A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of Guselkumab Subcutaneous Induction Therapy in Participants With Moderately to Severely Active Ulcerative Colitis
Phase: PHASE3
Conditions: Colitis, Ulcerative
Sponsor: Janssen Research & Development, LLC

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Status: Approved,  Date: 13 May 2025
Janssen Research & Development*
Clinical Protocol
Protocol Title
A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to
Evaluate the Efficacy and Safety of Guselkumab Subcutaneous Induction Therapy in Participants
with Moderately to Severely Active Ulcerative Colitis
ASTRO
Short Title
A Phase 3 Study to Evaluate the Efficacy and Safety of Guselkumab Subcutaneous Induction
Therapy in Participants with Moderately to Severely Active Ulcerative Colitis
Protocol CNTO1959UCO3004; Phase 3
Version: Amendment4
CNTO1959 (guselkumab)
*Janssen Research & Development is a global organization that operates through different legal entities in
various countries. Therefore, the legal entity acting as the sponsor for Janssen Research & Development
studies may vary, such as, but not limited to Janssen Biotech, Inc.; Janssen Products, LP; Janssen
Biologics, BV; Janssen-Cilag International NV; Janssen, Inc; Janssen Pharmaceutica NV; Janssen
Sciences Ireland UC; Janssen Biopharma Inc., or Janssen Research & Development, LLC. The term
“sponsor” is used throughout the protocol to represent these various legal entities; the sponsor is
identified on the Contact Information page that accompanies the protocol.
United States (US)sites of this study will be conducted under US Food & Drug Administration
Investigational New Drug (IND) regulations (21 CFR Part 312).
Studies conducted at sites in the European Economic Area (EEA) will be conducted under
Regulation [EU] No 536/2014.
Regulatory Agency Identifier Number(s)
IND: 140330
EU TRIAL NUMBER: 2023-504719-34
Status: 
Approved
Document Date: 
13 May2025
Prepared by: 
Janssen Research & Development, LLC
EDMS Number: 
EDMS-RIM-583808, 5.0
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory
requirements.
Confidentiality Statement
The information provided herein is considered trade secrets, commercial or financial, or privileged or confidential information that
we customarily hold close and treat as confidential. The information is being provided under the assurance that the recipient will
maintain the confidentiality of the information under the applicable statutes, regulations, rules, case law, contractual provisions,
protective orders, or as otherwise necessary to protect the information from disclosure.  The recipient agrees and acknowledges
that release of information considered trade secrets, commercial or financial, or privileged or confidential will result in competitive
harm and, as such, the information provided herein is exempt from disclosure under the Freedom of Information Act (“FOIA”), or
other similar law or regulation.  Particularly, the information shall not be utilized in any AI solutions, including GenAI, without
Company's prior written approval.
NCT05528510

CNTO1959  (guselkumab)
Clinical Protocol CNTO1959UCO3004 Amendment 4
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Status: Approved,  Date: 13 May 2025
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document 
Date
Amendment 4  
13 May2025
Amendment 3 
21 October 2024
Amendment 2  
16 August 2022
Amendment 1 
2 May 2022
Original Protocol 
11 February 2022
Amendment 4 (13 May 2025)
Overall Rationale for the Amendment:
To align with a health authority commitment to assess long-term safety outcomes, the protocol was updated
to include additional hematology, chemistry, and endoscopy assessments.
The changes made to the clinical protocol CNTO1959UCO3004 as part of Protocol Amendment 4 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 10.12 Appendix 12: Protocol Amendment History.
Section Number 
and Name
Description of Change 
Brief Rationale
1.2 Schema 
Updated schema to add endoscopy every 48 weeks
beginning at Week 96.
Schema updated to reflect
additional endoscopy assessments.
1.3 Schedule of 
Activities, Table 2: 
Schedule of 
Activities:
Extension
Treatment Period
Week 28 Through
Week 96
Added endoscopy assessment at Week 96 with
corresponding footnote h, i, and j updated for
endoscopy, partial Mayo score, and biopsy.
To align with the health authority
commitment to assess long-term
safety outcomes by adding
hematologyand chemistryevery 16
weeks, and endoscopy assessments
every 48 weeks beginning at Week
96.
1.3 Schedule of
Activities, Table 3:
Schedule of
Activities:
Extension
Treatment Period
Week 100 Through
Week 248
Added endoscopy assessment at Weeks 144,
192, 240, and ED.
Liver function tests replaced with hematology
and chemistry assessments.
4.1 Overall design  
Endoscopy added to safety assessments.
8.1.1 Mayo Score
8.2 Safety
assessments
4.2.1 Study-Specific 
Ethical Design 
Considerations
Total blood volume collected changed from 308
mL to 326 mL.
Updated to reflect additional
volume required for additional
assessments.
8 Study
Assessments and
Procedures
Throughout the 
protocol 
Minor grammatical, formatting, or spelling changes
were made
Improve clarity in the protocol.

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Clinical Protocol CNTO1959UCO3004 Amendment 4
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TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................................... 2
TABLE OF CONTENTS ............................................................................................................................... 3
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 6
1. 
PROTOCOL SUMMARY..................................................................................................................... 7
1.1. 
Synopsis........................................................................................................................................... 7
1.2. 
Schema.......................................................................................................................................... 12
1.3. 
Schedule of Activities (SoA)........................................................................................................... 13
2. 
INTRODUCTION................................................................................................................................ 25
2.1. 
Study Rationale.............................................................................................................................. 25
2.2. 
Background.................................................................................................................................... 26
2.3. 
Benefit-Risk Assessment............................................................................................................... 27
2.3.1. 
Risks for Study Participation....................................................................................................... 27
2.3.2. 
Benefits for Study Participation .................................................................................................. 29
2.3.3. 
Benefit-Risk Assessment for Study Participation ....................................................................... 30
3. 
OBJECTIVES AND ENDPOINTS ..................................................................................................... 31
4. 
STUDY DESIGN ................................................................................................................................ 33
4.1. 
Overall Design................................................................................................................................ 33
4.2. 
Scientific Rationale for Study Design............................................................................................. 35
4.2.1. 
Study-Specific Ethical Design Considerations ........................................................................... 36
4.3. 
Justification for Dose...................................................................................................................... 37
4.4. 
End of Study Definition................................................................................................................... 37
5. 
STUDY POPULATION ...................................................................................................................... 38
5.1. 
Inclusion Criteria............................................................................................................................ 38
5.2. 
Exclusion Criteria........................................................................................................................... 41
5.3. 
Lifestyle Considerations................................................................................................................. 46
5.4. 
Screen Failures.............................................................................................................................. 46
5.5. 
Criteria for Temporarily Delaying Administration of Study Intervention ......................................... 47
6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY............................................................ 48
6.1. 
Study Intervention(s) Administered................................................................................................ 48
6.1.1. 
Self-administration of Study Intervention.................................................................................... 49
6.1.2. 
Combination Products ................................................................................................................ 50
6.2. 
Preparation/Handling/Storage/Accountability ................................................................................ 51
6.3. 
Measures to Minimize Bias: Randomization and Blinding............................................................. 52
6.4. 
Study Intervention Compliance...................................................................................................... 53
6.5. 
Dose Modification........................................................................................................................... 54
6.5.1. 
Rescue Medication ..................................................................................................................... 54
6.6. 
Continued Access to Study Intervention After the End of the Study ............................................. 54
6.7. 
Treatment of Overdose .................................................................................................................. 54
6.8. 
Concomitant Therapy..................................................................................................................... 55
6.8.1. 
UC-related Concomitant Therapies............................................................................................ 55
6.8.1.1. 
Oral Corticosteroids and Tapering .......................................................................................... 56
6.8.2. 
Prohibited Concomitant Therapies ............................................................................................. 56
6.8.3. 
Vaccinations (including COVID-19)............................................................................................ 57
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL............................................................................................... 57
7.1. 
Discontinuation of Study Intervention ............................................................................................ 57
7.2. 
Participant Discontinuation/Withdrawal From the Study................................................................ 59
7.2.1. 
Withdrawal From the Use of Research Samples ....................................................................... 59

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7.3. 
Lost to Follow-up............................................................................................................................ 60
8. 
STUDY ASSESSMENTS AND PROCEDURES ............................................................................... 60
8.1. 
Efficacy Assessments .................................................................................................................... 62
8.1.1. 
................................................................................................................................. 63
8.1.2. 
Histologic Assessments.............................................................................................................. 64
8.1.3. 
C-Reactive Protein...................................................................................................................... 64
8.1.4. 
Fecal Calprotectin....................................................................................................................... 64
8.1.5. 
............................................................................... 65
8.1.6. 
................................................................................................................................ 65
8.1.7. 
............................................................... 65
8.2. 
Safety Assessments....................................................................................................................... 65
8.2.1. 
Physical Examinations................................................................................................................ 66
8.2.2. 
Vital Signs................................................................................................................................... 66
8.2.3. 
Electrocardiograms..................................................................................................................... 66
8.2.4. 
Clinical Safety Laboratory Assessments .................................................................................... 66
8.2.5. 
Pregnancy Testing...................................................................................................................... 67
8.2.6. 
Suicidal Ideation and Behavior Risk Monitoring ......................................................................... 67
8.2.7. 
Concomitant Medication Review ................................................................................................ 69
8.2.8. 
Injection-Site Reactions.............................................................................................................. 69
8.2.9. 
Hypersensitivity Reactions.......................................................................................................... 69
8.2.10. 
Infections .................................................................................................................................... 69
8.2.11. 
Tuberculosis Evaluations............................................................................................................ 69
8.3. 
Adverse Events, Serious Adverse Events, and Other Safety Reporting ....................................... 71
8.3.1. 
Time Period and Frequency for Collecting Adverse Event and Serious Adverse Event
Information.................................................................................................................................. 71
8.3.2. 
Method of Detecting Adverse Events and Serious Adverse Events .......................................... 72
8.3.3. 
Follow-up of Adverse Events and Serious Adverse Events ....................................................... 72
8.3.4. 
Regulatory Reporting Requirements for Serious Adverse Events and Anticipated
Events......................................................................................................................................... 72
8.3.5. 
Pregnancy................................................................................................................................... 73
8.3.6. 
Adverse Events of Special Interest............................................................................................. 73
8.4. 
Pharmacokinetics........................................................................................................................... 73
8.4.1. 
Evaluations ................................................................................................................................. 73
8.4.2. 
Analytical Procedures................................................................................................................. 74
8.4.3. 
Pharmacokinetic Parameters and Evaluations........................................................................... 74
8.5. 
Pharmacogenomics ....................................................................................................................... 74
8.6. 
Biomarkers..................................................................................................................................... 74
8.6.1. 
Serum-based Biomarkers........................................................................................................... 75
8.6.2. 
Whole Blood-based Biomarkers................................................................................................. 75
8.6.3. 
Biopsy-based Biomarkers........................................................................................................... 75
8.6.4. 
Pharmacodynamics .................................................................................................................... 75
8.7. 
Immunogenicity Assessments ....................................................................................................... 75
8.8. 
Medical Resource Utilization and Health Economics .................................................................... 76
9. 
STATISTICAL CONSIDERATIONS.................................................................................................. 76
9.1. 
Statistical Hypotheses.................................................................................................................... 76
9.2. 
Sample Size Determination ........................................................................................................... 76
9.3. 
Populations for Analysis Sets ........................................................................................................ 78
9.4. 
Statistical Analyses ........................................................................................................................ 78
9.4.1. 
General Considerations.............................................................................................................. 78
9.4.2. 
Primary Endpoint ........................................................................................................................ 79
9.4.2.1. 
Primary Estimand of Clinical Remission at Week 12 .............................................................. 79
9.4.2.2. 
Estimator for the Primary Endpoint.......................................................................................... 80
9.4.3. 
Secondary Efficacy Endpoints.................................................................................................... 80
9.4.3.1. 
Estimands and Estimators....................................................................................................... 81
9.4.3.2. 
Confirmatory Testing Procedure.............................................................................................. 83
9.4.4. 
Exploratory Efficacy Endpoints................................................................................................... 84
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Status: Approved,  Date: 13 May 2025
9.4.5. 
Safety Analyses.......................................................................................................................... 84
9.4.5.1. 
Adverse Events ....................................................................................................................... 84
9.4.5.2. 
Clinical Laboratory Tests......................................................................................................... 85
9.4.5.3. 
Suicidal Ideation and Behavior................................................................................................ 85
9.4.6. 
Other Endpoints.......................................................................................................................... 85
9.4.6.1. 
Patient-reported Outcomes ..................................................................................................... 85
9.4.6.2. 
Pharmacokinetic Analyses ...................................................................................................... 86
9.4.6.3. 
Immunogenicity Analyses........................................................................................................ 86
9.4.6.4. 
Biomarkers Analyses............................................................................................................... 86
9.4.6.5. 
Pharmacokinetic/Pharmacodynamic Analyses ....................................................................... 87
9.5. 
Interim Analysis.............................................................................................................................. 87
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ............................ 88
10.1. 
Appendix 1: Abbreviations and Definitions .................................................................................... 88
10.2. 
Appendix 2: Definition of Inadequate Response to or Intolerance of Corticosteroids or
AZA/6-MP and Corticosteroid Dependence................................................................................... 90
10.3. 
Appendix 3: Definition of Inadequate Initial Response, Loss of Response, or Intolerance
to TNFα Antagonist Therapies (eg, Infliximab, Adalimumab, Golimumab), Vedolizumab,
or Approved Biosimilars ................................................................................................................. 91
10.4. 
Appendix 4: Definition of Inadequate Initial Response, Loss of Response, or Intolerance
to Tofacitinib, Filgotinib, Upadacitinib, or Ozanimod...................................................................... 96
10.5. 
Appendix 5: Hepatitis B Virus (HBV) Screening With HBV DNA Testing.................................... 100
10.6. 
Appendix 6: Regulatory, Ethical, and Study Oversight Considerations....................................... 101
10.6.1. 
Regulatory and Ethical Considerations .................................................................................... 101
10.6.2. 
Financial Disclosure.................................................................................................................. 104
10.6.3. 
Informed Consent Process ....................................................................................................... 105
10.6.4. 
Recruitment Strategy................................................................................................................ 105
10.6.5. 
Data Protection ......................................................................................................................... 105
10.6.6. 
Long-term Retention of Samples for Additional Future Research............................................ 106
10.6.7. 
Use of Information and Publication........................................................................................... 107
10.6.8. 
Data Quality Assurance............................................................................................................ 107
10.6.9. 
Case Report Form Completion................................................................................................. 108
10.6.10. Source Documents ................................................................................................................... 108
10.6.11. Monitoring ................................................................................................................................. 109
10.6.12. On-site Audits ........................................................................................................................... 109
10.6.13. Record Retention...................................................................................................................... 110
10.6.14. Study and Site Start and Closure ............................................................................................. 110
10.7. 
Appendix 7: Adverse Events, Serious Adverse Events, Product Quality Complaints, and
Other Safety Reporting: Definitions and Procedures for Recording, Evaluating, Follow-up,
and Reporting............................................................................................................................... 112
10.7.1. 
Adverse Event Definitions and Classifications ......................................................................... 112
10.7.2. 
Attribution Definitions................................................................................................................ 113
10.7.3. 
Severity Criteria........................................................................................................................ 113
10.7.4. 
Special Reporting Situations .................................................................................................... 114
10.7.5. 
Procedures ............................................................................................................................... 114
10.7.6. 
Product Quality Complaint Handling......................................................................................... 115
10.7.7. 
Contacting Sponsor Regarding Product Quality....................................................................... 116
10.8. 
Appendix 8: Contraceptive and Barrier Guidance ....................................................................... 117
10.9. 
Appendix 9:
.............................................................................................................. 120
10.10. Appendix 10: Guideline Algorithm for Monitoring, Assessment and Evaluation of
Abnormal Liver Tests ................................................................................................................... 121
10.11. Appendix 11: Study Conduct During a Natural Disaster.............................................................. 125
10.12. Appendix 12: Protocol Amendment History................................................................................. 127
11. REFERENCES................................................................................................................................. 132
INVESTIGATOR AGREEMENT............................................................................................................... 135
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Clinical Protocol CNTO1959UCO3004 Amendment 4
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Status: Approved,  Date: 13 May 2025
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1: 
Schedule of Activities: Screening and Treatment Period Through Week 24............................ 13
Table 2: 
Schedule of Activities: Extension Treatment Period Week 28 Through Week 96.................... 18
Table 3: 
Schedule of Activities: Extension Treatment Period Week 100 Through Week 248................ 23
Table 4: 
Recommended Tapering Schedule for Oral Corticosteroids.................................................... 56
Table 5: 
Power for Secondary Endpoints at Week 12 with a Total of 399 Participants (2:1
Guselkumab:Placebo)............................................................................................................... 77
Table 6: 
Power for Secondary Endpoints at Week 24 with a Total of 399 Participants (133 per
Treatment Group) ..................................................................................................................... 77
Table 7: 
Analysis Populations................................................................................................................. 78
Table 8: 
Intercurrent Events and Respective Analysis Strategies.......................................................... 79
Table 9: 
Variable Attributes of Secondary Endpoints at Week 12.......................................................... 81
Table 10: Variable Attributes of Secondary Endpoints at Week 24.......................................................... 82
Table 11: Intercurrent Events and Respective Analysis Strategies.......................................................... 82
Table 12: Eligibility Based on Hepatitis B Virus Test Results................................................................. 100
Table 13: Patterns of DILI Based on Elevations of Liver Tests .............................................................. 124
FIGURES
Figure 1: Schematic Overview of the Study............................................................................................. 12
Figure 2: Dosing Schedule Through Week 248....................................................................................... 49
Figure 3: Multiple Testing Procedure for Primary and Secondary Endpoints.......................................... 84

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Clinical Protocol CNTO1959UCO3004 Amendment 4
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Status: Approved,  Date: 13 May 2025
1. 
PROTOCOL SUMMARY
1.1. 
Synopsis
A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate
the Efficacy and Safety of Guselkumab Subcutaneous Induction Therapy in Participants with Moderately
to Severely Active Ulcerative Colitis
IND: 140330
EU Trial Number: 2023-504719-34
A Phase 3 Study to Evaluate the Efficacy and Safety of Guselkumab Subcutaneous Induction Therapy in
Participants with Moderately to Severely Active Ulcerative Colitis
DESCRIPTION OF COMPOUND
Guselkumab is a fully human immunoglobulin G1 lambda monoclonal antibody that binds to human IL-23
with high specificity and affinity. The binding of guselkumab to IL-23 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 term “study intervention” throughout the protocol, refers to study drug.
BENEFIT-RISK ASSESSMENT
Guselkumab, an IL-23 antagonist, has a well-defined long-term safety profile and has been extensively
studied in the approved indications. 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 anticipated
benefits that may be provided to participants with moderately to severely active UC. More detailed
information about the known and expected benefits and risks of guselkumab may be found in the IB.
OBJECTIVES AND ENDPOINTS
The primary and secondary objectives and endpoints are listed below.
Objectives 
Endpoints
Primary
To evaluate the efficacy, including clinical remission, 
of guselkumab SC induction compared to placebo in 
participants with moderately to severely active UC  
Clinical remission at Week 12
(defined as a 
 
and not increased
from baseline, a rectal bleeding
subscore of 0, and an 
 with no friability
present on the endoscopy)
Secondary
To further evaluate the efficacy of guselkumab SC 
induction compared to placebo across a range of 
outcome measures 
Symptomatic remission at Week 12
(defined as a 
 
and not increased
from baseline, and a rectal bleeding
subscore of 0)
Endoscopic improvement at Week
12 (defined as an endoscopy
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Clinical Protocol CNTO1959UCO3004 Amendment 4
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Status: Approved,  Date: 13 May 2025
Objectives 
Endpoints
subscore of 0 or 1 with no friability
present on the endoscopy)
Clinical response at Week 12
(defined 
as 
a decrease 
from
induction baseline in the 
 by ≥30% and ≥2 points,
with either a ≥1-point decrease from
baseline in the rectal bleeding
subscore or a rectal bleeding
subscore of 0 or 1)
Clinical remission at Week 24
Symptomatic remission at Week 24
Endoscopic 
improvement 
at
Week 24
Clinical response at Week 24
Histologic-endoscopic 
mucosal
improvement at Week 12 (defined as
a 
combination 
of 
histologic
improvement [neutrophil infiltration
in <5% of crypts, no crypt
destruction, 
and 
no 
erosions,
ulcerations or granulation tissue
according to the 
 
