A Phase 3B, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Guselkumab Administered Subcutaneously in Participants With Active Psoriatic Arthritis Who Had an Inadequate Response and/or Intolerance to One Prior Anti-Tumor Necrosis Factor Alpha Agent
Phase: PHASE3
Conditions: Arthritis, Psoriatic
Sponsor: Janssen Research & Development, LLC

CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
1
Status: Approved,  Date: 04 September 2024
Janssen Research & Development *
Clinical Protocol
Protocol Title
A Phase 3B, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the
Efficacy and Safety of Guselkumab Administered Subcutaneously in Participants with Active
Psoriatic Arthritis who had an Inadequate Response and/or Intolerance to One Prior Anti-Tumor
Necrosis Factor α Agent
SOLSTICE
Short Title
Guselkumab versus Placebo for the Treatment of Active Psoriatic Arthritis in Participants with
Inadequate Response and/or Intolerance to One Prior Anti-Tumor Necrosis Factor α Agent
Protocol CNTO1959PSA3005; Phase 3b
AMENDMENT 2
Guselkumab  (Tremfya)
*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 Scientific Affairs; Janssen
Products, LP; Janssen Biologics, BV; Janssen-Cilag International NV; Janssen, Inc; Janssen
Pharmaceutica NV; or Janssen Research & Development, LLC. The term “Sponsor” is used throughout
the protocol to represent these various legal entities; the Sponsor is identified on the Contact Information
page that accompanies the protocol.
United States (US)sites of this study will be conducted under US Food & Drug Administration
Investigational New Drug (IND) regulations (21 CFR Part 312).
Studies conducted at sites in the European Economic Area (EEA) will be conducted under
Regulation [EU] No 536/2014.
IND:124177
EU TRIAL NUMBER:2023-504715-33
Status: 
Approved
Date: 
04 September 2024
Prepared by: Janssen Research & Development, LLC
EDMS number: 
EDMS-RIM-394927, 3.0
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory
requirements.
Confidentiality Statement
The information provided herein contains Company trade secrets, commercial or financial information that the Company
customarily holds close and treats as confidential.  The information is being provided under the assurance that the recipient
will maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or
otherwise.
NCT04936308

Guselkumab (Tremfya) 
Clinical Protocol CNTO1959PSA3005 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
2
Status: Approved,  Date: 04 September 2024
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document 
Date
Amendment 2 
04 September 2024
Amendment 1 
12 May 2022
Original Protocol 
13 April 2021
Amendment 2 (04September 2024)
Overall Rationale for the Amendment: The overall reason for this amendment is to update the protocol
to comply with the European Union /European Economic Area Clinical Trial Regulations (EU CTR)
requirements. In addition, revisions were made to correct errors and to improve clarity and consistency in
the protocol.
The changes made to the clinical protocol CNTO1959PSA3005 as part of Protocol Amendment 2 are listed
below, including the rationale of each change and a list of all applicable sections. Changes made in previous
protocol amendments are listed in Section 10.10 Appendix 10: Protocol Amendment History.
Section Number 
and Name
Description of Change 
Brief Rationale
Title Page; 
1.1. Synopsis 
Added text on EU regulation, and EU trial number 
per EU CTR requirement.
For compliance with EU CTR.
1.1 Synopsis 
Added Benefit-Risk Assessment section to
protocol synopsis.
8.3.4 Regulatory 
Reporting
Requirements for
Serious Adverse
Events and
Anticipated Events
Text in this section was updated.
10.5.7. Publication 
Policy/Dissemination 
of Clinical Study
Data
Text added to specify timing of submission of
Week 24 results to the EU database.
10.5.13. Record 
Retention  
Text added to specify length of time the content of
the trial master file will be archived after study
completion.
1.2. Schema 
Study visits removed from Weeks 60 and 92. 
Schema corrected to indicate
Weeks 60 and 92 are not required
site visits.
1.3. Schedule of 
Activities 
Study intervention administration added at 
Week 52. 
Added study intervention
administration at Week 52, which
was accidentally omitted
previously.
1.3. Schedule of 
Activities 
Footnote m. updated to indicate pregnancy tests 
administration is optional for participants who 
dose at home during at-home administration 
visits.
Clarification of use of pregnancy
test(s) during at-home
administration visits.
1.3. Schedule of 
Activities 
Physical examination at Week 80 was removed 
from schedule. 
Removed physical examination at
Week 80 to correct previous
addition error.
5.1. Inclusion 
Criteria 
Note regarding acceptability of a condom or 
occlusive cap as the sole method of contraception 
Note was incorrectly located in
criterion regarding male
NCT04936308

Guselkumab (Tremfya) 
Clinical Protocol CNTO1959PSA3005 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
3
Status: Approved,  Date: 04 September 2024
Section Number 
and Name
Description of Change 
Brief Rationale
moved from Inclusion Criteria 21 (removed) to 
Inclusion Criteria 17 (added). 
contraception. Note moved to
correct location in criteria regarding
female contraception.
6.8.3. Nonsteroidal 
Anti-Inflammatory 
Drugs and Other 
Analgesics 
Interval of maintenance of stable dose of NSAIDs 
and other analgesics, including topical analgesics 
from baseline updated from “through Week 52” to 
“through Week 24”. 
Updated for consistency within
section regarding initiation or
increase of NSAIDs or other
analgesics after Week 24.
6.8.5. 
Complementary 
Therapies 
Length of prohibition of use of complementary 
therapies corrected to through Week 112. 
The use of complementary therapies
is prohibited through the end of
study.
8. Study 
Assessments and 
Procedures, 
Overview
Maximum total volume of blood to be collected 
from each participant updated to 625 mL. 
Updated maximum blood draw
volume due to change in lab tubes
used for the study.
Throughout the 
protocol 
Minor grammatical, formatting, or spelling 
changes were made.
Minor errors were noted
NCT04936308

Guselkumab (Tremfya) 
Clinical Protocol CNTO1959PSA3005 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
4
Status: Approved,  Date: 04 September 2024
TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................................... 2
TABLE OF CONTENTS ............................................................................................................................... 4
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 8
1. 
PROTOCOL SUMMARY..................................................................................................................... 9
1.1. 
Synopsis........................................................................................................................................... 9
1.2. 
Schema.......................................................................................................................................... 15
1.3. 
Schedule of Activities (SoA)........................................................................................................... 16
2. 
INTRODUCTION................................................................................................................................ 24
2.1. 
Study Rationale.............................................................................................................................. 24
2.2. 
Background.................................................................................................................................... 25
2.2.1.1. 
Phase 3 Studies: CNTO1959PSA3001 (DISCOVER 1) and CNTO1959PSA3002
(DISCOVER 2)......................................................................................................................... 25
2.2.1.1.1. 
Study design......................................................................................................................... 25
2.2.1.1.2. 
Efficacy results ..................................................................................................................... 26
2.2.1.1.3. 
Safety results........................................................................................................................ 27
2.2.1.2. 
Phase 3b Study: CNTO1959PSA3003 (COSMOS)................................................................ 27
2.3. 
Benefit-Risk Assessment............................................................................................................... 28
2.3.1. 
Risks for Study Participation....................................................................................................... 28
2.3.2. 
Benefits for Study Participation .................................................................................................. 31
2.3.3. 
Benefit-Risk Assessment for Study Participation ....................................................................... 31
3. 
OBJECTIVES AND ENDPOINTS ..................................................................................................... 32
4. 
STUDY DESIGN ................................................................................................................................ 34
4.1. 
Overall Design................................................................................................................................ 34
4.2. 
Scientific Rationale for Study Design............................................................................................. 36
4.2.1. 
Study-Specific Ethical Design Considerations ........................................................................... 38
4.3. 
Justification for Dose...................................................................................................................... 38
4.4. 
End of Study Definition................................................................................................................... 39
5. 
STUDY POPULATION ...................................................................................................................... 40
5.1. 
Inclusion Criteria............................................................................................................................ 40
5.2. 
Exclusion Criteria........................................................................................................................... 45
5.3. 
Lifestyle Considerations................................................................................................................. 50
5.4. 
Screen Failures.............................................................................................................................. 51
5.5. 
Criteria for Temporarily Delaying Administration of Study Intervention ......................................... 52
6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY............................................................ 52
6.1. 
Study Intervention(s) Administered................................................................................................ 52
6.1.1. 
Combination Products ................................................................................................................ 53
6.2. 
Preparation/Handling/Storage/Accountability ................................................................................ 53
6.3. 
Measures to Minimize Bias: Randomization and Blinding............................................................. 54
6.4. 
Study Intervention Compliance...................................................................................................... 55
6.5. 
Dose Modification........................................................................................................................... 56
6.6. 
Continued Access to Study Intervention After the End of the Study ............................................. 56
6.7. 
Treatment of Overdose .................................................................................................................. 56
6.8. 
Concomitant Therapy..................................................................................................................... 57
6.8.1. 
Non-biologic DMARDs................................................................................................................ 59
6.8.1.1. 
Permitted Non-biologic DMARDs ............................................................................................ 59
6.8.1.2. 
Prohibited Non-biologic DMARDs and Apremilast.................................................................. 61
6.8.1.3. 
Systemic Immunosuppressive Drugs ...................................................................................... 61
6.8.2. 
Corticosteroids............................................................................................................................ 61
6.8.2.1. 
Oral Corticosteroids................................................................................................................. 61
NCT04936308

Guselkumab (Tremfya) 
Clinical Protocol CNTO1959PSA3005 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
5
Status: Approved,  Date: 04 September 2024
6.8.2.2. 
Corticosteroids –Intravenous, Intramuscular, or Epidural Administration .............................. 61
6.8.2.3. 
Corticosteroids –Intra-articular Injection................................................................................. 62
6.8.2.4. 
Corticosteroids –Other Routes of Administration ................................................................... 62
6.8.3. 
Nonsteroidal Anti-inflammatory Drugs and Other Analgesics .................................................... 62
6.8.4. 
Biologic Agents, Cytotoxic Drugs, JAK Inhibitors, or Investigational Agents ............................. 63
6.8.5. 
Complementary Therapies ......................................................................................................... 63
6.8.6. 
Topical Therapy and Ultraviolet B Light...................................................................................... 63
6.8.6.1. 
Systemic Therapy for Psoriasis............................................................................................... 63
6.8.7. 
Vaccinations (Including for COVID-19)....................................................................................... 64
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL............................................................................................... 64
7.1. 
Discontinuation of Study Intervention ............................................................................................ 64
7.1.1. 
Liver Chemistry Stopping Criteria............................................................................................... 66
7.1.2. 
Liver Chemistry Restart Criteria................................................................................................. 66
7.2. 
Participant Discontinuation/Withdrawal From the Study................................................................ 66
7.2.1. 
Withdrawal from the Use of Research Samples......................................................................... 67
7.3. 
Lost to Follow-up............................................................................................................................ 68
8. 
STUDY ASSESSMENTS AND PROCEDURES ............................................................................... 69
8.1. 
Efficacy Assessments .................................................................................................................... 70
8.1.1. 
Psoriatic Arthritis Response Evaluations.................................................................................... 70
8.1.1.1. 
Joint count (tender and swollen).............................................................................................. 70
8.1.1.2. 
Non-evaluable Joints ............................................................................................................... 71
8.1.1.3. 
American College of Rheumatology Response....................................................................... 71
8.1.1.4. 
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ............................................... 71
8.1.1.5. 
Dactylitis Score........................................................................................................................ 72
8.1.1.6. 
Enthesitis Assessments........................................................................................................... 72
8.1.1.7. 
Physician’s Global Assessment of Disease Activity................................................................ 73
8.1.1.8. 
Health Assessment Questionnaire –Disability Index (HAQ-DI).............................................. 73
8.1.1.9. 
Minimal Disease Activity.......................................................................................................... 73
8.1.1.10. 
Very Low Disease Activity....................................................................................................... 73
8.1.1.11. 
Disease Activity Index for Psoriatic Arthritis (DAPSA) ............................................................ 73
8.1.1.12. 
Psoriatic Arthritis Disease Activity Score (PASDAS) .............................................................. 74
8.1.2. 
Psoriasis Response Evaluations ................................................................................................ 74
8.1.2.1. 
Psoriasis Area and Severity Index (PASI)............................................................................... 74
8.1.2.2. 
Investigator’s Global Assessment (IGA) of Psoriasis.............................................................. 74
8.1.3. 
Patient Reported Outcomes ....................................................................................................... 75
8.1.3.1. 
PsA Impact of Disease (PSAID)-12......................................................................................... 75
8.1.3.2. 
Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue ................................... 75
8.1.3.3. 
Patient’s Global Assessment of Disease Activity.................................................................... 75
8.1.3.4. 
Patient’s Assessment of Pain.................................................................................................. 75
8.1.3.5. 
Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) ................ 76
8.1.3.6. 
Short-Form 36 (SF-36) ............................................................................................................ 76
8.2. 
Safety Assessments....................................................................................................................... 77
8.2.1. 
Physical Examinations................................................................................................................ 77
8.2.2. 
Vital Signs................................................................................................................................... 77
8.2.3. 
Height and Weight...................................................................................................................... 77
8.2.4. 
Electrocardiograms..................................................................................................................... 77
8.2.5. 
Clinical Safety Laboratory Assessments .................................................................................... 78
8.2.6. 
Pregnancy Testing...................................................................................................................... 78
8.2.7. 
Suicidal Ideation and Behavior Risk Monitoring ......................................................................... 78
8.2.8. 
Concomitant Medication Review ................................................................................................ 80
8.2.9. 
Injection-Site Reactions.............................................................................................................. 80
8.2.10. 
Hypersensitivity Reactions.......................................................................................................... 80
8.2.11. 
Infections .................................................................................................................................... 80
8.2.12. 
Tuberculosis Evaluations............................................................................................................ 81
8.2.12.1. 
Initial Tuberculosis Evaluation................................................................................................. 81
NCT04936308

Guselkumab (Tremfya) 
Clinical Protocol CNTO1959PSA3005 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
6
Status: Approved,  Date: 04 September 2024
8.2.12.2. 
Ongoing Tuberculosis Evaluation............................................................................................ 81
8.3. 
Adverse Events, Serious Adverse Events, and Other Safety Reporting ....................................... 82
8.3.1. 
Time Period and Frequency for Collecting Adverse Event and Serious Adverse Event
Information.................................................................................................................................. 83
8.3.2. 
Method of Detecting Adverse Events and Serious Adverse Events .......................................... 83
8.3.3. 
Follow-up of Adverse Events and Serious Adverse Events ....................................................... 83
8.3.4. 
Regulatory Reporting Requirements for Serious Adverse Events and Anticipated
Events......................................................................................................................................... 84
8.3.5. 
Pregnancy................................................................................................................................... 84
8.3.6. 
Adverse Events of Special Interest............................................................................................. 85
8.4. 
Pharmacokinetics........................................................................................................................... 85
8.4.1. 
Evaluations ................................................................................................................................. 85
8.4.2. 
Analytical Procedures................................................................................................................. 85
8.5. 
Pharmacogenomics ....................................................................................................................... 85
8.6. 
Biomarkers..................................................................................................................................... 86
8.6.1. 
Pharmacodynamics .................................................................................................................... 86
8.6.2. 
Serum and Plasma Biomarkers.................................................................................................. 86
8.6.3. 
Whole Blood Gene Expression Profile ....................................................................................... 87
8.6.4. 
Peripheral Blood Mononuclear Cells .......................................................................................... 87
8.6.5. 
Tissue Biomarkers...................................................................................................................... 87
8.7. 
Immunogenicity Assessments ....................................................................................................... 87
9. 
STATISTICAL CONSIDERATIONS.................................................................................................. 88
9.1. 
Statistical Hypotheses.................................................................................................................... 88
9.2. 
Sample Size Determination ........................................................................................................... 88
9.2.1. 
Primary Endpoint –ACR 20 Response at Week 24................................................................... 88
9.3. 
Populations for Analysis Sets ........................................................................................................ 89
9.4. 
Statistical Analyses ........................................................................................................................ 89
9.4.1. 
General Considerations.............................................................................................................. 89
9.4.2. 
Primary Endpoint(s).................................................................................................................... 90
9.4.3. 
Secondary Endpoint(s)............................................................................................................... 91
9.4.4. 
Safety Analyses.......................................................................................................................... 91
9.4.5. 
Other Analyses ........................................................................................................................... 92
9.5. 
Interim Analysis.............................................................................................................................. 94
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ............................ 95
10.1. 
Appendix 1: Abbreviations ............................................................................................................. 95
10.2. 
Appendix 2: Clinical Laboratory Tests ........................................................................................... 97
10.3. 
Appendix 3: Tuberculin Skin Testing ............................................................................................. 98
10.4. 
Appendix 4: Hepatitis B Virus (HBV) Screening with HBV DNA Testing..................................... 100
10.5. 
Appendix 5: Regulatory, Ethical, and Study Oversight Considerations....................................... 101
10.5.1. 
Regulatory and Ethical Considerations .................................................................................... 101
10.5.2. 
Financial Disclosure.................................................................................................................. 104
10.5.3. 
Informed Consent Process ....................................................................................................... 105
10.5.4. 
Data Protection ......................................................................................................................... 105
10.5.5. 
Long-Term Retention of Samples for Additional Future Research .......................................... 106
10.5.6. 
Committees Structure............................................................................................................... 106
10.5.7. 
Publication Policy/Dissemination of Clinical Study Data.......................................................... 107
10.5.8. 
Data Quality Assurance............................................................................................................ 108
10.5.9. 
Case Report Form Completion................................................................................................. 108
10.5.10. Source Documents ................................................................................................................... 109
10.5.11. Monitoring ................................................................................................................................. 110
10.5.12. On-Site Audits........................................................................................................................... 110
10.5.13. Record Retention...................................................................................................................... 111
10.5.14. Study and Site Start and Closure ............................................................................................. 111
10.6. 
Appendix 6: Adverse Events, Serious Adverse Events, Product Quality Complaints, and
Other Safety Reporting: Definitions and Procedures for Recording, Evaluating, Follow-up,
and Reporting............................................................................................................................... 113
NCT04936308

Guselkumab (Tremfya) 
Clinical Protocol CNTO1959PSA3005 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
7
Status: Approved,  Date: 04 September 2024
10.6.1. 
Adverse Event Definitions and Classifications ......................................................................... 113
10.6.2. 
Attribution Definitions................................................................................................................ 114
10.6.3. 
Severity Criteria........................................................................................................................ 114
10.6.4. 
Special Reporting Situations .................................................................................................... 115
10.6.5. 
Procedures ............................................................................................................................... 115
10.6.6. 
Product Quality Complaint Handling......................................................................................... 117
10.6.7. 
Contacting Sponsor Regarding Safety, Including Product Quality........................................... 117
10.7. 
Appendix 7: Contraceptive and Barrier Guidance ....................................................................... 118
10.8. 
Appendix 8: Liver Safety: Suggested Actions and Follow-up Assessments................................ 121
10.9. 
Appendix 9: Study Conduct During a Natural Disaster................................................................ 127
10.10. Appendix 10: Protocol Amendment History................................................................................. 129
11. REFERENCES................................................................................................................................. 132
INVESTIGATOR AGREEMENT............................................................................................................... 134
NCT04936308

Guselkumab (Tremfya) 
Clinical Protocol CNTO1959PSA3005 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
8
Status: Approved,  Date: 04 September 2024
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1: 
Potential Study Risks................................................................................................................ 28
Table 2: 
Study Interventions (Treatment Groups) .................................................................................. 52
Table 3: 
Permitted Concomitant Medications for PsA and the Maximum Allowed Doses During
the Study................................................................................................................................... 58
Table 4: 
Protocol Requirements of the Permitted Non-biologic Disease-Modifying
Antirheumatic Drugs ................................................................................................................. 60
Table 5: 
Power Calculations for Primary and Major Secondary Endpoints Based on 150 per
Treatment Group....................................................................................................................... 89
Table 6: 
Analysis Populations................................................................................................................. 89
NCT04936308

Guselkumab (Tremfya) 
Clinical Protocol CNTO1959PSA3005 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
9
Status: Approved,  Date: 04 September 2024
1. 
PROTOCOL SUMMARY
1.1. 
Synopsis
A Phase 3B, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy
and Safety of Guselkumab Administered Subcutaneously in Participants with Active Psoriatic Arthritis who
had an Inadequate Response and/or Intolerance to One Prior Anti-Tumor Necrosis Factor α Agent
IND:124177
EU TRIAL NUMBER:2023-504-715-33
Short Title:Guselkumab versus Placebo for the Treatment of Active Psoriatic Arthritis in Participants with
Inadequate Response and/or Intolerance to One Prior Anti-Tumor Necrosis Factor α Agent
Guselkumab (TREMFYA®, CNTO1959) is a fully human immunoglobulin G1 lambda (IgG1λ) monoclonal
antibody (mAb) that binds to the p19 protein subunit of interleukin (IL)-23 with high affinity. By binding
to the p19 protein subunit of IL-23, guselkumab blocks the binding of extracellular IL-23 to the cell surface
IL-23 receptor, inhibiting IL-23-mediated intracellular signaling, activation, and cytokine production.
Benefit-Risk Assessment for Study Participation
Additional data through 1 year of treatment from the PSA3001 and PSA3002 studies for both guselkumab
doses (ie, 100 mg SC q8w and q4w) under study in this protocol continue to support an overall favorable
benefit-to-risk profile for the use of guselkumab in active PsA.
Potential risks of guselkumab are being addressed via judicious inclusion/exclusion criteria, frequent study
visits to allow for close monitoring of patient safety, guidelines for participant management (including
monitoring of clinical laboratory tests and treatment discontinuation criteria), detailed description of
allowed and prohibited concomitant medications, and comprehensive medical monitoring of data by the
Sponsor/designee during the conduct of the studies.
Taking into account the measures taken to minimize risk to participants in this study, the potential risks
identified in association with guselkumab are justified by the benefits that may be provided to participants
with PsA.
OBJECTIVES AND ENDPOINTS
Objective 
Endpoint
Primary
To evaluate the efficacy of guselkumab 
treatment in participants with active PsA 
and IR and/or intolerance to a prior anti-
TNF by assessing the reduction in signs
and symptoms of PsA.
Proportion of participants who achieve an
ACR20 response at Week 24
Major Secondary
To evaluate the efficacy of guselkumab 
on additional measures of signs and 
symptoms of PsA, psoriasis, and patient 
well-being. 
Proportion of participants who achieve a
psoriasis response of IGA psoriasis score of 0
(cleared) or 1 (minimal) AND ≥2-grade
reduction from baseline at Week 24 among the
participants with ≥3% BSA psoriatic
involvement and an IGA score of ≥2 (mild) at
baseline
Proportion of participants who achieve PASI 90
response at Week 24 among the participants
NCT04936308

Guselkumab (Tremfya) 
Clinical Protocol CNTO1959PSA3005 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
10
Status: Approved,  Date: 04 September 2024
with ≥3% BSA psoriatic involvement and an
IGA score of ≥2 (mild) at baseline
Change from baseline in HAQ-DI at Week 24
Change from baseline in the SF-36 PCS at
Week 24
Change from baseline in Functional Assessment
of Chronic Illness Therapy –fatigue (FACIT-F)
score at Week 24
Proportion of participants achieving minimal
disease activity (MDA) at Week 24
Proportion of participants who achieve ACR20
response at Week 16
Proportion of participants who achieve ACR50
response at Week 16
Proportion of participants who achieve ACR50
response at Week 24
Proportion of participants who achieve ACR70
response at Week 24
The ordering of endpoints, 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 (SAP).
Other Secondary
To evaluate the safety of guselkumab in
participants with active PsA.
Other secondary:
Frequency and type of AEs, SAEs, reasonably
related AEs, AEs leading to discontinuation of
study intervention, infections, and injection-site
reactions
Laboratory abnormalities (chemistry,
hematology) maximum toxicity (Common
Terminology Criteria for Adverse Events
[CTCAE 5.0]) grades
To evaluate the pharmacokinetics (PK)
and immunogenicity of guselkumab in
participants with active PsA.
Serum guselkumab concentration over time
Incidence of antibodies to guselkumab
CCI
NCT04936308

Guselkumab (Tremfya) 
Clinical Protocol CNTO1959PSA3005 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
11
Status: Approved,  Date: 04 September 2024
CCI
NCT04936308

Guselkumab (Tremfya) 
Clinical Protocol CNTO1959PSA3005 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
12
Status: Approved,  Date: 04 September 2024
Hypothesis
The primary hypothesis of this study is that guselkumab is superior to placebo as assessed by the proportion
of participants who had an IR and/or intolerance to one prior anti-TNF achieving an ACR 20 response at
Week 24.
OVERALL DESIGN
This is a Phase 3b, multicenter, randomized, double-blind, placebo-controlled interventional study in
participants who had IR and/or intolerance to one prior anti-TNF. Stable doses of concomitant non-steroidal
anti-inflammatory drugs (NSAIDs), oral corticosteroids (≤ 10 mg/day prednisone equivalent), selected
non-biologic disease-modifying antirheumatic drugs (DMARDs) such as methotrexate (MTX),
sulfasalazine (SSZ), hydroxychloroquine (HCQ), or leflunomide (LEF) are not required but will be allowed
if participants are on stable doses.
There will be a screening phase of up to 6 weeks, a blinded treatment phase of approximately 2 years that
will include a placebo-controlled period from Week 0 to Week 24 and an active-controlled treatment phase
from Week 24 to Week 100, and a safety follow-up at Week 112 (approximately 12 weeks after the last
intended dose at Week 100 per protocol).
Database locks (DBLs) are scheduled at Week 24, Week 52, and the end of the study (Week 112). The end
of study is considered as the last visit for the last participant in the study.
STUDY POPULATION
The target study population is participants with active PsA who had an IR and/or intolerance to one prior
anti-TNF. This population is appropriate to provide relevant efficacy and safety information given that the
likely intended use of guselkumab for active PsA in pragmatic clinical settings would be as an alternative
mechanism of action after anti-TNF utilization.
