A 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 Crohn's Disease
Phase: PHASE3
Conditions: Crohn Disease
Sponsor: Janssen Research & Development, LLC

CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
1
Status: Approved, Date: 04 October 2024
Janssen Research & Development *
Clinical Protocol
Protocol Title
A 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 Crohn's Disease
GRAVITI
Short Title
A Phase 3 Study to Evaluate the Efficacy and Safety of Guselkumab Subcutaneous Induction
Therapy in Participants with Moderately to Severely Active Crohn’s Disease
Protocol CNTO1959CRD3004Amendment 2; Phase 3
AMENDMENT 2
CNTO 1959 (guselkumab)
*Janssen Research & Development is a global organization that operates through different legal entities in
various countries. Therefore, the legal entity acting as the sponsor for Janssen Research & Development
studies may vary, such as, but not limited to Janssen Biotech, Inc.; Janssen Products, LP; Janssen
Biologics, BV; Janssen-Cilag International NV; Janssen, Inc; Janssen 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.
IND:133845
EU TRIALNUMBER:2023-504737-41
Status: 
Approved
Date: 
04 October 2024
Prepared by: Janssen Research & Development, LLC
EDMS number: 
EDMS-RIM-163296, 3.0
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory
requirements.
Confidentiality Statement
The information provided herein contains Company trade secrets, commercial or financial information that the Company
customarily holds close and treats as confidential.  The information is being provided under the assurance that the recipient
will maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or
otherwise.
NCT05197049

CNTO 1959  (guselkumab) 
Clinical Protocol CNTO1959CRD3004 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
2
Status: Approved, Date: 04 October 2024
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
Document 
Date
Amendment 2 
04 October 2024
Amendment 1 
13 September 2023
Original Protocol 
03 September 2021
Amendment 2 (04October 2024)
Overall Rationale for the Amendment: Extended the overall duration of the GRAVITI study from
approximately  109 weeks to 265 weeks, to align with a health authority commitment. Timepoints for
assessments were added/updated accordingly. In addition, edits were made to bring this protocol into
compliance with European Union  Clinical Trial Regulation (EU-CTR) requirements (Regulation [EU]
536/2014).
The changes made to the clinical protocol CNTO1959CRD3004 as part of Protocol Amendment 2 are listed
below, including the rationale of each change and a list of all applicable sections. Changes made in previous
protocol amendments are listed in Section 10.11, Appendix 11: Protocol Amendment History.
Section Number 
and Name
Description of Change 
Brief Rationale
Synopsis, Overall Design, 
Intervention Groups and 
Duration; 
Section 1.3 Schedule of 
Activities, Table 3; 
Section 4.1 Overall Design; 
Section 6.3 Measures to 
Minimized Bias
Updated text to reflect that guselkumab treatment will 
continue for participants through Week 248. 
In the Synopsis only, also added clarification that 
participants will continue on guselkumab treatment if 
they are, in the opinion of the investigator, benefiting
from study intervention.
The study duration
was extended to
align with a health
authority
commitment.
Synopsis, Overall Design; 
Section 4.1 Overall Design  
Clarified that an additional DBL is planned for
Week 96.
Synopsis, Intervention Groups 
and Duration; 
Section 4.1 Overall Design; 
Section 4.2 Scientific Rationale 
for Study Design
Updated the study duration to reflect the extension of
the extension treatment phase (from 72 weeks to 224
weeks) and changed the overall study duration from up
to 109 weeks to 265 weeks (approximately 5 years).
Section 1.2 Schema, Figure 1 
Updated study schema to include the extension of the
study (also extended the extension period and
guselkumab treatment lines to Week 248).
Section 1.3 Schedule of 
Activities, Table 3 
Added “Dispense study intervention,”
“Self-administration training,” and “Administer study
intervention” to the Week 96 visit. Updated the notes for
these rows as needed.
Section 1.3 Schedule of 
Activities, Table 4
Added a new SoA for Weeks 100 to 248.
Section 1.3 Schedule of 
Activities, Table 5 
Removed the “Visits Required” column from Part a of
the table and deleted footnote c.
Updated the last 2 rows from Part a of the table to
account for the extension of the study (ie, changed
Week 96 to Week 248).
In the note for the second to last row of Part a of the
table, clarified that the video ileocolonoscopy at the SID
visit is optional for participants who discontinue after

CNTO 1959  (guselkumab) 
Clinical Protocol CNTO1959CRD3004 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 04 October 2024
Section Number 
and Name
Description of Change 
Brief Rationale
Week 48 and before Week 96. Also added that video
ileocolonoscopy should be performed if the SID visit
occurs at Week 96.
Added footnote “a” to Part b of the table to indicate
which assessments are not required for SID visits
occurring at Week 96 or afterwards.
Added footnote “b” to Part b of the table to indicate
which assessments are not required for FES visits
occurring after Week 108.
Also in Part b of the table, expanded the note for the
daily diary to clarify when the collection of daily diary
information will conclude.
Added a note to “Hematology and chemistry” row
describing when only chemistry laboratory assessments
should be performed.
Section 3 Objectives and 
Endpoints; 
Section 9 Statistical
Considerations
Edited the final sentence in the paragraph that refers to
the SAP.
Section 4.1 Overall Design; 
Section 6.1 Study
Intervention(s) Administered
Added references to the new Figure 3.
Section 4.2 Scientific Rationale 
for Study Design  
Clarified that the extension will give participants who in
the opinion of the investigator are benefiting from study
intervention continued access to treatment. Also
included a reference to the SoA in the final sentence.
Section 4.2.1 Study-specific 
Ethical Design Considerations; 
Section 8 Study Assessments
and Procedures
Updated the total blood volume to be collected (and the
timing for collection) from each participant.
Section 4.4 End of Study 
Definition  
Updated the statement on when a participant will be
considered to have completed the extension treatment
phase and the statement on participants who prematurely
discontinue study intervention after Week 24 (in both
statements updated Week 96 to Week 248, to account
for the extension of the study).
Section 6.1 Study 
Intervention(s) Administered 
Updated Figure 2 (Dose Regimens for the Treatment
Phases from Week 0 Through Week 96) to include
guselkumab dosing at Week 96.
Added Figure 3 to specify dose regimens for the
extension treatment phase from Week 100 through
Week 248.
In the “Self-administration of Study Intervention at
Home” subheading, added language on training at
Week 96 using the correct device based on assigned
treatment regimen. Also edited language on
self-administration of study intervention at home to
reflect the extension of the study.

CNTO 1959  (guselkumab) 
Clinical Protocol CNTO1959CRD3004 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 04 October 2024
Section Number 
and Name
Description of Change 
Brief Rationale
Section 6.8.1 Concomitant 
Medications 
Edited the title of the “After Week 48 and Through
Week 96” subheading (deleted “and Through Week 96”)
to reflect the extension of the study.
Section 8 Study Assessments 
and Procedures, Table 7 
Updated “Screening through Week 96” to “through
Week 248,” to reflect the extension of the study.
Section 8.2.4 Clinical Safety 
Laboratory Assessments 
Under “Pregnancy testing”, added that urine pregnancy
tests are to be performed before each study intervention
administration on-site, and added a reference to the
SoA.
Section 9.4.4 Tertiary 
Endpoints 
Edited text to clarify that the tertiary endpoints are
evaluated at applicable timepoints through Week 96.
Title Page 
Added sentence on new EU regulation. 
To comply with
EU-CTR
requirements.
Title Page; 
Synopsis 
Replaced EudraCT number with EU Clinical Trial 
Number. 
Synopsis 
Added a summary of Benefit/Risk Assessment.
Section 8.3.4 Regulatory 
Reporting Requirements for
Serious Adverse Events and
Anticipated Events
Updated safety reporting text.
Section 10.5.4 Data Protection  
Updated language under Privacy of Personal Data to
align with Sponsor’s protocol template and added a new
paragraph on measures to be taken in the event of a data
security breach.
Section 10.5.13 Record 
Retention  
Added text regarding record retention under EU
regulation, per EU-CTR requirement.
Synopsis 
Added IND number. 
To comply with the
Sponsor’s protocol
template.
Section 6.8.2 Prohibited 
Concomitant Medications 
Added “etrasimod” to the list of experimental Crohn’s 
disease medications. 
To update list of
treatment options
available.
Section 10.5.1 Regulatory and 
Ethical Considerations 
Added Post-marketing Study paragraph. 
To comply with
local regulations.
Section 10.6.1 Adverse Events 
Definitions and Classifications 
Added final sentence to “Unlisted (Unexpected)
AE/RSI” specifying that an AE will be determined by
whether it is listed in an appropriate document.
Throughout the protocol 
Minor grammatical, formatting, or spelling changes 
were made. 
Minor errors were
noted.

CNTO 1959  (guselkumab) 
Clinical Protocol CNTO1959CRD3004 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 04 October 2024
TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................................... 2
TABLE OF CONTENTS ............................................................................................................................... 5
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 8
1. 
PROTOCOL SUMMARY..................................................................................................................... 9
1.1. 
Synopsis........................................................................................................................................... 9
1.2. 
Schema.......................................................................................................................................... 15
1.3. 
Schedule of Activities (SoA)........................................................................................................... 16
2. 
INTRODUCTION................................................................................................................................ 30
2.1. 
Study Rationale.............................................................................................................................. 30
2.2. 
Background.................................................................................................................................... 31
2.3. 
Benefit-risk Assessment................................................................................................................. 32
2.3.1. 
Risks for Study Participation....................................................................................................... 32
2.3.2. 
Benefits for Study Participation .................................................................................................. 36
2.3.3. 
Benefit-risk Assessment for Study Participation......................................................................... 37
3. 
OBJECTIVES AND ENDPOINTS ..................................................................................................... 37
4. 
STUDY DESIGN ................................................................................................................................ 39
4.1. 
Overall Design................................................................................................................................ 39
4.2. 
Scientific Rationale for Study Design............................................................................................. 42
4.2.1. 
Study-specific Ethical Design Considerations ............................................................................ 44
4.3. 
Justification for Dose...................................................................................................................... 45
4.4. 
End of Study Definition................................................................................................................... 46
5. 
STUDY POPULATION ...................................................................................................................... 46
5.1. 
Inclusion Criteria............................................................................................................................ 46
5.2. 
Exclusion Criteria........................................................................................................................... 52
5.3. 
Lifestyle Considerations................................................................................................................. 57
5.4. 
Screen Failures.............................................................................................................................. 57
5.5. 
Criteria for Temporarily Delaying Enrollment, Randomization or Administration of Study
Intervention .................................................................................................................................... 58
6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY............................................................ 59
6.1. 
Study Intervention(s) Administered................................................................................................ 59
6.1.1. 
Combination Products ................................................................................................................ 62
6.2. 
Preparation/Handling/Storage/Accountability ................................................................................ 62
6.3. 
Measures to Minimize Bias: Randomization and Blinding............................................................. 64
6.4. 
Study Intervention Compliance...................................................................................................... 65
6.5. 
Dose Modification........................................................................................................................... 65
6.5.1. 
Rescue Medication ..................................................................................................................... 65
6.6. 
Continued Access to Study Intervention After the End of the Study ............................................. 66
6.7. 
Treatment of Overdose .................................................................................................................. 66
6.8. 
Concomitant Therapy..................................................................................................................... 66
6.8.1. 
Concomitant Medications ........................................................................................................... 66
6.8.1.1. 
Oral Corticosteroids Tapering.................................................................................................. 67
6.8.2. 
Prohibited Concomitant Medications .......................................................................................... 68
6.8.3. 
Vaccinations (Including COVID-19)............................................................................................ 69
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL............................................................................................... 69
7.1. 
Discontinuation of Study Intervention ............................................................................................ 69
7.2. 
Participant Discontinuation/Withdrawal From the Study................................................................ 71
7.2.1. 
Withdrawal From the Use of Research Samples ....................................................................... 71

CNTO 1959  (guselkumab) 
Clinical Protocol CNTO1959CRD3004 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 04 October 2024
7.3. 
Lost to Follow-up............................................................................................................................ 72
8. 
STUDY ASSESSMENTS AND PROCEDURES ............................................................................... 73
8.1. 
Efficacy Assessments .................................................................................................................... 75
8.2. 
Safety Assessments....................................................................................................................... 78
8.2.1. 
Physical Examinations................................................................................................................ 78
8.2.2. 
Vital Signs................................................................................................................................... 78
8.2.3. 
Electrocardiogram....................................................................................................................... 78
8.2.4. 
Clinical Safety Laboratory Assessments .................................................................................... 79
8.2.5. 
Columbia-Suicide Severity Rating Scale.................................................................................... 79
8.2.6. 
Concomitant Medication Review ................................................................................................ 81
8.2.7. 
Injection-site Reactions............................................................................................................... 81
8.2.8. 
Hypersensitivity Reactions.......................................................................................................... 81
8.2.9. 
Infections .................................................................................................................................... 82
8.2.10. 
Tuberculosis Evaluation.............................................................................................................. 82
8.2.10.1. 
Initial Tuberculosis Evaluation................................................................................................. 82
8.2.10.2. 
Ongoing Tuberculosis Evaluation............................................................................................ 83
8.3. 
Adverse Events, Serious Adverse Events, and Other Safety Reporting ....................................... 83
8.3.1. 
Time Period and Frequency for Collecting Adverse Event and Serious Adverse Event
Information.................................................................................................................................. 84
8.3.2. 
Method of Detecting Adverse Events and Serious Adverse Events .......................................... 84
8.3.3. 
Follow-up of Adverse Events and Serious Adverse Events ....................................................... 84
8.3.4. 
Regulatory Reporting Requirements for Serious Adverse Events and Anticipated
Events......................................................................................................................................... 85
8.3.5. 
Pregnancy................................................................................................................................... 85
8.3.6. 
Adverse Events of Special Interest............................................................................................. 85
8.4. 
Pharmacokinetics........................................................................................................................... 86
8.4.1. 
Evaluations ................................................................................................................................. 86
8.4.2. 
Analytical Procedures................................................................................................................. 86
8.4.3. 
Pharmacokinetic Parameters and Evaluations........................................................................... 86
8.5. 
Pharmacogenomics ....................................................................................................................... 87
8.6. 
Biomarkers..................................................................................................................................... 87
8.6.1. 
Serum-based Biomarkers........................................................................................................... 88
8.6.2. 
Whole Blood-based Biomarkers................................................................................................. 88
8.6.3. 
Biopsy-based Biomarkers........................................................................................................... 88
8.6.4. 
Pharmacodynamics .................................................................................................................... 88
8.7. 
Immunogenicity Assessments ....................................................................................................... 88
8.8. 
Medical Resource Utilization and Health Economics .................................................................... 89
9. 
STATISTICAL CONSIDERATIONS.................................................................................................. 89
9.1. 
Statistical Hypotheses.................................................................................................................... 89
9.2. 
Sample Size Determination ........................................................................................................... 89
9.3. 
Populations for Analysis Sets ........................................................................................................ 90
9.4. 
Statistical Analyses ........................................................................................................................ 91
9.4.1. 
General Considerations.............................................................................................................. 91
9.4.2. 
Primary Endpoints ...................................................................................................................... 91
9.4.3. 
Secondary Endpoints.................................................................................................................. 94
9.4.4. 
Tertiary Endpoints....................................................................................................................... 96
9.4.5. 
Safety Analyses.......................................................................................................................... 96
9.4.6. 
Other Analyses ........................................................................................................................... 97
9.5. 
Interim Analysis.............................................................................................................................. 98
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ............................ 99
10.1. 
Appendix 1: Abbreviations and Definitions .................................................................................. 100
10.2. 
Appendix 2: Definitions of Inadequate Response to or Intolerance of Corticosteroids or
6-Mercaptopurine/Azathioprine/Methotrexate and Corticosteroid Dependence.......................... 102

CNTO 1959  (guselkumab) 
Clinical Protocol CNTO1959CRD3004 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 04 October 2024
10.3. 
Appendix 3: Definition of Inadequate Initial Response, Loss of Response, or Intolerance
to Tumor Necrosis Factor Antagonist Therapies (Infliximab, Adalimumab, or Certolizumab
Pegol), Vedolizumab, or Approved Biosimilars............................................................................ 104
10.4. 
Appendix 4: Hepatitis B Virus (HBV) Screening With HBV DNA Testing.................................... 109
10.5. 
Appendix 5: Regulatory, Ethical, and Study Oversight Considerations....................................... 110
10.5.1. 
Regulatory and Ethical Considerations .................................................................................... 110
10.5.2. 
Financial Disclosure.................................................................................................................. 113
10.5.3. 
Informed Consent Process ....................................................................................................... 113
10.5.4. 
Data Protection ......................................................................................................................... 114
10.5.5. 
Long-term Retention of Samples for Additional Future Research............................................ 115
10.5.6. 
Committees Structure............................................................................................................... 115
10.5.7. 
Publication Policy/Dissemination of Clinical Study Data.......................................................... 115
10.5.8. 
Data Quality Assurance............................................................................................................ 117
10.5.9. 
Case Report Form Completion................................................................................................. 117
10.5.10. Source Documents ................................................................................................................... 118
10.5.11. Monitoring ................................................................................................................................. 119
10.5.12. On-Site Audits........................................................................................................................... 119
10.5.13. Record Retention...................................................................................................................... 119
10.5.14. Study and Site Start and Closure ............................................................................................. 120
10.6. 
Appendix 6: Adverse Events, Serious Adverse Events, Product Quality Complaints, and
Other Safety Reporting: Definitions and Procedures for Recording, Evaluating, Follow-up,
and Reporting............................................................................................................................... 121
10.6.1. 
Adverse Event Definitions and Classifications ......................................................................... 121
10.6.2. 
Attribution Definitions................................................................................................................ 122
10.6.3. 
Severity Criteria........................................................................................................................ 122
10.6.4. 
Special Reporting Situations .................................................................................................... 123
10.6.5. 
Procedures ............................................................................................................................... 123
10.6.6. 
Product Quality Complaint Handling......................................................................................... 125
10.6.7. 
Contacting Sponsor Regarding Safety, Including Product Quality........................................... 125
10.7. 
Appendix 7: Contraceptive and Barrier Guidance ....................................................................... 126
10.8. 
Appendix 8: Crohn’s Disease Activity Index ................................................................................ 129
10.9. 
Appendix 9: Guideline Algorithm for Monitoring, Assessment and Evaluation of Abnormal
Liver Tests.................................................................................................................................... 130
10.10. Appendix 10: Study Conduct During a Natural Disaster.............................................................. 134
10.11. Appendix 11: Protocol Amendment History................................................................................. 136
11. REFERENCES................................................................................................................................. 138
INVESTIGATOR AGREEMENT............................................................................................................... 140

CNTO 1959  (guselkumab) 
Clinical Protocol CNTO1959CRD3004 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 04 October 2024
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1: 
Schedule of Activities: Screening Phase .................................................................................. 16
Table 2: 
Schedule of Activities: Main Treatment Phase Weeks 0 to 24................................................. 18
Table 3: 
Schedule of Activities: Extension Treatment Phase Weeks 28 to 96....................................... 21
Table 4: 
Schedule of Activities: Extension Treatment Phase Weeks 100 to 248................................... 26
Table 5: 
Schedule of Activities: Study Intervention Discontinuation (SID) Visit and the Final
Efficacy and Safety (FES) Follow-up Visit................................................................................ 27
Table 6: 
Recommended Tapering Schedule for Oral Corticosteroids.................................................... 68
Table 7: 
Volume of Blood to be Collected From Each Participant.......................................................... 74
Table 8: 
Power to Detect a Treatment Effect of Guselkumab Based on Proportion of
Participants Achieving Clinical Remission at Week 12 or Endoscopic Response at
Week 12.................................................................................................................................... 90
Table 9: 
Eligibility Based on Hepatitis B Virus Test Results................................................................. 109
Table 10: Patterns of DILI Based on Elevations of Liver Tests .............................................................. 133
FIGURES
Figure 1: Schematic Overview of the Study............................................................................................. 15
Figure 2: Dose Regimens for the Treatment Phases From Week 0 Through Week 96.......................... 60
Figure 3: Dose Regimens for the Extension Treatment Phase From Week 100 Through Week
248............................................................................................................................................ 60

CNTO 1959  (guselkumab) 
Clinical Protocol CNTO1959CRD3004 Amendment 2
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 04 October 2024
1. 
PROTOCOL SUMMARY
1.1. 
Synopsis
Protocol Title: A 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 Crohn's Disease
IND: 133845
EU Trial Number: 2023-504737-41
Short Title: A Phase 3 Study to Evaluate the Efficacy and Safety of Guselkumab Subcutaneous Induction
Therapy in Participants with Moderately to Severely Active Crohn’s Disease
Guselkumab is a fully human immunoglobulin G1 lambda monoclonal antibody that binds to human
interleukin (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 of adults with moderate to severe psoriasis and adults with active
psoriatic arthritis. The Phase 2 results for guselkumab in participants with Crohn’s disease
(CNTO1959CRD3001; GALAXI 1) also provided a scientific and clinical rationale for pursuing the
development of guselkumab in patients with moderately to severely active Crohn’s disease and for the
investigation of guselkumab in this study. Taking into account the measures taken to minimize risk to
participants of this study, the potential risks identified in association with guselkumab are justified by the
anticipated benefits that may be afforded to participants with moderately to severely active Crohn’s disease.
More detailed information about the known and expected benefits and risks of guselkumab may be found
in the Investigator’s Brochure (IB).
OBJECTIVES AND ENDPOINTS
The primary and secondary objectives and endpoints of the study are listed below.
Objectives 
Endpoints
Primary
To evaluate the efficacy, including clinical 
remission and endoscopic response, of 
guselkumab SC induction
Clinical remission (CDAI score <150) at
Week 12
Endoscopic response (≥50% improvement
from baseline in the SES-CD score) at
Week 12
Secondary
To evaluate the efficacy of guselkumab SC 
across a range of outcome measures
Clinical remission at Week 24
PRO-2 remission (an AP mean daily score ≤1
and SF mean daily score ≤3 and no worsening
of AP or SF from baseline)at Week 12

CNTO 1959  (guselkumab) 
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CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 04 October 2024
Objectives 
Endpoints
Clinical response (decrease from baseline in
CDAI ≥100 points or clinical remission) at
Week 12
To evaluate the safety of guselkumab SC  
Summary of AEs, such as SAEs and AEs
leading 
to 
discontinuation 
of 
study
intervention
Abbreviations: AE=adverse event; AP=abdominal pain; CDAI=Crohn’s Disease Activity Index;
PRO=Patient-reported Outcome; SAE=serious adverse event; SC=subcutaneous; SES-CD=Simple Endoscopic
Score for Crohn’s Disease; SF=stool frequency
Hypotheses
The co-primary hypotheses of this study are that guselkumab is superior to placebo in inducing clinical
remission at Week 12 and guselkumab is superior to placebo in inducing endoscopic response at Week 12
among participants with moderately to severely active Crohn’s disease.
OVERALLDESIGN
This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate the
efficacy and safety of guselkumab subcutaneous (SC) induction dosing. The target population is adult
participants with moderately to severely active Crohn’s disease (of at least 3 months duration) with colitis,
ileitis, or ileocolitis previously confirmed by radiography, histology, and/or endoscopy. To be eligible for
the study, participants must also have endoscopic evidence of active Crohn’s disease, and have
demonstrated an inadequate response or failure to tolerate previous conventional therapy  (oral
corticosteroids or the immunomodulators azathioprine [AZA], 6-mercaptopurine [6-MP] or methotrexate
[MTX]; CON-Failure) or biologic therapy (infliximab, adalimumab, certolizumab pegol, vedolizumab, or
approved biosimilars for these agents; BIO-Failure).
Overall, the study will evaluate guselkumab SC treatment through 12 weeks of induction therapy and at
least 12 weeks of maintenance therapy. At Week 24, all participants will enter the extension phase and
receive the same treatment regimen that they were receiving at Week 24. The study will be unblinded after
the last participant completes the Week 48 evaluations and the Week 48 database lock (DBL)is completed.
Upon study unblinding, placebo participants who have not been rescued with guselkumab (see Intervention
Groups and Duration section) will be discontinued from study intervention and have a final efficacy and
safety (FES) follow-up visit. All other participants who in the opinion of the investigator are benefiting
from study intervention will continue on guselkumab treatment through Week 248.
In general, participants who are receiving oral 5-aminosalicylic acid compounds, oral corticosteroids,
conventional immunomodulators (AZA, 6-MP, or MTX), antibiotics, and/or enteral nutrition for the
treatment of Crohn’s disease at baseline should maintain a stable dose for a specified period before baseline
and through Week 48, with the exception of oral corticosteroids. 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.
Participants who discontinue study intervention early should return for a study intervention discontinuation
(SID) visit. All randomized participants should complete the FES follow-up visit approximately 12 weeks
after the last dose of study intervention.
Efficacy, safety, pharmacokinetics (PK), immunogenicity, and biomarkers will be assessed according to
the Schedule of Activities (SoA). A blood sample for pharmacogenomic research will be collected only
from participants who consent to this component of the protocol (where local regulations permit).

