild) at baseline.
6. Change from baseline in DLQI score by visit over time through Week 100 among the 
subjects with ≥ 3% BSA psoriatic involvement and an IGA score of ≥2 (mild) at baseline.
7. Proportion of subjects who achieve both PASI 75 and ACR 20 responses by visit over time 
through Week 100 among the subjects with ≥3% BSA psoriatic involvement and an IGA 
score of ≥2 (mild) at baseline.
8. Proportion of subjects who achieve both PASI 75 and modified PsARC response by visit 
over time through Week 100 among the subjects with ≥3% BSA psoriatic involvement and 
an IGA score of ≥2 (mild) at baseline.
Endpoints Related to Joint Structural Damage
NCT03158285
1. Change from baseline in modified vdH-S score by visit over time through Week 100. 
2. Change in total modified vdH-S score from Week 24 to Week 52, from Week 24 to 
Week 100, and from Week 52 to Week 100.
3. Change from baseline in modified vdH-S erosion score by visit over time through 
Week 100.
4. Change in modified vdH-S erosion score from Week 24 to Week 52, from Week 24 to 
Week 100, and from Week 52 to Week 100.
5. Change from baseline in modified vdH-S joint space narrowing (JSN) score by visit over 
time through Week 100.


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6. Change in modified vdH-S JSN score from Week 24 to Week 52, from Week 24 to 
Week 100, and from Week 52 to Week 100.
7. Change from baseline in modified vdH-S score by region and type of damage (ie, hand 
erosion, hand JSN, foot erosion, foot JSN subscores) by visit over time through Week 100.
8. Proportion of subjects with a change of ≤0 from baseline and proportion of subjects with a 
change of ≤ 0.5 from baseline in modified vdH-S score by visit over time through 
Week 100.
9. Proportion of subjects with a change of ≤0 from baseline and proportion of subjects with a 
change of ≤ 0.5 from baseline in modified vdH-S erosion score at by visit over time through 
Week 100.  
10.Proportion of subjects with a change of ≤0 from baseline and proportion of subjects with a 
change of ≤ 0.5 from baseline in modified vdH-S JSN score by visit over time through 
Week 100.  
11.Proportion of subjects with radiographic progression (based on the smallest detectable 
change [SDC]) from baseline by visit over time through Week 100.
12.Proportionof subjects with radiographic joint erosion progression (based on SDC) from 
baseline by visit over time through Week 100.
13.Proportion of subjects with radiographic JSN progression (based on the SDC) from baseline 
by visit over time through Week 100.
14.Proportion of subjects with pencil in cup or gross osteolysis deformities by visit over time 
through Week 100.
Endpoints Related to Health Related Quality of Life
NCT03158285
1. Change from baseline in PCSscore of the SF-36by visit over time through Week 100.
2. Change from baseline in MCS score of the SF-36by visit over time through Week 100.
3. Change from baseline in domain scales scores of SF-36 by visit over time through 
Week 100.
4. Proportion of subjects who achieve ≥ 5-point improvement from baseline in SF-36 MCS 
score by visit over time through Week 100.
5. Proportion of subjects who achieve ≥ 5-point improvement from baseline in SF-36 PCS 
score by visit over time through Week 100.
6. Change from baseline in Functional Assessment of Chronic Illness Therapy-fatigue 
(FACIT-Fatigue) by visit over time through Week 100.


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7. Proportion of subjects who achieve ≥ 4-point improvement from baseline in FACIT-Fatigue 
score improvement by visit over time through Week 100.
8. Change from baseline in EuroQol five-dimension questionnaire (EQ-5D) Visual Analogue 
Scale (VAS) and in EQ-5D index scores by visit over time through Week 100.
2.2.
Hypothesis
The primary hypothesis is that the guselkumab 100 mg q4w treatment groupis superior to 
placeboas assessed by the proportion of subjects achieving an ACR 20 response at Week 24.
3.
STUDY DESIGN AND RATIONALE
3.1.
Overview of Study Design
This is a Phase 3randomized, double-blind, placebo-controlled, multicenter, 3-arm study of 
guselkumab in subjects with active PsA who are biologic naïveand have had inadequate 
responseto standard therapies (eg, non-biologic DMARDs, apremilast, NSAIDs).  The study will 
include approximately 684 subjects.  Stable dosesof concomitant NSAIDs, oral corticosteroids, 
and selected non-biologic DMARDs (limited to MTX, SSZ, hydroxychloroquine[HCQ], LEF) 
will be allowed (see Table4) but arenot required.
The study consists ofthe following phases:
a screening phase of up to 6 weeks
a blinded treatment phase of approximately 2 years (ie, 100 weeks), including a 
placebo-controlled period from Week 0 to Week 24 and an active treatmentperiodfrom 
Week 24 to Week 100
a safety follow-up phase of 12 weeks after the last administration of study agent.
An overview of the study design is provided in Figure 1. 
At Week 0, approximately 684subjects who satisfy all inclusion and exclusion criteria will be 
randomly assigned to one of the following 3 treatment groups in a 1:1:1ratio using permuted 
block randomization stratified by baseline non-biologic DMARD(MTX, SSZ, HCQ, LEF) use
(yes/no) and the most recent available CRP value prior to randomization(<2.0 mg/dL vs 
≥2.0mg/dL):
Group I(n=228): Subjects will receive SC guselkumab 100 mg q4w from Week 0 through 
Week 100.

Group II(n=228): Subjects will receive SC guselkumab 100 mg at Weeks 0 and 4 then q8w 
(Weeks 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, and 100)and placebo injections at other 
visits (Weeks 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, and 96) to maintain the blind.

Group III
NCT03158285
(n=228): Subjects will receive SC placebo q4w from Week 0 to Week 20and 
will cross over at Week 24 to receive SC guselkumab 100 mg q4w from Week 24 through 
Week 100.


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At Week 16, all subjects in Groups I, II and III with <5% improvement from baseline in both 
tender and swollen joint countswill be considered as meeting early escape criteria. These 
subjectswillremainon the dosing regimen they were to randomizedat Week 0.AtWeek 16, 
subjects who meet early escape criteria will be allowedto initiate or increase the dose of one of 
the permitted concomitant medications up to the maximum allowed dose as specified in Table4, 
as selected by the investigator.  Titration to a stable dose of the medicationshould be completed 
for subjects qualifying for early escape by the Week 24 visit.
At Week 24, all subjects in the placebo group (Group III) will cross over to receive guselkumab 
100 mg SC q4w through Week 100; this will allow for collection of additional safetydata for the 
100 mg SC q4w dose.  Subjects in the guselkumab groups (Groups I andII) will remain on the 
dosingregimenthey were randomized to at Week 0, through Week100.
Subjects will be followed for AEs and SAEs up to 12 weeks following the last study agent 
administration.  The end of the study is defined as the time the last subject completes the last 
studyvisit. For subjects who complete the Week 100 visit, the last study visit is the Week 112 
visit.  For subjects who discontinuestudy agentprior to Week 100, the last study visit is the final 
safety visit.
Database locks (DBLs) are scheduled at Weeks 24, 52, and End of Study(Week 112).  The first 
DBL will occur when all randomized subjects have either completed the Week24 assessments or 
terminated study participation prior to the Week 24 visit (referred to as Week 24 DBL).  The 
second DBL will occur when all randomized subjects have either completed the Week 52 
assessments or terminated study participation prior to the Week 52 visit (referred to as Week 52 
DBL).  The third DBL will occur when all randomized subjects have either completed their final 
safety visitor have terminated study participation(referred to as Final DBL).
An independent Data Monitoring Committee (DMC) will be established to monitor unblinded 
data on an ongoing basis through at leastthe Week 24 DBLto ensurethe continuing safety of the 
subjects enrolled in this study.  Refer to Section 11.12for further detail.
Samples for the analysis of pharmacodynamic biomarkers will be collected from all subjects. 
A pharmacogenomic blood sample will be collected from subjects who consent separately to this 
component of the study where local regulations permit.  Subject participation in 
pharmacogenomic research is optional.
A diagram of the study design is provided in Figure 1
NCT03158285
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Figure 1:
Schematic Overview of the StudyThroughEnd of Study
3.2.
Study Design Rationale
3.2.1.
Study Population
The target study population is subjects with active PsA who are biologic naïve and have had 
inadequate response to standard therapies (eg, non-biologic DMARDs, apremilast, and/or 
NSAIDs). This population is considered appropriate to provide relevant efficacy and safety 
information for the intended use of guselkumab in PsA.  Additionally, a biologic naïve 
population with a CRP ≥0.6 mg/dL is required to enrich the population for radiographic
progression and increase the power for detection of treatment effect on radiographic endpoints.
3.2.2.
Study Control, Randomization, and Blinding 
A placebo control will be used to establish the frequency and magnitude of changes in endpoints 
that may occur in the absence of active treatment.
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Randomization will be used to minimize bias in the assignment of subjects to treatment groups, 
to increase the likelihood that known and unknown subject attributes (eg,demographic and 
baseline characteristics) are evenly balanced across treatment groups, and to enhance the validity 
of statistical comparisons across treatment groups.
Blinded treatment will be used to reduce potential bias during data collection and evaluation of 
clinical endpoints.
3.2.3.
Study Phases and Duration of Treatment
There will be 4phases in this study: Screening, double-blind placebo-controlled, active 
treatment, and safety follow-up. 
The screening phase of up to 6 weeks will allow for sufficient time to perform screening 
study evaluations and determine study eligibility.  

The second phase ofthe study will be the double-blind, placebo-controlled phase from 
Week 0 to Week 24.The primary endpoint is evaluated at Week 24 as guselkumab is 
expected to achieve maximal efficacy between Weeks20 and 24 of treatment basedon the 
findings in the guselkumab Phase 2 study (CNTO1959PSA2001)in PsA. 
The third phase of the study will be the double-blind, active treatment phase from Week 24 
through Week 100. This duration will provide adequate time to evaluate the maintenance of
the efficacy and long-term safety of guselkumab in PsA over a 2-year exposure period.

The fourth phase of the study will be the safety follow-up phase and will be 12weeks from 
the last administration of study agent to the final safety visit. The safety follow-up allows for 
monitoring of the subjectsfor a period equivalent to approximately 5times the half-life of 
guselkumab.  
The placebo-controlled period is limited to 24 weeks.  An early escape option is included in the 
study design to provide additional treatment options for subjects who have <5% improvement in 
swollen and tender joint counts at Week 16. 
3.2.4.
Study Evaluations
Efficacy evaluations chosen for this study were established in previous studiesof therapeutic 
biologic agents for the treatment of PsA.  Patient reported outcomes (PROs) chosen for this study 
are also consistent with clinically relevant measurements that are accepted in the medical 
literature for other studies in PsA and applicable United States/European Union regulatory 
guidance documents.
Subjects will be monitored closely for safety with visits at the clinical site as described in the 
Time and Events Schedule(Table 1and Table 2)while on therapy. Safety monitoring will 
include collecting information on AEs, review of concomitant medications, vital signs, 
laboratory assessments, physical exams, and early detection of TB as described in Section 9.7
NCT03158285
. 
Safety data will be reviewed by the Sponsor’s Medical Monitor on an ongoing basis. An 
independent DMCcomposed of clinicians and statisticians not associated with the conduct of the 
study will review unblinded study data for safety purposes on a periodic basisthroughat leastthe 
Week 24 DBL.


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Serum samples will be collected to evaluate the PK of guselkumab, as well as the 
immunogenicity of guselkumab (antibodies to guselkumab) as described in the Timeand Events 
Schedule(Table 1and Table 2).
DNA and Biomarker Collection
It is recognized that genetic variation can be an important contributory factor to interindividual 
differences in drug distribution and response and can also serve as a marker for disease 
susceptibility and prognosis. Pharmacogenomic research may help to explain interindividual 
variability in clinical outcomes and may help to identify population subgroups that respond 
differently to a drug. The goal of the pharmacogenomic component is to collect deoxyribonucleic 
acid(DNA)to allow the identification of genetic factors that may influence efficacyof
guselkumaband to identify genetic factors associated with PsA.
Biomarker samples will be collected to better understand the biology of PsA, to provide a 
biological assessment of the response of patients to treatment with guselkumab, to analyze 
differences between responders and non-responders, and to determine if the markers can be used 
to classify patients as potential responders prior to treatment.  The goal of the biomarker analyses 
is to evaluatethe pharmacodynamicsof guselkumaband aid in evaluating the drug-clinical 
response relationship.
DNA andbiomarkersamples may be used to help address emerging issues and to enable the 
development of safer, more effective, and ultimately individualizedtherapies.
4.
SUBJECT POPULATION
Adult subjects age 18 and older with active PsA are eligible for the study.
Screening for eligible subjects will be performed within6 weeksbefore the first administration
of the study agent.
The inclusion and exclusion criteria for enrolling subjects in this study are described in the 
following2 subsections. If there is a question about the inclusion or exclusion criteria below, the 
investigator mustconsult with the appropriate Sponsor representativeor delegate and resolve any 
issues before enrolling a subject in the study.  Waivers are not allowed. 
For a discussionof the statistical considerations of subject selection, refer to Section11.2.
4.1.
Inclusion Criteria
Each potentialsubject must satisfy all of the following criteria to be enrolled in the study:
1. Be a man or a woman at least 18 years of age (or the legal age of consent in the jurisdiction 
in which the study is taking place).
2. Have a diagnosis of PsA for at least 6 months before the first administration of study agent 
and meet ClASsification criteria for Psoriatic ARthritis (CASPAR) at screening
(Attachment1
NCT03158285
).


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3. Have active PsA as defined by:
a. At least 5swollen joints and at least 5tenderjoints at screening and at baseline
-AND-
b. CRP≥0.6 mg/dL at screening from the central laboratory.
NOTE: A one-time repeat assessment of CRP level is allowed during the 6-week screening 
phase and the Investigator may consider the subject eligible if the test result is within 
acceptable range on repeat testing in the central laboratory.
4. Have at least 1 of the PsA subsets: distal interphalangeal joint involvement, polyarticular 
arthritis with absence of rheumatoid nodules, arthritis mutilans, asymmetric peripheral 
arthritis, or spondylitis with peripheral arthritis(confirmation of sacroiliitis shouldbe 
performed at the screeningvisit by a locally performed pelvic x-ray [single anterior-
posterior view] unless a pelvic or SI joint x-ray or pelvic magnetic resonance imaging(MRI)
has been previously performed.  Results must be documented).
5. Have active plaque psoriasis, with at least one psoriatic plaque of ≥2cmdiameter or nail 
changes consistent with psoriasis or documented history of plaque psoriasis.
6. Have active PsA despiteprevious non-biologic DMARD,apremilast, and/or NSAID 
therapy.

Non-biologic DMARD therapy is defined as taking a non-biologic DMARD for at least 
3months or evidence of intolerance.
Apremilast therapy is defined as taking apremilast at the marketed dose approved in the 
country where the study is being conductedfor at least 4 months or evidence of 
intolerance.

NCT03158285
NSAID therapy is defined as taking an NSAID for at least 4weeks or evidence of 
intolerance.  
7. If currently using non-biologic DMARDs (limited to MTX, SSZ, HCQ, or LEF), subjects 
should have started treatment at least 3 monthsand the dose must be stable for at least 
4weeksbefore first administration of study agent and should have no serious toxic side 
effects attributable to the non-biologic DMARD. If currently not using MTX, SSZ, or HCQ, 
must not have received for at least 4 weeks before first administration of study agent. If 
currently not using LEF, must not have received for at least 12 weeks before first 
administration of study agent.  
a.
If usingMTX, theroute of administration and dose must bestable and the dose must 
be ≤25mg/week.
b.
If receiving SSZ,the dose must be ≤3g/day. 
c.
If receiving HCQ,the dose must be ≤400 mg/day. 
d.
If receiving LEF, the dose must be ≤20 mg/day.
8. If currently using NSAIDs or other analgesics for PsA,subjects must be on a stable dose for 
at least 2 weeks before first administration of study agent. If currently not using NSAIDs or 
other analgesics for PsA, must not have received NSAIDs or other analgesics for PsA within 
2weeks before first administration of study agent.


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9. If currently using oral corticosteroidsfor PsA,subjects must be on a stable dose equivalent 
to ≤10 mg of prednisone/day for at least 2 weeks before first administration of study agent. 
Ifcurrently not using oral corticosteroids, the subject must not have received oral 
corticosteroids within 2weeks before first administration of study agent.
10.Contraceptive use by men or women should be consistent with local regulations regarding 
the use of contraceptive methods for subject participating in clinical studies.
Before randomization, a woman must be either:
Not of childbearing potential defined as:

Premenarchal: A premenarchal state is one in which menarche has not yet 
occurred.

Postmenopausal: A postmenopausal state is defined as no menses for 12 months 
without an alternative medical cause. A high follicle stimulating hormone (FSH) 
level (>40 IU/L or mIU/mL) in the postmenopausal range may be used to confirm 
a postmenopausal state in women not using hormonal contraception or hormonal 
replacement therapy, however in the absence of 12 months of amenorrhea, a single 
FSH measurement is insufficient.

Permanently sterile: Permanent sterilization methods include hysterectomy, 
bilateral salpingectomy, bilateral tubal occlusion/ligation procedures, and bilateral 
oophorectomy.
Of childbearing potential and practicing a highly effective method of contraception 
(failure rate of <1% per year when used consistently and correctly). Examples of highly 
effective contraceptives include:

User-independent methods: implantableprogestogen-only hormone contraception 
associated with inhibition of ovulation; intrauterine device (IUD); intrauterine 
hormone-releasing system (IUS); vasectomized partner; sexual abstinence (sexual 
abstinence is considered a highly effective method only if defined as refraining 
from heterosexual intercourse during the entire period of risk associated with the 
study drug. The reliability of sexual abstinence needs to be evaluated in relation to 
the duration of the study and the preferred and usual lifestyle of the subject).

User-dependent methods: combined (estrogen- and progestogen-containing) 
hormonal contraception associated with inhibition of ovulation: oral, intravaginal, 
and transdermal; progestogen-only hormone contraception associated with 
inhibition of ovulation: oral and injectable.
Typical use failure rates may differ from those when used consistently and 
correctly. Use should be consistent with local regulations regarding the use of 
contraceptive methods for subjects participating in clinical studies.

NCT03158285
Agree to remain on a highly effective method throughout the study and for at least 
12 weeks after the last dose of study agent.


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Note: If the childbearing potential changes after start of the study (eg, a premenarchal 
woman experiences menarche) or the risk of pregnancy changes (eg, a woman who is not 
heterosexually active becomes active,) a woman must begin a highly effective method of 
contraception, as described throughout the inclusion criteria.
If reproductive status is questionable, additional evaluation should be considered.
11.A woman of childbearing potential must have a negative serum pregnancy test at screening 
and a negative urine pregnancy test at Week 0.
12.A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted 
reproductionfrom first administration of study agent through at least 12 weeks after 
receiving the last administration of study agent.
13.A man who is sexually active with a woman of childbearing potential and who has not had a 
vasectomy must agree to use a barrier method of birth control (eg, either a condom [with 
spermicidal foam/gel/film/cream/suppository if available in their locale] or a partner with an 
occlusive 
cap 
[diaphragm 
or 
cervical/vault 
caps] 
plus 
spermicidal 
foam/gel/film/cream/suppository if availablein their locale), during the study and for at least 
12 weeks after receiving the last administration of guselkumab. All men must also agree to 
not donate spermduring the study and for at least 12 weeks after receiving the last 
administration of guselkumab.
14.Are considered eligible according to the following TB screening criteria:
Have no history of latent or active TB prior to screening. An exception is made for 
subjects who have a history of latent TB and are currently receiving treatment for latent 
TB, will initiate treatment for latent TB prior to first administration of study agent, or 
have documentation of having completed appropriate treatment for latent TB within 
5years prior tothe first administration of study agent. It is the responsibility of the 
investigator to verify the adequacy of previous anti-TB treatment and provide 
appropriate documentation.
Have no signs or symptoms suggestive of active TB upon medical history and/or 
physical examination.
Have had no recent close contact with a person with active TB or, if there has been such 
contact, will be referred to a physician specializing in TB to undergo additional 
evaluation and, if warranted, receive appropriate treatment for latent TB prior tothe 
first administration of study agent.
Within 8weeks prior tothe first administration of study agent, have a negative 
QuantiFERON®-TB Gold test result(Attachment 2), or have a newly identified positive 
QuantiFERON®-TB Gold test result in which active TB has been ruled out and for 
which appropriate treatment for latent TB (Section 9.1.3) has been initiated prior tothe 
first administration of study agent. Within 8weeks prior tothe first administration of 
study agent, a negative tuberculin skin test (Attachment 3), or a newly identified 
positive tuberculin skin test in which active TB has been ruled out and for which 
appropriate treatment for latent TB (Section 9.1.3) has been initiated prior to the first 
administration of study agent, is additionally required if the QuantiFERON®
NCT03158285
-TB Gold 
test is not approved/registered in that country* or the tuberculin skin test is mandated by 
local health authorities.


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Indeterminate results should be handled as outlined in Section 9.1.3.  Subjects with 
persistently indeterminate QuantiFERON®-TB Gold test results may be enrolled 
without treatment for latent TB, if active TB is ruled out, their chest radiograph shows 
no abnormality suggestive of TB (active or old, inactive TB), and the subject has no 
additional risk factors for TB as determined by the investigator. This determination 
must be promptly reported to the Sponsor’s medical monitor and recorded in the 
subject
's source documents and initialed by the investigator.
NOTE: The QuantiFERON®-TB Gold test and the tuberculin skin test (is/are)not 
required to be performed at screening for subjects with a history of latent TB and 
ongoing treatment for latent TB or documentation of having completed adequate 
treatment as described above; subjects with documentation of having completed 
adequate treatment as described above are not required to initiate additional treatment 
for latent TB.

Have a chest radiograph (posterior-anterior view)taken within 3 months prior to the 
first administration of study agent and read by a qualified radiologist, with no evidence 
of current, active TB or old, inactive TB.
15.Agree not to receive a live virus or live bacterial vaccination during the study, or within 
12weeks after the last administration of study agent. 
16.Agree not to receive a bacillus Calmette-Guérin (BCG) vaccination during the study, and 
within 12 months after the last administration of studyagent.
17.Have screening laboratory test results within the following parameters:
a. Hemoglobin
≥8.5 g/dL
(SI: ≥85g/L) 
b. White blood cells
≥3.5 x 103/μL
(SI: ≥3.5 GI/L)
c. Neutrophils
≥1.5 x 103/μL
(SI: ≥1.5GI/L)
d. Platelets
≥100 x 103/μL
(SI: ≥100 GI/L)
e. Serum creatinine
≤1.5 mg/dL
(SI: ≤133 μmol/L)
f. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline 
phosphatase levels must be ≤1.5times the upper limit of normal range for the central 
laboratory conducting the test.
NOTE:
NCT03158285
A one-time repeat of these screening laboratory tests is allowed during the 6-week 
screening phase and the Investigator may consider the subject eligible if the previously 
abnormal laboratory test result is within acceptable the range on repeat testing in the central 
laboratory.
18.Agree to avoid prolonged sun exposure and agree not to use tanning booths or other 
ultraviolet (UV) light sources from the first administration of study agent through 12 weeks 
after the final dose of study agent(for patients with skin lesions or with documented history 
of psoriasis).


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19.Are willing to refrain from the use of complementary therapies for PsA or psoriasis 
including ayurvedic medicine, traditional Taiwanese, Korean, or Chinese medication(s) and 
acupuncture within 2weeks before the first study agent administration and through 
Week 52.
20.Be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
21.Sign an informed consent form (ICF) indicating that he or she understands the purpose of 
and procedures required for the study and is willing to participate in the study.
22.Sign a separate ICF if he or she agrees to provide an optional DNA sample for research 
(where local regulations permit).  Refusal to provide consent for the optional DNA research 
sample does not exclude a subject from study participation.
4.2.
Exclusion Criteria
Any potential subject who meets any of the following criteria will be excluded from participating 
in the study:
1. Has other inflammatory diseases that might confound the evaluations orbenefit of 
guselkumab therapy, including but not limited to RA, axial spondyloarthritis(this does not
include a primary diagnosis of PsA with spondylitis), systemic lupus erythematosus, or 
Lyme disease.
2. Has previously received any biologic treatment including, but not limited to, guselkumab, 
ustekinumab, secukinumab (AIN457), anti-TNFα agents (such as adalimumab, etanercept, 
infliximab, golimumab SC orintravenous [IV], certolizumab pegol, or their respective 
biosimilars), tildrakizumab (MK3222), ixekizumab (LY2439821), brodalumab (AMG827), 
risankizumab (BI-655066), or other investigative biologictreatment for PsA or psoriasis.
3. Has ever received tofacitinib, baricitinib, filgotinib, peficitinib (ASP015K),decernotinib 
(VX-509), or any other Janus kinase (JAK) inhibitor.    
4. Has received any systemic immunosuppressants (eg, azathioprine, cyclosporine, 
6thioguanine, mercaptopurine, mycophenolate mofetil, hydroxyurea, tacrolimus)within
4weeks of the first administration of study agent.
5. Is currently receiving 2 or more non-biologic DMARDs specified in Table4. 
6. Has received non-biologic DMARDs (other than MTX, SSZ, HCQ, LEF)including, but not 
limited to chloroquine, gold preparations, and penicillamine within 4 weeks before the first 
administration of study agent.
7. Has received apremilast within 4 weeksprior to the first administration of study agent.
8. Has received phototherapyor any systemic medications/treatments that could affect 
psoriasis evaluations (including, but not limited to, retinoids, 1,25-dihydroxy vitamin D3 
and analogues, psoralens, fumaric acid derivatives, with the exception of those in Table4
NCT03158285
) 
within 4 weeks of the first administration of study agent. 
9. Has used topical medications/treatments that could affect psoriasis evaluations (including, 
but not limited to, topical or intralesional injection of corticosteroids, anthralin, 
calcipotriene, topical vitamin D derivatives, retinoids, tazarotene, methoxsalen, 
trimethylpsoralens, pimecrolimus, tacrolimus, or topical traditional Taiwanese, Korean, or 
Chinese medicines) within 2 weeks of the first administration of any study agent. 


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10.Has received epidural,intra-articular, intramuscular, or IV corticosteroids, including 
adrenocorticotropic hormone during the 4 weeks before first administration of study agent.
11.Has received lithium within 4 weeks of the first administration of any study agent. 
12.Has received an experimental antibody or biologic therapywithin 6 months prior to the first 
administration of study agent, or received any other experimental therapy, including an 
investigational medical device, or new investigational agent within 90days or 5 half-lives 
(whichever is longer) prior to the first administration of study agent or is currently enrolled 
in another study using an investigational agent or procedure. 
13.Has unstable suicidal ideation or suicidal behaviorin the last 6 months, that may be defined 
as an eC-SSRS rating at screening of: 
Ideation level 4: Some intent to act, no plan;OR

Ideation level 5: Specific plan and intent;OR

NCT03158285
Any ofthe following suicidal behaviors:
– actualsuicide attempts
– interrupted attempts
– abortedattempts
–
preparatory actions
ANDis confirmed to be at risk by the investigator based on an evaluation by a mental health 
professional. The final decision on excluding a subject will be made at the judgment of the 
investigator.
14.Has a history or current signs or symptoms of severe, progressive, or uncontrolled renal, 
hepatic, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, 
rheumatologic (with the exception of PsA), psychiatric, genitourinary, or metabolic 
disturbances. 
15.Has unstable cardiovascular disease, defined as a recent clinical deterioration (eg, unstable 
angina, rapid atrial fibrillation, or transient ischemic attack) in the last 3 months prior to 
screening or a cardiac hospitalization within the last 3 months prior to screening. 
16.Currently has a malignancy or has a history of malignancy within 5 years before screening 
(with the exception of a nonmelanoma skin cancer that has been adequately treated with no 
evidence of recurrence for at least 3 months before the first study agent administration or 
cervical carcinoma in situ that has been treated with no evidence of recurrence for at least 
3months before the first study agent administration). 
17.Has a history of lymphoproliferative disease, including lymphoma; a history of monoclonal 
gammopathy of undetermined significance; or signs and symptoms suggestive of possible 
lymphoproliferative disease, such as lymphadenopathy or splenomegaly. 
18.Has a history of chronic or recurrent infectious disease, including but not limited to chronic 
renal infection, chronic chest infection (eg, bronchiectasis), recurrent urinary tract infection 
(eg, recurrent pyelonephritis or chronic nonremitting cystitis), fungal infection (eg, 
mucocutaneous candidiasis), or open, draining, or infectedskin wounds or ulcers. 
19.Has a transplanted organ (with exception of a corneal transplant >3 months before the first 
administration of study agent). 


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20.Has a history of an infected joint prosthesis, or has ever received antibiotics for a suspected 
infection of a joint prosthesis, if that prosthesis has not been removed or replaced. 
21.Has or has had a serious infection (eg, sepsis, pneumonia, or pyelonephritis) or has been 
hospitalized or received IV antibiotics for an infection within 2 months before screening.
22.Has or has had a herpes zoster infection within 2 months before screening.
23.Iscurrentlypregnant, breastfeeding, or planning a pregnancy (both men and women) within
12 weeks after receiving the last administration of study agent. 
24.Has a nonplaque form ofpsoriasis (eg, erythrodermic, guttate, or pustular). 
25.Has current drug-induced psoriasis (eg, a new onset of psoriasis or an exacerbation of 
psoriasis from beta blockers, calcium channel blockers, or lithium). 
26.Has received, or is expected to receive, anylive virus or bacterial vaccination within 3 
months before the first administration of study agent.
27.Has had a BCG vaccination within 12 months of screening.
28.Has known intolerance or hypersensitivity to any biologic medication, or known allergies or 
clinically significant reactions to murine, chimeric, or human proteins, mAbs, or antibody 
fragments. 
29.Subject has known allergies, hypersensitivity, or intolerance to guselkumab or its excipients 
(refer to Investigator’s Brochure). 
30.Has a history of active granulomatous infection, including histoplasmosis or 
coccidioidomycosis, before screening. Refer to Inclusion Criterion 14for information 
regarding eligibility with a history of latent TB. 
31.Has a chest radiograph within 3 months prior to the first administration of study agent that 
shows an abnormality suggestive of a malignancy, significant cardiovascular or pulmonary 
disease or current active infection, including TB. 
32.Has ever had a nontuberculous mycobacterial infection or opportunistic infection (eg, 
cytomegalovirus, pneumocystosis, aspergillosis). 
33.Is infected with human immunodeficiency virus (HIV, a confirmed positive serology for 
HIV antibody). 
34. Tests positive for hepatitis B virus (HBV) infection (Attachment 4)at screening.
35.Is seropositivefor antibodies to hepatitisC virus (HCV)at screening, unless thesubjecthad 
2 negative HCV ribonucleic acid(RNA)test results at least 6 months apartprior to 
screeningandhavea third negative HCV RNA test result at screening.
NCT03158285
36.Has had major surgery (eg, requiring general anesthesia and hospitalization) within 8 weeks 
before screening, or will not have fully recovered from such surgery, or has such major 
surgery planned during the time the subject is expected to participate in the study 
(112weeks).
Note: Subjects with planned surgical procedures to be conductedunder local anesthesia 
may participate.
37.Is known to have had a substance abuse (drug or alcohol) problem within the previous 
12months prior to the first administration of study agent. 


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38.Is unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack 
of easy access to veins. 
39.Lives in an institution on court or authority order. 
40.Has any condition that, in the opinion of the investigator, would make participation not be in 
the best interest (eg, compromise the well-being) of the subject or that could prevent, limit, 
or confound the protocol-specified assessments. 
41.Is an employee of the investigator or study site, with direct involvement in the proposed 
study or other studies under the direction of that investigator or study site, as well as family 
members of the employees or the investigator. 
42.Is an employee of the Sponsor.
NOTE:
Investigators should ensure that all study enrollment criteria have been met at 
screening and at baseline before randomization. If a subject
's status changes 
(including laboratory results or receipt of additional medical records) before 
randomization such that he or she no longer meets all eligibility criteria, then the 
subject should be excluded from participation in the study. Section 17.4describesthe 
required documentation to support meeting the enrollment criteria.  
4.3.
Prohibitions and Restrictions
Potential subjects must be willing and able to adhere to the following prohibitions and 
restrictions during the course of the study to be eligible for participation:
1. A woman of childbearing potential who is heterosexually active must remain on a highly 
effective method of birth control (Inclusion Criterion10) from the first administration of 
study agent throughat least 12weeks after receiving the last administration of study agent.
2. A woman must not currently be pregnant or breastfeeding and shouldagree to plan to not 
become pregnant.
3. A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted 
reproduction from the first administration of study agent through at least 12 weeks after 
receiving the last administration of study agent.
4. A man who is sexually active with a woman of childbearing potential and has not had a 
vasectomy must agree to use a barrier method of birth control (ie, male condom, female 
diaphragm or cervical cap, or condom, Inclusion Criterion13) from the first administration 
of study agent throughat least 12 weeks after receiving the last administration of study 
agent.  Additionally, he should agree to not plan a pregnancy. 
5. All men must agree to not donate sperm from the first administration of study agent through
at least 12 weeks after receiving the last administration of study agent.
6. Subjects must not receive a live virus or bacterial vaccination during the study and for 
12weeks after the last administration of study agent, with the exception of a BCG 
vaccination, which is prohibited for 12 months after the last administration of study agent; 
see Prohibition 7
NCT03158285
.
7. Subjects must not receive a BCG vaccination during the study and for 12 months after the 
last administration of study agent.


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8. Subjects must comply with restrictions on concomitantmedications and therapies during the 
study as specified in Section 8.
9. Subjects must avoid prolonged sun exposure and not to use tanning booths or other UV light 
sources during the study (for patients with skin lesions or with documented history of 
psoriasis).
5.
TREATMENT ALLOCATIONAND BLINDING
Treatment Allocation
Central randomization will be implemented in this study.  At Week 0, subjects will be randomly 
assigned (1:1:1) to 1 of 3treatment groups (guselkumab 100 mg q4w, guselkumab 100 mg at 
Weeks 0 and 4 then q8w, or placebo) based on a computer-generated randomization schedule 
prepared before the study by or under the supervision of the Sponsor.  Permuted block 
randomization with stratification bythe most recentavailable CRP value prior to randomization
(<2.0 mg/dL vs ≥2.0 mg/dL)and baseline non-biologic DMARD (MTX, SSZ, HCQ, or LEF) use
(yes/no) will be used.  The interactiveweb response system (IWRS) will assign a unique 
treatment code, whichwill dictate the treatment assignment and matching study agent kit for the 
subject. The requestor must use his or her own user identification and personal identification 
number when contacting theIWRSand will then give the relevant subject details to uniquely 
identify the subject.
Blinding
NCT03158285
To maintain the study blind, the study agentcontainer will have a multipart label containing the 
appropriate regulatory requirements for clinical supplies.  Each unit will be uniquely identifiable 
through a medication number. A tear-off label is designed to be torn off, separated from the 
study agentcontainer, and attached to the subject
's source documents. The label will not identify 
the study agentin the container. However, if it is necessary for a subject
's safety, the study blind 
may be broken and the identity of the study agentascertained. The study agentnumber will be 
entered in the case report form (CRF) when the study agentis administered. The study agents
will be identical in appearance and will be packaged in identical containers.
The investigator will not be provided with randomization codes. The codes will be maintained 
within the IWRS,which has the functionality to allow the investigator to break the blind for an 
individual subject.  In general, randomization codes will be disclosed fully only if the study is 
completed and the clinical database is closed.
Under normal circumstances, the blind should not be broken for individual subjects until the End 
of StudyDBLof the study.  Otherwise, the blind should be broken only ifspecific emergency 
treatment/course of action would be dictated by knowing the treatment status of the subject.  In
the event of an emergency, the investigator may determine the identity of the treatment from 
IWRS. It is recommended that the investigator contact the Sponsor or its designee if possible to 
discuss the particular situation, before breaking the blind.  Telephone contact with the Sponsor or 
its designee will be available 24 hours per day, 7 days per week.  In the event the blind is broken, 
the Sponsor must be informed as soon as possible.  The date and reason for the unblinding must 


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be documented by site personnel in theappropriate section of theCRF and in the source 
document.  The investigator is also advised not to reveal the study treatment assignment to the 
study site or Sponsor personnel.
Subjects who have had their treatment assignment unblinded are expected to continue to return 
for scheduled evaluations.  Further study agent administrations should be discussed with the 
study responsible physician.  At the Week 24 DBL, the data will be unblinded for analysis to 
someSponsor personnel while subjects are still participating in the study.  Identification of 
Sponsor personnel who will have access to the unblinded subject-level data will be documented 
prior to unblinding.  Investigative study sites and subjects will remain blinded to initial treatment 
assignment until afterthe final database islocked.
Data that may potentially unblind the treatment assignment (ie, study agent serum 
concentrations, antibodies to study agent, treatment allocation) will be handled with special care 
so that, prior to unblinding, such data will only be available to data management staff for 
purposes of data cleaning and, if applicable, clinical pharmacology representatives for the 
purposes of performing PKand antibodies to guselkumab analyses and quality assurance 
representatives for the purposes of conducting independent drug audits.
A given subject’s treatment assignment may be unblinded to the Sponsor,Institutional Review 
Board/Independent Ethics Committee (IRB/IEC), and site personnel to fulfill regulatory 
reporting requirements.
6.
DOSAGE AND ADMINISTRATION
Guselkumab 100 mg and matching liquid placebo for guselkumab will be provided in a 
single-use prefilled syringe (PFS)assembled with the UltraSafe PLUSTM
NCT03158285
Passive Needle Guard 
(PFS-U).
Study agent will be administered at the site by a health care professional(HCP)until the subject 
(or caregiver) is trained for self-administration. Study agent will be administered by site 
personnel at Week 0 and Week 4.Beginning at Week 8, at the discretion of the investigator and 
subject, and after appropriate and documented training, subjects mayself-administer study agent 
at the investigative site under the supervision of an HCP. A caregiver may also be trained to 
administer study agent. Subjects unable or unwilling to self-administer will continue to have 
study agent injections performed by anHCP. 
The option to begin self-administration of study agent at home will begin after Week 52.After 
Week 52, subjects (or a caregiver) who are able to self-administer will be supplied study agent 
for self-administration away from the site (ie, at home).Subjects will be instructed to contact the 
investigator promptly in the event of any signs of an allergic reaction, infection, or 
bleeding.Subjects unable to have injection(s)administered away from the site will be required 
to return to the site for administration of study agent injection(s)by a health care
professional.After Week 52, subjects will have study visits and assessments at Weeks 68, 76, 
84, 100, and 112.


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Through Week 24, study agent administration at the site should be ± 4 days from the scheduled 
day of study agent administration; afterWeek 24, alladministrations should be ± 7 days from 
scheduled study agent administration day.Study agent administrations must always be at least 
14days apart.
The dose regimens are as follows:
Group I(n=228): Subjects will receive SC guselkumab 100 mg q4w from Week 0 through 
Week 100;
Group II(n=228): Subjects will receive SC guselkumab 100 mg at Weeks 0 and 4 then q8w
(Weeks 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, and 100) and placebo injections at other 
visits (Weeks 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, and 96)to maintain the blind.
Group III(n=228): Subjects will receive SC placebo q4w from Week 0 to Week 20, and 
will cross over at Week 24 to receive SC guselkumab 100 mg q4w from Week 24 through 
Week 100.
At Week 16, all subjects in Groups I, II and III with <5% improvement from baseline in both 
tender and swollen joint counts will be considered as meeting early escape criteria. These 
subjects will remain on the dosing regimen they were randomized to at Week 0.  At Week 16, 
subjects who meet early escape criteria will be allowed to initiate or increase the dose of one of 
the permitted concomitant medications up to the maximum allowed dose asspecified in Table4, 
as selected by the investigator. Titration to a stable dose of the medicationshould be completed 
for subjects qualifying for early escape by the Week 24 visit.
7.
TREATMENT COMPLIANCE
NCT03158285
Study agent will be administered at the investigational site through Week 52and study personnel
will maintain a log of all study agent administrations.Study agent supplies for each subject will 
be inventoried and accounted for.All ongoing therapies administered at the time of screening 
must be recorded.
Subjects will receive instructions on compliance with study treatment when they begin 
self-administration of study agent at home. When subjects begin selfadministration at home, the 
investigator or designated study personnel will maintain a log of all study agentdispensed and 
returned.
When study agent is selfadministered by subjects at home, subjects will record all study drug 
administrationson a diary card.
During the course of the study, the investigator or designated study research personnel will be 
responsiblefor providing additional instruction to reeducate any subject who is not compliant 
with taking the study agent.
Compliance with the treatment schedule is strongly encouraged.  It is understood that treatment 
may be interrupted for health-related or safety reasons.  Therefore, if for any reason a subject 
cannot receive a dose of study agent at the scheduled visit, the subject must make every effort to 


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still come in for the scheduled assessmentsfor that visit.  The dose should be administered 
within 2weeks of that scheduled visit.  The subject should then resume the normal study 
schedule relative to the baseline visit (Week0).  In the case when a subject does not come in to 
the investigational site for a scheduled visit, the site will follow-up with that subject.  Due 
diligence could include telephone calls, certified letters, and email requests. Measures taken to 
obtain follow-up information must be documented.
Study-site personnel will keep a log of all study drug dispensed and will compare the amount of 
study drug dispensed with the amount returned.  Additional details may be provided in the Site 
Investigational Product Manual that is provided separately and noted in Section 15.
All post-baseline visits up to and including Week 24 will have a visit window of ±4days 
counting from Week 0 as Day 1. After Week 24, all visits will have a visit window of ±7 days. 
The Week 112 visitorthe final safety visit (12 weeks after the last dosein subjects who 
discontinued study treatment)will have a visit window of ±14 days.  If a study visit occurs 
outside this window, the Sponsor should be consulted about how the subject should resume his 
or her normal dose schedule.
Information regarding study agentadministrations that are administered outside of the scheduled 
windows or missed will be recorded. Subject charts and worksheets may be reviewedand 
compared with the data entrieson the CRFs to ensure accuracy.
8.
PRESTUDY ANDCONCOMITANT THERAPY
The Sponsor must be notified in advance (or as soon as possible thereafter) of any instances in 
which prohibited therapies are administered.
Every effort should be made to keep subjects’ concomitant medications for PsA stable through 
Week 24or as specified in the following sections. The concomitant medication dose may be 
reduced or temporarily discontinued because of abnormal laboratory values, adverse effects or 
intolerance, concurrent illness, or the performance of a surgical procedure but the change and 
reason for the change should be clearly documented in the subject’s medical record.
Subjects may not be receiving more than one non-biologic DMARD from baseline (see 
Exclusion Criterion 5) through Week 52.  After Week 52 and through the end of the study, 
subjects may receive another non-biologic DMARD.
Permitted concomitant medications for PsA andthe maximum allowed doses during the study as 
specified in the following sections are summarized in Table4
NCT03158285
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Table4:
Permitted Concomitant Medications for PsA and the Maximum Allowed Doses During the 
Study 
Permitted Concomitant Medications
for PsA
a,b
Maximum Allowed Dose
NSAIDs and other analgesics
Marketed dose approved in in the countrywhere 
the study is being conducted
Oral corticosteroids
Equivalent to 10 mg/day of prednisone
Non-biologic DMARDs:
Methotrexate (MTX)c
25 mg/week
Sulfasalazine (SSZ)
3 g/day
Hydroxychloroquine (HCQ)
400mg/day
Leflunomide (LEF)
20 mg/day
a Permitted concomitant medications are not supplied by the Sponsor.
b Subjects may not be receiving more than one non-biologic DMARD frombaseline(see Exclusion 
Criterion 5) through Week 52.  After Week 52 and through the end of the study, subjects may receive 
another non-biologic DMARD.
c It is recommended that all subjects taking MTX in this study receive at least 5 mg oral folate or 5 mg 
folinic acid weekly. Guidelines for dose adjustment in the event of MTX toxicity are included in the 
Trial Center File.
Subjects should not initiate any new treatment for PsA through Week 52, except at Week 16 for 
those subjects who have < 5% improvement from baseline in both tender and swollen joint 
counts (early escape criteria).  Subjects who meet early escape criteriawill be allowed to initiate 
or increase the dose of one of the permitted concomitant medications up to the maximum 
alloweddose as specified inTable4, as selected by the investigator.  Titration to a stable dose of 
the medication should be completed for subjects qualifying for early escape by the Week 24 
visit.
Beginning at Week 52, the treatment options in Table4are allowed to be initiated or dose 
increased up to the maximum allowed dose specified in Table4forsubjects with ongoing PsA 
disease activity at the investigator’s judgment; the rationale should be clearly documented in the 
subject’s medical record.
Concomitant medication review will occur at study visits identified in the Time and Events 
Schedule.
8.1.
Non-biologicDMARDs
8.1.1.
Permitted Non-biologic DMARDs
Subjects are permittedto enterthe study on a stable dose ofone non-biologic DMARD(limited 
to MTX, SSZ, HCQ, or LEF)up to the maximum allowed dose specified in Table4
NCT03158285
.  Only 1 of
thesenon-biologic DMARDs is allowedfrom baseline through Week 52; subjects receiving 2 or 


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more non-biologic DMARDs at baseline are excluded from study participation.  After Week 52 
and through the end of the study, subjects may receive another non-biologic DMARD.
At any time during the study, the dose of the permitted non-biologic DMARD may be reduced or 
temporarily discontinued due to abnormal laboratory values, side effects, concurrent illness, or 
the performance of a surgical procedure. 
Refer to Table5
NCT03158285
for protocol requirements of the permitted non-biologic DMARDs.


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Table5:
Protocol Requirements of the Permitted Non-biologic DMARDs
Permitted Non-
biologic DMARDs
Baseline 
Usage
Prior to Week 0
Week 0 through 
Week 52
Week 52 through Week 
112
Methotrexate (MTX)
Used 
Treatment should have 
started at least 3 
months prior to the 
first administration of 
study agent. MTX 
routes of 
administration and 
doses should be stable 
for at least 4 weeks 
prior to the first 
administration of the 
study agentand must 
be ≤ 25mg/week.
Stable dose and route 
of administration 
(oral, intramuscular, 
or SC permitted) 
required unless early 
escape or 
unacceptable side 
effects
Dose changes allowed up 
to the maximum dose 
specified in Table4or 
change of the route of 
administration, at the 
investigator’s discretion
Not Used
Discontinued at least 4 
weeks prior to the first 
administration of study 
agent
Not allowed unless 
early escape(see 
Section 6)
Allowed up to the 
maximum dose specified 
in Table4at 
investigator’s discretion
Sulfasalazine (SSZ) 
or 
Hydroxychloroquine 
(HCQ)
Used 
Treatment should have 
started at least 3 
months prior to the 
first administration of 
study agent. Dose 
should be stable for at 
least 4 weeks prior to 
the first administration 
of the study agentand 
must be ≤ 3 g/day
(SSZ) or ≤ 400mg/day 
(HCQ).
Stable dose required 
unless early escape or 
unacceptable side 
effects
Dose changes allowedup 
to the maximum dose 
specified in Table4, at the 
investigator’s discretion
Not Used
Discontinued at least 4 
weeks prior to the first 
administration of study
agent
Not allowed unless 
early escape (see 
Section 6)
Allowed up to the 
maximum dose specified 
in Table4at 
investigator’s discretion
Leflunomide (LEF)
Used 
Treatment should have 
started at least 3 
months prior to the 
first administration of 
study agent. Dose 
should be stable for at 
least 4 weeks prior to 
the first administration 
of the study agentand 
must be ≤ 20mg/day.
Stable dose required 
unless early escape or 
unacceptable side 
effects
Dose changes allowed up 
to the maximum dose 
specified in Table4at the 
investigator’s discretion
Not Used
Discontinued at least 
12weeks prior to the 
first administrationof 
study agent. 
Not allowed unless 
early escape (see 
Section 6)
Allowed up to the 
maximum dose specified 
in Table4at 
investigator’s discretion
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8.1.2.
Prohibited Non-biologic DMARDsand Apremilast
All other non-biologic DMARDs (including, but not limited to chloroquine, gold preparations, 
penicillamine) and apremilastmust be discontinued at least 4 weeks prior to the first 
administration of study agent and remain prohibited through Week 112.
8.1.3.
Systemic Immunosuppressive Drugs
Systemic immunosuppressants (including, but not limited to azathioprine, cyclosporine, 
6thioguanine, mercaptopurine, mycophenolate mofetil, hydroxyurea, or tacrolimus) must be 
discontinued at least 4 weeks prior to the first administration of study agent and remain 
prohibited through Week 112.  If any of these systemic immunosuppressants is initiated during 
the study, study agent must be permanently discontinued.
Systemic immunosuppressants do not refer to corticosteroids; see Section 8.2for restrictions 
regarding the use of corticosteroids.
8.2.
Corticosteroids
8.2.1.
Oral Corticosteroids
Subjects using oral corticosteroids at baseline for PsAmust be on a stable dose equivalent to 
≤10mgprednisone per day for at least 2 weeks prior to the first administration of study agent 
and continue on this dose through Week 52 unless early escape atWeek 16 (see Section 3).  
After Week 24 and through Week 52, a one-time dose decrease in oral corticosteroids is allowed.
Starting at Week 52, the dose and type of oral corticosteroid may be adjusted, at the discretion of
the investigator, for subjects with ongoing PsA disease activity.  
Otherwise, throughout the study, the dose and type of oral corticosteroid may be changed at the 
discretion of the investigator only if the subject develops unacceptable side effects. 
Subjects not using oral corticosteroids at baseline for PsA must have discontinued oral 
corticosteroidsat least 2weeks prior to the first administration of study agent and must not 
receive oral corticosteroids through Week 52 of the study for PsA. An exception is made for 
subjects who qualify for early escape at Week 16 (see Section 3).
8.2.2.
Corticosteroids –Intravenous, Intramuscular, or Epidural 
Administration 
NCT03158285
Intravenous, intramuscular, or epidural administration of corticosteroids for the treatment of PsA 
arenot allowed through Week 112.  
Long-term, (>2 weeks), oral or IV corticosteroid use for indications other than PsA or psoriasis 
isnot allowed through Week 112.  Short-term (≤2 weeks) oral, IV, intramuscular, or epidural 
corticosteroid used for indications other than PsA should be limited to situations where, in the 
opinion of the investigator, there are no adequate alternatives.


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8.2.3.
Corticosteroids –Intra-articular Injection 
Attempts should be made to avoid intra-articular corticosteroid injections for PsA, especially 
during the first 24 weeks of the study.  However,if necessary, subjects may receive up to 2 
intra-articular, tendon sheath, or bursal corticosteroid injections in no more than 2 affected sites 
within any 24-week period of the study.  In the case of severe tenderness or swelling in a single 
joint, it is suggested that the subject be evaluated for infection prior to receiving an intra-articular 
corticosteroid injection.
8.2.4.
Corticosteroids –Other Routes of Administration
Inhaled, otic, ophthalmic, intranasal, and other routes of mucosal delivery of corticosteroids for 
indicationsother than PsA and psoriasis are allowed throughout the course of the study.
8.3.
Nonsteroidal Anti-inflammatory Drugs and Other Analgesics
For subjects receiving NSAIDs, including aspirin and selective cyclooxygenase 2 inhibitors, or 
other analgesics for PsA at baseline, treatment with a stable dose of NSAIDs or other analgesics 
should have been initiated at least 2 weeks prior to the first administration of study agent and 
continue through Week 52 unless early escape at Week 16 (see Section 3).  The dose 
administered should be the usual marketed dose approved in the country where the study is being 
conducted. 
The useof topical analgesics including capsaicin and diclofenac is allowedand should be 
recorded in the CRF. For topical and analgesic patches, the dose should be stable through 
Week 52 and may be changed only if the subject develops unacceptable side effects.
Subjects not receiving NSAIDs or other analgesics for PsA at baseline must have discontinued 
NSAIDs or other analgesics at least 2 weeks prior to the first administration of study agent and 
must not receive NSAIDs or other analgesics for PsA through Week 52 of the study.  An 
exception is made for subjects who qualify for early escape at Week 16 (see Section 3).
Starting at Week 52, subjects with ongoing PsA disease activity can initiate or increase the dose 
of NSAIDs or other analgesics based on the investigator’s clinical judgment.
At any time during the study, the dose of NSAIDs or other analgesics may be reduced or 
temporarily discontinued due to abnormal laboratory values, side effects, concurrent illness, or 
the performance of a surgical procedure.
Use of NSAIDs and other analgesics for indications other than PsA are permitted throughout the 
study.
8.4.
Biologic Agents, Cytotoxic Drugs, JAK Inhibitors, or Investigational 
Agents
NCT03158285
The concomitant use of biologic agents, cytotoxic agents, JAK inhibitors, and investigational 
drugs is not allowed.  Biologic agents include, but are not limited to golimumab, anakinra, 
etanercept, adalimumab, infliximab, ustekinumab, alefacept, efalizumab, rituximab, natalizumab, 


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certolizumab pegol, tildrakizumab (MK3222), secukinumab (AIN457), ixekizumab 
(LY2439821), brodalumab (AMG827), and respective biosimilars as applicable.  Cytotoxic 
agents include, but are not limited to chlorambucil, cyclophosphamide, nitrogen mustard, and 
other alkylating agents.  JAK inhibitors include, but are not limitedto tofacitinib, baricitinib, 
filgotinib, peficitinib (ASP015K),and decernotinib (VX-509).  If any of these medications are 
used,study agent must be permanently discontinued.
8.5.
Complementary Therapies
The use of complementary therapies, including ayurvedic medicine, traditional Chinese 
medications or non-medicinal therapy such as acupuncture for PsA or psoriasis, is not allowed 
from 2 weeks prior to the first administration of study agent through Week 52.  
8.6.
Topical Therapy and Ultraviolet B Light
Concurrent use of topical medications/treatments for psoriasis (eg, topical or intralesional 
corticosteroids, keratolytics (with the exception of salicylic acid shampoos, which are allowed 
throughout the study), coal tar (with the exception of coal tar shampoos, which are allowed 
throughout the study), anthralin, vitamin D3 analogues, or topical tacrolimus, and retinoids) are 
not permitted through Week 24.  
Use of salicylic acid-and tar-containing shampoos is not permitted on the morning prior to a 
study visit; non-medicated shampoos may be used on the day of a study visit.
Low and mid-potency topical or intralesional corticosteroids (Class III-VII) may be used after 
Week 24 for psoriasis. High and ultra-high potency corticosteroids (Class I and II) are prohibited 
through Week 112. 
Phototherapy including UVB or tanning beds are not permitted during the study through 
Week 112.  Subjects shouldbe encouraged to avoid prolonged sun exposure during the study.  
8.7.
Systemic Therapy for Psoriasis
Concurrent use of systemic therapy for psoriasis (eg, psoralen with ultraviolet light A, systemic 
retinoids, cyclosporine or tacrolimus, with the exception of those in Table4) must be 
discontinued at least 4 weeks prior to the first administration of study agent and is not permitted 
through Week 112; if a systemic antipsoriatic treatment (except those in Table4) is initiated 
during the study, study agent must be permanently discontinued.
9.
STUDY EVALUATIONS
9.1.
Study Procedures
9.1.1.
Overview
The Time and Events Schedule (Table 1and Table 2
NCT03158285
) summarizes the frequency and timing of 
efficacy, PK, immunogenicity, biomarker, and safety measurements applicable to this study.


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For women of childbearing potential only, additional serum or urine pregnancy tests may be
performed, as determined necessary by the investigator or required by local regulation, to 
establish the absence of pregnancy at any time during the subject
's participation in the study. 
Also additional TB tests may be performed as determined necessary bythe investigator or 
required by local regulation.
Except at the screening visit, all PRO assessments should be conducted/completedbefore any 
tests, procedures, or other consultations at all other visits as specified in the Time and Events 
Schedule to prevent influencing subject perceptions.  For additional detailsand the order for 
which that are to be performed, refer to the PRO user manuals.
To minimize unnecessary x-rays, it is recommended that subjects have the baseline radiographs 
of hands and feet taken after the inclusion and exclusion criteria have been checked and the 
subject appears eligible to enter the study.  All eligible subjects shouldhave radiographs taken 
approximately 2 weeks but not greater than 4 weeks prior to randomization.
During screening, each subject will be provided with an electronic device to enter study-related 
dataas applicable. Study-site personnel will train the subjects on how to use the electronic
device, including instructions to capture the data according to the study design.
9.1.2.
Blood SampleCollection
Blood samples should be collected at the visits indicated in the Time and Events Schedule. The 
date and time of collection will be recorded. When blood samples are to be collected for safety, 
PK, efficacy, biomarkers, and pharmacogenomics/epigenetic evaluations at the same time point, 
the order of blood draws will be samples for: CRP, chemistry/lipids, hematology, 
PK/Immunogenicity, serum biomarkers, pharmacogenomics, epigenetics, and RNA expression.
The total blood volume tobe collected in this study from each subject will be approximately 
313.5mL.  Subjects who consent to participate in the optional pharmacogenomics will have an 
additional blood volume collected of approximately 50 mL, for a total of approximately
363.5mL.  
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the 
samples.
9.1.3.
ScreeningPhase
NCT03158285
Screening procedures will be performed as indicated in the Time and Events Schedule.
After written informed consent has been obtained and within a period of 6 weeks before 
randomization, all screening evaluations will be performed. The screening visit may be 
completed in a single visit or may be divided into more than 1 visit. 
It is recommended thatafter obtaining informed consent, the investigator complete all laboratory 
tests at the first visit. The subject may then return for the remainder of the screening procedures 
only if the subject is eligible for the study as determined by the central laboratory test results. 