and 
endoscopic
improvement as defined above)
To evaluate the safety of guselkumab SC induction 
compared to placebo 
Frequency 
and 
type 
of AEs
(including SAEs)
HYPOTHESIS
The primary hypothesis of this study is that guselkumab SC induction is superior to placebo SC in achieving
clinical remission at Week 12 among participants with moderately to severely active UC.
OVERALL DESIGN
This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate the
efficacy and safety of guselkumab SC induction therapy in adult participants with moderately to severely
active UC who have demonstrated an inadequate response to or intolerance of conventional (ie, 6-MP,
AZA, or corticosteroids) or advanced therapy (ADT; ie, TNFα antagonists, vedolizumab, ozanimod, or
approved JAK inhibitors).
The main treatment period will evaluate guselkumab SC treatment through 24 weeks of therapy. Starting
at Week 12, all participants who were taking corticosteroids at Week 0 must begin tapering their
corticosteroid dose. This tapering is mandatory, unless not medically feasible. All participants who reach
the Week 24 visit and are benefiting from study intervention in the opinion of the investigator are eligible
for the study extension with treatment up to Week 248. At Week 24, participants entering the extension
period will continue the same treatment regimen they were receiving prior to Week 24. The study will be
unblinded after the last participant completes the Week 48 assessments and the Week 48 DBL and analyses
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occur. Upon study unblinding, placebo participants who have not been rescued with guselkumab will be
discontinued from study intervention and have a safety follow-up visit. All other participants will continue
on guselkumab treatment up to Week 248.
Efficacy, safety, PK, immunogenicity, and biomarkers will be assessed according to the SoA.
Participants will complete an ED visit upon discontinuation of study intervention and before termination of
study participation. All randomized and treated participants are to complete the safety follow-up visit
12 weeks after the last dose of study intervention.
Database locks are planned for Week 24, Week 48, and when the last participant completes the last
scheduled assessment as shown in the SoA. Additional DBLs may be added as necessary.
End of Study
The end of study is considered as the last scheduled study assessment shown in the Schedule of Activities
for the last participant in the study or if a decision has been made by the sponsor not to pursue an indication
in UC or SC induction and appropriate follow-up has been completed. The final data from the study site
will be sent to the sponsor (or designee) after completion of the final participant assessment at that study
site, in the time frame specified in the Clinical Trial Agreement.
NUMBER OF PARTICIPANTS
The target sample size is 399 participants, with 133 participants per intervention group. Participants who
have demonstrated an inadequate response to or intolerance of advanced therapy (ADT-IR) will comprise
approximately 40% to 50% of the population.
INTERVENTION GROUPS AND DURATION
The overall study duration is up to 268 weeks. The study comprises of the following periods
Screening period: up to 8 weeks
Main treatment period: 24 weeks
Extension treatment period: 224 weeks
SafetyFollow-up period: until approximately 12 weeks after the last dose of study intervention.
At Week 0, eligible participants will be randomly assigned in a 1:1:1 ratio to one of the following SC
treatments:
133 participants to guselkumab
 at Weeks 0, 4, and 8 followed by guselkumab 200 mg SC
q4w through Week 24
133 participants to guselkumab
 at Weeks 0, 4, and 8 followed by guselkumab 100 mg SC
q8w through Week 24
133 participants to placebo SC q4w from Week 0 through Week 24
Participants will be allocated to an intervention group using permuted block randomization stratified by
ADT-IR status (Yes/No) and
 at baseline (moderate [2] or severe [3]) obtained
during central review of the video endoscopy.
All participants in the placebo group who meet rescue criteria at Week 16 will receive rescue treatment, ie,
guselkumab 
 at Weeks 16, 20, and 24 followed by guselkumab 100 mg SC q8w. Participants
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randomized to guselkumab who meet rescue criteria at Week 16 will continue their assigned treatment
regimen and receive blinded sham rescue with matching placebo SC injections at Weeks 16, 20, and 24.
Description of Interventions
Participants will receive the study interventions as described above in the Intervention Groups and Duration
section.
Guselkumab will be provided in 2 dose strengths: guselkumab 
 in a single-dose PFS-Y and
 in a single-dose PFS-U. Matching placebo will be provided as 
 in a single-dose PFS-Y
and as
 in a single-dose PFS-U.
EFFICACY EVALUATIONS
Efficacy evaluations will include the following:
Inflammatory PD markers including CRP and fecal calprotectin
Histological assessments (eg, 
Patient-reported outcome measures to assess 
 outcomes, fatigue, and UC symptoms and signs
(ie, 
PHARMACOKINETIC EVALUATIONS
Serum samples will be analyzed to determine concentrations of guselkumab using validated, specific and
sensitive immunoassay methods by or under the supervision of the sponsor.
IMMUNOGENICITY EVALUATIONS
Serum samples will be screened for antibodies binding to guselkumab and the titer of confirmed positive
samples will be reported. Other analyses may be performed to verify the stability of antibodies to
guselkumab and/or further characterize the immunogenicity of guselkumab.
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 ulcerative colitis. Assessments will include
the evaluation of relevant biomarkers in serum, whole blood, and endoscopic biopsy samples, where local
regulations permit.
SAFETY EVALUATIONS
Safety assessments include AEs, clinical laboratory tests, vital signs and physical examinations, a screening
electrocardiogram, suicidality assessment, concomitant medication review, monitoring for injection-site
reactions and hypersensitivity reactions, a tuberculosis evaluation and other infection assessments.
STATISTICAL METHODS
Sample Size Determination
Sample size was determined by the power to detect significant differences in the primary endpoint of
clinical remission at Week 12, and by the objective of maintaining at least 85% power across secondary
endpoints at Week 12 between the combined guselkumab SC induction groups and the placebo SC group
and secondary endpoints at Week 24 between each guselkumab group and the placebo group, using 2-sided
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Clinical Protocol CNTO1959UCO3004 Amendment 4
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chi-square tests with significance level 0.05. The assumed rates are 22% versus 8% (guselkumab vs
placebo) for clinical remission at Week 12. The study is sized such that the guselkumab therapy achieves a
>95% power for the primary endpoint and a ≥85% power for all secondary endpoints.
Efficacy Analyses
Descriptive statistics (eg, mean, median, SD, IQ range, minimum, and maximum) will be used to summarize
continuous variables. Counts and percentages will be used to summarize categorical variables. Graphical
data displays (eg, line plots) may also be used to summarize data.
Analyses suitable for categorical data (eg, chi-square tests, CMH tests, or logistic regression, as appropriate)
will be used to compare the proportions of participants achieving selected endpoints (eg, clinical response).
In cases of rare events, the Fisher’s exact test will be used for treatment comparisons. Continuous response
parameters measured at more than one post-baseline visit will be compared using an MMRM model (unless
otherwise specified). If the normality assumption is in question, an appropriate transformation may be
implemented before fitting the MMRM model. Continuous response parameters measured at only one
post-baseline visit will be compared using a ANOVA or ANCOVA, unless otherwise specified. In cases of
small sample size, t-test will be used for treatment comparisons.
Efficacy analyses will be based on  all randomized participants who received at least 1 dose of study
intervention (the Full Analysis Set). Participants will be analyzed according to the treatment group to which
they were randomized regardless of the treatment they received.
The primary endpoint (clinical remission at Week 12) will be analyzed based on the primary estimand,
considering treatment groups, population, variable, ICE strategies, and population-level summary. After
accounting for the ICEs, any participants who are missing any or all of the 3 subscores that comprise the
primary endpoint at Week 12 will be considered not to be in clinical remission at Week 12 (ie, nonresponder
imputation).
Summaries of the proportion of participants in clinical remission at Week 12 will be presented by treatment
group. The common risk difference and the associated 95% confidence interval between the combined
guselkumab SC induction group and the placebo group will be computed by use of Mantel-Haenszel stratum
weights and the Sato variance estimator. The primary endpoint will be tested by a two-sided
Mantel-Haenszel test for the common risk difference. Stratification will be bythe ADT-IR status (Yes/No),
and 
 at baseline (moderate [2], severe [3]) as obtained during central review of
the video endoscopy. The study will be considered successful if the test for the primary endpoint is positive.
While a multiplicity-controlled testing procedure will be implemented to control for the type I error rate at
the 0.05 significance level (2-sided) across the primary and secondary endpoints, the primary endpoint will
be tested at full significance level. Only if this test is significant, secondary endpoints will be tested in a
confirmatory manner.
Safety Analyses
Safety data, including but not limited to, AEs, SAEs, infections, injection-site reactions, changes in
laboratory parameters (hematology and chemistry), and suicidal ideation and behavior will be summarized.
All reported AEs will be included in the analysis.
Other Analyses
Patient-reported Outcomes
Analysis of patient-reported outcomes will follow the general considerations. The testing of these endpoints
will not be controlled for multiplicity and nominal p-values will be provided.
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Table 1: 
Schedule of Activities: Screening and Treatment Period Through Week 24
Period  
Screening 
Treatment Period  
EDa
Safety
Follow-
Upb
Notes
Week 
(≤8 weeks) 
0 
4 
8 
12 
16 
20 
24
Visit Windows 
±4 days 
±7 days
Study Assessments/
Proceduresc
should be obtained prior to and approximately
30 minutes after the SC injection, or if the participant
reports any symptoms.
Serum pregnancy test 
X
Urine pregnancy test 
X 
X 
X 
X 
X 
X 
X 
X 
X
A urine pregnancy test must be performed before any
study intervention administration for women of
childbearing potential.
FSH 
X
Consider testing in women with no menses for
≥52 weeks without an alternative medical cause.
Concomitant
medication review
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
AE Review  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
 
X 
X 
X 
X 
X 
X 
X 
X 
X
At the screening visit, the 
 should be
completed as the first assessment, after signing the
informed consent and before any other tests,
procedures, or other consultations. For subsequent
visits, the
 should be completed after all PROs
and before any other tests, procedures, or other
consultations.
TB evaluation/other
infection assessment
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
Screening TB assessment must include specific
questions about 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 imaging, tuberculin skin, or other
TB testing results. Additionally, investigators are
required to evaluate participants for any signs or
symptoms of active TB or other infections.
If TB reactivation or new TB infection is suspected at
any time during the study, study intervention must be
withheld and an immediate and thorough investigation
should be undertaken, including, where possible,
consultation with a physician specializing in TB.
Review of UC-related
procedures and
surgeries
X 
X 
X 
X 
X 
X 
X 
X 
X
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h. 
This assessment/procedure is only required if the ED visit occurs at or after the Week 44 visit through Week 48. After Week 96, endoscopy is not recommended for the ED
visit if the participant had a study-related endoscopy within 24 weeks.
i. 
A flexible sigmoidoscopy is generally acceptable for endoscopic assessments. A full colonoscopy should replace a sigmoidoscopy if screening for polyps or dysplasia is
required or deemed clinically necessary by the investigator. PI must review local pathology results and report any abnormal findings to sponsor.
j. 
For ED visits prior to Week 48, biopsies are required to be performed.

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2. 
INTRODUCTION
Guselkumab is a fully human immunoglobulin G1 lambda monoclonal antibody that binds to the
p19 protein subunit of human IL-23 with high specificity and affinity. By binding to the p19
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
including IL-17A, IL-17F, and IL-22.
A rapidly growing body of literature suggests that the IL-23 pathway contributes to the chronic
inflammation underlying the pathophysiology of many immune-mediated diseases including
psoriasis, psoriatic arthritis, ankylosing spondylitis, and IBD. Susceptibility to psoriasis, psoriatic
arthritis, and IBD has been shown to be associated with genetic polymorphisms in IL-23/IL-23
receptor components.
Guselkumab is currently being studied in participants with UC (see details in Section 2.2).
For the most comprehensive nonclinical and clinical information regarding guselkumab, refer to
the latest version of the IB for guselkumab.
The term “study intervention” throughout the protocol, refers to study drug as defined in
Section 6.1, Study Intervention(s) 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
Ulcerative colitis is a chronic inflammatory bowel disorder of unknown etiology which involves
the surface mucosa, the crypt epithelium, and submucosa of the colon (Ordás 2012; Stenson 2000).
Ulcerative colitis is most commonly diagnosed in late adolescence and early adulthood, but a
diagnosis may occur at any age (Loftus 2004). Clinically, patients with UC suffer from diarrhea,
rectal bleeding, weight loss, abdominal pain, fever, and may also display prominent extraintestinal
manifestations, most commonly arthritis (Ordás 2012; Stenson 2000). Ulcerative colitis is
characterized by a life-long course of remissions and exacerbations, with 15% of patients having
an acute attack requiring hospitalization at some time during their illness (Willert 2008). In severe
UC, the bowel wall may become extremely thin, the mucosa denuded, and the inflammation may
extend to the serosa leading to dilatation, toxic megacolon, and subsequent perforation
(Glickman 1998; Stenson 2000). Within 10 years of diagnosis, approximately 20% ofadults with
UC were reported to have undergone colectomy (Van Limbergen 2008).
Despite the availability of advanced therapies, many patients either inadequately respond (ie,
primary nonresponse) or lose their initial response (ie, secondary nonresponse) to treatment,
highlighting the significant unmet medical need for more effective therapies. Given the anal and
safety of anti-IL-23 treatment demonstrated to date in both Crohn’s disease and UC, there is strong
rationale for the development of guselkumab in UC (Feagan 2018; Feagan 2017; Feagan 2016;
Sandborn 2018; Sandborn 2012; Sands 2017).

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Subcutaneous (SC) delivery of biologic agents has become a valuable alternative to IV
administration across many disease areas. Although the pharmacokinetic profiles of SC and IV
formulations differ, SC administration has proven effective, safe, well-tolerated, generally
preferred by patients and healthcare providers due to the greater flexibility and ease of
administration for patients or their caregivers at their preferred setting. For IBD  patients, IV
infusions represent an extra burden which takes time away from other activities (Buisson 2013).
In addition, SC administration has resulted in reduced drug delivery-related healthcare costs and
resource utilization (Bittner 2018). In short, SC administration has become an attractive alternative
to more invasive, expensive, and time-consuming intravenous infusions. However, despite a
growing number of therapeutic options for UC, few biologic therapies allow for SC induction and
maintenance.
Considering the potential benefits of anti-IL-23 therapy and SC induction dosing, the aim of this
study is to evaluate the efficacy, safety, and PK/PD profile of guselkumab SC induction compared
to placebo in participants with moderately to severely active UC.
2.2. 
Background
Guselkumab Nonclinical Studies
A full nonclinical development program was conducted with guselkumab in support of initial
global submissions and approvals. This program included general toxicology and toxicokinetic
studies in support of first-in-human dosing, studies in support of Phase 2 and Phase 3 clinical
development, and developmental and reproductive toxicology studies. A comprehensive overview
of nonclinical data are presented in Section 3 of the guselkumab IB.
Guselkumab Clinical Studies
Guselkumab has received marketing approval in several countries and regions globally for the
treatment of adults with moderate to severe plaque psoriasis and active PsA. The approved
guselkumab dose for psoriasis and PsA is 100 mg by SC injection at Weeks 0, 4, and q8w
thereafter. In the EU, for treatment of PsA, a dose of 100 mg q4w may also be considered for
patients at high risk for joint damage according to clinical judgement.
Two global Phase 2/3 clinical programs are ongoing in Crohn’s disease (CNTO1959CRD3001;
GALAXI) and UC (CNTO1959UCO3001; QUASAR) evaluating induction dose regimens up to
1200 mg IV in GALAXI and
 in QUASAR administered at Weeks 0, 4, and 8, as well
as maintenance dose regimens of 100 mg SC q8w and 200 SC q4w in both programs. A separate
Phase 3 SC induction study is planned for Crohn’s disease (GRAVITI; CNTO1959CRD3004),
evaluating the same 
 induction dose regimen included in this protocol.
As mentioned above, guselkumab is being investigated in several other indications. Details about
these guselkumab clinical development programs are provided in Section 4 of the latest version of
the guselkumab IB.
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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 Investigator's Brochure.
2.3.1. 
Risks for Study Participation
Potential Risks of 
Clinical Significance 
Summary of Data/
Rationale for Risk
Mitigation Strategy
Clinical worsening of UC 
The benefit-risk of
guselkumab in the
treatment of moderately
to severely active UC has
not been established.
During the study, participants will be permitted to
continue treatment of UC with certain concomitant
medications (Section 6.8).
Participants will discontinue study intervention if
it is not in their best interest or if they need to
initiate protocol-prohibited medications including
certain biologics (Sections 6.8.2 and 7.1).
Participants in the placebo arm who meet rescue
criteria will receive guselkumab (Section 6.5.1).
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. 
Infections have been  
identified as adverse 
reactions for guselkumab, 
including respiratory 
infections, herpes 
simplex, tinea infections, 
and gastroenteritis. 
Participants with a history of, or ongoing, chronic
or recurrent infectious disease, including HIV,
HBV and HCV, will be excluded from the study.
Similarly, participants with evidence of active or
untreated latent TB will be excluded from the
study (Section 5.2).
Participants who have received a live viral or live
bacterial vaccination within 4 weeks before the
first dose of study intervention 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
(Sections 5.2 and 5.3).
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 tuberculosis
(Sections 8.2.10 and 8.2.11).
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 (Sections 7.1 and 8.2.10).
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(Section 5.2).
Sites are instructed that before any administration
of study intervention, appropriately trained
personnel and medications (eg, injectable

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Potential Risks of
Clinical Significance
Summary of Data/
Rationale for Risk
Mitigation Strategy
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, itching,
hives) (Section 8.2.9).
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
a participant in a Phase 2
Crohn’s disease study
who received guselkumab
1200 mg IV at Weeks 0,
4, and 8, and 200 mg SC
at Week 12. This event
may represent drug-
induced liver injury
possibly related to
guselkumab (see
Section 5.1.3 of IB
[guselkumab]).
Transaminase increases
have been identified as an
adverse reaction of
guselkumab. In 2 Phase 3
PsA clinical studies,
increased ALT and/or
AST was observed more
During the conduct of the study, liver function
tests will be monitored at regular intervals in
accordance with regulatory guidance (Food and
Drug Administration 2019). In addition, the
induction doses evaluated in this clinical program
will not exceed 
(systemic exposure
comparable to guselkumab
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(Appendix 10,
Section 10.10). 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).
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Potential Risks of
Clinical Significance
Summary of Data/
Rationale for Risk
Mitigation Strategy
frequently in patients
treated with guselkumab
100 mg SC q4w
compared to patients
treated with guselkumab
100 mg SC q8w or
placebo.
Immunosuppression  
It is unknown if 
guselkumab in 
combination with other 
immunosuppressives 
increases the risk of 
diseases associated with 
immunosuppression, such 
as infections 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 corticosteroids on study entry
is limited to ≤20 mg prednisone or its equivalent
per day, or 9 mg/day of budesonide, or 5 mg/day
beclomethasone, which must be tapered during the
from Week 12 onwards. Furthermore, participants
receiving AZA, 6-MP, or MTX, must have been
taking them for ≥12 weeks and been on a stable
dose for at least 4 weeks before baseline.
Additionally, participants are also excluded from
the study if they have received cyclosporine,
mycophenolate mofetil, tacrolimus, or sirolimus
within 4 weeks, or anti-TNF α therapy within 8
weeks, or vedolizumab within 12 weeks prior to
the first dose of study intervention. Further detail
regarding concomitant medications is provided in
Sections 5.1 and 5.2.
During study participation, the use of
immunomodulators other than AZA, 6-MP, and
MTX (eg, cyclosporine) as well as biologic
immunomodulators (eg, TNFs α antagonists,
vedolizumab) is prohibited. Participants initiating
these treatments will be discontinued from further
study intervention administration (see
Section 6.8.2 for further details on prohibited
concomitant medications).
Risks Due to Study Procedures
Risks associated with the 
endoscopy procedure 
including bleeding and 
colonic perforation  
These risks are well 
recognized but are 
considered rare
(Arora 2009;
Rabeneck 2008).
Trained and experienced endoscopists will be
performing the procedure during this study.
2.3.2. 
Benefits for Study Participation
There is no established benefit to participants of receiving study intervention; however, given the
well-established scientific and clinical rationale for IL-23 blockade in the treatment of UC,
participants may experience an improvement in disease status during treatment with Guselkumab.
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the knowledge gained from this study has the potential to benefit many more patients suffering
with UC, and thus offers potential public health benefits.
2.3.3. 
Benefit-Risk Assessment for Study Participation
Taking into account the measures taken to minimize risk to participants ofthis study, the potential
risks identified in association with guselkumab are justified by the anticipated benefits that may
be afforded to participants with ulcerative colitis.
Guselkumab has undergone extensive nonclinical and clinical development as summarized in the
latest version of the IB and described briefly in Section 2.2. The collective efficacy and safety
results of the Phase 1, Phase 2, and Phase 3 clinical studies in healthy volunteers and patients with
plaque psoriasis and psoriatic arthritis established a favorable benefit-risk profile for guselkumab
in the treatment of plaque psoriasis and regulatory approval for both  indications. This clinical
experience provided support for the ongoing development of guselkumab in other inflammatory
diseases such as UC and Crohn’s disease.
In Crohn’s disease, results from the GALAXI 1 study show that guselkumab IV induction
demonstrated greater improvements compared to placebo across the key clinical efficacy and
endoscopic outcome measures at Week 12 (Danese 2021; Sandborn 2020b). The safety profile of
guselkumab in the GALAXI 1 study population is consistent with the safety profile of guselkumab
established from clinical studies across investigational and approved indications.
In  UC, animal and human data support the critical role of IL-23 in the disease pathogenesis.
Clinical data from Phase 2 and Phase 3 studies of mirikizumab, an  anti-IL-23 mAb, has
demonstrated POC for this mechanism in UC (Geert 2019; Sandborn 2018). Importantly, in the
QUASAR Phase 2b induction study, guselkumab has shown efficacy when compared with placebo
at Week 12 and a consistent safety profile to that previously observed.
 However, safety of these doses is supported
by the available data from preclinical toxicology studies and ongoing clinical studies, including
those in IBD (See Section 4.3). The Phase 2b portion of the QUASAR program in UC tested
induction dose regimens up to 
 the guselkumab induction dose for this study is based
on favorable efficacy and safety data from the induction portion of that program.
Potential risks of guselkumab, including those of serious infection and malignancy, 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 during the conduct of the studies.
In summary, the collective preclinical and clinical evidence for guselkumab provide strong
scientific and clinical rationale for the potential benefit in participants with moderately to severely
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active UC. Taking into account the measures taken to minimize risk to participants in this study,
the potential risks associated with guselkumab are justified by the anticipated benefits.
3. 
OBJECTIVES AND ENDPOINTS
The objectives and endpoints of this study are as follows:
Objectives 
Endpoints
Primary
To evaluate the efficacy, including clinical
remission, of guselkumab SC induction
compared to placebo in participants with
moderately to severely active UC
Clinical remission at Week 12 (defined as a
 and not increased
from baseline, a rectal bleeding subscore of 0,
and an 
 with no
friability present on the endoscopy)
Secondary
To further evaluate the efficacy of
guselkumab SC induction compared to
placebo across a range of outcome measures
Symptomatic remission at Week 12 (defined as 
 and not
increased from baseline, and a rectal bleeding
subscore of 0)
Endoscopic improvement at Week 12 (defined as
an
 with no friability
present on the endoscopy)
Clinical response at Week 12 (defined as a
decrease from induction baseline in the
 by ≥30% and ≥2 points, with either
a ≥1-point decrease from baseline in the rectal
bleeding subscore or a rectal bleeding subscore
of 0 or 1)
Clinical remission at Week 24
Symptomatic remission at Week 24
Endoscopic improvement at Week 24
Clinical response at Week 24
Histologic-endoscopic mucosal improvement at
Week 12 (defined as a combination of histologic
improvement [neutrophil infiltration in <5% of
crypts, no crypt destruction, and no erosions,
ulcerations or granulation tissue according to the
 
