Clinical trial NCT05784129
Conditions: Crohn's Disease
Keywords: Endoscopy, Postoperative, Ileocolonic resection
Sponsor: Janssen Research & Development, LLC
Start date: 2023-02-21; Completion date: 2023-10-10
Enrollment: 4 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate the effectiveness of guselkumab treatment compared with placebo (an inactive substance with no medicine) in preventing recurrence of Crohn's disease in participants after surgery.

Detailed description:

Arms: arm 1: Participants will receive Guselkumab Dose 1 subcutaneously (SC) followed by Dose 2 SC thereafter through Week 144. Participants with disease recurrence will receive guselkumab SC treatment. arm 2: Participants will receive matching placebo injections subcutaneously. Participants with disease recurrence will receive guselkumab SC treatment.
Interventions: intervention 1: Guselkumab intervention 2: Placebo
Intervention descriptions: intervention 1: Guselkumab will be administered subcutaneously. intervention 2: Placebo will be administered subcutaneously.

Protocol documents:
Prot_000.pdf: 
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
1
Status: Approved,  Date: 02 December 2022
Janssen Research & Development *
Clinical Protocol
Protocol Title
A Randomized, Double-blind, Placebo-controlled Study Evaluating the Safety and Efficacy 
of Guselkumab for the Treatment of Participants with Crohn’s Disease After Surgical 
Resection
Prevention of Recurrence post Operatively with Guselkumab Relative to Endoscopy and 
SymptomS: The PROGRESS Study
Protocol CNTO1959CRD3007; Phase 3
Version: Amendment 1
CNTO1959 (guselkumab)
*Janssen Research & Development is a global organization that operates through different legal entities in
various countries/territories. 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.
Studies conducted at sites in the United States (US) will be conducted under US Food & Drug 
Administration Investigational New Drug (IND) regulations (21 CFR Part 312).
IND:  133845
EudraCT NUMBER: 2022-002389-33
Status:
Approved
Date:
02 December 2022
Prepared by:
Janssen Research & Development, LLC
EDMS number:
EDMS-RIM-786244, 2.0
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.
NCT05784129


CNTO1959 (guselkumab)
Clinical Protocol CNTO1959CRD3007 Amendment 1
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
2
Status: Approved,  Date: 02 December 2022
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document
Date
Amendment 1
02 December 2022
Original Protocol
08 July 2022
Amendment 1 (02 December 2022)
Overall Rationale for the Amendment:  The overall rationale for the amendment was to further clarify 
how cross over to open-label guselkumab treatment for participants is handled, which includes the addition 
of a separate Schedule of Activities for participants who cross over to guselkumab. Additional reasons for 
the amendment were to:

Correct mentions of clinical recurrence to be consistent with Health Authority recommendation to use 
“disease recurrence” instead of “clinical recurrence”

Add clarification to the statistical analysis including (1) adding cross over to open-label guselkumab 
induction as an intercurrent event, (2) censoring participants at cross over for the time to disease 
recurrence endpoint if they have confirmed endoscopic recurrence at Week 24 or 48 and cross over to 
open-label guselkumab treatment, (3) censoring participants who cross over for endoscopic recurrence 
at Week 24 rather than being included in the definition for disease recurrence.

Make changes to the original Schedule of Activities relating to visits.
The changes made to the clinical protocol CNTO1959CRD3007 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
Synopsis/3 Objectives and 
Endpoints, Secondary Objectives
Reworded the secondary objective 
for evaluating steroid use. 
Pharmacokinetics analyses added to 
secondary objectives.
Clarification.
Clarification.
Synopsis/9.1 Statistical 
Hypotheses;
4.1 Endpoints;
9.2 Sample Size Determination; 
9.4.2 Primary Endpoint
Wording altered to state superiority 
based on endoscopic recurrence 
prior to or at Week 48 (rather than 
at Week 48).  
Correction.
1.2 Study Schema
Corrected symbols for 
 dose 
(will be 
 doses) 
Clarification.
1.3 Schedule of Activities
Created a separate SOA for 
participants who cross over to 
guselkumab treatment, such that 
there is one SOA for participants 
who do not cross over (and
separating the Flare and End of 
Treatment visits for clarity), and 
one for participants who do.
Clarification.
Added vital signs collection 
Week 24.
Inadvertently omitted in original 
protocol.
Added physical exam for Flare and 
Early Termination visits.
Inadvertently omitted in original 
protocol.
CCI
CCI
NCT05784129


CNTO1959 (guselkumab)
Clinical Protocol CNTO1959CRD3007 Amendment 1
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
3
Status: Approved,  Date: 02 December 2022
Section Number and Name
Description of Change
Brief Rationale
Separated the Flare and Early 
Termination visits, and removed 
PROs (WPAI, PROMIS-29, and 
PROMIS-Fatigue 7a) from the 
Flare visit.
The PROs were intended to be 
completed at the Early Termination 
visit only.
Split the row pertaining to the 
CDAI assessment into 2 rows, one 
for reminder to complete the 
electronic CDAI and one for 
calculation of CDAI.
Clarification.
Added footnote for final visit: If 
clinically appropriate and allowed 
by local regulations, the Week 156 
visit can be done by telephone.
Reducing participant burden of 
frequent site visits, since they will 
have an on-site visit for the Week 
152 Final Efficacy Visit.
Details added for footnote for the 
Flare visit.
Clarification.
Throughout protocol
Where relevant, changed “clinical 
recurrence” to “endoscopic” or 
“disease recurrence,” as 
appropriate.
To align with Health Authority
feedback.
2.3.1 Risks for Study Participation, 
Risks Table: For risk of clinical 
worsening of CD  
Added all criteria for cross over to 
open-label induction and removed 
mention of clinical recurrence. 
Clarification.
4.1 Overall Design, Overall Design
4.1 Overall Design, Study Length
Edited to clarify that the optional 
cross over at Week 24 is at the 
discretion of the investigator when 
there is ONLY endoscopic 
recurrence.
Clarified that participation follow-
up may vary for the main study 
period. 
Clarification.
Clarification.
4.3 Justification for Dose
Added all criteria for cross over to 
open-label induction and removed 
mention of clinical recurrence.
Clarification
4.4 End of Study Definition, 
Participant Study Completion 
Definition
Added details for study completion 
criteria.
Clarification.
5.1 Inclusion Criteria, #3
Clarified that participants can have 
undergone an ileocolonic surgical 
resection for CD prior to the 
baseline visit.
Added to allow for 
screening/consent of participants 
prior to surgery.
5.1 Inclusion Criteria, #13
Edited criterion pertaining to 
adherence to all specified 
requirements in this protocol to 
include an ileocolonoscopy at 
1 year or upon concern for clinical 
flare.
Clarification.
6.1 Study Interventions 
Administered, Table 1: Description 
of Interventions, Dose Formulation, 
Unit Dose Strength, Dosing 
Instructions 
Details added for dosing upon cross 
over, and to clarify induction vs 
maintenance dosing details. 
Clarifications added for induction 
vs maintenance dosing.
Clarification and to allow for cross 
over guselkumab doses 1 and 3 to 
be administered at a scheduled visit 
in order to correspond with cross 
over visit schedule. 
Clarification.
NCT05784129


CNTO1959 (guselkumab)
Clinical Protocol CNTO1959CRD3007 Amendment 1
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
4
Status: Approved,  Date: 02 December 2022
Section Number and Name
Description of Change
Brief Rationale
6.2 Preparation/Handling/Storage/
Accountability
Added that guselkumab will also be 
supplied as 
.
Correction.
6.5.1 Open Label/Cross Over 
Treatment
Added criteria for not needing an 
ileocolonoscopy before crossing 
over.
Clarification.
6.7 Treatment of Overdose
Deleted text about considering dose 
reduction, and for the duration of 
overdosing.
Removed bullet requiring obtaining 
a serum sample for PK analysis if 
requested by Medical Monitor.
Corrections.
There is no clinical indication for, 
or analysis needed for this serum 
sample.
6.8 Concomitant Therapy
Deleted requirement to record dose 
of concomitant therapies.
There is no clinical or analysis need 
for these data (other than 
corticosteroid dosing, which will be 
recorded in the CRF). 
8 Study Assessments and 
Procedures, Week 0 Visit
Deleted mention of informed 
consent (is already mentioned under 
Screening).
Correction.
8 Study Assessments and 
Procedures, Post-baseline Visits
Changed last CDAI diary 
completion to Week 152 (from 
Week 156).
Correction.
8 Study Assessments and 
Procedures, Cross Over Visit
Added details describing dosing 
and subsequent study visits for 
participants who cross over to 
guselkumab treatment. 
To simplify and clarify the cross 
over schedule and procedures for 
sites, a separate cross over schedule 
was added.
8 Study Assessments and 
Procedures, Study-Specific 
Materials
Clarified the instructions for use.
Deleted Symptom and Health Diary 
Cards. Added that study medication 
diary is for home dosing.
Added Laboratory Manual and 
Source Documents as applicable, as 
well as manual and quick reference 
guide for PROs.
Clarification.
An electronic diary will instead be 
used for PROs.
Clarifications.
8.1.3 Endoscopic Assessments of 
the Intestinal Mucosa
Edits made to clarify endoscopic vs 
disease recurrence.
Clarification.
8.4.6 Injection Site Reactions
Noted that injection sites will be 
evaluated for reactions only at on-
site visits.
Clarification.
8.4.8 Infections
Deleted requirement to discuss any 
serious infections with the medical 
monitor or designee.
Clarification so decision to 
discontinue study intervention is at 
the discretion of the investigator 
without requirement to consult with 
sponsor.
8.8.2 Mucosal Biopsy (Histology, 
RNA, and Single Cell Isolation)
Added details for protein and gene 
expression measurement.
For completeness.
8.8.3 Serum-based Biomarkers
Clarified language and noted 
analyses will include IL-17A and 
IL-22.
Clarification.
1.3 Schedule of Activities; 
8.8 Biomarkers
Reorganized text to clarify samples 
to be taken for analysis of DNA vs 
RNA, and added details to align 
with current sponsor’s text for 
Clarification and additional details.
CCI
NCT05784129


CNTO1959 (guselkumab)
Clinical Protocol CNTO1959CRD3007 Amendment 1
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
5
Status: Approved,  Date: 02 December 2022
Section Number and Name
Description of Change
Brief Rationale
protocols describing procedures for 
these. 
9.4.2 Primary Endpoint, Primary 
Estimand of Endoscopic Recurrence 
prior to or at Week 48, Treatment by 
Week 48
Added cross over to open-label 
guselkumab as an intercurrent 
event. 
For completeness.
9.4.3 Secondary Endpoints
Edited details regarding censoring 
at cross over for time to disease
recurrence endpoint.
Clarification.
9.4.3 Secondary Endpoints, 
Estimands and Estimators (for 
Clinical Remission without Disease 
Recurrence at Week 48)
Estimators (for Disease 
Recurrence)
Changed mention of primary 
endpoint to first secondary 
endpoint.
Updated details for ICEs and 
estimators.
Added the (specific) list of other 
secondary endpoints; however, 
frequency of AEs and SAEs was 
deleted as another secondary 
endpoint.
Correction.
For completeness and to eliminate 
redundancy.
Correction.
9.4.4 Other/Exploratory Endpoints
Added endpoint of endoscopic 
recurrence prior to or at Week 24.
Added exploratory analysis for risk 
factors of endoscopic and disease 
recurrence.
Added a sensitivity analysis of the 
primary endpoint using a Rutgeerts 
score of > i3 to define endoscopic 
recurrence.
Inadvertently omitted from original 
protocol.
Inadvertently omitted from original 
protocol.
For completeness.
9.4.6.2 Pharmacogenomic 
Analyses; 9.4.6.3 Biomarker 
Analyses 
Deleted text that was redundant 
with text in Sections 8.7 and 8.8,
and added text pertaining to the 
analyses.
Clarification and more complete 
descriptions of analyses.
Appendix 7: Liver Safety: 
Suggested Actions and Follow-up 
Assessments
Replaced prior version of appendix 
with a version with similar 
instructions but in a format that is 
easier to follow. 
Clarification.
New Appendix 9: Clinical Disease 
Activity Index
Added a sample CDAI measure as 
Appendix 9.
Information added as tools to aid 
sites in calculating CDAI.
NCT05784129


CNTO1959 (guselkumab)
Clinical Protocol CNTO1959CRD3007 Amendment 1
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
6
Status: Approved,  Date: 02 December 2022
TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................................... 2
TABLE OF CONTENTS ............................................................................................................................... 6
LIST OF IN-TEXT TABLES.......................................................................................................................... 9
1.
PROTOCOL SUMMARY ................................................................................................................... 10
1.1.
Synopsis......................................................................................................................................... 10
1.2.
Schema .......................................................................................................................................... 15
1.3.
Schedule of Activities (SoA)........................................................................................................... 16
2.
INTRODUCTION................................................................................................................................ 34
2.1.
Study Rationale.............................................................................................................................. 34
2.2.
Background .................................................................................................................................... 35
2.2.1.
Clinical Development of Guselkumab in Crohn’s Disease ......................................................... 35
2.2.2.
Rationale for the Use of Guselkumab in Postoperative Crohn’s Disease.................................. 37
2.3.
Benefit-risk Assessment................................................................................................................. 39
2.3.1.
Risks for Study Participation....................................................................................................... 39
2.3.2.
Benefits for Study Participation .................................................................................................. 42
2.3.3.
Benefit-risk Assessment for Study Participation......................................................................... 42
3.
OBJECTIVES AND ENDPOINTS ..................................................................................................... 43
4.
STUDY DESIGN ................................................................................................................................ 45
4.1.
Overall Design................................................................................................................................ 45
4.2.
Scientific Rationale for Study Design............................................................................................. 47
4.2.1.
Participant Input Into Design ...................................................................................................... 48
4.2.2.
Study-specific Ethical Design Considerations ............................................................................ 48
4.3.
Justification for Dose...................................................................................................................... 49
4.4.
End of Study Definition................................................................................................................... 50
5.
STUDY POPULATION ...................................................................................................................... 51
5.1.
Inclusion Criteria ............................................................................................................................ 51
5.2.
Exclusion Criteria ........................................................................................................................... 54
5.3.
Lifestyle Considerations................................................................................................................. 59
5.4.
Screen Failures .............................................................................................................................. 60
6.
STUDY INTERVENTION AND CONCOMITANT THERAPY............................................................ 60
6.1.
Study Interventions Administered .................................................................................................. 60
6.2.
Preparation/Handling/Storage/Accountability ................................................................................ 64
6.3.
Measures to Minimize Bias: Randomization and Blinding............................................................. 65
6.4.
Study Intervention Compliance...................................................................................................... 67
6.5.
Dose Modification........................................................................................................................... 67
6.5.1.
Open Label / Cross over Treatment ........................................................................................... 68
6.6.
Continued Access to Study Intervention After the End of the Study ............................................. 68
6.7.
Treatment of Overdose .................................................................................................................. 69
6.8.
Concomitant Therapy..................................................................................................................... 69
6.8.1.
Concomitant Conventional CD Medications............................................................................... 69
6.8.1.1.
Oral Corticosteroids................................................................................................................. 69
6.8.2.
Prohibited Concomitant Medications .......................................................................................... 70
6.8.3.
Vaccinations (including COVID-19)............................................................................................ 71
7.
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ............................................................................................... 71
7.1.
Discontinuation of Study Intervention ............................................................................................ 71
7.2.
Participant Discontinuation/Withdrawal From the Study................................................................ 73
7.3.
Lost to Follow up............................................................................................................................ 74
NCT05784129


CNTO1959 (guselkumab)
Clinical Protocol CNTO1959CRD3007 Amendment 1
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
7
Status: Approved,  Date: 02 December 2022
8.
STUDY ASSESSMENTS AND PROCEDURES ............................................................................... 74
8.1.
Efficacy Assessments .................................................................................................................... 78
8.1.1.
CDAI ........................................................................................................................................... 78
8.1.2.
PRO-2: Unweighted Mean Daily CDAI Components of the Total Number of Liquid or 
Very Soft Stools and the AP ....................................................................................................... 79
8.1.3.
Endoscopic Assessments of the Intestinal Mucosa ................................................................... 79
8.1.4.
Histologic Assessments Based on Global Histologic Disease Activity (GHAS), Geboes 
Score, and Robarts Histopathology Index (RHI) ........................................................................ 80
8.1.5.
Inflammatory PD markers: CRP and Fecal Calprotectin............................................................ 81
8.1.6.
External Perianal Fistula Assessment........................................................................................ 81
8.2.
Patient-reported Outcomes............................................................................................................ 81
8.2.1.
Patient-reported Outcomes Measurement Information System (PROMIS)-29 ......................... 81
8.2.2.
PROMIS Fatigue-7a ................................................................................................................... 82
8.2.3.
Work Productivity and Activity Index for Crohn’s disease (WPAI-CD)....................................... 82
8.3.
Healthcare Resource Utilization Data............................................................................................ 82
8.4.
Safety Assessments....................................................................................................................... 82
8.4.1.
Physical Examinations................................................................................................................ 83
8.4.2.
Vital Signs................................................................................................................................... 83
8.4.3.
Clinical Safety Laboratory Assessments .................................................................................... 83
8.4.4.
Pregnancy Testing...................................................................................................................... 83
8.4.5.
Suicidal Ideation and Behavior Risk Monitoring ......................................................................... 84
8.4.6.
Injection Site Reactions .............................................................................................................. 85
8.4.7.
Hypersensitivity Reactions.......................................................................................................... 85
8.4.8.
Infections .................................................................................................................................... 86
8.4.9.
Tuberculosis Evaluations............................................................................................................ 86
8.4.9.1.
Initial Tuberculosis Evaluation................................................................................................. 86
8.4.9.2.
Ongoing Tuberculosis Evaluation............................................................................................ 86
8.5.
Adverse Events, Serious Adverse Events, and Other Safety Reporting ....................................... 87
8.5.1.
Time Period and Frequency for Collecting Adverse Event and Serious Adverse Event 
Information.................................................................................................................................. 87
8.5.2.
Method of Detecting Adverse Events and Serious Adverse Events .......................................... 88
8.5.3.
Follow-up of Adverse Events and Serious Adverse Events ....................................................... 88
8.5.4.
Regulatory Reporting Requirements for Serious Adverse Events and Anticipated 
Events......................................................................................................................................... 89
8.5.5.
Pregnancy................................................................................................................................... 89
8.5.6.
Adverse Events of Special Interest............................................................................................. 90
8.6.
Pharmacokinetics........................................................................................................................... 90
8.6.1.
Evaluations ................................................................................................................................. 90
8.6.2.
Analytical Procedures................................................................................................................. 90
8.6.3.
Pharmacokinetic Parameters and Evaluations........................................................................... 90
8.7.
Genetics and Pharmacogenomics................................................................................................. 90
8.8.
Biomarkers ..................................................................................................................................... 91
8.8.1.
Whole-Blood-based Biomarkers................................................................................................. 91
8.8.2.
Mucosal Biopsy (Histology, RNA, and Single Cell Isolation)...................................................... 92
8.8.3.
Serum-based Biomarkers........................................................................................................... 92
8.9.
Immunogenicity Assessments ....................................................................................................... 92
9.
STATISTICAL CONSIDERATIONS.................................................................................................. 93
9.1.
Statistical Hypotheses.................................................................................................................... 93
9.2.
Sample Size Determination ........................................................................................................... 93
9.3.
Participant Analysis Sets................................................................................................................ 95
9.4.
Statistical Analyses ........................................................................................................................ 96
9.4.1.
General Considerations.............................................................................................................. 96
9.4.2.
Primary Endpoint ........................................................................................................................ 96
9.4.3.
Secondary Endpoints.................................................................................................................. 98
9.4.4.
Other/Exploratory Endpoints .................................................................................................... 101
9.4.5.
Safety Analyses ........................................................................................................................ 102
9.4.6.
Other Analyses ......................................................................................................................... 103
NCT05784129