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Subjects who meet all of the inclusion and none of the exclusion criteria will be enrolled in the 
study.  Subjects who chose to participatein the optional pharmacogenomicsresearch component 
of the study must provideconsenton a separateICF.
The recording of AEs and concomitant medications will start after the signing of the informed 
consent and will continue until the last study-related procedure has been completed.
If the screening is a single visit, the electronic Columbia-Suicide Severity Rating Scale
(eC-SSRS) (Lifetimeversion) shouldbeperformed after the joint assessment(after signing 
informed consent). If the screening visit is divided into more than 1 visit, the eC-SSRS shouldbe 
performed after the joint assessment andafter the subject is determined to be eligible by the 
central laboratory test results.  
Females of childbearing potential must have a negative serum pregnancy testprior to 
randomization and a negative urine pregnancy test at all dosing visits prior to administration of 
study agent. Femalesof childbearing potential and males capable of fathering a child must 
consent to use a highly effective method of contraception and continue to use contraception for 
theduration of the study and for at least 12weeks after receiving the last administration of 
blinded study agent. The method(s) ofcontraception used by each subject must be documented. 
For details, see Section4.1.
A 12-lead electrocardiogram (ECG) will be performed locally at baseline prior to administration 
of study agent to ensure that,should the subject require an ECG during the study for any reason,
an ECG before first study agentadministration is available for comparison to detect changes.
A chest radiograph (posterior-anterior view) will be performed at screening to ensure that the 
subject does not have any abnormality suggestive current, active TB or old, inactive TB. Chest 
radiographs taken up to 3 months before the first administration of study agentmay be used.  
The BASDAI will be completed only in subjects with spondylitis with peripheral arthritis as their 
primary arthritic presentation of PsA(confirmation of sacroiliitis shouldbe performed at the 
screeningvisit by a locally performed pelvic x-ray [single anterior-posterior view] unless a
pelvic or SI joint x-ray or pelvic MRI has been previously performed.  Results must be 
documented).       
Subjects as outlined inInclusion Criterion14must undergo testing for TB (Attachment 2or 
Attachment 3) and their medical history assessment must include specific questions about a 
history of TB or known occupational or other personal exposure to individuals with active TB.  
The subject should be asked about past testing for TB, including chest radiograph results and 
responses to tuberculin skin or other TB testing.  Investigators have the option to use both the 
QuantiFERON®-TB Gold test and the tuberculin skin test to screen for latent TB if they believe, 
based on their judgment, that the use of both tests is clinically indicated in order to evaluate a 
subject who has high risk of having latent TB.  If either the QuantiFERON®
NCT03158285
-TB Gold test or the 
tuberculin skin test is positive, the subject is considered to have latent TB infection for the 
purposes of eligibility for this study.


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Subjects with a negative QuantiFERON®-TB Gold test result (and a negative tuberculin skin test 
result in countries in which the QuantiFERON®-TB Gold test is not approved/registered*orthe 
tuberculin skin test is mandated by local health authorities) are eligible to continue with 
prerandomization procedures. Subjects with a newly identified positive QuantiFERON®-TB 
Gold or tuberculin skin test result must undergo an evaluation to rule out active TB and initiate 
appropriate treatment for latent TB.  Appropriate treatment for latent TB is defined according to 
local country guidelines for immunocompromised patients.  If no local country guidelines for 
immunocompromised patients exist, United Statesguidelines must be followed, or the subject 
will be excluded from the study.
* Exceptions are made for those countries where the tuberculin skin test is not feasible due to 
various reasons (eg, shortage of test reagents) with the permission of respective health 
authorities, as applicable.
A subject whose first QuantiFERON®-TB Gold test result is indeterminate should have the test 
repeated.  In the event that the second QuantiFERON®-TB Gold test result is also indeterminate, 
the subject may be enrolled without treatment for latent TB if active TB is ruled out, their chest 
radiograph shows no abnormality suggestive of TB (active or old, inactive TB), and the subject 
has no additional risk factors for TB as determined by the investigator.  This determination must 
be promptly reported to the Sponsor’s medical monitor and recorded in the subject
's source 
documents and initialed by the investigator.
Subjects will undergo screening for HBV (Attachment 4) and antibodies to HCV and HIV.
The baseline radiographs of the hands and feet must be taken prior to randomization. To 
minimize unnecessary x-rays, it is recommended that subjects have the baseline radiographs of 
hands and feet taken after the inclusion and exclusion criteria have been checked and the subject 
appears eligible to enter the study.  All eligible subjects shouldhave radiographs taken 
approximately 2 weeks but not greater than 4 weeks prior to randomization.
Retesting
The re-testing of abnormal screeninglaboratory blood tests and CRP levels,which are 
exclusionary,is allowed only once using an unscheduled visit during the screening period (to 
reassess eligibility).
Repeat Screening
NCT03158285
If a subject was a screen failure in the past but currently the subject is expected to be able to meet 
the subject eligibility criteria, the subject may be screened again on one occasion only after 
consultation with the Sponsor(ie, study responsible physician, scientists,or designee). For the 
second screening, the subject will be assigned a new subject number, and must undergo the 
informed consent process and all other screening procedures again as in the Time and Events 
Schedule.


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Chest x-raysand radiographs of hands and feet, if done within the specified allowed time, are not 
required to be repeated.
If the QuantiFERON®-TB Gold test and/or the tuberculin skin test was positive in the first 
screening, these tests should not be repeated.  Also, if the QuantiFERON®-TB Gold test and 
tuberculin skin test were done within the specified allowed time, they should not be repeated.
9.1.4.
Treatment Phase
The treatment phase includes the placebo-controlled and active treatment phases. At Week 0, 
eligible subjects will be randomly assigned to receive 1 of 3treatments:  guselkumab SC 100 mg 
q4w, guselkumab SC 100 mg at Weeks 0 and 4 then q8w, or placebo SC. For additional details, 
see Section 6. Safety and efficacy assessments must be performed before study agent
administration as noted in the Time and Events Schedule.
Early Detection of Active Tuberculosis
To aid in the early detection of TB reactivation or new TB infection during study participation, 
subjects must be evaluated for signsand symptoms of active TB at scheduled visits (refer to 
Time and Events Schedule) or by telephone contact approximately every 8 to 12 weeks if a 
subject misses scheduled visits.  The following series of questions is suggested for use during the 
evaluation:
“Have you had a new cough of >14 days’ duration or a change in a chronic cough?”
“Have you had any of the following symptoms:
Persistent fever?
Unintentional weight loss?
Night sweats?”
“Have you had close contact with an individual with active TB?” (If there is uncertainty 
as to whether a contact should be considered “close,” a physician specializing in TB 
should be consulted.)
If the evaluation raises suspicion that a subject may have TB reactivation or new TB infection, 
an immediate and thorough investigation should be undertaken, including, where possible, 
consultationwith a physician specializing in TB.
Investigators should be aware that TB reactivation in immunocompromised subjects may present 
as disseminated disease or with extrapulmonary features.Subjects with evidence of active TB 
should be referred for appropriate treatment.
Subjects who experience close contact with an individual with active TB during the conduct of 
the study must have a repeat chest radiograph, a repeat QuantiFERON®-TB Goldtest, a repeat 
tuberculin skin test in countries in which the QuantiFERON®
NCT03158285
-TB Gold test is not 
approved/registered or the tuberculin skin test is mandated by local health authorities, and, if 
possible, referral to a physician specializing in TB to determine the subject’s risk of developing 


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active TB and whether treatment for latent TB is warranted.  If the QuantiFERON
®-TB Gold test 
result is indeterminate, the test should be repeated as outlined in Section 9.1.3.  
Subjects should be encouraged to return for all subsequent scheduled study visits according to 
the protocol.
Columbia-Suicide Severity Rating Scale
At all visitsexcept during screening, the eC-SSRS (Since Last Contactversion) shouldbe the 
first assessment/questionnaire that the subject must complete.
9.1.5.
PostTreatment Phase (Follow-Up)
All subjects who complete the Week 100 visit assessments will be asked to return for a final 
safety visitat Week 112.
Subjects Who Discontinue Study Agent
Prior to Week 24
If a subject discontinues study agent before the Week 24 visit, the subject should return for all 
visitsthrough Week 24. The final safety visit assessments will be conducted atthenext 
scheduled visit that occurs approximately 12 weeks after the last administration of studyagent.  
If a subject discontinues before the Week 24 visit and after the Week 12study agent 
administration, the subject should return for the Week 24 visit and also 12 weeks after the last 
administration of study agent for a final safety visit(refer to the Week 112 visit in Table 1and 
Table 2).   
For subjects who discontinue study agent prior to Week 24, radiographs of the hands and feet 
should be performed at the time of study agent discontinuation. If the discontinuation occurs 
prior toor at Week 16, the subject should also have radiographs performed at the Week 24 visit. 
If the discontinuation occurs after Week 16, the radiographs do not need to be repeated at 
Week 24.
At or After Week 24 andPrior to Week 100
If a subject discontinues study agent at or after Week 24 and before the Week 100 visit, the final 
efficacy visit (refer to the Week 100 visit in Table 2) should be performed as soon as possible. 
The subject should return 12 weeks after their last dose for their final safety visit(refer to the 
Week 112 visit in Table 2
NCT03158285
).  
Forsubjects who permanently discontinue study agent after Week 24 but prior to Week 100, 
radiographs of hands and feet should be performed at the time of discontinuation of study agent
or as soon as possible unless another set of radiographs has been obtained within the past 
6weeks.


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Subjects Who Discontinue Study Participation
For subjects who discontinue study participation at any time during the study,radiographs of the 
handsand feet should be performed at the time of study discontinuation unless another set of 
radiographs has been obtained within the past 6 weeks.
No proceduresand evaluations should be conducted after a subject withdraws consent.
9.2.
EfficacyEvaluations
Efficacy assessments will be performed at the site by applicablesite personnel trained by the 
Sponsor asindicated in the Time and Events Schedule.
9.2.1.
Psoriatic Arthritis Response Evaluations
9.2.1.1.
Joint Assessment
NCT03158285
Each of 68 joints will be evaluated for tenderness, and each of 66 joints will be evaluated for 
swelling (hips are excluded for swelling).
An independent joint assessor (IJA) with adequate training and experience in performing joint 
assessments will be designated at each study site to perform all joint assessments. The IJA 
should preferably be a rheumatologist but if a rheumatologist is not available, it should be a 
health care provider with at least 1 year ofexperience in performing joint assessments.  Health 
care providers with less than 1 year of experience may serve as an IJA based upon the discretion 
and approval of the Sponsor. It is strongly recommended that the designated IJA identify an 
appropriate back-up IJA for coverage in the event of absences of the designated IJA. It is 
strongly recommended that the same IJA who performs the baseline joint assessments for a 
subject should also perform the joint assessments for that subject at every subsequent visit 
through Week 52. 
Through Week 112, the IJA should have no other contact with the subject once the subject is 
randomized, should not be the treating physician, should not discuss the subject’s clinical status 
with the subject or other site personnel during the joint assessment, and will not be permitted to 
review the subject’s medical records or the CRFs, or any of the previous joint assessments. The 
IJA should maintain a neutral attitude during joint assessment and should limit interactions with 
the subject only to activities associated with performing joint assessmentor enthesitis or 
dactylitis assessments.
The IJA will perform only joint assessmentsand enthesitis and dactylitis assessments; this
individual will not perform or assist in any other assessments in this study such as but not limited 
to administering patient and/or physician global assessments or administering study agent.
The Sponsor will provide training for each site’s designated IJA prior to the screening of the first 
subject at each site. A back-up IJA must complete training before performing a joint assessment 
for a subject’s study visit.  


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If an IJA was trained by the Sponsor (with joint assessments) in a previous clinical study within 
the last 3 years and there is adequate documentation of this training (certification), that training 
will be considered adequate for this study; however, repeat training prior to start of the study is 
encouraged. Training documentation of each IJA should be maintained at the study site.
All IJA performing the joint evaluation at a site must be listed on the Delegation Log at the study 
site.
9.2.1.2.
Nonevaluable Joints
While it may be reasonable in clinical practice to identify as nonevaluable any joint which in the 
past or during study participation has been surgically altered (ie, prosthesis placement) or 
medically treated (ie, intra-articular injection), the designation of nonevaluable joints for the 
purposes of this study is slightly different.
Joints should only be designated as “non-evaluable” by the IJA if it is physically impossible to 
assess the joint (ie, joint inaccessible due to a cast, joint not present due to an amputation, or a 
recent wound near or at the joint so as to make it impossible to assess).  In all other cases, the 
IJA should assess each joint for tenderness and swelling (hips are excluded for swelling).  This 
should be completed regardless of any visual indications of prior surgeries (eg, scars) or 
knowledge they may have of a subject’s prior joint procedures/injections (eg, if the subject was 
the IJA’s patient prior to study participation).
9.2.1.3.
American College of Rheumatology Response
American College of Rheumatology responses are presented as the numerical measurement of 
improvementin multiple disease assessment criteria. For example, an ACR 20 response
10is 
defined as:
1. ≥20% improvement from baseline in both swollen joint count (66 joints) and tender joint 
count (68 joints),
AND
2. ≥20% improvement from baseline in 3 of the following 5 assessments:
Patient’s assessment of pain (VAS)
Patient’s Global Assessment of Disease Activity (arthritis, VAS)
Physician’s Global Assessment of Disease Activity (VAS)
Patient’s assessment of physical function as measured by HAQ-DI

NCT03158285
CRP
ACR 50 and ACR 70similarly defined except improvement threshold from baseline is 50%and 
70%, respectively.


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9.2.1.4.
Dactylitis Assessment
Presence and severity of dactylitis will be assessedby theIJA in both hands and feet using a 
scoring systemfrom 0 to 3 (0 –no dactylitis, 1 –mild dactylitis, 2 –moderate dactylitis, and 3 –
severe dactylitis)
17,19. 
The Sponsor will provide dactylitis assessment training.  Documentation of this training will be 
maintained in the study site’s training files. Previous dactylitis assessment training by the 
Sponsor within the last 3 years with adequate documentation (eg, training certification) will be 
considered adequate for this study; however, repeat training prior to start of the study is 
encouraged.
It is strongly recommended that the same person who performs the baseline dactylitis 
assessmentsfor a subject should also perform the dactylitis assessments for that subject at every 
subsequent visit through Week 100.
9.2.1.5.
Enthesitis Assessment
Enthesitis will be assessed by the IJA using the LEI.
21  The LEI was developedto assess 
enthesitis in subjects with PsA, and evaluates the presence or absence of pain by applying local 
pressure to the following entheses:
Lateral epicondylehumerus, left and right

Medial femoral condyle, left and right

Achilles tendon insertion, left and right
The Sponsor will provide enthesitis assessment training.  Documentation of this training will be 
maintained in the study site’s training files. Previous enthesitis assessment (LEI) training by the 
Sponsor within the last 3 years with adequate documentation (eg, training certification) will be 
considered adequate for this study; however, repeat training prior to start of the study is 
encouraged.
It is strongly recommended that the same person who performs the baseline enthesitis 
assessments for a subject should also perform the enthesitis assessments for that subject at every 
subsequent visit through Week 100.
9.2.1.6.
Imaging Evaluation
NCT03158285
Single radiographs of the hands (posteroanterior) and feet (anteroposterior) will be performed at 
visits as specified in the Time and Events Schedule.  To minimize unnecessary x-rays, it is 
recommended that subjects have the baseline radiographs of hands and feet taken after the 
inclusion and exclusion criteria have been checked and the subject appears eligible to enter the 
study.  All eligible subjects shouldhave radiographs taken approximately 2 weeks but not greater 
than 4 weeks prior to randomization; and at Week 24, Week 52,and Week 100 within ±2weeks 
of the scheduled visit.


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Subjects Who Discontinue Study Agent
For subjects who discontinue study agent prior to Week 24, radiographs of the hands and feet 
should be performed at the time of study agent discontinuation. If the discontinuation occurs
prior to or at Week 16, thesubjectshould also have radiographs performed at the Week 24visit. 
If the discontinuation occurs after Week 16, the radiographs donot need to be repeated at 
Week24.
Forsubjects who permanently discontinue study agent after Week 24 but prior to Week 100, 
radiographs of hands and feet should be performed at the time of discontinuation of study agent 
or as soon as possible unless another set of radiographs hasbeen obtained within the past 
6weeks.
Subjects Who Discontinue Study Participation
For subjects who discontinue study participationat any time duringthe studyradiographs of the 
hands and feet should be performed at the time of study discontinuation unless another set of 
radiographs has been obtained within the past 6 weeks.
The radiographs will be evaluated by central independent readers and scored using total modified 
vdH-S score. Totalmodified vdH-Sis an original vdH-S score
51,modified for the purpose of 
PsA radiological damage assessment, by addition of distal interphalangeal jointsof the hands and 
assessment of pencil in cup and gross osteolysis deformities. The total modified vdH-S score 
includes the joint erosion score and the JSNscore.The joint erosion score is a summary of 
erosion severity in 40 joints of the hands and 12 joints in thefeet. Each hand joint is scored, 
according to surface area involved, from 0 indicating no erosion through 5 indicating extensive 
loss of bone from more than one half of the articulating bone.  Because each side of the foot joint 
is graded on this scale, the maximum erosion score for a foot joint is 10. Thus, the maximal 
erosion score is 320.  TheJSN score summarizes the severity of JSN in 40 joints in the hands and 
12 joints of the feet. Assessment of JSN is scored from 0 through 4, with 0 indicating no JSN and 
with 4 indicating complete loss of joint space, bony ankylosis, or complete luxation. Thus, the 
maximal JSN score is 208 and 528 is the worst possible total modified vdH-S score for PsA.
Detailed information on the acquisition of radiographs will be provided in an Imaging Manual 
and the Central Read Campaigns will be defined in the Imaging Charter.
9.2.1.7.
Disability Index of the Health Assessment Questionnaire
The functional status of the subject will be assessed by the HAQ-DI.
13 This 20-question 
instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional 
areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily 
living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, 
indicating inability to perform a task in that area (ie, lower scores are indicative of better 
functioning). Properties of the assessment have been evaluated and its validity in PsA has been 
determined.25  It has also been shown to be responsive to changes in a subject’s disease.
34  In 
PsA, a decrease in score of 0.35has been determined to indicate a meaningful improvement.
NCT03158285
35


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9.2.1.8.
Minimal Disease Activity
The PsA MDA criteria are a composite of 7 outcome measures used in PsA. Subjects are 
classified as achieving MDA if they fulfilled 5 of 7 outcome measures: tender joint count ≤1; 
swollen joint count ≤1; psoriasis activity and severity index ≤1; patient pain VAS score of ≤15; 
patient global disease activity VAS (arthritis and psoriasis) score of ≤20; Health Assessment 
Questionnaire (HAQ) score ≤0.5; and tender entheseal points ≤1.
6
9.2.1.9.
Psoriatic Arthritis Disease Activity Score
The PASDAS is calculated using the following variables: patient global VAS (arthritis and 
psoriasis, to 0–100), physician global VAS (range0–100), swollen joint count(0-66), tender 
joint count(0-68), CRP level (mg/L), enthesitis (measured by the LEI), tender dactylitis count 
(scoring each digit from 0–3 and recoding to 0–1, where any score >0 equaled 1), and, finally, 
the PCS scale of the SF-36 health survey.
24,23
PASDAS= {[(0.18 × √Physician global VAS) + (0.159 × √Patient global VAS) –(0.253 × 
√SF36 –PCS) + (0.101 × LN (Swollen joint count + 1)) + (0.048 × LN (Tender joint count + 1)) 
+ (0.23 × LN (Leeds Enthesitis Count + 1)) + (0.377 × LN (Dactylitis count + 1)) + (0.102 × LN 
(CRP + 1))] +2} ×1.5
The cutoffs for disease activity are 3.2 (low) to 5.4 (high).
22
9.2.1.10.
Group for Research and Assessment of Psoriasis and Psoriatic 
Arthritis (GRAppa) CompositeScore (GRACE)
The GRAPPAComposite score(GRACE) is a composite score of Group for Research and 
Assessment 
of 
Psoriasis 
and 
Psoriatic 
Arthritis 
(GRAPPA), derived 
as 
GRACEIndex=(1 -AMDF) x 10, where, AMDF is the Arithmetic Mean of the Desirability 
Function (AMDF).
22-24
The AMDF is calculated by transforming the followingvariables, using predefined algorithms 
and expressing the total score as amean with a score range of 0–1, where 1 indicates a better 
state than0:22, 23
Tender joint count (0-68)
Swollen joint count (0-66)
HAQ-DI score(0-3)
Patient’s global assessment of disease activity (arthritis and psoriasis, 0-100VAS)
Patient’s assessment of skin disease activity (0-100 VAS)
Patient’s global assessment of disease activity (arthritis) (0-100 VAS)

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Psoriatic arthritis Quality of Life Index (PsAQoL) which is derived as follows:
PsAQoL = 25.355 + (2.367 × HAQ-DI) –(0.234 × SF-PCS) –(0.244 × SF-MCS), 
where,
o HAQ-DI: HAQ-DI score (0-3)
o SF-PCS: PCS score of SF-36 Health Survey
o SF-MCS: MCS score of SF-36 Health Survey.
9.2.1.11.
Disease Activity Index Score 28
The DAS28 using CRP is a statistically derived index combining tender joints (28 joints), 
swollen joints (28 joints), CRP, and Patient’s Global Assessment of Disease Activity (GH).
52  
The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist,
metacarpophalangeal (MCP) 1, MCP2, MCP3, MCP4, MCP5, proximal interphalangeal (PIP1), 
PIP2, PIP3, PIP4, PIP5 joints of both the upper right extremity and the upper left extremity as 
well as the knee joints of lower right and lower left extremities.  The DAS28 using CRP is a
continuous parameter and is defined as follows:
DAS28(CRP) = 0.56 × SQRT(TEN28) + 0.28 × SQRT(SW28) + 0.36 × ln (CRP+1) + 
0.014 × GH + 0.96;where:

TEN28 is 28 joint count for tenderness

SW28 is 28 joint count for swelling

Ln (CRP+1) is natural logarithm of (CRP value [mg/L] + 1)
SQRT(TEN28) is square root of TEN28
SQRT(SW28) is square root of SW28
GH is Patient’s Global Assessment of Disease Activity (arthritis).
DAS Response
To be classified as a DAS28 responder, subjects should have a good or moderate response.  The 
DAS28 response criteria are defined in Table 6.
53
Table 6:
DAS Response
Improvement in DAS28 score
Present DAS28 score
> 1.2
> 0.6 to 1.2
0.6
3.2
Good response
Moderate response
No response
> 3.2 to 5.1
Moderate response 
Moderate response
No response
> 5.1
Moderate response
No response
No response
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9.2.1.12.
Modified Composite Psoriatic DiseaseActivity Index
The mCPDAIassesses 4 domains (joints, skin, entheses, and dactylitis). The mCPDAI scores are 
calculated using the following assessments: joints (66 swollen and 68 tender joint counts), 
HAQ-DI score, PASI, dactylitis, and enthesitis. Within each domain a score (range 0–3) is 
assigned according to predefined cutoffs
23, as below. The scores for each domain are then added 
together to givea final score range of 0 to 12.
9.2.1.13.
Disease Activity Index for Psoriatic Arthritis
Disease Activity Index for Psoriatic Arthritis is calculated as the sum of the following 
components: tender joint count (0–68), swollen joint count (0–66), CRP level (mg/dL), patient 
assessment of painfor pain (0–10VAS), and patient globalassessment ofdisease activity 
(arthritis, 0 –10VAS).
23  The cutoffs for disease activity are 18.5 (low) to 45.1 (high).
22
9.2.1.14.
Modified Psoriatic Arthritis Responder Criteria
Subjects will be assessed using the modified PsARC.  A subject is considered a responder if they 
have improvement in at least 2 of the following criteria, including at least one of the joint criteria 
and with no deterioration in the other criteria
42:
≥ 30% decrease in the swollen joint count(66joints);

≥ 30% decrease in the tender joint count(68joints);

≥ 20% improvement in the patient
's overall assessmentof disease(arthritis) on a VAS; 
and
≥ 20% improvement in the physician’s overall assessment of disease on a VAS. 
9.2.1.15.
Bath Ankylosing Spondylitis Disease Activity Index
The BASDAI was developed as a subject self-assessment for ankylosing spondylitisthat consists 
of 6 questions relating to the 5 major symptoms of ankylosing spondylitis.
14  Only subjects with 
spondylitis with peripheral arthritis as their primary arthritic presentation of PsA will complete 
the BASDAI using a 10-unit VASto indicate the degree of their symptoms overthe past week 
on the following criteria:
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A. Fatigue
B. Spinal pain
C. Joint pain
D. Enthesitis
E. Qualitative morning stiffness
F. Quantitative morning stiffness
The BASDAI score = 0.2 (A + B + C + D + 0.5[E + F]).  Higher scores indicate greater disease 
severity and a score decrease of 50% or 2 points is considered clinically meaningful(49).
58
9.2.2.
Psoriasis Response Evaluations
9.2.2.1.
Investigator’s Global Assessment of Psoriasis
The IGA documents the investigator’s assessment of the subject’s psoriasis at a given time point. 
Overall lesions are graded for induration, erythema, and scalingusing 0 (no evidence), 
1(minimal), 2 (mild), 3 (moderate) and 4 (severe) scale. The IGA score of psoriasis isbased 
upon theaverageof induration, erythema and scaling scores.The patient’spsoriasis is assessed 
as cleared(0), minimal(1), mild (2), moderate (3), or severe (4).
Every effort should be made to ensure that the physician or designee who performed the IGA
evaluations for a subject at baseline should also perform the IGAevaluations for the subject at all 
subsequent visits through Week 52. The Sponsor will provide IGAtraining. Documentation of 
this training will be maintained in the site’s training files. Previous IGAtraining by the Sponsor 
within the last 3 years with adequate documentation (eg, training certification) will be considered 
adequate for this study; however, repeat training prior to start of the study is encouraged.
9.2.2.2.
Psoriasis Area and Severity Index
The PASI is a system used for assessing and grading the severity of psoriatic lesions and their 
response to therapy.
12  The PASI produces a numeric score that can range from 0 to 72. A
PASI75 response is defined as ≥75% improvement in PASI score from baseline; PASI 90 and 
PASI 100 are similarly defined.
Every effort should be made to ensure that the physician or designee who performed the PASI 
evaluations for a subject at baseline should also perform the PASI evaluations for the subject at 
all subsequent visits through Week 52. The Sponsor will provide PASI training. Documentation 
of this training will be maintained in the site’s training files. Previous PASI training by the 
Sponsor within the last 3 years with adequate documentation (eg, training certification) will be 
considered adequate for this study; however, repeat training prior to start of the study is 
encouraged.
9.2.2.3.
Dermatology Life Quality Index
The DLQI questionnaire is frequently used to assess the patient’s perspective on the impact of 
skin disorders on daily living.  The development of the instrument included a wide variety of 
dermatologic conditions.
11  The content validity and other psychometric properties were further 
assessed in a subsequent study in patients with psoriasis9and other conditions
1
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.  The DLQI, a 


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10item instrument, has 4 item response options, and has a recall period of 1 week.  The total 
score of DLQI range from 0-30 with lower scores indicating lesser impact of psoriasis on the 
patients’ daily lives. In dermatologic disease, a change of 5 points has been determined to be 
meaningful.
27
9.2.3.
Other Patient Reported Outcomes
9.2.3.1.
36-Item Short-form Health Survey
The SF-36questionnaire was developed as part of the Rand Health Insurance Experiment and 
consists of 8 multi-item domain scales:
Limitations in physical functioning due to health problems;

Limitations in usual role activities due to physical health problems;
Bodily pain;
General mental health (psychological distress and well-being);
Limitations in usual role activities due to personal or emotional problems;
Limitations in social functioning due to physical or mental health problems;
Vitality (energy and fatigue);

General health perception.
These scales are scored from 0 to 100 with higher scores indicating better health. Another 
algorithm yields 2 summary scores, the PCS and the MCS. These summary scores are also scaled
with higher scores indicating better health but are scored using a norm-based system where linear 
transformations are performed to transform scores to a mean of 50 and standard deviations of 10, 
based upon generalUSpopulation norms.
54  It has been demonstrated in a study of patients with 
RAthat a change of 4.4 in PCS and 4.7 in MCS was the minimally important change.
28There is 
no specific cut-off for a clinically meaningful change in patients with PsA and a conservative 
threshold of ≥5 points change in both PCSand MCS have been used in the clinical studiesto 
define clinically meaningful improvement for various diseases.  The concepts measured by the 
SF-36 are not specific to any age, disease, or treatment group, allowing comparisonof relative 
burden of different diseases and the relative benefit of different treatments.
55
9.2.3.2.
EQ-5D Questionnaire
The EQ-5D is a standardized measure of health status developed by the EuroQoL Group to 
provide a simple, generic measure of health for clinical and economic appraisal.
8
NCT03158285
  TheEQ-5D is 
applicable to a wide range of health conditions and treatments.  EQ-5D essentially consists of 2 
elements:  The EQ-5D descriptive system and the EQ VAS.  The EQ-5D descriptive system 
comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and 
anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate 
problems, severe problems, and extreme problems.  The respondent is asked to indicate his/her 
health state by ticking (or placing a cross) in the box against the most appropriate statement in 
each of the 5 dimensions.  This decision results in a 1-digit number expressing the level selected 


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for that dimension.  The digits for 5 dimensions can be combined in a 5-digit number describing 
therespondent’s health state,which can be converted into a single summary index (EQ-5D 
index) by applying a formula that attaches values (also called weights) to each of the levels in 
each dimension.  The EQ VAS records the respondent’s self-rated health ona vertical line, VAS 
where the endpoints are labeled ‘Best imaginable health state’ and ‘Worst imaginable health 
state’.  The EQ VAS can be used as a quantitative measure of health outcome as judged by the 
individual respondents.
9.2.3.3.
Functional Assessment of Chronic Illness Therapy -Fatigue
Fatigue has been identified as an important symptom and a unique concept in addition to the core 
disease measures of patients with PsA.
4 The FACIT-Fatigue questionnaire consists of 13 
questions that assess a subject’s level of fatigue and tiredness over the last 7 days.  Each question 
is graded on a 5-point scale (0 = not at all; 1=a little bit; 2 = somewhat; 3 = quite a bit; 4 = very 
much); accordingly, scores can range from 0 to 52.  Lower scores reflect more severe fatigue.  
Although not developed for PsA, FACIT-Fatiguehas demonstrated strong internal consistency 
and test-test reliability.  It distinguishes between healthy and PsA patients and is correlated with 
swollen joint count and actively inflamed joint count.  In rheumatology, a change of 4points is 
considered meaningful and has been used in the PsA population.
3
9.3.
Health Economics
The Work Productivity and Activity Impairment Questionnaire -Specific Health Problem 
(WPAI-SHP) is a validated instrument that has been used to study the impact of various diseases 
on 
patients’ 
ability 
to 
work 
and 
perform 
daily 
activities 
(http://www.reillyassociates.net/WPAI_General.html).  The WPAI:PsA assesses the impact of 
PsA on work and other daily activities during the past 7 days. The WPAI: PsA consists of six 
questions to determine employment status, hours missed from work due to PsA, hours missed 
from work for other reasons, hours actually worked, the degree to which AS affected work 
productivity while at work and the degree to which PsA affected activities outside of work. Four 
scores are derived: percentage of absenteeism, percentage of presenteeism (reduced productivity 
while at work), an overall work impairment score that combines absenteeism and presenteeism 
and percentage of impairment in activities performed outside of work. Greater scores indicate 
greater impairment.
9.4.
Pharmacokinetics and Immunogenicity
Serum samples will be used to evaluate the PK of guselkumabas well as the immunogenicity of 
guselkumab (antibodies to guselkumab). Serum collected for PK and immunogenicity analyses 
may additionally be used to evaluate safety or efficacy aspects that address concerns arising 
during or after the study period. Genetic analyses will not be performed on these serum samples. 
Subject confidentiality will be maintained.
9.4.1.
Serum Collection and Handling
NCT03158285
Venous blood samples will be collected at the time points shown in the Time and Events 
Schedule for the determination of serum guselkumab concentrations and antibodies to 


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guselkumab. Serum samples will also be collected at the final visit from subjects who terminate 
study participation early. At visits where PK and immunogenicity will be evaluated, 1 blood 
draw of sufficient volume can be used. Each sample will be split into 3 aliquots (1 aliquot for 
serum guselkumab concentration, 1 aliquot for antibodies to study agent, and 1 aliquot as a 
back-up). Samples must be collected before study agent administration at visits when a study 
agent administration is scheduled. The exact dates and times of blood sample collection must be
recorded in the laboratory requisition form.
A random venous blood sample for population PK analysis will be collected from all subjects on 
any day between Weeks 4 to 12, except on the days of the scheduled study visit at Weeks 4, 8, 
and 12.  Additionally, this blood sample must be collected at least 24 hours prior to or after the 
actual time of study agent administration at Weeks 4, 8, or 12 (ie, it cannot be collected within 
24 hours before or after study agent administration).  Each population PK serum sample will be 
split into 2 aliquots (1 aliquot for serum guselkumab concentration and 1 aliquot as a back-up 
sample).  
Additional information about the collection, handling, and shipment of biological samples can be 
found in the Laboratory Manual.
9.4.2.
Analytical Procedures
Serum samples will be analyzed to determine serum guselkumab concentrations using a 
validated, specific, and sensitive immunoassay method bytheSponsor’s bioanalytical facility or 
under the supervision of the Sponsor. The Sponsor, or its designee, under conditions in which the 
subjects’ identity remains blinded, will assay these samples.  
9.4.3.
Pharmacokinetic Parameters
If feasible, the apparent total systemic clearance and apparent volume of distribution of 
guselkumab will be estimated using a nonlinear mixed-effects modeling approach.
9.4.4.
Immunogenicity Assessments
Antibodies to guselkumab will be detected using a validated immunoassay method in serum 
samples collected from all subjects according to the Time and Events Schedule. Serum samples 
that test positive for antibodies to guselkumab will be further characterized to determine if 
antibodies to guselkumab could neutralize the biological effects of guselkumab in vitro (ie, 
neutralizing antibodies [NAbs] to guselkumab). All samples will be tested by the Sponsor or 
Sponsor
's designee.
9.5.
Biomarkers
NCT03158285
Samples for serum biomarkers will be collected for all subjects as indicated in the Time and 
Events Schedule.
Samples for the analysis of pharmacodynamic biomarkers will be collected from all subjects. 
The samples will be used to better understand the biology of PsA, to provide a biological 
assessment of the response of patients to treatment with guselkumab, to analyze differences 


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between responders and non-responders, and to determine if the markers can be used to classify 
patients as potential responders prior to treatment. They may also be used to develop tests/assays 
related to guselkumab and PsA. Serum samples will be used to analyze inflammation and 
spondyloarthropathy related proteins. Markers related to the biology of PsA, including (but not 
limited to) Th17, IL-17A, IL-17F, IL-21, IL-22 and IL-23, metabolomics and bone homeostasis 
pathways will also be measured. Ribonucleic acidfrom whole blood samples will be used for 
gene expression analysis to determine the molecular profile of PsA and to assess changes in gene 
expression post guselkumab treatment.
9.6.
Pharmacogenomics (DNA) Evaluations
A whole blood sample will be utilized for pharmacogenomics evaluation.  The analysis may 
includecompletegenome-wide testing and/or targeted sequencing.  The testing will be done to 
search for links of specific genes to disease or response to drug. Genes of interestmay include 
(but are not limited to) HLA-B27 and HLAcw6.  DNA methylation testing may also be
performed. Only DNA research related to guselkumab or to the diseases for which this drug is 
developed will be performed. Pharmacogenetics testing as well as methylation testing will be 
undertaken in this study in consenting subjects.   Subjects participating in this portion of the 
study must sign a separate informed consent. Further, a subject may withdraw such consent at 
any time without affecting their overall participation in the study.
9.7.
Safety Evaluations
Safety assessments will be collected for all subjects as indicated in the Time and Events 
Schedule.
The safety and tolerability of study agent (guselkumab and placebo) will be monitored by 
collectinginformation on AEs(including injection site and allergic reactions), clinical laboratory 
tests, physical examinations, vital signs, suicidalideation or behavior (using the eC-SSRS 
questionnaires), concomitant medication review,and early detection of TB, as specified in the 
Time and Events Schedule. Serum and/or plasma samples collected for PK or PD analyses may 
also be used to evaluate safety concerns that may arise during or after the study period.
Detailsregarding the independent DMC are provided in the DMC Charter.
Safety will be monitored through Week 112. Any clinically relevant changes occurring during
the study must be recorded on the AE section of the CRF.
Clinicallyimportant abnormalities persisting at the end of the study/early withdrawal may be 
followed by the investigator until resolution or until a clinically stable endpoint is reached.
9.7.1.
Evaluations of Safety and Tolerability
NCT03158285
The study will include the following evaluations of safety and tolerability according to the time 
pointsprovided in the Time and Events Schedule: 


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Adverse Events
Adverse events will be reported by the subject for the duration of the study. Adverse events will 
be followed by the investigator.
At each of the visits, subjects will be questioned about the occurrence of new AEs since the 
previous visit, or the outcome of any AEs reported at previous visits.
Allergic Reactions
The Sponsor will proactively monitor reported AEs and query the study site, if necessary, to 
capture anaphylactic reaction/serum sickness events in the CRFs.
Injection-Site Reactions
An injection site reaction is any unfavorable or unintended sign that occurs at the study agent 
injection site. Any adverse reaction (eg, pain, erythema, and/or induration) should be noted on 
the AE page of the CRF.
Through Week 52, all subjects will be carefully observed at the study site for at least 30 minutes 
after the SC injection of study agentfor symptoms of an injection-site reaction. If an injection 
site reaction is observed, the subject should be treated at the investigator’s discretion. Subjects 
self-administering study agentaway from the study site will be trained in the recognition and 
documentation of injection site reactions.
Clinical Laboratory Tests
Blood samples for serum chemistry and hematology will be collected. The investigator must 
review the laboratory report, document this review, and record any clinically relevant changes 
occurring during the study in the AE section of the CRF. The laboratory reports must be filed 
with the source documents.
All abnormal laboratory values will be evaluated for clinical significance by the investigator. If 
clinically significant abnormal laboratory values (in the opinion of the investigator) are detected, 
the test(s) should be repeated as necessary and in discussion with the study responsible 
physician.
Instructions for the collection, handling, and shipping of blood samples are provided in the 
Laboratory Manual.
The following tests will be performed by the central laboratory:

NCT03158285
Hematology Panel
-hemoglobin
-neutrophils
-hematocrit
-bands
-red blood cell count
-eosinophils
-white blood cell count
-basophils


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-lymphocytes
-platelets
-monocytes
Serum Chemistry Panel
-sodium
-calcium
-potassium
-albumin
-chloride
-total protein
-alkaline phosphatase
-ALT
-blood urea nitrogen (BUN)
-bicarbonate
-creatinine
-total bilirubin, with fractionation if 
hyperbilirubinemia
-glucose
-uric acid
-AST

Lipid Panel
-total cholesterol
-high density lipoprotein cholesterol
-low density lipoprotein cholesterol
-triglycerides
Serology:HBV, including HBV serology and HBV DNA (when indicated),antibodyto 
HCV and HCV RNA (when indicated), and antibody to HIV.
Rheumatoid Factor test (optional, if needed for checking CASPAR criteria at screening)
High sensitivity CRP
FSHis optional. It is only needed for determining childbearing potential of a female subject 
of any age with amenorrhea for less than 12 months. In the absence of 12 months of 
amenorrhea, 2 FSH measurements are needed.FSH is not needed for female subjects with 
amenorrhea for at least 12 months or any female subject of childbearing potential. Refer to 
Inclusion Criterion 10for detail.
Pregnancy Testing
Women of childbearing potential must have a negative serum pregnancy test at screening and a 
negative urine pregnancy test at baseline before randomization. Additionally, urine pregnancy 
testing is required for all women of childbearing potential at every study agent administration 
visit. Pregnancy tests must be completed and the result must be negative before the 
administration of any agent for that visit. All pregnancy test results must be recorded in study 
source documents.
Electrocardiogram
NCT03158285
(ECG)
A supine 12-lead ECG will be performed locally at Week 0prior to administration of study 
agent, asspecified in the Time and Events Schedule. A full 12-lead ECG will be recorded and


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the ECG data,including a copy of tracing as well as interpretation,should be stored in the 
subject
's source document.
PhysicalExamination
Physical examinations will be performed by the investigator or designated physician as specified 
in the Time and Events Schedule. Any abnormalities or changes in severity noted during the 
review of body systems should be documented in the source document.
Height and Weight 
Height and weight will be measured as specified in the Time and Events Schedule.  
Vital Signs
Blood pressure and heart rate measurements will be assessed at the time points specified in the 
Time and Events Schedule.
If any clinically significant changes in vital signs are noted, they must be reported as AEs and 
followed to resolution, or until reaching a clinically stable endpoint.
9.7.2.
Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS)
No signal of suicidal ideation and behavior has been observed in the clinicaltrials of guselkumab 
to date.
However, in lightof the recent reports concerning suicidal ideation and behavior in patients with 
plaquepsoriasis treated with an IL-17R antagonist (brodalumab), the eC-SSRS will be used as a 
screening tool to prospectivelyevaluate the potential of guselkumab to induce suicidal ideation 
and behavior.The eC-SSRS measures five possible levels of suicidal ideation and four possible 
suicidal behaviors, as well as non-suicidal self-injurious behavior. The assessment is a fully-
structured, subject self-report eC-SSRS questionnaire, including standardized questions, follow-
up prompts, error handling routines, and scoring conventions.
37,43Two versions of the eC-SSRS 
will be used in this study, the Lifetimeversion and the Since Last Contactversion. TheLifetime
version will be conducted during the screening visit and the Since Last Contact
NCT03158285
version will be 
conductedat all other visits through Week 112.
Subjects will complete the eC-SSRS questionnaire using the Sponsor-provided electronic tablets
(or throughanInteractive Voice Response System [IVRS], if available). Studysite personnel 
will train the subjects on how to use the electronic deviceand/or a telephone system. The 
eCSSRS will be provided in the local languages in accordance with local guidelines.
The eC-SSRS will be performed during each evaluation visit according to the Time and Events
schedule. During a visit, subjects will be directed to a private, quiet place with the electronic 
deviceand/or a telephoneto complete the assessment. Subjects who do not have suicidal 
behavior or ideation will answer a limited number of questions and will usually complete the 
assessment in about 3minutes. Subjects with significant suicidal ideation and behavior may 
require up to 10 minutes to answer all relevant questions. The eC-SSRS should be performed 


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after the joint assessment at the screening visit (after signing informed consent). At Week 
0/baselineand at all post-baseline visits,the eC-SSRS will be the first assessment/questionnaire 
that the subject completesprior to study agent administration.
At the conclusion of each assessment, the site will receive an eC-SSRS Findings Report. At 
screening (In the last 6 months”) and Week 0, subjects with anIdeation level (1-5)or any 
suicidal behaviors or with a response of “YES” for non-suicidal,self-injurious behaviormust be 
determined to be not at risk by the investigator based on an evaluation by a mental health 
professional in order to be randomized. Subjects with anIdeation level (1-5)on the eC-SSRS or 
any suicidal behaviors or with a response of “YES” for non-suicidal,self-injurious behavior at 
any post-baseline visit will also be referred to an appropriate mental health professional for 
evaluation. If a subject’s psychiatric disorder can be adequately treatedwith psychotherapy 
and/or pharmacotherapy then the subject, at the discretion of the investigator, should be 
continued with treatment. Ultimately, the determination of suicidality and risk is up to the 
investigator’s clinical judgment following evaluationby a mental health professional (eg, 
psychiatrist, psychologist, or appropriately trained social worker or nurse).
Positivereports are generated from the eC-SSRS vendor for ANY of the following findings:
Ideation level 4: Some intent to act, no plan
Ideation level 5: Specific plan and intent

Behaviors: Actualsuicide attempts
Behaviors: Interrupted attempts
Behaviors: Aborted attempts
Behaviors: Preparatory actions.
Negativesuicidality indication reports are generated from the eC-SSRS vendor when there are 
NO indications of the above.
The subject should not be released from the site until the eC-SSRS Findings Report (both for 
negative and positive reports) is reviewed by theinvestigator and the subject’s risk has been 
assessed and follow-up determined, as appropriate.
Foreach Ideation Level and Behavior, the following actions and associated alerts will be 
generated, if applicable:
No ideation with No Behaviors: No further action is needed. 
Ideation Levels (1-5) or suicidal behavior: Subject risk assessed and referral to a mental 
health professional.

NCT03158285
Ideation Level of a 1, 2, or 3with No Behaviors: Negative findings report will be 
generated.


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Ideation Level of a 4 or 5 or any suicidal behavior: Positive findings report will be 
generated. When the system reports that the subject has a positive suicidal indication 
(including for an incomplete-positiveassessment), the site will be immediately notified 
by fax/email and a telephone call from the eC-SSRS vendor.
Non-suicidal, self-injurious behavior = YES: Subject risk assessed and referral to a mental 
health professional. Negative findings report will be generated.
Interruption or the discontinuation of study treatment should be considered for any subject who 
reports suicidal IdeationLevel 4(someintentto act, no plan), Ideation Level 5 (specific plan and 
intent), or anysuicidal behavior(actual suicide attempts, interrupted attempts, aborted attempts, 
or preparatory actions) on a post-baseline(after Week 0)eC-SSRS assessment and who is 
deemed to be at risk by the investigator based upon evaluation by a mentalhealth professional. 
Discussion of such subjects with the medical monitor or designee is required (See Section 10.2). 
The final decision on suitability for continuing in the study will be made by the investigator.
Any eC-SSRS findings, which in the opinion of the investigator arenew or considered to be a 
worsening and clinically significant, should be reported on the AE eCRF (see Section 12).
9.7.3.
Anticipated Events
Anticipatedevents will be recorded and reported in this study. 
An anticipated event is an AE (serious or non-serious) that commonly occurs as a consequence 
of the underlying disease or condition under investigation (disease related) or background 
regimen.
For thepurposes of this study the following events will be considered anticipated events:
Worsening of psoriasis
Worsening of PsA
These events will be captured on the CRF and in the database, and will be reported to the 
Sponsor as described in All Adverse Events(Section 12.3.1
NCT03158285
). Any event thatmeets SAE criteria
will be reported to the Sponsor within the appropriate timeline as described in Serious Adverse 
Events. These anticipated events are exempt from expedited reporting as individual single cases 
to Health Authorities. However, if based on an aggregate review, it is determined that an 
anticipated event is possibly related to study agent, the Sponsor will report these events in an 
expedited manner.
An Anticipated Event Review Committee (ARC) will be established to perform reviews of 
pre-specified anticipated events at an aggregate level. The ARC is a safety committee within the 
Sponsor’s organization that is independent of the Sponsor’s study team. The ARCwill meet to 
aid in the recommendation to the Sponsor’s study team as to whether there is a reasonable 
possibility that an anticipated event is related to the study agent.


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Details of statistical analysis of anticipated events, including the frequency of review and 
threshold to trigger an aggregate analysis of anticipated events will be provided in a separate 
Anticipated Events Safety Monitoring Plan.
9.8.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in thelaboratory requisition 
form. Refer to the Time and Events Schedule for the timing and frequency of all sample
collections.
Instructionsfor the collection, handling, storage, and shipment of samples are found in the 
Laboratory Manual that will be provided. Collection, handling, storage, and shipment of samples 
must be under the specified, and where applicable, controlled temperature conditions as indicated 
in the Laboratory Manual.
10.
SUBJECT COMPLETION/DISCONTINUATION OF STUDY 
TREATMENT/WITHDRAWALFROM THE STUDY
10.1. Completion
A subject will be considered to have completed the study if he or she has completed assessments 
at Week 112 of the study. Subjects who prematurely discontinue study treatment for any reason 
before completion of the final safety visit at Week 112will not be consideredto have completed 
the study.
10.2. Discontinuation of Study Treatment
A subject will not be automatically withdrawn from the study if he or shehasto discontinue
treatment before the end of the treatment regimen.
A subject
'sstudy treatment mustbe discontinued if:
The investigator believes that for safety reasonsor tolerability reasons(eg,AE) it is in the 
best interest of the subject to discontinue studytreatment.
Thesubject becomes pregnantor plans to become pregnant.

The subject is diagnosed with a malignancy, with the exception of no more than 2localized 
basal cell skin cancers that are treated with no evidence of recurrence or residual disease.

The subject is deemed ineligible according to the following TB screening criteria: 
A diagnosis of active TB is made.
A subject has symptoms suggestive of active TB based on follow-up assessment 
questions and/or physical examination, or has had recent close contact with a person 
with active TB, and cannot or will not continue to undergo additional evaluation.
A subject undergoing evaluation has a chest radiograph with evidence of current active 
TB and/or a positive QuantiFERON®-TB Gold test result (or a positive tuberculin skin 
test result in countries in which the QuantiFERON®
NCT03158285
-TB Gold test is not 
approved/registeredor the tuberculin skin test is mandated by local health authorities), 


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unless active TB can be ruled out and appropriate treatment for latent TBcan be 
initiated before the next administration of study agentand continued to completion. 
Indeterminate QuantiFERON®-TB Gold test results should be handled as described in 
Section 9.1.3.  Subjects with persistently indeterminate QuantiFERON®-TB Gold test 
results may continue without treatment for latent TB if active TB is ruled out, their 
chest radiograph shows no abnormality suggestive of TB (active or old, inactive TB) 
and the subject has no additional risk factors for TB as determined by the investigator. 
This determination must be promptly reported to the Sponsor’s medical monitor and 
recorded in the subject
's source documents and initialed by the investigator.
A subject receiving treatment for latent TB discontinues this treatment prematurely or is 
noncompliantwith the therapy.
The subject initiates the following protocol-prohibited medications:  apremilast,systemic 
immunosuppressive drugs (Section 8.1.3), biologic agents, cytotoxic drugs, JAK inhibitors, 
or investigational agents (Section 8.4), and systemic therapy for psoriasis (Section8.7).
The subject withdraws consent for administration of study agent.
The subject is unable to adhere to the study visit schedule or comply with protocol 
requirements.

The subject develops an allergic reaction such as bronchospasm with wheezing and/or 
dyspnea requiring ventilatory support, or symptomatic hypotension that occurs following a 
study agentadministration.

NCT03158285
The subject has a reaction resulting in myalgia and/or arthralgia with fever and/or rash 
(suggestive of serum sickness and not representative of signs and symptoms of other 
recognized clinical syndromes) occurring 1 to 14 days after an injection of study agent.  
These may be accompanied by other events including pruritus, facial, hand, or lip edema, 
dysphagia, urticaria, sore throat, and/or headache.
Discontinuation of study treatment should be considered for subjects who report suicidal Ideation 
Level 4 (some intent to act, no plan), Ideation Level 5 (specific plan and intent), or anysuicidal 
behavior(actual suicide attempts, interrupted attempts, aborted attempts, or preparatory actions)
on a post-baseline(after Week 0)eC-SSRS assessment. Discussion of such subjects with the 
medical monitor or designee is required.
Discontinuationof study agentshould be considered and discussed with the studyresponsible 
physician or designee for subjects who develop a serious or opportunistic infection.
Subjectswho decide to discontinue study agentadministration must be interviewed by the 
investigator to determine if a specific reason for discontinuing study agentcan be identified. 
Subjects should be explicitly asked about the contribution of possible AEs or lack of efficacy to 
their decision to discontinue study agent; investigators should confirm that any AE information 
elicited or lack of efficacy has been documented. If a subject elects to discontinue study agent
due to an AE or lack of efficacy, the event or lack of efficacy should be recorded as the reason 
for study agentdiscontinuation, even if the investigator
's assessment is that the AE or the 
patient’s PsA condition would not require study agentdiscontinuation. The reason for study 


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agentdiscontinuation must be documented in the CRF and in source documents. Study agent
assigned to a subject who discontinues may not be assigned to another subject.
If a subject discontinues study agent administrations before the Week 100 visit, he/she should be 
encouraged toreturnfor all visits as outlined in the Time and Events Schedule (see 
Section9.1.5).
If a subject permanently discontinues study agent at orafter Week 24, the final efficacy visit 
should occur at the time of discontinuationor as soon as possibleand all assessments under the 
final efficacy/Week 100visitshould be performed, including radiograph of hands andfeet, with 
the exception of study agent administration.  The subject should also return for a final safety visit
approximately 12 weeksafter the last study agentadministration.
10.3. Withdrawal From the Study
A subjectwill be withdrawn from the study for any of the following reasons:
Lost to follow-up
Withdrawal of consent

NCT03158285
Death
To ensure access for subject follow-up, study sites should try to obtain both primary and 
secondary telephone contact numbers from subjects (eg, home, work, and mobile phones), as 
well as other contact information such as email addresses, and emphasize the importance of 
follow-up information to the subject, before randomization.
If a subject fails to return for study visits, study site personnel must make all reasonable efforts to 
contact the subject to determine the subject’s reason for discontinuation/withdrawal before 
considering the subject to be lost to follow-up. Due diligence should include repeated telephone 
calls, certified letters, and email requests. Measures taken to obtain follow-up information must 
be documented.
Withdrawal of consent should be a very unusual occurrence in a clinicaltrial; the investigator 
should make every effort to maintain good subject relationships to avoid withdrawals of consent. 
For subjects who truly request withdrawal of consent, it is recommended that the subject 
withdraw consent in writing and provide a reason, if possible; if the subject or the subject’s 
representative refuses to do so or is physically unavailable, the study site should document the 
reason for the subject’s failure to withdraw consent in writing, sign the documentation, and 
maintain it withthe subject’s source records.
When a subject withdraws before completing the study, the reason for withdrawal is to be 
documented in the CRF and in the source document. Study agentassigned to the withdrawn 
subject may not be assigned to another subject. Subjects who withdraw from the study will not 
be replaced.


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10.4. Withdrawal From the Use of Research Samples
A subject who withdraws from the study will have the following options regarding the optional 
researchsample(s):

The collected sample(s) will be retained and used in accordance with the subject
's original 
separate informed consent for optional research samples.

The subject may withdraw consent for optional research sample(s), in which case the 
sample(s) will be destroyed and no further testing will take place. To initiate the sample 
destruction process, the investigator must notify the Sponsor study site contact of 
withdrawal of consent for the optional research samples and to request sample destruction. 
The Sponsor study site contact will, in turn, contact the biomarker representative to execute 
sample destruction. If requested, the investigator will receivewritten confirmation from the 
Sponsor that the sample(s) have been destroyed.
Withdrawal From theOptional Research Samples While Remaining in the Main Study
The subjectmay withdraw consent for optional research samples while remaining in the study. In 
such a case, the optional research sample(s) will be destroyed. The sample destruction process 
will proceed as described above.
Withdrawal From the Use of Samplesin Future Research
The subject may withdraw consent for use of samples for future research (refer to 
Section16.2.5).  Insuch a case, samples will be destroyed after they are no longer needed for the 
clinical study. Details of the sample retention for future research are presented in the main ICF 
and in the separate ICF for optional research samples.
11.
STATISTICAL METHODS
NCT03158285
Statistical analysis will be done by the Sponsor or under the authority of the Sponsor. A general 
description of the statistical methods to be used to analyze subject information and efficacy and 
safety data is outlined below. Specific details will be provided in the Statistical Analysis Plan 
(SAP).
In general, efficacy and subject information analyses will be based on Full Analysis Set (FAS) 
and include all randomized subjects who received at least 1 dose (complete or partial) of study 
treatment and will be analyzed based on the randomized treatment groups, regardless of the 
treatment they actuallyreceived. 
Safety analyses will include all subjects who received at least 1 dose (complete or partial) of 
study treatment and subjects will be analyzed based on the treatment groups theyactually 
received, regardless of the treatment groups they were assigned to.
Pharmacokinetics (PK) analysis for guselkumab will include subjects who receive at least one 
completedose of guselkumab and have at least one post-dose sample collection. Antibodies to 
guselkumab will be analyzed for subjects who receive at least one dose of guselkumaband have 
at least one post-dose sample collection.


