Conditions: Arthritis, Psoriatic
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 383
Healthy volunteers: no

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

Detailed description:
This is a study of guselkumab in participants with active Psoriatic Arthritis (PsA) who had inadequate response to standard therapies. It will evaluate the clinical efficacy of guselkumab in the reduction of signs and symptoms and the safety profile of guselkumab in the treatment of PsA. The study will consists of 4 phases: a screening phase of up to 6 weeks, a blinded treatment phase of approximately 1 year (that is, 52 weeks), including a placebo controlled period from Week 0 to Week 24 and double-blind active treatment period from Week 24 to Week 52, and a safety follow-up phase of 8 weeks after Week 52 (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. Efficacy, safety, pharmacokinetic, immunogenicity, and biomarker evaluations will be performed in the study at defined schedule.

Arms:
arm 1: Participants will receive subcutaneous (SC) guselkumab 100 milligram (mg) once every 4 weeks (q4w) from Week 0 through Week 48. arm 2: Participants will receive SC guselkumab 100 mg at Weeks 0 and 4, then once every 8 weeks (q8w) (Weeks 12, 20, 28, 36, and 44) and placebo injections at other visits (Weeks 8, 16, 24, 32, 40, 48) to maintain the blind. arm 3: Participants will receive SC placebo q4w from Week 0 to Week 20, and will crossover at Week 24 to receive guselkumab 100 mg q4w from Week 24 through Week 48.

Interventions: intervention 1: Guselkumab intervention 2: Placebo
Intervention descriptions: intervention 1: Participants will receive 100mg of guselkumab as a sterile liquid for SC injection. intervention 2: Participants will receive matching placebo as SC injection.

Protocol document:
Prot_000.pdf: 
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.
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CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
2
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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Clinical Protocol CNTO1959PSA3001 Amendment 1
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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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Approved, Date: 25 January 2018
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
6
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
7
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
8
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)
NCT03162796


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
11
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.
NCT03162796


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
19
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.
NCT03162796


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
20
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
24
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
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CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
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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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CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
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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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CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
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Approved, Date: 25 January 2018
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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CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
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Approved, Date: 25 January 2018
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. 
NCT03162796


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
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Approved, Date: 25 January 2018

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.
NCT03162796


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


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


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
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Approved, Date: 25 January 2018
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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CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
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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)
Clinical Protocol CNTO1959PSA3001 Amendment 1
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Approved, Date: 25 January 2018
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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CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSA3001 Amendment 1
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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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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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Gottlieb A, Menter A, Mendelsohn A, et al. Ustekinumab, a human interleukin 12/23 monoclonal antibody, for 
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Helliwell PS, Kavanaugh A. Comparison of composite measures of disease activity in psoriatic arthritis using 
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radiographic data from the phase 3, multicentre, randomised, double-blind, placebo-controlled PSUMMIT-1 
and PSUMMIT-2 trials. Ann Rheum Dis. 2014;73(6):1000-1006.
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Kosinski M, Zhao SZ, Dedhiya S, et al.  Determining minimally important changes in generic and disease-
specific health-related quality of life questionnaires in clinical trials of rheumatoid arthritis.  
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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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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 
patient-rated importance and satisfaction. J Rheumatol. 2011;38(11):2461-2465.
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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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Ritchlin C, Rahman P, Kavanaugh A, et al. Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, 
ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-
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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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Clinical Protocol CNTO1959PSA3001 Amendment 1
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Approved, Date: 25 January 2018
Attachment 3:
Tuberculin Skin Testing
Administering the Mantoux Tuberculin Skin Test

The Mantoux tuberculin skin test (CDC, 2000) is the standard method of identifying persons infected with 
Mycobacterium tuberculosis.  Multiple puncture tests (Tine and Heaf) should not be used to determine whether a 
person is infected because the amount of tuberculin injected intradermally cannot be precisely controlled.  
Tuberculin skin testing is both safe and reliable throughout the course of pregnancy.  The Mantoux tuberculin test is 
performed by placing an intradermal injection of 0.1 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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Clinical Protocol CNTO1959PSA3001 Amendment 1
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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.  
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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.
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Approved, Date: 25 January 2018
INVESTIGATOR AGREEMENT
NCT03162796

SAP_001.pdf: 
1
Approved, Date: 21 March 2019
Janssen Research & Development *
Statistical Analysis Plan
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating 
the Efficacy and Safety of Guselkumab Administered Subcutaneously in Subjects with 
Active Psoriatic Arthritis including those Previously Treated with Biologic Anti-TNFα 
Agent(s)
Protocol CNTO1959PSA3001; Phase 3
AMENDMENT 3
CNTO1959 (guselkumab)
Status:
Approved
Date:
21 March 2019
Prepared by:
Janssen Research & Development, LLC
Document No.: EDMS-ERI-146207736
Compliance: The study described in this report was performed according to the principles of Good Clinical Practice (GCP). 
Confidentiality Statement
The information in this document contains trade secrets and commercial information that are privileged or confidential and may 
not be disclosed unless such disclosure is required by applicable law or regulations. In any event, persons to whom the 
information is disclosed must be informed that the information is privileged or confidential and may not be further disclosed by 
them. These restrictions on disclosure will apply equally to all future information supplied to you that is indicated as privileged or 
confidential.
NCT03162796
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CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959PSA3001 Amendment 3
2
Approved, Date: 21 March 2019
TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
LIST OF TABLES......................................................................................................................................... 6
LIST OF FIGURES ....................................................................................................................................... 6
AMENDMENT HISTORY.............................................................................................................................. 7
AMENDMENT 1 (APPROVAL DATE: MAY 25, 2018) ................................................................................ 7
AMENDMENT 2............................................................................................................................................ 9
AMENDMENT 3.......................................................................................................................................... 11
ABBREVIATIONS ...................................................................................................................................... 15
1.
INTRODUCTION................................................................................................................................17
1.1.
Trial Objectives ..............................................................................................................................17
1.2.
Trial Design.................................................................................................................................... 17
1.3.
Statistical Hypotheses for Trial Objectives..................................................................................... 20
1.4.
Sample Size Justification ............................................................................................................... 21
1.5.
Randomization and Blinding .......................................................................................................... 21
1.5.1.
Randomization............................................................................................................................21
1.5.2.
Maintenance of the Blind ............................................................................................................ 22
2.
GENERAL ANALYSIS DEFINITIONS ..............................................................................................23
2.1.
Visit Windows................................................................................................................................. 23
2.1.1.
Visit Windows for Dosing and PK Analysis................................................................................. 23
2.2.
Pooling Algorithm for Analysis Centers..........................................................................................23
2.3.
Analysis Sets.................................................................................................................................. 23
2.3.1.
Efficacy Analysis Set(s) .............................................................................................................. 23
Full Analysis Set 1 (Week 0 – Week 24)................................................................................. 23
2.3.1.1.
Full Analysis Set 2 (Week 24 – Week 52)............................................................................... 24
2.3.1.2.
Per-Protocol Analysis Set (Week 0 – Week 24)...................................................................... 24
2.3.1.3.
2.3.2.
Safety Analysis Set..................................................................................................................... 24
2.3.3.
PK Analysis Set ..........................................................................................................................24
2.3.4.
Immunogenicity Analysis Set...................................................................................................... 24
2.3.5.
PD Analysis Set ..........................................................................................................................24
2.4.
Definition of Subgroups.................................................................................................................. 25
2.5.
Treatment Failure...........................................................................................................................26
3.
INTERIM ANALYSIS AND DATA MONITORING COMMITTEE REVIEW....................................... 26
3.1.
Interim Analysis..............................................................................................................................26
3.2.
Data Monitoring Committee ........................................................................................................... 26
4.
SUBJECT INFORMATION................................................................................................................ 27
4.1.
Subject information will be summarized by randomized treatment group based on the 
FAS1. Treatment exposure (e.g., number of treatment administrations, and cumulative 
dose received) and duration of study follow-up time will be summarized by treatment 
actually received based on the safety analysis set (Section 4.4).Demographics and 
Baseline Characteristics................................................................................................................. 27
4.2.
Disposition Information................................................................................................................... 27
4.3.
Treatment Compliance................................................................................................................... 28
4.4.
Treatment Exposure and Study Follow-up..................................................................................... 28
4.5.
Protocol Deviations ........................................................................................................................28
4.6.
Prior and Concomitant Medications...............................................................................................28
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5.
EFFICACY ......................................................................................................................................... 29
5.1.
General Method of Analysis........................................................................................................... 29
5.2.
Analysis Specifications................................................................................................................... 30
5.2.1.
Level of Significance................................................................................................................... 30
5.2.2.
The overall type I error will be controlled among the primary and major secondary 
endpoints at 5% as specified in Section 5.2.2.  Multiplicity Adjustment for Testing 
Procedures.................................................................................................................................. 30
US-Specific Multiplicity Adjustment for Testing Procedures ................................................... 31
5.2.2.1.
Global Multiplicity Adjustment for Testing Procedures............................................................33
5.2.2.2.
5.2.3.
Data Handling Rules................................................................................................................... 34
Missing Data Non-Responder Imputation (NRI)...................................................................... 34
5.2.3.1.
Missing Data Exhaustive Scenario Imputation........................................................................ 35
5.2.3.2.
Multiple Imputation (MI)........................................................................................................... 35
5.2.3.3.
MI for Binary Endpoints for Tipping Point Sensitivity Analysis................................................ 35
5.2.3.4.
Missing Data as Missing for Continuous Endpoints................................................................36
5.2.3.5.
Missing Data Handling for Tipping Point Sensitivity Analysis for Continuous 
5.2.3.6.
Endpoints................................................................................................................................. 36
5.2.4.
Estimands ................................................................................................................................... 36
Composite Strategy................................................................................................................. 36
5.2.4.1.
Alternative Composite Strategy...............................................................................................37
5.2.4.2.
Per-Protocol Strategy .............................................................................................................. 38
5.2.4.4.
5.3.
Primary Efficacy Endpoint(s).......................................................................................................... 38
5.3.1.
Definition..................................................................................................................................... 38
5.3.2.
Analysis Methods........................................................................................................................40
Primary Analysis...................................................................................................................... 40
5.3.2.1.
Sensitivity and Supplementary Analyses ................................................................................ 40
5.3.2.2.
Subgroup Analyses ................................................................................................................. 41
5.3.2.3.
Summary of Analyses Related to the Primary Endpoint of ACR 20 Response at Week 
5.3.2.4.
24............................................................................................................................................. 41
5.4.
Major Secondary Endpoints........................................................................................................... 42
5.4.1.
Change from Baseline in HAQ-DI Score at Week 24................................................................. 43
Definition.................................................................................................................................. 43
5.4.1.1.
Analysis Methods .................................................................................................................... 44
5.4.1.2.
5.4.2.
Proportion of Subjects with ACR 50 Response at Week and 24, Proportion of Subjects 
with ACR 20 Response at Week 16, Proportion of Subjects with ACR 50 Response at 
Week 16, and Proportion of Subjects with ACR 70 Response at Week 24 ...............................44
Definition.................................................................................................................................. 44
5.4.2.1.
Analysis Methods .................................................................................................................... 44
5.4.2.2.
5.4.3.
Proportion of Subjects Who Achieve a Psoriasis IGA Response at Week 24 Among the 
Subjects with ≥3% BSA Psoriatic Involvement and an IGA Score of ≥2 (mild) at 
Baseline ...................................................................................................................................... 45
Definition.................................................................................................................................. 45
5.4.3.1.
Analysis Methods .................................................................................................................... 45
5.4.3.2.
5.4.4.
Change from Baseline in Enthesitis Score at Week 24 and Proportion of subjects with 
Resolution of Enthesitis at Week 24 in Subjects with Enthesitis at Baseline.............................45
Definition.................................................................................................................................. 45
5.4.4.1.
Analysis Methods .................................................................................................................... 46
5.4.4.2.
5.4.5.
Change from Baseline in Dactylitis Scores at Week 24 and Proportion of subjects with 
Resolution of Dactylitis at Week 24 in Subjects with Dactylitis at Baseline................................46
Definition.................................................................................................................................. 46
5.4.5.1.
Analysis Methods .................................................................................................................... 46
5.4.5.2.
5.4.6.
Change from Baseline in SF-36 PCS Score at Week 24 and Change from Baseline in 
SF-36 MCS score at Week 24.................................................................................................... 47
Definition.................................................................................................................................. 47
5.4.6.1.
Analysis Methods .................................................................................................................... 47
5.4.6.2.
5.4.7.
Change from Baseline in DAS28 (CRP) at Week 24.................................................................. 48
Definition.................................................................................................................................. 48
5.4.7.1.
Analysis Methods .................................................................................................................... 48
5.4.7.2.
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5.4.8.
Summary of Analyses Related to Major Secondary Endpoints.................................................. 49
5.4.9.
Additional Tipping Point Analyses ..............................................................................................50
5.5.
Other Efficacy Variable(s) .............................................................................................................. 51
5.5.1.
Efficacy Endpoints Related to Reduction of Signs and Symptoms and Physical 
Function ...................................................................................................................................... 51
Definition.................................................................................................................................. 51
5.5.1.1.
5.5.1.1.1.
ACR Related Endpoints ....................................................................................................... 51
5.5.1.1.2.
HAQ-DI Related Endpoints .................................................................................................. 52
5.5.1.1.3.
DAS28 Related Endpoints.................................................................................................... 52
5.5.1.1.4.
Responders Based on Modified Psoriatic Arthritis Responder Criteria (PsARC) ................ 53
5.5.1.1.5.
Enthesitis Related Endpoints ...............................................................................................53
5.5.1.1.6.
Dactylitis Related Endpoints ................................................................................................53
5.5.1.1.7.
PASDAS Related Endpoints ................................................................................................54
5.5.1.1.8.
GRACE Index.......................................................................................................................55
5.5.1.1.9.
DAPSA Related Endpoints................................................................................................... 55
5.5.1.1.10.
Minimal Disease Activity (MDA) and Very Low Disease Activity (VLDA) ............................56
5.5.1.1.11.
BASDAI Related Endpoints.................................................................................................. 57
Analysis Method ...................................................................................................................... 57
5.5.1.2.
5.5.2.
Efficacy Endpoints Related to Skin Disease............................................................................... 61
Definitions................................................................................................................................62
5.5.2.1.
5.5.2.1.1.
PASI Related Endpoints....................................................................................................... 62
Analysis Methods .................................................................................................................... 63
5.5.2.2.
5.5.3.
Other Efficacy Endpoints Related to Health-Related Quality of Life and Health 
Economics .................................................................................................................................. 64
Definition.................................................................................................................................. 65
5.5.3.1.
5.5.3.1.1.
SF-36 Questionnaire ............................................................................................................ 65
5.5.3.1.2.
FACIT-Fatigue Questionnaire ..............................................................................................65
5.5.3.1.3.
PROMIS 29 ..........................................................................................................................66
Analysis Method ...................................................................................................................... 66
5.5.3.2.
5.5.4.
Other Tipping Point Analyses ..................................................................................................... 69
6.
SAFETY............................................................................................................................................. 70
6.1.
Safety Table Presentation.............................................................................................................. 70
6.1.1.
Summaries Through Week 24.................................................................................................... 70
6.1.2.
For subjects who started treatment with placebo only but later received any amount of 
guselkumab prior to Week 24 (due to inadvertency), the safety events/measurements 
on and after the first dose of guselkumab will be excluded from the data summaries 
through Week 24.  Only the safety events/measurements that occurred while the 
subjects had been receiving placebo only will be included in the data summaries 
through Week 24.  Summaries Through End of Study (Week 60) ............................................. 71
6.2.
Adverse Events..............................................................................................................................72
6.3.
Clinical Laboratory Tests................................................................................................................ 72
6.4.
Vital Signs and Physical Examination Findings............................................................................. 73
6.5.
Electrocardiogram..........................................................................................................................73
6.6.
Other Safety Parameters ............................................................................................................... 73
6.6.1.
Suicidal Ideation and Behavior ................................................................................................... 73
7.
PHARMACOKINETICS/PHARMACODYNAMICS ........................................................................... 75
7.1.
Pharmacokinetics...........................................................................................................................75
7.2.
Immunogenicity (Antibodies to Guselkumab) ................................................................................ 77
7.3.
Pharmacodynamics........................................................................................................................78
7.4.
Pharmacokinetic/Pharmacodynamic Relationships....................................................................... 78
REFERENCES............................................................................................................................................ 79
APPENDICES............................................................................................................................................. 81
APPENDIX 1:  RULES APPLIED IN DEFINITIONS OF ENDPOINTS...................................................... 81
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Statistical Analysis Plan CNTO1959PSA3001 Amendment 3
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APPENDIX 2:  STATISTICAL HYPOTHESES .......................................................................................... 82
APPENDIX 3:  DESCRIPTION OF STATISTICAL MODELS.................................................................... 85
APPENDIX 4:  SUMMARY OF MULTIPLE IMPUTATION METHODS ..................................................... 87
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Statistical Analysis Plan CNTO1959PSA3001 Amendment 3
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LIST OF TABLES
Table 1:
Permitted Concomitant Medications for PsA and Maximum Doses Allowed During the 
Study......................................................................................................................................... 19
Table 2:
Statistical Power for the ACR 20 Response Rate Comparing to Placebo at Week 24 ............ 21
Table 3:
Summary of Analyses Related to the Primary Endpoint of ACR 20 Response at Week 
24 .............................................................................................................................................. 42
Table 4:
Summary of Analyses Related to Major Secondary Endpoints................................................ 49
Table 5:
Summary of Estimands, Analysis Sets, Data Handling Rules, and Analysis Methods 
for Endpoints of Signs & Symptoms and Physical Function..................................................... 58
Table 6:
Summary of Estimands, Analysis Sets, Data Handling Rules, and Analysis Methods 
for Endpoints of Skin Disease................................................................................................... 63
Table 7:
Summary of Estimands, Analysis Sets, Data Handling Rules, and Analysis Methods 
for HRQOL Endpoints............................................................................................................... 67
LIST OF FIGURES
Figure 1:
Schematic Overview of the Study Through End of Study......................................................... 18
Figure 2:
Multiplicity Control Procedure for Major Secondary Endpoints ..Error! Bookmark not defined.
Figure 3:
US-Specific Multiple Comparison Procedure ........................................................................... 32
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Statistical Analysis Plan CNTO1959PSA3001 Amendment 3
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Approved, Date: 21 March 2019
AMENDMENT HISTORY
AMENDMENT 1 (APPROVAL DATE: MAY 25, 2018)
Summary of Major Changes and Modifications
This statistical analysis plan (SAP) was amended to implement the following major changes and 
modifications to the original SAP:
1. Modified treatment failure (TF) rules
2. Modified multiplicity control method to separate US and rest of the world

Rest of the world: modified overall control for all endpoints and both dose levels to 
control 2 doses for the primary endpoints, and control within dose level for primary 
and all major secondary endpoints

US:  added overall control for all endpoints and both dose levels to control selective 
endpoints and both dose levels by removing highly correlated major secondary 
endpoints from controlled list 
3. Modified the Multiple Imputation (MI) methods

Impute the continuous components for binary endpoints instead of the composite 
binary endpoint itself

Use the Full Conditional Specifications (FCS) to replace the imputation first imputed 
non-monotone missing values and then imputed monotone missing values.

Added Appendix 4 to detail the MI methods for endpoints with possibility to use MI 
method
4. Modified or added definitions for estimands and list of efficacy endpoints using each of the 
estimands

Modified the composite estimand for binary endpoints with 4 components for clarity 
and expanded endpoints using composite estimand from primary and major secondary 
to all binary endpoints

Modified the treatment policy estimand with 4 components for clarity and expanded 
endpoints using this estimand from primary endpoint only to also including major 
secondary endpoints of change from baseline in HAQ score, DAS28(CRP), SF36-
PCS and SF36-MCS at Week 24

Replaced the treatment efficacy estimand with the composite estimand for continuous 
endpoints and used this estimand for all continuous endpoints
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Statistical Analysis Plan CNTO1959PSA3001 Amendment 3
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Approved, Date: 21 March 2019

Added an expanded composite estimand to incorporate expanded treatment failure 
rules and used this estimand as a supplementary analysis for the primary endpoint

Added a Per-Protocol estimand and used this estimand as a supplementary analysis 
for primary endpoint
5. Added and modified analysis methods for efficacy endpoints

Modified MMRM model by adding the interactions of the fixed effects to use a model 
with full parameters, and added cLDA method if more than 2% subjects have missing 
baseline measurements.