 
 and endoscopic
improvement as defined above)
To evaluate the safety of guselkumab SC
induction compared to placebo
Frequency and type of AEs (including SAEs)
Exploratory
To further evaluate the efficacy of
guselkumab SC compared to placebo across
a range of outcome measures
Endoscopic normalization at Week 12 and at
Week 48 (defined as an 
 of
0)
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Objectives 
Endpoints
Histologic improvement at Week 12 and at
Week 48 (defined as neutrophil infiltration in
<5% of crypts, no crypt destruction, and no
erosions, ulcerations or granulation tissue
according to the
Histologic remission at Week 12 and at
Week 48 (defined as absence of neutrophils
from the mucosa [both lamina propria and
epithelium], no crypt destruction, and no
erosions, ulcerations or granulation tissue
according to the
Symptomatic remission over time
Corticosteroid-free clinical remission at
Week 24
Change from baseline in the modified
 at Week 12
Change from baseline in the partial
over time
Change from baseline in the stool frequency and
 at each visit over time
 of 0 at each visit over
time
 of 0 or 1 at each visit
over time
Change from baseline in the 
 at Week 12
Change from baseline in the full 
 at
Week 12
Clinical remission at Week 48
Endoscopic improvement at Week 48
Clinical response at Week 48
Histologic-endoscopic mucosal improvement at
Week 48
Corticosteroid-free clinical remission at
Week 48
To evaluate the impact of guselkumab SC on 
biomarkers 
Change from baseline in CRP and fecal
calprotectin
To evaluate the impact of guselkumab SC on  
patient-reported outcomes (PROs) 
Endpoints based on 
 and
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Objectives 
Endpoints
To evaluate the PK and immunogenicity of 
guselkumab SC
Serum concentrations of guselkumab
Incidence and titers of antibodies to guselkumab
Refer to Section 8, Study Assessments and Procedures for evaluations related to endpoints and
Section 9 for further details on the analyses of the endpoints. Exploratory endpoints are not limited
to those specified above. Refer to the SAP for further details.
HYPOTHESIS
The primary hypothesis of this study is that guselkumab SC induction is superior to placebo SC in
achieving clinical remission at Week 12 among participants with moderately to severely active
UC.
4. 
STUDY DESIGN
4.1. 
Overall Design
This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study to
evaluate the efficacy and safety of guselkumab SC induction therapy in adult participants with
moderately to severely active UC who have demonstrated an inadequate response to or intolerance
of conventional (ie, 6-MP, AZA, or corticosteroids) or advanced therapy (ADT; ie, TNFα
antagonists, vedolizumab, ozanimod, or approved JAK inhibitors).
A target of 399 participants will be enrolled in this study with 133 participants planned per
intervention group. Participants who had an inadequate response to or intolerance of advanced
therapy (ADT-IR) will comprise a minimum of approximately 40% and a maximum of
approximately 50% of the population. Consented participants will be screened for study eligibility
within 8 weeks of the Week 0 visit. Eligible participants will be randomized in a 1:1:1 ratio to the
following intervention groups:
guselkumab
 at Weeks 0, 4, and 8 followed by guselkumab 200 mg SC q4w through
Week 24
guselkumab
 at Weeks 0, 4, and 8 followed by guselkumab 100 mg SC q8w through
Week 24
placebo SC q4w from Week 0 through Week 24
Participants will be allocated to an intervention group using permuted block randomization
stratified by ADT-IR status (Yes/No) and 
 at baseline (moderate [2] or
severe [3]) as obtained during central review of the video endoscopy.
All participants in the placebo group who meet rescue criteria at Week 16 will receive rescue
treatment, ie, guselkumab 
 at Weeks 16, 20, and 24 followed by guselkumab 100 mg
SC q8w. Participants randomized to guselkumab who meet rescue criteria at Week 16 will continue
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their assigned treatment regimen and receive blinded sham rescue with matching placebo SC
injections at Weeks 16, 20, and 24.
Rescue criteria are defined as:
No improvement (ie, no decrease)in
 at Week 12 as obtained during
central review, when compared with baseline
AND
A <2 point improvement (ie, <2 point decrease) in 
 score at Weeks 12 and 16,
when compared with baseline
All participants who reach the Week 24 visit and are benefiting from study intervention in the
opinion of the investigator are eligible for the study extension with treatment up to Week 248. At
Week 24, participants entering the extension period will continue the same treatment regimen they
were receiving prior to Week 24 (either the treatment regimen assigned at randomization or the
rescue regimen as described above).
The study will be unblinded after the last participant completes the Week 48 assessments and the
Week 48 DBL and analyses occur. Upon study unblinding, placebo participants who have not been
rescued with guselkumab will be discontinued from study intervention and have a safety follow-up
visit. All other participants will continue on guselkumab treatment up to Week 248.
Participants who are receiving oral 5-ASA compounds, oral corticosteroids, or conventional
immunomodulators (AZA, 6-MP, or MTX) for the treatment of UC at baseline should maintain a
stable dose through Week 48; with the exception of oral corticosteroids which require mandatory
tapering at Week 12. See Section 6.8.1 for instructions on concomitant medications.
Starting at Week 12, all participants who were taking corticosteroids at Week 0 must begin
tapering their corticosteroid dose (for additional details, see Section 6.8.1.1, Table 4). This tapering
is mandatory, unless not medically feasible.
Participants will complete an ED visit upon discontinuation of study intervention and before
termination of study participation. All randomized and treated participants are to complete the
safety follow-up visit 12 weeks after the last dose of study intervention.
Efficacy, safety, PK, immunogenicity, and biomarkers will be assessed according to the Schedule
of Activities (SoA, Section 1.3).
Safety assessments include AEs, clinical laboratory tests (hematology and chemistry), vital signs,
physical examination, screening ECG, suicidality assessment, and monitoring for hypersensitivity
reactions, injection-site reactions, and early detection of active TB. Endoscopies will also be
performed to assess long term safety.
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Database locks are planned for Week 24, Week 48, and when the last participant completes the
last scheduled assessment as shown in the SoA (Section 1.3). Additional DBLs may be added as
necessary. An overview of the study design is presented in Section 1.2.
4.2. 
Scientific Rationale for Study Design
This SC induction study is intended to provide clinical evidence to support efficacy and safety of
guselkumab SC induction dosing, compared to placebo. The safety and efficacy endpoints in this
study are similar to those in the ongoing guselkumab Phase 3 UC program (QUASAR) designed
to demonstrate the efficacy and safety of guselkumab IV induction. Additionally, the study
population is generally consistent with the QUASAR population, which evaluates participants with
moderately to severely active UC who demonstrated an inadequate response to or intolerance of
conventional or advanced therapies. These similarities may enable indirect studycomparison of
guselkumab IV induction versus SC induction treatment.
Blinding, Control, Study Periods, Intervention Groups
Blinded intervention will be used to reduce potential bias during data collection and evaluation of
clinical endpoints. 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. To minimize
risk to participants, they will be evaluated for rescue treatment and participants in the placebo
group who meet the rescue criteria will receive guselkumab 
 at Weeks 16, 20, and 24
followed by guselkumab 100 mg SC q8w (see Section 6.5).
Participants initially randomized to either guselkumab groups who meet the rescue criteria will
receive a blinded sham rescue at Weeks 16, 20, and 24. Published data from both IL-12/23
(ustekinumab) and IL-23 (mirikizumab) therapies suggest that participants may achieve a delayed
induction response (Sands 2019; Sandborn 2020). Thus, participants undergoing sham rescue may
still benefit from continued guselkumab therapy.
A study duration of 24 weeks is thought to be sufficient to evaluate efficacy and safety of SC
induction followed by SC maintenance of guselkumab in UC. The guselkumab maintenance
dosing regimen after Week 8 in this study is identical to that in the ongoing guselkumab Phase 3
UC program  (QUASAR). After Week 24, no differences in guselkumab concentrations and
exposures are expected between 
 induction (in this study) and 
 induction
(QUASAR) dose regimens (see Section 4.3 for more details). Consequently, this study is a
24-week study with a 224-week extension, giving participants who are deemed by the investigator
to be benefiting from study intervention access to treatment for approximately 5 years. The
follow-up period (approximately 12 weeks after the last dose of study intervention) is designed to
collect the final safety data.
Biomarker Collection
Biomarker samples (where local regulations permit) will be collected to evaluate the cellular and
molecular mechanism of action of guselkumab, or help to explain interindividual variability in
clinical outcomes, or may help to identify population subgroups that respond differently to an
intervention. Serum biomarkers will be collected from whole blood in all participants to assess PD
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markers associated with the IL-23 pathway, and with response to guselkumab. Whole blood
samples will be collected from all participants to assess the effect of study intervention on RNA
expression profiles. Colonic biopsies will also be obtained from all participants to assess cellular
and molecular changes within the intestinal mucosal tissue. The goal of the biomarker analyses is
to further define the mechanism of action of the selective blockade of IL-23 with guselkumab in
UC, and aid in evaluating the intervention-clinical response relationship.
Biomarker sample may be used to help address emerging issues and to enable the development of
safer, more effective, and ultimately individualized therapies.
Patient-reported Outcomes on Health-related Quality of Life
Patient-reported outcome evaluations (ie, 
will be used to assess the benefits
of guselkumab treatment on disease-specific and general 
 Patient-reported outcome
evaluations are only being collected in countries where translations of the evaluations are
available. See Section 8.1, Efficacy Assessments for more details.
Oral Corticosteroids Tapering
Participants on corticosteroids will undergo mandatory tapering from Week 12 onwards according
to pre-defined recommended tapering schedule given that obtaining corticosteroid-free clinical
remission is an important goal of therapy (Lichtenstein 2018) (see Section 6.8).
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.
Written consent/assent may be obtained through various sources (eg, paper or electronic such as
eConsent, eSignature, or digital signature) as determined by regulations as well as study and/or
patient preferences.
The primary ethical concern is that one third of the participants in this study with moderately to
severely active UC will receive placebo; however, these participants will be rescued upon meeting
the rescue criteria (see Section 6.5). The use of placebo in participants with active disease is
considered clinically acceptable in support of scientific research and is still considered necessary
in IBD clinical trials (Danese 2016). A placebo-control period facilitates the evaluation of the
efficacy and safety of a new treatment compared with placebo.
The total blood volume to be collected from each participant in this study (approximately 326 mL
over 268 weeks) 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
(approximately 475 mL every 8 weeks).
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4.3. 
Justification for Dose
Participants will be randomly assigned in a 1:1:1 ratio to receive the following dose regimens:
Guselkumab
 at Weeks 0, 4, and 8 followed by guselkumab 200 mg SC q4w
Guselkumab
 at Weeks 0, 4, and 8 followed by guselkumab 100 mg SC q8w
Placebo SC q4w
A single SC induction guselkumab dose regimen 
 at Weeks 0, 4, and 8) was selected
for this study based on data from the Phase 2 dose-ranging study of guselkumab IV in UC
(QUASAR). The QUASAR Phase 2 Week 12 analyses demonstrated similar efficacy with
guselkumab induction doses of 
 and 
 administered 
 at Weeks 0, 4, and 8,
respectively. There was no clear dose/exposure-response within the range of guselkumab IV
induction doses tested. As a result, the 
 induction dose regimen was selected for
confirmatory evaluation in the guselkumab QUASAR Phase 3 studies.
With an estimated bioavailability of approximately 50% for guselkumab SC (TREMFYA® SmPC
2021; TREMFYA® USPI 2021), a 
 dose of guselkumab is expected to result in
comparable overall guselkumab exposure (AUC) to the
 dose. Population PK modeling
and simulation demonstrate that while peak concentrations were higher with the 
induction dose regimen, trough concentrations following the 
 induction dose regimen
were non-inferior when compared with the IV induction dose regimen. Experience from biologics
approved for both IV and SC administration demonstrate that achieving similar overall exposure
(Cavg,ss) with non-inferior trough concentrations results in comparable efficacy for both routes of
administration (Ji 2019; Sandborn 2020a). In addition, serum peak concentrations in the induction
period may not be a dominant driver of efficacy for biologics in IBD (Rutgeerts 2015). Given this,
a single guselkumab induction dose regimen of
 at Weeks 0, 4, and 8 will be evaluated
in participants with moderately to severely active UC. Of note, this same SC guselkumab induction
dose regimen was selected for evaluation in the Crohn’s disease indication.
Two guselkumab maintenance dose regimens (200 mg SC q4w and 100 mg SC q8w) will be
evaluated in this study. These are the same doses being evaluated in the ongoing Phase 3 QUASAR
study. The selection of the same maintenance dose regimens will enable cross-study comparison
of SC induction followed by SC maintenance regimen (in this study) versus IV induction followed
by SC maintenance regimen (in the QUASAR study). Overall, the 2 guselkumab maintenance dose
regimens (ie, 200 mg SC q4w and 100 mg SC q8w) would provide an approximately 4-fold dose
range of exposure that should support dose/exposure-response assessment of maintenance therapy
in the treatment of UC.
4.4. 
End of Study Definition
End of Study Definition
The end of study is considered as the last scheduled study assessment shown in the Schedule of
Activities for the last participant in the study or if a decision has been made by the sponsor not to
pursue an indication in UC or SC induction and appropriate follow-up has been completed. The
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final data from the study site will be sent to the sponsor (or designee) after completion of the final
participant assessment at that study site, in the time frame specified in the Clinical Trial
Agreement.
Participant Study Completion Definition
A participant will be considered to have completed the studyif they have completed assessments
at Week 248 and completed the safety follow-up visit.
Participants who prematurely discontinue study intervention for any reason before completion of
the Week 248 visit can be considered to have completed the studyif they have completed the safety
follow-up visit assessments as indicated in the SoA (Section 1.3).
5. 
STUDY POPULATION
Screening for eligible participants will be performed within 8 weeks before administration of the
study intervention. Refer to Section 5.4, for conditions under which the repeat of any screening
procedures is 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.
For a discussion of the statistical considerations of participant selection, refer to Section 9.2,
Sample Size Determination.
5.1. 
Inclusion Criteria
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
Age
1. 
18 years of age or older (or the legal age of consent in the jurisdiction in which the
study is taking place).
Type of Participant and Disease Characteristics
2. 
Documented diagnosis (histological and either endoscopic or radiographic) of UC at
least 12 weeks prior to screening. A biopsy report supporting the diagnosis must be
available in the source documentation.
3. 
Moderately to severely active UC, defined as baseline (Week 0)
of 5 to 9, inclusive, using the 
 obtained during central
review of the screening video endoscopy.
4. 
5. 
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6. 
A participant who had extensive colitis for ≥8 years, or disease limited to the left side
of the colon for ≥10 years, must either have had a full colonoscopy to assess for the
presence of dysplasia within 1 year before the first dose of study intervention or a full
colonoscopy to assess for the presence of malignancy at the screening visit.
7. 
A participant ≥45 years of age must either have had a full colonoscopy to assess for
the presence of adenomatous polyps within 5 years before the first dose of study
intervention or a full colonoscopy to assess for the presence of adenomatous polyps at
the screening visit. The adenomatous polyps must be removed before the first dose of
study intervention (see Exclusion Criterion 2).
Concomitant or Previous Medical Therapies Received
8. 
Criterion modified per Amendment 1
8.1 Criterion modified per Amendment 2
8.2 A participant must:
a. Have received treatment with 1 or more TNFα antagonists, vedolizumab,
ozanimod, or approved JAK inhibitors at a dose approved for the treatment of UC,
and have a documented history of inadequate response to or intolerance of such
treatment as defined in Appendix 3 (Section 10.3)and Appendix 4 (Section 10.4);
OR
b. Be naïve to advanced therapy (ie, TNFα antagonists, vedolizumab, ozanimod, or
approved JAK inhibitors) or not have demonstrated an inadequate response to or
intolerance of advanced therapy AND  have a prior or current UC medication
history that includes at least 1 of the following:
1) Inadequate response to or intolerance of current treatment with oral
corticosteroids or immunomodulators (6-MP or AZA) as defined in
Appendix 2 (Section 10.2).
OR
2) History of an inadequate response to or intolerance of at least 1 of the
following therapies: oral or IV corticosteroids or immunomodulators (6-MP
or AZA) as defined in Appendix 2 (Section 10.2).
OR
3) History of corticosteroid dependence (ie, an inability to successfully taper
corticosteroids without a return of the symptoms of UC) as defined in
Appendix 2 (Section 10.2).
9. 
Criterion modified per Amendment 1
9.1  Before the first dose of study intervention, the following conditions must be met:
a. If receiving conventional immunomodulators (ie, AZA, 6-MP, or MTX), must have
been taking them for ≥12 weeks, and on a stable dose for at least 4 weeks.
b. If AZA, 6-MP, or MTX has been recently discontinued, it must have been stopped
for at least 4 weeks.
c. If receiving oral 5-ASA compounds, the dose must have been stable for at least
2 weeks.
d. If receiving oral corticosteroids other than budesonide or beclomethasone
dipropionate, the dose must be ≤20 mg/day prednisone or its equivalent and must
have been stable for at least 2 weeks.
e. If receiving oral budesonide or beclomethasone dipropionate, the dose must be
≤9 mg/day of budesonide, or ≤5 mg/day beclomethasone dipropionate and have
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f. If oral 5-ASA compounds or oral corticosteroids have been recently discontinued,
they must have been stopped for at least 2 weeks.
10. 
Criterion modified per Amendment 1
10.1  The following medications/therapies must have been discontinued before the first
dose of study intervention:
a. TNFα-antagonist therapy (eg, infliximab, adalimumab, or golimumab [or approved
biosimilars for these therapies]) for at least 8 weeks.
b. Vedolizumab for at least 12 weeks.
Note for a and b: If there is proper documentation of an undetectable drug level
measured by the site using a commercially available assay for any of the approved
biologics above, there is no minimum washout prior to baseline.
c. Tofacitinib, filgotinib, upadacitinib and other JAK inhibitors for at least 2 weeks or
5 half-lives, whichever is longer.
d. Ozanimod or other S1PR modulators for at least 4 weeks or 5 half-lives, whichever
is longer.
e. Cyclosporine, mycophenolate mofetil, tacrolimus, or sirolimus for at least 4 weeks.
f. 6-thioguanine must have been discontinued for at least 4 weeks.
g. Rectal corticosteroids (ie, corticosteroids administered to the rectum or sigmoid
colon via foam or enema or suppository) for at least 2 weeks.
h. Rectal 5-ASA compounds (ie, 5-ASAs administered to the rectum or sigmoid colon
via foam or enema or suppository) for at least 2 weeks.
i. Parenteral corticosteroids for at least 2 weeks.
j. Total parenteral nutrition for at least 2 weeks.
k. Antibiotics for the primary treatment of UC (eg, ciprofloxacin, metronidazole, or
rifaximin) for at least 2 weeks.
Sex and Contraceptive/Barrier Requirements
11. 
Before randomization, a woman must be:
a. Not of childbearing potential
OR
b. Of childbearing potential and:
Have a negative serum pregnancy test at screening and a negative urine
pregnancy test at Week 0
AND
If heterosexually active, practicing 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 of study intervention (ie, the end of relevant
systemic exposure).
Note: If a participant’s 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 using
a highly effective method of contraception, as described above.
12. 
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
condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive
cap (diaphragm or cervical/vault caps) with spermicidal
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13. 
Participants must agree not to donate eggs (ova, oocytes) or sperm for the purposes of
reproduction during the study and for 12 weeks after the last dose of study
intervention.
Informed Consent
14. 
Must sign an ICF indicating that participant understands the purpose of, and procedures
required for, the study and is willing to participate in the study.
Note: In regions where a participant is ≥18 but has not yet reached the local legal age
of consent, informed consent must be obtained from and signed by both the participant
and his or her legallyacceptable representative.
15. 
Criterion deleted per Amendment 1.
16. 
Must be willing and able to adhere to all specified requirements, including but not
limited to completion of the required assessments, adherence to the visit schedule,
and compliance with the lifestyle restrictions as specified in this protocol.
5.2. 
Exclusion Criteria
Any potential participant who meets any of the following criteria will be excluded from
participating in the study:
Medical Conditions
1. 
Criterion modified per Amendment 1
1.1 Severe extensive colitis as evidenced by:
a. Current hospitalization for the treatment of UC.
OR
b. Investigator judgement that the participant is likely the require a colectomy within
12 weeks of baseline.
OR
c. Symptom complex at screening or baseline visits that includes at least 4 of the
following:
i. Diarrhea with >6 bowel movements/day with macroscopic blood in stool
ii. Focal severe or rebound abdominal tenderness
iii. Persistent fever (temperature >38°C)
iv. Tachycardia (>100 beats/minute)
v. Anemia (hemoglobin <8.5 g/dL [SI: <85.0 g/L])
2. 
Presence on screening endoscopy of adenomatous colonic polyps, if not removed
before study entry, or history of adenomatous colonic polyps that have not been
removed.
3. 
Diagnosis of indeterminate colitis, microscopic colitis, ischemic colitis, or Crohn's
disease or clinical findings suggestive of Crohn's disease.
4. 
Positive stool culture or other examination for an enteric pathogen, including
Clostridioides difficile (formerly known as Clostridium difficile)toxin, within
16 weeks before the first dose of study intervention, unless a repeat examination is
negative and there are no signs of ongoing infection with that pathogen. If time
allows, treatment and repeat testing can occur in the current screening period. Note:

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Participants with a history of cytomegalovirus colitis only remain eligible if, in the
opinion of the investigator, the infection resolved at least 12 weeks prior to screening.
5. 
UC limited to the rectum only or to <20 cm of the colon.
6. 
Presence of a stoma.
7. 
Presence or history of a fistula.
8. 
Surgery within 8 weeks before screening or planned surgery during the study that
may confound the evaluation of benefit from study intervention (eg, surgery for
active gastrointestinal bleeding, peritonitis, intestinal obstruction, or intra-abdominal
or pancreatic abscess requiring surgical drainage).
9. 
Presence of symptomatic colonic or small bowel obstruction, confirmed by objective
radiographic or endoscopic evidence of a stricture with resulting obstruction (dilation
of the colon or small bowel proximal to the stricture on barium radiograph or an
inability to traverse the stricture at endoscopy).
Malignancy or Increased Potential for Malignancy:
10. 
History of malignancy within 5 years before screening (with the exception of a
nonmelanoma skin cancer that has been adequately treated with no evidence of
recurrence for at least 12 weeks before the first dose of study intervention or cervical
carcinoma in situ that has been treated with no evidence of recurrence for at least 12
weeks before the first dose of study intervention).
11. 
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.
Coexisting Medical Conditions or Past Medical History
12. 
History of severe, progressive, or uncontrolled renal, genitourinary, hepatic,
hematologic, endocrine, cardiac, vascular, pulmonary, rheumatologic, neurologic,
psychiatric, or metabolic disturbances, or signs and symptoms thereof.
13. 
History of a transplanted organ (with the exception of corneal transplant performed
>12 weeks before screening).
14. 
Poor tolerability of venipuncture or lacks adequate venous access for required blood
sample collections during the study period.
15. 
Active alcohol or substance abuse within 1 year before screening; use of marijuana is
not necessarily exclusionary, unless deemed abuse by the investigator.
16. 
Suicidal ideation or suicidal behavior in the last 6 months (assessed at Screening). May
be defined as a 
 rating of any of the following:
a. 
b. 
c. Suicidal behavior (actual suicide attempt, interrupted suicide attempt, aborted
suicide attempt, or preparatory behaviors for making a suicide attempt), and is
considered to be at risk by the investigator based on an evaluation by a mental
health professional.
Participants with
 or non-suicidal
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self-injurious behavior who are determined to be at risk by the investigator may not
be randomized.
17. 
Known allergy, hypersensitivity, or intolerance to guselkumab or its excipients (refer
to the guselkumab IB).
18. 
A woman who is pregnant, breastfeeding, or planning to become pregnant while
enrolled in this study or within 12 weeks after the last dose of study intervention.
19. 
A man who plans to father a child while enrolled in this study or within 12 weeks
after the last dose of study intervention.
Prior/Concomitant Therapy
20. 
Has received the following medications or therapies:
a. A biologic therapy targeted at IL-12 and/or IL-23 (eg, ustekinumab, briakinumab,
guselkumab, mirikizumab, tildrakizumab, brazikumab, or risankizumab).
b. Natalizumab within 1 year of the first dose of study intervention.
c. Agents that deplete B or T cells (eg, rituximab, alemtuzumab) within 24 weeks of
the first dose of study intervention.
d. Any investigational drug/therapy within 4 weeks before the first dose of study
intervention or within 5 half-lives of the investigational agent, whichever is longer.
e. Apheresis (eg, Adacolumn or Cellsorba apheresis) within 2 weeks before the first
dose of study intervention.
f. Fecal microbiota transplantation within 12 weeks before the first dose of study
intervention.
Infections or Predisposition to Infections:
21. 
History of latent or active granulomatous infection, including histoplasmosis or
coccidioidomycosis, before screening. Participants with radiographic evidence of
possible prior histoplasmosis or coccidioidomycosis will be excluded. Note: See
Exclusion Criterion 32 regarding tuberculosis-related granulomatous disease.
22. 
History of, or ongoing, chronic or recurrent infectious disease, including but not
limited to, recurrent sinopulmonary infections, bronchiectasis, recurrent renal/urinary
tract infection (eg, pyelonephritis, cystitis), an open, draining, or infected skin wound,
or an ulcer.
23. 
Abnormal chest radiograph within 12 weeks before the first dose of study
intervention with clinically significant findings such as malignancy, previously
unrecognized pulmonary pathology, as well as active or latent infections from TB,
histoplasmosis, or coccidiomycosis. A chest CT scan obtained outside of the protocol
instead of a chest radiograph is also acceptable. Refer to Exclusion Criterion 32 for
information regarding eligibility with a history of latent TB.
24. 
History of being HIV antibody positive, or tests positive for HIV at screening.
25. 
Seropositive for antibodies to HCV, unless they satisfy 1 of the following conditions:
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
b. While seropositive, has a negative HCV RNA test result at least 12 weeks prior to
screening and a negative HCV RNA test at screening.
26. 
Tests positive for HBV infection. (Appendix 5 [Section 10.5])

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Note: For participants who are not eligible for this study due to HIV, HCV, and HBV
test results, consultation with a physician with expertise in the treatment of those
infections is recommended.
27. 
BCG vaccination within 1 year or any other live bacterial or live viral vaccination
within 4 weeks of baseline or plans to receive such vaccines during the study.
28. 
History of nontuberculous mycobacterial infection or clinically significant
opportunistic infection (eg, pneumocystosis, invasive aspergillosis, PML). See
Exclusion Criterion 4 regarding cytomegalovirus colitis.
29. 
Clinically significant infection (eg, hepatitis, sepsis, pneumonia, pyelonephritis),
hospitalization for an infection, or treatment with parenteral antibiotics for an
infection within 8 weeks before the first dose of study intervention. Treated and
resolved infections not considered clinically significant at the discretion of the
investigator need not be exclusionary (eg, acute upper respiratory tract infection,
uncomplicated urinary tract infection).
30. 
Evidence of a herpes zoster infection within 8 weeks before the first dose of study
intervention.
31. 
During the 6 weeks prior to baseline (Week 0), have had ANY of the following
(regardless of vaccination status): (a) confirmed 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-CoV-2 infection
Exception: May be included with a documented negative result for a validated SARS-
CoV-2 test
a. 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
b. With the absence of ALL conditions (a), (b), (c) above during the period between
the negative test result and the baseline study visit.
Note on COVID-19-related exclusion:
The field of COVID-19-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: Those participants who may carry a higher risk for severe COVID-19
illness should follow guidance from local health authorities when weighing the
potential benefits and risks of enrolling in the study, and during participation in the
study
32. 
Criterion modified per Amendment 2
32.1 Meeting ANYof the following TB screening criteria is exclusionary:
Note: IGRA testing includes either QuantiFERON-TB® or T-SPOT®.TB.
a. History of active TB or shows signs or symptoms suggestive of active TB upon
medical history and/or physical examination at screening.
b. History of untreated latent TB prior to screening. An exception is made for
participants who are receiving treatment or will initiate treatment for latent TB prior
to first administration of study intervention.