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Simple descriptive summary statistics, such as n, mean, standard deviation (SD), median, inter 
quantile (IQ) range, minimum, and maximum for continuous variables, and counts and 
percentages for discrete variables will be used to summarize most data.  
In general, for response efficacy endpoints, treatment comparisons will be performed using a 
Cochran-Mantel-Haenszel (CMH) test stratified by baseline non-biologicDMARD (MTX, SSZ, 
HCQ, LEF) use (yes/no) andthe most recentavailable CRP value prior to randomization 
(<2.0mg/dL or≥2.0mg/dL).  
In general, for continuous endpoints of efficacy data, treatment comparisons will be performed 
using either a Mixed-Effect Model Repeated Measure model or an analysis of covariance model.  
All the models will have treatment group, the baseline non-biologic DMARD (MTX, SSZ, HCQ, 
LEF)use (yes/no), the most recentavailable CRP value prior to randomization(<2.0 mg/dL or 
≥2.0mg/dL), and baseline valueas explanatory factors  
In general, for continuous endpoints of radiographic data, treatment comparisons will be 
performedusing an ANOVA test on the van der Waerden normal score.
In general, all statistical tests will be performed at a 2-sided significance level of α=0.05.
In addition, graphical data displays (eg, line plots) and subject listings may also be used to 
summarize/present the data. 
11.1. Subject Information
Descriptive statistics by the randomized treatment group will be provided for demographics, 
baseline disease characteristics, and prior and concomitant medications.
11.2. Sample Size Determination
The sample size selection was determined based onthe primary endpoint of proportion of 
subjects who achieve ACR 20 response at Week 24 and the major secondary endpoint of change 
frombaseline invdH-S score at Week 24.
Primary Endpoint –ACR 20 Response at Week 24
In the Phase 3 CNTO1275PSA3001 study with ustekinumab, the ACR 20 response rates at 
Week 24 were22.8%, 42.4% and 49.5%, respectively, for the placebo, ustekinumab 45 mg, and 
ustekinumab 90 mg treatment groups. In the Phase 2 CNTO1959PSA2001 study with 
guselkumab, the ACR 20 response rates at Week 24 were 18.4% and 58.0%, respectively, for the 
placebo and guselkumab 100 mg treatment groups.  
Assuminga 45% ACR 20 response rate in the guselkumab group and a 25% ACR 20 response 
rate in the placebo group, a sample size of 228 subjects per treatment group (684 in total) will 
provide a power of approximately 99% to detect a significant treatment difference at a 2-sided 
significance level of 0.05.  Table 7
NCT03158285
provides the statistical power under various assumptions 
using a 2-sided chi-square test.  


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For this study, the sample size was also evaluatedbased on the following assumptions:  

20% to25% ACR 20 response rates at Week 24 in subjects treated with placebo 
40% to 50% ACR 20 response rates at Week 24 in subjects treated with guselkumab
Table 7:
Statistical Power for Treatment Difference in ACR 20 Response at Week 24
Sample size per arm
ACR 20 Response Rate
Power
Placebo Group
Guselkumab Group
Difference (Δ) 
228
20%
40%
20%
>99%
228
20%
45%
25%
>99%
228
25%
45%
20%
99%
228
25%
50%
25%
>99%
228
30%
50%
20%
99%
Major Secondary Endpoint –Change from Baseline in vdH-S Score at Week 24
For change from baseline in vdH-S score, subjects in each treatment group can be considered a 
mixture of 2 subpopulations: 1 subpopulation with a change score of 0 and 1 subpopulation with 
a change score sampled from a normal distribution.  Therefore, the distributionof the vdH-S 
change scores is determined by 3parameters: the probability that a subject has a change score of 
0, mean of the normal distribution, and SD of the normal distribution.  The overall mean (ie, 
crude mean) of the change scores for a treatment group is the overall average of the change 
scores among all subjects (including both subpopulations 1 and 2) in that treatment group.
In the Phase3 CNTO1275PSA3001 study with ustekinumab, the following statistics were 
observed on change from baseline in vdH-S score at Week 24:
The overall mean (SD) of change from baseline in vdH-S score at Week 24 (after excluding 
one extreme outlier, eg, the subject with a change score of 58) was 0.92 (2.15), 0.28 (1.94), 
and 0.17 (1.45) in the placebo, ustekinumab 45 mg and 90 mg treatment groups, 
respectively. 
Approximately 49%, 47%, and 46% subjects had a change score of 0 in the placebo, 
ustekinumab 45 mg and 90 mg treatment groups, respectively.
Approximately 40% of 0’s in each group was true 0’s (that is, the difference in the 
reader-level vdH-S score between the 2 readers selected was ≤ 2 and the average of the 
reader-level vdH-S score between the 2 readers selected was 0).

NCT03158285
Excluding the above subjects with a true 0 change score, the mean (SD) change score 
(after one excluding extreme outlier) was 1.59 (2.60), 0.47 (2.50), and 0.32 (1.96) in the 
placebo, ustekinumab 45 mg and 90 mg treatment groups, respectively. Excluding all 
0’s, the mean (SD) change score for the 3 groups was 1.82 (2.75), 0.52 (2.64), and 0.32 
(1.96).


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Assuming an overall mean change of 0.9 from baseline in vdH-S score in the placebo group, and 
an overall mean change of 0.3in the guselkumab group, and an SDof 2.5 for each treatment 
group, a sample size of 228 subjects per treatment group (684 in total) will provide a power of 
approximately 90% to detect a significant treatment difference at a 2-sided significance level of 
0.05.  Table 8provides the statistical power under various assumptions.  The statistical power 
was estimated based on 10000simulations with treatment comparison performed at each 
simulation using an ANOVA test on the van der Waerden normal score.  
For this study, the sample size was determined based on the following assumptions:

The overall mean difference in change from baseline in vdH-S score at Week 24 between 
the placebo group and a guselkumab group ranges from 0.6 to 0.8.
40% –50% subjects in each treatment group have a change score of 0 from baseline in 
vdH-S score at Week 24 (ie, the subpopulation with a change score of 0). 

For the other subjects (those from the normal distributions), the SD of the normal 
distributions is 2.5 for all treatment groups and the mean of the normal distribution is 
1.80 for the placebo group. 
If the SD of the normal distributionsis 3.0, the power will go down to as low as approximately
80%. 
Table 8:
Statistical Power for Treatment Difference in vdH-S Change from Baseline at Week 24 
Placebo Group
Guselkumab Group
Overall
Mean 
Difference 
Power
%subjects 
without change
Rest of 
subjects
Overall
mean
%subjects
without change
Rest of 
subjects
Overall
mean
Mean
SD
Mean
SD
45%
1.80
2.5
1.00
45%
0.71
2.5
0.40 
0.60
89.0%
45%
1.80
2.5
1.00
45%
0.35
2.5
0.20 
0.80
98.9%
50%
1.80
2.5
0.90
50%
0.60
2.5
0.30 
0.60
91.7%
50%
1.80
2.5
0.90
50%
0.20
2.5
0.10 
0.80
99.4%
50%
1.80
2.5
0.90
45%
0.55
2.5
0.30 
0.60
91.1%
50%
1.80
2.5
0.90
45%
0.18
2.5
0.10 
0.80
99.2%
11.3. Efficacy Analyses
11.3.1.
Primary Endpoint Analyses
NCT03158285
The primary endpoint to be analyzed for the primary analysis is proportion of subjects who 
achieved an ACR 20 response at Week 24.Note that the intercurrent event of Treatment Failure 
prior to Week 24 (defined below) will be treated as non-response for the primary analysis, 
regardless of the observed ACR 20 response status.


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Subjects who meet the following treatment failure criteria includesubjects who:
1. Discontinued study agent injections due to lack of efficacy.
2. Terminate study participation for any reason.
3. Initiated or increased the dose of non-biologic DMARDs (MTX, SSZ, HCQ, LEF) or 
oral corticosteroids over baseline for PsA.
4. Initiated protocol prohibited medications/therapies for PsA. 
Subjects with missing data at Week 24 will be considered non-responders. 
The treatment effect of each guselkumab group versus placebo will be tested usinga CMHtest 
stratified by baseline non-biologic DMARD (MTX, SSZ, HCQ, LEF)use(yes/no) and the most 
recentavailable CRP value prior to randomization(<2.0 mg/dL or ≥2.0mg/dL). The magnitude 
of the effect will be estimated by the difference in ACR 20 response rates betweenthe 
guselkumab and placebo groups with the 95% confidence interval calculated based on Wald 
statistics.
In order to control the overall Type 1 error rate, the primary analysis will be tested in a fixed 
sequence.
1. Guselkumab 100 mg q4w versus placebo in ACR 20 response at Week 24
2. Guselkumab 100 mg at Weeks0, 4, and then q8w versus placebo in ACR 20 response at 
Week 24
With the above specified order, each of the hypotheses will be tested at a 2-sided α-level of 0.05 
provided that significance isachieved for the preceding hypothesis in the specified order. If a 
given comparison is not significant at the 2-sided α-level of 0.05, the remaining treatment group 
comparisons will be considered as supportive analysis.
To evaluate the robustness of the primaryendpointanalysis results,the exhaustive scenario 
tipping pointsensitivity analyses will be performedby varying the amount of non-responder 
imputation for missing data.
Additional sensitivity/supplemental analyses which vary how intercurrent events (eg, treatment 
failures) are handled, how observed data are used, and how missing data are treated will be 
specified in the SAP to further address the robustness of treatment effect of ACR 20 at Week 24 
for the primary and alternative estimands (which will also be defined in the SAP).
Subgroup Analyses
NCT03158285
Subgroup analysis will be performed to evaluate consistency in the primary efficacyendpointby 
demographic characteristics, baseline disease characteristics, and baseline medications. 
Interaction testbetween the subgroups and treatment group will also be provided ifappropriate.


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11.3.2.
Major Secondary Analyses
The major secondary endpointsare provided in Section 2.1.2.
The methods of analysis and the approach to control the Type I error for multiplicity, as well as 
the data-handling rules for the major secondary endpoints will be specified in the SAP.  
11.3.3.
Other Planned Secondary Analyses
In addition to the primaryanalyses andmajor secondary analyses, all other secondary endpoints 
(Section 2.1.2) will be descriptively summarized over time by treatment groups. Treatment 
comparisons will be performed by visit through Week24.  The methods of analysis and the data-
handling rules will be provided in the SAP.
11.4. Pharmacokinetic Analyses
Serum guselkumab concentrations over time will be summarized for each treatment group using 
descriptive statistics. All concentrations below the lowest quantifiable sample concentration of 
the assay (BQL) or missing data will be labeled as such in the concentration data listing or 
statistical analysis system dataset. The BQL concentrations will be treated as zero in the 
summary statistics.
If feasible, a population PK analysis using a nonlinear mixed effects modeling approach will be 
used to characterize the disposition characteristics of guselkumab. The apparent total systemic 
clearance and apparent volume of distribution values will be estimated. The influence of 
important variables (such as body weight, antibodies to guselkumab, and concomitant 
medications) on the population PK parameter estimates may be evaluated. Details will be given 
in a population PK analysis plan and the results of the population PK analysis will be presented 
in a separate technical report.
11.5. Immunogenicity Analyses
The incidence and titers of antibodies to guselkumab will be summarized for all subjects who 
receive at least 1 dose of guselkumab and have appropriate samples for detection of antibodies to 
guselkumab (ie, subjects with at least 1 sample obtained after their first dose of guselkumab). 
The incidence of NAbs to guselkumab will be summarized for subjects who are positive for 
antibodies to guselkumab and have samples evaluable for NAbs.
11.6. Biomarkers Analyses
Results will be presented in a separate biomarker technical report.
11.7.
Pharmacokinetic/Pharmacodynamic Analyses
NCT03158285
If data permit, the relationships between serum guselkumab concentration and efficacy may be 
analyzed graphically.  If a relationship is observed, a suitable PK/PD model may be developed to 
describe the exposure-response relationship and will be presented in a separate technical report.


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11.8. Pharmacogenomic Analyses
Results will be presented in a separate pharmacogenomics technical report.
11.9. Health Economics Analysis
The change from baseline in impact of disease on work productivity and daily activity via 
WPAI:PsAwill be descriptively summarized by treatment group over time and compared 
between treatment groups at Week 24.
11.10. Safety Analyses
Routine safety evaluations will be performed.  Adverse events, serious AEs (SAEs), and 
infections will be summarized by treatment group.
The following analyses will also be used to assess the safety of subjects in the study:

The incidence and type of AEs.
The incidence and type of SAEs.
The incidence and type of infections.
The incidence and type of injection site reactions.
The laboratory parameters and change from baseline in selected laboratory parameters 
(hematology and chemistry).

The incidence of Common Terminology Criteria for Adverse Events Grade 3 or 
Grade4 abnormal laboratory parameters (hematology and chemistry).
Listings of serious infections and anaphylactic reaction/serum sickness reactions will also be 
provided.  All safety analyses will be based on the population of subjects who received at least 1 
injection of study agent; subjects will be summarized by the treatment they actually received. 
11.11. Interim Analysis
No interim analysis is planned for this study.
11.12. Data Monitoring Committee
NCT03158285
An independent DMC will be established to monitor unblinded data on an ongoing basis through 
at least the Week 24 database lock (DBL)to ensure the continuing safety of the subjects enrolled 
in the study.
The DMC will have 3 to 6 members who are independent of the Sponsor.  None of the members 
will be participating in the current study. The DMC will consist of at least 1 medical expert in 
the relevant therapeutic area and at least 1 statistician. The members of the committee will be 
specified prior to study initiation. The major function of this committee will be to monitor the 
safety of the study agent and to provide recommendations for placing the study on hold or 
stopping the study in the event that any unanticipated serious events occur.


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The committee will meet periodically to review interim data. After the review, the DMC will 
make recommendations regarding the continuation of the study. 
SAE reports will be provided to the DMC members on an ongoing monthly basis.  Periodic 
safety reviewswill occur every 4months.  The DMC may change the frequency or number of 
reviews based on interim safety findings and may request additional data.  The safety reviews 
will focus on particular AEs, SAEs, and mortality.  
In addition, during the study, theSponsor
's study responsible physician (or designee) will 
regularly review blinded safety data from the sites and notify the DMC and appropriate Sponsor 
personnel of any issues.  
The content of the safety summaries, the DMC role and responsibilities and the general 
procedures (including communications) and their recommendations on the study conduct will be 
defined and documented in the DMC charter prior to the first DMC review.
12.
ADVERSE EVENT REPORTING
Timely, accurate, and complete reporting and analysisof safety information from clinical studies 
are crucial for the protection of subjects, investigators, and the Sponsor, and are mandated by 
regulatory agencies worldwide. The Sponsor has established Standard Operating Procedures in 
conformity with regulatory requirements worldwide to ensure appropriate reporting of safety 
information; all clinical studies conducted by the Sponsor or its affiliateswill be conducted in 
accordance with those procedures.
Method of Detecting AdverseEvents and Serious Adverse Events
Care will be taken not to introduce bias when detecting AEs or SAEs. Open-ended and 
nonleadingverbal questioning of the subject is the preferred method to inquire about AE 
occurrence. 
SolicitedAdverse Events
SolicitedAEs are predefined local andsystemic events for which the subject is specifically 
questioned(see Section 9.1.1).
UnsolicitedAdverse Events
UnsolicitedAEs are allAEsfor which the subject isspecifically not questioned.
12.1. Definitions
12.1.1.
Adverse Event Definitions and Classifications
Adverse Event
NCT03158285
An AEis any untoward medical occurrence in a clinical study subject administered a medicinal 
(investigational or non-investigational) product. An AE does not necessarily have a causal
relationship with the treatment. An AE can therefore be any unfavorable and unintended sign 
(including an abnormal finding), symptom, or disease temporally associated with the use of a 


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medicinal (investigational or non-investigational) product, whether or not related to that 
medicinal (investigational or non-investigational) product. (Definition per International 
Conference on Harmonisation [ICH])
This includesany occurrence that is new in onset or aggravated in severity or frequency from the 
baseline condition, or abnormal results of diagnostic procedures, including laboratory test 
abnormalities.
Note: The Sponsor collects AEs starting with the signing of the ICF(refer to Section12.3.1for 
time of last AErecording).
Serious Adverse Event
An SAE based on ICH and European UnionGuidelines on Pharmacovigilance for Medicinal 
Productsfor Human Use is any untoward medical occurrence that at any dose:
Results in death
Is life-threatening
(The subject was at risk of death at the time of the event. It does not refer to an event that 
hypothetically might have caused death if it were more severe.)
Requires inpatient hospitalization or prolongation of existing hospitalization
Results in persistent or significant disability/incapacity
Is a congenital anomaly/birth defect
Is a suspected transmission of any infectious agent via a medicinal product
Is Medically Important*
*
Medical and scientific judgment should be exercised in deciding whether expedited 
reporting is also 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 subject or may require intervention to prevent one of the other outcomes 
listed in the definition above. These should usually be considered serious.
If a serious and unexpected AE occurs for which there is evidence suggesting a causal 
relationship between the study agentand the event (eg, death from anaphylaxis), the event must 
be reported as a serious and unexpected suspected adverse reaction even if it is a component of 
the study endpoint (eg, all-cause mortality).
Unlisted (Unexpected) Adverse Event/ReferenceSafety Information
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An AE is considered unlisted if the nature or severity is not consistent with the applicable 
product referencesafety information. For guselkumab, the expectedness of an AE will be 
determined by whether or not it is listed in the Investigator
's Brochure.


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Adverse Event Associated With theUse of the Drug
An AEis considered associated with the use of the drug if the attribution is possible, probable, or 
very likely (Section12.1.2).
12.1.2.
Attribution Definitions
Not Related
An AEthat is notrelated to the use of the drug.
Doubtful
An AEfor which analternative explanation is more likely, eg,concomitant drug(s), concomitant 
disease(s), or the relationship in time suggests that a causal relationship is unlikely.
Possible
An AEthat might be due to the use of the drug. An alternative explanation, eg,concomitant 
drug(s), concomitant disease(s), is inconclusive. The relationship in time is reasonable; therefore, 
the causal relationship cannot be excluded.
Probable
An AE that might be due to the use of the drug. The relationship in time is suggestive 
(eg,confirmed by dechallenge). An alternative explanation is less likely, eg,concomitant 
drug(s), concomitantdisease(s).
Very Likely
An AEthat is listed as a possible adverse reaction and cannot be reasonably explained by an 
alternative explanation, eg,concomitant drug(s), concomitant disease(s). The relationship in time 
is verysuggestive (eg,it is confirmed by dechallenge and rechallenge).
12.1.3.
Severity Criteria
An assessment of severity grade will be made using the following general categorical 
descriptors:
Mild:
Awareness of symptoms that are easily tolerated, causing minimal discomfort and 
not interfering with everyday activities.
Moderate:
Sufficient discomfort is present to cause interference with normal activity.
Severe
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:
Extreme distress, causing significant impairment of functioning or incapacitation. 
Prevents normal everyday activities.
The investigator should use clinical judgment in assessing the severity of events not directly 
experienced by the subject (eg,laboratory abnormalities).


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12.2. Special Reporting Situations
Safety events of interest on a Sponsor study agentthat may require expedited reporting or safety 
evaluation include, but are not limited to:
Overdoseof a Sponsorstudy agent
Suspected abuse/misuse of a Sponsorstudy agent
Accidentalor occupationalexposure to a Sponsorstudy agent
Medication error involving a Sponsorproduct (with or without subject/patient exposure to 
the Sponsorstudy agent, eg, name confusion)
Exposure to a Sponsorstudy agentfrom breastfeeding
Special reporting situations should be recorded in the CRF. Any special reporting situation that 
meets the criteria of an SAE should be recorded on the SAEpage of the CRF.
12.3. Procedures
12.3.1.
All Adverse Events
All AEs and special reporting situations, whether serious or non-serious, will be reported from 
the time a signed and dated ICFis obtained until completion of the subject
's last study-related 
procedure,which may include contact for follow-up of safety.  Serious AEs, including those 
spontaneously reported to the investigator within12 weeks after the last dose of study agent, 
mustbe reported using the Serious Adverse Event Form. The Sponsor will evaluate any safety 
information that is spontaneously reported by an investigator beyond the time frame specified in 
the protocol.
All events that meet the definition of an SAE will be reported as SAEs, regardless of whether 
they are protocol-specific assessments.  Anticipated events will be recorded and reported as 
described in Attachment 5
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.
All AEs, regardless of seriousness, severity, or presumed relationship to study agent, must be 
recorded using medical terminology in the source document and the CRF. Whenever possible, 
diagnoses should be given when signs and symptoms are due to a common etiology (eg,cough, 
runny nose, sneezing, sore throat, and head congestion should be reported as “upper respiratory 
infection”). Investigators must record in the CRF their opinion concerning the relationship of the 
AEto study therapy. All measures required for AEmanagement must be recorded in the source 
document and reported according to Sponsorinstructions.
The Sponsor assumes responsibility for appropriate reporting of AEs to the regulatory 
authorities. The Sponsor will also report to the investigator (and the head of the investigational 
institute where required) all suspected unexpected serious adverse reactions (SUSARs). The 
investigator (or Sponsor where required) must report SUSARs to the appropriate IEC/IRBthat 
approved the protocol unless otherwise required and documented by the IEC/IRB.A SUSAR 


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will be reported to regulatory authorities unblinded. Participating investigators and IEC/IRB will 
receive a blinded SUSAR summary, unless otherwise specified.
For all studies with an outpatient phase, including open-label studies, the subject must be 
provided with a "wallet (study)card" and instructed to carry this card with them for the duration 
of the study indicating the following:
Studynumber

Statement, in the local language(s), that the subject is participating in a clinical study

Investigator
's name and 24-hour contact telephone number
Local Sponsor
's name and 24-hour contact telephone number(for medical staff only)
Sitenumber
Subject number
Any other information that is required to do an emergency breaking of the blind
12.3.2.
Serious Adverse Events
All SAEsoccurring during thestudymust be reported to the appropriate Sponsor contact person 
bystudy-site personnelwithin 24hoursof theirknowledge of the event.
Information regarding SAEs will be transmitted to the Sponsor using the Serious Adverse Event 
Form, which must be completed and signed by a physician fromthe study site, and transmitted to 
the Sponsor within 24 hours. The initial and follow-up reports of an SAE should be made by 
facsimile (fax).
All SAEs that have not resolved by the end of the study, or that have not resolved upon 
discontinuation of the subject
's participation in the study, must be followed until any of the 
following occurs:
Theevent resolves
Theevent stabilizes
The event returns to baseline, if a baseline value/status is available
The event can be attributed to agents other than the study agentor to factors unrelated to 
study conduct

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It becomes unlikely thatany additional information can be obtained (subject or health care 
practitioner refusal to provide additional information, lost to follow-up after demonstration 
of due diligence with follow-up efforts)
Suspected transmission of an infectious agent by a medicinal product will be reported as an SAE. 
Any event requiring hospitalization (or prolongation of hospitalization) that occurs during the 
course of a subject
's participation in a study must be reported as an SAE, except hospitalizations 
for the following:


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Hospitalizations not intended to treat an acute illness or AE (eg, social reasons such as 
pending placement in long-term care facility).
Surgery or procedureplanned before entry into the study (must be documented in theCRF).
Note:
Hospitalizations thatwere planned before the signing of the ICF, and where the 
underlying condition for which the hospitalization was planned has not worsened,
will not be considered SAEs. Any AEthat results in a prolongation of the originally 
planned hospitalization is to be reported as a new SAE.
For convenience the investigator may choose to hospitalize the subject for the duration of 
the treatmentperiod.
The cause of death of a subject in a studywithin12 weeks after the last doseof study agent,
whether or not the event is expected or associated with the study agent, is considered an SAE.
12.3.3. 
Pregnancy
All initial reports of pregnancy in female subjects or partners of male subjects must be reported 
to the Sponsor by the study-site personnelwithin 24 hours of their knowledge of the event using 
the appropriate pregnancy notification form. Abnormal pregnancy outcomes (eg, spontaneous 
abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are considered SAEs 
and must be reported using the Serious Adverse Event Form.  Any subject who becomes 
pregnant during the study must be promptly withdrawn from the studyanddiscontinue further 
study treatment.
Because the effect of the study agenton sperm is unknown,pregnancies in partners of male 
subjects included in the study will be reported as noted above.
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the 
infant will be required.
12.3.4.
Events of Special Interest
Any newly identified malignancy or case of active TB occurring after the first administration of 
study agent in subjects participating in this clinical study must be reported by the investigator 
according to the procedures in Section12.2.  Investigators are also advised that active TB is 
considered a reportable disease in most countries.  These events are to be considered serious only 
if they meet the definition of an SAE.
12.4. Contacting Sponsor Regarding Safety
The names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding safety issues or questions regarding the study are listed in the Contact Information 
page(s), which will be provided as a separate document.
13.
PRODUCT QUALITY COMPLAINT HANDLING
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A product quality complaint (PQC) is defined as any suspicion of a product defect related to 
manufacturing, labeling, or packaging, ie, any dissatisfaction relative to the identity, quality, 
durability, or reliability of a product, including its labeling or package integrity. A PQC may 


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have an impact on the safety and efficacy of the product. Timely, accurate, and complete 
reporting and analysis of PQC information from studies are crucial for the protection of subjects, 
investigators, and the Sponsor, and are mandated by regulatory agencies worldwide. The 
Sponsor has established procedures in conformity with regulatory requirements worldwide to 
ensure appropriate reporting of PQC information; all studies conducted by the Sponsor or its 
affiliates will be conducted in accordance with those procedures.
13.1. Procedures
All initial PQCs must be reported to the Sponsor by the study-site personnel within 24 hours 
after being made aware of the event.
If the defect is combined with an SAE, the study-site personnelmust report the PQC to the 
Sponsor according to the SAEreporting timelines (refer to Section12.3.2, Serious Adverse 
Events). A sample of the suspected product should be maintained for further investigation if 
requested by the Sponsor.
13.2. Contacting Sponsor Regarding Product Quality
The names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding product quality issues are listed in the Contact Information page(s), which will be 
provided as a separate document.
14.
STUDY AGENTINFORMATION
14.1. Physical Description of Study Agents
The guselkumab supplied for this study is a sterile liquid for SC injection in a single-use PFS 
assembledin aPFS-U.  Each single-use PFS-U contains 100 mg (1 mL fill of liquid) in a 1 mL 
glass syringe with a 27 gauge, 1/2 inch fixed needle and a latex-free rigid needle shield. No 
preservatives are present. The guselkumab solution should be essentially free of visible 
particulate matter. The PFS-U is a passive safety needle guard that is permanently assembled on 
the syringe and incorporates a spring driven shield that automatically extends beyond the PFS 
needle following complete injection of the guselkumab PFS contents. Guselkumab will be 
manufactured and provided under the responsibility of the Sponsor. Refer to the Investigator
's 
Brochure for a list of excipients.
Placebo for guselkumabis supplied as a sterile liquid for SC injection at a nominal volumeof 
1.0mL in a single-use PFS assembled with the PFS-U. 
Concomitantmedications, including those in Table4, will not be supplied by the Sponsor but 
rather must be acquired from a commercial pharmacy.
14.2. Packaging
NCT03158285
The investigational supplies will be uniquely packaged to assure that they are appropriately 
managed throughout the supply chain process.


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14.3. Labeling
Study agentlabels will contain information to meet the applicable regulatory requirements.
14.4. Preparation, Handling, and Storage 
All study agentmust be stored at controlled temperatures ranging from 36°F to 46°F (2°C to 
8°C) and protected from light. Vigorous shaking of the product should be avoided. The sterile 
product does not contain preservatives and is designed for single use only. Protection from light 
is not required during administration. 
After Week 52, subjects who are able and who have been appropriately trained in the self-
administration of study agent may self-administer study agent at home, as per the Time and 
Events Schedule.Study personnel will instruct subjects on how to transport, store, and 
administer study agent for at-home use as indicated for thisprotocol.
Further details regarding the storage of guselkumab and placebo will be provided in the Site 
Investigational Product Manual.
14.5. Drug Accountability
NCT03158285
The investigator is responsible for ensuring that all study agentreceived at the site is inventoried 
and accounted for throughout the study. The study agentadministered to the subject must be 
documented on the drug accountability form. All study agentwill be stored and disposed of 
according to the Sponsor
's instructions. Study-site personnel must not combine contents of the 
study agentcontainers.
Study agentsmust be handled in strict accordance with the protocol and the container label, and 
must be stored at the study site in a limited-access area or in a locked cabinet under appropriate 
environmental conditions.Unused study agent(including guselkumab and placebo,) must be 
available for verification by the Sponsor
's study site monitor during on-site monitoring visits.
The return to the Sponsor of unused study agents(including guselkumab and placebo) will be 
documented on the drug return form. When the study site is an authorized destruction unit and 
study agentsupplies are destroyed on-site, this must also be documented on the drug return form.
Potentially hazardous materials such as used ampules, needles, syringes and vials containing 
hazardousliquidsshould be disposed of immediately in a safe manner and therefore will not be 
retained for drug accountability purposes. The immediate destruction of these drug supplies 
should be documented in the drug accountability records on site.
Study agentsshould be dispensed under the supervision of the investigator or a qualified member 
of the study-site personnel, or by a hospital/clinic pharmacist. Study agentswill be supplied only 
to subjects participating in the study. Study agentsmay not be relabeled or reassigned for use by 
other subjects.The investigator agrees neither to dispense the study agentfrom, nor store it at, 
any site other than the study sites agreed upon with the Sponsor.


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Subjects whowill be self-administering study agent at home will receive detailed instructions for 
study drug storage and disposal of used syringes and handling of unused study material. These 
subjects will receive a sharps containerto dispose of used syringesand will be instructed to 
return the sharps container and/or unused cartons with syringes. Subjects who self administer at 
home will record study drugadministrations with time and date information on a diary card.
15.
STUDY-SPECIFIC MATERIALS
The investigator will be provided with the following supplies:

Investigator
'sBrochure 
Study site investigational product and procedures manual
Laboratory manual and laboratory supplies
ePRO device and user manual
Interactive voice response system/IWRS manual 

Electronic data capture (eDC)manual
Sample ICF
Imaging manual
iPad
®and site user guide, if the study site is participating in electronic informed consent
16.
ETHICAL ASPECTS
16.1. Study-Specific Design Considerations
NCT03158285
Potential subjects will be fully informed of the risks and requirements of the study and, during 
the study, subjects will be given any new information that may affect their decision to continue 
participation. They will be told that their consent to participate in the study is voluntary and may 
be withdrawn at any time with no reason given and without penalty or loss of benefits to which 
they would otherwise be entitled. Only subjects who are fully able to understand the risks, 
benefits, and potential AEs ofthe study, and provide their consent voluntarily will be enrolled.
The primary ethical concern isthat subjects with active disease may receive placebo for 
24weeks. However, the placebo controlis necessary to capture the change in clinical endpoints 
that may occur in the absence of active treatment and is recommended by regulatory authorities. 
The disease activity of each subject will be closely monitored during the study and early escape 
has been incorporated in the study design to allow subjects receive additional concomitant 
medications for PsA at the investigator’s discretion if the early escape criterion is met. The
duration of the placebo exposure is limited to 24 weeks and is considered acceptable byICH
(http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E10/Step4/E
10_Guideline.pdf).
The total blood volume to be collected is considered to be an acceptable amount of blood to be 
collected over this time period from the population in this study based upon the standard of the 
American Red Cross for blood donation.


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Subjects will be exposed to radiation during radiography of hands/feet collected at Weeks 0, 24, 
52, and100. A total of 0.012 mSV radiation exposure is expected from these procedures, which 
is comparable to ~3 days of exposure to natural background radiation. Additionally 1 Chest X-
ray may be performed at screening if the subject does not have a chest X-ray within 12 weeks 
prior to the first administration of study agent. The exposure from 1 standard chest X-ray is 
0.1mSV,comparable to 10 days of exposure to natural background radiation. 
16.2. Regulatory Ethics Compliance
16.2.1.
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the 
protocol, current ICH guidelines on Good Clinical Practice (GCP), and applicable regulatory and 
country-specific requirements.
Good Clinical Practice is an international ethical and scientific quality standard for designing, 
conducting, recording, and reporting studies that involve the participation of human subjects. 
Compliance with this standard provides public assurance that the rights, safety, and well-being of 
study subjects are protected, consistent with the principles that originated in the Declaration of 
Helsinki, and that the study data are credible.
16.2.2.
Independent Ethics Committee or Institutional Review Board
Before the start of the study, the investigator (or Sponsor where required) will provide the 
IEC/IRB with current and complete copies of the following documents (as required by local 
regulations):
Final protocol and, if applicable, amendments
Sponsor-approved ICF (and any other written materials to be provided to the subjects)

Investigator
's Brochure (or equivalent information)and amendments/addenda
Sponsor-approved subject recruiting materials
Information on compensation for study-related injuries or payment to subjects for 
participation in the study, if applicable

Investigator
's curriculum vitae or equivalent information (unless not required, as 
documented by the IEC/IRB)

Information regarding funding, name of the Sponsor, institutional affiliations, other potential 
conflicts of interest, and incentives for subjects

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Any other documents that the IEC/IRB requests to fulfill its obligation
This study will be undertaken only after the IEC/IRB has given full approval of the final 
protocol, amendments (if any, excluding the ones that are purely administrative, with no 
consequences for subjects, data or study conduct, unless required locally), the ICF, applicable 
recruiting materials, and subject compensation programs, and the Sponsor has received a copy of 
this approval. This approval letter must be dated and must clearly identify the IEC/IRB and the 
documents being approved.


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Approvalfor the collection of optional samples for research and for the corresponding ICF must 
be obtained from the IEC/IRB. Approval for the protocol can be obtained independent of this 
optional research component. 
During the study the investigator (or Sponsor where required) will send the following documents 
and updates to the IEC/IRB for their review and approval, where appropriate:
Protocol amendments (excluding the ones that are purely administrative, with no 
consequences for subjects, data or study conduct)
Revision(s) to ICF and any other written materials to be provided to subjects

If applicable, new or revised subject recruiting materials approved by the Sponsor
Revisions to compensation for study-related injuries or payment to subjects for participation 
in the study, if applicable
New edition(s) of the Investigator
's Brochure and amendments/addenda
Summaries of the status of the study at intervals stipulated in guidelines of the IEC/IRB (at 
least annually)
Reports of AEs that are serious, unlisted/unexpected, and associated with the study agent

New information that may adversely affect the safety of the subjects or the conduct of the 
study
Deviations from or changes to the protocol to eliminate immediate hazards to the subjects
Report of deaths of subjectsunder the investigator
's care

Notification if a new investigator is responsible for the study at the site
Development Safety Update Report and Line Listings, where applicable

Any other requirements of the IEC/IRB
For all protocol amendments (excluding theones that are purely administrative, with no 
consequences for subjects, data or study conduct), the amendment and applicable ICF revisions 
must be submitted promptly to the IEC/IRB for review and approval before implementation of 
the change(s). 
At least once a year, the IEC/IRB will be asked to review and reapprove this study, where 
required.
At the end of the study, the investigator (or Sponsor where required) will notify the IEC/IRB 
about the study completion (if applicable, the notification will be submitted through the head of 
investigational institution). 
16.2.3.
Informed Consent
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Each subjectmust give written consent according to local requirements after the nature of the 
study has been fully explained. The ICF(s) must be signed before performance of any study-
related activity. The ICF(s) that is/are used must be approved by both the Sponsor and by the 


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reviewing IEC/IRB and be in a language that the subject can read and understand. The informed 
consent should be in accordance with principles that originated in the Declaration of Helsinki, 
current ICH and GCP guidelines, applicable regulatory requirements, and Sponsorpolicy.
Before enrollment in the study, the investigator or an authorized member of the study-site 
personnel must explain to potential subjects the aims, methods, reasonably anticipated benefits, 
and potential hazards of the study,and any discomfort participation in the study may entail. 
Subjects will be informed that their participation is voluntary and that they may withdraw 
consent to participate at any time. They will be informed that choosing not to participate will not 
affectthe care the subject will receive for the treatment of his or her disease. Subjects will be 
told that alternative treatments are available if they refuse to take part and that such refusal will 
not prejudice future treatment. Finally, they will be told that the investigator will maintain a 
subject identification register for the purposes of long-term follow up if needed and that their 
records may be accessed by health authorities and authorized Sponsor personnel without 
violating the confidentiality of thesubject, to the extent permitted by the applicable law(s) or 
regulations. By signing the ICF the subject is authorizing such access. 
The subject will be given sufficient time to read the ICF and the opportunity to ask questions. 
After this explanation and before entry into the study, consent should be appropriately recorded 
by means of the subject
's personally dated signature. After having obtained the consent, a copy 
of the ICF must be given to the subject.
Subjects will be asked for consent to provide optional samples for research (where local 
regulations permit). After informed consent for the study is appropriately obtained, the subject 
will be asked to sign and personally date a separate ICF indicating agreement to participate in the 
optional researchcomponent. Refusal to participate in the optional research will not result in 
ineligibility for the study. A copy of this signed ICF will be given to the subject.
The subject must be able to read and write and should personally sign the ICF. An impartial 
witness or legally acceptable representative should not sign the ICF on the subject’s behalf.
A limited number of study sites may be asked by the Sponsorto obtain informed consent using a 
validated electronic system instead of a paper-based process.If both parties (Sponsorand the 
study site) agree, and if participation is allowed by local regulations and IEC/IRB requirements, 
the means to facilitate such a process will be provided to the sites by Sponsor. The actual 
mechanism of consenting will be facilitated by the use of an eTablet device (eg, iPad®), but 
overall the consent process will remain the same, as described in this section. At these study 
sites, subjects will still be required to review the entire informed consent as a written document 
on the eTablet and then to apply their handwritten signature electronically by the use of a stylus 
directly onto the eTablet.Alternately, the site will also have the option to print the electronic 
version of the ICF and apply a handwritten signature.
16.2.4.
Privacy of Personal Data
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The collection and processing of personal data from subjects enrolled in this study will be 
limited to those data that are necessary to fulfill the objectives of the study.


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These data must be collected and processed with adequate precautions to ensure confidentiality 
and compliance with applicable data privacy protection laws and regulations. Appropriate 
technical and organizational measures to protect the personal data against unauthorized 
disclosures or access, accidental or unlawful destruction, or accidental loss or alteration must be 
put in place. Sponsor personnel whose responsibilities require access to personal data agree to 
keep the identity of subjects confidential.
The informed consent obtained from the subject includes explicit consent for the processing of 
personal data and for the investigator/institution to allow direct access to his or her original 
medical records (source data/documents) for study-related monitoring, audit, IEC/IRB review, 
and regulatory inspection. This consent also addresses the transfer of the data to other entities 
and to other countries.
The subject has the right to request through the investigator access to his or her personal data and 
the right to request rectification of any data that are not correct or complete. Reasonable steps 
will be taken to respond to such a request, taking into consideration the nature of the request, the 
conditions of the study, and the applicable laws and regulations.
Exploratory DNA, PD, PK, and immunogenicity research is not conducted under standards 
appropriate for the return of data to subjects. In addition, the Sponsor cannot make decisions as 
to the significance of any findings resulting from exploratory research. Therefore, exploratory 
research data will not be returned to subjects or investigators, unless required by law or local 
regulations. Privacy and confidentiality of data generated in the future on stored samples will be 
protected by the same standards applicable to all other clinical data.
16.2.5.
Long-Term Retentionof Samples for Additional Future Research
Samples collected in this study may be stored for up to 15 years, starting from last patient, last 
visit(or according to localregulations) for additional research. Samples will only be used to 
understand guselkumab, to understand PsA, to understand differential drug responders, and to 
develop tests/assays related to guselkumaband PsA.  The research may begin at any time during 
the study or the post-studystorage period. 
Stored samples will be coded throughout the sample storage and analysis process and will not be 
labeled with personal identifiers. Subjects may withdraw their consent for their samples to be 
stored for research (refer to Section 10.3).
16.2.6.
Country Selection
This study will only be conducted in those countries where the intent is to launch or otherwise 
help ensure access to the developed productif the need for the product persists, unless explicitly 
addressed as a specific ethical consideration in Section16.1
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17.
ADMINISTRATIVE REQUIREMENTS
17.1. Protocol Amendments
Neither the investigator nor the Sponsor will modify this protocol without a formal amendment 
by the Sponsor. All protocol amendments must be issued by the Sponsor, and signed and dated 
by the investigator. Protocol amendments must not be implemented without prior IEC/IRB 
approval, or when the relevant competent authority has raised any grounds for non-acceptance, 
except when necessary to eliminate immediate hazards to the subjects, in which case the 
amendment must be promptly submitted to the IEC/IRB and relevant competent authority. 
Documentation of amendment approval by the investigator and IEC/IRB must be provided to the 
Sponsor. When the change(s) involves only logistic or administrative aspects of the study, the 
IEC/IRB (where required) only needs to be notified.
During the course of the study, in situations where a departure from the protocol is unavoidable, 
the investigator or other physician in attendance will contact the appropriate Sponsor 
representative listed in the Contact Information page(s), which will be provided as a separate 
document. Except in emergency situations, this contact should be made before implementing any 
departure from the protocol. In all cases, contact with the Sponsor must be made as soon as 
possible to discuss the situation and agree on an appropriate course of action. The data recorded 
in the CRF and source documents will reflect any departure from the protocol, and the source
documents will describe this departure and the circumstances requiring it.
17.2. Regulatory Documentation
17.2.1.
Regulatory Approval/Notification
This protocol and any amendment(s) must be submitted to the appropriate regulatory authorities 
in each respective country, if applicable. A study may not be initiated until all local regulatory 
requirements are met.
17.2.2.
Required Prestudy Documentation
The following documents must be provided to the Sponsor before shipment of study agentto the 
study site:
Protocol and amendment(s), if any, signed and dated by the principal investigator

A copy of the dated and signed (or sealed, where appropriate per local regulations), written 
IEC/IRB approval of the protocol, amendments, ICF, any recruiting materials, and if 
applicable, subject compensation programs. This approvalmust clearly identify the specific 
protocol by title and number and must be signed (or sealed, where appropriate per local 
regulations) by the chairman or authorized designee.

NCT03158285
Name and address of the IEC/IRB, including a current list of the IEC/IRB members and 
their function, with a statement that it is organized and operates according to GCP and the 
applicable laws and regulations. If accompanied by a letter of explanation, or equivalent, 
from the IEC/IRB, a general statement may be substituted for this list. If an investigator or a 
member of the study-site personnel is a member of the IEC/IRB, documentation must be 


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obtained to state that this person did not participate in the deliberations or in the 
vote/opinion of the study.
Regulatory authority approvalor notification, if applicable
Signed and dated statement of investigator (eg,Form FDA 1572), if applicable
Documentation of investigator qualifications (eg,curriculum vitae)
Completed investigator financial disclosure form from the principal investigator, where 
required

Signed and dated clinical trial agreement, which includes the financial agreement

Any other documentation required by local regulations
The followingdocuments must be provided to the Sponsor before enrollment of the first subject:
Completed investigator financial disclosure forms from all subinvestigators
Documentation of subinvestigator qualifications (eg,curriculum vitae)
Name and address of any local laboratory conducting tests for the study, and a dated copy of 
current laboratory normal ranges for these tests, if applicable
Local laboratory documentation demonstrating competence and test reliability 
(eg,accreditation/license), if applicable
17.3. Subject Identification, Enrollment, and Screening Logs
The investigator agrees to complete a subject identification and enrollment log to permit easy 
identification of each subject during and after the study. This document will be reviewed by the 
Sponsor study-site contact for completeness.
The subject identification and enrollment log will be treated as confidential and will be filed by 
the investigator in the study file. To ensure subject confidentiality, no copy will be made. All 
reports and communications relating to the study will identify subjects by subject identification 
and date of birth if permitted by the local authorities. In cases where the subject is not 
randomized into the study, the date seen and date of birth (as appropriate) will be used.
The investigator must also complete a subject screening log, which reports on all subjects who 
were seen to determine eligibility for inclusion in the study.
17.4. Source Documentation
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At a minimum, source documents consistent in the type and level of detail with that commonly 
recorded at the study site as a basis for standard medical care must be available for the following: 
subject identification, eligibility, and study identification; study discussion and date of signed 
informed consent; dates of visits; results of safety and efficacy parameters as required by the 
protocol; record of all AEs and follow-up of AEs;prior andconcomitant medication; drug 
receipt/dispensing/return records; study agentadministration information; and date of study 


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completion and reason for early discontinuation of study agentor withdrawal from the study, if 
applicable.
The author of an entry in the source documents should be identifiable.
Specific details required as source data for the study and source data collection methods will be 
reviewed with the investigator before the study and will be described in the monitoring 
guidelines (or other equivalent document).
The following subject-and investigator-completed PsAscales and assessments designated by the 
Sponsorwill be recorded directly into an electronic device and will be considered source data:  
Joint Assessment, Subject’s Assessment of Pain, Subject’s Global Assessment of Disease 
Activity, Physician’s Global Assessment of Disease Activity, Dactylitis and Enthesitis 
Assessments, HAQ-DI, SF-36, FACIT-Fatigue, BASDAI, PASI, DLQI, BSA, EQ-5D, eC-SSRS.
If available,subjects may also use the telephone as an alternative method to complete the 
eC-SSRS assessment.
The minimum source documentation requirements for Section 4.1and Section 4.2that specify a 
need for documented medical history are as follows:

Referral letter from treating physician or

Complete history of medical notes at the site

Discharge summaries
Inclusion and exclusion criteria not requiring documented medical history must be verified at a 
minimum by subject interview or other protocol required assessment (eg, physical examination, 
laboratory assessment) and documented in the source documents.
An electronic source system may be utilized, which contains data traditionally maintained in a 
hospital or clinic record to document medical care (eg,electronic source documents) as well as 
the clinical study-specific data fields as determined by the protocol. This data is electronically 
extracted for use by the Sponsor. If the electronic source system is utilized, references made to 
the CRF inthe protocol include the electronic source system but information collected through 
the electronic source system may not be limited to that found in the CRF. Data in this system 
may be considered source documentation.
Duringat-home administration (Weeks56, 60, 64, 72, 80, 88, 92, and 96), subjects will enter
information on their study agent administration on a patient diary.
17.5. Case Report Form Completion
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Case report forms are prepared and provided by the Sponsor for each subject in electronic 
format. All CRF entries, corrections, and alterations must be made by the investigator or 
authorized study-site personnel. The investigator must verify that all data entries in the CRF are 
accurate and correct.


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The study data will be transcribed by study-site personnel from the source documents onto an 
electronic CRF, if applicable.  Study-specific data will be transmitted in a secure manner to the 
Sponsor.
Worksheets may be used for the capture of some data to facilitate completion of the CRF. Any 
such worksheets will become part of the subject
's source documents.  Data must be entered into 
CRF in English. The CRF must be completed as soon as possible after a subject visit and the 
forms should be available for review at the next scheduled monitoring visit.
All subjective measurements (eg, pain scale information or other questionnaires) will be 
completed by the same individual who made the initial baseline determinations whenever 
possible.
If necessary, queries will be generated in the eDC tool. If corrections to a CRF are needed after 
the initial entry into the CRF, this can be done in either of the following ways:
Investigator and study-site personnel can make corrections in the eDC tool at their own 
initiative or as a response to an auto query (generated by the eDC tool).

Sponsor or Sponsor delegate can generate a query for resolution by the investigator and 
study-site personnel.
17.6. Data Quality Assurance/Quality Control
Steps to be taken to ensure the accuracy and reliability of data include the selection of qualified 
investigators and appropriate study sites, review of protocol procedures with the investigator and 
study-site personnel before the study, periodic monitoring visits by the Sponsor,direct 
transmission of clinical laboratory data from a central laboratoryto the Sponsor’s clinical 
database, and electronic transmission of ePRO data to the ePRO vendor database then to the 
Sponsor’s clinical database. Written instructions will be provided for collection, handling, 
storage, and shipment of samples. 
Guidelines for CRF completion will be provided and reviewed with study-site personnel before 
the start of the study 
The Sponsor will review CRF for accuracy and completeness during on-site monitoring visits
and after transmission to the Sponsor; any discrepancies will be resolved with the investigator or 
designee, as appropriate. After upload of the data into the study database they will be verified for 
accuracy and consistency with the data sources.
17.7. Record Retention
NCT03158285
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all CRF 
and all source documents that support the data collected from each subject, as well as all study 
documents as specified in ICH/GCP Section8, Essential Documents for the Conduct of a 
Clinical Trial, and all study documents as specified by the applicable regulatory requirement(s). 
The investigator/institution will take measures to prevent accidental or premature destruction of 
these documents.


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Essential documents must be retained until at least 2years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or until at least 2years have elapsed since the formal 
discontinuation of clinical development of the investigationalproduct. These documents will be 
retained for a longer period if required by the applicable regulatory requirements or by an 
agreement with the Sponsor. It is the responsibility of the Sponsor to inform the 
investigator/institution as to when these documents no longer need to be retained.
If the responsible investigator retires, relocates, or for other reasons withdraws from the 
responsibility of keeping the study records, custody must be transferred to a person who will 
accept the responsibility. The Sponsor must be notified in writing of the name and address of the 
new custodian. Under no circumstance shall the investigator relocate or dispose of any study 
documents before having obtained written approval from the Sponsor.
17.8. Monitoring
NCT03158285
The Sponsor will use a combination of monitoring techniques(central, remote, on-site 
monitoring)to monitor this study.
The Sponsor will perform on-site monitoring visits as frequently as necessary. The monitor will 
record dates of the visits in a study site visit log that will be kept at the study site. The first post-
initiation visit will be made as soon as possible after enrollment has begun. At these visits, the 
monitor will compare data entered into the CRF with the source documents (eg, 
hospital/clinic/physician’s officemedical records); a sample may be reviewed. The nature and 
location of all source documents will be identified to ensure that all sources of original data 
required to complete the CRF are known to the Sponsor and study-site personnel and are 
accessible for verification by the Sponsor study-site contact. If electronic records are maintained 
at the study site, the method of verification must be discussed with the study-site personnel. 
Direct access to source documents (medical records) must be allowed for the purpose of 
verifying that the recorded data are consistent with the original source data. Findings from this 
review will be discussed with the study-site personnel. The Sponsor expects that, during 
monitoring visits, the relevant study-site personnel will be available, the source documents will 
be accessible, and a suitable environment will be provided for review of study-related 
documents. The monitor will meet with the investigator on a regular basis during the study to 
provide feedback on the study conduct.
In addition to on-site monitoring visits, remote contacts can occur. It is expected that during 
these remote contacts, study-site personnel will be available to provide an update on the progress 
of the study at the site. 
Central monitoring will take place for data identified by the Sponsor as requiring central review.


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17.9. Study Completion/Termination
17.9.1.
Study Completion/End of Study
The study is considered completed with the last visit forthe last subject participating in the 
study. The final data from the study site will be sent to the Sponsor (or designee) after 
completion of the final subject visit at that study site, in the time frame specified in the Clinical 
Trial Agreement.
17.9.2.
Study Termination
The Sponsor reserves the right to close the study site or terminate the study at any time for any 
reasonat 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:
Failure of the investigator to comply with the protocol, the requirements of the IEC/IRB or
local health authorities, the Sponsor
's procedures, or GCP guidelines

Inadequate recruitment of subjects bythe investigator
Discontinuation of further study agentdevelopment
17.10. On-Site Audits
Representatives of the Sponsor
's clinical quality assurance department may visit the study site at 
any time during or after completion of the study to conduct an audit of the study in compliance 
with regulatory guidelines and company policy. These audits will require access to all study 
records, including source documents, for inspection. Subject privacy must, however, be 
respected. The investigator and study-site personnel are responsible for being present and 
available for consultation during routinely scheduled study-site auditvisits conducted by the 
Sponsor or its designees.
Similar auditing procedures may also be conducted by agents of any regulatory body, either as 
part of a national GCP compliance program or to review the results of this study in support of a 
regulatory submission. The investigator should immediately notify the Sponsor if he or she has 
been contacted by a regulatory agency concerning an upcoming inspection.
17.11. Use of Information and Publication
NCT03158285
All information, including but not limited to information regarding guselkumabor the Sponsor
's 
operations (eg,patent application, formulas, manufacturing processes, basic scientific data, prior 
clinical data, formulation information) supplied by the Sponsor to the investigator and not 
previously published, and any data, including pharmacogenomic or exploratory biomarker 


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research data, generated as a result of this study, are considered confidential and remain the sole 
property of the Sponsor. The investigator agrees to maintain this information in confidence and 
use this information only to accomplish this study, and will not use it for other purposes without 
the Sponsor
's prior written consent.
The investigator understands that the information developed inthe study will be used by the 
Sponsor in connection with the continued development of guselkumab, and thus may be 
disclosed as required to other clinical investigators or regulatory agencies. To permit the 
information derived from the clinical studies to be used, the investigator is obligated to provide 
the Sponsorwith all data obtained in the study.
The results of the study will be reported in a ClinicalStudy Report generated by the Sponsor and 
will contain data from all study sites that participated in the study as per protocol. Recruitment 
performance or specific expertise related to the nature and the key assessment parameters of the 
study will be used to determine a coordinating investigator. Results of pharmacogenomic or 
biomarker analyses performed after the Clinical Study Report has been issued will be reported in 
a separate report and will not require a revision of the Clinical Study Report. Study subject 
identifiers will not be used in publication of results. Any work created in connection with 
performance of the study and contained in the data that can benefit from copyright protection 
(except any publication by the investigator as provided for below) shall be the property of the 
Sponsor as author and owner of copyright in such work.
Consistent with Good Publication Practices and International Committee ofMedical Journal 
Editors guidelines,the Sponsor shall have the right to publish such primary (multicenter) data 
and information without approval from the investigator. The investigator has the right to publish 
study site-specific data after the primary data are published. If an investigator wishes to publish 
information from the study, a copy of the manuscript must be provided to the Sponsor for review 
at least 60days before submission for publication or presentation. Expedited reviews will be 
arranged for abstracts, poster presentations, or other materials. If requested by the Sponsor in 
writing, the investigator will withhold such publication for up to an additional 60days to allow 
for filing of a patent application. In the event that issues arise regarding scientific integrity or 
regulatory compliance, the Sponsor will review these issues with the investigator. The Sponsor 
will not mandate modifications to scientific content and does not have the right to suppress 
information. For multicenter study designs and substudy approaches, secondary results generally 
should not be published before the primary endpoints of a study have been published. Similarly, 
investigators will recognize the integrity of a multicenter study by not submitting for publication 
data derived from the individual study site until the combined results from the completed study 
have been submitted for publication, within 12months of the availability of the final data (tables, 
listings, graphs), or the Sponsor confirms there will be no multicenter study publication. 
Authorship of publications resulting from this study will be based on the guidelines on 
authorship, such as those described in the Uniform Requirements for Manuscripts Submitted to 
Biomedical Journals, which state that the named authors must have made a significant 
contribution to the design of the study or analysis and interpretation of the data, provided critical 
review of the paper, and given final approval of the final version.


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Registration of Clinical Studies and Disclosureof Results
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The Sponsor will register and disclose the existence of and the results of clinical studies as 
required by law.


