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 Including Those Previously Treated With Biologic Anti-TNF Alpha Agents
Phase: PHASE3
Conditions: Arthritis, Psoriatic
Sponsor: Janssen Research & Development, LLC

1
Status: Approved, Date: 25 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 including those Previously Treated with Biologic Anti-TNFα 
Agent(s)
Discover-1
Protocol CNTO1959PSA3001; 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 Sciences Ireland UC; 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 IND regulations (21 CFR 
Part 312).
EudraCT NUMBER: 2016-001163-37 
Status:
Approved
Date:
25 January 2018
Prepared by:
Janssen Research & Development, LLC
EDMS number:
EDMS-ERI-125132843
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory 
requirements. 
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.
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
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Approved, Date: 25 January 2018
TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
LIST OF ATTACHMENTS............................................................................................................................ 5
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 5
PROTOCOL AMENDMENTS....................................................................................................................... 6
SYNOPSIS.................................................................................................................................................. 18
TIME AND EVENTS SCHEDULE .............................................................................................................. 27
ABBREVIATIONS ...................................................................................................................................... 34
1.
INTRODUCTION................................................................................................................................ 36
1.1.
Background .................................................................................................................................... 36
1.1.1.
Disease Background................................................................................................................... 36
1.1.2.
Treatment Options ...................................................................................................................... 36
1.1.3.
Clinical Studies ........................................................................................................................... 37
1.1.3.1.
Phase 2 Study in Psoriatic Arthritis (CNTO1959PSA2001) .................................................... 38
1.1.3.2.
Phase 2 Study in Psoriasis (CNTO1959PSO2001, X-PLORE) .............................................. 40
1.1.3.3.
Phase 3 Studies in Psoriasis (CNTO1959PSO3001, CNTO1959PSO3002, and 
CNTO1959PSO3003).............................................................................................................. 42
1.1.3.3.1.
Efficacy................................................................................................................................. 42
1.1.3.3.2.
Safety ................................................................................................................................... 42
1.1.3.4.
Phase 2 Study in Rheumatoid Arthritis (CNTO1275ARA2001) .............................................. 42
1.2.
Overall Rationale for the Study...................................................................................................... 43
1.2.1.
Role of Interleukin-23 and TH17 Pathways in the Treatment of Psoriatic Arthritis .................... 43
1.2.2.
Study Rationale .......................................................................................................................... 44
1.2.3.
Dose Rationale ........................................................................................................................... 44
1.2.3.1.
Rationale for Guselkumab 100 mg at Weeks 0 and 4, then Every 8 Weeks Dose 
Regimen .................................................................................................................................. 44
1.2.3.2.
Rationale for Guselkumab 100 mg Every 4 Weeks Dose Regimen........................................ 45
2.
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS........................................................................... 46
2.1.
Objectives and Endpoints .............................................................................................................. 46
2.1.1.
Objectives ................................................................................................................................... 46
2.1.2.
Endpoints.................................................................................................................................... 46
2.2.
Hypothesis ..................................................................................................................................... 49
3.
STUDY DESIGN AND RATIONALE ................................................................................................. 49
3.1.
Overview of Study Design.............................................................................................................. 49
3.2.
Study Design Rationale.................................................................................................................. 51
3.2.1.
Study Population......................................................................................................................... 51
3.2.2.
Study Control, Randomization, and Blinding.............................................................................. 51
3.2.3.
Study Phases and Duration of Treatment .................................................................................. 52
3.2.4.
Study Evaluations ....................................................................................................................... 52
4.
SUBJECT POPULATION.................................................................................................................. 53
4.1.
Inclusion Criteria ............................................................................................................................ 53
4.2.
Exclusion Criteria ........................................................................................................................... 58
4.3.
Prohibitions and Restrictions ......................................................................................................... 61
5.
TREATMENT ALLOCATION AND BLINDING................................................................................. 62
6.
DOSAGE AND ADMINISTRATION .................................................................................................. 64
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7.
TREATMENT COMPLIANCE............................................................................................................ 65
8.
PRESTUDY AND CONCOMITANT THERAPY ................................................................................ 65
8.1.
Non-biologic DMARDs ................................................................................................................... 66
8.1.1.
Permitted Non-biologic DMARDs ............................................................................................... 66
8.1.2.
Prohibited Non-biologic DMARDs and Apremilast ..................................................................... 67
8.1.3.
Systemic Immunosuppressive Drugs ......................................................................................... 67
8.2.
Corticosteroids ............................................................................................................................... 68
8.2.1.
Oral Corticosteroids.................................................................................................................... 68
8.2.2.
Corticosteroids – Intravenous, Intramuscular, or Epidural Administration ................................. 68
8.2.3.
Corticosteroids – Intra-articular Injection.................................................................................... 68
8.2.4.
Corticosteroids – Other Routes of Administration ...................................................................... 68
8.3.
Nonsteroidal Anti-inflammatory Drugs and Other Analgesics........................................................ 69
8.4.
Biologic Agents, Cytotoxic Drugs, JAK Inhibitors, or Investigational Agents................................. 69
8.5.
Complementary Therapies............................................................................................................. 69
8.6.
Topical Therapy and Ultraviolet B Light......................................................................................... 70
8.7.
Systemic Therapy for Psoriasis ..................................................................................................... 70
9.
STUDY EVALUATIONS .................................................................................................................... 70
9.1.
Study Procedures........................................................................................................................... 70
9.1.1.
Overview..................................................................................................................................... 70
9.1.2.
Blood Sample Collection............................................................................................................. 71
9.1.3.
Screening Phase ........................................................................................................................ 71
9.1.4.
Treatment Phase ........................................................................................................................ 73
9.1.5.
Post Treatment Phase (Follow-Up) ............................................................................................ 74
9.2.
Efficacy Evaluations....................................................................................................................... 75
9.2.1.
Psoriatic Arthritis Response Evaluations.................................................................................... 75
9.2.1.1.
Joint Assessments................................................................................................................... 75
9.2.1.2.
Nonevaluable Joints ................................................................................................................ 76
9.2.1.3.
American College of Rheumatology Responses..................................................................... 76
9.2.1.4.
Dactylitis Assessments............................................................................................................ 77
9.2.1.5.
Enthesitis Assessments........................................................................................................... 77
9.2.1.6.
Disability Index of the Health Assessment Questionnaire....................................................... 78
9.2.1.7.
Minimal Disease Activity.......................................................................................................... 78
9.2.1.8.
Psoriatic Arthritis Disease Activity Score................................................................................. 78
9.2.1.9.
Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 
Composite Score (GRACE)..................................................................................................... 79
9.2.1.10.
Disease Activity Index Score 28.............................................................................................. 79
9.2.1.11.
Disease Activity Index for Psoriatic Arthritis ............................................................................ 80
9.2.1.12.
Modified Psoriatic Arthritis Responder Criteria........................................................................ 80
9.2.1.13.
Bath Ankylosing Spondylitis Disease Activity Index................................................................ 80
9.2.2.
Psoriasis Response Evaluations ................................................................................................ 81
9.2.2.1.
Investigator’s Global Assessment of Psoriasis........................................................................ 81
9.2.2.2.
Psoriasis Area and Severity Index .......................................................................................... 81
9.2.3.
Other Patient Reported Outcomes ............................................................................................. 81
9.2.3.1.
36-Item Short-form Health Survey........................................................................................... 81
9.2.3.2.
Functional Assessment of Chronic Illness Therapy - Fatigue ................................................. 82
9.2.3.3.
Patient-Reported Outcomes Measurement Information System-29 ....................................... 82
9.3.
Pharmacokinetics and Immunogenicity ......................................................................................... 83
9.3.1.
Serum Collection and Handling .................................................................................................. 83
9.3.2.
Analytical Procedures................................................................................................................. 84
9.3.3.
Pharmacokinetic Parameters ..................................................................................................... 84
9.3.4.
Immunogenicity Assessments .................................................................................................... 84
9.4.
Safety Evaluations ......................................................................................................................... 84
9.4.1.
Evaluations of Safety and Tolerability ........................................................................................ 84
9.4.2.
Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS)................................................ 87
9.4.3.
Anticipated Events...................................................................................................................... 89
9.5.
Sample Collection and Handling.................................................................................................... 90
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CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
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Approved, Date: 25 January 2018
10.
SUBJECT COMPLETION/DISCONTINUATION OF STUDY TREATMENT/ WITHDRAWAL 
FROM THE STUDY ........................................................................................................................... 90
10.1.
Completion ..................................................................................................................................... 90
10.2.
Discontinuation of Study Treatment............................................................................................... 90
10.3.
Withdrawal From the Study............................................................................................................ 92
10.4.
Withdrawal From the Use of Research Samples........................................................................... 92
11.
STATISTICAL METHODS................................................................................................................. 93
11.1.
Subject Information ........................................................................................................................ 94
11.2.
Sample Size Determination ........................................................................................................... 94
11.3.
Efficacy Analyses ........................................................................................................................... 95
11.3.1.
Primary Endpoint Analyses ........................................................................................................ 95
11.3.2.
Major Secondary Analyses......................................................................................................... 96
11.3.3.
Other Planned Secondary Analyses........................................................................................... 96
11.4.
Pharmacokinetic Analyses............................................................................................................. 96
11.5.
Immunogenicity Analyses .............................................................................................................. 96
11.6.
Biomarker Analyses ....................................................................................................................... 96
11.7.
Pharmacokinetic/Pharmacodynamic Analyses.............................................................................. 97
11.8.
Pharmacogenomic Analyses ......................................................................................................... 97
11.9.
Safety Analyses ............................................................................................................................. 97
11.9.1.
Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS)................................................ 97
11.10.
Interim Analysis.............................................................................................................................. 97
11.11.
Data Monitoring Committee ........................................................................................................... 97
12.
ADVERSE EVENT REPORTING ...................................................................................................... 98
12.1.
Definitions ...................................................................................................................................... 98
12.1.1.
Adverse Event Definitions and Classifications ........................................................................... 98
12.1.2.
Attribution Definitions.................................................................................................................. 99
12.1.3.
Severity Criteria ........................................................................................................................ 100
12.2.
Special Reporting Situations........................................................................................................ 100
12.3.
Procedures................................................................................................................................... 101
12.3.1.
All Adverse Events.................................................................................................................... 101
12.3.2.
Serious Adverse Events ........................................................................................................... 102
12.3.3.
Pregnancy................................................................................................................................. 103
12.3.4.
Events of Special Interest......................................................................................................... 103
12.4.
Contacting Sponsor Regarding Safety......................................................................................... 103
13.
PRODUCT QUALITY COMPLAINT HANDLING............................................................................ 103
13.1.
Procedures................................................................................................................................... 103
13.2.
Contacting Sponsor Regarding Product Quality .......................................................................... 104
14.
STUDY AGENT INFORMATION..................................................................................................... 104
14.1.
Physical Description of Study Agents .......................................................................................... 104
14.2.
Packaging .................................................................................................................................... 104
14.3.
Labeling........................................................................................................................................ 104
14.4.
Preparation, Handling, and Storage............................................................................................. 104
14.5.
Drug Accountability ...................................................................................................................... 105
15.
STUDY-SPECIFIC MATERIALS..................................................................................................... 105
16.
ETHICAL ASPECTS ....................................................................................................................... 106
16.1.
Study-Specific Design Considerations......................................................................................... 106
16.2.
Regulatory Ethics Compliance..................................................................................................... 106
16.2.1.
Investigator Responsibilities ..................................................................................................... 106
16.2.2.
Independent Ethics Committee or Institutional Review Board ................................................. 107
16.2.3.
Informed Consent ..................................................................................................................... 108
16.2.4.
Privacy of Personal Data .......................................................................................................... 109
16.2.5.
Long-Term Retention of Samples for Additional Future Research .......................................... 110
16.2.6.
Country Selection ..................................................................................................................... 110
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CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
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17.
ADMINISTRATIVE REQUIREMENTS ............................................................................................ 110
17.1.
Protocol Amendments.................................................................................................................. 110
17.2.
Regulatory Documentation .......................................................................................................... 111
17.2.1.
Regulatory Approval/Notification .............................................................................................. 111
17.2.2.
Required Prestudy Documentation........................................................................................... 111
17.3.
Subject Identification, Enrollment, and Screening Logs .............................................................. 112
17.4.
Source Documentation................................................................................................................. 112
17.5.
Case Report Form Completion .................................................................................................... 113
17.6.
Data Quality Assurance/Quality Control ...................................................................................... 114
17.7.
Record Retention ......................................................................................................................... 114
17.8.
Monitoring .................................................................................................................................... 115
17.9.
Study Completion/Termination..................................................................................................... 115
17.9.1.
Study Completion/End of Study................................................................................................ 115
17.9.2.
Study Termination..................................................................................................................... 115
17.10.
On-Site Audits .............................................................................................................................. 116
17.11.
Use of Information and Publication.............................................................................................. 116
REFERENCES.......................................................................................................................................... 118
INVESTIGATOR AGREEMENT ............................................................................................................... 127
LIST OF ATTACHMENTS
Attachment 1:
The CASPAR Criteria .................................................................................................. 121
Attachment 2:
QuantiFERON® TB Gold Testing................................................................................ 122
Attachment 3:
Tuberculin Skin Testing ............................................................................................... 124
Attachment 4:
Hepatitis B Virus (HBV) Screening with HBV DNA...................................................... 125
Attachment 5:
Anticipated Events ....................................................................................................... 126
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1:
TIME AND EVENTS SCHEDULE FROM SCREENING THROUGH WEEK 60 ...................... 27
Table 2:
Summary of Efficacy Results at Week 24 (CNTO1959PSA2001) ........................................... 39
Table 3:
Permitted Concomitant Medications for PsA and the Maximum Allowed Doses During 
the Study................................................................................................................................... 66
Table 4:
Protocol Requirements of the Permitted Non-biologic DMARDs ............................................. 67
Table 5:
DAS Response ......................................................................................................................... 80
Table 6:
Statistical Power for the ACR 20 Response Rate Comparing to Placebo at Week 24 ............ 94
FIGURES
Figure 1:
Study Schema – Study CNTO1959PSA3001........................................................................... 51
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
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Approved, Date: 25 January 2018
PROTOCOL AMENDMENTS
Protocol Version
Issue Date
Original Protocol
26 April 2017
Amendment 1
25 January 2018
Amendments below are listed beginning with the most recent amendment.
Amendment 1 (25 January 2018)
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of Directive 
2001/20/EC of the European Parliament and the Council of the European Union. 
The overall reason for the amendment: The protocol is being amended due to FDA feedback and correction of 
errors.
Applicable Section(s)
Description of Change(s)
Rationale: Incorrect EudraCT Number updated to correct EudraCT Number.
Cover page; Synopsis
EudraCT Number changed from:
2016-001163-27
To:
2016-001163-37
Rationale: DLQI assessment is not being completed in this study.
Synopsis, Time and 
Events Schedule, 
Abbreviations, 
Endpoints, Efficacy 
Evaluations, Source 
Documentation
Remove all references to DLQI (endpoints, Psoriasis Response Assessments, T&E, etc.) 
as this assessment is not included in this study and should not have been included in the 
original protocol.
Rationale: DLQI assessment is not being completed in this study and is needed for calculating mCPDAI.
Synopsis, 
Section 2.1.2. 
Endpoints
Section 9.2.1.11. 
Modified Composite 
Psoriatic Disease 
Activity Index
Remove from Other Secondary Endpoints, Endpoints Related to Reduction of Signs and 
Symptoms and Physical Function:
16. Change from baseline in modified Composite Psoriatic Disease Activity Index 
(mCPDAI) score by visit over time through Week 52.
Entire section removed.
Rationale: FSH testing is not performed at Week 0.
Time & Events 
Schedule 
Remove FSH testing from Week 0.
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
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Approved, Date: 25 January 2018
Applicable Section(s)
Description of Change(s)
Rationale: To update the footnotes in Table 1 to provide clarification.
Table 1, Time and 
Events Schedule from 
screening through 
Week 60
Footnote ‘w’ was modified from:
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 11 for details.
Updated to:
Prior to randomization, FSH is required for selected female subjects with amenorrhea for 
less than 12 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 with amenorrhea for at least 12 months. Refer to Inclusion Criterion 11
for details.
Rationale: All visits through Week 24 have a visit window of ± 4 days, all visits after Week 24 up to Week 60 have 
a visit window of ± 7 days, and the Week 60 visit or the safety visit (12 weeks after the last dose in subjects who 
discontinued study treatments) will have a visit window of ±14 days instead of all visits through Week 60 have a 
visit window of ±7 days.
Time & Events 
Schedule
Update footnote b in the T&E from:
All other visits through Week 60 will have a visit window of ±7 days counting from 
Week 0 as Day 1; Week 60 visit will have a visit window of ±14 days.
Updated to:
Through Week 24, study visits will have a visit window of ± 4 days; after Week 24, study 
visits at the site will have a visit window of ± 7 days; Week 60 visit or the final safety 
visit (12 weeks after the last dose in subjects who discontinued study treatment) will have 
a visit window of ±14 days.
Section 7 Treatment 
Compliance
Updated paragraph 7 from:
All post-baseline visits through Week 52 will have a visit window of ±7 days counting 
from Week 0 as Day 1. The safety follow-up visit at 12 weeks after the last study agent 
administration 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.
Updated to:
Through Week 24, study visits will have a visit window of ±4 days. After Week 24, study 
visits at the site will have a visit window of ±7 days. The Week 60 visit or the safety visit 
(12 weeks after the last dose in subjects who discontinue 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.
Rationale: Revised for clarification.
Time and Events 
Schedule
Footnote ‘r’ revised from:
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 will be completed/recorded on the tablet.
To: 
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.
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
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Approved, Date: 25 January 2018
Applicable Section(s)
Description of Change(s)
Rationale: This is a physician or site assessment and not a subject questionnaire. Therefore footnote ‘r’ no longer 
applies.
Time and Events 
Schedule
Remove footnote ‘r’ from PsA Evaluations for Arthritis.
Rationale: Typographical error.
Time & Events 
Schedule 
Footnote ‘t’ should be footnote ‘u’ for the following items in the T&E: 
Hepatitis B and C Serologies
HIV Antibody Test
Chemistry
Lipid Panel
C-reactive Protein
Rheumatoid factor
Follicle Stimulating Hormone.
Rationale: Typographical error.
Section 4.1. Inclusion 
Criteria
Update Inclusion criterion 18 from:
Have screening laboratory test results within the following parameters:
a.
Hemoglobin
≥8.5 g/dL
(SI: ≥ 100 g/L) 
b.
White blood cells
≥3.5 x 103/µL
(SI: ≥3.5 GI/L)
c.
Neutrophils
≥1.5 x 103/µL
(SI: ≥1.5 GI/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 ≤1.5 times the upper limit of normal range 
for the central laboratory conducting the test.
To:
Have screening laboratory test results within the following parameters:
a.
Hemoglobin
≥8.5 g/dL
(SI: ≥ 85 g/L) 
b.
White blood cells
≥3.5 x 103/µL
(SI: ≥3.5 GI/L)
c.
Neutrophils
≥1.5 x 103/µL
(SI: ≥1.5 GI/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 ≤1.5 times the upper limit of normal range 
for the central laboratory conducting the test.
Rationale: Revised for clarification.
Sections 4.2 Exclusion 
Criteria #16; 9.1.3 
Screening Phase; 9.1.4 
Treatment Phase; 9.4.2 
eC-SSRS
The eC-SSRS ideation level language was revised for better clarity.
The Baseline/Screening version name was changed to Lifetime version.
The Since Last Visit version was changed to Since Last Contact version
Clarified that the eC-SSRS measures five possible levels of suicidal ideation and four 
possible suicidal behaviors.
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
9
Approved, Date: 25 January 2018
Applicable Section(s)
Description of Change(s)
Rationale: 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. eC-SSRS is performed as the first of the PRO assessments at the Week 0 visit and all post-
baseline visits.
Time & Events 
Schedule; Study 
Procedures; 9.1.3. 
Screening Phase; 
9.1.4. Treatment 
Phase; 9.4.2. 
eC-SSRS
Change the order of the PRO assessments at screening so eC-SSRS is completed after the 
joint assessment.
Rationale: Endpoints were duplicated. 
Synopsis; 2.1.2. 
Endpoints
Endpoints related to Health-Related Quality of Life Endpoints from:
Endpoints Related to Health-Related Quality of Life
1.
Change from baseline in Physical Component Summary (PCS) score of the 36-item 
short form health survey (SF-36) by visit over time through Week 52.
2.
Change from baseline in Mental Component Summary (MCS) score of the 36-item 
short form health survey (SF-36) by visit over time through Week 52.
3.
Change from baseline in domain scales scores of SF-36 by visit over time through 
Week 52.
4.
Proportion of subjects who achieve ≥5-point improvement from baseline in SF-36 
MCS score by visit over time through Week 52.
5.
Proportion of subjects who achieve ≥5-point improvement from baseline in SF-36 
PCS score by visit over time through Week 52.
6.
Change from baseline in Physical Component Summary (PCS) score of the 36-item 
short form health survey (SF-36) by visit over time through Week 52.
7.
Change from baseline in Mental Component Summary (MCS) score of the 36-item 
short form health survey (SF-36) by visit over time through Week 52.
8.
Change from baseline in domain scales scores of SF-36 by visit over time through 
Week 52.
9.
Proportion of subjects who achieve ≥5-point improvement from baseline in SF-36 
MCS score by visit over time through Week 52.
10.
Proportion of subjects who achieve ≥5-point improvement from baseline in SF-36 
PCS score by visit over time through Week 52.
11.
Change from baseline in Functional Assessment of Chronic Illness Therapy 
(FACIT-Fatigue) by visit over time through Week 52.
12.
Proportion of subjects who achieve ≥4-point improvement from baseline in 
FACIT-Fatigue score improvement by visit over time through Week 52.
13.
Change from baseline in PROMIS 29 scores by visit over time through Week 52.
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
10
Approved, Date: 25 January 2018
Applicable Section(s)
Description of Change(s)
To:
Endpoints Related to Health-Related Quality of Life
1.
Change from baseline in SF-36 PCS score by visit over time through Week 52.
2.
Change from baseline in SF-36 MCS score by visit over time through Week 52.
3.
Change from baseline in domain scales scores of SF-36 by visit over time through 
Week 52.
4.
Proportion of subjects who achieve ≥5-point improvement from baseline in SF-36 
MCS score by visit over time through Week 52.
5.
Proportion of subjects who achieve ≥5-point improvement from baseline in SF-36 
PCS score by visit over time through Week 52.
6.
Change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue 
(FACIT-Fatigue) by visit over time through Week 52.
7.
Proportion of subjects who achieve ≥4-point improvement from baseline in 
FACIT-Fatigue score improvement by visit over time through Week 52.
8.
Change from baseline in Patient-Reported Outcomes Measurement Information 
System (PROMIS) 29 scores by visit over time through Week 52.
Rationale: Revise Exclusion Criteria #7 so that it is consistent with Section 8.1.3. regarding previous use of 
systemic immunosuppressants not permitted within 4 weeks of the first administration of study agent.
4.2 Exclusion Criteria
Section 4.2 Exclusion criteria; #7 from:
7.
Has previously received any systemic immunosuppressants (eg, azathioprine, 
cyclosporine, 6-thioguanine, mercaptopurine, mycophenolate mofetil, hydroxyurea, 
tacrolimus).
To:
7.
Has previously received any systemic immunosuppressants (eg, azathioprine, 
cyclosporine, 6-thioguanine, mercaptopurine, mycophenolate mofetil, hydroxyurea, 
tacrolimus) within 4 weeks of the first administration of study agent.
Rationale: Revise for clarification
9.2.1.9. Group for 
Research and 
Assessment of 
Psoriasis and Psoriatic 
Arthritis (GRAPPA) 
Composite Score 
(GRACE)
Update from:
Arithmetic Mean of the Desirability Group for Research and Assessment of 
Psoriasis and Psoriatic Arthritis (GRAPPA) Composite Score (GRACE 
Index)
The Arithmetic Mean of the Desirability Function (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 0:19,18