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Note: For participants with a history of treated latent TB there must be documentation
of appropriate treatment prior to the first administration of study intervention. It is the
responsibility of the investigator to verify the adequacy of previous TB treatment and
provide appropriate documentation. IGRA testing is not required at screening for
participants with a history of treated latent TB or ongoing treatment for latent TB.
c. Recent close contact with a person with active TB. An exception is made if such
participants are referred to a physician specializing in TB to determine if treatment
is warranted or not. This evaluation must be adequately documented and, if
treatment is recommended, the participant must be receiving appropriate treatment
prior to the first administration of study intervention.
d. Positive IGRA test result within 8 weeks before the first dose of study intervention.
An exception is made for participants with:
History of adequately treated latent TB as described above.
Newly identified positive IGRA test result in which active TB has been ruled
out and for which appropriate treatment for latent TB has been initiated prior to
the first dose of study intervention.
False-positive IGRA test as determined by the following:
A suspected false-positive initial IGRA test must be repeated. If repeat testing
is NOT positive, the participant must be referred to a physician specializing in
TB to determine if the initial test can be considered a false-positive. This
evaluation must be adequately documented prior to the first dose of study
intervention. If repeat testing is positive, however, it will be considered a true-
positive and the participant is only eligible if active TB has been ruled out and
appropriate treatment for latent TB has been initiated as described above.
e. Chest radiograph or chest CT (if obtained outside of the protocol) within 12 weeks
before the first dose of study intervention that shows abnormalities suggestive of
active or inactive TB.
Screening Laboratory Tests
33. 
Screening laboratory test results outside the following parameters, and if 1 or more of
the laboratory parameters are out of range, a single retest of laboratory values is
permitted during the approximately 8-week screening period:
a. Hemoglobin <8.0 g/dL (SI: <80.0 g/L)
b. WBC <3 × 103 cells/µL (SI: <3.0 × 109 cells/L)
c. Neutrophils <1.5 × 103 cells/µL (SI: <1.5 × 109 cells/L)
d. Platelets <100 × 103 cells/µL (SI: <100 × 109 cells/L)
e. eGFR <30 mL/min/1.73 m2 using the CKD-EPI formula (Levey 2009)
f. Alanine aminotransferase or aspartate aminotransferase concentrations >2 times
the ULN range
g. TBili >1.5 times the ULN range (Isolated total bilirubin >1.5 times the ULN
range is allowed for those participants with known Gilbert’s syndrome. Note:
Gilbert’s syndrome is suggested by direct bilirubin <30% [Palmer 2020])
Other Exclusions
34. 
Currently participating or intends to participate in any other study using an
investigational agent or procedure during the conduct of this study.

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35. 
Any condition for which, in the opinion of the investigator, participation would not be
in the best interest of the participant (eg, compromise the well-being) or that could
prevent, limit, or confound the protocol-specified assessments.
36. 
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.
Note: Investigators must 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 before the first dose of study intervention is given
such that the participant no longer meets all eligibility criteria, then the participant must be
excluded from participation in the study. Section 5.4, Screen Failures, describes options for
retesting. The required source documentation to support meeting the enrollment criteria are noted
in Appendix 6, Regulatory, Ethical, and Study Oversight Considerations (Section 10.6).
5.3. 
Lifestyle Considerations
Potential participants must be willing and able to adhere to the following lifestyle restrictions
during 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, live vaccines, contraceptive
requirements).
3. It is recommended that participants are up to date on age-appropriate
vaccinations prior to screening as per routine local medical guidelines. It is
strongly recommended that participants will have completed a locally-approved
(or emergency use-authorized) COVID-19 vaccination regimen at least 2 weeks
prior to study-related visits or procedures. Study participants should follow
applicable local vaccine labeling, guidelines, and standards of care for patients
receiving immune-targeted therapy when determining an appropriate interval
between vaccination and study enrollment (see also Section 6.8, Concomitant
Therapy).
4. Willing and able to complete a daily diary to document clinical symptoms, AEs,
etc.
5.4. 
Screen Failures
Participant Identification, Enrollment, and Screening Logs

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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 studysite contact for completeness. This study will use IWRS. The investigator will
not generate screening and enrollment logs directly from IWRS.
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.
Completion of screening and randomization procedures within the specified screening window of
approximately 8 weeks is required. If any delay leads to the expiration of time-specific assessments
(eg, IGRA testing, chest radiograph, endoscopy), the participant will be considered a screen failure
because theywill not meet eligibility criteria, and the expired assessment(s) (along with the non-
time-specific laboratory tests) will have to be repeated on rescreening. Additional criteria for
retesting and rescreening are outlined below.
Retesting
Retesting of abnormal screening laboratory results that may lead to exclusion will be allowed once.
A second retest of abnormal screening laboratory results may be allowed upon consultation and
approval bythe sponsor’s medical monitor. Retesting can occur at an unscheduled visit during the
screening period, as long as this is done within the specified screening window.
Rescreening
Individuals who do not meet the criteria for participation in this study (screen failure) may be
rescreened once.
Rescreened participants will be assigned a new participant number, undergo the informed consent
process, and then start a new screening period including the collection and testing of new
laboratory specimens. Previous TB evaluation results (including an IGRA test and chest imaging),
and endoscopy results from the first screening event may be used if they meet the specified
protocol criteria as described in Section 5.1. Medical monitor approval is required prior to the
study site obtaining a new informed consent for rescreening.
5.5. 
Criteria for Temporarily Delaying Administration of Study Intervention
Guidelines for study intervention administration affected by the COVID-19 pandemic are found
in Section 10.11 (Appendix 11, Study Conduct During a Natural Disaster). Criteria for temporary
discontinuation of study intervention are described in Section 7.1.

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6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY
6.1. 
Study Intervention(s) Administered
Designation 
Product
Investigational Medicinal Product(s) 
Authorization status in the EU/EEA:
Authorized 
N/A
Unauthorized 
Guselkumab
Placebo
Study intervention administration must be captured in the source documents and the CRF.
Study-site personnel will instruct participants on how to store study intervention for at-home use
as indicated for this protocol.
Guselkumab will be manufactured and provided under the responsibility of the sponsor. Refer to
the IB for a list of excipients.
For details on rescue medications, refer to Section 6.5.1, Rescue Medication. For a definition of
study intervention overdose, refer to Section 6.7, Treatment of Overdose.
Description of Interventions
Arm Name 
Arm A  
Arm B  
Arm C
Intervention Name 
Guselkumab  
Guselkumab  
Placebo
Dose Formulation 
Active guselkumab  
 
 
Active guselkumab  
 
 
Active guselkumab 
 
 
 
Matching placebo of
Matching placebo of
Unit Dose Strength(s) 
 
 
SC 100 mg
Placebo
Dosage Level(s) 
Guselkumab
 
 
at 
Weeks 0, 4, and 8 
followed by 
guselkumab 200 mg 
q4w SC at Week 12. 
Guselkumab 
 
 
at 
Weeks 0, 4, and 8 
followed by 
guselkumab 100 mg
q8w SC at Week 16.
Placebo SC (2 placebo
at
Weeks 0, 4, and 8
followed by placebo
q4w SC at Week 12.
Route of Administration 
SC 
SC 
SC
Use 
Experimental 
Experimental 
Placebo
Investigational Medicinal Product 
(IMP)
Yes 
Yes 
Yes
Non-Investigational Medicinal 
Product/Auxiliary Medicinal
Product(NIMP/AxMP)
No 
No 
No
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At-home
Starting from Week 52 up to Week 92, participants may self-administer (or their caregivers may
administer) study intervention at home every 8 weeks, according to the visits outlined in the SoA
(Section 1.3), if allowed per local regulation.
After Week 96, participants may self-administer (or their caregivers may administer) study
intervention  doses at home q4w or q8w (based on their assigned treatment regimen  prior to
Week 96). As study unblinding will have occurred, all sham injections will cease. A medication
supply will be provided during on-site study visits.
Participants who are unable or unwilling to have study injections administered at home will be
required to return to the site for administration of study intervention injection. Participants will
receive instructions on compliance with study intervention, dosing instructions and instructions
for study intervention storage at-home for when they begin self-administration of study
intervention. Participants are provided a study medication diary to record at-home study
intervention administration and will receive instructions on how to self-evaluate any injection-site
reaction. Participants will also be instructed to contact the investigator promptly in the event of
any signs of an allergic reaction, infection, or bleeding.
6.1.2. 
Combination Products
The sponsor-manufactured combination products (or those manufactured for the sponsor by a third
party) provided for use in this study are the 
)and the 
The sponsor manufactures the 100 and 200 mg guselkumab PFS. The sponsor also assembles the
PFS with the devices to form the PFS-U and PFS-Y combination products. The YpsoMate device
(Y) is manufactured by Ypsomed. The UltraSafe device (U) is manufactured by medical device
manufacturer Becton-Dickinson.
Picture-based instructions for the 
 will be provided for
participants as part of training on how to use the device.
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 in combination product, these deficiencies
will be reported as PQC (see Appendix 7: Adverse Events Serious Adverse Events, Product
Quality Complaints, and Other Safety Reporting: Definitions and Procedures for Recording,
Evaluating, Follow-up, and Reporting) and appropriately managed by the sponsor.
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6.2. 
Preparation/Handling/Storage/Accountability
Preparation/Handling/Storage
Guselkumab will be supplied as a
 Matching placebo will be supplied as a 1
 respectively.
All study intervention must be stored at controlled temperatures ranging from 36°F to 46°F (2°C
to 8°C) and protected from exposure to light. Do not freeze the study interventions. The products
are designed for single-use only.
Guselkumab and matching placebo should be clear and colorless to slightlyyellow solution that may
contain small translucent particles. Do not use guselkumab or matching placebo 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; avoid direct exposure to sunlight.
Aseptic procedures must be used during the preparation and administration of the study intervention
material.
Study personnel will instruct participants on how to transport, store, and administer study
intervention for at-home use.
Refer to the site IPPM and IFU for additional guidance on study intervention preparation, handling,
and storage of study intervention materials.
Accountability
The investigator is responsible for ensuring that all study intervention (study drug) 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 and used study intervention with empty outer
box/carton must be available for verification by the sponsor’s study site monitor during on-site
monitoring visits for study intervention accountability.
Potentially hazardous materials containing hazardous liquids, such as used needles and syringes,
should be disposed of immediately in a safe manner and therefore will not be retained for
intervention accountability purposes. The immediate destruction of these drug supplies should be
documented in the study intervention accountability records on site.
Study intervention should be dispensed under the supervision of the investigator or a qualified
member of the studysite 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
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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.
For at-home administration if permitted by local regulation, participants will receive instructions
for at-home storage and handling of used and unused study intervention materials. Participants
who self-administer (or whose caregiver administers) at home will record study intervention
administration with time and date information in the studymedication diary. Participants will be
instructed to return the outer box/carton from the prefilled syringe/autoinjector and/or any unused
study intervention at the next on-site visit. The actual used syringe/autoinjector should be disposed
in the provided sharps container which should only be returned to the site as needed at the last
study visit. Intervention accountability will be based upon the returned outer box/carton for used
study intervention and any unused study intervention if not administered.
6.3. 
Measures to Minimize Bias: Randomization and Blinding
Intervention Allocation
Procedures for Randomization and Stratification
Central randomization will be implemented in this study. Randomization minimizes 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. 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 by ADT-IR status (ie, inadequate response to or intolerance of
approved TNFα antagonists, vedolizumab, ozanimod, or approved JAK inhibitors) (Yes/No), and
 at baseline (moderate [2] or severe [3]) as obtained during central
review of the video endoscopy.
The IWRS will assign a unique intervention code, which will dictate the intervention assignment
and matching study 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 study
name, study intervention number, and reference number. The study intervention number will be
entered in the eCRF when the study intervention is dispensed. Each active study intervention and
its matching placebo will be identical in appearance and will be packaged in identical containers.
All participants will receive the same device(s), which could be either active or matching placebo
at 4-week intervals (double-dummy; see Figure 2) in order to maintain treatment blinding.
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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.
Data that may potentially unblind the intervention assignment (eg, study intervention serum
concentrations, anti-guselkumab antibodies) 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 unblinding.
At the Week 24 DBL, data will be unblinded for analysis to the sponsor only. Treatment
assignment will remain blinded to the study sites, site monitors, and participants until the full study
unblinding following the Week 48 DBL. Identification of sponsor personnel who will have access
to the unblinded participant-level data at the Week 24 DBL will be documented before the
unblinding.
Under normal circumstances, the blind should not be broken until the Week 48 DBL is completed
and the database is finalized. Otherwise, the blind should be broken only if specific emergency
intervention/course of action would be dictated by knowing the intervention status of the
participant. In such cases, the investigator may in an emergency determine the identity of the
intervention by contacting the IWRS. It is recommended that the investigator contact the sponsor
or its designee if possible to discuss the particular situation, before breaking the blind. Telephone
contact with the sponsor or its designee will be available 24 hours per day, 7 days per week. In the
event the blind is broken, the sponsor must be informed as soon as possible. The date and reason
for the unblinding must be documented in the appropriate section of the eCRF, and/or 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 by the investigator will not be
eligible to receive further study intervention, but should complete evaluations specified in the SoA
for participants who discontinue study intervention.
6.4. 
Study Intervention Compliance
When study intervention is administered by qualified staff, the details of each administration
(including date and time of SC injection) will be recorded in the eCRF.
Throughout the study, the investigator or designated study research personnel will be responsible
for providing additional instruction to re-educate any participant who is not compliant with taking
study intervention.
Compliance with the treatment schedule is strongly encouraged. 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. Additional details may be provided in the site IPPM and IFU
that is provided separately.

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6.5. 
Dose Modification
6.5.1. 
Rescue Medication
All participants in the placebo group who meet rescue criteria at Week 16 will receive rescue
treatment, ie, guselkumab 
 at Weeks 16, 20, and 24 followed by guselkumab 100 mg
SC q8w. Participants randomized to guselkumab who meet rescue criteria at Week 16 will continue
their assigned treatment regimen and receive blinded sham rescue with matching placebo SC
injections at Weeks 16, 20, and 24.
Rescue criteria are defined below.
No improvement (ie, no decrease)in
 at Week 12 as obtained during
central review, when compared with baseline
AND
A <2 point improvement (ie, <2 point decrease) in 
 at Weeks 12 and 16,
when compared with baseline
The above rescue criteria are not applicable after Week 16. As described in Section 7.1,
discontinuation of a participant’s study intervention must be strongly considered if they have a
persistent inadequate response or worsening of UC based on signs, symptoms, and/or laboratory
values.
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 ofcare; however, local regulations on continued access will take
precedence.
6.7. 
Treatment of Overdose
For this study, any dose of guselkumab greater than the highest dose at a single dosing visit
specified in this protocol 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:
Closely monitor the participant for adverse event/serious adverse event and laboratory
abnormalities.
Contact the medical monitor immediately.
Document the quantity of the excess dose as well as the duration of the overdosing in the CRF.
Decisions regarding dose interruptions or modifications will be made by the investigator in
consultation with the medical monitor based on the clinical evaluation of the participant.
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6.8. 
Concomitant Therapy
Pre-study therapies administered up to 30 days before the first dose of study intervention must be
recorded on the eCRF. Any COVID-19 vaccines administered, regardless of timing, must be
recorded on the eCRF. Concomitant therapies must also be recorded throughout the study, from
signing of the informed consent to the last study visit. This includes all prescription or over-the-
counter medications (eg, vaccines, vitamins, herbal supplements) different from the study
intervention.
Recorded information will include a description of the type of therapy, treatment period, dosage,
route of administration, and indication.
Modification of an effective pre-existing therapy should not be made for the explicit purpose of
entering a participant into the study.
6.8.1. 
UC-related Concomitant Therapies
Week 0 through Week 48
Participants who are receiving oral 5-ASA compounds, oral corticosteroids, or conventional
immunomodulators (AZA, 6-MP, or MTX) for the treatment of UC at baseline should maintain a
stable dose through Week 48; with the exception of oral corticosteroids which require mandatory
tapering at Week 12 as described in Section 6.8.1.1.
From Week 0 through Week 48, enrolled participants should not initiate any of the following
concomitant UC-specific medical therapies at any time:
Oral or rectal 5-ASA compounds.
Oral, parenteral, or rectal corticosteroids, including budesonide and beclomethasone
dipropionate.
6-MP, AZA, or MTX.
Antibiotics as a primary treatment for UC.
Total parenteral nutrition as a treatment for UC.
If the above medical therapies are initiated or medication doses are changed based on medical
necessity as assessed by the investigator, participants should continue to attend all study visits and
have all assessments. This does not represent a deviation from the study protocol and the
participants may remain on their assigned therapy (guselkumab or placebo).
Week 48 through Week 248
Concomitant therapies for UC, including 5-ASA compounds, corticosteroids, antibiotics,
immunomodulators (ie, AZA, 6-MP, or MTX), and/or total parenteral nutrition, may be
administered and changed at the discretion of the investigator.

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6.8.1.1. 
Oral Corticosteroids and Tapering
Participants who are receiving oral corticosteroids for the treatment of UC at baseline (Week 0)
should maintain a stable dose through Week 12. The oral corticosteroid dose should not be
increased above the baseline dose unless due to medical necessity.
At Week 12, all participants who were taking corticosteroids at Week 0 must begin tapering
corticosteroids. This tapering is mandatory (unless medically not feasible) and should follow the
recommended schedule shown in Table 4. If participants experience worsening disease activity
while tapering corticosteroids, further dose decreases may be suspended, and/or their oral
corticosteroid dose may be temporarily increased up to their baseline corticosteroid dose per the
discretion of the investigator. For participants whose corticosteroid taper is interrupted,
investigators are encouraged to resume tapering within 4 weeks. Tapering may exceed this
schedule only if warranted by medical necessity (eg, participant experiencing corticosteroid-
related side effects). After Week 48, corticosteroids may be administered and dose changed at the
discretion of the investigator.
Table 4: 
Recommended Tapering Schedule for Oral Corticosteroids
Recommended Tapering Schedule for Oral Corticosteroids (Other than Oral Budesonide and Oral
Beclomethasone dipropionate)
Dose >15 mg/day prednisone or 
equivalent 
Taper daily dose by 5 mg/week until receiving 10 mg/day, then
continue tapering at 2.5 mg/week until 0 mg/day
Dose 11 to 15 mg/day prednisone or 
equivalent 
Taper daily dose to 10 mg/day for 1 week, then continue at
2.5 mg/week until 0 mg/day
Dose ≤10 mg/day prednisone or 
equivalent:
Taper daily dose by 2.5 mg/week until 0 mg/day
Recommended Tapering Schedule for Oral Budesonide or Oral Beclomethasone dipropionate
Participants receiving oral budesonide or oral beclomethasone dipropionate should have their daily dose
tapered according to local clinical practice until 0 mg/day.
6.8.2. 
Prohibited Concomitant Therapies
Participants who initiate the following treatments will be discontinued from further study
intervention administration and should have a final safety follow-up visit approximately 12 weeks
after their last dose of study intervention:
Immunomodulatory agents other than 6-MP, AZA, or MTX (eg, 6-thioguanine, cyclosporine,
mycophenolate mofetil, tacrolimus, sirolimus, ozanimod, and JAK inhibitors).
Immunomodulatory biologic agents (eg, TNFα antagonists, ustekinumab, vedolizumab,
abatacept, anakinra).

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Experimental IBD medications (eg, etrolizumab, brazikumab, mirikizumab, risankizumab) or
other investigational medications/therapies.
Thalidomide or related agents.
The sponsor must be notified as soon as possible of any instances in which prohibited therapies
are administered or planned to be administered.
Participants must not receive guselkumab 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
an ED visit as described in Section 1.3.
6.8.3. 
Vaccinations (including COVID-19)
Participants must not receive a live virus, live bacterial, or BCG vaccination during the study and
for 12 weeks after receiving the last dose of study intervention.
When considering use of locally-approved (including emergency use-authorized) COVID-19
vaccines in study participants, consider protocol life style considerations (Section 5.3) and follow
applicable local vaccine labeling, guidelines, and standards of care for patients receiving immune-
targeted therapy. Additionally, it is recommended that, where possible, 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
If a participant discontinues study intervention or withdraws from the study before the end of the
study, assessments should be obtained as specified in the SoA (Section 1.3).
7.1. 
Discontinuation of Study Intervention
A participant who discontinues study intervention will not be automatically withdrawn from the
study (see Section 7.2).
A participant’s study intervention mustbe 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 a pregnancy within the study period. Refer to
Appendix 8 (Section 10.8), Contraceptive and Barrier Guidance.
The participant initiates treatment with a prohibited therapy(Section 6.8.2).
The participant receives a live viral, live bacterial, or BCG vaccination.
The participant has a colectomy.