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REFERENCES
NCT03158285
1.
Basra MKA, Fenech R, Gatt RM, Salek MS, Finlay AY. The Dermatology Life Quality Index 1994–2007: a 
comprehensive reviewof validation data and clinical results. Br J Rheumatol. 2008;159:997-1035.
2.
Bowes J, Orozco G, Flynn E, et al. Confirmation of TNIP1 and IL23A as susceptibility loci for psoriatic 
arthritis. Ann Rheum Dis. 2011;70(9):1641-1644.
3.
Cella D, Yount S, Sorensen M, Chartash E, Sengupta N, Grober J. Validation of the Functional Assessment of 
Chronic Illness Therapy Fatigue Scale relative to other instrumentation in patients with rheumatoid arthritis. J 
Rheumatol. 2005;32(5):811-819.
4.
Chandran V, Bhella S, Schentag C, Gladman D. Functional Assessment of Chronic Illness Therapy-Fatigue 
Scale is valid in patients with psoriatic arthritis. Ann Rheum Dis. 2007;66:936-939.
5.
Chen Z, Tato CM, Muul L, Laurence A, O
'Shea JJ. Distinct regulation of interleukin-17 in human T helper 
lymphocytes. Arthritis Rheum. 2007;56(9):2936-2946.
6.
Coates LC, Helliwell PS. Validation of minimal disease activity criteria for psoriatic arthritis using 
interventional ta. Arthritis Care Res (Hoboken). 2010; 62(7):965-969.
7.
Duerr RH, Taylor KD, Brant SR, et al. A genome-wide association study identifies IL23R as an inflammatory 
bowel disease gene. Science. 2006;314(5804):1403-1405.
8.
EuroQol Group. EuroQol -a new facility for the measurement of health-related quality of life. Health Policy. 
1990;16:199-208.
9.
Feldman SR, Gordon KB, Bala M, et al. Infliximab treatment results in significant improvement in the quality 
of life of patients with severe psoriasis:  a double-blind placebo-controlled trial. British Journal of 
Dermatology. 2005;152:954-960.
10. FelsonDT, Anderson JJ, Boers M, et al. American College of Rheumatology. Preliminary definition of 
improvement in rheumatoid arthritis. Arthritis Rheum. 1995;38(6):727-735.
11. Finlay AY, Khan GK.  Dermatology Life Quality Index (DLQI)--a simple practical measure for routine clinical 
use.  Clin Exp Dermatol.  1994;19(3):210-216.
12. Fredriksson T, Pettersson U.  Severe psoriasis –oral therapy with a new retinoid.  Dermatologica.  
1978;157(4):238-244.
13. Fries JF, Spitz P, Kraines RG, Holman HR.  Measurement of patient outcomes in arthritis.  Arthritis Rheum.  
1980;23(2):137-145.
14. Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A. A new approach to defining disease 
status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol. 
1994;21(12):2286-2291.
15. GladmanDD, AntoniC, MeaseP, CleggCO, NashP. Psoriatic arthritis: epidemiology, clinical features, 
course, and outcome. Ann Rheum Dis 2005;64:ii14-ii17.
16. Gladman DD, Farewell VT, Wong K, Husted J. Mortality Studies In Psoriatic Patients. Results from a single 
outpatient center.  Prognostic indicators for death. Arthritis Rheum. 1998;41(6):1103-1110.
17. Gladman DD, Inman RD, Cook RJ, et al. International spondyloarthritis interobserver reliability exercise--the 
INSPIRE study: II. Assessment of peripheral joints, enthesitis, and dactylitis. J Rheumatol. 2007;34(8):1740-
1745.
18. Gladman DD, Shuckett R, Russell ML, Thorne JC, Schachter RK. Psoriatic arthritis (PSA)--an analysis of 220 
patients. Q J Med. 1987;62(238):127-141.
19. Gladman DD, Ziouzina O, Thavaneswaran A, Chandran V. Dactylitis in psoriatic arthritis: prevalence and 
response to therapy in the biologic era. J Rheumatol. 2013;40(8):1357-1359.
20. Gottlieb A, Menter A, Mendelsohn A, et al. Ustekinumab, a human interleukin 12/23 monoclonal antibody, for 
psoriatic arthritis: randomised, double-blind, placebo-controlled, crossover trial. Lancet. 
2009;373(9664):633-640.


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21. Healy PJ, Helliwell PS. Measuring clinical enthesitis in psoriatic arthritis: assessment of existing measures and 
development of an instrument specific to psoriatic arthritis. Arthritis Rheum. 2008;59(5):686-691.
22. Helliwell PS, FitzGerald O, Fransen J. Composite disease activity and responder indices for psoriatic arthritis: 
A report from the GRAPPA 2013 Meeting on development of cutoffs for both disease activity states and 
response. J Rheum. 2014;41(6):1212-1217.
23. Helliwell PS, Kavanaugh A. Comparison of composite measures of disease activity in psoriatic arthritis using 
data from an interventional study with golimumab. Arthritis Care Res. 2014;66(5):749-756.
24. Helliwell PS, FitzGerald O, Fransen J, et al. The development of candidate composite disease activity and 
responder indices for psoriatic arthritis (GRACE project). Ann Rheum Dis. 2013;72(6):986-991.
25. Husted JA, Gladman DD, Cook RJ, Farewell VT. Responsiveness of health status instruments to changes in 
articular status and perceived health in patients with psoriatic arthritis. J Rheumatol. 1998;25(11):2146-2155. 
26. Kavanaugh A, Ritchlin C, Rahman P, et al. Ustekinumab, ananti-IL-12/23 p40 monoclonal antibody, inhibits 
radiographic progression in patients with active psoriatic arthritis: results of an integrated analysis of 
radiographic data from the phase 3, multicentre, randomised, double-blind, placebo-controlled PSUMMIT-1 
and PSUMMIT-2 trials. Ann Rheum Dis. 2014;73(6):1000-1006.
27. Khilji FA, Gonzalez M, Finlay AY. Clinical meaning of change in dermatology life quality index scores. Br J 
Dermatol. 2002;147(suppl 62): 25-54.
28. Kosinski M, Zhao SZ, Dedhiya S, et al.  Determining minimally important changes in generic and disease-
specific health-related quality of life questionnaires in clinical trials of rheumatoid arthritis.  
NCT03158285
Arthritis&Rheumatology. 2000;43(7):1478-1487.
29. Langrish CL, Chen Y, Blumenschein WM, et al. IL-23 drives a pathogenic T cell population that induces 
autoimmune inflammation. J Exp Med. 2005;201(2):233-240.
30. Liu Y, Helms C, Liao W, et al. A genome-wide association study of psoriasis and psoriatic arthritis identifies 
new disease loci. PLoS Genet. 2008;4(3):e1000041.
31. McInnes IB, Kavanaugh A, Gottlieb AB, et al, on behalf of the PSUMMIT 1 Study Group. Efficacy and safety 
of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, 
double-blind, placebo-controlled PSUMMIT 1 trial. Lancet. 2013;382(9894):780-789.
32. Mease PJ, McInnes IB, Kirkham B, et al. Secukinumab Inhibition of Interleukin-17A in Patients with Psoriatic 
Arthritis (FUTURE 1). N Engl J Med. 2015;373(14):1329-1339.
33. Mease PJ, van der Heijde D, Ritchlin CT, Cuchacovich R, Shuler CL, Lee CH, Samanta S, Lin CY, Gladman 
DD, Vangerow H. A Randomized, Double-Blind, Active-and Placebo-Controlled Phase 3 Study of Efficacy 
and Safety of Ixekizumab, Adalimumab, and Placebo Therapy in Patients Naïveto Biologic Disease 
Modifying Anti-Rheumatic Drugs with Active Psoriatic Arthritis [abstract].Arthritis Rheumatol.2015; 67 
(suppl 10).
34. Mease PJ, Kivitz AJ, Burch FX, et al.  Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on 
disease progression.  Arthritis Rheum. 2004;50(7):2264-2272.
35. Mease PJ, Woolley JM, Bitman B, Wang BC, Globe DR, Singh A. Minimally important difference of Health 
Assessment Questionnaire in psoriatic arthritis: relating thresholds of improvement in functional ability to 
patient-rated importance and satisfaction. J Rheumatol. 2011 Nov;38(11):2461-2465.
36. McInnes IB, Mease PJ, Kirkham B, et al. Secukinumab, a human anti-interleukin-17A monoclonal antibody, in 
patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial. 
Lancet. 2015;386(9999):1137-1146.
37. Mundt JC, Greist JH, Jefferson JW, et al. Prediction of suicidal behavior in clinical research by lifetime 
suicidal ideation and behavior ascertained by the electronic Columbia-Suicide Severity Rating Scale. J Clin 
Psych. 2013;74(9):887-893.
38. Nair RP, Duffin KC, Helms C, et al. Genome-wide scan reveals association of psoriasis with IL-23 and NF κB 
pathways. Nat Genet. 2009;41(2):199-204.


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
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NCT03158285
Approved, Date: 23 January 2018
39. Oppmann B, Lesley R, Blom B, et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with 
biological activities similar as well as distinct from IL-12. Immunity. 2000;13(5):715-725.
40. O
'Rielly DD, Rahman P. Genetics of susceptibility and treatment response in psoriatic arthritis. NatRev 
Rheumatol. 2011;7(12):718-732.
41. Ouyang W, Kolls JK, Zheng Y. The biological functions of T helper 17 cell effector cytokines in 
inflammation. Immunity. 2008; 28(4):454-467.
42. Pham T, Guillemin F, Claudepierre P, et al. TNFα antagonist therapy in ankylosing spondylitis and psoriatic 
arthritis:  recommendations of the French Society for Rheumatology. Joint Bone Spine. 2006;73:547–553.
43. Posner K, Brown GK, Stanley B, et al. The Columbia-Suicide Severity Rating Scale: Initial validity and 
internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry. 
2011;168(12):1266-1277.
44. Ritchlin C, Rahman P, Kavanaugh A, et al. Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, 
ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-
tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo 
controlled, randomised PSUMMIT 2 trial. Ann Rheum Dis. 2014;73:990-999.
45. Ritchlin CT. From skin to bone: translational perspectives on psoriatic disease. J Rheumatol. 2008;35(7):1434-
1437.
46. Setty AR, Choi HK. Psoriatic arthritis epidemiology. Curr Rheumatol Rep 2007;9(6):449-454.
47. Sokoll KB, Helliwell PS.  Comparison of disabilityand quality of life in rheumatoid and psoriatic arthritis.  J 
Rheumatol.  2001;28(8):1842-1846.
48. Tato CM, O
'Shea JJ. Immunology: what does it mean to be just 17? Nature. 2006;441(7090):166-168.
49. Torre Alonso JC, Rodriguez Perez A, Arribas Castrillo JM, et al. Psoriatic arthritis (PsA):  a clinical, 
immunological and radiological study of 180 Patients. Br J Rheumatol. 1991;30:245-250.
50. Wilson NJ, Boniface K, Chan JR, et al. Development, cytokine profile and function of human interleukin 17 
producing helper T cells. Nat Immunol. 2007;8(9):950-957.
51. van der Heijde DM, van Leeuwen MA, van Riel PL, et al. Biannual radiographic assessments of hands and feet 
in a three-year prospective followup of patients with early rheumatoid arthritis. Arthritis Rheum. 
1992;35(1):26-34.
52. van der Linden MA.  Disease Activity Scores using C-reactive protein. April 5, 2004. Available at: 
http://www.umcn.nl/scientist/afdelingen/reumatologie/the_das/the_das_crp. Accessed 19 August 2005.
53. van Riel PL, van Gestel AM, Scott DL, for the EULAR Standing Committee for International Clinical Studies 
Including Therapeutic Trials –ESCISIT. EULAR Handbook of Clinical Assessments in Rheumatoid Arthritis.  
Alphen Aan Den Rijn, The Netherlands: Van Zuiden Communications B.V.; 2000:40.
54. Ware JE, Kosinski M, Keller SD. Interpretation: Norm-Based. In: SF-36 Physical and Mental Health Summary 
Scales: A User’s Manual. Boston, MA: The Health Institute; 1994:8:1-8:42.
55. Ware JE Jr, Sherbourne CD. The MOS 36 item short form health survey (SF 36), I: conceptual framework and 
item selection. Med Care. 1992;30(6):473 483.
56. Wong K, Gladman D, Husted J, Long JA, Farewell VT. Mortality studies in psoriatic arthritis. Results from a 
single outpatient clinic. Causes and risk of death. Arthritis Rheum.  1997;40(10):1868-1872.
57. Zangger P, Gladman DD, Bogoch ER. Musculoskeletal surgery in psoriatic arthritis. J Rheumatol 1998; 25(4): 
725-729.
58. Zochling J, van der Heijde D, Burgos-Vargas R, et al. ASAS/EULAR recommendations for the management of 
ankylosing spondylitis. Ann Rheum Dis. 2006;65(4):442-452.


CNTO 1959  (guselkumab)
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Approved, Date: 23 January 2018
Attachment 1:The CASPAR Criteria
To meet the CASPAR (ClASsification criteria for Psoriatic ARthritis) criteria, a patient must have inflammatory 
articular disease (joint, spine, or entheseal) with ≥3 points from the following 5 categories:
1. Evidence of current psoriasis, a personal history of psoriasis, or a family history of psoriasis.

Current psoriasis is defined as psoriatic skin or scalp disease present today as judged by a 
rheumatologist or dermatologist.†

A personal history of psoriasis is defined as a history of psoriasis that may be obtained from a patient, 
family physician, dermatologist, rheumatologist, or other qualified health care provider.

A family history of psoriasis is defined as a history of psoriasis in a first-or second-degree relative 
according to patient report.
2. Typical psoriatic nail dystrophy including onycholysis, pitting, and hyperkeratosis observed on current physical 
examination.
3. A negative test result for the presence of rheumatoid factor by any method except latex but preferably by enzyme-
linked immunosorbent assay or nephelometry, according to the local laboratory reference range.
4. Either current dactylitis, defined as swelling of an entire digit, or a history of dactylitis recorded by a 
rheumatologist.
5. Radiographic evidence of juxtaarticular new bone formation, appearing as ill-defined ossification near joint 
margins (but excluding osteophyte formation) on plain radiographs of the hand or foot.
†Current psoriasis is assigned a score of 2; all other features are assigned a score of 1.
Reference
NCT03158285
Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H; CASPAR Study Group. Classification 
criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis & Rheumatism. 
2006;54(8):2665-2673.


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
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Approved, Date: 23 January 2018
Attachment 2:QuantiFERON® TB Gold Testing
The QuantiFERON®-TB Gold test is one of the interferon-(IFN-) based blood assays for TB screening (Cellestis, 
2009).  It utilizes the recently identified M.tuberculosis-specific antigens ESAT-6 and CFP-10 in the standard 
format, as well as TB7.7 (p4) in the In-Tube format, to detect in vitro cell-mediated immune responses in infected 
individuals.  The QuantiFERON®-TB Gold assay measures the amount of IFN-produced by sensitized T-cells 
when stimulated with the synthetic M. tuberculosis-specific antigens.  In M. tuberculosis-infected persons, sensitized 
Tlymphocytes will secrete IFN-in response to stimulation with the M. tuberculosis-specific antigens and,thus, the 
QuantiFERON®-TB Gold test should be positive.  Because the antigens used in the test are specific to M. 
tuberculosisand not found in BCG, the test is not confounded by BCG vaccination, unlike the tuberculin skin test.  
However, there is some cross-reactivity with the 3 Mycobacterium species, M. kansasii, M. marinum, and 
M.szulgai.  Thus, a positive test could be the result of infection with one of these 3species of Mycobacterium, in 
the absence of M. tuberculosisinfection.
In a study of the QuantiFERON®-TB Gold test (standard format) in subjects with active TB, sensitivity has been 
shown to be approximately 89% (Moriet al, 2004).  Specificity of the test in healthy BCG-vaccinated individuals 
has been demonstrated to be more than 98%.  In contrast, the sensitivity and specificity of the tuberculin skin test 
was noted to be only about 66% and 35% in a study of Japanesepatients with active TB and healthy BCG-
vaccinated young adults, respectively.  However, sensitivity and specificity of the tuberculin skin test depend on the 
population being studied, and the tuberculin skin test performs best in healthy young adults whohave not been 
BCG-vaccinated.
Data from a limited number of published studies examining the performance of the QuantiFERON®-TB Gold assay 
in immunosuppressed populations suggest that the sensitivity of the QuantiFERON®-TB Gold test is better than the 
tuberculin skin test even in immunosuppressed patients (Ferrara et al, 2005; Kobashi et al, 2007; Matulis et al, 
2008).  The ability of IFN--based tests to detect latent infection has been more difficult to study due to the lack of a 
gold standard diagnostic test; however, several TB outbreak studies have demonstrated that the tests correlated 
better than the tuberculin skin test with the degree of exposure that contacts had to the index TB case (Brock et al, 
2004; Ewer et al, 2003).  In addition, TB contact tracing studies have shown that patients who had a positive 
QuantiFERON®-TB Gold test result and were not treated for latent TB infection were much more likely to develop 
active TB during longitudinal follow-up than those who had a positive tuberculin skin test and a negative 
QuantiFERON®-TB Gold test result (Higuchi et al, 2007; Diel et al, 2008).
Although the performance of the new IFN--based blood tests for active or latent M.tuberculosisinfection have not 
been well validated in the immunosuppressed population, experts believe these new tests will be at least as, if not 
more, sensitive, and definitely more specific, than the tuberculin skin test (Barnes, 2004; personal communication, 
April, 2008 TB Advisory Board).
Performing the QuantiFERON®-TB Gold Test
The QuantiFERON®-TB Gold test In-Tube format will be provided for this study.  The In-Tube format contains 1 
additional M. tuberculosis-specific antigen, TB7.7 (p4), which is thought to increase the specificity of the test.  
To perform the test using the In-Tube format, blood is drawn through standard venipuncture into supplied tubes that 
already contain the M. tuberculosis-specific antigens.  Approximately 3 tubes will be needed per subject, each 
requiring 1mL of blood.  One tube contains the M. tuberculosis-specific antigens, while the remaining tubes contain 
positive and negative control reagents.  Thorough mixing of the blood with the antigens is necessary prior to 
incubation.  The blood is then incubated for 16 to 24 hours at 37C, after which tubes are centrifuged for 
approximately 15 minutes at 2000 to 3000g.  Following centrifugation, plasma is harvested from each tube, frozen, 
and shipped on dry ice to the central laboratory.  The central laboratory will perform an ELISA to quantify the 
amount of IFN-
NCT03158285
present in the plasma using spectrophotometry and computer software analysis.
The central laboratory will analyze and report results for each subject, and sites will be informed of the results.  
Subjects who have an indeterminate result should have the test repeated.
In the rare instance that the site isnot able to perform the QuantiFERON®-TB Gold test handling process prior to  
sending to Covance, this test may be performed locally by another laboratory, as approved by the Sponsor.


CNTO 1959  (guselkumab)
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Adherence toLocal Guidelines
Local country guidelines for immunocompromised patientsshould be consulted for acceptable antituberculous 
treatment regimens for latent TB.  If no local country guidelines for immunocompromised patients exist, US 
guidelines must be followed. 
In countries in which the QuantiFERON®-TB Gold test is not considered approved/registered, a tuberculin skin test 
is additionally required.
References
Barnes PF. Diagnosing latent tuberculosis infection: Turning glitter to gold [editorial]. Amer J Respir Crit Care 
Med.2004;170:5-6.
Brock I, Weldingh K, Lillebaek T, et al. Comparison of tuberculin skin test and new specific blood test in 
tuberculosis contacts. Am J Respir Crit Care Med.2004;170:65-69.
Cellestis.  QuantiFERON-TB Gold clinicians guide and QuantiFERON-TB Gold In-Tube Method package insert.  
Downloaded from www.cellestis.com, February 2009.
Diel R, Loddenkemper R, Meywald-Walter K, Niemann S, Nienhaus A. Predictive value of a whole blood IFN-
assay for the development of active tuberculosis disease after recent infection with mycobacterium tuberculosis. Am 
J Respir Crit Care Med. 2008;177:1164-1170.
Ewer K, Deeks J, Alvarez L, et al. Comparison of T-cell-based assay with tuberculin skin test for diagnosis of 
Mycobacterium tuberculosisinfection in a school tuberculosis outbreak. Lancet.2003;361:1168-73.
Ferrara G, Losi M, Meacci M, et al. Routine hospital use of a new commercial whole blood interferon-assay for 
the diagnosis of tuberculosis infection. Am J Respir Crit Care Med. 2005; 172:631-635.
Higuchi K, Nobuyuki H, Mori T, Sekiya Y. Use of QuantiFERON-TB Gold to investigate tuberculosis contacts in a 
high school.  Respirology.  007;12:88-92.
Kobashi Y, Mouri K, Obase Y, et al. Clinical evaluation of QuantiFERON TB-2G test for immunocompromised 
patients. Eur Respir J. 2007; 30:945-950.
Matulis G, Jüni P, Villiger PM, Gadola SD. Detection of latent tuberculosis in immunosuppressed patients with 
autoimmune diseases: performance of a Mycobacterium tuberculosis antigen-specific interferon assay. Ann 
Rheum Dis. 2008;67:84-90
Mori T, Sakatani M, Yamagishi F, et al. Specific detection of tuberculosis infection:  An interferon-
NCT03158285
-based assay 
using new antigens. Am J Respir Crit Care Med.2004;170:59-64.


CNTO 1959  (guselkumab)
Protocol CNTO1959PSA3002Amendment 1
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Approved, Date: 23 January 2018
Attachment 3:Tuberculin Skin Testing
Administering the Mantoux Tuberculin Skin Test
The Mantoux tuberculin skin test (CDC, 2000) is the standard method of identifying persons infected with 
Mycobacterium tuberculosis.  Multiple puncture tests (Tine and Heaf) should not be used to determine whether a 
person is infected because the amount of tuberculin injected intradermally cannot be precisely controlled.  
Tuberculin skin testing is both safe and reliable throughout the course of pregnancy.  The Mantoux tuberculin test is 
performed by placing an intradermal injection of 0.1mL of tuberculin into the inner surface of the forearm.  The test 
must be performed with tuberculin that has at least the same strength as either 5tuberculin units (TU) of standard 
purified protein derivative (PPD)-S or 2TU of PPD-RT23, Statens Seruminstitut, as recommended by the World 
Health Organization.  PPD strengths of 1TU or 250TU are not acceptable (Menzies, 2000).  Using a disposable 
tuberculin syringe with the needle bevel facing upward, the injection should be made just beneath the surface of the 
skin.  This should produce a discrete, pale elevation of the skin (a wheal) 6mm to 10mm in diameter.  To prevent 
needle-stick injuries, needles should not be recapped, purposely bent or broken, removed from disposable syringes, 
or otherwise manipulated by hand.  After they are used, disposable needles and syringes should be placed in 
puncture-resistant containers for disposal.  Institutional guidelines regarding universal precautions for infection 
control (eg, the use of gloves) should be followed.  A trained health care worker, preferably the investigator, should 
read the reaction to the Mantoux test 48 to 72 hours after the injection.  Subjects should never be allowed to read 
their own tuberculin skin testresults.  If a subject fails to show up for the scheduled reading, a positive reaction may 
still be measurable up to 1week after testing.  However, if a subject who fails to return within 72 hours has a 
negative test, tuberculin testing should be repeated.  The area of induration (palpable raised hardened area) around 
the site of injection is the reaction to tuberculin.  For standardization, the diameter of the induration should be 
measured transversely (perpendicular) to the long axis of the forearm.  Erythema (redness) should not be measured.  
All reactions should be recorded in millimeters, even those classified as negative.
Interpreting the Tuberculin Skin Test Results
In the US and many other countries, the most conservative definition of positivity for the tuberculin skin test is 
reserved for immunocompromised patients, and this definition is to be applied in this study to maximize the 
likelihood of detecting latent TB, even though the subjects may not be immunocompromised at baseline. 
In the US and Canada, an induration of 5mm or greater in response to the intradermal tuberculin skin test is 
considered to be a positive result and evidence for either latent or active TB. 
In countries outside the US and Canada, country-specific guidelines for immunocompromised patients should be 
consulted for the interpretation of tuberculin skin test results.  If no local country guidelines for 
immunocompromised patients exist, US guidelines must be followed. 
Treatment of Latent Tuberculosis
Local country guidelinesfor immunocompromised patientsshould be consulted for acceptable antituberculous 
treatment regimens for latent TB.  If no local country guidelines for immunocompromised patients exist, US 
guidelines must be followed.
References
NCT03158285
Centers for Disease Control and Prevention. Core curriculum on tuberculosis: What the clinician should know 
(Fourth Edition).  Atlanta, GA: Department of Health and Human Services; Centers for Disease Control and 
Prevention; National Center for HIV, STD, and TB Prevention; Divisionof Tuberculosis Elimination; 2000:25-86.
Menzies RI.  Tuberculin skin testing. In: Reichman LB, Hershfield ES (eds). Tuberculosis, a comprehensive 
international approach. 2nd ed.  New York, NY: Marcel Dekker, Inc; 2000:279-322.


CNTO 1959  (guselkumab)
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Attachment 4:Hepatitis B Virus (HBV) Screening with HBV DNA
Subjects must undergo screening for hepatitis B virus (HBV). At a minimum, this includes testing for HBsAg (HBV 
surface antigen), anti-HBs (HBV surface antibody), and anti-HBc total (HBV core antibody total): 

Subjects who test negative for all HBV screening tests (ie, HBsAg-, anti-HBc-, and anti-HBs-) are eligible
for this study.

Subjects who test negativefor surface antigen (HBsAg-) and test positive for core antibody (anti-HBc+) 
andsurface antibody (anti-HBs+) are eligiblefor this study.

Subjects who test positive onlyfor surface antibody(anti-HBs+) are eligiblefor this study.

Subjects who test positivefor surface antigen (HBsAg+) are NOTeligiblefor this study, regardless of the 
results of other hepatitis B tests.

Subjects who test positive only for core antibody (anti-HBc+) must undergo further testing for the 
presence of hepatitis B virus deoxyribonucleic acid (HBV DNA test). If the HBV DNA test is positive, the 
subject is NOT eligiblefor this study. If the HBV DNA test is negative, the subject is eligiblefor this 
study. In the event the HBV DNA test cannot be performed, the subject is NOT eligiblefor this study. 
For subjects who are not eligible for this study due to HBV test results, consultation with a physician with 
expertise in the treatment of hepatitis B virus infection is recommended.  
Eligibility based on hepatitis B virus test results
Hepatitis B test result
Action
Hepatitis B surface 
antigen
(HBsAg)
Hepatitis B surface
antibody
(anti-HBs)
Hepatitis B core 
antibody
(anti-HBc total)
Include
—
—
—
—
+
—
—
+
+
Exclude
+
— or+
— or+
Require testing for presence 
HBV DNA*
—
—
+
* If HBV DNA is detectable, exclude from the  clinical study. If HBV DNA testing cannot be performed, 
or there is evidence of chronic liver disease, exclude from the clinical study.  
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CNTO 1959  (guselkumab)
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Approved, Date: 23 January 2018
Attachment5:Anticipated Events
Anticipated Event
Anticipated events will be recorded and reported in this study. 
An anticipated event is an AE(serious or non-serious) that commonly occurs as a consequence of the 
underlying disease or condition under investigation (disease related) or background regimen.
For the purposes of this study the following events will be considered anticipated events:
Worsening of psoriasis
Worsening of PsA
Reporting of Anticipated Events
These events will be captured on the CRF and in the database, and will be reported to the Sponsor as 
described in All Adverse Events. Any event that meets SAEcriteria will be reported to the Sponsor within 
the appropriate timeline as described in Serious Adverse Events(Section 12.3.2). These anticipated events 
are exempt from expedited reporting as individual single cases to Health Authorities. However, if based 
on an aggregate review, it is determined that an anticipatedevent is possibly related to study agent, the 
Sponsor will report these events in an expedited manner.
Anticipated Event Review Committee (ARC)
An Anticipated Event Review Committee (ARC) will be established to perform reviews of pre-specified 
anticipatedevents at an aggregate level. The ARC is a safety committee within the Sponsor’s organization 
that is independent of the Sponsor’s study team. The ARC will meet to aid in the recommendation to the 
Sponsor’s study team as to whether there is a reasonable possibility that an anticipated event is related to 
the study agent.
Statistical Analysis
NCT03158285
Details of statistical analysis of anticipated events, including the frequency of review and threshold to 
trigger an aggregate analysis of anticipated events will be provided in a separate Anticipated Events 
Safety Monitoring Plan.


CNTO 1959  (guselkumab)
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INVESTIGATOR AGREEMENT
NCT03158285

SAP_001.pdf: 
1
Approved, Date: 21 March 2019
Janssen Research & Development *
Statistical Analysis Plan
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating 
the Efficacy and Safety of Guselkumab Administered Subcutaneously in Subjects with 
Active Psoriatic Arthritis
Protocol CNTO1959PSA3002; Phase 3
Amendment 3
CNTO1959   (guselkumab)
Status:
Approved
Date:
21 March 2019
Prepared by:
Janssen Research & Development, LLC
Document No.: EDMS-ERI-146207739
Compliance: The study described in this report was performed according to the principles of Good Clinical Practice (GCP). 
Confidentiality Statement
The information in this document contains trade secrets and commercial information that are privileged or confidential and may 
not be disclosed unless such disclosure is required by applicable law or regulations. In any event, persons to whom the 
information is disclosed must be informed that the information is privileged or confidential and may not be further disclosed by 
them. These restrictions on disclosure will apply equally to all future information supplied to you that is indicated as privileged or 
confidential.
NCT03158285
Title:
Version:
EDMS-ERI-196141432
2.0


CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959PSA3002 Amendment 3
2
Approved, Date: 21 March 2019
TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
ABBREVIATIONS ........................................................................................................................................ 6
SUMMARY OF CHANGES IN AMENDMENT 1 TO THE SAP (APPROVAL DATE: MAY 24, 
2018) ................................................................................................................................................... 8
SUMMARY OF CHANGES IN AMENDMENT 2 TO THE SAP.................................................................. 11
SUMMARY OF CHANGES IN AMENDMENT 3 TO THE SAP.................................................................. 13
1.
INTRODUCTION................................................................................................................................18
1.1.
Trial Objectives ..............................................................................................................................18
1.2.
Trial Design.................................................................................................................................... 18
1.3.
Statistical Hypotheses for Trial Objectives..................................................................................... 21
1.4.
Sample Size Justification ............................................................................................................... 22
1.4.1.
Primary Endpoint – ACR 20 Response at Week 24................................................................... 22
1.4.2.
Major Secondary Endpoint – Change from Baseline in Modified vdH-S Score at Week 
24 ................................................................................................................................................ 23
1.5.
Randomization and Blinding .......................................................................................................... 24
1.5.1.
Randomization............................................................................................................................24
1.5.2.
Maintenance of the Blind ............................................................................................................ 25
1.6.
Radiographic Image Reading and Scoring.................................................................................... 27
2.
GENERAL ANALYSIS DEFINITIONS ..............................................................................................28
2.1.
Visit Windows................................................................................................................................. 28
2.1.1.
Visit Windows for Dosing and PK Analysis................................................................................. 28
2.1.2.
Visit Windows for Radiographic Assessments and Analyses..................................................... 28
2.2.
Pooling Algorithm for Analysis ....................................................................................................... 28
2.3.
Analysis Sets.................................................................................................................................. 28
2.3.1.
Efficacy Analysis Set(s) .............................................................................................................. 28
Full Analysis Set 1 (Week 0 – Week 24)................................................................................. 28
2.3.1.1.
Full Analysis Set 2 (Week 24 – Week 52)............................................................................... 28
2.3.1.2.
Full Analysis Set 3 (Week 52 – Week 100)............................................................................. 28
2.3.1.3.
Full Analysis Set 1 for Structural Damage (Read Campaign 1).............................................. 29
2.3.1.4.
Full Analysis Set 2 for Structural Damage (Read Campaign 2).............................................. 29
2.3.1.5.
Full Analysis Set 3 for Structural Damage (Read Campaign 3).............................................. 29
2.3.1.6.
Per-Protocol Analysis Set (Week 0 – Week 24)...................................................................... 29
2.3.1.7.
2.3.2.
Safety Analysis Set..................................................................................................................... 29
2.3.3.
PK Analysis Set ..........................................................................................................................29
2.3.4.
Immunogenicity Analysis Set...................................................................................................... 30
2.3.5.
Pharmacodynamics Analysis Set ...............................................................................................30
2.4.
Definition of Subgroups.................................................................................................................. 30
2.5.
Treatment Failure...........................................................................................................................31
3.
INTERIM ANALYSIS AND DATA MONITORING COMMITTEE REVIEW....................................... 31
3.1.
Interim Analysis..............................................................................................................................31
3.2.
Data Monitoring Committee ........................................................................................................... 31
4.
SUBJECT INFORMATION................................................................................................................ 32
4.1.
Demographics and Baseline Characteristics................................................................................. 32
4.2.
Disposition Information................................................................................................................... 33
4.3.
Treatment Compliance................................................................................................................... 33
4.4.
Treatment Exposure and Study follow-up...................................................................................... 33
4.5.
Protocol Deviations ........................................................................................................................33
4.6.
Prior and Concomitant Medications...............................................................................................34
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5.
EFFICACY ......................................................................................................................................... 34
5.1.
General Method of Analysis........................................................................................................... 34
5.2.
Analysis Specifications................................................................................................................... 36
5.2.1.
Level of Significance................................................................................................................... 36
5.2.2.
Multiplicity Adjustment for Testing Procedures........................................................................... 36
US-Specific Multiplicity Adjustment for Testing Procedures ................................................... 37
5.2.2.1.
Global(Ex-US) Multiplicity Adjustment for Testing Procedures............................................... 39
5.2.2.2.
5.2.3.
Data Handling Rules................................................................................................................... 41
Missing Data Non-Responder Imputation (NRI)...................................................................... 41
5.2.3.1.
Missing Data Exhaustive Scenario Imputation........................................................................ 41
5.2.3.2.
Multiple Imputation (MI)........................................................................................................... 41
5.2.3.3.
5.2.3.3.1.
MI Using FCS Regression ................................................................................................41
5.2.3.3.2.
MI for Binary Endpoints for Tipping Point Sensitivity Analysis of MAR Assumption............... 42
5.2.3.3.3.
Missing Data Handling for Tipping Point Sensitivity Analysis for Continuous 
Endpoints................................................................................................................................. 42
5.2.3.3.4.
2-Step MI (for X-ray Imaging Data) .........................................................................................42
Missing Data Linear Extrapolation (LEXT) .............................................................................. 43
5.2.3.4.
Missing Data Last Observation Carried Forward (LOCF) ....................................................... 43
5.2.3.5.
Missing Data as Missing for Continuous Endpoints................................................................43
5.2.3.6.
5.2.3.6.1.
Missing Data Handling for Tipping Point Analysis Evaluating the Assumption of 
MCAR for Continuous Endpoints.............................................................................................43
5.2.4.
Estimands ................................................................................................................................... 44
Composite Strategy................................................................................................................. 44
5.2.4.1.
Alternative Composite Strategy...............................................................................................45
5.2.4.2.
Treatment Policy Strategy ....................................................................................................... 45
5.2.4.3.
Per-Protocol Strategy .............................................................................................................. 45
5.2.4.4.
5.3.
Primary Efficacy Endpoint(s).......................................................................................................... 46
5.3.1.
Definition..................................................................................................................................... 46
5.3.2.
Analysis Methods........................................................................................................................47
Sensitivity and Supplementary Analyses ................................................................................ 48
5.3.2.1.
Subgroup Analyses ................................................................................................................. 49
5.3.2.2.
Summary of Analyses Related to the Primary Endpoint of ACR 20 Response at Week 
5.3.2.3.
24............................................................................................................................................. 49
5.4.
Major Secondary Endpoints........................................................................................................... 51
5.4.1.
Change from Baseline in HAQ-DI Score at Week 24................................................................. 52
Definition.................................................................................................................................. 52
5.4.1.1.
Analysis Methods .................................................................................................................... 52
5.4.1.2.
5.4.2.
Proportion of Subjects with ACR 50 Response at Week 24, Proportion of Subjects with 
ACR 50 Response at Week 16, Proportion of Subjects with ACR 20 Response at Week 
16, and Proportion of Subjects with ACR 70 Response at Week 24.......................................... 53
Definition.................................................................................................................................. 53
5.4.2.1.
Analysis Methods .................................................................................................................... 53
5.4.2.2.
5.4.3.
Proportion of Subjects who Achieve a Psoriasis IGA Response at Week 24 Among the 
Subjects with ≥3% BSA Psoriatic Involvement and an IGA Score of ≥2 (mild) at 
Baseline ...................................................................................................................................... 53
Definition.................................................................................................................................. 53
5.4.3.1.
Analysis Methods .................................................................................................................... 53
5.4.3.2.
5.4.4.
Change from Baseline in Modified vdH-S Score at Week 24..................................................... 54
Definition.................................................................................................................................. 54
5.4.4.1.
Analysis Methods .................................................................................................................... 55
5.4.4.2.
5.4.4.2.1.
Sensitivity Analysis............................................................................................................... 55
5.4.4.2.2.
Subgroup Analysis ............................................................................................................... 57
5.4.5.
Change from Baseline in Enthesitis Score at Week 24 and Proportion of subjects with 
Resolution of Enthesitis at Week 24 in Subjects with Enthesitis at Baseline.............................58
Definition.................................................................................................................................. 58
5.4.5.1.
Analysis Methods .................................................................................................................... 58
5.4.5.2.
5.4.6.
Change from Baseline in Dactylitis Scores at Week 24 and Proportion of subjects with 
Resolution of Dactylitis at Week 24 in Subjects with Dactylitis at Baseline................................59
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Definition.................................................................................................................................. 59
5.4.6.1.
Analysis Methods .................................................................................................................... 59
5.4.6.2.
5.4.7.
Change from Baseline in SF-36 PCS Score at Week 24 and Change from Baseline in 
SF-36 MCS score at Week 24.................................................................................................... 60
Definition.................................................................................................................................. 60
5.4.7.1.
Analysis Methods .................................................................................................................... 60
5.4.7.2.
5.4.8.
Change from Baseline in DAS28 (CRP) at Week 24.................................................................. 61
Definition.................................................................................................................................. 61
5.4.8.1.
Analysis Methods .................................................................................................................... 61
5.4.8.2.
5.4.9.
Summary of Analyses Related to Major Secondary Endpoints.................................................. 62
5.4.10.
Additional Tipping Point Analyses ..............................................................................................63
5.5.
Other Efficacy Variable(s) .............................................................................................................. 64
5.5.1.
Efficacy Endpoints Related to Reduction of Signs and Symptoms and Physical 
Function ...................................................................................................................................... 65
Definition.................................................................................................................................. 65
5.5.1.1.
5.5.1.1.1.
ACR Related Endpoints ....................................................................................................... 65
5.5.1.1.2.
HAQ-DI Related Endpoints .................................................................................................. 65
5.5.1.1.3.
DAS28 Related Endpoints.................................................................................................... 66
5.5.1.1.4.
Responders Based on Modified Psoriatic Arthritis Responder Criteria (PsARC)................ 66
5.5.1.1.5.
Enthesitis Related Endpoints ...............................................................................................66
5.5.1.1.6.
Dactylitis Related Endpoints ................................................................................................67
5.5.1.1.7.
PASDAS Related Endpoints ................................................................................................67
5.5.1.1.8.
GRACE Related Endpoints .................................................................................................. 68
5.5.1.1.9.
mCPDAI Related Endpoints................................................................................................. 69
5.5.1.1.10.
DAPSA Related Endpoints................................................................................................... 69
5.5.1.1.11.
Minimal Disease Activity (MDA) and Very Low Disease Activity (VLDA) ............................70
5.5.1.1.12.
BASDAI Related Endpoints.................................................................................................. 70
Analysis Methods .................................................................................................................... 71
5.5.1.2.
5.5.2.
Efficacy Endpoints Related to Skin Disease............................................................................... 76
Definitions................................................................................................................................77
5.5.2.1.
5.5.2.1.1.
PASI Related Endpoints....................................................................................................... 77
5.5.2.1.2.
Endpoints Related to DLQI................................................................................................... 78
Analysis Methods .................................................................................................................... 78
5.5.2.2.
5.5.3.
Other Radiographic Endpoints.................................................................................................... 80
Definition.................................................................................................................................. 81
5.5.3.1.
Analysis Methods .................................................................................................................... 82
5.5.3.2.
5.5.3.2.1.1.
Radiographic Reader’s Agreement................................................................................... 85
5.5.4.
Other Efficacy Endpoints Related to Health-Related Quality of Life and Health 
Economics .................................................................................................................................. 86
Definition.................................................................................................................................. 87
5.5.4.1.
5.5.4.1.1.
SF-36 Questionnaire ............................................................................................................ 87
5.5.4.1.2.
FACIT-Fatigue Questionnaire ..............................................................................................87
5.5.4.1.3.
EQ-5D Questionnaire........................................................................................................... 87
5.5.4.1.4.
WPAI Questionnaire............................................................................................................. 88
Analysis Methods .................................................................................................................... 89
5.5.4.2.
5.5.5.
Other Tipping Point Analyses ..................................................................................................... 92
6.
SAFETY............................................................................................................................................. 93
6.1.
Safety Tables Presentation............................................................................................................ 93
6.1.1.
Summaries Through Week 24.................................................................................................... 93
6.1.2.
Summaries Through Week 52.................................................................................................... 94
6.1.3.
Summaries Through End of Study..............................................................................................94
6.2.
Adverse Events..............................................................................................................................95
6.3.
Clinical Laboratory Tests................................................................................................................ 96
6.4.
Vital Signs and Physical Examination Findings............................................................................. 96
6.5.
Electrocardiogram..........................................................................................................................97
6.6.
Other Safety Parameters ............................................................................................................... 97
6.6.1.
Suicidal Ideation and Behavior ................................................................................................... 97
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Statistical Analysis Plan CNTO1959PSA3002 Amendment 3
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7.
PHARMACOKINETICS/PHARMACODYNAMICS ........................................................................... 98
7.1.
Pharmacokinetics........................................................................................................................... 98
7.2.
Immunogenicity (Antibodies to Guselkumab) .............................................................................. 100
7.3.
Pharmacodynamics...................................................................................................................... 101
7.4.
Pharmacokinetic/Pharmacodynamic Relationships..................................................................... 102
REFERENCES.......................................................................................................................................... 103
APPENDICES........................................................................................................................................... 105
APPENDIX 1:   RULES APPLIED IN DEFINITIONS OF ENDPOINTS................................................... 105
APPENDIX 2:  STATISTICAL HYPOTHESIS.......................................................................................... 109
APPENDIX 3:   DESCRIPTION OF STATISTICAL MODELS................................................................. 113
1.
MIXED-EFFECT MODEL REPEATED MEASURES (MMRM)....................................................... 113
2.
CONSTRAINED LONGITUDINAL DATA ANALYSIS (CLDA) MODEL ........................................ 113
3.
MIXED EFFECT LINEAR GROWTH CURVE MODEL................................................................... 113
4.
MEDIATION ANALYSIS.................................................................................................................. 114
APPENDIX 4:   SUMMARY OF ANALYSES BASED ON MULTIPLE IMPUTATION ............................ 115
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ABBREVIATIONS
ACR
American College of Rheumatology
AE
adverse event
ALT
Alanine aminotransferase
ANA
Antinuclear antibodies
ANCOVA
analysis of covariance
ANOVA
Analysis of variance
AST
Aspartate aminotransferase
BASDAI
Bath Ankylosing Spondylitis Disease Activity Index
BMI
Body mass index
BSA
Body surface area
CASPAR
Classification Criteria for Psoriatic Arthritis
CI
confidence interval
CMH
Cochran-Mantel-Haenszel
CRF
case report form
CRP
C-reactive protein
CSR
Clinical Study Report
DAS28
Disease Activity Index Score 28 
DBL
database lock
DICOM
Digital Imaging and Communications in Medicine
DIP
Distal interphalangel
DLQI
Dermatology Life Quality Index
DMARDS
Disease-Modifying Antirheumatic Drugs
DMC
Data Monitoring Committee
dsDNA
Double-stranded DNA
ECG
Electrocardiogram
eCRF
electronic case report form
EE
Early escape
EQ-5D
EuroQol 5 Dimensions Health-Related Quality of Life
FACIT-Fatigue
Functional Assessment of Chronic Illness Therapy - Fatigue
FAS
Full analyses set
FDA
Food and Drug Administration
GDEV
Physician’s Global Assessment of Disease Activity
GDPT
Patient’s Global Assessment of Disease Activity
GMS
Global Medical Safety
GO
Gross Osteolysis
HAQ-DI
Health Assessment Questionnaire Disability Index
ICH
International Conference on Harmonization
IRC
Imaging research center
ITT
Intent-to-Treat
IWRS
interactive web response system
JSN
Joint space narrowing
LEF
Leflunomide
LEI
Leeds Enthesitis Index
LLOQ
Lower limit of quantification
LOCF
last observation carried forward
LSmeans
Least square means
MCP
Metacarpophalangeal Joint
MCS
Mental Component Score
MDA
Minimal Disease Activity
MedDRA
Medical Dictionary for Regulatory Activities
mITT
Modified Intent to Treat
MMRM
Mixed effect repeated measures
MTX
Methotrexate
NAPSI
Nail Psoriasis Severity Index
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NCI-CTCAE
National Cancer Institute - Common Terminology Criteria for Adverse Events
NRI
Non-responder imputation
NSAIDs
non-steroidal anti-inflammatory drug
PAIN
Patient’s assessment of pain
PASDAS
Psoriatic ArthritiS Disease Activity Score
PASI
Psoriasis Area and Severity Index
PD
Pharmacodynamic
PI
principal investigator
PIC
Pencil in cup
PIP
proximal interphalangeal
PK
pharmacokinetic(s)
PRO
patient reported outcome
PsA
Psoriatic Arthritis
PsARC
Psoriatic Arthritis Response Criteria
RA
Rheumatoid arthritis
RBC
Red blood cell
SAE
serious adverse event
SAP
Statistical Analysis Plan
SD
standard deviation
SDC
Smallest detectable difference
SF-36
36-Item Short Form Survey Instrument
SJC
Swollen joint count
SMQ
Standarized MedDRA Query
SSG
Statistical support group
SSZ
Sulfasalazine
SUA
Serious unexpected adverse event
TB
tuberculosis
TF
Treatment failure
TNF
tumor necrosis factor
TJC
Tender joint count
ULN
Upper limit of normal
VAS
Visual analog scale
vdH-S
Van der Heijde Sharp
WBC
White blood cell
WLQ
Work limitations questionnaire
WPAI
Work productivity and activity impairment
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SUMMARY OF CHANGES IN AMENDMENT 1 TO THE SAP (APPROVAL DATE: 
MAY 24, 2018)
This statistical analysis plan (SAP) was amended to implement the following modifications to 
the original SAP:
1. Modified Treatment failure rules
2. Modified multiplicity control method to separate US and rest of the world

Rest of the world: modified overall control for all endpoints and both dose levels to 
control 2 doses for the primary endpoints, and control within dose level for primary 
and all major secondary endpoints

US:  modified overall control for all endpoints and both dose levels to control 
selective endpoints and both dose levels by removing highly correlated major 
secondary endpoints from controlled list 
3. Modified the Multiple Imputation (MI) methods

Impute the continuous components for binary endpoints instead of the composite 
binary endpoint itself

Use the Full Conditional Specifications (FCS) to replace the imputation first imputed 
non-monotone missing values and then imputed monotone missing values.

Added a 2 step MI for X-ray

Added an appendix table to specify details and summarize the MI imputation methods
for endpoints with possibility to use MI method
2. Modified/added definition of estimands and list of endpoints using each of the estimand

Modified composite estimand for binary endpoints with 4 components for clarity and 
expanded endpoints using composite estimand from primary and major secondary to 
all binary endpoints.

Modified the treatment policy estimand with 4 components for clarity and expanded 
endpoints using composite estimand from primary and x-ray endpoints to include 
change from baseline in HAQ, DAS28(CRP), SF36-PCS and SF36-MCS at Week 24.

Replace the treatment efficacy estimand with composite estimand for continuous 
endpoints and use this estimand for all non-x-ray continuous endpoints.

Added an expanded composite estimand to incorporate expanded treatment failure 
rules and use this estimand as supplementary analysis for the primary endpoint.
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
Added a per-protocol estimand and use this estimand as supplementary analysis for 
the primary endpoint.
3. Added/modified analysis methods

Modified MMRM by adding the interactions of the fix effects to use a model with full 
parameters, and added cLDA method if more than 2% subjects have missing baseline 
measurements.

For non-x-ray continuous major secondary endpoints, added analysis methods when 
the data have extreme departure from normality

Switched ANCOVA on the original scale from sensitivity analysis to main analysis 
for change from baseline in vdHS score

Changed analysis method of other binary endpoints from GLMM model or logistic 
regression to CMH test 

Modified or added sensitivity/supplementary analysis for ACR20 at Week 24
a) For composite estimand when the main analysis is based on non-responder 
imputation, replace the sensitivity analysis based on MAR tipping point analysis 
to Exhaustive Scenario Imputation tipping analysis to cover all possible scenarios
b) Added analyses based on expanded composite estimand 
c) Added analyses based on per-protocol estimand

Added/modified sensitivity analysis for Change from baseline in vDHS score at 24
a) Switched ANOVA analysis based on van der Waerden normal score from main 
analysis to sensitivity analysis
b) Added analyses based on 2 step MI
c) Modified the name of mixed effect regression model to mixed effect linear curve 
model and incorporated missing data imputation in this analysis
d) Modified completers analysis by using the ANCOVA on original scale from 
ANOVA on van der Waerden normal score
e) To evaluate the MCAR assumption added a 2-dimensional tipping point analysis.

Modified summary tables of analysis methods to the end of the sections for each type 
of endpoints

Added a section for suicidal ideation and behavior.
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Additionally, non-content related wording or formatting changes were made to enhance clarity 
and to generate 2 consistent SAPs.
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SUMMARY OF CHANGES IN AMENDMENT 2 TO THE SAP
This statistical analysis plan (SAP) was amended to implement the following modifications to 
the original SAP:
1. Section 2.4.
a.
Revised the categories for the race subgroup - #1b
b. Instead of subgrouping by geographical region defining a subgroup called 
participating countries - #1g.
c.
Added subgroups #2l, #3d, #3e, and #3f.
2. Added clarification to treatment failure (section 2.5) criterion #1 to include adverse events 
caused by worsening of PsA. 
3. Modified multiplicity control method (section 5.2.2)
4. Added a supplementary analysis for IGA response based on the treatment policy estimand to 
section 5.4.3 and Table 6.
5. Modified assessment of normality of residuals from MMRM/cLDA models by using Q-Q 
plots in addition to the Shapiro-Wilks test (sections 5.1 and 5.4.1.2, and Table 6) .
6. Added clarification to section 5.2.3.1 regarding the imputation of each variable within its 
possible range of values.
7. Modified/added clarification to the first step of the 2-step MI procedure in section 5.2.3.3.4.
8. Section 5.4.4.2.1 (in-text as well as Table 5):
a.
Modified sensitivity analyses #4. No longer applying using bootstrapping to estimate 
the SD.
b. Modified sensitivity analyses #5, and #6 such that they do not use the Multiple 
Imputation technique to impute missing vdH-S scores.
9. Subgroup analysis for the change from baseline in vdH-S score (section 5.4.4.2.2 and Table 
5) are based on observed data and not MI imputed datasets.
10. Modified the enthesitis scoring for subjects with an incomplete set of 6 evaluated sites at a 
particular visit (section 5.4.5.1). Removed the use of non-missing site score based imputation 
to adjust for sites with missing scores.
11. Modified analysis methods for enthesitis and dactylitis related endpoints (sections 5.4.5.2 and
5.4.6.2) in accordance with the multiplicity control method (section 5.2.2).
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12. Added clarification to analysis methods for enthesitis and dactylitis related endpoints 
(sections 5.4.5.2 and 5.4.6.2) that the MI method will be applied to each study separately to 
obtain the MI datasets for each study.
13. Added the definition for low or very lose disease activity based on the PASDAS score 
(section 5.5.1.1.7) and a corresponding analysis to Table 8.
14. Added the definition of low disease activity based on the GRACE index score (section 
5.5.1.1.8) and a corresponding analysis to Table 8.
15. Added the definition of low disease activity based on the mCPDAI score (section 5.5.1.1.9) 
and a corresponding analysis to Table 8.
16. Added the definition of remission or low disease activity based on the DAPSA score (section 
5.5.1.1.10) and a corresponding analysis to Table 8.
17. Added the definition of very low disease activity (section 5.5.1.1.11) and a corresponding 
analysis to Table 8.
18. Added the requirement of BASDAI>0 at baseline for the analysis of the change from 
baseline in BASDAI score (section 5.5.1.1.12 and Table 8).
19. Changed threshold for DLQI to 5 instead of 1(sections 5.5.2 and 5.5.2.1.2, and Table 9)
20. Added clarification to section 6.4, regarding reporting of abnormalities or changes during 
physical examination as adverse events.
21. Added section on suicidal ideation (section6.6)
22. Separated joint evaluability rules for surgical joint procedures and injections administered 
due to PsA or non-PsA reasons in Appendix 1 (Joint Evaluability Rules for Sign and 
Symptom Data).
23. Added clarification to Table 12 in Appendix 5
a.
Imputation variables to be used for MIdataset2.
b. Use of enthesitis-4, which is the tender entheses count based on 4 sites (left and right 
achilles tendon insertion, and left and right humeral epicondyle lateral) instead of 6 
sites at baseline and Week 2, in the imputation of enthesitis scores.
c.
Change from baseline at Week 24 in enthesitis score will be calculated among 
subjects with at least one tender enthesis at baseline.
d. Added footnotes “d”, “e”, and “f”.
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SUMMARY OF CHANGES IN AMENDMENT 3 TO THE SAP
1. Revised definition of FAS1-SD. It includes all randomized subjects who received at least 
1 (partial or complete) dose of study agent, regardless of whether they had a modified 
vdH-S score at baseline.
2. Similar revision to the definitions of FAS2-SD and FAS3-SD.
3. Revised the definition of subgroups (section 3.4):
a.
Age at baseline (year):  < 45, ≥ 45 and < 65, ≥65 (revised definition)
Age at baseline (year):  < 65, ≥ 65 (previous definition)
b. Participating countries: Removed Canada and Germany as they are not 
participating in this study.
c.
CRP at baseline (mg/dL): < 1, 1-2, ≥ 2(lab data) 
d. Clarified that the following disease characteristics are assessed at baseline:
PsA duration, number of swollen joints, number of tender joints, HAQ-DI, 
dactylitis, enthesitis, PASI, BSA, and IGA.
e.
Clarified that the subgroup of use of non-biologic DMARDs at baseline is based 
on the eCRF data and not on IWRS randomization factor.
f.
Removed the category of “any DMARDs” from the subgroup of non-biologic 
DMARDs at baseline. The revised definition includes only three categories: 
None, MTX, non-MTX DMARDs.
g. Edited the descriptors for the reason of discontinuation of prior DMARDs.
4. Added the following paragraph to Section 4
Subject information will be summarized by randomized treatment group based on the 
FAS1. Treatment exposure (e.g., number of treatment administrations, and 
cumulative dose received) and duration of study follow-up time will be summarized 
by treatment actually received based on the safety analysis set (Section 4.4).  
5. Added the following information to Section 5.1 for binary response efficacy endpoints:
The Mantel Fleiss criterion will be used to determine the appropriateness of using the 
CMH test at each visit for each treatment pair under comparison. If the Mantel Fleiss 
criterion is not satisfied the Fisher’s exact test will be used instead of the CMH test to 
compare the two treatment groups.
For analyses based on Multiple Imputation, the inferences from the analysis of each 
imputed data are pooled. The within imputation variance and between imputation 
variance are combined to estimate the total variance of the stratum adjusted difference 
of proportions. This estimate of the variance and critical values from the t-distribution 
are used to calculate the confidence interval for the stratum adjusted difference of 
proportions. The SAS procedure PROC MIANALYZE is used where the critical 
value is based on the t-distribution which is different from the analysis not based on 
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MI where normal distribution is used. The large number of observations in our data 
imply that the critical values from the t-distribution are almost identical to the critical 
values from the standard normal distribution. 
The Wilson-Hilferty34 transformation is used to pool the p-values from each imputed 
data set.
For endpoints (resolution of enthesitis and  resolution of dactylitis) that are based on 
data combined from studies CNTO1959PSA3001 and CNTO1959PSA3002 the 
analysis will be stratified by the combination of study and randomization 
stratification factors.
6. For major secondary efficacy endpoints other than radiographic endpoints the analysis 
will be performed using an ANCOVA model based on MI data and will no longer use a 
Mixed Effect Repeated Measures or Constrained Longitudinal Data Analysis Model. The 
previously planned sensitivity analyses using an ANOVA model based on the van der 
Waerden normal score will not be performed. These changes to the plan are reflected in 
the edits in Section 5.1 for major secondary continuous efficacy endpoints. Added details 
regarding the calculation of the  confidence intervals and p-values.
7. Revisions to section 5.2.2.1 (US-Specific Multiplicity Adjustment for Testing 
Procedures); switched order in which the endpoints for enthesitis and dactylitis are tested 
in the graphical testing procedure.
8. Added section 5.2.2.2 (Global Multiplicity Adjustment for Testing Procedure)
9. Added the following to Section 5.2.3.3.1:
For categorical endpoints (IGA response, enthesitis resolution, dactylitis resolution), 
the above imputation will be performed for the respective scores on a continuous 
scale, then rounded to the nearest integer prior to deriving the response or resolution.
10. Revised the definition of the Treatment Failure Criteria (Section 2.5). The TF criteria are 
expanded by considering discontinuation of study agent due to other reasons (in addition 
to lack of efficacy) as a criterion for TF. This is reflected in criterion 1 which now states -  
Discontinued study agent injections due to any reason.
11. Added a definition for the alternative composite estimand (Section 5.2.4.2).
12. Added the following to Section 5.2.4.3:
The Treatment Policy Estimand will be analyzed for all major secondary endpoints, 
and selected endpoints (Table 11a) analyzed at Week 16.
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13. In section 5.3.2.1, for the primary endpoint, deleted the supplementary analyses based on 
the previously defined expanded composite estimand, and added a supplementary 
analysis based on the alternative composite estimand. This is also reflected in Table 4.
14. Added clarification to Section 5.4 about the analysis sets to be used for psoriasis response 
of IGA, change from baseline in enthesitis score, resolution of enthesitis, change from 
baseline in dactylitis score. and resolution of dactylitis.
15. Section 5.4.1.2 reflects changes to the analysis methods for HAQ-DI score as those 
described in item 6 (above) and in Section 5.1.
16. Sections 5.4.5.2, 5.4.6.2, 5.4.7.2, and 5.4.8.2 reflect changes as those described in item 6 
above. These changes are also reflected in Table 6, which summarizes analyses related to 
major secondary endpoints other than the change from baseline in modified vdH-S score.
17. Added section 5.4.10 (Additional Tipping Point Analyses) that describes the tipping point 
analyses to be performed on the major secondary endpoints based on the Treatment 
Policy Estimand.
18. In section 5.5.1.2, added that change from baseline in HAQ-DI, DAS28 (CRP), dactylitis, 
and enthesitis scores will be analysed using an ANCOVA model on MI data.
19. Added endpoint - Proportion of subjects with an IGA score of 0 (cleared) at Week 16
among the subjects with ≥3% BSA psoriatic involvement and an IGA score of ≥2 (mild) 
at baseline – to Section 5.5.2.
20. In section 5.5.2 -  changed the requirement for baseline DLQI score to be >1 instead of ≥ 
5 for the endpoint :
“Proportion of subjects who achieve a DLQI score of 0 or 1 by visit through Week 
100 among the subjects with baseline DLQI score > 1 and with ≥ 3% BSA psoriatic 
involvement and an IGA score of ≥ 2 (mild) at baseline”
21. In Section 5.5.3 the following 3 endpoints were changed from:
Proportion of subjects with radiographic progression (based on the smallest 
detectable change [SDC]) from baseline by visit through Week 100.
Proportion of subjects with radiographic joint erosion progression (based on SDC) 
from baseline by visit through Week 100.
Proportion of subjects with radiographic JSN progression (based on the SDC) from 
baseline by visit through Week 100.
To,
Proportion of subjects without radiographic progression (based on the smallest 
detectable change [SDC]) from baseline by visit through Week 100.
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Proportion of subjects without radiographic joint erosion progression (based on SDC) 
from baseline by visit through Week 100.
Proportion of subjects without radiographic JSN progression (based on the SDC) 
from baseline by visit through Week 100.
22. Added 2 endpoints - Change from baseline in FACIT-fatigue score at Week 24 by ACR 
20 response at Week 24, and Proportion of subjects who achieve ≥ 4-point improvement 
from baseline in FACIT-fatigue score at Week 24 by ACR 20 response at Week 24 – to 
Section 5.5.4.
23. In Section 5.5.4.2:

added that the change from baseline in SF-36 PCS score and SF-36 MCS score 
will be also be analyzed using an ANCOVA model on MI data. 