Tender joint count (0-68)

Swollen joint count (0-66)
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CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
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Approved, Date: 25 January 2018
Applicable Section(s)
Description of Change(s)

HAQ (0-3)

Patient’s global assessment of disease activity by VAS (arthritis and psoriasis, 
0-100 mm)

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:
o
PsAQoL = 25.355 + (2.367 × HAQ) – (0.234 × PCS) – (0.244 × MCS)
GRACE index = (1-AMDF) ×1020
To:
Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 
(GRAPPA) Composite Score (GRACE)
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).
The 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 0:19,18

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, 0-100 
VAS)

Patient’s assessment of skin disease activity (0-100 VAS)

Patient’s global assessment of disease activity (arthritis) (0-100 VAS) 

PASI score (0-72)

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,
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
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
12
Approved, Date: 25 January 2018
Applicable Section(s)
Description of Change(s)
Rationale: Revised for clarification.
Section 9.4.2. 
eC-SSRs
Revised language to clarify eC-SSRS questionnaires will be completed using a Sponsor-
provided electronic tablet or through IVRS.
Section 17.4. Source 
Documentation
Revised language to clarify eC-SSRS questionnaires can be completed through IVRS as 
an alternative method.
Rationale: Treatment failure criteria 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.
Section 11 Statistical 
Methods; 
Section 11.3.1 Primary 
Endpoint Analyses
Updated second paragraph from:
In general, efficacy and subject information analyses will 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 actually 
received. 
Updated to:
In general, efficacy and subject information analyses will be based on the Full Analysis 
Set (FAS) including all randomized subjects who received at least 1 dose (complete or 
partial) of study treatment, which will be analyzed based on the randomized treatment 
groups, regardless of the treatment subjects actually received. 
Updated from:
The primary endpoint to be analyzed in this study is the proportion of subjects who 
achieve an ACR 20 response at Week 24 and had not met the following treatment failure 
(TF) criteria prior to Week 24.  Subjects who met one of the TF criteria prior to Week 24 
will be considered an ACR 20 non-responder at Week 24 regardless of the observed 
ACR 20 response status.
Treatment Failure Criteria
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 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.
The treatment effect of each guselkumab group versus placebo will be tested using the 
Cochran-Mantel-Haenszel test stratified by prior exposure to anti-TNF agents (yes/no) 
and baseline DMARD (MTX, SSZ, HCQ, LEF) use (yes/no). 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.
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
13
Approved, Date: 25 January 2018
Applicable Section(s)
Description of Change(s)
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 nonresponders at Week 24. 
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 Week 0, 4 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.
Sensitivity Analysis
To evaluate the robustness of the primary endpoint analysis, 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 set to missing. Subjects with missing ACR 20 response
will be imputed by Multiple Imputation (MI) method under the assumption of 
Missing At-Random (MAR).
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 (MAR).  And 2-dimensional tipping point analyses based on 
MI will be performed to assess the MAR assumption.
Additional sensitivity analyses may be specified in the SAP to further address the 
robustness of the primary analysis. 
Subgroup Analyses
Subgroup analysis will be performed to evaluate consistency in the primary efficacy 
endpoint by demographic characteristics, baseline disease characteristics, and prior and 
baseline medications.  Interaction test between the subgroups and treatment group will 
also be provided if appropriate.
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
14
Approved, Date: 25 January 2018
Applicable Section(s)
Description of Change(s)
Updated to:
The primary endpoint to be analyzed in this study is the proportion of subjects who 
achieve 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.
Treatment Failure Criteria
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 nonresponders.
The treatment effect of each guselkumab group versus placebo will be tested using the 
Cochran-Mantel-Haenszel test stratified by prior exposure to anti-TNF agents (yes/no) 
and baseline DMARD (MTX, SSZ, HCQ, LEF) use (yes/no). 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 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 Week 0, 4 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.
To evaluate the robustness of the primary endpoint analysis, the exhaustive scenario 
tipping point sensitivity analyses will be performed by varying the amount of non-
responder imputation for missing data.
Additional sensitivity/supplemental analyses which vary how intercurrent events (e.g. 
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 
ACR20 at Week 24 for the primary and alternative estimands (which will also be defined 
in the SAP).
Subgroup Analyses
Subgroup analysis will be performed to evaluate consistency in the primary efficacy 
endpoint by demographic characteristics, baseline disease characteristics, and prior and 
baseline medications.  Interaction test between the subgroups and treatment group will 
also be provided if appropriate.
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
15
Approved, Date: 25 January 2018
Applicable Section(s)
Description of Change(s)
Rationale: Subjects must be able to read and write and must sign the ICF independently to participate in this study.
16.2.3. Informed 
Consent
Updated from:
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 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.
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.
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
16
Approved, Date: 25 January 2018
Applicable Section(s)
Description of Change(s)
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 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.
Updated to:
16.2.3 Informed Consent
Each subject 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 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 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.
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
17
Approved, Date: 25 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 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.
The subject must be able to read and write and should personally sign the ICF.
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 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.
Rationale: To clarify the sample storage period.
Section 16.2.5 Long-
Term Retention of 
Samples
Samples collected in this study may be stored for up to 15 years, starting from last 
patient, last visit.
Rationale: Revised for clarification.
Section 17.4 Source 
Documentation
The last paragraph updated from:
During the at-home administration phase of the study (Weeks 56-100), subjects will enter 
information on their study agent administration on a patient diary.
Updated to:
During at-home administration (Weeks 32, 40, and 48), subjects will enter information on 
their study agent administration on a patient diary.
Rationale: Minor errors were noted
Throughout the 
protocol
Minor grammatical, formatting, or spelling changes were made.
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
18
Approved, Date: 25 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 including those Previously Treated with Biologic Anti-TNFα Agent(s)
CNTO1959 (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: 2016-001163-37
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 