For continuous major secondary endpoints, added analysis methods when the data have 
extreme departure from normality

Changed analysis method of other binary endpoints from a GLMM model or logistic 
regression to a CMH test 

Modified or added sensitivity/supplementary analyses for primary endpoint of ACR 20 
response at Week 24
a) For the composite estimand, when the main analysis is based on non-responder 
imputation, replace the sensitivity analysis based on MAR tipping point analysis 
to Exhaustive Scenario Imputation tipping analysis to cover all possible scenarios
b) Added analyses based on the expanded composite estimand 
c) Added analyses based on the Per-Protocol estimand

Added a summary table for analysis methods at the end of each section by the category of 
efficacy endpoints

Removed the endpoints related to mCPDAI and related analyses since DLQI, a 
component of mCPDAI, is not collected
6. Added a section for analysis of suicidal ideation and behavior data
Additionally, non-content related wording or formatting changes were made to enhance clarity 
and to generate 2 consistent SAPs.
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Statistical Analysis Plan CNTO1959PSA3001 Amendment 3
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AMENDMENT 2
Summary of Major Changes and Modifications
This statistical analysis plan (SAP) was amended to implement the following modifications to 
the original SAP:
1. Section 2.4.
a.
Revised the categories for the race subgroup - #1b
b. Instead of subgrouping by geographical region defining a subgroup called 
participating countries - #1g.
c.
Added subgroups #2l, #3g, #3h, and #3i.
2. Added clarification to treatment failure (section 2.5) criterion #1 to include adverse events 
caused by worsening of PsA. 
3. Modified multiplicity control method (section 5.2.2).
4. Added clarification to section 5.2.3.3 regarding the imputation of each variable within its 
possible range of values.
5. Added a supplementary analysis for IGA response based on the treatment policy estimand to
section 5.4.3.3 and Table 6.
6. Modified assessment of normality of residuals from MMRM/cLDA models by using Q-Q 
plots in addition to the Shapiro-Wilks test (sections 5.1 and 5.4.1.2, and Table 4).
7. Modified the enthesitis scoring for subjects with an incomplete set of 6 evaluated sites at a 
particular visit (section 5.4.4.1). Removed the use of non-missing site score based imputation 
to adjust for sites with missing scores.
8. Modified analysis methods for enthesitis and dactylitis related endpoints (sections 5.4.4.2, 
5.4.5.2, and 5.5.1.2) in accordance with the multiplicity control method (section 5.2.2).
9. Added an assessment for the presence of tender dactylitis (section 5.5.1.1.6)
10. Added the definition for low or very lose disease activity based on the PASDAS score 
(section 5.5.1.1.7) and a corresponding analysis to Table 5.
11. Added the definition of low disease activity based on the GRACE index score (section 
5.5.1.1.8) and a corresponding analysis to Table 5.
12. Added the definition of remission or low disease activity based on the DAPSA score (section 
5.5.1.1.9) and a corresponding analysis to Table 5.
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13. Added the definition of very low disease activity (section 5.5.1.1.10) and a corresponding 
analysis to Table 5.
14. Added the requirement of BASDAI>0 at baseline for the analysis of the change from 
baseline in BASDAI score (section 5.5.1.1.11 and Table 5).
15. Deleted DLQI related endpoints from section 5.5.2 as these had been erroneously included in 
this Statistical Analysis Plan.
16. Added clarification to section 6.4, regarding reporting of abnormalities or changes during 
physical examination as adverse events.
17. Separated joint evaluability rules for surgical joint procedures and injections administered 
due to PsA or non-PsA reasons in Appendix 1 (Joint Evaluability Rules for Sign and 
Symptom Data).
18. Added clarifications to the summary of multiple imputation methods in Appendix 4.
a.
Imputation variables to be used for MIdataset2.
b. Use of enthesitis-4, which is the tender entheses count based on 4 sites (left and right 
achilles tendon insertion, and left and right humeral epicondyle lateral) instead of 6 
sites at baseline and Week 2, in the imputation of enthesitis scores.
c.
Change from baseline at Week 24 in enthesitis score will be calculated among 
subjects with at least one tender enthesis at baseline.
d. Added footnotes “c” and “d”.
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AMENDMENT 3
Summary of Changes in Amendment 3 to the SAP
1. Revised the definition of subgroups (section 3.4):
a.
Age at baseline (year):  < 45, ≥ 45 and < 65, ≥65 (revised definition)
Age at baseline (year):  < 65, ≥ 65 (previous definition)
b. Clarified that the following disease characteristics are assessed at baseline:
PsA duration, number of swollen joints, number of tender joints, HAQ-DI, 
dactylitis, enthesitis, PASI, BSA, and IGA.
c.
Clarified that the subgroup of use of non-biologic DMARDs at baseline (Yes, No) 
and prior anti-TNFα use (Yes, No) are based on the eCRF data and not the IWRS 
randomization factors.
d. Removed the category of “any DMARDs” from the subgroup of non-biologic 
DMARDs at baseline. The revised definition includes only three categories: 
None, MTX, non-MTX DMARDs.
e.
Edited the descriptors for the reason of discontinuation of prior DMARDs and 
prior anti-TNFα use.
2. Revised the definition of the Treatment Failure Criteria (Section 2.5). The TF criteria are 
expanded by considering discontinuation of study agent due to other reasons (in addition 
to lack of efficacy) as a criterion for TF. This is reflected in Criterion 1 which now states 
-  Discontinued study agent injections due to any reason.
3. Added the following paragraph to Section 4:
Subject information will be summarized by randomized treatment group based on the 
FAS1. Treatment exposure (e.g., number of treatment administrations, and 
cumulative dose received) and duration of study follow-up time will be summarized 
by treatment actually received based on the safety analysis set (Section 4.4).  
4. Added the following information to Section 5.1 for binary response efficacy endpoints:
The Mantel Fleiss criterion will be used to determine the appropriateness of using the 
CMH test at each visit for each treatment pair under comparison. If the Mantel Fleiss 
criterion is not satisfied the Fisher’s exact test will be used instead of the CMH test to 
compare the two treatment groups.
For analyses based on Multiple Imputation, the inferences from the analysis of each 
imputed data are pooled. The within imputation variance and between imputation 
variance are combined to estimate the total variance of the stratum adjusted difference 
of proportions. This estimate of the variance and critical values from the t-distribution 
are used to calculate the confidence interval for the stratum adjusted difference of 
proportions. The SAS procedure PROC MIANALYZE is used where the critical 
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value is based on the t-distribution which is different from the analysis not based on 
MI where normal distribution is used. The large number of observations in our data 
imply that the critical values from the t-distribution are almost identical to the critical 
values from the standard normal distribution. The Wilson-Hilferty27 transformation is 
used to pool the p-values from each imputed data set.
5. For major secondary efficacy endpoints the analysis will be performed using an 
ANCOVA model based on MI data and will no longer use a Mixed Effect Repeated 
Measures or Constrained Longitudinal Data Analysis Model. The previously planned 
sensitivity analyses using an ANOVA model based on the van der Waerden normal score 
will not be performed. These changes to the plan are reflected in the edits in Section 5.1 
for major secondary continuous efficacy endpoints. Added details regarding the 
calculation of the  confidence intervals and p-values.
6. Revisions to section 5.2.2.1 (US-Specific Multiplicity Adjustment for Testing 
Procedures).
7. Added section 5.2.2.2 (Global Multiplicity Adjustment for Testing Procedure)
8. Added the following to Section 5.2.3.3.1:
For categorical endpoints (IGA response, enthesitis resolution, dactylitis resolution), 
the above imputation will be performed for the respective scores on a continuous 
scale, then rounded to the nearest integer prior to deriving the response or resolution.
9. Revised the definition of the Treatment Failure Criteria (Section 2.5). The TF criteria are 
expanded by considering discontinuation of study agent due to other reasons (in addition 
to lack of efficacy) as a criterion for TF. This is reflected in criterion 1 which now states -  
Discontinued study agent injections due to any reason.
10. Added a definition for the alternative composite estimand (Section 5.2.4.2).
11. Added the following to Section 5.2.4.3:
The Treatment Policy Estimand will be analyzed for all major secondary endpoints
(Table 4a), and selected endpoints (Table 7a) analyzed at Week 16.
12. In section 5.3.2.1, for the primary endpoint, deleted the supplementary analyses based on 
the previously defined expanded composite estimand, and added a supplementary 
analysis based on the alternative composite estimand. This is also reflected in Table 3.
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13. Added clarification to Section 5.4 about the analysis sets to be used for psoriasis response 
of IGA, change from baseline in enthesitis score, resolution of enthesitis, change from 
baseline in dactylitis score. and resolution of dactylitis.
14. Section 5.4.1.2 reflects changes to the analysis methods for HAQ-DI score as those 
described in item 5 (above) and in Section 5.1.
15. Sections 5.4.6.2 and 5.4.7.2 reflect changes as those described in item 5 above. These 
changes are also reflected in Table 4, which summarizes analyses related to major 
secondary endpoints.
16. Added section 5.4.9 (Additional Tipping Point Analyses) that describes the tipping point 
analyses to be performed on the major secondary endpoints based on the Treatment 
Policy Estimand.
17. In section 5.5.1.2, added that change from baseline in HAQ-DI, DAS28 (CRP), dactylitis, 
and enthesitis scores will be analysed using an ANCOVA model on MI data.
18. Added 4 endpoints - Change from baseline in FACIT-fatigue score at Week 24 by ACR 
20 response (primary endpoint) at Week 24, Proportion of subjects who achieve ≥ 4-point 
improvement from baseline in FACIT-fatigue score at Week 24 by ACR 20 response 
(primary endpoint) at Week 24,  Proportion of subjects who achieve an improvement of ≥ 
3 points in PROMIS-29 domain scores by visit through Week 24, and Proportion of 
subjects who achieve an improvement of ≥ 5 points in PROMIS-29 domain scores by 
visit through Week 24 – to Section 5.5.3 and Table 7.
19. In Section 5.5.3.2:

added that the change from baseline in SF-36 PCS score and SF-36 MCS score 
will be also be analyzed using an ANCOVA model on MI data. 

Added a description of additional analyses for FACIT-Fatigue.
20. Added section 5.5.4, that explains tipping point analyses to be performed for endpoints 
other than the primary and major secondary endpoints.
21. Added the following 3 references:
Yeonhee Kim, Seunghyun Won. Adjusted proportion difference and confidence interval in stratified 
randomized trials. PharmaSUG 2013 – Paper SP04.
Bohdana Ratitch, et al. Combining analysis results from multiply imputed cartegorical data. PharmaSUG 
2013- Paper SP03.
L. Valeri and T. J. VanderWeele (2013), “ Meidation Analysis Allowing for Exposure-Mediator 
Interactions and Causal Interpretation: Theoretical Assumptions and Implementation with SAS and SPSS 
Macros”, Psychological Methods, Vol. 18, No.2: 137-150.
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22. Added description of Mediation Analysis to Appendix 3.
23. Revisions to Appendix 4:
a.
Changed “at” to “through” for endpoints HAQ-DI score, DAS28 (CRP) score, 
Enthesitis score, Dactylitis score, PCS score, and MCS score.
b. Added MI for IGA change from baseline through Week 24.
c.
Edit to footnote “a”:
i. MIdataset2 is different from MIdataset1 as the joint scores used in DAS 
28 (CRP) are different from those used in ACR. (current footnote)
ii. MIdataset2 is different from MIdataset1 as it is based on a different 
Estimand. The same, MIdataset2, data set can be used for both HAQ-DI 
and DAS28(CRP) analyses. (previous footnote).
d. Edits to footnote “d”:
i. Enthesitis-4 is the tender entheses count based on 4 sites (left and right 
achilles tendon insertion, and left and right humeral epicondyle lateral) 
instead of 6 sites. Only baseline, Week 2, Week 4 are included as ancillary 
variables. (current footnote)
ii. Enthesitis-4 is the tender entheses count based on 4 sites (left and right 
achilles tendon insertion, and left and right humeral epicondyle lateral) 
instead of 6 sites at baseline and Week 2. (previous footnote)
24. Revised Appendix 2.
Note that changes to the analytic approaches in these amended SAPs also apply to the 
analysis plan for the Integrated Summary of Efficacy.
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ABBREVIATIONS
ACR
American College of Rheumatology
AE
adverse event
ALT
Alanine aminotransferase
AMDF
Arithmetic Mean of the Desirability Function
ANA
Antinuclear antibodies
ANCOVA
analysis of covariance
ANOVA
Analysis of variance
ARMA
Autoregressive moving average 
AST
Aspartate aminotransferase
BASDAI
Bath Ankylosing Spondylitis Disease Activity Index
BMI
Body mass index
BSA
Body surface area
CI
confidence interval
CMH
Cochran-Mantel-Haenszel
CRP
C-reactive protein
CSR
Clinical Study Report
DAPSA
Disease Activity Index for Psoriatic Arthritis
DAS28
Disease Activity Index Score 28 
DBL
database lock
DIP
Distal interphalangel
DLQI
Dermatology Life Quality Index
DMARDS
Disease-Modifying Antirheumatic Drugs
DMC
Data Monitoring Committee
ECG
Electrocardiogram
eCRF
electronic case report form
EE
Early escape
EQ-5D
EuroQol 5 Dimensions Health-Related Quality of Life
FACIT-Fatigue
Functional Assessment of Chronic Illness Therapy - Fatigue
FAS
Full Analyses Set
FCS
Full Conditional Specification 
GDEV
Physician’s Global Assessment of Disease Activity
GDPT
Patient’s Global Assessment of Disease Activity
GMS
Global Medical Safety
GRAPPA
Group for Research and Assessment of Psoriasis and Psoriatic Arthritis
HAQ-DI
Health Assessment Questionnaire Disability Index
HCQ
Hydroxychloroquine
ITT
Intent-to-Treat
IWRS
interactive web response system
LEF
Leflunomide
LEI
Leeds Enthesitis Index
LLOQ
Lower limit of quantification
LS means
Least square means
MCP
Metacarpophalangeal Joint
MCS
Mental Component Score
MDA
Minimal Disease Activity
MedDRA
Medical Dictionary for Regulatory Activities
MI
Multiple imputation
MMRM
Mixed-effect repeated measures
MTX
Methotrexate
NCI-CTCAE
National Cancer Institute - Common Terminology Criteria for Adverse Events
NRI
Non-responder imputation
NSAID
non-steroidal anti-inflammatory drug
PAIN
Patient’s assessment of pain
PASDAS
Psoriatic ArthritiS Disease Activity Score
PASI
Psoriasis Area and Severity Index
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PCS
Physical Component Summary
PsARC
Modified Psoriatic Arthritis Responder Criteria
PD
Pharmacodynamic
PIP
proximal interphalangeal
PK
pharmacokinetic(s)
PRO
patient reported outcome
PROMIS 
Patient-Reported Outcomes Measurement Information System
PsA
Psoriatic Arthritis
q4w
every 4 weeks
q8w
every 8 weeks
RA
Rheumatoid arthritis
RBC
Red blood cell
SAE
serious adverse event
SAP
Statistical Analysis Plan
SC
subcutaneous
SD
standard deviation
SF-36
36-Item Short Form Survey Instrument
SJC
Swollen joint count
SPARCC
Spondyloarthritis Research Consortium of Canada
SSG
Statistical support group
SSZ
Sulfasalazine
SUA
Serious unexpected adverse event
TB
Tuberculosis
TF
Treatment failure
TJC
Tender joint count
TNF
tumor necrosis factor
VAS
Visual analog scale
WBC
White blood cell
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1.
INTRODUCTION
This statistical analysis plan (SAP) contains definitions of analysis sets, derived variables, and 
statistical
methods 
for 
the 
analysis 
of 
efficacy,
safety, 
pharmacokinetics 
(PK), 
pharmacodynamics (PD),
Immunogenicity
and health related quality of life
in the 
CNTO1959PSA3001 study.
1.1.
Trial Objectives
Primary Objective 
The primary objective of this study is to evaluate the efficacy of SC administration of 
guselkumab 100 mg in subjects with active psoriatic arthritis (PsA) by assessing the reduction in 
signs and symptoms of PsA. 
Secondary Objectives 
The secondary objectives are to assess the following for guselkumab treatment in subjects with 
active PsA: 

Efficacy in improving psoriatic skin lesions, physical function, health-related quality of life, 
and patient-reported health outcomes 

Safety 

PK, PD, and immunogenicity 
1.2.
Trial 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 DMARDs, apremilast, or NSAIDs). In addition, subjects (approximately 30%) may
have been previously treated with up to 2 anti-TNFα agents. An overview of the study design is
provided in Figure 1.  
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Figure 1:
Schematic Overview of the Study Through End of Study
At Week 0, approximately 360 subjects who have met the study inclusion and exclusion criteria 
are to be randomized in a blinded fashion in a 1:1:1 ratio to 1 of the following 3 treatment groups 
using permuted block randomization stratified by baseline use of non-biologic DMARD (MTX, 
SSZ, HCQ, LEF) use (yes, no) and 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.
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Through the study, stable doses of concomitant NSAIDs, oral corticosteroids, and selected non-
biologic DMARDs (limited to MTX, SSZ, HCQ, LEF, see Table 1) will be allowed but are not 
required.  Subjects should not initiate any new treatment for PsA through Week 60, except at 
Week 16.  At Week 16, subjects in all treatment groups who have < 5% improvement from 
baseline in both swollen and tender joint counts will be considered as meeting early escape (EE) 
criteria and will, be allowed to initiate or increase the dose of one of the permitted concomitant 
medications up to the maximum dose allowed as specified in Table 1, as selected by the 
investigator.  
Table 1:
Permitted Concomitant Medications for PsA and Maximum Doses Allowed During the Study
Permitted Concomitant Medications for PsAa,b
Maximum Dose Allowed
NSAIDs and other analgesics
Marketed dose approved in the country where the 
study is being conducted
Oral corticosteroids
Equivalent to 10 mg/day of prednisone
Non-biologic DMARDS:
Methotrexate (MTX)c
25 mg/week
Sulfasalazine (SSZ)
3 g/day
Hydroxychloroquine (HCQ)
400 mg/day
Leflunomide (LEF)
20 mg/day
a Permitted concomitant medications are not supplied by the Sponsor.
b Subjects may not be receiving more than one non-biologic DMARD from baseline through Week 60.  
c It is recommended that all subjects taking MTX in this study receive at least 5 mg oral folate or 5 mg folinic acid 
weekly. Guidelines for dose adjustment in the event of MTX toxicity are included in the Trial Center File.
At Week 24, all subjects who are still on treatment in the placebo group (Group III) will cross
over to receive guselkumab 100 mg SC q4w from Week 24 through Week 48. Subjects in the 
guselkumab groups (Groups I and II) will remain on the same dose regimen at Week 24 and 
after, that is, there will be no change to the dose regimen.
Subjects will be followed for adverse events (AE) and serious adverse events (SAE) up to 12 
weeks following the last study treatment administration. 
The end of the study is defined as the last visit for the last subject.  The last visit is the last safety 
follow-up visit for subjects who complete the Week 48 study treatment and for subjects who 
terminate study treatment prior to Week 48.
There are 2 planned database locks (DBLs) in this study.  Each of these 2 DBLs will result in a 
study report.  The first DBL will occur when all subjects randomized in this study have either 
completed the Week 24 assessments or terminated study participation prior to the Week 24 visit 
(referred to as Week 24 DBL hereafter).  The second DBL will occur when all subjects 
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randomized in this study have either completed the Week 60 assessments or terminated study 
participation prior to the Week 60 visit [referred to as Final (Week 60) DBL hereafter].  
The primary endpoint of this study is the proportion of subjects who achieve a 20% improvement 
from baseline in the American College of Rheumatology criteria (ACR 20) at Week 24 (refer to 
Section 5.3 for endpoint definition and analyses).  This endpoint was chosen because it is well-
accepted by regulatory authorities and the clinical PsA community.  Additionally, there are 13
major secondary endpoints in the study (Section 5.4 – definitions and analyses methods).  The 
primary and major secondary endpoints will be analyzed at Week 24 DBL.
The study will remain blinded for the duration of the trial, until after the Final (Week 60) DBL.  
Selected Sponsor personnel will be unblinded at Week 24 DBL for the purposes of performing 
data analysis and data review.  The details regarding the Sponsor personnel that will be 
unblinded at Week 24 DBL will be provided in the Data Release Plans.  
An independent, external Data Monitoring Committee (DMC) will monitor the safety of the 
study in an unblinded fashion on a regular basis and whenever deemed necessary.  Additional 
details related to DMC are provided in Section 3.2.
1.3.
Statistical Hypotheses for Trial Objectives
The primary endpoint of this study is proportion of subjects who achieved an ACR 20 response 
at Week 24 (refer to Section 5.3 for endpoint definition and analyses). This endpoint was chosen 
because it is well-accepted by regulatory authorities and the clinical PsA community.
The hypotheses related to the primary endpoint are that:
1.
treatment with guselkumab 100 mg SC q4w is superior to treatment with placebo SC with 
respect to reduction of PsA signs and symptoms as measured by proportion of subjects who 
achieved an ACR 20 response at Week 24 (primary hypothesis); and
2.
treatment with guselkumab 100 mg SC at Week 0, Week 4 and then q8w is superior to 
treatment with placebo SC with respect to reduction of PsA signs and symptoms as 
measured by proportion of subjects who achieved an ACR 20 response at Week 24 (major 
secondary hypotheses).
The first hypothesis is the primary hypothesis for this study. If the first hypothesis achieves the 
statistical significance at a 2-sided α-level of 0.05, the study will be considered positive.
In addition to the primary endpoint, there are 13 major secondary endpoints in this study (refer to 
Section 5.4 for the list of these endpoints and their definitions). The hypotheses related to the 
major secondary endpoints (all are major secondary hypotheses) are provided in Appendix 2. 
For hypothesis testing order and multiplicity adjustment, refer to Section 5.2.2.
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1.4.
Sample Size Justification
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 in CNTO1275PSA3002 study 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 a 2-sided α-level of 0.05,
assuming a 40% ACR 20 response rate in the guselkumab group and a 20% ACR 20 response 
rate in the placebo group 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 2 provides the power evaluation of various 
assumptions.
Table 2:
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%
1.5.
Randomization and Blinding
1.5.1.
Randomization
A central randomization is to be implemented in this study using an interactive web response 
system (IWRS).  When a subject is eligible for randomization at a study site, the randomization 
requestor at that study site will contact the IWRS using the requester’s own user identification
and personal identification number and provide the relevant subject details to uniquely identify 
that subject.  Based on a computer-generated randomization schedule prepared before the study 
under the supervision of the Sponsor, the IWRS will then assign a unique treatment code, which 
will dictate the treatment assignment and matching study agent kit for that subject.  
To assure relatively even treatment balance within each stratum defined by baseline use of non-
biologic DMARD (yes, no) and prior exposure to anti-TNFα agents (yes, no) randomization at 
Week 0 is determined using permuted block randomization stratified by baseline use of non-
biologic DMARD (yes, no) and prior exposure to anti-TNFα agents (yes, no). Specific details are 
provided in the IWRS Specification Unbinding Randomization for CNTO1959PAS3001
(JAN333).
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At Week 24, all subjects who were randomized to placebo at Week 0 and who are still on study 
treatment at Week 24 will be switched to receive guselkumab 100 mg q4w by the IWRS to 
receive guselkumab 100 mg q4w starting from Week 24.  
1.5.2.
Maintenance of the Blind
The study blind will be maintained for the duration of the study, until after the Final (Week 60)
DBL at end of study.
To maintain the study blind, the study agent container will have a multipart label with directions 
for use and other information, but not the identity of the study agent, on each part.  One part of 
the label is designed to be torn off, separated from the study agent container, and attached to the 
subject’s source documents.  The rest of the label will remain affixed to the study agent 
container.  Thus, the study agent assigned to a subject will be linked between the container and 
the subject without breaking the study blind.  The study agent kit number will be entered in the 
electronic case report form (eCRF) or other equivalent data capture method when the drug is 
administered. The investigator will not be provided with treatment codes, but the codes will be 
maintained within the IWRS, which has the functionality to allow the investigator to break the 
blind for an individual subject when there is a need based on medical judgment. 
Data that may potentially unblind the treatment assignment (i.e., study agent serum 
concentrations, antibodies to study agent) will be handled with special care to ensure that the 
integrity of the blind is maintained and the potential for bias is minimized.  This may include 
making special provisions, such as segregating the data in question from view by the 
investigators, clinical team, or others as appropriate. 
An investigator may be unblinded to a given subject’s treatment allocation when specific 
emergency treatment would be dictated by knowing the treatment status of the subject.  In such 
cases, the investigator may determine the identity of the treatment by contacting the IWRS 
provider. It is strongly recommended that the investigator contact the Sponsor or its designee if 
possible to discuss the particular situation prior to unblinding via IWRS.  Telephone contact with 
the Sponsor or its designee will be available 24 hours per day, 7 days per week.  In the event that 
the investigator is unable to contact the Sponsor, or emergency unblinding is considered 
medically necessary, the investigator may determine the identity of the treatment via /IWRS.  
However, the Sponsor must be informed as soon as possible.  The date, time, and reason for the 
unblinding must be documented in the appropriate section of the eCRF, and in the source 
document.  The documentation received from the /IWRS indicating the code break must be 
retained with the subject's source documents in a secure manner (e.g., sealed envelope) so as to 
not unblind the treatment assignment to the subject, the study site, or Sponsor personnel.  The 
investigator is also advised not to reveal the study treatment assignment to the subject, the study 
site, or Sponsor personnel. Subjects who have had their treatment assignment unblinded are 
expected to continue to return for scheduled evaluations.  Further study agent administrations 
should be discussed with the study responsible physician.
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A given subject’s treatment assignment may be unblinded to the Sponsor, Institutional Review 
Board/Independent Ethics Committee (IRB/IEC), and site personnel to fulfill regulatory 
reporting requirements for suspected unexpected serious adverse reactions (SUSARs).  A 
separate code break procedure will be available for use by Janssen Global Medical Safety (GMS) 
to allow for unblinding of individual subjects to comply with specific requests from regulatory or 
health authorities.
A number of prospectively identified Sponsor individuals will be unblinded at the Week 24 DBL
for the purposes of performing data analysis and review.  Identification of sponsor personnel 
who will have access to the unblinded data at subject-level and who will have access to the 
unblinded data at group-level will be documented in the Data Release Plan prior to unblinding at 
the Week 24 DBL.  Investigative sites and subjects will remain blinded to treatment assignment 
for the duration of the study, till after the Final (Week 60) DBL.
An independent, external DMC will monitor the safety of the study in unblinded fashion on a 
regular basis and whenever deemed necessary.  In addition, the Sponsor Medical Monitor will 
review safety data in a blinded manner as the study is ongoing.  The DMC’s roles and 
responsibilities, the safety data for DMC review, and other related information (such as, the 
general procedures, communications, etc.) are defined and documented in the DMC charter.  
2.
GENERAL ANALYSIS DEFINITIONS
2.1.
Visit Windows
2.1.1.
Visit Windows for Dosing and PK Analysis 
All post-baseline visits through Week 24 will have a visit window of ± 4 days. All the visits after 
Week 24 through Week 52 will have a visit window of ± 7 days (1 Week). The final safety visit 
will have a visit window of 14 days (± 2 weeks).  
Study agent administrations must always be at least 14 days apart.
For PK analyses, if a subject has an administration outside the visit window at a visit, the 
concentration data collected at and after that visit will be excluded from the by-visit data 
analyses. 
2.2.
Pooling Algorithm for Analysis Centers
Data from all investigational centers/sites will be pooled for analyses.
2.3.
Analysis Sets
2.3.1.
Efficacy Analysis Set(s)
Full Analysis Set 1 (Week 0 – Week 24)
2.3.1.1.
The full analysis set 1 (FAS1) includes all randomized subjects who received at least 1 dose 
(complete or partial) of study agent.  This analysis set will be used for the efficacy analyses of 
endpoints through Week 24.  
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Full Analysis Set 2 (Week 24 – Week 52)
2.3.1.2.
The full analysis set 2 (FAS2) includes all randomized subjects who were still on study treatment 
at Week 24.  This analysis set will be used for the efficacy analysis of endpoints from Week 24
through Week 52.  
Per-Protocol Analysis Set (Week 0 – Week 24)
2.3.1.3.
The per-protocol analysis set (PPAS) includes all subjects in FAS1 who met all inclusion and 
exclusion criteria and had no major protocol deviation that could have impacted efficacy 
assessment per clinical judgement.  This analysis set will be used for the analyses of selected
efficacy endpoints through Week 24.  Subjects to be excluded from this analysis will be 
identified prior to Week-24 DBL and unblinding.
In the efficacy analyses, subjects will be analyzed according to the randomized treatment groups 
they were assigned to, regardless of the treatments they actually received.  
2.3.2.
Safety Analysis Set
The safety analysis set includes all subjects who received at least 1 (partial or complete) dose of 
study agent, i.e., the treated population.
In the safety analyses, subjects will be analyzed according to the treatment they actually 
received, regardless of the treatments they are randomized to.
2.3.3.
PK Analysis Set
The PK analysis set includes all subjects who received at least 1 complete dose of guselkumab 
and had at least 1 valid blood sample drawn for PK analysis.
In the PK analyses, subjects will be analyzed according to the treatment they actually received, 
regardless of the treatments they are randomized to.
2.3.4.
Immunogenicity Analysis Set
The immunogenicity analysis set includes all subjects who received at least 1 (partial or 
complete) dose of guselkumab and who have at least 1 sample obtained after their first dose of
guselkumab for the detection of antibodies to guselkumab.
In the immunogenicity analyses, subjects will be analyzed according to the treatment they 
actually received, regardless of the treatments they are randomized to.
2.3.5.
PD Analysis Set
The PD analysis set includes all subjects who received at least 1 (partial or complete) dose of 
study agent, i.e., the treated population.
In the PD analyses, subjects will be analyzed according to the treatment they actually received, 
regardless of the treatments they are randomized to.
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2.4.
Definition of Subgroups
To evaluate the consistency in the primary efficacy endpoint (proportion of subjects who achieve 
ACR 20 at Week 24) over demographics, baseline characteristics, prior and baseline medication 
use, subgroup analyses will be performed.  The subgroups include, but are not limited to, the 
following:
1.
Demographic subgroups 
a.
Gender: Male, Female
b.
Race: White, Other
c.
Age at baseline (year):  < 45, ≥ 45 and < 65, ≥65
d.
Body weight at baseline (kg): ≤90, >90 
e.
Body weight at baseline (kg): (quartiles)
f.
Body mass index (BMI) at baseline: Normal [< 25], Overweight [≥ 25 to < 30], 
Obese [≥ 30]
g.
Participating countries: Poland, Russia, Ukraine, Western countries (USA, Canada, 
Spain, and Germany), Other countries (combining countries in Asia and Eastern 
European countries other than Poland, Russia and Ukraine)
2.
Baseline disease characteristics subgroups
a.
PsA duration at baseline (year): < 1, ≥ 1 to < 3, ≥ 3  
b.
PsA subtype: distal interphalangeal joint involvement, polyarticular arthritis with 
absence of rheumatoid nodules, arthritis mutilans, asymmetric peripheral arthritis, 
spondylitis with peripheral arthritis 
c.
Number of swollen joints at baseline: < 10, 10 -15, > 15
d.
Number of tender joints at baseline: < 10, 10 -15, > 15
e.
HAQ-DI at baseline: < 1, 1 - 2, > 2
f.
CRP at baseline (mg/dL): < 1, 1-2, ≥ 2
g.
CRP at baseline (mg/dL): (quartiles)
h.
Dactylitis at baseline: Yes, No 
i.
Enthesitis at baseline: Yes, No
j.
PASI at baseline: <12, 12-20, >20 
k.   BSA affected by psoriasis at baseline: <3, 3-10%, 10-20%, >20% 
l.
  IGA at baseline: <2, ≥2
3.
Prior and baseline medication use subgroups:
a.
Prior anti-TNFα use (eCRF): Yes, No
b.
Number of prior anti-TNFα agents: 1, 2. 
c.
Reason for discontinuation for prior anti-TNFα: Efficacy - inadequate response
(IR), Safety - contraindication or intolerance (but not IR), Other 
d.
Use of non-biologic DMARDs (MTX, SSZ, HCQ, LEF) at baseline (eCRF): Yes, 
No 
e.
Oral corticosteroids at baseline: Yes, No
f.
NSAIDs at baseline: Yes, No
g.
Number of prior non-biologic treatments including DMARDs, systemic 
immunosuppressive drugs, and apremilast: 0, 1, 2, ≥3.
h.
Non-biologic DMARDS (MTX, SSZ, HCQ, LEF) at baseline: None, MTX, non-
MTX DMARDs
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i.
Reason for discontinuation of prior DMARDs: Efficacy - inadequate response (IR), 
Safety - contraindication or intolerance (but not IR), Other
Note that some of the above subgroup cut-off points may be changed if there are no or few 
subjects within a subgroup category.
2.5.
Treatment Failure
A subject will be considered a treatment failure (TF) from the earliest date that the subject meets 
any of the following TF criteria onward through Week 24: 
1. Discontinued study agent injections due to any reason.
2. Terminated study participation due to any reason.
3. Initiated or increased the dose of non-biologic DMARDs (MTX, SSZ, HCQ, LEF) or oral 
corticosteroids over baseline for PsA.
4. Initiated protocol prohibited medications/therapies for PsA. 
Note that all subjects who meet criterion 2 will always have met criterion 1.
3.
INTERIM ANALYSIS AND DATA MONITORING COMMITTEE REVIEW
3.1.
Interim Analysis
No interim analysis is planned for this study.
3.2.
Data Monitoring Committee
An independent, external DMC has been established to monitor data on an ongoing basis to 
ensure the continuing safety of the subjects while participating in this study.  All subjects are to 
be followed by the DMC from the first dose administered through at least the Week 24 DBL. 
The DMC consists of 3 members (including 2 medical experts in the relevant therapeutic areas 
and 1 statistician) who are independent of the Sponsor. None of the members is participating in 
the current study.  An independent statistical support group (SSG), not affiliated to the sponsor, 
supports the DMC and serves the liaison between the DMC and the sponsor.
The major function of the DMC is to monitor the safety of the study agent by reviewing the 
serious adverse events (SAEs) each month and by periodically reviewing the interim study safety 
data every 4-months.  After each review, the DMC is to make recommendations regarding the 
continuation of the study or, in the event that any unanticipated serious events occur, placing the 
study on hold or stopping the study. 
The DMC will have access to unblinded data and review tabulated safety summaries (if 
appropriate) and any additional data as deemed necessary during the conduct of the study.  No 
formal statistical hypothesis testing is planned.  
The content of the safety summaries, the DMC role and responsibilities and the general 
procedures (including communications) and their recommendations on the study conduct are
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defined and documented in the DMC charter, which will be finalized prior to the first DMC 
review.
In addition, during the study, the Sponsor's study responsible physician (or designee) will 
regularly review blinded safety data from the sites and notify the DMC and appropriate Sponsor 
personnel of any issues.  
4.
SUBJECT INFORMATION
4.1.
Subject information will be summarized by randomized treatment group 
based on the FAS1. Treatment exposure (e.g., number of treatment 
administrations, and cumulative dose received) and duration of study 
follow-up time will be summarized by treatment actually received based on 
the safety analysis set (Section 4.4).Demographics and Baseline 
Characteristics
Demographic and baseline characteristic variables will be descriptively summarized by 
randomized treatment group. No formal statistical comparison is planned.  P-values will not be 
provided.
Demographic variables to be summarized will include sex, race, age, height, baseline weight, and 
baseline body mass index (BMI).  Baseline characteristic variables to be summarized will 
include, but not be limited to, baseline disease characteristics of PsA (e.g., duration of disease, 
PsA subtypes, baseline efficacy assessments), medical history, prior medication exposure, prior 
joint procedures/injections, and baseline medication usage for PsA.
In addition, balance between randomized treatment groups will also be explored for the 
subpopulations used for analyses below:

subjects with baseline ≥3% body surface area (BSA) psoriatic involvement and an IGA 
score of ≥2 (mild) at baseline (for skin disease related endpoint analyses).

subjects with enthesitis at baseline

subjects with dactylitis at baseline
4.2.
Disposition Information
The number of subjects randomized and treated will be summarized by geographic region, 
country, and investigational site.
Disposition will also include tabulations, by randomized treatment group, of the number of 
subjects who discontinued study agent administration early and the primary reasons for 
discontinuation of study agent administration early, and the number of subjects who discontinued 
study participation early and the primary reason for discontinuation of study participation early.  
Tabulations by randomized treatment group will also be provided for subjects who met EE 
criteria at Week 16 and for subjects who met 1 or more TF criteria as defined in Section 2.5.
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In addition, subjects who were randomized but never treated and subjects who met any TF 
criteria will be presented in data listings.
4.3.
Treatment Compliance
Treatment compliance will be assessed by the number of study agent administrations completed 
versus the number of study agent administrations planned.
Tabulations of the number of subjects by the study agent lot(s) and by treatment assigned versus 
treatment received will also be provided.
4.4.
Treatment Exposure and Study Follow-up
The overall treatment exposure (e.g., duration of study treatment, number of treatment 
administrations, and cumulative dose received) and duration of study follow-up time will be 
summarized by treatment actually received based on the safety analysis set, ie, all treated 
subjects.  
4.5.
Protocol Deviations
Subjects with major protocol deviations, defined as having the potential to impact subjects’ 
rights, safety or well-being, or the integrity and/or result of the clinical trial, will be listed or 
descriptively summarized by randomized treatment group.  The major protocol deviations will be 
grouped into the following 5 categories:

Developed withdrawal criteria but not withdrawn

Entered but did not satisfy criteria

Received a disallowed concomitant treatment

Received wrong treatment or incorrect dose

Other
The study selection criteria will be grouped into the following 5 categories: PsA disease criteria, 
medication criteria, laboratory criteria, medical history criteria, and other.   
Subjects with protocol deviations in study agent administration will be summarized by type of 
deviations and by treatment group.
4.6.
Prior and Concomitant Medications
Prior medications taken for PsA and psoriasis (e.g., DMARDs, oral corticosteroids and NSAIDS) 
will be summarized by randomized treatment group.  Concomitant medications taken for PsA 
will also be summarized by randomized treatment group.  
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5.
EFFICACY
5.1.
General Method of Analysis
In general, descriptive statistics, such as mean, standard deviation (SD), median, inter quartile 
(IQ) range, minimum, and maximum for continuous variables, and counts and percentages for 
discrete variables will be used to summarize most data.  
Statistical comparison between a guselkumab group (100 mg q4w or 100 mg at Weeks 0, 4 and
then q8w) and the placebo group will be performed by visit through Week 24. No treatment
comparison will be performed after Week 24.
Binary Response Efficacy Endpoints
For binary response efficacy endpoints, treatment comparisons will generally be performed using 
a Cochran-Mantel-Haenszel (CMH) test stratified by baseline use of non-biologic DMARD (yes, 
no) and prior exposure to anti-TNFα agents (yes, no). The magnitude of the treatment difference 
will be estimated by the difference in response rates between the guselkumab and placebo groups 
with a 95% confidence interval (CI) calculated based on Wald statistics.26 In these analyses, 
subjects with missing data will be imputed as not achieving the response as described in 
Section 5.2.3.1.
The Mantel Fleiss criterion will be used to determine the appropriateness of using the CMH test 
at each visit for each treatment pair under comparison. If the Mantel Fleiss criterion is not 
satisfied the Fisher’s exact test will be used instead of the CMH test to compare the two 
treatment groups.
For analyses based on Multiple Imputation, the inferences from the analysis of each imputed data 
are pooled. The within imputation variance and between imputation variance are combined to 
estimate the total variance of the stratum adjusted difference of proportions. This estimate of the 
variance and critical values from the t-distribution are used to calculate the confidence interval 
for the stratum adjusted difference of proportions. The SAS procedure PROC MIANALYZE is 
used where the critical value is based on the t-distribution which is different from the analysis 
not based on MI where normal distribution is used. The large number of observations in our data 
imply that the critical values from the t-distribution are almost identical to the critical values 
from the standard normal distribution. The Wilson-Hilferty27 transformation is used to pool the 
p-values from each imputed data set.
Major Secondary Continuous Efficacy Endpoints
For the major secondary continuous endpoints (Section 5.4) and related continuous efficacy 
endpoints in Section 5.5, treatment comparisons will be performed using an analysis of 
covariance (ANCOVA) model based on MI data. The MI method will be applied to impute the 
missing value under the assumption of missing at random (MAR). The estimate of the mean 
change from baseline is the average of the mean change taken over all the MI data sets. The 
estimate of the variance of the mean change from baseline is the weighted sum of the average 
within-imputation variance and the between-imputation variance. The confidence interval for the 
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mean change from baseline uses critical values from the t-distribution. The treatment difference 
between each guselkumab group versus the placebo group will be tested for each imputation 
dataset and then the analysis results across all imputation datasets will be combined. The 
treatment difference in the change from baseline is estimated by the average of the treatment 
differences over the MI data sets. The estimate of the variance of the treatment difference in the 
change from baseline is the weighted sum of the average within-imputation variance and the 
between-imputation variance, under the assumption of homogeneity of variance between 
treatment groups for performing ANCOVA within each imputation dataset. The confidence 
interval is based on the critical values from the t-distribution.
The ANCOVA model will be based on the original scale and will include treatment group, 
baseline score, baseline use of non-biologic DMARD (yes, no) and prior exposure to anti-TNFα 
agents (yes, no) as the explanatory factors. The model will include data from all the 3 treatment 
groups.  
Other Continuous Efficacy Endpoints
For all other continuous efficacy endpoints, treatment comparisons will be performed using a 
MMRM model (Appendix 3) or a cLDA Model (Appendix 3).  The model will include all 
available data from the 3 treatment groups through Week 24. The treatment difference between a 
guselkumab group and the placebo group will be estimated by the difference in the LSmeans. 
The 95% CIs for the differences in LSmeans and p-values will be calculated.
In addition, graphical data displays (eg, line plots) and subject listings may also be used to 
summarize/present the data. 
5.2.
Analysis Specifications
5.2.1.
Level of Significance
5.2.2.
The overall type I error will be controlled among the primary and 
major secondary endpoints at 5% as specified in Section 5.2.2.  
Multiplicity Adjustment for Testing Procedures
This study has 1 primary endpoint (proportion of subjects who achieved an ACR 20 response at 
Week 24) and 13 major secondary endpoints.  With 14 endpoints and 2 treatment comparisons 
for each of these endpoints, there are a total of 28 hypotheses to be tested. Refer to Appendix 2
for the list of hypotheses to be tested.  
The primary hypothesis in this study is that treatment with guselkumab 100 mg SC q4w is 
superior to treatment with placebo SC with respect to reduction of PsA signs and symptoms as 
measured by proportion of subjects who achieved an ACR 20 response at Week 24. Due to 
regional differences in regulatory requirements on multiplicity control from health authorities, 2 
multiplicity control procedures are pre-specified. Details for the US-specific multiplicity 
adjustment are provided in Section Error! Reference source not found. and for the Global(ex-
US) multiplicity adjustment procedure are provided in Section 5.2.2.2.
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With respect to endpoints of enthesitis and dactylitis, the important soft tissue manifestations of 
PsA, the resolution of enthesitis and resolution of dactylitis endpoints will be tested by 
combining data from studies CNTO1959PSA3001 and CNTO1959PSA3002 to provide a more 
robust comparison with greater power than using data from 
only 1 study of 
CNTO1959PSA30021 or CNTO1959PSA3002..
US-Specific Multiplicity Adjustment for Testing Procedures
5.2.2.1.
The multiple comparison procedure pre-specified to address the requirement of the Food and 
Drug Administration (FDA) of the United States (US) for family-wise control of the primary and 
major secondary endpoints is described in this section.
Per FDA review comment dated 
03OCT2017 [IND 124177 – Guselkumab (CNTO 1959) – Guidance regarding statistical 
analysis plans for CNTO1959PSA3001 and CNTO1959PSA3002 submitted on August 10, 
2017], only the primary and major secondary endpoints that are important and access different 
attributes of disease will be controlled.   
The overall Type I error of the treatment comparisons of both doses versus placebo for the 
primary and the 7 selected major secondary endpoints will be controlled at a significance level of 
≤ 0.05. Refer to Appendix 2 for the 16 hypotheses to be tested and controlled with the graphical 
procedure as specified in Figure 3. For all endpoints specified in the graphical procedure, both 
adjusted and nominal p-values will be provided. In the instance that an adjusted p-value is not 
significant, the nominal p-value must only be interpreted as supportive.
The method of controlling the type I error across the testing of the hypotheses is described below 
and in Figure 3.

In addition to the primary endpoint, ACR20 at Week 24, 3 major secondary endpoints are 
identified as important and assess different attributes of the disease:Proportion of subjects 
who achieved a psoriasis IGA response at Week 24 among the subjects with ≥ 3% BSA 
psoriatic involvement and an IGA score of ≥ 2 at baseline

Change from baseline in HAQ-DI score at Week 24

Change from baseline in SF-36 PCS at Week 24
The overall Type I error of the treatment comparisons of both doses versus placebo for the 
primary and the 3 selected major secondary endpoints will be controlled at a significance level of 
≤ 0.05. Refer to Appendix 2 for the 8 hypotheses to be tested and controlled with the graphical 
procedure as specified in Figure 3. For all endpoints specified in the graphical procedure, both 
adjusted and nominal p-values will be provided. In the instance that an adjusted p-value is not 
significant, the nominal p-value must only be interpreted as supportive.
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The method of controlling the type I error across the testing of the hypotheses is described below 
and in Figure 3.
Nominal p-values will be reported for the major secondary endpoints of the resolution of 
enthesitis, resolution of dactylitis, the change from baseline in the dactylitis, enthesitis, and SF-
36 MCS score at Week 24. Refer to Appendix 2 for the list of these 10 hypotheses. The treatment 
comparisons are underpowered for these hypotheses.
Figure 2:
US-Specific Multiple Comparison Procedure
The major secondary endpoints of ACR 20 at Week 16, ACR 50 at Week 16, ACR 50 at Week 
24, ACR 70 at Week 24, and change from baseline in DAS28 at Week 24 are closely related to 
the primary endpoint (ACR 20 at Week 24) in assessing PsA signs and symptoms. When ACR
20 at Week 24 is significant for a guselkumab group versus the placebo group, these 5 major 
secondary endpoints will be formally tested for that guselkumab group versus the placebo group 
at a 2-sided α-level of 0.05. Otherwise, the p-values for the treatment group comparisons will be 
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considered nominal. A total of 10 hypotheses tests fall in this category of weakly controlled. 
Refer to Appendix 2 for the list of these 10 hypotheses.
Nominal p-values will be provided for treatment comparisons on the following major secondary 
endpoints:

proportion of subjects with resolution of dactylitis at Week 24

Proportion of subjects with resolution of enthesitis at Week 24

Change from baseline in the dactylitis at Week 24

Change from baseline in the enthesitis at Week 24

Change from baseline in the SF-36 MCS score at Week 24
Refer to Appendix 2 for the list of these 10 hypotheses. The treatment comparisons are 
underpowered for these hypotheses.

Global Multiplicity Adjustment for Testing Procedures
5.2.2.2.
There are 2 hypotheses for the primary endpoint with 2 treatment comparisons:

The Guselkumab 100 mg q4w group is superior to placebo group as measured by ACR20 
response at Week 24 (primary hypothesis). 

The Guselkumab 100 mg at Weeks 0, 4, and then q8w group is superior to placebo group as 
measured by ACR20 response at Week 24. 
These 2 hypotheses will be tested in a fixed sequence in the order specified above. The overall 
type 1 error of treatment comparison for the primary endpoint be controlled at a significance 
level of ≤0.05. If the primary hypothesis achieves statistical significance at a 2-sided α-level of 
0.05, the study will be considered positive. If the primary hypothesis does not achieve statistical 
significance (ie, the Guselkumab 100mg q4w dose group comparison against placebo is not 
significant), the treatment group comparison for the second hypothesis will not be formally 
tested and the p-value for the treatment group comparison of the Guselkumab 100mg at Weeks 0 
,4, and then q8w group against placebo will be considered nominal.. 
For each Guselkumab dose group, the overall Type I error of treatment comparison for primary 
and the selected major secondary endpoints will be controlled at a significance level of ≤0.05 as 
specified below:

The hypotheses for the selected major secondary endpoints for a Guselkumab dose group 
will be formally tested only if the primary endpoint is significant for that Guselkumab 
dose group. For each Guselkumab dose group, the overall Type I error of treatment 
comparison for the selected major secondary endpoints will be controlled at a 
significance level of ≤0.05 according to the graphical procedure shown in Figure 4. 
Refer to Appendix 2 for the 18 hypotheses for the major secondary endpoints to be tested 
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and controlled as specified in Figure 4. For all endpoints specified in the graphical 
procedure, both adjusted and nominal p-values will be provided. In the instance that an 
adjusted p-value is not significant, the nominal p-value must only be interpreted as 
supportive.