CNTO1959 (guselkumab)
Clinical Protocol CNTO1959CRD3007 Amendment 1
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
8
Status: Approved,  Date: 02 December 2022
9.4.6.1.
Pharmacokinetic Analyses .................................................................................................... 103
9.4.6.2.
Pharmacogenomic Analyses................................................................................................. 103
9.4.6.3.
Biomarkers Analyses............................................................................................................. 103
9.4.6.4.
Immunogenicity Analyses...................................................................................................... 104
9.4.6.5.
Pharmacokinetic/Pharmacodynamic Analyses ..................................................................... 104
9.5.
Interim Analysis............................................................................................................................ 104
10.
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .......................... 105
10.1.
Appendix 1: Abbreviations ........................................................................................................... 105
10.2.
Appendix 2: Clinical Laboratory Tests ......................................................................................... 107
10.3.
Appendix 3: Regulatory, Ethical, and Study Oversight Considerations....................................... 108
10.3.1.
Regulatory and Ethical Considerations .................................................................................... 108
10.3.2.
Financial Disclosure.................................................................................................................. 111
10.3.3.
Informed Consent Process Form.............................................................................................. 111
10.3.4.
Data Protection ......................................................................................................................... 112
10.3.5.
Long-term Retention of Samples for Additional Future Research............................................ 113
10.3.6.
Publication Policy/Dissemination of Clinical Study Data .......................................................... 113
10.3.7.
Data Quality Assurance............................................................................................................ 115
10.3.8.
Case Report Form Completion................................................................................................. 115
10.3.9.
Source Documents ................................................................................................................... 116
10.3.10.
Monitoring ................................................................................................................................. 117
10.3.11.
On-site Audits ........................................................................................................................... 117
10.3.12.
Record Retention...................................................................................................................... 118
10.3.13.
Study and Site Start and Closure ............................................................................................. 118
10.4.
Appendix 4: Adverse Events, Serious Adverse Events, Product Quality Complaints, and 
Other Safety Reporting: Definitions and Procedures for Recording, Evaluating, Follow-up, 
and Reporting............................................................................................................................... 119
10.4.1.
Adverse Event Definitions and Classifications ......................................................................... 119
10.4.2.
Attribution Definitions................................................................................................................ 120
10.4.3.
Severity Criteria ........................................................................................................................ 120
10.4.4.
Special Reporting Situations .................................................................................................... 121
10.4.5.
Procedures ............................................................................................................................... 121
10.4.6.
Product Quality Complaint Handling......................................................................................... 123
10.4.7.
Contacting Sponsor Regarding Safety, Including Product Quality........................................... 123
10.5.
Appendix 5: Contraceptive Guidance .......................................................................................... 124
10.6.
Appendix 6: Hepatitis B Virus (HBV) Screening with HBV DNA Testing..................................... 127
10.7.
Appendix 7: Liver Safety: Suggested Actions and Follow-up Assessments................................ 128
10.8.
Appendix 8: Study Conduct During a Natural Disaster/Major Disruption/ Pandemic .................. 132
10.9.
Appendix 9: Clinical Disease Activity Index ................................................................................. 134
11.
REFERENCES................................................................................................................................. 135
INVESTIGATOR AGREEMENT ............................................................................................................... 138
NCT05784129


CNTO1959 (guselkumab)
Clinical Protocol CNTO1959CRD3007 Amendment 1
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
9
Status: Approved,  Date: 02 December 2022
LIST OF IN-TEXT TABLES
Table 1:
Description of Interventions ...................................................................................................... 62
Table 2:
Recommended Tapering Schedule for Oral Corticosteroids.................................................... 70
Table 3:
Modified Rutgeerts Score ......................................................................................................... 80
Table 4:
Endoscopic Recurrence, Placebo Group.................................................................................. 93
Table 5:
Power to Detect a Treatment Effect Based on Different Scenarios in Endoscopic 
Recurrence ............................................................................................................................... 94
Table 6:
Power to Detect a Treatment Effect Based on Different Scenarios in Clinical 
Remission without Disease Recurrence................................................................................... 94
Table 7:
Disease Recurrence, Placebo Group ....................................................................................... 95
Table 8:
Power to Detect a Treatment Effect Based on Different Scenarios in Disease 
Recurrence ............................................................................................................................... 95
Table 9:
Description of Analysis Populations.......................................................................................... 96
NCT05784129


CNTO1959 (guselkumab)
Clinical Protocol CNTO1959CRD3007 Amendment 1
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
10
Status: Approved,  Date: 02 December 2022
1.
PROTOCOL SUMMARY
1.1.
Synopsis
A Randomized, Double-blind, Placebo-controlled Study Evaluating the Safety and Efficacy of Guselkumab 
for the Treatment of Participants with Crohn’s Disease After Surgical Resection: PROGRESS
Guselkumab is a fully human immunoglobulin G1 lambda (IgG1 lambda) monoclonal antibody (mAb) that 
binds to the p19 subunit of human interleukin (IL)-23 with high specificity and affinity. The binding of 
guselkumab to the IL-23p19 subunit blocks the binding of extracellular IL-23 to the cell surface IL-23 
receptor, thus inhibiting IL-23 specific intracellular signaling and downstream activation and cytokine 
production. In this manner, guselkumab inhibits the biological activity of IL-23 in all in vitro assays 
examined.
BENEFIT-RISK ASSESSMENT
The benefit-risk assessment is described in detail in Section 2.3. 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 to prevent recurrence of Crohn’s 
disease (CD)
postoperatively
based on promising efficacy results in a Phase 2 study 
(CNTO1959CRD3001). 
Risks of the study intervention include clinical worsening of CD, serious infection or reactivation of latent 
infection, hypersensitivity reactions, malignancy, liver injury and immunosuppression. Risks associated 
with study procedures include rare risks of associated with video ileocolonoscopy (eg bleeding, intestinal 
perforation) or risk of minimal radiation exposure from a chest x-ray.
Potential benefits to study participation include possible prevention of recurrence of CD postoperatively, 
improved disease control related to the frequent study visits and medical care, and the satisfaction of 
contributing to scientific research.
The use of placebo is justified because there are currently no approved treatments for the indication of 
reducing the risk of recurrent CD after surgical resection and therefore a placebo comparator is necessary 
to establish whether there is meaningful benefit from the study intervention. Furthermore, the study 
population consists of participants with inactive CD at baseline, and participants who experience disease 
recurrence will then receive open-label, full subcutaneous guselkumab induction.
OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary

To evaluate the efficacy of guselkumab treatment 
versus 
placebo 
in 
preventing 
endoscopic 
recurrence of CD in participants after surgery

Endoscopic recurrence prior to or at Week 48
(as defined by modified Rutgeerts score ≥ i2a in 
the neo-terminal ileum, anastomotic site, or its 
equivalent elsewhere in the GI tract [eg colonic 
ulceration])
Secondary

To evaluate clinical remission without disease 
recurrence 
in 
participants 
treated 
with 
guselkumab versus placebo after surgery

Clinical remission (CDAI < 150) without 
disease recurrence at Week 48 (as defined in 
Section 9.4.3)
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Clinical Protocol CNTO1959CRD3007 Amendment 1
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
11
Status: Approved,  Date: 02 December 2022
Objectives
Endpoints

To evaluate disease recurrence in participants 
treated with guselkumab versus placebo after 
surgery

Time-to-disease recurrence (as defined by 
CDAI/event driven criteria as described in 
Section 9.4.3) at the main study database lock, 
which will incorporate all available follow-up of 
enrolled participants at the time that the last 
participant dosed has completed the Week 48
study procedures, including the ileocolonoscopy

To evaluate symptoms such as stool frequency 
and abdominal pain scores in guselkumab versus 
placebo after surgery

Abdominal pain free (abdominal pain [AP] 
score = 0) at Week 48

Time-to-recurrence of symptoms, defined as 
time to attaining an AP mean daily score >1 (and 
also >1 point higher than baseline) along with 
stool frequency (SF) mean daily score >3 (and 
also >3 higher per day than baseline) for 2 
consecutive weeks through Week 48

To evaluate the safety and pharmacokinetics of 
guselkumab in participants with CD in the 
postoperative period

Frequency and type of adverse events (AEs) and 
serious adverse events (SAEs)

Describe serum guselkumab concentrations
over time

To evaluate the efficacy of guselkumab in 
limiting steroid use and maintaining remission in 
the postoperative period

Steroid free clinical remission at Week 48, 
defined as CDAI <150 and no corticosteroids 
within 30 days
Other

To evaluate fatigue and other patient reported 
outcomes in guselkumab versus placebo  after 
surgery

Change in PROMIS-Fatigue Short Form 7a 
score over 48 weeks

Change in PROMIS-Fatigue SF 7a at each post 
baseline visit through Week 152

Change in PROMIS-29 score, both overall score 
and individual domain scores at each post 
baseline visit through Week 152

Change from baseline in the WPAI at each post 
baseline visit through Week 152

Abdominal pain (AP score = 0) at each post 
baseline visit through Week 152

To evaluate steroid use and healthcare utilization 
in participants within the postoperative period

The 
number 
of 
participants 
not 
on 
corticosteroids and without disease recurrence 
at each post baseline visit through Week 152

The 
number 
of 
participants 
not 
on 
corticosteroids and who have not experienced 
endoscopic or disease recurrence at each post 
baseline visit through Week 152

To evaluate histologic status in CD patients after 
surgery

Histologic score (as measured by Geboes 
scale/RHI/GHAS) at Week 48 ileocolonoscopy
NCT05784129


CNTO1959 (guselkumab)
Clinical Protocol CNTO1959CRD3007 Amendment 1
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
12
Status: Approved,  Date: 02 December 2022
Objectives
Endpoints

The number of participants with Geboes score 
of 2.0 or less at Week 48 ileocolonoscopy

The number of participants with Geboes score 
over 3.1 at Week 48 ileocolonoscopy

To evaluate the efficacy and safety of open-label 
guselkumab SC induction and maintenance 
treatment in the cross over population after  
postoperative endoscopic or disease recurrence 
of CD has occurred

Clinical remission (CDAI < 150) at 24 weeks
after initiation of guselkumab SC induction

Clinical response (CDAI decrease of <100 
points or CDAI <150) at 24 weeks after 
initiation of guselkumab SC induction

Endoscopic remission (SES-CD of 3 or less) 24 
weeks after guselkumab SC induction

Endoscopic remission (modified Rutgeerts 
score <i2a) 24 weeks after guselkumab SC 
induction

To evaluate the efficacy of guselkumab treatment 
versus placebo in changes to inflammatory 
biomarkers after surgery

The change from baseline in CRP concentration 
at all postbaseline visits through Week 152

The change from baseline in fecal calprotectin 
concentration at all postbaseline visits through 
Week 152

Fecal calprotectin recurrence, defined by 
calprotectin of >200 μg/g with a 100 μg/g 
increase over baseline

To evaluate the clinical efficacy of guselkumab 
treatment 

Disease recurrence (using CDAI/Event-driven 
definition as described in Section 9.4.3) at Week 
152  

Clinical remission (CDAI <150) at each post 
baseline visit

Time to a flare of abdominal pain

To 
evaluate 
the 
endoscopic 
efficacy 
of 
guselkumab treatment

Endoscopic remission (SES-CD of 3 or less) at 
Week 24, Week 48, Week 152

Endoscopic recurrence (modified Rutgeerts 
score >i2a) at Week 24, Week 152
Key: AE = adverse event; AP = abdominal pain; CD = Crohn’s disease; CDAI = Crohn’s disease activity index; CRP 
= C-reactive protein; GI = gastrointestinal; PROMIS = Patient-Reported Outcomes Measurement Information System; 
SC = subcutaneous; SAE = serious adverse event; SES-CD = Simple Endoscopic Score - Crohn’s disease; SF = stool 
frequency
Hypothesis
It is hypothesized that guselkumab, when initiated after recent ileocolonic surgical resection for CD, is 
superior to placebo in reducing the recurrence of CD in adult patients, as measured by endoscopic 
recurrence prior to or at Week 48.
NCT05784129


NCT05784129


CNTO1959 (guselkumab)
Clinical Protocol CNTO1959CRD3007 Amendment 1
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
14
Status: Approved,  Date: 02 December 2022
Study Assessments
A complete list of efficacy and safety assessments can be found in Section 8.  Efficacy, safety, 
pharmacokinetics (PK), immunogenicity, and biomarkers will be assessed according to the Schedule of 
Activities. Efficacy assessments include the CDAI, PRO-2 score; endoscopic assessments; inflammatory 
biomarkers; external perianal fistula assessment; patient reported outcome (PRO) measures; and histologic 
assessments. 
Key safety assessments include AEs, clinical laboratory tests (hematology and chemistry), vital signs, 
screening physical examination, concomitant medication review, monitoring for hypersensitivity reactions, 
injection site reactions, suicidal ideation and behavior by the Columbia Suicide Severity Rating Scale (C-
SSRS), and early detection of active tuberculosis (TB).  
An optional pharmacogenomic blood sample will be collected to allow for pharmacogenomic research
(where local regulations permit).
STATISTICAL METHODS
A sample size of 185 participants for each cohort will have >90% power to detect differences between the 
guselkumab treatment group and placebo group for the primary endpoint, assuming a 2-sided alpha level 
of 0.05. 
Descriptive statistics (eg, mean, median, standard deviation [SD], interquartile [IQ] range, minimum, and 
maximum) will be used to summarize continuous variables. Counts and percentages will be used to 
summarize categorical variables. Graphical data displays (eg, line plots) may also be used to summarize 
data.
Analyses suitable for categorical data (eg, chi-square tests, Cochran-Mantel-Haenszel 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), analysis of covariance (ANCOVA), or a mixed model for repeated measures (MMRM), unless 
otherwise specified. If the normality assumption is in question, an ANOVA or ANCOVA on the van der 
Waerden normal scores will be used. For time to event endpoints, survival analysis techniques will be used.
The primary endpoint is endoscopic recurrence prior to or at Week 48 defined by modified Rutgeerts score 
≥ i2a in the neo-terminal ileum, anastomotic site, or its equivalent elsewhere in the gastrointestinal tract 
(eg, colonic ulceration). The primary endpoint will be analyzed based on the estimands defined in 
Section 9. The overall Type I error rate will be controlled at the significance level of 0.05 (2-sided) for the
primary and major secondary endpoints. Hierarchical testing will be performed for primary and secondary 
endpoints, the ordering of which will be described in the Statistical Analysis Plan. No multiplicity control 
will be made for other endpoints and nominal p-values will be reported.
For safety analyses, for each AE, the percentage of participants who experience at least 1 occurrence of the 
given event will be summarized by treatment group. The analyses of AEs will be performed for safety 
measures including but not limited to, AEs, SAEs, infections, and injection site reactions. Descriptive 
statistics will be calculated for selected laboratory analytes at baseline, observed values and changes from 
baseline at each scheduled timepoint.
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Clinical Protocol CNTO1959CRD3007 Amendment 1
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
29
Status: Approved,  Date: 02 December 2022
a:
Study visits should occur at the specified times post-Week 0 +/- 10 days. Note that while visits out of this window should be documented as a protocol deviation, 
performing them out of window is preferable to not performing them at all, unless so much time has passed that it is time for the next visit.  All assessments
described in this table are to be completed prior to study intervention administration, unless otherwise specified. PRO assessments should be completed first, then 
C-SSRS and then any other clinical procedures, tests, or consultations.
b:
If clinically appropriate and allowed by local regulations, the Week 156 visit can be done by telephone and no labs drawn.
c:
If a flare visit coincides with a scheduled visit, procedures for the scheduled visit should be performed, along with any additional procedures required by a flare 
visit. Flare visit blood tests are not required if performed within 2 weeks of the Flare visit.
d:
Early termination visits should ideally take place approximately 12 weeks after last study intervention administration, though if a patient intends to withdraw their 
consent sooner than this milestone the ET visit should be scheduled as needed to accommodate with the patient’s intent.
e:
Blood collected from one venipuncture will be divided into multiple aliquots of serum for the measurement of guselkumab concentration, antibodies to 
guselkumab, and a back-up sample. Details will be provided in the Laboratory Manual.
f:
Ileocolonoscopy does not need to be repeated if an ileocolonoscopy for a flare visit occurred within 12 weeks of the visit date, unless patient and investigator wish 
to, for example due to subsequent change in clinical status.
Key: AE = adverse event; CD = Crohn’s disease; CDAI = Clinical Disease Activity Index; CRP = C-reactive protein; CT = computed tomography; C-SSRS = Columbia 
Suicide Severity Rating Scale; eCRF = electronic case report form; ET = Early Termination; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human 
immunodeficiency virus; IGRA = interferon gamma release assay; OTC = over the counter; PK = pharmacokinetics; PRO = patient-reported outcome; PROMIS = 
Patient-Reported Outcomes Measurement Information System; 
; 
; TB = tuberculosis; WPAI = Work 
Productivity Activity Impairment.
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CNTO1959 (guselkumab)
Clinical Protocol CNTO1959CRD3007 Amendment 1
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Status: Approved,  Date: 02 December 2022
Cross Over (CO) Schedule of Activities (Follow if participant meets cross over criteria)
Study Visits (Week) a
Study Procedure
COb
CO+8
wks
CO+16
wks c
Every 16 
wks (up to 
Week 128) 
d
Week 144 -
Final 
Dosing 
Visit e
Week 152 -
Final 
Efficacy 
Visit f
Week 156 
-Final 
Safety 
Visit g
Early 
Terminati
on Visit
Notes
Directed physical exam, with 
full physical exam where 
noted (F)
X
X
X
X
X
X(F)
X
Directed physical exam for abdominal 
mass and fistulas at all visits.
Urine pregnancy test 
X
X
X
X
X
X
Must be performed at on-site visits prior 
to dispensing study intervention in 
participants of childbearing potential.
C-SSRS
X
X
X
X
X
X
X
X
The C-SSRS should be completed after all 
PRO assessments and before any other 
tests, procedures, or other consultations to 
prevent influencing participant 
perceptions. The investigator or trained 
study site personnel will interview the 
participant and complete the C SSRS.
Vital signs
X
X
X
Includes temperature, pulse/heart rate, 
respiratory rate, and blood pressure, 
obtained prior to and approximately 30 
minutes after the SC injection
TB evaluation / other infection 
assessment
X
X
X
X
X
X
X
X
If TB reactivation or new TB infection is 
suspected at any time during the study, 
study intervention must be withheld and 
an immediate and thorough investigation 
should be undertaken, including, where 
possible, consultation with a physician 
specializing in TB.
Concomitant therapy
X
X
X
X
X
X
X
X
Record all prescribed and OTC 
medications as specified in the eCRF, 
including initiation of any biologic 
therapy outside of that provided in this 
study.
Adverse events
X
X
X
X
X
X
X
X
Adverse events are to be recorded 
beginning after the informed consent form 
is signed through the end of the study. 
After a participant’s participation in the 
study has ended, adverse events should be 
followed as described in Section 8.5.
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CNTO1959 (guselkumab)
Clinical Protocol CNTO1959CRD3007 Amendment 1
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Status: Approved,  Date: 02 December 2022
Study Visits (Week) a
Study Procedure
COb
CO+8
wks
CO+16
wks c
Every 16 
wks (up to 
Week 128) 
d
Week 144 -
Final 
Dosing 
Visit e
Week 152 -
Final 
Efficacy 
Visit f
Week 156 
-Final 
Safety 
Visit g
Early 
Terminati
on Visit
Notes
Injection site evaluation 
X
X
X
X
X
X
X
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.
Hematology and chemistry, 
CRP
X
X
X
X
X
X
X
X
Blood collection for serum 
guselkumab concentration 
and/or anti-drug antibodies h
X
X 
X
X
X
Blood samples should be collected before 
the administration of study intervention. 
Record the actual times of PK sample 
collections.
Serum biomarkers
X
X
Serum biomarkers will be collected from 
all participants in the study to assess 
peripheral proteins related to both Crohn’s 
disease and response to guselkumab 
including (but not limited to) IL-17A and 
IL-22.
Complete daily diary
X
X
X
X
X
X
X
Diary information should be completed 
daily for the length of the study. The daily 
diary includes patient-reported data for 
the CDAI (includes PRO-2 components). 
CDAI assessment
X
X
X
X
X
X
X
For calculation of CDAI.
CDAI: The hematocrit value obtained 
during screening will be used to calculate 
CDAI at Week 0. For all other visits, the 
most recent hematocrit value obtained 
will be
used to calculate the CDAI.
Weight (component of CDAI)
X
X
X
X
X
X
X
In kilograms (kg)
Fistula assessment
X
X
X
X
X
X
X
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CNTO1959 (guselkumab)
Clinical Protocol CNTO1959CRD3007 Amendment 1
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved,  Date: 02 December 2022
Study Visits (Week) a
Study Procedure
COb
CO+8
wks
CO+16
wks c
Every 16 
wks (up to 
Week 128) 
d
Week 144 -
Final 
Dosing 
Visit e
Week 152 -
Final 
Efficacy 
Visit f
Week 156 
-Final 
Safety 
Visit g
Early 
Terminati
on Visit
Notes
Video ileocolonoscopy with 
biopsy and histology
X
X
XO+16 [OPTIONAL] May be performed 
between week 16 and 24.  If performed on 
the day of the designated visit, the 7 days 
before the initiation of the colonoscopy 
preparation should be utilized to calculate 
CDAI scores for these visits.
Final efficacy visit ileocolonoscopy  does 
not need to be repeated if the XO+16 
ileocolonoscopy occurred within 24
weeks of the visit date
Stool sample (fecal 
calprotectin) 
X
X
X
WPAI-CD
X
X
X
X
PROMIS-29
X
X
X
X
PROMIS Fatigue 7a
X
X
X
X
Crohn’s disease-related 
hospitalizations and surgeries 
X
X
X
X
X
X
X
X
Items to be recorded are listed in the 
healthcare resource utilization worksheet.
Administer (or dispense) study 
intervention i
X
X
X
X
X
All assessments described in this 
table are to be completed prior to 
study intervention administration, 
unless otherwise specified. PRO 
assessments should be completed 
first, and then any other clinical 
procedures, tests, or 
consultations. Cross over dosing: 
GUS 400 mg SC at CO, CO+4 
(home dose), CO+8; and then 
 