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
1.
Change from baseline in Health Assessment Questionnaire-Disability Index (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 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 DAS28 (C-reactive protein [CRP]) at Week 24.
6.
Proportion of subjects who achieve an ACR 70 response at Week 24.
7.
Proportion of subjects who achieve an ACR 50 response at Week 16.
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CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
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Approved, Date: 25 January 2018
8.
Change from baseline in 36-item short form health survey (SF-36) Physical Component Summary 
(PCS) at Week 24.
9.
Proportion of subjects with resolution of enthesitis at Week 24 among the subjects with enthesitis at 
baseline.
10. Change from baseline in enthesitis score (based on Leeds Enthesitis Index [LEI]) at Week 24 among 
the subjects with enthesitis at baseline. 
11. Change from baseline in SF-36 Mental Component Summary (MCS) at Week 24. 
12. Proportion of subjects with resolution of dactylitis at Week 24 among the subjects with dactylitis at 
baseline.
13. Change from baseline in dactylitis scores at Week 24 among the subjects with dactylitis at baseline. 
Other Secondary Endpoints
Endpoints Related to Reduction of Signs and Symptoms and Physical Function
1.
Proportion of subjects who achieve ACR 20, ACR 50, and ACR 70 responses by visit over time 
through Week 52.
2.
Percent change from baseline in ACR components by visit over time through Week 52.
3.
Change from baseline in HAQ-DI score by visit over time through Week 52.
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 52 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 52.
6.
Proportion of subjects who achieve a DAS28 (CRP) remission by visit over time through Week 52.
7.
Change from baseline in DAS28 (CRP) by visit over time through Week 52.
8.
Proportion of subjects who achieve a response based on modified Psoriatic Arthritis Response 
Criteria (PsARC) by visit over time through Week 52.
9.
Proportion of subjects with resolution of enthesitis by visit over time through Week 52 among the 
subjects with enthesitis at baseline.
10. Proportion of subjects with resolution of dactylitis by visit over time through Week 52 among 
subjects with dactylitis at baseline.
11. Change from baseline in enthesitis score (based on LEI) by visit over time through Week 52 among 
the subjects with enthesitis at baseline.
12. Change from baseline in enthesitis score (based on Spondyloarthritis Research Consortium of 
Canada [SPARCC]) by visit over time through Week 52 among the subjects with enthesitis at
baseline.
13. Change from baseline in dactylitis score by visit over time through Week 52 among the subjects with 
dactylitis at baseline.
14. Change from baseline in Psoriatic ArthritiS Disease Activity Score (PASDAS) by visit score over 
time through Week 52.
15. Change from baseline in GRAppa Composite scorE (GRACE) Index by visit over time through 
Week 52.
16. Change from baseline in Disease Activity Index for Psoriatic Arthritis (DAPSA) score by visit over 
time through Week 52.
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CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
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Approved, Date: 25 January 2018
17. Proportion of subjects who maintain an ACR 20 response at Week 52 among subjects who achieved 
an ACR 20 response at Week 24.  
18. Proportion of subjects who maintain an ACR 50 response at Week 52 among subjects who achieved 
an ACR 50 response at Week 24.
19. Proportion of subjects who maintain an ACR 70 response at Week 52 among subjects who achieved 
an ACR 70 response at Week 24.
20. Proportion of subjects who maintain a HAQ-DI response (ie, ≥0.35 improvement from baseline in 
HAQ-DI score) at Week 52 among subjects who achieved a HAQ-DI response at Week 24.
21. Proportion of subjects who achieve minimal disease activity (MDA) by visit over time through 
Week 52.
22. 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 52 among subjects with spondylitis and peripheral joint involvement as their primary arthritic 
presentation of PsA.
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 52 among subjects with 
≥3% BSA psoriatic involvement and an IGA score of ≥2 (mild) at baseline.
2.
Proportion of subjects with IGA score of 0 (cleared) by visit over time through Week 52 among 
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 52 among subjects with ≥3% 
BSA psoriatic involvement and an IGA score of ≥2 (mild) at baseline.
4.
Proportion of subjects who achieve both PASI 75 and ACR 20 responses by visit over time through 
Week 52 among subjects with ≥3% BSA psoriatic involvement and an IGA score of ≥2 (mild) at 
baseline.
5.
Proportion of subjects who achieve both PASI 75 and modified PsARC response by visit over time 
through Week 52 among subjects with ≥3% BSA psoriatic involvement and an IGA score of ≥2 
(mild) at baseline.
Endpoints Related to Health Related Quality of Life
1.
Change from baseline in PCS score of the 36-item short form health survey (SF-36) by visit over 
time through Week 52.
2.
Change from baseline in MCS score of the 36-item short form health survey (SF-36) by visit over 
time through Week 52.
3.
Change from baseline in domain scales scores of SF-36 by visit over time through Week 52.
4.
Proportion of subjects who achieve ≥ 5-point improvement from baseline in SF-36 MCS score by 
visit over time through Week 52.
5.
Proportion of subjects who achieve ≥ 5-point improvement from baseline in SF-36 PCS score by 
visit over time through Week 52.
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
21
Approved, Date: 25 January 2018
6.
Change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue) by 
visit over time through Week 52.
7.
Proportion of subjects who achieve ≥4-point improvement from baseline in FACIT-Fatigue score 
improvement by visit over time through Week 52.
8.
Change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS)
29 scores by visit over time through Week 52.
Hypothesis
The primary hypothesis is that 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 Week 24.
OVERVIEW OF STUDY DESIGN
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, 3-arm study of guselkumab 
in subjects with active PsA who had inadequate response to standard therapies (eg, non-biologic 
disease-modifying antirheumatic drugs [DMARDs], apremilast, or nonsteroidal anti-inflammatory drugs 
[NSAIDs]). In addition, subjects (approximately 30%) may have been previously treated with up to 
2 anti-tumor necrosis factor alpha (anti-TNFα) agents.
Stable doses (as defined below) of concomitant NSAIDs, oral corticosteroids, and selected non-biologic 
disease-modifying antirheumatic drugs (DMARDs; limited to methotrexate [MTX], sulfasalazine [SSZ], 
hydroxychloroquine [HCQ], and leflunomide [LEF]) will be allowed but are not required:

NSAIDs and 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

SSZ: ≤3 g/day

HCQ: ≤400 mg/day

LEF: ≤20 mg/day
The study will include approximately 360 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 by prior exposure to anti-TNFα agents (yes/no):

Group I (n=120): Subjects will receive subcutaneous (SC) guselkumab 100 mg every 4 weeks (q4w) 
from Week 0 through Week 48.

Group II (n=120): Subjects will receive SC guselkumab 100 mg at Weeks 0 and 4, then every 
8 weeks (q8w; Weeks 12, 20, 28, 36, and 44) and placebo injections at other visits (Weeks 8, 16, 24, 
32, 40, 48) to maintain the blind. 

Group III (n=120): Subjects will receive SC placebo q4w from Week 0 to Week 20, and will 
crossover at Week 24 to receive guselkumab 100 mg q4w through Week 48.
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
22
Approved, Date: 25 January 2018
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 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 52; 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 Week 52. 
Subjects will be followed for new adverse events (AEs) and serious adverse events (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 study visit. For subjects who complete the Week 52 visit, the last study visit is 
the Week 60 visit.  For subjects who discontinue study agent prior to Week 52, the last study visit is the 
final safety visit (12 weeks after the last study agent administration).
An independent Data Monitoring Committee (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 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.
Database locks are scheduled at Weeks 24 and End of Study (Week 60).  
SUBJECT POPULATION
The target study population is subjects with active PsA who have had inadequate response to standard 
therapies (eg, non-biologic DMARDs, apremilast or NSAIDs). In addition, approximately 30% of the 
study population may have been previously exposed to up to 2 anti-TNFα agents. Stable doses of 
concomitant NSAIDs, oral corticosteroids, and selected non-biologic DMARDs (limited to MTX, SSZ, 
HCQ, or LEF) will be allowed but are not required. This population is considered appropriate to provide 
relevant efficacy and safety information for the intended use of guselkumab in PsA.
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 PLUSTM 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 
Weeks 0 and 4. Beginning at Week 8, at the discretion of the investigator and subject, and after 
appropriate and documented training, subjects may self-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 an HCP.
The option to begin self-administration of study agent at home will begin at Week 32. At Week 28, 
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 
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
23
Approved, Date: 25 January 2018
promptly in the event of any signs of an allergic reaction, infection, or bleeding. Subjects unable to have 
injection(s) administered away from site will be required to return to the site for administration of study 
agent by an HCP. After Week 28, subjects will have study visits and assessments approximately 
every 8 weeks through Week 52.
The three dose groups (Groups I, II, and III) are described above.
EFFICACY EVALUATIONS
Psoriatic Arthritis Response Evaluations

Joint Assessments

Nonevaluable Joints

American College of Rheumatology Response

Dactylitis Assessments

Enthesitis Assessments

Disability Index of the Health Assessment Questionnaire

Minimal Disease Activity

Psoriatic Arthritis Disease Activity Score

Group for Research and Assessment of Psoriasis and Psoriatic Arthritis Composite Score (GRACE)

Disease Activity Index Score 28

Modified Composite Psoriatic Disease Activity Index

Disease Activity Index for Psoriatic Arthritis

Modified Psoriatic Arthritis Responder Criteria

Bath Ankylosing Spondylitis Disease Activity Index
Psoriasis Response Evaluations

Investigator’s Global Assessment of Psoriasis

Psoriasis Area and Severity Index
Other Patient Reported Outcomes

36-Item Short-form Health Survey

FACIT – Fatigue

PROMIS 29
PHARMACOKINETIC AND IMMUNOGENICITY EVALUATIONS
Serum samples will be used to evaluate the pharmacokinetic (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.
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
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Approved, Date: 25 January 2018
BIOMARKER EVALUATIONS

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.

Ribonucleic acid (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, a whole 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 (using the electronic Columbia-Suicide 
Severity Rating Scale questionnaires), concomitant medication review, and early detection of 
tuberculosis.
Serum and/or plasma samples collected for pharmacokinetic or pharmacodynamic analyses may also be 
used to evaluate safety concerns that may arise during or after the study period.
Safety will be monitored through Week 60.
STATISTICAL METHODS
Simple descriptive summary statistics, such as n, mean, standard deviation (SD), 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 was chosen based on the data from a Sponsor’s recent PsA study with ustekinumab, 
CNTO1275PSA3002, that included subjects previously treated with biologic anti-TNFα agents. The 
ACR 20 response rates at Week 24 from CNTO1275PSA3002 were 20.2%, 43.7% and 43.8%, 
respectively, for the placebo, ustekinumab 45 mg, and ustekinumab 90 mg treatment groups. In order to 
ensure a statistical power of >90% at the significance level of 0.05 (2-sided), assuming that each of 
guselkumab 100 mg groups achieves an ACR 20 response of 40% compared with the placebo group 
response of 20% at Week 24, a total of 360 subjects are planned to be randomized in a 1:1:1 ratio to each 
of treatment groups. The table below provides the power evaluation of various assumptions.
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
25
Approved, Date: 25 January 2018
Statistical Power for the ACR 20 Response Rate Comparing to Placebo at Week 24
Treatment group
Sample size
ACR 20 
response
Δ (difference)
Power
1
Placebo
120
20%
20%
93%
Guselkumab 100 mg
120
40%
2
Placebo
120
25%
20%
91%
Guselkumab 100 mg
120
45%
3
Placebo
120
20%
25%
99%
Guselkumab 100 mg
120
45%
4
Placebo
120
25%
25%
98%
Guselkumab 100 mg
120
50%
Primary Endpoint Analysis
The primary endpoint to be analyzed in this study is the proportion of subjects who achieve 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.
Treatment Failure Criteria
1.
Discontinued study agent injections due to lack of efficacy.
2.
Terminate study participation for any reason.
3.
Initiated or increased the dose of 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 nonresponders.
The treatment effect of each guselkumab group versus placebo will be tested using the Cochran-Mantel-
Haenszel test stratified by prior exposure to anti-TNF agents (yes/no) and baseline DMARD (MTX, SSZ, 
HCQ, LEF) use (yes/no). 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 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 Week 0, 4 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.
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
26
Approved, Date: 25 January 2018
To evaluate the robustness of the primary endpoint analysis, the exhaustive scenario tipping point 
sensitivity analyses will be performed by varying the amount of non-responder imputation for missing 
data.
Additional sensitivity/supplemental analyses which vary how intercurrent events (e.g. 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 ACR20 at Week 24 for the primary and alternative 
estimands (which will also be defined in the SAP).
Subgroup Analyses
Subgroup analysis will be performed to evaluate consistency in the primary efficacy endpoint by 
demographic 
characteristics, 
baseline 
disease 
characteristics, 
and 
prior 
and 
baseline 
medications. Interaction test between the subgroups and treatment group will also be provided if 
appropriate.
Major Secondary Analyses
The major secondary endpoints are listed above.  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 Statistical Analysis Plan.  
Safety Analysis
Routine safety evaluations will be performed.  Adverse events, serious adverse events, and infections will 
be summarized by treatment group.  The following analyses will also be used to assess the safety of 
subjects in the study:  incidence and type of AEs, incidence and type of SAEs, incidence and type of 
infections, and incidence and type of injection site reactions.
Laboratory parameters, change from baseline in selected laboratory parameters (hematology and 
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
No interim analysis is planned for this study.
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
27
Approved, Date: 25 January 2018
TIME AND EVENTS SCHEDULE
Table 1:
TIME AND EVENTS SCHEDULE FROM SCREENING THROUGH WEEK 60
Phase
Screeninga
Placebo-controlled Treatmentb
Active Treatmentb
Safety 
Follow-
up
Week
0c
4
8
12
16
20
24
28
32
36
40
44
48
Final 
Efficacy 
Visitd/
Week 52
Final 
Safety
Visitb/ 
Week 60
Study Proceduresd
Screening/Administrative
Informed consent
(ICF/eICFe)
X
Pharmacogenomics 
(DNA) (optional)f
ICF/eICFe
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
X
Xh
X
Xh
X
Xh
Early Escape
Early Escape 
Xi
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
28
Approved, Date: 25 January 2018
Table 1:
TIME AND EVENTS SCHEDULE FROM SCREENING THROUGH WEEK 60
Phase
Screeninga
Placebo-controlled Treatmentb
Active Treatmentb
Safety 
Follow-
up
Week
0c
4
8
12
16
20
24
28
32
36
40
44
48
Final 
Efficacy 
Visitd/
Week 52
Final 
Safety
Visitb/ 
Week 60
Study Proceduresd
Safety Assessments
Physical examination 
(including skin)
X
X
X
eC-SSRSj
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital signsk
X
X
X
X
X
X
X
X
X
X
X
X
X
Height
X
Weight
X
X
X
Local 12-lead ECG
Xl
Tuberculosis evaluationm
X
X
X
X
X
X
X
X
X
X
X
X
X
Chest radiographn
X
Pregnancy testo
X
X
X
X
X
X
X
X
X
Xp
X
Xp
X
Xp
X
X
Injection site reaction 
evaluation
X
X
X
X
X
X
X
X
Xp
X
Xp
X
Xp
Efficacy Assessments
PsA Evaluations for 
Arthritisq
X
X
X
X
X
X
X
X
X
X
X
X
HAQ-DIr
X
X
X
X
X
X
X
X
X
X
X
Patient’s Global 
Assessment of Disease 
Activity (arthritis and 
psoriasis)r
X
X
X
X
X
Patient’s Assessment of 
Skin Disease Activity 
(Skin VAS)r
X
X
X
X
X
Dactylitis assessments
X
X
X
X
X
X
X
X
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
29
Approved, Date: 25 January 2018
Table 1:
TIME AND EVENTS SCHEDULE FROM SCREENING THROUGH WEEK 60
Phase
Screeninga
Placebo-controlled Treatmentb
Active Treatmentb
Safety 
Follow-
up
Week
0c
4
8
12
16
20
24
28
32
36
40
44
48
Final 
Efficacy 
Visitd/
Week 52
Final 
Safety
Visitb/ 
Week 60
Study Proceduresd
Enthesitis assessments 
(LEI, SPARCC)
X
X
X
X
X
X
X
X
BASDAIr,s
X
X
X
X
X
SF-36r
X
X
X
X
X
X
FACIT-fatiguer
X
X
X
X
X
X
PROMIS 29r
X
X
X
X
X
X
BSA % Involvement of 
Psoriasis
X
IGA – Psoriasis
X
X
X
X
PASI
X
X
X
X
Clinical Laboratory Assessments
QuantiFERON®-TB testt
X
Hepatitis B and C 
Serologiesu
X
HIV Antibody Testu
X
Hematologyu
X
X
X
X
X
X
X
X
X
X
X
X
X
Chemistryu
X
X
X
X
X
X
X
X
X
X
X
X
X
Lipid Panelu
X
C-reactive Proteinu
X
X
X
X
X
X
X
X
X
X
X
X
X
Rheumatoid factoru,v
X
Follicle Stimulating 
Hormoneu,w
X
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
30
Approved, Date: 25 January 2018
Table 1:
TIME AND EVENTS SCHEDULE FROM SCREENING THROUGH WEEK 60
Phase
Screeninga
Placebo-controlled Treatmentb
Active Treatmentb
Safety 
Follow-
up
Week
0c
4
8
12
16
20
24
28
32
36
40
44
48
Final 
Efficacy 
Visitd/
Week 52
Final 
Safety
Visitb/ 
Week 60
Study Proceduresd
Pharmacokinetics/ Immunogenicityx
Serum guselkumab 
concentration
X
X
X
X
X
X
X
X
X
X
X
X
Population PK
Xy
Antibodies to study 
agent
X
X
X
X
X
X
X
Pharmacogenomics (DNA)
DNA Collection (Whole 
Blood in EDTA)f
X
X
X
X
Other Biomarkers
Serum Biomarkers
X
X
X
X
Whole Blood (RNA)
X
X
X
X
Ongoing Subject Review
Concomitant therapy
X-----------------------------------------------------------------------------------------------------------------------------------------------------------------X
Adverse events
X-----------------------------------------------------------------------------------------------------------------------------------------------------------------X
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
31
Approved, Date: 25 January 2018
Table 1:
TIME AND EVENTS SCHEDULE FROM SCREENING THROUGH WEEK 60
Phase
Screeninga
Placebo-controlled Treatmentb
Active Treatmentb
Safety 
Follow-
up
Week
0c
4
8
12
16
20
24
28
32
36
40
44
48
Final 
Efficacy 
Visitd/
Week 52
Final 
Safety
Visitb/ 
Week 60
Study Proceduresd
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 the remainder 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 ± 4 days; after Week 24, study visits at the site will have a visit window of ± 7 days; Week 60 or the
final safety visit (12 weeks after the last dose in subjects who discontinued study treatment) will have a visit window of ±14 days.
c: Subjects must fast (ie, no food or beverages [except water]) for at least 8 hours before blood is drawn for lipid panel (Week 0). All other visits can be non-fasting.
d: If a subject permanently discontinues study agent administration at or after the Week 24 and before the Week 52 visit, the final efficacy visit should occur at the 
time of discontinuation or as soon as possible and all assessments under the Week 52/final efficacy visit should be performed. 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 consent to participate in the study, and to obtain informed consent to participate in the 
optional DNA research component of the study, as applicable.
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 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.
Safety and efficacy assessments, including blood samples for clinical laboratory and pharmacokinetics/immunogenicity, should be performed before study agent 
administration.
h: The option to begin self-administration of study agent at home will begin at Week 32; subjects will record study agent administration on a diary card. Subjects who 
self-administer are not required to visit the study site at Weeks 32, 40 and 48. 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 site 
at the time of injection.
i: At Week 16, all subjects who qualify for early escape will continue on the dosing regimen to which they were randomized 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 Table 3, at the discretion of the 
investigator. Titration to a stable dose of the medication should be completed for subjects qualifying for early escape by the Week 24 visit.
j: 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 should be the first assessment/questionnaire that the subject completes prior to study agent administration. See Section 9.4.2 for more details.
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
32
Approved, Date: 25 January 2018
Table 1:
TIME AND EVENTS SCHEDULE FROM SCREENING THROUGH WEEK 60
Phase
Screeninga
Placebo-controlled Treatmentb
Active Treatmentb
Safety 
Follow-
up
Week
0c
4
8
12
16
20
24
28
32
36
40
44
48
Final 
Efficacy 
Visitd/
Week 52
Final 
Safety
Visitb/ 
Week 60
Study Proceduresd
k: Vital signs include blood pressure and heart rate.
l: 12-lead ECG must be done prior to administration of study agent.
m: Subjects (as outlined in Inclusion Criterion 15) must undergo testing for TB (Attachment 2 or 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.
n: The chest radiograph may be taken within 3 months prior to the first administration of study agent.
o: Females of childbearing potential who are dosed at the clinic must have a negative urine pregnancy test at all dosing visits prior to administration of study agent.  For 
subjects not dosed at the clinic a urine pregnancy test is not required prior to administration of study agent.
p: Only performed for subjects who are dosed at the site.
q: 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. 
r: 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.  
s: The BASDAI will be completed only in subjects with spondylitis with peripheral arthritis as their primary arthritic presentation of PsA (confirmation of sacroiliitis 
should be performed at the screening visit by the investigator, with documentation of spondylitis from a prior pelvic or SI joint x-ray or pelvic MRI when 
available).     
t: 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 Criterion 15.
u: Laboratory tests are listed in Section 9.4.1.
v: This test is optional.  It can be done only if needed to confirm whether CASPAR criteria are met.
w: Prior to randomization, FSH is required for selected female subjects with amenorrhea for less than 12 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 with amenorrhea for at least 12 
months. Refer to Inclusion Criterion 11 for details.
x: 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.
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
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Approved, Date: 25 January 2018
y: 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 cannot be collected 
within 24 hours (either prior to or after) of the actual time of study agent administration at Weeks 4, 8 or 12.  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; 
DNA = deoxyribonucleic acid; ECG = electrocardiogram; eC-SSRS = electronic Columbia-Suicide Severity Rating Scale; EDTA = ethylenediaminetetraacetic acid; 
eICF = electronic informed consent form; 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; PROMIS = Patient-Reported Outcomes Measurement 
Information System; PsA = psoriatic arthritis; RNA = ribonucleic acid; SF-36 = 36-item short form health survey; SPARCC = Spondyloarthritis Research 
Consortium of Canada; TB = tuberculosis; VAS = visual analog scale
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
34
Approved, Date: 25 January 2018
ABBREVIATIONS
ACR
American College of Rheumatology
AE
adverse event
ALT
alanine aminotransferase
AMDF
Arithmetic Mean of the Desirability Function
ARC
Anticipated Event Review Committee
AST
aspartate aminotransferase
BASDAI
Bath Ankylosing Spondylitis Disease Activity Index
BCG
bacille Calmette-Guérin
BSA
body surface area
CASPAR
ClASsification criteria for Psoriatic Arthritis
CMH
Cochran-Mantel-Haenszel 
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
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
eICF
electronic informed consent form
FACIT
Functional Assessment of Chronic Illness Therapy
FAS
full analysis set
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GH
Patient’s Global Assessment of Disease Activity
GRACE
GRAppa Composite score
GRAppa
Group for Research and Assessment of Psoriasis and Psoriatic Arthritis
HAQ
Health Assessment Questionnaire
HAQ-DI
Health Assessment Questionnaire-Disability Index
HBsAg
hepatitis B surface antigen
HBV
Hepatitis B virus
HCP
Health care profressional
HCQ
Hydroxychloroquine
HCV
hepatitis C virus
HIV
human immunodeficiency virus
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Conference on Harmonisation
IEC
Independent Ethics Committee
IGA
Investigator’s Global Assessment
IgG
Immunoglobulin G
IJA
independent joint assessor
IL
Interleukin
IRB
Institutional Review Board
IV
Intravenous
IWRS
interactive web response system
JAK
Janus kinase
LEF
Leflunomide
LEI
Leeds Enthesitis Index
MAR
missing at random
MCP
metacarpophalangeal 
MCS
Mental Component Summary
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MDA
minimal disease activity
MI
multiple imputation
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
pharmacodynamics(s)
PFS
prefilled syringe
PFS-U
prefilled syringe with an UltraSafe PLUSTM Passive™ Delivery System
PGA
Physician’s Global Assessment
PK
pharmacokinetic(s)
PQC
Product Quality Complaint
PRO
patient-reported outcome(s) (paper or electronic as appropriate for this study)
PROMIS 
Patient-Reported Outcomes Measurement Information System
PsA
psoriatic arthritis
PsARC
Psoriatic Arthritis Response Criteria
PsAQOL
Psoriatic Arthritis Quality of Life Index
q4w
Every 4 weeks
q8w
every 8 weeks
q12w
every 12 weeks
RA
rheumatoid arthritis
RNA
ribonucleic acid
SAE
serious adverse event
SAP
Statistical Analysis Plan
SC
Subcutaneous
SF-36
36-item short form health survey
SPARCC
Spondyloarthritis Research Consortium of Canada
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
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1.
INTRODUCTION
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.
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 Brochure for 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
Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy of the peripheral and axial joints 
associated with psoriasis.42 The estimated prevalence of PsA in the general population varies 
from 0.02% to 1.0% across the world.11,42  In patients with psoriasis, the prevalence of PsA 
ranges from 6% to 42%.11 Psoriatic arthritis is a multi-faceted disease that impacts the joints, soft 
tissues, and skin, all of which affect quality of life.14,41  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.52  Psoriatic arthritis not only results in functional disability 
and impaired quality of life, but patients with this disease have increased mortality.12,43,45,51
1.1.2.
Treatment Options
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-17 inhibitor) 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.
Despite these recent advances in treatment options for PsA, there remains an unmet medical need 
for novel therapeutic agents that address the heterogeneous clinical manifestations of PsA and 
offer an improved benefit/risk profile for the individual patient. 
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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, 15 clinical 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 
Part 2 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 active rheumatoid arthritis (RA) despite concomitant MTX therapy. 
Further development of guselkumab in the RA indication has been 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.