If the primary endpoint is not significant for that Guselkumab dose group, all treatment 
group comparisons for the major secondary endpoints for that Guselkumab dose group 
will not be formally tested and the p-values for the treatment group comparisons will be 
considered nominal.
Nominal p-values will be reported for the major secondary endpoint of the resolution of 
enthesitis, and dactylitis, the change from baseline in the dactylitis, enthesitis, and SF-36 MCS 
score. Refer to Appendix 2 for the list of these 10 hypotheses. The treatment comparisons are 
underpowered for these hypotheses.
Figure 4:
Global Multiple Comparison Procedure
DAS28 at 
Wk 24
0
HAQ DI at 
Wk 24
0
PCS at Wk 
24
0
1
1
1
IGA at Wk 
24
1
1
ACR 20 at 
Wk 16
0
1
ACR 50 at 
Wk 24
0
ACR 50 at 
Wk 16
0
ACR 70 at 
Wk 24
0
0.2
0.8
1
1
Guselkumab High Dose
vs Placebo
DAS28 at 
Wk 24
0
HAQ DI at 
Wk 24
0
PCS at Wk 
24
0
1
1
1
IGA at Wk 
24
1
1
ACR 20 at 
Wk 16
0
1
ACR 50 at 
Wk 24
0
ACR 50 at 
Wk 16
0
ACR 70 at 
Wk 24
0
0.2
0.8
1
1
ACR20 at 
Week 24
ACR20 at 
Week 24
If p≤0.05
Guselkumab Low Dose
vs Placebo
If p≤0.05
Graphical Procedure: 
Treatment of comparison of Guselkumab High Dose vs Placebo for selected  major secondary endpoints 
Graphical Procedure: 
Treatment of comparison of Guselkumab High Dose vs Placebo for selected major secondary endpoints 
5.2.3.
Data Handling Rules
Missing Data Non-Responder Imputation (NRI) 
5.2.3.1.
For response efficacy endpoints, subjects with missing response status will be considered non-
responders.
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Missing Data Exhaustive Scenario Imputation
5.2.3.2.
For selected response efficacy endpoints, the exhaustive scenario tipping point analyses will be 
performed to evaluate the deviation of the imputation of all missing data as non-responder, by 
varying the amount of non-responder and responder imputation for missing data. 
Let   be the total number of imputed values to-be-varied in the Active arm, where i of them 
will be set to ‘Yes’ response and (-i) of them set to ‘No’ response.  In the same vein, let  be 
the total number of imputed values to-be-varied in the Placebo arm, where j of them will be set 
to ‘Yes’ response and (-j) of them set to ‘No’ response. The range of i is from 0 to , and a 
range of j is from 0 to , which is an ‘exhaustive approach’.
Multiple Imputation (MI)  
5.2.3.3.
Under the assumption of missing at random (MAR), multiple imputation (MI) will be used to 
impute the missing data for the continuous/ordinal measurements. The missing data will be 
imputed using the predicted value from an imputation model using the Full Conditional 
Specification (FCS) regression method for any missing pattern. Each variable will be restricted 
to only impute within its possible range of values (eg, HAQ Score may only be imputed to within 
0-3. The explanatory variables in the imputation model include imputation variables and 
ancillary variables as specified in Appendix 4.
The number of imputations (N) and the starting seeds are also specified in Appendix 4. 
For the composite continuous endpoints (such as DAS28), the above imputation will be 
performed on components with missing data and then composite score will be derived based on 
such imputed components.  
For categorical endpoints (IGA response, enthesitis resolution, dactylitis resolution), the above 
imputation will be performed for the respective scores on a continuous scale, then rounded to the 
nearest integer prior to deriving the response or resolution.
For the composite binary endpoints (such as ACR 20), the above imputation will be performed 
on each component with missing data and then response status will be determined based on such 
imputed components.  
The treatment comparisons between a guselkumab group versus the placebo group will be 
performed using the analysis method specified for each of the N imputation datasets. The 
analysis results from all the N imputation datasets will be combined according to Rubin20 and the 
p-value for testing the treatment difference will be obtained.
MI for Binary Endpoints for Tipping Point Sensitivity Analysis
5.2.3.4.
For selected binary endpoints, the tipping point analyses based on imputed data by MI will be 
performed to evaluate the impact of missing data when deviating from MAR assumption.

A pair of deltas (e.g., Dg =-0.1, Dp =0.2) will be added to the predicted response rates of 
each missing data from the MI method depending on guselkumab or placebo group. 
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
With the new response rate, the missing response will be imputed for N (e.g., N=200) times 
to generate N multiple imputations based on a Bernoulli distribution. Treatment 
comparisons will then be performed same as treatment comparison with MI 

The range of delta values include the scenarios where subjects on guselkumab have worse 
outcomes than subjects on placebo.
Missing Data as Missing for Continuous Endpoints
5.2.3.5.
For continuous endpoints, when treatment comparisons are performed using a Mixed-Effect 
Model Repeated Measures (MMRM) or Constrained Longitudinal Data Analysis (cLDA) Model
(Appendix 3), all available data from the 3 treatment groups through Week 24 will be included. 
Missing data will not be imputed. Under the assumption of MAR, the missing data will be 
accounted for through correlation of repeated measures in the model.
Missing Data Handling for Tipping Point Sensitivity Analysis for 
5.2.3.6.
Continuous Endpoints
For the change from baseline in selected endpoints, tipping point analyses based on imputed data 
by MI will be performed to evaluate the impact of missing data when deviating from the MAR 
assumption

A delta (e.g., Dg =0.2, Dp =0.1) will be added to the imputed value for each subject with 
missing value from the MI depending on whether the subject is in the guselkumab or 
placebo group.  

With the new datasets, treatment comparisons will be performed similar to treatment 
comparisons with MI data.

The analysis will be repeated for a range of Dg and Dp by varying Dg and Dp 
independently, including the scenarios where subjects on guselkumab have worse 
outcomes than subjects on placebo.
5.2.4.
Estimands
The same population, ie, all subjects with active psoriatic arthritis including those previously 
treated with biologic anti-TNFα who meet inclusion/exclusion criteria will be used for all 
estimands defined below.  The FAS1 (Section 2.3.1.1) or a subset of FAS1 so that the endpoint 
measurement is meaningful, will be used to analyze data. 
Composite Strategy
5.2.4.1.
The Composite Strategy assesses the treatment effects not only based on the variable 
measurements, but also based on intercurrent events defined in TF criteria. When subjects 
maintain their background PsA medications at their baseline levels, the values based on the 
variable measurements will be used. If a subject met any of the TF criteria the subject will be a 
non-responder for response variables and will have a score of no improvement for continuous 
variables for signs and symptoms. This estimand acknowledges that meeting the TF criteria is an 
unfavorable outcome. 
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Variables:

Binary: The endpoint (e.g. ACR 20) is defined as responders who had not met any TF 
criteria prior to the specific visit at which the endpoint was assessed.

Continuous: The endpoint is defined as change from baseline score prior to meeting TF 
criteria and 0 (no improvement) after meeting TF criteria. This is based on the placebo 
response observed in prior PsA studies: the over-time mean improvements in the placebo 
group is generally greater than 0 by a meaningful amount. Therefore, no change is 
considered an extremely unfavorable outcome. 
Intercurrent Events: The intercurrent event is captured through variable definitions.
Population level summary: 

Binary: difference in proportion of responders between guselkumab group and placebo 
group.

Continuous: difference in mean changes between guselkumab group and placebo group.
The Composite Estimand will be analyzed for all efficacy endpoints through Week 24. 
Alternative Composite Strategy 
5.2.4.2.
The Alternative Composite Strategy is similar to the Composite Strategy described in Section 
5.2.4.1, however, discontinuation of study agent due to reasons other than lack of efficacy 
(including adverse events caused by worsening of PsA) are not treatment failure. In other words, 
the intercurrent events include TF criterion 2, 3, 4, and a subset of criterion 1 from those listed in 
section 2.5.
This estimand is only used at Week 24, the last visit of the placebo-controlled period.
The Alternative Composite Estimand (Binary) will be analyzed for ACR 20 at Week 24.
The Alternative Composite Estimand (Binary) will be analyzed for ACR 20 at Week 24.
Treatment Policy Strategy 
5.2.4.3.
The treatment policy strategy is to use all observed data collected for the endpoint. The 
occurrence of the intercurrent event is irrelevant: the value for the variable of interest is used 
regardless of whether or not the intercurrent event occurs. This is the supplementary strategy 
aiming to achieve a robust treatment effect for regulatory decision making for primary and some 
major secondary endpoints. 
Variable: 

Binary: response endpoint (e.g. ACR 20)

Continuous: change from baseline
Intercurrent Events: Regardless of the intercurrent event of meeting TF criteria 
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Population level summary: 

Binary: difference in proportion of responders between guselkumab group and placebo 
group.

Continuous: difference in mean changes between guselkumab group and placebo group.
The Treatment Policy Estimand will be analyzed for all major secondary endpoints (Table 4a),
and selected endpoints (Table 7a) analyzed at Week 16.
Per-Protocol Strategy
5.2.4.4.
The per-protocol strategy is to use the last assessment while on randomized treatment up to a 
specific visit (e.g., Week 24). For subjects who met TF criteria 3 or 4 prior to the said visit, the 
last assessment while on randomized treatment is the last assessment prior to meeting TF criteria 
3 or 4.  This is the supplementary strategy aiming to achieve a robust treatment effect for 
regulatory decision making for the primary endpoint of ACR 20 response at Week 24. 
Variable: last measurement while on randomized treatment prior to meeting TF criteria 3 and 4
(Section 2.5) or up to a specific visit (e.g., Week 24), whichever is earlier, where,
while on randomized treatment is defined as the time from first administration of 
randomized treatment through onset of TF criteria 3 or 4 being met or through 4 weeks 
after last administration of randomized treatment up to the said specific visit (e.g., 
Week 24), whichever is earlier.
Intercurrent Events: the intercurrent event is captured through variable definitions.
Population level summary: 

Binary: difference in proportion of responders between guselkumab group and placebo 
group.
The Per-Protocol Strategy Estimand will be analyzed for ACR20 at Week 24.
5.3.
Primary Efficacy Endpoint(s)
The primary endpoint of this study is proportion of subjects who achieved an ACR 20 response 
at Week 24. This section outlines the definitions and analyses of this primary endpoint.
5.3.1.
Definition
ACR response is a composite measurement of change in PsA signs and symptoms and is 
presented as the numerical measurement of improvement in multiple disease assessment 
criteria.3,4 An ACR20 response is defined as: 
1.
≥ 20% improvement from baseline in both tender joint count (68 joints) [TJC68] and 
swollen joint count (66 joints) [SJC66]  
AND
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2.
≥ 20% improvement from baseline in at least 3 of the following 5 assessments:
a.
Patient’s Assessment of Pain (VAS) [PAIN]
b.
Patient’s Global Assessment of Disease Activity (arthritis, VAS) [GDPT]
c.
Physician’s Global Assessment of Disease Activity (VAS) [GDEV]
d.
Patient’s Assessment of Physical Function as measured by HAQ-DI
e.
C-reactive protein (CRP)
Following are the definitions of each of the forgoing disease assessment criteria (components) 
that are used in the determination of ACR20 response:
1.
Tender Joint Count 68 (TJC68): a total number of tender joints among the 68 joints 
evaluated for tenderness.  Each of the 68 joints will be evaluated for tenderness, categorized 
as tender or not tender.  Joint evaluability rules specified in Appendix 1 for overwriting joint 
evaluation will be applied to those joints with joint injection(s)/surgical joint procedure(s).  
For subjects with any joint not evaluable in the 68 joint set, joint count adjustment rules
described in Appendix 1 will be applied in determining the ultimate count of tender joints. 
2.
Swollen Joint Count 66 (SJC66): a total number of swollen joints among the 66 joints 
evaluated for swelling. (Note: The 2 hip joints are excluded from swelling assessment.)  
Each of the 66 joints will be evaluated for swelling, categorized as swollen or not swollen.  
Joint evaluability rules specified in Appendix 1 for overwriting joint evaluation will be 
applied to those joints with joint injection(s)/surgical joint procedure(s).  For subjects with 
any joint not evaluable in the 66 joint set, joint count adjustment rules described in 
Appendix 1 will be applied in determining the ultimate count of swollen joints.
3.
Patient’s Assessment of Pain (PAIN): a measure from 0 (no pain) to 10 (the worst possible 
pain) on a 10-unit VAS. 
4.
Patient’s Global Assessment of Disease Activity (arthritis, GDPT): a measure from 0 (very 
well) to 10 (very poor) on a 10-unit VAS. 
5.
Physician’s Global Assessment of Disease Activity (GDEV): a measure from 0 (no arthritis 
activity) to 10 (extremely active arthritis) on a 10-unit VAS.
6.
HAQ-DI: a measure of difficulty a subject may have in accomplishing tasks in 8 functional 
areas.  For additional details, please refer to the definition of HAQ-DI in Section 5.4.1.1.
7.
C-reactive protein (CRP): a lab parameter measured in mg/dL.  LLOQ rule specified in 
Appendix 1 will be applied to values < LLOQ. 
If a subject’s baseline value for a component is zero (ie, no disease activity as measured by that 
component), the subject should be considered as not achieving 20% improvement from baseline
for that component since there is no room for improvement.
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5.3.2.
Analysis Methods
Primary Analysis
5.3.2.1.
The primary endpoint will be analyzed at Week 24 DBL based on the Composite Estimand 
(Section 5.2.4.1).  In the primary efficacy analysis, data from all subjects in FAS1 (Section 2.3.1) 
will be analyzed according to randomized treatment group regardless of the treatment actually 
received.  
The primary endpoint to be analyzed is proportion of subjects who achieved an ACR 20 response 
at Week 24 and who did not meet any TF criteria (Section 2.5) prior to Week 24.  Subjects who 
met any TF criteria prior to Week 24 will be considered non-responders at Week 24 regardless of 
the observed ACR 20 response status.   
The treatment difference between each guselkumab group versus the placebo group will be 
tested using a CMH test stratified by baseline use of non-biologic DMARD (yes, no) and prior
exposure to anti-TNFα agents (yes, no). The magnitude of the treatment difference will be 
estimated by the difference in ACR 20 response rates between the guselkumab and placebo 
groups with a 95% CI calculated based on Wald statistics.
Data Handling Rules

Missing Data NRI rules (Section 5.2.3.1) will be applied, i.e., subjects with missing data for 
ACR 20 response at Week 24 will be considered ACR 20 non-responders at Week 24.
In order to control the overall Type 1 error rate, the primary endpoint will be tested in a fixed 
sequence.
1. Guselkumab 100 mg q4w versus placebo in ACR 20 response at Week 24
2. Guselkumab 100 mg at Weeks 0, 4, and then q8w versus placebo in ACR 20 response at 
Week 24
If the first test is significant at a 2-sided α-level of 0.05, the study will be considered positive and 
the second test can then be performed.
Sensitivity and Supplementary Analyses
5.3.2.2.
1. To evaluate the robustness of the Composite Estimand regarding the assumption of all
missing data as non-responder, a sensitivity analysis with the exhaustive scenario tipping 
point analyses will be performed. The analysis will be conducted for an ‘exhaustive 
approach’ testing all combinations of missing data imputation as responder and NR
(Section 5.2.3.2). A chi-square test will be used to compare each guselkumab group versus 
the placebo group. This will avoid the complication of having to incorporate baseline 
stratification in the mix when generating all combinations of responders and non-responders 
for the missing data for CMH test.  As all combinations will be presented, both the points 
where tipping occurs, as well as the proportion of non-tipping combinations, are of interest.
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2. To support regulatory decision making, the Treatment Policy Estimand (Section 5.2.4.3) will 
also be evaluated as a supplementary analysis. In this analysis, however, the observed 
ACR 20 response for all subjects will be used regardless of whether or not TF criteria are met 
prior to Week 24, and the missing ACR 20 response for all subjects will be imputed by MI 
method (Section 5.2.3.3) under the assumption of MAR.  Treatment comparisons for each 
imputation data set will be based on a CMH test stratified by baseline use of non-biologic 
DMARD (yes, no) and prior exposure to anti-TNFα agents (yes, no).  And then the analysis 
results from the N imputation datasets will be combined, according to Rubin20 and the 
p-value for testing the treatment difference will be obtained.
3. Two-dimensional tipping point analyses based on MI imputed data will be performed as a 
supplemental analysis to assess the robustness for Treatment Policy Estimand regarding the 
assumption of MAR. A pair of deltas will be added to the predicted response rates from MI 
method 
depending 
on 
guselkumab 
or 
placebo 
group
to
new 
MI 
datasets
(Section 5.2.3.4). The same analysis method as in sensitivity and supplementary analysis 2 
will be applied for the pairs of deltas. The analysis will be done for pairs of delta values 
include the scenarios where subjects on guselkumab have worse outcomes than subjects on 
placebo.
4. In addition, the Alternative Composite Estimand will also be evaluated as a supplemental 
analysis (section 5.2.4.2). Subjects with missing data will be considered non-responders. The 
same analysis method as that used for the primary analysis will be applied.
5. A supplemental analysis will be performed similar to the primary analysis (Section 5.3.2.1), 
however, based on the Per-Protocol Strategy Estimand (Section 5.2.4.4).  In this analysis, 
ACR response status will be determined based on the last assessment up to Week 24 while
subjects on randomized treatment or the last non-missing assessment prior to meeting TF 
criteria 3 or 4, whichever is earlier. Note that this analysis will use the Per-Protocol Analysis 
Set (PPAS).
Subgroup Analyses
5.3.2.3.
Subgroup analyses will be performed using a logistic regression model to evaluate treatment 
consistency in proportion of subjects who achieve an ACR 20 response at Week 24 over baseline 
demographics, baseline disease characteristics, and prior and baseline medication use. A forest 
plot will be produced for all subgroups listed in Section 2.4. Odds ratios and the corresponding 
95% CIs will also be provided for each of subgroups. In addition, the p-values for interaction of 
the treatment groups and the subgroups will also be provided when a subgroup has at least 2 
categories.  
If the number of subjects in a subgroup is too small (eg., < 10), subgroups may be pooled for 
analyses.
Summary of Analyses Related to the Primary Endpoint of ACR 20 
5.3.2.4.
Response at Week 24
Table 3 below provides an overview on all the analyses related to the primary endpoint of 
ACR 20 response at Week 24, the estimands, the analysis sets, the data handling rules to be used, 
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and the analysis methods and summary statistics. Note that, for subgroup analyses, the analysis 
sets are the individual subgroups (Section 2.4) of FAS1. 
Table 3:
Summary of Analyses Related to the Primary Endpoint of ACR 20 Response at Week 24
Analysis 
(Analysis Set)
Missing data
Analysis method/Summary statistics
Analyses based on Composite Estimand, in which, subjects meeting any TF criteria (defined in Section 2.5) prior to
Week 24 will be considered as ACR 20 non-responders at Week 24.  
Primary Analysis
(FAS1)
Subjects with 
missing data are 
considered to be 
non-responders

Response rates

Treatment difference in response rates and 95% CI 

P-value from the CMH test (stratified by randomization 
stratification factors) for treatment comparison
Sensitivity Analysis
(FAS1)
Subjects with 
missing data are 
considered to be 
non-responders

Exhaustive tipping point analysis

The chi-squared test to compare treatment groups.

Analysis results to be presented graphically
Subgroup Analyses 
(Individual 
subgroup levels 
defined in 
Section 2.4)
Subjects with 
missing data are 
considered to be 
non-responders

Response rates

Odds ratio and 95% CI for treatment comparison

P-value from logistic regression for the interaction of treatment 
group and subgroup variable

Analysis results to be presented in forest plots
Analyses based on Treatment Policy Estimand, in which, all observed data will be used, regardless of whether or 
not the subjects meet any TF criteria.
Supplementary 
Analysis 1
(FAS1)
Multiple 
imputation with 
FCS regression of 
component scores

Response rates

Treatment difference in response rates and 95% CI 

P-value from the CMHa test (stratified by randomization 
stratification factors) for treatment comparisons.
Supplementary 
Analysis 2
(FAS1)
Multiple 
imputation with 
FCS regression of 
component scores

Tipping point analysis.

The CMHa test (stratified by randomization stratification factors) to 
compare treatment groups.

Analysis results to be presented graphically
Analyses based on Alternative Composite Estimand, in which, subjects meeting any TF criteria (defined in 
Section 2.5) except  discontinuation of study agent due to reasons other lack of efficacy, prior to Week 24 will be
considered as ACR 20 non-responders at Week 24..
Supplementary 
Analyses 3
(FAS1)
Subjects with 
missing data are 
considered to be 
non-responders

Response rates

Treatment difference in response rates and 95% CI 

P-value from the CMH test (stratified by randomization 
stratification factors) for treatment comparison
Analyses based on Per-Protocol Strategy Estimand, in which, ACR 20 response is determined based on the last 
measurement while subjects on randomized treatment up to Week 24 or prior to meeting TF criteria 3 or 4, whichever 
is earlier. 
Supplementary 
Analysis 4
(PPAS)
Not Applied