every 8 weeks (every other 
maintenance dose after the 
CO+16 visit will be home 
administration.
Record drug accountability
X
X
X
X
X
X
Participants will return study intervention 
packaging (cartons) when administered at 
home, for drug accountability, including 
any unadministered syringes.
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Clinical Protocol CNTO1959CRD3007 Amendment 1
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
33
Status: Approved,  Date: 02 December 2022
Footnotes:
a:
Study visits should occur at the specified times post-cross over +/- 10 days. Note that while visits out of this window should be documented as a protocol 
deviation, performing them out of window is preferable to not performing them at all. If sufficient time has passed that it is now in-window for the next subsequent 
visit, it is advised to contact the medical monitor for assistance in how to best manage the situation. All assessments described in this table are to be completed 
prior to study intervention administration, unless otherwise specified. PRO assessments should be completed first, then C-SSRS and then any other clinical 
procedures, tests, or consultations.
b:
Laboratory assessments do not need to be performed if performed within 2 weeks prior to the CO visit
c:
Approximately 16-24 weeks after cross over, it will be determined, based on investigator’s judgement, whether treatment with open-label SC guselkumab should be continued or not. 
It is recommended to include an ileocolonoscopy in this assessment. If a decision is undertaken to discontinue further study agent in the course of this assessment, an early 
termination visit should subsequently be performed.
d:
Additional follow up in cross over arm post Cross over Week 16 to occur every 16 weeks until the last dose of IP given.
e:
The final dose of IP should be given at the Final Dosing Visit, which will fall between Week 137 and Week 144 from the original randomization date. The final dose of IP should not 
be given past Week 144 from the original randomization date.
f:
The Final Efficacy Visit will occur 8 weeks after the Final Dosing Visit, between Week 145 and Week 152 from the original randomization date.
g:
The Final Safety Visit should occur 4 weeks after the Final Efficacy Visit, between Week 149 and Week 156 from the original randomization date.  If allowed by local regulations 
and if clinically appropriate, the Final Safety Visit can be done by telephone and no safety laboratory blood samples drawn.  
h
Blood collected from one venipuncture will be divided into multiple aliquots of serum for the measurement of guselkumab concentration, antibodies to 
guselkumab, and a back-up sample. Details will be provided in the Laboratory Manual.
i
Participants who discontinue study drug should have early termination visit as per protocol.
Key: AE = adverse event; CD = Crohn’s disease; CDAI = Clinical Disease Activity Index; CRP = C-reactive protein; CT = computed tomography; C-SSRS = Columbia 
Suicide Severity Rating Scale; eCRF = electronic case report form; ET = Early Termination; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human 
immunodeficiency virus; IGRA = interferon gamma release assay; OTC = over the counter; PK = pharmacokinetics; PRO = patient-reported outcome; PROMIS = 
Patient-Reported Outcomes Measurement Information System; 
; TB = tuberculosis; WPAI = Work 
Productivity Activity Impairment.
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CNTO1959 (guselkumab)
Clinical Protocol CNTO1959CRD3007 Amendment 1
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
34
Status: Approved,  Date: 02 December 2022
2.
INTRODUCTION
Guselkumab is a fully human immunoglobulin G1 lambda (IgG1 lambda) monoclonal antibody 
(mAb) that binds to the p19 subunit of human interleukin (IL)-23 with high specificity and affinity. 
The binding of guselkumab to the IL-23p19 subunit blocks the binding of extracellular IL-23 to 
the cell surface IL-23 receptor, thus inhibiting IL-23 specific intracellular signaling and 
downstream activation and cytokine production. In this manner, guselkumab inhibits the biological 
activity of IL-23 in all in vitro assays examined.
Guselkumab (CNTO1959, TREMFYA®) is currently approved for the treatment of adults with 
moderate-to-severe plaque psoriasis (in patients who are candidates for systemic therapy or 
phototherapy) and moderate-to-severe psoriatic arthritis, in the United States (US), European 
Union (EU), Canada, and several countries in Latin America and the Asia-Pacific region. 
Guselkumab has also been approved for the treatment of generalized pustular psoriasis, 
erythrodermic psoriasis, and palmoplantar pustulosis in Japan. In addition, guselkumab is being 
evaluated in both moderate to severe ulcerative colitis (UC) and Crohn’s disease (CD), as well as 
in several other immune-mediated dermatologic and rheumatologic diseases globally.
For the most comprehensive nonclinical and clinical information regarding guselkumab, refer to 
the latest version of the Investigator's Brochure (IB) and Addenda for guselkumab.
The term “study intervention” throughout the protocol, refers to study drug as defined in 
Section 6.1, Study Interventions Administered. 
The term "sponsor" used throughout this document refers to the entities listed in the Contact 
Information page(s), which will be provided as a separate document.
2.1.
Study Rationale
Crohn’s disease (CD) is a chronic debilitating inflammatory disease of the digestive tract with a 
remitting and relapsing course. Despite the use of immunosuppressants and biologic therapies, 
approximately 26-47% of all patients with CD will require surgery within 10 years of diagnosis 
(Peyrin-Biroulet 2010, Frolkis 2013, Tsai 2021). Surgery is not a cure and disease recurrence after 
surgery is common. 
Postoperative Crohn’s disease (POCD) can affect all patients with CD regardless of their previous 
disease severity, and the two types of postoperative recurrences described in the literature -
endoscopic recurrence and clinical recurrence - are common. Meta-analyses of placebo-controlled 
randomized clinical trials in POCD demonstrated that postoperative endoscopic recurrence occurs 
in 50-58% of placebo-treated patients within 52 weeks (Renna 2008, Pascua 2008). Clinical 
recurrence at 52 weeks after intestinal resection for CD has been demonstrated in 10-38% of 
placebo-treated patients in a pooled analysis of randomized controlled trials (Buisson 2012). In the 
PREVENT trial - the first, large, multicenter placebo-controlled POCD study with a biologic 
(infliximab) - the placebo clinical recurrence and placebo endoscopic recurrence rates at or before 
Week 76 were 20% and 60%, respectively (Reguiero 2016). 
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Clinical Protocol CNTO1959CRD3007 Amendment 1
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Status: Approved,  Date: 02 December 2022
About 25% of patients with CD who undergo a first resection will need a second surgery within 5 
years, and just over one-third will require a second resection within 10 years (Frolkis 2014). 
Prevention of POCD is paramount because of the morbidity associated with clinical relapse and 
repeated surgeries, including the risk of short-bowel syndrome.
Despite how common disease recurrence is in the postoperative population, there are no approved 
treatments for the prevention of POCD. Various pharmacologic interventions have been studied, 
including antibiotics, mesalamine, immunomodulators, and biologic medications. A network 
meta-analysis evaluating medical therapy for postoperative prophylaxis in CD suggested that 
antibiotics, immunomodulators and anti-tumor necrosis factor (TNF)α monotherapy were more 
effective than placebo in preventing endoscopic recurrence, whereas mesalamine and budesonide 
were not (Singh 2015). At the primary endpoint at Week 76 in the PREVENT trial, infliximab 
reduced endoscopic recurrence compared with placebo (30.6% versus 60.0%; absolute risk 
reduction with infliximab 29.4%; 95% confidence interval [CI]: 18.6%-40.2%; nominal p <0.001), 
but the reduction in clinical recurrence (the primary endpoint) with infliximab compared with 
placebo was not statistically significant (Regueiro 2016).
In summary, there is a high unmet need for effective treatment to prevent disease recurrence in 
patients after surgery. Since the PREVENT trial, there have been no large, randomized trials of 
newer biologic therapies for prevention of POCD including inhibitors of interleukin-23. The 
American Gastroenterology Association maintained that “the prevention of postoperative disease 
recurrence is a high priority given the morbidity associated with clinical and surgical recurrence 
and the long-term risk of short gut syndrome that may arise from multiple bowel resections” and 
emphasized the need to determine the role of newer classes of biologics for the prevention of 
POCD (Nguyen 2017). Likewise, in their recommendations for standardizing clinical trial design 
in POCD, an international consensus panel stated that “effective medical treatment for prevention 
of postoperative Crohn’s disease is a substantial unmet need.” (Hanzel 2021)
2.2.
Background
2.2.1.
Clinical Development of Guselkumab in Crohn’s Disease
The ongoing clinical program for guselkumab in CD, CNTO1959CRD3001 (GALAXI; 
ClinicalTrials.gov Identifier: NCT03466411; hereafter referred to as CRD3001), is designed to 
evaluate the safety and efficacy of guselkumab compared with placebo and an active control 
(ustekinumab). The study is being conducted under a single seamless protocol: a Phase 2/3, 
randomized, double-blind, placebo-
and active-controlled (ustekinumab), parallel-group, 
multicenter protocol to evaluate the safety and efficacy of guselkumab in participants with 
moderately to severely active CD who have demonstrated an inadequate response or failure to 
tolerate previous conventional therapy or biologic therapy. 
Three studies are included in the CRD3001 protocol:  The Phase 2 portion of CRD3001 is a 48-
week, Phase 2, dose-ranging study of the efficacy of guselkumab with induction doses of 
 
 administered 
 at Weeks 0, 4, and 8, followed by 
 doses of 
 every 
 or 
 
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Clinical Protocol CNTO1959CRD3007 Amendment 1
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Status: Approved,  Date: 02 December 2022
 which also includes a long-term extension (LTE). The initial 48-week study has undergone 
database lock and continuing participants are currently in the LTE.  
Within CRD3001 there are also 2 ongoing identical 48-week, Phase 3, confirmatory studies, with 
induction doses of 
 administered at Weeks 0, 4, and 8, followed by maintenance doses 
of 
 or 
. Through Week 12, analyses are based on comparisons 
between each guselkumab group and placebo. The main comparison at Week 48 is guselkumab 
versus placebo as well, although after Week 12 placebo non-responders are permitted to cross over 
to receive active treatment. Ustekinumab was included as a reference arm through Week 12, and 
as an active comparator to guselkumab for the maintenance portion of the trial.  Participants who 
complete the 48-week visit in either the Phase 2 or Phase 3 studies may be eligible to enter the 
LTE (Weeks 48 to 252) and receive approximately 4 additional years of treatment. 
Induction results from the Phase 2 portion of CRD3001 showed that all 3 induction doses of 
guselkumab met the primary endpoint of change from baseline in Crohn’s Disease Activity Index 
(CDAI) score at Week 12 (Sandborn 2022).  No dose-response relationship was identified between 
the 3 induction doses of guselkumab, and the combined group produced a mean drop of 148-points 
from baseline CDAI, compared to a 36.2-point drop in the placebo group. Further, the 3 induction 
groups performed similarly in the major secondary endpoint of endoscopic response at Week 12 
(defined by at least 50% improvement from baseline in Simple Endoscopic Score – Crohn’s 
Disease (SES-CD) score or SES-CD score <2); in the combined guselkumab groups, 35.7% of 
participants achieved endoscopic response compared to 11.5% of participants in the placebo group.  
At Week 12, all participants in the Phase 2 portion of CRD3001 who received guselkumab
 
induction continued on guselkumab
 or 
 weeks, while placebo 
responders continued on placebo, placebo non-responders crossed over to active treatment with 
ustekinumab, and the ustekinumab arm continued 
 
dosing through 
Week 48.  Clinical remission at maintenance Week 48 in the combined guselkumab groups was 
64.9%, with the group receiving 
 dosing achieving a remission rate 
of 63.9%. In addition, 44.9% of the participants from the 3 guselkumab groups were in endoscopic 
response at Week 48. 
Safety analysis from the Phase 2 portion of CRD3001 showed that rates for adverse events (AEs), 
serious adverse events, AEs leading to discontinuation, infections and serious infections were all 
comparable across treatment arms and overall, guselkumab was well tolerated.
In addition to the CRD3001 program, a single Phase 3 study (GRAVITI or CNTO1959CRD3004; 
hereafter referred to as CRD3004) is in progress that evaluates guselkumab SC induction for CD, 
employing a dose regimen of 
 at Weeks 0, 4, and 8.
More detailed information about the clinical development program of guselkumab may be found 
in the IB.
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2.2.2.
Rationale for the Use of Guselkumab in Postoperative Crohn’s 
Disease
As reviewed in Section 2.2.1, the Phase 2 portion of the GALAXI trial suggested that guselkumab 
treatment was both safe and effective for induction and maintenance of remission is patients with 
moderate to severely active CD.  Previously, the PREVENT study examined the proactive use of 
a biologic, safe and effective for moderate to severely active CD, in the post-operative population.
There are extensive learnings from the PREVENT study, in which 297 participants were 
randomized to 5 mg/kg of IV infliximab or placebo q8w. As mentioned above, while the primary 
endpoint of clinical recurrence before or at Week 76 did not meet statistical significance (20% in 
the placebo group, 12.9% in the infliximab group, p=0.097), the major secondary endpoint of 
endoscopic recurrence before or at Week 76 was strongly positive in favor of infliximab: 60.0% 
of the placebo group had an endoscopic recurrence versus 30.6% for the infliximab group (nominal 
p<0.001).
There are some aspects of guselkumab treatment which may be advantageous compared to 
infliximab treatment. For example, in PREVENT there was a difference in the persistence of 
infliximab compared to placebo. Considering that participants did not have active disease at 
baseline, the infliximab arm had a discontinuation rate of 37% (compared to 26% for placebo). In 
the infliximab arm, 22% had discontinuations specifically due to AEs (compared to 13% for 
placebo). These AEs included 9 patients (6.2% of the sample size) with infections (compared to 5 
in the placebo group) and also 5 patients (3.4% of the sample size) with infusion-related reactions 
(compared to none in the placebo group). In comparison, the safety profile of guselkumab is 
expected to be better than that of infliximab, and to result in fewer discontinuations due to AEs.
While antibodies to infliximab and drug levels were only assessed at baseline and at Week 72 in 
PREVENT, it was clear that immunogenicity was  common  in the infliximab arm. Using a drug 
tolerant assay, 62% of participants in the infliximab arm were found to have anti-drug antibodies. 
While no therapeutic drug level has been defined for POCD to date, participants with antibodies 
had a median trough level of 0.58 µg/mL, which is far below what is considered a therapeutic level
for moderate to severe CD.  In contrast, participants without antibodies had a substantially higher 
median trough level of 4.63 µg/mL, comparable to the median Week 14 trough level of 4.0 µg/mL 
in ACCENT-1 which was associated with durable sustained response through Week 54 (Cornillie
2014). Accordingly, participants with antibodies to infliximab had an endoscopic recurrence rate 
(40%) of nearly twice that of infliximab participants without antibodies (21%) and a higher serum 
infliximab concentration was associated with a lower endoscopic recurrence. Similarly, of the 
participants randomized to infliximab who did not develop antibodies, none (0/39) had a clinical 
recurrence at Week 76 while 10.9% (6/55) of patients with antibodies to infliximab had a clinical 
recurrence. 
In comparison, the incidence of antibodies to guselkumab in CD participants, as part of the Week 
48 analysis of the Phase 2 portion of CRD3001, is lower, with an anti-drug antibody rate of 1.4% 
(3/215) through Week 48. In the larger experience with guselkumab in psoriasis, as described in 
the USPI, the anti-drug antibody rate is 6% through Week 52 among patients with plaque psoriasis 
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and 2% through Week 24 among patients with psoriatic arthritis. As described in the Investigator’s
sta for guselkumab, in pooled Phase 2 and Phase 3 analyses in patients with psoriasis and psoriatic 
arthritis, 5% (n=145) of patients treated with guselkumab developed antidrug antibodies in up to 
52 weeks of treatment. In pooled Phase 3 analyses in patients with psoriasis, a population in which 
patients were not on immunomodulators, 15% of patients treated with guselkumab developed
antibodies in up to 264 weeks exposure; however, only 5% of that group of patients had 
neutralizing antibodies, which equates to 0.76% of all patients treated with guselkumab. 
Despite these limitations, infliximab did result in marked differences in rates of endoscopic 
recurrence compared with placebo, and had a numerical, but not significant, difference for 
preventing clinical recurrence. The use of guselkumab has additional potential advantages over 
that of infliximab as described above. From an administration perspective, guselkumab will be 
given SC which is generally better tolerated and preferred by patients.  Finally, IL-23 blockade 
may have fewer safety concerns overall compared to traditional TNF inhibition.  These analyses 
of the PREVENT trial and the Phase 2 safety and efficacy data from CRD3001 suggest that
guselkumab may be an effective and safe agent for the prevention of POCD. 
In the ten years that have passed since the PREVENT trial, endoscopic recurrence has been adopted 
as the standard endoscopic outcome in many trials of POCD therapy (Rutgeerts 1990, Ewe 1999, 
Hellers 1999, Lochs 2000, Hanauer 2004, Rutgeerts 2005, Marteau 2006, D’Haens 2008, Reguiero 
2016) and these trials demonstrate that endoscopic recurrence in POCD patients is more common 
than clinical recurrence at the same timepoint, and may be a more objective endpoint than 
symptoms.  With this increase in importance in endoscopic outcomes has come the more common 
utilization of them as primary or co-primary endpoints in pivotal trials, including that of 
guselkumab.
Recently, an international group of 19 widely-published experts on the management of POCD
(Hanzel 2021) made recommendations regarding clinical trial design. This group, which included 
experts from the United States as well as Australia, Belgium, Canada, Germany, the Netherlands 
and Slovenia, found it appropriate to use endoscopic recurrence as the sole primary end point (as 
opposed to using clinical recurrence or having co-primary end points). This recommendation was 
based primarily on several advantages of an endoscopic end point, including its association with 
subsequent clinical recurrence and its objective nature, which is further magnified by the 
availability of central reading. Among the different endoscopic scoring systems available, the 
group recommended the modified Rutgeerts score as the most appropriate, a similar 
recommendation to that of the International Organization for the Study of Inflammatory Bowel 
Disease (IOIBD) 5 years earlier (Vuitton 2016). In addition, they favored a placebo-controlled 
trial with one year as appropriate follow up for the primary end point.  
While the scientific communities have continued to focus on endoscopic outcomes as a primary 
endpoint, it is critical to also ensure a clinically meaningful benefit to patients. Clinical remission 
without disease recurrence is a composite major secondary endpoint that can be assessed for at the 
6-month time point and will take both clinical as well as endoscopic data into account using CDAI 
as well as other clinical features in addition to endoscopic data. This can allow for an outcome that 
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can capture the importance of clinical remission while providing an opportunity to ensure 
endoscopic remission at the same time. 
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
Risks Due to Study Intervention(s)
Clinical Worsening of CD
The benefit-risk of guselkumab for 
the treatment of CD patients who 
have had recent ileal or ileocolonic 
resection has not been established.