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.

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. 
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CNTO 1959 (guselkumab)
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
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) 
are presented 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 details are provided in the guselkumab Investigator’s Brochure (IB).
1.1.3.1.
Phase 2 Study in Psoriatic Arthritis (CNTO1959PSA2001)
Study Design
CNTO1959PSA2001 is a Phase 2a, multicenter, randomized, double-blind, placebo-controlled, 
study evaluating the efficacy and safety of guselkumab in subjects with active PsA and ≥3% 
body surface area (BSA) of plaque psoriasis despite current or previous treatment with 
standard-of-care therapies, including those previously exposed to anti-TNFα agents.  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 counts qualified for early escape and switched to open-label therapy 
with ustekinumab.  At Week 24, subjects remaining in the placebo group crossed over to receive 
guselkumab 100 mg at Weeks 24, 28, then q8w through Week 44. All subjects will have a final 
follow-up visit at Week 56.
Preliminary efficacy, safety and PK results through Week 24 are summarized below:
Efficacy Results
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 2). 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 
(60.0% vs. 16.3%, p<0.001) versus placebo. Other secondary efficacy endpoints are summarized 
in Table 2. These results demonstrated that treatment with guselkumab significantly improved 
joint symptoms, physical function, psoriasis, enthesitis, dactylitis and quality of life in this 
population.
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Table 2:
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 Enthesitis 
Index (LEI)a
-33.33%
-100.00%
p=0.009
% of patients with unresolved enthesitis a
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; 
MCS = mental component summary; MDA = minimal disease activity; PASI = Psoriatic Area and Severity Index; 
PCS = physical component summary; SD = standard deviation
Safety Results
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 was reported in 5 (10.2%) 
subjects in the placebo group and 6 (6.0%) subjects in the guselkumab group. No injection site 
reactions were reported in the guselkumab group. Two serious adverse events (SAEs) were 
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 
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administration after the Week 24 visit. 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 requiring oral 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 
following SC 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 
demonstrated robust efficacy across all efficacy endpoints on joint signs and symptoms, physical 
function, skin disease, enthesitis, dactylitis, and health-related quality of life.
Efficacy was generally demonstrated both in subjects receiving MTX and in subjects not 
receiving MTX.  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 SC dose 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®) 80 mg at Week 0, 40 mg at 
Week 1, and then 40 mg every 2 weeks (q2w). 
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 
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CNTO 1959 (guselkumab)
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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 a PGA 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 adverse events (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, 
1 malignancy (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
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.
Conclusions
Treatment with guselkumab was well tolerated across a wide range of doses and led to 
substantial, clinically meaningful improvements in psoriasis, with several dose regimens yielding 
superior outcomes to those observed with adalimumab.
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Approved, Date: 25 January 2018
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 0, 4, and every 8 weeks thereafter:  

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
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: 
placebo, ustekinumab 90 mg q8w, ustekinumab 90 mg q12w, guselkumab 50 mg q8w, or 
guselkumab 200 mg q8w through Week 28 with induction doses at Weeks 0 and 4. After the last 
study agent administration at Week 28, subjects were followed for safety through Week 48.
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CNTO 1959 (guselkumab)
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Conclusions
The primary efficacy endpoint (ACR 20 response at Week 28) was not met in the guselkumab 
groups and 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-23.35  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 downstream pro-inflammatory cytokines, IL-17A, IL-17F, IL-22, IL-6, 
and TNFα.4,24,46
Inhibition of upstream signaling by IL-23 blockade is expected to interrupt Th17 pathways that 
contribute to the chronic inflammation underlying the pathophysiology of many immune 
mediated diseases37,44 including 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
components.1,6,25,34,36
In addition to the robust efficacy demonstrated in the treatment of psoriasis, biologic treatments 
targeting Th17 pathways, including ustekinumab, secukinumab, and ixekizumab, have been 
shown to induce rapid and significant improvement of arthritis and psoriasis in subjects with 
active PsA. The efficacy and safety of ustekinumab, a fully human IgG1κ 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 (1 Phase 2 study, 
C0743T1016; 
and 
2 
Phase 
3 
studies, 
CNTO1275PSA3001 
[PSUMMIT1]22,27
and 
CNTO1275PSA3002 [PSUMMIT240]).  In the Phase 3 PsA studies FUTURE 128,  FUTURE 232, 
and SPIRIT-P129, 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 endpoints in the Phase 2 PsA study (CNTO1959PSA2001; Section 1.1.3.1), highlights 
the central role that IL-23/IL-17 axis has in the pathogenesis of both psoriasis and PsA.
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Approved, Date: 25 January 2018
1.2.2.
Study Rationale
Psoriatic arthritis is 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 which the primary and all secondary endpoints were met.

Efficacy and safety results of guselkumab observed in Phase 2 and Phase 3 studies in 
psoriasis including the subset of subjects with PsA (Sections 1.1.3.2 and 1.1.3.3, 
respectively).
The purpose of this study is to further define the clinical efficacy of guselkumab in the reduction 
of signs and symptoms and to evaluate the safety profile of guselkumab in the treatment of PsA.
1.2.3.
Dose Rationale
Based upon guselkumab clinical efficacy, safety, PK data, and exposure-response modeling 
analysis using data from the Phase 2 study (CNTO1959PSA2001) in subjects with PsA, 2 dose 
regimens have been chosen for evaluation in the guselkumab Phase 3 PsA program: 

100 mg Weeks 0 and 4 then q8w 

100 mg q4w  
The rationale for these dose regimens of guselkumab is presented below in Section 1.2.3.1
(100 mg Weeks 0 and 4 then q8w) and Section 1.2.3.2 (100 mg q4w).
1.2.3.1.
Rationale for Guselkumab 100 mg at Weeks 0 and 4, then Every 
8 Weeks Dose Regimen

This dose regimen was evaluated in the Phase 2 PsA study (CNTO1959PSA2001) and in the 
3 global Phase 3 studies in psoriasis. In the CNTO1959PSA2001 study, robust efficacy and 
clinically meaningful improvement was observed with this dose regimen in all important 
domains of PsA including joint signs and symptoms, physical function, psoriasis, enthesitis, 
dactylitis, and quality of life in patients with active PsA and ≥3% BSA of psoriasis 
(Section 1.1.3.1). Additionally, significant benefit was also observed with this dose regimen 
on plaque psoriasis in patients with moderate-to-severe psoriasis in the Phase 3 psoriasis 
studies (Section 1.1.3.3).  

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 
Ctrough in the first 12 weeks than those at steady state (~21% and ~18%, respectively) and 
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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 psoriasis studies support 
further evaluation of this dose regimen in the Phase 3 PsA studies.
1.2.3.2.
Rationale for Guselkumab 100 mg Every 4 Weeks Dose Regimen

A dose regimen of 100 mg q4w is being included in this study in order to determine if more 
frequent dosing may achieve higher efficacy in PsA.

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 modeling and simulation, the 100 mg 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 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 have lower efficacy (ie, ACR responses).

Patients who have had inadequate response to anti-TNFα or other biologic treatments are 
more difficult to treat and may benefit from a higher dose.27  

Treatment with the 100 mg q4w dose regimen is expected to result in acceptable safety 
based on the exposure-safety analysis in the Phase 3 psoriasis program:

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.