Response rates

Treatment difference in response rates and 95% CI 

P-value from the CMH test (stratified by randomization 
stratification factors) for treatment comparison
a When combining analysis results for CMH test, Wilson-Hilferty transformation will be applied to the test statistics to 
achieve an approximate normal distribution.
5.4.
Major Secondary Endpoints
The major secondary endpoints in this study are: 
1.
Change from baseline in HAQ-DI score at Week 24.
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2.
Proportion of subjects who achieve an ACR 50 response at Week 24.
3.
Proportion of subjects with a psoriasis response of an Investigator Global Assessment (IGA) 
(ie, an IGA psoriasis score of 0 [cleared] or 1 [minimal]) AND ≥2-grade reduction from 
baseline) at Week 24 among the subjects with ≥3% body surface area (BSA) psoriatic 
involvement and an IGA score of ≥2 (mild) at baseline.
4.
Proportion of subjects who achieve an ACR 20 response at Week 16.
5.
Proportion of subjects with resolution of enthesitis at Week 24 among the subjects with 
enthesitis at baseline.
6.
Proportion of subjects with resolution of dactylitis at Week 24 among the subjects with 
dactylitis at baseline.
7.
Change from baseline in enthesitis score (based on Leeds Enthesitis Index [LEI]) at 
Week 24 among the subjects with enthesitis at baseline. 
8.
Change from baseline in dactylitis scores at Week 24 among the subjects with dactylitis at 
baseline. 
9.
Change from baseline in SF-36 Physical Component Score (PCS) at Week 24.
10. Change from baseline in DAS28 (CRP) at Week 24.
11. Change from baseline in SF-36 Mental Component Score (MCS) at Week 24. 
12. Proportion of subjects who achieve an ACR 50 response at Week 16.
13. Proportion of subjects who achieve an ACR 70 response at Week 24.
This section outlines the definition and analyses of these major secondary endpoints. All the 
secondary endpoints will be analyzed at Week 24 DBL according to the randomized treatment 
groups.  Data from all subjects in FAS1 (Section 2.3.1) will be included with the following 
exceptions:
the analysis of the psoriasis response of IGA will be based on FAS1 among the subjects with 
a ≥ 3% BSA psoriatic involvement and an IGA score of   ≥ 2 (mild) at baseline
the analysis of change from baseline in enthesitis score change and resolution of enthesitis 
will be based on FAS1 among the subjects with enthesitis at baseline
the analysis of change from baseline in dactylitis score and resolution of dactylitis will be 
based on FAS1 among the subjects with dactylitis at baseline
5.4.1.
Change from Baseline in HAQ-DI Score at Week 24
Definition
5.4.1.1.
HAQ disability index (HAQ-DI) score is an evaluation of the functional status for a subject.6 The 
20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 
functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of 
daily living).  Responses in each functional area are scored from 0, indicating no difficulty, to 3, 
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indicating inability to perform a task in that area (i.e., lower scores are indicative of better 
functioning). 
The HAQ-DI score is the sum of computed category scores divided by the number of categories 
answered.  The HAQ-DI score will not be computed if the subject does not have scores for at 
least 6 of the 8 categories.
The scoring algorithm (including adjusting the use of aids or devices) is provided by 
http://patienteducation.stanford.edu/research/haq20.html and is detailed in a separate document.  
Change from baseline in HAQ-DI score is a measure of the change in the functional status, 
where a negative change reflects an improvement and a positive change reflects a worsening.
Analysis Methods
5.4.1.2.
The change from baseline in HAQ–DI score at Week 24 will be analyzed at Week 24 DBL based 
on the Composite Estimand (Section 5.2.4.1). In this analysis, data from all subjects in FAS1 
(Section 2.3.1) will be analyzed according to randomized treatment group regardless of the 
treatment received.  
Analysis of the change from baseline in HAQ–DI score at Week 24 will be performed using an 
ANCOVA model based on MI data. The MI method will be applied to impute, under the 
assumption of MAR, the missing change score of HAQ-DI from baseline at Week 24 defined in 
the Composite Estimand (i.e., change from baseline with no change assumed at and after meeting 
TF criteria). The treatment difference between each guselkumab group versus the placebo group 
will be tested for each imputation dataset and then the analysis results across all imputation 
datasets will be combined.
To support regulatory decision making, a supplementary analysis will be provided in FAS1 
based on the Treatment-Policy-Estimand. Analysis of the change from baseline in HAQ–DI 
score at Week 24 will be performed using an ANCOVA model based on MI data similar to the 
main analysis.
5.4.2.
Proportion of Subjects with ACR 50 Response at Week and 24, 
Proportion of Subjects with ACR 20 Response at Week 16, Proportion 
of Subjects with ACR 50 Response at Week 16, and Proportion of 
Subjects with ACR 70 Response at Week 24
Definition
5.4.2.1.
ACR 50 and ACR 70 responses are defined similarly to ACR 20 response (Section 5.3.1), except 
that the improvement threshold of 20% from baseline in ACR 20 response is replaced by 50% 
and 70%, respectively.   
Analysis Methods
5.4.2.2.
Data from all subjects in FAS1 (Section 2.3.1) will be analyzed according to randomized 
treatment group regardless of the treatment actually received.  
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The same analysis method as described in Section 5.3.2.1 will be applied to the treatment 
comparisons on proportion of subjects with ACR 50 response at Week 24, proportion of subjects 
with ACR 20 response at Week 16, proportion of subjects with ACR 50 response at Week 16, 
and proportion of subjects with ACR 70 response at Week 24. The analyses are based on the 
Composite Estimand (Section 5.2.4.1).  
5.4.3.
Proportion of Subjects Who Achieve a Psoriasis IGA Response at 
Week 24 Among the Subjects with ≥3% BSA Psoriatic Involvement 
and an IGA Score of ≥2 (mild) at Baseline
Definition
5.4.3.1.
The Investigator’s Global Assessment (IGA) documents the investigator’s assessment of the 
subject’s psoriasis at a given time point.  Overall lesions are graded for induration, erythema, and 
scaling.  The subject’s psoriasis is assessed as cleared (0), minimal (1), mild (2), moderate (3), or 
severe (4).
A psoriasis IGA response is defined as an IGA psoriasis score of 0 (cleared) or 1 (minimal) 
AND ≥2-grade reduction from baseline in the IGA psoriasis score.  
A psoriasis IGA response is only applicable to subjects who had an IGA psoriasis score of ≥2 
(mild) at baseline.
Analysis Methods
5.4.3.2.
Data from all subjects in FAS1 who had ≥ 3% BSA psoriatic involvement and an IGA score of 
≥2 (mild) at baseline will be included and analyzed according to the randomized treatment 
groups.  
The same analysis method as described in Section 5.3.2.1 will be applied to the treatment 
comparisons on proportion of subjects with a psoriasis IGA response at Week 24. The analyses 
are based on the Composite Estimand (Section 5.2.4.1).  
5.4.4.
Change from Baseline in Enthesitis Score at Week 24 and Proportion 
of subjects with Resolution of Enthesitis at Week 24 in Subjects with 
Enthesitis at Baseline
Definition 
5.4.4.1.
Enthesitis is an important feature of psoriatic arthritis and other spondyloarthropathies. In this 
study, enthesitis will be assessed by an independent joint assessor using the Leeds Enthesitis 
Index (LEI).10 The LEI was developed to assess enthesitis in subjects with PsA and evaluates the 
presence (score of 1) or absence (score of 0) of pain by applying local pressure to the following 
entheses: 

Lateral epicondyle humerus, left and right 
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
Medial femoral condyle, left and right 

Achilles tendon insertion, left and right 
The enthesitis index score is a total score of the 6 evaluated sites as listed above, with range from 
0 to 6. For subjects who have an incomplete set of 6 evaluated sites, the enthesitis index score 
based on the observed data cannot be calculated.
Change from baseline in enthesitis score measures the change in enthesitis, where a negative 
change indicates an improvement and a positive change indicates a worsening.
Subject with enthesitis at baseline are those subjects with at least at one tender enthesis among 
the 6 sites include in the LEI.
Subjects with resolution of enthesitis are those subjects who had at least one tender enthesis at 
baseline and none at the analysis visit among the 6 sites included in the LEI.
Analysis Methods
5.4.4.2.
For this endpoint, using data from the CNTO1959PSA3001 study, treatment groups will be 
compared in the CNTO1959PSA3002 study and will be reported with the analysis results from 
that study.
5.4.5.
Change from Baseline in Dactylitis Scores at Week 24 and Proportion 
of subjects with Resolution of Dactylitis at Week 24 in Subjects with 
Dactylitis at Baseline
Definition 
5.4.5.1.
Presence and severity of dactylitis will be assessed in both hands and feet using a scoring system 
from 0 to 3 (0 – no dactylitis, 1 – mild dactylitis, 2 – moderate dactylitis, and 3 – severe 
dactylitis).8,9
The results for each digit are summed to produce a final dactylitis score with a range from 0 to 
60.  
Change from baseline in dactylitis score measures the change in dactylitis, where a negative 
change indicates an improvement and a positive change indicates a worsening.
Subject with dactylitis at baseline are those subjects with a dactylitis score > 0 at baseline.  
Subjects with resolution of dactylitis are those subjects who had a dactylitis score > 0 at 
baseline and a score of 0 at the analysis visit.
Analysis Methods
5.4.5.2.
For this endpoint, using data from the CNTO1959PSA3001 study, treatment groups will be 
compared in the CNTO1959PSA3002 study and will be reported with the analysis results from 
that study.
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5.4.6.
Change from Baseline in SF-36 PCS Score at Week 24 and Change 
from Baseline in SF-36 MCS score at Week 24
Definition
5.4.6.1.
The questionnaire of the 36-item short form health survey (SF-36) is a health-related quality of 
life instrument with 36 questions, developed as part of the Rand Health Insurance Experiment.  
Version 2 will be used.  This instrument consists of 8 multi-item scales (domains).24

Limitations in physical functioning due to health problems

Limitations in usual role activities due to physical health problems

Bodily pain

General mental health (psychological distress and well-being)

Limitations in usual role activities due to personal or emotional problems

Limitations in social functioning due to physical or mental health problems

Vitality (energy and fatigue)

General health perception
Each of these 8 scales (domains) is scored from 0 to 100 with higher scores indicating better 
health.  Based on the scale scores, the 2 summary scores, physical component summary (PCS)
score and mental component summary (MCS) score, will be derived.  These summary scores are 
also scaled with higher scores indicating better health.   
Note that, the SF-36 scale scores will be derived based on the algorithm and software provided 
by the developer.21 The norm-based score will be used for data analysis and derived by using the 
2009 general US population with missing value estimated based on Advanced Data Recovery 
with Missing Score Estimator (MSE) provided in the user manual.21
Change from baseline in PCS score measures the change in health-related quality of life, where 
a positive change indicates an improvement and a negative change indicates a worsening.
Similarly, change from baseline in MCS score measures the change in health-related quality of 
life, where a positive change indicates an improvement and a negative change indicates a 
worsening.
Analysis Methods
5.4.6.2.
Data from all subjects in FAS1 will be included and analyzed according to the randomized 
treatment groups.  
The same analysis methods as described in Section 5.4.1.2 (ANCOVA on MI data) will be 
applied to treatment comparisons on the change from baseline in SF-36 PCS at Week 24 and 
change from baseline in SF-36 MCS at Week 24, based on the Composite Estimand (Section
5.2.4.1).  
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5.4.7.
Change from Baseline in DAS28 (CRP) at Week 24
Definition
5.4.7.1.
The Disease Activity Index Score 28 using CRP [DAS28 (CRP)]22 is a derived score combining 
tender joints (28 joints), swollen joints (28 joints), CRP, and Patient’s Global Assessment of 
Disease Activity.  The 28 joints evaluated for swelling and tenderness are shoulder, elbow, wrist, 
MCP1, MCP2, MCP3, MCP4, MCP5, PIP1, PIP2, PIP3, PIP4, PIP5 joints of the upper right and 
upper left extremities as well as the knee joints of the lower right and lower left extremities.
The DAS28 (CRP) is a continuous parameter and is defined as follows:
DAS28 (CRP) = 0.56* SQRT(TJC28) + 0.28*SQRT(SJC28) + 0.36* Ln (CRPmg/L +1) 
+ 0.014*GDPTmm + 0.96, where
1.
TJC28: a total number of tender joints among the 28 joints evaluated for tenderness.  Each 
of the 28 joints will be evaluated for tenderness, categorized as tender or not tender.  Joint 
evaluability rules specified in Appendix 1 for overwriting joint evaluation will be applied to 
those joints with joint injection(s)/surgical joint procedure(s).  For subjects with any joint 
not evaluable in the 28 joint set, joint count adjustment rules described in Appendix 1 will 
be applied in determining the ultimate count of tender joints.
2.
SJC28: a total number of swollen joints among the 28 joints evaluated for swelling.  Each of 
the 28 joints will be evaluated for swelling, categorized as swollen or not swollen.  Joint
evaluability rules specified in Appendix 1 for overwriting joint evaluation will be applied to 
those joints with joint injection(s)/surgical joint procedure(s).  For subjects with any joint 
not evaluable in the 28 joint set, joint count adjustment rules described in Appendix 1 will 
be applied in determining the ultimate count of swollen joints.
3.
CRPmg/L: CRP in mg/L. In the calculation of DAS28 (CRP) value, the natural logarithm of 
(CRPmg/L + 1) is used.  LLOQ rule specified in Appendix 1 will be applied to values 
< LLOQ.
4.
GDPTmm: Patient’s Global Assessment of Disease Activity scaled from 0 (very well) to 100 
(very poor) on a 100-unit VAS for the calculation of DAS28 (CRP) value.  
If any of the components required for computing the DAS28 (CRP) value is missing, the DAS 28 
(CRP) score will be set to missing.
Change from baseline in DAS28 (CRP) measures the change in disease activity, where a 
negative change indicates an improvement and a positive change indicates a worsening.  
Analysis Methods
5.4.7.2.
Data from all subjects in FAS1 will be included and analyzed according to the randomized 
treatment groups.  
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The same analysis methods as described in Section 5.4.1.2 (ANCOVA on MI data ) will be 
applied for treatment comparisons on change from baseline in DAS28 (CRP) at Week 24, based 
on the Composite Estimand (Section 5.2.4.1).  
5.4.8.
Summary of Analyses Related to Major Secondary Endpoints
Table 4 below provides an overview on all the analyses related to the major secondary endpoints, 
the estimands, the analysis sets, the data handling rules to be used, and the analysis methods and 
summary statistics.   
Table 4:
Summary of Analyses Related to Major Secondary Endpoints
Endpoints
(Analysis Set)
Missing data
Analysis method/Summary statistics
Analyses of Response Endpoints based on Composite Estimand, in which, subjects meeting any TF criteria 
(defined in Section 2.5) prior to a visit (e.g., Week 16) will be considered as non-responders at the said visit (e.g., 
Week 16).  
ACR 50 Response at 
Week 24 (FAS1)
ACR 70 Response at 
Week 24 (FAS1)
ACR 20 Response at 
Week 16 (FAS1)
ACR 50 at Week 16
(FAS1)
IGA Response at 
Week 24 (FAS1 with 
≥3% BSA psoriatic 
involvement and an 
IGA score of ≥2 at 
baseline)
Subjects with 
missing data are 
considered to be 
non-responders

Response rates

Treatment difference in response rates and 95% CI 

P-value from the
CMH test (stratified by randomization 
stratification factors) for treatment comparison
Analyses of Continuous Endpoints based on Composite Estimand, in which, subjects meeting any TF criteria 
(defined in Section 2.5) prior to a visit (e.g., Week 24) will be considered as no change (no improvement) from 
baseline at the said visit (e.g., Week 24).  
Change from baseline at 
Week 24 in:
HAQ-DI score (FAS1)
DAS28(CRP) (FAS1)
SF-36 PCS score (FAS1)
SF-36 MCS score (FAS1)
MI (Section 
5.2.3.3)
Main Analysis:

Descriptive summary statistics

ANCOVA for each MI dataset and then analysis results across all MI 
datasets combined 

LS mean (95% CI) for each treatment group and for differences 
between groups.

P-values for treatment comparisons
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5.4.9.
Additional Tipping Point Analyses
To support regulatory decision making per the FDA review comment dated 14MAR2019 [IND 
124177 – Guselkumab (CNTO 1959) – Comments for IND 124177], additional tipping point 
analyses will be performed for each major secondary endpoint to evaluate the impact when the 
missing data deviate from the MAR assumption.  Analyses will be performed for the Treatment 
Policy Estimand (Section Error! Reference source not found.), where observed data is 
included regardless of whether or not TF criteria are met prior to the time at which the endpoint 
is assessed.
Missing data in binary endpoints will first be imputed using multiple imputation, then a pair of 
deltas will be added to the predicted response or resolution rates of each missing subject from the 
MI method depending on guselkumab or placebo group to new MI datasets (Section
5.2.3.4). The same CMH test as that used for the main analysis of the endpoint will be used for 
each imputation set, and the analysis results from the N imputation datasets will be combined for 
each pair of deltas, according to Rubin20, and the p-values for testing the treatment difference 
will be obtained.  When combining analysis results for the CMH test, the Wilson-Hilferty
transformation27 will be applied to the test statistics to achieve an approximate normal 
distribution.
Missing data for continuous endpoints will first be imputed using multiple imputation, then a 
pair of deltas will be added to the imputed values from the MI method depending on guselkumab 
or placebo group (Section 5.2.3.6). The same ANCOVA model as that used for the main 
analysis of the endpoint will be used for each imputation set, and the analysis results from the N 
imputation datasets will be combined for each pair of deltas, according to Rubin20, and the p-
values for testing the treatment difference will be obtained.
Table 4a below summarizes the tipping point analyses for major secondary endpoints.  For the 
summary of additional tipping point analyses other than for primary and major secondary 
endpoints see Section 5.5.5.
Table 4a: Summary of Tipping Point Analyses for Major Secondary Endpoints 
Endpoints
(Analysis Set)
Missing data
Analysis method
Supplementary Analyses of Continuous Endpoints based on Treatment Policy Estimand, in which all observed 
data will be used, regardless of whether or not the subjects meet any TF criteria.
Change from baseline at Week 24 in:
HAQ-DI score (FAS1)
SF-36 PCS score (FAS1)
SF-36 MCS score (FAS1)
DAS28(CRP) (FAS1)
Enthesitis (LEI) among subjects with 
enthesitis (LEI) at baseline (FAS1)
Dactylitis among subjects with dactylitis 
at baseline (FAS1)
MI with FCS 
regression (Section 
5.2.3.6, Error! 
Reference source not 
found.)

Two-dimensional tipping point analysis

Treatment comparison using ANCOVA model 

Analysis results to be presented graphically
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Table 4a: Summary of Tipping Point Analyses for Major Secondary Endpoints 
Endpoints
(Analysis Set)
Missing data
Analysis method
Supplementary Analyses of Binary Endpoints based on Treatment Policy Estimand in which, all observed data 
will be used, regardless of whether or not the subjects meet any TF criteria.
ACR 50 Response at Week 24 (FAS1)
ACR 70 Response at Week 24 (FAS1)
ACR 20 Response at Week 16 (FAS1)
ACR 50 at Week 16 (FAS1) 
IGA Response at Week 24 (FAS1 with 
≥3% BSA psoriatic involvement and an 
IGA score of ≥2 at baseline)
Resolution of enthesitis (LEI) at Week 
24 among subjects with enthesitis (LEI) 
at baseline
Resolution of dactylitis at Week 24 
among subjects with dactylitis at 
baseline
MI with FCS 
regression (Section 
Error! Reference 
source not found., 
Error! Reference 
source not found.)

Two-dimensional tipping point analysis.

The CMHa test (stratified by randomization 
stratification factors) to compare treatment groups.

Analysis results to be presented graphically
a When combining analysis results for the CMH test, the Wilson-Hilferty transformation will be applied to the test statistics to 
achieve an approximate normal distribution.
5.5.
Other Efficacy Variable(s)
In addition to the primary and major secondary endpoints, other efficacy analyses related to 
reduction of signs and symptoms and physical function, skin disease and health related quality of 
life will be analyzed.
This section outlines the definition and analyses of the other efficacy endpoints. 
5.5.1.
Efficacy Endpoints Related to Reduction of Signs and Symptoms and 
Physical Function 
Definition
5.5.1.1.
5.5.1.1.1.
ACR Related Endpoints
Other efficacy endpoints related to ACR include:

Proportion of subjects who achieve an ACR 20 response by visit through Week 52

Proportion of subjects who achieve an ACR 50 response by visit through Week 52

Proportion of subjects who achieve an ACR 70 response by visit through Week 52

ACR components by visit through Week 52  

Percent change (improvement) from baseline in ACR components by visit through Week 52   

Proportion of subjects who maintain an ACR 20 response at Week 52 among the subjects 
who achieved an ACR 20 response at Week 24.  

Proportion of subjects who maintain an ACR 50 response at Week 52 among the subjects 
who achieved an ACR 50 response at Week 24.  
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
Proportion of subjects who maintain an ACR 70 response at Week 52 among the subjects 
who achieved an ACR 70 response at Week 24.  
For definition of ACR 20 response, refer to Section 5.3.1. For definition of ACR 50 response
and ACR 70 response, refer to Section 5.4.2.1.
5.5.1.1.2.
HAQ-DI Related Endpoints
The other efficacy endpoints related to HAQ-DI include:

Change from baseline in HAQ-DI score by visit overtime through Week 52.  

Proportion of subjects who achieve a HAQ-DI response (i.e., a ≥ 0.35 improvement from 
baseline in HAQ-DI score) by visit overtime through Week 52 among those subjects with 
HAQ-DI score ≥ 0.35 at baseline.

Proportion of subjects who maintain a HAQ-DI response at Week 52 among the subjects 
who achieved a HAQ-DI response at Week 24.  
For definitions of HAQ-DI and change from baseline in HAQ-DI score, refer to 
Section 5.4.1.1. 
HAQ-DI responders are subjects who achieved ≥0.35 improvement in HAQ-DI score.
Note that a ≥ 0.35 improvement in HAQ-DI score is considered a clinically meaningful 
improvement in PsA.14 The responders are only applicable to subjects whose baseline HAQ-DI 
score ≥0.35.
5.5.1.1.3.
DAS28 Related Endpoints
The other efficacy endpoints related to DAS28 (CRP) include:

Proportion of subjects with DAS28 (CRP) response by visit overtime through Week 52

Proportion of subjects with DAS28 (CRP) remission by visit overtime through Week 52

Change from baseline in DAS28 (CRP) by visit overtime through Week 52 
For definitions of DAS28 (CRP), refer to Section 5.4.7.1. 
DAS28 Response for DAS28 (CRP) is as defined in Table below.23
DAS28 (CRP) Response Criteria
DAS28 (CRP) at the visit
Improvement from Baseline
> 1.2
> 0.6 – 1.2
≤0.6
≤ 3.2
Good response
Moderate response
No response
> 3.2 – 5.1
Moderate response
Moderate response
No response
> 5.1
Moderate response
No response
No response
DAS28 (CRP) remission is defined as a DAS28 (CRP) value of < 2.6 at a visit.
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5.5.1.1.4.
Responders Based on Modified Psoriatic Arthritis Responder Criteria
(PsARC)
A subject will be considered a responder based on Modified Psoriatic Arthritis Responder 
Criteria (PsARC) if the subject meets at least 2 of the following criteria at a visit, including at 
least 1 of the 2 joint criteria and with no deterioration in the other criteria.18 No deterioration 
means ≥ 0% improvement.

≥ 30% decrease in swollen joint count (SJC66)

≥ 30% decrease in tender joint count (TJC68)

≥ 20% improvement in Patient’s Global Assessment of Disease Activity (arthritis) on a VAS

≥ 20% improvement in Physician’s Global Assessment of Disease Activity on a VAS
5.5.1.1.5.
Enthesitis Related Endpoints
Refer to Section 5.4.4.1 for definitions of enthesitis score, change from baseline in enthesitis 
score, and subjects with resolution of enthesitis based on LEI.
Enthesitis will also be assessed by the Spondyloarthritis Research Consortium of Canada 
(SPARCC).15 The SPARCC developed a measure for enthesitis in general spondyloarthritis 
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-tibia, left and right

Achilles tendon insertion, left and right

Plantar fascia, left and right
Tenderness on examination is recorded as either present (1) or absent (0) for each of the 16 sites 
for an overall score range of 0–16.