NUMBER OF PARTICIPANTS
A target of 450 participants will be randomly assigned in this study with 150 participants planned per
intervention group: Guselkumab every 8 weeks (n=150), guselkumab every 4 weeks (n=150), or placebo
(n=150).
INTERVENTION GROUPS AND DURATION
At Week 0, participants who satisfy all inclusion and exclusion criteria will be randomly assigned to 1 of
the following 3 treatment groups in a 1:1:1 ratio using permuted block randomization stratified by baseline
non-biologic DMARD use (yes/no).
Group I (n=150),guselkumab 100 mg subcutaneously (SC)every 8 weeks (q8w): Participants will
receive guselkumab 100 mg SC at Weeks 0, 4, then q8w at Weeks 12, 20, 28, 36, 44, 52, 60, 68, 76,
84, 92, and 100. Participants will receive placebo at Weeks 8, 16, 24, 32, 40, 48, 56, 64, 72, 80, 88,
and 96 to maintain the blind.
Group II (n=150), guselkumab 100 mg SC every 4 weeks (q4w): Participants will receive
guselkumab 100 mg SC at Weeks 0, 4, then q4w at Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52,
56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100.
CCI
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Guselkumab (Tremfya) 
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CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved,  Date: 04 September 2024
Group III (n=150), placebo and placebo cross-over to guselkumab 100 mg SC q4w: Participants
will receive placebo SC at Weeks 0, 4, 8, 12, 16 and 20, and will cross over at Week 24 to receive
guselkumab 100 mg SC at Weeks 24, 28, then q4w at Weeks 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72,
76, 80, 84, 88, 92, 96, and 100.
At Week 16, all participants in Groups I, II, and III with <20% improvement from baseline in both tender
and swollen joint counts will qualify for early escape 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.
At Week 24, all participants in the placebo group (Group III) will cross over in a blinded fashion to receive
guselkumab 100 mg SC q4w through Week 100; this will allow for collection of additional safety data for
the 100 mg SC q4w dose. Participants in the guselkumab groups (Groups I and II) will remain on the dosing
regimen they were randomized to at Week 0, through Week 100.
Description of Interventions
Group/Arm Name 
Group I (q8w) 
Group II (q4w) 
Group III
Intervention Name 
Guselkumab 
Guselkumab 
Placebo
Dose Formulation  
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).
Guselkumab 100 mg 
will be provided in a
single-use PFS
assembled with the
PFS-U.
Placebo
Unit Dose Strength(s) 
100 mg 
100 mg
Dosage Level(s) 
100 mg at Weeks 0, 4, then q8w 
through Week 100 (placebo at 
alternate visits) 
100 mg q4w through 
Week 100 
Placebo q4w through
Week 20, then
guselkumab 100 mg
q4w through Week 100
Route of Administration  
subcutaneous 
subcutaneous 
subcutaneous
EFFICACY EVALUATIONS
Efficacy assessments of arthritis: Joint count (tender and swollen), nonevaluable joints, ACR Responses,
dactylitis score, enthesitis assessments, Health Assessment Questionnaire-Disability Index (HAQ-DI), Bath
Ankylosing Spondylitis Disease Activity Index (BASDAI) in participants with spondylitis with peripheral
arthritis as their primary arthritic presentation of PsA at baseline, Disease Activity index for PSoriatic
Arthritis (DAPSA), Minimal Disease Activity (MDA), Very Low Disease Activity (VLDA), and Psoriatic
ArthritiS Disease Activity Score (PASDAS) will be performed at visits according to the Schedule of
Activities.
Efficacy assessments of psoriasis: Psoriasis Area and Severity Index (PASI) and Investigator’s Global
Assessment (IGA), will be performed at visits according to the Schedule of Activities.
Patient-reported outcomes: PsA Impact of Disease (PsAID)-12, Functional Assessment of Chronic Illness
Therapy (FACIT)-Fatigue, Patient-Reported Outcomes Measurement Information System (PROMIS)-29,
and 36-item Short Form Health Survey (SF-36) will be performed at visits according to the Schedule of
Activities.
PHARMACOKINETIC/IMMUNOGENICITYEVALUATIONS
Venous blood samples will be collected for measurement of serum concentrations of guselkumab and
antibodies to guselkumab at the timepoints shown in the Schedule of Activities. Serum collected for PK
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Guselkumab (Tremfya) 
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and immunogenicity analyses may additionally be used to evaluate safety or efficacy aspects that address
concerns arising during or after the study period.
PHARMACODYNAMIC AND BIOMARKER EVALUATIONS
Biomarker assessments will be made to examine the biologic response to treatment and to identify
biomarkers that are relevant to guselkumab treatment and/or PsA, where local regulations permit.
Assessments may  include the evaluation of relevant biomarkers in serum, plasma, whole blood, and
(optional) skin biopsy collected as specified in the Schedule of Activities, where local regulations permit.
PHARMACOGENOMIC (DNA) EVALUATIONS
Participation in  the pharmacogenomic research is optional. A pharmacogenomic blood sample will be
collected from participants who consent separately to this component of the study to allow for
pharmacogenomic research, where local regulations permit.
SAFETY EVALUATIONS
Safety assessments will consist of physical examinations, vital signs, height and weight,
electrocardiograms, clinical safety laboratory assessments, suicidal ideation or behavior using the electronic
Columbia-Suicide Severity Rating Scale (eC-SSRS), and concomitant medication review. Injection  site
reactions, hypersensitivity reactions, infections, tuberculosis evaluations and pregnancy testing will be
collected or performed as specified in the Schedule of Activities.
STATISTICAL METHODS
A sample size of 150 participants per group for each of the guselkumab treatment groups and placebo will
have >90% power to detect differences between each guselkumab treatment group and placebo for the
primary endpoint assuming a 2-sided alpha level of 0.05.
In general, descriptive statistics, such as mean, standard deviation (SD), median, interquartile (IQ) range,
minimum, and maximum for continuous variables, and counts and percentages for discrete variables will
be used to summarize most data.  For binary response efficacy endpoints, treatment comparisons will
generally be performed using a Chi-square test or a Cochran-Mantel-Haenszel (CMH) test. For continuous
endpoints of efficacy data, treatment comparisons will be performed using an analysis of covariance
(ANCOVA), a mixed model for repeated measures (MMRM) or a constrained longitudinal data analysis
(cLDA) model.
In general, statistical testing will be performed using 2-sided tests. The overall type I error will be controlled
among the primary and major secondary endpoints at 5%.
The primary endpoint to be analyzed for the primary analysis is the proportion of participants who achieved
an ACR 20 response at Week 24. This endpoint will be analyzed based on the estimands defined in
Section 9. Participants with missing data at Week 24 will be considered non-responders.
The Type 1 error will be multiplicity controlled for the primary and major secondary endpoints. All other
secondary endpoints will be summarized over time by treatment groups. Treatment comparisons will be
performed by visit through Week 24.
For safety analyses, for each AE, the percentage of participants who experience at least 1 occurrence of the
given event will be summarized by treatment group. The analyses of AEs will be performed for safety
measures including but not limited to, AEs, SAEs, infections, and injection site reactions. Descriptive
statistics will be calculated for selected laboratory analytes at baseline and for observed values and changes
from baseline at each scheduled timepoint.
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of a screening X-ray (and if not of sufficient quality, a new screening X-ray would then be performed and centrally read). Participants who have confirmed
sacroiliitis will complete the BASDAI at specified visits in the SoA.
g. 
Study intervention will be administered SC q4w by a healthcare professional during visits to the site until the participant (or caregiver) is trained for self-
administration. Study intervention will be administered by site personnel at Weeks 0 and 4. Beginning at Week 8, at the discretion of the investigator and
participant, and after appropriate and documented training, participants (or caregiver) may administer study intervention at the investigative site under the
supervision of a health care professional. After appropriate training, beginning at Week 32, participants (or caregiver) may administer study intervention at home
and on-site visits are only required at Weeks 36, 44, and 52. Safety and efficacy assessments, including blood samples for clinical laboratory and
pharmacokinetics/immunogenicity, as specified in the SoA should be performed prior to study intervention administration.
h. 
At the screening visit (after signing informed consent), the eC-SSRS should be performed after the joint assessment. At Week 0/baseline and at all post-baseline
visits, the eC-SSRS should be completed after all PRO, but before other tests, procedures or other consultations. At Weeks 32, 40, 48, the eC-SSRS is only
completed by participants who have study intervention administration at the investigative site. See Section 8.2.7 for more details.
i. 
Vital signs include blood pressure and heart rate. At Weeks 32, 40, 48, vital signs are only assessed for participants who have study intervention administration at
the investigative site.
j. 
12-lead ECG must be done prior to first administration of study intervention.
k. 
Participants (as outlined in Inclusion Criterion 13) must undergo testing for TB (Appendix 10.2) 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.
l. 
The chest radiograph may be taken within 3 months prior to the first administration of study intervention.
m. Females of childbearing potential will have a serum pregnancy test at screening. Those who are dosed at the clinic must have a negative urine pregnancy test at all
dosing visits prior to administration of study intervention. For those who choose to dose at home during the at-home administration visits (Weeks 32, 40, 48, 56,
60, 64, 72, 80, 88, 92, and 96), pregnancy test(s) are not required.
n. 
At Week 16, all participants 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 a permitted concomitant medication intervention 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 participants qualifying for early escape by the Week 24 visit.
o. 
These efficacy evaluations should be performed prior to study intervention administration at each visit, as applicable.
p. 
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.
q. 
The BASDAI will be completed only in participants with spondylitis with peripheral arthritis as their primary arthritic presentation of PsA based on confirmation
of sacroiliitis by a centrally read pelvic X-ray (ie, anteroposterior views of the sacrum) during screening (see footnote f).
r. 
A tuberculin skin test is additionally required if the QuantiFERON®-TB test is not approved/registered in the country in which this study is being conducted, with
the exception noted in Inclusion Criterion 13. All participants will undergo QuantiFERON-TB testing. The frequency of TB testing can be increased depending on
local health authority requirements. In Ukraine, while the QuantiFERON-TB test is not approved/registered, it is accepted, and a tuberculin skin test is not
required.
s. 
Laboratory tests are listed in Appendix 10.2.
t. 
This test is optional. It can be done only if needed to confirm whether CASPAR criteria are met.
u. 
Prior to randomization, FSH is required for female participants with amenorrhea for less than 12 months. A second FSH measurement may be needed to confirm
amenorrhea in these participants. This test should not be done for any female participant of childbearing potential or female participants with amenorrhea for at
least 12 months.
v. 
All blood samples must be collected before study intervention administration at visits when a study intervention administration is scheduled. Blood collected from
1 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.
w. To participate in the optional DNA research component of this study, participants must sign the DNA research ICF indicating willingness to participate.
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Blood samples for pharmacogenomic and epigenetic research will be collected only from participants who give informed consent for DNA research. The
pharmacogenomic (DNA) sample should be collected at the specified timepoint; however, if necessary, it may be collected at a later timepoint without constituting
a protocol deviation.
x. 
PBMCs will be collected at sites where logistically feasible.
y. 
Optional skin biopsies may be collected at select sites, if feasible. Samples from a lesional and a non-lesional region will be collected at Week 0 and only a sample
from a lesional region will be collected at Week 24.
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;
FACIT = Functional Assessment of Chronic Illness Therapy; FSH = follicle stimulating hormone; HAQ-DI = Health Assessment Questionnaire- Disability Index;
HIV = human immunodeficiency virus; ICF = informed consent form; IGA = Investigator’s Global Assessment; LEI = Leeds Enthesitis Index; PASI = Psoriatic Area
and Severity Index; PBMC = peripheral blood mononuclear cell; PsAID-12 = psoriatic arthritis impact of disease score; PROMIS = Patient-Reported Outcome Measure
Information System; q4w =every 4 weeks; RNA = ribonucleic acid; SC=subcutaneous; SF-36 = 36-item short form health survey; SPARCC = Spondyloarthritis
Research Consortium of Canada; TB = tuberculosis.
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f. These efficacy evaluations should be performed prior to study intervention administration at each visit, as applicable.
g. All patient questionnaires should be completed before any other tests, procedures, or evaluations on the day of the visit for post-baseline visits.
h. The BASDAI will be completed only in participants with spondylitis with peripheral arthritis as their primary arthritic presentation of PsA based on confirmation of
sacroiliitis by a centrally read pelvic X-ray (ie, anteroposterior views of the sacrum) during screening.
i. 
Laboratory tests are listed in Appendix 10.2.
j. 
All blood samples must be collected before study intervention administration at visits when a study intervention administration is scheduled. Blood collected from
1 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.
k. PBMCs will be collected at sites where logistically feasible.
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2. 
INTRODUCTION
Guselkumab (TREMFYA®, CNTO1959) is a fully human immunoglobulin (IgG)1λ monoclonal
antibody (mAb) that binds to the p19 protein subunit of interleukin (IL)-23 with high affinity. By
binding to the p19 protein subunit of IL-23, guselkumab blocks the binding of extracellular IL-23
to the cell surface IL-23 receptor, inhibiting IL-23-mediated intracellular signaling, activation, and
cytokine production.
The clinical development program for guselkumab includes completed, ongoing, or planned
studies in adult participants with psoriatic arthritis (PsA), psoriasis, lupus nephritis, inflammatory
bowel disease, rheumatoid arthritis, palmoplantar pustulosis, generalized pustular psoriasis,
erythrodermic psoriasis and familial adenomatous polyposis, giant cell arteritis, Hidradenitis
Suppurativa as well as an ongoing study in pediatric participants with psoriasis.
For the most comprehensive nonclinical and clinical information regarding guselkumab, refer to
the latest version of the Investigator's Brochure (IB)and the Prescribing Information.
The term “study intervention” throughout the protocol, refers to guselkumab or placebo
administered using an UltraSafe PlusTM  Passive Needle Guard (PFS-U) device as defined in
Section 6.1, Study Interventions Administered.
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.
2.1. 
Study Rationale
Despite 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. Although anti-tumor necrosis factor (TNF)agents are frequently
chosen as the first biologic therapy for patients with PsA, a substantial proportion of patients
assessed in clinical trials do not achieve meaningful American College of Rheumatology (ACR)-
defined responses, and some patients may not tolerate or may have medical contraindications to
these agents. In addition, patients who have had an inadequate response (IR) to an anti-TNF may
be more difficult to treat and may require dose flexibility to attain improved efficacy.
Guselkumab is the first IL-23 inhibitor to be approved for the treatment of active PsA in numerous
countries globally, offeringan alternative to currently used biologics and conventional and targeted
synthetic disease-modifying anti-rheumatic drugs (DMARDs). The guselkumab PsA clinical
development program evaluated guselkumab subcutaneous (SC) dose regimens of 100 mg at
Weeks 0, 4 followed by every 8 weeks (q8w) or every 4 weeks (q4w) dosing thereafter.
As of March 2021, guselkumab 100 mg at Weeks 0 and 4 then q8w is now the approved dose
regimen in the US, Canada, Australia, Taiwan, and Japan for both psoriasis and PsA, while both
guselkumab q8w and q4w dose regimens have been approved in Brazil, Ecuador, and the European
Union (EU)for PsA.
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While both guselkumab dose regimens produced clinically meaningful benefit on the improvement
in the signs and symptoms of PsA compared with placebo, there may be incremental benefit of
higher dosing in a more treatment refractory population, therefore, the current study is intended to
provide additional data on the impact of the 2 guselkumab dose regimens on signs and symptoms
in patients with active PsA who have previously failed or been intolerant to one prior anti-TNF.
2.2. 
Background
Psoriatic arthritis (PsA) is a chronic, immune-mediated inflammatory disease characterized by
peripheral joint inflammation, enthesitis, dactylitis, axial disease and the skin lesions associated
with psoriasis. Psoriatic arthritis affects approximately 0.02% to 0.25% of the general population
(Setty, 2007). In patients with psoriasis, the prevalence of PsA ranges from 6% to 48%; however,
arthritis is not correlated with extent of psoriasis skin disease (Gladman, 2009).
In addition to joint disease, PsA is also associated with a number of metabolic co-morbidities,
including cardiovascular disease, diabetes and obesity as well as psychological co-morbidities,
including depression and anxiety (Ogdie, 2015). Early clinic-based studies suggested an increased
risk of mortality, although this risk improved over time (Gladman, 2008). However, recent studies
suggest no increased risk of mortality among patients with PsA (Ogdie, 2014; Buckley, 2010).
Clinical Studies
The clinical development program for guselkumab in the treatment of active PsA includes a Phase
2 global Study CNTO1959PSA2001 (hereafter referred to as PSA2001) and 2 Phase 3 global
Studies, PSA3001 (DISCOVER 1) and PSA3002 (DISCOVER 2). These studies evaluated the
efficacy and safety of the guselkumab 100 mg q8w and q4w dose regimens in a broad population,
including both participants who had IR and/or intolerance to conventional DMARDs, and
participants who had IR and/or intolerance also to anti-TNFs.
A Phase 3b study, PSA3003 (COSMOS), evaluated the efficacy and safety of the guselkumab
100 mg q8w dose regimen in participants with PsA who had IR and/or intolerance to DMARDs
and up to 2 prior anti-TNFs.
A high level summary of the study design, and efficacy and safety results for Studies PSA3001,
PSA3002, and PSA3003 are provided in Section 2.2.1.1. For the most comprehensive clinical
information regarding guselkumab, refer to the latest version of the guselkumab IB.
2.2.1.1. 
Phase 3 Studies: CNTO1959PSA3001 (DISCOVER 1) and
CNTO1959PSA3002 (DISCOVER 2)
2.2.1.1.1. 
Study design
The PSA3001 and PSA3002 studies are global, multicenter, randomized, double-blind, placebo-
controlled, 3-arm studies of guselkumab in participants with active PsA who had inadequate
response to standard therapies (eg, non-biologic DMARDs, apremilast, or nonsteroidal anti-
inflammatory drug [NSAIDs]). Both studies included a screening phase of up to 6 weeks and a
treatment period including a placebo-controlled period from Week 0 to Week 24, and both have
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an active treatment period that began at Week 24 and a safety follow-up period of 12 weeks after
the last administration of study treatment. Stable doses of concomitant NSAIDs, oral
corticosteroids, and selected DMARDs (limited to methotrexate [MTX], sulfasalazine [SSZ],
hydroxychloroquine [HCQ], and leflunomide [LEF]) were allowed but not required.
PSA3001 and PSA3002 had similar study designs. Some differences in study population, sample
size, and study duration reflected the additional study objective in PSA3002 to assess the
progression of radiographic structural damage.
The PSA3001 study allowed approximately 30% of participants who had prior anti-TNF exposure
to enroll, ie, participants who had been previously treated with up to 2 anti-TNFs. In the PSA3002
study, however, participants were required to be naïve to biologic agents. Additionally, the higher
C-reactive protein (CRP) and joint count requirements in PSA3002, listed below, were intended
to enrich the population for participants at greater risk for structural damage progression so that
the impact of guselkumab on radiographic parameters could be assessed:
PSA3001: ≥3 swollen joints and ≥3 tender joints at screening and baseline, and
CRP ≥0.3 mg/dL at screening.
PSA3002:≥5 swollen joints and ≥5 or more tender joints at screening and baseline, and
CRP ≥0.6 mg/dL at screening.
2.2.1.1.2. 
Efficacy results
Refer to the latest version of the guselkumab IB for detailed efficacy results of PSA3001 and
PSA3002.
Through Week 24
In both PSA3001 and PSA3002, both guselkumab dose regimens (100 mg SC q4w or 100 mg SC
q8w) demonstrated efficacy and produced clinically meaningful benefit on the improvement in the
signs and symptoms of PsA and psoriasis, physical function, enthesitis, dactylitis and health-
related quality of life (HRQoL). In addition, in PSA3002, inhibition of radiographic progression
as measured by mean change in total modified van der Heijde-Sharp (vdH-S) score was observed
in both guselkumab dose groups compared to placebo, however, only the q4w dose demonstrated
a statistically significant change in vdH-S score compared with placebo at Week 24.
Through Week 52
The results of PSA3001 and PSA3002 (from Week 24 through Week 52) demonstrated that
guselkumab 100 mg SC q8w and guselkumab 100 mg SC q4w were both effective in the
maintenance of clinical responses through 1 year in the 3 major manifestations of psoriatic disease
(joint, soft tissue, and skin), and physical function and HRQoL improvement in adults with active
PsA. In addition, in PSA3002, inhibition of radiographic progression as measured by mean change
in total modified vdH-S was also maintained post Week 24 through Week 52 (0.62) compared to
baseline to Week 24 (0.46) in the guselkumab 100 mg q4w group.
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2.2.1.1.3. 
Safety results
Refer to the latest version of the guselkumab IB for detailed safety results of PSA3001 and
PSA3002.
Overall, the guselkumab safety profile in the PsA population was generally comparable with that
established in the psoriasis population.
Through 1 year, the pooled safety data from PSA3001 (through Week 60) and PSA 3002 (through
Week 52) indicated that both guselkumab dose regimens (ie, 100 mg SC administered at Weeks 0
and 4 and then q8w or q4w)were well tolerated in participants with active PsA. Similar proportions
of participants in the guselkumab q8w and q4w groups experienced adverse events (AEs), serious
adverse events (SAEs), AEs leading to study discontinuation, AEs with severe intensity,
infections, serious infections, and injection-site reactions through 1 year of follow-up. Frequencies
of events of suicidal ideation, malignancy, and major adverse cardiovascular events were low and
comparable in the guselkumab q8w and q4w groups. There were no events of opportunistic
infections, active tuberculosis (TB), anaphylaxis or serum sickness reactions, or suicidal behavior
or self-injurious behavior without suicidal intent in guselkumab-treated participants in either of
the PSA3001 or PSA3002 studies through 1 year. The proportion of participants experiencing
increases in transaminases was slightly higher in the guselkumab q4w group compared with the
q8w group. In addition, the number of participants with AEs, SAEs, AEs leading to discontinuation
of study intervention, infections, and serious infections per 100 subject-years of follow-up were
generally comparable between the guselkumab 100 mg q8w and q4w groups through 1 year and
the placebo-controlled period through Week 24.
2.2.1.2. 
Phase 3b Study: CNTO1959PSA3003 (COSMOS)
The COSMOS study is an ongoing Phase 3b study in participants with PsA who had an IR and/or
intolerance to up to 2 anti-TNFs. Treatment with guselkumab 100 mg at Week 0 and Week 4 and
then q8w demonstrated superiority of guselkumab over placebo with respect to the primary
endpoint of ACR 20 response at Week 24, and superiority of guselkumab over placebo with respect
to all 4 key secondary endpoints at Week 24, based on a predefined hierarchical testing procedure:
Health Assessment Questionnaire –Disability Index (HAQ-DI), ACR 50 response, 36-item short
form health survey (SF-36) PCS, and Psoriasis Area and Severity Index (PASI) 100. The results
were robust and generally consistent across the primary and supplementary analyses.
Overall, guselkumab demonstrated robust efficacy on signs and symptoms of the joints and skin
psoriasis, improved physical function, and improvement in the physical component of health-
related quality of life.
The guselkumab dosing regimen was safe and well tolerated through Week 24 in this study. The
safety profile of guselkumab through Week 24 in this population of patients with PsA who were
refractory to anti-TNF therapy is generally consistent with that demonstrated in the psoriasis and
the bionaïve PsA indications.
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2.3. 
Benefit-Risk Assessment
More detailed information about the known and expected benefits and risks of guselkumab may
be found in the Package Insert and Summary of Product Characteristics.
2.3.1. 
Risks for Study Participation
Table 1: 
Potential Study Risks
Potential Risks of Clinical 
Significance 
Summary of Data/ 
Rationale for Risk
Mitigation Strategy
Potential risks due to study intervention (guselkumab)
Serious infections and reactivation 
of latent infections 
Available animal and human data 
suggest that blockade of IL-23 may be 
associated with an increased infection 
risk. 
• Participants with a history of, or
ongoing, chronic or recurrent infectious
disease, including human
immunodeficiency virus (HIV), or
hepatitis B or C virus (HBV, HCV),
will be excluded from the study.
Similarly, participants with evidence of
active or untreated TB will be excluded
from the study (Section 5.2).
• Participants who have received a
live viral or bacterial vaccination within
12 weeks of baseline will be excluded
from the study. In addition, participants
must agree not to receive a live viral or
live bacterial vaccination during the
study and for 12 weeks after receiving
the last dose of study intervention
(Section 5.2).
• Participants will be instructed to
seek medical attention if they develop
signs or symptoms suggestive of an
infection, and investigators are
instructed in the protocol to monitor for
signs or symptoms of infections,
including TB (Sections 8.2.11 and
8.2.12).
•  Discontinuation of a participant’s
study intervention must be strongly
considered if the participant develops a
serious infection, including but not
limited to sepsis or pneumonia. In
addition, any serious infection should be
discussed with the medical monitor or
designee, and study intervention should
be withheld until the clinical assessment
is complete.
Hypersensitivity 
reactions, 
including serious hypersensitivity 
reactions 
Serious hypersensitivity reactions 
including anaphylaxis have been 
reported in postmarketing experience 
with guselkumab in psoriasis patients. 
• Participants with known allergy,
hypersensitivity, or intolerance to
guselkumab or its excipients will be
excluded from the study.
• Sites are instructed that before any
administration of study intervention,
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appropriately trained personnel and
medications (eg, injectable
epinephrine) must be available to treat
hypersensitivity reactions, including
anaphylaxis. In addition, all
participants must be observed carefully
for signs and symptoms of a
hypersensitivity reaction (eg, urticaria,
pruritis, angioedema, wheezing,
dyspnea, or hypotension)
(Section 8.2.10).
• Any participant who develops a serious
hypersensitivity 
reaction 
such 
as
anaphylaxis must discontinue study
intervention (Section 7.1).
Malignancy  
The preponderance of preclinical data 
suggests that blockade of endogenous 
IL-23 would not be detrimental and 
may in fact be beneficial in tumor 
immunosurveillance 
and 
host
protection; however, a risk of
malignancy cannot be excluded.