CNTO 1959  (guselkumab) 
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Status: Approved, Date: 04 October 2024
Database locks are planned for Week 24, Week 48, Week 96, 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 study is considered completed when the last participant completes the last scheduled study assessment
shown in the SoA or if a decision has been made by the sponsor not to pursue an indication in Crohn’s
disease 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 318 participants. Participants who had an inadequate response or failure to tolerate
biologic therapy will comprise approximately 35% to 65% of the population.
INTERVENTION GROUPS AND DURATION
The overall study duration is up to 265 weeks. The study comprises of the following phases:
1. 
Screening phase: up to 5 weeks
2. 
Main treatment phase: 24 weeks
3. 
Extension treatment phase: 224 weeks
4. Post-treatment phase (FES follow-up visit): 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:
106 participants to guselkumab 
 at Weeks 0, 4, and 8 followed by guselkumab 
every 4 weeks (q4w) through Week 24
106 participants to guselkumab 
 at Weeks 0, 4, and 8 followed by guselkumab 
every 8 weeks (q8w) through Week 24
106 participants to placebo SC q4w from Week 0 through Week 24
The randomization will be stratified by baseline Crohn’s Disease Activity Index (CDAI) score (≤300 or
>300), baseline Simple Endoscopic Score for Crohn’s Disease (SES-CD) score (≤12 or >12), and
BIO-Failure status (Yes or No) at baseline (Week 0).
During the extension phase, all participants will continue to receive the same treatment regimen that they
were receiving at Week 24.
Upon study unblinding after Week 48 DBL, placebo participants who have not been rescued with
guselkumab will be discontinued from study intervention and have an  FES follow-up visit. All other
participants who in the opinion of the investigator are benefiting from study intervention will continue on
guselkumab treatment through Week 248.
All participants in the placebo group who meet at least 1 of the rescue criteria at Weeks 12 and 16 will
receive rescue treatment, ie, guselkumab 
 at Weeks 16, 20, and 24 followed by guselkumab
 every 8 weeks (q8w). To maintain the blind, participants randomized to guselkumab who meet
at least 1 of the rescue criteria will continue their assigned treatment regimen and receive blinded sham
rescue matching placebo SC injection.
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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 prefilled
syringe with YpsoMate autoinjector (PFS-Y) and 
 in a single-dose prefilled syringe with an
UltraSafe PlusTM  Passive Needle Guard (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:
CDAI
PRO-2 (the unweighted CDAI components of the total number of liquid or very soft stools and the
abdominal pain [AP] score)
Endoscopic assessments of the intestinal mucosa based on the presence and absence of mucosal
ulcerations and the SES-CD
Histologic assessments
Inflammatory pharmacodynamic (PD) markers including C-reactive protein  (CRP) and fecal
calprotectin
Fistula assessment
PRO measures to assess health-related quality of life outcomes including Inflammatory Bowel Disease
Questionnaire (IBDQ) and Patient-reported Outcomes Measurement Information System
(PROMIS)-29
Patient-reported symptom measures including Bristol Stool Form Scale (BSFS) and AP-Numerical
Rating Scale (AP-NRS)
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.
PHARMACOGENOMIC (DNA) EVALUATIONS
A pharmacogenomic blood sample will be collected only from participants who consent separately to this
component of the study to allow for pharmacogenomic research, as necessary (where local regulations
permit). Participation in the pharmacogenomic research is optional. Deoxyribonucleic acid (DNA)samples
will be analyzed for identification of genetic factors that may be associated with clinical response.
PHARMACODYNAMIC AND BIOMARKER EVALUATIONS
Inflammatory PD markers (CRP and fecal calprotectin) will be evaluated using blood and fecal samples.
Biomarker assessments will be made to examine the biologic response to treatment and to identify
biomarkers that are relevant to guselkumab treatment and/or Crohn’s disease. Assessments will include the
evaluation of relevant biomarkers in serum, whole blood, and ileocolonic biopsy samples, where local
regulations permit.
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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.
SAFETY EVALUATIONS
Safety assessments include adverse events (AEs), clinical laboratory tests, vital signs and physical
examinations, a screening electrocardiogram, suicidality assessment, concomitant medication review,
injection-site reactions, monitoring for hypersensitivity reactions, a tuberculosis evaluation, and other
infection assessment.
STATISTICAL METHODS
Sample Size Determination
Sample sizes were determined by the power to detect a significant difference in clinical remission at
Week 12 and in endoscopic response at Week 12 (co-primary endpoints) between the combined
guselkumab group and the placebo group, using a 2-sided chi-square test with 0.05 significance level. The
assumed rates are 50% versus 15% (guselkumab versus placebo) for clinical remission and 30% versus
13% for endoscopic response. The study is sized such that the guselkumab therapy achieves >90% power
for the co-primary endpoints compared with placebo. This sample size also provides >90% power for all
secondary endpoints.
Efficacy Analyses
Descriptive statistics (eg, mean, median, standard deviation [SD], interquartile 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, Cochran-Mantel-Haenszel (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 will be compared using an analysis of variance
(ANOVA) or analysis of covariance (ANCOVA), unless otherwise specified. If the normality assumption
is in question, an ANOVA or ANCOVA on the van der Waerden normal scores will be used.
The co-primary endpoints (clinical remission at Week 12 and endoscopic response at Week 12) will be
analyzed based on the primary estimand, considering treatment groups, population, variable, intercurrent
event (ICE) strategies, and population-level summary. After accounting for the ICE strategies, participants
whose responder status is missing for a co-primary endpoint will be considered to be a non-responder for
that co-primary endpoint.
Statistical testing will be performed at a significance level of 0.05 (2-sided). The Type I error will be
controlled over the co-primary, secondary, and selected Week 48 tertiary  endpoints in the
multiplicity-controlled testing procedure. The testing procedure begins with sequential tests as follows:
For the co-primary endpoints, clinical remission at Week 12 will be tested first, followed by
endoscopic response at Week 12.
The analyses for the 3 secondary endpoints listed below will be performed sequentially contingent
upon the success of both co-primary endpoint analyses.

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Clinical remission (CDAI score <150) at Week 24, the test between the high dose group
 q4w) and the placebo group will be performed first, followed by the test between the low dose
group (
 q8w) and the placebo group
PRO-2 remission at Week 12 (defined as an AP mean daily score at or below 1 and stool
frequency (SF) mean daily score at or below 3, ie, AP ≤1 and SF ≤3, and no worsening of AP or
SF from baseline)
Clinical response (decrease from baseline in CDAI ≥100 points or clinical remission) at Week 12
Two tertiary endpoints (clinical remission at Week 48, endoscopic response at Week 48) will be added at
the end of the multiplicity-controlled testing procedure above; the full testing procedure will be specified
in the Statistical Analysis Plan. Other tertiary endpoints will not be multiplicity-controlled, and nominal p-
values will be presented.
Safety Analyses
Safety data, including but not limited to, AEs, serious adverse events (SAEs), infections, injection-site
reactions, changes in laboratory parameters (hematology and chemistry), and suicidal ideation and behavior
will be summarized. All reported treatment-emergent AEs will be included in the analysis.
Other Analyses
Pharmacokinetic Analyses
Serum guselkumab concentration over time will be summarized for each treatment group using descriptive
statistics. Population PK modeling may be conducted when appropriate. If these population PK analyses
are conducted, the results of these analyses will be presented in a separate report.
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. Results of the population PK/PD analysis will be
presented in a separate technical report.
Pharmacogenomic Analyses
Genetic (DNA) analyses will be conducted only in participants who sign the consent form to participate in
the pharmacogenomic substudy. These analyses are considered exploratory and will be summarized in a
separate technical report.
Biomarker Analyses
Changes in serum protein analytes and whole blood ribonucleic acid (RNA) obtained over time will be
summarized by intervention group where local regulations permit. Associations between baseline levels
and changes from baseline in select biomarkers and response to treatment will be explored. RNA analyses
will be summarized in a separate technical report.
Immunogenicity Analyses
The incidence and titers of antibodies to guselkumab will be summarized for all participants who receive a
dose of guselkumab and have appropriate samples for detection of antibodies to guselkumab
(ie, participants with at least 1 sample obtained after their first dose of guselkumab). 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.
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Table 5: 
Schedule of Activities: Study Intervention Discontinuation (SID) Visit and the Final Efficacy and Safety (FES) Follow-up Visit
(a) Participants should complete the SID and/or the FES visits, as outlined below
SIDa 
FESb 
Notes
Participant terminates study participation at any 
time during the study
X 
Evaluations for SID should be completed prior to participant terminating study participation
Participant discontinues study intervention at or 
prior to the Week 12 visit 
X* 
X# 
* If the SID visit occurs at or after the Week 8 time point, video ileocolonoscopy and biopsy samples should be
done at the SID visit.
# If the SID visit occurs prior to the Week 8 time point, video ileocolonoscopy and biopsy samples should be
done at the FES follow-up visit instead of the SID visit.
Participant discontinues study intervention after 
Week 12 and up to the Week 48 visit 
X 
X 
Discontinuation after Week 12 (visit and ileocolonoscopy) and before Week 44: A video ileocolonoscopy (with
biopsy samples) is optional to be performed as part of the SID visit.
Discontinuation at Week 44 or Week 48: A video ileocolonoscopy (with biopsy samples) is required at the
Week 48 visit (or can be performed as part of SID visit).
Participant discontinues study intervention after 
Week 48 and up to Week 248 
X 
X 
The video ileocolonoscopy at the SID visit is optional for participants who discontinue after Week 48 and
before Week 96, since these participants would have completed the procedure as part of the Week 48 visit.
Discontinuation at Week 96: A video ileocolonoscopy (with biopsy samples) is required at the Week 96 visit
(or can be performed as part of SID visit if the SID visit occurs at Week 96).
Note: Upon study unblinding (after Week 48 DBL), placebo participants who have not been rescued with
guselkumab will be discontinued from study intervention and will have only an FES follow-up visit.
Participant completes the 248-week study  
X 
The FES follow-up visit should occur approximately 12 weeks after the last study intervention administration.
Footnotes:
a. 
The SID visit should be completed at the time of SID.
b. 
The FES follow-up visit should be completed approximately 12 weeks after the last dose of study intervention.
Abbreviations: DBL=database lock; FES=final efficacy and safety; SID=study intervention discontinuation (visit)

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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 interleukin (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 inflammatory bowel disease (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 Crohn’s disease (see details in
Section 2.2).
For the most comprehensive nonclinical and clinical information regarding guselkumab, refer to
the latest version of the Investigator’s Brochure (IB)for guselkumab (IB guselkumab).
The term “study intervention” throughout the protocol, refers to study drug.
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.
The term “participant” throughout the protocol refers to the common term “subject”.
2.1. 
Study Rationale
Crohn’s disease is a chronic, progressive and potentially life-threatening disorder which may affect
any part of the gastrointestinal (GI) tract. Inflammation penetrates the lining of the GI tract and
often causes ulcers to form. Symptoms may include abdominal pain (AP), diarrhea, fatigue, and
weight loss/anorexia. Painful perianal disease, strictures, and fistulas are common. Patients with
high disease burden often require at least one surgical intervention.
The pathophysiology of IBD is complex and thought to be multifactorial. The primary aim of
pharmacotherapy is to control the inflammatory response, thereby relieving symptoms and
promoting mucosal healing. The specific goals of IBD management include the treatment of acute
exacerbations, prevention of relapses, treatment of specific complications, and surveillance of
malignant transformation (D’Haens 2014; Lichtenstein 2018).
Historically, the treatment of Crohn’s disease has relied mainly on corticosteroids and
immunosuppressive medications such as thiopurines or methotrexate. Although corticosteroids
reduce mortality in Crohn’s disease patients, corticosteroids are associated with multiple
significant adverse effects and therefore are not suitable for long-term treatment. Approximately
2 decades ago, tumor necrosis factor alpha (TNFα) inhibitors such as infliximab, adalimumab, and

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certolizumab became available for treatment of patients with moderately to severely active
Crohn’s disease, especially those who did not respond to corticosteroids, or were refractory or
intolerant to conventional immunosuppressive medications (Nielsen 2013). In recent years, other
biologics have become available, such as the anti-α4β7-integrin monoclonal antibody (ie,
vedolizumab) and the IL-12/23p40 antibody (ie, ustekinumab). Current treatment guidelines
recommend the use of TNFα inhibitors, vedolizumab, or ustekinumab based on their efficacy and
safety profiles (Lichtenstein 2018; Torres 2020). However, despite the availability of these
therapies, many patients experience primary or secondary nonresponse, hence the unmet medical
need remains high  and underscores the need for novel treatment options that provide greater
therapeutic value to patients (Gordon 2015; Sandborn 2016).
Currently, the GALAXI clinical program is evaluating guselkumab intravenous (IV) induction
dosing followed by subcutaneous (SC) maintenance dosing in participants with moderately to
severely active Crohn’s disease who have demonstrated an inadequate response or failure to
tolerate previous conventional therapy or biologic therapy. Under the GALAXI protocol, there are
3 separate studies (Phase 2 study GALAXI 1 and Phase 3 studies GALAXI 2 and GALAXI 3).
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).
In the current study, the sponsor is interested in assessing SC administration of guselkumab for the
induction phase of Crohn’s disease treatment. Subcutaneous delivery of biologic agents has
become a valuable alternative to IV administration across many disease areas (De Cock 2016;
Gardulf 2007; Tetteh 2014; Usmani 2021). Although the pharmacokinetic (PK)profiles of SC and
IV routes of administrations differ, SC administration has proven effective, safe, well-tolerated,
and is generally preferred by patients and healthcare providers due to the greater flexibility and
ease of administration for patients or their caregivers in their preferred setting (Gardulf 2007;
Usmani 2021). 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 and time-consuming IV infusions.
Considering the GALAXI 1 results and the potential benefits of SC induction dosing to patients
and healthcare systems, the aim  of this study is to evaluate the efficacy, safety, and
PK/pharmacodynamics (PD) profile of guselkumab SC induction compared with placebo in
participants with moderately to severely active Crohn’s disease.
2.2. 
Background
Nonclinical Studies
For the most current information on nonclinical development, refer to the guselkumab IB.

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Clinical Studies
The clinical development program for guselkumab includes studies in adult participants with
psoriasis, psoriatic arthritis, palmoplantar pustulosis, rheumatoid arthritis, Crohn’s disease,
ulcerative colitis, familial adenomatous polyposis, hidradenitis suppurativa, lupus nephritis, and
giant cell arteritis, as well as healthy participants. For a full list of completed and ongoing clinical
studies, refer to the guselkumab IB.
Overall, through July 2021 (the data cutoff date for the guselkumab IB edition 12), an estimated
7,827 participants have been exposed to guselkumab across all indications in the clinical
development program. As of July 2021, an estimated 703 healthy participants, 4,068 participants
with psoriasis, 109 participants with rheumatoid arthritis, 1,509 participants with psoriatic
arthritis, 182 participants with palmoplantar pustulosis, 472 participants with Crohn’s disease,
175 participants with hidradenitis suppurativa, 540 participants with ulcerative colitis,
51 participants with familial adenomatous polyposis, 2 participants with giant cell arteritis,
7 participants with lupus nephritis, and 9 participants with systemic sclerosis have been exposed
to guselkumab.
The overall clinical development program of guselkumab in participants with moderately to
severely active Crohn’s disease consists of the GALAXI program (CNTO1959CRD3001) and the
CNTO1959CRD3004 SC induction study. The ongoing clinical program for guselkumab in
Crohn’s disease (CNTO1959CRD3001; GALAXI) is designed to evaluate the safety and efficacy
of guselkumab compared with placebo and an active control (ustekinumab) in participants with
moderately to severely active Crohn’s disease, who have demonstrated an inadequate response or
failure to tolerate previous conventional therapy or biologic therapy. The GALAXI program
consists of 3 separate studies being conducted under a single protocol. GALAXI 1 was a 48-week
Phase 2 dose-ranging study of the efficacy of guselkumab IV induction with doses of 
 IV administered at Weeks 0, 4, and 8. GALAXI 2 and GALAXI 3 studies are
2 identical 48-week Phase 3 confirmatory studies. Participants who complete the 48-week Phase 2
or Phase 3 studies may be eligible to enter the long-term extension.
2.3. 
Benefit-risk Assessment
More detailed information about the known and expected benefits and risks of guselkumab may
be found in the IB.
2.3.1. 
Risks for Study Participation
Potential Risks of Clinical
Significance
Summary of Data/
Rationale for Risk  
Mitigation Strategy
Clinical worsening of Crohn’s
disease
The benefit-risk of guselkumab for
the treatment of moderately to
severely active Crohn’s disease has
not been established.
During the study, participants
will be permitted to continue
treatment of Crohn’s disease
with certain concomitant
medications (Section 6.8).
Participants will discontinue
study intervention if it is not in
their best interest or if they
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Potential Risks of Clinical
Significance
Summary of Data/
Rationale for Risk  
Mitigation Strategy
need to initiate
protocol-prohibited
medications including certain
biologics (Sections 6.8 and
7.1).
Participants in the placebo
group who meet at least 1 of
the 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 of guselkumab,
including respiratory infections,
herpes simplex and tinea infections
and gastroenteritis.
Participants with a history of,
or ongoing, chronic or recurrent
infectious disease, including
HIV, HBV or HCV, will be
excluded from the study.
Similarly, participants with
evidence of active or untreated
latent TB will be excluded from
the study (Sections 5.1 and
5.2).
Participants who have received
a live viral or bacterial
vaccination within 4 weeks
prior to screening 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 8.2.9 and
8.2.10).
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

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Potential Risks of Clinical
Significance
Summary of Data/
Rationale for Risk  
Mitigation Strategy
intervention should be withheld
until the clinical assessment is
complete (Sections 7.1 and
8.2.9).
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
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 8.2.8).
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

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Potential Risks of Clinical
Significance
Summary of Data/
Rationale for Risk  
Mitigation Strategy
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 
 IV
at Weeks 0, 4, and 8, and 
SC at Week 12. This event may
represent drug-induced liver injury
(DILI) possibly related to
guselkumab (see Section 5.13.3 in
the IB).
Transaminase increases have been
identified as an adverse reaction of
guselkumab. In 2 Phase 3 psoriatic
arthritis studies, increased ALT
and/or AST was observed more
frequently in patients treated with
guselkumab
compared to patients treated with
guselkumab
or
placebo.
During the conduct of the
study, liver function tests will
be monitored at regular
intervals in accordance with
regulatory guidance
(FDA 2009). In addition, the
induction doses evaluated in
this clinical program will not
exceed 
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 9, Section 10.9). A
participant must have their
study intervention discontinued
if the participant has severe
liver test abnormalities that are
not transient and are not
explained by other etiologies
(Section 7.1).
Immunosuppression  
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 ≤40 mg
prednisone or its equivalent per
day, or 9 mg/day of
budesonide, or 5 mg/day
beclomethasone, which must be
tapered 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
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Potential Risks of Clinical
Significance
Summary of Data/
Rationale for Risk  
Mitigation Strategy
least 4 weeks before the
baseline visit. Additionally,
participants are also excluded
from the study if they have
received cyclosporine,
mycophenolate mofetil,
tacrolimus, sirolimus,
ustekinumab, or anti-TNFα
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, TNFα antagonists,
vedolizumab) is prohibited.
Participants initiating these
treatments will be discontinued
from further study intervention
administration (see Section 6.8
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 rare (Arora 2009; 
Rabeneck 2008). 
Trained and experienced
endoscopists will be performing the
procedure during this study.
Abbreviations: 6-MP=6-mercaptopurine; ALT=alanine transaminase; AST=aspartate transaminase;
AZA=azathioprine; DILI=drug induced liver injury; FDA=Food and Drug Administration; HBV=hepatitis B
virus; HCV=hepatitis C virus; HIV=human immunodeficiency virus; IB=Investigator’s Brochure; IL=interleukin;
IV=intravenously; MTX=methotrexate; q4w= every 4 weeks; q8w=every 8 weeks; SAE=serious adverse event;
SC=subcutaneously; TB=tuberculosis; TNF=tumor necrosis factor alpha
2.3.2. 
Benefits for Study Participation
Available animal and human data support the critical role of IL-23 in the pathogenesis of Crohn’s
disease. Studies with other anti-IL-23 monoclonal antibodies suggest that selective targeting of
IL-23 may achieve higher levels of efficacy than that observed with other mechanisms of action
in patients with moderately to severely active Crohn’s disease. Participants in the study will help
in furthering development of this drug to treat Crohn’s disease. The knowledge gained from this
study has the potential to benefit patients suffering with Crohn’s disease, and thus offers potential
public health benefits.