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The participant develops an opportunistic infection as determined by the investigator.
The participant meets ANY of the following TB related conditions:
–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 chest imaging with evidence of current active
TB and/or a positive IGRA test result, unless active TB can be ruled out and appropriate
treatment for latent TB can be initiated prior to the next administration of study
intervention and continued to completion. Indeterminate/borderline results should be
handled as outlined in Section 8.2.11.
–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
resulting in bronchospasm with wheezing and/or dyspnea that requires ventilatory support OR
that results in symptomatic hypotension with a decrease in systolic blood pressure >40 mm Hg
or blood pressure <90/60 mm Hg.
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/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 localized basal cell skin cancers that are
adequately treated with no evidence of recurrence or 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 Section 8.2.4 and Appendix 10 (Section 10.10; Guideline
Algorithm for Monitoring, Assessment and Evaluation of Abnormal Liver Tests).
Discontinuation of a participant’s study intervention must be strongly considered under the
following conditions:
Persistent inadequate response or worsening of UC based on signs, symptoms, and/or
laboratory values. If the participant experiences AEs consistent with clinically significant
worsening of UC at any time during the study, these events should be evaluated by the
investigator and the study medical monitor to decide on discontinuation of study intervention.
Discontinuation of study intervention should be considered in participants with clinically
significant worsening of UC where continuation of the study intervention is not in the best
interest of the participant.
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.

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The participant reports suicidal ideation with intention to act 
on a post-baseline
 assessment. If a participant can be adequately treated with
psychotherapy and/or pharmacotherapy based on an evaluation by a mental health
professional, then the participant, at the discretion of the investigator, may be continued with
treatment if agreed to by the medical monitor or designee. Discussion of such participants with
the medical monitor or designee is required.
The participant develops a severe injection-site reaction.
If a participant discontinues study intervention for any reason before the end of the treatment
period, then the assessments as specified in the SoA (Section 1.3) must be obtained. If the reason
for discontinuation of study intervention is withdrawal of consent, every effort should be made to
conduct the ED  visit assessment, as indicated in the SoA, prior to terminating the study
participation. After termination of study participation, no additional assessments are allowed.
Study intervention assigned to the participant who discontinued study intervention may not be
assigned to another participant. Additional participants will not be entered to replace participants
who discontinue study intervention or withdraw from the study.
7.2. 
Participant Discontinuation/Withdrawal From the Study
A participant will be withdrawn from the study for any of the following reasons:
Lost to follow-up
Withdrawal of consent
Death
Sponsor decision (eg, participating in any other clinical study with an investigational agent)
When a participant withdraws before study completion, the reason for withdrawal is to be
documented in the CRF and in the source document. If the reason for withdrawal from the study
is withdrawal ofconsent then no additional assessments are allowed.
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 (eg, consult with family members, contacting the participant’s other physicians,
medical records, database searches, use of locator agencies at study completion,) as local
regulations permit.
7.2.1. 
Withdrawal From the Use of Research Samples
Withdrawal from the Use of Samples in Future Research
The participant may withdraw consent for use of samples for research (refer to Long-Term
Retention of Samples for Additional Future Research in  Appendix 6, Regulatory, Ethical, and
Study Oversight Considerations). In such a case, samples will be destroyed after they are no longer
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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 the participant 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 studysite 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, they 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 may be transferred to another study
site if feasible.
8. 
STUDY ASSESSMENTS AND PROCEDURES
Overview
The SoA (Section 1.3) summarizes the frequency and timing of scheduled visits, and the timing of
efficacy, safety, PK, immunogenicity, PRO, and other assessments applicable to this study.
The visit window should be ±4 days for each visit up to and including Week 12; after Week 12 to
Week 24, the visit window should be ±7 days, after Week 24 to the end of study the visit window
should be ±10 days (as described in the SoA). All post-randomization visits should be scheduled
relative to the participant’s randomization date. If a study visit cannot be held within the
recommended visit window, the subsequent visit should be conducted as closely as possible to the
study visit schedule and the site should bring the participant in gradually closer to the expected
visit date by applying the allowable ± visit window.
All PRO assessments should be conducted/completed before any tests, procedures, or other

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consultations to prevent influencing participant responses. Refer to the PRO completion guidelines
for instructions on the administration of PROs.
The 
 should be completed after all PRO assessments and before any other tests,
procedures, or other consultations to prevent influencing participant perceptions.
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 time points if needed. Actual
dates and times of assessments will be recorded in the source documentation and eCRF.
For women of childbearing potential only, additional urine pregnancy tests may be performed, as
determined necessary by the investigator or required by local regulation, to establish the absence
of pregnancy at any time during the participation in the study.
Screening
The screening period is up to 8 weeks duration before randomization. After written informed
consent has been obtained, all screening evaluations (eg, laboratory test results, clinical data, and
concomitant medication  data) that establish participant eligibility will be performed by the
principal investigator or designee to confirm that the participant satisfies all inclusion criteria and
does not violate any exclusion criteria. Participants who meet all of the inclusion and none of the
exclusion criteria can be randomized in the study. Every effort should be made to adhere to the
SoA (Section1.3) for each participant. The collection of AEs will start at the time informed consent
is obtained.
Diaries and/or instructions for use of a personal device will be provided to each participant. A
 diary will be completed from recall at screening and will be used to assess the participant’s
eligibility for further screening and to train the participant on the use of the diary. Participants with
a combined stool frequencyand
can proceed with endoscopy.
Participants will be instructed to complete the 
 and 
 daily diary entries for the
10 days immediately before Week 0 through Week 4, and for the 10 days immediately before each
visit thereafter, as per SoA (Section 1.3).
The screening endoscopy should be performed within 2 weeks (and at least 4 days) before the
baseline visit. Participants who are identified as being at increased risk for colon cancer
(Section 5.1, Inclusion Criterion 6) or for adenomatous polyps (Section 5.1, Inclusion Criterion 7)
will undergo a full colonoscopy instead of a sigmoidoscopy to allow screening for dysplasia or to
assess for the presence of adenomatous polyps, respectively. Any screening colonoscopy for
malignancy should include surveillance biopsies consistent with local practice. At least 48 hours
should elapse between a colonoscopy with polypectomy and the Week 0 visit.  Local pathology
results from the screening endoscopy must be reviewed before the first dose of study intervention.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the CRF  or laboratory
requisition form.
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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.
The total blood volume to be collected from each participant will be approximately 326 mL.
Study-Specific Materials
The investigator will be provided with the following supplies:
Investigator Site File (includes protocol and IB)
ICF
IFU
IPPM
IWRS manual
Participant diaries (and/or instructions for use of a personal device) and study medication
diaries
eCRF completion instructions
Central laboratory manual
Laboratory kits
Biopsy manual
Endoscopy kit
Imaging manual
Electronic patient-reported outcome equipment
Patient recruitment materials
At home stool collection kits
Ancillary supplies as required
8.1. 
Efficacy Assessments
Efficacy evaluations will include the following:
Inflammatory PD markers including CRP and fecal calprotectin
Histological assessments (eg, 
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Patient-reported outcome measures to assess 
 outcomes, fatigue, and UC symptoms
and signs (eg, 
8.1.1. 
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8.1.2. 
Histologic Assessments
Histologic assessments will be performed using biopsy samples collected during endoscopy (see
endoscopy manual for biopsy details). Histologic assessments will be conducted by a central reader
who is blinded to treatment groups and visit. The 
will be used to
evaluate histologic activity. Analyses will be specified in the SAP.
8.1.3. 
C-Reactive Protein
C-reactive protein has been demonstrated to be useful as a marker ofinflammation in participants
with IBD. In UC, elevated CRP has been associated with severe clinical activity, an elevated
sedimentation rate, and active disease as detected by colonoscopy (Solem 2005; Vermeire 2004).
Serum samples for the measurement of CRP will be collected from all participants at visits
indicated in the SoA (Section  1.3). C-reactive protein will be assayed using a validated, high
sensitivity CRP assay.
8.1.4. 
Fecal Calprotectin
Fecal calprotectin has been demonstrated to be a sensitive and specific marker in identifying
colonic inflammation and response to treatment in participants with IBD, especially in UC
(Abraham 2012). Stool samples for calprotectin concentrations will be collected from all
participants at visits as indicated in the SoA (Section 1.3).
Assays for fecal calprotectin will be performed by the central laboratory using a validated method.
Additional tests may also be performed on the stool samples for markers that are related to colonic
inflammation, response to treatment, or changes in the microbiome.
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8.1.5. 
8.1.6. 
8.1.7. 
8.2. 
Safety Assessments
Safety assessments will include the monitoring of AEs, injection-site reactions, symptoms of a
hypersensitivity reaction, UC-related surgeries and procedures, and any signs or symptoms of
infection or TB. In addition, vital signs, physical examinations, ECGs, clinical safety laboratory
tests, and 
 will be performed, as well as review of concomitant medication. Endoscopies
will be performed every 48 weeks beginning at Week 96 to assess long term safety.
Adverse events will be reported and followed by the investigator as specified in Section 8.3,
Adverse Events, Serious Adverse Events, and Other Safety Reporting and Appendix 7, Adverse
Events, Serious Adverse Events, Product Quality Complaints, and Other Safety Reporting:
Definitions and Procedures for Recording, Evaluating, Follow-up, and Reporting.
Any clinically relevant changes occurring during the study must be recorded on the Adverse Event
section of the eCRF.
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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 time
points provided in the SoA.
8.2.1. 
Physical Examinations
Physical examinations, including height and weight, will be performed as specified in the SoA.
While assessment of the participants for safety and efficacy requires some physical examination
by an investigator at all visits, a more complete, detailed physical exam should be performed as
specified in the SoA. Participants will be instructed to remove shoes and outdoor apparel and gear
prior to measurements for height and weight.
8.2.2. 
Vital Signs
Temperature (any method is acceptable), pulse/heart rate, respiratory rate, blood pressure will be
assessed.
Blood pressure and pulse/heart rate measurements should be assessed with a completely automated
device. Manual techniques should be used only if an automated device is not available. 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).
At a study intervention administration visit, vital signs should be obtained before and
approximately 30 minutes after the SC injection, or if the participant reports any symptoms.
8.2.3. 
Electrocardiograms
A 12-lead ECG will be performed locally at screening.
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 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 time point as ECG recording, the procedures should
be performed in the following order: ECG(s), vital signs, blood draw.
8.2.4. 
Clinical Safety Laboratory Assessments
Blood samples for serum chemistry and hematology will be collected as noted in  the SoA
(Section 1.3). 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.
Any clinically significant laboratory abnormality should be assessed and repeated as warranted.
The laboratory reports must be filed with the source documents.
The following tests will be performed by the central laboratory unless otherwise specified or
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Hematology assessments will include but are not limited to the following: hemoglobin,
hematocrit, platelet count, total and differential WBC count.
Blood chemistry assessments will include but are not limited to the following: chemistry
panel (total and direct bilirubin, ALT, AST, ALP, albumin, total protein, calcium, phosphate,
sodium, potassium, chloride, blood urea nitrogen/urea, and creatinine).
A medical monitor or delegate and the clinical site will be notified if prespecified abnormal
laboratory values defined in the laboratory manual are identified in any participant during the
conduct of the study.
Serology: HIV antibody, HBV antibodies and surface antigen, and HCV antibody. Additional
details regarding HBV are provided in Appendix 5 (Section 10.5).
Liver chemistry: If laboratory testing for a participant who is enrolled in the study and
receiving study intervention reveals a possible Hy’s Law case (Section 8.3.1), study
intervention should be suspended immediately. In addition, laboratory tests for ALT, AST,
ALP, and TBili should be confirmed by a retest within 24 hours if possible, but no later than
72 hours following notification of test results. Additional clinical and laboratory studies may
be performed to evaluate the underlying etiology of abnormal findings. See Appendix 10
(Section 10.10) for additional information on monitoring and assessment of abnormal liver
function tests.
FSH: Refer to Appendix 8 (Section 10.8) for instances when a screening FSH test should be
considered.
Details on the laboratory tests that will be performed are provided in the laboratory manual.
8.2.5. 
Pregnancy Testing
Women participants of childbearing potential will undergo pregnancy testing as indicated in the
SoA (Section 1.3). Additional urine pregnancy tests may be performed, as determined necessary
by the investigator or required by local regulation, to establish the absence of pregnancy at any
time during the participation in the study.
8.2.6. 
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) (Danesh 2016), the
 will
be used as a screening tool to prospectively evaluate suicidal ideation and behavior among study
participants.
 
 
 
 
 
 
 
 
 
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The investigator or trained study site personnel will interview the participant and complete the
 The
 will be provided in the local languages in accordance with local guidelines.
At screening, the 
 will be the first assessment performed after signing informed consent,
before any other study procedure. At all subsequent visits, the 
 will be performed
according to the assessment schedule as outlined in the SoA (Section 1.3) and should be performed
after other PROs but before any other study procedures. Participants will be interviewed by the
investigator or trained study site personnel in a private, quiet place.
At the conclusion of each assessment, the trained personnel administering the 
 will
determine the level of suicidal ideation or behavior, if any. They will then determine the next
course of action if any level of suicidal ideation or behavior is reported. The participant should not
be released from the site until the 
 has been reviewed by the investigator and the
participant’s risk has been assessed and follow-up is determined, as appropriate.
At screening (within the last 6 months) and Week 0, participants with a 
 or suicidal behavior (actual suicide attempt, interrupted suicide
attempt, aborted suicide attempt, or preparatory behaviors for making a suicide attempt), must be
determined to not be at risk by the investigator based on an evaluation by a mental health
professional (eg, psychiatrist, psychologist, or appropriately trained social worker or nurse) in
order to be randomized.
Participants with 
or non-suicidal self-injurious behavior must be
determined not to be at risk by the investigator in order to be randomized in the study. Any
questions regarding eligibility of such participants should be discussed with the medical monitor
or designee.
For each assessment after Week 0, the following actions should be taken, if applicable:
No suicidal ideation or behaviors (including self-injurious behavior without suicidal intent):
No further action is needed.
 Participant risk is assessed
by the investigator.
 Participant risk assessed and referral
to a mental health professional.
Interruption or the discontinuation of studyintervention should be considered for any participant
who reports Suicidal Ideation with Intention to Act 
 or suicidal behavior (actual suicide attempt,
interrupted suicide attempt, aborted suicide attempt, or preparatory behaviors for making a suicide
attempt) on a postbaseline
 assessment and who is deemed to be at risk by the investigator
based upon evaluation by a mental health professional. If a participant can be adequately treated
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with psychotherapy and/or pharmacotherapy, then the participant, at the discretion of the
investigator, may be continued with treatment if agreed to by the medical monitor or designee.
Discussion of such participants with the medical monitor or designee is required.
Any 
 finding, which in the opinion of the investigator is new or considered to be a
worsening and clinically significant, should be reported on the AE eCRF (see Appendix 7
[Section 10.7], Adverse Events, Serious Adverse Events, Product Quality Complaints, and Other
Safety Reporting).
8.2.7. 
Concomitant Medication Review
Concomitant medications will be reviewed and recorded at each visit.
8.2.8. 
Injection-Site Reactions
An injection-site reaction is any adverse reaction at a SC study intervention injection-site. Injection
sites will be evaluated for reactions and any injection-site reaction will be recorded as an AE.
Participants are provided a study medication diary to record at-home study intervention
administration (see Section 6.1) and will receive instructions on how to self-evaluate any injection-
site reaction. Participants will also be instructed to report AEs related to injection-site reactions to
the site promptly.
8.2.9. 
Hypersensitivity Reactions
Before any administration of study intervention at the study site, appropriately trained personnel
and medications (eg, injectable epinephrine) must be available to treat hypersensitivity reactions,
including anaphylaxis. All participants must be observed carefully for signs and symptoms of a
hypersensitivityreaction (eg, urticaria, pruritis, angioedema, wheezing, dyspnea, or hypotension).
8.2.10. 
Infections
Investigators are required to evaluate participants for any signs or symptoms of infection at
scheduled visits (see SoA, Section  1.3). Study intervention should not be administered 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.
8.2.11. 
Tuberculosis Evaluations
Initial Tuberculosis Evaluation
Participant 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 imaging results and responses to
tuberculin skin or other TB testing. Investigators have the option to use the tuberculin skin test in
addition to IGRA testing to screen for latent TB if preferred by local health authorities, or if they
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believe based on their judgment that both tests are clinically indicated to evaluate a participant at
high risk for latent TB.
Participants with a negative IGRA test result are eligible to continue with prerandomization
procedures. Participants with a newly identified positive IGRA test result must undergo an
evaluation for active or latent TB, or suspected false-positive initial testing, and initiate appropriate
treatment if needed (see Section 5.2). Appropriate treatment for latent TB is defined according to
local country/territory guidelines for immunocompromised patients. If no local country/territory
guidelines for immunocompromised patients exist, US guidelines must be followed.
Participants with indeterminate/borderline IGRA test results should have the test repeated.
Participants with persistently indeterminate/borderline IGRA test results may be randomized or
continued in the studywithout treatment for latent TB, if active TB is ruled out, chest imaging
shows no abnormality suggestive of TB (active or inactive), 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 medical monitor and recorded in the participant’s source documents and
initialed by the investigator.
Ongoing Tuberculosis Evaluation
To aid in the early detection of TB infection or exposure during study participation, participants
must be evaluated for TB signs, symptoms, and close contacts at scheduled visits (refer to
Section 1.3) or by telephone 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?”
“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 for TB infection or the participant has had a close contact
exposure to TB, study intervention must be withheld and an immediate and thorough investigation
must be undertaken, including consultation with a physician specializing in TB to determine if
treatment is warranted prior to any further study intervention. Participants should be encouraged
to return for all subsequent scheduled study visits according to the protocol.
Note: Investigators should be aware that TB reactivation in immunocompromised participants may
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8.3. 
Adverse Events, Serious Adverse Events, and Other Safety Reporting
Timely, accurate, and complete reporting and analysis of safety information, including AEs,
serious AEs, and 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 PQCs can be found in Appendix 7, Adverse Events, Serious
Adverse Events, Product Quality Complaints, and Other Safety Reporting: Definitions and
Procedures for Recording, Evaluating, Follow-up, and Reporting.
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 occurring during the study must be reported to the appropriate sponsor contact person
by studysite personnel immediately.
Serious adverse events, including those spontaneously reported to the investigator within 12 weeks
after the last dose of study intervention, must be reported. The sponsor will evaluate any safety
information that is spontaneously reported by an investigator beyond the time frame specified in
the protocol.
A possible Hy’s law Case is defined by the occurrence of ALT/AST ≥3 x ULN together with total
bilirubin ≥2 x ULN or INR >1.5 (if measured). Any possible Hy’s Law case is considered an
important medical event and must be reported to the sponsor in an expedited manner, even before
all other possible causes of liver injury have been excluded.
A confirmed Hy’s law case must be reported as an SAE.
Information regarding SAEs will be transmitted to the sponsor using an SAE form which must be
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immediately but no later than within 24 hours. The initial and follow-up reports of an SAE should
be made per sponsor reporting process.
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.
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.
Adverse events and the special reporting situation of pregnancy will be followed by the
investigator as specified in Appendix 7, 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/IECs/IRBs in each respective country/territory, as applicable.
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:
Adverse events related to symptoms of ulcerative colitis
Adverse events related to worsening or progression of ulcerative colitis
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.

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8.3.5. 
Pregnancy
All initial reports of pregnancy in female participants or partners of male participants must be
reported to the sponsor by the studysite personnel within 24 hours of their knowledge of the event
using the appropriate pregnancy notification form. Abnormal pregnancy outcomes (eg,
spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are
considered SAEs and must be reported using the Serious Adverse Event form.
Any participant who becomes pregnant during the study must discontinue further study
intervention.
Follow-up information regarding the outcome of the pregnancy for female participants who
become pregnant, or where the pregnancy was the result of male participant and his partner, and
any postnatal sequelae in the infant will be required.
8.3.6. 
Adverse Events of Special Interest
Any newly identified malignancy or case of active TB occurring after the first administration of
study intervention must be reported by the investigator according to the procedures in Appendix 7
(Section 10.7).  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 a
serious adverse event.
8.4. 
Pharmacokinetics
Serum samples will be used to evaluate the PK ofguselkumab at time points presented in the SoA
(Section 1.3). Serum collected for PK may additionally be used to evaluate safety or efficacy
aspects that address concerns arising during or after the study period, or for the evaluation of
relevant biomarkers. Participant confidentiality will be maintained.
8.4.1. 
Evaluations
At visits where only serum concentrations of guselkumab will be evaluated (ie, no antibodies to
guselkumab will be evaluated), 1 venous blood sample of sufficient volume should be collected.
Each serum sample will be divided into 2 aliquots: 1 for serum concentration of guselkumab and
a back-up.
At visits where serum concentrations of guselkumab and antibodies to guselkumab will be
evaluated, 1 venous blood sample of sufficient volume should be collected. Each serum sample
will be divided into 3 aliquots: 1 for serum concentration of guselkumab, 1 for antibodies to
guselkumab, and a back-up.
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.