• Those participants who currently
have a malignancy or have a history of
malignancy within 5 years prior to
screening (with exceptions noted in
Section 5.2) will be excluded from the
study. Additionally, participants who
have 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 will
be excluded from the study
(Section 5.2).
• During the conduct of the study,
participants will undergo regular
clinical monitoring including routine
safety labs to assess for any changes in
health status that may indicate a
possible malignancy.
• Participants 
who 
develop 
a
malignancy during the study (with the
exception of no more than 2 localized
basal cell skin cancers that are treated
with no evidence of recurrence or
residual disease) will be discontinued
from study intervention (Section 7.1).
Liver injury  
An SAE of ‘toxic hepatitis’ was 
reported in the ongoing Phase 2/3 
guselkumab Crohn’s disease (CD) 
program in a participant who received 
guselkumab 1200 mg intravenously
(IV) at Weeks 0, 4, and 8, and 200 mg
SC at Week 12. Based on the
hepatocellular pattern of injury, 
temporal relationship of the event to 
guselkumab 
exposure, 
and 
the 
exclusion of alternative etiologies,
• During the conduct of the study,
liver function tests will be monitored at
regular intervals. In addition, the doses
included in this study will be lower and
will not exceed 100 mg SC q4w. The
100 mg SC q8w dosage is approved in
the major regions in which this study
will be conducted and the 100 mg SC
q4w dosage is approved in the EU,
Australia, Taiwan, Brazil, Ecuador and
Japan.
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Status: Approved,  Date: 04 September 2024
this event may represent drug-induced 
liver injury possibly related to 
guselkumab. 
A review of available guselkumab 
Phase 2 and 3 clinical trial data across 
multiple indications (psoriasis, PsA, 
rheumatoid 
arthritis 
[RA], 
palmoplantar pustulosis [PPP], and 
CD) was performed by the Sponsor - 
demonstrated 
previously 
noted 
association 
between 
guselkumab
exposure and mild (≤3 x upper limit
of normal [ULN]) elevations in liver
transaminases at exposures of 100 mg
q4w or higher - significant elevations
of alanine aminotransferase [ALT]
(>5 x ULN) or cases satisfying the
biochemical criteria for Hy’s Law
during guselkumab exposure have
been infrequent. These cases have
been confounded by concomitant
medications, alcohol use, medical
history, and/or concurrent diagnoses.
• 
Participants with marked liver
enzyme elevations or symptoms or signs
of liver dysfunction (eg, jaundice),
should undergo a thorough investigation
for possible causes of liver injury. A
participant must have their study
intervention 
discontinued 
if 
the
participant 
has 
severe 
liver 
test
abnormalities that are not transient and
are not explained by other etiologies
(Section 7.1).
Immunosuppression  
Although guselkumab has been 
studied 
with 
other 
immunosuppressives 
in 
other 
diseases, there may be an increased 
risk of infection or malignancy.
In order to minimize the theoretical
increased risk of infection or
malignancy with the combination of
guselkumab with immunosuppressive
therapy, the baseline dose of oral
glucocorticoids on study entry is
limited to a dose equivalent to ≤10 mg
of prednisone/day. Additionally,
participants are also excluded from the
study if they have received any
systemic immunosuppressants (eg,
azathioprine, cyclosporine,
6 thioguanine, mercaptopurine,
mycophenolate mofetil, hydroxyurea,
tacrolimus within 4 weeks of the first
administration of study intervention or
are receiving 2 or more non-biologic
DMARDs specified in Table 3 at
baseline.
Further detail regarding concomitant
medications is provided in Section 6.8.
Risks due to study procedures
Radiation  
A chest X-ray will be performed at 
screening if the participant does not 
have a chest X-ray within 12 weeks 
prior to the first administration of 
study intervention. The exposure
from 1 standard chest X-ray is
Exposure 
to 
radiation 
through
radiographs is kept to a minimum by not
requiring a chest X-ray be performed at
screening if one is available from within
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0.1 mSV, comparable to 10 days of 
exposure to natural background 
radiation (https://www.acr.org).
A subset of participants 
with
spondylitis with peripheral arthritis at
baseline will have a pelvic X-ray,
approximately 0.7 mSV, comparable
to 3 months of exposure to natural
background radiation
(https://hps.org/physicians/document/
doses_from_Medical_X-
Ray_Procedures.pdf)
12 weeks prior to the first administration
of study intervention.
2.3.2. 
Benefits for Study Participation
Guselkumab has demonstrated benefit in improving the signs and symptoms of PsA in the Phase 2
and Phase 3 studies (see Section 2.1), resulting in the registration of guselkumab in numerous
countries to date; and ongoing regulatory reviews for approval globally. The demonstration of
clinical benefit was observed in participants who are biologic treatment naïve or experienced. The
target population under study in this protocol are participants who have had IR and/or intolerance
to one prior anti-TNF. These patients may be more difficult to treat and may require higher dosing
to achieve optimal efficacy. Consistent with prior studies, it is anticipated that individual
participants may benefit from participation in the current study. Additionally, participation will
help to obtain additional data on the impact of guselkumab on joint damage, and in the general
knowledge of the treatment and natural history of PsA.
Participants may also experience some benefit from the participation in a clinical study irrespective
of receiving study intervention, due to regular visits and assessments monitoring their overall
health.
2.3.3. 
Benefit-Risk Assessment for Study Participation
Additional data through 1 year of treatment from the PSA3001 and PSA3002 studies for both
guselkumab doses (ie, 100 mg SC q8w and q4w) under study in this protocol continue to support
an overall favorable benefit-to-risk profile for the use of guselkumab in active PsA.
Potential risks of guselkumab, including those of clinically relevant infections and serious
infections, malignancy, and liver injury; are being addressed via judicious inclusion/exclusion
criteria, frequent study visits to allow for close monitoring of patient safety, guidelines for
participant management (including monitoring of clinical laboratory tests and treatment
discontinuation criteria), detailed description of allowed and prohibited concomitant medications,
and comprehensive medical monitoring of data by the Sponsor/designee during the conduct of the
studies.
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Status: Approved,  Date: 04 September 2024
Taking into account the measures taken to minimize risk to participants in this study, the potential
risks identified in association with guselkumab are justified by the benefits that may be provided
to participants with PsA.
3. 
OBJECTIVES AND ENDPOINTS
Objective 
Endpoint
Primary
To evaluate the efficacy of guselkumab 
treatment in participants with active 
PsA and IR and/or intolerance to a prior
anti-TNF by assessing the reduction in
signs and symptoms of PsA.
Proportion of participants who achieve an ACR
20 response at Week 24
Major Secondary
To evaluate the efficacy of guselkumab 
on additional measures of signs and 
symptoms of PsA, psoriasis, and patient 
well-being. 
Proportion of participants who achieve a
psoriasis response of IGA psoriasis score of 0
(cleared) or 1 (minimal) AND ≥2-grade
reduction from baseline at Week 24 among the
participants with ≥3% BSA psoriatic
involvement and an IGA score of ≥2 (mild) at
baseline
Proportion of participants who achieve PASI 90
response at Week 24 among the participants
with ≥3% BSA psoriatic involvement and an
IGA score of ≥2 (mild) at baseline
Change from baseline in HAQ-DI at Week 24
Change from baseline in the SF-36 PCS at
Week 24
Change from baseline in Functional Assessment
of Chronic Illness Therapy –fatigue (FACIT-F)
score at Week 24
Proportion of participants achieving minimal
disease activity (MDA) at Week 24
Proportion of participants who achieve ACR 20
response at Week 16
Proportion of participants who achieve ACR 50
response at Week 16
Proportion of participants who achieve ACR 50
response at Week 24
Proportion of participants who achieve ACR 70
response at Week 24
The ordering of endpoints, 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 (SAP).
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Status: Approved,  Date: 04 September 2024
Other Secondary
To evaluate the safety of guselkumab in 
participants with active PsA. 
Frequency and type of AEs, SAEs, reasonably
related AEs, AEs leading to discontinuation of
study intervention, infections, and injection-site
reactions
Laboratory abnormalities (chemistry,
hematology) maximum toxicity (Common
Terminology Criteria for Adverse Events
[CTCAE 5.0]) grades
To evaluate the pharmacokinetics (PK) 
and immunogenicity of guselkumab in 
participants with active PsA.
Serum guselkumab concentration over time
Incidence of antibodies to guselkumab
CCI
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Status: Approved,  Date: 04 September 2024
HYPOTHESIS
The primary hypothesis of this study is that guselkumab is superior to placebo as assessed by the
proportion of anti-TNF-IR and/or intolerant participants achieving an ACR 20 response at
Week 24.
4. 
STUDY DESIGN
4.1. 
Overall Design
This is a Phase 3b, multicenter, randomized, double-blind, placebo-controlled interventional study
in participants with active PsA who had an IR and/or intolerance to one prior anti-TNF.
A target of 450 participants will be randomly assigned in this study with 150 participants planned
per intervention group: Guselkumab q8w (n=150), guselkumab q4w (n=150), or placebo (n=150).
Participants impacted by major disruptions may be replaced. Stable doses of concomitant NSAIDs,
oral corticosteroids (≤ 10 mg/day prednisone equivalent), selected non-biologic DMARDs (MTX,
SSZ, HCQ, LEF) will be allowed but are not required.
CCI
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Status: Approved,  Date: 04 September 2024
There will be a screening phase of up to 6 weeks, a treatment phase of approximately 2 years that
will include a double-blind placebo-controlled period from Week 0 to Week 24 and an active-
controlled treatment phase from Week 24 to Week 100, and a safety follow-up at Week 112
(approximately 12 weeks after the last intended dose at Week 100 per protocol).
At Week 0, participants who satisfy all inclusion and exclusion criteria will be randomly assigned
to 1 of the following 3 treatment groups in a 1:1:1 ratio using permuted block randomization
stratified by baseline non-biologic DMARD use (yes/no).
Group I (n=150), guselkumab 100 mg SC every 8 weeks (q8w): Participants will receive
guselkumab 100 mg SC at Weeks 0, 4, then q8w at Weeks 12, 20, 28, 36, 44, 52, 60, 68, 76,
84, 92, and 100. Participants will receive placebo SC at Weeks 8, 16, 24, 32, 40, 48, 56, 64,
72, 80, 88, and 96 to maintain the blind.
Group II (n=150), guselkumab 100 mg SC every 4 weeks (q4w): Participants will receive
guselkumab 100 mg SC at Weeks 0, 4, then q4w at Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40,
44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100.
Group III (n=150), placebo and placebo crossover to guselkumab 100 mg SC q4w:
Participants will receive placebo SC at Weeks 0, 4, 8, 12, 16 and 20, and will cross over at
Week 24 to receive guselkumab 100 mg SC at Weeks 24, 28, then q4w at Weeks 32, 36, 40,
44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100.
At Week 16, all participants in Groups I, II, and III with <20% improvement from baseline in both
tender and swollen joint counts will qualify for early escape 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.
At Week 24, all participants in the placebo group (Group III) will cross over in a blinded fashion
to receive guselkumab 100 mg SC q4w through Week 100; this will allow for collection of
additional safety data for the guselkumab 100 mg SC q4w dose. Participants in the guselkumab
groups (Groups I and II) will remain on the dosing regimen they were randomized to at Week 0,
through Week 100.
Database locks (DBLs) are scheduled at Week 24, Week 52 and the end of the study (Week 112).
The first DBL will occur when all randomized participants 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 participants have either completed the
Week 52 assessments or terminated study participation prior to the Week 52 visit (referred to as
Week 52 DBL).  The third DBL will occur when all participants have either completed their final
safety visit or have terminated study participation (referred to as Final DBL).
The end of study is considered as the last visit for the last participant in the study.
A diagram of the study design is provided in Section 1.2, Schema.
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4.2. 
Scientific Rationale for Study Design
Study population
The target study population is participants with active PsA who have had an IR and/or intolerance
to one prior anti-TNF. This population is appropriate to provide relevant efficacy and safety
information given that the likely intended use of guselkumab for active PsA in real world
pragmatic clinical settings would be as an alternative mechanism of action after anti-TNF
utilization.
In PSA3001 and PSA3002, both the guselkumab 100 mg q8w and q4w dose regimens produced
clinically meaningful benefit on the improvement in the signs and symptoms of PsA in the overall
population. While the studies were not designed nor powered to evaluate relative benefit between
the guselkumab q8w and q4w dose regimens, potential incremental benefit of higher guselkumab
dosing (ie, q4w) in PsA was observed for certain efficacy outcomes, and especially in the anti-
TNF treatment experienced and IR population.
Potentialincremental benefit withhigher dosing in the overall population
In PSA3002 (in participants with IR to prior DMARDs only, and biologic naïve), while there was
not a significant dose response noted for changes in signs and symptoms of PsA as assessed by
ACR responses and other relevant joint and skin endpoints, analysis of radiographic data
demonstrated that the guselkumab 100 mg q4w dose regimen significantly inhibited structural
damage progression compared to the placebo group while the guselkumab 100 mg q8w dose
regimen did not reach statistical significance. In high-risk participants (ie, those with baseline risk
factors), there appeared to be a dose-response trend with the guselkumab 100 mg q4w dose
regimen showing greater benefit than the 100 mg q8w dose regimen in inhibiting structural damage
progression.
In PSA3001 (in patients with IR to prior DMARDs and/or prior TNF), the ACR 20/50/70 response
rates compared with placebo (22.2%, 8.7%, 5.6%), were modestly numerically higher in the
guselkumab 100 mg q4w group (59.4%, 35.9%, 20.3%) than those in the guselkumab100 mg q8w
group (52.0%, 29.9%, 11.8%) at Week 24, and also generally numerically higher at each timepoint
evaluated between Week 4 through Week 24.
Potentialincremental benefit withhigher dosing in the anti-TNFIR population
Results from PSA3001 also provide some evidence, though limited, to suggest there may be
potential to achieve better efficacy with a guselkumab dose of 100 mg q4w than with q8w in a
subset of participants with IR to an anti-TNF  (Deodhar, 2020). In PSA3001, 118 treated
participants across the 3 treatment groups (approximately 30% of all participants) were anti-TNF-
experienced. Among these, a total of 44 participants were anti-TNF-IR. A dose response between
the q4w and q8w guselkumab dose regimens was not evident for the anti-TNF-naïve population,
but a potential dose response may exist for the anti-TNF-IR population, especially driven by the
greater treatment effects vs placebo observed for ACR50 and ACR 70 responses. However, this
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Status: Approved,  Date: 04 September 2024
observation was based on a very small number of patients (17 in the q4w group and 15 in the q8w
group).
A recent Phase 3b study, PSA3003 (COSMOS), in which participants with PsA who had an IR to
up to 2 prior anti-TNFs were treated with guselkumab 100 mg q8w, demonstrated the efficacy of
guselkumab compared with placebo for signs and symptoms of peripheral arthritis, soft tissue
inflammation, skin psoriasis, improved physical function, and improvement in the physical
component of health-related quality of life (at Week 24). However, as a consequence of only the
q8w dosing regimen being studied vs placebo in PSA3003, the need exists to determine whether a
guselkumab q4w dosing regimen provides additional benefit with respect to clinical efficacy in
anti-TNF-IR patients, which is the primary objective of this present study.
Consistent with the studies of guselkumab in participants with PsA, other previous studies in
overlapping mechanisms of actions (targeting the IL-17 pathway) have also suggested that anti-
TNF-IR patients are harder to treat than anti-TNF-naïve patients. In the FUTURE-1 study of
secukinumab for the treatment of PsA, a higher proportion of participants who were anti-TNF‐
naïve achieved an ACR 20 response versus participants who were anti-TNF‐IR. Sustained efficacy
through Week 104 was shown in participants naive to prior anti‐TNF therapy as well as in those
with prior incomplete response, although it was more marked in the former population
(Kavanaugh, 2017). In the FUTURE-2 study, data have demonstrated greater clinical
improvements with secukinumab 300 mg versus 150 mg in psoriasis symptoms and ACR scores
in anti-TNF‐IR patients, indicating that a higher dose of secukinumab seems appropriate for these
patients (McInnes, 2017).
In summary, based on the overall evidence to date, the hypothesis that more frequent dosing, or
higher doses, that result in higher serum drug concentrations, especially during the early course of
treatment may result in better efficacy for TNF-IR patients is clinically relevant to study and
represents an unmet need for a sizable population of patients with PsA.
Blinding, Control, Study Phase/Periods, Intervention Groups
A placebo control will be used to establish the frequency and magnitude of changes in clinical
endpoints that may occur in the absence of active intervention. Randomization will be used to
minimize bias in the assignment of participants to intervention groups, to increase the likelihood
that known and unknown participant attributes (eg, demographic and baseline characteristics) are
evenly balanced across intervention groups, and to enhance the validity of statistical comparisons
across intervention groups. Blinded intervention will be used to reduce potential bias during data
collection and evaluation of clinical endpoints.
While guselkumab has been approved in a number of countries and is expected to be approved in
more, the use of a placebo control is still necessary in the context of this study because the primary
objective is to establish the efficacy of guselkumab in the anti-TNF population for which there is
a paucity of data. In addition, the potential incremental relative benefit of the higher vs the lower
guselkumab dose, each compared with placebo, is being evaluated. For these reasons, having a
placebo control is appropriate in this trial.
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Status: Approved,  Date: 04 September 2024
DNA and Biomarker Collection
Optional pharmacogenomic samples may be obtained from participants only when specific consent
is provided by signing the optional genetic research informed consent form (ICF). It is recognized
that genetic variation can be an important contributory factor to inter-individual differences in
intervention distribution and response and can also serve as a marker for disease susceptibility and
prognosis. Pharmacogenomic research may help to explain inter-individual variability in clinical
outcomes and may help to identify population subgroups that respond differently to an
intervention. The goal of the pharmacogenomic component is to collect DNA to allow the
identification of genetic factors that may influence the pharmacokinetics (PK), PD, efficacy,
safety, or tolerability of guselkumab and to identify genetic factors associated with PsA.
Biomarker samples will be collected to evaluate the mechanism of action of guselkumab or help
to explain inter-individual variability in clinical outcomes or may help to identify population
subgroups that respond differently to an intervention. The goal of the biomarker analyses is to
evaluate the pharmacodynamics of guselkumab and aid in evaluating the intervention-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.
Collection of biomarker samples, including samples from the optional pharmacogenomic
collection, will only occur where local regulations permit and may not occur at all clinical sites.
4.2.1. 
Study-Specific Ethical Design Considerations
Potential participants will be fully informed of the risks and requirements of the study and, during
the study, participants 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 participants who are fully able to understand the risks, benefits,
and potential AEs of the study, and provide their consent voluntarily will be enrolled.
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 (www.redcrossblood.org).
The amount of radiation is within a safe range, with the exposure from 1 standard chest X-ray
being comparable to 10 days of exposure to natural background radiation, and the exposure to a
pelvic X-ray (in a subset of participants), approximately 0.7 mSV, comparable to 3 months of
exposure to natural background radiation (www.acr.org).
4.3. 
Justification for Dose
The 2 dose regimens which were evaluated in the Phase 3 PSA3001 and PSA3002 studies (100 mg
at Weeks 0 and 4 then q8w and 100 mg q4w) and which demonstrated clinically meaningful
benefits across domains of PsA were selected to be evaluated in this study. As of March 2021,
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guselkumab 100 mg at Weeks 0 and 4 then q8w is now the approved dose regimen in the US,
Canada, Australia, Taiwan, and Japan for both psoriasis and PsA, while both guselkumab q8w and
q4w dose regimens have been approved in Brazil, Ecuador, and the EU for PsA.
Efficacy results from PSA3001/3002 demonstrated that both guselkumab q8w and q4w dose
regimens were generally similarly effective in treating the signs and symptoms of PsA, as
measured by ACR responses, DAS28 with CRP, dactylitis, enthesitis, IGA and PASI responses,
improving overall physical function measured by HAQ-DI and health-related quality of life as
measured by the SF-36 PCS. The magnitude of treatment effects for both guselkumab dose
regimens in treating signs and symptoms compared to placebo were consistent among all major
endpoints across the individual Phase 3 studies and for the pooled data from both studies.
Consistent with the biological plausibility that more treatment refractory patients could benefit
from higher dosing and drug exposure, a potential greater benefit of the q4w regimen compared
with the q8w regimen was observed in PSA3001, especially among patients with prior anti-TNF
treatment experience including prior inadequate response (see Section 4.2). Specifically, in anti-
TNF-IR patients in PSA3001, a greater proportion of participants in the guselkumab q4w group
compared with the q8w group  achieved ACR 50 (29% vs 13%) and ACR 70 (18% vs 7%)
responses at Week 24. In addition, analysis of guselkumab serum concentration vs ACR response
data at Week 24 from PSA3001 indicated a potential exposure-response relationship in patients
with prior anti-TNF treatment experience (ie, a greater proportion of participants with guselkumab
serum concentration above the median achieved higher ACR 50 and ACR 70 response compared
with patients who had guselkumab serum concentration below the median concentration).
Overall, the 2 proposed dose regimens demonstrated clinically meaningful efficacy and were well
tolerated with an acceptable safety profile in participants with active PsA. Including both dose
regimens in this study will provide additional data to support an evaluation of the relative efficacy
and safety of the q8w and q4w dosing regimens vs placebo in treating the signs and symptoms of
PsA in anti-TNF IR patients.
4.4. 
End of Study Definition
End of Study Definition
The end of study is considered as the last visit for the last participant in the study. The final data
from the study site will be sent to the Sponsor(or designee) after completion of the final participant
visit at that study site, in the time frame specified in the Clinical Trial Agreement.
Study Completion Definition
A participant will be considered to have completed the main study if he or she has completed
assessments at the 12-week safety follow-up visit at Week 112.
Participants who prematurely discontinue study intervention for any reason prior to Week 100
should complete the specified study visits and the final safety follow-up visit as outlined in
Section 1.3 and Section 7.2. Participants will not be considered to have completed the study unless
they complete the safety follow-up.
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5. 
STUDY POPULATION
Screening for eligible participants will be performed within approximately 6 weeks before
administration of the study intervention. Refer to Section 5.4, Screen Failures for conditions under
which the repeat of any screening procedures may be allowed.
The inclusion and exclusion criteria for enrolling participants in this study are described below. If
there is a question about these criteria, the investigator must consult with the appropriate Sponsor
representative and resolve any issues before enrolling a participant in the study.  Waivers are not
allowed.
5.1. 
Inclusion Criteria
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
PsA and psoriasis
1. 
Be 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 prior to the first administration of study
intervention and meet ClASsification criteria for Psoriatic ARthritis (CASPAR) criteria
at screening.
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.  CRP ≥0.3 mg/dL at screening from the central laboratory.
NOTE: A 1-time repeat assessment of CRP level is allowed during the 6-week screening
phase and the investigator may consider the participant eligible if the test result is within
acceptable range on repeat testing in the central laboratory.
4. 
Have at least 1 of the following PsA subsets: distal interphalangeal joint involvement,
polyarticular arthritis with absence of rheumatoid nodules, asymmetric peripheral
arthritis, or spondylitis with peripheral arthritis.
5. 
Have an inadequate response and/or intolerance to anti-TNFα  therapy, defined as
presence of active PsA despite previous treatment with one prior anti-TNFα  agent.
Participants may meet either one or both of the following criteria:
a. Lack of benefit of no more than one prior anti-TNFα therapy, as documented in
the patient history by the treating physician, after at least 12 weeks of
etanercept, adalimumab, golimumab, or certolizumab pegol therapy (or their
biosimilars) or at least a 14-week dosage regimen (ie, at least 4 doses) of
infliximab (or its biosimilars). Documented lack of benefit may include
inadequate improvement in joint counts, physical function, or disease activity
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AND/OR
b. Intolerance to no more than one prior anti-TNFα therapy, as documented in the
patient history by the treating physician, to etanercept, adalimumab, golimumab,
certolizumab pegol, or infliximab (or their biosimilars).
6. 
Participants are permitted to enter the study on a stable dose of 1 non-biologic DMARD
(limited to MTX, SSZ, HCQ, or LEF). If currently using non-biologic DMARDs,
participants should have started treatment for at least 3 months and the dose must be
stable for at least 4 weeks before first administration of study intervention and should
have no serious toxic side effects attributable to the non-biologic DMARD.  If currently
not using MTX, SSZ, or HCQ, must not have received for at least 4 weeks before first
administration of study intervention. If currently not using LEF, must not have received
for at least 12 weeks before first administration of study intervention.
In addition, the following stable dose criteria must be met:
a. 
If using MTX, the route of administration and dose must be stable and the dose
must be ≤25 mg/week.
b. 
If receiving SSZ, the dose must be ≤3g/day.
c. 
If receiving HCQ, the dose must be ≤400 mg/day.
d. 
If receiving LEF, the dose must be ≤20 mg/day
7. 
If using NSAIDs or other analgesics for PsA at baseline, participants must be on a stable
dose for at least 2 weeks prior to the first administration of study intervention. If currently
not using NSAIDs or other analgesics for PsA, must not have received NSAIDs or other
analgesics for PsA within 2 weeks prior to the first administration of study intervention.
8. 
If using oral corticosteroids at baseline, participants must be on a stable dose equivalent
to ≤10 mg of prednisone/day for at least 2 weeks prior to the first administration of study
intervention. If not currently using oral corticosteroids, the participant must not have
received oral corticosteroids within 2 weeks prior to the first administration of study
intervention.
9. 
Have active plaque psoriasis, with at least 1 psoriatic plaque of ≥2 cm diameter and/or
nail changes consistent with psoriasis, or documented history of plaque psoriasis.
10. 
Agree to avoid prolonged sun exposure and agree not to use tanning booths or other
ultraviolet (UV) light sources during study (for participants with skin lesions or with
documented history of psoriasis).
11. 
Are willing to refrain from the use of complementary therapies for PsA or psoriasis
including ayurvedic medicine, traditional Taiwanese, Korean, or Chinese medication(s)
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and acupuncture within 2 weeks prior to the first study intervention administration and
through Week 52
Screening laboratory tests and vaccinations
12. 