During the study, participants will be 
permitted to continue treatment of CD
with certain concomitant medications 
(Section 6.8.1), including corticosteroids 
(Section 6.8.1.1).

Participants will discontinue study 
intervention if it is not in their best 
interest or if they need to initiate protocol 
prohibited medications including certain 
biologics (Sections 6.8.2 and 7.1).

Participants with confirmed disease 
recurrence, endoscopic recurrence prior to 
or at Week 48, or, at the investigator’s 
discretion, with endoscopic recurrence at 
Week 24, will receive open-label 
induction treatment with guselkumab and 
continue maintenance treatment 
(Section 6.5.1).
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 that have been identified 
as adverse reactions to guselkumab 
are listed in the informed consent 
form.

Discontinuation of a participant’s study 
intervention must be  considered if the 
participant develops a serious infection. In 
addition, any serious infection should be 
discussed with the Medical Monitor or 
designee, and study intervention should 
be withheld until the clinical assessment 
is complete (Section 8.4.8). 

Potential overlap period between prior 
advanced therapies and study therapy is 
brief (Section 5.1).

Participants with a history of, or ongoing 
chronic or recurrent infectious disease, 
including human immunodeficiency virus 
(HIV), hepatitis B (HBV), and hepatitis C 
virus (HCV) will be excluded. Similarly, 
participants with evidence of active or 
untreated latent TB will be excluded from 
the study (Section 5.2).
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(DILI) possibly related to 
guselkumab (see Section 5.15.3 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
participants treated with
guselkumab 
compared to participants treated
with guselkumab 
or placebo.
(systemic exposure comparable to 
guselkumab 
  

Participants with marked liver enzyme 
elevations or symptoms or signs of liver 
dysfunction (eg, jaundice), should undergo 
a thorough investigation for possible 
causes of liver injury (Appendix 7, 
Section 10.7). 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, including 
short period of overlap between 
prior biologics that are washing out 
at the beginning of study, increases 
the risk of diseases associated with 
immunosuppression, such as 
infections or malignancy.
In order to minimize the theoretical 
increased risk of infection or malignancy 
with the combination of guselkumab with 
immunosuppressive therapy, the baseline 
dose of oral corticosteroids on study entry 
is limited to ≤20 mg prednisone or its 
equivalent per day, or 9 mg/day of 
budesonide, or 5 mg/day beclomethasone. 
Participants who enter the study on steroids 
should initiate, or continue, tapering of 
corticosteroids for CD without any delay 
upon study entry at Week 0, unless 
medically inappropriate.  Furthermore, per 
protocol, participants receiving AZA, 6 
MP, or MTX, must discontinue them prior 
to randomization. Additionally, 
participants are also excluded from the 
study if they have received approved 
biologics for CD, including anti-TNFα 
therapy (eg, infliximab, etanercept, 
certolizumab pegol, adalimumab, 
golimumab), natalizumab, vedolizumab, 
ustekinumab, or rizankizumab within 6 
weeks of baseline, unless the participant 
has an available drug level of ≤ 1 mcg/mL.  
Participants are also excluded if they have 
received cyclosporine, tacrolimus, 
sirolimus, 6-thioguanine, or mycophenolate 
mofetil within 4 weeks of baseline or 
approved or investigational small 
molecules for IBD (eg, JAK inhibitors [eg, 
tofacitinib, upadacitinib] or S1P inhibitors 
[eg, ozanimod] within 4 weeks prior to 
baseline, or 5 half-lives, whichever is 
longer). 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. 
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Participants initiating these treatments will 
be discontinued from further study 
intervention administration (see 
Section 6.8.2 for further details on 
prohibited concomitant medications).
Risks Due to Study Procedures
Risks associated with 
video ileocolonoscopy 
including bleeding or 
intestinal perforation.
These risks are well recognized,
but rare. (Arora 2009; Rabeneck
2008)
Trained and experienced endoscopists will be 
performing the procedure during this study.
Radiation
A chest X-ray will be performed at
screening if the participant does 
not have a chest X-ray or chest CT
within 3 months prior to the first 
administration of study 
intervention. The exposure from 1 
standard chest X-ray is 0.1 mSV, 
comparable to 10 days of exposure 
to natural background radiation 
(Acr.org). 
Exposure to radiation through radiographs is 
kept to a minimum by not requiring a chest 
Xray be performed at screening if a chest 
Xray or chest CT is available from within 3 
months prior to the first administration of 
study intervention.
Key: ALT = alanine aminotransferase; AST = aspartate aminotransferase; AZA = azathioprine; CD = Crohn’s 
disease; CT = computed tomography; HBC = hepatitis B virus; HCV = hepatitis C virus; HIV = human 
immunodeficiency virus; IBD = inflammatory bowel disease; MP = mercaptopurine; MTX = methotrexate; SC = 
subcutaneous; TNF = tumor necrosis factor
2.3.2.
Benefits for Study Participation
There is no established benefit to participants who will be receiving study intervention with
guselkumab. However, given the data from clinical studies of IL-23 antagonists in CD, participants 
in the study may experience prevention of recurrence of CD postoperatively. The frequent visits 
and medical care to be provided during the course of this study can also lead to improved disease
control. Participants in the study will also contribute to furthering development of this therapy to 
prevent POCD.
2.3.3.
Benefit-risk Assessment for Study Participation
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 to prevent recurrence of CD postoperatively.
Potential risks of guselkumab, including those of infections including serious infections, 
malignancy, hypersensitivity reactions, and liver injury are being addressed via judicious 
inclusion/exclusion criteria, frequent study visits to allow for close monitoring of patient safety, 
guidelines for participant management (including monitoring of clinical laboratory tests and 
treatment discontinuation criteria), detailed description of allowed and prohibited concomitant 
medications, and comprehensive medical monitoring of data by the Sponsor/designee during the 
conduct of the studies. 
The underlying risk of postoperative recurrence of CD must be considered, such as poor quality of 
life, malnutrition, and intestinal strictures or bowel perforations and abscesses that require surgical 
intervention. Multiple mitigation measures are in place, including full-dose induction and 
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maintenance treatment of those with confirmed disease recurrence from either the placebo group 
or the treatment group. 
Taking into account the measures taken to minimize risk to participants of this study and the known 
complications of POCD, the potential risks identified in association with guselkumab are justified 
by the anticipated benefits that may be afforded to participants who have had surgery for their CD.
3.
OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary

To evaluate the efficacy of guselkumab treatment 
versus 
placebo 
in 
preventing 
endoscopic 
recurrence of CD in participants after surgery

Endoscopic recurrence prior to or at Week 48 
(as defined by modified Rutgeerts score ≥ i2a in 
the neo-terminal ileum, anastomotic site, or its 
equivalent elsewhere in the gastrointestinal (GI)
tract [eg colonic ulceration])
Secondary

To evaluate clinical remission without disease 
recurrence 
in 
participants 
treated 
with 
guselkumab versus placebo after surgery

Clinical remission (CDAI < 150) without 
disease recurrence at Week 48 (as defined in 
Section 9.4.3)

To evaluate disease recurrence in participants 
treated with guselkumab versus placebo after 
surgery

Time-to-disease recurrence (as defined by 
CDAI/event driven criteria as described in 
Section 9.4.3) at the main study database lock, 
which will incorporate all available follow-up of 
enrolled participants at the time that the last 
participant dosed has completed the Week 48 
study procedures, including the ileocolonoscopy

To evaluate symptoms such as stool frequency 
and abdominal pain scores in guselkumab versus 
placebo after surgery

Abdominal pain free (abdominal pain [AP] 
score = 0) at Week 48

Time-to-recurrence of symptoms, defined as 
time to attaining an AP mean daily score >1 (and 
also >1 point higher than baseline) along with 
stool frequency (SF) mean daily score >3 (and 
also >3 higher per day than baseline) for 2 
consecutive weeks through Week 48

To evaluate the safety and PK of guselkumab in 
participants with CD in the postoperative period

Frequency and type of AEs and serious adverse 
events (SAEs)

Describe serum guselkumab concentrations
over time

The evaluate the efficacy of guselkumab in 
limiting steroid use and maintaining remission in 
the postoperative period

Steroid free clinical remission at Week 48, 
defined as CDAI <150 and no corticosteroids 
within 30 days
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Objectives
Endpoints
Other

To evaluate fatigue and other patient reported 
outcomes in guselkumab versus placebo  after 
surgery

Change 
in 
Patient-Reported 
Outcomes 
Measurement Information System  (PROMIS)-
Fatigue Short Form 7a score over 48 weeks

Change in PROMIS-Fatigue SF 7a at each post 
baseline visit through Week 152

Change in PROMIS-29 score, both overall score 
and individual domain scores at each post 
baseline visit through Week 152

Change from baseline in the WPAI at each post 
baseline visit through Week 152

Abdominal pain (AP score = 0) at each post 
baseline visit through Week 152

To evaluate steroid use and healthcare utilization 
in participants within the postoperative period

The 
number 
of 
participants 
not 
on 
corticosteroids and without disease recurrence 
at each post baseline visit through Week 152

The 
number 
of 
participants 
not 
on 
corticosteroids and who have not experienced 
endoscopic or disease recurrence at each post 
baseline visit through Week 152

To evaluate histologic status in CD patients after 
surgery

Histologic score (as measured by Geboes 
scale/RHI/GHAS) at Week 48 ileocolonoscopy

The number of participants with Geboes score 
of 2.0 or less at Week 48 ileocolonoscopy

The number of participants with Geboes score 
over 3.1 at Week 48 ileocolonoscopy

To evaluate the efficacy and safety of open-label 
guselkumab SC induction and maintenance 
treatment in the cross over population after  
postoperative endoscopic or disease recurrence 
of CD has occurred

Clinical remission (CDAI < 150) at 24 weeks
after initiation of guselkumab SC induction

Clinical response (CDAI decrease of <100 
points or CDAI <150) at 24 weeks after 
initiation of guselkumab SC induction

Endoscopic remission (SES-CD of 3 or less) at 
24 weeks after guselkumab SC induction

Endoscopic remission (modified Rutgeerts 
score <i2a) at 24 weeks after guselkumab SC 
induction

To evaluate the efficacy of guselkumab treatment 
versus placebo in changes to inflammatory 
biomarkers after surgery

The change from baseline in CRP concentration 
at all postbaseline visits through Week 152

The change from baseline in fecal calprotectin 
concentration at all postbaseline visits through 
Week 152
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Status: Approved,  Date: 02 December 2022
Objectives
Endpoints

Fecal calprotectin recurrence, defined by 
calprotectin of >200 μg/g with a 100 μg/g 
increase over baseline

To evaluate the clinical efficacy of guselkumab 
treatment 

Disease recurrence (using CDAI/Event-driven 
definition as described in Section 9.4.3) at Week 
152  

Clinical remission (CDAI <150) at each post 
baseline visit

Time to a flare of abdominal pain

To 
evaluate 
the 
endoscopic 
efficacy 
of 
guselkumab treatment

Endoscopic remission (SES-CD of 3 or less) at 
Week 24, Week 48, Week 152

Endoscopic recurrence (modified Rutgeerts 
score >i2a) at Week 24, Week 152
Key: AE = adverse event; AP = abdominal pain; CD = Crohn’s disease; CDAI = Crohn’s disease activity index; 
CRP = C-reactive protein; GI = gastrointestinal; PROMIS = Patient-Reported Outcomes Measurement Information 
System; SC = subcutaneous; SAE = serious adverse event; SES-CD = Simple Endoscopic Score -  Crohn’s disease; 
SF = stool frequency
ESTIMANDS
Estimands are discussed in Section 9.
Refer to Section 8, Study Assessments and Procedures for evaluations related to endpoints.
HYPOTHESIS
It is hypothesized that guselkumab, when initiated after recent ileocolonic surgical resection for 
CD, is superior to placebo in preventing postoperative recurrence of CD, as measured by 
endoscopic recurrence prior to or at Week 48.
4.
STUDY DESIGN
4.1.
Overall Design
This is a Phase 3, multicenter, randomized, placebo-controlled, prospective double-blind study 
designed to evaluate the efficacy and safety of SC guselkumab in reducing the recurrence of CD 
in adult patients who have recently undergone a surgical resection for CD. A diagram of the study 
design is provided in Section 1.2, Schema.
A target of approximately 370 participants will be enrolled from approximately 150 sites.  The 
target population consists of participants with CD who have undergone a recent (<49 days) 
ileocolonic resection with ileocolonic anastomosis for CD, without evidence of active disease 
postoperatively. Participants must not have had their qualifying surgery for the purpose of 
resecting known dysplasia.  
Participants will have a baseline CDAI <200 and will be eligible regardless of prior biologic use. 
Participants who are low risk for recurrent CD (ie, participants whose qualifying surgery was their 
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first in >10 years since their diagnosis of CD and was performed for fibrostenotic stricturing 
disease involving <10 cm of the intestine) will be excluded. Participants must be able to undergo 
randomization no later than 49 days after surgery. For a full list of entry criteria, refer to 
Section 5.1.
Randomization will occur in a 1:1 ratio with participants receiving either:

Arm 1 (Guselkumab): Guselkumab 
 at Week 0 and then
 at Week 8, 
then 
thereafter through the end of the total study period.

Arm 2 (Placebo): Matched placebo
 at Week 0 and then
 thereafter through the 
end of the total study period.
Randomization will be stratified by clinical remission status at baseline (CDAI < 150, CDAI >
150), region (North America, Western Europe, rest of world) and number of prior surgeries (1 
surgery versus > 1 surgery, with the qualifying surgery counting as 1 surgery).
A Week 48 video ileocolonoscopy will be performed between Weeks 48 and 51 and participants 
with endoscopic recurrence confirmed by a central reader will cross over to open-label treatment 
with guselkumab SC induction. An optional video ileocolonoscopy can be performed at Week 24 
and optional cross over may occur at the discretion of the principal investigator if there is only
endoscopic recurrence without disease recurrence (defined in Section 9.4.3). If participants meet 
criteria for disease recurrence after Week 8 they will also cross over to open-label treatment.
Participants who discontinue study intervention early will return for an early termination visit at 
least 12 weeks after study intervention discontinuation, which will also serve as their final safety 
visit. This visit will include a video ileocolonoscopy at the time of discontinuation, except those 
participants who have already had demonstrated endoscopic recurrence in a study 
ileocolonoscopy. 
Study Length
After the screening period, the total study duration is 156 weeks, with the final dose of study 
intervention given at Week 144 and the final efficacy visit at Week 152 followed by the final safety 
visit at Week 156. The end of the study is defined as when all participants have completed the 
Week 156 visit assessments, or have terminated study participation prior to Week 156 and had 
their last follow-up assessment (12 weeks after the last dose of study intervention or at early 
termination visit). 
The main study period is defined as when the last randomized participant has completed the Week 
48 assessments at which point the main study database lock will occur. Participant follow-up for 
the main study period may vary depending upon when they enrolled in the trial (estimated to be 
from 12 to 30 months, based upon an anticipated accrual time of 18 months, but with an upper 
limit of 36 months [total study treatment duration], should accrual time exceed 18 months).
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Endpoints
The primary endpoint is endoscopic recurrence prior to or at Week 48. Video ileocolonoscopy will 
be performed at the Week 48 visit and centrally read, using a definition of a modified Rutgeerts 
score of ≥ i2a disease activity to define endoscopic recurrence.  
The first secondary endpoint of clinical remission without disease recurrence at Week 48 is defined 
in Section 9.4.3. Disease recurrence is a composite endpoint defined by a ≥70-point increase in 
baseline CDAI and a CDAI of ≥200 and evidence of endoscopic recurrence; OR other disease 
recurrence-defining events as described in Section 9.4.3. The second secondary endpoint of disease 
recurrence is defined in Section 9.4.3 and will be a time-to-event analysis incorporating all follow-
up available for all participants at the time of the main study database lock (from last randomized 
participant completing Week 48 though data beyond Week 48, where available) specifically 
including all events of disease recurrence that have occurred through the full follow-up available 
at the time of the main study database lock. Thus, for this endpoint, participant follow-up may vary 
depending upon when they enrolled in the trial (estimated to be from 12 to 30 months, based upon 
an anticipated accrual time of 18 months, but with an upper limit of 36 months [total study 
treatment duration], should accrual time exceed 18 months).
4.2.
Scientific Rationale for Study Design
Blinding, Control, Study Phase/Periods, Intervention Groups
A placebo control will be used to establish the frequency and magnitude of changes in clinical
endpoints that may occur in the absence of active intervention. Randomization will be used to 
minimize bias in the assignment of participants to intervention groups, to increase the likelihood 
that known and unknown participant attributes (eg, demographic and baseline characteristics) are 
evenly balanced across intervention groups, and to enhance the validity of statistical comparisons 
across intervention groups. Blinded intervention will be used to reduce potential bias during data 
collection and evaluation of clinical endpoints.
Database Locks and Maintenance of the Blind
The first database lock (DBL) is the main study DBL. It will occur when all participants have 
completed the Week 48 visit assessments, or have terminated study participation prior to Week 
48, and will include all assessments performed as of that date (even those beyond Week 48).  The 
final DBL will occur after the last participant completes the final safety visit at Week 156. 
Additional DBLs may be added between Weeks 48 and 156, as warranted.
The study blind will be maintained for the investigative sites, site monitors, and study participants 
until after the final participant has completed their Week 156 visit. In the event of an emergency, 
the investigator may also unblind a participant’s treatment if such knowledge would change the 
participants’ clinical care. The sponsor will remain blinded to the original treatment assignments 
until after the main study DBL has occurred. 
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RNA and Biomarker Collection
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. Pharmacogenomic research may help to explain interindividual 
variability in clinical outcomes and may help to identify population subgroups that respond 
differently to an intervention. The goal of the pharmacogenomic component is to collect RNA to 
allow the identification of genetic factors that may influence the efficacy, safety, or tolerability of
guselkumab and to identify genetic factors associated with Crohn’s disease.
Biomarker samples will be collected to evaluate the 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. The goal of the biomarker analyses is to 
evaluate the pharmacodynamics of guselkumab and aid in evaluating the intervention-clinical 
response relationship.
Medical Resource Utilization and Health Economics Data Collection
Treatment of POCD with guselkumab versus placebo may result in lower utilization of CD-related 
emergency department visits, hospitalizations, and surgeries; therefore, comparison will be done 
across intervention groups.
4.2.1.
Participant Input Into Design
Input into the study design was obtained from a patient engagement research council which was 
formed to integrate the voice of inflammatory bowel disease (IBD) patients into study 
development, execution, and dissemination. Participant insights that informed study design 
include the importance of including Patient Reported Outcomes (PROs) as endpoints and insights 
regarding patient perceptions of receiving a biologic postoperatively.
The results of the study may be made available to all participants through a plain language 
summary, a technical summary of results on clinicaltrials.gov and/or clinicaltrialsregister.eu 
and/or other national registries
at the conclusion of the study according to local 
standards/restrictions.
4.2.2.
Study-specific Ethical Design Considerations
Potential participants and/or their legally acceptable representative will be fully informed of the 
risks and requirements of the study and, during the study, participants and/or their legally 
acceptable representative will be given any new information that may affect their decision to 
continue participation. They will be told that their consent to participate in the study is voluntary 
and may be withdrawn at any time with no reason given and without penalty or loss of benefits to 
which they would otherwise be entitled. Only participants who are fully able to understand the 
risks, benefits, and potential AEs of the study, and provide their consent voluntarily will be 
enrolled. Written consent may be obtained through various sources (eg, paper or electronic such 
as eConsent, eSignature, or digital signature) as determined by regulations as well as study and/or 
patient preferences. 
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One ethical concern is that one half of the participants in the study will be randomized to placebo.
Currently, there are no treatments with Food and Drug Administration (FDA) or European 
Medicines Agency (EMA) approval for the indication of reducing the risk of recurrent CD after 
surgical resection, and it is important to be able to have a placebo comparison in order to establish 
whether there is meaningful benefit from the study intervention. The use of placebo is also justified 
because the study population consists of participants with inactive CD at baseline, and participants 
will be crossed over to active treatment as soon as they meet the criteria for disease recurrence (see 
Section 9.4.3). A placebo-controlled design minimizes subject and investigator bias in evaluating 
the efficacy and safety of guselkumab in the selected patient population (FDA Guidance for 
Industry E10). Additionally, in their recommendations for clinical trial design in postoperative 
CD, a recent international panel of 19 international expert IBD specialist gastroenterologists 
recommended that in  regulatory trials assessing the effectiveness of a therapy for prevention of 
postoperative CD recurrence, participants in the control arm should receive placebo (Hanzel 2021).
The total blood volume to be collected is considered to be an acceptable amount of blood to be 
collected over this time period from the population in this study based upon the standard of the
American Red Cross for whole blood donation (approximately 475 mL q8w) as well the allowable 
blood sample volumes described in the EU guideline on clinical trials conducted with minors (EU 
2017). 
4.3.
Justification for Dose
As reviewed above, in the Phase 2/3 moderate-to-severely active CD (ie, participants must have a 
baseline CDAI of 220 to 450) CRD3001 studies, participants are receiving IV induction doses at 
Weeks 0, 4 and 8 (
 and 2 maintenances doses are being studied, 
 and 
 