Guselkumab has been shown to have an acceptable safety profile in multiple patient 
populations, including with a higher dose regimen that was studied in a Phase 2 RA study 
(200 mg q8w).  Therefore, guselkumab 100 mg q4w is expected to be well tolerated in the 
Phase 3 PsA population. 
Overall, the two dose regimens of guselkumab (100 mg at Weeks 0 and 4 then q8w and 100 mg 
q4w) selected for the Phase 3 PsA program will allow for an adequate assessment of the optimal 
benefit/risk profile of guselkumab in PsA.
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2.
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS
2.1.
Objectives and Endpoints
2.1.1.
Objectives
Primary Objectives
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 

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 9 for evaluations related to endpoints.
Primary Endpoint
The primary endpoint is the proportion of subjects who achieve an ACR 20 response at Week 24.
Major Secondary Endpoints
1.
Change from baseline in Health Assessment Questionnaire-Disability Index (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 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 DAS28 (C-reactive protein [CRP]) at Week 24.
6.
Proportion of subjects who achieve an ACR 70 response at Week 24.
7.
Proportion of subjects who achieve an ACR 50 response at Week 16.
8.
Change from baseline in 36-item short form health survey (SF-36) Physical Component
Summary (PCS) at Week 24.
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9.
Proportion of subjects with resolution of enthesitis at Week 24 among the subjects with
enthesitis at baseline.
10. Change from baseline in enthesitis score (based on Leeds Enthesitis Index [LEI]) at 
Week 24 among the subjects with enthesitis at baseline. 
11. Change from baseline in SF-36 Mental Component Summary (MCS) at Week 24. 
12. Proportion of subjects with resolution of dactylitis at Week 24 among the subjects with   
dactylitis at baseline.
13. Change from baseline in dactylitis scores at Week 24 among the subjects with dactylitis at
baseline. 
Other Secondary Endpoints
Endpoints Related to Reduction of Signs and Symptoms and Physical Function
1.
Proportion of subjects who achieve ACR 20, ACR 50, and ACR 70 responses by visit over 
time through Week 52.
2.
Percent change from baseline in ACR components by visit over time through Week 52.
3.
Change from baseline in HAQ-DI score by visit over time through Week 52.
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 52
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 52.
6.
Proportion of subjects who achieve a DAS28 (CRP) remission by visit over time through 
Week 52.
7.
Change from baseline in DAS28 (CRP) by visit over time through Week 52.
8.
Proportion of subjects who achieve a response based on modified Psoriatic Arthritis 
Response Criteria (PsARC) by visit over time through Week 52.
9.
Proportion of subjects with resolution of enthesitis by visit over time through Week 52 
among the subjects with enthesitis at baseline.
10. Proportion of subjects with resolution of dactylitis by visit over time through Week 52 
among subjects with dactylitis at baseline.
11. Change from baseline in enthesitis score (based on LEI) by visit over time through Week 52 
among the subjects with enthesitis at baseline.
12. Change from baseline in enthesitis score (based on Spondyloarthritis Research Consortium 
of Canada [SPARCC]) by visit over time through Week 52 among the subjects with 
enthesitis at baseline.
13. Change from baseline in dactylitis score by visit over time through Week 52 among the 
subjects with dactylitis at baseline.
14. Change from baseline in Psoriatic ArthritiS Disease Activity Score (PASDAS) by visit score
over time through Week 52.
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15. Change from baseline in GRAppa Composite scorE (GRACE) Index by visit over time 
through Week 52.
16. Change from baseline in Disease Activity Index for Psoriatic Arthritis (DAPSA) score by 
visit over time through Week 52.
17. Proportion of subjects who maintain an ACR 20 response at Week 52 among subjects who 
achieved an ACR 20 response at Week 24. 
18. Proportion of subjects who maintain an ACR 50 response at Week 52 among subjects who 
achieved an ACR 50 response at Week 24.
19. Proportion of subjects who maintain an ACR 70 response at Week 52 among subjects who 
achieved an ACR 70 response at Week 24.
20. Proportion of subjects who maintain a HAQ-DI response (ie, ≥0.35 improvement from 
baseline in HAQ-DI score) at Week 52 among subjects who achieved a HAQ-DI response at 
Week 24.
21. Proportion of subjects who achieve minimal disease activity (MDA) by visit over time 
through Week 52.
22. 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 52 among subjects with spondylitis and peripheral joint 
involvement as their primary arthritic presentation of PsA.
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 52 among 
subjects with ≥3% BSA psoriatic involvement and an IGA score of ≥2 (mild) at baseline.
2.
Proportion of subjects with an IGA score of 0 (cleared) by visit over time through Week 52 
among 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 52 among subjects 
with ≥3% BSA psoriatic involvement and an IGA score of ≥2 (mild) at baseline.
4.
Proportion of subjects who achieve both PASI 75 and ACR 20 responses by visit over time 
through Week 52 among subjects with ≥3% BSA psoriatic involvement and an IGA score of 
≥2 (mild) at baseline.
5.
Proportion of subjects who achieve both PASI 75 and modified PsARC response by visit 
over time through Week 52 among subjects with ≥3% BSA psoriatic involvement and an 
IGA score of ≥2 (mild) at baseline.
Endpoints Related to Health Related Quality of Life
1.
Change from baseline in SF-36 PCS score by visit over time through Week 52.
2.
Change from baseline in SF-36 MCS score by visit over time through Week 52.
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3.
Change from baseline in domain scales scores of SF-36 by visit over time through Week 52.
4.
Proportion of subjects who achieve ≥5-point improvement from baseline in SF-36 MCS 
score by visit over time through Week 52.
5.
Proportion of subjects who achieve ≥5-point improvement from baseline in SF-36 PCS 
score by visit over time through Week 52.
6.
Change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue
(FACIT-Fatigue) by visit over time through Week 52.
7.
Proportion of subjects who achieve ≥4-point improvement from baseline in FACIT-Fatigue 
score improvement by visit over time through Week 52.
8.
Change from baseline in Patient-Reported Outcomes Measurement Information System
(PROMIS) 29 scores by visit over time through Week 52.
Refer to Section 9, Study Evaluations for evaluations related to endpoints.
2.2.
Hypothesis
The primary hypothesis is that the guselkumab 100 mg q4w treatment group is superior to 
placebo as 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 3, multicenter, randomized, double-blind, placebo-controlled, 3-arm study of 
guselkumab in subjects with active PsA who had inadequate response to standard therapies (eg, 
non-biologic disease-modifying antirheumatic drugs [DMARDs], apremilast, or NSAIDs). In 
addition, subjects (approximately 30%) may have been previously treated with up to 2 anti-
TNFα agents. The study will include approximately 360 subjects. Stable doses of concomitant 
NSAIDs, oral corticosteroids, and selected non-biologic DMARDs (limited to MTX, SSZ, HCQ, 
and LEF) will be allowed (Table 3) but are not required.
The study consists of the following phases:

a screening phase of up to 6 weeks

a blinded treatment phase of approximately 1 year (ie, 52 weeks), including a 
placebo-controlled period from Week 0 to Week 24 and an active treatment period from 
Week 24 to Week 52.

a safety follow-up phase of 8 weeks after Week 52.
An overview of the study design is provided in Figure 1.
At Week 0, approximately 360 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 
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block randomization stratified by baseline non-biologic DMARD (MTX, SSZ, HCQ, LEF) use 
(yes/no) and by prior exposure to anti-TNFα agents (yes/no):

Group I (n=120): Subjects will receive SC guselkumab 100 mg every 4 weeks (q4w) from 
Week 0 through Week 48.

Group II (n=120): Subjects will receive SC guselkumab 100 mg at Weeks 0 and 4, then 
q8w (Weeks 12, 20, 28, 36, and 44) and placebo injections at other visits (Weeks 8, 16, 24, 
32, 40, 48) to maintain the blind. 

Group III (n=120): Subjects will receive SC placebo q4w from Week 0 to Week 20, and 
will crossover at Week 24 to receive guselkumab 100 mg q4w through Week 48.
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 as specified in Table 3
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 52; 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 Week 52.
Subjects will be followed for new 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 
study visit. For subjects who complete the Week 52 visit, the last study visit is the Week 60 visit.  
For subjects who discontinue study agent prior to Week 52, the last study visit is the final safety 
visit (12 weeks after the last study agent administration).
Database locks are scheduled at Weeks 24 and End of Study (Week 60).  The first DBL will 
occur when all randomized subjects have either completed the Week 24 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 their final safety 
visit or 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 least the Week 24 DBL to ensure the continuing safety of the 
subjects enrolled in this study. Refer to Section 11.11 for 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.
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The study schema through Week 60 is presented in Figure 1.
Figure 1:
Study Schema – Study CNTO1959PSA3001
3.2.
Study Design Rationale
3.2.1.
Study Population
The target study population is subjects with active PsA who have had inadequate response to 
standard therapies (eg, non-biologic DMARDs, apremilast or NSAIDs). In addition, 
approximately 30% of the study population may have been previously exposed to up to
2 anti-TNFα agents. Stable doses of concomitant NSAIDs, oral corticosteroids, and selected 
non-biologic DMARDs (limited to MTX, SSZ, HCQ, or LEF) will be allowed but are not 
required. This population is considered appropriate to provide relevant efficacy and safety 
information for the intended use of guselkumab in PsA. 
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 4 phases 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 of the 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 Weeks 20 to 24 of treatment based on 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 52. This duration will provide adequate time to evaluate the maintenance of 
the efficacy and long-term safety of guselkumab in PsA over a 1-year exposure period. 

The fourth phase of the study will be the safety follow-up phase (Week 52 to 60) and will be 
12 weeks from the last administration of study agent (at Week 48) to the final safety 
follow-up visit. The safety follow-up allows for monitoring of the subjects for a period 
equivalent to approximately 5 times 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 studies of 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 1) 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 9.4. Safety data will be 
reviewed by the Sponsor’s Medical Monitor on an ongoing basis. An independent DMC 
composed of clinicians and statisticians not associated with the conduct of the study will review 
unblinded study data for safety purposes on a periodic basis through at least the 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 Time and Events 
Schedule (Table 1).
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 efficacy of
guselkumab and 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 evaluate the pharmacodynamics of guselkumab and aid in evaluating the drug-clinical 
response relationship.
DNA and biomarker samples may be used to help address emerging issues and to enable the 
development of safer, more effective, and ultimately individualized therapies.
4.
SUBJECT POPULATION
Adult subjects age 18 and older with active PsA are eligible for the study.
Screening for eligible subjects will be performed within 6 weeks before administration of the 
study agent.
The inclusion and exclusion criteria for enrolling subjects in this study are described in the
following 2 subsections. If there is a question about the inclusion or exclusion criteria below, the 
investigator must consult with the appropriate Sponsor representative and resolve any issues 
before enrolling a subject in the study. Waivers are not allowed.
For a discussion of the statistical considerations of subject selection, refer to Section 11.2.
4.1.
Inclusion Criteria
Each potential subject 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 
(Attachment 1).
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3.
Have active PsA as defined by:
a.
At least 3 swollen joints and at least 3 tender joints at screening and at baseline
-AND-
b. C-reactive protein (CRP) ≥0.3 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.
5.
Have active plaque psoriasis, with at least one psoriatic plaque of ≥2 cm diameter or nail 
changes consistent with psoriasis or documented history of plaque psoriasis.
6.
Have active PsA despite previous non-biologic DMARD, apremilast, and/or NSAID 
therapy.

Non-biologic DMARD therapy is defined as taking a non-biologic DMARD for at least 
3 months or evidence of intolerance.

Apremilast therapy is defined as taking apremilast at the marketed dose approved in the 
country where the study is being conducted for at least 4 months or evidence of 
intolerance.

NSAID therapy is defined as taking an NSAID for at least 4 weeks or evidence of 
intolerance.
7.
Subjects may have been previously treated with up to 2 anti-TNFα agents (approximately 
30% of the overall study population), and must document the reason for discontinuation.
a.
Lack of benefit to an anti-TNFα therapy, as assessed by the treating physician, after at 
least 12 weeks of etanercept, adalimumab, golimumab, or certolizumab pegol therapy 
(or biosimilar) and/or at least a 14 week dosage regimen (ie, at least 4 doses) of 
infliximab (or biosimilar).  Documented lack of benefit may include inadequate 
improvement in joint counts, physical function, or disease activity.
b.
Intolerance to an anti-TNFα biologic therapy, as assessed by the treating physician, to 
etanercept, adalimumab, golimumab, certolizumab pegol, or infliximab (or biosimilars).
c.
If no intolerance or lack of benefit, the reason for discontinuation must be documented.
8.
If currently using non-biologic DMARDs (limited to MTX, SSZ, HCQ, or LEF) subjects 
should have started treatment at least 3 months and the dose must be stable for at least 4 
weeks before first administration of study agent and should have no serious toxic side 
effects attributable to the non-biologic DMARD. If currently not using a MTX, SSZ, or 
HCQ, must have not 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 using MTX, the route of administration and dose must be stable and the dose must be 
≤25 mg/week.
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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.
9.
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 
2 weeks before first administration of study agent.
10. If currently using oral corticosteroids for 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. 
If currently not using oral corticosteroids, the subject must not have received oral 
corticosteroids within 2 weeks before first administration of study agent.
11. Contraceptive use by men or women should be consistent with local regulations regarding 
the use of contraceptive methods for subjects 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: implantable progestogen-only hormone contraception 
associated with inhibition of ovulation; intrauterine device; intrauterine hormone-
releasing system; 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 
agent. 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.
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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.

Agree to remain on a highly effective method throughout the study and for at least 12 
weeks after the last dose of study agent.
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. 
12. A woman of childbearing potential must have a negative serum pregnancy test at screening 
and a negative urine pregnancy test at Week 0.
13. 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.
14. 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 or a partner with an occlusive cap 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 available in their locale], during the study 
and for at least 12 weeks after receiving the last administration of study agent. All men must 
also agree to not donate sperm during the study and for at least 12 weeks after receiving the 
last administration of study agent.
15. 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 5 
years prior to the first administration of study agent. It is the responsibility of the 
investigator to verify the adequacy of previous anti-tuberculosis 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 to the 
first administration of study agent.

Within 8 weeks prior to the 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 to the 
first administration of study agent. Within 8 weeks prior to the first administration of 
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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®-TB Gold 
test is not approved/registered in that country* or the tuberculin skin test is mandated by 
local health authorities.

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.
16. Agree not to receive a live virus or live bacterial vaccination during the study, or within 
12 weeks after the last administration of study agent.
17. Agree not to receive a Bacillus Calmette-Guérin (BCG) vaccination during the study, and 
within 12 months after the last administration of study agent.
18. Have screening laboratory test results within the following parameters:
a.
Hemoglobin
≥8.5 g/dL
(SI: ≥85 g/L) 
b. White blood cells
≥3.5 x 103/µL
(SI: ≥3.5 GI/L)
c.
Neutrophils
≥1.5 x 103/µL
(SI: ≥1.5 GI/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 ≤1.5 times the upper limit of normal range for the central 
laboratory conducting the test.
NOTE: 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.
19. 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 
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after the final dose of study agent (Week 60) (for patients with skin lesions or with 
documented history of psoriasis).
20. Are willing to refrain from the use of complementary therapies for PsA or psoriasis 
including ayurvedic medicine, traditional Taiwanese, Korean, or Chinese medications and 
acupuncture within 2 weeks before the first study agent administration and through 
Week 52.
21. Be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
22. Sign an informed consent form (ICF/eICF) indicating that he or she understands the purpose 
of and procedures required for the study and is willing to participate in the study.
23. 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 of benefit 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 ever received more than 2 anti-TNFα agents.
3.
Has received an anti-TNF agent within the following timeframes:
Anti-TNFtherapy
Treatment prior to first study agent 
administration
Infliximab (or biosimilar), golimumab IV
8 weeks
Golimumab SC, adalimumab (or biosimilar) 
certolizumab pegol
6 weeks
Etanercept (or biosimilar)
4 weeks
a.
Has received infliximab (or its biosimilars) or golimumab (IV) within 8 weeks before 
the first administration of study agent.
b.
Has received golimumab SC, adalimumab (or its biosimilars) or certolizumab pegol 
within 6 weeks before the first administration of study agent.
c.
Has received etanercept (or its biosimilars) within 4 weeks before the first 
administration of study agent.
4.
Has previously been treated with guselkumab.
5.
Has previously received any biologic treatment (other than anti-TNFα agents), including, 
but not limited to ustekinumab, abatacept, secukinumab, tildrakizumab, ixekizumab, 
brodalumab, risankizumab, or other investigative biologic treatment.
6.
Has previously received tofacitinib, baricitinib, filgotinib, peficitinib (ASP015K), 
decernotinib (VX-509), or any other Janus kinase (JAK) inhibitor.
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7.
Has previously received any systemic immunosuppressants (eg, azathioprine, cyclosporine, 
6-thioguanine, mercaptopurine, mycophenolate mofetil, hydroxyurea, tacrolimus) within 4 
weeks of the first administration of study agent.
8.
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.
9.
Is currently receiving 2 or more non-biologic DMARDs specified in Table 3 at baseline.
10. Has received apremilast within 4 weeks prior to the first administration of study agent.
11. Has received phototherapy or 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 Table 3
within 4 weeks of the first administration of study agent.
12. 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.
13. Has received epidural, intra-articular, intramuscular, or IV corticosteroids, including 
adrenocorticotropic hormone during the 4 weeks before first administration of study agent.
14. Has received lithium within 4 weeks of the first administration of any study agent. 
15. Has received an experimental antibody or biologic therapy (other than the anti-TNFs 
described in Exclusion Criterion 3) or received any other experimental therapy, including an 
investigational medical device within 90 days 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.
16. Has unstable suicidal ideation or suicidal behavior in the last 6 months, that may be defined 
as an electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) rating at screening of:

Ideation Level 4: Some intent to act, no plan, OR

Ideation Level 5: Specific plan and intent, OR 

Any of the following suicidal behaviors:
–
Actual suicide attempts
–
Interrupted attempts
–
Aborted Attempts
–
Preparatory actions
AND is 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.
17. Has a history or current signs or symptoms of severe, progressive, or uncontrolled renal, 
hepatic, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, 
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rheumatologic (with the exception of PsA), psychiatric, genitourinary, or metabolic 
disturbances.
18. 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.
19. 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 
3 months before the first study agent administration).
20. 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.
21. 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 infected skin wounds or ulcers.
22. Has a transplanted organ (with exception of a corneal transplant >3 months before the first 
administration of study agent).
23. 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.
24. 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.
25. Has or has had a herpes zoster infection within 2 months before screening.
26. Is pregnant, nursing, or planning a pregnancy (both men and women) within 12 weeks after 
receiving the last administration of study agent.
27. Has a nonplaque form of psoriasis (eg, erythrodermic, guttate, or pustular).
28. Has current drug-induced psoriasis (eg, a new onset of psoriasis or an exacerbation of 
psoriasis from beta blockers, calcium channel blockers, or lithium).
29. Has received, or is expected to receive, any live virus or bacterial vaccination within 
3 months before the first administration of study agent.
30. Has had a BCG vaccination within 12 months of screening.
31. 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.
32. Subject has known allergies, hypersensitivity, or intolerance to guselkumab or its excipients 
(refer to IB).
33. Has a history of active granulomatous infection, including histoplasmosis or 
coccidioidomycosis, before screening. Refer to Inclusion Criterion 15 for information 
regarding eligibility with a history of latent TB.
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34. 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.
35. Has ever had a nontuberculous mycobacterial infection or opportunistic infection (eg, 
cytomegalovirus, pneumocystosis, aspergillosis).
36. Is infected with human immunodeficiency virus (HIV, a confirmed positive serology for 
HIV antibody).
37. Tests positive for hepatitis B virus (HBV) infection (Attachment 4) at screening.
38. Is seropositive for antibodies to hepatitis C virus (HCV) at screening, unless the subject had 
2 negative HCV ribonucleic acid (RNA) test results at least 6 months apart prior to 
screening and have a third negative HCV RNA test result at screening.
39. 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.
Note: Subjects with planned surgical procedures to be conducted under local anesthesia may 
participate.
40. Is known to have had a substance abuse (drug or alcohol) problem within the previous 
12 months prior to the first administration of study agent.
41. Is unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack 
of easy access to veins.
42. Lives in an institution on court or authority order.
43. 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.
44. 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.
45. Is an employee of the Sponsor.
NOTE: Investigators should ensure that all study enrollment criteria have been met at screening. 
If a subject's clinical status changes (including any available laboratory results or receipt of 
additional medical records) after screening but before the first dose of study agent is given such 
that he or she no longer meets all eligibility criteria, then the subject should be excluded from 
participation in the study. Section 17.4 describes the 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:
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1.
A woman of childbearing potential who is heterosexually active must remain on a highly 
effective method of birth control (Inclusion Criteria 11) during the study and for at least 
12 weeks after receiving the last administration of study agent.
2.
A woman must not currently be pregnant or breastfeeding and should agree to plan to not 
become pregnant.
3.
A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted 
reproduction during the study and for 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 Criterion 14) during the study and for at 
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 during the study and for 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 
12 weeks 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.
7.
Subjects must not receive a BCG vaccination during the study and for 12 months after the 
last administration of study agent.
8.
Subjects must comply with restrictions on concomitant medications and therapies during the 
study (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 ALLOCATION AND BLINDING
Treatment Allocation
Procedures for Randomization and Stratification
Central randomization will be implemented in this study.  At Week 0, subjects will be randomly 
assigned (1:1:1) to 1 of 3 treatment groups (guselkumab 100 mg q4w, guselkumab 100 mg 
Weeks 0, 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 by baseline non-biologic DMARD (MTX, SSZ, HCQ, LEF) 
use (yes / no) and by prior exposure to anti-TNFα agents (yes/no) will be used.  The interactive 
web response system (IWRS) will assign a unique treatment code, which will 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 the IWRS and 
will then give the relevant subject details to uniquely identify the subject.
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Blinding
To maintain the study blind, the study agent container 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 agent container, and attached to the subject's source documents. The label will not identify 
the study agent in the container. However, if it is necessary for a subject's safety, the study blind 
may be broken and the identity of the study agent ascertained. The study agent number will be 
entered in the case report form (CRF) when the study agent is 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 Study DBL of the study.  Otherwise, the blind should be broken only if specific 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 
be documented by site personnel in the appropriate section of the case report form (CRF) 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 
some Sponsor 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 after the final database is locked.
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 PK and 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.
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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 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 Weeks 0 and 4. Beginning at Week 8, at the discretion of the investigator and 
subject, and after appropriate and documented training, subjects may self-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 an HCP. 
The option to begin self-administration of study agent at home will begin at Week 32. At 
Week 28, 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 or unwilling to have injection(s) administered away from site will be 
required to return to the site for administration of study agent injection(s) by an HCP. After 
Week 28, subjects will have study visits and assessments approximately every 8 weeks through 
Week 52.
Through Week 24, study agent administration at the site should be ±4 days from the scheduled 
day of study agent administration; after Week 24 all administrations should be ±7 days from 
scheduled study agent administration day. Study agent administrations must always be at least 
14 days apart.
The dose regimens are as follows:

Group I (n=120): Subjects will receive SC guselkumab 100 mg q4w from Week 0 through 
Week 48;

Group II (n=120): Subjects will receive SC guselkumab 100 mg at Weeks 0 and 4, then 
q8w (at Weeks 12, 20, 28, 36, 44) and placebo injections at other visits (Weeks 8, 16, 24, 
32, 40, 48) to maintain the blind.

Group III (n=120): 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 48.
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, 
they will be allowed to initiate or increase the dose of one of the permitted concomitant 
medications up to the maximum allowed dose as specified in Table 3, 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.
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7.
TREATMENT COMPLIANCE
Study agent will be administered at the investigational site through Week 28 and 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 self-administration at home, the 
investigator or designated study personnel will maintain a log of all study agent dispensed and 
returned.
When study agent is self-administered by subjects at home, subjects will record all study agent 
administrations on a diary card.
During the course of the study, the investigator or designated study research personnel will be 
responsible for 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 
still come in for the scheduled assessments at that visit.  The dose should be administered within 
2 weeks of that scheduled visit.  The subject should then resume the normal study schedule 
relative to the baseline visit (Week 0). In the case when a subject does not come into 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 agent 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.
Through Week 24, study visits will have a visit window of ±4 days. After Week 24, study visits 
at the site will have a visit window of ±7 days. The Week 60 visit or the safety visit (12 weeks 
after the last dose in subjects who discontinue 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 agent administrations that are administered outside of the scheduled 
windows or missed will be recorded. Subject charts and worksheets may be reviewed and 
compared with the data entries on the CRFs to ensure accuracy. 
8.
PRESTUDY AND CONCOMITANT THERAPY
The Sponsor must be notified in advance (or as soon as possible thereafter) of any instances in 
which prohibited therapies are administered.
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Every effort should be made to keep subjects’ concomitant medications for PsA stable through 
Week 60 or as specified in the following sections. The concomitant medication dose may be 
reduced or temporarily discontinued because of abnormal laboratory values, side effects, 
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.
Permitted concomitant medications for PsA and the maximum allowed doses during the study as 
specified in the following sections are summarized in Table 3.
Table 3:
Permitted Concomitant Medications for PsA and the Maximum Allowed Doses During the 
Study
Permitted Concomitant Medications
for PsAa,b
Maximum Allowed Dose
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 60. See 
Exclusion Criterion 9. 
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. For subjects receiving the allowed DMARDs, every effort should be made to maintain stable doses and 
route of administration of this medication through Week 60 of the study. 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 60, except at Week 16 for 
those subjects who have <5% improvement from baseline in both tender and swollen joint counts 
and will be allowed to initiate or increase the dose of one of the permitted concomitant
medications up to the maximum allowed dose as specified in Table 3, 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.
Concomitant medication review will occur at study visits identified in the Time and Events 
Schedule.
8.1.
Non-biologic DMARDs 
8.1.1.
Permitted Non-biologic DMARDs 
Subjects are permitted to enter the study on a stable dose of a non-biologic DMARD (limited to 
MTX, SSZ, HCQ, or LEF) up to the maximum allowed doses specified in Table 3. Only 1 of 
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these non-biologic DMARDs is allowed; subjects receiving 2 or more non-biologic DMARDs at 
baseline are excluded from study participation. For subjects receiving DMARDs, every effort 
should be made to maintain stable doses and route of administration of this medication through 
Week 60 of the study.
At any time during the study, the dose of the permitted non-biologic DMARDs may be reduced 
or temporarily discontinued due to abnormal laboratory values, side effects, concurrent illness, or 
the performance of a surgical procedure.
Refer to Table 4 for protocol requirements of the permitted non-biologic DMARDs.
Table 4:
Protocol Requirements of the Permitted Non-biologic DMARDs
Permitted Non-
biologic DMARDs
Baseline 
Usage
Prior to Week 0
Week 0 through Week 60
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 
agent and must be ≤ 25mg/week.
Stable dose and route of 
administration (oral, 
intramuscular, or SC 
permitted) required unless
early escape or unacceptable 
side effects
Not Used
Discontinued at least 4 weeks prior to the first 
administration of study agent
Not allowed unless early 
escape (see Section 6)
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 agent and must be ≤ 3 g/day (SSZ) or ≤ 
400mg/day (HCQ).
Stable dose required unless 
early escape or unacceptable 
side effects
Not Used
Discontinued at least 4 weeks prior to the first 
administration of study agent
Not allowed unless early 
escape (see Section 6)
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 agent and must be ≤ 20mg/day.
Stable dose required unless 
early escape or unacceptable 
side effects
Not Used
Discontinued at least 12 weeks prior to the 
first administration of study agent
Not allowed unless early 
escape (see Section 6)
8.1.2.
Prohibited Non-biologic DMARDs and Apremilast
All other non-biologic DMARDs (including, but not limited to chloroquine, gold preparations, 
and penicillamine) and apremilast must be discontinued at least 4 weeks prior to the first 
administration of study agent and remain prohibited through Week 60.
8.1.3.
Systemic Immunosuppressive Drugs
Systemic immunosuppressants (including, but not limited to azathioprine, cyclosporine, 
6-thioguanine, mercaptopurine, mycophenolate mofetil, hydroxyurea, or tacrolimus) must be 
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discontinued at least 4 weeks prior to the first administration of study agent and remain 
prohibited through Week 60. 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 8.2 for restrictions 
regarding the use of corticosteroids.
8.2.
Corticosteroids
8.2.1.
Oral Corticosteroids
Subjects not using oral corticosteroids at baseline for PsA must have discontinued oral 
corticosteroids at least 2 weeks prior to the first administration of study agent and must not 
receive oral corticosteroids through Week 60 of the study for PsA. An exception is made for 
subjects who qualify for early escape at Week 16 (see Section 3).
Subjects using oral corticosteroids at baseline for PsA must be on a stable dose equivalent to 
≤10 mg prednisone per day for at least 2 weeks prior to the first administration of study agent 
and continue on this dose through Week 60 unless early escape at Week 16 (see Section 3).
After Week 24 and through Week 60, a one-time dose decrease in oral corticosteroids is allowed; 
otherwise the dose and type of oral corticosteroid may be changed at the discretion of the 
investigator only if the subject develops unacceptable side effects.
8.2.2.
Corticosteroids – Intravenous, Intramuscular, or Epidural 
Administration 
Intravenous, intramuscular, or epidural administration of corticosteroids for the treatment of PsA 
is not allowed through Week 60.
Long-term, (>2 weeks), oral or IV corticosteroid use for indications other than PsA or psoriasis 
are not allowed through Week 60. 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.
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 
indications other than PsA and psoriasis are allowed throughout the course of the study.
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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, subjects must be on a stable dose for at least 2 weeks prior 
to the first administration of study agent and continue through Week 60 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 use of topical analgesics including capsaicin and diclofenac is allowed and should be 
recorded in the CRF. For topical and analgesic patches, the dose should be stable through 
Week 60 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 60 of the study. An 
exception is made for subjects who qualify for early escape at Week 16 (see Section 3).
After Week 24, a one-time dose decrease is allowed; otherwise, prescriptions of NSAIDs and 
other analgesics may be changed only if the subject develops unacceptable side effects.
Use of NSAIDs and other analgesics for indications other than PsA are permitted throughout the 
study.
In this study, aspirin is considered an NSAID, except for low-dose aspirin prescribed for
cardiovascular or cerebrovascular disease.
8.4.
Biologic Agents, Cytotoxic Drugs, JAK Inhibitors, or Investigational 
Agents
Biologic agents include, but are not limited to golimumab, anakinra, etanercept, adalimumab, 
infliximab, ustekinumab, alefacept, efalizumab, rituximab, natalizumab, 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. Janus 
kinase inhibitors include, but are not limited to tofacitinib, baricitinib, filgotinib, peficitinib 
(ASP015K), and decernotinib (VX-509).
The concomitant use of biologic agents, cytotoxic agents, JAK inhibitors, and investigational 
drugs is not allowed. 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 60.
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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 60.
Phototherapy including UVB or tanning beds are not permitted during the study through 
Week 60. Subjects should be 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 Table 3) must be 
discontinued at least 4 weeks prior to the first administration of study agent and is not permitted 
through Week 60; if a systemic anti-psoriatic treatment (except those in Table 3) 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 1) summarizes the frequency and timing of efficacy, PK,
immunogenicity, biomarker, and safety, measurements applicable to this study.
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 by the investigator or 
required by local regulation.
Except at the screening visit, all PRO assessments should be conducted/completed before 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 details, and the order for 
which they are to be performed, refer to the PRO user manuals.
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During screening, each subject will be provided with an electronic device to enter study-related 
data as 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 Sample Collection
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 to be collected in this study from each subject will be approximately
269 mL. Subjects who consent to participate in the optional pharmacogenomics will have an 
additional blood volume collected of approximately 40 mL, for a total of approximately 309 mL. 
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the 
samples.
9.1.3.
Screening Phase
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 that after obtaining informed consent, the investigator may 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. Subjects who meet all of the inclusion and none of the exclusion criteria will be enrolled 
in the study. Subjects who choose to participate in the optional pharmacogenomics research 
component of the study must provide consent on a separate ICF.
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 visit is a single visit, the electronic Columbia-Suicide Severity Rating Scale
(eC-SSRS; Lifetime version) should be performed after the joint assessment (after signing 
informed consent). If the screening visit is divided into more than 1 visit, the eC-SSRS should be 
performed after the joint assessment and the subject is determined to be eligible by the central 
laboratory test results.  
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. Females of 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 
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the duration of the study and for at least 12 weeks after receiving the last administration of 
blinded study agent. The methods of contraception used by each subject must be documented. 
For details, see Section 4.1.
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 agent administration 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 of current, active TB or old, inactive TB. Chest 
radiographs taken up to 3 months before the first administration of study agent may 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 should be performed at the 
screening visit by the investigator, with evidence of spondylitis from a prior pelvic or SI joint 
x-ray or pelvic magnetic resonance imaging (MRI) when available.  Results must be 
documented.)
Subjects as outlined in Inclusion Criterion 15 must undergo testing for TB (Attachment 2 or 
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®-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.
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* or the 
tuberculin skin test is mandated by local health authorities) are eligible to continue with 
pre-randomization procedures. 
*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.
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 States guidelines must be followed, or the subject will be excluded from the study.
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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.
Retesting
The re-testing of abnormal screening laboratory 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
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, scientist, 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.
Chest x-rays, if done within the specified allowed time, are not required to be repeated.
If the QFT and/or TST is positive in the first screening, these tests should not be repeated.  Also 
if the QFT and TST 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 3 treatments: guselkumab SC 100 mg 
q4w, guselkumab SC 100 mg at Weeks 0, 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 signs and 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:
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
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, 
consultation with 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 Gold test, a repeat 
tuberculin skin test in countries in which the QuantiFERON®-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 
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 post-baseline visits except during screening, the eC-SSRS (Since Last Contact version) 
should be the first assessment/questionnaire that the subject must complete.
9.1.5.
Post Treatment Phase (Follow-Up)
Subjects will be followed for safety, efficacy, and PK and immunogenicity information through 
Week 60 as listed in the Time and Events Schedule.
Subjects who discontinue Study Agent
Prior to Week 24
If a subject permanently discontinues study agent before the Week 24 visit, the subject should 
return for all visits through Week 24. The final safety visit assessments will be conducted at the 
next scheduled visit that occurs approximately 12 weeks after the last administration of study 
agent (Week 60 visit in Table 1 ).   
At or After Week 24 and prior to Week 52
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If a subject permanently discontinues study agent at or after Week 24 and before the Week 52 
visit, the final efficacy visit (Week 52 visit in Table 1) should occur at the time of 
discontinuation or as soon as possible. The subject should return 12 weeks after their last dose 
for their final safety visit (Week 60 visit in Table 1).   
Subjects who discontinue Study Participation
No procedures and evaluations should be conducted after a subject withdraws consent.
9.2.
Efficacy Evaluations
Efficacy assessments will be performed at the site by applicable site personnel trained by the 
Sponsor as indicated in the Time and Events Schedule.
9.2.1.
Psoriatic Arthritis Response Evaluations
9.2.1.1.
Joint Assessments
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 of experience 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 60, 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 or 
enthesitis/dactylitis assessments. The IJA should maintain a neutral attitude during 
joint/enthesitis/dactylitis assessments and should limit interactions with the subject only to 
activities associated with performing assessment.
The IJA will perform only joint, 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 Responses
American College of Rheumatology responses are presented as the numerical measurement of 
improvement in multiple disease assessment criteria. For example, an ACR 20 response7 is 
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 Visual Analogue Scale (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