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 (ULN) range for
the central laboratory conducting the test.
NOTE:A 1-time repeat of screening laboratory tests (a-e) is allowed during the 6-week
screening phase and the investigator may consider the participant eligible if the
previously abnormal laboratory test result is within an acceptable range on repeat testing
in the central laboratory. No rescreening for ineligible ALT or AST levels is
permitted.
13. 
Are considered eligible according to the following TB screening criteria:
a. Have no history of latent or active TB before screening. An exception is made for
participants who have a history of latent TB and:
o are currently receiving treatment for latent TB, OR
o will initiate treatment for latent TB before the first administration of study
intervention, OR
o have documentation of having completed appropriate treatment (as per local
guidelines) for latent TB within 5 years before the first dose of study
intervention. It is the responsibility of the investigator to verify the adequacy of
previous anti-tuberculous treatment and provide appropriate documentation.
Participants with a history and documentation of having completed appropriate
treatment for latent TB more than 5 years before the first dose of study
intervention are not eligible.
b. Have no signs or symptoms suggestive of active TB upon medical history and/or
physical examination.
c. Have had no known 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
before the first administration of study intervention.
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Status: Approved,  Date: 04 September 2024
d. Within 8 weeks before the first administration of study intervention, have a negative
QuantiFERON®-TB test result, or have a newly identified positive QuantiFERON-
TB test result in which active TB has been ruled out and for which appropriate
treatment for latent TB has been initiated before the first administration of study
intervention.
NOTE: A negative tuberculin skin test result is required if the
QuantiFERON-TB test is not approved/registered in the country in which this
protocol is being conducted. The frequency of TB testing can be increased
depending on local health authority requirements. In Ukraine, while the
QuantiFERON-TB  test is not approved/registered, it is acceptable, and an
additional tuberculin skin test is not required. The QuantiFERON-TB test and
the tuberculin skin test are not required at screening for participants with a
history of latent TB, if active TB has been ruled out, and if appropriate treatment
has been initiated/completed as described above in Inclusion Criterion 13a.
e. Have a chest radiograph (both posterior-anterior and lateral views, or per country
regulations where applicable), taken within 12 weeks before the first administration
of study intervention and read by a radiologist or qualified pulmonologist, with no
evidence of current, active TB or old, inactive TB. A chest CT scan is also
acceptable if already available or obtained outside of the study protocol. Participants
with persistently indeterminate QuantiFERON-TB test results may continue without
treatment for latent TB if active TB is ruled out, their chest radiograph shows no
abnormality suggestive of TB (active or old, inactive TB) and the participant has no
additional risk factors for TB as determined by the investigator. This determination
must be promptly reported to the medical monitor or designee and recorded in the
participant's source documents and initialed by the investigator.
14. 
Agree not to receive a live virus or live bacterial vaccination during the study, or within
12 weeks after the last administration of study intervention.
15. 
Agree not to receive a Bacillus Calmette-Guérin (BCG) vaccination during the study,
and within 12 weeks after the last administration of study intervention.
16. 
It is recommended that patients are up-to-date on age-appropriate vaccinations prior to
screening as per routine local medical guidelines. For study patients who received locally
approved (and including emergency use-authorized) COVID-19 vaccines recently prior
to study entry, follow applicable local vaccine labelling, guidelines, and standards of
care for patients receiving immune-targeted therapy when determining an appropriate
interval between vaccination and study enrolment (see also Section 6.8.7).
Pregnancy and contraception
17. 
Criterion modified per Amendment 2.
17.1 
Before randomization, a woman must be
Not of childbearing potential OR
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Status: Approved,  Date: 04 September 2024
Of childbearing potential and practicing (if heterosexually active) a highly
effective method of contraception (failure rate of <1% per year when used
consistently and correctly) and agrees to remain on a highly effective method
while receiving study intervention and until 12 weeks after last dose - the end
of relevant systemic exposure. The investigator should evaluate the potential
for contraceptive method failure (eg, noncompliance, recently initiated) in
relationship to the first dose of study intervention. Examples of highly
effective methods of contraception are provided in Appendix 10.7.
NOTE: If a female participant’s childbearing potential changes after start
of the study  (eg, a woman who is not heterosexually active becomes
active, a premenarchal woman experiences menarche), she must begin
practicing a highly effective method of birth control, as described above.
A 
condom 
or 
occlusive 
cup 
with 
spermicidal
foam/gel/film/cream/suppository is not acceptable if used as the sole
method of contraception in this study. For examples of acceptable and
unacceptable methods of contraception, please refer to Appendix 10.7.
18. 
A woman of childbearing potential must have a negative serum ( -human chorionic
gonadotropin [ -hCG]) pregnancy test at screening and a negative urine pregnancy test
at Week 0.
19. 
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 intervention.
20. 
All men must agree not to donate sperm from the first administration of study
intervention through at least 12 weeks after receiving the last administration of study
intervention.
21. 
Criterion modified per Amendment 2.
21.1 A man who is sexually active with a woman of childbearing potential and who
has not had a vasectomy must agree to use a barrier method of birth control (eg,
either a condom [with spermicidal foam/gel/film/cream/suppository if available
in their locale] or a partner with an occlusive cap [diaphragm or cervical/vault
caps] plus spermicidal foam/gel/film/cream/suppository if available in their
locale), during the study and for at least 12 weeks after receiving the last
administration of study intervention.
General
22. 
Be willing and able to adhere to the prohibitions and restrictions specified in this
protocol.
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Status: Approved,  Date: 04 September 2024
23. 
Must sign an ICF indicating that he or she understands the purpose of and procedures
required for the study and is willing to participate in the study.
24. 
Must 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 participant from study participation.
5.2. 
Exclusion Criteria
Any potential participant who meets any of the following criteria will be excluded from
participating in the study:
PsA and Psoriasis
1. 
Has other inflammatory diseases that might confound the evaluations of benefit of
guselkumab therapy in the treatment of PsA, including but not limited to rheumatoid
arthritis, ankylosing spondylitis/non-radiographic axial spondyloarthritis (note: this does
not include a primary diagnosis of PsA with spondylitis), systemic lupus erythematosus,
or Lyme disease (confirmed by Western blot).
2. 
Has received more than 1 prior anti-TNFα agent (or biosimilars).
3. 
Has received an anti-TNFα agent within the following timeframes:
- Infliximab (or its biosimilars) or golimumab (IV), within 8 weeks prior to the first
administration of study intervention.
- Golimumab SC, adalimumab or certolizumab pegol (or their biosimilars), within
6 weeks prior to the first administration of study intervention.
- Etanercept (or its biosimilars) within 4 weeks prior to the first administration of
study intervention.
4. 
Has previously received any biologic treatment other than an anti-TNFα agent including,
but not limited to, guselkumab, ustekinumab, secukinumab, tildrakizumab,
ixekizumab,brodalumab, risankizumab or other investigative biologic treatment.
5. 
Has ever received Janus kinase (JAK) inhibitor including but not limited to tofacitinib,
baricitinib, filgotinib, peficitinib, decernotinib, upadacitinib or any other investigational
JAK inhibitor.
6. 
Has received any systemic immunosuppressants (eg, azathioprine, cyclosporine,
6-thioguanine, mercaptopurine, mycophenolate mofetil, hydroxyurea, tacrolimus)
within 4 weeks prior to the first administration of study intervention.
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Status: Approved,  Date: 04 September 2024
7. 
Has received apremilast within 4 weeks prior to the first administration of study
intervention.
8. 
Has received non-biologic DMARDs other than MTX, SSZ, HCQ, LEF, within 4 weeks
prior to the first administration of study intervention.
9. 
Is receiving 2 or more non-biologic DMARDs specified in Table 3 at baseline.
10. 
Has a nonplaque form of psoriasis (eg, erythrodermic, guttate, or pustular).
11. 
Has current drug-induced psoriasis (eg, a new onset of psoriasis or an exacerbation of
psoriasis from beta blockers, calcium channel blockers, or lithium).
12. 
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 intervention.
13. 
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 intervention. Low potency topical corticosteroids on the face or groin are
allowed at any time.
14. 
Has received epidural, intra-articular, intramuscular (IM), or IV corticosteroids,
including adrenocorticotropic hormone during the 4 weeks prior to the first
administration of study intervention.
15. 
Has received lithium within 4 weeks of the first administration of study intervention.
16. 
Has received an experimental antibody or biologic therapy (other than those listed
everywhere else in this section) within 6 months prior to the first administration of study
intervention, or received any other experimental therapy, including an investigational
medical device, or new investigational agent within 3 months or 5 half-lives (whichever
is longer) prior to the first administration of study intervention or is currently enrolled
in another study using an investigational intervention or procedure.
Coexisting medical conditions or past medical history
17. 
Has a history or current signs or symptoms of severe, progressive, or uncontrolled renal,
hepatic, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic,
hematologic, rheumatologic (with the exception of PsA), psychiatric, genitourinary, or
metabolic disturbances.
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Status: Approved,  Date: 04 September 2024
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 prior to
screening (with the exception of a nonmelanoma skin cancer that has been adequately
treated with no evidence of recurrence for at least 3 months prior to the first study
interventionadministration or cervical carcinoma in situ that has been adequately treated
with no evidence of recurrence for at least 3 months prior to the first study intervention
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. 
Is currently undergoing or has previously undergone allergy immunotherapy for a
history of anaphylactic reactions.
22. 
Has a transplanted organ (with exception of a corneal transplant >3 months prior to the
first administration of study intervention).
23. 
Has known hypersensitivity to any biologic medication, or known allergies or clinically
significant reactions to murine, chimeric, or human proteins, mAbs, or antibody
fragments.
24. 
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 participant will be made at the judgment
of the investigator.
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25. 
Has known allergies, hypersensitivity, or intolerance to guselkumab or its excipients
(refer to the IB).
26. 
Is pregnant, nursing, or planning a pregnancy (both men and women) within 12 weeks
after receiving the last administration of study intervention.
27. 
Has had major surgery (eg, requiring general anesthesia and hospitalization) within
8 weeks prior to screening, or will not have fully recovered from such surgery, or has
such surgery planned during the time the participant is expected to participate in the
study (52 weeks). Note: Participants with planned surgical procedures to be conducted
under local anesthesia may participate.
28. 
Is known to have had a substance abuse (drug or alcohol) problem within the previous
12 months prior to the first administration of study intervention.
Infections or predisposition to infections
29. 
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 non-remitting cystitis), fungal
infection (eg, mucocutaneous candidiasis), or open, draining, or infected skin wounds
or ulcers.
30. 
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.
31. 
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 prior to
screening.
32. 
Has or has had a herpes zoster infection within 2 months before screening.
33. 
Has received, or is expected to receive, any live virus or bacterial vaccination within
3 months prior to the first administration of study intervention.
34. 
Has had a BCG vaccination within 12 months of first administration of study
intervention.
35. 
Has a history of active granulomatous infection, including histoplasmosis, or
coccidioidomycosis, before screening. Refer to Inclusion Criterion 13 for information
regarding eligibility with a history of latent TB.
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36. 
Has a chest radiograph within 3 months prior to the first administration of study
intervention  that shows an abnormality suggestive of a malignancy, significant
cardiovascular or pulmonary disease or current active infection, including TB.
37. 
Has ever had a nontuberculous mycobacterial infection or opportunistic infection (eg,
cytomegalovirus, pneumocystis, aspergillosis).
38. 
Has persistently indeterminate (indeterminate on repeat sampling) QuantiFERON-TB
test results. Indeterminate results should be handled as described in Section 8.2.12.
39. 
Is infected with HIV (a confirmed positive serology for HIV antibody).
40. 
During the 6 weeks prior to baseline, have had ANY of
a) confirmed severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2)/COVID 19 infection (test positive), OR
b) suspected SARS –CoV –2 infection (clinical features without documented
test results), OR
c) close contact with a person with known or suspected SARS –SoV –2
infection.
An exception to this criterion maybe granted if a participant has a documented
negative result for a validated SARS-CoV-2 test:
Obtained at least 2 weeks after conditions (a), (b), (c) above (timed from
resolution of key clinical features if present, eg, fever, cough, dyspnea)
AND
with absence of ALL conditions (a), (b), (c) above during the period between
the negative test result and the baseline study visit.
NOTES on COVID-related exclusion:
The field of COVID-related testing (for presence of, and immunity to, the SARS-
CoV-2 virus) is rapidly evolving. Additional testing may be performed as part of
screening and/or during the study if deemed necessary by the investigator and in
accordance with current regulations / guidance from authorities / standards of
care.
Precaution: for those who may carry a higher risk for severe COVID-19 illness, follow
guidance from local health authorities when weighing the potential benefits and risks
of enrolling in the study, and during participation in the study.
41. 
Tests positive for hepatitis B virus (HBV) infection (see Appendix 4 in Section 10)or is
seropositive for antibodies to hepatitis C virus (HCV) at screening, unless the participant
meets 1 of the following conditions:
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Status: Approved,  Date: 04 September 2024
i. 
Has a history of successful treatment (defined as being negative for HCV
RNA at least 12 weeks after completing antiviral treatment) and has a
negative HCV RNA test result at screening, OR
ii. While seropositive has a negative HCV RNA test result at least 12 weeks
prior to screening and a negative HCV RNA test result at screening.
General
42. 
Is unable or unwilling to undergo multiple venipunctures because of poor tolerability or
lack of easy access to veins.
43. 
Lives in an institution on court or authority order.
44. 
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 participant or that could
prevent, limit, or confound the protocol-specified assessments.
45. 
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.
46. 
Is an employee of the Sponsor.
NOTE: Investigators should ensure that all study enrollment criteria have been met at screening.
If a participant's clinical status changes (including any available laboratory results or receipt of
additional medical records) after screening but prior to the first dose of study intervention is given
such that the participant no longer meets all eligibility criteria, then the participant should be
excluded from participation in the study, Section 5.4, describes options for retesting. The required
source documentation to support meeting the enrollment criteria are noted in Appendix 10.5.
5.3. 
Lifestyle Considerations
Potential participants must be willing and able to adhere to the following lifestyle restrictions
during the course of the study to be eligible for participation:
1. Refer to Section  6.8, Concomitant Therapy  for details regarding prohibited and
restricted therapy during the study.
2. Agree to follow all requirements that must be met during the study as noted in the
Inclusion and Exclusion Criteria (eg, contraceptive requirements).
3. Must not receive guselkumab outside of this protocol or participate in any other clinical
study with an investigational agent while in this study and must terminate study
participation if they do.
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5.4. 
Screen Failures
If, during the screening phase, the participant has not met all inclusion criteria or met any exclusion
criteria or is unable or unwilling to adhere to the prohibitions and restrictions of the study, the
participant is considered to be a screen failure and is not eligible to be randomized at that time. A
participant who might be considered a screen failure due to circumstances unrelated to the protocol
(eg, site closure due to COVID-19, other unforeseen circumstances resulting in site closure, etc)
could be eligible for screening and rescreening if applicable.
Participant Identification, Enrollment, and Screening Logs
The investigator agrees to complete a participant identification and enrollment log to permit easy
identification of each participant during and after the study. This document will be reviewed by
the Sponsor study site contact for completeness.
The participant identification and enrollment log will be treated as confidential and will be filed
by the investigator in the study file. To ensure participant confidentiality, no copy will be made.
All reports and communications relating to the study will identify participants by participant
identification and age at initial informed consent. In cases where the participant is not randomized
into the study the date seen and age at initial informed consent will be used.
Rescreening
Individuals who do not meet the criteria for participation in this study (screen failure) may be
rescreened on  1 occasion only after consultation with the Sponsor or designee (ie, study
responsible physician, scientists).
Rescreened participants will be assigned a new participant number, undergo the informed consent
process, and then start a new screening phase.
Chest x-rays, if done within the specified allowed time, are not required to be repeated.
If the QuantiFERON-TB test and/or the tuberculin skin test were positive in the first screening,
these tests should not be repeated. Also, if the QuantiFERON-TB test and tuberculin skin test were
done within the specified allowed time, they should not be repeated.
Retesting
Retesting of abnormal laboratory values that may lead to exclusion will be allowed once with the
exception of AST and ALT. Retesting can occur at an unscheduled visit during the specified
screening phase.
If a laboratory abnormality occurs, the site is encouraged to wait for all laboratory tests to be
completed to ensure other laboratory tests do not need to be repeated, as only 1 retest of laboratory
tests is allowed.
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5.5. 
Criteria for Temporarily Delaying Administration of Study Intervention
Guidelines for study intervention administration affected by the COVID-19 pandemic are found
in Appendix 10.9.
6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY
6.1. 
Study Intervention(s) Administered
Study intervention administration must be captured in the source documents and the electronic
case report form (eCRF). Study site personnel will instruct participants on how to store study
intervention for at-home use as indicated for this protocol.
Guselkumab and placebo will be manufactured and provided under the responsibility of the
Sponsor. Refer to the guselkumab prescribing information for a list of excipients.
Detailed instructions on the administration of study intervention will be provided in the Site
Investigational Product Procedures Manual.
For a definition of study intervention overdose, refer to Section 6.7.
Guidelines for study intervention affected by the COVID-19 pandemic are provided in
Appendix 10.9.
Description of Interventions
Table 2: 
Study Interventions (Treatment Groups)
Group/Arm Name 
Group I (q8w) 
Group II (q4w) 
Group III (placebo)
Intervention Name 
Guselkumab 
Guselkumab 
Placebo
Dose Formulation  
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).
Guselkumab 100 mg will 
be provided in a single-
use PFS assembled with
the PFS-U.
Placebo
Unit Dose Strength(s) 
100 mg 
100 mg
Dosage Level(s) 
100 mg at Weeks 0, 4, then 
q8w through Week 100 
(placebo 
at 
alternate 
visits) 
100 mg q4w through 
Week 100 
Placebo 
q4w 
through
Week 
20, 
then
guselkumab 100 mg q4w
through Week 100
Route of Administration  
subcutaneous 
subcutaneous 
subcutaneous
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6.1.1. 
Combination Products
For this protocol, the term combination product refers to the single integral drug-device
combination.
The Sponsor-manufactured combination product for use in this study is the pre-filled syringe (PFS)
assembled in an UltraSafe PlusTM  PFS-U. Additional details on the PFS-U are provided in
Section 6.2 and the guselkumab IB.
All combination product deficiencies (including failure, malfunction, improper or inadequate
design, manufacturer error, use error, and inadequate labeling) shall be documented and reported
by the investigator throughout the study. For studies with combination products, these deficiencies
will be reported as product quality complaints (PQC, see Appendix 10.6).
6.2. 
Preparation/Handling/Storage/Accountability
Preparation/Handling/Storage
For SC administration, guselkumab will be supplied as a 100 mg/mL sterile liquid in a single-dose
PFS assembled in a PFS-U. For SC administration, placebo will be supplied as a 1 mL sterile liquid
in a single-dose PFS-U.
Guselkumab and placebo for guselkumab should be a clear and colorless to light yellow solution
that may contain translucent particles. Do not use guselkumab or placebo for guselkumab if the
liquid is cloudy or discolored or has large particles. Protection from light is not required during
the preparation and administration of the study intervention material but avoid direct exposure to
sunlight. Aseptic procedure must be used during the preparation and administration of the study
intervention material.
After Week 28 (ie, starting at the Week 32 visit), participants (or caregivers) who are able and who
have been appropriately trained in the administration of study intervention may administer study
intervention at home, as per the schedule of Activities (SoA). Study personnel will instruct
participants on how to transport, store, and administer study intervention for at-home use as
indicated for this protocol.
Refer to the study Site Investigational Product and Procedures Manual for additional guidance on
study intervention preparation, handling, and storage.
Accountability
The investigator is responsible for ensuring that all study intervention received at the site is
inventoried and accounted for throughout the study. All study intervention will be stored and
disposed of according to the Sponsor's instructions. Study  site personnel must not combine
contents of the study intervention containers.
Study intervention 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 intervention  must be available for verification by the
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Sponsor's study site monitor during on-site monitoring visits. The return to the Sponsor of unused
study intervention will be documented on the intervention return form. When the study site is an
authorized destruction unit and study intervention supplies are destroyed on-site, this must also be
documented on the intervention return form.
Potentially hazardous materials such as used ampules, needles, syringes and vials should be
disposed of immediately in a safe manner and therefore will not be retained for intervention
accountability purposes.
Study intervention 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 intervention will be
supplied only to participants participating in the study. Returned study intervention must not be
dispensed again, even  to the same participant. Study intervention may not be relabeled or
reassigned for use by other participants. The investigator agrees neither to dispense the study
intervention from, nor store it at, any site other than the study sites agreed upon with the Sponsor.
Further guidance and information for the final disposition of unused study interventions are
provided in the Site Investigational Product and Procedures Manual.
6.3. 
Measures to Minimize Bias: Randomization and Blinding
Intervention Allocation
Procedures for Randomization and Stratification
Central randomization will be implemented in this study. Participants will be randomly assigned
to 1 of 3 intervention groups based on a computer-generated randomization schedule prepared
before the study by or under the supervision of the Sponsor. The randomization will be balanced
by using randomly permuted blocks and will be stratified at the study level by baseline non-
biologic DMARD use (yes/no).
The interactive web response system (IWRS) will assign a unique intervention code, which will
dictate the intervention assignment and matching intervention kit for the participant. The requestor
must use his or her own user identification and personal identification number when contacting
the IWRS and will then give the relevant participant details to uniquely identify the participant.
Blinding
To maintain the study blind, the study intervention container will have a label containing the study
name, study intervention number, reference number, and storage instructions. The label will not
identify the study intervention in the container. However, if it is necessary for a participant's safety,
the study blind may be broken and the identity of the study intervention ascertained. The study
intervention number will be entered in the eCRF when the study intervention is administered. The
study interventions 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 participant.
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Data that may potentially unblind the intervention  assignment (ie, study intervention  serum
concentrations, anti-guselkumab antibody levels) will be handled with special care to ensure that
the integrity of the blind is maintained and the potential for bias is minimized. This can include
making special provisions, such as segregating the data in question from view by the investigators,
clinical team, or others as appropriate until the time of database lock and unblinding.
The results of the post-baseline CRP measurements performed by the central laboratory will be
blinded to the investigative sites.
Under normal circumstances, the blind should not be broken until all participants have completed
the study and the database is finalized. The investigator may in an emergency determine the
identity of the intervention  by contacting the IWRS. While the responsibility to break the
intervention code in emergency situations resides solely with the investigator, 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 the
IWRS, 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 participant's source
documents in a secure manner.
Participants who have had their intervention assignment unblinded should continue to return for
scheduled evaluations and may not be eligible for further treatment.
At the Week 24 database lock, the data will be unblinded for analysis to some Sponsor personnel
while participants 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 participants will remain blinded to initial treatment assignment until
after the final database is locked.
6.4. 
Study Intervention Compliance
When participants have self- (or caregiver-) administration of study intervention at home,
compliance with study intervention will be assessed at each visit. Compliance will be assessed by
direct questioning during the site visits and documented in the source documents and eCRF.
Deviation(s) from the prescribed dosage regimen should be recorded in the eCRF.
Participants will receive instructions on compliance with study treatment when they begin
self-administration of study intervention at home. When participants begin self-administration at
home, the investigator or designated study personnel will maintain a log of all study intervention
dispensed and returned.
When study intervention is self-administered by participants (or caregivers) at home, participants
will record all study intervention administrations on a diary card.
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During the study, the investigator or designated study research personnel will be responsible for
providing additional instruction to reeducate any participant who is not compliant with taking the
study intervention.
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 participant
cannot receive a dose of study intervention at the scheduled visit, the participant must make every
effort to still come in for the scheduled assessments for that visit. In general, the dose should be
administered within approximately 2 weeks of that scheduled visit. The participant should then
resume the normal study schedule relative to the baseline visit (Week 0). In the case when a
participant does not come into the investigational site for a scheduled visit, the site will follow-up
with that participant. 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 intervention dispensed and will compare the
amount of study intervention dispensed with the amount returned.
All post-baseline visits up to and including Week 24 will have a visit window of ±4 days counting
from Week 0 as Day 1. After Week 24, all visits will have a visit window of ±7 days. The final
safety visit (12 weeks after the last dose in participants who discontinued study treatment) will
have a visit window of ±14 days. If a study visit occurs outside this window, the Sponsor should
be consulted about how the participant should resume his or her normal dose schedule.
Information regarding study intervention administrations that are administered outside of the
scheduled windows or missed will be recorded. Participant charts and worksheets may be reviewed
and compared with the data entries on the eCRFs to ensure accuracy.
6.5. 
Dose Modification
Not applicable.
6.6. 
Continued Access to Study Intervention After the End of the Study
Participants will be instructed that study intervention will not be made available to them after they
have completed/discontinued study intervention and that they should return to their primary
physician to determine standard of care.
Local regulations on continued access will always take precedence. Plans for continued access
stated in this protocol may change if new information on the benefit-risk profile of guselkumab
becomes available during the study or program.
6.7. 
Treatment of Overdose
For this study, any dose ofguselkumab greater than the highest dose at a single dosing visit will
be considered an overdose. The Sponsor does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator or treating physician should:
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Contact the Medical Monitor (or designee) immediately.
Evaluate the participant to determine, in consultation with the Medical Monitor (or designee),
whether study intervention should be interrupted or whether the dose should be reduced.
Closely monitor the participant for AE/SAE and laboratory abnormalities.
Obtain a serum sample for PK analysis if requested by the Medical Monitor (or designee),
determined on a case-by-case basis.
Document the quantity of the excess dose as well as the duration of the overdosing in the
eCRF.
6.8. 
Concomitant Therapy
Therapies administered up to 30 days before first dose of study intervention must be recorded at
screening.
Concomitant therapies must be recorded throughout the study beginning with start of the first dose
of study intervention to after the last dose of study intervention. Concomitant therapies should also
be recorded beyond that point only in conjunction with SAEs that meet the criteria outlined in
Serious Adverse Events in Section 8.3.1.