Added a description of additional analyses for FACIT-Fatigue.
24. Added section 5.5.5, that explains tipping point analyses to be performed for endpoints 
other than the primary and major secondary endpoints.
25. Added the following 3 references:
Yeonhee Kim, Seunghyun Won. Adjusted proportion difference and confidence interval in stratified 
randomized trials. PharmaSUG 2013 – Paper SP04.
Bohdana Ratitch, et al. Combining analysis results from multiply imputed cartegorical data. PharmaSUG 
2013- Paper SP03.
L. Valeri and T. J. VanderWeele (2013), “ Meidation Analysis Allowing for Exposure-Mediator 
Interactions and Causal Interpretation: Theoretical Assumptions and Implementation with SAS and SPSS 
Macros”, Psychological Methods, Vol. 18, No.2: 137-150.
26. Added description of Mediation Analysis to Appendix 3.
27. Revisions to Table 12:
a.
Changed “at” to “through” for endpoints HAQ-DI score, DAS28 (CRP) score, 
Enthesitis score, Dactylitis score, PCS score, and MCS score.
b. Added MI for IGA change from baseline through Week 24.
c.
Edit to footnote “a”:
i. MIdataset2 is different from MIdataset1 as the joint scores used in DAS 
28 (CRP) are different from those used in ACR. (current footnote)
ii. MIdataset2 is different from MIdataset1 as it is based on a different 
Estimand. The same, MIdataset2, data set can be used for both HAQ-DI 
and DAS28(CRP) analyses. (previous footnote).
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d. Edit to footnote “c”:
i. Levels for Treatment and Discontinuation of treatment DT combination 
(HDT: High dose of Guselkumab + disc. of treatment; LDT: Low dose of 
Guselkumab + disc. of treatment): placebo, HDT, LDT (current footnote)
ii. Levels for Treatment and Discontinuation of treatment DT combination 
(HDT: High dose of Guselkumab + disc. of treatment; LDT: Low dose of 
Guselkumab + disc. of treatment): placebo, HDT0-16, HDT16-24, H, 
LDT0-16, LDT16-24, L. HDT0-16 and HDT16-24 maybe collapsed into 
HDT, and LDT0-16 and LDT16-24 maybe collapsed into HDT if there are 
too many missing values within the subgroup of incomplete cases 
(previous footnote).
e.
Edits to footnote “d”:
i. Enthesitis-4 is the tender entheses count based on 4 sites (left and right 
achilles tendon insertion, and left and right humeral epicondyle lateral) 
instead of 6 sites. Only baseline, Week 2, Week 4 are included as ancillary 
variables. (current footnote)
ii. Enthesitis-4 is the tender entheses count based on 4 sites (left and right 
achilles tendon insertion, and left and right humeral epicondyle lateral) 
instead of 6 sites at baseline and Week 2. (previous footnote)
28. Revised Appendix 2. Deleted the appendix that was numbered Appendix 3 in SAP 
Amendment 2. Renumbered Appendices 4 and 5 to 3 and 4, respectively.
Note that changes to the analytic approaches in these amended SAPs also apply to the 
analysis plan for the Integrated Summary of Efficacy.
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1.
INTRODUCTION
This statistical analysis plan contains definitions of analysis sets, derived variables, and statistical
methods for the analysis of efficacy, safety, pharmacokinetics (PK), and pharmacodynamics 
(PD), and Immunogenicity in the CNTO1959PSA3002 study.
1.1.
Trial Objectives
Primary Objective 
The primary objective of this study is to evaluate the efficacy of SC administration of 
guselkumab 100 mg in subjects with active psoriatic arthritis (PsA) by assessing the reduction in 
signs and symptoms of PsA. 
Secondary Objectives 
The secondary objectives are to assess the following for guselkumab treatment in subjects with 
active PsA:

Efficacy in improving psoriatic skin lesions

Improvement in physical function 

Inhibition of progression of structural damage

Efficacy in improving general and disease specific health-related quality of life and patient-
reported health outcomes 

Safety 

PK, PD, and immunogenicity 
1.2.
Trial Design
This is a Phase 3, randomized, double-blind, placebo-controlled, multicenter study of 
guselkumab in subjects with active PsA who are biologic naïve and have had inadequate 
response to standard therapies (eg, non-biologic DMARDs, apremilast, NSAIDs).  The study
consists of a screening phase of up to 6 weeks, a blinded treatment phase of approximately 2
years (i.e., 100 weeks) including a placebo controlled period from Week 0 to Week 24 and an 
active treatment period from Week 24 to Week 100, and, a safety follow-up phase of 12 weeks
after the last administration of study treatment. An overview of the study design is provided in 
Figure 1.  
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Statistical Analysis Plan CNTO1959PSA3002 Amendment 3
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Figure 1:
Schematic Overview of the Study Through End of Study
At Week 0, approximately 684 subjects who have met the study inclusion and exclusion criteria 
are to be randomized in a blinded fashion in a 1:1:1 ratio to 1 of the following 3 treatment groups 
using permuted block randomization stratified by baseline non-biologic DMARD (methotrexate
[MTX], sulfasalazine [SSZ], hydroxychloroquine [HCQ], leflunomide [LEF]) use (yes, no) and 
the most recent available CRP value prior to randomization (<2.0, ≥2.0 mg/dL):

Group I (n=228): Guselkumab 100 mg SC every 4 weeks (q4w) from Week 0 through 
Week 100.

Group II (n=228): Guselkumab 100 mg SC at Weeks 0, 4, then every 8 weeks (q8w) (at 
Weeks 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, and 100) and placebo SC at other visits to 
maintain the blind.

Group III (n=228): Placebo SC q4w from Week 0 to Week 20 and then cross over at 
Week 24 to receive guselkumab 100 mg SC q4w from Week 24 through Week 100.
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CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959PSA3002 Amendment 3
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Through the study, stable doses of concomitant NSAIDs, oral corticosteroids, and selected non-
biologic DMARDs (limited to MTX, SSZ, HCQ, LEF, see Table 1) will be allowed but are not 
required.  At Week 16, subjects in all treatment groups who have < 5% improvement from 
baseline in both swollen and tender joint counts will be considered as meeting early escape (EE) 
criteria and will be allowed to initiate or increase the dose of one of the permitted concomitant 
medications up to the maximum dose allowed as specified in Table 1, as selected by the 
investigator.
Titration to a stable dose of the medication should be completed for subjects 
qualifying for EE by the Week 24 visit. Note that subjects who did not meet EE criteria should 
not initiate any new treatment for PsA through Week 52.
Table 1:
Permitted Concomitant Medications for PsA and Maximum Doses Allowed During the Study
Permitted Concomitant Medications for PsAa,b
Maximum Dose Allowed
NSAIDs and other analgesics
Marketed dose approved in the country where the 
study is being conducted
Oral corticosteroids
Equivalent to 10 mg/day of prednisone
Non-biologic DMARDS:
Methotrexate (MTX)c
25 mg/week
Sulfasalazine (SSZ)
3 g/day
Hydroxychloroquine (HCQ)
400 mg/day
Leflunomide (LEF)
20 mg/day
a   Permitted concomitant medications are not supplied by the Sponsor.
b Subjects may not be receiving more than one non-biologic DMARD from baseline through Week 52.  After 
Week 52 and through the end of the study, subjects may receive another non-biologic DMARD.
c    It is recommended that all subjects taking MTX in this study receive at least 5 mg oral folate or 5 mg folinic acid 
weekly. Guidelines for dose adjustment in the event of MTX toxicity are included in the Trial Center File.
At Week 24, all subjects who are still on treatment in the placebo group (Group III) will cross 
over to receive guselkumab 100 mg SC q4w from Week 24 through Week 100. Subjects in the 
guselkumab groups (Groups I and II) will remain on the same dose regimen at Week 24 and 
after, that is, there will be no change to the dose regimen.
Starting from Week 52, subjects with ongoing PsA disease activity in all treatment groups will 
be allowed to initiate any of the permitted concomitant medication (and combinations of them)
as specified in Table 1, at the investigator’s discretion, or increase the dose(s) of permitted 
concomitant medication(s) up to the maximum dose(s) allowed.
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Subjects will be followed for adverse events (AE) and serious adverse events (SAE) up to 12 
weeks following the last study treatment administration. 
The end of the study is defined as the last visit for the last subject.  The last visit is the last safety 
follow-up visit for subjects who complete the Week 100 study treatment and for subjects who 
terminate study treatment prior to Week 100.
There are 3 planned DBLs in this study.  Each of these 3 DBLs will result in a study report.  The 
first DBL will occur when all subjects randomized in this study have either completed the 
Week 24 assessments or terminated study participation prior to the Week 24 visit (referred to as 
Week 24 DBL hereafter).  The second DBL will occur when all subjects randomized in this 
study have either completed the Week 52 assessments or terminated study participation prior to 
the Week 52 visit (referred to as Week 52 DBL hereafter).  The third DBL will occur when all 
subjects randomized in this study have either completed their final safety visit (approximately 12
weeks after the last administration of study agent) or have terminated study participation
[referred to as Final (Week 112) DBL hereafter].    
The primary endpoint of this study is the proportion of subjects who achieve a 20% improvement 
from baseline in the American College of Rheumatology criteria (ACR 20) at Week 24 (refer to 
Section 5.3 for endpoint definition and analyses).  This endpoint was chosen because it is well-
accepted by regulatory authorities and the clinical PsA community.  Additionally, there are 14
major secondary endpoints in the study (Section 5.4 – definitions and analyses methods).  The 
primary and major secondary endpoints will be analyzed at Week 24 DBL.
The study will remain blinded for the duration of the trial, until after the final DBL.  Selected 
Sponsor personnel will be unblinded at Week 24 and Week 52 DBLs for the purposes of 
performing data analysis and data review.  The details regarding the Sponsor personnel that will
be unblinded at each DBL will be provided in the Data Release Plans.
An independent, external Data Monitoring Committee (DMC) will monitor the safety of the 
study in an unblinded fashion on a regular basis and whenever deemed necessary.  Additional 
details related to DMC are provided in Section 3.2.
1.3.
Statistical Hypotheses for Trial Objectives
The primary endpoint of this study is proportion of subjects who achieved an ACR 20 response 
at Week 24 (refer to Section 5.3 for endpoint definition and analyses). This endpoint was chosen 
because it is well-accepted by regulatory authorities and the clinical PsA community.
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The hypotheses related to the primary endpoint are that:
1.
treatment with guselkumab 100 mg SC q4w is superior to treatment with placebo SC with 
respect to reduction of PsA signs and symptoms as measured by proportion of subjects who 
achieved an ACR 20 response at Week 24 (primary hypothesis); and
2.
treatment with guselkumab 100 mg SC at Week 0, Week 4 and then q8w is superior to 
treatment with placebo SC with respect to reduction of PsA signs and symptoms as 
measured by proportion of subjects who achieved an ACR 20 response at Week 24 (major 
secondary hypotheses).
The first hypothesis is the primary hypothesis for this study. If the first hypothesis achieves the 
statistical significance at a 2-sided α-level of 0.05, the study will be considered positive.
In addition to the primary endpoint, there are 14 major secondary endpoints in this study (refer to 
Section 5.4 for endpoint definitions and analyses).  The hypotheses related to the major 
secondary endpoints (all are major secondary hypotheses) are provided in Appendix 2. 
For hypothesis testing order and multiplicity adjustment, refer to Section 5.2.2.
1.4.
Sample Size Justification
The sample size selection was determined based on the primary endpoint of proportion of 
subjects who achieve ACR 20 response at Week 24 and the major secondary endpoint of change 
from baseline in modified vdH-S score at Week 24.
1.4.1.
Primary Endpoint – ACR 20 Response at Week 24
In the Phase 3 CNTO1275PSA3001 PsA study with ustekinumab, the ACR 20 response rates at 
Week 24 were 22.8%, 42.4% and 49.5%, respectively, for the placebo, ustekinumab 45 mg, and 
ustekinumab 90 mg treatment groups.
In the Phase 2 CNTO1959PSA2001 PsA study with 
guselkumab, the ACR 20 response rates at Week 24 were 18.4% and 58.0%, respectively, for the 
placebo and guselkumab 100 mg treatment groups.  
For this study, assuming a 45% ACR 20 response rate in the guselkumab group and a 25% 
ACR 20 response rate in the placebo group, a sample size of 228 subjects per treatment group 
(684 in total) will provide a power of approximately 99% to detect a significant treatment 
difference at a 2-sided significance level of α=0.05.  The sample size was also evaluated based 
on the following assumptions:  

20% to 25% ACR 20 response rates at Week 24 in subjects treated with placebo 

40% to 50% ACR 20 response rates at Week 24 in subjects treated with guselkumab
Table 2 provides the statistical power under various assumptions using a 2-sided chi-square test.  
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Table 2:
Statistical Power for Treatment Difference in ACR 20 Response at Week 24
Sample size per arm
ACR 20 Response Rate
Power
Placebo Group
Guselkumab Group
Difference (Δ) 
228
20%
40%
20%
>99%
228
20%
45%
25%
>99%
228
25%
45%
20%
99%
228
25%
50%
25%
>99%
228
30%
50%
20%
99%
1.4.2.
Major Secondary Endpoint – Change from Baseline in Modified vdH-S 
Score at Week 24
For change from baseline in modified vdH-S score, subjects in each treatment group can be 
considered a mixture of 2 subpopulations: 1 subpopulation with a change score of 0 and 1 
subpopulation with a change score sampled from a normal distribution.  Therefore, the 
distribution of the vdH-S change scores is determined by 3 parameters: the probability that a 
subject has a change score of 0, mean of the normal distribution, and standard deviation (SD) of 
the normal distribution.  The overall mean (ie, crude mean) of the change scores for a treatment 
group is the overall average of the change scores among all subjects (including both 
subpopulations 1 and 2) in that treatment group.
In the Phase 3 CNTO1275PSA3001 PsA study with ustekinumab, the following statistics were 
observed on change from baseline in modified vdH-S score at Week 24:

The overall mean (SD) of change from baseline in modified vdH-S score at Week 24 (after 
excluding one extreme outlier who had a change score of 58) was 0.92 (2.15), 0.28 (1.94), 
and 0.17 (1.45) in the placebo, ustekinumab 45 mg and 90 mg treatment groups, 
respectively. 

Approximately 49%, 47%, and 46% subjects had a change score of 0 in the placebo, 
ustekinumab 45 mg and 90 mg treatment groups, respectively.
o
Approximately 40% of 0’s in each group were ‘true’ 0’s (that is, a difference of ≤ 2
and an average of 0 in the reader-level vdH-S scores from the 2 readers selected).

Excluding the true 0’s, the mean (SD) change score (after excluding extreme outlier) 
was 1.59 (2.60), 0.47 (2.50), and 0.32 (1.96) in the placebo, ustekinumab 45 mg and 
90 mg treatment groups, respectively (ie, the subjects from the normal distributions). 
Excluding all 0’s, the mean (SD) change score for the 3 groups was 1.82 (2.75), 0.52 
(2.64), and 0.32 (1.96).
For this study, assuming an overall mean change of 0.9 from baseline in modified vdH-S score in 
the placebo group, and an overall mean change of 0.3 in the guselkumab group, and a standard 
deviation of 2.5 for each treatment group, a sample size of 228 subjects per treatment group (684 
in total) will provide a power of approximately 90% to detect a significant treatment difference 
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at a 2-sided significance level of α=0.05.  The sample size was also evaluated based on the 
following assumptions:  

The overall mean difference in change from baseline in modified vdH-S score at Week 24 
between the placebo group and a guselkumab group ranges from 0.6 to 0.8.

40% – 50% subjects in each treatment group have a change score of 0 from baseline in 
modified vdH-S score at Week 24 (ie, the subpopulation with a change score of 0). 

For the other subjects (those from the normal distributions), the SD of the normal 
distributions is 2.5 for all treatment groups and the mean of the normal distribution is 
1.80 for the placebo group. 
Table 3 provides the statistical power under various assumptions.  The statistical power was 
estimated based on 10000 simulations with treatment comparison performed at each simulation 
using an analysis of variance (ANOVA) test on the van der Waerden normal score.  Under these 
assumptions, the study power ranges approximately from 89% to 99%. 
Table 3:
Statistical Power for Treatment Difference in Modified vdH-S Change from Baseline at 
Week 24
Placebo Group
Guselkumab Group
Overall
Mean 
Difference 
Power
% subjects 
without change
Rest of 
subjects
Overall
mean
% subjects
without change
Rest of 
subjects
Overall
mean
Mean
SD
Mean
SD
45%
1.80
2.5
1.00
45%
0.71
2.5
0.40
0.60
89%
45%
1.80
2.5
1.00
45%
0.35
2.5
0.20
0.80
99%
50%
1.80
2.5
0.90
50%
0.60
2.5
0.30
0.60
92%
50%
1.80
2.5
0.90
50%
0.20
2.5
0.10
0.80
99%
50%
1.80
2.5
0.90
45%
0.55
2.5
0.30
0.60
91%
50%
1.80
2.5
0.90
45%
0.18
2.5
0.10
0.80
99%
Note that, if the SD of the normal distributions is 3.0, the power will go down to as low as 
approximately 80%.
1.5.
Randomization and Blinding
1.5.1.
Randomization
A central randomization is to be implemented in this study using an interactive web response 
system (IWRS).  When a subject is eligible for randomization at a study site, the randomization 
requestor at that study site will contact the IWRS using the requester’s own user identification 
and personal identification number and provide the relevant subject details to uniquely identify 
that subject.  Based on a computer-generated randomization schedule prepared before the study 
under the supervision of the Sponsor, the IWRS will then assign a unique treatment code, which 
will dictate the treatment assignment and matching study agent kit for that subject.  
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At Week 0, approximately 684 subjects will be randomized in a blinded fashion in a 1:1:1 ratio 
to 1 of the following 3 treatment groups:

Group I (n=228): Guselkumab 100 mg q4w

Subjects in this group will receive guselkumab 100 mg q4w from Week 0 through 
Week 100.

Group II (n=228): Guselkumab 100 mg at Weeks 0, 4, then q8w

Subjects in this group will receive guselkumab 100 mg at Weeks 0, 4, and then q8w (at 
Weeks 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, and 100) with placebo at other visits (at 
Weeks 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, and 96), i.e., an administration q4w with 
either guselkumab or placebo, to maintain the blind.

Group III (n=228): Placebo q4w

Subjects in this group will receive placebo q4w from Week 0 to Week 20 and then cross 
over at Week 24 to receive guselkumab 100 mg q4w from Week 24 through Week 100.
To assure relatively even treatment balance within each stratum defined by baseline use of non-
biologic DMARD (yes, no) and the most recent available CRP value prior to randomization 
(<2.0, ≥2.0 mg/dL), randomization at Week 0 is determined using permuted block randomization
stratified by baseline use of non-biologic DMARD (yes, no) and the most recent available CRP 
value prior to randomization (<2.0, ≥2.0 mg/dL). Specific details are provided in the IWRS 
Project Requirements Specification Biostatistical Addendum for CNTO1959PsA3002.
At Week 24, all subjects who randomized to placebo at Week 0 and who are still on study 
treatment at Week 24 will be switched to guselkumab 100 mg q4w by the IWRS to receive 
guselkumab 100 mg q4w starting from Week 24.  
1.5.2.
Maintenance of the Blind
The study blind will be maintained for the duration of the study, until after the final DBL at end 
of study.
To maintain the study blind, the study agent container will have a multipart label with directions 
for use and other information, but not the identity of the study agent, on each part.  One part of 
the label is designed to be torn off, separated from the study agent container, and attached to the 
subject’s source documents.  The rest of the label will remain affixed to the study agent 
container.  Thus, the study agent assigned to a subject will be linked between the container and 
the subject without breaking the study blind.  The study agent kit number will be entered in the 
electronic case report form (eCRF) or other equivalent data capture method when the drug is 
administered. The investigator will not be provided with treatment codes, but the codes will be 
maintained within the IWRS, which has the functionality to allow the investigator to break the 
blind for an individual subject when there is a need based on medical judgment. 
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Data that may potentially unblind the treatment assignment
(ie, study agent serum 
concentrations, antibodies to study agent) will be handled with special care to ensure that the 
integrity of the blind is maintained and the potential for bias is minimized.  This may include
making special provisions, such as segregating the data in question from view by the 
investigators, clinical team, or others as appropriate. 
An investigator may be unblinded to a given subject’s treatment allocation when specific 
emergency treatment would be dictated by knowing the treatment status of the subject.  In such 
cases, the investigator may determine the identity of the treatment by contacting the IWRS 
provider. It is strongly recommended that the investigator contact the Sponsor or its designee if 
possible to discuss the situation prior to unblinding via IWRS.  Telephone contact with the 
Sponsor or its designee will be available 24 hours per day, 7 days per week.  In the event that the 
investigator is unable to contact the Sponsor, or emergency unblinding is considered medically 
necessary, the investigator may determine the identity of the treatment via IWRS.  However, the 
Sponsor must be informed as soon as possible.  The date, time, and reason for the unblinding 
must be documented in the appropriate section of the eCRF, and in the source document.  The 
documentation received from the IWRS indicating the code break must be retained with the 
subject's source documents in a secure manner (e.g., sealed envelope) so as to not unblind the 
treatment assignment to the subject, the study site, or Sponsor personnel.  The investigator is also 
advised not to reveal the study treatment assignment to the subject, the study site, or Sponsor 
personnel. Subjects who have had their treatment assignment unblinded are expected to continue 
to return for scheduled evaluations.  Further study agent administrations should be discussed 
with the study responsible physician.
A given subject’s treatment assignment may be unblinded to the Sponsor, Institutional Review 
Board/Independent Ethics Committee (IRB/IEC), and site personnel to fulfill regulatory 
reporting requirements for suspected unexpected serious adverse reactions (SUSARs).  A 
separate code break procedure will be available for use by Janssen Global Medical Safety (GMS) 
to allow for unblinding of individual subjects to comply with specific requests from regulatory or 
health authorities.
A group of prospectively identified Sponsor individuals will be unblinded at the Week 24 DBL
and Week 52 DBL for the purposes of performing data analysis and review.  Identification of 
sponsor personnel who will have access to the unblinded data at subject-level and who will have 
access to the unblinded data at group-level will be documented in the Data Release Plan prior to 
unblinding at the Week 24 DBL and Week 52 DBL.  Investigative sites and subjects will remain 
blinded to treatment assignment for the duration of the study, till after the Final (Week 112) 
DBL.
An independent, external DMC will monitor the safety of the study in unblinded fashion on a 
regular basis and whenever deemed necessary.  In addition, the Sponsor Medical Monitor will 
review safety data in a blinded manner as the study is ongoing.  The DMC’s roles and 
responsibilities, the safety data for DMC review, and other related information (such as, the 
general procedures, communications, etc.) is defined and documented in the DMC charter.  
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1.6.
Radiographic Image Reading and Scoring
In this study, radiographic images will be read in 3 read campaigns:

Read Campaign 1: Baseline and Week 24 (or End of Treatment if the subjects are not to 
continue the scheduled visits through Week 24 and no radiograph was obtained within the 
previous 6 weeks) for the Week 24 DBL.

Read Campaign 2:  Baseline, Week 24, and Week 52 (or End of Treatment if no radiograph 
was obtained within the previous 6 weeks) for Week 52 DBL

Read Campaign 3:  Baseline, Week 24, Week 52, and Week 100 (or End of Treatment if no 
radiograph was obtained within the previous 6 weeks) for Final DBL
Adjudication will be conducted in all read campaigns.  During each read campaign, the 
designated radiographic images will be evaluated independently by the 2 primary readers and, in
the case of adjudication, by the adjudicator.  
Refer to Section 5.4.4.1 and Appendix 1 for scoring method and adjudication criteria.
The radiographic images from a subject at all time points during a given read campaign will be 
presented to the readers in random order.  To maintain objectivity in the evaluations, the readers 
will be blinded to treatment group, subject’s demographics, and the time point identity.
The radiographic images will be presented to the readers electronically using workstations and 
high-resolution monitors.  All study image data received will be processed and saved in Digital 
Imaging and Communications in Medicine (DICOM) format.  During this process, relevant 
electronic header information (eg, subject identifiers) will be blinded within the digital data set.  
When presented with an image, the reader will evaluate and score for erosions and joint space 
narrowing (JSN) of individual joints in a region.  Once the reader completes the assessments for 
erosion/JSN, the scores will be locked and changes to completed assessments will not be 
permitted. 
In order to assess intra-reader variability, images of 10% of subjects will be randomly selected 
and re-read by each of the 2 primary readers in all Read Campaigns. 
The intra-reader and inter-reader variability will be monitored by the Sponsor. A high variability 
is defined as the interclass correlation coefficient (ICC) < 0.5, or smallest detectable change 
(SDC) > 5, or an absolute difference of ≥ 10 between readers’ change scores or in a reader’s 
change score between the initial read and the corresponding subsequent re-read. In the event of
high variability, the source of greatest variance will be investigated and, if possible, corrective 
action such as retraining of the readers will be taken.
For more details regarding imaging acquisition, standardization, reading, and data transfer, refer 
to the Imaging Charter.
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2.
GENERAL ANALYSIS DEFINITIONS
2.1.
Visit Windows
2.1.1.
Visit Windows for Dosing and PK Analysis 
All post-baseline visits from Baseline through Week 24 will have a visit window of ± 4 days, and 
from Week 28 through Week 100 will have a visit window of ± 1 week (7 days). The final safety 
follow-up at Week 112 will have a visit window of ± 2 weeks (14 days).  
For PK analyses, if a subject has an administration outside the visit window at a visit, the 
concentration data collected at and after that visit will be excluded from the by-visit data 
analyses. 
2.1.2.
Visit Windows for Radiographic Assessments and Analyses
The windows for taking radiographs of hands and feet at respective scheduled visits are specified 
in the protocol.  
An analytical window of 8 weeks inclusive will be used in radiographic data analyses at all 
scheduled visits (Weeks 0, 24, 52, and 100).  Radiographs taken at end of study treatment will be 
slotted based the analysis window to the appropriate visits to be included in the data analysis.
2.2.
Pooling Algorithm for Analysis 
Data from all investigational centers/sites will be pooled for analyses.
2.3.
Analysis Sets
2.3.1.
Efficacy Analysis Set(s)
Full Analysis Set 1 (Week 0 – Week 24)
2.3.1.1.
The full analysis set 1 (FAS1) includes all randomized subjects who received at least 1 dose 
(complete or partial) of study agent.  This analysis set will be used for the efficacy analyses of 
non-radiographic endpoints through Week 24.  
Full Analysis Set 2 (Week 24 – Week 52)
2.3.1.2.
The full analysis set 2 (FAS2) includes all randomized subjects who were still on study treatment 
at Week 24.  This analysis set will be used for the efficacy analysis of non-radiographic 
endpoints from Week 24 through Week 52.  
Full Analysis Set 3 (Week 52 – Week 100)
2.3.1.3.
The full analysis set 3 (FAS3) includes all randomized subjects who were still on study treatment 
at Week 52.  This analysis set will be used for the efficacy analyses of non-radiographic 
endpoints from Week 52 through Week 100.    
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Full Analysis Set 1 for Structural Damage (Read Campaign 1)
2.3.1.4.
The full analysis set 1 for structural damage (FAS1-SD) includes all randomized subjects who 
received at least 1 (partial or complete) dose of study agent.  This analysis set is the same as Full 
Analysis Set 1 (FAS1) and is labeled as FAS1-SD to indicate that this analysis set will be used 
for the efficacy analyses of radiographic endpoints through Week 24 based on data generated 
from Read Campaign 1.  
Full Analysis Set 2 for Structural Damage (Read Campaign 2)
2.3.1.5.
The full analysis set 2 for structural damage (FAS2-SD) includes all randomized subjects who 
were still on study treatment at Week 24.  This analysis set is the same as Full Analysis Set 2 
(FAS2) and is labeled as FAS2-SD to indicate that this analysis set will be used for the efficacy 
analysis of radiographic endpoints from Week 24 through Week 52 based on data generated from 
Read Campaign 2.
Full Analysis Set 3 for Structural Damage (Read Campaign 3)
2.3.1.6.
The full analysis set 3 for structural damage (FAS3-SD) includes all randomized subjects who 
were still on study treatment at Week 52.  This analysis set is the same as Full Analysis Set 3 
(FAS3) and is labeled as FAS3-SD to indicate that this analysis set will be used for the analyses 
of radiographic endpoints from Week 52 through Week 100 based on data generated from Read 
Campaign 3.  
In the efficacy analyses, subjects will be analyzed per the randomized treatment groups they 
were assigned to, regardless of the treatments they actually received.  
Per-Protocol Analysis Set (Week 0 – Week 24)
2.3.1.7.
The per-protocol analysis set (PPAS) includes all subjects in FAS1 who met all inclusion and 
exclusion criteria and had no major protocol deviations that could have impacted efficacy 
assessment per clinical judgement.  This analysis set will be used for the analyses of selected
efficacy endpoints through Week 24.  Subjects to be excluded from this analysis will be 
identified prior to the Week-24 DBL and un-blinding.
In the efficacy analyses, subjects will be analyzed according to the randomized treatment groups 
they were assigned to, regardless of the treatments they actually received.  
2.3.2.
Safety Analysis Set
The safety analysis set includes all subjects who received at least 1 (partial or complete) dose of 
study agent, i.e., the treated population.
In the safety analyses, subjects will be analyzed per the treatment they actually received, 
regardless of the treatments they are randomized to.
2.3.3.
PK Analysis Set
The PK analysis set includes all subjects who received at least 1 complete dose of guselkumab 
and had at least 1 valid blood sample drawn for PK analysis.
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In the PK analyses, subjects will be analyzed per the treatment they actually received, regardless 
of the treatments they are randomized to.
2.3.4.
Immunogenicity Analysis Set
The immunogenicity analysis set includes all subjects who received at least 1 (partial or 
complete) dose of guselkumab and who have appropriate samples for detection of antibodies to 
guselkumab (ie, subjects with at least 1 sample obtained after their first dose of guselkumab).
In the immunogenicity analyses, subjects will be analyzed per the treatment they actually 
received, regardless of the treatments they are randomized to.
2.3.5.
Pharmacodynamics Analysis Set
The pharmacodynamics (PD) analysis set includes all subjects who received at least 1 (partial or 
complete) dose of study agent, i.e., the treated population.
In the PD analyses, subjects will be analyzed per the treatment they actually received, regardless 
of the treatments they are randomized to.
2.4.
Definition of Subgroups
To evaluate the consistency in the primary efficacy endpoint (proportion of subjects who achieve 
ACR 20 at Week 24) and the major secondary endpoint of structural damage (change from 
baseline in vdH-S score at Week 24) over demographics, baseline characteristics, prior and 
baseline medication use, subgroup analyses will be performed.  The subgroups include, but are 
not limited to, the following:
1.
Demographic subgroups 
a.
Gender: Male, Female
b.
Race: White, Other
c.
Age at baseline (year):  < 45, ≥ 45 and < 65, ≥65
d.
Body weight at baseline (kg): ≤90,>90 
e.
Body weight at baseline (kg): (quartiles)
f.
Body mass index at baseline: Normal [< 25], Overweight [≥ 25 to < 30], Obese [≥ 
30]
g.
Participating countries: Poland, Russia, Ukraine, Western countries (USA and 
Spain), Other countries (combining countries in Asia and Eastern European 
countries other than Poland, Russia and Ukraine)
2.
Baseline disease characteristics subgroups
a.
PsA duration at baseline (year): < 1, ≥ 1 to < 3, ≥ 3  
b. PsA subtype: distal interphalangeal joint involvement, polyarticular arthritis with 
absence of rheumatoid nodules, arthritis mutilans, asymmetric peripheral arthritis, 
spondylitis with peripheral arthritis 
c.
Number of swollen joints at baseline: < 10, 10 to 15, > 15  
d. Number of tender joints at baseline:  < 10, 10 to 15, > 15  
e.
HAQ-DI at baseline: < 1, 1 to 2, > 2
f.
CRP at baseline (mg/dL): < 1, 1-2, ≥ 2(lab data) 
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g. CRP at baseline (mg/dL): (quartiles)
h. Dactylitis at baseline: Yes, No 
i.
Enthesitis at baseline: Yes, No
j.
PASI at baseline: <12, ≥ 12 to < 20, ≥ 20 
k. BSA at baseline: < 3%, ≥ 3% to < 10%, ≥ 10% to < 20%, ≥ 20% 
l.
IGA at baseline: <2, ≥2
3.
Prior and baseline medication use subgroups:
a.
Use of non-biologic DMARDs (MTX, SSZ, HCQ, LEF) at baseline: Yes, No 
(eCRF)
b.
Oral corticosteroids at baseline: Yes, No
c.
NSAIDs at baseline: Yes, No
d.
Number of prior non-biologic treatments including DMARDs, systemic 
immunosuppressive drugs, and apremilast: 0, 1, 2, ≥3.
e.
Non-biologic DMARDS (MTX, SSZ, HCQ, LEF) at baseline: None, MTX, non-
MTX DMARDs
f.
Reason for discontinuation of prior DMARDs: Efficacy - inadequate response (IR), 
safety - contraindication or intolerance (but not IR), Other
Note that some of the above subgroup cut-off points may be changed if there are no or few 
subjects within a subgroup category.
2.5.
Treatment Failure
A subject will be considered a treatment failure (TF) from the earliest date that the subject meets 
any of the following TF criteria onward through Week 24: 
1.
Discontinued study agent injections due to any reason.
2.
Terminated study participation due to any reason.
3.
Initiated or increased the dose of non-biologic DMARD (MTX, SSZ, HCQ, LEF) or 
oral corticosteroids over baseline for PsA.
4.
Initiated protocol prohibited medications/therapies for PsA. 
All subjects who meet criterion 2 will always meet criterion 1.
3.
INTERIM ANALYSIS AND DATA MONITORING COMMITTEE REVIEW
3.1.
Interim Analysis
No interim analysis is planned for this study.
3.2.
Data Monitoring Committee
An independent, external DMC has been established to monitor data on an ongoing basis to 
ensure the continuing safety of the subjects while participating in this study.  All subjects are to 
be followed by the DMC from the first dose administrated through at least the Week 24 DBL. 
The DMC consists of 3 members (including 2 medical experts in the relevant therapeutic areas 
and 1 statistician) who are independent of the Sponsor. None of the members is participating in 
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the current study.  An independent statistical support group (SSG), not affiliated to the sponsor, 
supports the DMC and serves the liaison between the DMC and the sponsor.
The major function of the DMC is to monitor the safety of the study agent by reviewing the 
serious adverse events (SAEs) each month and by periodically reviewing the interim study safety 
data every 4-month.  After each review, the DMC is to make recommendations regarding the 
continuation of the study or, in the event that any unanticipated serious events occur, placing the 
study on hold or stopping the study. 
The DMC will have access to unblinded data and review tabulated safety summaries (if 
appropriate) and any additional data as deemed necessary during the conduct of the study.  No 
formal statistical hypothesis testing is planned.  
The content of the safety summaries, the DMC role and responsibilities and the general 
procedures (including communications) and their recommendations on the study conduct are
defined and documented in the DMC charter, which will be finalized prior to the first DMC 
review. 
In addition, during the study, the Sponsor's study responsible physician (or designee) will 
regularly review blinded safety data from the sites and notify the DMC and appropriate Sponsor 
personnel of any issues.  
4.
SUBJECT INFORMATION
Subject information will be summarized by randomized treatment group based on the FAS1.
Treatment exposure (e.g., number of treatment administrations, and cumulative dose received) 
and duration of study follow-up time will be summarized by treatment actually received based on 
the safety analysis set (Section 4.4).  
4.1.
Demographics and Baseline Characteristics
Demographic and baseline characteristic variables will be descriptively summarized by 
randomized treatment group.  No formal statistical comparison is planned.  P-values will not be 
provided.
Demographic variables to be summarized will include sex, race, age, height, baseline weight, and 
baseline body mass index (BMI).  Baseline characteristic variables to be summarized will 
include, but not be limited to, baseline disease characteristics of PsA (e.g., duration of disease, 
PsA subtypes, baseline efficacy assessments), medical history, prior exposure to non-biologic 
medications, prior joint procedures/injections, and baseline medication usage for PsA.
In addition, balance between randomized treatment groups will also be explored for the 
subpopulations used for analyses below:

subjects with baseline ≥3% body surface area (BSA) psoriatic involvement and an IGA 
score of ≥2 (mild) at baseline (for skin disease related endpoint analyses).
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
subjects with enthesitis at baseline

subjects with dactylitis at baseline
4.2.
Disposition Information
The number of subjects screened, randomized and treated will be summarized by geographic 
region, country, and investigational site.
Disposition will also include tabulations, by randomized treatment group, of the number of 
subjects who discontinued study agent administration early and the primary reasons for 
discontinuation of study agent administration early, and the number of subjects who discontinued 
study participation early and the primary reason for discontinuation of study participation early.  
Tabulations by randomized treatment group will also be provided for subjects who met EE 
criteria at Week 16 and for subjects who met 1 or more TF criteria as defined in Section 2.5.
In addition, subjects who were randomized but never treated and subjects who met any TF 
criteria will be presented in data listings.
4.3.
Treatment Compliance
Treatment compliance will be assessed by the number of study agent administrations completed 
versus the number of study agent administrations planned.  
Tabulations of the number of subjects by the study agent lot(s) and by treatment assigned versus 
treatment received will also be provided.
4.4.
Treatment Exposure and Study follow-up
The overall treatment exposure (e.g., duration of treatment exposure, number of treatment 
administrations, and cumulative dose received) and duration of study follow-up time will be 
descriptively summarized by treatment actually received based on the safety analysis set, ie, all 
treated subjects.  
4.5.
Protocol Deviations
Subjects with major protocol deviations, defined as having the potential to impact subjects’ 
rights, safety or well-being, or the integrity and/or result of the clinical trial, will be listed or 
descriptively summarized by randomized treatment group.  The major protocol deviations will be 
grouped into the following 5 categories:

Developed study withdrawal criteria but not withdrawn

Entered the study without satisfying study selection criteria

Received a disallowed concomitant treatment

Received wrong treatment or incorrect dose

Other
The study selection criteria will be grouped into the following 5 categories: PsA disease criteria, 
medication criteria, laboratory criteria, medical history criteria, and other.   
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Protocol deviation in study agent administrations includes missing doses, incorrect doses, and 
treatments administered out of the dosing windows defined in Section 2.1.1.  
4.6.
Prior and Concomitant Medications
Prior medications taken for PsA and/or psoriasis (e.g., non-biologic DMARDs, apremilast, and 
NSAIDS) will be summarized by randomized treatment group.  
Subjects taking concomitant medications for PsA and/or psoriasis at baseline and post-baseline 
will be tabulated by drug and randomized treatment group.  Additionally, selected concomitant 
medications may be tabulated by randomized treatment group.
5.
EFFICACY
5.1.
General Method of Analysis
In general, descriptive statistics, such as mean, standard deviation (SD), median, inter quartile 
(IQ) range, minimum, and maximum for continuous variables, and counts and percentages for 
discrete variables will be used to summarize most data.  
Statistical comparison between a guselkumab group (100 mg q4w or 100 mg at Weeks 0, 4 and
then q8w) and the placebo group will be performed by visit through Week 24. No treatment
comparison will be performed after Week 24.
Binary Response Efficacy Endpoints
For binary response efficacy endpoints, treatment comparisons will generally be performed using 
a Cochran-Mantel-Haenszel (CMH) test stratified by baseline use of non-biologic DMARD (yes, 
no) and most recent CRP value prior to randomization (<2.0 mg/dL, ≥2.0 mg/dL). The 
magnitude of the treatment difference will be estimated by the difference in response rates 
between the guselkumab and placebo groups with a 95% confidence interval (CI) calculated 
based on Wald statistics33. In these analyses, subjects with missing data will be imputed as not 
achieving the response as described in Section 5.2.3.1.
The Mantel Fleiss criterion will be used to determine the appropriateness of using the CMH test
at each visit for each treatment pair under comparison. If the Mantel Fleiss criterion is not 
satisfied the Fisher’s exact test will be used instead of the CMH test to compare the two
treatment groups.
For analyses based on Multiple Imputation, the inferences from the analysis of each imputed data 
are pooled. The within imputation variance and between imputation variance are combined to 
estimate the total variance of the stratum adjusted difference of proportions. This estimate of the 
variance and critical values from the t-distribution are used to calculate the confidence interval 
for the stratum adjusted difference of proportions. The SAS procedure PROC MIANALYZE is 
used where the critical value is based on the t-distribution which is different from the analysis 
not based on MI where normal distribution is used. The large number of observations in our data 
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imply that the critical values from the t-distribution are almost identical to the critical values 
from the standard normal distribution. 
The Wilson-Hilferty34 transformation is used to pool the p-values from each imputed data set.
For endpoints (resolution of enthesitis and  resolution of dactylitis) that are based on data 
combined from studies CNTO1959PSA3001 and CNTO1959PSA3002 the analysis will be 
stratified by the combination of study and randomization stratification factors.
Major Secondary Continuous Efficacy Endpoints
For the major secondary continuous endpoints (Section 5.4) and related continuous efficacy 
endpoints in Section 5.5.5, treatment comparisons will be performed using an ANCOVA model 
based on MI data. The MI method will be applied to impute the missing value under the 
assumption of missing at random (MAR). The estimate of the mean change from baseline is the 
average of the mean change taken over all the MI data sets. The estimate of the variance of the 
mean change from baseline is the weighted sum of the average within-imputation variance and 
the between-imputation variance. The confidence interval for the mean change from baseline 
uses critical values from the t-distribution. The treatment difference between each guselkumab 
group versus the placebo group will be tested for each imputation dataset and then the analysis 
results across all imputation datasets will be combined. The treatment difference in the change 
from baseline is estimated by the average of the treatment differences over the MI data sets. The 
estimate of the variance of the treatment difference in the change from baseline is the weighted 
sum of the average within-imputation variance and the between-imputation variance, under the 
assumption of homogeneity of variance between treatment groups for performing ANCOVA 
within each imputation dataset. The confidence interval is based on the critical values from the t-
distribution.
The ANCOVA model will be based on the original scale and will include treatment group, 
baseline score, baseline use of non-biologic DMARD (yes, no and most recent CRP value prior 
to randomization (<2.0 mg/dL, ≥2.0 mg/dL) as the explanatory factors. The model will include 
data from all the 3 treatment groups.
For endpoints (change from baseline in enthesitis and change from baseline in dactylitis) that are 
based on data combined from studies CNTO1959PSA3001 and CNTO1959PSA3002, the 
ANCOVA model will include treatment group, baseline score, and the combination of study and 
randomization stratification factors as the explanatory factors. The model will include data from 
all 3 treatment groups.
.
Other Continuous Efficacy Endpoints
For all other continuous efficacy endpoints, treatment comparisons will be performed using a 
MMRM model or a cLDA Model (Appendix 3).  The model will include all available data from
the 3 treatment groups through Week 24. The treatment difference between a guselkumab group 
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and the placebo group will be estimated by the difference in the LSmeans. The 95% CIs for the 
differences in LSmeans and p-values will be calculated.
In addition, graphical data displays (eg, line plots) and subject listings may also be used to 
summarize/present the data.
5.2.
Analysis Specifications
5.2.1.
Level of Significance
The overall type I error will be controlled among the primary and major secondary endpoints at 
5% as specified in Section 5.2.2.  
5.2.2.
Multiplicity Adjustment for Testing Procedures
This study has 1 primary endpoint (proportion of subjects who achieved an ACR 20 response at 
Week 24) and 14 major secondary endpoints.  With 15 endpoints and 2 treatment comparisons 
for each of these endpoints, there are a total of 30 hypotheses to be tested.   
The primary hypothesis in this study is that treatment with guselkumab 100 mg SC q4w is 
superior to treatment with placebo SC with respect to reduction of PsA signs and symptoms as 
measured by proportion of subjects who achieved an ACR 20 response at Week 24. Due to 
regional differences in regulatory requirements on multiplicity control from health authorities, 
two multiplicity control procedurs are pre-specified. Details for the US-specific multiplicity 
adjustment are provided in Section 5.2.2.1, and for the Global(ex-US) multiplicity adjustment 
procedure are provided in Section 5.2.2.2.
With respect to enthesitis and dactylitis, important soft tissue manifestations of PsA, the 
resolution of enthesitis and resolution of dactylitis endpoints will be tested by combining data 
from studies CNTO1959PSA3001 and CNTO1959PSA3002 to provide a more robust 
comparison with greater power than using data only from study CNTO1959PSA3002. The 
rationale for combining the two studies for testing the 2 hypotheses associated with each of these 
2 endpoints is based on the consideration of a relatively small sample of subjects with enthesitis 
or dactylitis at baseline. As treatment comparisons for these endpoints are only meaningful in 
subjects with enthesitis or dactylitis at baseline, the treatment comparisons are extremely 
underpowered for CNTO1959PSA3001 and slightly under powered for CNTO1959PSA3002, to 
detect a clinically meaningful difference between each Guselkumab treatment group vs placebo.
The study design and populations of these two studies are in general quite similar and therefore 
are not a hindrance to the pooling of data from these studies. The data in each treatment group 
from the two studies will be pooled; however, the data from the two Guselkumab dose groups 
will not be combined. For each treatment comparison between each Guselkumab dose and 
placebo based on the combined study data, treatment effects for that Guselkumab dose in each 
study separately are required to be numerically positive to further justify pooling.
There will be total of 38 hypotheses. This includes the hypotheses pertaining to tests based on 
pooled data from the two studies.  Refer to Appendix 2 for the list of all hypotheses to be tested.
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US-Specific Multiplicity Adjustment for Testing Procedures
5.2.2.1.
The multiple comparison procedure pre-specified to address the requirement of the Food and 
Drug Administration (FDA) of the United States (US) for family-wise control of the primary and 
major secondary endpoints is described in this section.
Per FDA review comment dated 
03OCT2017 [IND 124177 – Guselkumab (CNTO 1959) – Guidance regarding statistical 
analysis plans for CNTO1959PSA3001 and CNTO1959PSA3002 submitted on August 10, 
2017], only the primary and major secondary endpoints that are important and assess different 
attributes of disease will be controlled.   
In addition to the primary endpoint, ACR20 at Week 24, 7 major secondary endpoints are 
identified as important and assess different attributes of the disease:

Proportion of subjects who achieved a psoriasis IGA response at Week 24 among the 
subjects with ≥ 3% BSA psoriatic involvement and an IGA score of ≥ 2 at baseline

Change from baseline in HAQ-DI score at Week 24

Change from baseline in modified van der Heijde-Sharp (vdH-S) score at Week 24

Change from baseline in SF-36 PCS at Week 24

Proportion of subjects with resolution of dactylitis at Week 24 among the subjects with 
dactylitis at baseline
with combined data from studies CNTO1959PSA3002 and 
CNTO1959PSA3002

Proportion of subjects with resolution of enthesitis (based on the Leeds Enthesitis Index 
[LEI]) at Week 24 among the subjects with enthesitis at baseline with combined data from 
studies CNTO1959PSA3002 and CNTO1959PSA3002

Change from baseline in SF-36 MCS at Week 24.
The overall Type I error of the treatment comparisons of both doses versus placebo for the 
primary and the 7 selected major secondary endpoints will be controlled at a significance level of 
≤ 0.05. Refer to Appendix 2 for the 16 hypotheses to be tested and controlled with the graphical 
procedure as specified in Figure 2. For all endpoints specified in the graphical procedure, both 
adjusted and nominal p-values will be provided. In the instance that an adjusted p-value is not 
significant, the nominal p-value must only be interpreted as supportive.
The method of controlling the type I error across the testing of the hypotheses is described below 
and in Figure 2.
The 2 hypotheses associated with the endpoint of the change from baseline at Week 24 in MCS 
will be tested only for study CNTO1959PSA3002.
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Figure 2:
US-Specific Multiple Comparison Procedure
Some major secondary endpoints that are important but assess similar attributes of the disease as 
those that are included in Figure 2 are listed below:

ACR 20 at Week 16, ACR 50 at Week 16, ACR50 at Week 24, ACR 70 at Week 24, and 
DAS28 (CRP) change from baseline at Week 24 are closely related to the primary 
endpoint (ACR 20 at Week 24) in assessing PsA signs and symptoms.

The change from baseline in dactylitis score at Week 24 with combined data from 
CNTO1959PSA3001 and CNTO159PSA3002 is closely related to the proportion of 
subjects with resolution of dactylitis at Week 24
with combined data from 
CNTO1959PSA3001 and CNTO159PSA3002.

The change from baseline in enthesitis score at Week 24 with combined data from 
CNTO1959PSA3001 and CNTO159PSA3002 is closely related to the proportion of 
subjects with enthesitis at Week 24 with combined data from CNTO1959PSA3001 and 
CNTO159PSA3002.
When an endpoint included in Figure 2 (ACR 20 at Week 24, or proportion of subjects with 
resolution of dactylitis at Week 24, or proportion of subjects resolution of enthesitis at week 24)
is significant for a guselkumab dose group versus the placebo group, correlated major secondary 
endpoints which are not included in Figure 2 as  specified above will be tested for that 
guselkumab dose group versus the placebo group at a 2-sided α-level of 0.05 without strict 
control of the overall type I error. A total of 14 tests fall in this category of weakly controlled 
hypothesis tests. Refer to Appendix 2 for the list of these 14 hypotheses:
Nominal p-values for the proportion of subjects with resolution of dactylitis at Week 24, the 
proportion of subjects with resolution of enthesitis at Week 24, the change from baseline in the 
dactylitis, and the change from baseline in the enthesitis using data from CNTO1959PSA3002 
only. Refer to Appendix 2 for the list of these 8 hypotheses. The treatment comparisons are 
underpowered for these hypotheses
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Global(Ex-US) Multiplicity Adjustment for Testing Procedures
5.2.2.2.
There are 2 hypotheses for the primary endpoint with 2 treatment comparisons:

The Guselkumab 100 mg q4w group is superior to placebo group as measured by ACR20 
response at Week 24 (primary hypothesis). 

The Guselkumab 100 mg at Weeks 0, 4, and then q8w group is superior to placebo group as 
measured by ACR20 response at Week 24. 
These 2 hypotheses will be tested in a fixed sequence in the order specified above. The overall 
type 1 error of treatment comparison for the primary endpoint be controlled at a significance 
level of ≤0.05. If the primary hypothesis achieves statistical significance at a 2-sided α-level of 
0.05, the study will be considered positive. If the primary hypothesis does not achieve statistical 
significance (ie, the Guselkumab 100mg q4w dose group comparison against placebo is not 
significant), the treatment group comparison for the second hypothesis will not be formally 
tested and the p-value for the treatment group comparison of the Guselkumab 100mg at Weeks 0 
,4, and then q8w group against placebo will be considered nominal. 
For each Guselkumab dose group, the overall Type I error of treatment comparison for primary 
and the selected major secondary endpoints will be controlled at a significance level of ≤0.05 
as specified below:

The hypotheses for the selected major secondary endpoints for a Guselkumab dose group 
will be formally tested only if the primary endpoint is significant for that Guselkumab 
dose group. For each Guselkumab dose group, the overall Type I error of treatment 
comparison for the selected major secondary endpoints will be controlled at a 
significance level of ≤0.05 according to the graphical procedure shown in Figure 3. 
Refer to Appendix 2 for the 24 hypotheses for the major secondary endpoints to be tested 
and controlled as specified in Figure 3. For all endpoints specified in the graphical 
procedure, both adjusted and nominal p-values will be provided. In the instance that an 
adjusted p-value is not significant, the nominal p-value must only be interpreted as 
supportive.