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2.3.3. 
Benefit-risk Assessment for Study Participation
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 established a favorable benefit-risk profile for guselkumab in the treatment of
plaque psoriasis and regulatory approval for the plaque psoriasis indication. This clinical
experience provided support for the ongoing development of guselkumab in other inflammatory
diseases such as psoriatic arthritis, generalized pustular psoriasis, erythrodermic psoriasis,
palmoplantar pustulosis, and ulcerative colitis.
Available animal and human data support the critical role of IL-23 in the pathogenesis of Crohn’s
disease, and studies with other anti-IL-23 monoclonal antibodies suggest that selective targeting
of IL-23 may achieve higher levels of efficacy than that observed with other mechanisms of action,
in patients with moderately to severely active 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 trials across investigational and approved indications.
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 nonclinical and clinical evidence for the critical role of IL-23 in the
pathogenesis of Crohn’s disease, the benefit-risk profile of guselkumab established to date in
psoriasis and other immune-mediated diseases, and the GALAXI 1 results provide a strong
scientific and clinical rationale for pursuing development of guselkumab in patients with
moderately to severely active Crohn’s disease and for the investigation of guselkumab in this
study. Taking into account the measures taken to minimize risk to participants of this study, the
potential risks identified in association with guselkumab are justified by the anticipated benefits
that may be afforded to participants with moderately to severely active Crohn’s disease.
3. 
OBJECTIVES AND ENDPOINTS
The objectives of this study are to assess the effects of guselkumab SC in moderately to severely
active Crohn’s disease.
The endpoints at Week 12 will be based on comparisons of the combined guselkumab induction
dose group (who received guselkumab
 at Weeks 0, 4, and 8) with the placebo group.
Endpoints after Week 12 will be based on comparisons of each guselkumab group (guselkumab
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 at Weeks 0, 4, and 8, followed by guselkumab
 every 4 weeks [q4w] in one
group and
 every 8 weeks [q8w] in the other group) with the placebo group. For more
details on the treatment groups, see Section 4.1.
Objectives 
Endpoints
Primary
To evaluate the efficacy, including clinical 
remission and endoscopic response, of 
guselkumab SC induction
Clinical remission (CDAI score <150) at
Week 12
Endoscopic response (≥50% improvement
from baseline in the SES-CD score) at
Week 12
Secondary
To evaluate the efficacy of guselkumab SC 
across a range of outcome measures
Clinical remission at Week 24
PRO-2 remission (an AP mean daily score ≤1
and SF mean daily score ≤3 and no worsening
of AP or SF from baseline)at Week 12
Clinical response (decrease from baseline in
CDAI ≥100 points or clinical remission) at
Week 12
To evaluate the safety of guselkumab SC  
Summary of AEs, such as SAEs and AEs
leading 
to 
discontinuation 
of 
study
intervention
Tertiary (analyses at applicable time points through Week 24, Week 48, and Week 96)
To evaluate the efficacy of guselkumab SC 
across a range of outcome measures
Clinical remission
PRO-2 remission
Clinical response
Corticosteroid-free clinical remission
Change in CDAI score from baseline
AP and SF score, and change in AP and SF
score from baseline
Change in SES-CD score from baseline
Endoscopic response
Endoscopic remission
Endoscopic healing
Change in histologic assessments from
baseline
To evaluate the impact of guselkumab SC on 
biomarkers 
Change in CRP and fecal calprotectin from
baseline
Clinical-biomarker response
To evaluate the PK and immunogenicity of 
guselkumab SC
Serum concentrations of guselkumab
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Objectives 
Endpoints
Incidence and titers of antibodies to
guselkumab
To evaluate the impact of guselkumab SC on
PROs
Endpoints based on  IBDQ, PROMIS-29,
AP-NRS, and BSFS
Abbreviations: AE=adverse event; AP=abdominal pain; AP-NRS=Abdominal Pain-Numerical Rating Scale;
BSFS=Bristol Stool Form Scale; CDAI=Crohn’s Disease Activity Index; CRP=C-reactive protein;
IBDQ=Inflammatory Bowel Disease Questionnaire; PK=pharmacokinetic(s); PRO=Patient-reported Outcome;
PROMIS=Patient-reported Outcomes Measurement Information System; SAE=serious adverse event;
SC=subcutaneous; SES-CD=Simple Endoscopic Score for Crohn’s Disease; SF=stool frequency
Refer to Section 8 for evaluations related to endpoints and Section 9 for further details on the
analyses of the endpoints. The tertiary endpoints include but are not limited to the endpoints
specified above. Analyses will be performed at applicable timepoints through Week 24, Week 48,
and Week 96 at the corresponding database locks (DBLs). Refer to the Statistical Analysis Plan
(SAP) for further details.
HYPOTHESIS
The co-primary hypotheses of this study are that guselkumab is superior to placebo in inducing
clinical remission at Week 12 and guselkumab is superior to placebo in inducing endoscopic
response at Week 12 among participants with moderately to severely active Crohn’s disease.
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 dosing. The target population is adult
participants with moderatelyto severely active Crohn’s disease (of at least 3 months duration) with
colitis, ileitis, or ileocolitis previously confirmed by radiography, histology, and/or endoscopy. To
be eligible for the study, participants must also have endoscopic evidence of active Crohn’s
disease, and have demonstrated an inadequate response or failure to tolerate previous conventional
therapy or biologic therapy.
The two groups based on prior therapies comprising the target population are briefly described
below. Detailed eligibility criteria for prior exposure to conventional therapy or biologic therapy
are described in Section 5.1 and Section 10 (Appendix 2 [Section 10.2] and Appendix 3
[Section 10.3]).
Conventional therapy failure or intolerance (CON-Failure)
Participants must have demonstrated an inadequate response to, or have failed to tolerate,
at least 1 of the following conventional Crohn’s disease therapies: oral corticosteroids
(including prednisone, budesonide, and beclomethasone dipropionate) or the
immunomodulators azathioprine (AZA), 6-mercaptopurine (6-MP) or methotrexate
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Participants who have demonstrated corticosteroid dependence (ie, an inability to
successfully taper corticosteroids without a return of the symptoms of Crohn’s disease)
are also eligible.
Participants may either be naïve to biologic therapy (ie, infliximab, adalimumab,
certolizumab pegol, vedolizumab, or approved biosimilars for these agents) or may have
been exposed to biologic therapy and have not demonstrated inadequate response or
intolerance.
Biologic therapy failure or intolerance (BIO-Failure)
Participants must have demonstrated an inadequate response to, or have failed to tolerate,
at least 1 or more biologic therapies (ie, infliximab, adalimumab, certolizumab pegol,
vedolizumab, or approved biosimilars for these agents) at a dose that is, at minimum, a
locally approved dose for the treatment ofCrohn’s disease.
Inadequate response is defined as: primary nonresponse (ie, no initial response) or
secondary nonresponse (ie, response initially but subsequently lost response).
Participants with prior exposure to IL-12/23 or IL-23 agents are ineligible for this study.
A diagram of the study design is provided in Section 1.2. Study intervention will be administered
as presented in Figure 2 and Figure 3.
The target sample size is 318 participants. Participants who had an inadequate response or failure
to tolerate biologic therapy will comprise approximately 35% to 65% of the population. Eligible
participants will be randomly assigned in a 1:1:1 ratio to one of the following SC treatments:
106 participants to guselkumab 
at Weeks 0, 4, and 8 followed by guselkumab
 q4w through Week 24
106 participants to guselkumab 
 at Weeks 0, 4, and 8 followed by guselkumab
 q8w through Week 24
106 participants to placebo SC q4w from Week 0 through Week 24
The randomization will be stratified by baseline Crohn’s Disease Activity Index (CDAI) score
(≤300 or >300), baseline Simple Endoscopic Score for Crohn’s Disease (SES-CD) score (≤12 or
>12), and BIO-Failure status (Yes or No) at baseline (Week 0).
All participants in the placebo group who meet at least 1 of the rescue criteria at Weeks 12 and 16
will receive rescue treatment, ie, guselkumab 
 at Weeks 16, 20, and 24 followed by
guselkumab 
 q8w. To maintain the blind, participants randomized to guselkumab who
meet at least 1 of the rescue criteria will continue their assigned treatment regimen and receive
blinded sham rescue matching placebo SC injection. For more details, refer to Section 6.5.1. Each
active study intervention and its matching placebo will be identical in appearance (Figure 2).
At Week 24, all participants will enter the extension phase and receive the same treatment regimen
that they were receiving at Week 24.
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The study will be unblinded after the last participant completes the Week 48 evaluations and the
Week 48 DBL is completed. Upon study unblinding, placebo participants who have not been
rescued with guselkumab will be discontinued from study intervention and have a final efficacy
and safety (FES) visit. All other participants will continue on guselkumab treatment through
Week 248.
In general, participants who are receiving oral 5-aminosalicylic acid (5-ASA) compounds, oral
corticosteroids, conventional immunomodulators (AZA, 6-MP, or MTX), antibiotics, and/or
enteral nutrition for the treatment of Crohn’s disease at baseline should maintain a stable dose for
the specified period before baseline, as defined in the inclusion criteria (Section 5.1), and through
Week 48, with the exception of oral corticosteroids (Section  6.8.1). 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 6). This tapering is mandatory, unless not
medically feasible.
Participants who discontinue study intervention early should return for a study intervention
discontinuation (SID) visit. All randomized participants should complete the FES follow-up visit
approximately 12 weeks after the last dose of study intervention.
The overall study duration is up to 265 weeks. The study comprises ofthe following phases:
1. Screening phase: up to 5 weeks
2. Main treatment phase: 24 weeks
3. Extension treatment phase: 224 weeks
4. Post-treatment phase (FES follow-up visit): until approximately 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). Key efficacy assessments include CDAI, Patient-reported
Outcome (PRO)-2 (based on the unweighted CDAI components of the total number of liquid or
very soft stools and the AP score), endoscopic assessments of the intestinal mucosa based on SES-
CD, histologic assessments, inflammatory PD markers including C-reactive protein (CRP) and
fecal calprotectin, fistula assessment, PRO measures such as Inflammatory Bowel Disease
Questionnaire (IBDQ) and Patient-reported Outcomes Measurement Information System
(PROMIS)-29 and patient-reported symptom measures such Bristol Stool Form Scale (BSFS) and
Abdominal Pain-Numerical Rating Scale (AP-NRS).
A blood sample for pharmacogenomic research will be collected only  from participants who
consent to this component of the protocol (where local regulations permit; see SoA in Section 1.3).
Participation in pharmacogenomic research is optional. Deoxyribonucleic acid (DNA) samples
will be analyzed for identification of genetic factors that may be associated with clinical response.
Key safety assessments include adverse events (AEs), clinical laboratory tests (hematology and
chemistry), vital signs, physical examinations, screening electrocardiogram (ECG), monitoring for
hypersensitivity reactions, injection-site reactions, and early detection of active tuberculosis (TB).

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Database locks are planned for Week 24, Week 48, Week 96 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.
4.2. 
Scientific Rationale for Study Design
This SC induction study is intended to provide clinical evidence to support the 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 Crohn’s disease program
(GALAXI 2 and 3) designed to demonstrate the efficacy and safety of guselkumab IV induction,
and therefore, will enable cross-study comparison of guselkumab IV induction versus SC induction
treatment.
The study population is generally consistent with  the population in the ongoing guselkumab
Phase 3 GALAXI program, which evaluates participants with moderately to severely active
Crohn’s disease who demonstrated an inadequate response or failure to tolerate conventional or
biologic therapies. This population  reflects the high unmet need in Crohn’s disease as many
patients experience primary or secondary nonresponse to existing treatments.
With 
an 
estimated 
bioavailability 
of 
approximately 
50% 
for 
guselkumab SC
(TREMFYA® SmPC 2021; TREMFYA® USPI 2020), a 
 dose of guselkumab is
expected to result in systemic guselkumab exposure (area under the curve [AUC]) comparable
with that from a 
 the confirmatory
Phase 3 studies GALAXI 2 and 3 (see Section 4.3 for more details), and for the guselkumab Phase
3 Ulcerative Colitis program (QUASAR).
The optimal maintenance dose regimen is yet to be determined from the GALAXI Phase 3 studies;
therefore, after guselkumab SC induction, participants in this study will receive 1 of the
2 maintenance dose regimens of guselkumab (ie, 
 q8w or 
 q4w) also being
evaluated in the GALAXI studies.
Blinding, Control, Study Phase/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
 q8w (see Section 6.5.1).
In the maintenance study of the ustekinumab Phase 3 Crohn’s disease program (IM-UNITI), the
sponsor assessed the effect of a single dose adjustment of ustekinumab (an IL-12/23 antagonist)
in participants with Crohn’s disease. Participants were randomized to receive placebo,
ustekinumab 90 mg q12w, or ustekinumab 90 mg q8w (approved dose). In the ustekinumab 90 mg
q8w group, 28 participants met pre-specified loss of response criteria and received a sham dose
adjustment. After 16 weeks, 32.1% were in clinical remission and 46.4% were in clinical response
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16 weeks later (Sands 2016). These results demonstrate that some participants with inadequate/loss
of clinical response might benefit from continuing on the same dose regimen over time. Therefore,
the guselkumab groups in this study will not receive a dose adjustment, but will receive a blinded
sham rescue.
Randomization will be used to minimize bias in the assignment of participants to intervention
groups, to increase the likelihood that known and unknown participant attributes (eg, demographic
and baseline characteristics) are evenly balanced across intervention groups, and to enhance the
validity of statistical comparisons across intervention groups. In addition, to minimize imbalance
between intervention groups, randomization will be stratified by factors that influence prognosis
or treatment response (ie, stratified at baseline, by baseline CDAI score, SES-CD score, and
BIO-Failure status).
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 Crohn’s disease. The guselkumab dose
regimen after Week 8 in this study is identical to that in the ongoing guselkumab Phase 3 Crohn’s
studies (GALAXI 2 and 3). After Week 24, no differences in guselkumab concentrations and
exposures are expected between 
 induction (in this study) and 
 induction
(GALAXI) dose regimens (see Section 4.3 for more details). Consequently, this study is a 24-week
study with a 224-week extension. The extension will give participants who, in the opinion ofthe
investigator are benefiting from study intervention, access to treatment for approximately 5 years.
The follow-up phase (approximately 12 weeks after the last dose of study intervention) is designed
to assess the FES data as well as to collect samples for determination of PK and antibodies to
guselkumab, as specified in the SoA (Section 1.3).
Biomarker and DNA 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
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
ribonucleic acid (RNA) expression profiles. Ileocolonic 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 Crohn’s disease, and aid in evaluating the intervention-clinical response
relationship.
An optional pharmacogenomic substudy is planned. It is recognized that genetic variation can be
an important contributory factor to interindividual differences in intervention distribution and
response and can also serve as a marker for disease susceptibility and prognosis. The goal of the
pharmacogenomic component is to collect DNA to allow the identification of genetic factors that
may influence the PK, PD, efficacy, safety, or tolerability of guselkumab and to identify genetic
factors associated with Crohn’s disease or the response to guselkumab treatment. The focus of this
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analysis will be the evaluation of genetic single nucleic polymorphisms associated with Crohn’s
disease and response to treatment with guselkumab.
Biomarker and DNA samples 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, IBDQ, PROMIS-29) will be used to assess the benefits
of guselkumab treatment on disease-specific and general health-related quality of life (HRQOL).
Patient-reported outcome evaluations are only being collected in countries where translations of
the evaluations are available. See Section 8.1 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.
The primary ethical concern is that one third of the participants in this study with moderately to
severely active Crohn’s disease will receive placebo; however, these participants will have the
option to be rescued upon meeting the rescue criteria (see Section 6.5.1). 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 328 mL
over approximately 265 weeks) is far less than the American Red Cross standard limit for whole
blood donation (approximately 475 mL every 8 weeks) and is, therefore, considered to be an
acceptable amount of blood to be collected over this time period. For more details regarding blood
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4.3. 
Justification for Dose
This section provides the rationale for the guselkumab dose regimens that will be evaluated in this
study.
Participants will be randomly assigned in a 1:1:1 ratio to receive the following dose regimens:
Guselkumab 
 SC at Weeks 0, 4, and 8 followed by guselkumab
 q4w
Guselkumab
 SC at Weeks 0, 4, and 8 followed by guselkumab
 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 Crohn’s
disease (GALAXI 1). The GALAXI 1 Week 12 analyses demonstrated similar efficacy with
guselkumab induction doses of
 administered IV at Weeks 0, 4, and
8, respectively. There was no clear dose/exposure-response within the range of guselkumab IV
induction doses tested (Danese 2021; Sandborn 2020b). As a result, the
 IV induction dose
regimen was selected for confirmatory evaluation in the guselkumab Phase 3 studies (GALAXI 2
and 3).
With an estimated bioavailability of approximately 50% for guselkumab SC (TREMFYA® SmPC
2021; TREMFYA® USPI 2020), 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
(average steady-state serum study intervention concentration [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 Crohn’s disease.
Two guselkumab maintenance dose regimens 
 q4w and 
 q8w) will be
evaluated in this study. These are the same doses being evaluated in the ongoing Phase 3 GALAXI
studies. 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 GALAXI studies). Overall, the 2 guselkumab maintenance dose
regimens (ie, 
 q4w and
 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 Crohn’s disease.
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4.4. 
End of Study Definition
End of Study Definition
The study is considered completed when the last participant completes the last scheduled study
assessment shown in the SoA (Section 1.3) or if a decision has been made by the sponsor not to
pursue an indication in Crohn’s disease 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.
Study Completion Definition
A participant will be considered to have completed the main treatment phase if he or she has
completed assessments at Week 24 and completed the FES follow-up visit if applicable.
A participant will be considered to have completed the extension treatment phase if he or she has
completed assessments at Week 248 and completed the FES follow-up visit.
Participants who prematurely discontinue study intervention for any reason before completion of
the Week 24 visit can be considered to have completed the main treatment phase if they have
completed the FES follow-up visit assessments as indicated in the SoA (Section 1.3). Similarly,
participants who prematurely discontinue study intervention for any reason after Week 24 and
before completion of the Week 248 visit can be considered to have completed the extension
treatment phase if they have completed the FES follow-up visit assessments as indicated in the
SoA (Section 1.3).
5. 
STUDY POPULATION
Screening for eligible participants will be performed within 5 weeks before administration of the
study intervention. Refer to Section 5.4 for conditions under which the repeat of any screening
procedures are 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.
5.1. 
Inclusion Criteria
Each potential participant must satisfy all ofthe following criteria to be enrolled in the study:
1. 
Man or woman  (according to their reproductive organs and functions assigned by
chromosomal complement) of ≥18 years of age (or the legal age of consent in the
jurisdiction in which the study is taking place).

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2. 
Have Crohn’s disease or fistulizing Crohn’s disease of at least 3 months duration (defined
as a minimum of 12 weeks), with colitis, ileitis, or ileocolitis, confirmed at any time in
the past by radiography, histology, and/or endoscopy.
3. 
Have clinically active Crohn’s disease, defined as a baseline CDAI score ≥220 but ≤450
and either:
a. Mean daily SF count ≥4, based on the unweighted CDAI component of the
number of liquid or very soft stools
OR
b. Mean daily AP score ≥2, based on the unweighted CDAI component of AP
4. 
Have endoscopic evidence of active ileocolonic Crohn’s disease as assessed by central
endoscopy reading at the screening endoscopy (SoA [Section 1.3]) defined as a screening
SES-CD score ≥6 (or ≥4 for participants with isolated ileal disease), based on the presence
of ulceration in at least 1 of the 5 ileocolonic segments, resulting in the following specified
ulceration component scores:
a. A minimum score of 1 for the component of “size of ulcers”
AND
b. A minimum score of 1 for the component of “ulcerated surface”
5. 
A participant who has had extensive colitis for ≥8 years, or disease limited to a segment
of the colon for ≥10 years, must:
a. Have had a full colonoscopy to assess for the presence of dysplasia within 1 year
before the first dose of study intervention
OR
b. Have a full colonoscopy with biopsy surveillance for dysplasia as the baseline
endoscopy during the screening period. Results from these surveillance biopsies
must be negative for dysplasia (low-grade, high-grade, or “indefinite dysplasia
in reactive atypia”) prior to the first dose of study intervention
Concomitant or Previous Medical Therapies Received
6. 
Prior or current medication for Crohn’s disease must include at least 1 of the following,
and must fulfill additional criteria as described in Appendix 2 (Section 10.2) and
Appendix 3 (Section 10.3)as applicable:
a. Current treatment with oral corticosteroids (including budesonide and
beclomethasone dipropionate) and/or immunomodulators (AZA, 6-MP, MTX)
OR
b. History of failure to respond to, or tolerate, at least 1 of the following therapies:
oral corticosteroids (including budesonide and beclomethasone dipropionate) or
immunomodulators (AZA, 6-MP, MTX)

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OR
c. History of corticosteroid dependence (ie, an inability to successfully taper
corticosteroids without a return of the symptoms of Crohn’s disease)
OR
d. Has previously demonstrated lack of initial response (ie, primary
nonresponders), responded initially but then lost response with continued
therapy (ie, secondary nonresponders), or were intolerant to 1 or more biologic
agents at a dose that is, at minimum, a locally approved dose for the treatment
of Crohn's disease (ie, infliximab, adalimumab, certolizumab pegol,
vedolizumab, or approved biosimilars for these agents)
Note: Participants meeting criteria 6a-c may either be naïve to biologic therapy (ie,
infliximab, adalimumab, certolizumab pegol, vedolizumab, or approved biosimilars for
these agents) or may have been exposed to these biologic therapies and did not
demonstrate an inadequate response or intolerance.
7. 
Adhere to all of the following requirements for concomitant medication for the treatment
of Crohn’s disease. The following medications are permitted provided that doses meeting
the requirements listed below are stable or have been discontinued prior to baseline within
the timeframes specified below:
a. Oral 5-ASA compounds on stable doses for at least 2 weeks; or if recently
discontinued, must have been stopped for at least 2 weeks.
b. Oral corticosteroids at a prednisone-equivalent dose at or below 40 mg/day, or
9 mg/day of budesonide, or 5 mg/day beclomethasone dipropionate, and on
stable dosing for at least 2 weeks; or if recently discontinued, must have been
stopped for at least 2 weeks.
c. Conventional immunomodulators (ie, AZA, 6-MP, or MTX) for at least
12 weeks and have been on a stable dose for at least 4 weeks; or if recently
discontinued, must have been stopped for at least 4 weeks.
d. If receiving antibiotics as a primary treatment of Crohn’s disease, doses must be
stable for at least 3 weeks; or if recently discontinued, must have been stopped
for at least 3 weeks.
e. If receiving enteral nutrition as a primary treatment for Crohn’s disease, must
have been receiving for at least 2 weeks; or if recently discontinued, must have
been stopped for at least 2 weeks.
Screening Laboratory Tests
8. 
Have screening laboratory test results within 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 5-week screening period:
a. Hemoglobin ≥8.0 g/dL

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b. White blood cells (WBCs) ≥3.0 x 103/μL
c. Neutrophils ≥1.5 x 103/μL
d. Platelets ≥100 x 103/μL
e. Serum creatinine ≤1.5 mg/dL
f. Alanine transaminase (ALT) (or aspartate transaminase [AST])≤2 x upper limit
of normal (ULN)
g. Total bilirubin  (TBili) ≤1.5 x ULN (Isolated total bilirubin >1.5 x ULN is
allowed for those participants with known Gilbert’s syndrome. Gilbert’s
syndrome is suggested by direct bilirubin <30% [Palmer 2020].)
Tuberculosis
9. 
A potential participant is considered eligible if the participant meets all of the following
TB screening criteria:
Note: Interferon gamma release assay (IGRA) testing includes either QuantiFERON-TB®
or T-SPOT®.TB.
a. Have no history of active TB or show signs or symptoms suggestive of active
TB upon medical history and/or physical examination at screening.
b. Have no history of latent TB prior to screening. An exception is made for
participants who have a history of latent TB AND who satisfy one of the
following criteria:
1) Currently receiving treatment for latent TB
OR
2) Will initiate treatment for latent TB prior to the first administration of
study intervention
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. Have had no recent close contact with a person with active TB. If there has been
contact, 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. Have a negative IGRA test result within 2 months prior to the first administration
of study intervention, or who:
o Have a history of adequately treated latent TB described above.