All therapies (prescription or over-the-counter medications, including vaccines, vitamins, herbal
supplements; non-pharmacologic therapies such as electrical stimulation, acupuncture, special
diets, exercise regimens, or other specific categories of interest) different from the study
intervention must be recorded in the eCRF.
Recorded information will include a description of the type of therapy, treatment period, dosage,
route of administration and indication. Modification of an effective preexisting therapy should not
be made for the explicit purpose of entering a participant into the study.
The Sponsor or designee must be notified in advance (or as soon as possible thereafter) of any
instances in which prohibited therapies are administered.
Every effort should be made to keep participants’ concomitant medications for PsA stable through
Week 112 or as specified in the following sections. The concomitant medication dose may be
reduced or temporarily discontinued because of abnormal laboratory values, adverse effects or
intolerance, concurrent illness, or the performance of a surgical procedure but the change and
reason for the change should be clearly documented in the participant’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.
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Table 3: 
Permitted Concomitant Medications for PsA and the Maximum Allowed Doses During the
Study
Permitted Concomitant Medications 
for Psoriatic Arthritis (PsA)a
Maximum Allowed Dose
NSAIDs and other analgesics 
Marketed dose approved in in the country where the
study is being conducted
Oral corticosteroids 
Equivalent to 10 mg/day of prednisone
Methotrexate (MTX)b 
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 It is recommended that all participants 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.
Participants should not initiate any new treatment for PsA through Week 52 except at Week 16
for those participants who have <20% improvement from baseline in both tender and swollen
joint counts (early escape criteria). Participants who meet early escape criteria will be allowed
to initiate or increase the dose of 1 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 participants qualifying for early escape
by the Week 24 visit.
Participants may not be receiving more than 1 non-biologic DMARD from baseline through
Week 52 (with the exception of participants who are eligible for early escape at Week 16, who
may receive up to 2 non-biologic DMARDs, see further details in Section 6.8.1). At baseline,
participants are permitted to enter the study on a stable dose of 1 non-biologic DMARD
(limited to MTX, SSZ, HCQ, or LEF) up to the maximum allowed dose specified in Table 3.
At Week 16, participants who meet criteria for early escape may initiate or increase the dose
of non-biologic DMARD depending on status of baseline use (see Table 4). Note: participants
cannot be on concomitant MTX and LEF. After Week 52 and through the end of the study,
participants may receive another non-biologic DMARD.
Beginning at Week 52, the treatment options in Table 3 are allowed to be initiated or dose
increased up to the maximum allowed dose specified in Table 4 for participants with ongoing
PsA disease activity at the investigator’s judgment; the rationale should be clearly documented
in the participants medical record.
The concomitant medication review will occur at study visits identified in the SoA (Section 1.3).
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6.8.1. 
Non-biologic DMARDs
6.8.1.1. 
Permitted Non-biologic DMARDs
Participants are permitted to enter the study on a stable dose of1 non-biologic DMARD (limited
to MTX, SSZ, HCQ, or LEF) up to the maximum allowed dose specified in Table 3. Only 1 of
these non-biologic DMARDs is allowed from baseline through Week 52 (with the exception of
participants who are eligible for early escape at Week 16, who may receive up to 2 non-biologic
DMARDs). Note: participants cannot be on concomitant MTX and LEF. Participants receiving 2
or more non-biologic DMARDs at baseline are excluded from study participation.
At any time during the study, the dose of the permitted non-biologic DMARD may be reduced or
temporarily discontinued due to abnormal laboratory values, side effects, concurrent illness, or the
performance of a surgical procedure.
Refer to Table 4 for protocol requirements of the permitted non-biologic DMARDs, including
allowances at early escape. Note: participants cannot be on concomitant MTX and LEF.
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Table 4: 
Protocol Requirements of the Permitted Non-biologic Disease-Modifying Antirheumatic Drugs
Permitted Non- 
biologic DMARDs 
Baseline 
Usage
Prior to Week 0 
Week 0 through Week 52 
Week 52 through Week 112
Methotrexate (MTX) 
Used 
Treatment should have started at least 
3 months prior to the first administration of 
study intervention. MTX routes of 
administration and doses should be stable 
for at least 4 weeks prior to the first 
administration of the study intervention, and
must be ≤25 mg/week.
Stable dose and route of 
administration (oral, intramuscular, or 
subcutaneous permitted) required 
unless early escape or unacceptable 
side effects 
Dose changes allowed up to the
maximum dose specified in Table 3
or changes of the route of
administration, at the investigator’s
discretion
Not Used 
Discontinued at least 4 weeks prior to the 
first administration of study intervention. 
Not allowed unless early escape 
Allowed up to the maximum dose
specified in Table 3 at investigators
discretion
Sulfasalazine (SSZ) 
or 
Hydroxychloroquine 
(HCQ) 
Used 
Treatment should have started at least 3 
months prior to the first administration of 
study intervention. Dose should be stable 
for at least 4 weeks prior to the first
administration of the study intervention and
must be ≤3 g/day (SSZ) or ≤400mg/day
(HCQ).
Stable dose required unless early 
escape or unacceptable side effects 
Dose changes allowed up to the
maximum dose specified in Table 3 at
the investigator’s discretion
Not Used 
Discontinued at least 4 weeks prior to the 
first administration of study intervention. 
Not allowed unless early escape 
Allowed up to the maximum dose
specified in Table 3 at investigators
discretion
Leflunomide (LEF) 
Used 
Treatment should have started at least 3 
months prior to the first administration of 
study intervention. Dose should be stable 
for at least 4 weeks prior to the first
administration of the study intervention and
must be ≤20 mg/day.
Stable dose required unless early 
escape or unacceptable side effects 
Dose changes allowed up to the
maximum dose specified in Table 3 at
the investigator’s discretion
Not Used 
Discontinued at least 12 weeks prior to the 
first administration of study intervention. 
Not allowed unless early escape 
Allowed up to the maximum dose
specified in Table 3 at investigators
discretion
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6.8.1.2. 
Prohibited Non-biologic DMARDs and Apremilast
All other non-biologic DMARDs (including, but not limited to chloroquine, gold preparations,
penicillamine) and apremilast must be discontinued at least 4 weeks prior to the first administration
of study intervention and remain prohibited through Week 112.
6.8.1.3. 
Systemic Immunosuppressive Drugs
Systemic immunosuppressants (including, but not limited to azathioprine, cyclosporine,
6-thioguanine, mercaptopurine, mycophenolate mofetil, hydroxyurea, or tacrolimus) must be
discontinued at least 4 weeks prior to the first administration of study intervention and remain
prohibited through Week 112.  If any of these systemic immunosuppressants is initiated during the
study, study intervention must be permanently discontinued.
Systemic immunosuppressants do not refer to corticosteroids; see Section 6.8.2 for restrictions
regarding the use of corticosteroids.
6.8.2. 
Corticosteroids
6.8.2.1. 
Oral Corticosteroids
Participants not using oral corticosteroids at baseline for PsA must have discontinued oral
corticosteroids at least 2 weeks prior to the first administration of study intervention and must not
receive oral corticosteroids through Week 52 of the study for PsA. An exception is made for
participants who qualify for early escape at Week 16.
Participants 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
intervention and continue on this dose through Week 52 unless early escape at Week 16.
After Week 24 and through Week 52, a one-time dose decrease in oral corticosteroids is allowed;
otherwise, throughout the study, the dose and type of oral corticosteroid may be changed at the
discretion of the investigator only if the participant develops unacceptable side effects.
6.8.2.2. 
Corticosteroids –Intravenous, Intramuscular, or Epidural
Administration
Intravenous, intramuscular, or epidural administration of corticosteroids for the treatment of PsA
are not allowed through Week 112.
Long-term (>2 weeks) oral, IV, intramuscular, or epidural corticosteroid use for indications other
than PsA or psoriasis are not allowed through Week 112. Short-term (≤2 weeks) oral, IV,
intramuscular, or epidural corticosteroid used for indications other than PsA should be limited to
situations where, in the opinion of the investigator, there are no adequate alternatives.
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6.8.2.3. 
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, participants 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 participant be evaluated for infection prior to receiving an
intra-articular corticosteroid injection.
6.8.2.4. 
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.
6.8.3. 
Nonsteroidal Anti-inflammatory Drugs and Other Analgesics
For participants receiving NSAIDs, including aspirin and selective cyclooxygenase 2 inhibitors,
or other analgesics for PsA at baseline, treatment with a stable dose of NSAIDs or other analgesics
should have been initiated at least 2 weeks prior to the first administration of study intervention
and continue through Week 24 unless early escape at Week 16. 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 eCRF. For topical and analgesic patches, the dose should be stable through Week 24 and
may be changed only if the participant develops unacceptable side effects.
Participants 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 intervention
and must not receive NSAIDs or other analgesics for PsA through Week 24 of the study. An
exception is made for participants who qualify for early escape at Week 16.
After Week 24, participants with ongoing PsA disease activity can initiate or increase the dose of
NSAIDs or other analgesics based on the investigator’s clinical judgment.
At any time during the study, the dose of NSAIDs or other analgesics may be reduced or
temporarily discontinued due to abnormal laboratory values, side effects, concurrent illness, or the
performance of a surgical procedure.
Use of NSAIDs and other analgesics for indications other than PsA are permitted throughout the
study.
In this study, aspirin is considered an NSAID, except for low-dose aspirin prescribed for
cardiovascular or cerebrovascular disease.
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6.8.4. 
Biologic Agents, Cytotoxic Drugs, JAK Inhibitors, or Investigational
Agents
The concomitant use of biologic agents, cytotoxic agents, JAK inhibitors, and/or investigational
drugs is not allowed, with the exception of limited emergency use for treatment of COVID-19
infection.  Biologic agents include, but are not limited to golimumab, anakinra, etanercept,
adalimumab, infliximab, ustekinumab, alefacept, efalizumab, rituximab, natalizumab,
certolizumab pegol, bimekizumab, tildrakizumab, secukinumab, ixekizumab, brodalumab, and
respective biosimilars as applicable. Cytotoxic agents include, but are not limited to chlorambucil,
cyclophosphamide, nitrogen mustard, and other alkylating agents.  JAK inhibitors include, but are
not limited to tofacitinib, baricitinib, filgotinib, peficitinib, upadacitinib and decernotinib. If any
of these medications are used, study intervention must be permanently discontinued, with the
exception of limited emergency use for treatment of COVID-19 infection. Continuation of study
intervention in such cases should be discussed with the Sponsor’s medical monitor
6.8.5. 
Complementary Therapies
The use of complementary therapies, including ayurvedic medicine, traditional Chinese,
Taiwanese, or Korean  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 intervention through
Week 112.
6.8.6. 
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-potency topical corticosteroids may be used on the face and groin only. Low and mid-potency
topical or intralesional corticosteroids (Class III-VII) may be used after Week 24 for psoriasis.
High and ultra-high potency corticosteroids (Class I and II) are prohibited through Week 112.
Phototherapy including UVB or tanning beds are not permitted during the study  through
Week 112. Participants should be encouraged to avoid prolonged sun exposure during the study.
6.8.6.1. 
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 intervention and is not permitted during
the study through Week 112; if a systemic antipsoriatic treatment (except those in Table 3) is
initiated during the study, study intervention must be permanently discontinued.
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Participants must not receive any biologic outside of the protocol or participate in any other clinical
study with an investigational agent while in this study and must terminate study participation if
they do. Prior to termination of study participation, participants should complete evaluations for a
study intervention discontinuation visit.
6.8.7. 
Vaccinations (Including for COVID-19)
When considering use of locally approved, non-live vaccines (including emergency use-authorized
COVID-19 vaccines) in study participants, follow applicable local vaccine labelling, guidelines,
and standard of care for participants receiving immune-targeted therapy.
For study participants receiving a locally approved (including emergency use-authorized)
COVID-19 vaccine in order to help identify acute reactions potentially related to the COVID-19
vaccine, it is recommended, where possible, that vaccine and study intervention be administered
on different days, separated by as large an interval as is practical within the protocol.
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL
7.1. 
Discontinuation of Study Intervention
A participant's study intervention must be discontinued if:
The participant withdraws consent to receive study intervention.
The investigator believes that for safety reasons or tolerability reasons (eg, AE) it is in the
best interest of the participant to discontinue study intervention.
The participant becomes pregnant or plans to come pregnant within the study period. Refer to
Appendix 10.7.
A systemic opportunistic infection.
The participant is unable to adhere to the study visit schedule or comply with protocol
requirements.
The participant is deemed ineligible according to the following TB screening criteria:
A diagnosis of active TB is made.
A participant 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 participant undergoing evaluation has a chest radiograph  with evidence of current
active TB and/or a positive QuantiFERON-TB test result, and/or 2 indeterminate
QuantiFERON-TB test results on repeat testing (refer to Section 8.2.12.) (and/or a
positive tuberculin skin test result in countries in which the QuantiFERON-TB test is not
approved/registered or the tuberculin skin test is mandated by local health authorities).
Note: In Ukraine, while the QuantiFERON-TB test is not approved/registered, it is
acceptable, and an additional tuberculin skin test is not required.
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The frequency of TB testing can be increased depending on local health authority
requirements.
A participant receiving treatment for latent TB discontinues this treatment prematurely
or is noncompliant with the therapy.
The participant has a serious adverse reaction that is temporally related to an injection
including a hypersensitivity reaction resulting in bronchospasm, wheezing and/or dyspnea that
requires ventilatory support OR that results in symptomatic hypotension with a decrease in
systolic blood pressure of 30% from a participant’s baseline value or systolic blood pressure
<90 mm Hg (Sampson, 2006). In general, discontinuation of studyintervention administration
must be considered for participants who develop a severe injection-site reaction.
The participant 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 intervention.
These may be accompanied by other events including pruritus, facial, hand, or lip edema,
dysphagia, urticaria, sore throat, and/or headache.
The participant has a malignancy including squamous cell skin cancer. Consideration may be
given to allowing participants who develop ≤2 basal cell skin cancers that are adequately
treated with no evidence of residual disease to continue to receive study intervention.
The participant has severe liver test abnormalities that are not transient and are not explained
by other etiologies, as described in Appendix 10.8.
The Sponsor may elect to terminate the study at any time, and if the Sponsor decides not to
continue development for any reason, study medication/drug will no longer be provided to
any participants.
Discontinuation of a participant’s study intervention should be considered under the
following conditions:
If the participant initiates treatment with prohibited therapies, the medical monitor or designee
should be notified for possible discontinuation of study intervention.
Recurrent or chronic serious infection.
The participant develops a serious infection, including but not limited to sepsis or pneumonia.
Note: Any serious infection should be discussed with the medical monitor or designee, and
study intervention should be withheld until the clinical assessment is complete.
Discontinuation of study treatment should be considered for participants 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 postbaseline (after Week 0) electronic Columbia-Suicide Severity
Rating Scale (eC-SSRS)assessment. Discussion of such participants with the medical monitor
or designee is required.
The participant develops a severe injection-site reaction, but not meeting criteria specified
above.
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If a participant discontinues study intervention for any reason before the end of the study, they
should be encouraged to continue in the study  to complete protocol specified evaluations as
outlined in the SoA (Section 1.3)and Section 7.2.
Study intervention assigned to the participant who discontinued study intervention may not be
assigned to another participant. Additional participants may be entered to ensure the protocol-
specified number of participants complete the study.
7.1.1. 
Liver Chemistry Stopping Criteria
Discontinuation of study intervention for abnormal liver tests is required by the investigator when
a participant meets 1 of the conditions in Appendix 10.8A or in the presence of abnormal liver
chemistries not meeting protocol-specified stopping rules if the investigator believes that it is in
best interest of the participant.
7.1.2. 
Liver Chemistry Restart Criteria
Refer to Appendix 10.8B for study intervention restart guidelines following abnormal liver test
results. Study Sponsor must provide written approval before study intervention is restarted.
7.2. 
Participant Discontinuation/Withdrawal From the Study
A participant will be withdrawn from the study for any of the following reasons:
Loss to follow-up
Withdrawal of consent
Death
Sponsor decision
When a participant withdraws before study  completion, the reason for withdrawal is to be
documented in the eCRF and in the source document. If the reason for withdrawal from the study
is withdrawal ofconsent then no additional assessments are allowed.
Participants who Discontinue Study Intervention Prior to the Week 24 Visit
If a participant permanently discontinues study drug intervention prior to the Week 24 visit, they
should be encouraged to return for all remaining study visits through Week 24. The participant
should also return for a final safety visit to perform assessments under the Week 112/final safety
visit approximately 12 weeks after the last study intervention administration.
Participants who Discontinue Study Intervention at or after Week 24 and Prior to the
Week 100 Visit
If a participant discontinues study intervention at or after Week 24, the final efficacy visit should
occur at the time of discontinuation or as soon as possible and all assessments under the Week 100
final efficacy visit should be performed with the exception of study intervention administration.
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The participant should also return for a final safety visit to perform assessments under the
Week 112/final safety visit approximately 12 weeks after the last study.
Withdrawal of Consent
A participant declining to return for scheduled visits does not necessarily constitute withdrawal of
consent. Alternate follow-up mechanisms that the participant agreed to when signing the consent
form apply as local regulations permit.
Withdrawal of consent should be an infrequent occurrence in clinical studies (Rodriguez, 2015),
therefore, prior to the start of the study the Sponsor and the investigator should discuss and reach
a clear understanding of what constitutes withdrawal of consent in the context of the available
reduced follow-up mechanisms listed.
Circumstances for Reduced Follow-up
In the situation where a participant may be at risk for withdrawal of consent and is unable to return
for scheduled visits at the protocol-defined frequency, the investigator may consider options for
reduced follow-up with consultation of the Sponsor/designee and/or medical monitor. These may
include (as local regulations permit):
Less frequent clinical visits.
Telephone, email, letter, social media, fax, or other contact with:
participant
relatives of the participant
participant’s physicians (general or specialist)
Review of any available medical records.
Details regarding these contacts must be properly documented in source records including
responses by participants.
7.2.1. 
Withdrawal from the Use of Research Samples
A participant who withdraws from the study will have the following options regarding the optional
research samples:
The collected samples will be retained and used in accordance with the participant's original
separate informed consent for optional research samples.
The participant may withdraw consent for optional research samples, in which case the
samples 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 samples have been destroyed.
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Withdrawal from the Optional Research Samples While Remaining in the Main Study
The participant may withdraw consent for optional research samples while remaining in the study.
In such a case, the optional research samples will be destroyed. The sample destruction process
will proceed as described above.
Withdrawal from the Use of Samples in Future Research
The participant may withdraw consent for use of samples for research (refer to Appendix 10.5.3).
In such a case, samples will be destroyed after they are no longer needed for the clinical study.
Details of the sample retention for research are presented in the main ICF and in the separate ICF
for optional research samples.
7.3. 
Lost to Follow-up
To reduce the chances of a participant being deemed lost to follow-up, prior to randomization,
attempts should be made to obtain contact information from each participant, eg, home, work, and
mobile telephone numbers and email addresses for both the participant as well as appropriate
family members.
A participant will be considered lost to follow-up if he or she repeatedly fails to return for
scheduled visits and is unable to be contacted by the study site. A participant cannot be deemed
lost to follow-up until all reasonable efforts made by the study  site personnel to contact the
participant are deemed futile. The following actions must be taken if a participant fails to return to
the study site for a required study visit:
The study site personnel must attempt to contact the participant to reschedule the missed visit
as soon as possible, to counsel the participant on the importance of maintaining the assigned
visit schedule, to ascertain whether the participant wishes to or should continue in the study.
Before a participant is deemed lost to follow-up, the investigator or designee must make every
reasonable effort to regain contact with the participant (where possible, 3 telephone calls,
e-mails, fax, and, if necessary, a certified letter to the participant’s last known mailing address,
or local equivalent methods. These contact attempts should be documented in the participant’s
medical records.
Should the participant continue to be unreachable, he or she will be considered to have
withdrawn from the study.
Should a study site close, eg, for operational, financial, or other reasons, and the investigator cannot
reach the participant to inform them, their contact information will be transferred to another study
site.
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8. 
STUDY ASSESSMENTS AND PROCEDURES
Overview
The SoA summarizes the frequency and timing of efficacy, PK, immunogenicity, PD, biomarker,
pharmacogenomic, and safety measurements applicable to this study.
All patient-reported outcome (PRO)assessments should be conducted/completed before any tests,
procedures, or other consultations to prevent influencing participant responses. Refer to the PRO
completion guidelines for instructions on the administration of PROs.
Urine and blood collections for PK and PD assessments should be kept as close to the specified
time as possible. Other measurements may be done earlier than specified timepoints if needed.
Actual dates and times of assessments will be recorded in the source documentation and eCRF.
The total blood volume to be collected from each participant will be no more than 625 mL. Repeat
or unscheduled samples may be taken for safety reasons or for technical issues with the samples.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the eCRF or laboratory
requisition form. Refer to the SoA (Section 1.3) 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.
Study-Specific Materials
The investigator will be provided with the following supplies:
Investigator Site File (includes protocol and IB for guselkumab)
Study site investigational product and procedures manual
Laboratory manual and laboratory supplies
PRO device and user manual
IWRS Manual
Sample ICF
eCRF completion instructions
Participant recruitment materials
Participant diary cards
Imaging manual
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8.1. 
Efficacy Assessments
8.1.1. 
Psoriatic Arthritis Response Evaluations
8.1.1.1. 
Joint count (tender and swollen)
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 participant should also perform
the joint assessments for that participant at every subsequent visit.
Through Week 112, the IJA should have no other contact (other than joint assessments) with the
participant once the participant is randomized, should not be the treating physician, should not
discuss the participant’s clinical status with the participant or other site personnel during the joint
assessment, and will not be permitted to review the participants medical records or the eCRFs, or
any of the previous joint assessments. The IJA should maintain a neutral attitude during joint
assessment and should limit interactions with the participant only to activities associated with
performing joint assessment or enthesitis or dactylitis assessments.
The IJA will perform only joint assessments and 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 participant and/or performing physician global assessments or administering
study intervention.
The Sponsor will provide training for each site’s designated IJA prior to the screening of the first
participant at each site. A back-up IJA must complete training before performing a joint assessment
for a participant’s study visit.
If an IJA was trained by the Sponsor (with joint assessments) in a previous Janssen 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.
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8.1.1.2. 
Non-evaluable Joints
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, artificial
joint, 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 participant’s prior joint procedures/injections (eg, if the participant was the
IJA’s patient prior to study participation).
8.1.1.3. 
American College of Rheumatology Response
American College of Rheumatology (ACR) responses are presented as the numerical measurement
of improvement in multiple disease assessment criteria. For example, an ACR 20 response
(Felson 1995) 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 are similarly defined except improvement threshold from baseline is 50%
and 70% for all endpoints, respectively.
The assessments (other than joint counts) that are used to calculate ACR responses are described
below.
8.1.1.4. 
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
The BASDAI was developed as a participant self-assessment for ankylosing spondylitis that
consists of 6 questions relating to the 5 major symptoms of ankylosing spondylitis (Garrett, 1994).
Only participants 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
B. Spinal pain
C. Joint pain
D. Enthesitis
E. Qualitative morning stiffness
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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
(Zochling, 2006).
8.1.1.5. 
Dactylitis Score
Presence and severity of dactylitis will be assessed by the 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) (Gladman, 2007; Gladman, 2013).
The Sponsor will provide dactylitis assessment training.  Documentation of this training will be
maintained in the study site’s training files. Previous dactylitis assessment training by the Sponsor
within the last 3 years with adequate documentation (eg, training certification) will be considered
adequate for this study; however, repeat training prior to start of the study is encouraged.
It is strongly recommended that the same person who performs the baseline dactylitis assessments
for a participant should also perform the dactylitis assessments for that participant at every
subsequent visit through Week 100.
8.1.1.6. 
Enthesitis Assessments
Enthesitis will be assessed by the IJA using the LEI (Healy, 2008) and the SPARCC.
The LEI was developed to assess enthesitis in participants 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 ankylosing spondylitis) 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. Documentation of this training will be
maintained in the study site’s training files. Previous enthesitis assessment training by the Sponsor
within the last 3 years with adequate documentation (eg, training certification) will be considered
adequate for this study; however, repeat training prior to start of the study is encouraged.
It is strongly recommended that the same person who performs the baseline enthesitis assessments
for a participant should also perform the enthesitis assessments for that participant at every
subsequent visit.
8.1.1.7. 
Physician’s Global Assessment of Disease Activity
The physician is asked to assess the patient’s arthritis on a 100 mm VAS, with the left end
indicating “No arthritis activity” and the right end indicating “Extremely active arthritis”.
8.1.1.8. 
Health Assessment Questionnaire –Disability Index (HAQ-DI)
The functional status of the participant will be assessed by the Health Assessment Questionnaire
–Disability Index (HAQ-DI) (Fries, 1980). 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 demonstrated (Husted, 1998).  It has also been shown
to be responsive to changes in a participant’s disease (Mease, 2015). In PsA, a decrease in score
of 0.35 has been determined to indicate a meaningful improvement (Mease, 2011).
8.1.1.9. 
Minimal Disease Activity
The PsA minimal disease activity (MDA) criteria are a composite of 7 outcome measures used in
PsA. Participants are classified as achieving MDA if they fulfill 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; HAQ score
≤0.5; and tender entheseal points ≤1 (Coates, 2010).
8.1.1.10. 
Very Low Disease Activity
Remission or very low disease activity (VLDA) is achieved when 7 of the 7 MDA cutoffs are met.
8.1.1.11. 
Disease Activity Index for Psoriatic Arthritis (DAPSA)
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 (0–10 VAS), and patient global assessment of disease activity (arthritis, 0 –10
VAS) (Helliwell, 2014b). The cutoffs for disease activity are 18.5 (low) to 45.1 (high)
(Helliwell, 2014a).
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8.1.1.12. 
Psoriatic Arthritis Disease Activity Score (PASDAS)
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 the PCS scale of the SF-36 health survey
(Helliwell 2013; Helliwell 2014b).
The formula to calculate 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) (Helliwell, 2014a).
8.1.2. 