.  In the CRD3004 study, 3 induction doses of 
 at Weeks 0, 4, and 8 are 
being examined, followed by maintenance doses of either 
 or 
.
The participant population in the current study is distinct in that they will not have moderate-to-
severely active CD (eg, baseline CDAI will be < 200) and will have had the source of disease 
activity removed as a result of their recent surgery.  Therefore, it is hypothesized that full induction 
dosing is not necessary . Nevertheless, it has been shown that some patients continue to have some 
lingering mildly elevated fecal calprotectin for up to 3 months postoperatively (Boube 2020), as 
well as an elevated CRP post-operatively (Iaculli 2016), which may be associated with somewhat 
higher drug clearance in patients with CD (Boyle 2017, Grinman 2020). Accordingly, in this study,  
participants will receive a 
 loading dose at Week 0 followed by 
.  The 
 loading dose at Week 0 is considered appropriate in this setting because it will result 
in higher initial concentrations in comparison to the eventual steady-state concentration from the 
 regimen.
While not specifically powered to detect a difference between maintenance doses, results from the 
Phase 2 portion of the GALAXI trial did not appear to show a dose response relationship in the 
doses studied.  For example, the clinical remission rate at Week 48 was similar in the highest dose 
(
 followed by 
) to the remission rate of the lowest tested dose 
(
 followed by 
) at 57.4% and 63.9% respectively.  Of note, the 
CCI
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proposed maintenance dose of this study, 
, is the same as the currently approved 
regimen for guselkumab for the treatment of moderate-to-severe plaque psoriasis.  Since psoriasis 
is a chronic immune mediated disease requiring long-term therapy to maintain disease control, the 
2 pivotal Phase 3 studies (CNTO1959PSO3001 and CNTO1959PSO3002) included long-term 
extensions through a total of up to 5 years. The analyses of pooled data support the conclusion that 
guselkumab is well tolerated through 5 years of treatment, and the safety profile remains consistent 
when compared to Week 48 data, at the approved dose regimen of 
 administered 
 at 
Weeks 0, 4, and then 
 in adult participants with moderate to severe plaque psoriasis.
When infliximab was previously studied in this patient population in the PREVENT trial, the 
standard induction dosing of 5 mg/kg at Weeks 0, 2, and 6 was also not utilized. Instead, 
participants were immediately started on the 5 mg/kg IV q8w established maintenance regimen. 
While this study did not show significance for clinical recurrence at the Week 76 primary endpoint, 
it showed clear separation in rates of endoscopic recurrence versus placebo and in the time-to-
event analysis for clinical recurrence, with the greatest separation seen in the first 6 months, 
supporting that it is appropriate to forgo a full induction regimen in this patient population.
In the event a participant experiences confirmed disease recurrence, endoscopic recurrence at 
Week 48, or, at the investigator’s discretion for endoscopic recurrence at the optional Week 24 
ileocolonoscopy, they will cross over to receive open-label treatment with guselkumab using the 
regimen under study for moderately-severely active CD in the ongoing Phase 3 study 
CNTO1959CRD3004.  As these patients will, per protocol, have a CDAI that is ≥220 (or at a 
minimum is very close, at 201-219) and/or confirmed endoscopic activity, giving induction dosing 
of 
for 3 doses is appropriate to treat this level of ongoing inflammatory and disease 
activity from CD that has recurred such that it is now in the moderately-to-severely active category.
4.4.
End of Study Definition
The end of study is considered as the Week 156 visit for the last participant in the study.  The final 
data from the study site will be provided to the sponsor (or designee) after completion of the final 
participant Week 156 assessments at that study site, in the time frame specified in the Clinical 
Trial Agreement.
Participant Study Completion Definition
A participant will be considered to have completed the study if the participant has completed 
assessments at the Week 156 visit (including participants who crossed over).
Participants who prematurely discontinue study intervention for any reason before completion of 
the Week 144 study intervention administration can be considered to have completed the study if 
they have completed an early termination visit which should occur approximately 12 weeks after 
the last dose of study agent. This scenario includes participants who crossed over to open-label 
treatment and subsequently did not respond, precluding further continuation in the study.
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5.
STUDY POPULATION
Screening for eligible participants will be performed within 5 weeks before administration of the 
study intervention. 
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.
The definition of baseline as applied to the inclusion and exclusion criteria below is defined as the 
Week 0 randomization visit.
The target population is male or female participants (minimum age 18) with a diagnosis of CD 
who have a qualifying surgery (eg, ileocolonic resection) a maximum of 49 days before 
randomization.  Participants will be excluded if they have a short segment of bowel affected (ie,
less than 10 cm) for fibrostenotic disease and they had their first surgery more than 10 years after 
diagnosis of CD.  There is no requirement that participants have failed prior biologics.
5.1.
Inclusion Criteria
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
Age
1.
Participants ≥18 (or the legal age of consent in the jurisdiction in which the study is taking 
place).
Type of Participant and Disease Characteristic
2.
Have a documented diagnosis of CD confirmed by endoscopic, histologic, and/or 
radiologic studies prior to resection or by tissue obtained at resection.  
3.
Have undergone an ileocolonic surgical resection (ie, an intestinal resection with an 
ileocolonic anastomosis) for CD prior to the baseline visit with the following criteria:

Have no known active CD anywhere in the gastrointestinal (GI) tract, including 
the findings at surgery,

Be able to undergo randomization no later than 49 days after surgery, and at least 
10 days after surgery (or 8 days after resumption of bowel activity, eg, in case of 
postoperative ileus),

Ileocolonic resection was not for the purpose of removing known dysplasia,

If ileocolonic resection occurs > 10 years since the diagnosis of CD and only 
fibrostenotic stricturing is present, then length of stricture must be > 10 cm
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4.
Have a baseline CDAI < 200.
Concomitant or previous medical therapies received
5.
Meets the following requirements for prior or current medications for CD. The following 
medications are permitted provided that doses meeting the requirements listed below are 
stable or have been discontinued within the timeframes prior to baseline specified below:

Oral corticosteroids at a prednisone-equivalent dose at or below 20 mg/day, or 9
mg/day of budesonide. Participants on corticosteroids should initiate/continue
tapering after baseline, per the recommended schedule (see Section 6.8.1.1).

Conventional immunomodulators (ie, azathioprine [AZA], 6-mercaptopurine [6-
MP], or methotrexate [MTX]) must be discontinued prior to randomization.
Screening Laboratory Tests
6.
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 screening period:
a. Hemoglobin ≥8.0 g/dL (International System of Units [SI]: ≥80.0 g/L)
b. White blood cells ≥3.0 × 103/μL (SI: ≥3.0 × 109/L)
c. Neutrophils ≥1.5 × 103/μL (SI: ≥1.5 × 109/L)
d. Platelets ≥100 × 103/μL (SI: ≥100 × 109/L)
e. Serum creatinine ≤1.5 mg/dL (≤133 µmol/L)
f. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 
concentrations must be ≤2 times the upper limit of the normal (ULN) range for the 
laboratory conducting the test
g. Total bilirubin ≤1.5 × ULN (isolated bilirubin ≥1.5 × ULN is allowed for those 
participants with known Gilbert’s syndrome).
Sex and Contraceptive/Barrier Requirements
7.
Male or female (according to their reproductive organs and functions assigned by 
chromosomal complement), to guide the criteria below.
8.
A woman of childbearing potential must have a negative highly sensitive serum (beta 
human chorionic gonadotropin [B-hCG]) test result during screening and a negative urine 
pregnancy test at week 0, prior to randomization.
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9.
Before randomization, a woman must be
a.
Not of childbearing potential
b.
Of childbearing potential and
i. 
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. The investigator should evaluate 
the potential for contraceptive method failure (eg, noncompliance, 
recently initiated) in relationship to the first dose of study 
intervention; however, 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 as described throughout the inclusion and 
exclusion criteria.
10.
A woman must agree not to donate eggs (ova, oocytes) or freeze for future use for the 
purposes of assisted reproduction during the study and for a period of 12 weeks after the 
last administration of study intervention.
11.
During the study and for at least 12 weeks after the last administration of study 
intervention, a male participant:

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).

Who is sexually active with a pregnant female must use a condom.

Must agree not to donate sperm for the purpose of reproduction or plan to father 
a child.
Informed Consent
12.
Must sign an informed consent form (ICF) (or their legally acceptable representative must 
sign) indicating that the participant understands the purpose of, and procedures required 
for, the study and is willing to participate in the study.
13.
Be willing and able to adhere to all specified requirements in this protocol, including but 
not limited to completion of assessments (which includes an ileocolonoscopy at one year 
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or upon concern for clinical flare), adherence to visit schedule, multiple blood draws, and 
compliance with the lifestyle restrictions.
5.2.
Exclusion Criteria
Any potential participant who meets any of the following criteria will be excluded from 
participating in the study:
Medical Conditions
1.
Has complications of CD, such as symptomatic strictures or stenoses, short bowel 
syndrome, a draining (ie, functioning) stoma or ostomy, 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. 
3.
Have had any active perianal disease within 3 months of screening (except skin tags) or 
have had any draining fistula within 3 months of screening unless the fistula was 
removed at the index surgery.
4.
Had, in association with their most recent intra-abdominal surgery, postoperative 
complications such as, but not limited to, postoperative intraabdominal abscess, wound 
dehiscence, anastomotic leak, the need for a second operation, or have evidence of 
macroscopically active CD which was not resected at the time of surgery or had active 
CD in regions beyond the site of surgery in the GI tract within 1 year of the time of 
enrollment.
5.
Evidence of a herpes zoster infection within 8 weeks before the first dose of study 
intervention.
6.
Meet ANY of the following TB screening criteria:
Note: Interferon gamma release assay (IGRA) testing includes either QuantiFERON-
TB® or T-SPOT® TB.
a.
Have a history of active TB or show signs or symptoms suggestive of active 
TB upon medical history and/or physical examination at screening.
b.
Have a history of untreated latent TB prior to screening. An exception is made 
for participants who are currently receiving treatment or will initiate treatment 
for latent TB prior to 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 
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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 recent close contact with a person with active TB. An exception is 
made if such participants are referred to a physician specializing in TB to 
determine if treatment is warranted or not. This evaluation must be adequately 
documented and, if treatment is recommended, the participant must be
receiving appropriate treatment prior to the first administration of study 
intervention.
d.
Have a positive IGRA test result within 2 months prior to the first 
administration of study intervention. An exception is made for participants 
who:
-
have a history of adequately treated latent TB described above.
-
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.
-
have a false-positive IGRA test as determined by the following:
o
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.
e.
Have a chest radiograph or chest computed tomography within 3 months prior 
to the first administration of study intervention that shows abnormalities 
suggestive of active or inactive TB.
7.
Has or has had any other clinically significant infection (eg, hepatitis, sepsis, 
pneumonia, or pyelonephritis, enteric 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, and clinically resolved infections 
related to the participant’s Crohn’s-related surgical resection).
8.
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), latent or active granulomatous infection 
(including histoplasmosis or coccidioidomycosis), an open, draining, or infected skin 
wound, or an ulcer, or active enteric infections (eg, Clostridium difficile that is untreated 
and unresolved, without subsequent negative testing). Has current signs or symptoms 
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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).
9.
Currently has a malignancy or has a history of malignancy within 5 years before 
screening (with the exception of a nonmelanoma skin cancer and/or cervical carcinoma 
in situ 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).
10.
Has a known history of lymphoproliferative disease, including lymphoma, multiple 
myeloma, monoclonal gammopathy of undetermined significance; or signs and 
symptoms 
suggestive 
of 
possible 
lymphoproliferative 
disease, 
such 
as 
lymphadenopathy or splenomegaly.
11.
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.
12.
Has a transplanted organ (with exception of a corneal transplant >12 weeks before 
screening).
13.
Poor tolerability of venipuncture or lacks adequate venous access for required blood 
sample collections during the study period.
14.
History of drug or alcohol abuse according to Diagnostic and Statistical Manual of 
Mental Disorders (5th edition) criteria within 1 year before screening.
15.
Has unstable suicidal ideation or suicidal behavior in the last 6 months that may be 
defined as a 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, 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.
16.
Has known allergy, hypersensitivity, or intolerance to guselkumab or its excipients 
(refer to the guselkumab IB).
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Prior/Concomitant Therapy
17.
Has received any of the following prescribed medications or therapies within the 
specified period prior to baseline:

If previously receiving antibiotics as a primary treatment for CD, must have 
been stopped for at least 2 weeks.

If previously receiving parenteral or enteral nutrition as a primary treatment for 
CD, must have been stopped for at least 2 weeks.

IV corticosteroids received within 2 weeks.

Approved biologics for CD, including anti-TNFα therapy (eg, infliximab, 
etanercept, certolizumab pegol, adalimumab, golimumab), natalizumab, 
vedolizumab, ustekinumab, or rizankizumab received within 6 weeks of 
baseline.  If the participant has an available drug level of ≤1 mcg/mL, they can 
be randomized despite receiving a biologic within 6 weeks of baseline.  

Investigational immunomodulatory biologic agents for CD received within 6 
weeks of baseline, or 4 half-lives, whichever is longer.

Cyclosporine, tacrolimus, sirolimus, 6-thioguanine, or mycophenolate mofetil 
received within 4 weeks of baseline.

Approved or investigational small molecules for IBD (eg, JAK inhibitors [eg, 
tofacitinib, upadacitinib] or S1P inhibitors [eg, ozanimod], 4 weeks prior to 
baseline, or 5 half-lives, whichever is longer).
18.
Bacille Calmette-Guérin (BCG) vaccination within 12 months or any other live 
bacterial or live viral vaccination within 4 weeks prior to baseline, or plans to receive 
such vaccines during the study.
Prior/Concurrent Clinical Study Experience
19.
Currently participating or intends to participate in any other study using an 
investigational agent or procedure during the conduct of this study.
Infections or Predisposition to Infections
20.
History of human immunodeficiency virus (HIV) antibody positive, or tests positive for 
HIV at screening.
21.
Is seropositive for antibodies to hepatitis C virus (HCV), unless they satisfy one of the 
following conditions: 
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
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

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.
22.
Tests positive for hepatitis B virus (HBV) infection (see Appendix 6 [Section 10.6]).
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.
23.
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 for a validated 
SARS CoV-2 test:

Obtained at least 2 weeks after conditions (a), (b), (c) above (timed 
from resolution of key clinical features if present, eg, fever, cough, 
dyspnea)
AND