Change from baseline in enthesitis score (based on SPARCC) measures the change in 
enthesitis, where a negative change indicates an improvement and a positive change 
indicates a worsening.
5.5.1.1.6.
Dactylitis Related Endpoints
Refer to Section 5.4.5.1 for definitions of dactylitis score, change from baseline in dactylitis 
score, and subjects with resolution of dactylitis.
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
In addition, 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. The change from baseline in this 
tender dactylitis score will be assessed over time through Week 52.
5.5.1.1.7.
PASDAS Related Endpoints
The Psoriatic ArthritiS Disease Activity Score (PASDAS) is a derived score combining Patient’s 
Global Assessment of Disease Activity (arthritis and psoriasis, on a 100-unit VAS), Physician’s 
Global Assessment of Disease Activity (on a 100-unit VAS), swollen joint count (66 joints), 
tender joint count (68 joints), CRP (mg/L), enthesitis based on LEI (scaled to a 0–6 range),
tender dactylitis count (scoring each digit from 0–3 and recoding to 0–1, where any score > 0 
equaled 1), and the PCS score of the SF-36 health survey.11,13
The PASDAS is a continuous parameter and is defined as follows:
PASDAS = 1.5*{[0.18* SQRT(GDEVmm) + 0.159* SQRT(GDPTSmm) - 0.253 × 
SQRT(SF_PCS) + 0.101 * Ln (SJC66 +1) + 0.048 * Ln (TJC68 + 1) + 0.23 * Ln (ENTHE + 1) + 
0.377 * Ln (DACTY + 1) + 0.102* Ln (CRPmg/L +1)] + 2}, where
1.
GDEVmm: Physician’s Global Assessment of Disease Activity on a 100-unit VAS.  
2.
GDPTSmm: Patient’s Global Assessment of Disease Activity (arthritis and psoriasis) on a 
100-unit VAS.  
3.
SF-PCS: PCS score of the SF-36 health survey.
4.
SJC66: a total number of swollen joints among the 66 joints evaluated for swelling.  Each of 
the 66 joints will be evaluated for swelling, categorized as swollen or not swollen.  Joint 
evaluability rules specified in Appendix 1 for overwriting joint evaluation will be applied to 
those joints with joint injection(s)/surgical joint procedure(s).  For subjects with any joint 
not evaluable in the 66 joint set, joint count adjustment rules described in Appendix 1 will 
be applied in determining the ultimate count of swollen joints.
5.
TJC68: a total number of tender joints among the 68 joints evaluated for tenderness.  Each 
of the 68 joints will be evaluated for tenderness, categorized as tender or not tender.  Joint 
evaluability rules specified in Appendix 1 for overwriting joint evaluation will be applied to 
those joints with joint injection(s)/surgical joint procedure(s).  For subjects with any joint 
not evaluable in the 68 joint set, joint count adjustment rules described in Appendix 1 will 
be applied in determining the ultimate count of tender joints.
6.
ENTHE: enthesitis score based on LEI with a range from 0 to 6.
7.
DACTY: dactylitis count (scoring each digit from 0–3 and recoding to 0–1, where any score 
> 0 equaled 1).
8.
CRPmg/L:
CRP in mg/L. LLOQ rule specified in Appendix 1 will be applied to values 
< LLOQ.
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If any of the components required for computing the PASDAS value is missing, the PASDAS
will be set to missing.
Change from baseline in PASDAS measures the change in disease activity, where a negative 
change indicates an improvement and a positive change indicates a worsening.  
Subjects with low or very low disease activity based on the PASDAS score are those subjects 
who have a PASDAS score less than or equal to 1.9, or greater than 1.9 and less than or equal to 
3.2, respectively.
5.5.1.1.8.
GRACE Index
GRAppa Composite scorE (GRACE) Index score is a composite score of Group for Research 
and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), derived as GRACE Index = (1 -
AMDF) x 10, where, AMDF is the Arithmetic Mean of the Desirability Function (AMDF).13,12
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 0:13,12

Tender joint count (68 joints)

Swollen joint count (66 joints)

HAQ-DI score

Patient’s Global Assessment of Disease Activity (arthritis and psoriasis) on a 100-unit VAS

Patient’s Assessment of Skin Disease Activity on a 100-unit VAS

Patient’s Global Assessment of Disease Activity (arthritis) on a 100-unit VAS

Psoriasis Area and Severity Index PASI score (Section 5.5.2.1.1)

Psoriatic Arthritis Quality of Life Index (PsAQOL) score, which is derived as follows:
PsAQOL = 25.355 + (2.367 × HAQ-DI) – (0.234 × SF-PCS) – (0.244 × SF-MCS) where,
HAQ-DI: HAQ-DI score (0-3)
SF-PCS: PCS score of SF-36 Health Survey
SF-MCS: MCS score of SF-36 Health Survey
Change from baseline in GRACE index score measures the change in disease activity, where a 
negative change indicates an improvement and a positive change indicates a worsening.  
Subjects with low disease activity based on the GRACE index score are those subjects who 
have a GRACE index score less than or equal to 2.3.
5.5.1.1.9.
DAPSA Related Endpoints
The Disease Activity Index for Psoriatic Arthritis (DAPSA) score is a derived score combining
swollen joint count (66 joints), tender joint count (68 joints), CRP (mg/dL), Patient’s Assessment 
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of Pain (on a 10-unit VAS), and Patient’s Global Assessment of Disease Activity (arthritis, on a 
10-unit VAS).13
The DAPSA is a continuous parameter and is defined as follows:
DAPSA = STC66 + TJC68 + CRP (mg/dL) + PAIN + GDPT, where

SJC66 and TJC68 are defined similarly as in DAS28 (CRP) (Section 5.4.7.1).

CRPmg/dL: CRP in mg/dL. LLOQ rule specified in Appendix 1 will be applied to values 
< LLOQ.

PAIN: Patient’s Assessment of Pain on a 10-unit VAS.  

GDPT: Patient’s Global Assessment of Disease Activity (arthritis) on a 10-unit VAS.  
If any of the components required for computing the DAPSA score is missing, the DAPSA score 
will be set to missing.
Change from baseline in DAPSA measures the change in disease activity, where a negative 
change indicates an improvement and a positive change indicates a worsening.  
Subjects in remission, or with low disease activity based on the DAPSA score are those 
subjects who have a DAPSA score less than or equal to 4, or greater than 4 and less than or equal 
to 14, respectively.
5.5.1.1.10.
Minimal Disease Activity (MDA) and Very Low Disease Activity 
(VLDA)
The PsA minimal disease activity (MDA) criteria are a composite of 7 outcome measures used in 
PsA.  A subject is considered as having achieved the PsA MDA at a visit if the subject has 
fulfilled at least 5 of the following 7 criteria at that visit:2

Tender joint count (68 joints) 1

Swollen joint count (66 joints) 1

Psoriasis activity and severity index ≤1 

Patient’s Assessment of Pain 15 on a 100-unit VAS

Patient’s Global Assessment of Disease Activity (arthritis and psoriasis) 20 on a 100-unit 
VAS

HAQ-DI score 0.5

Tender entheseal points ≤1 (LEI index score ≤ 1)
A subject is considered as having achieved VLDA at a visit if the subject has fulfilled all 7 
criteria described above at that visit.
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5.5.1.1.11.
BASDAI Related Endpoints 
The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was developed as a subject 
self-assessment for and consists of 6 questions relating to the 5 major symptoms of ankylosing 
spondylitis.7 Only subjects with spondylitis with peripheral arthritis as their primary arthritic 
presentation of PsA will complete the BASDAI using a 10-unit VAS to indicate the degree of 
their symptoms over the past week on the following criteria: 
A. Fatigue on a 10-unit VAS
B. Spinal pain on a 10-unit VAS
C. Joint pain on a 10-unit VAS
D. Enthesitis on a 10-unit VAS
E. Qualitative morning stiffness on a 10-unit VAS
F. Quantitative morning stiffness on a 10-unit VAS
The BASDAI score = 0.2 * (A + B + C + D + 0.5*[E + F]).  If any of the components required 
for computing the BASDAI score is missing, the BASDAI score will be set to missing.
Higher BASDAI scores indicate greater disease severity and a score decrease of 50% or 2 points 
is considered clinically meaningful.25
Change from baseline in BASDAI score measures the change in disease activity, where a 
negative change indicates an improvement and a positive change indicates a worsening.  
Note that change from baseline in BASDAI score, and ≥ 20%, ≥ 50%, ≥70 %, and ≥ 90% 
improvement from baseline in BASDAI score are only applicable to subjects with spondylitis 
and peripheral joint involvement as their primary arthritic presentation of PsA and BASDAI >0 
at baseline.
Analysis Method 
5.5.1.2.
Endpoints through Week 24 will be analyzed at Week 24 DBL based on FAS1 (Section 2.3.1.1)
with the following exceptions:
HAQ-DI response, among FAS1 subjects with HAQ-DI score ≥ 0.35 at baseline.
BASDAI: among FAS1 subjects with spondylitis and peripheral joint involvement as their 
primary arthritic presentation of PsA and BASDAI >0 at baseline.
Endpoints from Week 24 through Week 52 will be analyzed at Final (Week 60) DBL based on 
FAS2 (Section 2.3.1.2).
All endpoints will be descriptively summarized by treatment groups.  Treatment comparisons 
will be performed by visit through Week 24. Nominal p-values and 95% CIs for the difference 
between each guselkumab group and placebo group will be provided. No treatment comparison 
will be performed after Week 24.
Note that for endpoints of Enthesitis and Dactylitis:
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
Analyses using data of CNTO1959PSA3001 study only will be performed and all the p-
values will be considered nominal (including those at Weeks 16 and 24).  

However, analyses
using
pooled data from
studies CNTO1959PSA3001 and 
CNTO1959PSA3002 will be analyzed in the CNTO1959PSA3002 study (refer to the 
SAP CNTO136PSA3002 – Amendment 3). The results from the pooled data analyses
will be reported along with the analysis results from that study.
For binary response endpoints, treatment comparisons will be performed using a CMH test as 
described in Section 5.3.2.1. For continuous endpoints, treatment comparisons will be 
performed using an ANCOVA model on the MI data for HAQ-DI, DA 28 (CRP), dactylitis, and 
enthesitis endpoints as described in Section 5.1 and Appendix 3. 
The following Table 5 outlines the other efficacy endpoints related to reduction of signs and 
symptoms and physical function, the estimands, the methods for analyses, and the data handling 
rules to be used.
Table 5:
Summary of Estimands, Analysis Sets, Data Handling Rules, and Analysis Methods for 
Endpoints of Signs & Symptoms and Physical Function
Endpoint
Estimand
Analysis Set
Missing 
Data 
Rules
Analysis Methods
ENDPOINTS BY VISIT THROUGH WEEK 24 AT WEEK-24 DBL
1
Proportions of subjects 
who achieved an ACR 
20, ACR 50, and ACR 70 
responses 
Composite
(Section 
5.2.4.1)
FAS1
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% CI 
calculated based on the 
Wald statistics
2
ACR components
NA
FAS1
-

Summarized descriptively
3
Percent change from 
baseline in ACR 
components
NA
FAS1
-

Summarized descriptively 
4
Change from baseline in 
HAQ-DI score
Composite
(Section 
5.2.4.1)
FAS1
MI Section 
(5.2.3.3)

Descriptive summary 
statistics

ANCOVA for each MI 
dataset and then analysis 
results across all MI 
datasets combined 

LS mean (95% CI) for each 
treatment group and for 
differences between groups.
o
P-values for treatment 
comparisons
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Table 5:
Summary of Estimands, Analysis Sets, Data Handling Rules, and Analysis Methods for 
Endpoints of Signs & Symptoms and Physical Function
Endpoint
Estimand
Analysis Set
Missing 
Data 
Rules
Analysis Methods
5
Proportion of HAQ-DI 
responders 
(≥0.35 Improvement 
from baseline in HAQ-DI
score)
Composite
(Section 
5.2.4.1)
FAS1 whose 
baseline HAQ-
DI score ≥ 0.35
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% CI 
calculated based on the 
Wald statistics
6
Proportions of subjects 
with DAS28 (CRP) 
responses 
Composite
(Section 
5.2.4.1)
FAS1
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% CI 
calculated based on the 
Wald statistics
7
Proportions of subjects 
with DAS28 remission 
Composite
(Section 
5.2.4.1)
FAS1
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% CI 
calculated based on the 
Wald statistics
8
Change from baseline in 
DAS28 (CRP)
Composite
(Section 
5.2.4.1)
FAS1
MI Section 
(5.2.3.3)

Descriptive summary 
statistics

ANCOVA for each MI 
dataset and then analysis 
results across all MI 
datasets combined 

LS mean (95% CI) for each 
treatment group and for 
differences between groups.
o
P-values for treatment 
comparisons
9
Proportions of subjects 
with PsARC response 
Composite
(Section 
5.2.4.1)
FAS1
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% CI 
calculated based on the 
Wald statistics
10
Proportions of subjects 
with resolution of 
enthesitis
Composite
(Section 
5.2.4.1)
FAS1 with 
enthesitis at 
baseline
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% CI 
calculated based on the 
Wald statistics 
11
Change from baseline in 
enthesitis score
Composite
(Section 
5.2.4.1)
FAS1 with 
enthesitis at 
baseline
MI Section 
(5.2.3.3)

Descriptive summary 
statistics

ANCOVA for each MI 
dataset and then analysis 
results across all MI 
datasets combined 

LS mean (95% CI) for each 
treatment group and for 
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Table 5:
Summary of Estimands, Analysis Sets, Data Handling Rules, and Analysis Methods for 
Endpoints of Signs & Symptoms and Physical Function
Endpoint
Estimand
Analysis Set
Missing 
Data 
Rules
Analysis Methods
differences between groups.
o
P-values for treatment 
comparisons
12
Proportions of subjects 
with resolution of 
dactylitis
Composite
(Section 
5.2.4.1)
FAS1 with 
dactylitis at 
baseline
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% CI 
calculated based on the 
Wald statistics
13
Change from baseline in 
dactylitis score
Composite
(Section 
5.2.4.1)
FAS1 with 
dactylitis at 
baseline
MI Section 
(5.2.3.3)

Descriptive summary 
statistics

ANCOVA for each MI 
dataset and then analysis 
results across all MI 
datasets combined 

LS mean (95% CI) for each 
treatment group and for 
differences between groups.
o
P-values for treatment 
comparisons
14
Change from baseline in 
PASDAS
Composite
(Section 
5.2.4.1)
FAS1
-

Summarized descriptively

MMRM model for
o
LS mean (SD) 
o
Treatment difference in 
LS mean (95% CI) 
o
P-value of comparing 
LS mean
15
Change from baseline in 
GRACE index score
Composite
(Section 
5.2.4.1)
FAS1
-

Summarized descriptively

MMRM model for
o
LS mean (SD) 
o
Treatment difference in 
LS mean (95% CI) 
o
P-value of comparing 
LS mean
16
Change from baseline in 
DAPSA score
Composite
(Section 
5.2.4.1)
FAS1
-

Summarized descriptively

MMRM model for
o
LS mean (SD) 
o
Treatment difference in 
LS mean (95% CI) 
o
P-value of comparing 
LS mean
17
Proportions of subjects 
with minimal disease 
activity
Composite
(Section 
5.2.4.1)
FAS1
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% CI 
calculated based on the 
Wald statistics
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Table 5:
Summary of Estimands, Analysis Sets, Data Handling Rules, and Analysis Methods for 
Endpoints of Signs & Symptoms and Physical Function
Endpoint
Estimand
Analysis Set
Missing 
Data 
Rules
Analysis Methods
18
Proportions of subjects 
with ≥20%, ≥50%, ≥70%, 
and ≥90% improvement 
from baseline in 
BASDAI score
Composite
(Section 
5.2.4.1)
FAS1 with 
spondylitis and 
peripheral joint 
involvement as 
their primary 
arthritic 
presentation of 
PsA and 
BASDAI>0 at 
baseline
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% CI 
calculated based on the 
Wald statistics
19
Change from baseline in 
BASDAI score
Composite
(Section 
5.2.4.1)
FAS1 with 
spondylitis and 
peripheral joint 
involvement as 
their primary 
arthritic 
presentation of 
PsA and 
BASDAI>0 at 
baseline
-

Summarized descriptively

MMRM model for
o
LS mean (SD) 
o
Treatment difference in 
LS mean (95% CI) 
o
P-value of comparing 
LS mean
20
Proportion of subjects 
with low or very low 
disease activity based on 
PASDAS
Composite
(Section 
5.2.4.1)
FAS1
NRI
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value
21
Proportion of subjects 
with low disease activity 
based on GRACE score
Composite
(Section 
5.2.4.1)
FAS1
NRI
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value
22
Proportion of subjects 
with low disease activity 
or remission based on 
DAPSA
Composite
(Section 
5.2.4.1)
FAS1
NRI
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value
23
Proportions of subjects 
with very low disease 
activity
Composite
(Section 
Error! 
Reference 
source not 
found.)
FAS1
NRI
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% CI 
calculated based on the 
Wald statistics
‘NA’ = Not Applicable; ‘–‘ indicates Missing Data Rules not to be applied.
ENDPOINTS BY VISIT FROM WEEK 24 THROUGH WEEK 52 AT Final (WEEK 60) DBL

Subjects in FAS2 will be the analysis population.

All the endpoints will be descriptively summarized by visit. 

No treatment comparison will be performed. 

No data handling rules will be applied and all analyses will be based on observed data. 
5.5.2.
Efficacy Endpoints Related to Skin Disease 
Other efficacy endpoints related to skin disease include:
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
Proportions of subjects who achieve a PASI 75, 90 and 100 responses by visit through 
Week 52 among the subjects with ≥3% BSA psoriatic involvement and an IGA score of ≥2 
(mild) at baseline.Proportion of subjects with an IGA score of 0 (cleared) by visit through 
Week 52 among the subjects with ≥3% BSA psoriatic involvement and an IGA score of ≥2 
(mild) at baseline.

Change from baseline in PASI score by visit through Week 52 among the subjects with 
≥3% BSA psoriatic involvement and an IGA score of ≥2 (mild) at baseline.

Proportion of subjects who achieve both PASI 75 and ACR 20 responses by visit through 
Week 52 among the subjects with ≥3% BSA psoriatic involvement and an IGA score of ≥2 
(mild) at baseline.

Proportion of subjects who achieve both PASI 75 and modified PsARC response by visit 
through Week 52 among the subjects with ≥3% BSA psoriatic involvement and an IGA 
score of ≥2 (mild) at baseline.
This section outlines the definitions and analyses for the above skin disease endpoints.
Definitions
5.5.2.1.
5.5.2.1.1.
PASI Related Endpoints 
The Psoriasis Area and Severity Index (PASI) is a system used for assessing and grading the 
severity of psoriatic lesions and their response to therapy.5 In the PASI system, the body is 
divided into 4 regions: neck and head, trunk (including axillae and groin), upper extremities, and 
lower extremities (including buttocks), which account for 10%, 30%, 20%, and 40% of the total 
BSA, respectively. Each of these 4 regions is assessed separately for erythema, induration and 
scaling on a scale of 0 - 4. The PASI score is a continuous endpoint calculated as follows:
PASI = 0.1 (Eh + Ih + Sh) Ah + 0.3 (Et + It + St) At + 0.2 (Eu + Iu + Su) Au + 0.4 (El + Il + Sl) 
Al, where

E, I, S are, respectively, the state of erythema (E), induration (I) and scaling (S) assessed on 
a scale of 0 = none, 1 = slight, 2 = moderate, 3 = severe, and 4 = very severe.

h, t, u, l are the 4 body regions in the PASI system: neck and head (h), trunk (t), upper 
extremities (u), and lower extremities (l), respectively. 

A is the area of involvement for psoriatic lesions. The scale for estimating the area of 
involvement is outlined below:
0 = no involvement
1 = 1% to 9% involvement
2 = 10% to 29% involvement
3 = 30% to 49% involvement
4 = 50% to 69% involvement
5 = 70% to 89% involvement
6 = 90% to 100% involvement
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
Coefficients 0.1, 0.3, 0.2, and 0.4 corresponds to that head (h), trunk (t), upper extremities
(u) and lower extremities (l) account for 10%, 30%, 20%, and 40% of the total BSA, 
respectively.
If any of the components required for computing the PASI score is missing, the PASI score will 
be set to missing.  The PASI score ranges from 0 to 72, with a higher score indicating a more 
severe disease.
Change from baseline in PASI scores measures the change in disease activity, where a 
negative change from baseline in PASI score indicates an improvement and a positive change 
indicates a worsening.  
PASI 75 response is defined as ≥ 75% improvement from baseline in PASI scores.
PASI 90 response and PASI 100 response (and 50 response) are defined similarly, with 
improvement threshold replaced by 90% and 100% respectively.
Analysis Methods
5.5.2.2.
Endpoints through Week 24 will be analyzed at Week 24 DBL based on FAS1 (Section 2.3.1.1)
who had ≥3% BSA psoriatic involvement and an IGA score of ≥2 (mild) at baseline; endpoints 
from Week 24 through Week 52 will be analyzed at Final (Week 60) DBL based on FAS2 
(Section 2.3.1.2) who had ≥3% BSA psoriatic involvement and an IGA score of ≥2 (mild) at 
baseline.
All endpoints will be descriptively summarized by treatment groups. Treatment comparisons 
will be performed by visit through Week 24. Nominal p values and 95% CIs for the difference 
between each guselkumab group and placebo group will be provided. No treatment comparison 
will be performed after Week 24. 
For binary response endpoints, treatment comparisons will be performed using a CMH test as 
described in Section 5.3.2.1. For continuous endpoints, treatment comparisons will be 
performed using an MMRM model as described in Section 5.1 and Appendix 3. 
The following Table 6 outlines the other efficacy endpoints related to skin disease, the 
estimands, the analysis sets, the data handling rules to be used, and the methods for analyses.
Table 6:
Summary of Estimands, Analysis Sets, Data Handling Rules, and Analysis Methods for 
Endpoints of Skin Disease
Endpoint
Estimand
Analysis Set
Missing 
Data 
Rules
Analysis Methods
ENDPOINTS BY VISIT THROUGH WEEK 24 AT WEEK-24 DBL
1
Proportions of subjects 
who achieve a PASI 
75, 90, 100 responses 
Composite
(Section 
5.2.4.1)
FAS1 who had ≥3% 
BSA psoriatic 
involvement and an 
IGA score of ≥2 (mild) 
at baseline
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% CI 
calculated based on the Wald 
NCT03162796
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CNTO1959 (guselkumab)
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Approved, Date: 21 March 2019
Table 6:
Summary of Estimands, Analysis Sets, Data Handling Rules, and Analysis Methods for 
Endpoints of Skin Disease
Endpoint
Estimand
Analysis Set
Missing 
Data 
Rules
Analysis Methods
statistics
2
Proportions of subjects 
who achieve who 
achieve both PASI 75 
and ACR 20 responses
Composite
(Section 
5.2.4.1)
FAS1 who had ≥3% 
BSA psoriatic 
involvement and an 
IGA score of ≥2 (mild) 
at baseline
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% CI 
calculated based on the Wald 
statistics
3
Proportions of subjects 
who achieve who 
achieve both PASI 75 
and modified PsARC 
responses
Composite
(Section 
5.2.4.1)
FAS1 who had ≥3% 
BSA psoriatic 
involvement and an 
IGA score of ≥2 (mild) 
at baseline
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% CI 
calculated based on the Wald 
statistics
4
Proportions of subjects 
with an IGA score of 0 
(cleared)
Composite
(Section 
5.2.4.1)
FAS1 who had ≥3% 
BSA psoriatic 
involvement and an 
IGA score of ≥2 (mild) 
at baseline
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in 
response rates and 95% CI 
calculated based on the Wald 
statistics
5
Change from baseline 
in PASI scores
Composite
(Section 
5.2.4.1)
FAS1 who had ≥3% 
BSA psoriatic 
involvement and an 
IGA score of ≥2 (mild) 
at baseline
-

Summarized descriptively

MMRM model
o
LS mean (SD) 
o
Treatment difference in 
LS mean (95%CI)
o
P-value of comparing 
LS mean 
‘–‘ indicates Missing Data Rules not to be applied.
ENDPOINTS BY VISIT FROM WEEK 24 THROUGH WEEK 52 AT FINAL (WEEK 60) DBL

Subjects in FAS2 will be the analysis population.

All the endpoints will be descriptively summarized by visit. 

No treatment comparison will be performed. 

No data handling rules will be applied and all analyses will be based on observed data. 
5.5.3.
Other Efficacy Endpoints Related to Health-Related Quality of Life 
and Health Economics
In this study, health related quality of life (HRQOL) measures include questionnaires of SF-36 
health survey, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), and 
Work Productivity and Activity Impairment (PROMIS-29). 
Other efficacy endpoints related to HRQOL include:

Change from baseline in SF-36 PCS score by visit through Week 52.

Change from baseline in SF-36 MCS score by visit through Week 52.
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
Change from baseline in domain scores of SF-36 scales by visit through Week 52.

Proportion of subjects who achieve ≥ 5-point improvement from baseline in SF-36 MCS
score by visit through Week 52.

Proportion of subjects who achieve ≥ 5-point improvement from baseline in SF-36 PCS 
score by visit through Week 52.

Change from baseline in FACIT-Fatigue score by visit through Week 52.