If the primary endpoint is not significant for that Guselkumab dose group, all treatment 
group comparisons for the major secondary endpoints for that Guselkumab dose group 
will not be formally tested and the p-values for the treatment group comparisons will be 
considered nominal.
Nominal p-values will be reported for the major secondary endpoints of the change from baseline 
in the dactylitis and enthesitis scores with data combined from CNTO1959PSA3001 and 
CNTO1959PSA3002. Nominal p-values will also be reported for proportion of subjects with 
resolution of dactylitis at Week 24 with data combined from CNTO1959PSA3001 and 
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CNTO1959PSA3002, the proportion of subjects with resolution of enthesitis at Week 24 with 
data combined from CNTO1959PSA3001 and CNTO1959PSA3002, the change from baseline in 
the dactylitis score at Week 24 using data from CNTO1959PSA3002 only, and the change from 
baseline in the enthesitis score using data from CNTO1959PSA3002 only. Refer to Appendix 2
for the list of these 12 hypotheses. The treatment comparisons are underpowered for these 
hypotheses.
Figure 3:        Global Multiple Comparison Procedure
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5.2.3.
Data Handling Rules
Missing Data Non-Responder Imputation (NRI) 
5.2.3.1.
For response efficacy endpoints, subjects with missing response status will be considered non -
responders.
Missing Data Exhaustive Scenario Imputation
5.2.3.2.
For selected response efficacy endpoints, the exhaustive scenario tipping point analyses will be 
performed to evaluate the deviation of the imputation of all missing data as non-responder, by 
varying the amount of non-responder and responder imputation for missing data. 
Let   be the total number of imputed values to-be-varied in the Active arm, where i of them 
will be set to ‘Yes’ response and (-i) of them set to ‘No’ response.  In the same vein, let  be 
the total number of imputed values to-be-varied in the Placebo arm, where j of them will be set 
to ‘Yes’ response and (-j) of them set to ‘No’ response. The range of i is from 0 to , and a 
range of j is from 0 to , which is an ‘exhaustive approach’.
Multiple Imputation (MI)  
5.2.3.3.
5.2.3.3.1.
MI Using FCS Regression
Under the assumption of missing at random (MAR), multiple imputation (MI) will be used to 
impute the missing data for the continuous/ordinal measurements. The missing data will be 
imputed using the predicted value from an imputation model using the Full Conditional 
Specification (FCS) regression method for any missing pattern. Each variable will be restricted 
to only impute within its possible range of values (eg, HAQ Score may only be imputed to within 
0-3. The explanatory variables in the imputation model include imputation variables and 
ancillary variables which are specified in Table 12. For these variables all measurements from 
baseline through Week 24 are included.
The number of imputations (N) and the starting seeds are specified in Table 12 (Appendix 4).
For the composite continuous endpoints (such as DAS28), the above imputation will be 
performed on components with missing data and then the composite score will be derived based 
on the imputed components.  
For categorical endpoints (IGA response, enthesitis resolution, dactylitis resolution), the above 
imputation will be performed for the respective scores on a continuous scale, then rounded to the 
nearest integer prior to deriving the response or resolution.
For the composite binary endpoints (such as ACR 20), the above imputation will be performed 
on each component with missing data and then response status will be determined based on such 
imputed components.  
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The treatment comparisons between a guselkumab group versus the placebo group will be 
performed using the analysis method specified for each of the N imputation datasets. The 
analysis results from all the N imputation datasets will be combined according to Rubin25, and 
the p-value for testing the treatment difference will be obtained.
5.2.3.3.2.
MI for Binary Endpoints for Tipping Point Sensitivity Analysis of MAR
Assumption
For selected binary endpoints, the tipping point analyses based on imputed data by MI will be 
performed to evaluate the impact of missing data when deviating from MAR assumption.

A pair of deltas (e.g., Dg =-0.1, Dp =0.2) will be added to the predicted response rates of 
each missing data from the MI method depending on guselkumab or placebo group. 

With the new response rate, the missing response will be imputed for N (e.g., N=200) times 
to generate N multiple imputations based on a Bernoulli distribution. Treatment 
comparisons will then be performed same as treatment comparison with MI 

The range of delta values include the scenarios where subjects on guselkumab have worse 
outcomes than subjects on placebo.
5.2.3.3.3.
Missing Data Handling for Tipping Point Sensitivity Analysis for 
Continuous Endpoints
For the change from baseline in selected endpoints, tipping point analyses based on imputed data 
by MI will be performed to evaluate the impact of missing data when deviating from the MAR 
assumption

A delta (e.g., Dg =0.2, Dp =0.1) will be added to the imputed value for each subject with 
missing value from the MI depending on whether the subject is in the guselkumab or 
placebo group.  

With the new datasets, treatment comparisons will be performed similar to treatment 
comparisons with MI data.

The analysis will be repeated for a range of Dg and Dp by varying Dg and Dp 
independently, including the scenarios where subjects on guselkumab have worse 
outcomes than subjects on placebo.
5.2.3.3.4.
2-Step MI (for X-ray Imaging Data)
Due to the slow progression in structural damage and over a short period of time, it is reasonable 
to assume that progression in structural damage is linear. To utilize all available post-treatment 
data that are collected outside of the analytical window for Week 24 and to properly account for 
uncertainty, missing Week 24 data, from subjects with an x-ray measurement at baseline and at a 
timepoint prior to week 24, will be imputed multiple times using a mixed effect linear growth 
curve model (Appendix 3) and multiple imputation.
1.
Only subjects with postbaseline data will be included to fit the model. The missing data will 
be sampled N times from the subject specific distribution of predictive change at week 24 
from MLGC model.
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2.
Missing data from subjects with only a baseline x-ray measurement will be imputed once
with the FCS regression method (Section 5.2.3.3) for each imputed dataset from the 1st step. 
Missing Data Linear Extrapolation (LEXT)  
5.2.3.4.
For comparison to historical radiographic data analyses, the missing values of selected 
continuous radiographic endpoint(s) will be imputed using linear extrapolation (LEXT), i.e., the 
predicted value at the time of interest using a linear regression model based on all observed 
values (including baseline) prior to the visit of interest for each applicable subject.  When no 
post-baseline value is available, the missing value will be replaced by the baseline value. For a 
continuous composite endpoint, LEXT will be applied first to each of its missing components
(hand erosion scores, foot erosion scores, hand JSN scores, and foot JSN score) and then the 
value of the composite endpoint will be derived based on the imputed components.
The LEXT method will be used for missing data imputation in sensitivity analysis 2 of change 
from baseline in modified vdH-S score at Week 24 (Section 5.4.4.2.1).
Missing Data Last Observation Carried Forward (LOCF)  
5.2.3.5.
For comparison to historical radiographic data analyses, the missing values of selected 
continuous radiographic endpoint(s) will be imputed using the last observation (including 
baseline) carried forward (LOCF).  For a continuous composite endpoint, LOCF will be applied 
to its missing components first and then the value of the composite endpoint will be derived 
based on the imputed components.
The LOCF method will be used for missing data imputation in sensitivity analysis 3 of change 
from baseline in modified vdH-S score at Week 24 (Section 5.4.4.2.1).
Missing Data as Missing for Continuous Endpoints
5.2.3.6.
For continuous endpoints, when treatment comparisons are performed using a Mixed-Effect 
Model Repeated Measures (MMRM) or Constrained Longitudinal Data Analysis (cLDA) Model 
(Appendix 3), all available data from the 3 treatment groups through Week 24 will be included.
Missing data will not be imputed. Under the assumption of MAR, the missing data will be 
accounted for through correlation of repeated measures in the model.
5.2.3.6.1.
Missing Data Handling for Tipping Point Analysis Evaluating the 
Assumption of MCAR for Continuous Endpoints
For the change from baseline in the modified vdH-S score, tipping point analyses based on 
observed data will be performed to evaluate the impact of missing data when deviating from the 
MCAR assumption

An ANCOVA model will be fitted to obtain the LS mean for each treatment group and 
SE of LS mean based on subjects with observed data.

The LS mean of subject with missing data will be assumed to be LS mean of subjects 
with observed data plus a delta (e.g., Dg =0.2, Dp =0.1) for each treatment group.
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
The overall LSmean will be obtained as the weighted average of the LSmean of subjects 
with observed data and with missing data. The treatment comparisons will be based on 
the F test using overall LSmean difference and SE of LSmean from the Analysis of 
Covariance model from 1st step

The analysis will be repeated for a range of Dg and Dp by varying Dg and Dp 
independently, including the scenarios where subjects on guselkumab have worse 
outcomes than subjects on placebo.
5.2.4.
Estimands
The same population, ie, all subjects with active psoriatic arthritis who are biologic naive will be 
used for all estimands defined below.  The FAS1 (Section 2.3.1.1) or a subset of FAS1 so that 
the endpoint measurement is meaningful, will be used to analyze data. 
Composite Strategy
5.2.4.1.
The Composite Strategy assesses the treatment effects not only based on the variable 
measurements, but also based on intercurrent events defined in TF criteria. When subjects 
maintain their background PsA medications at their baseline levels, the values based on the 
variable measurements will be used. If a subject met any of the TF criteria the subject will be a 
non-responder for response variables and will have a score of no improvement for continuous 
variables for signs and symptoms. This estimand acknowledges that meeting the TF criteria is an 
unfavorable outcome. 
Variables: 

Binary: The endpoint (e.g. ACR 20) is defined as responders who had not met any TF 
criteria prior to the specific visit at which the endpoint was assessed.

Continuous: The endpoint is defined as change from baseline score prior to meeting TF 
criteria and 0 (no improvement) after meeting TF criteria. This is based on the placebo 
response observed in prior PsA studies: the over-time mean improvements in the placebo 
group is generally greater than 0 by a meaningful amount. Therefore, no change is 
considered an extremely unfavorable outcome. 
Intercurrent Events: The intercurrent event is captured through variable definitions.
Population level summary:

Binary: difference in proportion of responders between guselkumab group and placebo 
group.

Continuous: difference in mean changes between guselkumab group and placebo group.
The Composite Estimand will be analyzed for all efficacy endpoints through Week 24. 
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Alternative Composite Strategy 
5.2.4.2.
The Alternative Composite Strategy is similar to the Composite Strategy described in 
Section 5.2.4.1, however, discontinuation of study agent due to reasons other than lack of 
efficacy (including adverse events caused by worsening of PsA) are not considered treatment 
failure. In other words, the intercurrent events include TF criterion 2, 3, 4, and a subset of 
criterion 1 from those listed in section 2.5.
This estimand is only used at Week 24, the last visit of the placebo-controlled period.
The Alternative Composite Estimand (Binary) will be analyzed for ACR 20 at Week 24.
Treatment Policy Strategy 
5.2.4.3.
The treatment policy strategy is to use all observed data collected for the endpoint. The 
occurrence of the intercurrent event is irrelevant: the value for the variable of interest is used 
regardless of whether or not the intercurrent event occurs. This is the supplementary strategy 
aiming to achieve a robust treatment effect for regulatory decision making for primary and some 
major secondary endpoints. 
Variable: 

Binary: response endpoint (e.g. ACR 20)

Continuous: change from baseline
Intercurrent Events: Regardless of the intercurrent event of meeting TF criteria 
Population level summary:

Binary: difference in proportion of responders between guselkumab group and placebo 
group.

Continuous: difference in mean changes between guselkumab group and placebo group.
The Treatment Policy Estimand will be analyzed for all major secondary endpoints (Table 6a),
and selected endpoints (Table 11a) analyzed at Week 16.
Per-Protocol Strategy
5.2.4.4.
The per-protocol strategy is to use the last assessment while on randomized treatment up to a 
specific visit (e.g., Week 24). For subjects who met TF criteria 3 or 4 prior to the said visit, the 
last assessment while on randomized treatment is the last assessment prior to meeting TF criteria 
3 or 4.  This is the supplementary strategy aiming to achieve a robust treatment effect for 
regulatory decision making for the primary endpoint of ACR 20 response at Week 24. 
Variable: last measurement while on randomized treatment prior to meeting TF criteria 3 and 4 
(Section 2.5) or up to a specific visit (e.g., Week 24), whichever is earlier, where, 
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while on randomized treatment is defined as the time from first administration of 
randomized treatment through onset of TF criteria 3 or 4 being met or through 4 weeks 
after last administration of randomized treatment up to the said specific visit (e.g., Week 
24), whichever is earlier. 
Intercurrent Events: the intercurrent event is captured through variable definitions.
Population level summary: 

Binary: difference in proportion of responders between guselkumab group and placebo 
group.
The Per-Protocol Strategy Estimand will be analyzed for ACR20 at Week 24.
5.3.
Primary Efficacy Endpoint(s)
The primary endpoint of this study is proportion of subjects who achieved an ACR 20 response 
at Week 24. This section outlines the definitions and analyses of this primary endpoint.
5.3.1.
Definition
ACR response is a composite measurement of change in PsA signs and symptoms and is 
presented as the numerical measurement of improvement in multiple disease assessment 
criteria.7,8  An ACR20 response is defined as: 
1.
≥ 20% improvement from baseline in both tender joint count (68 joints) [TJC68] and 
swollen joint count (66 joints) [SJC66]  
AND
2.
≥ 20% improvement from baseline in at least 3 of the following 5 assessments:
a.
Patient’s Assessment of Pain (VAS) [PAIN]
b.
Patient’s Global Assessment of Disease Activity (arthritis, VAS) [GDPT]
c.
Physician’s Global Assessment of Disease Activity (VAS) [GDEV]
d.
Patient’s Assessment of Physical Function as measured by HAQ-DI
e.
C-reactive protein (CRP)
Following are the definitions of each of the forgoing disease assessment criteria (components) 
that are used in the determination of ACR20 response:
3.
Tender Joint Count 68 (TJC68): a total number of tender joints among the 68 joints 
evaluated for tenderness.  Each of the 68 joints will be evaluated for tenderness, categorized 
as tender or not tender. Joint evaluability rules specified in Appendix 1 for overwriting joint
evaluation will be applied to those joints with joint injection(s)/surgical joint procedure(s).  
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For subjects with any joint not evaluable in the 68 joint set, joint count adjustment rules 
described in Appendix 1 will be applied in determining the ultimate count of tender joints.
4.
Swollen Joint Count 66 (SJC66): a total number of swollen joints among the 66 joints 
evaluated for swelling. (Note: The 2 hip joints are excluded from swelling assessment.)  
Each of the 66 joints will be evaluated for swelling, categorized as swollen or not swollen.  
Joint evaluability rules specified in Appendix 1 for overwriting joint evaluation will be 
applied to those joints with joint injection(s)/surgical joint procedure(s).  For subjects with 
any joint not evaluable in the 66 joint set, joint count adjustment rules described in 
Appendix 1 will be applied in determining the ultimate count of swollen joints.
5.
Patient’s Assessment of Pain (PAIN): a measure from 0 (no pain) to 10 (the worst possible 
pain) on a 10-unit VAS. 
6.
Patient’s Global Assessment of Disease Activity (arthritis, GDPT): a measure from 0 (very 
well) to 10 (very poor) on a 10-unit VAS. 
7.
Physician’s Global Assessment of Disease Activity (GDEV): a measure from 0 (no arthritis 
activity) to 10 (extremely active arthritis) on a 10-unit VAS.
8. HAQ-DI: a measure of difficulty a subject may have in accomplishing tasks in 8 functional 
areas.  For additional details, please refer to the definition of HAQ-DI in Section 5.4.1.1.
9.
C-reactive protein (CRP): a lab parameter measured in mg/dL.  LLOQ rule specified in 
Appendix 1 will be applied to values < LLOQ. 
If a subject’s baseline value for a component is zero (ie, no disease activity as measured by that 
component), the subject should be considered as not achieving 20% improvement from baseline
for that component since there is no room for improvement.
5.3.2.
Analysis Methods
The primary endpoint will be analyzed at Week 24 DBL based on the Composite Estimand 
(Section 5.2.4.1).  In the primary efficacy analysis, data from all subjects in FAS1 
(Section 2.3.1.1) will be analyzed according to randomized treatment group regardless of the 
treatment actually received.  
The primary endpoint to be analyzed is proportion of subjects who achieved an ACR 20 response 
at Week 24 and who did not meet any TF criteria (Section 2.5) prior to Week 24.  Subjects who 
met any TF criteria prior to Week 24 will be considered non-responders at Week 24 regardless of 
the observed ACR 20 response status.   
The treatment difference between each guselkumab group versus the placebo group will be 
tested using a CMH test stratified by baseline use of non-biologic DMARD (yes, no) and most 
recent CRP value prior to randomization (<2.0 mg/dL, ≥2.0 mg/dL). The magnitude of the 
treatment difference will be estimated by the difference in ACR 20 response rates between the 
guselkumab and placebo groups with a 95% CI calculated based on Wald statistics.
Data Handling Rules

Missing Data NRI rules (Section 5.2.3.1) will be applied, i.e., subjects with missing data for 
ACR 20 response at Week 24 will be considered ACR 20 non-responders at Week 24.
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In order to control the overall Type 1 error rate, the primary endpoint will be tested in a fixed 
sequence.
1. Guselkumab 100 mg q4w versus placebo in ACR 20 response at Week 24
2. Guselkumab 100 mg at Weeks 0, 4, and then q8w versus placebo in ACR 20 response at 
Week 24
If the first test is significant at a 2-sided α-level of 0.05, the study will be considered positive and 
the second test can then be performed.
Sensitivity and Supplementary Analyses
5.3.2.1.
1. To evaluate the robustness of the Composite Estimand regarding the assumption of all 
missing data as non-responder, sensitivity analyses with the exhaustive scenario tipping point 
analyses will be performed. The analysis will be conducted for an ‘exhaustive approach’ 
testing all combinations of missing data imputation as responder and NR (Section 5.2.3.2). 
The chi-square test will be used to compare each guselkumab group versus the placebo 
group. This will avoid the complication of having to incorporate baseline stratification in the 
mix when generating all combinations of responders and non-responders for the missing data 
for CMH test.  As all combinations will be presented, both the points where tipping occurs, 
as well as the proportion of non-tipping combinations, are of interest.
2. To support regulatory decision making, the Treatment Policy Estimand will also be evaluated 
(Section 5.2.4.3) as a supplementary analysis. In this analysis, however, the observed 
ACR 20 response for all subjects will be used regardless of whether or not TF criteria are met 
prior to Week 24, and the missing ACR 20 response for all subjects will be imputed by MI 
method (Section 5.2.3.3) under the assumption that data are MAR.  Treatment comparisons 
for each imputation data set will be based on a CMH test stratified by baseline use of non-
biologic DMARD (yes, no) and most recent CRP value prior to randomization (<2.0 mg/dL, 
≥2.0 mg/dL.  The analysis results from the N imputation datasets will be combined, 
according to Rubin25, and the p-value for testing the treatment difference will be obtained.
3. Two-dimensional tipping point analyses based on MI imputed data will be included for the 
Treatment Policy Estimand (Section 5.2.4.3) to assess the robustness for Treatment Policy 
Estimand regarding the assumption that data are MAR. A pair of deltas will be added to the 
predicted response rates from MI method depending on guselkumab or placebo group to new 
MI datasets (Section
5.2.3.3.2). The same analysis method as in sensitivity and 
supplementary analysis 2 will be applied for the pairs of deltas. The analysis will be done for 
pairs of delta values include the scenarios where subjects on guselkumab have worse 
outcomes than subjects on placebo.
4. In addition, the Alternative Composite Estimand will also be evaluated as a supplemental 
analysis (section 5.2.4.2). Subjects with missing data will be considered non-responders. The 
same analysis method as that used for the primary analysis will be applied.
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5. A supplemental analysis will be performed similar to the primary analysis (Section 5.3.2), 
however, based on the Per-Protocol Strategy Estimand (Section 5.2.4.4).  In this analysis, 
ACR response status will be determined based on the last assessment up to Week 24 while 
subjects on randomized treatment or the last non-missing assessment prior to meeting TF 
criteria 3 or 4, whichever is earlier. This analysis will use the per protocol analysis set.
Subgroup Analyses
5.3.2.2.
Subgroup analyses will be performed using a logistic regression model to evaluate treatment 
consistency in proportion of subjects who achieve an ACR 20 response at Week 24 over baseline 
demographics, baseline disease characteristics, and prior and baseline medication use.  A forest 
plot will be produced for all subgroups listed in Section 2.4.  Odds ratios and the corresponding 
95% CIs will also be provided for each of subgroups. In addition, the p-values for interaction of 
the treatment groups and the subgroups will also be provided when a subgroup has at least 2 
categories.  
If the number of subjects in a subgroup is too small (eg., < 10), subgroups may be pooled for 
analyses.
Summary of Analyses Related to the Primary Endpoint of ACR 20 
5.3.2.3.
Response at Week 24
Table 4 below provides an overview on all the analyses related to the primary endpoint of ACR 
20 response at Week 24, the estimands, the data handling rules to be used, and the analysis 
methods and summary statistics. All the analyses, except the subgroup analyses, will be based on 
the FAS1.  For subgroup analyses, the analysis sets are the individual subgroups (Section 2.4) of 
FAS1. Table 12 provides a summary of the Multiple Imputation method.
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Table 4: Summary of Analyses Related to the Primary Endpoint of ACR 20 Response at 
Week 24
Analysis 
(Analysis Set)
Missing data
Analysis method/Summary statistics
Analyses based on the Composite Estimand, in which, subjects meeting any TF criteria (defined in Section 2.5) 
prior to Week 24 will be considered as ACR 20 non-responders at Week 24.  
Primary Analysis
(FAS1)
Subjects with 
missing data are 
considered to be 
non-responders

Response rates

Treatment difference in response rates and 95% CI 

P-value from the CMH test (stratified by randomization 
stratification factors) for treatment comparison
Sensitivity 
Analysis
(FAS1)
Subjects with 
missing data are 
considered to be 
non-responders

Exhaustive tipping point analysis

The chi-squared test to compare treatment groups.

Analysis results to be presented graphically
Subgroup 
Analyses 
(Individual 
subgroup levels 
defined in 
Section 2.4)
Subjects with 
missing data are 
considered to be 
non-responders

Response rates

Odds ratio and 95% CI for treatment comparison

P-value from logistic regression for the interaction of treatment
group and subgroup variable

Analysis results to be presented in forest plots
Analyses based on the Treatment Policy Estimand, in which, all observed data will be used, regardless of 
whether or not the subjects meet any TF criteria (defined in Section 2.5).
Supplementary 
Analysis 1
(FAS1)
Multiple 
imputation with 
FCS regression of 
component scores
(Table 12)

Response rates

Treatment difference in response rates and 95% CI 

P-value from the CMHa test (stratified by randomization 
stratification factors) for treatment comparisons.
Supplementary 
Analysis 2
(FAS1)
Multiple 
imputation with 
FCS regression of 
component scores
(Table 12)

Tipping point analysis.

The CMHa test (stratified by randomization stratification 
factors) to compare treatment groups.

Analysis results to be presented graphically
Analyses based on the Alternative Composite Estimand, in which, subjects meeting any TF criteria (defined in 
section .2.5) except  discontinuation of study agent due to reasons other lack of efficacy will be considered as 
ACR 20 non-responders at Week 24. 
Supplementary 
Analyses 3
Subjects with 
missing data 
considered to be 
non-responders

Response rates

Treatment difference in response rates and 95% CI

P-value from the CMH test (stratified by randomization 
stratification factors) for treatment comparison
Analyses based on Per-Protocol Strategy Estimand, in which, ACR 20 response is determined based on the 
last measurement while subjects on randomized treatment up to Week 24 or prior to meeting TF criteria 3 or 4, 
whichever is earlier. 
Supplementary 
Analysis 3
(PPAS)

Response rates

Treatment difference in response rates and 95% CI 

P-value from the CMH test (stratified by randomization 
stratification factors) for treatment comparison
a When combining analysis results for the CMH test, the Wilson-Hiferty transformation will be applied to the 
test statistics to achieve an approximate normal distribution.
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5.4.
Major Secondary Endpoints
The major secondary endpoints in this study are: 
1.
Change from baseline in HAQ-DI score at Week 24.
2.
Proportion of subjects who achieve an ACR 50 response at Week 24.
3.
Proportion of subjects with a psoriasis response of an Investigator Global Assessment (IGA) 
(ie, an IGA psoriasis score of 0 [cleared] or 1 [minimal]) AND ≥2-grade reduction from 
baseline) at Week 24 among the subjects with ≥3% body surface area (BSA) psoriatic 
involvement and an IGA score of ≥2 (mild) at baseline.
4.
Proportion of subjects who achieve an ACR 20 response at Week 16.
5.
Change from baseline in modified van der Heijde-Sharp (vdH-S) score at Week 24.
6.
Proportion of subjects with resolution of enthesitis at Week 24 among the subjects with 
enthesitis at baseline.
7.
Proportion of subjects with resolution of dactylitis at Week 24 among the subjects with 
dactylitis at baseline.
8.
Change from baseline in enthesitis score (based on Leeds Enthesitis Index [LEI]) at 
Week 24 among the subjects with enthesitis at baseline. 
9.
Change from baseline in dactylitis scores at Week 24 among the subjects with dactylitis at 
baseline. 
10. Change from baseline in SF-36 Physical Component Score (PCS) at Week 24.
11. Change from baseline in DAS28 (CRP) at Week 24.
12. Change from baseline in SF-36 Mental Component Score (MCS) at Week 24. 
13. Proportion of subjects who achieve an ACR 50 response at Week 16.
14. Proportion of subjects who achieve an ACR 70 response at Week 24.
This section outlines the definition and analyses of these major secondary endpoints. All the 
secondary endpoints will be analyzed at Week 24 DBL according to the randomized treatment 
groups.  Data from all subjects in FAS1 (Section 2.3.1.1) will be included with the following 
exceptions:
the analysis of the psoriasis response of IGA will be based on FAS1 among the subjects with 
a ≥ 3% BSA psoriatic involvement and an IGA score of   ≥ 2 (mild) at baseline
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the analysis of change from baseline in enthesitis score change and resolution of enthesitis 
will be based on FAS1 among the subjects with enthesitis at baseline based on data combined 
from studies CNTO1959PSA3001 and CNTO1959PSA3002.
the analysis of change from baseline in dactylitis score and resolution of dactylitis will be 
based on FAS1 among the subjects with dactylitis at baseline based on data combined from 
studies CNTO1959PSA3001 and CNTO1959PSA3002.
5.4.1.
Change from Baseline in HAQ-DI Score at Week 24
Definition
5.4.1.1.
HAQ11 disability index (HAQ-DI) score is an evaluation of the functional status for a subject.
The 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks 
in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and 
activities of daily living).  Responses in each functional area are scored from 0, indicating no 
difficulty, to 3, indicating inability to perform a task in that area (i.e., lower scores are indicative 
of better functioning). 
The HAQ-DI score is the sum of computed category scores divided by the number of categories 
answered.  The HAQ-DI score will not be computed if the subject does not have scores for at 
least 6 of the 8 categories.
The scoring algorithm (including adjusting the use of aids or devices) is provided by 
http://patienteducation.stanford.edu/research/haq20.html and is detailed in a separate document.  
Change from baseline in HAQ-DI score is a measure of the change in the functional status, 
where a negative change reflects an improvement and a positive change reflects a worsening.
Analysis Methods
5.4.1.2.
The change from baseline in HAQ–DI score at Week 24 will be analyzed at Week 24 DBL based 
on the Composite Estimand (Section 5.2.4.1). In this analysis, data from all subjects in FAS1 
(Section 2.3.1.1) will be analyzed according to randomized treatment group regardless of the 
treatment received.
Analysis of the change from baseline in HAQ–DI score at Week 24 will be performed using an 
ANCOVA model based on MI data. The MI method will be applied to impute, under the 
assumption of MAR, the missing change score of HAQ-DI from baseline at Week 24 defined in 
the Composite Estimand (i.e., change from baseline with no change assumed at and after meeting 
TF criteria). The treatment difference between each guselkumab group versus the placebo group 
will be tested for each imputation dataset and then the analysis results across all imputation 
datasets will be combined.
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5.4.2.
Proportion of Subjects with ACR 50 Response at Week 24, Proportion 
of Subjects with ACR 50 Response at Week 16, Proportion of 
Subjects with ACR 20 Response at Week 16, and Proportion of 
Subjects with ACR 70 Response at Week 24
Definition
5.4.2.1.
For definition of ACR 20 response, refer to Section 5.2.1. 
ACR 50 and ACR 70 responses are defined similarly to ACR 20 response, except that the 
improvement threshold of 20% from baseline in ACR 20 response is replaced by 50% and 70%, 
respectively.   
Analysis Methods
5.4.2.2.
Data from all subjects in FAS1 will be analyzed according to randomized treatment group 
regardless of the treatment actually received.  
The same analysis method as described in Section 5.3.2 will be applied to the treatment 
comparisons on proportion of subjects with ACR 50 response at Week 24, proportion of subjects 
with ACR50 response at Week 16, proportion of subjects with ACR 20 response at Week 16, and 
proportion of subjects with ACR 70 response at Week 24. The analyses are based on the 
Composite Estimand (Section 5.2.4.1).
5.4.3.
Proportion of Subjects who Achieve a Psoriasis IGA Response at 
Week 24 Among the Subjects with ≥3% BSA Psoriatic Involvement 
and an IGA Score of ≥2 (mild) at Baseline
Definition
5.4.3.1.
The Investigator’s Global Assessment (IGA) documents the investigator’s assessment of the 
subject’s psoriasis at a given time point.  Overall lesions are graded for induration, erythema, and 
scaling using a scale of 0 (no evidence), 1 (minimal), 2 (mild), 3 (moderate) and 4 (severe). The 
subject’s psoriasis is assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4).
A psoriasis IGA response is defined as an IGA psoriasis score of 0 (cleared) or 1 (minimal) 
AND ≥2-grade reduction from baseline in the IGA psoriasis score.  
Analysis Methods
5.4.3.2.
Data from all subjects in FAS1 who had ≥ 3% BSA psoriatic involvement and an IGA score of 
≥2 (mild) at baseline will be included and analyzed according to the randomized treatment 
groups.  
The same analysis method as described in Section 5.3.2 will be applied to the treatment 
comparisons on proportion of subjects with a psoriasis IGA response at Week 24. The analyses 
are based on the Composite Estimand (Section 5.2.4.1).
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5.4.4.
Change from Baseline in Modified vdH-S Score at Week 24
Definition
5.4.4.1.
The vdH-S score is an original vdH-S score,28 modified for PsA. The modification for PsA 
includes addition of distal inter-phalangeal (DIP) joints of both hands scored for erosions and 
joint space narrowing (JSN), and assessments of radiographic features known as “pencil in cup” 
(PIC) and “gross osteolysis” (GO) that are specific to PsA. The vdH-S score is a measurement of 
progression in structural damage.  It is the sum of joint erosion score and JSN score. The erosion 
score and JSN score, respectively, is a measurement of 2 types of structural damage.
The joint erosion score is a summary of erosion severity in 40 joints of the hands (20 joints per 
hand) and 12 joints in the feet (6 in each foot).   Each joint is scored according to the surface area 
involved, from 0 to 5, with 0 indicating no erosion and 5 indicating complete collapse of bone.  
To identify the presence of pencil in cup (PIC) and gross osteolysis (GO) in the hands, a 
modification of erosions scores of 6 and 7 are applied by IRC radiologists.  For joints with one of 
these abnormalities, the maximum score of 5 will be applied. To identify the presence of PIC and 
GO in the feet, a modification of erosions scores of 11 and 12 are applied by IRC radiologists.  
For joints with one of these abnormalities the maximum score of 10 will be applied. Therefore,
the maximum erosion score for a hand joint is 5 and the maximum erosion score for hands is 
200. Because each side of a foot joint is graded on the scale of 0 to 5, the maximum erosion 
score for a foot joint is 10 and the maximum erosion score for feet is 120. Thus, the maximal 
erosion score (i.e., hand erosion score + foot erosion score) is 320.  
The joint space narrowing score summarizes the severity of JSN in 40 joints in the hands and 
12 joints of the feet. Assessment of JSN is scored from 0 to 4, with 0 indicating no JSN and with 
4 indicating absence of a joint space, presumptive evidence of ankylosis or complete luxation. 
Therefore, the maximum JSN score for a hand joint is 4 and the maximum JSN score for hands is 
160. The maximum JSN score for a foot joint is 4 and the maximum JSN score for feet is 48. 
Thus, the maximal JSN score (i.e., hand JSN score + foot JSN score) is 208.
The maximal erosion score of 320 combined with the maximal JSN score of 208 gives worst 
possible modified vdH-S score (ie, erosion score + JSN score) of 528.
Joint Evaluability Rules specified in Appendix 1 for overwriting joint evaluation will be applied 
to those joints with surgery/joint replacement or with radiographically insufficient data for 
reading.  For subjects with incomplete set of evaluable joints, Erosion and JSN Score Adjustment 
Rules described in Appendix 1 will be applied to determine the ultimate sub-scores (i.e., scores 
of hand erosion, hand JSN, foot erosion, and foot JSN) for each reader.  A composite score 
[including erosion, JSN, hand (i.e., hand erosion + hand JSN), foot (i.e., foot erosion + food 
JSN), and vdH-S scores)] will be set to missing if any of its corresponding sub-scores is missing. 
Adjudication will occur when the 2 primary readers do not agree with each other with respect to 
change from baseline in vdH-S score at any post-baseline visit.  The criteria for triggering 
adjudication can be found in Appendix 1.  Note that the criteria for triggering adjudication 
should be determined based on the observed data (i.e., data without application of those data 
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handling rules specified in Section 5.2.3).  Appendix 1 outlines the rules to select which 2 
readers’ scores to be used in the analysis for subjects with adjudication.  
The final scores or sub-scores at each visit are the average of corresponding scores from the 
2 primary readers for a subject without adjudication or from one of the 2 primary readers and 
adjudicator for a subject with adjudication.  
Change from baseline in vdH-S score measures the change in progression of structural 
damage, where a negative change indicates an improvement and a positive change indicates a 
worsening.
Analysis Methods
5.4.4.2.
Change from baseline in modified vdH-S score at Week 24 will be analyzed at the Week 24
DBL based on data from Read Campaign 1, data from all subjects in FAS1-SD will be included 
and analyzed according to the randomized treatment groups.  The De Facto (Treatment Policy) 
Estimand (Section 1.1) will be used for all radiographic analysis.
Due to non-normality of the modified vdH-S score, MI as described in Section 5.2.3.3 will be 
applied to account for missing data at Week 24 under the assumption that data are MAR where 
data from unscheduled visits will not be used.  Treatment comparisons for each imputation data 
set will be based on an ANCOVA model adjusted for baseline score, baseline use of non-
biologic DAMRDS (yes, no), and most recent CRP value prior to randomization (<2.0 mg/dL, ≥
2.0 mg/dL). The analysis results from the N imputation datasets will be combined, according to 
Rubin25, and the p-value for testing the treatment difference will be obtained.
5.4.4.2.1.
Sensitivity Analysis
To test the robustness of the above analysis results, the following sensitivity analyses will be 
performed:
1.
This analysis will use the same MI imputed dataset as that used for the main analysis, 
however, this analysis will be performed with ANOVA on the van der Waerden normal 
score for each imputed dataset (Section 5.2.3.3). 
2.
Two-dimensional tipping point analyses based on MI imputed data will be performed to 
evaluate the deviation from the assumption of MAR for missing data (Section 5.2.3.3.3)
using the same MI imputed dataset as that used for the main analysis. The same analyses 
method as that described in Section 5.4.4.2 for the main analysis, will be fitted. The analysis 
results from the N imputation datasets will be combined, according to Rubin 25, and the p-
value for testing the treatment difference will be obtained.
3.
Using the same ANCOVA model as the main analysis to compare the treatment differences 
based on multiple imputed dataset, however, a 2-step MI will be used: 1) Missing week 24 
data from subjects with an x-ray measurement at baseline and a measurement post baseline 
during the placebo controlled period will be imputed through a mixed effect linear growth 
curve model (see Appendix 3) (2) Missing data from subjects with only baseline x-ray 
measurements will be imputed with FCS regression method based on the imputed dataset 
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from the 1st step. The 2-step imputation will be applied only to the total vdH-S score and not 
to the erosion/JSN scores for hand and feet.
4.
Using the MI imputed dataset as that used for the main analysis for subjects with just a 
baseline value, a mixed effect linear growth curve model (see Appendix 3) will be used to
assess the statistical significance of the treatment difference of the progression rate in 24 
weeks. The analysis results from the N imputation datasets will be combined, according to 
Rubin25, and the p-value for testing the treatment difference will be obtained.
5.
The same analysis model as sensitivity analysis 1 will be applied to analyze the observed 
data as an additional supportive analysis. In this analysis, treatment comparisons will be 
performed using an ANOVA test on the van der Waerden normal score of change from 
baseline in modified vdH-S score at Week 24 based on imputed data, where. the missing 
vdH-S score at Week 24 will be imputed by Missing Data LOCF rules (Section 5.2.3.5).
6.
An analysis similar to sensitivity analysis 5, however, Missing Data LEXT Rules 
(Section 5.2.3.4) will be applied for subjects with missing vdH-S score at Week 24.
7.
An analysis similar to main analysis, however, based on the observed data.  Subjects with 
missing vdH-S score at Week 24 will be excluded from the analysis. This analysis assumes 
that missing data is MCAR.
8.
Two-dimensional tipping point analyses based on observed data will be performed to 
evaluate the impact of missing data when the pattern of missing data deviates from the 
assumption of MCAR (section5.2.3.6.1). The same ANCOVA model as that described in 
Section 5.4.4.2 for the main analysis, will be fitted.
The following table summarizes the primary and sensitivity analyses of the modified vdH-S 
score change at Week 24.
Table 5: Summary of Analyses Related to the Major Secondary Endpoint of change from 
baseline in vdH-S score at Week 24
Analysis 
(Analysis Set)
Missing data
Analysis method/Summary statistics
Analyses based on the Treatment Policy Estimand, in which, all observed data will be used, regardless of whether 
or not the subjects meet any TF criteria (defined in section 2.5).
MainAnalysis
(FAS1-SD)
MI with FCS 
regression (Section 
5.2.3.3, Table 12)

Summarized descriptively

For each imputed dataset, treatment 
comparison using ANCOVA model 

P-value by combining treatment 
differences from all MI imputed 
datasets
1
Sensitivity Analysis
(FAS1-SD)
MI with FCS 
regression (Section 
5.2.3.3, Table 12)

Summarized descriptively

For each imputed dataset, treatment 
comparison using ANOVA model on 
van der Waerden normal score

P-value by combining treatment 
differences from all MI imputed 
datasets
2
Sensitivity Analysis
(FAS1-SD)
MI with FCS 
regression (Section 
5.2.3.3, Table 12)

Two-dimensional tipping point analysis

Treatment comparison using ANCOVA 
model 

Analysis results to be presented 
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Table 5: Summary of Analyses Related to the Major Secondary Endpoint of change from 
baseline in vdH-S score at Week 24
Analysis 
(Analysis Set)
Missing data
Analysis method/Summary statistics
graphically
3
Sensitivity Analysis
(FAS1-SD)
2 step MI

Summarized descriptively

For each imputed dataset, treatment 
comparison using ANCOVA model 

P-value by combining treatment 
differences from all MI imputed 
datasets
4
Sensitivity Analysis
(FAS1-SD)
MI with FCS 
regression (Section 
5.2.3.3, Table 12)

Summarized descriptively

For each imputed dataset, treatment 
comparison using a mixed effect linear 
growth curve model

P-value by combining treatment 
differences from all MI imputed 
datasets
5
Sensitivity Analysis
(FAS1-SD)
LOCF
(Section5.2.3.5 ).

Summarized descriptively

ANOVA model on van der Waerden 
normal score
6
Sensitivity Analysis
(FAS1-SD)
LEXT
(Section 5.2.3.4)

Summarized descriptively

Treatment comparison using ANOVA 
model on van der Waerden normal 
score
7
Sensitivity Analysis
(FAS1-SD)
No imputation of 
missing data. 
Exclude subjects 
with missing Week 
24 vdH-S score

Summarized descriptively

Treatment comparison using ANCOVA 
model 
8
Sensitivity Analysis
(FAS1-SD)
The LSmean of 
subjects with 
missing data will 
be assumed to be 
the LSmean of 
subjects with 
observed data plus 
a delta.

Two-dimensional tipping point analysis

Treatment comparison using ANCOVA 
model 

Analysis results to be presented 
graphically
Subgroup Analyses (Individual 
subgroup levels defined in 
Section 2.4)
MI with FCS 
regression (Section 
5.2.3.3, Table 12)

LSMeans (95% CI) for treatment 
groups

P-value for the interaction of treatment 
group and subgroup variable using 
observed data and not MI imputed 
datasets.

Comparison using ANCOVA model 
5.4.4.2.2.
Subgroup Analysis
Subgroup analyses will be performed to evaluate treatment consistency in modified vdH-S score 
change from baseline at Week 24 over baseline demographics, baseline disease characteristics, 
and prior and baseline medication use.  The LS Means of the difference between treatment 
groups in modified vdH-S score change from baseline at Week 24 and the associated 95% CI 
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estimated by the ANCOVA model will be plotted for each of the subgroup factors defined in 
Section 2.4.
5.4.5.
Change from Baseline in Enthesitis Score at Week 24 and Proportion 
of subjects with Resolution of Enthesitis at Week 24 in Subjects with 
Enthesitis at Baseline
Definition 
5.4.5.1.
Enthesitis is an important feature of psoriatic arthritis and other spondyloarthropathies. In this 
study, enthesitis will be assessed by an independent joint assessor using the Leeds Enthesitis 
Index (LEI).15 The LEI was developed to assess enthesitis in subjects with PsA and evaluates the 
presence (score of 1) or absence (score of 0) of pain by applying local pressure to the following 
entheses: 

Lateral epicondyle humerus, left and right 

Medial femoral condyle, left and right 

Achilles tendon insertion, left and right 
The enthesitis index score is a total score of the 6 evaluated sites as listed above, with range from 
0 to 6. For subjects who have an incomplete set of 6 evaluated sites, the enthesitis index score 
based on the observed data cannot be calculated.
Change from baseline in enthesitis score measures the change in enthesitis, where a negative 
change indicates an improvement and a positive change indicates a worsening.
Subject with enthesitis at baseline are those subjects with at least at one tender enthesis among 
the 6 sites include in the LEI.
Subjects with resolution of enthesitis are those subjects who had at least one tender enthesis at 
baseline and none at the analysis visit among the 6 sites included in the LEI.
Analysis Methods
5.4.5.2.
Data from all subjects in FAS1 who had at least one tender enthesis among the 6 sites included in 
the LEI, at baseline, will be included and analyzed according to the randomized treatment 
groups. The data from studies CNTO1959PSA3001 and CNTO1959PSA3002 will be combined 
together for the analysis of the major secondary endpoints and the analysis will be stratified by 
the combination of study and randomization stratification factors. However, nominal p-values for 
the CNTO1959PSA3002 study will also be reported. Refer to section 5.2.2.1 for details on the 
multiplicity adjusted testing procedure for the resolution of enthesitis and the change from 
baseline in enthesitis score endpoints.
Similar analysis methods as described in Section 5.4.1.2 (ANCOVA on MI data) will be applied
to treatment comparisons on the change from baseline in enthesitis score at Week 24. The MI 
method will be applied to each study separately to obtain the MI data sets for each study. The 
analyses are based on the Composite Estimand (Section 5.2.4.1).
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The same analysis method as described in Section 5.3.2 will be applied to the treatment 
comparisons on proportion of subjects with resolution of enthesitis at Week 24. The analyses are 
based on the Composite Estimand (Section 5.2.4.1).
5.4.6.
Change from Baseline in Dactylitis Scores at Week 24 and Proportion 
of subjects with Resolution of Dactylitis at Week 24 in Subjects with 
Dactylitis at Baseline
Definition 
5.4.6.1.
Presence and severity of dactylitis will be assessed in both hands and feet using a scoring system 
from 0 to 3 (0 – no dactylitis, 1 – mild dactylitis, 2 – moderate dactylitis, and 3 – severe 
dactylitis).12,13
The results for each digit are summed to produce a final dactylitis score with a range from 0 
to 60.  
Change from baseline in dactylitis score measures the change in dactylitis, where a negative 
change indicates an improvement and a positive change indicates a worsening.
Subject with dactylitis at baseline are those subjects with a dactylitis score > 0 at baseline.  
Subjects with resolution of dactylitis are those subjects who had a dactylitis score > 0 at 
baseline and a score of 0 at the analysis visit.
Analysis Methods
5.4.6.2.
Data from all subjects in FAS1 who had dactylitis at baseline will be included and analyzed 
according to the randomized treatment groups. The data from studies CNTO1959PSA3001 and 
CNTO1959PSA3002 will be combined together for the analysis of the major secondary 
endpoints and the analysis will be stratified by the combination of study and randomization 
stratification factors. However, nominal p-values for the CNTO1959PSA3002 study will also be 
reported. Refer to section 5.2.2.1 for details on the multiplicity adjusted testing procedure for the 
resolution of dactylitis and the change from baseline in dactylitis score endpoints.
The same analysis methods as described in Section 5.4.1.2 (ANCOVA on MI data) will be 
applied to treatment comparisons on the change from baseline in dactylitis score at Week 24. The 
MI method will be applied to each study separately to obtain the MI data sets for each study. The 
analyses are based on the Composite Estimand (Section 5.2.4.1).
The same analysis method as described in Section 5.3.2 will be applied to the treatment 
comparisons on proportion of subjects with resolution of dactylitis at Week 24. The analyses are 
based on the Composite Estimand (Section 5.2.4.1).
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5.4.7.
Change from Baseline in SF-36 PCS Score at Week 24 and Change 
from Baseline in SF-36 MCS score at Week 24
Definition
5.4.7.1.
The questionnaire of the 36-item short form health survey (SF-36) is a health-related quality of 
life instrument with 36 questions, developed as part of the Rand Health Insurance Experiment.  
Version 2 will be used.  This instrument consists of 8 multi-item scales (domains).30

Limitations in physical functioning due to health problems

Limitations in usual role activities due to physical health problems

Bodily pain

General mental health (psychological distress and well-being)

Limitations in usual role activities due to personal or emotional problems

Limitations in social functioning due to physical or mental health problems

Vitality (energy and fatigue)

General health perception
Each of these 8 scales (domains) is scored from 0 to 100 with higher scores indicating better 
health.  Based on the scale scores, the 2 summary scores, physical component summary (PCS)
score and mental component summary (MCS) score, will be derived.  These summary scores are 
also scaled with higher scores indicating better health.   
Note that, the SF-36 scale scores will be derived based on the algorithm and software provided 
by the developer.26 The norm-based score will be used for data analysis and derived by using the 
2009 general US population with missing value estimated based on Advanced Data Recovery 
with Missing Score Estimator (MSE) provided in the user manual.26
Change from baseline in PCS score measures the change in health-related quality of life, where 
a positive change indicates an improvement and a negative change indicates a worsening.
Similarly, change from baseline in MCS score measures the change in health-related quality of 
life, where a positive change indicates an improvement and a negative change indicates a 
worsening.
Analysis Methods
5.4.7.2.
Data from all subjects in FAS1 will be included and analyzed according to the randomized 
treatment groups.  
The same analysis methods as described in Section 5.4.1.2 (ANCOVA on MI data) will be 
applied to treatment comparisons on change from baseline in PCS at Week 24 and change from 
baseline in MCS at Week 24. The analyses are based on the Composite Estimand (Section
5.2.4.1).
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.
5.4.8.
Change from Baseline in DAS28 (CRP) at Week 24
Definition
5.4.8.1.
The Disease Activity Index Score 28 using CRP [DAS28 (CRP)] is a derived score combining 
tender joints (28 joints), swollen joints (28 joints), CRP, and Patient’s Global Assessment of 
Disease Activity.29 The 28 joints evaluated for swelling and tenderness are shoulder, elbow, 
wrist, MCP1, MCP2, MCP3, MCP4, MCP5, PIP1, PIP2, PIP3, PIP4, PIP5 joints of the upper 
right and upper left extremities as well as the knee joints of the lower right and lower left 
extremities.
The DAS28 (CRP) is a continuous parameter and is defined as follows:
DAS28 (CRP) = 0.56* SQRT(TJC28) + 0.28*SQRT(SJC28) + 0.36* Ln 
(CRPmg/L +1) + 0.014*GDPTmm + 0.96, where
1.
TJC28: a total number of tender joints among the 28 joints evaluated for tenderness.  Each
of the 28 joints will be evaluated for tenderness, categorized as tender or not tender.  Joint 
evaluability rules specified in Appendix 1 for overwriting joint evaluation will be applied to 
those joints with joint injection(s)/surgical joint procedure(s).  For subjects with any joint 
not evaluable in the 28 joint set, joint count adjustment rules described in Appendix 1 will 
be applied in determining the ultimate count of tender joints.
2.
SJC28: a total number of swollen joints among the 28 joints evaluated for swelling.  Each of 
the 28 joints will be evaluated for swelling, categorized as swollen or not swollen.  Joint 
evaluability rules specified in Appendix 1 for overwriting joint evaluation will be applied to 
those joints with joint injection(s)/surgical joint procedure(s).  For subjects with any joint 
not evaluable in the 28 joint set, joint count adjustment rules described in Appendix 1 will 
be applied in determining the ultimate count of swollen joints.
3.
CRPmg/L: CRP in mg/L. In the calculation of DAS28 (CRP) value, the natural logarithm of 
(CRPmg/L + 1) is used.  LLOQ rule specified in Appendix 1 will be applied to values 
< LLOQ.
4.
GDPTmm: Patient’s Global Assessment of Disease Activity (arthritis) scaled from 0 (very
well) to 100 (very poor) on a 100-unit VAS for the calculation of DAS28 (CRP) value.  
If any of the components required for computing the DAS28 (CRP) value is missing, the DAS 28 
(CRP) score will be set to missing.
Change from baseline in DAS28 (CRP) measures the change in disease activity, where a 
negative change indicates an improvement and a positive change indicates a worsening.  
Analysis Methods
5.4.8.2.
Data from all subjects in FAS1 will be included and analyzed according to the randomized 
treatment groups.  
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The same analysis methods as described in Section 5.4.1.2 (ANCOVA on MI data) will be 
applied to treatment comparisons on change from baseline in DAS28 (CRP) at Week 24. The 
analyses are based on the Composite Estimand (Section 5.2.4.1).
5.4.9.
Summary of Analyses Related to Major Secondary Endpoints
Table 6 below provides an overview of all the analyses related to the major secondary endpoints
other than the analyses for the change from baseline in modified vdH-S score, the estimands, the 
data handling rules to be used, and the analysis methods and summary statistics. All the analyses 
will be based on the FAS1. Table 12 provides a summary of the Multiple Imputation method. For 
the summary of analyses related to the change from baseline in modified vdH-S score refer to 
Table 5.
Table 6: Summary of Analyses Related to Major Secondary Endpoints Other Than Change 
from baseline in Modified vdH-S Score.
Endpoints
(Analysis Set)
Missing data
Analysis method/Summary statistics
Analyses of Response Endpoints based on Composite Estimand, in which, subjects meeting any TF criteria 
(defined in Section 2.5) prior to a visit (e.g., Week 16) will be considered as non-responders at the said visit (e.g., 
Week 16).  
ACR 50 Response at 
Week 24 (FAS1)
ACR 70 Response at 
Week 24 (FAS1)
ACR 20 Response at 
Week 16 (FAS1)
ACR 50 at Week 16
(FAS1)
IGA Response at 
Week 24 (FAS1 with 
≥3% BSA psoriatic 
involvement and an 
IGA score of ≥2 at 
baseline)
Resolution of 
enthesitis (LEI) at 
Week 24 among 
subjects with enthesitis 
(LEI) at baseline
Resolution of dactylitis 
at Week 24 among 
subjects with dactylitis 
at baseline
Subjects with 
missing data are 
considered to be 
non-responders

Response rates

Treatment difference in response rates and 95% CI 

P-value from the CMH test (stratified by randomization 
stratification factors) for treatment comparison
Analyses of Continuous Endpoints based on Composite Estimand, in which, subjects meeting any TF criteria 
(defined in Section 2.5) prior to a visit (e.g., Week 24) will be considered as no change (no improvement) from 
baseline at the said visit (e.g., Week 24).  
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Table 6: Summary of Analyses Related to Major Secondary Endpoints Other Than Change 
from baseline in Modified vdH-S Score.
Endpoints
(Analysis Set)
Missing data
Analysis method/Summary statistics
Change from baseline at 
Week 24 in:
HAQ-DI score (FAS1)
DAS28(CRP) (FAS1)
Enthesitis (LEI) score 
(FAS1 in subjects with 
enthesitis (LEI at 
baseline)
Dactylitis score (FAS1 in 
subjects with dactylitis at 
baseline)
SF-36 PCS score (FAS1)
SF-36 MCS score (FAS1)
MI 
(Section 5.2.3.3)
Main Analysis:

Descriptive summary statistics

ANCOVA for each MI dataset and then analysis results across all MI 
datasets combined 

LS mean (95% CI) for each treatment group and for differences 
between groups.

P-values for treatment comparisons
5.4.10.
Additional Tipping Point Analyses
To support regulatory decision making per the FDA review comment dated 14MAR2019 [IND 
124177 – Guselkumab (CNTO 1959) – Comments for IND 124177], additional tipping point 
analyses will be performed for each major secondary endpoint to evaluate the impact when the 
missing data deviate from the MAR assumption.  Analyses will be performed for the Treatment 
Policy Estimand (Section 5.2.4.3), where observed data is included regardless of whether or not 
TF criteria are met prior to the time at which the endpoint is assessed.
Missing data in binary endpoints will first be imputed using multiple imputation, then a pair of 
deltas will be added to the predicted response or resolution rates of each missing subject from the 
MI method depending on guselkumab or placebo group to new MI datasets (Section 
5.2.3.3.2). The same CMH test as that used for the main analysis of the endpoint will be used for 
each imputation set, and the analysis results from the N imputation datasets will be combined for 
each pair of deltas, according to Rubin25, and the p-values for testing the treatment difference 
will be obtained.  When combining analysis results for the CMH test, the Wilson-Hilferty-
transformation24 will be applied to the test statistics to achieve an approximate normal 
distribution.
Missing data for continuous endpoints will first be imputed using multiple imputation, then a 
pair of deltas will be added to the imputed values from the MI method depending on guselkumab 
or placebo group (Section 5.2.3.3.3). The same ANCOVA model as that used for the main 
analysis of the endpoint will be used for each imputation set, and the analysis results from the N 
imputation datasets will be combined for each pair of deltas, according to Rubin25, and the p-
values for testing the treatment difference will be obtained.
Table 6a below summarizes the tipping point analyses for major secondary endpoints other than 
the modified vdH-S Score.  For the summary of additional tipping point analyses other than for 
primary and major secondary endpoints see Section 5.5.5.
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Table 6a: Summary of Tipping Point Analyses for Major Secondary Endpoints Other Than 
Change from baseline in Modified vdH-S Score
Endpoints
(Analysis Set)
Missing data
Analysis method
Supplementary Analyses of Continuous Endpoints based on Treatment Policy Estimand, in which all observed 
data will be used, regardless of whether or not the subjects meet any TF criteria.
Change from baseline at Week 24 in:
HAQ-DI score (FAS1)
SF-36 PCS score (FAS1)
SF-36 MCS score (FAS1)
DAS28(CRP) (FAS1)
Enthesitis (LEI) among subjects with 
enthesitis (LEI) at baseline (FAS1)
based on data combined from studies 
CNTO1959PSA3001 and 
CNTO1959PSA3002
Dactylitis among subjects with dactylitis 
at baseline (FAS1) based on data 
combined from studies 
CNTO1959PSA3001 and 
CNTO1959PSA3002
MI with FCS 
regression (Section 
5.2.3.3.3, Table 12)

Two-dimensional tipping point analysis

Treatment comparison using ANCOVA model 

Analysis results to be presented graphically
Supplementary Analyses of Binary Endpoints based on Treatment Policy Estimand in which, all observed data 
will be used, regardless of whether or not the subjects meet any TF criteria.
ACR 50 Response at Week 24 (FAS1)
ACR 70 Response at Week 24 (FAS1)
ACR 20 Response at Week 16 (FAS1)
ACR 50 at Week 16 (FAS1) 
IGA Response at Week 24 (FAS1 with 
≥3% BSA psoriatic involvement and an 
IGA score of ≥2 at baseline)
Resolution of enthesitis (LEI) at Week 
24 among subjects with enthesitis (LEI) 
at baseline based on data combined from 
studies CNTO1959PSA3001 and 
CNTO1959PSA3002
Resolution of dactylitis at Week 24 
among subjects with dactylitis at 
baseline based on data combined from 
studies CNTO1959PSA3001 and 
CNTO1959PSA3002
MI with FCS 
regression (Section 
5.2.3.3.2, Table 12)

Two-dimensional tipping point analysis.

The CMHa test (stratified by randomization 
stratification factors) to compare treatment groups.