With absence of ALL conditions (a), (b), (c) above during the period 
between the negative test result and the baseline study visit
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.
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Other Exclusions
24.
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.
25.
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.
26.
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
NOTE: Investigators must ensure that all study enrollment criteria have been met at screening, 
prior to randomization at the baseline visit (Week 0). If a participant's clinical status changes 
(including any available laboratory results or receipt of additional medical records) after screening 
but before the first dose of study intervention is given such that the participant no longer meets all 
eligibility criteria, then the participant must be excluded from participation in the study.
5.3.
Lifestyle Considerations
Potential participants must be willing and able to adhere to the following lifestyle restrictions 
during the study to be eligible for participation:
1.
Refer to Section 6.8, Concomitant Therapy for details regarding prohibited and 
restricted therapy during the study.
2.
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 participants receiving immune-targeted 
therapy when determining an appropriate interval between vaccination and study 
enrollment (see also Section 5.2).
3.
Agree to follow all requirements that must be met during the study as noted in the 
Inclusion and Exclusion Criteria (eg, contraceptive requirements, agrees not to get 
pregnant or father children while enrolled in this study or within 12 weeks after the last 
dose of study intervention).
4.
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 
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study with an investigational agent should undergo an early termination visit before he 
or she terminates study participation.
5.
Must agree not to receive a live virus or live bacterial vaccination during the study and 
for 12 weeks after receiving the last dose of study intervention.
6.
Must agree not to receive a BCG vaccination during the study and for 12 months after 
receiving the last dose of study intervention.
7.
Participants who require treatment for latent TB must complete the appropriate course 
of TB therapy.
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 study site contact for completeness. When available, the investigator may generate 
screening and enrollment logs directly from interactive web response system (IWRS).
The participant identification and enrollment log will be treated as confidential and will be filed 
by the investigator in the study file. To ensure participant confidentiality, no copy will be made. 
All reports and communications relating to the study will identify participants by participant 
identification and age at initial informed consent. In cases where the participant is not randomized 
into the study, the date seen and age at initial informed consent will be used.
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened on 1 occasion only after consultation with the Sponsor or designee (eg, study 
responsible physician, scientists). Rescreened participants must be assigned new participant 
numbers, undergo the informed consent process, and then start a new screening phase.
Previous TB evaluation results (including the IGRA and Chest x-ray), if done within the specified 
allowed time, are not required to be repeated.
6.
STUDY INTERVENTION AND CONCOMITANT THERAPY
6.1.
Study Interventions Administered
Study intervention administration (see Table 1) must be captured in the source documents and the 
electronic case report form (eCRF). Study site personnel will instruct participants and/or caregiver 
on how to perform self
 and store study intervention for at-home use as indicated for this 
protocol. When multiple 
 are administered at a visit, each 
 of study 
intervention should be given at a different location of the body.
Guselkumab and placebo will be manufactured and provided under the responsibility of the 
sponsor. Refer to the guselkumab IB for a list of excipients.
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Detailed instructions on the administration of study intervention will be provided in the Site 
Investigational Product Procedures Manual.
For a definition of study intervention overdose, refer to Section 6.7. Guidelines for study 
intervention affected by the COVID-19 pandemic are provided in Section 10.8.
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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.
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.
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.
Sourcing
Provided centrally by the Sponsor
Provided centrally by the Sponsor
Provided centrally by the Sponsor
Packaging and Labeling (Labels 
will contain information to meet 
the applicable regulatory 
requirements.)
See individual kits
See individual kits
See individual kits
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6.2.
Preparation/Handling/Storage/Accountability
Combination Products
For this protocol, the term combination product refers to the single integral drug-device 
combination.
The Sponsor-manufactured combination product for use in this study is the pre-filled syringe (PFS) 
assembled in an
 Additional details on the 
 are provided in the 
guselkumab Investigator Brochure.
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 as product quality complaints (PQC, see Section 10.4.6).
Preparation/Handling/Storage
For 
 administration, guselkumab will be supplied as a 
 sterile liquid in a single-dose 
PFS assembled in a 
in doses of 1 mL and 2 mL. For 
 administration, placebo will be 
supplied as a 1 mL sterile liquid in a single-dose 
All study intervention must be stored at 
controlled temperatures ranging from 36°F to 46°F (2°C to 8°C).
Guselkumab and placebo for guselkumab should be a clear and colorless to light yellow solution 
that may contain translucent particles. Do not use guselkumab or placebo for guselkumab if the 
liquid is cloudy or discolored or has large particles. Protection from light is not required during 
the preparation and administration of the study intervention material but avoid direct exposure to 
sunlight. Aseptic procedure must be used during the preparation and administration of the study 
intervention material.
Study drug may be administered at the study site or at home by the trained participant or their 
caregiver (without a study visit) and will be routinely done beginning at Week 56. Study personnel 
will instruct participants on how to transport, store, and administer study intervention for at-home 
use as indicated for this protocol. 
The study intervention may be delivered directly to the participants from the site by a courier, if 
needed. Each courier will adhere to privacy requirements approved by the Independent Ethics 
Committee (IEC)/Institutional Review Board (IRB). The capability to utilize these direct-to-
patient shipments will be assessed by the sponsor to ensure that it is allowable per local regulations.
Refer to the study Site Investigational Product and Procedures Manual for additional guidance on 
study intervention preparation, handling, and storage
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Accountability
The investigator is responsible for ensuring that all study intervention received at the site is 
inventoried and accounted for throughout the study. All study intervention will be stored and 
disposed of according to the Sponsor's instructions. Study site personnel must not combine 
contents of the study intervention containers.
Study intervention must be handled in strict accordance with the protocol and the container label, 
and must be stored at the study site in a limited-access area or in a locked cabinet under appropriate 
environmental conditions. Unused study intervention must be available for verification by the 
Sponsor's study site monitor during on-site monitoring visits. The return to the Sponsor of unused 
study intervention will be documented on the intervention return form. When the study site is an 
authorized destruction unit and study intervention supplies are destroyed on-site, this must also be 
documented on the intervention return form.
Potentially hazardous materials such as used ampules, needles, syringes and vials should be 
disposed of immediately in a safe manner and therefore will not be retained for intervention 
accountability purposes.
The dispensing of study drug to the participant, and the return of study drug from the participant, 
must be documented on the drug accountability form. Participants must be instructed to return all 
original containers, whether empty or containing study drug.
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 individuals participating in the study. Returned study intervention must not be 
dispensed again, even to the same participant. Study intervention may not be relabeled or 
reassigned for use by other participants. The investigator agrees neither to dispense the study 
intervention from, nor store it at, any site other than the study sites agreed upon with the Sponsor. 
Further guidance and information for the final disposition of unused study interventions are 
provided in the Site Investigational Product and Procedures Manual.
Since, once they are trained, participants may potentially be self-administering study drug at home, 
they will receive detailed instructions for study drug storage and disposal of used syringes and 
handling of unused study material. Participants will receive a sharps container to dispose of used 
syringes. Participants will be instructed to return the sharps container and/or unused cartons with 
syringes. Participants will record study drug administrations with time and date information in 
their participant diary.
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 2 intervention groups in a 1:1 ratio (see Section 4.1) based on a 
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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 clinical remission status at baseline (CDAI < 150, CDAI ≥150), region (North 
America, Western Europe, rest of world) and number of prior surgeries (1 surgery versus > 1 
surgery, with the qualifying surgery counting as 1 surgery). The IWRS will assign a unique 
intervention code, which will dictate the intervention assignment and matching study intervention 
kit for 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 8-week intervals 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.
At the Week 48 DBL (main study DBL), data will be unblinded for analysis to the sponsor only. 
Treatment assignment will remain blinded to the study sites and participants until the last 
participant completes the Week 156 evaluations.
Under normal circumstances, the investigator blind should not be broken until the Week 156 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.
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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 participants have self- (or caregiver-) administration of study intervention at home, 
compliance with study intervention will be assessed at each visit. Compliance will be assessed via 
the return of boxes that contained study drug and will then be documented in the source documents 
and eCRF. Deviation(s) from the prescribed dosage regimen should be recorded in the eCRF.
Participants will receive instructions on compliance with study treatment when they begin self-
administration of study intervention at home. When participants begin self-administration at home, 
the investigator or designated study personnel will maintain a log of all study intervention 
dispensed and returned.
When study intervention is self-administered by participants (or caregivers) at home, participants 
will record all study intervention administrations on a diary card. 
During the study, the investigator or designated study research personnel will be responsible for 
providing additional instruction to reeducate any participant who is not compliant with taking the 
study intervention.
Compliance with the treatment schedule is strongly encouraged.  It is understood that treatment 
may be interrupted for health-related or safety reasons.  Therefore, if for any reason a participant 
cannot receive a dose of study intervention at the scheduled visit, the participant must make every 
effort to still come in for the scheduled assessments for that visit. In general, the dose should be 
administered within approximately 2 weeks of that scheduled visit. The participant should then 
resume the normal study schedule relative to the baseline visit (Week 0). In the case when a 
participant does not come into the investigational site for a scheduled visit, the site will follow-up 
with that participant. Due diligence could include telephone calls, certified letters, and email 
requests. Measures taken to obtain follow-up information must be documented.
Study-site personnel will keep a log of all study intervention dispensed and will compare the 
amount of study intervention dispensed with the amount returned.  
All post-baseline visits up to and including Week 56 will have a visit window of ± 10 days counting 
from Week 0 as Day 1.  If a study visit occurs outside this window, the Sponsor should be consulted 
about how the participant should resume his or her normal dose schedule.
Information regarding study intervention administrations that are administered outside of the 
scheduled windows or missed will be recorded. Participant charts and worksheets may be reviewed 
and compared with the data entries on the eCRFs to ensure accuracy.
6.5.
Dose Modification
The dose level of study treatments will not be adjusted. 
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6.5.1.
Open Label / Cross over Treatment
Starting after the Week 8 visit, if disease recurrence is confirmed and the definition as described 
in Section 9.4.3 is satisfied, participants will cross over to open-label treatment with guselkumab. 
Similarly, participants who are determined to have endoscopic recurrence by central read on the 
Week 48 or flare visit ileocolonoscopy will also cross over to open-label treatment; for the optional 
Week 24 ileocolonoscopy, if the central reader confirms endoscopic recurrence (modified 
Rutgeerts score of i2a or greater), cross over may be done at the discretion of the principal 
investigator with the participant’s agreement. If a participant does not cross over at Week 24 for 
endoscopic recurrence but, within the following 16 weeks, develops an increase in CDAI > 70 or 
meets the corticosteroid-related disease recurrence criteria (see Section 9.4.3), then the participant 
may cross over without the need for a repeat ileocolonoscopy.
As discussed in Section 8, at the cross over visit, participants, regardless of the treatment arm to 
which they were randomized, will receive guselkumab 
 for 3 doses, followed by 
maintenance guselkumab 
. This regimen matches the regimen under study in the 
ongoing Phase 3 study, CRD3004. The 
induction will be open-label and the participant and 
investigator will remain blinded to original randomized treatment assignment. Participants will not 
be allowed to cross over after the Week 128 visit and, while awaiting their confirmatory 
ileocolonoscopy, regularly scheduled study intervention may be held.  
In the event a participant meets CDAI criteria for recurrence, but endoscopic recurrence is not 
confirmed on ileocolonoscopy, participants will continue on assigned study intervention, and will 
not cross over to open-label treatment with guselkumab.  At investigator discretion, a repeat 
evaluation, to include an ileocolonoscopy, could be performed as early as the next scheduled visit. 
It is recommended that such repeat assessment be undertaken only if/when there are clinical 
reasons to warrant such re-assessment, eg, there is worsening of symptoms and/or an increase in 
objective measures of inflammation such as C-reactive protein (CRP) or fecal calprotectin (and 
clinical criteria for recurrence must still be satisfied).  In addition, if a confirmatory 
ileocolonoscopy was of poor quality or otherwise unreadable such that confirmatory endoscopic 
recurrence could not be determined, an ileocolonoscopy is recommended to be repeated as soon 
as feasible.   
As it takes time for endoscopic disease to resolve, participants who cross over to open-label 
guselkumab should then be re-assessed with an ileocolonoscopy approximately 16 to 24 weeks
later.  At that time, it will be determined, based on investigator judgement, whether treatment with 
open-label SC guselkumab should be continued or not. It is recommended to include an 
ileocolonoscopy in this assessment.  
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.
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Local regulations on continued access will always take precedence. Plans for continued access 
stated in this protocol may change if new information on the benefit-risk profile of guselkumab
becomes available during the study or program.
6.7.
Treatment of Overdose
For this study, any single dose of guselkumab greater than the highest dose planned (eg 400 mg
for the cross over group) will be considered an overdose. The Sponsor does not recommend 
specific treatment for an overdose. As discussed in Section 10.4.4, overdose is a special reporting 
situation such that the event requires expedited reporting.
In the event of an overdose, the investigator or treating physician should:

Contact the Medical Monitor (or designee) immediately.

Evaluate the participant to determine, in consultation with the Medical Monitor (or designee), 
whether study intervention should be interrupted.

Closely monitor the participant for AE/SAE and laboratory abnormalities.

Document the quantity of the excess dose of the overdosing in the eCRF.
6.8.
Concomitant Therapy
Concomitant therapies must be recorded throughout the study from signing of consent to the last 
study visit.
All concomitant therapies (prescription or over-the-counter medications, including vaccines, 
vitamins, herbal supplements) must be recorded in the eCRF. Recorded information will include 
the name of the medication, start and stop dates, and its reason for use.
6.8.1.
Concomitant Conventional CD Medications
Standard immunomodulators (MTX, AZA, and 6-MP) or IV/oral corticosteroids should not be 
initiated (or increased in dose) unless medically necessary as rescue therapy as this will impact the 
efficacy analyses in this study and will be considered treatment failure (see the SAP for full 
treatment failure criteria). If initiated as rescue therapy, these treatments should be discontinued 
or tapered off as soon as medically tolerable and appropriate; however, participants can (and 
should) continue to receive study intervention and attend all study visits despite initiation (or 
increasing dose) of any of these CD related medications, except for those described as prohibited 
medications below (see Section 6.8.2).
6.8.1.1.
Oral Corticosteroids
It is recognized that some participants will have been steroid dependent prior to their surgery and 
may be unable to safely complete tapering of their steroid therapy prior to randomization.  
However, as participants enter the study without residual active CD, participants who enter the 
study on steroids should initiate, or continue, tapering of corticosteroids for CD without any delay 
upon study entry at Week 0, unless medically inappropriate.  Corticosteroid tapering should follow 
the below-recommended schedule (Table 2), without exceeding the prescribed magnitude or rate 
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
Immunosuppressant biologic agents, including but not limited to commercial TNF-
antagonists (eg, infliximab, adalimumab, certolizumab), IL 12-23 inhibitors (ie, 
ustekinumab), IL-23 inhibitors (eg, risankizumab), integrin inhibitors (eg, natalizumab,
vedolizumab), and abatacept

Experimental or investigational CD medications
Note: Until the study treatment period is completed (ie, Week 152), participants must not receive 
commercial guselkumab outside of the protocol or participate in any other CD clinical study with 
an investigational agent while in this study. Further, participants must discontinue any further 
study intervention and also terminate study participation in these circumstances, with performance 
of the early termination visit prior to initiating these drugs. If the decision or realization that this 
is about to occur coincides with a scheduled visit, then the early termination visit should be 
performed in place of the scheduled visit, with the scheduling and performance of the follow-up 
ileocolonoscopy occurring as soon as possible.  The rationale for handling initiation of these agents 
in this way is that subsequent efficacy and safety data in the context of the study would be 
uninterpretable.
As protection of human research participants is paramount, it is recognized that initiating these 
prohibited therapies may rarely be required due to medical necessity. However, initiation of the 
above prohibited medications prior to Week 152 should be documented as a deviation from the 
study protocol (unless study intervention has already been discontinued or completed), and 
participants must be discontinued from receiving further study intervention once these agents are 
started.
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.
7.
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1.
Discontinuation of Study Intervention
A participant’s study treatment should be discontinued if: 

The investigator or the medical monitor believes that for safety reasons (eg, an AE) it is in the 
best interest of the participant to stop treatment. 
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
The participant becomes pregnant or plans a pregnancy within the study period or within 
12 weeks after the last study intervention administration. 

The participant meets ANY of the following TB related conditions:
– A diagnosis of active TB is made.
– A participant has symptoms suggestive of active TB based on follow-up assessment 
questions and/or physical examination or has had recent close contact with a person 
with active TB and cannot or will not continue to undergo additional evaluation.
– A participant undergoing evaluation has chest imaging with evidence of current active 
TB and/or a positive IGRA test result, unless active TB can be ruled out and appropriate 
treatment for latent TB can be initiated prior to the next administration of study 
intervention and continued to completion.
– A participant receiving treatment for latent TB discontinues this treatment prematurely 
or is noncompliant with the therapy.

The participant has a serious adverse reaction that is related to an 
 resulting in 
bronchospasm with wheezing and/or dyspnea that requires ventilatory support OR that results 
in symptomatic hypotension with a decrease in systolic blood pressure >40 mm Hg or blood 
pressure <90/60 mm Hg. In general, discontinuation of study intervention administration must 
be considered for participants who develop non-serious, but severe 
 site reactions.

The participant develops a malignancy including squamous cell skin cancer. Consideration 
may be given to allow participants to continue to receive study intervention if they develop 
≤2 basal cell skin cancers that are adequately treated with no evidence of residual disease. 

The initiation of the following protocol-prohibited medications at any time during the study
as listed in Section 6.8.2.

A serious opportunistic infection occurs.

The participant (or the participant’s representative) withdraws consent (or assent) for further
administration of study intervention. 

The participant has CD-related surgeries that will preclude the future ability to assess efficacy 
through the CDAI. Surgeries that are thought to represent a lack of efficacy of study 
intervention should be considered for discontinuation at the discretion of the Investigator other 
than minor procedures (eg, placement of a seton or cutaneous drainage of an abscess).

The participant has severe liver test abnormalities that are not transient and are not explained 
by other etiologies; see Section 10.7 for definitions of abnormal values.

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 (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.
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
A participant who has crossed over to receive open-label treatment with guselkumab and is 
assessed not to have subsequently attained improvement, in the investigator’s judgement 
(recommended to be initially assessed approximately 16-24 weeks after initiating open-label 
guselkumab treatment).
Participants who discontinue study intervention (for the reasons above) before the end of planned 
study treatment (Week 144), should not terminate their study participation (unless enrolling in an 
investigational advanced therapy CD study or initiating commercial guselkumab prior to cross
over to open-label treatment, as described further below). Instead, participants discontinuing study 
intervention are encouraged to complete study visits through the next 12 weeks, at which time an 
early termination visit (see SoA, Section 1.3) must be performed. Should the early termination 
visit be due within 4 weeks of a regularly scheduled visit, it is appropriate to perform the 
procedures specified for the early termination visit at the appointed time in place of the regular 
scheduled visit.
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 for study participation (distinct from desire to/withdrawal of consent 
to receive further study intervention)

Death

Sponsor decision (eg, participating in any other interventional clinical study with an 
investigational agent or initiating commercial guselkumab treatment prior to cross over to 
open-label guselkumab treatment)
When a participant withdraws or is withdrawn/terminated prior to study completion, the reason for
withdrawal is to be documented in the eCRF and in the source document. These participants should 
complete the safety and efficacy evaluations specified for the early termination visit in the SoA 
(Section 1.3). If participants refuse to remain in the study to perform the early termination visit 
12 weeks after last study intervention administration, the participant’s desire to withdraw their 
consent for further study participation should be accommodated by performing the early 
termination visit as soon as necessary/possible. Thus, if possible, the early termination visit should 
be moved up and performed prior to when the participant might withdraw their consent.  If/when 
a participant decides to withdraw their consent to participate in the study, then no additional 
assessments are allowed, or can be performed.
Withdrawal of Consent
A participant declining to return for one or more 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.
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If the participant also chooses to withdraw consent for use of samples for research (refer to Long-
Term Retention of Samples for Additional Future Research in Appendix 3: Regulatory, Ethical, 
and Study Oversight Considerations), 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.
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, 
emails, 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.
8.
STUDY ASSESSMENTS AND PROCEDURES
Overview
The Schedule of Activities (Section 1.3) summarizes the frequency and timing of efficacy, safety, 
and other (ie, PK, immunogenicity, pharmacodynamics (PD), biomarker, pharmacogenomic, 
medical resource utilization, and health economic) measurements applicable to this study.
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. 
If multiple assessments are scheduled for the same timepoint, it is recommended that procedures 
be performed in the following sequence: PROs, C-SSRS, blood sample collection, urine pregnancy 
test if required, then study intervention administration.
PK (urine and blood) and PD (fecal calprotectin and CRP) assessments should be kept as close to 
the specified time as possible. Other measurements may be done earlier than specified timepoints 
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if needed. Actual dates and times of assessments will be recorded in the source documentation and 
eCRF.
The total blood volume to be collected from each participant will be no more than approximately 
250 mL. However, additional repeat or unscheduled samples may be taken for safety reasons or 
for technical issues with the samples.
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.
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. 
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 Week 0.
Participants must undergo testing for TB (Section 8.4.9.1) and their medical history assessment 
must include specific questions about a history of TB or known occupational or other personal 
exposure to individuals with active TB. The participant should be asked about past testing for TB, 
including chest radiograph results and responses to tuberculin skin or other TB testing. A 
participant’s eligibility according to TB screening criteria is described in Section 5.2, Exclusion 
Criteria.
Week 0 Visit
Prior to entering the study, the participant must be evaluated for eligibility. 
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An assessment of all previous laboratory results, clinical data, and concomitant medication data
will be made by the principal investigator or designee to confirm that the participant satisfies all
inclusion criteria and does not violate any exclusion criteria prior to randomization.
Post-baseline Visits
Study visits should occur at the week indicated ± 10 days. Note that while out of window visits 
should be recorded as protocol deviations, it is preferable to perform visits and procedures out of 
window than not perform them at all. One exception may be if sufficient time has passed that it is 
now in-window for the next subsequent visit, in which case it is advised to contact the medical 
monitor for assistance in how to best manage the situation.
Study agent administration should not occur when a participant is experiencing a clinically 
important, active infection, an example of an appropriate reason to deviate from protocol-specified 
windows (which should then be documented appropriately).
The participant will be instructed to complete the CDAI daily diary through Week 152. For all
visits where a score needs to be calculated in real-time, the most recent hematocrit value available
will be used when calculating the CDAI score.
Flare Visit
During the study, participants who are suspected to be having a flare of disease activity (eg, 
example, an increase in the PRO-2 [as described in Section 8.1.2] score of at least 50 points over
a 7-day period compared to baseline, or suspicion of a new fistula or abscess) can present for 
further evaluation at the flare visit (see SoA).  This visit may include an endoscopy if it is 
determined that participant has a both a CDAI score of over 200 and an increase of at least 70 
points over baseline.   
Participants in clinical flare should undergo endoscopy, unless it can be determined without 
endoscopy that they have met criteria for disease recurrence (see Section 9.4.3). 
Cross Over Visit
After Week 8, if a determination has been made that the participant has had a disease recurrence 
(by meeting the criteria outlined in Section 9.4.3 and confirmed by the central reader of i2a or 
greater disease when applicable) a cross over visit should be scheduled. Participants who have 
endoscopic recurrence confirmed by the central reader at the scheduled Week 48 ileocolonoscopy 
or on a flare visit ileocolonoscopy will be scheduled for a cross over visit. In addition, participants
who are determined by the central reader to have endoscopic recurrence at the Week 24 (but do 
not have disease recurrence) can also schedule a cross over visit at the discretion of the principal 
investigator.  
Procedures to be performed at the cross over visits are outlined in the Cross Over SoA 
(Section 1.3). Participants will receive their first dose of open-label guselkumab 400 mg SC at the 
cross over visit.  Participants will then get a second 
 dose4 weeks after the cross over visit 
which will be self-administered at home. The third 
 dose will be given 8 weeks after the 
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cross over visit at a scheduled post-cross over visit. After the three
 induction doses, 
participants will receive open-label guselkumab 
. The first open-label 
 dose will be given at a scheduled visit. Subsequent study visits will occur every 16 weeks 
during which the 
 dose will be administered, with every other dose administered at home.
The final dose will be given at the Final Dosing Visit, which will fall between Week 137 and Week 
144 from the original randomization date. The Final Efficacy Visit will occur 8 weeks after the 
Final Dosing Visit, and will therefore fall between Weeks 145 and 152 from the original 
randomization date. The Final Safety Visit should occur 4 weeks after the Final Efficacy Visit (12 
weeks after last dose of study agent), and will therefore fall between Weeks 149 and Weeks 156 
from the original randomization date. If allowed by local regulation and if clinically appropriate, 
the Final Safety Visit can be done by telephone and no safety laboratory blood samples drawn. 
The study assessments for the Final Dosing Visit, Final Efficacy Visit, and Final Safety Visit will 
match the Week 144, Week 152 and Week 156 assessments in the original SoA, respectively.
Home Health Care and Telehealth Visits 
Telehealth visits (conducted via phone or video conference) may be implemented by or with 
approval from the sponsor and per clinical judgement of the investigator for certain circumstances 
when warranted where feasible and permissible by local policy, regulations (as applicable) and for 
participants for whom there is no safety concern.
The nature of study procedures which may be performed with home health care and telehealth 
visits as circumstances necessitate will be defined by the Sponsor (see Section 10.8 for more 
details).
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the eCRF or laboratory 
requisition form. Refer to the SoA (Section 1.3) for the timing and frequency of all sample 
collections. 
Instructions for the collection, handling, storage, and shipment of samples are found in the 
laboratory manual that will be provided. Collection, handling, storage, and shipment of samples 
must be under the specified, and where applicable, controlled temperature conditions as indicated 
in the laboratory manual.
Study-Specific Materials
The investigator will be provided with the following supplies:

Investigator Site File (includes protocol and IB)

Investigational Product Procedures Manual (IPPM)

Instructions for Use (IFU) for at home administration of guselkumab/placebo

Central laboratory manual 

eCRF completion instructions
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
Patient recruitment materials

ICF

Home dosing study medication diary

IWRS manual

Biopsy manual

Electronic patient-reported outcome equipment, questionnaires and quick reference guide

Endoscopy kit

Imaging manual

Laboratory manual

Laboratory kits

Source documents as applicable
8.1.
Efficacy Assessments
Efficacy assessments 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 modified Rutgeerts score and 
SES-CD

Histologic assessments based on the Global Histology Activity Score (GHAS), Robarts 
histopathology index (RHI), and Geboes score

Inflammatory PD markers, including CRP and fecal calprotectin

Fistula assessment

PRO measures to assess health-related quality of life and work productivity outcomes 
including PROMIS-29, PROMIS Fatigue-7a, Work Productivity and Activity Index for 
Crohn’s Disease (WPAI-CD)
8.1.1.
CDAI
The CDAI (Crohn’s Disease Activity Index) 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 (Appendix 9). The abdominal mass is 
assessed through physical examination. Total number of liquid or very soft stools, AP/cramping, 
use of antidiarrheal drug(s) and/or opiates, and general well-being are recorded by the participant 
on an electronic home diary or diary card on a daily basis.
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8.1.2.
PRO-2: Unweighted Mean Daily CDAI Components of the Total 
Number of Liquid or Very Soft Stools and the AP
The PRO-2 includes the CDAI components of the total number of liquid or very soft stools and 
the AP score.
8.1.3.
Endoscopic Assessments of the Intestinal Mucosa
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 Schedule of Activities (Section 1.3). Video endoscopies will be assessed by a central facility 
that will be blinded to treatment group and visit. If the video ileocolonoscopy is inconclusive (eg 
the recording fails, poor preparation obscures the ability to identify recurrence), then it is 
recommended to repeat the procedure as soon as feasible, if the participant is willing. The modified 
Rutgeerts score (Table 3) will be used to evaluate endoscopic recurrence. 
The Rutgeerts score is widely accepted as a clinical and research tool and is commonly utilized in 
clinical practice as well.  It is used to assess endoscopic severity and predict the risk of clinical 
postoperative recurrence based on early endoscopic findings in the neo-terminal ileum and 
anastomosis after ileocolonic resection (Rutgeerts 1984, Rutgeerts 1990). Ileal lesions are scored 
at ileocolonoscopy and characterized as i0 (no lesions) through i4 (diffuse inflammation with large 
ulcers, nodules or narrowing). In the 1990 study by Rutgeerts et al, the Rutgeerts score (see 
Section 8.1) was found to be the most important predictor of symptomatic recurrence of CD 
(p=0.0001). Furthermore, 80% of patients with a score of i0 or i1 had no progression of endoscopic 
disease activity at 3 years, whereas 92% of patients with i3 or i4 lesions had progression of 
endoscopic disease at 3 years. The outcomes of patients with i2 lesions have been heterogenous, 
therefore, a modified Rutgeerts score was proposed to divide the i2 category into lesions at the 
ileocolonic anastomosis (i2a) and > 5 aphthous ulcers in the neo-terminal ileum with normal 
mucosa in between (i2b). However, recent studies did not show a difference in clinical recurrence 
amongst patients with Rutgeerts scores of i2a versus i2b (Bayart 2016, Rivière 2019).
Endoscopic recurrence defined as a Rutgeerts score > i2 (modified Rutgeerts > i2a) has been 
adopted as the standard endoscopic outcome in most trials of POCD therapy (D’Haens 2008, 
Hanauer 2004, Hellers 1999, Reguiero 2016). The International Organization for the Study of 
Inflammatory Bowel Disease performed a technical review and then a 2-round vote among 14 IBD 
specialists using the Delphi method, and all agreed on a Rutgeerts’ score of i0-i1 as the definition 
of postoperative endoscopic remission (Vuitton 2016). Additionally, in their recommendations for 
clinical trial design in POCD, an international panel of IBD experts recommended the modified 
Rutgeerts score as an appropriate measure of postoperative endoscopic CD activity in regulatory 
clinical trials (Hanzel 2021). Endoscopic recurrence has also been shown to be a strong predictor 
of subsequent clinical recurrence. In a meta-analysis of randomized controlled trials, the relative 
risk for clinical recurrence among patients who experienced endoscopic recurrence was 10.77 
(95% CI 4.08-28.40).  An accompanying meta-analysis of 11 cohort studies showed an even higher 
relative risk of 21.33 (95% CI 9.55-47.66). In addition, a single cohort study in the analysis showed 
a linear relationship between Rutgeerts score and clinical recurrence risk (Ble 2021).
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While the study is ongoing, the modified Rutgeerts score as interpreted by the central reader will 
be used to determine whether endoscopic recurrence has occurred. As discussed in Section 6.5.1, 
cross over to open-label induction with guselkumab is permissible, at the discretion of the principal 
investigator, if endoscopic recurrence is confirmed on optional Week 24 ileocolonoscopy, and is 
mandatory after confirmed endoscopic recurrence on Week 48 ileocolonoscopy or after confirmed 
disease recurrence. If a participant does not cross over at Week 24 for endoscopic recurrence but 
within the following 16 weeks develops a CDAI in > 70 or meets the corticosteroid-related disease 
recurrence criteria (see Section 9.4.3), then the participant may cross over without the need for a 
repeat ileocolonoscopy. Results of the video ileocolonoscopies read by the central reader will also 
be the basis for the primary and secondary analyses of disease and endoscopic recurrence.
Table 3:
Modified Rutgeerts Score
Score
Endoscopic Findings
i0
No lesions
i1
< 5 aphthous lesions
i2
> 5 aphthous lesions with normal mucosa between the lesions or skip areas of larger lesions 
or lesions confined to the ileocolonic anastomosis (ie, < 1 cm in length)
i2a
Lesions confined to the ileocolonic anastomosis (including anastomotic stenosis)
i2b
More than 5 aphthous ulcers or larger lesions, with normal mucosa in-between, in the 
neoterminal ileum (with or without anastomotic lesions)
i3
Diffuse aphthous ileitis with diffusely inflamed mucosa
i4
Large ulcers with diffuse mucosal inflammation or nodules or stenosis in the neoterminal 
ileum
Ileocolonoscopies will also be read by central reader(s) using the SES-CD for 
scientific/exploratory purposes. 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.
8.1.4.
Histologic Assessments Based on Global Histologic Disease Activity 
(GHAS), Geboes Score, and Robarts Histopathology Index (RHI)
Histologic assessments will be performed using biopsy samples collected during video 
ileocolonoscopy (see endoscopy manual for biopsy details). Histologic assessments will be 
conducted by a central reader who is blinded to treatment groups and visit. The GHAS, Geboes 
score, and Robarts Histopathology Index will be used to evaluate histologic improvements and 
healing (Geboes 2000; Mosli 2017; D’Haens 1999).
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8.1.5.
Inflammatory PD markers: CRP and Fecal Calprotectin
Inflammatory pharmacodynamic markers will be evaluated using blood samples as indicated by 
the Schedule of Activities (Section 1.3). 
CRP has been demonstrated to be useful as a marker of inflammation in patients with IBD.  In CD, 
elevated CRP concentrations have been associated with severe clinical activity, elevated 
sedimentation rate, and active disease as detected by ileocolonoscopy. Blood samples for the 
measurement of CRP will be collected from all participants. 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. Stool samples for fecal 
calprotectin concentration will be collected from all participants. The assay for fecal calprotectin 
concentration will be performed using a validated method.
8.1.6.
External Perianal Fistula Assessment
Fistula assessment will be performed in all participants on an ongoing basis throughout the 
duration of the study. All participants will be assessed for fistulas at baseline. For participants with 
perianal 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).
8.2.
Patient-reported Outcomes 
The PRO instrument will be provided in the local language in accordance with local guidelines.
Details regarding the PROs will be available for regulators and for IRB/IEC submissions and will 
be provided separately in a companion manual with the instruments that will be submitted with 
the protocol.
The PRO and AE data will not be reconciled with each other.
8.2.1.
Patient-reported Outcomes Measurement Information 
System (PROMIS)-29
The Patient-Reported Outcomes Measurement Information System (PROMIS)-29 is a validated 
general health profile instrument that is not disease-specific (Hayes 2018). 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 an activities). They 
assess all domains over the past seven days except for Physical Function which has no timeframe 
specified. PROMIS-29 also includes an overall average pain intensity 0-10 numeric rating scale. 
The raw score of each domain is converted into a standardized score with a mean of 50 and a 
standard deviation (SD) of 10 (T-Score). The standardized T-score is reported as the final score 
for each participant. Pain Intensity is presented as raw responses (0-10). Norm-based scores have 
been calculated for each domain on the PROMIS measures, with a score of 50 representing the 
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mean or average of the reference population. On symptom-oriented domains of PROMIS-29 
(anxiety, depression, fatigue, pain interference, and sleep disturbance), higher scores represent 
worse symptomatology. On the function-oriented domains (physical functioning and social role), 
higher scores represent better functioning.
8.2.2.
PROMIS Fatigue-7a
The PROMIS Fatigue 7-items Short Form (PROMIS Fatigue Short Form 7a) contains 7 items 
evaluating fatigue-related symptoms (ie, tiredness, exhaustion, mental tiredness, and lack of 
energy) and associated impacts on daily activities (ie, activity limitations related to work, selfcare, 
and exercise) (Ameringer 2016). PROMIS Fatigue Short Form 7a has a recall period of past 7 
days. Compared to the fatigue scale of PROMIS-29, PROMIS Fatigue Short Form 7a provides 
additional information to evaluate severity of fatigue. The raw total score is converted into a 
standardized score with a mean of 50 and a SD of 10 (T-Score). The standardized T-score is 
reported as the final score for each participant.
8.2.3.
Work Productivity and Activity Index for Crohn’s disease (WPAI-CD)
The WPAI-CD is a validated instrument created as a patient-reported quantitative assessment of 
the amount of absenteeism, presenteeism, and daily activity impairment attributable to CD (Reilly 
2008). The WPAI-CD consists of 6 questions to determine employment status, hours missed from 
work due to CD, hours missed from work for other reasons, hours worked, the degree to which 
CD affected work productivity while at work, and the degree to which CD affected activities 
outside of work. Higher scores indicate greater impairment.
8.3.
Healthcare Resource Utilization Data 
CD-related hospitalizations,  surgeries,  emergency room visits,  medication  use,  and physician  
visits will  be  used  to  evaluate  healthcare  resource  utilization, which  are  important 
considerations when assessing ideal therapy selection in CD patients.
8.4.
Safety Assessments
Safety evaluations will include the assessment of AEs, clinical laboratory tests (hematology and 
chemistry), vital signs, screening physical examination, concomitant medication review, and 
monitoring for hypersensitivity reactions, 
site reactions, suicidal ideation and behavior 
by the C-SSRS, and early detection of active TB. 
Evaluations of safety and tolerability will occur at time points specified in the SoA (Section 1.3). 
Adverse events will be reported and followed by the investigator as specified in Section 8.5, 
Adverse Events, Serious Adverse Events, and Other Safety Reporting, and Appendix 4: Adverse 
Events, Serious Adverse Events, Product Quality Complaints, and Other Safety Reporting: 
Definitions and Procedures for Recording, Evaluating, Follow-up, and Reporting.
Any clinically relevant changes occurring during the study must be recorded on the Adverse Event 
section of the eCRF.
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Any clinically significant abnormalities (ie, SAEs) 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 Schedule of Activities.
8.4.1.
Physical Examinations
A complete, detailed physical examination, including height and weight, will be performed as per
local practice standards for eligibility assessment. While assessment of the participants for safety
and efficacy requires a full physical examination at screening and at Week 152, a directed physical 
exam for abdominal mass and fistulas, (perianal and other) will be performed at all visits. 
Participants will be instructed to remove shoes and outdoor apparel and gear prior to measurements 
for height and weight.
Physical examination data will not be included in the study database as such; abnormal physical 
examination findings are to be reported as AEs. 
8.4.2.
Vital Signs
Temperature, pulse/heart rate, respiratory rate, and blood pressure will be assessed at the Week 0, 
48, and 152 visits. Vital signs should be recorded before and approximately 30 minutes after the 
study intervention 
 during the main treatment period through Week 48, or if the 
participant reports symptoms.
Study participants who are trained to self-inject (or will have a trained caregiver to inject) study
intervention at home will be trained to perform self-evaluation for 
site reactions and
reporting of AEs after administering study interventions at home. Vital signs will only be assessed 
at the study site when study participants receive study intervention administration at the study site.
Vital signs data, which are considered source data, are not to be entered into the study database or 
analyzed. Abnormal vital signs are to be recorded as AEs.
8.4.3.
Clinical Safety Laboratory Assessments
Blood samples for serum chemistry and hematology will be collected as noted in Appendix 2:
Clinical Laboratory Tests. 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.
8.4.4.
Pregnancy Testing
Pregnancy testing will consist of a serum pregnancy test at screening and urine testing at on-site 
study visits. Additional serum or urine pregnancy tests may be performed, as determined necessary 
by the investigator or required by local regulation, or if a participant suspects pregnancy, to 
establish the absence of pregnancy at any time during the participation in the study.
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8.4.5.
Suicidal Ideation and Behavior Risk Monitoring
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 
evaluation of safety. The C-SSRS is an investigator-administered questionnaire and will be 
generally conducted on the electronic clinical outcomes assessment (eCOA) device provided to 
the site. The C-SSRS will be provided in the local languages in accordance with local guidelines.
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 Week 0 and all other site visits through the end of the study. 
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 PROs but before any other study procedure.  The investigator or 
trained study-site personnel will interview the participant in a private place and complete the C-
SSRS. 
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. 
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
Suicidal ideation levels 4 or 5 or any suicidal behavior: Participant risk assessed and referral 
to a mental health professional. 
Interruption or the discontinuation of study intervention should be considered for any participant 
who reports 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) 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 (Section 7.1). 
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. The completed C-SSRS 
and AE data will not be reconciled with each other.
8.4.6.
Site Reactions
A study intervention 
site reaction is any adverse reaction at a SC study intervention 
site. The 
 sites will be evaluated for reactions at on-site visits and any 
site reaction will be recorded as an AE.
8.4.7.
Hypersensitivity Reactions
Before any administration of study intervention at the study site, appropriately trained personnel 
and medications (eg, antihistamines, injectable epinephrine) must be available to treat 
hypersensitivity reactions, including anaphylaxis. All participants must be alert for or, when on 
site, observed carefully for signs and symptoms of a hypersensitivity reaction (eg, urticaria, 
pruritus, angioedema, wheezing, dyspnea, or hypotension). If a mild or moderate hypersensitivity 
reaction 
is 
observed, 
acetaminophen, 
nonsteroidal 
anti-inflammatory 
drugs, 
and/or 
diphenhydramine may be administered. Participants who experience serious adverse reactions 
related to an infusion must strongly be considered to be discontinued from further study 
intervention administrations. 
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 infusions are being administered. 
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 infusion 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 headache.
CCI
CCI
CCI
CCI
CCI
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8.4.8.
Infections
Investigators are required to evaluate participants for any signs or symptoms of infection at 
scheduled visits. Study intervention administration should not be given to a participant with a 
clinically significant, active infection. If a participant develops a serious infection, discontinuation 
of study intervention should be considered. 
8.4.9.
Tuberculosis Evaluations
8.4.9.1.
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, or 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 test result 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. Appropriate treatment for latent TB is defined according to local country 
guidelines 
for 
immunocompromised 
patients. 
If 
no 
local 
country 
guidelines 
for 
immunocompromised patients exist, US guidelines must be followed.  
Participants with indeterminate/borderline IGRA test results should have the test repeated. 
Participants with persistently indeterminate/borderline IGRA test results may be randomized or 
continued in the trial 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.
8.4.9.2.
Ongoing Tuberculosis Evaluation
To aid in the early detection of TB infection or exposure during study participation, participants 
must be evaluated for TB signs, symptoms, and close contacts at scheduled visits (refer to 
Section 1.3) or by telephone approximately every 8 to 12 weeks. The following series of questions 
is suggested for use during the evaluation:
–
“Have you had a new cough of > 14 days’ duration or a change in a chronic cough?”
–
“Have you had any of the following symptoms:
Persistent fever?
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Unintentional weight loss?
Night sweats?”
–
“Have you had close contact with an individual with active TB?”  (If there is uncertainty as 
to whether a contact should be considered “close,” a physician specializing in TB should be 
consulted.)
If the evaluation raises suspicion for TB infection or the participant has had a close contact 
exposure to TB, study intervention must be withheld and an immediate and thorough investigation 
must be undertaken, including consultation with a physician specializing in TB to determine if 
treatment is warranted prior to any further study intervention. Participants should be encouraged 
to return for all subsequent scheduled study visits according to the protocol.
Note: Investigators should be aware that TB reactivation in immunocompromised participants may 
also present as extrapulmonary or disseminated disease.
8.5.
Adverse Events, Serious Adverse Events, and Other Safety Reporting
Timely, accurate, and complete reporting and analysis of safety information, including AEs, 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 a PQC.
Further details on AEs, SAEs, and PQCs can be found in Appendix 4: Adverse Events, Serious 
Adverse Events, Product Quality Complaints, and Other Safety Reporting: Definitions and 
Procedures for Recording, Evaluating, Follow-up, and Reporting.
8.5.1.
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 immediately, but no later than 24 hours of their knowledge of the event.
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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, alkaline 
phosphatase (ALP) <2 x ULN together with total bilirubin ≥2 x ULN or International Normalized 
Ratio (INR) >1.5 (if measured) (see Appendix 10.7). Any possible Hy’s Law case is considered an 