Proportion of subjects who achieve ≥ 4-point improvement from baseline in FACIT-Fatigue 
scores by visit through Week 52.

Change from baseline in FACIT-fatigue score at Week 24 by ACR 20 response (primary 
endpoint) at Week 24.

Proportion of subjects who achieve ≥4-point improvement from baseline in FACIT-fatigue 
score at Week 24 by ACR 20 response (primary endpoint) at Week 24.

Change from baseline in PROMIS-29 scores by visit through Week 52.

Proportion of subjects who achieve an improvement of ≥3 points in PROMIS-29 domain 
scores by visit through Week 24.

Proportion of subjects who achieve an improvement of ≥5 points in PROMIS-29 domain 
scores by visit through Week 24.
This section outlines the definitions and analyses for the above HRQOL endpoints.
Definition
5.5.3.1.
5.5.3.1.1.
SF-36 Questionnaire
The SF-36 questionnaire is defined in Section 5.4.6.1.
Change from baseline in SF scores measures the change in health-related quality of life, where 
a positive change indicates an improvement and a negative change indicates a worsening.
5.5.3.1.2.
FACIT-Fatigue Questionnaire
The FACIT-Fatigue is a questionnaire that assesses self-reported tiredness, weakness, and 
difficulty conducting usual activities due to fatigue.1 The questionnaire consists of 13 questions 
that assess a subject’s level of fatigue and tiredness over the last 7 days.  Each question is graded 
on a 5-point scale (0 - 4); and accordingly, the total FACIT-Fatigue scores can range from 0 to 
52, with lower score reflecting more fatigue and higher scores reflecting less fatigue.  Note that, 
when at least 7 questions are answered, the score can be calculated and should be adjusted by the 
number of available questions.
Although not developed for PsA, the FACIT-Fatigue has been used to assess fatigue in clinical 
trials of subjects with RA and has demonstrated sensitivity to change in these subjects. In 
rheumatology, a change of 4 points is considered clinical meaningful and has been used as 
response definition in the RA population.1
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Change from baseline in FACIT-Fatigue scores measures the change in fatigue where a 
positive change indicates an improvement and a negative change indicates a worsening.
5.5.3.1.3.
PROMIS 29 
PROMIS-29 profile instrument is intended for adults (ages 18+). 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).16 PROMIS-29 also includes an additional pain intensity 0-10 numeric rating scale
(NRS). 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) 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.
Analysis Method 
5.5.3.2.
Endpoints through Week 24 will be analyzed at Week 24 DBL based on FAS1 (Section 2.3.1.1); 
endpoints from Week 24 through Week 52 will be analyzed at Final (Week 60) DBL based on 
FAS2 (Section 2.3.1.2).
All endpoints will be descriptively summarized by treatment groups. Treatment comparisons 
will be performed by visit through Week 24. Nominal p values and 95% CIs for the difference 
between each guselkumab group and placebo group will be provided. No treatment comparison 
will be performed after Week 24. 
For binary response endpoints, treatment comparisons will be performed using a CMH test as 
described in Section 5.3.2.1. For continuous endpoints, treatment comparisons will be 
performed using ANCOVA on the MI data for MCS and PCS analyses as described in Section 
5.4.1.2, and an MMRM or cLDA model as described in Section 5.1 and Appendix 3.
The following Table 7 outlines the other efficacy endpoints related to skin disease, the 
estimands, the analysis sets, the data handling rules to be used, and the methods for analyses.
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Table 7:
Summary of Estimands, Analysis Sets, Data Handling Rules, and Analysis Methods for HRQOL 
Endpoints
Endpoint
Estimand
Analysis Set
Missing 
Data 
Rules
Analysis Methods
ENDPOINTS BY VISIT THROUGH WEEK 24 AT WEEK-24 DBL
1
Change from 
baseline in SF-36 
PCS score 
Composite
(Section 
5.2.4.1)
FAS1  
MI 
(Section 
5.2.3.3)

Descriptive summary statistics

ANCOVA for each MI dataset and 
then analysis results across all MI 
datasets combined 

LS mean (95% CI) for each 
treatment group and for differences 
between groups.
o
P-values for treatment 
comparisons
2
Change from 
baseline in SF-36 
MCS score 
Composite
(Section 
5.2.4.1)
FAS1  
MI 
(Section 
5.2.3.3)

Descriptive summary statistics

ANCOVA for each MI dataset and 
then analysis results across all MI 
datasets combined 

LS mean (95% CI) for each 
treatment group and for differences 
between groups.
o
P-values for treatment 
comparisons
3
Change from 
baseline in SF-36 
domain scores of 
SF-36 scale 
Composite
(Section 
5.2.4.1)
FAS1  
-

Summarized descriptively

MMRM model
o
LS mean (SD) for
o
Treatment difference in LS 
mean (95%CI)
o
P-value of comparing LS mean
4
Proportion of 
subjects who 
achieve ≥ 5-point 
improvement from 
baseline in SF-36 
PCS  
Composite
(Section 
5.2.4.1)
FAS1 
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in response 
rates and 95% CI calculated based 
on the Wald statistics
5
Proportion of 
subjects who 
achieve ≥ 5-point 
improvement from 
baseline in SF-36 
MCS  
Composite
(Section 
5.2.4.1)
FAS1 
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in response 
rates and 95% CI calculated based 
on the Wald statistics
6
Change from 
baseline in 
FACIT-Fatigue
Composite
(Section 
5.2.4.1)
FAS1  
-

Summarized descriptively

MMRM model
o
LS mean (SD) for
o
Treatment difference in LS 
mean (95%CI)
o
P-value of comparing LS mean
7
Change from 
baseline in 
FACIT-Fatigue at 
Week 24 by ACR 
20 response at 
Week 24(primary 
Composite
(Section 
Error! 
Reference 
source not 
found.)
FAS1  
-

Summarized descriptively

MMRM model
o
LS mean (SD) for
o
Treatment difference in LS 
mean (95%CI)
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Table 7:
Summary of Estimands, Analysis Sets, Data Handling Rules, and Analysis Methods for HRQOL 
Endpoints
Endpoint
Estimand
Analysis Set
Missing 
Data 
Rules
Analysis Methods
endpoint)

P-value of comparing LS mean
8
Proportions of 
subjects who 
achieve ≥4-point 
improvement from 
baseline in 
FACIT-Fatigue 
score at Week 24 
by ACR 20 
response at Week 
24 (primary 
endpoint)
Composite
(Section 
Error! 
Reference 
source not 
found.)
FAS1 
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in response 
rates and 95% CI calculated based 
on the Wald statistics
9
Proportions of 
subjects who 
achieve ≥ 4-point 
improvement from 
baseline in 
FACIT-Fatigue 
score
Composite
(Section 
5.2.4.1)
FAS1 
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in response 
rates and 95% CI calculated based 
on the Wald statistics
10
Change from 
baseline in 
PROMIS-29 score
Composite
(Section 
5.2.4.1)
FAS1 
-

Summarized descriptively

MMRM model for
o
LS mean (SD) 
o
Treatment difference in LS 
mean (95% CI) 
o
P-value of comparing LS mean
11
Proportions of 
subjects who 
achieve ≥3-point 
improvement from 
baseline in 
PROMIS-29 
domain scores
Composite
(Section 
5.2.4.1)
FAS1 
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in response 
rates and 95% CI calculated based 
on the Wald statistics
12
Proportions of 
subjects who 
achieve ≥5-point 
improvement from 
baseline in 
PROMIS-29 
domain scores
Composite
(Section 
5.2.4.1)
NRI 
(Section 
5.2.3.1)

Summarized descriptively

CMH test for p-value

Treatment difference in response 
rates and 95% CI calculated based 
on the Wald statistics
‘–‘ indicates Missing Data Rules not to be applied.
ENDPOINTS BY VISIT FROM WEEK 24 THROUGH WEEK 52 AT FINAL (WEEK 60) DBL

Subjects in FAS2 will be the analysis population.

All the endpoints will be descriptively summarized by visit. 

No treatment comparison will be performed. 

No data handling rules will be applied and all analyses will be based on observed data. 
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Additional Analyses for FACIT-Fatigue
Subgroup analysis comparing change in fatigue score between treatment and control will 
be conducted in ACR20 non-responder subgroup and ACR20 responder subgroup 
separately. Propensity score-based methods will be used to account for potential 
imbalances in baseline covariates. Covariates to be used in the propensity score models 
will include baseline fatigue score and selected demographics and disease related variables 
such as age, gender, BMI, PsA duration, physician global assessment, patient global 
assessment, HAQ-DI score, pain assessment, swollen joints 66 and tender joints 68. 
Logistic regression or Covariate Balancing Propensity Score (CBPS) models will be used 
to estimate the propensity score.
A mediation analysis will be performed to examine the mediating role of 24-week ACR20 
response on change from baseline in fatigue score at week 24 provided both endpoints 
demonstrate a statistically significant difference between treatment arms (Appendix 3).
5.5.4.
Other Tipping Point Analyses
Additional tipping point analyses aside from those for primary and major secondary endpoints 
will be performed to evaluate the impact when the missing data deviate from the MAR 
assumption and are summarized in the below Table 7a.  The analysis methods used are the same 
as those described in Table 4a.
Table 7a: Summary of Tipping Point Analyses Other Than for Primary and Major 
Secondary Endpoints
Endpoints
(Analysis Set)
Missing data
Analysis method
Supplementary Analyses of Continuous Endpoints based on Treatment Policy Estimand, in which all observed 
data will be used, regardless of whether or not the subjects meet any TF criteria.
Change from baseline at Week 16 in:
HAQ-DI score (FAS1)
SF-36 PCS score (FAS1)
SF-36 MCS score (FAS1)
DAS28(CRP) (FAS1)
Enthesitis (LEI) among subjects with 
enthesitis (LEI) at baseline (FAS1)
Dactylitis among subjects with dactylitis 
at baseline (FAS1)
MI with FCS 
regression (Section 
5.2.3.6, Error! 
Reference source not 
found.)

Two-dimensional tipping point analysis

Treatment comparison using ANCOVA model 

Analysis results to be presented graphically
Supplementary Analyses of Binary Endpoints based on Treatment Policy Estimand, in which all observed data 
will be used, regardless of whether or not the subjects meet any TF criteria.
ACR 70 Response at Week 16 (FAS1)
IGA Response at Week 16 (FAS1 with 
≥3% BSA psoriatic involvement and an 
IGA score of ≥2 at baseline)
Resolution of enthesitis (LEI) at Week 
16 among subjects with enthesitis (LEI) 
at baseline
Resolution of dactylitis at Week 16 
among subjects with dactylitis at 
baseline 
MI with FCS 
regression (Section 
Error! Reference 
source not found., 
Error! Reference 
source not found.)

Two-dimensional tipping point analysis.

The CMHa test (stratified by randomization 
stratification factors) to compare treatment groups.

Analysis results to be presented graphically
a When combining analysis results for the CMH test, the Wilson-Hilferty transformation will be applied to the test statistics to 
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Table 7a: Summary of Tipping Point Analyses Other Than for Primary and Major 
Secondary Endpoints
Endpoints
(Analysis Set)
Missing data
Analysis method
achieve an approximate normal distribution.
6.
SAFETY
Safety will be assessed by summarizing the occurrences and type of AEs, vital signs (pulse, 
blood pressure, and weight) and examining the changes in the laboratory parameters.  
In all the safety analysis, subjects who were randomized and received at least 1 (partial or 
complete) dose of study agent administration will be included and analyzed according to the 
treatment they actually received, regardless of the treatments they are randomized to. No formal 
statistical comparison is planned.
6.1.
Safety Table Presentation
There are 2 DBLs in this study, respectively, at Week 24 and End of Study (Week 60).  
Depending on the safety data categories, the cumulative safety data will be analyzed through 
different study periods which include, but are not limited to, through Week 24 and through End 
of Study (Week 60).  Tabular summaries of safety events for key study periods are in general 
presented as follows:
6.1.1.
Summaries Through Week 24
Safety data through Week 24 will be analyzed according to the following treatment groups:
1.
Placebo: Subjects who received placebo only and no guselkumab prior to Week 24.
2.
Guselkumab 100 mg at Weeks 0, 4, and then q8w: Subjects who received guselkumab 
100 mg q8w prior to Week 24 with an additional dose at Week 4. 
3.
Guselkumab 100 mg q4w: Subjects who received guselkumab 100 mg q4w prior to
Week 24. 
4.
Guselkumab Combined: Combined 2 and 3.
The above treatment groups 1-3 are mutually exclusive.  This allows between-group 
comparisons of safety between a guselkumab group and the placebo group based on similar 
follow-up period in each group.  The safety tables will have the column headings below:
Guselkumab
Placebo 
100 mg q8w
100 mg q4w 
Combined 
Analysis set: Safety Analysis Set
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6.1.2.
For subjects who started treatment with placebo only but later 
received any amount of guselkumab prior to Week 24 (due to 
inadvertency), the safety events/measurements on and after the first 
dose of guselkumab will be excluded from the data summaries 
through Week 24.  Only the safety events/measurements that 
occurred while the subjects had been receiving placebo only will be 
included in the data summaries through Week 24.  Summaries 
Through End of Study (Week 60)
Safety data through End of Study (Week 60) will be analyzed according to the following 
treatment groups:
1.
Placebo: Subjects who received placebo only. Follow-up will be based on the period that 
the subject was on placebo from the first dose up to end of study (Week 60).
a.
For subjects who started treatment with placebo and later received treatment with 
guselkumab (due to CO or inadvertently), follow-up will end at the first dose of 
guselkumab. And only the safety events/measurements that occurred prior to the first 
dose of guselkumab will be included in this group.
2.
Placebo →Guselkumab 100 mg q4w: Subjects who started treatment with placebo and 
later received treatment with guselkumab (due to CO or inadvertently).  Follow-up will start 
from the first dose of guselkumab up to End of Study (Week 60).

All the safety events/measurements that occurred on and after the first dose of 
guselkumab will be included in this group.
3.
Guselkumab 100 mg at Weeks 0, 4, and then q8w: Subjects who received guselkumab 
100 mg q8w prior to Week 24 with an additional dose at Week 4.  Follow-up will be from 
the first dose up to end of study.
4.
Guselkumab 100 mg q4w: Subjects who received guselkumab 100 mg q4w prior to 
Week 24.  Follow-up will be from the first dose through end of study.
5.
Guselkumab 100 mg q4w Combined: Combined 2 and 4.
6.
All Guselkumab Combined: Combined 2, 3, and 4.
The above treatment groups 1-2 are not mutually exclusive.  The safety tables will have the 
column headings below:
Guselkumab 
Placebo 
Crossover
(Placebo 
→ 
100 mg q4w)
100 mg q8w 
100 mg q4w 
100 mg q4w 
Combined
All 
Combined
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6.2.
Adverse Events
AEs that occurred any time over the study will be reported and coded using MedDRA.  Analyses 
of AEs will be performed on those events that are considered treatment emergent.  Treatment 
emergent AEs (TEAEs) are those AEs that occurred after the start of initial study agent 
administration and those AEs that were present at baseline but worsened in severity after the start 
of initial study agent administration.  
TEAEs will be summarized by MedDRA system organ class, preferred term, and actual 
treatment group.  The numbers of subjects reporting at least 1 event of the following AE 
categories will be summarized:

Any TEAEs

Treatment emergent serious AEs (SAEs)

TEAEs with severe intensity

TEAEs that led to permanent discontinuation of study agent administration

Treatment emergent infections

Treatment emergent serious infections

Treatment emergent infections requiring oral or parenteral anti-microbial treatment

Injection-site reactions

Anaphylactic reactions or serum sickness reactions
All AE summary tables will include average weeks of follow-up and average number of study 
agent administrations for each treatment group.
In addition to the summary tables, a by-subject listing will be provided for deaths that occurred 
during the study and, respectively, for the following TEAEs:
1.
SAEs
2.
AEs that led to permanent discontinuation of study agent administration
3.
Anaphylactic reactions or serum sickness reactions
4.
Malignancies
5.
Serious infections including TB
6.3.
Clinical Laboratory Tests
The clinical laboratory parameters to be evaluated by the central laboratory include but are not 
limited to:

Hematology: bands,
basophils,
eosinophils,
hemoglobin, hematocrit, lymphocytes, 
monocytes, neutrophils, platelets, red blood cell (RBC) count and white blood cell (WBC)
count

Clinical chemistry: albumin, alkaline phosphatase, alanine aminotransferase (serum 
glutamate pyruvate transaminase) [ALT (SGPT)], aspartate aminotransferase (serum 
glutamic oxaloacetic transaminase) [AST (SGOT)], bicarbonate, blood urea nitrogen 
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(BUN), calcium, chloride, creatinine, glucose, potassium, sodium, total bilirubin, total 
protein, uric acid
The following analyses will be performed as appropriate by actual treatment group: 

Plots of the observed values and changes from baseline over time for selected clinical 
laboratory parameters 

Number of subjects with post-baseline values by maximum toxicity grade according to 
National Cancer Institute’s Common Terminology Criteria for Adverse Events 
(NCI-CTCAE) for parameters with NCI-CTCAE criteria defined

Listings of subjects with any post-baseline lab value of NCI-CTCAE toxicity Grade 3 or 
higher
6.4.
Vital Signs and Physical Examination Findings
Vital signs will be measured at visits as per the schedule of events in the protocol. Descriptive 
statistics of the observed value and change from baseline of the vital signs will be summarized 
by treatment group. The numbers of subjects with any markedly abnormal post-baseline 
measurements will also be summarized over time by treatment group. The criteria for markedly 
abnormal vital signs are defined in the following table.
Abnormalities or changes in severity noted during physical examination will be reported as 
adverse events and are included in the analysis of adverse events.
Parameter
Markedly Abnormal Low 
Markedly Abnormal High
Systolic blood 
pressure
Absolute value 90 mmHg and a decrease 
from baseline by 20 mmHg
Absolute value 180 mmHg and an increase 
from baseline by 20 mmHg
Diastolic blood 
pressure
Absolute value 50 mmHg and a decrease 
from baseline by 15 mmHg
Absolute value 105 mmHg and an increase 
from baseline by 15 mmHg
Pulse
Absolute value ≤ 50 bpm and a decrease 
from baseline ≥ 15 bpm
Absolute value ≥ 120 bpm and an increase 
from baseline ≥ 15 bpm
6.5.
Electrocardiogram
This section does not apply to this study.
6.6.
Other Safety Parameters
6.6.1.
Suicidal Ideation and Behavior
The electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) will be used as a screening 
tool to prospectively evaluate the potential of guselkumab to induce suicidal ideation and 
behavior. The eC-SSRS defines five subtypes of suicidal ideation and behavior in addition to 
self-injurious behavior with no suicidal intent, and is a fully-structured subject self-report 
questionnaire, including standardized questions, follow-up prompts, error handling routines, and 
scoring conventions.17,19 Two versions of the eC-SSRS will be used in this study, the Lifetime 
version and the Since Last Contact version. The Lifetime version will be conducted during the 
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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. The eC-SSRS should be performed after the joint assessment at the screening visit 
(after signing informed consent). At Week 0/baseline and at all post-baseline visits, the eC-SSRS 
will be the first assessment/questionnaire that the subject completes prior to study agent 
administration.
At the conclusion of each assessment, the site will receive an eC-SSRS Findings Report from the 
eC-SSRS vendor. Positive reports are generated from the eC-SSRS vendor for ANY of the 
following findings: 

Ideation Level 4: Some intent to act, no plan

Ideation Level 5: Specific plan and intent

Behaviors: Actual Suicide Attempts

Behaviors: Interrupted Attempts

Behaviors: Aborted Attempts

Behaviors: Preparatory actions
Negative suicidality indication reports are generated from the eC-SSRS vendor when there are 
NO indications of the above.
Any eC-SSRS findings, which in the opinion of the investigator are new or considered to be a 
worsening and clinically significant, should be reported on the AE eCRF.
Suicidal ideation and behavior will be categorized as follows, with higher scores indicating 
greater severity:
Suicidal Ideation (1-5)
1 = Wish to be Dead
2 = Non-specific Active Suicidal Thoughts
3 = Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act
4 = Active Suicidal Ideation with Some Intent to Act, without Specific Plan
5 = Active Suicidal Ideation with Specific Plan and Intent
Suicidal Behavior (6-10)
6 = Preparatory Acts or Behavior
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7 = Aborted Attempt
8 = Interrupted Attempt
9 = Actual Attempt (non-fatal)
10 = Completed Suicide
The baseline is defined as the most severe/maximum score at screening and Week 0. Suicidal 
ideation and behavior will be analyzed by the most severe/maximum post baseline outcome. In 
addition, a shift table from baseline to post-baseline will also be provided.  Subjects with positive 
(i.e., score > 0) ideation and behavior will be presented in a data listing.
7.
PHARMACOKINETICS/PHARMACODYNAMICS
7.1.
Pharmacokinetics
Pharmacokinetics (PK) samples for measuring serum guselkumab concentrations will be
collected from all subjects at the specified visits as shown in the schedule of events of the
protocol. Serum samples will also be collected at the final visit from subjects who terminate 
study participation early. Samples must be collected before study agent administration at visits 
when a study agent administration is scheduled.  A random venous blood sample for population 
PK analysis will be collected from all subjects on any day between Weeks 4 to 12, except on the 
days of the scheduled study visit at Weeks 4, 8, and 12. Additionally, this blood sample must be 
collected at least 24 hours prior to or after the actual time of study agent administration at 
Weeks 4, 8, or 12 (ie, it cannot be collected within 24 hours before or after study agent 
administration).
All PK analyses will be based on the PK Analysis Set (Section 2.3.3). Subjects will be analyzed 
according to the treatment groups that they actually received. No imputation for missing 
concentration data will be performed. 
For analysis on serum guselkumab concentrations, descriptive statistics, including arithmetic 
mean, SD, median, interquartile range, minimum and maximum will be calculated, where 
appropriate, by treatment group at each serum sampling time.  PK data may be displayed 
graphically.  The following analyses will be performed by treatment group as appropriate:

Summary of serum guselkumab concentrations at each visit by treatment group

Proportion of subjects without detectable serum guselkumab concentration at each visit by 
treatment group

Summary of serum guselkumab concentrations at each visit by treatment group and body 
weight

Summary of serum guselkumab concentrations at each visit by treatment group and baseline 
MTX use (Yes, No)

Summary of serum guselkumab concentrations by baseline CRP levels

Plot of median serum guselkumab concentrations over time by treatment group
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In addition, the relationship between serum guselkumab concentrations and safety or efficacy 
may be explored. 
For summary statistics of serum guselkumab concentrations, concentration values below the 
lower limit of quantification will be treated as zero. Once a subject meets one of the following 
dosing deviation criteria, the subject’s data will be excluded from the by-visit data analyses from 
that point onwards.
Dosing deviation criteria:

Discontinue SC guselkumab administrations.

Skipped an SC guselkumab administration.

Received an incomplete/ incorrect SC dose.

Received an incorrect SC study agent.