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o Have a 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 administration of study intervention.
o Have a 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 administration 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.
Note: Indeterminate/borderline results should be handled as outlined in
Section 8.2.10.
e. Have a chest radiograph (both posterior-anterior and lateral views, or per
local/country regulations where applicable), or chest computed tomography
(CT) within 3 months prior to the first administration of study intervention that
shows no abnormalities suggestive of active or inactive TB.
Contraception
10. 
A woman of childbearing potential must have a negative serum pregnancy test result at
screening.
11. 
Before randomization, a woman must be (as defined in Appendix 7 [Section 10.7])
a. Not of childbearing potential (refer to Section 10.7 for instances when a
screening follicle stimulating hormone (FSH)test should be considered)
OR
b. Of childbearing potential and
o 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 –the end of relevant
systemic exposure. Note: The method selected must meet local/regional
regulations/guidelines for highly effective contraception.
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.

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12. 
A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted
reproduction during the study and for a period of 12 weeks after the last administration of
study intervention.
13. 
During the study and for at least 12 weeks after the last administration of study
intervention, a male participant:
a. Who is sexually active with a female of childbearing potential must agree to use
a barrier method of contraception (ie, condom with spermicidal
foam/gel/film/cream/suppository or female condom/occlusive cap [diaphragm
or cervical/vault caps] with spermicidal foal/gel/film/cream/suppository)
b. Who is sexually active with a pregnant female must use a condom
c. Must agree not to donate sperm for the purpose of reproduction
General
14. 
Each participant must sign an informed consent form (ICF) indicating that he or she
understands the purpose of, and procedures required for, the study and is willing to
participate in the study.
Note: In regions where the legal age of consent is older than 18 years, informed consent
must be obtained from and signed by both the participant and his or her legally acceptable
representative.
15. 
Must sign a separate ICF  if he or she agrees to provide an optional DNA sample for
research (where local regulations permit). Refusal to give consent for the optional DNA
research sample does not exclude a participant from participation in the study.
Note: In regions where the legal age of consent is older than 18 years, informed consent
must be obtained from and signed by both the participant and his or her legally acceptable
representative.
16. 
Be willing and able to adhere to all specified requirements, including but not limited to
completion of assessments, adherence to visit schedule, and compliance with the lifestyle
restrictions.

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5.2. 
Exclusion Criteria
Any potential participant who meets any of the following criteria will be excluded from
participating in the study:
1. 
Has complications of Crohn’s disease, such as symptomatic strictures or stenoses, short
gut syndrome, or any other manifestation, that might be anticipated to require surgery,
could preclude the use of the CDAI to assess response to therapy, or would possibly
confound the ability to assess the effect of treatment with guselkumab.
2. 
Currently has or is suspected to have an abscess. Recent cutaneous and perianal
abscesses are not exclusionary if drained and adequately treated at least 3 weeks before
baseline, or 8 weeks before baseline for intra-abdominal abscesses, provided that there
is no anticipated need for any further surgery. Participants with active fistulas may be
included if there is no anticipation of a need for surgery and no abscesses are currently
identified.
3. 
Has had any kind of bowel resection within 24 weeks, or any other intra-abdominal or
other major surgery within 12 weeks, before first dose of study intervention.
4. 
Has a draining (ie, functioning) stoma or ostomy.
5. 
Presence on screening endoscopy of adenomatous colonic polyps, if not removed before
study entry, or history of adenomatous colonic polyps that were not removed.
6. 
Has a stool culture or other examination positive for an enteric pathogen, including
Clostridioides difficile (formerly known as Clostridium difficile) toxin, within 4 months
before the first dose of study intervention, unless a repeat examination is negative and
there are no signs of ongoing infection with that pathogen.
Note: Treatment and repeat testing can occur in the current screening period.
Concomitant or Previous Medical Therapies Received
7. 
Has received any of the following prescribed medications or therapies within the
specified period:
a. IV corticosteroids received within 3 weeks of baseline
b. Cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil received
within 8 weeks of baseline
c. 6-thioguanine received within 4 weeks of baseline
d. Biologic agents:
1) Anti-TNFα therapy (eg, infliximab, etanercept, certolizumab pegol,
adalimumab, golimumab) received within 8 weeks of baseline
2) Vedolizumab received within 12 weeks of baseline

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3) Other immunomodulatory biologic agents, including approved and
investigational biologic agents, received within 12 weeks of baseline or
within 5 half-lives of baseline, whichever is longer
e. Any investigational intervention received within 4 weeks of baseline or within
5 half-lives of baseline, whichever is longer. (Refer to exclusion criterion 7.d.3
for investigational biologic agents).
f. Non-autologous stem cell therapy (eg, Prochymal), natalizumab, efalizumab,
or biologic agents that deplete B- or T-cells (eg, rituximab, alemtuzumab, or
visilizumab) received within 12 months of baseline.
g. Treatment with apheresis (eg, Adacolumn apheresis) or total parenteral
nutrition for Crohn’s disease within 3 weeks of baseline.
8. 
Has previously received a biologic agent targeting IL-12/23 or IL-23, including but not
limited to ustekinumab, briakinumab, brazikumab, guselkumab, mirikizumab, and
risankizumab.
Infections or Predisposition to Infections:
9. 
Has a 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.
10. 
Has a history of, or ongoing, chronic or recurrent infectious disease, including but not
limited to, sinopulmonary infections, bronchiectasis, recurrent renal/urinary tract
infections (eg, pyelonephritis, cystitis), an open, draining, or infected skin wound, or an
ulcer.
11. 
Chest radiograph must be obtained within 12 weeks before the first dose of study
intervention. Results that shows an abnormality suggestive of an undiagnosed
pulmonary pathology including but not limited to a malignancy, a previously
unrecognized pulmonary pathology, as well as active or latent infections from TB,
histoplasmosis, or coccidiomycosis would be exclusionary. A chest CT scan obtained
outside of the protocol instead of a chest radiograph is also acceptable. Refer to
inclusion criteria 9 for information regarding eligibility with a history of latent TB.
12. 
History of human immunodeficiency virus (HIV) antibody positive, or tests positive for
HIV at screening.
13. 
Is seropositive for antibodies to hepatitis C virus (HCV), unless they satisfy one of the
following conditions:
a. Has a history of successful treatment, defined as being negative for HCV RNA
at least 12 weeks after completing antiviral treatment, and has a negative HCV
RNA test result at screening,
OR

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b. While seropositive has a negative HCV RNA test result at least 12 weeks prior
to screening and a negative HCV RNA test result at screening.
14. 
Tests positive for hepatitis B virus (HBV) infection (Appendix 4 [Section 10.4]).
Note: For participants who are not eligible for this study due to HIV, HCV, or HBV test
results, consultation with a physician with expertise in the treatment of those infections
is recommended.
15. 
Bacille Calmette-Guérin (BCG) vaccination  within 12 months or any other live
bacterial or live viral vaccination within 4 weeks prior to screening, or plans to receive
such vaccines during the study.
16. 
Has or has had a nontuberculous mycobacterial infection or clinically significant
opportunistic infection (eg, cytomegalovirus colitis, pneumocystosis, invasive
aspergillosis).
17. 
Has had a clinically significant infection (ie, hepatitis, sepsis, pneumonia, or
pyelonephritis), has been hospitalized for an infection, or has been treated 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 (ie, acute upper respiratory tract
infection, uncomplicated urinary tract infection).
18. 
Has current signs or symptoms of a clinically significant infection. Ongoing infections
not considered clinically significant at the discretion of the investigator need not be
exclusionary (ie, acute upper respiratory tract infection, uncomplicated urinary tract
infection).
19. 
Has evidence of a herpes zoster infection within 8 weeks before the first dose of study
intervention.
20. 
During the 6 weeks prior to baseline, have had ANY of (a) confirmed severe acute
respiratory syndrome coronavirus-2 (SARS-CoV-2) (Coronavirus Disease 2019
[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 from 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

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b. With 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: for those who may carry a higher risk for severe COVID-19 illness,
follow guidance from local health authorities when weighing the potential benefits
and risks of enrolling in the study, and during participation in the study.
Malignancy or Increased Potential for Malignancy:
21. 
Currently has a malignancy or has a history of malignancy within 5 years before
screening (with the exception of a nonmelanoma skin cancer that has been adequately
treated with no evidence of recurrence for at least 3 months [defined as a minimum of
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 3 months before the first
dose of study intervention).
22. 
Has a known 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
23. 
Has a history of severe, progressive, or uncontrolled renal, genitourinary, hematologic,
endocrine, cardiac, vascular, pulmonary, rheumatologic, neurologic, psychiatric, or
metabolic disturbances, or signs and symptoms thereof.
24. 
Has a transplanted organ (with exception of a corneal transplant >12 weeks before
screening).
25. 
Poor tolerability of venipuncture or lacks adequate venous access for required blood
sample collections during the study period.
26. 
History of drug or alcohol abuse according to Diagnostic and Statistical Manual of
Disorders (5th edition) criteria within 1 year before screening.
27. 
Has unstable suicidal ideation or suicidal behavior in the last 6 months that may be
defined as a Columbia-Suicide Severity Rating Scale (C-SSRS) rating at screening of:
suicidal ideation with intention to act (“Ideation level 4”), suicidal ideation with specific
plan and intent (“Ideation level 5”), or suicidal behavior (actual suicide attempt,

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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. In addition, participants with C-SSRS
ratings of wish to be dead (“Ideation level 1”), non-specific active suicidal thoughts
(“Ideation level 2”), active suicidal ideation with any methods (not plan) without intent
to act (“Ideation level 3”) or non-suicidal self-injurious behavior who are determined to
be at risk by the investigator may not be randomized.
28. 
Has known allergy, hypersensitivity, or intolerance to guselkumab or its excipients
(refer to the guselkumab IB).
29. 
Is a woman who is pregnant, or breastfeeding, or planning to become pregnant while
enrolled in this study or within 12 weeks after the last dose of study intervention.
30. 
Is a man who plans to father a child while enrolled in this study or within 12 weeks after
the last dose of study intervention.
General
31. 
Currently participating or intends to participate in any other study using an
investigational agent or procedure during the conduct of this study.
32. 
Has 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.
33. 
Is an employee of the investigator or study site, with direct involvement in the proposed
study or other studies under the direction of that investigator or study site, as well as
family members of the employees or the investigator.
Note: Investigators should ensure that all study enrollment criteria have been met at screening. If
a participant’s clinical status changes (including any available laboratory results or receipt of
additional medical records) after screening but before the first dose of study intervention is given
such that he or she no longer meets all eligibility criteria, then the participant should be excluded
from participation in the study. Section 5.4 describes options for retesting. The required source
documentation to support meeting the enrollment criteria are noted in Appendix 5 (Section 10.5).

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5.3. 
Lifestyle Considerations
Potential participants must be willing and able to adhere to the following lifestyle restrictions
during the course of the study to be eligible for participation:
1. 
Refer to Section 6.8 for details regarding prohibited and restricted therapy during the
study.
It is recommended that participants are up-to-date on appropriate vaccinations prior to
screening per routine local medical guidelines. For study participants who received
locally-approved (including emergency use-authorized) COVID-19 vaccines recently
prior to study entry, consider study eligibility and follow applicable local vaccine
labelling, guidelines, and standards of care for patients receiving immune-targeted
therapy when determining an appropriate interval between vaccination and study
enrollment (see also Section 6.8.3).
2. 
Agree to follow all requirements that must be met during the study as noted in the
Inclusion and Exclusion Criteria (eg, contraceptive requirements).
3. 
Must not receive guselkumab outside of this protocol or participate in any other clinical
study with an investigational agent while in this study and must terminate study
participation if they do. A participant who intends to participate in any other clinical
study with an investigational agent should undergo a SID visit before he or she
terminates study participation.
4. 
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.
5. 
Must agree not to receive a BCG vaccination during the study and for 12 weeks after
receiving the last dose of study intervention.
6. 
Participants who require treatment for latent TB must complete the appropriate course
of TB therapy.
7. 
Must be willing and able to complete a daily diary to document clinical symptoms, AEs,
etc.
5.4. 
Screen Failures
Participant Identification, Enrollment, and Screening Logs
The investigator agrees to complete a participant identification and enrollment log to permit easy
identification of each participant during and after the study. This document will be reviewed by
the sponsor or designee study site contact for completeness.
The participant identification and enrollment log will be treated as confidential and will be filed
by the investigator in the study file. To ensure participant confidentiality, no copy will be made.

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All reports and communications relating to the study will identify participants by participant
identification and date of birth (as allowed by local regulations). In cases where the participant is
not randomized into the study, the date seen and date of birth (as allowed by local regulations)will
be used.
Completion of screening and randomization procedures within the specified screening window of
approximately 5 weeks is required.
If any delay leads to the expiration of time-specific assessments (eg, TB, chest radiograph, stool
analysis, ileocolonoscopy), the participant will be considered a screen failure because he/she will
not meet eligibility criteria, and the expired assessments (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 values that may lead to exclusion will be allowed once.
A second retest of an abnormal screening laboratory test may be allowed upon consultation with
and approval by the sponsor’s medical monitor. Retesting can occur at an unscheduled visit during
the screening phase, as long as this is done within the specified screening window of approximately
5 weeks.
Rescreening
Individuals who do not meet the criteria for participation in this study (screen failure) may be
rescreened once. A second retest of an abnormal screening laboratory test may be allowed (see
above).
Rescreened participants will be assigned a new participant number, undergo the informed consent
process, and then start a new screening phase including the collection and testing of new laboratory
specimens. Previous TB evaluation results (including an IGRA test and chest imaging) and stool
study results, and ileocolonoscopy 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. 
Criteriafor Temporarily Delaying Enrollment, Randomization or
Administration of Study Intervention
Not applicable.

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6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY
6.1. 
Study Intervention(s) Administered
Study intervention will be administered as presented in Figure 2 and Figure 3.
Description of Study Interventions
Intervention 
Name
Guselkumab 
Guselkumab 
Placebo
Dose 
Formulation 
Active guselkumab 
 in a 
single-dose PFS-Y 
Active guselkumab 
 in a single-dose 
PFS-U 
Matching placebo for each
dose and device
PFS-Y and 
 PFS-U)
Unit Dose 
Strength(s) 
 
 
Matching placebo for each
dose and device
Frequency  
q4w  
q8w  
Placebo will be administered
at the same frequency as the
active groups.
Route of 
Administration
 
 
SC
Storage 
Must be stored at controlled 
temperatures ranging from 
36°F to 46°F (2°C to 8°C) 
and protected from exposure 
to light. The sterile product 
does not contain 
preservatives and is designed 
for single use only. It should 
be clear to slightly yellow 
and may contain tiny white or 
clear particles. Do not use 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. Aseptic 
procedures must be used 
during the preparation and 
administration of the study 
intervention material. 
Must be stored at controlled 
temperatures ranging from 
36°F to 46°F (2°C to 8°C) 
and protected from exposure 
to light. The sterile product 
does not contain 
preservatives and is designed 
for single use only. It should 
be clear to slightly yellow 
and may contain tiny white or 
clear particles. Do not use 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. Aseptic 
procedures must be used 
during the preparation and 
administration of the study 
intervention material. 
Must be stored at controlled
temperatures ranging from
36°F to 46°F (2°C to 8°C)
and protected from exposure
to light. The sterile product
does not contain
preservatives and is designed
for single use only. It should
be clear to slightly yellow
and may contain tiny white or
clear particles. Do not use 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. Aseptic
procedures must be used
during the preparation and
administration of the study
intervention material.
Use 
Experimental 
Experimental 
Placebo comparator
IMP 
Yes 
Yes 
Yes
NIMP 
No 
No 
No
Abbreviations: IMP=Investigational Medicinal Product; NIMP=Non-investigational Medicinal Product;
PFS-U= prefilled syringe with an UltraSafe PlusTM Passive Needle Guard; PFS-Y=prefilled syringe with
YpsoMate autoinjector; q4w=every 4 weeks; q8w=every 8 weeks; SC=subcutaneous
CCI
CCI
C
CCI
CCI
C
CCI
CCI

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When multiple SC injections are administered at a visit, each injection of study intervention should
be given at a different location of the body.
Study intervention administration must be captured in the source documents and/or the electronic
case report form (eCRF). Study site personnel will instruct participants on how to store study
intervention for at-home use as indicated for this protocol.
Guselkumab and matching placebo will be manufactured and provided under the responsibility of
the sponsor. Refer to the guselkumab IB for a list of excipients.
Detailed instructions on the preparation and administration of study intervention will be provided
in the site Investigational Product Procedures Manual (IPPM) and the Instructions for Use (IFU).
For a definition of study intervention overdose, refer to Section 6.7.
Self-administration of Study Interventions (or Administration by Caregiver) at Home
Beginning at Week 36, at the discretion of the investigator and participant, and after appropriate
and documented training at Weeks 28 and 32, participants may self-administer study intervention
at the investigative site. A caregiver may also be trained to administer study intervention. The
self-administrations of study intervention on-site should be done in the presence of study site staff.
If needed, participants (or their caregivers)can be trained at later time points. Note that at Week 96
(or at the next visit if after Week 96), all participants continuing in the study who were not
previously trained should be trained to self-administer study intervention using the device (either
PFS-Y or PFS-U) based on their assigned treatment regimen, if allowed per local regulation. The
training with the correct device based on assigned treatment regimen must be documented prior to
starting at-home administration after Week 96.
Starting from Week 52 up to Week 92, participants may self-administer (or their caregivers may
administer) study intervention at home every 8 weeks, at the visits where only a single injection is
required, if allowed per local regulation.
Starting from Week 96 up to Week 244, participants may self-administer (or their caregivers may
administer) study intervention at home every 4 or 8 weeks based on their treatment assignment, if
allowed per local regulation. On-site visits are required every 16 weeks after Week 96 and at
Week 248 (the last dosing visit) for all participants allowed to self-administer at home. 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 every 4 or 8 weeks, based on
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Participants will receive instructions on compliance with study intervention when they begin
self-administration of study intervention. They will be given dosing instructions and instructions
for study intervention storage for at-home use. 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.
6.1.1. 
Combination Products
The sponsor-manufactured combination products provided for use in this study are the 
prefilled syringe (PFS) with YpsoMate Autoinjector (hereafter referred to as
The sponsor manufactures the
 The sponsor also assembles the
Picture-based instructions for use 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 products, these deficiencies
will be reported as Product Quality Complaints (PQC) (see Appendix 6 [Section 10.6]) and
appropriately managed by the sponsor.
6.2. 
Preparation/Handling/Storage/Accountability
Preparation/Storage
Guselkumab will be supplied as a 
 Matching placebo will be supplied as a 
respectively. All study intervention must be stored according
to the labeled storage condition, 2°C to 8°C (36°F to 46°F) 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 light yellow 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.
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

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Refer to the site IPPM and IFU for additional guidance on study intervention preparation, handling,
and storage of study intervention materials.
Handling/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 the empty
outer box/carton  must be available for verification by the sponsor’s or designee’s study site
monitor during on-site monitoring visits for study intervention accountability.
Potentially hazardous materials containing hazardous liquids, such as used needles, syringes and
vials, should be disposed of immediately in a safe manner and therefore will not be retained for
study 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 study site personnel, or by a hospital/clinic pharmacist. Study intervention will be
supplied only to participants participating in the study. Returned study intervention must not be
dispensed again, even  to the same participant. Study intervention may not be relabeled or
reassigned for use by other participants. The investigator agrees neither to dispense the study
intervention from, nor store it at, any site other than the study sites agreed upon with the sponsor.
For at-home administration if permitted by local regulation, participants will receive instructions
for study intervention 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 study medication diary.
Participants will be instructed to return the outer box/carton from the pre-filled
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
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6.3. 
Measures to Minimize Bias: Randomization and Blinding
Intervention Allocation
Procedures for Randomization and Stratification
Central randomization will be implemented in this study. At Week 0, participants will be randomly
assigned to 1 of 3 intervention  groups in a 1:1:1 ratio (see Section 4.1) 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 baseline CDAI score (≤300 or >300), baseline SES-CD score (≤12 or >12), and
BIO-Failure status (Yes or No) at baseline (Week 0). The interactive web response system (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 be
given the relevant participant details to uniquely identify the participant.
Blinding
To maintain the study blind, the study intervention container will have a label containing the study
name, study intervention number, 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.
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 (ie, 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.
The full sponsor unblinding will occur at the Week 48 DBL. However, at the Week 24 DBL, data
will be unblinded for analysis to a limited number of sponsor personnel only. Identification of
sponsor personnel who will have access to the unblinded participant-level data at the time of the
Week 24 DBL will be documented before unblinding. The method by which the study integrity
will be maintained will be described in the SAP.
Treatment assignment will remain  blinded to the study sites and participants until the last
participant completes the Week 48 evaluations, and the Week 48 DBL is completed. Upon study
unblinding, placebo participants who have not been rescued with guselkumab will be discontinued
from study intervention and have an FES follow-up visit. All other participants will continue on
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Under normal circumstances, the investigator blind should not be broken until the Week 48 DBL
is completed, unless specific emergency treatment/course of action would be dictated by knowing
the treatment status of the participant. In such case, the investigator may in an emergency
determine the identity of the intervention by contacting the IWRS. It is recommended that the
investigator contacts 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
(Section 1.3) for participants who discontinue study intervention.
6.4. 
Study Intervention Compliance
When study intervention is administered as an SC injection 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.
6.5. 
Dose Modification
6.5.1. 
Rescue Medication
All participants in the placebo group who meet at least 1 of the following rescue criteria will
receive rescue medication:
CDAI score >220 and <70-point reduction from baseline CDAI at both Week 12 and Week 16
OR
SES-CD score increase by at least 50% from baseline at Week 12
Upon meeting at least 1 of the rescue criteria, participants in the placebo group will receive
guselkumab 
 at Weeks 16, 20, and 24 followed by guselkumab
 q8w.
To maintain the blind, participants randomized to guselkumab who meet at least 1 of the rescue
criteria will continue their assigned treatment regimen and receive blinded sham rescue matching
placebo SC injection at Weeks 16, 20, and 24. Each active study intervention and its matching
CCI
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placebo are identical in appearance. Details regarding the analysis rules for placebo participants
receiving rescue medication will be included in the SAP.
6.6. 
Continued Access to Study Intervention After the End of the Study
Participants will be instructed that study intervention will not be made available to them after they
have completed/discontinued study intervention and that they should return to their primary
physician to determine standard of care.
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:
Contact the medical monitor immediately.
Closely monitor the participant for AEs/serious adverse events (SAEs) and laboratory
abnormalities.
Document the quantity of the excess dose in the eCRF.
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.
6.8. 
Concomitant Therapy
Prestudy 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 be recorded throughout the study, from signing of the informed
consent to the last study visit.
All therapies (prescription or over-the-counter medications, including vaccines, vitamins, herbal
supplements; non-pharmacologic therapies such as electrical stimulation, acupuncture) different
from the study intervention must be recorded in the eCRF. Recorded information will include a
description of the type of therapy, treatment period, dosage, route of administration, and indication.
Modification of an effective pre-existing therapy should not be made for the explicit purpose of
entering a participant into the study.
6.8.1. 
Concomitant Medications
Participants who are receiving oral 5-ASA compounds, oral corticosteroids, conventional
immunomodulators (AZA, 6-MP, or MTX), antibiotics, and/or enteral nutrition for the treatment
of Crohn’s disease at baseline should maintain a stable dose for the specified period before
baseline, as defined in the inclusion criteria (Section 5.1).