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8.4.2. 
Analytical Procedures
Pharmacokinetics
Serum samples will be analyzed to determine concentrations of guselkumab  using a validated,
specific, and sensitive immunoassay methods by or under the supervision of the sponsor. The
sponsor, or its designee, under conditions’ in which the participants’ identities remains blinded,
will assay these samples.
8.4.3. 
Pharmacokinetic Parameters and Evaluations
Parameters
Serum samples will be used to evaluate guselkumab PK parameters based on blood drawn from
all participants according to the SoA (Section 1.3). A population PK analysis approach may be
used to derive PK parameters when appropriate.
Pharmacokinetic/Pharmacodynamic Evaluations
The relationship between serum concentrations of guselkumab and efficacy measures or relevant
biomarker(s) may be examined when appropriate.
8.5. 
Pharmacogenomics
Pharmacogenomics are not evaluated in this study.
8.6. 
Biomarkers
Biomarker assessments will be made to examine the biologic response to treatment and to identify
biomarkers that are relevant to guselkumab treatment and/or UC. Assessments (detailed below)
will include the evaluation of relevant biomarkers in serum, whole blood and endoscopic biopsy
samples collected as specified in the SoA (Section 1.3), where local regulations permit. Digital
images of biopsy histology slides and endoscopy videos may be used to support exploratory
research to develop artificial intelligence algorithms to aide in the evaluation of mucosal changes
in UC.
Data collected from these samples will be used for exploratory research that will include the
following objectives:
1. To understand the molecular effects of guselkumab
2. To understand UC pathogenesis
3. To understand why an individual may respond differently to guselkumab
4. To understand the impact of treatment with guselkumab on intestinal mucosal inflammation
in participants with moderately to severely active UC
5. To develop diagnostic tests to identify UC populations that may be responsive or
non-responsive to treatment with guselkumab
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

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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 earlyor shows poor clinical efficacy,
completion of biomarker assessments is based on justification and intended utility of the data.
8.6.1. 
Serum-based Biomarkers
Blood samples for serum-based biomarker analyses will be collected from all participants where
local regulations permit. Assays to be performed may include proteins associated with
proinflammatory and anti-inflammatory effects, the recruitment and proliferation of cells
associated with inflammation and repair, and markers associated with tissue injury or repair. These
analyses will include but will not be limited to IL-17A and IL-22. Proprietary algorithms and
standard statistical techniques, such as ANOVA and ANCOVA, will be used to identify individual
proteins exhibiting statistically significantly different changes in their levels between samples
and/or between groups of samples. This will enable the evaluation of changes in proteome profiles
that may correlate with biologic response relating to UC or the mechanism of action of
guselkumab.
8.6.2. 
Whole Blood-based Biomarkers
Whole blood samples will be collected from all participants to assess the effect of study
intervention on RNA expression profiles where local regulations permit. Whole blood analyses
may also examine RNA expression associated with the pathogenesis of UC. Transcriptome studies
may be conducted using RNA sequencing, and/or alternative equivalent technologies, which
facilitates the simultaneous measurement of the relative abundances of thousands of RNA species
resulting in a transcriptome profile for each blood sample. This will enable the evaluation of
changes in transcriptome profiles that may correlate with biologic response relating to UC or the
action of guselkumab.
The same samples may also be used to confirm findings by application of alternative technologies.
8.6.3. 
Biopsy-based Biomarkers
Mucosal biopsy samples will be collected during endoscopy to evaluate the effect of study
intervention on histologic activity. Biopsies will also be analyzed for exploratory gene and protein
expression analysis where local regulations permit.
8.6.4. 
Pharmacodynamics
Inflammatory PD markers (CRP and fecal calprotectin [see Section 8.1]) will be evaluated using
blood and fecal samples collected at visits as indicated in the SoA (Section 1.3)
8.7. 
Immunogenicity Assessments
Antibodies to guselkumab  will be evaluated in serum samples 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. These samples
will be tested by the sponsor or sponsor's designee.

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Serum samples will be screened for antibodies binding to guselkumab and the titer of confirmed
positive samples will be reported. Other analyses may be performed to verify the stability of
antibodies to guselkumab and/or further characterize the immunogenicity of guselkumab.
Serum  samples will be used to evaluate the immunogenicity of anti-guselkumab antibodies.
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.
Analytical Procedures
The detection and characterization of antibodies to guselkumab will be performed using a validated
assay method by or under the supervision of the sponsor.
8.8. 
Medical Resource Utilization and Health Economics
UC-related surgeries and procedures will be collected and reviewed in this study.
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. Further details will be provided in the SAP.
9.1. 
Statistical Hypotheses
The primary hypothesis is that guselkumab SC induction is superior to placebo SC as measured
by clinical remission at Week 12 among participants with moderately to severely active UC.
9.2. 
Sample Size Determination
Sample size was determined by the power to detect significant differences in the primary endpoint
of clinical remission at Week 12, and by the objective of maintaining at least 85% power across
secondary endpoints at Week 12 between the combined guselkumab SC induction groups and the
placebo SC group as well as for secondary endpoints at Week 24 between each guselkumab group
and the placebo group, using 2-sided chi-square tests with significance level 0.05. Combination of
guselkumab SC induction groups for the primary endpoint and other Week 12 endpoints is
warranted by the fact their treatment is identical through the induction period, and only differs
after assessment of the primary endpoint at Week 12.
With assumed clinical remission rates of 8% for placebo and 22% for the combined guselkumab
groups (based on data from Phase 2b guselkumab UC IV induction study [CNTO1959UCO3001])
and Phase 3 ustekinumab UC program [CNTO1275UCO3001], a total of 399 participants
(randomized 1:1:1 for guselkumab 
 q4w (Weeks 0, 4, and 8) followed by guselkumab
200 mg SC q4w: guselkumab 
 q4w (Weeks 0, 4, and 8) followed by guselkumab 100
mg SC q8w: Placebo, yielding a 2:1 guselkumab:placebo randomization ratio for Week 12
comparisons) will ensure >95% power for the primary endpoint. This sample size also protects
against a slightly lower remission rate of 20% for the combined guselkumab groups or a slightly
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higher remission rate of 9.5% in the placebo group (as observed in CNTO1959UCO3001), yielding
a power of 90% in both cases.
Individual power values (ie, without consideration of an adjustment for multiplicity) achieved for
secondary endpoints at Week 12 are described in Table 5.
Table 5: 
Power for Secondary Endpoints at Week 12 with a Total of 399 Participants (2:1
Guselkumab:Placebo)
Endpoints 
Proportion achieving 
endpoint in Placebo group  
Proportion achieving endpoint in 
combined Guselkumab group
Power
Symptomatic remission 
20% 
45% 
>99%
Endoscopic improvement 
13%  
28% 
94%
Clinical response 
30% 
60%  
>99%
Histologic-endoscopic
mucosal improvement
8% 
19%  
85%
Assumed rates were based on data from Phase 2b guselkumab UC IV induction study  and Phase 3
ustekinumab UC program
For the secondary endpoints at Week 24, power is determined by the pairwise comparison of
individual guselkumab groups to placebo (see Table 6).
Table 6: 
Power for Secondary Endpoints at Week 24 with a Total of 399 Participants (133 per Treatment
Group)
Endpoints 
Proportion achieving endpoint 
in Placebo group  
Proportion achieving endpoint in an 
individual Guselkumab group
Power
Clinical remission 
10%  
27% 
95%
Symptomatic
remission
30% 
60%  
>99%
Endoscopic
improvement
13%  
28% 
86%
Clinical response 
35%  
70% 
99%

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9.3. 
Populations for Analysis Sets
For purposes of analysis, the following populations are defined:
Table 7: 
Analysis Populations
Population 
Description
Enrolled 
All participants who sign the ICF
Randomized 
All participants who were randomized in the study.
Full analysis set 
All randomized participants who received at least 1 dose of study intervention
Safetyanalysis 
set
All randomized participants who received at least 1 dose of study intervention.
PK analysis set 
All randomized participants who received at least 1 dose of study intervention and have at least
one valid blood sample drawn post-baseline for PK analysis
Immunogenicity 
analysis set 
All randomized participants who received at least 1 dose of study intervention and have
appropriate samples for anti-drug antibody detection
9.4. 
Statistical Analyses
The statistical analysis plan will be finalized prior to the Week 24 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 the
primary and secondary endpoints.
9.4.1. 
General Considerations
Descriptive statistics (eg, mean, median, SD, IQ range, minimum, and maximum) will be used to
summarize continuous variables. Counts and percentages will be used to summarize categorical
variables. Graphical data displays (eg, line plots) may also be used to summarize data.
Analyses suitable for categorical data (eg, chi-square tests, CMH chi-square tests, or logistic
regression, as appropriate) will be used to compare the proportions of participants achieving
selected endpoints (eg, clinical response). In cases of rare events, the Fisher’s exact test will be
used for treatment comparisons. Continuous response parameters measured at more than one
post-baseline visit will be compared using a MMRM model (unless otherwise specified). If the
normality assumption is in question, an appropriate transformation may be implemented before
fitting the MMRM model. Continuous response parameters measured at only one post-baseline
visit will be compared using an ANOVA or ANCOVA, unless otherwise specified. In cases of
small sample size, t-test will be used for treatment comparisons.
The overall Type I error rate will be controlled at the significance level of 0.05 (2-sided). Methods
for multiplicity control over primary and secondary endpoints are described in Section 9.4.3.2.
Unless otherwise specified, the analysis of endpoints related to the endoscopy subscore, including
the 
 will be based on the final reported 
(Section 8.1.1).
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9.4.2. 
Primary Endpoint
The primary endpoint is clinical remission at Week 12, defined as a
and not increased from baseline, a 
 and an
 with no friability present on the endoscopy.
9.4.2.1. 
Primary Estimand of Clinical Remission at Week 12
The primary estimand (ie, a precise definition of the primary targeted treatment effect) is defined
by the following 5 attributes:
i) Treatment through Week 12:
Experimental: Combined guselkumab 
 induction dose group (ie, both guselkumab
groups who received
 at Weeks 0, 4, and 8; see Section 4.1)
Control: Placebo SC q4w (Weeks 0, 4, 8)
ii) Population: Participants with moderately to severely active ulcerative colitis as reflected in the
inclusion/exclusion criteria (Section 5).
iii) Variable (Endpoint): A binary response variable (response/nonresponse) where response is
defined as achieving a
 a
 and an
 with no friability present on the endoscopy at Week 12, where the
 has not increased from baseline and none of the ICEs in categories 1 to
3 and 5 outlined in Table 8 has occurred prior to the Week 12 visit.
iv) Intercurrent Events and Corresponding Strategies: ICEs and the corresponding analysis
strategies are defined in Table 8. Note that meeting rescue criteria at Week 12/Week 16 is not an
intercurrent event for the primary endpoint and is therefore not contained in Table 8.
Table 8: 
Intercurrent Events and Respective Analysis Strategies
ICE (between Baseline and Week 12) 
Analysis strategy for ICE
1. An ostomy or colectomy (partial or total) 
Composite strategy: Occurrence of these ICEs will be
treated as an unfavorable outcome
2. A prohibited change in medications for UC  
3. Discontinuation from study intervention due to lack
of efficacy or an AE of UC worsening
4. Discontinuation of study intervention due to COVID-
19 related reasons (excluding COVID-19 infection)
Treatment policy strategy: Observed values will be
used if available
5. Discontinuation of study intervention due to reasons
other than ICEs 3 or 4 as described above
Composite strategy: Occurrence of these ICEs will be
treated as an unfavorable outcome
v) Population-level summary: Difference in proportions of participants who achieved the binary
response at Week 12 as defined in the variable attribute above between the combined guselkumab
group and the placebo group.
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9.4.2.2. 
Estimator for the Primary Endpoint
The analysis of the primary endpoint will be based on the Full Analysis Set. Participants will be
analyzed according to the treatment group to which they were randomized regardless of the
treatment they received.
After accounting for the ICE strategies, any participants who are missing any or all of the 3
 that comprise the primary endpoint at Week 12 will be considered not to be in clinical
remission at Week 12 (ie, nonresponder imputation).
Summaries of the proportion of participants in clinical remission at Week 12 will be presented by
treatment group. The common risk difference and the associated 95% confidence interval between
the combined guselkumab SC induction group and the placebo group will be computed by use of
Mantel-Haenszel stratum weights and the Sato variance estimator. The primary endpoint will be
tested by a two-sided Mantel-Haenszel test for the common risk difference. Stratification will be
by the ADT-IR status (Yes/No), and
 at baseline (moderate [2] orsevere
[3]) as obtained during central review of the video endoscopy. The study will be considered
successful if the test for the primary endpoint is positive.  While a multiplicity-controlled testing
procedure will be implemented to control for the Type I error rate at the 0.05 significance level
(2-sided) across the primary and secondary endpoints, the primary endpoint will be tested at full
significance level. Only if this test is significant, secondary endpoints will be tested in a
confirmatory manner.
To evaluate the robustness of the primary analysis results, sensitivity analyses using alternative
missing data handling rules may be performed and supplementary estimands will be evaluated;
these analyses will be described in the SAP. In particular, this includes the use of the treatment
policy strategy for ICEs 3, 4, and 5 in Table 8 while continuing to use the composite strategy for
ICEs 1 and 2.
In addition, subgroup analyses of the primary endpoint will be performed based on demographic
and baseline disease characteristics, and baseline use and history of use of UC medications
(including ADT-IR status).
9.4.3. 
Secondary Efficacy Endpoints
The following are the secondary endpoints:
Symptomatic remission at Week 12 (defined as a 
and not
increased from baseline, and a 
Endoscopic improvement at Week 12 (defined as an 
 with no
friability present on the endoscopy)
Clinical response at Week 12 (defined as a decrease from baseline in the
by ≥30% and ≥2 points, with either a ≥1-point decrease from baseline in the rectal bleeding
subscore or a rectal bleeding subscore of 0 or 1)
Clinical remission at Week 24
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Symptomatic remission at Week 24
Endoscopic improvement at Week 24
Clinical response at Week 24
Histologic-endoscopic mucosal improvement at Week 12 (defined as a combination of
histologic improvement [neutrophil infiltration in <5% of crypts, no crypt destruction, and no
erosions, ulcerations or granulation tissue according to the 
 and
endoscopic improvement as defined above)
9.4.3.1. 
Estimands and Estimators
Secondary endpoints at Week 12
For secondary endpoints at Week 12, the same estimand that is specified for the primary endpoint
will be used (except for the “variable attribute”). The variable attributes are given in Table 9 below:
Table 9: 
Variable Attributes of Secondary Endpoints at Week 12
Endpoint 
Variable attribute
Symptomatic 
remission at 
Week 12  
A binary response variable (response/nonresponse) where response is defined as achieving a
 and not increased from baseline, and a rectal bleeding
subscore of 0 at Week 12 and none of the ICEs in categories 1 to 3 and 5 outlined in Table 8
has occurred prior to the Week 12 visit.
Endoscopic 
improvement at 
Week 12  
A binary response variable (response/nonresponse) where response is defined as achieving an
 with no friability present on the endoscopy at Week 12, where
none of the ICEs in categories 1 to 3 and 5 outlined in Table 8 has occurred prior to the Week
12 visit.
Clinical response 
at Week 12 
A binary response variable (response/nonresponse) where response is defined as achieving a
decrease from induction baseline in the 
 by ≥30% and ≥2 points, with
either a ≥1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding
subscore of 0 or 1 at Week 12, where none of the ICEs in categories 1 to 3 and 5 outlined in
Table 8 has occurred prior to the Week 12 visit.
Histologic- 
endoscopic 
mucosal 
improvement at 
Week 12
A binary response variable (response/nonresponse) where response is defined as a combination
of histologic improvement [neutrophil infiltration in <5% of crypts, no crypt destruction, and
no erosions, ulcerations or granulation tissue according to the 
 and
endoscopic improvement
 with no friability present] at Week 12,
where none of the ICEs in categories 1 to 3 and 5 outlined in Table 8 has occurred prior to the
Week 12 visit
Secondary endpointsat Week 24
The estimand (ie, a precise definition of the targeted treatment effect) is defined by the following
5 attributes:
i) Treatment through Week 24:
Experimental 1: Guselkumab 
 q4w [Weeks 0, 4, and 8] followed by
guselkumab 200 mg SC q4w (see Section 4.1)
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Experimental 2: Guselkumab 
 q4w [Weeks 0, 4, and 8] followed by
guselkumab 100 mg SC q8w (see Section 4.1)
Control: Placebo SC q4w (Weeks 0, 4, 8, 12, 16, 20)
ii) Population: Participants with moderately to severely active ulcerative colitis as defined bythe
inclusion/exclusion criteria (Section 5).
iii) Variable (Endpoint): The variable attributes for secondary endpoints at Week 24 are given in
Table 10 below.
Table 10: 
Variable Attributes of Secondary Endpoints at Week 24
Endpoint 
Variable attribute
Clinical 
remission at 
Week 24  
A binary response variable (response/nonresponse) where response is defined as achieving a
and not increased from baseline, a rectal bleeding subscore
of 0, and an
 with no friability present on the endoscopy at Week
24, where none of the ICEs in categories 1 to 4 and 6 outlined in Table 11 has occurred prior
to the Week 24 visit.
Symptomatic 
remission at 
Week 24  
A binary response variable (response/nonresponse) where response is defined as achieving a
 and not increased from baseline, and a rectal bleeding
subscore of 0 at Week 24, and none of the ICEs in categories 1 to 4 and 6 outlined in Table 11
has occurred prior to the Week 24 visit.
Endoscopic 
improvement at 
Week 24  
A binary response variable (response/nonresponse) where response is defined as achieving  an
 with no friability present on the endoscopy at Week 24, where
none of the ICEs in categories 1 to 4 and 6 outlined in Table 11 has occurred prior to the Week
24 visit.
Clinical response 
at Week 24 
A binary response variable (response/nonresponse) where response is defined as achieving a
decrease from induction baseline in the 
 by ≥30% and ≥2 points, with
either a ≥1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding
subscore of 0 or 1 at Week 24, where none of the ICEs in categories 1 to 4 and 6 outlined in
Table 11 has occurred prior to the Week 24 visit.
iv) Intercurrent Events and Corresponding Strategies: ICEs and the corresponding analysis
strategies are defined in Table 11.
Table 11: 
Intercurrent Events and Respective Analysis Strategies
ICE (between Baseline and Week 24) 
Analysis strategy for ICE
1. An ostomy or colectomy (partial or total) 
Composite strategy: Occurrence of these ICEs will be
treated as an unfavorable outcome
2. A prohibited change in medications for UC  
3. Discontinuation from study intervention due to lack
of efficacy or an AE of UC worsening
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ICE (between Baseline and Week 24) 
Analysis strategy for ICE
4. Meeting rescue criteria according to Section 6.5.1
5. Discontinuation of study intervention due to COVID-
19 related reasons (excluding COVID-19 infection)
Treatment policy strategy: Observed values will be
used if available
6. Discontinuation of study intervention due to reasons
other than ICEs 3 or 5 as described above
Composite strategy: Occurrence of these ICEs will be
treated as an unfavorable outcome
v) Population-level summary: Difference in proportions of participants who achieved the binary
response at Week 24 as defined in the variable attribute above between each of the guselkumab
groups and the placebo group.
Estimator for Secondary Efficacy Endpoints
The analysis of the secondary endpoints will be based on the Full Analysis Set. Participants will
be analyzed according to the treatment group to which they were randomized regardless of the
treatment they received.
After accounting for the ICE strategies, any participants who are missing any or all of the
components that define the secondary endpoints at Week 12/Week 24 will be considered not to
meet the respective endpoint (ie, nonresponder imputation).
Summaries of the proportion of participants achieving each secondary endpoint will be presented
by treatment group. The common risk difference and the associated 95% confidence interval
between the combined guselkumab SC induction group (Week 12 endpoints) / individual
guselkumab SC induction groups (Week 24 endpoints) and the placebo group will be computed
by use of Mantel-Haenszel stratum weights and the Sato variance estimator. The secondary
endpoints will be tested by a two-sided Mantel-Haenszel test for the common risk difference.
Stratification will be by the ADT-IR status (Yes/No), and 
 at baseline
(moderate [2] or severe [3]) obtained during central review of the screening video endoscopy.
9.4.3.2. 
Confirmatory Testing Procedure
A multiple testing procedure is planned to control the overall Type 1 error rate in the study at the
2-sided 0.05 significance level. The planned procedure is depicted in Figure 3. It follows a fixed
sequence approach, where the primary endpoint and the Week 12 secondary endpoints (with the
exception of histologic-endoscopic mucosal improvement) for the combined guselkumab groups
vs placebo are tested prior to the secondary endpoints at Week 24. For the Week 24 endpoints, the
testing sequence continues with testing all 4 endpoints in the guselkumab
 q4w (Weeks
0, 4, and 8)followed by guselkumab 200 mg SC q4w group against placebo and then testing all 4
endpoints in the guselkumab 
 q4w (Weeks 0, 4, and 8) followed by guselkumab 100
mg SC q8w group against placebo. Histologic-endoscopic mucosal improvement at Week 12 is
the last element of the testing sequence and is tested for the combined guselkumab groups against
placebo.
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following the last dose) is considered to be treatment emergent. All reported treatment-emergent
AEs will be included in the analysis. For each AE, the percentage of 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:
Frequency and type of AEs;
Frequency and type of SAEs;
Frequency and type of related AEs as assessed by the investigator;
Frequency and type of AEs leading to discontinuation of study intervention;
Frequency 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.
9.4.5.2. 
Clinical Laboratory Tests
Laboratory data will be summarized by type of laboratory test. Reference ranges and markedly
abnormal results (specified in the SAP) will be used in the summary of laboratory data. Descriptive
statistics for changes from baseline in clinical laboratory results will be summarized by treatment
group.
9.4.5.3. 
Suicidal Ideation and Behavior
Suicidal ideation and behavior based on the 
 and AEs will be summarized descriptively.
9.4.6. 
Other Endpoints
9.4.6.1. 
Patient-reported Outcomes
Analysis of patient-reported outcomes will follow the general considerations as given in
Section 9.4.1. The testing of these endpoints will not be controlled for multiplicity and nominal
p-values will be provided. These endpoints include but are not limited to the endpoints described
below. A complete list of the PRO endpoints will be provided in the SAP.
 remission at Week 12 and Week 24 (defined as total 
 score ≥170)
Proportion of participants with >20 points change in 
 total score at Week 12 and
Week 24
Change from baseline in Domains T-scores of
 and pain intensity at Week 12 and
Week 24
Proportion of participants with clinically meaningful change in Domains T-scores of
 and pain intensity (as defined in SAP) at Week 12 and Week 24
CCI
CCI
CCI
CCI
CCI
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Change from baseline in 
 functional domain score and bowel domain score at
Week 12 and Week 24
Proportion of participants with clinically meaningful change (as defined in SAP) in
 functional domain score and bowel domain score at Week 12 and Week 24
Change from baseline in score of urgency of bowel movement by 
 at Week 12
and Week 24
Proportion of participants with clinically meaningful change in score of urgency of bowel
movement (as defined in SAP) by
 at Week 12 and Week 24
9.4.6.2. 
Pharmacokinetic Analyses
Unless otherwise noted, PK analyses will be based on the PK analysis set. Serum guselkumab
concentrations over time will be summarized. Descriptive statistics, including arithmetic mean,
SD, CV%, median, interquartile range, minimum, and maximum will be calculated at each
nominal sampling time point. All concentrations below the lowest quantifiable concentration or
missing data will be labeled as such in the concentration database or data presentations.
Concentrations below the lowest quantifiable concentration will be treated as zero in the
calculation of the summary statistics.
Population PK modeling may be conducted when appropriate. If population PK analysis is
conducted, the results of the modeling analysis will be presented in a separate report.
9.4.6.3. 
Immunogenicity Analyses
The incidence of antibodies to guselkumab will be summarized for all participants in the
immunogenicity analysis set.
A listing of participants who are positive for antibodies to guselkumab  will be provided. The
maximum titers of antibodies to guselkumab will be summarized for participants who are positive
for antibodies to guselkumab.
The incidence of neutralizing antibodies to guselkumab will be summarized for participants who
are positive for antibodies to guselkumab and have samples evaluable for neutralizing antibodies
to guselkumab.
9.4.6.4. 
Biomarkers Analyses
Changes in serum protein analytes, whole blood RNA, and colonic biopsy RNA obtained over
time (where local regulations permit) will be summarized by treatment group. Associations
between baseline levels and changes from baseline in select biomarkers and response to treatment
will be explored.
The biomarker analyses will 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. Results of serum, whole blood analyses, stool, and colonic biopsy analyses will be
reported in separate technical reports.
CCI
CCI
CCI
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9.4.6.5. 
Pharmacokinetic/Pharmacodynamic Analyses
The relationship between serum guselkumab concentrations and efficacy measures will be
analyzed graphically. If feasible, a suitable exposure-response model may be developed to describe
the relationship between serum guselkumab exposure and efficacy. Details will be provided in a
population PK/PD analysis plan and results of the population PK/PD analysis will be presented in
a separate technical report.
9.5. 
Interim Analysis
No interim analysis is planned.