Psoriasis Response Evaluations
8.1.2.1. 
Psoriasis Area and Severity Index (PASI)
The PASI is a system used for assessing and grading the severity of psoriatic lesions and their
response to therapy (Fredriksson, 1978). 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 participant at baseline should also perform the PASI evaluations for the
participant at all subsequent visits through Week 100. 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.
8.1.2.2. 
Investigator’s Global Assessment (IGA) of Psoriasis
The IGA documents the investigator’s assessment of the participants psoriasis at a given timepoint.
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 participant at baseline should also perform the IGA evaluations for the participant
at all subsequent visits through Week 100. The Sponsorwill 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.
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8.1.3. 
Patient Reported Outcomes
The PRO instruments will be provided in the local language in accordance with local guidelines.
The PRO instruments must be available for regulators and for IRB/ERC submissions, therefore
the PRO instrument or screen shots need to be attached to the protocol or provided in a companion
manual with the instruments that will be submitted with the protocol.
The PRO and AE data will not be reconciled with one another.
8.1.3.1. 
PsA Impact of Disease (PSAID)-12
The PsAID-12 is made up of 0-10 questions, with a final result included between 0 (no difficulty)-
10 (extreme difficulty). The 12 domains examine different perspectives, both physical and
psychological, that are considered important in patients with PsA. Each domain has a different
weight: pain, fatigue, and skin problems are those with a greater effect (DiCarlo, 2017).
8.1.3.2. 
Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue
Fatigue has been identified as an important symptom and a unique concept in addition to the core
disease measures of patients with PsA (Chandran, 2007). The Functional Assessment of Chronic
Illness Therapy (FACIT)-Fatigue questionnaire consists of 13 questions that assess a participant’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 (Cella, 2005).
8.1.3.3. 
Patient’s Global Assessment of Disease Activity
Patient’s global assessment of disease activity (arthritis and psoriasis): Participants will be asked
to rate how they felt during the prior week regarding their psoriasis and arthritis on a 100 mm
VAS, with the left end indicating “Excellent” and the right end indicating “Poor”.
Patient’s global assessment of disease activity (arthritis): Participants will be asked to rate how
they felt during the prior week regarding their arthritis on a 100 mm VAS, with the left end
indicating “Very Well” and the right end indicating “Very Poor”.
8.1.3.4. 
Patient’s Assessment of Pain
Patient’s assessment of pain: Participants will be asked to assess their average pain during the
prior week on a 100 mm VAS, with the left end indicating “no pain” and the right end indicating
“the worst possible pain”.
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8.1.3.5. 
Patient-Reported Outcomes Measurement Information System-29
(PROMIS-29)
Patient-Reported Outcomes Measurement Information System (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). 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) 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.
8.1.3.6. 
Short-Form 36 (SF-36)
The SF-36 questionnaire was developed as part of the Rand Health Insurance Experiment and
consists of 8 multi-item domain scales:
Limitations in physical functioning due to health problems
Limitations in usual role activities due to physical health problems
Bodily pain
General mental health (psychological distress and well-being)
Limitations in usual role activities due to 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 (Ware et al, 1994). 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
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change (Kosinski et al, 2000). 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 (Ware et al, 1992).
8.2. 
Safety Assessments
Adverse events will be reported and followed by the investigator as specified in Section 8.3 and
Appendix 10.6.
Any clinically relevant changes occurring during the study must be recorded on the Adverse Event
section of the eCRF.
Any clinically significant abnormalities persisting at the end of the study/early withdrawal will be
followed by the investigator until resolution or until a clinically stable condition is reached.
The study will include the following evaluations of safety and tolerability according to the
timepoints provided in the SoA (Section 1.3).
8.2.1. 
Physical Examinations
Physical examinations will be performed by the investigator or designated physician as specified
in the SoA (Section 1.3). Any abnormalities or changes in severity noted during the review of body
systems should be documented in the source document.
8.2.2. 
Vital Signs
Pulse/heart rate and blood pressure will be assessed at each visit.
Blood pressure and pulse/heart rate measurements will be assessed with a completely automated
device. Manual techniques will be used only if an automated device is not available.
If feasible, blood pressure and pulse/heart rate measurements should be preceded by at least
5 minutes of rest in a quiet setting without distractions (eg, television, cell phones).
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.
8.2.3. 
Height and Weight
Height and weight will be measured as specified in the SoA (Section 1.3).
8.2.4. 
Electrocardiograms
A 12-lead electrocardiogram (ECG) will be performed as specified in the SoA (Section 1.3).
During the collection of ECGs, participants should be in a quiet setting without distractions
(eg, television, cell phones). Participants should rest in a supine position for at least 5 minutes
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before ECG collection and should refrain from talking or moving arms or legs. If blood sampling
or vital sign measurement is scheduled for the same timepoint as ECG recording, the procedures
should be performed in the following order: ECG(s), vital signs, blood draw.
8.2.5. 
Clinical Safety Laboratory Assessments
Blood samples for serum chemistry and hematology will be collected as noted in Appendix  10.2.
The investigator must review the laboratory results, document this review, and record any
clinically relevant changes occurring during the study in the AE section of the eCRF. The
laboratory reports must be filed with the source documents.
The tests that will be performed by the central laboratory unless otherwise specified or approved
by the medical monitor/designee are specified in Appendix 10.2.
8.2.6. 
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 intervention
administration visit. Pregnancy tests must be completed, and the result must be negative before the
administration of any intervention for that visit. All pregnancy test results must be recorded in
study source documents.
8.2.7. 
Suicidal Ideation and Behavior Risk Monitoring
No signal of suicidal ideation and behavior has been observed in the clinical trials of guselkumab
to date. However, in light of 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 suicidal ideation and behavior among study participants.
The eC-SSRS measures 5 possible levels of suicidal ideation and 4 possible suicidal behaviors, as
well as non-suicidal self-injurious behavior. The assessment is a fully  structured, participant
self-report eC-SSRS-questionnaire, including standardized questions, follow-up prompts, error
handling routines, and scoring conventions (Mundt, 2013; Posner, 2011).
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. Participants will complete the eC-SSRS
questionnaire using the Sponsor-provided electronic device. Study site personnel will train the
participants on how to use the electronic device. 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 SoA (Section 1.3).
During a visit, participants will be directed to a private, quiet place with the electronic device to
complete the assessment. Participants 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.
Participants with significant suicidal ideation and behavior may require up to 10 minutes to answer
all relevant questions.
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At the screening visit, the eC-SSRS should be completed as the first assessment after signing
informed consent and joint assessment, but before any other tests, procedures, or other
consultations. For subsequent visits, the eC-SSRS should be completed after all PROs and before
any other tests, procedures, or other consultations. At the conclusion of each assessment, the
eC-SSRS Findings Report can be viewed electronically. At screening (“In the last 6 months”) and
Week 0, participants 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.
Participants 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 postbaseline visit will also be
referred to an appropriate mental health professional for evaluation. If a participant’s psychiatric
disorder can be adequately treated with psychotherapy and/or pharmacotherapy then the
participant, 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 participant should not leave the site at screening or be dosed at dosing visits before the
eC-SSRS Findings Report (both for negative and positive reports) is reviewed by the investigator
and the participant’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: Participant 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 participant has a positive suicidal indication
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(including for an incomplete-positive assessment), the site can immediately see the
outcome via the electronic device.
Non-suicidal, self-injurious behavior = YES: Participant risk assessed and referral to a mental
health professional. Negative findings report will be generated.
Interruption or the discontinuation of study treatment should be considered for any participant 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 postbaseline (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 participants with the medical monitor or designee is required (see Section 7.1). 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.
8.2.8. 
Concomitant Medication Review
Concomitant medications will be reviewed at each visit and recorded in the source documents and
eCRF.
8.2.9. 
Injection-Site Reactions
A study intervention injection-site reaction is any adverse reaction at a SC study intervention
injection-site. The injection sites will be evaluated for reactions and any injection-site reaction will
be recorded as an AE.
8.2.10. 
Hypersensitivity Reactions
Before any administration of study intervention at the study site, appropriately trained personnel
and medications (eg, antihistamines, injectable epinephrine) must be available to treat
hypersensitivity reactions, including anaphylaxis. All participants must be observed carefully for
signs and symptoms of a hypersensitivity reaction (eg, urticaria, pruritus, angioedema, wheezing,
dyspnea, or hypotension).
8.2.11. 
Infections
Investigators are required to evaluate participants for any signs or symptoms of infection at
scheduled visits. Study intervention administration should not be given to a participant with a
clinically significant, active infection. If a participant develops a serious infection, including but
not limited to sepsis or pneumonia, discontinuation of study intervention must be strongly
considered (Section 7.1). Any serious infection should be discussed with the medical monitor or
designee, and study intervention should be withheld until the clinical assessment is complete.
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8.2.12. 
Tuberculosis Evaluations
8.2.12.1. 
Initial Tuberculosis Evaluation
Participants must undergo testing for TB (refer to Appendix  10.3) 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 participant 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 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 to evaluate a participant who is high risk of having latent TB. If either the QuantiFERON-
TB test or the tuberculin skin test is positive, the participant is considered to have latent TB
infection for the purposes of eligibility for this study.
Participants with a negative QuantiFERON-TB test result (and a negative tuberculin skin test result
in countries in which the QuantiFERON-TB test is not approved/registered or the tuberculin skin
is mandated by local health authorities) are eligible to continue with pre-randomization procedures.
Participants with a newly identified positive QuantiFERON-TB 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, US guidelines
should be followed, or the participant will be excluded from the study.
A participant whose first QuantiFERON-TB test result is indeterminate should have the test
repeated. In the event that the second QuantiFERON-TB test result is also indeterminate, the
participant 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 participant
has no additional risk factors for TB as determined by the investigator. This determination must
be promptly reported to the Sponsor’s or designee’s medical monitor and recorded in the
participant's source documents and initialed by the investigator.
8.2.12.2. 
Ongoing Tuberculosis Evaluation
Early Detection of Active Tuberculosis
To aid in the early detection of TB reactivation or new TB infection during study participation,
participants must be evaluated for signs and symptoms of active TB at scheduled visits (refer to
the SoA in Section 1.3) or by telephone contact approximately every 8 to 12 weeks. The following
series of questions is suggested for use during the evaluation:
“Have you had a new cough of >14 days’ duration or a change in a chronic cough?”
“Have you had any of the following symptoms:
Persistent fever?
Unintentional weight loss?
Night sweats?”
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“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 participant 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 participants may
present as disseminated disease or with extrapulmonary features. Participants with evidence of
active TB should be referred for appropriate treatment.
Participants 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 test, a repeat tuberculin
skin test in countries in which the QuantiFERON-TB 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 participant’s risk of developing active TB and whether
treatment is warranted. Study intervention administration should be interrupted during the
investigation. A positive QuantiFERON-TB test or tuberculin skin test result should be considered
detection of latent TB. Participants with a newly identified positive QuantiFERON-TB 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, US guidelines should be followed, or the participant will be excluded from the study. If the
QuantiFERON-TB test result is indeterminate, the test should be repeated. Participants should be
encouraged to return for all subsequent scheduled study visits according to the protocol.
Participants who discontinue treatment for latent TB prematurely or who are noncompliant with
therapy must immediately discontinue further administration of study intervention and be
encouraged to return for all subsequent scheduled study visits according to the SoA (Section 1.3).
8.3. 
Adverse Events, Serious Adverse Events, and Other Safety Reporting
Timely, accurate, and complete reporting and analysis of safety information, including AEs, SAEs,
and product quality complaints (PQCs), from clinical studies are crucial for the protection of
participants, 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.
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, surrogate,
or the participant's legally acceptable representative) for the duration of the study.
For study intervention that meets the definition of a combination product, malfunctions or
deficiencies of a device constituent will be reported as a PQC.
Further details on AEs, SAEs, and PQC can be found in Appendix 10.6.
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8.3.1. 
Time Period and Frequency for Collecting Adverse Event and Serious
Adverse Event Information
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 participant's last study-related
procedure, which may include contact for follow-up of safety.
Serious Adverse Events
All SAEs, as well as PQCs, 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). Telephone reporting should be the exception and the reporter should be asked to
complete the appropriate form(s) first.
Possible Hy’s law case
Any possible Hy’s law case (ALT or AST ≥3 x the upper limit of normal [ULN] together with
bilirubin ≥2 x ULN or INR >1.5 is considered an important medical event and must be reported to
the sponsor in an expedited manner using the Serious Adverse Event form, even before all other
possible causes of liver injury have been excluded (INR criterion is not applicable to participants
receiving anticoagulants). A confirmed Hy’s law case must be reported as an SAE.
8.3.2. 
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 nonleading
verbal questioning of the participant is the preferred method to inquire about AE occurrence.
Solicited Adverse Events
Solicited AEs are predefined local at the injection site and systemic events for which the participant
is specifically questioned and which are noted by participants in their diary (see Section 8, Study
Assessments and Procedures).
Unsolicited Adverse Events
Unsolicited AEs are all AEs for which the participant is not specifically questioned in the
participant diary.
8.3.3. 
Follow-up of Adverse Events and Serious Adverse Events
The investigator is obligated to perform or arrange for the conduct of supplemental measurements
and evaluations as medically indicated to elucidate the nature and causality of the AE, SAE, or
PQC as fully as possible. This may include additional laboratory tests or investigations,
histopathological examinations, or consultation with other health care professionals.
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Adverse events, including pregnancy, will be followed by the investigator as specified in
Appendix 10.6, Adverse Events, Serious Adverse Events, Product Quality Complaints, and Other
Safety Reporting: Definitions and Procedures for Recording, Evaluating, Follow-up, and
Reporting.
8.3.4. 
Regulatory Reporting Requirements for Serious Adverse Events and
Anticipated Events
The Sponsor assumes responsibility for appropriate reporting of the Safety Information to the
Regulatory Authorities/Independent Ethics Committee (IEC)/Institutional Review Board (IRB)in
each respective country/territory, as applicable. 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.
An anticipated event is an AE that commonly occurs in the study population independent of
exposure to the drug under investigation.  For the purposes of this study the following SAEs will
be considered anticipated events:
Worsening of psoriasis
Worsening of PsA
These anticipated events will be periodically analyzed in aggregate by the Sponsor during study
conduct.  The Sponsor will prepare a safety report in narrative format if the aggregate analysis
indicates that the anticipated event occurs more frequently in the intervention group than in the
control group and the Sponsor concludes there is a reasonable possibility that the drug under
investigation caused the anticipated event.
The plan for monitoring and analyzing the anticipated events is specified in a separate Anticipated
Events Safety Monitoring Plan.  The assessment of causality will be made by the Sponsor’s
unblinded safety assessment committee.
The Sponsor assumes responsibility for appropriate reporting of the listed anticipated events
according to the requirements of the countries in which the studies are conducted.
8.3.5. 
Pregnancy
All initial reports of pregnancy in female participants or partners of male participants must be
reported to the Sponsor or designee 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 an SAE reporting form. Any participant who becomes
pregnant during the study must discontinue further study intervention.
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the
infant will be required.
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8.3.6. 
Adverse Events of Special Interest
Any newly identified malignancy or case of active TB occurring after the first study intervention
administration(s) in participants in this clinical study must be reported by the investigator to the
Sponsor or designee within 24 hours after being made aware of the event, according to the
procedures in Appendix 10.6.4. 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.
8.4. 
Pharmacokinetics
Serum samples will be used to evaluate the PK of guselkumab. Serum collected for PK 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. Participant
confidentiality will be maintained.
8.4.1. 
Evaluations
Venous blood samples will be collected for measurement of serum concentrations of guselkumab
and antibodies to guselkumab at the timepoints shown in the SoA (Section 1.3). Serum samples
will also be collected at the final visit from participants who discontinue study intervention or were
withdrawn from the study. 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 intervention, and 1 aliquot as a
back-up). Samples must be collected before study intervention administration at visits when a
study intervention administration is scheduled. The exact dates and times of blood sample
collection must be recorded in the laboratory requisition form.
Additional information about the collection, handling, and shipment of biological samples can be
found in the Laboratory Manual.
8.4.2. 
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
participants’ identity remains blinded, will assay these samples.
8.5. 
Pharmacogenomics
A pharmacogenomic blood sample will be collected from participants who consent separately to
this component of the study to allow for pharmacogenomic research, as necessary where local
regulations permit. Participant participation in pharmacogenomic research is optional.
Genetic (DNA) variation may be an important contributory factor to inter-individual variability in
drug response and associated clinical outcomes. Genetic and epigenetic factors may also serve as
markers for disease susceptibility and prognosis and may identify population subgroups that
respond differently to an intervention.
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The optional pharmacogenomic samples may be analyzed for identification of genetic and
epigenetic factors that may be associated with the disease and/or the response to the treatments.
This research may consist of the analysis of 1 or more candidate genes, or the analysis of genetic
and epigenetic markers throughout the genome, or analysis of the entire genome (as appropriate)
in relation to the disease and the treatments.
8.6. 
Biomarkers
Samples for serum biomarkers will be collected for all participants as indicated in the SoA
(Section 1.3).
Biomarker assessments will be made to examine the biologic response to treatment and to identify
biomarkers that are relevant to guselkumab treatment and/or PsA, where local regulations permit.
Assessments (detailed below) will include the evaluation of relevant biomarkers in serum, plasma,
and whole blood collected as specified in the SoA, where local regulations permit.
Data collected from these samples may be used for exploratory research that include the following
objectives:
1. To understand the molecular effects of guselkumab.
2. To understand PsA pathogenesis.
3. To understand why individual participants may respond differently to guselkumab.
4. To develop diagnostic tests to identify PsA populations that may be responsive or non-
responsive to treatment with guselkumab.
Stopping Analysis
Biomarker analyses are dependent upon the availability of appropriate biomarker assays and
clinical response rates. Biomarker analysis may be deferred or not performed, if during or at the
end of the study, it becomes clear that the analysis will not have sufficient scientific value for
biomarker evaluation, or if there are not enough samples or responders to allow for adequate
biomarker evaluation. In the event the study is terminated early or shows poor clinical efficacy,
completion of biomarker assessments is based on justification and intended utility of the data.
8.6.1. 
Pharmacodynamics
Samples for the analysis of pharmacodynamic biomarkers will be collected. Serum level of
T helper (Th)-17 cytokines, including but not limited to IL-17A, IL-17F, and IL-22, may be
measured to assess the pharmacodynamic effect of guselkumab.
8.6.2. 
Serum and Plasma Biomarkers
Blood samples will be collected from all participants for serum and plasma-based biomarker
analyses, where local regulations permit. Serum level of Th17 cytokines, such as IL-17A, IL-17F,
and IL-22, may be measured to assess the pharmacodynamic effect of guselkumab. Serum and
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plasma may be analyzed for other inflammation-related molecules, and/or broad panel of analytes
relevant to PsA pathogenesis and guselkumab treatment.
8.6.3. 
Whole Blood Gene Expression Profile
Whole blood will be collected by venipuncture from participants for RNA expression analysis,
where local regulations permit. Total RNA will be isolated and used for differential gene
expression analyses to identify gene expression patterns that are relevant to guselkumab treatment
and/or PsA, and to evaluate markers that can predict clinical response. Transcriptomic studies may
be conducted using microarray, and/or alternative equivalent technologies, which facilitate the
simultaneous measurement of the relative abundances of multiple RNA species resulting in a
transcriptome profile for each blood sample. The samples may also be used for targeted assessment
of genes relevant to the disease and/or the treatment. These analyses may be used to evaluate the
changes in gene expression profiles that may correlate with biological response relating to PsA
and/or the action of guselkumab, and may also be used to identify population subgroups that
respond differently to an intervention.
8.6.4. 
Peripheral Blood Mononuclear Cells
Whole blood will also be collected and processed for peripheral blood mononuclear cells (PBMC)
isolation and cryopreserved for later analysis. Analysis may include but is not limited to flow
cytometric assessment of cell populations, single cell transcriptomics, or functional assessment of
cells in response to guselkumab treatment and/or related to PsA pathogenesis. These analyses may
not be performed if cryopreserved PBMC samples do not meet the quality or quantity standard
required for the assessments.
8.6.5. 
Tissue Biomarkers
Biopsies from lesional and non-lesional skin may be collected from participants who meet
additional eligibility criteria and consent to this optional substudy component of the study (with a
separate ICF), as fixed blocks, slides, or fresh samples, where local regulations permit. Tissue
samples may be analyzed for levels of proteins, transcripts, and other inflammation-related
molecules and/or soluble factors relevant to PsA pathogenesis and guselkumab treatment. Analysis
may include, but is not limited to, tissue proteomic and transcriptomic assessment of cell
populations to identify cellular biomarkers associated with PsA pathogenesis and/or guselkumab
treatment as permitted by relevant and advancing technologies.
8.7. 
Immunogenicity Assessments
Serum samples for detection of antibodies to guselkumab will be collected from all participants
according to the SoA. Additionally, serum samples should also be collected at the final visit from
participants who discontinued study intervention or were withdrawn from the study. Samples
collected for 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. Participant confidentiality will be maintained.
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Serum samples will be used to evaluate the immunogenicity of guselkumab. Serum samples will
be screened for antibodies binding to guselkumab and the titer of confirmed positive samples will
be reported. 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 to guselkumab). Other analyses may be performed
to verify the stability of antibodies to guselkumab and/or further characterize the immunogenicity
of guselkumab.
Analytical Procedures
The detection and characterization of antibodies to guselkumabwill be performed using a validated
immunoassay method by or under the supervision of the Sponsor.
9. 
STATISTICAL CONSIDERATIONS
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).
9.1. 
Statistical Hypotheses
The primary hypothesis of this study is that guselkumab is superior to placebo as assessed by the
proportion of participants achieving an ACR 20 response at Week 24.
The method of addressing the multiplicity of hypotheses to keep the family-wise type I error
controlled at the 0.05 level will be specified in the SAP.
9.2. 
Sample Size Determination
The planned enrollment in the study is approximately 450 participants. Participants impacted by
major disruptions may be replaced. The sample size selection was determined based on the primary
endpoint of proportion of participants who achieve an ACR 20 response at Week 24. The
assumptions are based on the PSA3001 and PSA3003 studies.
9.2.1. 
Primary Endpoint –ACR 20 Response at Week 24
In the PSA3001 study, the ACR 20 response rates in the overall efficacy population at Week 24
were 22.2%, 52.0%, and 59.4%, for the placebo, guselkumab SC 100 mg q8w, and guselkumab
100 mg q4w treatment groups, respectively.
In the PSA3003 study which included participants who have an inadequate response or intolerance
to up to 2 prior anti-TNFs, the ACR 20 response rates at Week 24 were 19.8% and 44.4%, for
placebo and guselkumab SC 100 mg q8w, respectively.
For this study, assuming an ACR 20 response rate comparable to those in PSA3001 and PSA3003
in each of the guselkumab groups and the placebo group, a sample size of 150 participants per
group for each of the guselkumab treatment groups and placebo will have >90% power to detect
differences between each guselkumab treatment group and placebo for the primary endpoint
assuming a 2-sided alpha level of 0.05 (Table 5). The sample size calculations assume that 100%
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of the effect observed in PSA3001 and PSA3003 will be observed. If only 70 or 80% of the effect
seen in PSA3001 and PSA3003 is observed, the power will still exceed 90% for the Primary
endpoint.
Table 5: 
Power Calculations for Primary and Major Secondary Endpoints Based on 150 per Treatment
Group
Endpoint 
Source 
Mean or proportion 
p=0.05
Placebo 
Gus Q8W/Q4W  Effect size/diff Q8W/Q4W
Primary: ACR 20 at Week 24
PSA3001 
22% 
52% 
30% 
>99%
PSA3001 
59% 
37% 
>99%
PSA3003a 
19.8%  
44.4%  
24.6%  
>99%
a: PSA3003 (COSMOS) data is for Q8W only
9.3. 
Populations for Analysis Sets
For purposes of analysis, the populations defined in Table 6 will be used:
Table 6: 
Analysis Populations
Population 
Description
Enrolled 
All participants who signed the informed consent form (ICF).
Full Analysis Set 
All participants who were randomized in the study and received at least 1 (complete or
partial) administration of study intervention. This analysis set will be used for the
efficacy analyses.
Modified Full 
Analysis Set 
All participants who were randomized, excluding participants from sites rendered unable
to support key study operations due to major disruptions (eg, Natural Disaster or Other
Major Disruption). Details will be provided in the SAP.
Safety Analysis Set 
All participants who received at least 1 (complete or partial) administration of study
intervention, ie, the treated population.
Immunogenicity 
Analysis Set 
All participants who received at least 1 (complete or partial) administration of
guselkumab and who had at least 1 sample obtained after their first administration of
guselkumab.
PK Analysis Set 
All participants who received at least 1 complete administration of guselkumab and had
at least 1 valid blood sample drawn for PK analysis.
PD Analysis Set 
All participants who received at least 1 (complete or partial) administration of study
intervention.
9.4. 
Statistical Analyses
The SAP will be finalized prior to DBL and it will include a more technical and detailed description
of the statistical analyses described in this section. This section is a summary of the planned
statistical analyses of the most important endpoints including primary and key secondary
endpoints.
9.4.1. 
General Considerations
In general, descriptive statistics, such as mean, SD, median, interquartile (IQ) 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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For binary response efficacy endpoints, treatment comparisons will generally be performed using
a Chi-square test or a Cochran-Mantel-Haenszel (CMH) test. For continuous endpoint of efficacy
data, treatment comparisons will be performed using an analysis of covariance (ANCOVA), a
mixed model for repeated measures (MMRM) or a constrained longitudinal data analysis (cLDA)
model.
In general, statistical testing will be performed using 2-sided tests. The overall type I error will be
controlled among the primary and major secondary endpoints at 5%.
9.4.2. 
Primary Endpoint(s)
The primary endpoint is the proportion of participants who achieved an ACR 20 response at
Week 24. This endpoint will be analyzed based on the adjusted estimand defined by the
5 components:
Population: Participants with active PsA who have inadequate response and/or intolerance to
1 prior anti-TNF, and were randomized and treated with study intervention
Treatment:
Placebo
Guselkumab
Variable: ACR 20 at Week 24, where a responder is defined as a participant who achieves
ACR20 response at Week 24 and does not experience Intercurrent Events categories 1 to 3.