Received an additional SC guselkumab dose.
In addition, if a subject has an administration outside of visit windows (Section 2.1.1), the 
concentration data collected at and after that visit will be excluded from the by-visit data 
analyses. Additional exclusions for incongruous PK data to be implemented based on Janssen 
SOP-07948.
Population PK analyses will be performed to characterize the disposition characteristics of 
guselkumab based on the guselkumab concentration data from PsA studies. Data may be 
combined with other selected studies to support a relevant structural model. The population 
pharmacokinetic approach will also be used to identify significant covariates such as 
demographic characteristics (including but not limited to body weight, ethnic origin, sex, and 
age) and concomitant medications in subjects with PsA. A detailed analysis plan for population 
PK analysis will be developed separately, and a stand-alone technical report will be written to 
summarize the results of the population PK analysis.
PK analyses presentation
PK analyses will be summarized through the following time periods:

Through Week 24

Through End of Study (Week 60)
For the analyses, a subject is included in one and only one treatment group on the basis of the 
treatment regimen followed. The description of treatment groups are as follows:
1.
Placebo → Guselkumab 100 mg q4w: Subjects randomized to placebo and were switched 
over to Guselkumab 100 mg at Week 24 (for summary through Week 60 only).  
2.
Guselkumab 100 mg at Week 0, Week 4, and then q8w: Subjects randomized to 
guselkumab 100 mg at Week 0, Week 4, and then q8w and received guselkumab 100 mg 
q8w throughout with an additional dose at Week 4.
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3.
Guselkumab 100 mg q4w: Subjects randomized to guselkumab 100 mg q4w and received 
guselkumab 100 mg q4w throughout.
7.2.
Immunogenicity (Antibodies to Guselkumab)
Blood samples will be collected to examine the formation of antibodies to guselkumab at the 
specified visits as shown in the schedule of events of the protocol. Serum samples will also be 
collected at the final visit from subjects who terminate study participation early. 
The antibodies to guselkumab will be summarized based on Immunogenicity Analysis Set
(Section 2.3.4). Subjects will be analyzed according to the treatment groups that they actually 
received. No imputation for missing concentration data will be performed.
The following analysis of antibodies to guselkumab will be performed by treatment group:

Summary of antibodies to guselkumab status 

Summary of neutralizing antibodies to guselkumab status 

List of subjects positive for antibodies to guselkumab 
In addition, to explore the relationship between antibodies to guselkumab status and serum 
guselkumab concentrations, efficacy and safety, the following analysis may be performed as 
appropriate:  

Summary of clinical response (e.g., ACR 20 and ACR 50, PASI) by antibody to guselkumab 
status 

Summary of injection-site reactions by antibody to guselkumab status

Summary of serum guselkumab concentrations by antibody to guselkumab status

Plots of median trough serum guselkumab concentrations over time by antibody to 
guselkumab status 
Immunogenicity analyses presentation
Immunogenicity analyses will be summarized through the following time periods:

Through Week 24

Through End of Study (Week 60)
For the immunogenicity analyses, the description of treatment groups is as follows:
1.
Placebo → Guselkumab 100 mg q4w: Subjects randomized to placebo and were switched 
over to Guselkumab 100 mg at Week 24 (for summary through Week 60 only).  
2.
Guselkumab 100 mg at Week 0, Week 4, and then q8w: Subjects randomized to 
guselkumab 100 mg at Week 0, Week 4, and then q8w and received guselkumab 100 mg 
q8w throughout with an additional dose at Week 4.
3.
Guselkumab 100 mg q4w: Subjects randomized to guselkumab 100 mg q4w and received 
guselkumab 100 mg q4w throughout.
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4.
Guselkumab Combined: all subjects who received guselkumab in groups 1, 2 and 3.
7.3.
Pharmacodynamics
Samples for serum biomarkers will be collected for all subjects as indicated in the Time and 
Events Schedule of the protocol. The analyses on PD biomarkers are to better understand the 
biology of PsA, to provide a biological assessment of the subjects’ response to treatment with 
guselkumab, to analyze differences between responders and non-responders, and to determine if 
the markers can be used to classify subjects as potential responders prior to treatment.
All PD analyses will be based on the PD Analysis Set (Section 2.3.5). Subjects will be analyzed 
according to the treatment groups that they actually received. No imputation for missing 
concentration data will be performed. 
The PD analyses results will be provided in an 
independent technical report.
7.4.
Pharmacokinetic/Pharmacodynamic Relationships
If data permit, the relationships between serum guselkumab concentration and efficacy may be 
analyzed graphically. If any visual trend is observed, a suitable population PK/PD model may be 
developed to describe the exposure-response relationship. Details will be given in a population 
PK/PD analysis plan and results of the population PK/PD analysis will be presented in a separate 
technical report.
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Coates LC, Helliwell PS. Validation of minimal disease activity criteria for psoriatic arthritis using 
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Felson DT, Anderson JJ, Boers M, et al.  American College of Rheumatology Preliminary Core Set of Disease 
Activity Measures for Rheumatoid Arthritis Clinical Trials.  Arthritis Rheum. 1993; 36(6):729-740.
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Felson DT, Anderson JJ, Boers M, et al.  American College of Rheumatology Preliminary Definition of 
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Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A. A new approach to defining disease 
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Gladman DD, Inman RD, Cook RJ, et al. International spondyloarthritis interobserver reliability exercise--the 
INSPIRE study: II. Assessment of peripheral joints, enthesitis, and dactylitis. J Rheumatol. 2007;34(8):1740-
1745.
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Gladman DD, Ziouzina O, Thavaneswaran A, Chandran V. Dactylitis in psoriatic arthritis: prevalence and 
response to therapy in the biologic era. J Rheumatol. 2013;40(8):1357-1359.
10.
Healy PJ, Helliwell PS. Measuring clinical enthesitis in psoriatic arthritis: assessment of existing measures and 
development of an instrument specific to psoriatic arthritis. Arthritis Rheum. 2008;59(5):686-691.
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Helliwell PS, FitzGerald O, Fransen J, et al. The development of candidate composite disease activity and 
responder indices for psoriatic arthritis (GRACE project). Ann Rheum Dis. 2013;72(6):986-991.
12.
Helliwell PS, FitzGerald O, Fransen J. Composite disease activity and responder indices for psoriatic arthritis: 
A report from the GRAPPA 2013 Meeting on development of cutoffs for both disease activity states and 
response. J Rheum. 2014;41(6):1212-1217.
13.
Helliwell PS, Kavanaugh A. Comparison of composite measures of disease activity in psoriatic arthritis using 
data from an interventional study with golimumab. Arthritis Care Res. 2014;66(5):749-756.
14.
Kosinski M, Zhao SZ, Dedhiya S, et al. Determining minimally important changes in generic and disease-
specific health-related quality of life questionnaires in clinical trials of rheumatoid arthritis. Arthritis Rheum. 
2000;43(7):1478–1487.
15.
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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Maksymowych WP, Mallon C, Morrow S, Shojania K, Olszynski WP, Wong RL, et al. Development and 
validation of the Spondyloarthritis
17.
Mundt JC, Greist JH, Jefferson JW, et al. Prediction of suicidal behavior in clinical research by lifetime 
suicidal ideation and behavior ascertained by the electronic Columbia-Suicide Severity Rating Scale. J Clin 
Psych. 2013;74(9):887-893.
18.
Pham T, Guillemin F, Claudepierre P, et al. TNFα antagonist therapy in ankylosing spondylitis and psoriatic 
arthritis:  recommendations of the French Society for Rheumatology. Joint Bone Spine. 2006;73:547–553.
19.
Posner K, Brown GK, Stanley B, et al. The Columbia-Suicide Severity Rating Scale: Initial validity and 
internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry. 
2011;168(12):1266-1277.
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Rubin DB, Multiple Imputations for Nonresponse in Surveys. New York: John Wiley & Sons. 1987.
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21.
Saris-Baglama RN, Dewey CJ, Chisholm GB, et al. QualityMetric Health OutcomesTM Scoring Software 4.5 
User’s Guide. QualityMetric Health Outcomes Solutions. 2011.
22.
van der Linden MA.  Disease Activity Scores using C-reactive protein. April 5, 2004. Available at: 
http://www.umcn.nl/scientist/afdelingen/reumatologie/the_das/the_das_crp. Accessed 19 August 2005.
23.
van Riel PL, van Gestel AM, Scott DL. EULAR Handbook of Clinical Assessments in Rheumatoid Arthritis.  
Alphen Aan Den Rijn, The Netherlands: Van Zuiden Communications B.V.; 2000:40.
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Ware JE, Kosinski M, Bjorner JB, et al.  User’s manual for the SF-36v2 Health Survey (second edition). 
Lincoln, RI: QualityMetric Incorporated. 2007.
25.
Zochling J, van der Heijde D, Burgos-Vargas R, et al. ASAS/EULAR recommendations for the management of 
ankylosing spondylitis. Ann Rheum Dis. 2006;65(4):442-452.  
26.
Yeonhee Kim, Seunghyun Won. Adjusted proportion difference and confidence interval in stratified 
randomized trials. PharmaSUG 2013 – Paper SP04.
27.
Bohdana Ratitch, et al. Combining analysis results from multiply imputed cartegorical data. PharmaSUG 2013-
Paper SP03.
28.
L. Valeri and T. J. VanderWeele (2013), Meidation Analysis Allowing for Exposure-Mediator Interactions and 
Causal Interpretation: Theoretical Assumptions and Implementation with SAS and SPSS Macros, 
Psychological Methods, Vol. 18, No.2: 137-150.
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APPENDICES
APPENDIX 1: RULES APPLIED IN DEFINITIONS OF ENDPOINTS
1.
Joint Evaluability Rules for Sign and Symptom Data
For subjects having a joint injection(s)/surgical joint procedure(s) prior to the date of study entry 
(e.g., randomization) or during the study, the affected joint(s) will be valued according to the 
following rules:

For subjects having a joint injection and/or surgical joint procedure prior to the date of 
randomization, the affected joints will be analyzed according to the impact of the joint 
injection and/or surgical joint procedure on the evaluability of the involved joints.
o
If a joint is considered un-evaluable at baseline due to certain procedure/injection 
performed prior to the date of randomization, the joint will be considered un-evaluable 
throughout the study.

For subjects undergoing surgical joint procedures for the treatment of PsA during the study, 
the affected joints will be considered as swollen and tender from the date of procedure 
onwards. 

For subjects undergoing surgical joint procedures during the study for the treatment of non-
PsA disease indication, the affected joints will be analyzed according to the impact of the 
surgical joint procedure on the evaluability of the involved joints. 

For subjects undergoing joint injections for PsA during the study, the affected joints will be 
considered as swollen and tender from the date of injection for the next 90 days.

For subjects undergoing joint injections for non-PsA related reasons during the study, the 
affected joints will be considered as non-evaluable from the date of injection for the next 90 
days.
2.
Joint Count Adjustment Rule 
For subjects who have an incomplete set of evaluable joints the joint count/score will be adjusted 
to the total number joints of interest (e.g., 68 joints for tenderness and 66 joints for swelling) by 
dividing the number of affected joints by the number of evaluable joints and multiplying by the 
total number joints of interest.
3.
LLOQ rule 
Any value < LLOQ is considered equal to half of the value of LLOQ for numerical calculations. 
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APPENDIX 2: STATISTICAL HYPOTHESES 
Hypothesis
Global
US Specific
Primary Endpoints
H1.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by the proportion of subjects achieving an 
ACR 20 response at Week 24 (primary hypothesis)
Controlled as 
in figure 2
Controlled as 
in figure 3
H2.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by the proportion of 
subjects achieving an ACR 20 response at Week 24
Controlled as 
in figure 2
Controlled as 
in figure 3
Major Secondary Endpoints
H3.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by proportion of subjects who achieved a 
psoriasis IGA response at Week 24 among the subjects 
with ≥3% BSA psoriatic involvement and an IGA score of 
≥2 (mild) at baseline
Controlled as 
in figure 2
Controlled as 
in figure 3
H4.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by proportion of 
subjects who achieved a psoriasis IGA response at Week 
24 among the subjects with ≥3% BSA psoriatic 
involvement and an IGA score of ≥2 (mild) at baseline
Controlled as 
in figure 2
Controlled as 
in figure 3
H5.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by change from baseline in DAS28 (CRP) at 
Week 24
Controlled as 
in figure 2
Weakly-
controlled
H6.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by change from 
baseline in DAS28 (CRP) at Week 24
Controlled as 
in figure 2
Weakly-
controlled
H7.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by change from baseline in HAQ-DI score at 
Week 24
Controlled as 
in figure 2
Controlled as 
in figure 3
H8.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by change from 
baseline in HAQ-DI score at Week 24
Controlled as 
in figure 2
Controlled as 
in figure 3
H9.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by change from baseline in SF-36 PCS at Week 
24
Controlled as 
in figure 2
Controlled as 
in figure 3
H10.
Guselkumab 100 mg at Week 0, Week 4, then q8w Controlled as 
Controlled as 
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SC is superior to placebo as assessed by change from 
baseline in SF-36 PCS at Week 24
in figure 2
in figure 3
H11.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by proportion of subjects who achieved an 
ACR 50 response at Week 24
Controlled as 
in figure 2
Weakly-
controlled
H12.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by proportion of 
subjects who achieved an ACR 50 response at Week 24;
Controlled as 
in figure 2
Weakly-
controlled
H13.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by proportion of subjects achieved an ACR 20 
response at Week 16
Controlled as 
in figure 2
Weakly-
controlled
H14.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by proportion of 
subjects achieved an ACR 20 response at Week 16
Controlled as 
in figure 2
Weakly-
controlled
H15.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by proportion of subjects who achieve an ACR 
70 response at Week 24
Controlled as 
in figure 2
Weakly-
controlled
H16.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by proportion of 
subjects who achieve an ACR 70 response at Week 24
Controlled as 
in figure 2
Weakly-
controlled
H17.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by proportion of subjects who achieve an ACR 
50 response at Week 16
Controlled as 
in figure 2
Weakly-
controlled
H18.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by proportion of 
subjects who achieve an ACR 50 response at Week 16
Controlled as 
in figure 2
Weakly-
controlled
H19.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by proportion of subjects with resolution of 
enthesitis at Week 24 among the subjects with enthesitis at 
baseline
Nominal
Nominal
H20.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by proportion of 
subjects with resolution of enthesitis at Week 24 among 
the subjects with enthesitis at baseline
Nominal
Nominal
H21.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by proportion of subjects with resolution of 
dactylitis at Week 24 among the subjects with dactylitis at 
baseline
Nominal
Nominal
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H22.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by proportion of 
subjects with resolution of dactylitis at Week 24 among the 
subjects with dactylitis at baseline
Nominal
Nominal
H23.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by change from baseline in SF-36 MCS at 
Week 24
Nominal
Nominal
H24.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by change from 
baseline in SF-36 MCS at Week 24
Nominal
Nominal
H25.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by change from baseline in enthesitis score 
(based on Leeds Enthesitis Index [LEI]) at Week 24 among 
the subjects with enthesitis at baseline
Nominal
Nominal
H26.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by change from 
baseline in enthesitis score (based on Leeds Enthesitis 
Index [LEI]) at Week 24 among the subjects with 
enthesitis at baseline
Nominal
Nominal
H27.
Guselkumab 100 mg q4w SC is superior to placebo 
as assessed by change from baseline in dactylitis scores at 
Week 24 among the subjects with dactylitis at baseline
Nominal
Nominal
H28.
Guselkumab 100 mg at Week 0, Week 4, then q8w 
SC is superior to placebo as assessed by change from 
baseline in dactylitis scores at Week 24 among the subjects 
with dactylitis at baseline
Nominal
Nominal
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APPENDIX 3:  DESCRIPTION OF STATISTICAL MODELS
1. Mixed-effect Model Repeated Measures (MMRM)
To account for the missing data for continuous endpoints of change from baseline, a Mixed-
Effect Model Repeat Measures (MMRM) will be used, under the assumption of MAR, to test the 
difference between a guselkumab group and the placebo group. The explanatory variables of the 
model will include treatment group, an interaction term of visit with treatment group, an
interaction term of visit with baseline use of non-biologic DMARDs (yes, no), an interaction 
term of visit with prior exposure to anti-TNFα agents (yes, no), and an interaction term of visit 
with baseline score. An unstructured covariance matrix for repeated measure within a subject 
will be used. The F-test will use Kenward-Roger’s approximating for degree of freedom. In case 
of lack of convergence, empirical structured covariances will be used in the following order until 
convergence is reached: 1) Toeplitz 2) first order Autoregressive Moving Average.  The model 
will include data from all 3 treatment groups through Week 24.  The treatment difference 
between a guselkumab group and the placebo group will be estimated by the difference in the 
least squares means (LSmeans). The 95% confidence interval (CI) for the differences in 
LSmeans and p-values will be calculated based on the MMRM. 
2. Constrained Longitudinal Data Analysis (cLDA) Model
To account for the missing data for continuous endpoints when 2% or more subjects have 
baseline score missing, a Constrained Longitudinal Data Analysis (cLDA) model may be 
performed based on the original measurement score rather than on the change score, under the 
assumption of MAR, to test the difference between a guselkumab group and the placebo group. 
The explanatory variables of the model will include treatment group, an interaction term of visit 
with treatment group, an interaction term of visit with baseline use of non-biologic DMARDs
(yes, no), and an interaction term of visit with prior exposure to anti-TNFα agents (yes, no). An 
unstructured covariance matrix for repeated measure within a subject will be used. The F-test 
will use Kenward-Roger’s approximating for degree of freedom. In case of lack of convergence, 
empirical structured covariances will be used in the following order until convergence is 
reached: 1) Toeplitz 2) first order Autoregressive Moving Average.  The model will include data 
from all 3 treatment groups through Week 24.  The treatment difference between a guselkumab 
group and the placebo group will be estimated by the difference in the LS means. The 95% CIs
for the differences in LS means and p-values will be calculated based on the cLDA model.
3. Mediation Analysis
Mediation analysis will be performed to examine the mediating role of 24-week ACR20 
response on change from baseline in fatigue score at week 24 provided both endpoints 
demonstrate a statistically significant difference between treatment arms. In the mediation 
analysis framework, natural direct effect can be conceived of as independent treatment effect on 
the outcome (i.e. change in fatigue score) that is above and beyond its effect on the mediator (i.e. 
ACR20 response); controlled direct effect can be conceived of as the independent treatment 
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effect on the outcome controlling the mediator at a fixed level; and the natural indirect effect can 
be conceived of as a treatment effect on the outcome that is mediated by its effect on the 
mediator.
The parametric counterfactual approach implemented by Valeri and VanderWeele (2013)35 will 
be used to estimate the controlled direct effect (CDE), natural direct effect (NDE) and natural 
indirect effect (NIE).  Let  	  and  Mα denote the values of the outcome and mediator that 
would have been observed had the exposure A been set to level α and let Yαm denote the value 
of the outcome that would have been observed had the exposure A and mediator M been set to 
levels αand m respectively.  In the analysis of binary exposure, we will set α=1 for treated arm 
and α=0 for controlled arm. The average controlled direct effect (CDE) comparing treated (α =1) 
to control (α =0) given the mediator fixing to level m is defined by 
() = ( −). 
The average natural direct effect (NDE) is defined by  = ( −). The average 
natural indirect effect is defined by  = ( −). 
Covariates considered in this mediation analysis will include baseline fatigue score and 
demographics parameters and disease related parameters such as age, gender, BMI, PsA 
duration, physician Global Assessment (GDEV), patient global assessment (GDPT), HAQ-DI 
score, pain assessment (PAIN), Swollen Joints 66 (SJC66) and tender joints 68 (TJC68). We will 
also allow exposure-mediator interaction in this analysis. 
Bootstrap will be used to obtain final effect estimates and their corresponding confidence 
intervals and P values. Model and variable selection may be conducted as sensitivity analysis. 
Alternative implementations of mediation analysis may also be explored as part of sensitivity 
analysis.
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APPENDIX 4:  SUMMARY OF MULTIPLE IMPUTATION METHODS
Endpoints
MI specification
Analysis method/Summary statistics
ACR 20 response at Week 24
Supplementary analysis 1
Supplementary analysis 2
Multiple imputation 
with FCS regression 
of component scores
MIdataset1 (N=200, Seed c =4362478)

Imputation variables: 7 ACR components from Week 0 -  
24

Ancillary variables: Treatment group, randomization 
stratification factors
Change from baseline 
through Week 24 in:
HAQ-DI Score
DAS28(CRP) Score
Multiple imputation 
with FCS regression 
of component scores
MIdataset2a (N=200, Seed c =4237590)

Imputation variables: 5 ACR components other than joint 
counts from Week 0 - Week 24, tender joint counts based on 28 
joints, swollen joint counts based on the 28 joints.

Ancillary variables: Treatment group, randomization 
stratification factors
Change from baseline 
through Week 24 in 
Enthesitis score (LEI) among 
subjects with at least one 
tender enthesis at baseline
Multiple imputation 
with FCS regression 
of enthesitis scores
MIdata3 (N=200, Seed c =6509723)
Note: The MI is done only for the subset of subjects who have 
enthesitis at baseline and not all subjects in the study 
population.

Imputation variables: enthesitis score from Weeks 0 – 24. 

Ancillary variables b: Treatment group, randomization 
stratification factors, 7 ACR components from Weeks 0 –
24, enthesitis-4d
Dactylitis change from 
baseline through Week 24 
among subjects with 
dactylitis at baseline
Multiple imputation 
with FCS regression 
of dactylitis scores
MIdata4 (N=200, Seed c =1284097)
Note: The MI is done only for the subset of subjects who have 
dactylitis at baseline and not all subjects in the study 
population.

Imputation variables: dactylitis score from Weeks 0 – 24. 

Ancillary variables b: Treatment group, randomization 
stratification factors, 7 ACR components from Weeks 0 –
24
Change from baseline 
through Week 24 in:
SF-36 PCS score
SF-36 MCS score 
Multiple imputation 
with FCS regression 
of PCS, MCS scores
MIdata5 (N=200, Seed c =890473)

Imputation variables: PCS and MCS scores from Weeks 
0 – 24 

Ancillary variables b: Treatment group, randomization 
stratification factors, 7 ACR components from Weeks 0 -
24
IGA change from baseline 
through Week 24 among 
subjects with ≥3% BSA 
psoriatic involvement and an 
IGA score of ≥2 at baseline
Multiple imputation 
with FCS regression of 
IGA scores
MIdata6 (N=200, Seede = 413249)
Imputation variables: IGA scores from Weeks 0 – 24
Ancillary variables b: Treatment group, randomization stratification 
factors, 7 ACR components from Weeks 0 - 24
a MIdataset2 is different from MIdataset1 as the joint scores used in DAS 28 (CRP) are different from those used in 
ACR.
bAn ancillary variable may be removed if its correlation with an indicator variable that determines missing-ness of the 
variable to be imputed is low or, there are too many missing values for the ancillary variable within the subgroup of 
incomplete cases for the variable to be imputed. All the 7 ACR components (including all measurements from 
baseline through week 24) are in the list of the ancillary variables since they may be related to the mechanism of the 
NCT03162796
Title:
Version:
EDMS-ERI-196141431
2.0


CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959PSA3001 Amendment 3
88
Approved, Date: 21 March 2019
missing data.
c The starting seed for FCS regression MI is used to generate a series of imputation seeds using the algorithm: 
INT((2**31-2)*RANUNI(starting seed)), where each imputation seed will be used for a single imputation. To 
account for the possibility that some imputations may fail to complete due to out-of-range issues, 200+ initial 
imputation seeds will be prepared, and the first 200 successful imputations will be used for analysis.
d Enthesitis-4 is the tender entheses count based on 4 sites (left and right achilles tendon insertion, and left and right 
humeral epicondyle lateral) instead of 6 sites. Only baseline, Week 4 are included as ancillary variables.
NCT03162796
Title:
Version:
EDMS-ERI-196141431
2.0