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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Abbreviations and Definitions
5-ASA  
5-aminosalicylic acid
6-MP  
6-mercaptopurine
ADT  
advanced therapy
ADT-IR  
inadequate response to or intolerance of advanced therapy
AE 
adverse event
ALP  
alkaline phosphatase
ALT  
alanine aminotransferase
ANCOVA  
analysis of covariance
ANOVA  
analysis of variance
anti-HBc 
hepatitis B core antibody
Anti-HBs 
hepatitis B surface antibody
AST  
aspartate aminotransferase
AUC  
area under the concentration time curve
AZA  
azathioprine
BCG  
Bacille Calmette-guerin
Cavg,ss 
average steady-state serum study intervention concentration
CKD-Epi 
Chronic Kidney Disease Epidemiology Collaboration
CMH  
Cochran-Mantel-Haenszel
COVID-19 
Coronavirus disease 2019
CRO  
contract research organization
CRP  
C-reactive protein
 
CT  
Computed Tomography
CTM  
clinical trial manager
DBL 
database lock
DNA  
deoxyribonucleic acid
ECG  
electrocardiogram
eCRF  
electronic Case Report Form
ED  
Early Discontinuation
eDC  
electronic data capture
EEA  
European Economic Area
eGFR  
estimated glomerular filtration rate
EU  
European Union
EU-CTR  
European Union Clinical Trials Regulation
FSH  
Follicle Stimulating Hormone
GCP  
good clinical practice
GI 
gastrointestinal
GPSP  
good post-marketing study practice
HBsAg 
hepatitis B surface antigen
HBV  
Hepatitis B virus
HCV  
Hepatitis C virus
HIV  
Human Immunodeficiency Virus
 
IB  
Investigator's Brochure
IBD  
inflammatory bowel disease
 
ICE  
intercurrent events
ICF  
Informed Consent Form
IEC  
Independent Ethics Committee
IFU  
Instructions for Use
IGRA  
Interferon-gamma release assay
IL 
interleukin
IMP  
Investigational Medicinal Product
IND  
Investigational New Drug
CCI
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INR  
International Normalized Ratio
IPPM  
Investigational Product Procedure Manual
IQ  
interquartile
IRB  
Institutional Review Board
IV  
intravenous
IWRS  
interactive web response system
JAK  
janus kinase
LTM  
local trial manager
MedDRA  
Medical Dictionary for Regulatory Activities
MMRM  
mixed-effect model repeated measures
MTX  
methotrexate
N/A  
not applicable
PD 
pharmacodynamic
PFS  
Prefilled syringe
PFS-U 
PFS-UltraSafe Plus Passive Needle Guard
PFS-Y 
PFS-ypsomate autoinjector
PK 
pharmacokinetic
PML 
progressive multifocal leukoencephalopathy
POC  
proof of concept
PQC  
product quality complaints
PRO  
Patient-reported Outcomes
 
PsA  
psoriatic arthritis
q4w  
every 4 weeks
q8w  
every 8 weeks
RNA  
ribonucleic acid
S1PR 
sphingosine-1-phosphate receptor
SAE  
serious adverse event
SAP  
statistical analysis plan
SARS-CoV-2 
severe acute respiratory coronavirus syndrome coronavirus 2
SC 
subcutaneous
SD 
standard deviation
SF 
stool frequency
SFU  
safety follow-up
SoA  
Schedule of Activities
SUSAR  
suspected unexpected serious adverse reactions
T 
Telemedicine Visit
TB  
tuberculosis
Tbili 
total bilirubin
TNF  
tumor necrosis factor
UC  
ulcerative colitis
 
ULN  
upper limit of normal
WBC  
white blood cells
Definitions of Terms
COA  
An umbrella term encompassing different types of outcomes assessments.
Electronic source 
system  
Contains data traditionally maintained in a hospital or clinic record to document medical
care or data recorded in a CRF as determined by the protocol. Data in this system may be
considered source documentation.
PRO  
Reports directly from the patient without interpretation by clinician or anybody else.
CCI
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10.2. Appendix 2: Definition of Inadequate Response to or Intolerance of
Corticosteroids or AZA/6-MP and Corticosteroid Dependence
CORTICOSTEROIDS
Participants have failed to respond to corticosteroids if they have had evidence of an initial inadequate
response, recurrent disease, or a relapse despite receiving at least 0.75 mg/kg/day or >40 mg/day of
prednisone (or corticosteroid equivalent, given orally or intravenously) for 2 weeks; or ≥9 mg/day of
budesonide or ≥5 mg/day of beclomethasone dipropionate given orally for at least 4 weeks.
Participants are intolerant of corticosteroids if:
They have developed clinically significant adverse events (eg, osteonecrosis or osteoporosis,
psychosis, uncontrolled diabetes) unresponsive to dose reduction that, in the judgment of the
investigator, precluded the use of corticosteroids to treat ulcerative colitis (UC).
OR
They have a medical condition that precludes the use of corticosteroids as a treatment for UC.
Participants are corticosteroid dependent ifthey have failed to successfully taper their corticosteroid (ie,
had a flare of disease) within 12 weeks of starting therapy, or if a relapse occurs within 12 weeks after
stopping corticosteroids or if they are unable to discontinue these agents without flare within 12 weeks after
starting them.
6-MERCAPTOPURINE (6-MP) OR AZATHIOPRINE (AZA)
Participants have failed to respond to 6-MP or AZA if they have had evidence of an initial inadequate
response, recurrent disease, or a relapse despite receiving:
At least 12 weeks of therapy with 1 mg/kg/day of 6-MP or 2 mg/kg/day of AZA.
OR
A lower dosage of 6-MP or AZA when country/territory or local guidelines specify a different
treatment regimen. (In such an event, the country/territory or local guidelines needs to be included in
the source document).
OR
The dosage of 6-MP or AZA confirmed to be therapeutic for the participant with whole blood
thioguanine nucleotide levels >200 pmole/8 x 108 RBCs.
OR
The highest tolerated dosage due to leukopenia, elevated liver enzymes, or nausea.
Participants are intolerant of 6-MP or AZA if:
They have developed clinically significant adverse events (eg, pancreatitis, arthritis accompanied by
high fever and/or rash, leukopenia, or persistently elevated liver enzymes) unresponsive to dose
reduction that, in the judgment of the investigator, precluded the use of 6-MP or AZA to treat UC
within the past 5 years.
OR
Theyhave a medical condition that precludes the use of 6-MP or AZA.

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10.3. Appendix 3: Definition of Inadequate Initial Response, Loss of Response,
or Intolerance to TNFα Antagonist Therapies (eg, Infliximab, Adalimumab,
Golimumab), Vedolizumab, or Approved Biosimilars
The criteria for inadequate initial response, response followed by loss of response, or intolerance to
infliximab, adalimumab, golimumab, vedolizumab, or approved biosimilars are described in items I, II,
and III, below.
I. 
Inadequate initial response to at least 8 weeks of therapy with infliximab, adalimumab,
golimumab, vedolizumab, or approved biosimilars (primary nonresponse)
Eligible participants must satisfy criteria A, B, and C.
A. 
Have received induction doses of:
Infliximab; 3 intravenous (IV) doses 5 mg/kg at Weeks 0, 2, and 6
OR
Adalimumab; subcutaneous (SC) doses of 160 mg at Week 0 and 80 mg at
Week 2 followed by a dose 40 mg every 2 weeks
OR
Golimumab; SC doses of 200 mg at Week 0 and 100 mg at Week 2, followed by
50 or 100 mg every 4 weeks
OR
Vedolizumab; IV doses of 300 mg at Weeks 0, 2, and 6 or other approved dose
regimen/formulation
AND
B. 
Did not initially respond to these induction doses of infliximab, adalimumab,
golimumab, vedolizumab, or approved biosimilars, as evidenced by the presence of
at least 1 of the following signs or symptoms related to persistence of ulcerative colitis
(UC), as assessed by a treating physician:
Lack of improvement or worsening in stool frequency
Lack of improvement or worsening in rectal bleeding
Lack of improvement or worsening in daily abdominal pain
Lack of improvement or worsening in urgency
Lack of improvement or worsening in the endoscopic appearance of the colonic
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These signs and symptoms of UC must have occurred 2 weeks after receiving the last
induction dose of infliximab, adalimumab, golimumab, vedolizumab, or approved
biosimilars and are offered only as a benchmark of the minimally acceptable criteria
required to designate a participant as having had an inadequate initial response to
infliximab, adalimumab, golimumab, vedolizumab, or approved biosimilars.
AND
C. 
Have documentation available to the investigator that meets the following 2
requirements:
Provides the dates and doses of the failed induction therapy with infliximab,
adalimumab, golimumab, vedolizumab, or approved biosimilars.
Documents that the participant had persistence of disease activity following
induction therapy with infliximab, adalimumab, golimumab, vedolizumab, or
approved biosimilars.
Examples of acceptable documents include medical records, letter provided by a referring
physician, or other “reason for referral” documents (eg, insurance authorization form).
II. 
Initial response followed by loss of response to current or prior therapy with infliximab,
adalimumab, golimumab, vedolizumab, or approved biosimilars (secondary nonresponse)
Eligible participants must satisfy criteria A, B, C, and D.
A. 
Initially responded to induction therapy
AND
B. 
Have received at least 2 maintenance doses of:
Infliximab (at a dose 5 mg/kg)
or
Adalimumab (at a dose 40 mg)
or
Golimumab (at a dose of 50 or 100 mg)
or
Vedolizumab (at a dose 300 mg or other approved dose regimen/formulation)
AND
C. 
Have or had at least 1 of the following signs or symptoms related to recurrence of UC
disease activity, as assessed by a treating physician:
Worsening in stool frequency
Worsening in rectal bleeding
Worsening in dailyabdominal pain
Worsening in urgency

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Worsening in the endoscopic appearance of the colonic mucosa
These signs and symptoms of UC must have occurred 2 weeks after receiving the last
maintenance dose of infliximab, adalimumab, golimumab, vedolizumab, or approved
biosimilars and are offered only as a benchmark of the minimally acceptable criteria
required to designate a participant as having lost response to infliximab, adalimumab,
golimumab, vedolizumab, or approved biosimilars.
AND
D. 
Have documentation available to the investigator that meets the following 2
requirements:
Provides the dates and doses of the failed maintenance therapy with infliximab,
adalimumab, golimumab, vedolizumab, or approved biosimilars.
Documents that the participant had recurrence of UC disease activity despite
maintenance therapy with infliximab, adalimumab, golimumab, vedolizumab, or
approved biosimilars.
Examples of acceptable documents include medical records, letter provided by a referring
physician, or other “reason for referral” documents (eg, insurance authorization form).
III. 
Current or prior intolerance to therapy with infliximab, adalimumab, golimumab,
vedolizumab, or approved biosimilars.
Eligible participants must satisfy criteria A and B.
A. 
Have had an adverse reaction that meets 1 of the following 3 criteria:  1) significant
acute infusion/administration reaction; 2) significant delayed infusion/administration
reaction (eg, delayed hypersensitivity or serum-sickness-like reaction); or 3)
significant injection site reaction. Definitions of these 3 criteria are provided below.
Adverse reactions must have followed 1 dose of infliximab, adalimumab,
golimumab, vedolizumab, or approved biosimilars and, in the treating physician’s
opinion, precluded continued use of the therapy.
1) 
A significant acute infusion/administration reaction is defined as an adverse
reaction that was:
Manifested through 1 of the following symptoms.
a. 
Fever (ie, temperature greater than 100 F [38 C])
b. 
Chills or rigors
c. 
Pruritis
d. 
Rash
e. 
Flushing
f. 
Urticaria or angioedema
g. 
Respiratory distress (eg, dyspnea, chest pain or tightness,
shortness of breath, wheezing, stridor)
h. 
Clinical hypotension (eg, pallor, diaphoresis, faintness, syncope),
blood pressure <90 mm Hg systolic and 60 mm Hg diastolic, or a
systemic or orthostatic drop in systolic blood pressure >20 mm
Hg.

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and
Occurred 
24 hours after infusion/administration of infliximab,
adalimumab, golimumab, vedolizumab, or approved biosimilars.
and
Was considered related to the infusion/administration of infliximab,
adalimumab, golimumab, vedolizumab, or approved biosimilars.
2) 
A significant delayed infusion/administration reaction is defined as an
adverse reaction that:
Was manifested through 1 or more of the following symptoms:
a. 
Myalgias
b. 
Arthralgias
c. 
Fever (ie, temperature greater than 100 F [38 C])
d. 
Malaise
e. 
Rash
and
Occurred >24 hours and <15 days after infusion/administration of
infliximab, adalimumab, golimumab, vedolizumab, or approved
biosimilars.
and
Was considered related to the infusion/administration of infliximab,
adalimumab, golimumab, vedolizumab, or approved biosimilars.
3) 
A significant injection site reaction is defined as an adverse reaction that:
Was manifested through 1 or more of the following symptoms:
a. 
Significant bruising
b. 
Erythema
c. 
Hemorrhage
d. 
Irritation
e. 
Pain
f. 
Pruritus
g. 
“Injection site reaction”
and
Occurred within 24 hours of an SC injection of adalimumab, golimumab,
vedolizumab, or approved biosimilars.
and
Was considered related to the injection.

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B. 
Have documentation available to the investigator that meets the following 2
requirements:
Provides the date of discontinuation of infliximab, adalimumab, golimumab,
vedolizumab, or approved biosimilars.
Documents that the participant had intolerance to infliximab, adalimumab,
golimumab, vedolizumab, or approved biosimilars.
Examples of acceptable documents include medical records, letter provided by a referring
physician, or other “reason for referral” documents (eg, insurance authorization form).

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10.4. Appendix 4: Definition of Inadequate Initial Response, Loss of Response,
or Intolerance to Tofacitinib, Filgotinib, Upadacitinib, or Ozanimod
The criteria for inadequate initial response, response followed by loss of response, or intolerance
to tofacitinib, filgotinib, upadacitinib, or ozanimod are described in items I, II, and III, below.
I. Inadequate initial response to induction therapy with tofacitinib, filgotinib, upadacitinib,
or ozanimod (primary nonresponse)
Eligible participants must satisfy criteria A, B, and C.
A. Have received the following induction therapy (or other approved regimen):
Tofacitinib 10 mg by mouth (PO) twice daily for at least 8 weeks
or
Filgotinib 200 mg PO once daily for at least10 weeks
or
Upadacitinib 45 mg PO once daily for at least8 weeks
or
Ozanimod 0.92 mg PO once daily for at least 9 weeks after induction dose
titration/escalation
AND
B. 
Did not initially respond to induction therapy with tofacitinib, filgotinib,
upadacitinib, or ozanimod, as evidenced  by  the presence of at least 1 of the
following signs or symptoms related to persistence of ulcerative colitis (UC), as
assessed by a treating physician:
Lack of improvement or worsening in stool frequency
Lack of improvement or worsening in rectal bleeding
Lack of improvement or worsening in daily abdominal pain
Lack of improvement or worsening in urgency
Lack of improvement or worsening in the endoscopic appearance of the
colonic mucosa
These signs and symptoms of UC are offered only as a benchmark of the minimally
acceptable criteria required to designate a participant as having had an inadequate initial
response to tofacitinib, filgotinib, upadacitinib, or ozanimod.
AND

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C. 
Have documentation available to the investigator that meets the following 2
requirements:
Provides the dates and doses of the failed tofacitinib, filgotinib, upadacitinib, or
ozanimod induction therapy
Documents that the participant had persistence of disease activity following
tofacitinib, filgotinib, upadacitinib, or ozanimod induction therapy
Examples of acceptable documents include medical records, letter provided by a
referring physician, or other “reason for referral” documents (eg, insurance
authorization form).
II. Initial response followed  by loss of response to current or prior therapy with tofacitinib,
filgotinib, upadacitinib, or ozanimod (secondary nonresponse)
Eligible participants must satisfy criteria A, B, C, and D.
A. 
Initially responded to induction therapy
AND
B. 
Have received at least 8 weeks of the following (or other approved regimen):
Tofacitinib at a dose ≥5 mg PO twice daily
or
Filgotinib 200 mg PO once daily
or
Upadacitinib 15 mg or 30 mg PO once daily
or
Ozanimod at a dose of 0.92 mg daily
AND
C. 
Have or had at least 1 of the following signs or symptoms related to recurrence of
UC disease activity, as assessed by a treating physician:
Worsening in stool frequency
Worsening in rectal bleeding
Worsening in daily abdominal pain
Worsening in urgency
Worsening in the endoscopic appearance of the colonic mucosa

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These signs and symptoms of UC are offered only as a benchmark of the minimally
acceptable criteria required to designate a participant as having lost response to tofacitinib,
filgotinib, upadacitinib, or ozanimod therapy.
AND
D. 
Have documentation available to the investigator that meets the following
2 requirements:
Provides the dates and doses of the failed tofacitinib, filgotinib, upadacitinib,
or ozanimod maintenance therapy
Documents that the participant had recurrence ofUC disease activity
despite adequate tofacitinib, filgotinib, upadacitinib, or ozanimod
maintenance therapy
Examples of acceptable documents include medical records, letter provided by a
referring physician, or other “reason for referral” documents (eg, insurance
authorization form).
III. 
Current or prior intolerance to therapy with tofacitinib, filgotinib, upadacitinib, or
ozanimod
Eligible participants must satisfy criteria A and B.
A. Have developed a clinically significant adverse event unresponsive to dose reduction that,
in the judgment of the investigator, precluded continued use of tofacitinib, filgotinib,
upadacitinib, or ozanimod to treat UC
Examples of clinically significant adverse events associated with tofacitinib
include serious infection, thrombosis, gastrointestinal perforation,
lymphopenia, neutropenia, anemia, or persistently elevated liver enzymes.
Examples of clinically significant adverse events associated with filgotinib
include infections, neutropenia, anemia, or VTE.
Examples of clinically significant adverse events associated with upadacitinib
include serious infections, thrombosis, gastrointestinal perforation, major
adverse cardiac events, lymphopenia, neutropenia, anemia, or persistently
elevated liver enzymes.
Examples of clinically significant adverse events associated with ozanimod
include serious infection, bradyarrhythmias and Atrioventricular Conduction
Delays, increased blood pressure, a decline in pulmonary function and
respiratory effects, macular edema, persistently elevated liver enzymes, or
Posterior Reversible Encephalopathy Syndrome.
AND
B. 
Have documentation available to the investigator that meets the following 2
requirements:

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Provides the date of discontinuation of tofacitinib, filgotinib, upadacitinib, or
ozanimod.
Documents that the participant had intolerance to tofacitinib, filgotinib,
upadacitinib, or ozanimod
Examples of acceptable documents include medical records, letter provided by a referring
physician, or other “reason for referral” documents (eg, insurance authorization form).

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10.6. Appendix 6: Regulatory, Ethical, and Study Oversight Considerations
10.6.1. 
Regulatory and Ethical Considerations
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the
protocol, current ICH guidelines on Good Clinical Practice (GCP), and applicable regulatory and
country- or territory-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.
Post-marketing Study
In countries where, as required by local regulation, an ongoing clinical study may be considered a
post-marketing study after new drug approval, instances of ‘clinical trial’ and ‘clinical study’ in
this protocol can be considered synonymous with ‘post-marketing study.’ The studies will continue
to be performed in accordance with the protocol for the post-marketing study, GCP/GPSP, and
applicable regulatory and country-specific requirements following new drug approval for the
corresponding study indication.
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

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amendment approval by the investigator and IEC/IRB must be provided to the sponsor. When the
change(s) involves only logistic or administrative aspects of the study, the IEC/IRB (where
required) only needs to be notified.
In situations where a departure from the protocol is unavoidable during the study, 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 must be made before implementing any departure from the protocol. In all
cases, contact with the sponsor must be made as soon as possible to discuss the situation and agree
on an appropriate course of action. The data recorded in the CRF and source documents will reflect
any departure from the protocol, and the source documents will describe this departure and the
circumstances requiring it.
Regulatory Approval/Notification
This protocol and any amendment(s) must be submitted to the appropriate regulatory authorities
in each respective country/territory, 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 studysite 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

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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
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 sponsor where required) will provide the IEC/IRB
with current and complete copies of the following documents (as required by local regulations):
Final protocol and, if applicable, amendments
Sponsor-approved ICF (and any other written materials to be provided to the 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.
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

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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
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/Territory 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.
10.6.2. 
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 study and
for 1 year after completion of the study.

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Refer to Required Prestudy Documentation (above) for details on financial disclosure.
10.6.3. 
Informed Consent Process
Each participant (or a legally acceptable representative) must give 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 studysite personnel
must explain to potential participants or their legally acceptable representatives the aims, methods,
reasonably anticipated benefits, and potential hazards of the study, and any discomfort
participation in the study may entail. 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 or legally
acceptable representative is authorizing such access. 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 or legally acceptable representative will be given sufficient time to read the ICF
and the opportunity to ask questions. After this explanation and before entry into the study, consent
must be appropriately recorded by means of either the participant’s or his or her legally acceptable
representative’s personally dated signature. After having obtained the consent, a copy of the ICF
must be given to the participant.
Participants who are rescreened are required to sign a new ICF.
10.6.4. 
Recruitment Strategy
Not applicable. Recruitment has stopped, and no further enrollment is planned, therefore the
recruitment strategy is not further described. However, this section is being added to be compliant
with EU-CTR as part of the transition to EU-CTR.
10.6.5. 
DataProtection
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 (or his or her legally designated representative)
includes information about, and where required per applicable regulations, 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. The informed consent also provides information to address the
lawful 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, or make requests
concerning his or her personal data in accordance with applicable data protection law. 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 PD, biomarker, PK, and immunogenicityresearch 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.
10.6.6. 
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 UC,
to understand differential intervention responders, and to develop tests/assays related to
guselkumab and UC. 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 Samples in Future
Research).

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10.6.7. 
Use of Information and Publication
All information, including but not limited to information regarding guselkumab supplied by the
sponsor to the study site or investigator and not previously published, and any data or analysis
generated as a result of this study, are considered confidential and remain the sole property of the
sponsor. Study site and investigator shall not use this information except in the performance of
this study and shall not disclose this information to anyone except to persons involved in the study
that need such information to assist in conducting the study, and then only on like terms of
confidentiality and non-use.
Study site and investigator shall not publish study results except as required by law or as specified
in a separate, written agreement between the sponsor and the study site or investigator.
The sponsor will register the study and publish the study results in compliance with applicable law
and may register the study or publish study results when not required.
Authorship of any peer-reviewed publications will be determined by mutual agreement in line with
International Committee of Medical Journal Editors authorship guidelines.
In accordance with standard editorial and ethical practice, the sponsor will generally support
publication of multicenter studies only in their entirety and not as individual site data. In this case,
a coordinating investigator will be designated by mutual agreement.
Registration of Clinical Studies and Disclosure of Results
The sponsor will register and disclose the existence of and the results of clinical studies as required
by law. The disclosure of the final study results will be performed after the end of study in order
to ensure the statistical analyses are relevant.
10.6.8. 
DataQuality 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 CRF completion will be provided and reviewed with studysite personnel before
the start of the study.
The sponsor may review the CRF for accuracy and completeness during on-site monitoring visits
and after transmission to the sponsor; any discrepancies will be resolved with the investigator or
designee, as appropriate. After upload of the data into the study database they will be verified for
accuracy and consistency with the data sources.