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Week 0 Through Week 48
In general, participants who are receiving these medications for Crohn’s disease at baseline
(ie, Week 0) should maintain a stable dose through Week 48, with the exception of oral
corticosteroids. Therapies can only be discontinued or reduced in dose after Week 0 if in the
judgement of the investigator it is required because of toxicity or other medical necessity; even if
the toxicity resolves, the therapy should not be restarted. Corticosteroids must be maintained at
baseline doses through Week 12, and all participants must begin tapering corticosteroids at
Week 12, unless medically not feasible (see further details in Section 6.8.1.1).
From Week 0 through Week 48, enrolled participants should not initiate any of the following
concomitant Crohn’s disease-specific medical therapies:
Oral or rectal 5-ASA compounds
Immunomodulators (ie, AZA, 6-MP, or MTX)
Oral, parenteral, or rectal corticosteroids, including budesonide and beclomethasone
dipropionate
Antibiotics as a primary treatment for Crohn’s disease
Total parenteral nutrition or enteral nutrition as a treatment for Crohn’s disease
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). Details regarding the
analysis rules for participants who initiate any of the above concomitant Crohn’s disease-specific
medical therapies will be included in the SAP.
Week 12 and Through Week 48
From Week 12 through Week 48, participants may transiently use (ie, for <4 weeks) increased
doses of corticosteroids for reasons other than treatment for Crohn’s disease (eg, stress doses of
corticosteroids for surgery, asthma, adrenocortical insufficiency).
After Week 48
Concomitant therapies for Crohn’s disease including 5-ASAs, corticosteroids, antibiotics, and
immunomodulators (ie, AZA, 6-MP, or MTX), and/or total parenteral or enteral nutrition may be
administered and changed at the discretion of the investigator.
6.8.1.1. 
Oral Corticosteroids Tapering
At Week 12, all participants who were taking corticosteroids at Week 0 must begin tapering
corticosteroids. This tapering is mandatory, unless not medically feasible, and should follow the
recommended schedule shown in Table 6. If participants experience worsening of their disease
activity while tapering corticosteroids, further dose decreases may be suspended, and/or their oral
corticosteroid dose may be temporarily increased if deemed necessary by the investigator. The oral
corticosteroid dose, however, may not be increased above the Week 0 dose unless due to medical

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necessity. 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).
Table 6: 
Recommended Tapering Schedule for Oral Corticosteroids
Recommended Tapering Schedule for Oral Corticosteroids (Other Than Budesonide)
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
Participants receiving budesonide should have their daily dose tapered by 3 mg every 3 weeks until
0 mg/day.
6.8.2. 
Prohibited Concomitant Medications
Participants who initiate the following treatments during study participation will have their study
intervention discontinued:
Immunomodulatory agents other than AZA, 6-MP, or MTX (including, but not limited to
6-thioguanine, cyclosporine, mycophenolate mofetil, tacrolimus, and sirolimus)
Immunomodulatory biologic agents (including, but not limited to, TNFα antagonists,
natalizumab, ustekinumab, rituximab, vedolizumab)
Experimental Crohn’s disease medications (including, but not limited to upadacitinib,
filgotinib, etrasimod, ozanimod, etrolizumab, brazikumab, mirikizumab, risankizumab, and
andecaliximab)
Thalidomide or related agents
The sponsor or designee must be notified in advance (or as soon as possible thereafter) of any
instances in which prohibited therapies are administered.
As protection of human research participants is paramount, it is recognized that initiating such
therapies may rarely be required due to medical necessity. However, initiation of these prohibited
medications should be documented as a deviation from the study protocol, and participants will be
discontinued from receiving further study intervention. Participants who discontinue study
intervention administration should complete a SID visit and an FES follow-up visit as described
in Section 1.3.
Note: 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 a SID visit as described in Section 1.3.

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6.8.3. 
Vaccinations (Including COVID-19)
When considering use of locally-approved (including emergency use-authorized) COVID-19
vaccines in study participants, consider protocol lifestyle considerations (Section 5.3) and follow
applicable local vaccine labeling, guidelines, and standards of care for patients receiving
immune-targeted therapy.
For study participants receiving a locally-approved (including emergency use-authorized)
COVID-19 vaccine, in order to help identify acute reactions potentially related to the COVID-19
vaccine, it is recommended that, where possible, vaccine and study intervention be administered
on different days, separated by as large an interval as is practical within the protocol.
Participants must not receive live viral, live bacterial, or BCG vaccinations during the study and
for 12 weeks after receiving the last dose of study intervention (Section 5.3).
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 must be discontinued if:
1. The participant initiates treatment with prohibited therapies for Crohn’s disease (Section 6.8).
2. The participant has a Crohn’s disease-related surgery that represents a lack of efficacy of study
intervention or that will preclude the future ability to assess efficacy using the CDAI or other
instruments required for demonstration of efficacy endpoints.
Note: Other permitted Crohn’s disease-related surgeries (eg, to resolve long-standing
complications such as strictures or for symptomatic nonhealing fistulas, in participants
experiencing improvement on study intervention) other than minor procedures (eg, placement
of a seton or cutaneous drainage of an abscess) should be postponed until after the FES
follow-up visit, unless necessary to ensure participant well-being and/or safety.
3. The participant becomes pregnant or plans a pregnancy within the study period
(Section 8.3.5).
4. The participant (or the participant’s representative) withdraws consent to receive study
intervention.
5. The participant develops a systemic opportunistic infection.
6. The participant meets ANY ofthe following TB-related conditions:
A diagnosis of active TB is made.

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A participant has symptoms suggestive of active TB based on follow-up assessment
questions and/or physical examination or has had recent close contact with a person with
active TB and cannot or will not continue to undergo additional evaluation.
A participant undergoing evaluation has a chest 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 
(see 
also 
Section 
8.2.10).
Indeterminate/borderline results should be handled as outlined in Section 8.2.10.
A participant receiving treatment for latent TB discontinues this treatment prematurely or
is noncompliant with the therapy.
7. The participant has a serious adverse reaction that is related to an injection, including an
injection-site reaction, 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 mmHg or blood pressure <90/60 mmHg.
8. The participant has a reaction resulting in myalgia and/or arthralgia with fever and/or rash
(suggestive of serum sickness and not representative of signs and symptoms of other
recognized clinical syndromes) occurring 1 to 14 days after an injection of study intervention.
These may be accompanied by other events including pruritus, facial, hand, or lip edema,
dysphagia, urticaria, sore throat, and/or headache.
9. The participant has a malignancy including squamous cell skin cancer. Consideration may be
given to allowing participants who develop ≤2 basal cell skin cancers that are adequately
treated with no evidence of residual disease to continue to receive study intervention.
10. 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 9 (Section 10.9).
11. 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.
Discontinuation of a participant’s study intervention must be strongly considered under
the following conditions:
12. Persistent inadequate response or worsening of Crohn’s disease:
a. The participant has a CDAI score >220 and <70-point reduction from baseline CDAI at
both Week 20 and Week 24.
OR
b. The participant experiences AEs consistent with clinically significant worsening of
Crohn’s disease at any time during the study.
These events must be evaluated by the investigator. A consultation with the study medical
monitor may also be considered, at the investigator’s discretion. Discontinuation of study
intervention must be considered in participants with clinically significant worsening of
Crohn’s disease where continuation of the study intervention is not in the best interest of the
participant.
13. The participant develops a serious infection, including but not limited to sepsis or pneumonia.

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14. The participant reports suicidal ideation with intention to act (“Ideation level 4”), suicidal
ideation with specific plan and intent (“Ideation level 5”), or any suicidal behavior (actual
suicide attempt, interrupted suicide attempt, aborted suicide attempt, or preparatory behaviors
for making a suicide attempt) on a post-baseline C-SSRS 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.
15. 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) should be obtained. If the reason
for discontinuation of study intervention is withdrawal of consent, every effort should be made to
conduct the SID visit assessments, as indicated in the SoA, prior to terminating 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.
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 (see Section 7.3)
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 eCRF and in the source document. Participants who terminate study
participation will not be required to return for any follow-up assessments; however, these
participants should complete the safety and efficacy evaluations specified in the SoA (Section 1.3)
at the time they terminate study participation. If the reason for withdrawal from the study is
withdrawal of consent, 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 as local regulations permit.
7.2.1. 
Withdrawal From the Use of Research Samples
A participant who withdraws from the study will have the following options regarding the optional
research samples:
The collected samples will be retained and used for research activities in accordance with the
participant’s original separate informed consent for optional research samples.

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The participant may withdraw consent for optional research samples, in which case the
samples will be destroyed and no further testing will take place. To initiate the sample
destruction process, the investigator must notify the sponsor study site contact of withdrawal
of consent for the optional research samples and to request sample destruction. The sponsor
study  site contact will, in turn, contact the biomarker representative to execute sample
destruction. If requested, the investigator will receive written confirmation from the sponsor
that the samples have been destroyed.
Withdrawal From the Optional Research Samples While Remaining in the Main Study
The participant may withdraw consent for optional research samples while remaining in the study.
In such a case, the optional research samples will be destroyed. The sample destruction process
will proceed as described above.
Withdrawal From the Use of Samples in Future Research
The participant may withdraw consent for use of samples for research (refer to Long-term
Retention of Samples for Additional Future Research in Appendix 5 [Section 10.5.5]). In such a
case, samples will be destroyed after they are no longer needed for the clinical study. Details of
the sample retention for research are presented in the main ICF and may be in the separate ICF for
optional research samples.
7.3. 
Lost to Follow-up
To reduce the chances of a participant being deemed lost to follow-up, prior to randomization
attempts should be made to obtain contact information from each participant, eg, home, work, and
mobile telephone numbers and email addresses for both the participant as well as appropriate
family members.
A participant will be considered lost to follow-up if he or she repeatedly fails to return for
scheduled visits and is unable to be contacted by the study site. A participant cannot be deemed
lost to follow-up until all reasonable efforts made by the study  site personnel to contact the
participant are deemed futile. The following actions must be taken if a participant fails to return to
the study site for a required study visit:
The study site personnel must attempt to contact the participant to reschedule the missed visit
as soon as possible, to counsel the participant on the importance of maintaining the assigned
visit schedule, to ascertain whether the participant wishes to or should continue in the study.
Before a participant is deemed lost to follow up, the investigator or designee must make every
reasonable effort to regain contact with the participant (where possible, 3 telephone calls,
e-mails, fax, and, if necessary, a certified letter to the participant’s last known mailing address,
or local equivalent methods). These contact attempts should be documented in the
participant’s medical records.
Should the participant continue to be unreachable, they will be considered to have withdrawn
from the study.

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8. 
STUDY ASSESSMENTS AND PROCEDURES
Overview
The SoA (Section 1.3) summarizes the frequency and timing ofscheduled 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
end of study, the visit window should be ±7 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 where 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
consultations to prevent influencing participant responses. Refer to the PRO completion guidelines
for instructions on the administration of PROs.
The C-SSRS 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 Phase
At the screening visit, written informed consent must be obtained from the participant for this
program by the principal investigator or designee before performing any protocol-specific
procedure. Procedures to be performed at the screening visit are outlined in the SoA (Section 1.3).
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 enrolled in the study. Every effort should be
made to adhere to the SoA (Section 1.3) for each participant. The collection of AEs will start at
the time informed consent is obtained.
The CDAI diary will be completed by participants during the screening period. The investigator
or appropriate site personnel will use the hematocrit value obtained during screening to calculate
the CDAI score at Week 0.

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A minimum of 7 days of CDAI data during the screening period is required to calculate the CDAI
score at baseline (Week 0).
Women of childbearing potential must have a negative serum pregnancy test result at screening.
Participants must be reminded that they are required to use a highly effective method of
contraception during the study (as described in Inclusion Criterion 11) and must continue taking
such precautions for 12  weeks after receiving the last administration of study intervention. The
method(s) of contraception used by each participant must be documented.
Participants must undergo testing for TB (Section 8.2.10) and their medical history assessment
must include specific questions about a history of TB or known occupational or other personal
exposure to individuals with active TB. The participant should be asked about past testing for TB,
including chest imagingresults and responses to tuberculin skin or other TB testing. A participant’s
eligibility according to TB screening criteria is described in Inclusion Criterion 9.
Blood Sample Collection
Blood samples should be collected at the visits indicated in the SoA (Section 1.3). The date and
time of collection will be recorded. When blood samples are to be collected for safety,
PK/immunogenicity, efficacy, biomarker, and pharmacogenomic evaluations at the same time
point, the order of blood draws will be samples for CRP, chemistry/lipids, hematology,
PK/immunogenicity, serum biomarkers, pharmacogenomics, and whole blood RNA.
The total blood volume to be collected from each participant will be approximately 328 mL over
approximately 265 weeks (Table 7). This total may vary due to:
Whether or not the participant consents to take part in the optional pharmacogenomics study
(6 mL).
Repeat or unscheduled samples taken for safety reasons or technical issues with the samples.
Regional or country-specific variation in blood collection systems.
Table 7: 
Volume of Blood to be Collected From Each Participant
Study Period or Type of Sample 
Approximate Total Volume of Blood (mL)
Screening through Week 248 
307.5
Final visit (FES) 
14.5
Pharmacogenomics samplea 
6
Approximate Total 
328
a. Sample to be collected only from participants who have consented to provide an optional pharmacogenomics (DNA)
sample for research.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the eCRF or laboratory
requisition form.
Refer to the SoA (Section 1.3)for the timing and frequency of all sample collections.

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Instructions for the collection, handling, storage, and shipment of samples are found in the
laboratory manual that will be provided. Collection, handling, storage, and shipment of samples
must be under the specified, and where applicable, controlled temperature conditions as indicated
in the laboratory manual.
Study-specific Materials
The investigator will be provided with the following supplies:
Investigator Site File (includes protocol and IB)
ICF
IFU
IPPM
IWRS manual
Study medication diary
Symptom and Health Diary cards
eCRF completion instructions
Central laboratory manual
Laboratory kits
Biopsy manual
Endoscopy kit
Imaging manual
Electronic patient-reported outcome equipment
Patient recruitment materials
8.1. 
Efficacy Assessments
Efficacy evaluations will include the following:
CDAI
PRO-2 (the unweighted CDAI components of the total number of liquid or very soft stools
and the AP score)
Endoscopic assessments of the intestinal mucosa based on the presence and absence of
mucosal ulcerations and the SES-CD
Histologic assessments
Inflammatory PD markers including CRP and fecal calprotectin
Fistula assessment
PRO measures to assess HRQOL outcomes including IBDQ and PROMIS-29

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Patient-reported symptom measures including BSFS and AP-NRS
The CDAI (Appendix 8 [Section 10.8]) will be assessed by collecting information on 8 different
Crohn’s disease-related variables (Best 1976): extraintestinal manifestations, abdominal mass,
weight, hematocrit, total number of liquid or very soft stools, AP/cramping, use of antidiarrheal
drug(s) and/or opiates, and general well-being. The last 4 variables are scored over 7 days by the
participant on a diary card that participants are to complete on a daily basis. The abdominal mass
is assessed through physical examination. The PRO-2 includes the unweighted CDAI components
of the total number of liquid or very soft stools and the AP score.
Endoscopic assessments of the intestinal mucosa will be evaluated during ileocolonoscopy in
all participants. A video ileocolonoscopic examination will be performed at the time points
specified in the SoA (Section 1.3). Video endoscopies will be assessed by a central facility that
will be blinded to treatment group and visit. A complete video endoscopic examination does not
require assessment of the terminal ileum if it cannot be visualized. The SES-CD score will be used
to evaluate Endoscopic Improvement (Daperno 2004). The SES-CD is based on the evaluation
of 4 endoscopic components (presence/size of ulcers, proportion of mucosal surface covered by
ulcers, proportion of mucosal surface affected by any other lesions, and presence/type of
narrowing/strictures) across 5 ileocolonic segments. Each endoscopic component is scored from 0
to 3 for each segment, resulting in a total score of up to 15 for each component, except for the
narrowing component which can only attain a maximum total score of 11 because by definition,
the presence of a narrowing that cannot be passed can be only observed once. In summary, an
overall total SES-CD score is derived from the sum of all the component scores and can range
from 0 to 56. Endoscopic healing, which is traditionally defined as the resolution (absence) of
mucosal ulcers in response to a therapeutic intervention, will also be assessed.
Histologic assessments will be performed using biopsy samples collected during ileocolonoscopy.
Biopsy samples will be collected at the time points specified in the SoA (Section 1.3) from the
predefined anatomic locations as described in the biopsy manual. The biopsy samples collected
post-baseline will be obtained near where the screening biopsy samples were collected, as
clinically feasible. Refer to the biopsy manual for details on the biopsy sample collection.
Histologic assessments will be conducted by a central reader who is blinded to treatment group,
participant number, and visit. Type of histology analyses will be specified in the SAP.
C-reactive protein has been demonstrated to be useful as a marker of inflammation in patients
with IBD. In Crohn’s disease, elevated CRP concentrations have been associated with severe
clinical activity, elevated sedimentation rate, and active disease as detected by colonoscopy
(Solem 2005). Blood samples for the measurement of CRP will be collected from all participants
at the time points specified in the SoA (Section 1.3). CRP will be evaluated using a validated,
high-sensitivity assay.
Fecal calprotectin has been demonstrated to be a sensitive and specific marker in identifying
intestinal inflammation and response to treatment in patients with IBD (Costa 2005). Stool samples
for fecal calprotectin concentration will be collected from all participants at the time points

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specified in the SoA (Section 1.3) through on-site or at-home collection. The assay for fecal
calprotectin concentration will be performed using a validated method.
Fistula assessment will be performed in all participants on an ongoing basis throughout the
duration of the study through physical examination. All participants will be assessed for fistulas at
baseline. For participants with fistulizing disease, fistula closure will be assessed during the study.
Enterocutaneous fistulas (eg, perianal and abdominal) will be considered no longer draining (ie,
closed) when there is absence of drainage despite gentle compression. Rectovaginal fistulas will
be considered closed based on either physical examination or absence of relevant symptoms (eg,
passage of rectal material or flatus from the vagina).
Patient-reported outcome measures will be evaluated at visits as indicated in the SoA
(Section 1.3):
The IBDQ is a validated, 32-item, self-reported questionnaire for participants with IBD to
assess disease-specific HRQOL by evaluating PROs across 4 dimensions: bowel symptoms
(loose stools, AP), systemic symptoms (fatigue, altered sleep pattern), social function (work
attendance, need to cancel social events), and emotional function (anger, depression,
irritability) (Irvine 1994). Scores range from 32 to 224, with higher scores indicating better
outcomes. Participants will complete the IBDQ on site.
The PROMIS-29 is a validated general health profile instrument that is not disease-specific.
It is a collection of short forms containing 4 items for each of 7 domains (depression, anxiety,
physical function, pain interference, fatigue, sleep disturbance, and ability to participate in
social roles and activities). PROMIS-29 also includes an overall average pain intensity 0-10
numeric rating scale. Participants will complete the PROMIS-29 forms on site.
Patient-reported symptom measures will be evaluated at visits as indicated in the Schedule of
Activities (Section 1.3):
The BSFS is a medical aid to classify the form (or consistency) of human feces into
7 categories (Lewis 1997). It has been used as a research tool to evaluate the effectiveness of
treatments for various diseases of the bowel (eg, irritable bowel syndrome). Participants will
complete the BSFS as a daily diary entry from Week 0 through Week 48.
The AP-NRS is an 11-point (0-10) scale that will be used to evaluate AP. The score of 0
represents “no AP” and the score of 10 represents the “worst possible AP” with greater scores
indicating greater pain severity and intensity. Participants will complete the AP-NRS as a
daily diary entry from Week 0 through Week 48, selecting only one number that best reflects
their pain at its worst.
The PRO instrument will be provided in the local language in accordance with local guidelines.
The PRO instrument must be available for regulators and for Institutional Review Board (IRB)/
Independent Ethics Committee (IEC)submissions.
The PRO and AE data will not be reconciled with one another.

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8.2. 
Safety Assessments
Safety assessments will include the monitoring of AEs, injection-site reactions, symptoms of a
hypersensitivity reaction, CD-related surgeries and procedures, and any signs or symptoms of
infection or TB. In addition, physical examinations, vital signs, ECGs, clinical safety laboratory
tests, and C-SSRS will be performed, as well as review of concomitant medication.
Adverse events will be reported and followed by the investigator as specified in Section 8.3 and
Appendix 6 (Section 10.6).
Any clinically relevant changes occurring during the study must be recorded in the AE section of
the eCRF.
Any clinically significant abnormalities persisting at the end of the study/early withdrawal will be
followed by the investigator until resolution or until a clinically stable condition is reached.
The study will include the following evaluations of safety and tolerability according to the time
points provided in the SoA (Section 1.3).
8.2.1. 
Physical Examinations
Physical examinations, including height and weight, will be performed as specified in the SoA
(Section 1.3). While assessment of the participants for safety and efficacy requires some physical
examination by an investigator at all visits, a more complete, detailed physical examination should
be performed at the screening visit for study eligibility assessment. Participants should be
instructed to remove shoes and outdoor apparel and gear prior to measurements for height and
weight.
8.2.2. 
Vital Signs
Temperature, pulse/heart rate, respiratory rate, and blood pressure will be assessed.
Blood pressure and pulse/heart rate measurements will be assessed with a completely automated
device. Manual techniques will be used only if an automated device is not available.
If feasible, blood pressure and pulse/heart rate measurements should be preceded by at least
5 minutes of rest in a quiet setting without distractions (eg, television, cell phones).
Vital signs must be obtained prior to and approximately 30 minutes after the SC injection.
8.2.3. 
Electrocardiogram
A 12-lead ECG will be performed 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.