CRP
ACR 50 and ACR 70 similarly defined except improvement threshold from baseline is 50% and 
70%, respectively.
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9.2.1.4.
Dactylitis Assessments
Presence and severity of dactylitis will be assessed by an independent joint assessor (IJA) 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)13,15.  The presence of tender dactylitis will be 
assessed by the number of fingers and toes with tender dactylitis, with a range of 0 to 20.  Both 
of these assessments will be performed by the IJA.
The Sponsor will provide dactylitis assessment training to the appropriate IJA at the study site.  
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 IJA who performs the baseline dactylitis assessments 
for a subject should also perform the dactylitis assessments for that subject at every subsequent 
visit through Week 52.
9.2.1.5.
Enthesitis Assessments
Enthesitis will be assessed by the IJA using the Leeds Enthesitis Index (LEI)17 and the 
Spondyloarthritis Research Consortium of Canada (SPARCC).
The LEI was developed to assess enthesitis in subjects with PsA, and evaluates the presence or 
absence 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 SPARCC developed a measure for enthesitis in general spondyloarthritis (ie, not limited to 
PsA or AS) which evaluates the presence or absence of pain by applying local pressure to the 
following entheses:

Supraspinatus insertion, left and right

Medial epicondyle humerus, left and right

Lateral epicondyle humerus, left and right

Greater trochanter, left and right

Quadriceps –to-Patella, left and right

Patellar-to-tibia, left and right

Achilles tendon insertion, left and right

Plantar fascia, left and right
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The Sponsor will provide enthesitis assessment training to the appropriate IJA at the study site. 
Documentation of this training will be maintained in the study site’s training files. Previous 
enthesitis assessment (LEI and SPARCC) 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 IJA who performs the baseline enthesitis assessments 
for a subject should also perform the enthesitis assessments for that subject at every subsequent 
visit through Week 52.
9.2.1.6.
Disability Index of the Health Assessment Questionnaire
The functional status of the subject will be assessed by the HAQ-DI.9 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.21  It has also been shown to be responsive to changes in a subject’s disease.30  In 
PsA, a decrease in score of 0.35 has been determined to indicate a meaningful improvement.31
9.2.1.7.
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 ≤1.5
9.2.1.8.
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 (range 0–100), swollen joint count (0-66), tender 
joint count (0-68), CRP level (mg/L), enthesitis (measured by the LEI), dactylitis count (using 2 
different counts: [1] scoring each digit from 0–3 and recoding to 0–1, where any score 
>0 equaled 1 AND [2] scoring each digit for tenderness 0-1), and, finally, the PCS scale of the 
SF-36 health survey.20,19
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).18
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9.2.1.9.
Group for Research and Assessment of Psoriasis and Psoriatic 
Arthritis (GRAPPA) Composite Score (GRACE)
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).
The 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 0:19,18

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, 0-100 VAS)

Patient’s assessment of skin disease activity (0-100 VAS)

Patient’s global assessment of disease activity (arthritis, 0-100 VAS)

PASI score (0-72)

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,
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
9.2.1.10.
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).47  
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
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
SQRT(SW28) is square root of SW28

GH is Patient’s Global Assessment of Disease Activity (arthritis) (0-100 VAS)
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 5.48
Table 5:
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
9.2.1.11.
Disease Activity Index for Psoriatic Arthritis
Disease Activity Index for Psoriatic Arthritis (DAPSA) 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 pain for pain (0–10 VAS), and patient global assessment of disease activity 
(arthritis, 0 –10 VAS).19  The cutoffs for disease activity are 18.5 (low) to 45.1 (high).18
9.2.1.12.
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 criteria38:

≥ 30% decrease in the swollen joint count (66 joints);

≥ 30% decrease in the tender joint count (68 joints);

≥ 20% improvement in the patient's overall assessment of disease (arthritis) on a VAS; 
and

≥ 20% improvement in the physician’s overall assessment of disease on a VAS.
9.2.1.13.
Bath Ankylosing Spondylitis Disease Activity Index
The BASDAI was developed as a subject self-assessment for ankylosing spondylitis that consists 
of 6 questions relating to the 5 major symptoms of ankylosing spondylitis.10  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:
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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).53
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 scaling using 0 (no evidence), 1 
(minimal), 2 (mild), 3 (moderate) and 4 (severe) scale. The IGA score of psoriasis is based upon 
the average of induration, erythema and scaling scores. The patient’s psoriasis 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 IGA evaluations for the subject at all 
subsequent visits through Week 52. The Sponsor will provide IGA training. Documentation of 
this training will be maintained in the site’s training files. Previous IGA 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.
9.2.2.2.
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.8  The PASI produces a numeric score that can range from 0 to 72. A
PASI 75 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.
9.2.3.
Other Patient Reported Outcomes
9.2.3.1.
36-Item Short-form Health Survey
The SF-36 questionnaire was developed as part of the Rand Health Insurance Experiment and 
consists of 8 multi-item domain scales:
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
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 general US population norms.49  It has been demonstrated in a study of patients with 
RA that a change of 4.4 in PCS and 4.7 in MCS was the minimally important change.23 There is 
no specific cut-off for a clinically meaningful change in patients with PsA and a conservative 
threshold of ≥5 points change in both PCS and MCS have been used in the clinical studies to 
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 comparison of relative 
burden of different diseases and the relative benefit of different treatments.50
9.2.3.2.
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.3 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-Fatigue has 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 4 points is 
considered meaningful and has been used in the PsA population.2
9.2.3.3.
Patient-Reported Outcomes Measurement Information System-29
Patient-Reported Outcomes Measurement Information System (PROMIS)-29 profile instrument 
is intended for adults (ages 18+).26 It is a collection of short forms containing 4 items for each of 
seven PROMIS domains (Depression, Anxiety, Physical Function, Pain Interference, Fatigue, 
Sleep Disturbance, and Ability to Participate in Social Roles and Activities). PROMIS-29 also 
includes an additional pain intensity 0-10 numeric rating scale. The PROMIS-29 Profile is 
universal rather than disease-specific. They assess all domains over the past seven days except 
for Physical Function which has no timeframe specified.  The raw score of each domain is 
converted into a standardized score with a mean of 50 and a standard deviation (SD) 
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of 10 (T-Score). The standardized T-score is reported as the final score for each participant.   
Pain Intensity is presented as raw responses (0-10). For PROMIS domains of Depression, 
Anxiety, Physical Function, Pain Interference, Fatigue, a score of 50 is the average for the 
United States general population with a standard deviation of 10, because testing was performed 
on a large sample of the general population. However, the other two domains (Ability to 
Participate in Social Roles and Activities and Sleep Disturbance) were not centered in a national 
sample. For these two domains, a score of 50 represents the average of the calibration sample 
which was generally more enriched for chronic illness, and a score of 50 likely represents 
somewhat sicker people than the general population.  A higher PROMIS T-score represents more 
of the concept being measured. For negatively-worded concepts like Anxiety, a T-score of 60 is 
one SD worse than average. By comparison, an Anxiety T-score of 40 is one SD better than 
average. However, for positively-worded concepts like Physical Function, a T-score of 60 is 
better than average while a T-score of 40 is better.
9.3.
Pharmacokinetics and Immunogenicity
Serum samples will be used to evaluate the PK of guselkumab as 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.
9.3.1.
Serum Collection and Handling
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 
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.  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.
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9.3.2.
Analytical Procedures
Serum samples will be analyzed to determine serum guselkumab concentrations using a 
validated, specific, and sensitive immunoassay method by the Sponsor’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.
9.3.3.
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.
9.3.4.
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.
9.4.
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 
collecting information on AEs, including injection site and allergic reactions, clinical laboratory 
tests, physical examinations, vital signs, 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.
Details regarding the independent DMC are provided in the DMC Charter.
Safety will be monitored through Week 60. Any clinically relevant changes occurring during the 
study must be recorded on the AE section of the CRF.
Clinically important 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.
9.4.1.
Evaluations of Safety and Tolerability
The study will include the following evaluations of safety and tolerability according to the time 
points provided in the Time and Events Schedule: 
Adverse Events
Adverse events will be reported by the subject for the duration of the study. Adverse events will
be followed by the investigator.
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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. All subjects will be carefully observed at the study site for at least 30 minutes after 
the SC injection of study agent for 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 agent away from the study site (at Weeks 32, 40, and 48) 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:

Hematology Panel
-hemoglobin
-neutrophils
-hematocrit
-bands
-red blood cell count
-eosinophils
-white blood cell count
-basophils
-lymphocytes
-platelets
-monocytes

Serum Chemistry Panel
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-sodium
-calcium
-potassium
-albumin
-chloride
-total protein
-alkaline phosphatase
-ALT
- blood urea nitrogen 
-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), antibody to 
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

FSH is 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 11 for 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 (ECG)
A supine 12-lead ECG will be performed locally at Week 0 prior to administration of study 
agent, as specified in the Time and Events Schedule. A full 12-lead ECG will be recorded and
the ECG data, including a copy of tracing as well as interpretation, should be stored in the 
subject's source document.
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Physical Examination
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.
9.4.2.
Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS)
No signal of suicidal ideation and behavior has been observed in the clinical trials of guselkumab 
to date. However, in light of the recent reports concerning suicidal ideation and behavior in 
patients with plaque psoriasis treated with an IL-17R antagonist (brodalumab), the 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 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.33,39
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 60.
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. During a visit, subjects will be directed to a private, quiet place with the electronic 
device and/or a telephone to 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 3 minutes. Subjects with significant suicidal ideation and behavior may 
require up to 10 minutes to answer all relevant questions. 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.
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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 an Ideation Level (1-5) or any 
suicidal behaviors or with a response of “YES” for non-suicidal self-injurious behavior must 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 an Ideation 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 treated with 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 evaluation by a mental health professional (eg, 
psychiatrist, psychologist, or appropriately trained social worker or nurse).
Positive reports 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: 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.
The subject should not be released from the site until the eC-SSRS Findings Report (both for 
negative and positive reports) is reviewed by the investigator and the subject’s risk has been 
assessed and follow-up determined, as appropriate.
For each 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.

Ideation level of a 1, 2, or 3 with No Behaviors: Negative findings report will be 
generated.

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-positive assessment), 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.
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Interruption or the discontinuation of study treatment should be considered for any subject who 
reports suicidal Ideation Level 4 (Some intent to act, no plan), Ideation Level 5 (Specific plan 
and intent), or any suicidal 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 mental health 
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 are new or considered to be a 
worsening and clinically significant, should be reported on the AE eCRF (see Section 12).
9.4.3.
Anticipated Events
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
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). Any event that meets 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 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.
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.
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9.5.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the laboratory requisition 
form. Refer to the Time and Events Schedule for the timing and frequency of all sample 
collections.
Instructions for 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/ 
WITHDRAWAL FROM THE STUDY
10.1.
Completion
A subject will be considered to have completed the study if he or she has completed assessments 
at Week 60 of the study. Subjects who prematurely discontinue study treatment for any reason 
before completion of the final safety visit at Week 60 will not be considered to have completed 
the study.
10.2.
Discontinuation of Study Treatment
A subject will not be automatically withdrawn from the study if he or she has to discontinue 
treatment before the end of the treatment regimen.
A subject's study treatment must be discontinued if:

The investigator believes that for safety reasons or tolerability reasons (eg, AE) it is in the 
best interest of the subject to discontinue study treatment.

The subject becomes pregnant or plans to become pregnant.

The subject is diagnosed with a malignancy, with the exception of no more than 2 localized 
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®-TB Gold test is not 
approved/registered or the tuberculin skin test is mandated by local health authorities), 
unless active TB can be ruled out and appropriate treatment for latent TB can be 
initiated before the next administration of study agent and 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 
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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 
noncompliant with 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 (Section 8.7).

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 agent administration.

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 any suicidal 
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.
Discontinuation of study agent should be considered and discussed with the study responsible 
physician or designee for subjects who develop a serious or opportunistic infection.
Subjects who decide to discontinue study agent administration must be interviewed by the 
investigator to determine if a specific reason for discontinuing study agent can 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 agent discontinuation, even if the investigator's assessment is that the AE or the 
patient’s PsA condition would not require study agent discontinuation. The reason for study
agent discontinuation 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.
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If a subject discontinues study agent administrations before the Week 24 visit, he/she should
return for all visits through Week 24 as outlined in the Time and Events Schedule (see 
Section 9.1.5).
If a subject permanently discontinues study agent at or after Week 24 and prior to the Week 52 
visit, the final efficacy visit should occur at the time of discontinuation or as soon as possible and 
all assessments under the final efficacy visit/Week 52 should be performed. The subject should 
also return for a final safety visit approximately 12 weeks after the last study agent
administration.
10.3.
Withdrawal From the Study
A subject will be withdrawn from the study for any of the following reasons:

Lost to follow-up

Withdrawal of consent

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 clinical trial; 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 with the 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 agent assigned to the withdrawn 
subject may not be assigned to another subject. Subjects who withdraw from the study will not 
be replaced.
10.4.
Withdrawal From the Use of Research Samples
A subject who withdraws from the study will have the following options regarding the optional 
research sample(s):
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
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 receive written confirmation from the 
Sponsor that the sample(s) have been destroyed.
Withdrawal From the Optional Research Samples While Remaining in the Main Study
The subject may 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 Samples in Future Research
The subject may withdraw consent for use of samples for future research (refer to 
Section 16.2.5).  In such 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
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 the 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 the Full Analysis Set
(FAS), including all randomized subjects who received at least 1 dose (complete or partial) of 
study treatment, which will be analyzed based on the randomized treatment groups, regardless of 
the treatment subjects actually received. 
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 they actually 
received, regardless of the treatment groups to which they were assigned.
Pharmacokinetics analyses for guselkumab will include subjects who receive at least one 
complete dose 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 guselkumab and have 
at least one post-dose sample collection.
Simple descriptive summary statistics, such as n, mean, standard deviation (SD), median, 
inter quantile range, minimum, and maximum for continuous variables, and counts and 
percentages for discrete variables will be used to summarize most data.
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In general, for response efficacy endpoints, treatment comparisons will be performed using a 
Cochran-Mantel-Haenszel (CMH) test stratified by the baseline non-biologic DMARD (MTX, 
SSZ, HCQ, LEF) use (yes/no) and prior exposure to anti-TNF agents (yes/no).  
In general, for continuous efficacy endpoints, treatment comparisons will be performed using 
either a Mixed-Effect Model Repeated Measure model or an analysis of covariance model.  All 
of the models will have treatment group, the baseline non-biologic DMARD (MTX, SSZ, HCQ, 
LEF) use (yes/no), prior exposure to anti-TNF agents (yes/no), and baseline value as explanatory 
factors.  
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 was chosen based on the data from a Sponsor’s recent PsA study, 
CNTO1275PSA3002 that included the subjects previously treated with biologic anti-TNFα
agents. The ACR 20 response rates at Week 24 from CNTO1275PSA3002 were 20.2%, 43.7% 
and 43.8%, respectively, for the placebo, ustekinumab 45 mg, and ustekinumab 90 mg treatment 
groups. In order to ensure a statistical power of >90% at the significance level of 0.05 (2-sided), 
assuming that each of guselkumab 100 mg groups achieves an ACR 20 response of 40% 
compared with the placebo group response of 20% at Week 24, a total of 360 subjects are 
planned to be randomized in a 1:1:1 ratio to each of treatment groups. Table 6 provides the 
power evaluation of various assumptions.
Table 6:
Statistical Power for the ACR 20 Response Rate Comparing to Placebo at Week 24
Treatment group
Sample size
ACR 20 
response
Δ (difference)
Power
1
Placebo
120
20%
20%
93%
Guselkumab 100 mg
120
40%
2
Placebo
120
25%
20%
91%
Guselkumab 100 mg
120
45%
3
Placebo
120
20%
25%
99%
Guselkumab 100 mg
120
45%
4
Placebo
120
25%
25%
98%
Guselkumab 100 mg
120
50%
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11.3.
Efficacy Analyses
11.3.1.
Primary Endpoint Analyses
The primary endpoint to be analyzed in this study is the proportion of subjects who achieve 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.
Treatment Failure Criteria
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 nonresponders.
The treatment effect of each guselkumab group versus placebo will be tested using the 
Cochran-Mantel-Haenszel test stratified by prior exposure to anti-TNF agents (yes/no) and 
baseline DMARD (MTX, SSZ, HCQ, LEF) use (yes/no). 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 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 Week 0, 4 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.
To evaluate the robustness of the primary endpoint analysis, the exhaustive scenario tipping 
point sensitivity analyses will be performed by varying the amount of non-responder imputation 
for missing data.
Additional sensitivity/supplemental analyses which vary how intercurrent events (e.g. 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 ACR20 at Week 24
for the primary and alternative estimands (which will also be defined in the SAP).
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Subgroup Analyses
Subgroup analysis will be performed to evaluate consistency in the primary efficacy endpoint by 
demographic characteristics, baseline disease characteristics, and prior and baseline medications.  
Interaction test between the subgroups and treatment group will also be provided if appropriate.
11.3.2.
Major Secondary Analyses
The major secondary endpoints are 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 primary and major secondary endpoints, all other secondary endpoints 
(Section 2.1.2) will be summarized over time by treatment groups. Treatment comparisons will 
be performed by visit through Week 24.  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 or missing data will be labeled as such in the concentration data listing or statistical 
analysis dataset. The lowest quantifiable sample concentration of the assay 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.
Biomarker Analyses
Results will be presented in a separate biomarker technical report.
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11.7.
Pharmacokinetic/Pharmacodynamic Analyses
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.
11.8.
Pharmacogenomic Analyses
Results will be presented in a separate pharmacogenomics technical report.
11.9.
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 Grade 4 
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.
11.9.1.
Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS)
Suicide-related thoughts and behaviors based on the eC-SSRS will be summarized descriptively 
by treatment group.
11.10. Interim Analysis
No interim analysis is planned for this study.
11.11. Data Monitoring Committee
An independent DMC will 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 the study.
The committee will meet periodically to review interim data. After the review, the DMC will 
make recommendations regarding the continuation of the study. The details will be provided in a 
separate DMC charter.
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The DMC will consist of at least one medical expert in the relevant therapeutic area and at least 
one statistician. The DMC responsibilities, authorities, and procedures will be documented in its 
charter.
12.
ADVERSE EVENT REPORTING
Timely, accurate, and complete reporting and analysis of 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 affiliates will be conducted in 
accordance with those procedures.
Method of Detecting Adverse Events and Serious Adverse Events
Care will be taken not to introduce bias when detecting AEs or SAEs. Open-ended and 
non-leading verbal questioning of the subject is the preferred method to inquire about AE 
occurrence. 
Solicited Adverse Events
Solicited AEs are predefined local and systemic events for which the subject is specifically 
questioned (see Section 9.1.1).
Unsolicited Adverse Events
Unsolicited AEs are all AEs for which the subject is specifically not questioned.
12.1.
Definitions
12.1.1.
Adverse Event Definitions and Classifications
Adverse Event
An AE is 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 
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 includes any 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 Section 12.3.1 for 
time of last AE recording).
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Serious Adverse Event
An SAE based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for 
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 agent and 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/Reference Safety Information
An AE is considered unlisted if the nature or severity is not consistent with the applicable 
product reference safety information. For guselkumab, the expectedness of an AE will be 
determined by whether or not it is listed in the Investigator's Brochure.
Adverse Event Associated With the Use of the Drug
An AE is considered associated with the use of the drug if the attribution is possible, probable, or 
very likely (Section 12.1.2).
12.1.2.
Attribution Definitions
Not Related
An AE that is not related to the use of the drug.
Doubtful
An AE for which an alternative explanation is more likely, eg, concomitant drug(s), concomitant 
disease(s), or the relationship in time suggests that a causal relationship is unlikely.
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Possible
An AE that 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), concomitant disease(s).
Very Likely
An AE that 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 very suggestive (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:
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).
12.2.
Special Reporting Situations
Safety events of interest on a Sponsor study agent that may require expedited reporting or safety 
evaluation include, but are not limited to:

Overdose of a Sponsor study agent

Suspected abuse/misuse of a Sponsor study agent

Accidental or occupational exposure to a Sponsor study agent

Medication error involving a Sponsor product (with or without subject/patient exposure to 
the Sponsor study agent, eg, name confusion)

Exposure to a Sponsor study agent from breastfeeding
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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 SAE page 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 ICF is 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 within 12 weeks after the last dose of study agent, 
must be 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. 
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 
AE to study therapy. All measures required for AE management must be recorded in the source 
document and reported according to Sponsor instructions.
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/IRB that 
approved the protocol unless otherwise required and documented by the IEC/IRB. A SUSAR 
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: 

Study number

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)

Site number
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
Subject number

Any other information that is required to do an emergency breaking of the blind
12.3.2.
Serious Adverse Events
All SAEs occurring during the study must be reported to the appropriate Sponsor contact person 
by study-site personnel within 24 hours of their knowledge 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 from the 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:

The event resolves

The event stabilizes

The event returns to baseline, if a baseline value/status is available

The event can be attributed to agents other than the study agent or to factors unrelated to 
study conduct

It becomes unlikely that any 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:

Hospitalizations not intended to treat an acute illness or AE (eg, social reasons such as 
pending placement in long-term care facility).

Surgery or procedure planned before entry into the study (must be documented in the CRF).
Note:
Hospitalizations that were 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 AE that 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 treatment period.
The cause of death of a subject in a study within 12 weeks after the last dose of study agent, 
whether or not the event is expected or associated with the study agent, is considered an SAE.
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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 personnel within 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 study and discontinue further 
study treatment.
Because the effect of the study agent on 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 Section 12.2.  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
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 
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 personnel must report the PQC to the 
Sponsor according to the SAE reporting timelines (refer to Section 12.3.2, Serious Adverse 
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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 AGENT INFORMATION
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 
assembled in a PFS-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 guselkumab is supplied as a sterile liquid for SC injection at a nominal volume of 
1.0 mL in a single-use PFS assembled with the PFS-U. 
Concomitant medications, including those in Table 3, will not be supplied by the Sponsor but 
rather must be acquired from a commercial pharmacy.
14.2.
Packaging
The investigational supplies will be uniquely packaged to assure that they are appropriately 
managed throughout the supply chain process.
14.3.
Labeling
Study agent labels will contain information to meet the applicable regulatory requirements.
14.4.
Preparation, Handling, and Storage 
All study agent must 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 28, 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 & 
Events Schedule.
Study personnel will instruct subjects on how to transport, store, and 
administer study agent for at-home use as indicated for this protocol.
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Further details regarding the storage of guselkumab and placebo will be provided in the Site 
Investigational Product Manual.
14.5.
Drug Accountability
The investigator is responsible for ensuring that all study agent received at the site is inventoried 
and accounted for throughout the study. The study agent administered to the subject must be 
documented on the drug accountability form. All study agent will be stored and disposed of 
according to the Sponsor's instructions. Study-site personnel must not combine contents of the 
study agent containers.
Study agents must 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 agent supplies 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 
hazardous liquids should 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 agents should be dispensed under the supervision of the investigator or a qualified member 
of the study-site personnel, or by a hospital/clinic pharmacist. Study agents will be supplied only 
to subjects participating in the study. Study agents may not be relabeled or reassigned for use by 
other subjects. The investigator agrees neither to dispense the study agent from, nor store it at, 
any site other than the study sites agreed upon with the Sponsor.
Subjects who will be self-administering study agent at home will receive detailed instructions for 
study agent storage and disposal of used syringes and handling of unused study material.  These 
subjects will receive a sharps container to dispose of used syringes and will be instructed to 
return the sharps container and/or unused cartons with syringes. Subjects who self-administer at 
home will record study agent administrations with time and date information in a Diary.
15.
STUDY-SPECIFIC MATERIALS
The investigator will be provided with the following supplies:

Investigator's Brochure 

Study site investigational product and procedures manual

Laboratory manual and laboratory supplies

ePRO device and user manual

Subject diary cards
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
Interactive voice response system/IWRS manual 

Electronic data capture (eDC) manual

Sample ICF

iPad® and site user guide, if the study site is participating in electronic informed consent
16.
ETHICAL ASPECTS
16.1.
Study-Specific Design Considerations
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 of the study, and provide their consent voluntarily will be enrolled.
The primary ethical concern is that subjects with active disease may receive placebo for 
24 weeks. However, the placebo control is 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 to 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 by ICH 
(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.
A 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 0.1 mSV, 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 
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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

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.
Approval for 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
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
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 subjects under 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 the ones 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
Each subject 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 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 
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violating the confidentiality of the subject, 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 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.
The subject must be able to read and write and should personally sign the ICF. 
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 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
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.
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.
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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 Retention of 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 local regulations) 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 guselkumab and PsA.  The research may begin at any time during 
the study or the post-study storage 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 product if the need for the product persists, unless explicitly 
addressed as a specific ethical consideration in Section 16.1.
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 
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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 agent to 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 approval must 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.

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 
obtained to state that this person did not participate in the deliberations or in the 
vote/opinion of the study.

Regulatory authority approval or 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 following documents 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)
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
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
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 and concomitant medication; drug 
receipt/dispensing/return records; study agent administration information; and date of study 
completion and reason for early discontinuation of study agent or 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 PsA scales and assessments designated by the 
Sponsor will 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, PROMIS 29, BASDAI, IGA, PASI, BSA,
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 4.1 and Section 4.2 that specify a 
need for documented medical history are as follows:
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
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 in the 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.
During at-home administration (Weeks 32, 40, and 48), subjects will enter information on their 
study agent administration on a patient diary.
17.5.
Case Report Form Completion
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.
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).
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
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 laboratory to 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
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 Section 8, 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.
Essential documents must be retained until at least 2 years 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 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational product. 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.
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17.8.
Monitoring
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 office medical 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.
17.9.
Study Completion/Termination
17.9.1.
Study Completion/End of Study
The study is considered completed with the last visit for the 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 
reason at the sole discretion of the Sponsor. Study sites will be closed upon study completion. A 
study site is considered closed when all required documents and study supplies have been 
collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination.
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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 by the investigator

Discontinuation of further study agent development
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 audit visits 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
All information, including but not limited to information regarding guselkumab or 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 
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 in the 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 Sponsor with all data obtained in the study.
The results of the study will be reported in a Clinical Study 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 
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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 of Medical 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 60 days 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 60 days 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 12 months 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.
Registration of Clinical Studies and Disclosure of Results
The Sponsor will register and disclose the existence of and the results of clinical studies as 
required by law.
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Chandran V, Bhella S, Schentag C, Gladman D. Functional Assessment of Chronic Illness Therapy-Fatigue 
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Coates LC, Helliwell PS. Validation of minimal disease activity criteria for psoriatic arthritis using 
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Gladman DD, Antoni C, Mease P, Clegg CO, Nash P. Psoriatic arthritis: epidemiology, clinical features, 
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Gladman DD, Inman RD, Cook RJ, et al. International spondyloarthritis interobserver reliability exercise--the 
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Gladman DD, Ziouzina O, Thavaneswaran A, Chandran V. Dactylitis in psoriatic arthritis: prevalence and 
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Gottlieb A, Menter A, Mendelsohn A, et al. Ustekinumab, a human interleukin 12/23 monoclonal antibody, for 
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Healy PJ, Helliwell PS. Measuring clinical enthesitis in psoriatic arthritis: assessment of existing measures and 
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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 
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Helliwell PS, Kavanaugh A. Comparison of composite measures of disease activity in psoriatic arthritis using 
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Kavanaugh A, Ritchlin C, Rahman P, et al. Ustekinumab, an anti-IL-12/23 p40 monoclonal antibody, inhibits 
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radiographic data from the phase 3, multicentre, randomised, double-blind, placebo-controlled PSUMMIT-1 
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specific health-related quality of life questionnaires in clinical trials of rheumatoid arthritis.  
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autoimmune inflammation. J Exp Med. 2005;201(2):233-240.
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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.
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Maksymowych WP, Mallon C, Morrow S, et al. Development and validation of the Spondyloarthritis Research 
Consortium of Canada (SPARCC) Enthesitis Index. Ann Rheum Dis 2009;68:948 –53.
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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.
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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.
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Mease PJ, van der Heijde D, Ritchlin CT, et al. A Randomized, Double-Blind, Active- and Placebo-Controlled 
Phase 3 Study of Efficacy and Safety of Ixekizumab, Adalimumab, and Placebo Therapy in Patients Naïve to 
Biologic Disease Modifying Anti-Rheumatic Drugs with Active Psoriatic Arthritis [abstract]. Arthritis 
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Mease PJ, Kivitz AJ, Burch FX, et al.  Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on 
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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 
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McInnes IB, Mease PJ, Kirkham B, et al. Secukinumab, a human anti-interleukin-17A monoclonal antibody, in 
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Lancet. 2015;386(9999):1137-1146.
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Oppmann B, Lesley R, Blom B, et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with 
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O'Rielly DD, Rahman P. Genetics of susceptibility and treatment response in psoriatic arthritis. Nat Rev 
Rheumatol. 2011;7(12):718-732.
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Ritchlin C, Rahman P, Kavanaugh A, et al. Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, 
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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
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.
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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 T lymphocytes 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. tuberculosis and 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 3 species of Mycobacterium, in 
the absence of M. tuberculosis infection.

In a study of the QuantiFERON®-TB Gold test (standard format) in subjects with active TB, sensitivity has 
been shown to be approximately 89% (Mori et 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 Japanese patients 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 who have 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. tuberculosis infection 
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 1 mL 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 3000 g.  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-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 is not 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. 
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Adherence to Local Guidelines

Local country guidelines for immunocompromised patients should 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 tuberculosis infection 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--based assay 
using new antigens. Am J Respir Crit Care Med. 2004;170:59-64.
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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 0.1 mL 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 5 tuberculin units (TU) of standard 
purified protein derivative (PPD)-S or 2 TU of PPD-RT 23, Statens Seruminstitut, as recommended by the World 
Health Organization.  PPD strengths of 1 TU or 250 TU 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) 6 mm to 10 mm 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 test results.  If a subject fails to show up for the scheduled reading, a positive reaction may 
still be measurable up to 1 week 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 5 mm 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 guidelines for immunocompromised patients should 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
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; Division of 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.
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CNTO 1959 (guselkumab)
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Approved, Date: 25 January 2018
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 negative for surface antigen (HBsAg-) and test positive for core antibody (anti-HBc+) 
and surface antibody (anti-HBs+) are eligible for this study.

Subjects who test positive only for surface antibody (anti-HBs+) are eligible for this study.

Subjects who test positive for surface antigen (HBsAg+) are NOT eligible for 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 eligible for this study. If the HBV DNA test is negative, the subject is eligible for this 
study. In the event the HBV DNA test cannot be performed, the subject is NOT eligible for 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.  
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
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Approved, Date: 25 January 2018
Attachment 5:
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 SAE criteria 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 anticipated event 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 
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 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
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.
NCT03162796

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
127
Approved, Date: 25 January 2018
INVESTIGATOR AGREEMENT
NCT03162796