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10.6.9. 
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 the CRF. All CRF entries, corrections,
and alterations must be made by the investigator or authorized study site personnel. The
investigator must verify that all data entries in the CRF are accurate and correct.
The study data will be transcribed by study-site personnel from the source documents onto an
electronic CRF, if applicable. Study-specific data will be transmitted in a secure manner to the
sponsor. Worksheets may be used for the capture of some data to facilitate completion of the CRF.
Any such worksheets will become part of the participant's source documents. Data must be entered
into CRF in English. The CRF must be completed as soon as possible after a participant visit and
the forms must be available for review at the next scheduled monitoring visit.
If necessary, queries will be generated in the eDC tool. If corrections to CRF are needed after the
initial entry into the CRF, this can be done in either of the following ways:
Investigator and study-site personnel can make corrections in the eDC tool at their own
initiative or as a response to an auto query (generated by the eDC tool).
Sponsor or sponsor delegate can generate a query for resolution by the investigator and
study-site personnel.
10.6.10. 
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 must be identifiable.
Specific details required as source data for the study and source data collection methods will be
reviewed with the investigator before the study and will be described in the monitoring guidelines
(or other equivalent document).
The 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 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 CRF in the protocol include the
eSource system, but information collected through eSource may not be limited to that found in the
CRF.
10.6.11. 
Monitoring
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 may compare the data entered into the CRF  with the source documents
(eg, hospital/clinic/physician’s office medical records). At these visits, the monitor will compare
data entered into the CRF with the source documents (eg, hospital/clinic/physician’s office medical
records); a sample may be reviewed. The nature and location of all source documents will be
identified to ensure that all sources of original data required to complete the CRF are known to the
sponsor and study site personnel and are accessible for verification by the sponsor study site
contact. If electronic records are maintained at the study site, the method of verification must be
discussed with the studysite 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 studysite 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, studysite 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.
10.6.12. 
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
respected. The investigator and studysite personnel are responsible for being present and available

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for consultation during routinely scheduled studysite audit visits conducted by the sponsor or its
designees.
Similar auditing procedures may also be conducted by agents of any regulatory body, either as part
of a national GCP compliance program or to review the results of this study in support of a
regulatory submission. The investigator must immediately notify the sponsor if he or she has been
contacted by a regulatory agency concerning an upcoming inspection.
10.6.13. 
Record Retention
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all CRF and
all source documents that support the data collected from each 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.
10.6.14. 
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.
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

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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 intervention.
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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10.7. Appendix 7: Adverse Events, Serious Adverse Events, Product Quality
Complaints, and Other Safety Reporting: Definitions and Procedures for
Recording, Evaluating, Follow-up, and Reporting
10.7.1. 
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 Council 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 Event and Serious
Adverse Event 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
An  SAE based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for
Human Use is any untoward medical occurrence that at any dose:
Results in death
Is life-threatening
(The 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 was 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 must 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.
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. In countries where, as required by local regulation, an ongoing
clinical study may be considered a post-marketing study after new drug approval, the expectedness
of an AE will be determined by whether it is listed in an appropriate document (eg, package insert).
10.7.2. 
Attribution Definitions
Assessment of Causality
The causal relationship to study intervention  is assessed by the Investigator. The following
selection must 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.
10.7.3. 
Severity Criteria
An assessment of severity grade will be made using the following general categorical descriptors:
Mild: Awareness of symptoms that are easily tolerated, causing minimal discomfort and not
interfering with everyday activities.
Moderate: Sufficient discomfort is present to cause interference with normal activity.
Severe: Extreme distress, causing significant impairment of functioning or incapacitation.
Prevents normal everyday activities.

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The investigator must use clinical judgment in assessing the severity of events not directly
experienced by the participant (eg, laboratory abnormalities).
10.7.4. 
Special Reporting Situations
Safety events of interest on a sponsor study intervention in an interventional study that 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) of a sponsor study
intervention
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
Reporting of participant pregnancy or participant partner(s) pregnancy
Special reporting situations must be recorded in the CRF. Any special reporting situation that
meets the criteria of an SAE must be recorded on the SAE page of the CRF.
10.7.5. 
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 CRF. Whenever possible,
diagnoses should be given when signs and symptoms are due to a common etiology (eg, cough,
runny nose, sneezing, sore throat, and head congestion should be reported as "upper respiratory
infection"). Investigators must record in the CRF their opinion concerning the relationship of the
AE to study therapy. All measures required for AE management must be recorded in the source
document and reported according to sponsor instructions.
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:
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)

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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 reviewed 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
transmitted in a secure manner electronically or by facsimile (fax). Telephone reporting should be
the exception and the reporter should be asked to complete the appropriate form(s) first.
10.7.6. 
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,
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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 studysite 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.
10.7.7. 
Contacting Sponsor Regarding Product Quality
The names (and corresponding telephone numbers) of the individuals who must be contacted
regarding safetyissues, PQC, or questions regarding the studyare listed in the Contact Information
page(s), which will be provided as a separate document.

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10.8. Appendix 8: 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 7: 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, or bilateral salpingectomy, or
bilateral oophorectomy.
Has congenital abnormalities 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.
If reproductive status is questionable, additional evaluation should be considered.
Contraceptive (birth control) use by men or women must 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 must 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)
Tubal closure (eg, bilateral tubal occlusion, bilateral tubal ligation)
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 must 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 must 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 must not be used together (due to risk of failure with friction).

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10.9. Appendix 9: 
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4. Complete blood count with WBC, eosinophil, and platelet count (to further scrutinize potential
immune-mediated mechanism of injury)
5. INR, and total protein and albumin (compute globulin fraction) should also be documented
(to further scrutinize potential severity of the liver damage). If INR is abnormal, prothrombin
time, partial thromboplastin time should be obtained and these values should be followed until
normal, along with documentation of whether parenteral vitamin K was given along with the
effect of such treatment on INR.
6. If initial LTs and ultrasound do not suggest Gilbert’s syndrome, biliary tract disease or
obstruction, viral hepatitis serology should be obtained including anti-hepatitis A virus
immunoglobin (Ig)M, anti-hepatitis A virus total, HBsAg, anti-HBs, anti-HBc total, anti-HBc
IgM, anti-HCV, anti-hepatitis E virus IgM (even if has not traveled to an endemic area for
hepatitis E), Epstein-Barr virus, and cytomegalovirus screen.
If participant is immunosuppressed, test for HCV RNA and hepatitis E virus RNA by
polymerase chain reaction.
If HBsAg or anti-HBc IgM or anti-HBc IgG positive, also get HBV DNA to detect active
Hepatitis B, especially in patients who are immunosuppressed.
If all other hepatitis B serologic tests are negative and anti-HBc total is the only positive
test, HBV DNA should be obtained to detect reactivation of hepatitis B.
Steps 7-12 are optional; In consultation with the medical monitor, additional clinical and
laboratory studies may be performed to evaluate the underlying etiology of abnormal
findings.
7. Based on potential baseline confounders of the disease target population consider (optionally):
gamma-glutamyl transferase (to confirm the liver origin of elevated ALP levels), serum
creatine phosphokinase (to confirm the liver origin of elevated AST levels], lactate
dehydrogenase (to help exclude hemolysis), glutamate dehydrogenase (if muscle injury is
suspected or if muscle disease is target population).
8. Assuming that the history, physical, and initial imaging and laboratory has not revealed a
cause of elevated LTs, screen for other causes of liver disease including: antinuclear antibody,
anti-liver kidney microsomal antibody type 1, anti-liver-kidney microsomal antibodies,
anti-smooth muscle antibodies (to screen for additional immune-related etiologies),
erythrocyte sedimentation rate, and CRP (to screen for potential systemic inflammatory
causes).
9. If the pattern of laboratory abnormalities is not hepatocellular, but cholestatic or a mixed
pattern (see definitions in Table 13), then gamma-glutamyl transferase, anti-mitochondrial
antibody and anti-neutrophil cytoplasmic antibody should also be tested. If there is an
indication by history or elevated baseline LTs that there may be an underlying chronic liver
disease possibly exacerbated by exposure to the study intervention in the clinical trial or
making the participant more susceptible to DILI, test iron/total iron binding capacity and
ferritin (hemochromatosis), and alpha-1-antitrypsin level. If patient is <50 years of age,
ceruloplasmin should also be tested to screen for Wilson’s disease. If patient is sick enough
to be hospitalized and is under age 50, a slit lamp examination to detect Kayser-Fleischer rings
and a 24-hour urine collection for copper should be measured. Consider serum ethanol and/or
acetaminophen level and urine drug screen as clinically appropriate.

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10.11. Appendix 11: 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, self-isolation/quarantine by participants and study site personnel; travel
restrictions/limited access to public places, including hospitals; study site personnel being
reassigned to critical tasks.
In alignment with recent health authority guidance, the sponsor is providing options for
study-related 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 safety is considered to be at risk, study intervention will be discontinued, and study
follow-up will be conducted.
Scheduled visits that cannot be conducted in person at the study site will be performed to the extent
possible remotely/virtually or delayed until such time that on-site visits can be resumed. At each
contact, 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 via COVID-19 Appendix after consultation with the participant, investigator, and the
sponsor. 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.
The sponsor will continue to monitor the conduct and progress of the clinical study, and any
changes will be communicated to the sites and to the health authorities according to local guidance.
If a participant has tested positive for COVID-19, the investigator should contact the sponsor’s
responsible medical officer to discuss plans for study intervention 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.

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ADDITIONAL ELEMENTS, WHERE APPLICABLE:
Certain protocol-mandated visits to the study site may not be possible during the COVID-19
outbreak. Therefore, temporary measures may be implemented if considered appropriate by
the sponsor and investigator to maintain continuity of 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 participants for study procedures, eg, those related
to safety monitoring / efficacy evaluation / study intervention storage and administration
(including training where pertinent)
Procurement of study intervention by participants (or designee) or shipment of study
intervention from the study site directly to participants for at home administration
(including the potential for self-administration of study intervention)
Laboratory assessments using a suitably accredited local laboratory; for selected
measures (eg, urine pregnancy), home testing may be employed
Other procedures may be conducted at an appropriate facility
Missed assessments/visits will be captured in the clinical trial management system for
protocol deviations. Discontinuations of study 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 / labeled 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 / 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.

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10.12. Appendix 12: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located
directly before the Table of Contents.
Amendment 3 (21 October 2024)
Overall Rationale for the Amendment: Extend the overall duration of the study from approximately
112 weeks (92 weeks of treatment) to 268 weeks (248 weeks of treatment), to align with a Health Authority
commitment. Time points for assessments were added/updated accordingly. In addition, edits were made
to bring this protocol into compliance with EU-CTR requirements (Regulation [EU] 536/2014).
The changes made to the clinical protocol CNTO1959UCO3004 as part of Protocol Amendment 3 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 10.12 Appendix 12: Protocol Amendment History.
Section Number 
and Name 
Description of Change 
Brief
Rationale
1.1 Synopsis, 
1.3 Schedule of Activities Table 
2 (footnote c), 
4.1 Overall Design, 
4.2 Scientific Rationale for 
Study Design  
Updated the study duration to reflect the extension of the 
overall treatment period and to clarify that participants will 
continue on guselkumab treatment up to Week 248. 
The study
was extended
to align with
a Health
Authority
commitment.
1.1 Synopsis 
Updated overall study duration from up to 112 weeks to
268 weeks. Updated the extension treatment period duration
from 72 weeks to 224 weeks. Removed the statement that the
last scheduled dose of study intervention will be at Week 92.
1.2 Schema 
Updated the study schema to reflect the extended treatment
duration. Added a clarifying footnote.
1.3 Schedule of Activities, 
Table 1 
Edited footnote b to clarify that participants who discontinue
study intervention prior to Week 24 should have a safety
follow-up visit approximately 12 weeks after the last dose of
study intervention.
1.3 Schedule of Activities, 
Table 2 
Updated the table title (“Week 28 Through Week 96”).
Added “Dispense study intervention”, “Administer study
intervention”, “Dispense at-home study medication diary”,
and “Injection-site evaluation” at the Week 96 visit, and
updated the note for the “Dispense study intervention” row.
Edited footnote e to clarify that participants who discontinue
study intervention prior to Week 96 should have a safety
follow-up visit approximately 12 weeks after their last dose
of study intervention.
1.3 Schedule of Activities, 
Table 3 
Added a new SoA covering the extension treatment period
from Week 100 through Week 248.
3 Objectives and Endpoints, 
9 Statistical Considerations, 
9.4.4 Exploratory Efficacy
Endpoints
Edited the sentence referring to the SAP to state that further
details will be provided in the SAP.
4.2 Scientific Rationale for 
Study Design  
In the final paragraph in the subheading “Blinding, Control,
Study Periods, Intervention Groups”, clarified that, with the
extension of the overall treatment period, the study will
provide access to treatment for approximately 5 years. Also
edited the final statement regarding the follow-up period.
4.2.1 Study-Specific Ethical 
Design Considerations, 
Updated the total blood volume to be collected (and where
necessary, the timing for collection) from each participant.

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Section Number 
and Name 
Description of Change 
Brief
Rationale
8 Study Assessments and
Procedures
4.4 End of Study Definition  
Updated instances of Week 96 to Week 248 in the
“Participant Study Completion Definition” section.
6.1 Study Intervention(s) 
Administered 
Updated title of Figure 2 to “Dosing Schedule Through Week
248”. Updated the figure to include guselkumab dosing at
Week 96 and extended the duration of the study to Week
248.  Added a footnote to Week 48.
6.1.1 Self-administration of 
Study Intervention
Added language on at-home administration from Week 96.
6.8.1 UC-related Concomitant 
Therapies 
Updated the subheading “Week 48 through Week 96” to
“Week 48 through Week 248.”
8 Study Assessments and 
Procedures 
In the paragraph on
 and 
 daily diary
entries (under the “Screening” subheading), added a
reference to the SoA (Section 1.3).
8.2.5 Pregnancy Testing 
Edited first sentence to refer the reader to the SoA for details
on pregnancy testing for women participants of childbearing
potential.
Title page 
Added sentence on new EU regulation. 
To comply
with
EU-CTR
requirements
and comply
with the
Sponsor’s
protocol
template.
Title page, 
1.1 Synopsis 
Deleted EudraCT number (from title page) and added the EU 
Trial Number. 
1.1 Synopsis 
Added a summary of Benefit/Risk Assessment. 
5.4 Screen Failures 
Added text to specify usage of IWRS and its relationship to 
the generation of screening and enrollment logs. 
6.1 Study Intervention(s) 
Administered 
Added a table of IMPs and authorization status to the start of 
this section. 
8.3.4 Regulatory Reporting 
Requirements for SAEs and
Anticipated Events
Updated safety reporting text. 
10.6.4 Recruitment Strategy 
Added section and text indicating that it is not applicable to
this study, because recruitment for this study has stopped.
10.6.5 Data Protection  
Changed “legally acceptable representative” to “legally
designated representative”.
10.6.7 Use of Information and 
Publication
Updated text to match recent template update.
10.6.13 Record Retention  
Sentence on trials performed under EU Regulations added to
the end of the second paragraph.
Title page, 
1.1 Synopsis 
Added IND number. 
To comply
with the
Sponsor’s
protocol
template.
6.1.1 Self-Administration of 
Study Intervention  
Edited the first sentence under the subheading “At-home” to 
clarify that self-administration of study intervention should
occur as outlined in the SoA (Section 1.3).
For clarity.
8.2.6 Suicidal Ideation and 
Behavior Risk Monitoring 
Added a reference to the SoA (Section 1.3) in the fourth 
paragraph.
For clarity.
10.6.1 Regulatory and Ethical 
Considerations 
Added post-marketing study paragraph. 
To comply
with local
regulations.
10.7.1 Adverse Event 
Definitions and Classifications 
Added final sentence to text in “Unlisted (Unexpected) 
Adverse Event/Reference Safety Information” subheading
specifying that an AE will be determined by whether it is
listed in an appropriate document.
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Section Number 
and Name 
Description of Change 
Brief
Rationale
Throughout the protocol 
Minor grammatical, formatting, or spelling changes were 
made. 
Minor errors
were noted.
Amendment 2 (16 August 2022)
Overall Rationale for the Amendment: The overall reason for the amendment is to align with requests
received from Health Authorities. In addition, revisions were made to improve clarity and consistency in
the protocol. The changes made to the clinical protocol CNTO1959UCO3004 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 the previous protocol amendment are listed in Section 10.12 Appendix 12: Protocol
Amendment History.
Section number 
and Name
Description of Change 
Brief Rationale
1.3 Schedule of 
Activities 
Added endoscopy at Week 24  
Removed endoscopy,
 as well as
adjacent biopsy samples at Week 96
Addresses health authority request
1.1 Synopsis, 
3. Objectives and 
Endpoints, 
9.2 Sample Size 
Determination, 
9.4.3 Secondary 
Endpoints, 
9.4.3.2 Confirmatory 
Testing Procedure 
Week 24 endoscopy was added to enable 
inclusion of clinical remission at Week 24 as a
secondary endpoint. Along with clinical remission
at Week 24, endoscopic improvement at Week 24
and clinical response at Week 24 were also added
as secondary endpoints. These secondary
endpoints were incorporated in the confirmatory
testing sequence which now follows a purely
hierarchical approach. Individual power for the
additional secondary endpoints was added into the
sample size calculation section.
Addresses health authority request
1.2. Schema, 
6.1 Study 
Intervention(s) 
Administered
Modified Figures 1 and 2: 
Added endoscopy at Week 24
Removed endoscopy at Week 96
Addresses health authority request
1.3 Schedule of 
Activities 
Urine pregnancy test added at ED and SFU visits 
following the main treatment period. 
Inadvertently omitted from prior
protocol versions
1.1 Synopsis, 
9.4.2.2 Estimator for 
the Primary 
Endpoint,
9.4.3.1 Estimands
and Estimators
Changed CMH test to Mantel-Haenszel test for 
common risk difference with Mantel-Haenszel
weights and Sato variance estimator.
Addresses health authority request
9.4.5.1 Adverse 
Events 
Removed frequency and type of infections and 
serious infections analyses 
These analyses are redundant as
they will be included in summaries
of frequency and type of AEs and
SAEs, respectively
1.1 Synopsis, 
4.2.1 Study-specific 
Ethical Design 
Consideration
Updated duration of the study from 116 to 112 
weeks 
SFU visit is 12 weeks after the last
study medication dose, which is at
Week 92
1.3 Schedule of 
Activities, 
8. Study Assessments
and Procedures
Added details on how to complete daily diary 
entries
Improve clarity in the protocol
5.1 Inclusion Criteria, Updated inclusion criterion 8 and exclusion 
criterion 32
Improve clarity in the protocol
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5.2 Exclusion
Criteria
Throughout the
protocol
Minor grammatical, formatting, or spelling
changes were made
Improve clarity in the protocol
Throughout the
protocol
Updated “country” to “country/territory” when
referring to country-specific regulations and
requirements.
To clarify that the text specifying
country-specific regulations and
requirements are also applicable to
territories.
Amendment 1 (2 May 2022)
Overall Rationale for the Amendment: The overall reason for the amendment is to align with requests
received from the Health Authorities. In addition, revisions were made to improve clarity and consistency
in the protocol.
Section number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis, 1.2
Schema, 1.3
Schedule of
Activities, 4.1
Overall Design,
6.1.1 Self-
Administration of
Study Intervention,
6.3 Measures to
Minimize Bias:
Randomization and
Blinding, 6.8.1 UC-
related Concomitant
Therapies
Timing of endoscopy procedure moved from Week
56 to Week 48. Updated the study assessments and
text to allow for unblinding at Week 48 instead of
Week 56, and for optional at-home study
administration to begin at Week 52 instead of
Week 60.
Addresses health authority request.
1.1 Synopsis, 4.1
Overall Design, 5.1
Inclusion Criteria,
6.3 Measures to
Minimize Bias:
Randomization and
Blinding, 6.8.2
Prohibited
Concomitant
Therapies, 10.4
Appendix 4:
Definition of
Inadequate Initial
Response, Loss of
Response, or
Intolerance to
Tofacitinib,
Filgotinib,
Upadacitinib or
Ozanimod
Upadacitinib and filgotinib were added as
approved JAK inhibitors to the list of advanced
therapies. Appendix was updated to define primary
nonresponse, secondary loss of response, and
intolerance to upadacitinib and filgotinib.
Upadacitinib and filgotinib have
recently been approved to treat
moderately to severely active UC.
1.1 Synopsis, 1.3
Schedule of
Activities, 4.2
Scientific Rationale
for Study Design,
Optional genetic research sampling was removed
from the study.
Reduces participant burden.

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Section number
and Name
Description of Change 
Brief Rationale 
5.1 Inclusion
Criteria, 7.2.1
Withdrawal From
the Use of Research
Samples, 8.5
Pharmacogenomics,
9.4.6.6
Pharmacogenomic
Analyses, 10.6
Appendix 6
Regulatory, Ethical,
and Study Oversight
Considerations
1.3 Schedule of 
Activities, 8 Study 
Assessments and 
Procedures
Updated the visit window in the extension phase 
from ±7 days to ±10 days. 
To provide greater flexibility to
schedule study visits during the
extension phase.
3 Objectives and 
Endpoints 
Added exploratory endpoints at Week 48, 
including clinical response, clinical remission, and
endoscopic improvement.
Addresses health authority request.
5.1 Inclusion 
Criteria 
Updated the dose of budesonide or 
beclomethasone dipropionate allowed prior to
receiving study intervention.
Addresses health authority request.
8.1.1 
 
Updated the days that will be used to calculate the 
Addresses health authority request.
9.2 Sample Size 
Determination  
Added Phase 3 ustekinumab UC program 
[CNTO1275UCO3001], to rationale of sample size 
determination.
Clarify assumption for sample size
determination.
9.4.2.1 Primary 
Estimand of Clinical 
Remission, 9.4.2.2 
Estimator for the
Primary Endpoint,
9.4.3.1 Estimands
and Estimators
Changed analysis strategy for intercurrent events. 
Intercurrent event handling
strategies were updated to address
health authority request.
9.4.3.2 
Confirmatory 
Testing Procedure 
Updated the testing procedure for the endpoint of 
symptomatic remission at Week 24. 
Testing procedure for 4th secondary
endpoint was updated to address
health authority request.
Throughout the 
protocol 
Minor grammatical, formatting, or spelling 
changes were made.
Minor errors were noted.
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11. 
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135
Status: Approved,  Date: 13 May 2025
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

Signature
User 
Date 
Reason
 
13-May-2025
21:11:34
(GMT)
Document Approval
PPD