Intercurrent events (ICEs): Participants with an ICE in categories 1-3 will follow the
composite strategy, where participants who experience them prior to Week 24 will be
considered as non-responders regardless of the observed ACR 20 response status. Participants
with an ICE in categories 4 or 5 will follow the hypothetical strategy postulating a scenario
where the major disruption (eg, Natural Disaster or Other Major Disruption) and ICEs directly
resulting from them, did not occur, and observed data through Week 24 after meeting these
ICEs will not be used and will be assumed to be Missing at Random (MAR). For participants
experiencing multiple ICEs, an ICE in categories 1 to 3 will supersede an ICE in categories 4
and 5. Additional details for the ICEs below will be further defined in the SAP as applicable.
1. Discontinued study intervention injections due to any reason except due to Natural
Disaster or Major Disruption.
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. Discontinued study intervention injections due to Natural Disaster or Major Disruption.
5. Severe treatment non-compliance due to Natural Disaster or Major Disruption.
Population level summary: difference in proportion of responders between guselkumab group
and placebo group.
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Data from all participants in the modified full analysis set (mFAS) will be analyzed according to
randomized treatment group regardless of the treatment actually received. Participants with
missing data for any reason other than due to major disruptions (eg, Natural Disaster or Other
Major Disruption)will be considered nonresponders, while missing data due to major disruptions
(eg, Natural Disaster or Other Major Disruption)or data not used due to ICE categories 4 or 5 will
be assumed to be MAR and imputed using multiple imputation (MI). The treatment effect of each
guselkumab group versus placebo will be tested using a CMH test stratified by baseline
non-biologic DMARD 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.
To evaluate the robustness of the primary endpoint analysis results, 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 ICEs (eg, alternative estimand) are
handled, how observed data are used, and how missing data are treated will be specified in the
SAP to further address the robustness of treatment effect of ACR 20 at Week 24.
Subgroup Analyses
Subgroup analysis will be performed to evaluate consistency in the primary efficacy endpoint by
demographic characteristics, baseline disease characteristics, and baseline medications. Interaction
test between the subgroups and treatment group will also be provided if appropriate.
9.4.3. 
Secondary Endpoint(s)
Major secondary endpoints are provided in Section 3.
The ordering of endpoints, methods of analysis and the approach to control the Type 1 error for
multiplicity, as well as the data-handling rules for the major secondary endpoints (multiplicity
controlled and weakly controlled) will be specified in the SAP.
In addition to the primary and major secondary endpoints, all other secondary endpoints
(Section 3) will be summarized over time by treatment groups. Treatment comparisons will be
performed by visit through Week 24.
The estimand, analysis method, and data handling rules for major secondary endpoints, as well as
the approach to control the type I error for multiplicity will be specified in the SAP.
9.4.4. 
Safety Analyses
All safety analyses will be made on the Safety Population.
Adverse Events
The verbatim terms used in the eCRF by investigators to identify AEs will be coded using the
Medical Dictionary for Regulatory Activities (MedDRA). For each AE, the percentage of
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participants who experience at least 1 occurrence of the given event will be summarized by
intervention group.
The following analyses of AEs will be used to assess the safety of participants:
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.
Summaries, listings, datasets, or participant narratives may be provided, as appropriate, for those
participants who die, who discontinue intervention due to an AE, or who experience a severe or an
SAE.
Clinical Laboratory Tests
Laboratory data will be summarized by type of laboratory test. Descriptive statistics will be
calculated for selected laboratory analytes at baseline and for observed values and changes from
baseline at each scheduled timepoint. Number and percentage of participants by maximum
National Cancer Institute –Common Terminology Criteria for Adverse Events (NCI-CTCAE)
toxicity grades for laboratory analytes with NCI-CTCAE criteria defined will also be summarized,
and participants with maximum NCI-CTCAE Grade ≥3 will also be presented in a listing.
Vital Signs
Vital signs including pulse/heart rate and blood pressure (systolic and diastolic) will be
summarized over time, using descriptive statistics and/or graphically. The percentage of
participants with values beyond clinically important limits will be summarized.
9.4.5. 
Other Analyses
Pharmacokinetic Analyses
The PK evaluable population is defined as all the participants who received at least 1 complete
dose of guselkumab and had at least 1 valid blood sample drawn for PK analysis after their first
dose of guselkumab.
Serum guselkumab concentrations over time will be summarized for each treatment group using
descriptive statistics. All concentrations below the limit of quantitation (BQL) of the assay or
missing data will be labeled as such in the concentration data listing or statistical analysis system
dataset. The BQL concentrations will be treated as zero in the summary statistics.
Population PK modeling will be conducted when appropriate. 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
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analysis plan and the results of the population PK analysis will be presented in a separate technical
report.
Immunogenicity Analyses
The incidence and titers of antibodies to guselkumab will be summarized for all participants who
receive at least 1 dose of guselkumab and have appropriate samples for detection of antibodies to
guselkumab (ie, participants with at least 1 sample obtained after their first dose of guselkumab).
A listing of participants who are positive for antibodies to guselkumab will be provided.
The incidence of neutralizing antibodies (NAbs) to guselkumab will be summarized for
participants who are positive for antibodies to guselkumab and have samples evaluable for NAbs
to guselkumab. Other immunogenicity analyses may be performed to further characterize the
immune responses that are generated.
Biomarker and Pharmacodynamic Analyses
Planned biomarker analyses may be deferred if emerging study data show no likelihood of
providing useful scientific information or insufficient number of samples are available for
analyses. Any biomarker samples received by the contract vendor or Sponsor after the cutoff date
will not be analyzed, and therefore, excluded from the biomarker analysis.
The biomarker analyses will be used to understand PsA, characterize the effects of guselkumab to
identify PD markers and biomarkers relevant to treatment, and to determine if these markers can
predict response to guselkumab. The biomarker analysis may include but are not limited to serum
Th17 cytokines, inflammatory markers, whole blood RNA profile, and other categories of
biomarkers potentially involved in the development and the progression of PsA.
Changes in biomarkers over time may be summarized by intervention group. Associations between
baseline levels and changes from baseline in select markers and clinical response may be explored.
Results of biomarker analyses may be presented in a separate report.
Pharmacokinetic/Pharmacodynamic Analyses
If data permit, the relationships between serum guselkumab concentrations and efficacy and/or
relevant PD endpoints 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.
Pharmacogenomic Analyses
Genetic (DNA) analyses may be conducted only in participants who sign the consent form to
participate in the pharmacogenomic sampling. These analyses are considered exploratory. DNA
samples may be used for research related to guselkumab and/or PsA. They may also be used to
develop tests/assays related to guselkumab and PsA. Pharmacogenomic research may consist of
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the analysis of candidate genes or of the analysis of genetic markers throughout the genome or
analysis of the entire genome (as appropriate) in relation to guselkumab or PsA clinical endpoints.
Results may be presented in a separate report.
9.5. 
Interim Analysis
Not applicable.
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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Abbreviations
Abbreviation  
Definition
ACR  
American College of Rheumatology
AE 
adverse event
ALT  
alanine aminotransferase
ANCOVA  
analysis of covariance
AS  
ankylosing spondylitis
AST  
aspartate aminotransferase
BASDAI 
Bath Ankylosing Spondylitis Disease Activity Index
BCG  
Bacillus Calmette-Guérin
BQL 
below the limit of quantitation
BSA 
body surface area
CASPAR  
ClASsification criteria for Psoriatic Arthritis
CD  
Crohn’s disease
cLDA  
constrained longitudinal data analysis
CMH  
Cochran Mantel Haenszel
CRF  
case report form
CRP  
C-reactive protein
CTCAE 
Common Terminology Criteria for Adverse Events
DAPSA  
Disease Activity index for PSoriatic Arthritis
DBL  
database lock
DMARD  
disease modifying anti-rheumatic drug
ECG  
electrocardiogram
eC-SSRS  
electronic Columbia-Suicide Severity Rating Scale
eCRF  
electronic CRF
eDC  
electronic data capture
EEA  
European Economic Area
EU  
European Union
FACIT-F 
Functional Assessment of Chronic Illness Therapy –fatigue
FSH  
follicle-stimulating hormone
GCP  
Good Clinical Practice
HAQ-DI 
Health Assessment Questionnaire –Disability Index
HBsAg 
hepatitis B surface antigen
HBV  
hepatitis B virus
HCQ  
hydroxychloroquine
HCV  
hepatitis C virus
HIV  
human immunodeficiency virus
HRQoL 
health related quality of life
IB  
Investigator’s Brochure
ICF  
informed consent form
ICH  
International Conference on Harmonisation
ICMJE 
International Committee of Medical Journal Editors
IEC  
Independent Ethics Committee
Ig 
immunoglobulin
IGA  
Investigator’s Global Assessment
IJA  
independent joint assessor
IL 
interleukin
IM  
intramuscular
IQ  
interquartile
IRB  
Institutional Review Board
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IR  
inadequate response
IV  
intravenous(ly)
IWRS  
interactive web response system
JAK  
Janus kinase
LEF  
leflunomide
LEI 
Leeds Enthesitis Index
mAb 
monoclonal antibody
MCS  
Mental Component Score
MDA  
Minimal Disease Activity
MedDRA  
Medical Dictionary for Regulatory Activities
MMRM  
mixed model for repeated measures
MTX  
methotrexate
NAbs 
neutralizing antibodies
NCI 
National Cancer Institute
NSAID  
nonsteroidal anti-inflammatory drug
PASDAS  
Psoriatic ArthritiS Disease Activity Score
PASI 
Psoriasis Area and Severity Index
PBMC  
peripheral blood mononuclear cells
PCS  
Physical Component Score
PD 
pharmacodynamic(s)
PFS-U 
prefilled syringe with the Ultrasafe PLUSTM passive needle guard
PK 
pharmacokinetic(s)
PQC  
Product Quality Complaint
PRO  
patient-reported outcome(s) (paper or electronic as appropriate for this study)
PsA  
psoriatic arthritis
PsAID12 
psoriatic arthritis impact of disease score
PROMIS-29 
Patient-Reported Outcomes Measurement Information System-29
q4w, q8w  
every 4 weeks, every 8 weeks
RA  
rheumatoid arthritis
SAE 
serious adverse event
SAP  
Statistical Analysis Plan
SARS-COV-2 
Severe Acute Respiratory Syndrome Coronavirus 2 (Coronavirus disease 2019)
SC 
subcutaneous
SD 
standard deviation
SF-36 
36-item short form survey
SPARCC  
Spondyloarthritis Research Consortium of Canada
SSZ 
sulfasalazine
SoA  
Schedule of Activities
SUSAR  
suspected unexpected serious adverse reaction
TB  
tuberculosis
TNF  
tumor necrosis factor
ULN  
upper limit of normal
UV  
ultraviolet
VAS  
visual analog scale
vdH-S 
van der Heijde-Sharp score
VLDA  
very low disease activity
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10.3. Appendix 3: Tuberculin Skin Testing
The Mantoux tuberculin skin test (CDC, 2000) is a 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. Participants should never be allowed to read their own tuberculin skin test results. If a
participant fails to show up for the scheduled reading, a positive reaction may still be measurable
up to 1 week after testing. However, if a participant 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 participants 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.
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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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10.4. Appendix 4: Hepatitis B Virus (HBV) Screening with HBV DNA Testing
Participants 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):
Participants who test negative for all HBV screening tests (ie, HBsAg-, anti-HBc-, and anti-
HBs-) are eligible for this protocol.
Participants who test negative for surface antigen (HBsAg-) and test positive for core antibody
(antiHBc+) and surface antibody (anti-HBs+) are eligible for this protocol.
Participants who test positive only for surface antibody (anti-HBs+) are eligible for this
protocol.
Participants who test positive for surface antigen (HBsAg+) are NOT eligible for this protocol,
regardless of the results of other hepatitis B tests.
Participants who test positive only for core antibody (anti-HBc+) are NOT eligible for this
protocol.
These eligibility criteria based on HBV test results are also represented below.
Eligibility Based on the Hepatitis B Virus (HBV) Test Results
Test Result 
STATUS
Hepatitis B surface 
antigen (HBs-Ag) 
Hepatitis B surface 
antibody (anti-HBs) 
Hepatitis B core antibody
(anti-HBc total)
negative 
negative 
negative 
ELIGIBLE
negative 
positive 
negative
negative 
positive 
positive
positive 
negative or positive 
negative or positive 
NOT ELIGIBLE
negative 
negative 
positive 
Requires testing for
presence of HBV DNA*
* If HBV DNA is detectable, the participant is not eligible for this protocol. If HBV DNA testing cannot be performed,
or there is evidence of chronic liver disease, the participant is not eligible for this protocol.
For participants who are not eligible for this protocol due to HBV test results, consultation with a
physician with expertise in the treatment of HBV infection is recommended.
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10.5. Appendix 5: Regulatory, Ethical, and Study Oversight Considerations
10.5.1. 
Regulatory and Ethical Considerations
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the
protocol, current International Conference on Harmonisation (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 participants.
Compliance with this standard provides public assurance that the rights, safety, and well-being of
study participants are protected, consistent with the principles that originated in the Declaration of
Helsinki, and that the study data are credible.
Protocol Clarification Communications
If text within a final approved protocol requires clarification (eg, current wording is unclear or
ambiguous) that does not change any aspect of the current study conduct, a protocol clarification
communication (PCC) may be prepared. The PCC Document will be communicated to the
Investigational Site, Site Monitors, Local Trial Managers (LTMs), Clinical Trial Managers
(CTMs), and/or Contract Research Organizations (CROs) who will ensure that the PCC
explanations are followed by the investigators.
The PCC Document may be shared by the sites with Independent Ethics Committees/Institutional
Review Boards (IECs/IRBs) per local regulations.
The PCC Documents must NOT be used in place of protocol amendments, but the content of the
PCC Document must be included in any future protocol amendments.
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 participants, 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) involve only logistic or administrative aspects of the study, the IEC/IRB (where
required) only needs to be notified.
During the course of the study, in situations where a departure from the protocol is unavoidable,
the investigator or other physician in attendance will contact the appropriate Sponsor
representative listed in the Contact Information page(s), which will be provided as a separate
document. Except in emergency situations, this contact should be made before implementing any
departure from the protocol. In all cases, contact with the Sponsormust be made as soon as possible
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to discuss the situation and agree on an appropriate course of action. The data recorded in the eCRF
and source documents will reflect any departure from the protocol, and the source documents will
describe this departure and the circumstances requiring it.
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.
Required Prestudy Documentation
The following documents must be provided to the Sponsor before shipment of study intervention
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, participant 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
participant:
Completed investigator financial disclosure forms from all subinvestigators
Documentation of subinvestigator qualifications (eg, curriculum vitae)
Name and address of any local laboratory conducting tests for the study, and a dated copy of
current laboratory normal ranges for these tests, if applicable
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Local laboratory documentation demonstrating competence and test reliability
(eg, accreditation/license), if applicable
Independent Ethics Committee or Institutional Review Board
Before the start of the study, the investigator (or Sponsorwhere 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 participants)
IB (or equivalent information) and amendments/addenda
Sponsor-approved participant recruiting materials
Information on compensation for study-related injuries or payment to participants 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 participants
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
participants, data or study conduct, unless required locally), the ICF, applicable recruiting
materials, and participant 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 participants, data or study conduct)
Revision(s) to ICF and any other written materials to be provided to participants
If applicable, new or revised participant recruiting materials approved by the Sponsor
Revisions to compensation for study-related injuries or payment to participants for
participation in the study, if applicable
New edition(s) of the IB 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
intervention
New information that may adversely affect the safety of the participants or the conduct of the
study
Deviations from or changes to the protocol to eliminate immediate hazards to the participants
Report of deaths of participants 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 participants, 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).
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  4.2.1, Study-Specific Ethical Design
Considerations.
Other Ethical Considerations
For study-specific ethical design considerations, refer to Section 4.2.1.
10.5.2. 
Financial Disclosure
Investigators and subinvestigators will provide the Sponsor with sufficient, accurate financial
information in accordance with local regulations to allow the Sponsor to submit complete and
accurate financial certification or disclosure statements to the appropriate regulatory authorities.
Investigators are responsible for providing information on financial interests during the course of
the study and for 1 year after completion of the study.
Refer to Required Prestudy Documentation (above) and contracts for details on financial
disclosure.
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10.5.3. 
Informed Consent Process
Each participant 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 participant can read and understand. The informed consent
must 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 anauthorized member of the study site personnel
must explain to potential participants the aims, methods, reasonably anticipated benefits, and
potential hazards of the study, and any discomfort participation in the study may entail. Participants
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 participant will receive Finally, they will be told that the investigator will maintain a
participant 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 participant, to the extent permitted by the applicable law(s) or regulations.
By signing the ICF the participant is authorizing such access, which includes permission to obtain
information about his or her survival status. It also denotes that the participant agrees to allow his
or her study physician to recontact the participant for the purpose of obtaining consent for
additional safety evaluations, and subsequent disease-related treatments, if needed.
The participant 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 participant's personally dated signature. After having obtained the consent, a copy of
the ICF must be given to the participant.
Participants who are rescreened are required to sign a new ICF.
Participants 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 participant
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 participant.
Where local regulations require, a separate ICF may be used for the required DNA component of
the study.
10.5.4. 
Data Protection
Privacy of Personal Data
The collection and processing of personal data from participants enrolled in this study  will be
limited to those data that are necessary to fulfill the objectives of the study.
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These data must be collected and processed with adequate precautions to ensure confidentiality
and compliance with applicable data privacy protection laws and regulations. Appropriate
technical and organizational measures to protect the personal data against unauthorized disclosures
or access, accidental or unlawful destruction, or accidental loss or alteration must be put in place.
Sponsor personnel whose responsibilities require access to personal data agree to keep the identity
of participants confidential.
The informed consent obtained from the participant includes explicit consent for the processing of
personal data and for the investigator/institution to allow direct access to his or her original medical
records (source data/documents) for study-related monitoring, audit, IEC/IRB review, and
regulatory inspection. This consent also addresses the transfer of the data to other entities and to
other countries.
The participant 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.
In the event of a data security breach, the sponsor will apply measures to adequately manage and
mitigate possible adverse effects taking into consideration the nature of the data security breach as
necessary to address other obligations such as notifying appropriate authorities in accordance with
applicable data protection law.
Exploratory biomarker, PK, PD, and immunogenicity research is not conducted under standards
appropriate for the return of data to participants. 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 participants 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.
10.5.5. 
Long-Term Retention of Samples for Additional Future Research
Samples collected in this study may be stored for up to 15 years (or according to local regulations)
for additional research. Samples will only be used to understand guselkumab, to understand PsA
and differential intervention 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. Participants may withdraw their consent for their samples to be
stored for research (refer to Section 7.2.1, Withdrawal From the Use of Research Samples).
10.5.6. 
Committees Structure
Not applicable
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10.5.7. 
Publication Policy/Dissemination of Clinical Study Data
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 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 ofguselkumab 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 for the study. Results of biomarker
analyses performed after the Clinical Study Report has been issued may be reported in a separate
report and will not require a revision of the Clinical Study Report.
Study participant 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 (ICMJE) 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 sub-study 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 18 months after the study end date, or the Sponsor
confirms there will be no multicenter study publication. Authorship of publications resulting from
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this study will be based on the guidelines on authorship, such as those described in the ICMJE
Recommendations for the Conduct, Reporting, Editing and Publication of Scholarly Work in
Medical Journals, which state that the named authors must have made a significant contribution to
the conception or design of the work; or the acquisition, analysis, or interpretation of the data for
the work; and drafted the work or revised it critically for important intellectual content; and given
final approval of the version to be published; and agreed to be accountable for all aspects of the
work in ensuring that questions related to the accuracy or integrity of any part of the work are
appropriately investigated and resolved.
Registration of Clinical Studies and Disclosure of Results
The Sponsorwill register and disclose the existence of and the results of clinical studies as required
by law.
The summary of the results from the Week 24 Database Lock (DBL), will be submitted to the EU
database within one year of the data analysis date.
The disclosure of the final study results will be performed after the end of study in order to ensure
the statistical analyses are relevant.
10.5.8. 
Data Quality Assurance
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, and direct
transmission of clinical laboratory data from a central laboratory into the Sponsor's data base.
Written instructions will be provided for collection, handling, storage, and shipment of samples.
Guidelines for eCRF completion will be provided and reviewed with study site personnel before
the start of the study.
The Sponsor will review eCRF 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.
10.5.9. 
Case Report Form Completion
Case report forms are prepared and provided by the Sponsor for each participant in electronic
format. All data relating to the study must be recorded in eCRF. All eCRF 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 eCRF are accurate and correct.
The study data will be transcribed by study site personnel from the source documents onto an
eCRF, if applicable.  Study-specific data will be transmitted in a secure manner to the Sponsor.
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Worksheets may be used for the capture of some data to facilitate completion of the eCRF. Any
such worksheets will become part of the participant's source documents. Data must be entered into
the eCRF in English. The eCRF must be completed as soon as possible after a participant visit and
the forms should be available for review at the next scheduled monitoring visit.
All participative 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 electronic data capture (eDC) tool. If corrections to
an eCRF are needed after the initial entry into the eCRF, this can be done in either of the following
ways:
Investigator and study site personnel can make corrections in the eDC tool at their own
initiative or as a response to an auto query (generated by the eDC tool).
Sponsor or Sponsor delegate can generate a query for resolution by the investigator and study
site personnel.
10.5.10. 
Source Documents
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:
participant 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; concomitant medication; intervention
receipt/dispensing/return records; study intervention administration information; and date of study
completion and reason for early discontinuation of study intervention  or withdrawal from the
study, if applicable.
The author of an entry in the source documents should be identifiable. Given that PROs are reports
of a patient's health condition that come directly from the patient, without interpretation by a
clinician or anyone else, the responses to PRO measures entered by trial participants into source
records cannot be overridden by site staff or investigators.
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 minimum source documentation requirements for Section 5.1, Inclusion Criteria and
Section 5.2, Exclusion Criteria that specify a need for documented medical history are as follows:
Referral letter from treating physician or
Complete history of medical notes at the site
Discharge summaries
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Inclusion and exclusion criteria not requiring documented medical history must be verified at a
minimum by participant interview or other protocol required assessment (eg, physical
examination, laboratory assessment) and documented in the source documents.
An electronic source (eSource) 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 eSource is utilized, references made to
the eCRF in the protocol include the eSource system but information collected through eSource
may not be limited to that found in the eCRF.
10.5.11. 
Monitoring
The Sponsor will use a combination of monitoring techniques: central, remote, or 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 the data entered into the eCRF with the source documents
(eg, hospital/clinic/physician’s office medical records). The nature and location of all source
documents will be identified to ensure that all sources of original data required to complete the
eCRF 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.
10.5.12. 
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. Participant privacy must, however, be
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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 ofany 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.
10.5.13. 
Record Retention
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all eCRF
and all source documents that support the data collected from each participant, 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. For trials performed under Regulation [EU] No. 536/2014, the
Sponsor and the investigator shall archive the content of the clinical trial master file for at least
25 years after the end of the clinical trial.
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.
If it becomes necessary for the Sponsor or the appropriate regulatory authority to review any
documentation relating to this study, the investigator/institution must permit access to such reports.
10.5.14. 
Study and Site Start and Closure
First Act of Recruitment
The first participant screened is considered the first act of recruitment and it becomes the study
start date.
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Study/Site 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.
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 participants by the investigator
Discontinuation of further study intervention development
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10.6. Appendix 6: Adverse Events, Serious Adverse Events, Product Quality
Complaints, and Other Safety Reporting: Definitions and Procedures for
Recording, Evaluating, Follow-up, and Reporting
10.6.1. 
Adverse Event Definitions and Classifications
Adverse Event
An AE is any untoward medical occurrence in a clinical study participant administered a
pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have
a causal relationship with the intervention. 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 All Adverse Events
under Section  8.3.1, Time Period and Frequency for Collecting Adverse Events and Serious
Adverse Events Information, for time of last AE recording).
For combination products with a device constituent, AEs include those resulting from insufficient
or inadequate instructions for use, deployment, implantation, installation, or operation, or any
malfunction of the device. It includes any AE resulting from use error or from intentional misuse
of the investigational device.
Serious Adverse Event
A 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 participant 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*
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*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 participant 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 intervention 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).
For combination products with a device constituent, SAEs include adverse device effects that
resulted in any of the consequences characteristic of an SAE. An unanticipated serious adverse
device effect is a serious adverse device effect which by its nature, incidence, severity or outcome
has not been identified in the current version of the risk analysis report (see Section 2.3, Benefit-
Risk Assessment).
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 IB.
10.6.2. 
Attribution Definitions
Assessment of Causality
The causal relationship to study intervention is determined by the Investigator. The following
selection should be used to assess all AEs.
Related
There is a reasonable causal relationship between study intervention administration and the AE.
Not Related
There is not a reasonable causal relationship between study intervention administration and the
AE.
The term "reasonable causal relationship" means there is evidence to support a causal relationship.
10.6.3. 
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.
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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 participant (eg, laboratory abnormalities).
10.6.4. 
Special Reporting Situations
Safety events of interest on a Sponsorstudy intervention in an interventional studythat may require
expedited reporting or safety evaluation include, but are not limited to:
Overdose of a Sponsor study intervention
Suspected abuse/misuse of a Sponsor study intervention
Accidental or occupational exposure to a Sponsor study intervention
Any failure of expected pharmacologic action (ie, lack of effect if used according to the local
label) of a Sponsor study intervention (to be reported as a PQC for marketed products)
Unexpected therapeutic or clinical benefit from use of a Sponsor study intervention
Medication error, intercepted medication error, or potential medication error involving a
Johnson & Johnson medicinal product (with or without patient exposure to the Johnson &
Johnson medicinal product, eg, product name confusion, product label confusion, intercepted
prescribing or dispensing errors)
Exposure to a Sponsor study intervention from breastfeeding
Participant pregnancy or participant partner(s) pregnancy
Special reporting situations should be recorded in the eCRF. Any special reporting situation that
meets the criteria of an SAE should be recorded on the SAE page of the eCRF.