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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.
The laboratory reports must be filed with the source documents.
The following tests will be performed by the central laboratory unless otherwise specified or
approved by the medical monitor.
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, alkaline phosphatase (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. For
participants who are eligible with hepatitis B surface antigen (HBsAg) negative, hepatitis B
core antibody (anti-HBc) and/or hepatitis B surface antibody (anti-HBs) positive, and HBV
DNA  test is negative, HBV DNA quantitation should be monitored according to local
guidelines. Additional details are provided in Appendix 4 (Section 10.4).
Abnormal liver function tests: If laboratory testing for a participant who is enrolled in the
study and receiving study intervention reveals an increase of serum aminotransferases (ALT
or AST) to ≥3 x ULN and an increase of bilirubin to ≥2 x ULN, 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 9 (Section 10.9) for
additional information on monitoring and assessment of abnormal liver function tests.
Pregnancy testing: Female participants of childbearing potential will undergo a serum
pregnancy test at screening. Urine pregnancy tests will be performed before each study
intervention administration on-site, at the SID visit, and at the FES follow-up visit, except for
visits performed via telemedicine contact (if allowed per local regulation and per investigator
discretion)as specified in the SoA (Table 3 and Table 4).
FSH: Refer to Section 10.7 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. 
Columbia-Suicide Severity Rating Scale
The C-SSRS defines 5 subtypes of suicidal ideation and 4 possible suicidal behaviors, as well as
non-suicidal self-injurious behavior and completed suicide. It will be used as a screening tool to
prospectively evaluate suicidal ideation and behavior in this study, as part of a comprehensive

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evaluation of safety. The C-SSRS is an  investigator-administered questionnaire (Mundt 2013;
Posner 2011). Two versions of it will be used in this study: the ‘Baseline/Screening’ version of the
C-SSRS will be conducted during the screening visit and the ‘Since Last Visit’ version  of the
C-SSRS will be completed at all other visits through the end of the study.
The investigator or trained study site personnel will interview the participant and complete the
C-SSRS. The C-SSRS will be provided in the local languages in accordance with local guidelines.
At screening, the C-SSRS will be the first assessment performed, before any other study procedure.
At all subsequent visits, the C-SSRS will be performed according to the assessment schedule and
should be performed after other PRO  assessments but before any other study procedure.
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 C-SSRS 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 C-SSRS has been  reviewed by the investigator and the
participant’s risk has been assessed and follow-up determined, as appropriate.
At screening (within the last 6 months) and Week 0, participants with a C-SSRS rating of
suicidal ideation with intention to act (“Ideation level 4”), suicidal ideation with specific plan and
intent (“Ideation level 5”), 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 C-SSRS ratings of wish to be dead (“Ideation level 1”), non-specific active
suicidal thoughts (“Ideation level 2”), active suicidal ideation with any methods (not plan) without
intent to act (“Ideation level 3”) or non-suicidal self-injurious behavior must be determined not to
be at risk by the investigator in order to be randomized. 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.
Suicidal ideation levels 1-3 or non-suicidal self-injurious behavior: Participant risk is assessed
by the investigator.
Suicidal ideation levels 4 or 5 or any suicidal behavior: Participant risk  is assessed and
followed by referral to a mental health professional.
Interruption or the discontinuation of study treatment should be considered for any participant who
reports suicidal ideation with intention to act (“Ideation level 4”), suicidal ideation with specific

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plan and intent (“Ideation level 5”), or suicidal behavior (actual suicide attempt, interrupted suicide
attempt, aborted suicide attempt, or preparatory behaviors for making a suicide attempt) on a
post-baseline C-SSRS 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 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 (see Section 7.1,
Discontinuation of Study Intervention).
Any C-SSRS 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 6
[Section 10.6]).
8.2.6. 
Concomitant Medication Review
Concomitant medications will be reviewed at each visit.
8.2.7. 
Injection-site Reactions
An injection-site reaction is any adverse reaction at an  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.
8.2.8. 
Hypersensitivity Reactions
Before any administration of study intervention at the study site, appropriately trained personnel
and medications must be available to treat hypersensitivity reactions, including anaphylaxis. All
participants must be observed carefully for symptoms of a hypersensitivity reaction (eg, urticaria,
itching, hives). If a mild or moderate hypersensitivity  reaction is observed, acetaminophen,
nonsteroidal anti-inflammatory drugs, and/or diphenhydramine may be administered.
In the case of a severe hypersensitivity  reaction (eg, anaphylaxis), SC aqueous epinephrine,
corticosteroids, respiratory assistance, and other proper resuscitative measures are essential and
must be available at the study site where the injections are being administered.
Participants who experience serious adverse reactions related to an injection should be
discontinued from further study intervention administrations (see Section 7.1).
Participants who experience reactions following an injection that result in bronchospasm with
wheezing and/or dyspnea that requires ventilatory support, or symptomatic hypotension with a
decrease in systolic blood pressure greater than 40 mmHg or blood pressure <90/60 mmHg will
not be permitted to receive additional study intervention (see Section 7.1).

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Participants who experience reactions suggestive of serum sickness (resulting in symptoms such
as myalgia and/or arthralgia with fever and/or rash that are not representative of signs and
symptoms of other recognized clinical syndromes) occurring 1 to 14 days after an injection of
study intervention, should be discontinued from further study intervention administrations. Note
that these symptoms may be accompanied by other events including pruritus, facial, hand, or lip
edema, dysphagia, urticaria, sore throat, and/or headache (see Section 7.1).
8.2.9. 
Infections
Investigators are required to evaluate participants for any signs or symptoms of infection at
scheduled visits (see SoA, Section 1.3). Study intervention administration should not be given to
a participant with a clinically important, 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.
8.2.10. 
Tuberculosis Evaluation
8.2.10.1. 
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, if they
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 are eligible to continue with pre-randomization 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 5.1). Appropriate treatment for latent TB is defined according to local country
guidelines for immunocompromised patients. If no local country guidelines for
immunocompromised patients exist, United States (US)guidelines should 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 study without 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.

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8.2.10.2. 
Ongoing Tuberculosis Evaluation
To aid in the early detection of TB infection or exposure during study participation, participants
must be evaluated for signs, symptoms, and close contacts at scheduled visits (refer to the SoA in
Section 1.3) or by telephone contact approximately every 8 to 12 weeks. The following series of
questions is suggested for use during the evaluation:
“Have you had a new cough of >14 days’ duration or a change in a chronic cough?”
“Have you had any of the following symptoms:
Persistent fever?
Unintentional weight loss?
Night sweats?”
“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 should be withheld and an immediate and thorough
investigation should 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
present as extrapulmonary or disseminated disease.
8.3. 
Adverse Events, Serious Adverse Events, and Other Safety Reporting
Timely, accurate, and complete reporting and analysis of safety information (including AEs and
SAEs)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 PQC.
Further details on AEs, SAEs, and PQC can be found in Appendix 6 (Section 10.6).

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8.3.1. 
Time Period and Frequency for Collecting Adverse Event and Serious
Adverse Event Information
All Adverse Events
All AEs and special reporting situations, whether serious or non-serious, will be reported from the
time a signed and dated ICF is obtained until completion of the participant’s last study-related
procedure, which may include contact for follow-up of safety.
Serious Adverse Events
All SAEs occurring during the study must be reported to the appropriate sponsor contact person
by study site personnel within 24 hours of their knowledge of the event.
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 TBili
≥2 x ULN or international normalized ratio (INR)>1.5 (if measured). Any possible Hy’s law case
is considered an important medical event and should 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 the SAE Form, which must
be completed and reviewed by a physician from the study site, and transmitted to the sponsor
within 24 hours. The initial and follow-up reports of an SAE should be made 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, including pregnancy, will be followed by the investigator as specified in
Appendix 6 (Section 10.6).

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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 Crohn’s disease
Adverse events related to worsening or progression of Crohn’s disease
These anticipated events will be periodically analyzed in aggregate by the sponsor during study
conduct. The sponsor will prepare a safety report in narrative format if the aggregate analysis
indicates that the anticipated event occurs more frequently in the intervention group than in the
control group and the sponsor concludes there is a reasonable possibility that the drug under
investigation caused the anticipated event.
The plan for monitoring and analyzing the anticipated events is specified in a separate Anticipated
Events Safety Monitoring Plan. The assessment of causality will be made by the sponsor’s
unblinded safety assessment committee.
The sponsor assumes responsibility for appropriate reporting of the listed anticipated events
according to the requirements of the countries in which the studies are conducted.
8.3.5. 
Pregnancy
All initial reports of pregnancy in female participants or partners of male participants must be
reported to the sponsor by the study site personnel within 24 hours of their knowledge of the event
using the appropriate pregnancy notification form. Abnormal pregnancy outcomes (eg,
spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are
considered SAEs and must be reported using an SAE reporting form. Any participant who becomes
pregnant during the study must discontinue further study intervention (see Section 7.1).
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the
infant will be required (see Appendix 6 [Section 10.6] and Appendix 7 [Section 10.7]).
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 6
(Section 10.6). Investigators are also advised that active TB is considered a reportable disease in
most countries. These events are to be considered serious only if they meet the definition of an
SAE.

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8.4. 
Pharmacokinetics
Serum samples will be used to evaluate the PK ofguselkumab at the 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 concentration 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 concentration 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.
8.4.2. 
Analytical Procedures
Pharmacokinetics
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. 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.

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8.5. 
Pharmacogenomics
A pharmacogenomic blood sample will be collected only from participants who consent separately
to this component of the study to allow for pharmacogenomic research, as necessary (where local
regulations permit). Participation in pharmacogenomic research is optional.
Genetic (DNA) variation may be an important contributory factor to interindividual variability in
drug response and associated clinical outcomes. Genetic factors may also serve as markers for
disease susceptibility and prognosis and may identify population subgroups that respond
differently to an intervention.
DNA samples will be analyzed for identification of genetic factors that may be associated with
clinical response. This research may consist of the analysis of 1 or more candidate genes or
assessment of single nucleic polymorphisms in relation to guselkumab intervention and/or Crohn’s
disease. Whole blood samples of approximately 6 mL will be collected for genetic analyses as
specified in the SoA (Section 1.3).
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 Crohn’s disease. Assessments
(detailed below) will include the evaluation of relevant biomarkers in serum, whole blood, and
ileocolonic biopsy samples, and ileocolonic video biopsy  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 improvement in Crohn’s disease.
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 Crohn’s disease 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 Crohn’s disease
5. To develop diagnostic tests to identify Crohn’s disease 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
end of the study, it becomes clear that the analysis will not have sufficient scientific value for
biomarker evaluation, or if there are not enough samples or responders to allow for adequate
biomarker evaluation. In the event the study is terminated early or shows poor clinical efficacy,
completion of biomarker assessments is based on justification and intended utility of the data.

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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 analysis of variance (ANOVA) and analysis of covariance
(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 Crohn’s disease 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 Crohn’s disease.
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 Crohn’s disease 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 ileocolonoscopy to study the effect of study
intervention on the histological assessment of disease and healing. Biopsies will also be analyzed
for exploratory gene and protein expression analysis where local regulations permit. Ileocolonic
biopsy analyses may also examine gene and protein expression associated with the pathogenesis
of Crohn’s disease.
8.6.4. 
Pharmacodynamics
Inflammatory PD markers will be evaluated using blood and fecal samples collected at visits as
indicated in the SoA (Section 1.3). Post-baseline PD test results, with the exception of CRP and
fecal calprotectin (Section 8.1), will not be released to the investigators by the central laboratory.
8.7. 
Immunogenicity Assessments
Antibodies to guselkumab will be evaluated in serum samples collected from all participants
according to the SoA (Section 1.3). Additionally, serum samples should also be collected at the
SID and FES visits. 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 ofguselkumab.
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. 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
Crohn’s disease related surgeries and procedures are 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. Refer to the SAP for further details.
9.1. 
Statistical Hypotheses
Refer to Section 3 for the hypotheses.
9.2. 
Sample Size Determination
Sample sizes were determined by the power to detect a significant difference in clinical remission
at Week 12 and in endoscopic response at Week 12 (co-primary endpoints) between the combined
guselkumab group and the placebo group, using a 2-sided chi-square test with 0.05 significance
level. The assumed rates are 50% versus 15% (guselkumab versus placebo) for clinical remission
and 30% versus 13% for endoscopic response. The study is sized such that the guselkumab therapy
achieves >90% power for the co-primary endpoints compared with placebo. This sample size also
provides >90% power for all secondary endpoints.
Clinical Remission at Week 12
Assumptions for clinical remission at Week 12 were based on the Phase 2 data from the
CNTO1959CRD3001 Phase 2/3 program. In the Phase 2 study (GALAXI 1), the proportions of
participants who met the eligibility requirement for the GRAVITI study and who were in clinical
remission at Week 12, were 12.0%, 59.2%, 55.6% and 42.9% for placebo, guselkumab 
IV, guselkumab
 IV and guselkumab
 IV, respectively, for a treatment difference
of 31% to 47%. Of note, in GALAXI 1, approximately 50% of the participants were BIO-Failure.
Note that the eligibility criterion on SES-CD for this study is relatively new and notmany historical
studies have this requirement, hence the actual placebo rate could vary. Based on these
considerations and the data above, the clinical remission rates are assumed to be 15% for placebo
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and 50% for guselkumab 
(treatment difference of 35%), assuming about 50% of the
participants will be BIO-Failure in this study.
Endoscopic Response at Week 12
Assumptions for endoscopic response at Week 12 were also based on GALAXI 1. The proportions
of participants who met the eligibility requirement for this current study and who were in
endoscopic response at Week 12, were 12.0%, 34.7%, 35.6% and 22.4% for placebo, guselkumab
 IV, guselkumab 
 IV and guselkumab 
 IV, respectively, for a treatment
difference of 10% to 24%.
Based on these data, the endoscopic response rates are assumed to be 13% for placebo and 30%
for guselkumab
(treatment difference of 17%), assuming about 50% of the participants
will be BIO-Failure in this study.
In this study, 212 participants in  the combined guselkumab group and 106 participants in the
placebo group will provide at least 90% power for achieving the co-primary endpoints of clinical
remission at Week 12 and endoscopic response at Week 12 (Table 8), based on the assumptions
above.
Table 8: 
Power to Detect a Treatment Effect of Guselkumab Based on Proportion of Participants
Achieving Clinical Remission at Week 12 or Endoscopic Response at Week 12
Co-primary Endpoint of Clinical Remission at Week 12
Placebo 
(N=106) 
Guselkumab SC  
(N=212)
Power
15%  
45%  
>99%
15% 
50%  
>99%
15%  
55%  
>99%
Co-primary Endpoint of Endoscopic Response at Week 12
10%  
25%  
91%
13%  
30% 
94%
13%  
35%  
>99%
Abbreviations: SC=subcutaneous
9.3. 
Populations for Analysis Sets
For purposes of analysis, the following populations are defined:
Population 
Description
Randomized Analysis Set 
All randomized participants
Full Analysis Set 
All randomized participants who received at least 1 dose of study intervention
Safety Analysis 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 1 valid blood sample drawn post-baseline for PK analysis
Immunogenicity Analysis 
Set 
All participants who received at least 1 dose of study intervention and have
appropriate samples for anti-drug antibody detection
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9.4. 
Statistical Analyses
9.4.1. 
General Considerations
The SAP will be finalized prior to the first DBL (ie, Week 24), and it will include a more technical
and detailed description of the statistical analyses described in this section. This section is a
summary of the planned statistical analyses of the most important endpoints including primary and
secondary endpoints. Any modifications and/or clarifications to protocol-specified statistical
analyses or any other statistical analyses will be described in the SAP.
Descriptive statistics (eg, mean, median, standard deviation [SD], interquartile 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, Cochran-Mantel-Haenszel (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 will
be compared using an ANOVA or ANCOVA, unless otherwise specified. If the normality
assumption is in question, an ANOVA or ANCOVA on the van der Waerden normal scores will
be used.
Statistical testing will be performed at a significance level of 0.05 (2-sided). The Type I error will
be controlled over the co-primary, secondary, and selected Week 48 tertiary  endpoints
(Section 9.4.4) in the multiplicity-controlled testing procedure. For endpoints that are not
multiplicity-controlled, nominal p-values will be presented.
The co-primary and secondary endpoints (as well as all endpoints through Week 24) will be
evaluated at the Week 24 DBL. The evaluation of the Week 48 endpoints, including the Week 48
tertiary endpoints that are included in the testing procedure, will be evaluated at the subsequent
Week 48 DBL.
9.4.2. 
Primary Endpoints
The co-primary endpoints are:
Clinical remission (CDAI score <150) at Week 12
Endoscopic response (≥50% improvement from baseline in SES-CD score)at Week 12
Estimands and Estimators
Two co-primary estimands, ie, a precise definition of the primary targeted treatment effect, are
defined by the following 5 attributes: treatment by Week 12, population, intercurrent events (ICEs)
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Primary Estimand of Clinical Remission at Week 12
i. Treatment by 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, and 8)
ii. Population:Participants with moderately to severely active Crohn’s disease
iii. Variable (endpoint):
A binary response variable (response/non-response) where response is defined as achieving
CDAI score <150 at Week 12 without experiencing any of the ICEs in categories 1 to 3 as
outlined below prior to the Week 12 visit.
iv. Intercurrent events and corresponding strategies:
The following are the ICEs considered for this study:
1) A Crohn’s disease-related surgery (with the exception of minor procedures such as
drainage of a superficial abscess or seton placement, etc.)
2) A prohibited change in Crohn’s disease medication
3) Discontinuation of study intervention  due to lack of efficacy or an AE of worsening
Crohn’s disease
4) Discontinuation of study intervention due to COVID-19 related reasons (excluding
COVID-19 infection)
5) Discontinuation of study intervention due to COVID-19 infection, for reasons other than
lack of efficacy or an AE of worsening Crohn’s disease, or any other COVID-19 related
reasons
Intercurrent events in categories 1 to 3 will be handled by the composite strategy, ICE
category 4 will be handled by the hypothetical strategy, and ICE category 5 will be handled by
treatment policy strategy. The composite strategy assesses the treatment effects not only based
on the variable measurements, but also based on ICEs. This estimand acknowledges that
having an ICE in categories 1 to 3 is an unfavorable outcome. For participants experiencing
ICE 4, the hypothetical strategy envisages a scenario in which ICE category 4 would not occur
and data points after the occurrence of ICE category 4 and onward will not be used. For
participants experiencing ICE category 5, the treatment policy strategy considers the
occurrence of ICE category 5 is irrelevant in defining the treatment effect and so observed
values of the variable will be used, if available, regardless of the occurrence of ICE category 5.
v. Population-level summary:
Difference in proportions of responders (according to the variable defined in iii above)
between the combined guselkumab group and the placebo group.
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Primary Estimand of Endoscopic Response at Week 12
i. Treatment by 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, and 8)
ii. Population:Participants with moderately to severely active Crohn’s disease
iii. Variable (endpoint):
A binary response variable (response/non-response) where response is defined as achieving
endoscopic response (≥50% improvement from baseline in SES-CD score) at Week 12
without experiencing any of the ICEs in categories 1 to 3 as outlined above prior to the
Week 12 visit.
iv. Intercurrent events and corresponding strategies:
The same ICEs and corresponding strategies that are specified for the co-primary endpoint of
clinical remission at Week 12 will be used.
v. Population-level summary:
Difference in proportions of responders (according to the variable defined in iii above) between
the combined guselkumab group and the placebo group.
Estimators
The analyses of the co-primary endpoints will be based on the Full Analysis Set. Participants will
be analyzed according to the intervention group to which they were randomized regardless of the
study intervention they actually received.
The CDAI score will be calculated for a visit if at least 4 of the 8 components are available at that
visit. When at least 4 of the 8 components are available, any missing components will be imputed
by carrying forward the last available components. If the CDAI score cannot be calculated
(ie, <4 components available) at a visit, the CDAI score will be considered missing for that visit.
The total SES-CD score at a visit will be calculated based on all segments scored at the visit. If the
total SES-CD score cannot be calculated (ie, no segment is scored) at a visit, the total SES-CD
score will be considered missing.
After accounting for the ICE strategies, participants whose responder status is missing for a
co-primary endpoint will be considered to be a non-responder for that co-primary endpoint. To
examine the robustness of the co-primary endpoint analyses, sensitivity analyses using alternative
missing data handling rules may be performed and will be specified in the SAP.
To control the Type I error, a fixed sequence testing approach will be used for the co-primary
endpoints. In particular, clinical remission at Week 12 will be tested first, followed by the testing
ofendoscopic response at Week 12.
For testing of the co-primary endpoints, the efficacy of the induction dose of guselkumab versus
the placebo group will be compared. As such, the two guselkumab groups that are randomized to
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receive an identical guselkumab induction dose regimen through Week 12 will be combined for
these comparisons.
To compare the induction dose regimen of guselkumab versus placebo for the co-primary
endpoints, the CMH chi-square test (2-sided) stratified by baseline CDAI score (≤300 or >300),
baseline SES-CD score (≤12 or >12), and BIO-Failure status (Yes or No) at baseline will be used.
The study will be considered successful if both tests ofthe co-primary endpoints are positive.
In addition, subgroup analyses of the co-primary endpoints will be performed based on
demographic and baseline disease characteristics, and baseline and previous use of medications
for Crohn’s disease (including BIO-Failure status).
9.4.3. 
Secondary Endpoints
The analyses of the 3 secondary endpoints listed below will be performed after the tests of the
co-primary endpoints. For the endpoint of clinical remission at Week 24, the test between the high
dose group (
 q4w) and the placebo group will be performed first, followed by the test
between the low dose group (
 q8w) and the placebo group. The testing sequence will
continue for the next 2 endpoints in the order listed below. If any test in the sequence, including
the tests of the co-primary endpoints, does not achieve significance at the 2-sided 0.05 level, all
the p-values for the subsequent endpoints will be considered nominal.
Clinical remission (CDAI score <150) at Week 24
PRO-2 remission at Week 12 (defined as an AP mean daily score at or below 1 and SF mean
daily score at or below 3, ie, AP ≤1 and SF ≤3, and no worsening of AP or SF from baseline)
Clinical response (decrease from baseline in CDAI ≥100 points or clinical remission) at
Week 12
Estimands and Estimators
Secondary Estimand of Clinical Remission at Week 24
i. Treatment by Week 24:
Experimental: Guselkumab 
 q4w (Weeks 0, 4, and 8) followed by guselkumab
 q4w (Weeks 12, 16, and 20)
Experimental: Guselkumab 
 q4w (Weeks 0, 4, and 8) followed by guselkumab
 q8w at Week 16
Control: Placebo SC q4w (Weeks 0, 4, 8, 12, 16, and 20)
ii. Population:Participants with moderately to severely active Crohn’s disease
iii. Variable (endpoint):
A binary response variable (response/non-response) where response is defined as achieving
CDAI score <150 at Week 24 without experiencing any of the ICEs in categories 1 to 3 and 6
as outlined below prior to the Week 24 visit.
iv. Intercurrent events and corresponding strategies:
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1) A Crohn’s disease-related surgery (with the exception of minor procedures such as
drainage of a superficial abscess or seton placement, etc.)
2) A prohibited change in Crohn’s disease medication
3) Discontinuation of study intervention due to lack of efficacy or an AE of worsening
Crohn’s disease
4) Discontinuation of study intervention due to COVID-19 related reasons (excluding
COVID-19 infection)
5) Discontinuation of study intervention due to COVID-19 infection, for reasons other than
lack of efficacy or an AE of worsening Crohn’s disease, or any other COVID-19 related
reasons
6) Meet rescue criteria (see Section 6.5.1)
Intercurrent events in categories 1 to 5 will be handled in the same way as for the primary
estimands. Intercurrent events in categories 1 to 3 and 6 will be handled by the composite
strategy. This estimand acknowledges that having an ICE in categories 1 to 3 and 6 is an
unfavorable outcome. For participants experiencing ICE category 4, the data points after the
occurrence of ICE category 4 and onward will not be used. For participants experiencing ICE
category 5, the observed values of the variable will be used, if available, regardless of the
occurrence of ICE category 5.
v. Population-level summary:
Difference in proportions of responders (according to the variable defined in iii above) between
each guselkumab group and the placebo group.
Secondary Estimand of PRO-2 Remission at Week 12
The same estimand (except for the “variable” attribute) that is specified for the co-primary
endpoint analyses will be used.
Variable (endpoint):
A binary response variable (response/non-response) where response is defined as achievingPRO-2
remission (defined as AP ≤1 and SF ≤3, and no worsening of AP or SF from baseline) at Week 12
without experiencing any of the ICEs in categories 1 to 3 as outlined above, prior to the Week 12
visit.
Secondary Estimand of Clinical Response at Week 12
The same estimand (except for the “variable” attribute) that is specified for the co-primary
endpoint analyses will be used.
Variable (endpoint):
A binary response variable (response/non-response) where response is defined as achieving
clinical response (decrease in CDAI score ≥100 points or clinical remission) at Week 12 without
experiencing any of the ICEs in categories 1 to 3 as outlined above, prior to the Week 12 visit.