Analysis results to be presented graphically
a When combining analysis results for the CMH test, the Wilson-Hilferty transformation will be applied to the test statistics to 
achieve an approximate normal distribution.
5.5.
Other Efficacy Variable(s)
In addition to the primary and major secondary endpoints, other efficacy analyses related to 
reduction of signs and symptoms and physical function, skin disease, joint structural damage, 
and health related quality of life will be analyzed.
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This section outlines the definition and analyses of the other efficacy endpoints. 
Efficacy endpoints through Week 24 will be analyzed at Week 24 DBL based on the Composite 
Estimand (Section 5.2.4.1); efficacy endpoints from Week 24 through Week 52 will be analyzed 
at Week 52 DBL; and efficacy endpoints from Week 52 through Week 100 will be analyzed at 
Final (Week 112) DBL.
5.5.1.
Efficacy Endpoints Related to Reduction of Signs and Symptoms and 
Physical Function 
Definition
5.5.1.1.
5.5.1.1.1.
ACR Related Endpoints
Other efficacy endpoints related to ACR include:

Proportion of subjects who achieve an ACR 20 response by visit through Week 100

Proportion of subjects who achieve an ACR 50 response by visit through Week 100

Proportion of subjects who achieve an ACR 70 response by visit through Week 100

ACR components by visit through Week 100   

Percent change (improvement) from baseline in ACR components by visit through Week 
100   

Proportion of subjects who maintain an ACR 20 response at Week 52 and Week 100 among 
the subjects who achieved an ACR 20 response at Week 24.  

Proportion of subjects who maintain an ACR 50 response at Week 52 and Week 100 among 
the subjects who achieved an ACR 50 response at Week 24.  

Proportion of subjects who maintain an ACR 70 response at Week 52 and Week 100 among 
the subjects who achieved an ACR 70 response at Week 24.  
For definition of ACR 20 response, refer to Section 5.3.1. For definition of ACR 50 response
and ACR 70 response, refer to Section 5.4.2.1.
5.5.1.1.2.
HAQ-DI Related Endpoints
The other efficacy endpoints related to HAQ-DI include:

Change from baseline in HAQ-DI score by visit overtime through Week 100.  

Proportion of subjects who achieve a HAQ-DI response (i.e., a ≥0.35 improvement from 
baseline in HAQ-DI score) by visit overtime through Week 100 among those subjects with 
HAQ-DI score ≥ 0.35 at baseline. 

Proportion of subjects who maintain a HAQ-DI response at Week 52 and Week 100 among 
the subjects who achieved a HAQ-DI response at Week 24.  
For definitions of HAQ-DI and change from baseline in HAQ-DI score, refer to 
Section 5.4.1.1. 
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HAQ-DI responders are subjects who achieved ≥0.35 improvement in HAQ-DI score.
Note that a ≥0.35 improvement in HAQ-DI score is considered a clinically meaningful 
improvement in PsA.21  The responders are only applicable to subjects whose baseline HAQ-DI 
score ≥0.35.
5.5.1.1.3.
DAS28 Related Endpoints
The other efficacy endpoints related to DAS28 (CRP) include:

Proportion of subjects with DAS28 (CRP) response by visit overtime through Week 100

Proportion of subjects with DAS28 (CRP) remission by visit overtime through Week 100

Change from baseline in DAS28 (CRP) by visit overtime through Week 100  
For definitions of DAS28 (CRP), refer to Section 5.4.8.1. 
DAS28 Response for DAS28 (CRP) is as defined in Table 7.29
Table 7:
DAS28 (CRP) Response Criteria
DAS28 (CRP) at the visit
Improvement from Baseline
> 1.2
> 0.6 – 1.2
≤0.6
≤ 3.2
Good response
Moderate response
No response
> 3.2 – 5.1
Moderate response
Moderate response
No response
> 5.1
Moderate response
No response
No response
DAS28 (CRP) remission is defined as a DAS28 (CRP) value of < 2.6 at a visit.
5.5.1.1.4.
Responders Based on Modified Psoriatic Arthritis Responder Criteria
(PsARC)
A subject will be considered a responder based on Modified Psoriatic Arthritis Responder 
Criteria (PsARC) if the subject meets at least 2 of the following criteria at a visit, including at 
least 1 of the 2 joint criteria and with no deterioration in the other criteria.23 No deterioration 
means ≥ 0% improvement.

≥ 30% decrease in swollen joint count (SJC66)

≥ 30% decrease in tender joint count (TJC68)

≥ 20% improvement in Patient’s Global Assessment of Disease Activity (arthritis) on a VAS

≥ 20% improvement in Physician’s Global Assessment of Disease Activity on a VAS
5.5.1.1.5.
Enthesitis Related Endpoints
Refer to Section 5.4.5.1 for definitions of enthesitis score, change from baseline in enthesitis 
score, and subjects with resolution of enthesitis.
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5.5.1.1.6.
Dactylitis Related Endpoints
Refer to Section 5.4.6.1 for definitions of dactylitis score, change from baseline in dactylitis 
score, and subjects with resolution of dactylitis.
5.5.1.1.7.
PASDAS Related Endpoints
The Psoriatic ArthritiS Disease Activity Score (PASDAS) is a derived score combining Patient’s 
Global Assessment of Disease Activity (arthritis and psoriasis, on a 100-unit VAS), Physician’s 
Global Assessment of Disease Activity (on a 100-unit VAS), swollen joint count (66 joints), 
tender joint count (68 joints), CRP (mg/L), enthesitis based on LEI (scaled to a 0–6 range),
dactylitis count (scoring each digit from 0–3 and recoding to 0–1, where any score > 0 equaled 
1), and the PCS score of the SF-36 health survey.16,18
The PASDAS is a continuous parameter and is defined as follows:
PASDAS = 1.5*{[0.18* SQRT(GDEVmm) + 0.159* SQRT(GDPTSmm) - 0.253 × 
SQRT(SF_PCS) + 0.101 * Ln (SJC66 +1) + 0.048 * Ln (TJC68 + 1) +  0.23 * Ln (ENTHE + 1) 
+ 0.377 * Ln (DACTY + 1) +  0.102* Ln (CRPmg/L +1)] + 2} , where
1.
GDEVmm: Physician’s Global Assessment of Disease Activity on a 100-unit VAS.  
2.
GDPTSmm: Patient’s Global Assessment of Disease Activity (arthritis and psoriasis) on a 
100-unit VAS.  
3.
SF-PCS: PCS score of the SF-36 health survey.
4.
SJC66: a total number of swollen joints among the 66 joints evaluated for swelling.  Each of 
the 66 joints will be evaluated for swelling, categorized as swollen or not swollen.  Joint 
evaluability rules specified in Appendix 1 for overwriting joint evaluation will be applied to 
those joints with joint injection(s)/surgical joint procedure(s).  For subjects with any joint 
not evaluable in the 66 joint set, joint count adjustment rules described in Appendix 1 will 
be applied in determining the ultimate count of swollen joints.
5.
TJC68: a total number of tender joints among the 68 joints evaluated for tenderness.  Each 
of the 68 joints will be evaluated for tenderness, categorized as tender or not tender.  Joint 
evaluability rules specified in Appendix 1 for overwriting joint evaluation will be applied to 
those joints with joint injection(s)/surgical joint procedure(s).  For subjects with any joint 
not evaluable in the 68 joint set, joint count adjustment rules described in Appendix 1 will 
be applied in determining the ultimate count of tender joints.
6.
ENTHE: enthesitis score based on LEI with a range from 0 to 6.
7.
DACTY: dactylitis count (scoring each digit from 0–3 and recoding to 0–1, where any score 
> 0 equaled 1).
8.
CRPmg/L:  CRP in mg/L. LLOQ rule specified in Appendix 1 will be applied to values < 
LLOQ.
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If any of the components required for computing the PASDAS value is missing, the PASDAS 
will be set to missing.
Change from baseline in PASDAS measures the change in disease activity, where a negative 
change indicates an improvement and a positive change indicates a worsening.
Subjects with very low or low disease activity based on the PASDAS score are those subjects 
who have a PASDAS score less than or equal to 1.9, or greater than 1.9 and less than or equal to 
3.2, respectively.
5.5.1.1.8.
GRACE Related Endpoints
GRAppa Composite scorE (GRACE) Index score is a composite score of Group for Research 
and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), derived as GRACE Index = (1 -
AMDF) x 10, where, AMDF is the Arithmetic Mean of the Desirability Function (AMDF).18,17
AMDF is calculated by transforming the following variables using predefined algorithms and 
expressing the total score as a mean with a score range of 0 – 1, where 1 indicates a better state 
than 0:

Tender joint count (68 joints)

Swollen joint count (66 joints)

HAQ-DI score

Patient’s Global Assessment of Disease Activity (arthritis and psoriasis) on a 100-unit VAS

Patient’s Assessment of Skin Disease Activity on a 100-unit VAS

Patient’s Global Assessment of Disease Activity (arthritis) on a 100-unit VAS

Psoriasis Area and Severity Index PASI score (Section 5.5.2.1.1)

Psoriatic Arthritis Quality of Life Index (PsAQOL) score, which is derived as follows:
PsAQOL = 25.355 + (2.367 × HAQ-DI) – (0.234 × SF-PCS) – (0.244 × SF-MCS) where,

HAQ-DI: HAQ-DI score (0-3)

SF-PCS: PCS score of SF-36 Health Survey

SF-MCS: MCS score of SF-36 Health Survey
If any of the components required for computing the PsAQOL score is missing, the PsAQOL 
score will be set to missing.
Change from baseline in GRACE index score measures the change in disease activity, where a 
negative change indicates an improvement and a positive change indicates a worsening.  
Subjects with low disease activity based on the GRACE index score are those subjects who 
have a GRACE index score less than or equal to 2.3.
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5.5.1.1.9.
mCPDAI Related Endpoints
The modified Composite Psoriatic Disease Activity Index (mCPDAI) assesses 4 domains (joints, 
skin, entheses, and dactylitis). The mCPDAI scores are calculated using the following 
assessments: swollen or tender joint count (66/68 joints), HAQ-DI, PASI, Dermatology Life 
Quality Index (DLQI), dactylitis, and enthesitis. Within each domain a score (range 0–3) is 
assigned according to predefined cutoffs as shown below.18 The scores for each domain are then 
added together to give an mCPDAI score with a range of 0 to 12.
The DLQI (defined in section 5.5.2.1.2) score is based on the observed DLQI score and is not 
derived.
Change from baseline in mCPDAI score measures the change in disease activity, where a 
negative change indicates an improvement and a positive change indicates a worsening.  
Subjects with low disease activity based on the mCPDAI score are those subjects who have a 
mCPDAI score less than or equal to 3.2.
5.5.1.1.10.
DAPSA Related Endpoints
The Disease Activity Index for Psoriatic Arthritis (DAPSA) score is a derived score combining
swollen joint count (66 joints), tender joint count (68 joints), CRP (mg/dL), Patient’s Assessment 
of Pain (on a 10-unit VAS), and Patient’s Global Assessment of Disease Activity (arthritis, on a 
10-unit VAS). 18
The DAPSA is a continuous parameter and is defined as follows:
DAPSA = STC66 + TJC68 + CRP (mg/dL) + PAIN + GDPT, where

SJC66 and TJC68 are defined similarly as in DAS28 (CRP) (Section 5.4.8.1).

CRPmg/dL: CRP in mg/dL. LLOQ rule specified in Appendix 1 will be applied to values 
< LLOQ.

PAIN: Patient’s Assessment of Pain on a 10-unit VAS.  

GDPT: Patient’s Global Assessment of Disease Activity (arthritis) on a 10-unit VAS.  
If any of the components required for computing the DAPSA score is missing, the DAPSA score 
will be set to missing.
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Change from baseline in DAPSA measures the change in disease activity, where a negative 
change indicates an improvement and a positive change indicates a worsening.  
Subjects in remission, or with low disease activity based on the DAPSA score are those 
subjects who have a DAPSA score less than or equal to 4, or greater than 4 and less than or equal 
to 14, respectively.
5.5.1.1.11.
Minimal Disease Activity (MDA) and Very Low Disease Activity 
(VLDA)
The PsA minimal disease activity (MDA) criteria are a composite of 7 outcome measures used in 
PsA.  A subject is considered as having achieved the PsA MDA at a visit if the subject has 
fulfilled at least 5 of the following 7 criteria at that visit:5

Tender joint count (68 joints) 1

Swollen joint count (66 joints) 1

Psoriasis activity and severity index ≤1 

Patient’s Assessment of Pain 15 on a 100-unit VAS

Patient’s Global Assessment of Disease Activity (arthritis and psoriasis) 20 on a 100-unit 
VAS

HAQ-DI score 0.5

Tender entheseal points ≤1 (LEI index score ≤1)
A subject is considered as having achieved VLDA at a visit if the subject has fulfilled all 7 
criteria described above at that visit.
5.5.1.1.12.
BASDAI Related Endpoints
The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was developed as a subject 
self-assessment for ankylosing spondylitis and consists of 6 questions relating to the 5 major 
symptoms of ankylosing spondylitis.14 Only subjects with spondylitis with peripheral arthritis as 
their primary arthritic presentation of PsA will complete the BASDAI using a 10-unit VAS to 
indicate the degree of their symptoms over the past week on the following criteria: 
A. Fatigue on a 10-unit VAS
B. Spinal pain on a 10-unit VAS
C. Joint pain on a 10-unit VAS
D. Enthesitis on a 10-unit VAS
E. Qualitative morning stiffness on a 10-unit VAS
F. Quantitative morning stiffness on a 10-unit VAS
The BASDAI score = 0.2 * (A + B + C + D + 0.5*[E + F]).  If any of the components required 
for computing the BASDAI score is missing, the BASDAI score will be set to missing.
Higher BASDAI scores indicate greater disease severity and a score decrease of 50% or 2 points 
is considered clinically meaningful.32
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Change from baseline in BASDAI score measures the change in disease activity, where a 
negative change indicates an improvement and a positive change indicates a worsening.  
Note that change from baseline in BASDAI score, and ≥20%, ≥50%, ≥70 %, and ≥90% 
improvement from baseline in BASDAI score are only applicable to subjects with spondylitis 
and peripheral joint involvement as their primary arthritic presentation of PsA and BASDAI >0 
at baseline.
Analysis Methods
5.5.1.2.
Endpoints through Week 24 will be analyzed at Week 24 DBL based on FAS1 (Section 2.3.1.1)
with the following exceptions:
HAQ-DI response, among the FAS1 subjects with HAQ-DI score ≥ 0.35 at baseline.
BASDAI: among FAS1 subjects with spondylitis and peripheral joint involvement as their 
primary arthritic presentation of PsA and BASDAI >0 at baseline.
Endpoints from Week 24 through Week 52 will be analyzed at Week 52 DBL based on FAS2 
(Section 2.3.1.2); and endpoints from Week 52 through Week 100 will be analyzed at Final 
(Week 112) DBL based on FAS3 (Section 2.3.1.3).
All endpoints will be descriptively summarized by treatment groups.  Treatment comparisons 
will be performed by visit through Week 24. Nominal p values and 95% CIs for the difference 
between each guselkumab group and placebo group will be provided. No treatment comparison 
will be performed after Week 24. 
For binary response endpoints, treatment comparisons will be performed using a CMH test as 
described in Section 5.3.2.1. For continuous endpoints, treatment comparisons will be 
performed using an ANCOVA model on the MI data for HAQ-DI, DAS 28 (CRP), dactylitis, 
and enthesitis endpoints as described in Section 5.4.1.2, and an MMRM/cLDA model as 
described in Section 5.2.4.1. 
All the analyses will be based on the Composite Estimand (Section 5.2.4.1).  
Table 8 outlines the other efficacy endpoints related to reduction of signs and symptoms and 
physical function, the methods for analyses, and the data handling rules used.
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Table 8: Summary of Estimands, Analysis Sets, Data Handling Rules, and Analysis Methods for Endpoints of 
Signs & Symptoms and Physical Function
Endpoint
Estimand
Analysis Set
Missing 
Data Rules
Analysis Methods
ENDPOINTS BY VISIT THROUGH WEEK 24 AT WEEK-24 DBL
1
Proportions of subjects 
who achieved an ACR 20, 
ACR 50, and ACR 70 
responses 
Composite
(Section 
5.2.4.1)
FAS1
NRI 
(Section 
5.2.3.1)

Summarized 
descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% 
CI calculated based on 
the Wald statistics
2
ACR components
NA
FAS1
-

Summarized 
descriptively
3
Percent change from 
baseline in ACR 
components
NA
FAS1
-

Summarized 
descriptively 
4
Change from baseline in 
HAQ-DI score
Composite
(Section 
5.2.4.1)
FAS1
MI Section 
(5.2.3.3)

Descriptive summary 
statistics

ANCOVA for each MI 
dataset and then analysis 
results across all MI 
datasets combined 

LS mean (95% CI) for 
each treatment group 
and for differences 
between groups.
o
P-values for 
treatment 
comparisons
5
Proportion of HAQ-DI 
responders 
(≥0.35 Improvement from 
baseline in HAQ-DI 
score)
Composite
(Section 
5.2.4.1)
FAS1 whose 
baseline HAQ-
DI score ≥ 0.35
NRI 
(Section 
5.2.3.1)

Summarized 
descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% 
CI calculated based on 
the Wald statistics
6
Proportions of subjects 
with DAS28 (CRP) 
responses 
Composite
(Section 
5.2.4.1)
FAS1
NRI 
(Section 
5.2.3.1)

Summarized 
descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% 
CI calculated based on 
the Wald statistics
7
Proportions of subjects 
with DAS28 remission 
Composite
(Section 
5.2.4.1)
FAS1
NRI 
(Section 
5.2.3.1)

Summarized 
descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% 
CI calculated based on 
the Wald statistics
8
Change from baseline in 
DAS28 (CRP)
Composite
(Section 
5.2.4.1)
FAS1
MI (Section 
5.2.3.3)

Descriptive summary 
statistics

ANCOVA for each MI 
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Table 8: Summary of Estimands, Analysis Sets, Data Handling Rules, and Analysis Methods for Endpoints of 
Signs & Symptoms and Physical Function
Endpoint
Estimand
Analysis Set
Missing 
Data Rules
Analysis Methods
ENDPOINTS BY VISIT THROUGH WEEK 24 AT WEEK-24 DBL
dataset and then analysis 
results across all MI 
datasets combined 

LS mean (95% CI) for 
each treatment group 
and for differences 
between groups.
o
P-values for 
treatment 
comparisons
9
Proportions of subjects 
with PsARC response 
Composite
(Section 
5.2.4.1)
FAS1
NRI 
(Section 
5.2.3.1)

Summarized 
descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% 
CI calculated based on 
the Wald statistics
10
Proportions of subjects 
with resolution of 
enthesitis
Composite
(Section 
5.2.4.1)
FAS1 with 
enthesitis at 
baseline
NRI 
(Section 
5.2.3.1)

Summarized 
descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% 
CI calculated based on 
the Wald statistics 
11
Change from baseline in 
enthesitis score
Composite
(Section 
5.2.4.1)
FAS1 with 
enthesitis at 
baseline
MI (Section 
5.2.3.3)

Descriptive summary 
statistics

ANCOVA for each MI 
dataset and then analysis 
results across all MI 
datasets combined 

LS mean (95% CI) for 
each treatment group 
and for differences 
between groups.
o
P-values for 
treatment 
comparisons
12
Proportions of subjects 
with resolution of 
dactylitis 
Composite
(Section 
5.2.4.1)
FAS1 with 
dactylitis at 
baseline
NRI 
(Section 
5.2.3.1)

Summarized 
descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% 
CI calculated based on 
the Wald statistics
13
Change from baseline in 
dactylitis score
Composite
(Section 
5.2.4.1)
FAS1 with 
dactylitis at 
baseline
MI (Section 
5.2.3.3)

Descriptive summary 
statistics

ANCOVA for each MI 
dataset and then analysis 
results across all MI 
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Table 8: Summary of Estimands, Analysis Sets, Data Handling Rules, and Analysis Methods for Endpoints of 
Signs & Symptoms and Physical Function
Endpoint
Estimand
Analysis Set
Missing 
Data Rules
Analysis Methods
ENDPOINTS BY VISIT THROUGH WEEK 24 AT WEEK-24 DBL
datasets combined 

LS mean (95% CI) for 
each treatment group 
and for differences 
between groups.
o
P-values for 
treatment 
comparisons
14
Change from baseline in 
PASDAS
Composite
(Section 
5.2.4.1)
FAS1
-

Summarized 
descriptively

MMRM model for
o
LS mean (SD) 
o
Treatment 
difference in LS 
mean (95% CI) 
o
P-value of 
comparing LS mean
15
Change from baseline in 
GRACE index score
Composite
(Section 
5.2.4.1)
FAS1
-

Summarized 
descriptively

MMRM model for
o
LS mean (SD) 
o
Treatment 
difference in LS 
mean (95% CI) 
o
P-value of 
comparing LS mean
16
Change from baseline in 
DAPSA score
Composite
(Section 
5.2.4.1)
FAS1
-

Summarized 
descriptively

MMRM model for
o
LS mean (SD) 
o
Treatment 
difference in LS 
mean (95% CI) 
o
P-value of 
comparing LS mean
17
Proportions of subjects 
with minimal disease 
activity
Composite
(Section 
5.2.4.1)
FAS1
NRI 
(Section 
5.2.3.1)

Summarized 
descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% 
CI calculated based on 
the Wald statistics
18
Proportions of subjects 
with ≥20%, ≥50%, ≥70%, 
and ≥90% improvement 
from baseline in BASDAI 
score
Composite
(Section 
5.2.4.1)
FAS1 with 
spondylitis and 
peripheral joint 
involvement as 
their primary 
arthritic 
presentation of 
PsA and 
NRI 
(Section 
5.2.3.1)

Summarized 
descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% 
CI calculated based on 
the Wald statistics
NCT03158285
Title:
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Statistical Analysis Plan CNTO1959PSA3002 Amendment 3
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Table 8: Summary of Estimands, Analysis Sets, Data Handling Rules, and Analysis Methods for Endpoints of 
Signs & Symptoms and Physical Function
Endpoint
Estimand
Analysis Set
Missing 
Data Rules
Analysis Methods
ENDPOINTS BY VISIT THROUGH WEEK 24 AT WEEK-24 DBL
BASDAI>0 at 
baseline
19
Change from baseline in 
BASDAI score
Composite
(Section 
5.2.4.1)
FAS1 with 
spondylitis and 
peripheral joint 
involvement as 
their primary 
arthritic 
presentation of 
PsA
-

Summarized 
descriptively

MMRM model for
o
LS mean (SD) 
o
Treatment 
difference in LS 
mean (95% CI) 
o
P-value of 
comparing LS mean
20
Change from baseline in 
mCPDAI 
Composite
(Section 
5.2.4.1)
FAS1 
-

Summarized 
descriptively

MMRM model for
o
LS mean (SD) 
o
Treatment 
difference in LS 
mean (95% CI) 

P-value of comparing LS 
mean
21
Proportion of subjects 
with low or very low 
disease activity based on 
PASDAS
Composite
(Section 
5.2.4.1)
FAS1
NRI 
(Section 
5.2.3.1)

Summarized 
descriptively

CMH test for p-value
22
Proportion of subjects 
with low disease activity 
based on GRACE score
Composite
(Section 
5.2.4.1)
FAS1
NRI 
(Section 
5.2.3.1)

Summarized 
descriptively

CMH test for p-value
23
Proportion of subjects 
with low disease activity 
or remission based on 
DAPSA
Composite
(Section 
5.2.4.1)
FAS1
NRI 
(Section 
5.2.3.1)

Summarized 
descriptively

CMH test for p-value
24
Proportion of subjects 
with low disease activity 
based on mCPDAI
Composite
(Section 
5.2.4.1)
FAS1
NRI 
(Section 
5.2.3.1)

Summarized 
descriptively

CMH test for p-value
25
Proportions of subjects 
with very low disease 
activity
Composite
(Section 
5.2.4.1)
FAS1
NRI 
(Section 
5.2.3.1)

Summarized 
descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% 
CI calculated based on 
the Wald statistics
‘NA’ = Not Applicable; ‘–‘ indicates Missing Data Rules not to be applied.
ENDPOINTS BY VISIT FROM WEEK 24 THROUGH WEEK 52 AT WEEK-52 DBL

Subjects in FAS2 will be the analysis population.
NCT03158285
Title:
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Statistical Analysis Plan CNTO1959PSA3002 Amendment 3
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Approved, Date: 21 March 2019
Table 8: Summary of Estimands, Analysis Sets, Data Handling Rules, and Analysis Methods for Endpoints of 
Signs & Symptoms and Physical Function
Endpoint
Estimand
Analysis Set
Missing 
Data Rules
Analysis Methods
ENDPOINTS BY VISIT THROUGH WEEK 24 AT WEEK-24 DBL

All the endpoints will be descriptively summarized by visit. 

No treatment comparison will be performed. 

No data handling rules will be applied and all analyses will be based on observed data. 
ENDPOINTS BY VISIT FROM WEEK 52 THROUGH WEEK 100 AT WEEK-112 DBL

Subjects in FAS3 will be the analysis population.

All the endpoints will be descriptively summarized by visit. 

No treatment comparison will be performed. 

No data handling rules will be applied and all analyses will be based on observed data. 
5.5.2.
Efficacy Endpoints Related to Skin Disease 
Other efficacy endpoints related to skin disease include:

Proportions of subjects who achieve a PASI 75, 90 and 100 responses by visit through 
Week 100 among the subjects with ≥3% BSA psoriatic involvement and an IGA score of ≥2 
(mild) at baseline.Proportion of subjects with an IGA score of 0 (cleared) by visit through 
Week 100 among the subjects with ≥3% BSA psoriatic involvement and an IGA score of ≥2 
(mild) at baseline.

Change from baseline in PASI score by visit through Week 100 among the subjects with 
≥3% BSA psoriatic involvement and an IGA score of ≥2 (mild) at baseline.

Proportion of subjects who achieve a DLQI score of 0 or 1 by visit through Week 100 
among the subjects with baseline DLQI score > 1 and with ≥ 3% BSA psoriatic involvement 
and an IGA score of ≥2 (mild) at baseline.

Proportion of subjects who achieve ≥ 5-point improvement from baseline in DLQI score by 
visit through Week 100 among the subjects with baseline DLQI score ≥ 5 and with ≥ 3% 
BSA psoriatic involvement and an IGA score of ≥2 (mild) at baseline.

Change from baseline in DLQI score by visit through Week 100 among the subjects with ≥ 
3% BSA psoriatic involvement and an IGA score of ≥2 (mild) at baseline.

Proportion of subjects who achieve both PASI 75 and ACR 20 responses by visit through 
Week 100 among the subjects with ≥3% BSA psoriatic involvement and an IGA score of ≥
2 (mild) at baseline.

Proportion of subjects who achieve both PASI 75 and modified PsARC response by visit 
through Week 100 among the subjects with ≥3% BSA psoriatic involvement and an IGA 
score of ≥2 (mild) at baseline.
This section outlines the definitions and analyses for the above skin disease endpoints.
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Definitions
5.5.2.1.
5.5.2.1.1.
PASI Related Endpoints
The Psoriasis Area and Severity Index (PASI) is a system used for assessing and grading the 
severity of psoriatic lesions and their response to therapy.10 In the PASI system, the body is 
divided into 4 regions: neck and head, trunk (including axillae and groin), upper extremities, and 
lower extremities (including buttocks), which account for 10%, 30%, 20%, and 40% of the total 
BSA, respectively. Each of these 4 regions is assessed separately for erythema, induration and 
scaling on a scale of 0 - 4. The PASI score is a continuous endpoint calculated as follows:
PASI = 0.1 (Eh + Ih + Sh) Ah + 0.3 (Et + It + St) At + 0.2 (Eu + Iu + Su) Au + 0.4 (El + Il + Sl) 
Al, where

E, I, S are, respectively, the state of erythema (E), induration (I) and scaling (S) assessed on 
a scale of 0 = none, 1 = slight, 2 = moderate, 3 = severe, and 4 = very severe.

h, t, u, l are the 4 body regions in the PASI system: neck and head (h), trunk (t), upper 
extremities (u), and lower extremities (l), respectively. 

A is the area of involvement for psoriatic lesions. The scale for estimating the area of 
involvement is outlined below:
0 = no involvement
1 = 1% to 9% involvement
2 = 10% to 29% involvement
3 = 30% to 49% involvement
4 = 50% to 69% involvement
5 = 70% to 89% involvement
6 = 90% to 100% involvement

Coefficients 0.1, 0.3, 0.2, and 0.4 corresponds to that head (h), trunk (t), upper extremities
(u) and lower extremities (l) account for 10%, 30%, 20%, and 40% of the total BSA, 
respectively.
If any of the components required for computing the PASI score is missing, the PASI score will 
be set to missing.  The PASI score ranges from 0 to 72, with a higher score indicating a more 
severe disease. 
Change from baseline in PASI scores measures the change in disease activity, where a 
negative change from baseline in PASI score indicates an improvement and a positive change 
indicates a worsening.  
PASI 75 response is defined as ≥ 75% improvement from baseline in PASI scores.
PASI 90 response and PASI 100 response are defined similarly, with improvement threshold 
replaced by 90% and 100% respectively.
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5.5.2.1.2.
Endpoints Related to DLQI
The Dermatology Life Quality Index (DLQI) questionnaire is a dermatology-specific quality of 
life instrument designed to assess the impact of the disease on a subject’s HRQOL.9
It is a 
10-item questionnaire that, in addition to evaluating overall quality of life, can be used to assess 
6 different aspects that may affect quality of life:  symptoms and feelings, daily activities, 
leisure, work or school performance, personal relationships, and treatment. By summing the 
scores from each component item, a total DLQI score with a range of 0 to 30 and a sub-score for 
each of 6 related aspects are then derived, with a higher score indicates more severe disease. A 
score of ≤1 indicates no effect at all of disease on subject’s HRQOL, and a reduction of 5 points 
or more in total DLQI score is considered clinically meaningful improvement.20
The endpoints related to DLQI include:

Proportion of subjects with DLQI score of 0 or 1 among subjects with baseline DLQI 
score of >1, ≥3% BSA psoriatic involvement at baseline and an IGA score of ≥ 2 (mild) 
at baseline.

Proportion of subjects who achieve ≥ 5 improvement from baseline in DLQI among 
subjects with baseline DLQI score of ≥5, ≥3% BSA psoriatic involvement at baseline 
and an IGA score of ≥ 2 (mild) at baseline.

Change from baseline in DLQI score among subjects with ≥3% BSA psoriatic 
involvement at baseline and an IGA score of ≥ 2 (mild) at baseline.
Change from baseline in DLQI score measures the change in disease activity, where a 
negative change indicates an improvement and a positive change indicates a worsening.  
Analysis Methods
5.5.2.2.
All endpoints will be analyzed among subjects who had ≥3% BSA psoriatic involvement and an 
IGA score of ≥2 (mild) at baseline.
All endpoints will be descriptively summarized by treatment groups. Treatment comparisons 
will be performed by visit through Week 24. Nominal p values and 95% CIs for the difference 
between each guselkumab group and placebo group will be provided. No treatment comparison 
will be performed after Week 24. 
For binary response endpoints, treatment comparisons will be performed using a CMH test as 
described in Section 5.3.2.1. For continuous endpoints, treatment comparisons will be 
performed using an MMRM/cLDA model as described in Section 5.2.4.1. 
All the analyses will be based on the Composite Estimand (Section 5.2.4.1).  
Table 9 outlines the other efficacy endpoints related to skin disease, the methods for analyses, 
and the data handling rules used.
NCT03158285
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CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959PSA3002 Amendment 3
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Approved, Date: 21 March 2019
Table 9:
Summary of Estimands, Analysis Sets, Data Handling Rules, and Analysis Methods for 
Endpoints of Skin Disease 
Endpoint
Estimand
Analysis Set
Missing 
Data 
Rules
Analysis Methods
ENDPOINTS BY VISIT THROUGH WEEK 24 AT WEEK-24 DBL
1
Proportions of subjects 
who achieve a PASI 
75, 90, 100 responses 
Composite
(Section 
5.2.4.1)
FAS1 who had ≥3% 
BSA psoriatic 
involvement and an IGA 
score of ≥2 (mild) at 
baseline
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% CI 
calculated based on the 
Wald statistics
2
Proportions of subjects 
who achieve who 
achieve both PASI 75 
and ACR 20 responses
Composite
(Section 
5.2.4.1)
FAS1 who had ≥3% 
BSA psoriatic 
involvement and an IGA 
score of ≥2 (mild) at 
baseline
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% CI 
calculated based on the 
Wald statistics
3
Proportions of subjects 
who achieve who 
achieve both PASI 75 
and modified PsARC 
responses
Composite
(Section 
5.2.4.1)
FAS1 who had ≥3% 
BSA psoriatic 
involvement and an IGA 
score of ≥2 (mild) at 
baseline
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% CI 
calculated based on the 
Wald statistics
4
Proportions of subjects 
with an IGA score of 0 
(cleared)
Composite
(Section 
5.2.4.1)
FAS1 who had ≥3% 
BSA psoriatic 
involvement and an IGA 
score of ≥2 (mild) at 
baseline
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% CI 
calculated based on the 
Wald statistics
NCT03158285
Title:
Version:
EDMS-ERI-196141432
2.0


CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959PSA3002 Amendment 3
80
Approved, Date: 21 March 2019
Table 9:
Summary of Estimands, Analysis Sets, Data Handling Rules, and Analysis Methods for 
Endpoints of Skin Disease 
Endpoint
Estimand
Analysis Set
Missing 
Data 
Rules
Analysis Methods
ENDPOINTS BY VISIT THROUGH WEEK 24 AT WEEK-24 DBL
5
Change from baseline 
in PASI scores
Composite
(Section 
5.2.4.1)
FAS1 who had ≥3% 
BSA psoriatic 
involvement and an IGA 
score of ≥2 (mild) at 
baseline
-

Summarized descriptively

MMRM model
o
LS mean (SD) 
o
Treatment difference in 
LS mean (95%CI)
o
P-value of comparing 
LS mean 
6
Proportion of subjects 
with DLQI score of 0 
or 1 
Composite
(Section 
5.2.4.1)
FAS1 who had DLQI 
score of >1, ≥3% BSA 
psoriatic involvement 
and an IGA score of ≥2 
(mild) at baseline
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% CI 
calculated based on the 
Wald statistics
7
Proportion of subjects 
who achieve ≥ 5 
improvement from 
baseline in DLQI 
Composite
(Section 
5.2.4.1)
FAS1 who had DLQI 
score of ≥5, ≥3% BSA 
psoriatic involvement 
and an IGA score of ≥2 
(mild) at baseline
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% CI 
calculated based on the 
Wald statistics
8
Change from baseline 
in DLQI score 
Composite
(Section 
5.2.4.1)
FAS1 who had ≥3% 
BSA psoriatic 
involvement and an IGA 
score of ≥2 (mild) at 
baseline
-

Summarized descriptively

MMRM model
o
LS mean (SD) 
o
Treatment difference in 
LS mean (95%CI)

P-value of comparing LS 
mean 
‘–‘ indicates Missing Data Rules not to be applied.
ENDPOINTS BY VISIT FROM WEEK 24 THROUGH WEEK 52 AT WEEK-52 DBL

Subjects in FAS2 will be the analysis population.

All the endpoints will be descriptively summarized by visit. 

No treatment comparison will be performed. 

No data handling rules will be applied and all analyses will be based on observed data. 
ENDPOINTS BY VISIT FROM WEEK 52 THROUGH WEEK 100 AT FINAL DBL

Subjects in FAS3 will be the analysis population.

All the endpoints will be descriptively summarized by visit. 

No treatment comparison will be performed. 

No data handling rules will be applied and all analyses will be based on observed data. 
5.5.3.
Other Radiographic Endpoints
Other efficacy endpoints related to joint structural damage include:

Change from baseline in modified vdH-S score by visit through Week 100. 

Change in modified vdH-S score from Week 24 to Week 52, from Week 24 to Week 100, 
and from Week 52 to Week 100.
NCT03158285
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CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959PSA3002 Amendment 3
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
Change from baseline in modified vdH-S erosion score by visit through Week 100.

Change in modified vdH-S erosion score from Week 24 to Week 52, from Week 24 to 
Week 100, and from Week 52 to Week 100.

Change from baseline in modified vdH-S joint space narrowing (JSN) score by visit through 
Week 100.

Change in modified vdH-S JSN score from Week 24 to Week 52, from Week 24 to 
Week 100, and from Week 52 to Week 100.

Change from baseline in modified vdH-S score by region and type of damage (ie, hand 
erosion, hand JSN, foot erosion, foot JSN subscores) by visit through Week 100.

Proportion of subjects with a change of ≤0 from baseline and proportion of subjects with a 
change of ≤ 0.5 from baseline in modified vdH-S score by visit through Week 100.

Proportion of subjects with a change of ≤0 from baseline and proportion of subjects with a 
change of ≤ 0.5 from baseline in modified vdH-S erosion score at by visit through 
Week 100.  

Proportion of subjects with a change of ≤0 from baseline and proportion of subjects with a 
change of ≤ 0.5 from baseline in modified vdH-S JSN score by visit through Week 100.  

Proportion of subjects without radiographic progression (based on the smallest detectable 
change [SDC]) from baseline by visit through Week 100.

Proportion of subjects without radiographic joint erosion progression (based on SDC) from 
baseline by visit through Week 100.

Proportion of subjects without radiographic JSN progression (based on the SDC) from 
baseline by visit through Week 100.

Proportion of subjects with pencil in cup or gross osteolysis deformities by visit through 
Week 100.
This section outlines the definitions and analyses for the above radiographic endpoints.
Definition
5.5.3.1.
Refer to Section 5.4.4.1 for definitions of erosion, JSN, hand, foot, and modified vdH-S 
scores.
For definition of change from baseline in modified vdH-S score, refer to Section 5.4.4.1.
Change from baseline in erosion score measures the change in progression of structural 
erosion, where a negative change indicates an improvement and a positive change indicates a 
worsening.
Change from baseline in JSN score measures the change in progression of structural joint 
space narrowing, where a negative change indicates an improvement and a positive change 
indicates a worsening.
NCT03158285
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CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959PSA3002 Amendment 3
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Approved, Date: 21 March 2019
The smallest detectable change (SDC) is the smallest change in score that is considered to be 
assessed correctly based on the limits of agreement (i.e., above the measurement error).1 The 
SDC for change from baseline in vdH-S score is determined as follows: 
SDC= 1.96 * SD / (√2 * √	), where

SD is the standard deviation of the difference between 2 readers in change from 
baseline in vdH-S score

k is the number of readers (e.g., = 2 for this study)
Note that the SDC for change from baseline in erosion score and the SDC for change from 
baseline in JSN score are defined similarly.
Radiographic progression is defined as the change of modified vdH-S score > the SDC in 
modified vdH-S score. 
Radiographic erosion progression is defined as the change of erosion score > the SDC in 
erosion score. 
Radiographic JSN progression is defined as the change in JSN score > the SDC in JSN score.  
Analysis Methods
5.5.3.2.
Radiographic images will be read in 3 read campaigns.  Endpoints through Week 24 (i.e., 
placebo controlled period) based on data generated from Read Campaign 1 will be analyzed at 
Week 24 DBL based on the FAS1-SD defined in Section 2.3.1;  endpoints through Week 52
based on data generated from Read Campaign 2 will be analyzed at Week 52 DBL based on the 
FAS2-SD defined in Section 2.3.1; and endpoints from Week 52 through Week 100 based on 
data generated from Read Campaign 3 will be analyzed at Final (Week 112) DBL based on the 
FAS3-SD defined in Section 2.3.1.  In all these analyses, data will be analyzed according to the 
randomized treatment groups.  
All the radiographic endpoints will be summarized by treatment group.  Treatment comparison 
will be performed at Week 24.  No treatment comparison will be performed after Week 24.
Continuous endpoints, with missing data imputed by MI (Section 5.2.3.3), will be compared 
between a guselkumab group versus the placebo group similarly to the major secondary endpoint 
of change from baseline in modified vdH-S score at Week 24 as described in Section 5.4.4.2.
Response endpoints will be derived from the corresponding continuous endpoints for each 
imputation.  The treatment difference between each guselkumab group versus the placebo group 
will be tested using a CMH test stratified by baseline use of non-biologic DMARD (yes, no) and 
most recent CRP value prior to randomization (<2.0 mg/dL, ≥2.0 mg/dL). The magnitude of the 
treatment difference will be estimated by the difference in proportion of subjects without 
progression between the guselkumab and placebo groups with a 95% CI calculated based on 
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Statistical Analysis Plan CNTO1959PSA3002 Amendment 3
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Wald statistics. The analysis results from the N imputation datasets will be combined, according 
to Rubin25, and the p-value for testing the treatment difference will be obtained. When combining 
analysis results for CMH test, Wilson-Hilferty-transformation24 will be applied to the test 
statistics to achieve an approximate normal distribution.
For the Week 52 database lock, an exploratory analysis will be provided for subjects who 
remained on treatment to compare the change from Week 24 to Week 52 Gus arm with k (k=0, 
0.2, 0.4, 0.8, 1.0 and 1.2) times of change from baseline to Week 24 in placebo arm.
Table 10 outlines the efficacy endpoints related to joint structural damage, the methods for 
analyses, and the data handling rules used.
Table 10:
Summary of Estimands, Analysis Sets, Data Handling Rules, and Analysis Methods for 
Radiographic Endpoints
Endpoint
Estimand
Analysis Set
Missing 
Data 
Rules
Analysis Methods
ENDPOINTS BY VISIT THROUGH WEEK 24 AT WEEK-24 DBL 
1
Change from 
baseline in modified 
vdH-S scores a
De Facto 
(Treatment 
Policy, 
Section 
5.2.4.3)
FAS1-SD
MI

Summarized descriptively

For each imputed dataset, 
treatment comparison using 
ANCOVA model 

P-value by combining treatment 
differences from all MI imputed 
datasets
2
Change from 
baseline in modified 
vdH-S erosion 
scores a
De Facto 
(Treatment 
Policy, 
Section 
5.2.4.3)
FAS1-SD
MI

Summarized descriptively

For each imputed dataset, 
treatment comparison using 
ANCOVA model 

P-value by combining treatment 
differences from all MI imputed 
datasets
3
Change from 
baseline in modified 
vdH-S JSN scores a
De Facto 
(Treatment 
Policy, 
Section 
5.2.4.3)
FAS1-SD
MI

Summarized descriptively

For each imputed dataset, 
treatment comparison using 
ANCOVA model 

P-value by combining treatment 
differences from all MI imputed 
datasets
4
Change from 
baseline in modified 
vdH-S scores by 
region and damage 
type 
NA
FAS1-SD
-

Summarized descriptively
5
Proportion of 
subjects with a 
change of ≤ 0 from 
baseline in modified 
vdH-S scores 
Treatment 
Policy, 
section 
5.2.4.3
FAS1-SD 
MI

Pooled response rates

Pooled p-values from CMH 
tests

Pooled treatment difference in 
response rates and 95% CIs 
calculated based on the Wald 
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Table 10:
Summary of Estimands, Analysis Sets, Data Handling Rules, and Analysis Methods for 
Radiographic Endpoints
Endpoint
Estimand
Analysis Set
Missing 
Data 
Rules
Analysis Methods
ENDPOINTS BY VISIT THROUGH WEEK 24 AT WEEK-24 DBL 
statistics
6
Proportion of 
subjects with a 
change of ≤0 from 
baseline in modified 
vdH-S erosion 
scores 
Treatment 
Policy, 
section 
5.2.4.3
FAS1-SD 
MI

Pooled response rates

Pooled p-values from CMH 
tests

Pooled treatment difference in 
response rates and 95% CIs 
calculated based on the Wald 
statistics
7
Proportion of 
subjects with a 
change of ≤0 from 
baseline in modified 
vdH-S JSN scores 
Treatment 
Policy, 
section 
5.2.4.3
FAS1-SD 
MI

Pooled response rates

Pooled p-values from CMH 
tests

Pooled treatment difference in 
response rates and 95% CIs 
calculated based on the Wald 
statistics
8
Proportion of 
subjects with a 
change of ≤ 0.5 from 
baseline in modified 
vdH-S scores 
Treatment 
Policy, 
section 
5.2.4.3
FAS1-SD 
MI

Pooled response rates

Pooled p-values from CMH 
tests

Pooled treatment difference in 
response rates and 95% CIs 
calculated based on the Wald 
statistics
9
Proportion of 
subjects with a 
change of ≤0.5 
from baseline in 
modified modified 
vdH-S erosion 
scores 
Treatment 
Policy, 
section 
5.2.4.3
FAS1-SD 
MI

Pooled response rates

Pooled p-values from CMH 
tests

Pooled treatment difference in 
response rates and 95% CIs 
calculated based on the Wald 
statistics
10
Proportion of 
subjects with a 
change of ≤0.5 
from baseline in 
modified vdH-S JSN 
scores 
Treatment 
Policy, 
section 
5.2.4.3
FAS1-SD 
MI

Pooled response rates

Pooled p-values from CMH 
tests

Pooled treatment difference in 
response rates and 95% CIs 
calculated based on the Wald 
statistics
11
Proportion of 
subjects without
radiographic 
progression (based 
on SDC) from 
baseline at Week 24
Treatment 
Policy, 
section 
5.2.4.3
FAS1-SD 
MI

Pooled response rates

Pooled p-values from CMH 
tests

Pooled treatment difference in 
response rates and 95% CIs 
calculated based on the Wald 
statistics
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Table 10:
Summary of Estimands, Analysis Sets, Data Handling Rules, and Analysis Methods for 
Radiographic Endpoints
Endpoint
Estimand
Analysis Set
Missing 
Data 
Rules
Analysis Methods
ENDPOINTS BY VISIT THROUGH WEEK 24 AT WEEK-24 DBL 
12
Proportion of 
subjects without 
radiographic erosion 
progression (based 
on SDC) from 
baseline at Week 24
Treatment 
Policy, 
section 
5.2.4.3
FAS1-SD 
MI

Pooled response rates

Pooled p-values from CMH 
tests

Pooled treatment difference in 
response rates and 95% CIs 
calculated based on the Wald 
statistics
13
Proportion of 
subjects without 
radiographic JSN 
progression (based 
on SDC) from 
baseline at Week 24
Treatment 
Policy, 
section 
5.2.4.3
FAS1-SD 
MI

Pooled response rates

Pooled p-values from CMH 
tests

Pooled treatment difference in 
response rates and 95% CIs 
calculated based on the Wald 
statistics
14
Proportion of 
subjects with pencil 
in cup or gross 
osteolysis 
deformities at 
Baseline and Week 
24
NA
FAS1-SD
-

Summarized descriptively
‘NA’ = Not Applicable; ‘–‘ indicates no missing data rules to be applied.
ENDPOINTS BY VISIT FROM WEEK 24 THROUGH WEEK 52 AT WEEK-52 DBL

Subjects in FAS2-SD will be the analysis population.

All the endpoints will be descriptively summarized by visit. 

No treatment comparison will be performed. 

No data handling rules will be applied and all analyses will be based on observed data. 

For sensitivity analysis, missing vdH-S score at Week 52 will be imputed by MI.
a In addition to the change from baseline, change from Week 24 will also be calculated.
ENDPOINTS BY VISIT FROM WEEK 52 THROUGH WEEK 100 AT FINAL (WEEK-112) DBL

Subjects in FAS3-SD will be the analysis population.

All the endpoints will be descriptively summarized by visit. 

No treatment comparison will be performed. 

No data handling rules will be applied and all analyses will be based on observed data. 

For sensitivity analysis, missing vdH-S score at Week 100 will be imputed by MI.
a In addition to the change from baseline, change from Week 24, and change from Week 52 will also be calculated
5.5.3.2.1.1.
Radiographic Reader’s Agreement
The agreement between the 2 primary reader scores will be assessed at treatment group level, 
subject level, and individual joint level. 
In order to assess intra-reader variability, images of 10% of subjects will be randomly selected 
and re-read by each of the 2 primary readers (Read Campaigns 1, 2, and 3). The scores from the 
re-read will be used for intra-class correlation analysis.
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The readers’ agreement at treatment group level will be evaluated by descriptive summarization 
of each primary reader’s score by treatment group overtime.
The readers’ agreement at subject level will be evaluated using the methods of Bland and 
Altman, as applied by and referred to as the “limits of agreement” method by plots of the 
differences between the 2 primary readers’ vdH-S scores versus the mean of the 2 primary 
readers’ vdH-S scores.22
In addition, intra-reader and inter-reader variability will be assessed.  The scores from the re-read 
will be used for intra-class correlation analysis.  The intra-class correlation for intra-reader and 
inter-reader variability will be calculated on modified vdH-S score at baseline, Week 24, 
Week 52, and Week 100, and modified vdH-S score change from baseline at Weeks 24, 52, and 
100.
Data handling rules:

No data handling rules will be applied for assessment based on data from all Read 
Campaigns. 
5.5.4.
Other Efficacy Endpoints Related to Health-Related Quality of Life 
and Health Economics
In this study, health related quality of life (HRQOL) measures include questionnaires of SF-36 
health survey, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), 
EuroQol five-dimension (EQ-5D), and Work Productivity and Activity Impairment (WPAI). 
Other efficacy endpoints related to HRQOL include:

Change from baseline in SF-36 PCS score by visit through Week 100.

Change from baseline in SF-36 MCS score by visit through Week 100.

Change from baseline in domain scores of SF-36 scales by visit through Week 100.

Proportion of subjects who achieve ≥ 5-point improvement from baseline in SF-36 MCS
score by visit through Week 100.

Proportion of subjects who achieve ≥ 5-point improvement from baseline in SF-36 PCS 
score by visit through Week 100.

Change from baseline in FACIT-Fatigue score by visit through Week 100.

Proportion of subjects who achieve ≥ 4-point improvement from baseline in FACIT-Fatigue 
scores by visit through Week 100.

Change from baseline in FACIT-fatigue score at Week 24 by ACR 20 response at Week 24.

Proportion of subjects who achieve ≥4-point improvement from baseline in FACIT-fatigue 
score at Week 24 by ACR 20 response at Week 24.

Change from baseline in EQ-5D VAS scores by visit through Week 100.

Change from baseline in EQ-5D index scores by visit through Week 100.
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
Change from baseline in WPAI scores by visit through Week 100.
This section outlines the definitions and analyses for the above HRQOL endpoints.
Definition
5.5.4.1.
5.5.4.1.1.
SF-36 Questionnaire
The SF-36 questionnaire is defined in Section 5.4.7.1.
Change from baseline in SF scores measures the change in health-related quality of life, where 
a positive change indicates an improvement and a negative change indicates a worsening.
5.5.4.1.2.
FACIT-Fatigue Questionnaire
The FACIT-Fatigue is a questionnaire that assesses self-reported tiredness, weakness, and 
difficulty conducting usual activities due to fatigue.1,4 The questionnaire consists of 13 questions 
that assess a subject’s level of fatigue and tiredness over the last 7 days.  Each question is graded 
on a 5-point scale (0 - 4); and accordingly, the total FACIT-Fatigue scores can range from 0 to 
52, with lower score reflecting more fatigue and higher scores reflecting less fatigue.  Note that, 
when at least 7 questions are answered, the score can be calculated and should be adjusted by the 
number of available questions.
Although not developed for PsA, the FACIT-Fatigue has been used to assess fatigue in clinical 
trials of subjects with RA and has demonstrated sensitivity to change in these subjects.27,31  In 
rheumatology, a change of 4 points is considered clinical meaningful and has been used as 
response definition in the RA population.1
Change from baseline in FACIT-Fatigue scores measures the change in fatigue where a 
positive change indicates an improvement and a negative change indicates a worsening.
5.5.4.1.3.
EQ-5D Questionnaire
The EQ-5D questionnaire is a standardized measure of health status developed by the EuroQoL 
Group to provide a simple, generic measure of health for clinical and economic appraisal. 6 The
EQ-5D is applicable to a wide range of health conditions and treatments.  EQ-5D essentially 
consists of 2 elements:  The EQ-5D descriptive system and the EQ visual analogue scale (EQ 
VAS). 
The EQ-5D descriptive system comprises the following 5 dimensions: 

Mobility 

Self-Care,

Usual Activities, 

Pain/Discomfort 

Anxiety/Depression 
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The EQ-5D 5 level version (EQ-5D-5L) was used in this study.  Each of these 5 dimensions has 
5 levels: no problems, slight problems, moderate problems, severe problems, and extreme
problems. The respondent is asked to indicate his/her health state by ticking (or placing a cross) 
in the box against the most appropriate statement in each of the 5 dimensions.  This decision 
results in a 1-digit number expressing the level selected for that dimension. The digits for 5 
dimensions can be combined in a 5-digit number describing the respondent’s health state which 
can be converted into a single summary index (EQ-5D index) by applying a formula that attaches 
values (also called weights) to each of the levels in each dimension. 
The EQ VAS records the respondent’s self-rated health on a vertical, visual analog scale where 
the endpoints are labeled “Best imaginable health state” and “Worst imaginable health state.” 
The EQ VAS is used as a quantitative measure of health outcome as judged by the individual 
respondent.  The US/UK model will be used for analyses.
Change from baseline in ED-5Q scores measures the change in health status where a positive 
change indicates an improvement and a negative change indicates a worsening.
5.5.4.1.4.
WPAI Questionnaire
The WPAI Questionnaire - Specific Health Problem (WPAI-SHP) is a validated instrument that 
has been used to study the impact of various diseases on patients’ ability to work and perform 
daily activities (http://www.reillyassociates.net/WPAI_General.html). The WPAI-PsA assesses 
the impact of PsA on work and other daily activities during the past 7 days. The WPAI-PsA 
consists of the following 6 questions:
Q1: currently employed (working for pay)? (yes, no) If No, skip to Q6.
Q2: hours missed from work in the past 7 days due to PsA? (hours)
Q3: hours missed from work in the past 7 days due to other reasons? (hours)
Q4: hours actually worked in the past 7 days? (hours)
Q5: degree to which PsA affected work productivity while at work in the past 7 days? [0 (no 
effect) to 10 (completely prevented from working)] 
Q6: degree to which PsA affected regular activities outside of work in the past 7 days? [0 
(no effect) to 10 (completely prevented from daily activities)] 
Based on the answers to the above 6 questions, 4 types of scores (in percentage) are calculated, 
with higher scores indicating greater impairment and less productivity, i.e., worse outcomes, as 
follows.  Note that for subjects with answer=’No’ to Q1, only the 4th score (ie., percent activity 
impairment outside work due to PsA) can be calculated.
1.
Percent work time missed due to PsA (absenteeism): 100*Q2/(Q2+Q4)
2.
Percent impairment while working due to PsA (presenteeism): 100*Q5/10
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3.
Percent overall work impairment due to PsA (combining absenteeism and 
presenteeism): 100*{Q2/(Q2+Q4)+[(1-Q2/(Q2+Q4)) * (Q5/10)]}
4.
Percent activity impairment outside work due to PsA: 100* Q6/10
Change from baseline in WPAI scores measures the change in work productivity and/or 
activity impairment, where a positive change indicates a worsening and a negative change 
indicates an improvement.
Analysis Methods
5.5.4.2.
All endpoints will be descriptively summarized by treatment groups using descriptive statistics, 
such as mean, median, standard deviation, interquartile range, minimum and maximum for 
continuous variables, and counts and percentages for categorical variables. Treatment 
comparisons will be performed by visit through Week 24. Nominal p-values and 95% CIs for the 
difference between each guselkumab group and placebo group will be provided. 
For continuous endpoints, treatment comparisons will be performed using an MMRM model
(Appendix 3: Description of statistical methods). 
For binary response endpoints, treatment comparisons will be performed using a CMH test as 
described in Section 5.3.2.1. For continuous endpoints, treatment comparisons will be 
performed using ANCOVA on the MI data for MCS and PCS analyses as described in Section 
5.4.1.2, and an MMRM/cLDA model as described in Section 5.1 for other continuous endpoints. 
All the analyses will be based on the Composite Estimand (Section 5.2.4.1).  
Table 11:
Summary of Estimands, Analysis Sets, Data Handling Rules, and Analysis Methods for HRQOL 
Endpoints
Endpoint
Estimand
Analysis Set
Missing 
Data 
Rules
Analysis Methods
ENDPOINTS BY VISIT THROUGH WEEK 24 AT WEEK-24 DBL
1
Change from 
baseline in SF-36 
PCS score 
Composite
(Section 
5.2.4.1)
FAS1  
MI 
(Section 
5.2.3.3)

Descriptive summary statistics

ANCOVA for each MI dataset and 
then analysis results across all MI 
datasets combined 

LS mean (95% CI) for each 
treatment group and for differences 
between groups.
o
P-values for treatment 
comparisons
2
Change from 
baseline in SF-36 
MCS score 
Composite
(Section 
5.2.4.1)
FAS1  
MI 
(Section 
5.2.3.3)

Descriptive summary statistics

ANCOVA for each MI dataset and 
then analysis results across all MI 
datasets combined 

LS mean (95% CI) for each 
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Table 11:
Summary of Estimands, Analysis Sets, Data Handling Rules, and Analysis Methods for HRQOL 
Endpoints
Endpoint
Estimand
Analysis Set
Missing 
Data 
Rules
Analysis Methods
ENDPOINTS BY VISIT THROUGH WEEK 24 AT WEEK-24 DBL
treatment group and for differences 
between groups.
o
P-values for treatment 
comparisons
3
Change from 
baseline in SF-36 
domain scores of 
SF-36 scale 
Composite
(Section 
5.2.4.1)
FAS1  
-

Summarized descriptively

MMRM model
o
LS mean (SD) for
o
Treatment difference in LS 
mean (95%CI)
o
P-value of comparing LS mean
4
Proportion of 
subjects who 
achieve ≥ 5-point 
improvement from 
baseline in SF-36 
PCS  
Composite
(Section 
5.2.4.1)
FAS1 
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in response 
rates and 95% CI calculated based 
on the Wald statistics
5
Proportion of 
subjects who 
achieve ≥ 5-point 
improvement from 
baseline in SF-36 
MCS  
Composite
(Section 
5.2.4.1)
FAS1 
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in response 
rates and 95% CI calculated based 
on the Wald statistics
6
Change from 
baseline in 
FACIT-Fatigue
Composite
(Section 
5.2.4.1)
FAS1  
-

Summarized descriptively

MMRM model
o
LS mean (SD) for
o
Treatment difference in LS 
mean (95%CI)
o
P-value of comparing LS mean
7
Proportions of 
subjects who 
achieve ≥ 4-point 
improvement from 
baseline in 
FACIT-Fatigue 
score
Composite
(Section 
5.2.4.1)
FAS1 
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in response 
rates and 95% CI calculated based 
on the Wald statistics
8
Change from 
baseline in EQ-5D 
VAS score
Composite
(Section 
5.2.4.1)
FAS1 
-

Summarized descriptively

MMRM model for
o
LS mean (SD) 
o
Treatment difference in LS 
mean (95% CI) 

P-value of comparing LS mean
9
Change from 
baseline in EQ-5D 
index score
Composite
(Section 
5.2.4.1)
FAS1 
-

Summarized descriptively

MMRM model for
o
LS mean (SD) 
o
Treatment difference in LS 
mean (95% CI) 
o
P-value of comparing LS mean
10
Change from 
Composite
FAS1 
-

Summarized descriptively
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Table 11:
Summary of Estimands, Analysis Sets, Data Handling Rules, and Analysis Methods for HRQOL 
Endpoints
Endpoint
Estimand
Analysis Set
Missing 
Data 
Rules
Analysis Methods
ENDPOINTS BY VISIT THROUGH WEEK 24 AT WEEK-24 DBL
baseline in WPAI 
score
(Section 
5.2.4.1)

MMRM model for
o
LS mean (SD) 
o
Treatment difference in LS 
mean (95% CI) 

P-value of comparing LS mean
ENDPOINTS AT WEEK 24 AT WEEK-24 DBL
11
Change from 
baseline in 
FACIT-Fatigue at 
Week 24 by ACR 
20 response at 
Week 24
Composite
(Section 
5.2.4.1)
FAS1  
-

Summarized descriptively

MMRM model
o
LS mean (SD) for
o
Treatment difference in LS 
mean (95%CI)

P-value of comparing LS mean
12
Proportions of 
subjects who 
achieve ≥4-point 
improvement from 
baseline in 
FACIT-Fatigue 
score at Week 24 
by ACR 20 
response at Week 
24
Composite
(Section 
5.2.4.1)
FAS1 
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in response 
rates and 95% CI calculated based 
on the Wald statistics
‘–‘ indicates Missing Data Rules not to be applied.
ENDPOINTS BY VISIT FROM WEEK 24 THROUGH WEEK 52 AT WEEK-52 DBL

Subjects in FAS2 will be the analysis population.