10.6.5. 
Procedures
All Adverse Events
All AEs, regardless of seriousness, severity, or presumed relationship to study intervention, must
be recorded using medical terminology in the source document and the eCRF. 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 eCRF 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.
For all studies with an outpatient phase, including open-label studies, the participant 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:
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Study number
Statement, in the local language(s), that the participant 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 personnel only)
Site number
Participant number
Any other information that is required to do an emergency breaking of the blind
Serious Adverse Events
All SAEs that have not resolved by the end of the study, or that have not resolved upon  the
participant's discontinuation from 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 intervention or to factors unrelated
to study conduct
It becomes unlikely that any additional information can be obtained (participant or health care
practitioner refusal to provide additional information, lost to follow-up after demonstration of
due diligence with follow-up efforts)
Any event requiring hospitalization (or prolongation of hospitalization) that occurs during
participation in the 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 eCRF).
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.
The cause of death of a participant in a study within 12 weeks of the last dose of study intervention,
whether or not the event is expected or associated with the study intervention, is considered an
SAE.
Information regarding SAEs will be transmitted to the sponsor using an SAE reporting form, which
must be completed and signed by a physician from the study site, and transmitted in a secure
manner to the sponsor within 24 hours. The initial and follow-up reports of an SAE should be
made by facsimile (fax). Telephone reporting should be the exception and the reporter should be
asked to complete the appropriate form(s) first.
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10.6.6. 
Product Quality Complaint Handling
Definition
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, reliability, or performance of a distributed product, including its labeling, drug delivery
system, or package integrity. A PQC may have an impact on the safety and efficacy of the product.
In addition, it includes any technical complaints, defined as any complaint that indicates a potential
quality issue during manufacturing, packaging, release testing, stability monitoring, dose
preparation, storage or distribution of the product or the drug delivery system.
This definition includes any PQC related to a device constituent in a combination product,
including those used in the administration of the study intervention or the comparator. A device
deficiency is an inadequacy of a device with respect to its identity, quality, durability, reliability,
safety, or performance. Device deficiencies include malfunctions, use errors, and inadequate
labeling.
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.
A sample of the suspected product should be maintained under the correct storage conditions until
a shipment request is received from the Sponsor.
10.6.7. 
Contacting Sponsor Regarding Safety, Including Product Quality
The names (and corresponding telephone numbers) of the individuals who should be contacted
regarding safety issues, PQC, or questions regarding the study are listed in the Contact Information
page(s), which will be provided as a separate document.
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10.7. Appendix 7: Contraceptive and Barrier Guidance
Participants must follow contraceptive measures as outlined in Section  5.1, Inclusion Criteria.
Pregnancy information will be collected and reported as noted in Section 8.3.5, Pregnancy and
Appendix 6 Adverse Events, Serious Adverse Events, Product Quality Complaints, and Other
Safety Reporting: Definitions and Procedures for Recording, Evaluating, Follow-up, and
Reporting.
Definitions
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming postmenopausal unless
permanently sterile (see below).
Woman Not of Childbearing Potential
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 (HRT), however in the absence of
12 months 
of 
amenorrhea, 
a 
single 
FSH 
measurement 
is 
insufficient.
If there is a question about menopausal status in women on HRT, the woman will be required
to use one of the non-estrogen-containing hormonal highly effective contraceptive methods if
she wishes to continue HRT during the study.
permanently sterile (for the purpose of this study)
Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral
oophorectomy. Has congenital abnormality resulting in sterility.
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.
Contraceptive (birth control) use by men or women should be consistent with local regulations
regarding the acceptable methods of contraception for those participating in clinical studies.
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 participants in
clinical studies.
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Examples of Contraceptives for Female Participants
EXAMPLES OF CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE:
USER INDEPENDENT
Highly Effective Methods That Are User Independent Failure rate of <1% per year when used
consistently and correctly.
Implantable progestogen-only hormone contraception associated with inhibition of ovulationb
Intrauterine device (IUD)
Intrauterine hormone-releasing system (IUS)
Bilateral tubal occlusion
Azoospermic partner (vasectomized or due to medical cause)
(Vasectomized partner is a highly effective contraceptive method provided that the partner is the
sole sexual partner of the woman of childbearing potential and the absence of sperm has been
confirmed. If not, additional highly effective method of contraception should be used.
Spermatogenesis cycle is approximately 74 days.)
USER DEPENDENT
Highly Effective Methods That Are User Dependent Failure rate of <1% per year when used
consistently and correctly.
Combined (estrogen- and progestogen-containing) hormonal contraception associated with
inhibition of ovulationb
oral
intravaginal
transdermal
injectable
Progestogen-only hormone contraception associated with inhibition of ovulationb
oral
injectable
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 intervention.
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 participant.)
NOT ALLOWED AS SOLE METHOD OF CONTRACEPTION DURING THE STUDY (not
considered to be highly effective - failure rate of 1% per year)
Progestogen-only oral hormonal contraception where inhibition of ovulation is not the primary
mode of action.
Male or female condom with or without spermicidec
Cap, diaphragm, or sponge with spermicide
A combination of male condom with either cap, diaphragm, or sponge with spermicide (double-
barrier methods)c
Periodic abstinence (calendar, symptothermal, post-ovulation methods)
Withdrawal (coitus-interruptus)
Spermicides alone
Lactational amenorrhea method (LAM)
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a) 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 participants in
clinical studies.
b) Hormonal contraception may be susceptible to interaction with the study intervention, which may
reduce the efficacy of the contraceptive method. In addition, consider if the hormonal contraception
may interact with the study intervention.
c) Male condom and female condom should not be used together (due to risk of failure with friction).
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10.8. Appendix 8: Liver Safety: Suggested Actions and Follow-up Assessments
10.8A. STOPPING ALGORITHM
Liver Chemistry Stopping Criteria and Increased Monitoring Algorithm
Study intervention will be discontinued for a participant if liver chemistry stopping criteria are
met.
Abbreviations: ALT = alanine transaminase; AST = aspartate transaminase, INR = international normalized ratio;
SAE = serious adverse event; ULN = upper limit of normal, Tbili = Total bilirubin.
Refer to Appendix [8B]: Follow-up Assessments.
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Liver Chemistry Increased Monitoring Algorithm with Continued Study Intervention for
Participants with ALT or AST ≥3xULN but <8xULN
Study intervention will be discontinued for a participant if liver chemistry stopping criteria are
met.
Abbreviations: ALT = alanine transaminase; AST = aspartate transaminase, INR = international normalized ratio; SAE = serious adverse event;
ULN = upper limit of normal, Tbili = Total bilirubin.
Refer to Appendix [8B]: Follow-up Assessments.
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B. FOLLOW-UP ASSESSMENTS
Liver Safety: Follow-up assessments
Phase 3-4 liver chemistry stopping criteria are designed to assure participant safety and to evaluate
liver event etiology.
Phase 3-4 Liver Chemistry Stopping Criteria and Follow-Up assessments
Liver Chemistry Stopping Criteria
ALT or AST- 
absolute
ALT or AST 8xULN
ALT or AST- 
Increase 
ALT or AST 5xULN but <8xULN persists for 2 weeks
ALT or AST 3xULN but <5xULN persists for 4 weeks
Bilirubin1, 2 
ALT or AST  3xULN and total bilirubin 2xULN
INR2 
ALT or AST 3xULN and international normalized ratio (INR) >1.5
Cannot 
Monitor 
ALT or AST 5xULN but <8xULN and cannot be monitored weekly for
2 weeks
ALT or AST 3xULN but <5xULN and cannot be monitored weekly for
4 weeks
Symptomatic3 ALT or AST  3xULN associated with symptoms (new or worsening)
believed to be related to liver injury or hypersensitivity
Suggested Actions, Monitoring, and Follow up Assessments
Actions 
Follow Up Assessments
Immediately discontinue study 
intervention  
Report the event to the Sponsor within  
24hours 
Complete the hepatic event form and 
complete an SAE eCRF if the event 
also met the criteria for an SAE2 
Perform follow-up assessments as 
described in the Follow up Assessment 
column  
Monitor the participant until liver 
chemistry test abnormalities resolve, 
stabilize, or return to baseline 
MONITORING: 
If ALT or AST 3xULN AND total 
bilirubin 2xULN or INR >1.5: 
Repeat liver chemistry tests (include 
ALT, aspartate transaminase [AST], 
alkaline phosphatase, total bilirubin,
direct bilirubin, and INR) and perform
Viral hepatitis serology4
Obtain blood sample for pharmacokinetic
(PK)5 analysis within 1 week of the event of
ALT or AST 3×ULN.
Obtain serum creatine phosphokinase (CPK),
lactate dehydrogenase (LDH), gamma-
glutamyltransferase [GGT], and glutamate
dehydrogenase [GLDH], and serum albumin
Fractionate bilirubin, if total bilirubin 2xULN
Obtain complete blood count with differential
to assess eosinophilia
Record the appearance or worsening of clinical
symptoms of liver injury, or hypersensitivity,
on hepatic event form
Record use of concomitant medications
(including acetaminophen, herbal remedies,
recreational drugs, and other over-the-counter
medications)
Record alcohol use on the hepatic event form
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liver event follow-up assessments
within 24 hours
Monitor participant twice weekly until
liver chemistry test abnormalities
resolve, stabilize, or return to baseline
A specialist or hepatology consultation
is recommended
If ALT or AST  3xULN AND total
bilirubin <2xULN and INR 1.5:
Repeat liver chemistry tests (include
ALT, AST, alkaline phosphatase, total
bilirubin, direct bilirubin, and INR) and
perform liver chemistry follow-up
assessments within 24 to 72 hours
Monitor participants weekly until liver
chemistry abnormalities resolve,
stabilize, or return to baseline
RESTART
Do not restart participant with study
intervention unless allowed per
protocol and Sponsor approval is
granted
If restart is either not allowed per
protocol or not granted, permanently
discontinue study intervention. The
participant may continue in the study
for any protocol specified follow up
assessments
If ALT or AST 3xULN AND total bilirubin
2xULN or INR >1.5 obtain the following in
addition to the assessments listed above:
Anti-nuclear antibody, anti-smooth muscle
antibody, Type 1 anti-liver kidney microsomal
antibodies, and quantitative total
immunoglobulin G (IgG) or gamma globulins
Serum acetaminophen adduct assay, when
available, to assess potential acetaminophen
(paracetamol) contribution to liver injury in
participants with definite or likely
acetaminophen use in the preceding week
Liver imaging (ultrasound, magnetic
resonance, or computerized tomography) to
evaluate liver disease; complete liver Imaging
form
Liver biopsy may be considered and discussed
with local specialist if available, for instance:
In patients when serology raises the
possibility of autoimmune hepatitis (AIH)
In patients when suspected drug-induced
liver injury (DILI) progresses or fails to
resolve on withdrawal of study intervention
In patients with acute or chronic atypical
presentation
If liver biopsy conducted record in eCRF
1. Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not
immediately available, discontinue study intervention if ALT or AST 3xULN and total bilirubin 2xULN.
Additionally, if serum bilirubin fractionation testing is unavailable, record the absence/presence of detectable
urinary bilirubin on dipstick which is indicative of direct bilirubin elevations suggesting liver injury.
2. All events of ALT or AST 3xULN and total bilirubin 2xULN or ALT or AST 3xULN and INR >1.5 (if
measured), may indicate severe liver injury (possible ‘Hy’s Law’) and must be reported to sponsor in an
expedited manner using the SAE form, even before all other possible causes of liver injury have been excluded.
A confirmed Hy's law case must be reported as an SAE. The INR stated threshold value will not apply to
participants receiving anticoagulants.
3. New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right upper
quadrant pain or tenderness, or jaundice) or hypersensitivity (such as fever, rash or eosinophilia).
4. Includes hepatitis A immunoglobulin M (IgM) antibody; HBsAg and HBcAb; hepatitis C RNA; hepatitis C
antibody, cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable,
heterophile antibody or monospot testing); and hepatitis E IgM antibody.
5. PK sample may not be required for participants known to be receiving placebo or non-comparator interventions.
Record the date/time of the PK blood sample draw and the date/time of the last dose of study intervention prior
to the PK blood sample draw on the eCRF. If the date or time of the last dose is unclear, provide the participant’s
best approximation. If the date/time of the last dose cannot be approximated OR a PK sample cannot be collected
in the time period indicated above, do not obtain a PK sample. Instructions for sample handling and shipping are
in the laboratory Manual.
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A participant who met liver chemistry stopping criteria cannot restart study intervention unless all
of the following conditions are met:
Sponsor approval is granted (as described below)
Institutional Review Board/Independent Ethics Committee (IRB/IEC) has been consulted
The participant has been informed of the potential risks and has consented to resume study
intervention
If sponsor approval to restart/rechallenge the participant with study intervention is not granted,
then the participant must permanently discontinue study intervention and may continue in the
study for protocol-specified follow-up assessments.
Restart Following Transient Resolving Liver Chemistry Events Not Related to Study
Intervention
Restart refers to resuming study intervention following liver chemistry events for which there
are clear underlying causes (other than DILI) (eg, biliary obstruction, pancreatic events,
hypotension, acute viral hepatitis). Furthermore, restart is not permitted following liver
stopping event when the underlying cause was alcohol-related hepatitis. Approval by the
sponsor for study intervention restart can be considered when:
The investigator requests consideration for study intervention restart if liver chemistry
events have a clear underlying cause (eg, biliary obstruction, pancreatic events,
hypotension, acute viral hepatitis) and liver chemistry tests have improved to normal or
are within 1.5 x baseline and ALT or AST <3xULN.
The principle investigator (PI) requests consideration of rechallenge with study
intervention for a participant who is receiving compelling benefit with study intervention
that exceed risks and for whom no effective alternative therapy exists
Possible DILI has been excluded by the investigator and the study team. This includes
the absence of markers of hypersensitivity (otherwise unexplained fever, rash,
eosinophilia). Where a study intervention has an identified genetic marker associated with
liver injury (eg, lapatinib, abacavir, amoxicillin/clavulanate), the presence of the marker
should be excluded.
There is no evidence of alcoholic-related hepatitis.
IRB/IEC has been consulted regarding restart ofstudy intervention.
If restart of study intervention is approved by the sponsor in writing:
The participant must be provided with a clear description of the possible benefits and risks of
study intervention administration including the possibility of recurrent, more severe liver
injury, liver transplantation or death.
The participant must provide signed informed consent specifically for the restart of study
intervention. Documentation of informed consent must be recorded in the participant source
documents.
Study intervention must be administered at the dose specified by the sponsor.
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Participants approved by the sponsor for restart of study intervention must return to the clinic
twice a week for liver chemistry tests until stable liver chemistry tests have been demonstrated
and then standard laboratory monitoring may resume as per protocol.
If the participant meets protocol-defined liver chemistry stopping criteria after study
intervention restart, study intervention should be permanently discontinued.
The sponsor, Medical Monitor, and the IRB/IEC, must be informed of the outcome for the
participant following study intervention restart.
The sponsor must be notified of any AEs.
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10.9. Appendix 9: Study Conduct During a Natural Disaster
GUIDANCE ON STUDY CONDUCT DURING THE COVID-19 PANDEMIC
It is recognized that the COVID-19 pandemic may have an impact on the conduct of this clinical
study due to, for example, isolation or quarantine of participants and study site personnel; travel
restrictions/limited access to public places, including hospitals; study site personnel being
unavailable, isolated, or reassigned to critical tasks.
The sponsor is providing options for study related participant management in the event of
disruption to the conduct of the study. This guidance does not supersede any local or government
requirements or the clinical judgement of the investigator to protect the health and well-being of
participants and site staff. If, at any time, a participant’s travel to the study site is considered to be
dangerous, study participation may be interrupted, and study follow-up conducted. If the
participant’s safety is considered to be at unacceptable risk and it becomes necessary to discontinue
participation in the study, the procedures outlined in the protocol for discontinuing study
intervention will be followed.
If, as a result of the COVID-19 pandemic scheduled visits cannot be conducted in person at the
study site, they will be performed to the extent possible remotely/virtually or delayed until such
time that on-site visits can be resumed. At each contact, participants will be interviewed to collect
safety data. Key efficacy endpoint assessments should be performed if required and as feasible.
Participants will also be questioned regarding general health status to fulfill any physical
examination requirement.
Every effort should be made to adhere to protocol-specified assessments for participants on study
intervention, including follow up. Modifications to protocol-required assessments may be
permitted using the examples contained in this appendix, after consultation with the participant,
investigator, and the sponsor.
If the participant has tested positive for the COVID-19 pandemic, the investigator should contact
the sponsor’s medical officer or designee to discuss plans for administration of study intervention,
performing study assessments, and follow-up. Modifications made to the study conduct as a result
of the COVID-19 pandemic should be summarized in the clinical study report.
ADDITIONAL ELEMENTS, WHERE APPLICABLE:
Certain protocol-mandated visits to the study site may not be possible during the COVID-19
pandemic. Therefore, temporary measures may be implemented if considered appropriate by
the Sponsor and investigator to maintain continuity of patient care and study integrity. Certain
measures, such as those listed below, may be necessary and should be instituted in accordance
with applicable (including local) laws, regulations, guidelines, and procedures:
remote (eg, by phone/telemedicine) or in-person, off-site (eg, in-home) interactions
between site staff (or designees) and patients for study procedures eg, those related to
safety monitoring/efficacy evaluation/study intervention storage and administration
(including training where pertinent)
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procurement of study intervention by patients (or designee) or shipment of study
intervention from the study site directly to patients for at-home administration
laboratory assessments using a suitably accredited local laboratory; for selected measures
(eg, urine pregnancy), home testing may be employed
Missed assessments/visits will be captured in the clinical trial management system for
protocol deviations. Discontinuations of study interventions and withdrawal from the study
should be documented with the prefix “COVID-19-related” in the eCRF.
other relevant study data elements impacted by the pandemic should also be documented
as “COVID-19-related” in eCRFs and/or other study systems, as directed by detailed
Sponsor guidance. These may include missed/delayed/modified study visits or
assessments/dosing, and instances where temporary measures such as those above are
implemented.
The Sponsor will evaluate the totality of impact of COVID-19 on collection of key study data
and additional data analyses will be outlined in study SAP(s).
Precaution: for those who may carry a higher risk for severe COVID-19 illness (eg, those aged
over 65 years), follow guidance from local health authorities when weighing the potential
benefits and risks of enrolling in the study, and during participation in the study.
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10.10. Appendix 10: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located
directly before the Table of Contents.
Amendment 1 (12 May 2022)
Overall Rationale for the Amendment:The overall rationale for the amendment is to add a long-term
extension to this study. Additional changes are related to sites impacted by Natural Disaster or Major
Disruption, clarifications, and updates to align with current sponsor study conventions.
Section Number 
and Name
Description of Change
Rationale:A one-year long-term extension is being added for this study to evaluate longer term
improvements in signs and symptoms of psoriatic arthritis (PsA).
Schedule of Activities and 
anywhere study period is 
mentioned
The final study visit is now to occur at Week 112, after treatment
through Week 100. Study assessments were added through Week 112.
Rationale:Due to major disruptions in some countries where the study is being conducted, replacing
participants who are forced to discontinue from the study due to such major disruptions (eg, Natural
Disaster or Other Major Disruption) is being allowed.
4.1 Overall Design  
9.2 Sample Size
Determination
9.3. Population for Analysis 
Sets 
9.4.2 Primary Endpoint 
Participants impacted by major disruptions may be replaced.
Modified Full Analysis Set: All participants who were randomized,
excluding participants from sites rendered unable to support key study
operations due to major disruptions (eg, Natural Disaster or Other Major
Disruption). Details will be provided in the SAP.
Details for intercurrent events and missing data due to major disruptions
(eg, Natural Disaster or Other Major Disruption) are added.
Rationale:Clarifying the inclusion criterion regarding prior treatment failure.
5.1, Inclusion criteria, #5a 
Lack of benefit ….after at least 12 weeks of etanercept, adalimumab,
golimumab, or certolizumab pegol therapy (or their biosimilars) and/or
at least a 14-week dosage regimen (ie, at least 4 doses) of infliximab
Rationale:Correcting exclusion criterion that was worded incorrectly; it was only meant to address
hypersensitivity (and not intolerance which is covered in the inclusion criteria).
5.2, Exclusion Criteria, #23 
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
Rationale:The exclusion criterion regarding hepatitis C virus screening has been clarified to be
consistent with current practice guidelines (bold text added).
5.2 Exclusion Criteria, #41 
Tests positive for hepatitis B virus (HBV) infection (see Appendix 4 in
Section 10) or is seropositive for antibodies to hepatitis C virus
(HCV) at screening, unless the participant meets 1 of the following
conditions:
i. Has a history of successful treatment (defined as being
negative for HCV RNA at least 12 weeks after completing
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Section Number 
and Name
Description of Change
antiviral treatment) and has a negative HCV RNA test
result at screening, OR
ii. While seropositive has a negative HCV RNA test result at
least 12 weeks prior to screening and a negative HCV
RNA test result at screening.
Rationale: The emergency use of treatment for COVID-19 is now allowed.
6.8.4 Biologic Agents, 
Cytotoxic Drugs, JAK 
Inhibitors, or 
Investigational Agents 
The concomitant use of …is not allowed, with the exception of limited
emergency use for treatment of COVID-19 infection. Continuation
of study intervention in such cases should be discussed with the
Sponsor’s medical monitor.
Rationale:Clarification for when the eC-SSRS assessment should be performed is being added as the
timing was not described consistently in the original protocol.
8.2.7, Suicidal Ideation and 
Behavior Risk Monitoring 
At the screening visit, the eC-SSRS should be completed as the first
assessment after signing informed consent and joint assessment, but
before any other tests, procedures, or other consultations. For
subsequent visits, the eC-SSRS should be completed after all PROs and
before any other tests, procedures, or other consultations.
Schedule of Activities, 
footnote h  
At the screening visit (after signing informed consent), the eC-SSRS
should be performed after the joint assessment. At Week 0/baseline and
at all post-screening baseline visits, the eC-SSRS should be the first
assessment/questionnaire the patient completes completed after all
PRO, but before other tests, procedures or other consultations.
Rationale:Correction that measuring C-reactive Protein (CRP) is not optional.
Schedule of Assessments, 
footnote t
Removing footnote t for CRP assessment.
Rationale:Adding a physical examination at Week 52, which was accidentally omitted.
Schedule of Assessments 
Adding physical examination at Week 52
Rationale:For the primary endpoint, language referring to “treatment failure” has been updated.
1.1 Synopsis, Statistical 
Methods 
9.4.2 Primary Endpoint 
….This endpoint will be analyzed based on the estimands defined in
Section 9 under which the intercurrent event of treatment failure prior to
Week 24 will be treated as non response for the primary analysis,
regardless of the observed ACR 20 response status.
Participants with an ICE in categories 1-3 will follow the composite
strategy, where participants who experience them prior to Week 24 will
be considered treatment failures and will be treated as non-responders
Rationale:The timepoint for recommended changes for certain concomitant medications was revised
from Week 60 to Week 52, since Week 52 is the final efficacy visit for Year 1 of this 2-year study.
Inclusion Criteria, #11  
Use of complementary therapies
Rationale:Correcting administrative information.
Cover page 
Correcting the IND # on cover page from 105044 to 124177; also
adding a version number to the document identifier on the cover page
which was accidentally omitted in the prior version.
Rationale: Several updates were made to align with Janssen’s current protocol language, including
clarifications in the instructions for tuberculosis (TB) testing and guidance for enrollment of participants
with prior TB infection, and expedited reporting of a participant pregnancy or participant partner(s)
pregnancy.  These updates are necessary to gain alignment with updated CDC guidelines and continue
to ensure optimal participant safety is maintained.
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Section Number 
and Name
Description of Change
5.4 Screen Failures 
A participant who might be is considered a screen failure due to
circumstances unrelated to the protocol (eg, site closure due to COVID-
19, other unforeseen circumstances resulting in site closure, etc)
could be eligible to be for screening and rescreeninged if applicable.
7.2 Participant 
Discontinuation/Withdrawal
From the Study
(added as reason for withdrawal) Sponsor decision
10.6.4 Special Reporting 
Situations 
(added)
Participant pregnancy or participant partner(s) pregnancy
Appendix 7: Contraceptive 
and Barrier Guidance 
(added, under definition of permanently sterile)Has congenital
abnormality resulting in sterility.
Appendix 8: Liver Safety: 
Suggested actions and
Follow-up Assessments
Updates made to clarify steps for restarting of study intervention.
Appendix 9: Study Conduct 
During a Natural Disaster 
Updates made to align with current COVID-19-related
recommendations.
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11. 
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INVESTIGATOR AGREEMENT
I have read this protocol and agree that it contains all necessary details for carrying out this study. I will
conduct the study as outlined herein and will complete the study within the time designated.
I will provide copies of the protocol and all pertinent information to all individuals responsible to me who
assist in the conduct of this study. I will discuss this material with them to ensure that they are fully informed
regarding the study intervention, the conduct of the study, and the obligations of confidentiality.
Coordinating Investigator (where required):
Name (typed or printed):
Institution and Address:
Signature: 
Date:
(Day Month Year)
Principal (Site) Investigator:
Name (typed or printed):
Institution and Address:
Telephone Number:
Signature: 
Date:
(Day Month Year)
Sponsor's Responsible Medical Officer:
Name (typed or printed): 
Institution: 
Janssen Research & Development
Signature: electronic signature appended at the end of the protocol 
Date:
(Day Month Year)
Note: If the address or telephone number of the investigator changes during the study, written notification will be
provided by the investigator to the sponsor, and a protocol amendment will not be required.
PPD
NCT04936308

Signature
User 
Date 
Reason
 
09-Sep-2024
14:13:35
(GMT)
Document Approval
PPD
NCT04936308