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Estimators
The analyses will be based on the Full Analysis Set. Participants will be analyzed according to the
intervention group to which they were randomized regardless of the study intervention they
actually received.
For the secondary endpoints, the CMH chi-square test (2-sided) stratified by baseline CDAI score
(≤300 or >300), baseline SES-CD score (≤12 or >12), and BIO-Failure status (Yes or No) at
baseline will be used to compare guselkumab dose regimens versus placebo.
After accounting for the ICE strategies, participants whose responder status is missing for a
secondary endpoint will be considered to be a non-responder for that secondary endpoint.
9.4.4. 
Tertiary Endpoints
The tertiary endpoints are evaluated at applicable timepoints through Week 96; they include but
are not limited to the endpoints described in Section 3. A complete list of the tertiary endpoints
will be provided in the SAP. Two tertiary endpoints (clinical remission at Week 48, endoscopic
response at Week 48)will be controlled for multiplicity. These endpoints will be added at the end
of the multiplicity-controlled testing procedure described in Section 9.4.3; the full testing
procedure will be specified in the SAP. The testing of other tertiary endpoints will not be controlled
for multiplicity, and nominal p-values will be provided.
9.4.5. 
Safety Analyses
All safety analyses will be based on the Safety Analysis Set. For the safety analyses, participants
will be analyzed according to the study intervention they actually received regardless of the study
intervention they were randomized to.
Adverse Events
The verbatim terms used in the eCRF by investigators to identify AEs will be coded using the
Medical Dictionary for Regulatory Activities. Any AE occurring at or after the initial
administration of study intervention through the day of last dose plus 12 weeks 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.
Summaries, listings, datasets, or participant narratives may be provided, as appropriate, for those
participants who die, who discontinue intervention due to an AE, or who experience a severe or an
SAE.
Clinical Laboratory Tests
Laboratory data will be summarized by type of laboratory test. 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.

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Suicidal Ideation and Behavior
Suicidal ideation and behavior based on the C-SSRS and AEs will be summarized descriptively.
9.4.6. 
Other Analyses
Pharmacokinetic Analyses
The analyses are based on PK Analysis Set.
Descriptive statistics of the serum guselkumab concentrations will be calculated at each sampling
time point. These concentrations will be summarized over time for each treatment group.
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 summary statistics.
A population PK analysis approach using nonlinear mixed-effects modeling may  be used to
evaluate guselkumab PK parameters. The influence of important covariates on the population PK
parameter estimates may be evaluated. If performed, details will be given in a population PK
analysis plan and the results of the population PK analysis will be presented in a separate report.
Participants will be excluded from the PK analysis if their data do not allow for accurate
assessment of the PK (eg, incomplete administration of the study intervention; missing time of
study intervention administration). Detailed rules for the analysis will be specified in the SAP.
Immunogenicity Analyses
The analyses are based on Immunogenicity Analysis Set.
The incidence and titers of antibodies to guselkumab will be summarized for all participants who
receive a dose of guselkumab and have appropriate samples for detection of antibodies to
guselkumab (ie, participants with at least 1 sample obtained after their first dose ofguselkumab).
A listing of participants who are positive for antibodies to guselkumab will be provided. The
maximum titers of antibodies to guselkumab will be provided 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.
Biomarkers Analyses
Planned biomarker analyses may be deferred if emerging study data show no likelihood of
providing useful scientific information. Any biomarker samples received by the contract vendor
or sponsor after the cutoff date will not be analyzed, and therefore, excluded from the biomarker
analysis.

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Changes in serum protein analytes and whole blood RNA obtained over time will be summarized
by intervention group where local regulations permit. Associations between baseline levels and
changes from baseline in select biomarkers and response to treatment will be explored. RNA
analyses will be summarized in a separate technical report.
The biomarker analyses will characterize the effects of guselkumab to identify biomarkers relevant
to treatment, and to determine if these biomarkers can predict response to guselkumab. Results of
serum, whole blood analyses, and ileocolonic biopsy analyses will be reported in separate technical
reports.
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.
Pharmacogenomic Analyses
Genetic (DNA) analyses will be conducted only in participants who sign the consent form to
participate in the pharmacogenomic substudy. These analyses are considered exploratory and will
be summarized in a separate technical report.
9.5. 
Interim Analysis
No interim analysis is planned for this study.

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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS

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10.1. Appendix 1: Abbreviations and Definitions
5-ASA  
5-aminosalicylic acid
6-MP  
6-mercaptopurine
AE 
adverse event
ALP  
alkaline phosphatase
ALT  
alanine transaminase
ANCOVA  
analysis of covariance
ANOVA  
analysis of variance
anti-HBc 
hepatitis B core antibody
anti-HBs 
hepatitis B surface antibody
AP  
abdominal pain
AP-NRS  
Abdominal Pain-Numerical Rating Scale
AST 
aspartate transaminase
AUC  
area under the curve
AZA  
azathioprine
BCG  
Bacille Calmette-Guérin
BSFS 
Bristol Stool Form Scale
CDAI 
Crohn’s Disease Activity Index
CMH  
Cochran-Mantel-Haenszel
COVID-19 
Coronavirus Disease 2019
CRP  
C-reactive protein
C-SSRS  
Columbia-Suicide Severity Rating Scale
CT  
computed tomography
DBL  
database lock
DILI 
drug-induced liver injury
DNA  
deoxyribonucleic acid
ECG  
electrocardiogram
eCRF  
electronic case report form
eDC  
electronic data capture
eSource 
electronic source
EU  
European Union
EU-CTR  
European Union Clinical Trials Regulation
FDA  
Food and Drug Administration
FES  
final efficacy and safety
FOIA  
Freedom of Information Act
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
HRQOL 
health-related quality of life
HRT  
hormonal replacement therapy
IB  
Investigator’s Brochure
IBD  
inflammatory bowel disease
IBDQ  
Inflammatory Bowel Disease Questionnaire
ICE 
intercurrent event
ICF  
informed consent form
ICH  
International Conference on Harmonisation of Technical Requirements for Pharmaceuticals for
Human Use
ICMJE 
International Committee of Medical Journal Editors
IEC  
Independent Ethics Committee
IFU  
Instructions for Use
Ig 
immunoglobulin
IGRA  
interferon gamma release assay

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IL 
interleukin
IMP  
Investigational Medicinal Product
IND  
Investigational New Drug
INR  
international normalized ratio
IPPM  
Investigational Product Procedures Manual
IRB  
Institutional Review Board
IV  
intravenous
IWRS  
interactive web response system
LT  
liver tests
MRI 
magnetic resonance imaging
MTX  
methotrexate
NIMP  
Non-investigational Medicinal Product
PD 
pharmacodynamic(s)
PFS  
prefilled syringe
PFS-U 
prefilled syringe with an UltraSafe PlusTM Passive Needle Guard
PFS-Y 
prefilled syringe with YpsoMate autoinjector
PK 
pharmacokinetic(s)
PQC  
Product Quality Complaint
PRO  
Patient-reported Outcome
PROMIS  
Patient-reported Outcomes Measurement Information System
q4w  
every 4 weeks
q8w  
every 8 weeks
RNA  
ribonucleic acid
SAE  
serious adverse event
SAP  
Statistical Analysis Plan
SARS-CoV-2 
severe acute respiratory syndrome coronavirus-2
SC 
subcutaneous
SD 
standard deviation
SES-CD  
Simple Endoscopic Score for Crohn’s Disease
SF 
stool frequency
SID  
study intervention discontinuation
SoA  
Schedule of Activities
SUSAR  
suspected unexpected serious adverse reaction
TB  
tuberculosis
TBili 
total bilirubin
TNFα 
tumor necrosis factor alpha
ULN  
upper limit of normal
US  
United States
WBC  
white blood cell
Definitions of Terms
Electronic source
system
Contains data traditionally maintained in a hospital or clinic record to document medical
care or data recorded in an eCRF as determined by the protocol. Data in this system may
be considered source documentation.

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10.2. Appendix 2: Definitions of Inadequate Response to or Intolerance of
Corticosteroids or 6-Mercaptopurine/Azathioprine/Methotrexate 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. Evidence of CON-Failure must be documented in the participant’s source documentation.
Participants are intolerant of corticosteroids if:
They have developed clinically significant AEs (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 Crohn’s disease.
OR
They have a medical condition that precludes the use of corticosteroids as a treatment for
Crohn’s disease.
Participants are corticosteroid dependent if they have failed to successfully taper their
corticosteroid (ie, had a flare of disease) within 3 months of starting therapy, or if a relapse occurs
within 3 months after stopping corticosteroids or if they are unable to discontinue these agents
without flare within 3 months after starting them.
6-MERCAPTOPURINE, AZATHIOPRINE, OR METHOTREXATE
Participants have failed to respond to 6-MP, AZA, OR MTX if they have had evidence of an
initial inadequate response, recurrent disease, or a relapse despite receiving:
At least 3 months of therapy with 1 mg/kg/day of 6-MP, 2 mg/kg/day of AZA, or 25 mg/week
(intramuscular or subcutaneous) of MTX.
OR
A lower dosage of 6-MP, AZA, or MTX when country or local guidelines specify a different
treatment regimen. (In such an event, the country or local guidelines needs to be included in
the source document).
OR
The dosage of 6-MP, AZA, or MTX confirmed to be therapeutic for the participant with whole
blood thioguanine nucleotide levels >200 pmol/8 x 108 red blood cells.
OR
The highest tolerated dosage due to leukopenia, elevated liver enzymes, or nausea.

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Participants are intolerant of 6-MP, AZA, or MTX if:
They have developed clinically significant AEs (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, AZA, or
MTX to treat Crohn’s disease within the past 5 years.
OR
They have a medical condition that precludes the use of 6-MP, AZA, or MTX.

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10.3. Appendix 3: Definition of Inadequate Initial Response, Loss of Response,
or Intolerance to Tumor Necrosis Factor Antagonist Therapies (Infliximab,
Adalimumab, or Certolizumab Pegol), Vedolizumab, or Approved
Biosimilars
The criteria for inadequate initial response, response followed by loss of response, or intolerance
to infliximab, adalimumab, certolizumab pegol, vedolizumab, or approved biosimilars are
described in items 1, 2, and 3, below.
1. Inadequate initial response to current or prior therapy with infliximab, adalimumab,
certolizumab pegol, vedolizumab, or approved biosimilars (primary nonresponse)
Eligible participants must satisfy criteria a, b, and c.
a. Have received, at minimum, a locally approved induction dose, for example:
1) Infliximab (2 or 3 doses of ≥5 mg/kg)
OR
2) Adalimumab (at a dose of 160 mg followed by a dose ≥80 mg or at a dose of 80 mg
followed by a dose ≥40 mg)
OR
3) Certolizumab pegol (2 or 3 doses of ≥400 mg)
OR
4) Vedolizumab (at least 2 and up to 4 doses of 300 mg IV)
AND
b. Did not initially respond to these induction doses of infliximab, adalimumab,
certolizumab pegol, vedolizumab, or approved biosimilars as evidenced by the presence
of at least 1 of the following signs or symptoms related to persistence of Crohn’s disease,
as assessed by a treating physician:
1) Lack of improvement or worsening in stool frequency
2) Lack of improvement or worsening in daily abdominal pain
3) Occurrence, lack of improvement, or worsening of fever thought to be related to
Crohn’s disease
4) Lack of improvement or worsening in a draining fistula or development of a new
draining fistula
5) Lack of improvement or worsening in rectal bleeding
6) Initiation or increase in antidiarrheal medication
These signs and symptoms of Crohn’s disease must have occurred ≥2 weeks after
receiving the last induction dose of infliximab, adalimumab, certolizumab pegol,
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, certolizumab pegol, vedolizumab,

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or approved biosimilars. This benchmark acknowledges that the CDAI is not routinely
recorded in clinical practice.
It is acknowledged that previous treatment decisions could have been made based on
evaluation of other measures that may be indicative of worsening disease (eg, elevations
of inflammatory markers including but not limited to CRP or fecal calprotectin, etc,
and/or evidence of disease flare based on clinical imaging modalities including but not
limited to ileocolonoscopy, CT, and magnetic resonance imaging [MRI]). Under these
circumstances, documentation of these specified measures of worsening disease activity
can be accepted as evidence of inadequate response to prior biologic treatment. However,
investigators should note that participants must meet protocol-specified criteria for active
disease (ie, clinical and endoscopic) during the current screening period as described in
Section 5.1 to be eligible for enrollment.
AND
c. Have documentation available to the investigator that meets the following 2 requirements:
1) Provide the dates and doses of the failed induction therapy with infliximab,
adalimumab, certolizumab pegol, vedolizumab, or approved biosimilars.
2) Documents that the participant had persistence of disease activity following
induction therapy with infliximab, adalimumab, certolizumab pegol, 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).
2. Initial response followed by loss of response to current or prior therapy with infliximab,
adalimumab, certolizumab pegol, vedolizumab, or approved biosimilars (secondary
nonresponse)
Eligible participants must satisfy criteria a, b, c, d.
a. Initially responded to induction therapy
AND
b. Have received, at minimum, 2 doses of a locally approved maintenance dose, for
example:
1) Infliximab (at a dose of ≥5 mg/kg)
or
2) Adalimumab (at a dose of ≥40 mg)
or
3) Certolizumab pegol (at a dose of ≥400 mg)
or
4) Vedolizumab (at a dose of ≥300 mg IV or ≥108 mg SC)
AND
c. Have or had at least 1 of the following signs or symptoms related to recurrence of Crohn’s
disease, as assessed by a treating physician:

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1) Worsening in stool frequency
2) Worsening in daily abdominal pain
3) Occurrence or worsening in fever thought to be related to Crohn’s disease
4) Recurring drainage from a previously nondraining fistula or development of a new
draining fistula
5) Worsening in rectal bleeding
6) Initiation or increase in antidiarrheal medication
These signs and symptoms of Crohn’s disease must have occurred ≥2 weeks after
receiving the last maintenance dose of infliximab, adalimumab, certolizumab pegol,
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, certolizumab pegol, vedolizumab, or approved biosimilars.
This benchmark acknowledges that the CDAI is not routinely recorded in clinical
practice.
AND
d. Have documentation available to the investigator that meets the following 2 requirements:
1) Provide the dates and doses of the failed maintenance therapy with infliximab,
adalimumab, certolizumab pegol, vedolizumab, or approved biosimilars.
2) Documents that the participant had recurrence of disease activity despite
maintenance therapy with infliximab, adalimumab, certolizumab pegol,
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).
3. Current or prior intolerance to therapy with infliximab, adalimumab, certolizumab
pegol, 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
(for example, delayed hypersensitivity or serum sickness-like reaction); or 3) significant
injection-site reaction. Definitions of these 3 criteria are provided below. Adverse
reactions also must have followed ≥1 dose of infliximab, adalimumab, certolizumab
pegol, 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:
a) Manifested through ≥1 of the following symptoms.
Fever greater than 100°F (37.8°C)
Chills or rigors
Itching

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Rash
Flushing
Urticaria or angioedema
Breathing difficulties (dyspnea, chest paint or tightness, shortness of breath,
wheezing, stridor)
Clinical hypotension (pallor, diaphoresis, faintness, syncope), blood pressure
less than 90 mmHg systolic and 60 mmHg diastolic, or a systemic or orthostatic
drop in systolic blood pressure of greater than 20 mmHg
AND
b) Occurred ≤24 hours after infusion/administration of infliximab, adalimumab,
certolizumab pegol, vedolizumab, or approved biosimilars.
AND
c) Was considered related to the infusion/administration of infliximab,
adalimumab, certolizumab pegol, vedolizumab, or approved biosimilars.
2) A significant delayed infusion/administration reaction is defined as an adverse
reaction that:
a) Was manifested through 1 or more of the following symptoms:
Myalgias
Arthralgias
Fever greater than 100°F (37.8°C)
Malaise
Rash
AND
b) Occurred >24 hours and <15 days after infusion/administration of infliximab,
adalimumab, certolizumab pegol, vedolizumab, or approved biosimilars.
AND
c) Was considered related to the infusion/administration of infliximab,
adalimumab, certolizumab pegol, vedolizumab, or approved biosimilars.
3) A significant injection-site reaction is defined as an adverse reaction that:
a) Was manifested through 1 or more of the following symptoms:
Significant bruising
Erythema
Hemorrhage
Irritation
Pain

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Pruritus
“Injection-site reaction”
AND
b) Occurred within 24 hours of an SC injection of adalimumab, certolizumab pegol,
or approved biosimilars.
AND
c) Was considered related to the injection.
b. Have documentation available to the investigator that meets the following 2 requirements:
1) Provides the date of discontinuation of infliximab, adalimumab, certolizumab pegol,
vedolizumab, or approved biosimilars.
2) Documents that the participant had intolerance to infliximab, adalimumab,
certolizumab pegol, 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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10.5. Appendix 5: Regulatory, Ethical, and Study Oversight Considerations
10.5.1. 
Regulatory and Ethical Considerations
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the
protocol, current International Conference on Harmonisation of Technical Requirements for
Pharmaceuticals for Human Use [ICH] guidelines on Good Clinical Practice (GCP), and applicable
regulatory and country-specific requirements.
Good Clinical Practice is an international ethical and scientific quality standard for designing,
conducting, recording, and reporting studies that involve the participation of human participants.
Compliance with this standard provides public assurance that the rights, safety, and well-being of
study participants are protected, consistent with the principles that originated in the Declaration of
Helsinki, and that the study data are credible.
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/Good
Post-Marketing Study Practice (GPSP), and applicable regulatory and country-specific
requirements following new drug approval for the corresponding study indication.
Protocol Amendments
Neither the investigator nor the sponsor will modify this protocol without a formal amendment by
the sponsor. All protocol amendments must be issued by the sponsor, and signed and dated by the
investigator. Protocol amendments must not be implemented without prior IEC/IRB approval, or
when the relevant competent authority has raised any grounds for non-acceptance, except when
necessary to eliminate immediate hazards to the participants, in which case the amendment must
be promptly submitted to the IEC/IRB and relevant competent authority. Documentation of
amendment approval by the investigator and IEC/IRB must be provided to the sponsor. When the
change(s) involve only logistic or administrative aspects of the study, the IEC/IRB (where
required) only needs to be notified.
During the course of the study, in situations where a departure from the protocol is unavoidable,
the investigator or other physician in attendance will contact the appropriate sponsor representative
listed in the Contact Information page(s), which will be provided as a separate document. Except
in emergency situations, this contact should be made before implementing any departure from the
protocol. In all cases, contact with the 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 eCRF and source
documents will reflect any departure from the protocol, and the source documents will describe
this departure and the circumstances requiring it.

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Regulatory Approval/Notification
This protocol and any amendment(s) must be submitted to the appropriate regulatory authorities
in each respective country, if applicable. A study may not be initiated until all local regulatory
requirements are met.
Required Prestudy Documentation
The following documents must be provided to the sponsor before shipment of study intervention
to the study site:
Protocol and amendment(s), if any, signed and dated by the principal investigator
A copy of the dated and signed (or sealed, where appropriate per local regulations), written
IEC/IRB approval of the protocol, amendments, ICF, any recruiting materials, and if
applicable, participant compensation programs. This approval must clearly identify the
specific protocol by title and number and must be signed (or sealed, where appropriate per
local regulations) by the chairman or authorized designee.
Name and address of the IEC/IRB, including a current list of the IEC/IRB members and their
function, with a statement that it is organized and operates according to GCP and the
applicable laws and regulations. If accompanied by a letter of explanation, or equivalent, from
the IEC/IRB, a general statement may be substituted for this list. If an investigator or a
member of the study site personnel is a member of the IEC/IRB, documentation must be
obtained to state that this person did not participate in the deliberations or in the vote/opinion
of the study.
Regulatory authority approval or notification, if applicable
Signed and dated statement of investigator (eg, Form FDA 1572), if applicable
Documentation of investigator qualifications (eg, curriculum vitae)
Completed investigator financial disclosure form from the principal investigator, where
required
Signed and dated clinical trial agreement, which includes the financial agreement
Any other documentation required by local regulations
The following documents must be provided to the sponsor before enrollment of the first
participant:
Completed investigator financial disclosure forms from all subinvestigators
Documentation of subinvestigator qualifications (eg, curriculum vitae)
Name and address of any local laboratory conducting tests for the study, and a dated copy of
current laboratory normal ranges for these tests, if applicable
Local laboratory documentation demonstrating competence and test reliability
(eg, accreditation/license), if applicable

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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.
Approval for the collection of optional samples for research and for the corresponding ICF must
be obtained from the IEC/IRB. Approval for the protocol can be obtained independent of this
optional research component.
During the study the investigator (or sponsor where required) will send the following documents
and updates to the IEC/IRB for their review and approval, where appropriate:
Protocol amendments (excluding the ones that are purely administrative, with no
consequences for participants, data or study conduct)
Revision(s) to ICF and any other written materials to be provided to participants
If applicable, new or revised participant recruiting materials approved by the sponsor
Revisions to compensation for study-related injuries or payment to participants for
participation in the study, if applicable
New edition(s) of the IB and amendments/addenda
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

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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 ofthe IEC/IRB
For all protocol amendments (excluding the ones that are purely administrative, with no
consequences for participants, data or study conduct), the amendment and applicable ICF revisions
must be submitted promptly to the IEC/IRB for review and approval before implementation of the
change(s).
At least once a year, the IEC/IRB will be asked to review and reapprove this study, where required.
At the end of the study, the investigator (or sponsor where required) will notify the IEC/IRB about
the study completion (if applicable, the notification will be submitted through the head of
investigational institution).
Country Selection
This study will only be conducted in those countries where the intent is to launch or otherwise help
ensure access to the developed product if the need for the product persists, unless explicitly
addressed as a specific ethical consideration in Section 4.2.1.
Other Ethical Considerations
For study-specific ethical design considerations, refer to Section 4.2.1.
10.5.2. 
Financial Disclosure
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial
information in accordance with local regulations to allow the sponsor to submit complete and
accurate financial certification or disclosure statements to the appropriate regulatory authorities.
Investigators are responsible for providing information on financial interests during the course of
the study and for 1 year after completion of the study.
Refer to Required Prestudy Documentation (above) for details on financial disclosure.
10.5.3. 
Informed Consent Process
Each participant (and legally acceptable representative) must give written consent according to
local requirements after the nature of the study has been fully explained. The ICF(s) must be signed
before performance of any study-related activity. The ICF(s) that is/are used must be approved by
both the sponsor and by the reviewing IEC/IRB and be in a language that the participant can read
and understand. The informed consent should be in accordance with principles that originated in

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the Declaration of Helsinki, current ICH and GCP guidelines, applicable regulatory requirements,
and sponsor policy.
Before enrollment in the study, the investigator or an authorized member of the study site personnel
must explain to potential participants (and 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 (and 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 (and legally acceptable representative)will be given sufficient time to read the ICF
and the opportunity to ask questions. After this explanation and before entry into the study, consent
should be appropriately recorded by means of the participant’s (and 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.
Participants will be asked for consent to provide optional samples for research (where local
regulations permit). After informed consent for the study is appropriately obtained, the participant
(and his or her legally acceptable representative) will be asked to sign and personally date a
separate ICF indicating agreement to participate in the optional research component. Refusal to
participate in the optional research will not result in ineligibility for the study. A copy of this signed
ICF will be given to the participant.
10.5.4. 
Data Protection
Privacy of Personal Data
The collection and processing of personal data from participants enrolled in this study  will be
limited to those data that are necessary to fulfill the objectives of the study.
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.