All the endpoints will be descriptively summarized by visit. 

No treatment comparison will be performed. 

No data handling rules will be applied and all analyses will be based on observed data. 

ENDPOINTS BY VISIT FROM WEEK 52 THROUGH WEEK 100 AT FINAL DBL

Subjects in FAS3 will be the analysis population.

All the endpoints will be descriptively summarized by visit. 

No treatment comparison will be performed. 

No data handling rules will be applied and all analyses will be based on observed data. 
Additional Analyses for FACIT-Fatigue
Subgroup analysis comparing change in fatigue score between treatment and control will 
be conducted in ACR20 non-responder subgroup and ACR20 responder subgroup 
separately. Propensity score-based methods will be used to account for potential 
imbalances in baseline covariates. Covariates to be used in the propensity score models 
will include baseline fatigue score and selected demographics and disease related variables 
such as age, gender, BMI, PsA duration, physician global assessment, patient global 
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assessment, HAQ-DI score, pain assessment, swollen joints 66 and tender joints 68. 
Logistic regression or Covariate Balancing Propensity Score (CBPS) models will be used 
to estimate the propensity score.
A mediation analysis will be performed to examine the mediating role of 24-week ACR20 
response on change from baseline in fatigue score at week 24 provided both endpoints 
demonstrate a statistically significant difference between treatment arms (Appendix 3).
5.5.5. Other Tipping Point Analyses
Additional tipping point analyses aside from those for primary and major secondary endpoints 
will be performed to evaluate the impact when the missing data deviate from the MAR 
assumption and are summarized in the below Table 11a.  The analysis methods used are the 
same as those described in Table 6a.
Table 11a: Summary of Tipping Point Analyses Other Than for Primary and Major 
Secondary Endpoints
Endpoints
(Analysis Set)
Missing data
Analysis method
Supplementary Analyses of Continuous Endpoints based on Treatment Policy Estimand, in which all observed 
data will be used, regardless of whether or not the subjects meet any TF criteria.
Change from baseline at Week 16 in:
HAQ-DI score (FAS1)
SF-36 PCS score (FAS1)
SF-36 MCS score (FAS1)
DAS28(CRP) (FAS1)
Enthesitis (LEI) among subjects with 
enthesitis (LEI) at baseline (FAS1)
based on data combined from studies 
CNTO1959PSA3001 and 
CNTO1959PSA3002
Dactylitis among subjects with dactylitis 
at baseline (FAS1) based on data 
combined from studies 
CNTO1959PSA3001 and 
CNTO1959PSA3002
MI with FCS 
regression (Section 
5.2.3.3.3, Table 12)

Two-dimensional tipping point analysis

Treatment comparison using ANCOVA model 

Analysis results to be presented graphically
Supplementary Analyses of Binary Endpoints based on Treatment Policy Estimand, in which all observed data 
will be used, regardless of whether or not the subjects meet any TF criteria.
ACR 70 Response at Week 16 (FAS1)
IGA Response at Week 16 (FAS1 with 
≥3% BSA psoriatic involvement and an 
IGA score of ≥2 at baseline)
Resolution of enthesitis (LEI) at Week 
16 among subjects with enthesitis (LEI) 
at baseline based on data combined from 
studies CNTO1959PSA3001 and 
CNTO1959PSA3002
Resolution of dactylitis at Week 16 
among subjects with dactylitis at 
baseline based on data combined from 
studies CNTO1959PSA3001 and 
MI with FCS 
regression (Section 
5.2.3.3.2, Table 12)

Two-dimensional tipping point analysis.

The CMHa test (stratified by randomization 
stratification factors) to compare treatment groups.

Analysis results to be presented graphically
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Table 11a: Summary of Tipping Point Analyses Other Than for Primary and Major 
Secondary Endpoints
Endpoints
(Analysis Set)
Missing data
Analysis method
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a When combining analysis results for the CMH test, the Wilson-Hilferty transformation will be applied to the test statistics to 
achieve an approximate normal distribution.
6.
SAFETY
Safety will be assessed by summarizing the occurrences and type of AEs, vital signs (pulse, 
blood pressure, and weight) and examining the changes in the laboratory parameters.  
In all the safety analysis, subjects who were randomized and received at least 1 (partial or 
complete) dose of study agent administration will be included and analyzed according to the 
treatment they actually received, regardless of the treatments they are randomized to. No formal 
statistical comparison is planned.
6.1.
Safety Tables Presentation
There are 3 DBLs in this study, respectively, at Week 24, Week 52, and End of Study
(Week 112). Depending on the safety data categories, the cumulative safety data will be 
analyzed through different study periods which include, but are not limited to, through Week 24, 
through Week 52, and through end of study period.  Tabular summaries of safety events for key 
study periods are in general presented as follows:
6.1.1.
Summaries Through Week 24
Safety data through Week 24 will be analyzed according to the following treatment groups:
1.
Placebo: Subjects who received placebo only and no guselkumab prior to Week 24.
2.
Guselkumab 100 mg at Weeks 0, 4, and then q8w: Subjects who received guselkumab 
100 mg q8w prior to Week 24 with an additional dose at Week 4. 
3.
Guselkumab 100 mg q4w: Subjects who received guselkumab 100 mg q4w prior to
Week 24. 
4.
Guselkumab Combined: Subjects in Groups 2 and 3.
The above treatment groups 1-3 are mutually exclusive.  This allows between-group 
comparisons of safety between a guselkumab group and the placebo group based on similar 
follow-up period in each group.  The safety tables will have the column headings below:
Guselkumab
Placebo 
100 mg q8w
100 mg q4w 
Combined 
Analysis set: Safety Analysis Set
###
###
###
###
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For subjects who started treatment with placebo only but later received any amount of 
guselkumab prior to Week 24 inadvertently, the safety events/measurements on and after the first 
dose of guselkumab, will be excluded from the data summaries through Week 24.  Only the 
safety events/measurements that occurred while the subjects had been receiving placebo only
will be included in the data summaries through Week 24.  
6.1.2.
Summaries Through Week 52
Safety data through Week 52 will be analyzed according to the following treatment groups:
1.
Placebo: Subjects who received placebo only. Follow-up will be based on the period that 
the subject was on placebo from the first dose up to Week 52.
a.
For subjects who started treatment with placebo and later received treatment with 
guselkumab (due to CO or inadvertently), follow-up will end at the first dose of 
guselkumab, and only the safety events/measurements that occurred prior to the first 
dose of guselkumab will be included in this group
2.
Placebo →Guselkumab 100 mg q4w: Subjects who started treatment with placebo and 
later received treatment with guselkumab (due to CO or inadvertently).  Follow-up will start 
from the first dose of guselkumab up to Week 52. All the safety events/measurements that 
occurred on and after the first dose of guselkumab up to Week 52 will be included in this 
group.
3.
Guselkumab 100 mg at Weeks 0, 4, and then q8w: Subjects who received guselkumab 
100 mg q8w prior to Week 24 with an additional dose at Week 4.  Follow-up will be from 
the first dose up to Week 52.
4.
Guselkumab 100 mg q4w: Subjects who received guselkumab 100 mg q4w prior to 
Week 24.  Follow-up will be from the first dose up to Week 52.
5.
Guselkumab 100 mg q4w Combined: Subjects in Groups 2 and 4.
6.
All Guselkumab Combined: Subjects in Groups 2, 3, and 4.
The above treatment groups 1-2 are not mutually exclusive.  The safety tables will have the
column headings below:
Guselkumab 
Placebo 
Placebo 
→ 
100 mg q4w 
100 mg q8w 
100 mg q4w 
100 mg q4w 
Combined
All 
Combined
Analysis set: Safety Analysis Set
###
###
###
###
###
###
6.1.3.
Summaries Through End of Study
Safety data through End of Study (Week 112) will be analyzed according to the following 
treatment groups:
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1.
Placebo →Guselkumab 100 mg q4w: Subjects who started treatment with placebo and 
later received treatment with guselkumab (due to CO or inadvertently).  Follow-up will start 
from the first dose of guselkumab up to end of study.
2.
Guselkumab 100 mg at Weeks 0, 4, and then q8w: Subjects who received guselkumab 
100 mg q8w prior to Week 24 with an additional dose at Week 4. Follow-up will be from 
the first dose up to end of study.
3.
Guselkumab 100 mg q4w: Subjects who received guselkumab 100 mg q4w prior to 
Week 24. Follow-up will be from the first dose through end of study.
4.
Guselkumab 100 mg q4w Combined: Subjects in Groups 1 and 3.
5.
All Guselkumab Combined: Subjects in Groups 1, 2, and 3.
The safety tables will have the column headings below:
Guselkumab 
Placebo 
→ 
100 mg q4w 
100 mg q8w 
100 mg q4w 
100 mg q4w 
Combined
All 
Combined
Analysis set: Safety Analysis Set
###
###
###
###
###
6.2.
Adverse Events
AEs that occurred any time over the study will be reported and coded using MedDRA.  Analyses 
of AEs will be performed on those events that are considered treatment emergent.  Treatment 
emergent AEs (TEAEs) are those AEs that occurred after the start of initial study agent 
administration and those AEs that were present at baseline but worsened in severity after the start 
of initial study agent administration.  
TEAEs will be summarized by MedDRA system organ class, preferred term, and actual 
treatment group.  The numbers of subjects reporting at least 1 event of the following AE 
categories will be summarized:

Any TEAEs

Treatment emergent serious AEs (SAEs)

TEAEs with severe intensity

TEAEs that led to permanent discontinuation of study agent administration

Treatment emergent infections

Treatment emergent serious infections

Treatment emergent infections requiring oral or parenteral anti-microbial treatment

Injection-site reactions

Anaphylactic reactions or delayed hypersensitivity reactions
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All AE summary tables will include average weeks of follow-up and average number of study 
agent administrations for each treatment group.
In addition to the summary tables, a by-subject listing will be provided for deaths that occurred 
during the study and, respectively, for the following TEAEs:
1.
SAEs
2.
AEs that led to permanent discontinuation of study agent administration
3.
Anaphylactic reactions or serum sickness reactions
4.
Malignancies
5.
Serious infections including TB
6.3.
Clinical Laboratory Tests
The clinical laboratory parameters to be evaluated by the central laboratory include but are not 
limited to:

Hematology: bands,
basophils,
eosinophils,
hemoglobin, hematocrit, lymphocytes, 
monocytes, neutrophils, platelets, red blood cell (RBC) count and white blood cell (WBC)
count

Clinical chemistry: albumin, alkaline phosphatase, alanine aminotransferase (serum 
glutamate pyruvate transaminase) [ALT (SGPT)], aspartate aminotransferase (serum 
glutamic oxaloacetic transaminase) [AST (SGOT)], bicarbonate, blood urea nitrogen 
(BUN), calcium, chloride, creatinine, glucose, potassium, sodium, total bilirubin, total 
protein, uric acid
The following analyses will be performed as appropriate by actual treatment group: 

Plots of the observed values and changes from baseline over time for selected clinical 
laboratory parameters 

Number of subjects with post-baseline values by maximum toxicity grade according to 
National Cancer Institute’s Common Terminology Criteria for Adverse Events (NCI-
CTCAE) for parameters with NCI-CTCAE criteria defined 

Listings of subjects with any post-baseline lab value of NCI-CTCAE toxicity Grade 3 or 
higher
6.4.
Vital Signs and Physical Examination Findings
Vital signs will be measured at visits as per the schedule of events in the protocol. Descriptive 
statistics of the observed value and change from baseline in each vital sign parameter will be 
summarized by treatment group; the numbers of subjects with any markedly abnormal post-
baseline measurements will also be summarized over time by treatment group.  The criteria for 
markedly abnormal vital signs are defined in the following table.
Abnormalities or changes in severity noted during physical examination will be reported as 
adverse events and are included in the analysis of adverse events.
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Parameter
Markedly Abnormal Low 
Markedly Abnormal High
Systolic blood 
pressure
Absolute value 90 mmHg 
and a decrease from baseline 
by 20 mmHg
Absolute value 180 mmHg 
and an increase from baseline 
by 20 mmHg
Diastolic 
blood pressure
Absolute value 50 mmHg 
and a decrease from baseline 
by 15 mmHg
Absolute value 105 mmHg 
and an increase from baseline 
by 15 mmHg
Pulse
Absolute value ≤ 50 bpm and 
a decrease from baseline ≥ 15 
bpm
Absolute value ≥ 120 bpm and 
an increase from baseline ≥ 15 
bpm
6.5.
Electrocardiogram
No analysis is planned.
6.6.
Other Safety Parameters
6.6.1.
Suicidal Ideation and Behavior
The electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) will be used as a screening 
tool to prospectively evaluate the potential of guselkumab to induce suicidal ideation and 
behavior. The eC-SSRS defines five subtypes of suicidal ideation and behavior in addition to 
self-injurious behavior with no suicidal intent, and is a fully-structured subject self-report 
questionnaire, including standardized questions, follow-up prompts, error handling routines, and 
scoring conventions.17,19 Two versions of the eC-SSRS will be used in this study, the Lifetime
version and the Since Last Contact version. The Lifetime version will be conducted during the 
screening visit and the Since Last Contact version will be conducted at all other visits through 
Week 112.
Subjects will complete the eC-SSRS questionnaire using the Sponsor-provided electronic tablets 
(or through an Interactive Voice Response System, if available). Study site personnel will train 
the subjects on how to use the electronic device and/or a telephone system. The eC-SSRS will be 
provided in the local languages in accordance with local guidelines.
The eC-SSRS will be performed during each evaluation visit according to the Time and Events 
schedule.  The eC-SSRS should be performed after the joint assessment at the screening visit 
(after signing informed consent). At Week 0/baseline and at all post-baseline visits, the eC-SSRS 
will be the first assessment/questionnaire that the subject completes prior to study agent 
administration. 
At the conclusion of each assessment, the site will receive an eC-SSRS Findings Report from the 
eC-SSRS vendor. Positive reports are generated from the eC-SSRS vendor for ANY of the 
following findings: 

Ideation Level 4: Some intent to act, no plan
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
Ideation Level 5: Specific plan and intent

Behaviors: Actual Suicide Attempts

Behaviors: Interrupted Attempts

Behaviors: Aborted Attempts

Behaviors: Preparatory actions
Negative suicidality indication reports are generated from the eC-SSRS vendor when there are 
NO indications of the above.
Any eC-SSRS findings, which in the opinion of the investigator are new or considered to be a 
worsening and clinically significant, should be reported on the AE eCRF.
Suicidal ideation and behavior will be categorized as follows, with higher scores indicating 
greater severity:
Suicidal Ideation (1-5)
1 = Wish to be Dead
2 = Non-specific Active Suicidal Thoughts
3 = Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act
4 = Active Suicidal Ideation with Some Intent to Act, without Specific Plan
5 = Active Suicidal Ideation with Specific Plan and Intent
Suicidal Behavior (6-10)
6 = Preparatory Acts or Behavior
7 = Aborted Attempt
8 = Interrupted Attempt
9 = Actual Attempt (non-fatal)
10 = Completed Suicide
The baseline is defined as the most severe/maximum score at screening and Week 0. Suicidal 
ideation and behavior will be analyzed by the most severe/maximum post baseline outcome. In 
addition, a shift table from baseline to post-baseline will also be provided.  Subjects with positive 
(i.e., score >0) ideation and behavior will be presented in a data listing.
7.
PHARMACOKINETICS/PHARMACODYNAMICS
7.1.
Pharmacokinetics
Pharmacokinetics (PK) samples for measuring serum guselkumab concentrations will be 
collected from all subjects at the specified visits as shown in the schedule of events of the 
protocol.  Serum samples will also be collected at the final visit from subjects who terminate 
study participation early. Samples must be collected before study agent administration at visits 
when a study agent administration is scheduled.  A random venous blood sample for population 
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PK analysis will be collected from all subjects on any day between Weeks 4 to 12, except on the 
days of the scheduled study visit at Weeks 4, 8, and 12. Additionally, this blood sample must be 
collected at least 24 hours prior to or after the actual time of study agent administration at Weeks 
4, 8, or 12 (ie, it cannot be collected within 24 hours before or after study agent administration).
All PK analyses will be based on the PK Analysis Set (Section 2.3.3). Subjects will be analyzed 
according to the treatment groups that they actually received. No imputation for missing 
concentration data will be performed. 
For analysis on serum guselkumab concentrations, descriptive statistics, including arithmetic 
mean, SD, median, interquartile range, minimum and maximum will be calculated, where 
appropriate, by treatment group at each serum sampling time.  PK data may be displayed 
graphically.  The following analyses will be performed by treatment group as appropriate:

Summary of serum guselkumab concentrations at each visit by treatment group

Proportion of subjects without detectable serum guselkumab concentration at each visit by 
treatment group

Summary of serum guselkumab concentrations at each visit by treatment group and body 
weight

Summary of serum guselkumab concentrations at each visit by treatment group and baseline 
MTX use (Yes, No)

Summary of serum guselkumab concentrations by baseline CRP levels

Plot of median serum guselkumab concentrations over time by treatment group
In addition, the relationship between serum guselkumab concentrations and safety or efficacy 
may be explored.
For summary statistics of serum guselkumab concentrations, concentration values below the 
lower limit of quantification will be treated as zero. Once a subject meets one of the following 
dosing deviation criteria, the subject’s data will be excluded from the by-visit data analyses from 
that point onwards.
Dosing deviation criteria:

Discontinue SC guselkumab administrations.

Skipped an SC guselkumab administration.

Received an incomplete/ incorrect SC dose.

Received an incorrect SC study agent.

Received an additional SC guselkumab dose.
In addition, if a subject has an administration outside of visit windows (Section 2.1.1), the 
concentration data collected at and after that visit will be excluded from the by-visit data 
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analyses. Additional exclusions for incongruous PK data to be implemented based on Janssen 
SOP-07948.
Population PK analyses will be performed to characterize the disposition characteristics of 
guselkumab based on the guselkumab concentration data from PsA studies. Data may be 
combined with other selected studies to support a relevant structural model. The population 
pharmacokinetic approach will also be used to identify significant covariates such as 
demographic characteristics (including but not limited to body weight, ethnic origin, sex, and 
age) and concomitant medications in subjects with PsA. A detailed analysis plan for population 
PK analysis will be developed separately, and a stand-alone technical report will be written to 
summarize the results of the population PK analysis.
PK analyses presentation
PK analyses will be summarized through the following time periods:

Through Week 24

Through Week 52

Through End of Study (Week 112)
For the analyses, a subject is included in one and only one treatment group on the basis of the 
treatment regimen followed. The description of treatment groups are as follows:
1.
Placebo → Guselkumab 100 mg q4w: Subjects randomized to placebo and were switched 
over to Guselkumab 100 mg q4w (due to CO) at Week 24.  
2.
Guselkumab 100 mg at Week 0, Week 4, and then q8w: Subjects randomized to 
guselkumab 100 mg at Week 0, Week 4, and then q8w and received guselkumab 100 mg 
q8w throughout with an additional dose at Week 4.
3.
Guselkumab 100 mg q4w: Subjects randomized to guselkumab 100 mg q4w and received 
guselkumab 100 mg q4w throughout.
7.2.
Immunogenicity (Antibodies to Guselkumab)
Blood samples will be collected to examine the formation of antibodies to guselkumab at the 
specified visits as shown in the schedule of events of the protocol. Serum samples will also be 
collected at the final visit from subjects who terminate study participation early. 
The antibodies to guselkumab will be summarized based on Immunogenicity Analysis Set
(Section 2.3.4). Subjects will be analyzed according to the treatment groups that they actually 
received. No imputation for missing concentration data will be performed.
The following analysis of antibodies to guselkumab will be performed by treatment group:

Summary of antibodies to guselkumab status 

Summary of neutralizing antibodies to guselkumab status 
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
List of subjects positive for antibodies to guselkumab 
In addition, to explore the relationship between antibodies to guselkumab status and serum 
guselkumab concentrations, efficacy and safety, the following analysis may be performed as 
appropriate:  

Summary of clinical response (e.g., ACR 20 and ACR50, PASI) by antibody to guselkumab 
status 

Summary of injection-site reactions by antibody to guselkumab status

Summary of serum guselkumab concentrations by antibody to guselkumab status

Plots of median trough serum guselkumab concentrations over time by antibody to 
guselkumab status 
Immunogenicity analyses presentation
Immunogenicity analyses will be summarized through the following time periods:

Through Week 24

Through Week 52

Through End of Study (Week 112)
For the immunogenicity analyses, the description of treatment groups is as follows:
1.
Placebo → Guselkumab 100 mg q4w: Subjects randomized to placebo and were switched 
over to Guselkumab 100 mg (due to CO) at Week 24.  
2.
Guselkumab 100 mg at Week 0, Week 4, and then q8w: Subjects randomized to 
guselkumab 100 mg at Week 0, Week 4, and then q8w and received guselkumab 100 mg 
q8w throughout with an additional dose at Week 4.
3.
Guselkumab 100 mg q4w: Subjects randomized to guselkumab 100 mg q4w and received 
guselkumab 100 mg q4w throughout.
4.
Guselkumab Combined: all subjects who received guselkumab in groups 1, 2 and 3.
7.3.
Pharmacodynamics
Samples for serum biomarkers will be collected for all subjects as indicated in the Time and 
Events Schedule of the protocol. The analyses on PD biomarkers are to better understand the 
biology of PsA, to provide a biological assessment of the subjects’ response to treatment with 
guselkumab, to analyze differences between responders and non-responders, and to determine if 
the markers can be used to classify subjects as potential responders prior to treatment.
All PD analyses will be based on the PD Analysis Set (Section 2.3.5). Subjects will be analyzed 
according to the treatment groups that they actually received. No imputation for missing 
concentration data will be performed. 
The PD analyses results will be provided in an 
independent technical report.
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7.4.
Pharmacokinetic/Pharmacodynamic Relationships
If data permit, the relationships between serum guselkumab concentration and efficacy may be 
analyzed graphically. If any visual trend is observed, a suitable population PK/PD model may be 
developed to describe the exposure-response relationship. Details will be given in a population 
PK/PD analysis plan and results of the population PK/PD analysis will be presented in a separate 
technical report.
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REFERENCES
1.
Bruynesteyn K, Boers M, Kostense P, et al.  Deciding on progression of joint damage in paired films of 
individual patients: smallest detectable difference or change. Ann Rheum Dis 2005 64: 179-182.
2.
Cella D, Lai J, Chang C, et al.  Fatigue in cancer patients compared with fatigue in the general United States 
population.  Cancer. 2002; 94(2):528-538.
3.
Cella D, Yount S, Sorensen M, et al. Validation of the Functional Assessment of Chronic Illness Therapy 
Fatigue Scale relative to other instrumentation in patients with rheumatoid arthritis. J Rheum.2005; 32(5):811-
819.
4.
Chandran V, Bhella S, Schentag C, Gladman D. Functional Assessment of Chronic Illness Therapy-Fatigue 
Scale is valid in patients with psoriatic arthritis. Ann Rheum Dis. 2007;66:936-939.
5.
Coates LC, Helliwell PS. Validation of minimal disease activity criteria for psoriatic arthritis using 
interventional ta. Arthritis Care Res (Hoboken). 2010; 62(7):965-969.
6.
EuroQol Group. EuroQol - a new facility for the measurement of health-related quality of life. Health Policy. 
1990; 16(3):199-208.
7.
Felson DT, Anderson JJ, Boers M, et al.  American College of Rheumatology Preliminary Core Set of Disease 
Activity Measures for Rheumatoid Arthritis Clinical Trials.  Arthritis Rheum. 1993; 36(6):729-740.
8.
Felson DT, Anderson JJ, Boers M, et al.  American College of Rheumatology Preliminary Definition of 
Improvement in Rheumatoid Arthritis.  Arthritis Rheum. 1995; 38(6):727-735.
9.
Finlay AY, Khan GK.  Dermatology Life Quality Index (DLQI)--a simple practical measure for routine clinical 
use.  Clin Exp Dermatol.  1994;19(3):210-216.
10.
Fredriksson T, Pettersson U. Severe psoriasis-oral therapy with a new retinoid. Dermatologica. 
1978;157(4):238-244.
11.
Fries JF, Spitz P, Kraines RG, Holman HR.  Measurement of patient outcomes in arthritis.  Arthritis Rheum. 
1980; 23(2):137-145.
12.
Gladman DD, Inman RD, Cook RJ, et al. International spondyloarthritis interobserver reliability exercise--the 
INSPIRE study: II. Assessment of peripheral joints, enthesitis, and dactylitis. J Rheumatol. 2007;34(8):1740-
1745.
13.
Gladman DD, Ziouzina O, Thavaneswaran A, Chandran V. Dactylitis in psoriatic arthritis: prevalence and 
response to therapy in the biologic era. J Rheumatol. 2013;40(8):1357-1359.
14.
Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A. A new approach to defining disease 
status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol. 
1994;21(12):2286-2291
15.
Healy PJ, Helliwell PS. Measuring clinical enthesitis in psoriatic arthritis: assessment of existing measures and 
development of an instrument specific to psoriatic arthritis. Arthritis Rheum. 2008;59(5):686-691
16.
Helliwell PS, FitzGerald O, Fransen J, et al. The development of candidate composite disease activity and 
responder indices for psoriatic arthritis (GRACE project). Ann Rheum Dis. 2013;72(6):986-991.
17.
Helliwell PS, FitzGerald O, Fransen J. Composite disease activity and responder indices for psoriatic arthritis: 
A report from the GRAPPA 2013 Meeting on development of cutoffs for both disease activity states and 
response. J Rheum. 2014;41(6):1212-1217.
18.
Helliwell PS, Kavanaugh A. Comparison of composite measures of disease activity in psoriatic arthritis using 
data from an interventional study with golimumab. Arthritis Care Res. 2014;66(5):749-756.
19.
Hollander M, Wolfe DA. Nonparametric Statistical Methods, 2nd Edition. New York: Wiley. 1999.
20.
Khilji FA, Gonzalez M, Finlay AY. Clinical meaning of change in dermatology life quality index scores. Br J 
Dermatol. 2002;147(suppl 62): 25-54.
21.
Kosinski M, Zhao SZ, Dedhiya S, et al. Determining minimally important changes in generic and disease-
specific health-related quality of life questionnaires in clinical trials of rheumatoid arthritis. Arthritis Rheum. 
2000;43(7):1478–1487.
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22.
Lassere M, Boers M, van der Heijde D, et al. smallest detectable difference in radiographical progression. J 
Rheumatol. 1999; 26(3): 731-739
23.
Pham T, Guillemin F, Claudepierre P, et al. TNFα antagonist therapy in ankylosing spondylitis and psoriatic 
arthritis:  recommendations of the French Society for Rheumatology. Joint Bone Spine. 2006;73:547–553.
24.
Ratitch B, O’Kelly M.  Combining Analysis Results from Multiply Imputed Categorical Data. PharmaSUG 
2013 - Paper SP03.
25.
Rubin, DB. Multiple Imputations for Nonresponse in Surveys. New York: John Wiley & Sons. 1987.
26.
Saris-Baglama RN, Dewey CJ, Chisholm GB, et al. QualityMetric Health OutcomesTM Scoring Software 4.5 
User’s Guide. QualityMetric Health Outcomes Solutions. 2011.
27.
Smolen JS, Beaulieu A, Rubbert-Roth A, et al, for the OPTION Investigators. Effect of interleukin-6 receptor 
inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-
controlled, randomised trial.  Lancet.  2008; 371(9617):987-997.
28.
van der Heijde DM, van Leeuwen MA, van Riel PL, et al. Biannual radiographic assessments of hands and feet 
in a three-year prospective followup of patients with early rheumatoid arthritis. Arthritis Rheum. 
1992;35(1):26-34.  
29.
van Riel PL, van Gestel AM, Scott DL.  EULAR Handbook of Clinical Assessments in Rheumatoid Arthritis.  
Alphen Aan Den Rijn, The Netherlands:  Van Zuiden Communications B.V.; 2004
30.
Ware JE, Kosinski M, Bjorner JB, et al.  User’s manual for the SF-36v2 Health Survey (second edition). 
Lincoln, RI: QualityMetric Incorporated. 2007.
31.
Yount S, Sorensen MV, Cella D, et all. Adalimumab plus methotrexate or standard therapy is more effective 
than methotrexate or standard therapies alone in the treatment of fatigue in patients with active, inadequately 
treated rheumatoid arthritis. Clin Exp Rheum. 2007; 25(6):838-46
32.
Zochling J, van der Heijde D, Burgos-Vargas R, et al. ASAS/EULAR recommendations for the management of 
ankylosing spondylitis. Ann Rheum Dis. 2006;65(4):442-452.  
33.
Yeonhee Kim, Seunghyun Won. Adjusted proportion difference and confidence interval in stratified 
randomized trials. PharmaSUG 2013 – Paper SP04.
34.
Bohdana Ratitch, et al. Combining analysis results from multiply imputed cartegorical data. PharmaSUG 2013-
Paper SP03.
35.
L. Valeri and T. J. VanderWeele (2013), Meidation Analysis Allowing for Exposure-Mediator Interactions and 
Causal Interpretation: Theoretical Assumptions and Implementation with SAS and SPSS Macros, 
Psychological Methods, Vol. 18, No.2: 137-150.
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APPENDICES
APPENDIX 1:   RULES APPLIED IN DEFINITIONS OF ENDPOINTS 
1. Joint Evaluability Rules for Sign and Symptom Data
For subjects having a joint injection(s)/surgical joint procedure(s) prior to the date of study entry 
(e.g., randomization) or during the study, the affected joint(s) will be valued according to the 
following rules:

For subjects having a joint injection and/or surgical joint procedure prior to the date of 
randomization, the affected joints will be analyzed according to the impact of the joint 
injection and/or surgical joint procedure on the evaluability of the involved joints.
o
If a joint is considered un-evaluable at baseline due to certain procedure/injection 
performed prior to the date of randomization, the joint will be considered un-evaluable 
throughout the study.

For subjects undergoing joint procedures for the treatment of PsA during the study, the 
affected joints will be considered as swollen and tender from the date of procedure onwards. 

For subjects undergoing joint procedures during the study for the treatment of non-PsA 
disease indication, the affected joints will be analyzed according to the impact of the 
surgical joint procedure on the evaluability of the involved joints. 

For subjects undergoing joint injections for PsA during the study, the affected joints will be 
considered as swollen and tender from the date of injection for the next 90 days.

For subjects undergoing joint injections for non-PsA related reasons during the study, the 
affected joints will be considered as non-evaluable from the date of injection for the next 90 
days.
2. Joint Count Adjustment Rule 
For subjects who have an incomplete set of evaluable joints the joint count/score will be adjusted 
to the total number joints of interest (e.g., 68 joints for tenderness and 66 joints for swelling) by 
dividing the number of affected joints by the number of evaluable joints and multiplying by the 
total number joints of interest.
3. LLOQ rule 
Any value < LLOQ is considered equal to half of the value of LLOQ for numerical calculations. 
4. Joint Evaluability Rules for Radiographic Data
A joint may be not evaluable due to surgery/joint replacement or radiographically insufficient 
data for reading.  Joints with surgery/joint replacement or with radiographically insufficient data 
for reading will be considered as not evaluable for joint erosion/JSN.  
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For a joint that is considered as not evaluable at a given time point, both the joint-level erosion 
score and the joint-level JSN score will be set to missing at the said time point.
5. Erosion and JSN Score Adjustment Rules 
The regional erosion and JSN scores for hands and feet will be determined based on the 
evaluable joints.  For subjects who have an incomplete set of evaluable joints at a given time 
point, each reader’s regional erosion and JSN scores at the said time point will be adjusted using 
the following rules:
Rules for Adjustment of Erosion Scores by Region
Region
Adjustment for the incomplete set of evaluable joints
Hands/Wrists 
(40 joints)

If total number of joints evaluable at the given time point is ≥ 20 (ie, 50% of 40), then the 
erosion score for hands/wrists will be obtained by calculating the average erosion score for 
hands and wrists and multiplying with 40.

If the total number of joints evaluable at the given time point is < 20, then the erosion score
for hands and wrists will be set to missing.
Feet (12 joints)

If total number of joints evaluable at the given time point is ≥ 6 (i.e., 50% of 12), then the 
erosion score for feet will be obtained by calculating the average erosion score for feet and 
multiplying with 12.

If the total number of joints evaluable at the given time point is < 6, then the erosion score 
for feet will be set to missing.
Rules for Adjustment of JSN Scores by Region
Region
Adjustment for the incomplete set of evaluable joints
Hands/Wrists 
(40 joints)

If total number of joints evaluable at the given time point is ≥ 20 (i.e., 50% of 40), then the 
JSN score for hands/wrists will be obtained by calculating the average JSN score for hands 
and wrists and multiplying with 40.

If the total number of joints evaluable at the given time point is < 40, then the JSN score for 
hands and wrists will be set to missing.
Feet (12 joints)

If total number of joints evaluable at the given time point is ≥ 6 (i.e., 50% of 12), then the 
JSN score for feet will be obtained by calculating the average JSN score for feet and 
multiplying with 12.

If the total number of joints evaluable at the given time point is < 6, then the JSN score for 
feet will be set to missing.
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A reader’s vdH-S score is the sum of the reader’s erosion and JNS scores of both hands and feet.
If a reader’s regional score is missing for any region of erosion or JSN, the reader’s vdH-S score 
will be set to missing.
6. Reader Adjudication Rules 
For each subject, let Δ1 and Δ2 stand for the change from baseline in vdH-S score, respectively, 
of primary readers 1 and 2 at any post-baseline visit (i.e., Week 24 in Read Campaign 1, 
Week 24 or Week 52 in Read Campaign 2, and Week 24, Week 52 or Week 100 in Read 
Campaign 3).  If the absolute difference between Δ1 and Δ2 is greater than 10 (i.e., |Δ2 - Δ1| > 
10), or either Δ1 or Δ2 is missing (but not both Δ1 and Δ2 are missing), an adjudicator (a third 
reader) will then read all the radiographic images (including baseline and post-baseline images) 
in that given read campaign from that subject.
7. Reader Selection Rules 
For subjects who require adjudication (i.e., there are readings from 3 readers), the scores from 2 
selected readers will be used in the analysis.  
Let Δ1, Δ2, and Δ3 stand for the change from baseline in vdH-S score at Week 24, respectively, 
of primary reader 1 (Reader 1), primary reader 2 (Reader 2), and the adjudicator (Reader 3).  The 
2 readers whose scores will be used in the analysis will be selected from the 3 readers based on 
the criteria specified in the table below.  
Rules for Selection of Readers Following Adjudication
Scenarios based on change from
baseline in vdH-S score at Week 24
Readers whose scores will be used for the
analysis at each visit 
|Δ3 - Δ1| < |Δ3 - Δ2| 
Reader 1 and adjudicator (Reader 3)
|Δ3 - Δ2| < |Δ3 - Δ1| 
Reader 2 and adjudicator (Reader 3)
|Δ3 - Δ1| = |Δ3 - Δ2| 
Reader 1 and Reader 2
Δ1 is missing but Δ2 and Δ3
are non-missing
Reader 2 and adjudicator (Reader 3)
Δ2 is missing but Δ1 and Δ3
are non-missing
Reader 1 and adjudicator (Reader 3)
Δ3 is missing but Δ1 and Δ2
are non-missing 
Reader 1 and Reader 2
Both Δ1 and Δ3 are missing,
but Δ2 is non-missing
Reader 1 and adjudicator (Reader 3) 
Both Δ2 and Δ3 are missing,
but Δ1 is non-missing
Reader 2 and adjudicator (Reader 3) 
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8. Smallest Detectable Change
Smallest Detectable Change (SDC) is the smallest change in a score that is considered to be 
assessed correctly based on the limits of agreement (ie, above the measurement error) 
(Bruynesteyn et al 2005). 
The SDC in score of interest is determined as follows: 
       SDC= 1.96 * SD / (√2 * √	), where

SD is the standard deviation of the difference between the 2 selected readers in change 
from baseline in the score of interest 

k = 2, is the number of readers
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APPENDIX 2:  STATISTICAL HYPOTHESIS
Hypothesis
Global
US Specific
Primary Endpoints
H1.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by the proportion of subjects achieving an 
ACR 20 response at Week 24 (primary hypothesis)
Controlled as 
in figure 3
Controlled as 
in figure 2
H2.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by the proportion of 
subjects achieving an ACR 20 response at Week 24
Controlled as 
in figure 3
Controlled as 
in figure 2
Major Secondary Endpoints
H3.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by proportion of subjects who achieved a 
psoriasis IGA response at Week 24 among the subjects 
with ≥3% BSA psoriatic involvement and an IGA score of 
≥2 (mild) at baseline
Controlled as 
in figure 3
Controlled as 
in figure 2
H4.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by proportion of 
subjects who achieved a psoriasis IGA response at Week 
24 among the subjects with ≥3% BSA psoriatic 
involvement and an IGA score of ≥2 (mild) at baseline
Controlled as 
in figure 3
Controlled as 
in figure 2
H5.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by change from baseline in DAS28 (CRP) at 
Week 24
Controlled as 
in figure 3
Weakly-
controlled
H6.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by change from 
baseline in DAS28 (CRP) at Week 24
Controlled as 
in figure 3
Weakly-
controlled
H7.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by change from baseline in HAQ-DI score at 
Week 24
Controlled as 
in figure 3
Controlled as 
in figure 2
H8.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by change from 
baseline in HAQ-DI score at Week 24
Controlled as 
in figure 3
Controlled as 
in figure 2
H9.
Guselkumab 100 mg q4w SC is superior to 
treatment with placebo SC as measured by change from 
baseline in modified vdH-S score at Week 24
Controlled as 
in figure 3
Controlled as 
in figure 2
H10.
Guselkumab 100 mg at Week 0, Week 4, then q8w Controlled as 
Controlled as 
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SC is superior to treatment with placebo SC as measured 
by change from baseline in modified vdH-S score at Week 
24
in figure 3
in figure 2
H11.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by change from baseline in SF-36 PCS at Week 
24
Controlled as 
in figure 3
Controlled as
in figure 2
H12.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by change from 
baseline in SF-36 PCS at Week 24
Controlled as 
in figure 3
Controlled as 
in figure 2
H13.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by proportion of subjects who achieved an 
ACR 50 response at Week 24
Controlled as 
in figure 3
Weakly-
controlled
H14.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by proportion of 
subjects who achieved an ACR 50 response at Week 24;
Controlled as 
in figure 3
Weakly-
controlled
H15.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by proportion of subjects achieved an ACR 20 
response at Week 16
Controlled as 
in figure 3
Weakly-
controlled
H16.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by proportion of 
subjects achieved an ACR 20 response at Week 16
Controlled as 
in figure 3
Weakly-
controlled
H17.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by proportion of subjects who achieve an ACR 
70 response at Week 24
Controlled as 
in figure 3
Weakly-
controlled
H18.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by proportion of 
subjects who achieve an ACR 70 response at Week 24
Controlled as 
in figure 3
Weakly-
controlled
H19.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by proportion of subjects who achieve an ACR 
50 response at Week 16
Controlled as 
in figure 3
Weakly-
controlled
H20.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by proportion of 
subjects who achieve an ACR 50 response at Week 16
Controlled as 
in figure 3
Weakly-
controlled
H21.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by proportion of subjects with resolution of 
enthesitis at Week 24 among the subjects with enthesitis at 
baseline
Nominal
Nominal
H22.
Guselkumab 100 mg at Week 0, Week 4, then q8w Nominal
Nominal
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SC is superior to placebo as assessed by proportion of 
subjects with resolution of enthesitis at Week 24 among
the subjects with enthesitis at baseline
H23.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by proportion of subjects with resolution of 
dactylitis at Week 24 among the subjects with dactylitis at 
baseline
Nominal
Nominal
H24.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by proportion of 
subjects with resolution of dactylitis at Week 24 among the 
subjects with dactylitis at baseline
Nominal
Nominal
H25.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by change from baseline in SF-36 MCS at 
Week 24
Controlled as 
in figure 3
Controlled as 
in figure 2
H26.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by change from 
baseline in SF-36 MCS at Week 24
Controlled as 
in figure 3
Controlled as 
in figure 2
H27.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by change from baseline in enthesitis score 
(based on Leeds Enthesitis Index [LEI]) at Week 24 among 
the subjects with enthesitis at baseline
Nominal
Nominal
H28.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by change from 
baseline in enthesitis score (based on Leeds Enthesitis 
Index [LEI]) at Week 24 among the subjects with 
enthesitis at baseline
Nominal
Nominal
H29.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by change from baseline in dactylitis scores at 
Week 24 among the subjects with dactylitis at baseline
Nominal
Nominal
H30.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by change from 
baseline in dactylitis scores at Week 24 among the subjects 
with dactylitis at baseline
Nominal
Nominal
H31.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by proportion of subjects with resolution of 
enthesitis at Week 24 among the subjects with enthesitis at 
baseline with combined data from 3001 and 3002
Controlled as 
in figure 3
Controlled as 
in figure 2
H32.
Guselkumab 100 mg at Week 0, Week 4, then q8w Controlled as 
Controlled as 
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SC is superior to placebo as assessed by proportion of 
subjects with resolution of enthesitis at Week 24 among 
the subjects with enthesitis at baseline with combined data 
from 3001 and 3002
in figure 3
in figure 2
H33.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by proportion of subjects with resolution of 
dactylitis at Week 24 among the subjects with dactylitis at 
baseline with combined data from 3001 and 3002
Controlled as 
in figure 3
Controlled as 
in figure 2
H34.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by proportion of 
subjects with resolution of dactylitis at Week 24 among the 
subjects with dactylitis at baseline with combined data 
from 3001 and 3002
Controlled as 
in figure 3
Controlled as 
in figure 2
H35.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by change from baseline in enthesitis score 
(based on Leeds Enthesitis Index [LEI]) at Week 24 among 
the subjects with enthesitis at baseline with combined data 
from 3001 and 3002
Nominal
Weakly-
controlled
H36.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by change from 
baseline in enthesitis score (based on Leeds Enthesitis 
Index [LEI]) at Week 24 among the subjects with 
enthesitis at baseline with combined data from 3001 and 
3002
Nominal
Weakly-
controlled
H37.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by change from baseline in dactylitis scores at 
Week 24 among the subjects with dactylitis at baseline 
with combined data from 3001 and 3002
Nominal
Weakly-
controlled
H38.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by change from 
baseline in dactylitis scores at Week 24 among the subjects 
with dactylitis at baseline with combined data from 3001 
and 3002
Nominal
Weakly-
controlled
For hypothesis testing order and multiplicity adjustment, refer to Section 5.2.2.
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APPENDIX 3:   DESCRIPTION OF STATISTICAL MODELS
1.
MIXED-EFFECT MODEL REPEATED MEASURES (MMRM)
To account for the missing data for continuous endpoints, a Mixed-Effect Model Repeat 
Measures (MMRM) will be used on the change from baseline, under the assumption of MAR, to 
test the difference between a guselkumab group and the placebo group. The model will include 
treatment group, the interaction terms of visit with treatment group, randomization stratification 
factors (baseline use of non-biologic DMARDs (yes, no), and most recent CRP value prior to 
randomization (<2.0 mg/dL, ≥2.0 mg/dL), and baseline score as explanatory variables.  An 
unstructured covariance matrix for repeated measure within a subject will be used. The F-test 
will use Kenward-Roger’s approximating for degree of freedom. In case of lack of convergence, 
empirical structured covariances will be used in the following order until convergence is 
reached: 1) Toeplitz 2) first order Autoregressive Moving Average.  The model will include data 
from all 3 treatment groups through Week 24.  The treatment difference between a guselkumab 
group and the placebo group will be estimated by the difference in the least squares means 
(LSmeans). The 95% confidence interval (CI) for the differences in LSmeans and p-values will 
be calculated based on the MMRM. 
2.
CONSTRAINED LONGITUDINAL DATA ANALYSIS (CLDA) MODEL
To account for the missing data for continuous endpoints when 2% or more subjects have 
baseline score missing, a Constrained Longitudinal Data Analysis (cLDA) model may be 
performed on the measurement instead of the change, under the assumption of MAR, to test the 
difference between a guselkumab group and the placebo group. The model will include treatment 
group, the interaction terms of visit with treatment group, and randomization stratification factors 
(baseline use of non-biologic DMARDs (yes, no), and most recent CRP value prior to 
randomization (<2.0 mg/dL, ≥2.0 mg/dL). An unstructured covariance matrix for repeated 
measure within a subject will be used. The F-test will use Kenward-Roger’s approximating for 
degree of freedom. In case of lack of convergence, empirical structured covariances will be used 
in the following order until convergence is reached: 1) Toeplitz 2) first order Autoregressive 
Moving Average.  The model will include data from all 3 treatment groups through Week 24.  
The treatment difference between a guselkumab group and the placebo group will be estimated 
by the difference in the LS means. The 95% CIs for the differences in LS means and p-values 
will be calculated based on the cLDA model. 
3.
MIXED EFFECT LINEAR GROWTH CURVE MODEL 
Due to the slow progression in structural damage and over a short period of time, the assumption 
that progression follows a linear trend seems to be reasonable. To use all available post-treatment 
data that are collected out-side of the analytical window for Week 24, a mixed effect linear 
growth model will be fitted to the change from baseline in vdH-S score where, effect of 
treatment on the change from baseline in vdH-S score through Week 24 will be estimated by the
slope. The fixed effects in the model include the interaction of time with treatment group, and the 
interaction of time with randomization stratification factors. The model will include a random 
coefficient for time. Additionally, an intercept term will not be included in the model. Time will 
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be included as a continuous variable. All observed data post treatment in the placebo controlled 
period will be used.   
4.
MEDIATION ANALYSIS
Mediation analysis will be performed to examine the mediating role of 24-week ACR20 
response on change from baseline in fatigue score at week 24 provided both endpoints 
demonstrate a statistically significant difference between treatment arms. In the mediation 
analysis framework, natural direct effect can be conceived of as independent treatment effect on 
the outcome (i.e. change in fatigue score) that is above and beyond its effect on the mediator (i.e. 
ACR20 response); controlled direct effect can be conceived of as the independent treatment 
effect on the outcome controlling the mediator at a fixed level; and the natural indirect effect can 
be conceived of as a treatment effect on the outcome that is mediated by its effect on the 
mediator.
The parametric counterfactual approach implemented by Valeri and VanderWeele (2013)35 will 
be used to estimate the controlled direct effect (CDE), natural direct effect (NDE) and natural 
indirect effect (NIE).  Let    and  Mα denote the values of the outcome and mediator that 
would have been observed had the exposure A been set to level α and let Yαm denote the value 
of the outcome that would have been observed had the exposure A and mediator M been set to 
levels αand m respectively.  In the analysis of binary exposure, we will set α=1 for treated arm 
and α=0 for controlled arm. The average controlled direct effect (CDE) comparing treated (α =1) 
to control (α =0) given the mediator fixing to level m is defined by () = ( −). 
The average natural direct effect (NDE) is defined by  = ( −). The average 
natural indirect effect is defined by  = ( −). 
Covariates considered in this mediation analysis will include baseline fatigue score and 
demographics parameters and disease related parameters such as age, gender, BMI, PsA 
duration, physician Global Assessment (GDEV), patient global assessment (GDPT), HAQ-DI 
score, pain assessment (PAIN), Swollen Joints 66 (SJC66) and tender joints 68 (TJC68). We will 
also allow exposure-mediator interaction in this analysis. 
Bootstrap will be used to obtain final effect estimates and their corresponding confidence 
intervals and P values. Model and variable selection may be conducted as sensitivity analysis. 
Alternative implementations of mediation analysis may also be explored as part of sensitivity 
analysis.
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APPENDIX 4:   SUMMARY OF ANALYSES BASED ON MULTIPLE IMPUTATION
Table 12: Summary of Multiple Imputation Method
Endpoints
MI specification
Analysis method/Summary statistics
ACR20
Supplementary analysis 1
ACR20
Supplementary analysis 2
Multiple imputation with 
FCS regression of 
component scores
MIdataset1 (N=200, Seedd=4362478)
Imputation variables: 7 ACR components from Week 0 - 24
Ancillary variables: Treatment group, randomization stratification 
factors
Change from baseline 
through Week 24 in:
HAQ-DI Score
DAS28(CRP) Score
Multiple imputation with 
FCS regression of 
component scores
MIdataset2a (N=200, Seedd =4237590)
Imputation variables: 5 ACR components other than joint counts 
from Week 0 - Week 24, tender joint counts based on 28 joints, 
swollen joint counts based on the 28 joints.
Ancillary variables: Treatment group, randomization stratification 
factors
Change from baseline 
through Week 24 in 
Enthesitis score (LEI) 
among subjects with at 
least one tender enthesis at 
baseline
Multiple imputation with 
FCS regression of enthesitis
scores
MIdata3 (N=200, Seedd =6509723)
Note: The MI is done only for the subset of subjects who have 
enthesitis at baseline and not all subjects in the study population.
Imputation variables: enthesitis score from Weeks 0 – 24.
Ancillary variables b: Treatment group, randomization 
stratification factors, 7 ACR components from Weeks 0 – 24,  
enthesitis-4c
Dactylitis change from 
baseline through Week 24 
among subjects with 
dactylitis
Multiple imputation with 
FCS regression of dactylitis
scores
MIdata4 (N=200, Seedd =1284097)
Note: The MI is done only for the subset of subjects who have 
dactylitis at baseline and not all subjects in the study population.
Imputation variables: dactylitis score from Weeks 0 – 24.
Ancillary variables b: Treatment group, randomization 
stratification factors, 7 ACR components from Weeks 0 – 24
Change from baseline 
through Week 24 in:
PCS score
MCS score 
Multiple imputation with 
FCS regression of PCS, 
MCS scores
MIdata5 (N=200, Seedd =890473)
Imputation variables: PCS and MCS scores from Weeks 0 – 24
Ancillary variables b: Treatment group, randomization 
stratification factors, 7 ACR components from Weeks 0 - 24
IGA change from baseline 
through Week 24 among 
subjects with ≥3% BSA 
psoriatic involvement and 
an IGA score of ≥2 at 
baseline
Multiple imputation with 
FCS regression of IGA 
scores
MIdata6 (N=200, Seedd = 413249)
Imputation variables: IGA scores from Weeks 0 – 24
Ancillary variables b: Treatment group, randomization stratification 
factors, 7 ACR components from Weeks 0 - 24
Change from baseline at 
Week 24 in vDHS score
Main analysis
Multiple imputation with 
FCS regression of 
component scores
MIXdata1 (N=200, Seedd =4362478)
Imputation variables: hand erosion, foot erosion, hand JSN, 
and foot JSN at Week 24
Ancillary variables b: hand erosion score at baseline, foot 
erosion score at baseline, hand JSN score at baseline, foot 
JSN score at baseline, treatment group, randomization 
stratification factors, and 7 ACR component overtime 
through Week 24
NCT03158285
Title:
Version:
EDMS-ERI-196141432
2.0


CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959PSA3002 Amendment 3
116
Approved, Date: 21 March 2019
Table 12: Summary of Multiple Imputation Method
Change from baseline at 
Week 24 in vDHS score
Main analysis
2-step MI
1. MI with Mixed effect 
linear growth model 
(MLGC)
2. MI with FCS regression 
on vdHS score
1. MI through MLGC model (N=200, starting seede =46238)
All subjects with a postbaseline data will be included 
Imputed variables: vdHS score at Week 24
2. MIXdata2 (N=1 by each of 200 imputations from step 1, 
Seed =94764732)
Imputation variables: vdHS score at Week 24
Ancillary variables b: vdHS score at baseline, treatment 
group, randomization stratification factors, and 7 ACR 
component overtime through Week 24
a MIdataset2 is different from MIdataset1 as the joint scores used in DAS 28 (CRP) are different from those used in 
ACR.
b An ancillary variable may be removed if its correlation with an indicator variable that determines missing-ness of the 
variable to be imputed is low or, there are too many missing values for the ancillary variable within the subgroup of 
incomplete cases for the variable to be imputed. All the 7 ACR components (including all measurements from 
baseline through week 24) are in the list of the ancillary variables since they may be related to the mechanism 
leading to missing data.
c Enthesitis-4 is the tender entheses count based on 4 sites (left and right achilles tendon insertion, and left and right 
humeral epicondyle lateral) instead of 6 sites. Only baseline, Week 2, Week 4 are included as ancillary variables.
d The starting seed for FCS regression MI is used to generate a series of imputation seeds using the algorithm: 
INT((2**31-2)*RANUNI(starting seed)), where each imputation seed will be used for a single imputation. To 
account for the possibility that some imputations may fail to complete due to out-of-range issues, 200+ initial 
imputation seeds will be prepared, and the first 200 successful imputations will be used for analysis.
e The starting seed for the initial step of the 2-step MI is used to generate 200+ sets of random numbers from the 
normal distribution with mean 0 and standard deviation from the error of the predicted value at Week 24 taken from 
the MLGC model, which are then added to the predicted value get the imputed value. 
NCT03158285
Title:
Version:
EDMS-ERI-196141432
2.0