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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. This consent also addresses the transfer of the data to other
entities and to other countries.
The participant has the right to request through the investigator access to his or her personal data
and the right to request rectification of any data that are not correct or complete 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  DNA, PD, biomarker, PK, and immunogenicity research is not conducted under
standards appropriate for the return of data to participants. In addition, the sponsor cannot make
decisions as to the significance of any findings resulting from exploratory research. Therefore,
exploratory research data will not be returned to participants or investigators, unless required by
law or local regulations. Privacy and confidentiality of data generated in the future on stored
samples will be protected by the same standards applicable to all other clinical data.
10.5.5. 
Long-term Retention of Samples for Additional Future Research
Samples collected in this study may be stored for up to 15 years (or according to local regulations)
for additional research. Samples will only be used to understand guselkumab, to understand
Crohn’s disease, to understand differential intervention responders, and to develop diagnostic tests
to identify Crohn’s disease populations that may be responsive or non-responsive to treatment with
guselkumab. 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).
10.5.6. 
Committees Structure
No Data Monitoring Committee is planned for this study.
10.5.7. 
Publication Policy/Dissemination of Clinical Study Data
All information, including but not limited to information regarding guselkumab or the sponsor's
operations (eg, patent application, formulas, manufacturing processes, basic scientific data, prior
clinical data, formulation information) supplied by the sponsor to the investigator and not
previously published, and any data, including pharmacogenomic or exploratory  biomarker

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research data, generated as a result of this study, are considered confidential and remain the sole
property of the sponsor. The investigator agrees to maintain this information in confidence and use
this information only to accomplish this study and will not use it for other purposes without the
sponsor's prior written consent.
The investigator understands that the information developed in the study will be used by the
sponsor in connection with the continued development ofguselkumab, and thus may be disclosed
as required to other clinical investigators or regulatory agencies. To permit the information derived
from the clinical studies to be used, the investigator is obligated to provide the sponsor with all
data obtained in the study.
The results of the study will be reported in a Clinical Study Report generated by the sponsor and
will contain data from all study sites that participated in the study as per protocol. Recruitment
performance or specific expertise related to the nature and the key assessment parameters of the
study will be used to determine a coordinating investigator for the study. Results of
pharmacogenomic or exploratory biomarker analyses performed after the Clinical Study Report
has been issued will be reported in a separate report and will not require a revision of the Clinical
Study Report.
Study participant identifiers will not be used in publication of results. Any work created in
connection with performance of the study and contained in the data that can benefit from copyright
protection (except any publication by the investigator as provided for below) shall be the property
of the sponsor as author and owner of copyright in such work.
Consistent with Good Publication Practices and International Committee of Medical Journal
Editors (ICMJE) guidelines, the sponsor shall have the right to publish such primary (multicenter)
data and information without approval from the investigator. The investigator has the right to
publish study site-specific data after the primary data are published. If an investigator wishes to
publish information from the study, a copy of the manuscript must be provided to the sponsor for
review at least 60 days before submission for publication or presentation. Expedited reviews will
be arranged for abstracts, poster presentations, or other materials. If requested by the sponsor in
writing, the investigator will withhold such publication for up to an additional 60 days to allow for
filing of a patent application. In the event that issues arise regarding scientific integrity or
regulatory compliance, the sponsor will review these issues with the investigator. The sponsor will
not mandate modifications to scientific content and does not have the right to suppress information.
For multicenter study designs and sub-study approaches, secondary results generally should not
be published before the primary endpoints of a study have been published. Similarly, investigators
will recognize the integrity of a multicenter study by not submitting for publication data derived
from the individual study site until the combined results from the completed study have been
submitted for publication, within 18 months after the study end date, or the sponsor confirms there
will be no multicenter study publication. Authorship of publications resulting from this study will
be based on the guidelines on authorship, such as those described in the ICMJE Recommendations
for the Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals, which
state that the named authors must have made a significant contribution to the conception or design

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of the work; or the acquisition, analysis, or interpretation of the data for the work; and drafted the
work or revised it critically for important intellectual content; and given final approval of the
version to be published; and agreed to be accountable for all aspects of the work in ensuring that
questions related to the accuracy or integrity of any part of the work are appropriately investigated
and resolved.
Registration of Clinical Studies and Disclosure of Results
The 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.
10.5.8. 
Data Quality Assurance
Data Quality Assurance/Quality Control
Steps to be taken to ensure the accuracy and reliability of data include the selection of qualified
investigators and appropriate study sites, review of protocol procedures with the investigator and
study site personnel before the study, periodic monitoring visits by the sponsor, and direct
transmission of clinical laboratory data from a central laboratory into the sponsor’s database.
Written instructions will be provided for collection, handling, storage, and shipment of samples.
Guidelines for eCRF completion will be provided and reviewed with study site personnel before
the start of the study.
The sponsor will review the eCRF for accuracy and completeness during on-site monitoring visits
and after transmission to the sponsor; any discrepancies will be resolved with the investigator or
designee, as appropriate. After upload of the data into the study database they will be verified for
accuracy and consistency with the data sources.
10.5.9. 
Case Report Form Completion
Case report forms are prepared and provided by the sponsor for each participant in electronic
format. All data relating to the study must be recorded in the eCRF. All eCRF entries, corrections,
and alterations must be made by the investigator or authorized study site personnel. The
investigator must verify that all data entries in the eCRF are accurate and correct.
The study data will be transcribed by study site personnel from the source documents onto an
eCRF, if applicable. Study-specific data will be transmitted in a secure manner to the sponsor.
Worksheets may be used for the capture of some data to facilitate completion of the eCRF. Any
such worksheets will become part of the participant’s source documents. Data must be entered into
eCRF in English. The eCRF must be completed as soon as possible after a participant visit and the
forms should be available for review at the next scheduled monitoring visit.
If necessary, queries will be generated in the electronic data capture (eDC) tool. If corrections to
an eCRF are needed after the initial entry into the eCRF, this can be done in either of the following
ways:

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Investigator and study site personnel can make corrections in the eDC tool at their own
initiative or as a response to an auto query (generated by the eDC tool).
Sponsor or sponsor delegate can generate a query for resolution by the investigator and study
site personnel.
10.5.10. 
Source Documents
At a minimum, source documents consistent in the type and level of detail with that commonly
recorded at the study site as a basis for standard medical care must be available for the following:
participant identification, eligibility, and study identification; study discussion and date of signed
informed consent; dates of visits; results of safety and efficacy parameters as required by the
protocol; record of all AEs and follow-up of AEs; concomitant medication; intervention
receipt/dispensing/return records; study intervention administration information; and date of study
completion and reason for early discontinuation of study intervention  or withdrawal from the
study, if applicable.
The author of an entry in the source documents should be identifiable. Given that PROs are reports
of a patient’s health condition that come directly from the patient, without interpretation by a
clinician or anyone else, the responses to PRO measures entered by trial participants into source
records cannot be overridden by site staff or investigators.
Specific details required as source data for the study and source data collection methods will be
reviewed with the investigator before the study and will be described in the monitoring guidelines
(or other equivalent document).
The minimum source documentation requirements for Section 5.1 and Section 5.2 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
Inclusion and exclusion criteria not requiring documented medical history must be verified at a
minimum by participant interview or other protocol required assessment (eg, physical
examination, laboratory assessment) and documented in the source documents.
An electronic source (eSource) system may be utilized, which contains data traditionally
maintained in a hospital or clinic record to document medical care (eg, electronic source
documents) as well as the clinical study-specific data fields as determined by the protocol. This
data is electronically extracted for use by the sponsor. If eSource is utilized, references made to
the eCRF in the protocol include the eSource system but information collected through eSource
may not be limited to that found in the eCRF.

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10.5.11. 
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 will compare the data entered into the eCRF with the source documents
(eg, hospital/clinic/physician’s office medical records). The nature and location of all source
documents will be identified to ensure that all sources of original data required to complete the
eCRF are known to the sponsor and study site personnel and are accessible for verification by the
sponsor study site contact. If electronic records are maintained at the study site, the method of
verification must be discussed with the study site personnel.
Direct access to source documents (medical records) must be allowed for the purpose of verifying
that the recorded data are consistent with the original source data. Findings from this review will
be discussed with the study site personnel. The sponsor expects that, during monitoring visits, the
relevant study site personnel will be available, the source documents will be accessible, and a
suitable environment will be provided for review of study-related documents. The monitor will
meet with the investigator on a regular basis during the study to provide feedback on the study
conduct.
In addition to on-site monitoring visits, remote contacts can occur. It is expected that during these
remote contacts, study site personnel will be available to provide an update on the progress of the
study at the site.
Central monitoring will take place for data identified by the sponsor as requiring central review.
10.5.12. 
On-Site Audits
Representatives of the sponsor's clinical quality assurance department may visit the study site at
any time during or after completion of the study to conduct an audit of the study in compliance
with regulatory guidelines and company policy. These audits will require access to all study
records, including source documents, for inspection. Participant privacy must, however, be
respected. The investigator and study site personnel are responsible for being present and available
for consultation during routinely scheduled study site audit visits conducted by the sponsor or its
designees.
Similar auditing procedures may also be conducted by agents of any regulatory body, either as part
of a national GCP compliance program or to review the results of this study in support of a
regulatory submission. The investigator should immediately notify the sponsor if he or she has
been contacted by a regulatory agency concerning an upcoming inspection.
10.5.13. 
Record Retention
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all eCRF
and all source documents that support the data collected from each participant, as well as all study
documents as specified in ICH/GCP Section 8, Essential Documents for the Conduct of a Clinical
Trial, and all study documents as specified by the applicable regulatory requirement(s). The

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investigator/institution will take measures to prevent accidental or premature destruction of these
documents.
Essential documents must be retained until at least 2 years after the last approval of a marketing
application in an ICH region and until there are no pending or contemplated marketing applications
in an ICH region or until at least 2 years have elapsed since the formal discontinuation of clinical
development of the investigational product. These documents will be retained for a longer period
if required by the applicable regulatory requirements or by an agreement with the sponsor. It is the
responsibility of the sponsor to inform the investigator/institution as to when these documents no
longer need to be retained. For trials performed under Regulation [EU] No. 536/2014, the sponsor
and the investigator shall archive the content of the clinical trial master file for at least 25 years
after the end of the clinical trial.
If the responsible investigator retires, relocates, or for other reasons withdraws from the
responsibility of keeping the study records, custody must be transferred to a person who will accept
the responsibility. The sponsor must be notified in writing of the name and address of the new
custodian. Under no circumstance shall the investigator relocate or dispose of any study documents
before having obtained written approval from the sponsor.
If it becomes necessary for the sponsor or the appropriate regulatory authority to review any
documentation relating to this study, the investigator/institution must permit access to such reports.
10.5.14. 
Study and Site Start and Closure
First Act of Recruitment
The first site open 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
study site is considered closed when all required documents and study supplies have been collected
and a study site closure visit has been performed.
The investigator may initiate study site closure at any time, provided there is reasonable cause and
sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or investigator may include but are not
limited to:
Failure of the investigator to comply with the protocol, the requirements of the IEC/IRB or
local health authorities, the sponsor's procedures, or GCP guidelines
Inadequate recruitment of participants by the investigator
Discontinuation of further study intervention development

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10.6. Appendix 6: Adverse Events, Serious Adverse Events, Product Quality
Complaints, and Other Safety Reporting: Definitions and Procedures for
Recording, Evaluating, Follow-up, and Reporting
10.6.1. 
Adverse Event Definitions and Classifications
Adverse Event
An AE is any untoward medical occurrence in a clinical study participant administered a
pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have
a causal relationship with the intervention. An AE can therefore be any unfavorable and unintended
sign (including an abnormal finding), symptom, or disease temporally associated with the use of a
medicinal (investigational or non-investigational) product, whether or not related to that medicinal
(investigational or non-investigational) product. (Definition per 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, 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 European Union  Guidelines on Pharmacovigilance for Medicinal
Products for Human Use is any untoward medical occurrence that at any dose:
Results in death
Is life-threatening
(The participant was at risk of death at the time of the event. It does not refer to an event that
hypothetically might have caused death if it were more severe.)
Requires inpatient hospitalization or prolongation of existing hospitalization
Results in persistent or significant disability/incapacity
Is a congenital anomaly/birth defect
Is a suspected transmission of any infectious agent via a medicinal product
Is Medically Important*
*Medical and scientific judgment should be exercised in deciding whether expedited reporting is
also appropriate in other situations, such as important medical events that may not be immediately
life threatening or result in death or hospitalization but may jeopardize the participant or may

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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).
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).
10.6.2. 
Attribution Definitions
Assessment of Causality
The causal relationship to study intervention  is determined by the investigator. The following
selection should be used to assess all AEs.
Related
There is a reasonable causal relationship between study intervention administration and the AE.
Not Related
There is not a reasonable causal relationship between study intervention administration and the
AE.
The term "reasonable causal relationship" means there is evidence to support a causal relationship.
10.6.3. 
Severity Criteria
An assessment of severity grade will be made using the following general categorical descriptors:
Mild: Awareness of symptoms that are easily tolerated, causing minimal discomfort and not
interfering with everyday activities.
Moderate: Sufficient discomfort is present to cause interference with normal activity.
Severe: Extreme distress, causing significant impairment of functioning or incapacitation.
Prevents normal everyday activities.
The investigator should use clinical judgment in assessing the severity of events not directly
experienced by the participant (eg, laboratory abnormalities).

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10.6.4. 
Special Reporting Situations
Special reporting situations must be reported by the investigator or site staff personnel to the
sponsor or designee within 24 hours after being made aware of the event. 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
Special reporting situations should be recorded in the eCRF and/or applicable source documents.
Any special reporting situation that meets the criteria of an SAE should be recorded on the SAE
page of the eCRF.
10.6.5. 
Procedures
All Adverse Events
All AEs, regardless of seriousness, severity, or presumed relationship to study intervention, must
be recorded using medical terminology in the source document and the eCRF. Whenever possible,
diagnoses should be given when signs and symptoms are due to a common etiology (eg, cough,
runny nose, sneezing, sore throat, and head congestion should be reported as "upper respiratory
infection"). Investigators must record in the eCRF their opinion concerning the relationship of the
AE to study therapy. All measures required for AE management must be recorded in the source
document and reported according to sponsor instructions.
For all studies with an outpatient phase, including open-label studies, the participant must be
provided with a "wallet (study) card" and instructed to carry this card with them for the duration
of the study indicating the following:
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.

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10.6.6. 
Product Quality Complaint Handling
Definition
A PQC is defined as any suspicion of a product defect related to manufacturing, labeling, or
packaging, ie, any dissatisfaction relative to the identity, quality, durability, reliability, or
performance of a distributed product, including its labeling, drug delivery system, or package
integrity. A PQC may have an impact on the safety and efficacy of the product. In addition, it
includes any technical complaints, defined as any complaint that indicates a potential quality issue
during manufacturing, packaging, release testing, stability monitoring, dose preparation, storage
or distribution of the product or the drug delivery system.
This definition includes any PQC related to a device constituent in a combination product,
including those used in the administration of the study intervention or the comparator. A device
deficiency is an inadequacy of a device with respect to its identity, quality, durability, reliability,
safety, or performance. Device deficiencies include malfunctions, use errors, and inadequate
labeling.
Procedures
All initial PQCs must be reported to the sponsor by the study site personnel within 24 hours after
being made aware of the event.
A sample of the suspected product should be maintained under the correct storage conditions until
a shipment request is received from the sponsor.
10.6.7. 
Contacting Sponsor Regarding Safety, Including Product Quality
The names (and corresponding telephone numbers) of the individuals who should be contacted
regarding safety issues, PQC, or questions regarding the study are listed in the Contact Information
page(s), which will be provided as a separate document.

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10.7. Appendix 7: Contraceptive and Barrier Guidance
Participants must follow contraceptive measures as outlined in Section 5.1. Pregnancy information
will be collected and reported as noted in Section 8.3.5 and Appendix 6 (Section 10.6).
Definitions
Woman of Childbearing Potential
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 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.
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 should be consistent with local regulations
regarding the acceptable methods of contraception for those participating in clinical studies.
Typical use failure rates may differ from those when used consistently and correctly. Use should
be consistent with local regulations regarding the use of contraceptive methods for participants in
clinical studies.

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Examples of Contraceptives
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
Intrauterine hormone-releasing system
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 should be used.
Spermatogenesis cycle is approximately 74days.)
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

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a) Typical use failure rates may differ from those when used consistently and correctly. Use should be
consistent with local regulations regarding the use of contraceptive methods for participants in
clinical studies.
b) Hormonal contraception may be susceptible to interaction with the study intervention, which may
reduce the efficacy of the contraceptive method. In addition, consider if the hormonal contraception
may interact with the study intervention.
c) Male condom and female condom should not be used together (due to risk of failure with friction).

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10.8. Appendix 8: Crohn’s Disease Activity Index
       DISEASE ACTIVITY INDEX              
  SUM  X FACTOR  
    SUBTOTAL
Total number of liquid or very soft stools in the
previous 7 days 
x 2 
=
Sum abdominal pain/cramps ratings
(total for previous 7 days): 
x 5 
=
0 =  none 
2 =  moderate
1 =  mild 
3 =  severe
General well-being (total for previous 7 days): 
x 7 
=
0 =  generally well 
3 =  very poor
1 =  slightly under par 
4 =  terrible
2 =  poor
Categories currently present and
presumed to be related to Crohn’s disease:  0 = no; 1 = yes
= 
arthritis/arthralgia 
x 20 
=
= 
iritis/uveitis 
x 20 
=
= 
erythema nodosum/pyoderma
gangrenosum/aphthous stomatitis 
x 20 
=
= 
anal fissure, fistula or abscess 
x 20 
=
= 
other fistula 
x 20 
=
= 
fever over 100° F (37.8° C) during the
previous 7 days. 
x 20 
=
During the previous 7 days has subject received
antidiarrheal therapy at least once:
OR  
x 30 
=
During the previous 7 days has subject received
opiate therapy on each of the 7 days:
0 = no
1 = yes
Abdominal mass: 
x 10 
=
0 = none 
2 = questionable 
5 = definite
Hematocrit: 
x 6 
=
Males: (47-Hct) = SUM  
(add or subtract by sign)
Females: (42-Hct) = SUM
(Standard Weight - Actual Body Weight) 
x 100 =  
*
x 1 
=
Standard Weight 
(add or subtract by sign,  round to 3 decimal places)
* If this value is less than -10 then enter -10 here.
Standard weight and actual weight must be in same units (kg or lb)
TOTAL =
(round total to integer)

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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 10), 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

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10.10. Appendix 10: 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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10.11. Appendix 11: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located
directly before the Table of Contents.
Amendment 1 (13 September 2023)
Overall Rationale for the Amendment To address a
The changes made to the clinical protocol CNTO1959CRD3004 as part of Protocol Amendment 1 are listed
below, including the rationale of each change and a list of all applicable sections.
Section Number 
and Name
Description of Change 
Brief Rationale
Section 1.3
Schedule of
Activities, Table 4
Removed “additional study visits.” 
To clarify that there are no
additional visits.
Section 2.3.1 Risks
for Study
Participation
Participants who have received a live viral or 
bacterial vaccination within 4 weeks prior to 
screening will be excluded from the study.
For clarification and alignment with
Exclusion Criterion #15.
Section 6.1 Study
Intervention(s)
Administered,
Figure 2
Schema modified to add blinded sham rescue arms 
for the guselkumab treatment groups. 
To clarify the rescue treatment for
participants randomized to
guselkumab.
Section 6.3
Measures to
Minimize Bias:
Randomization and
Blinding
The full sponsor unblinding will occur at the
Week 48 DBL. At the Week 24 DBL, data will be
unblinded for analysis to a limited number of
sponsor personnel only. Identification of sponsor
personnel who will have access to the unblinded
participant-level data at the time of the Week 24
DBL will be documented before unblinding. The
method by which the study integrity will be
maintained will be described in the SAP.
To clarify that only a limited
number of sponsor personnel will
be unblinded at Week 24.
Section 8.6.4
Pharmacodynamics
Test results for CRP and fecal calprotectin are
accessible to investigators through the central
laboratory as previously outlined in a protocol
clarification communication.
To clarify laboratory results
accessible to investigators.
Section 9.4.1
General
Considerations
The SAP will be finalized prior to the first DBL
(ie, Week 24). Any modifications and/or
clarifications to protocol-specified statistical
analyses or any other statistical analyses will be
described in the SAP.
Clarification provided for analyses of key
endpoints at the Week 24 and Week 48 DBLs.
To clarify that the SAP contains all
planned analyses and supersedes
the protocol analyses and to clarify
the timing of the evaluation of the
endpoints with respect to the DBLs.
CCI
CCI
CCI
CCI

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Section Number 
and Name
Description of Change 
Brief Rationale
Throughout the 
protocol 
Minor grammatical, formatting, and spelling 
changes, and changes to ensure consistency across
the document were made.
Minor errors were noted.

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11. 
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INVESTIGATOR AGREEMENT
I have read this protocol and agree that it contains all necessary details for carrying out this study. I will
conduct the study as outlined herein and will complete the study within the time designated.
I will provide copies of the protocol and all pertinent information to all individuals responsible to me who
assist in the conduct of this study. I will discuss this material with them to ensure that they are fully informed
regarding the study intervention, the conduct of the study, and the obligations of confidentiality.
Coordinating Investigator (where required):
Name (typed or printed):
Institution and Address:
Signature: 
Date:
(Day Month Year)
Principal (Site) Investigator:
Name (typed or printed):
Institution and Address:
Telephone Number:
Signature: 
Date:
(Day Month Year)
Sponsor's Responsible Medical Officer:
Name (typed or printed): 
Institution: 
Janssen Research & Development
Signature: electronic signature appended at the end of the protocol 
Date: 
04 October 2024
(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
 
04-Oct-2024
21:48:44
(GMT)
Document Approval
PPD