important medical event and must be reported to the sponsor in an expedited manner, even before 
all other possible causes of liver injury have been excluded.  A confirmed Hy’s law case must be 
reported as a SAE.
Information regarding SAEs will be transmitted to the sponsor using the Serious Adverse Event 
Form, which must be completed and signed by a physician from the study site, and transmitted to 
the sponsor immediately but no later than within 24 hours. The initial and follow-up reports of an 
SAE should be made by facsimile (fax). Telephone reporting should be the exception and the 
reporter should be asked to complete the appropriate form(s) first.
8.5.2.
Method of Detecting Adverse Events and Serious Adverse Events
Care will be taken not to introduce bias when detecting AEs or SAEs. Open-ended and nonleading 
verbal questioning of the participant is the preferred method to inquire about AE occurrence.
Solicited Adverse Events
Solicited AEs are predefined as 
 site reactions and systemic events for which the 
participant is specifically questioned.
Unsolicited Adverse Events
Unsolicited AEs are all AEs for which the participant is not specifically questioned.
8.5.3.
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 or SAE as 
fully as possible. This may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other health care professionals.
Adverse events and the special reporting situation of pregnancy, will be followed by the 
investigator as specified in Appendix 4: Adverse Events, Serious Adverse Events, Product Quality 
Complaints, and Other Safety Reporting: Definitions and Procedures for Recording, Evaluating, 
Follow-up, and Reporting.
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8.5.4.
Regulatory Reporting Requirements for Serious Adverse Events and 
Anticipated Events
The sponsor assumes responsibility for appropriate reporting of AEs to the regulatory authorities. 
The sponsor will also report to the investigator (and the head of the investigational institute where 
required) all suspected unexpected serious adverse reactions (SUSARs). The investigator (or 
sponsor where required) must report SUSARs to the appropriate Independent Ethics 
Committee/Institutional Review Board (IEC/IRB) that approved the protocol unless otherwise 
required and documented by the IEC/IRB. A SUSAR will be reported to regulatory authorities 
unblinded. Participating investigators and IEC/IRB will receive a blinded SUSAR summary, 
unless otherwise specified.
An anticipated event is an AE that commonly occurs in the study population independent of 
exposure to the drug under investigation. For the purposes of this study the following SAEs will 
be considered anticipated events:
• 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/territories in which the studies are conducted.
8.5.5.
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 be promptly withdrawn from the study and discontinue further 
study intervention.
Follow-up information regarding the outcome of the pregnancy for female participants who 
become pregnant, or where the pregnancy was the result of male participant and his partner, and 
any postnatal sequelae in the infant will be requested.
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8.5.6.
Adverse Events of Special Interest
Any newly identified malignancy or case of active TB occurring after the first study intervention
administration(s) in participants participating in this clinical study must be reported by the
investigator to the sponsor or designee within 24 hours after being made aware of the event,
according to the procedures in Section 8.5.3 for SAEs. Investigators are also advised that active
TB is considered a reportable disease in most countries. These events are to be considered serious 
only if they meet the definition of an SAE.
8.6.
Pharmacokinetics
8.6.1.
Evaluations
Venous blood samples of sufficient volume will be collected for measurement of  serum 
concentrations of guselkumab.
Each  serum sample will be divided into 3 aliquots (1 each for PK, anti-guselkumab antibodies to 
guselkumab, and a back-up). Additional information about the collection, handling, and shipment 
of biological samples can be found in the Laboratory Manual.
8.6.2.
Analytical Procedures 
Pharmacokinetics
Serum samples will be analyzed to determine concentrations of guselkumab using a validated, 
specific, and sensitive immunoassay method 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.
8.6.3.
Pharmacokinetic Parameters and Evaluations
Parameters
Serum samples will be used to evaluate the PK of guselkumab. Serum collected for PK may 
additionally be used to evaluate safety or efficacy aspects that address concerns arising during or 
after the study period. Genetic analyses will not be performed on these serum samples. Participant 
confidentiality will be maintained.
Pharmacokinetic/Pharmacodynamic Evaluations
The relationship between serum concentrations of guselkumab and efficacy measures or relevant
biomarker(s) may be examined where appropriate.
8.7.
Genetics and Pharmacogenomics
Participation in pharmacogenomic research is optional. 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). 
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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.
Whole blood samples of approximately 6 mL will be collected for genetic analyses as specified in 
the SoA (Section 1.3). 
8.8.
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 treatment.
2.
To understand CD pathogenesis.
3.
To understand why an individual participant may respond differently to guselkumab.
4.
To understand the impact of treatment with guselkumab on intestinal inflammation.
5.
To develop diagnostic tests to identify CD populations, and IBD patients in general, that may 
be responsive or nonresponsive to treatment with guselkumab.
Stopping Analysis
Biomarker analyses are dependent upon the availability of appropriate biomarker assays and 
clinical response rates. Biomarker analysis may be deferred or not performed, if during or at the 
end of the study, it becomes clear that the analysis will not have sufficient scientific value for 
biomarker evaluation, or if there are not enough samples or responders to allow for adequate 
biomarker evaluation. In the event the study is terminated early or shows poor clinical efficacy, 
completion of biomarker assessments is based on justification and intended utility of the data.
8.8.1.
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 CD. 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 
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changes in transcriptome profiles that may correlate with biologic response relating to CD or the 
action of guselkumab.
8.8.2.
Mucosal Biopsy (Histology, RNA, and Single Cell Isolation)
Mucosal biopsy samples will be collected from all participants during ileocolonoscopy at the times 
specified in the SoA for histologic assessment, RNA expression analysis, and single cell isolation.
Total RNA will be isolated and used for differential gene expression analyses to identify mRNA 
or microRNA expression patterns that are relevant to guselkumab treatment and/or CD, and to 
evaluate markers that can predict therapeutic response. The biopsy samples collected will also be 
used for the histologic and immunohistochemical assessment of disease and healing. Protein and 
gene expression will be measured at higher resolution in various immune cell populations isolated 
from these biopsy samples.
8.8.3.
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. 
8.9.
Immunogenicity Assessments
Antibodies to guselkumab will be evaluated in serum samples collected from all participants 
according to the SoA. Additionally, serum samples should also be collected at the final visit from 
participants who discontinued study intervention or were withdrawn from the study. These samples 
will be tested by the sponsor or sponsor's designee.
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.
Samples collected for immunogenicity analyses may additionally be used to evaluate safety or 
efficacy aspects that address concerns arising during or after the study period. Genetic analyses 
will not be performed on these serum samples. Participant confidentiality will be maintained.
Analytical Procedures 
The detection and characterization of antibodies to guselkumab will be performed using a validated 
assay method by or under the supervision of the sponsor. Samples may be stored up to 15 years 
(or according to local regulations) following the last participant’s last visit for the study at a facility 
selected by the sponsor to enable further analysis of immune responses to guselkumab.
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9.
STATISTICAL CONSIDERATIONS
Statistical analysis will be done by the sponsor or under the authority of the sponsor. A general 
description of the statistical methods to be used to analyze the efficacy and safety data is outlined 
below. Specific details will be provided in the Statistical Analysis Plan (SAP).
9.1.
Statistical Hypotheses
The primary hypothesis is that guselkumab is superior to placebo in preventing endoscopic 
recurrence prior to or at Week 48.
9.2.
Sample Size Determination
A sample size of 370 participants (185 participants assigned to guselkumab and 185 assigned to 
placebo) will allow to have at least 90% power to detect 20% differences between guselkumab 
(30%) and placebo (50%) for endoscopic recurrence rate (primary endpoint) prior to or at Week 
48, assuming a 2-sided alpha level of 0.05.
This also will allow at least 90% power to detect 17% differences between guselkumab (37%) and 
placebo (20%) for clinical remission without disease recurrence at Week 48, assuming a 2-sided 
alpha level of 0.05. This also will allow 90% power to detect 10% differences between guselkumab 
(10%) and placebo (20%) for disease recurrence at the main study database lock, all available 
follow-up of all participants will be used to examine disease recurrence at the time of the database 
lock. 
Endoscopic Recurrence
Assumptions for endoscopic recurrence prior to or at Week 48 were based on previous studies, as 
described in Table 4.
Table 4:
Endoscopic Recurrence, Placebo Group
Reference 
Endoscopic 
Recurrence definition
Sample Size
Placebo rate 
Timepoint
Regueiro 2016
Rutgeerts > i2
150
60%
76 weeks
Yamamoto 2007
Rutgeerts > i2
20
70%
52 weeks
Marteau 2006
Rutgeerts > i2
47
64%
24 weeks
Rutgeerts 2005
Rutgeerts > i2
33
78.8% 
52 weeks
Hanauer 2004
Rutgeerts > i2
40
64% 
104 weeks
Lochs 2000
Rutgeerts > i2
166
50% 
72 weeks
Ewe 1999
Rutgeerts > i2
40
70% 
52 weeks
Hellers 1999
Rutgeerts > i2
66
58% 
52 weeks
Based on these data above, the endoscopic recurrence rates are assumed to be 50% for placebo and 
30% for guselkumab.
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To accommodate other potential scenarios, power was calculated based on different assumptions 
as listed in Table 5.
Table 5:
Power to Detect a Treatment Effect Based on Different Scenarios in Endoscopic Recurrence
Event rate at Week 48
for endoscopic 
recurrence in placebo 
group
Event rate at Week 
48 for endoscopic 
recurrence in 
guselkumab group
Difference to be 
detected
Power
50%
30%
20%
97.7%
50%
25%
25%
99.9%
50%
35%
15%
83.3%
45%
25%
20%
98.3%
40%
20%
20%
98.9%
60%
30%
30%
>99.9%
Clinical Remission without Disease Recurrence
Based on data from PREVENT (20% for placebo, and 36.7 for Infliximab), the rates of clinical 
remission without disease recurrence are assumed to be 20% for placebo and 37% for guselkumab.
To accommodate other potential scenarios, power was calculated based on different assumptions 
as listed in Table 6:
Table 6:
Power to Detect a Treatment Effect Based on Different Scenarios in Clinical Remission without 
Disease Recurrence
Event rate at Week 48
for clinical remission 
without disease 
recurrence in placebo 
group
Event rate at Week 
48 for clinical 
remission without 
disease recurrence
in guselkumab
group
Difference to be 
detected
Power
20%
35%
15%
90.0%
20%
36%
16%
93.1%
20%
37%
17%
95.4%
Disease Recurrence
Assumptions for disease recurrence were based on previous studies, as described in Table 7
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Table 7:
Disease Recurrence, Placebo Group
Reference
Disease Recurrence definition
Sample 
Size
Placebo rate
Timepoint
Regueiro 2016
CDAI > 200 and 70 point 
increase
150
20%
76 weeks
Ng 2009
Symptoms related to CD 
associated with endo, lab or 
radiologic findings
99
28%
52 weeks
Yamamoto 2007
CDAI > 150
20
35%
52 weeks
Rutgeerts 2005
CDAI > 250 or need for rescue 
medical therapy
40
37.5%
54 weeks
Prantera 2002
CDAI >150, confirmed by 
endoscopy
22
10.5%
52 weeks
Lochs 2000
CDAI >250 or CDAI > 200 with 
a 60 point increase
166
31.4%
72 weeks
Hellers 1999
CDAI > 200
66
31%
52 weeks
Ewe 1999
CDAI > 200, rise of 60 points
40
28%
52 weeks
Olaison 1992
CDAI > 150 or HBI >4
42
37%
52 weeks
For this endpoint, all follow-up data available at the primary DBL, including beyond one year 
when available, will be used.  Based on this, as well as these data above, the disease recurrence 
rates are assumed to be 20% for placebo and 10% for guselkumab.
To accommodate other potential scenarios, power was calculated based on different assumptions 
as listed in Table 8.
Table 8:
Power to Detect a Treatment Effect Based on Different Scenarios in Disease Recurrence
Event rate at Week 48
for disease recurrence 
in placebo group
Event rate at Week 48
for disease recurrence 
in guselkumab group
Difference to be 
detected
Power
20%
10%
10%
90.0%
8%
12%
98.5%
25%
15%
10%
80.9%
10%
15%
99.7%
30%
15%
15%
98.5%
Accrual time used here is 18 months, total time used here is 30 months. It is expected median 
follow-up time available at the time of, and thus incorporated in, the main database lock is 
approximately 18 months. Assuming non-uniform accrual pattern: 25% of participants will be 
enrolled in the first 6 months, 35% of participants will be enrolled in the next 6 months, and 40% 
will be enrolled in the last 6 months. Assuming dropout rate is 15% annually. Average duration of 
follow-up is expected to be approximately 20 months.
9.3.
Participant Analysis Sets
For purposes of analysis, the following populations are defined in Table 9.
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Table 9:
Description of Analysis Populations
Population
Description
Full Analysis Set
All randomized participants 
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 randomized participants who received at least 1 dose of study intervention and have 
appropriate samples for anti-drug antibody detection
9.4.
Statistical Analyses
The SAP will be finalized prior to the first DBL and it will include a more technical and detailed 
description of the statistical analyses described in this section. This section is a summary of the 
planned statistical analyses of the most important endpoints including primary and key secondary 
endpoints.
9.4.1.
General Considerations
This section is a summary of the planned statistical analyses of the most important endpoints 
including primary and secondary endpoints. The SAP will include a more technical and detailed 
description of the statistical analyses described in this section.
Descriptive statistics (eg, mean, median, standard deviation [SD], interquartile [IQ] range, 
minimum, and maximum) will be used to summarize continuous variables. Counts and percentages 
will be used to summarize categorical variables. Graphical data displays (eg, line plots) may also 
be used to summarize data. If significant imbalances were found between treatment groups, 
additional analyses may be conducted to adjust for the baseline difference. The Kaplan-Meier 
method will be used to summarize data for time-to-event variables. 
The overall Type I error rate will be controlled at the significance level of 0.05 (2-sided).
Hierarchical testing will be performed for primary and secondary endpoints, the ordering of which 
will be described in the SAP.
9.4.2.
Primary Endpoint
The primary endpoint is endoscopic recurrence prior to or at Week 48 as defined by modified 
Rutgeerts score ≥ i2a in the neo-terminal ileum, anastomotic site, or its equivalent elsewhere in the 
GI tract (eg, colonic ulceration).
Estimands and Estimators
Primary Estimand of Endoscopic Recurrence prior to or at Week 48
Treatment by Week 48: 
Experimental: Guselkumab 
 at Week 0 and then 
 at Week 8, then 
 
thereafter through the end of the total study period.
CCI
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Control: Matched placebo 
at Weeks 0 and 8 and then 
 thereafter through the end of 
the total study period.
i.
Population:
Participants with recent (<49 days) qualifying surgery and no evidence of active Crohn’s 
disease postoperatively.
ii.
Variable (endpoint):
A binary recurrence variable (recurrence/no recurrence) where recurrence is defined as 
Endoscopic Recurrence prior to or at Week 48 (as defined by modified Rutgeerts score greater 
than or equal to i2a) or experiencing intercurrent events (ICEs) 1-4 presented below.
iii. 
       Intercurrent events (ICEs) and corresponding strategies:
The following are the ICEs considered for this study:
1)
A CD-related surgery (with the exception of minor procedures such as drainage of a 
superficial abscess or seton placement, etc.)
2)
A prohibited change in CD medication
3)
Discontinuation of study intervention due to lack of efficacy or an AE of worsening CD 
4)
Cross over to open-label guselkumab
5)
Discontinuation of study intervention due to COVID-19 related reasons (excluding 
COVID-19 infection)
6)
Discontinuation of study intervention due to reasons other than those in ICE 3 or 5
Intercurrent events in categories 1-4 will be handled by the composite 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 1-4 is an 
unfavorable outcome. For participants experiencing ICEs in  category 5 and 6, the treatment 
policy strategy will be used and considers the occurrence of ICE category 5 and 6 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 and 6. 
iv.          Population-level summary: 

Difference in proportions of the binary recurrence variable of endoscopic recurrence, as 
described above, between guselkumab group and the placebo group.
Estimators
The analysis of the primary endpoint 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.
To compare the guselkumab versus placebo group for the primary endpoint, the Cochran Mantel 
Haenszel chi-square test (2-sided) will be used. The study will be considered successful if the test 
of the primary endpoint is positive at the 0.05 significance level.
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After accounting for the ICE strategies, missing data will be imputed by multiple imputation. To 
examine the robustness of the primary endpoint analyses, sensitivity analyses using alternative 
missing data handling rules (eg, treat missing as endoscopic recurrence) will be performed. Details 
will be specified in the SAP. 
In addition, subgroup analyses of the primary endpoint will be performed based on demographic 
and baseline disease characteristics, and baseline and previous use of medications for CD.
9.4.3.
Secondary Endpoints
The first secondary endpoint is clinical remission without disease recurrence at Week 48. The 
analyses of this endpoint will be performed after the test of the primary endpoint.

Clinical remission without disease recurrence is a composite endpoint defined by the 
following:
o
CDAI < 150 at Week 48 and
o
No endoscopic recurrence as defined by Rutgeerts score < i2 by Week 48 and
o
Have not experienced a disease recurrence as defined below
The second secondary endpoint is time to disease recurrence. The analyses of this endpoint will 
be performed after the test of the primary endpoint and the first secondary endpoint. 

Disease Recurrence is a composite endpoint defined by the following:

A ≥ 70-point increase from baseline in CDAI score at beyond 8 weeks after 
randomization; and a CDAI score of ≥ 200 and evidence of endoscopic recurrence. 
Endoscopic recurrence is defined as a modified Rutgeerts score of ≥ i2a at the anastomotic 
site or its equivalent elsewhere in the GI tract, unless a stool test for C. difficile toxin or 
other enteric pathogen is positive;

In event of a positive test for enteric pathogen including C. difficile toxin, the 
underlying infection should be treated and if ileocolonoscopy has not yet been 
performed, it should only be done when the infection has resolved, and if disease 
recurrence threshold is still met

OR initiation of a physician-prescribed corticosteroids, or an increase in the dose of 
steroids already being taken (by greater than 5 mg/day), for over one week for the 
treatment of CD and evidence of endoscopic recurrence as described above, unless a stool 
test for C. difficile toxin or other enteric pathogen is positive   

OR a new draining external fistula

OR the reopening and draining of a previously existing external fistula

OR developing a new internal fistula

OR developing a new perianal abscess
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
OR developing a new intra-abdominal abscess more than three months after the date of 
the index surgery
Participants who have confirmed endoscopic recurrence without disease recurrence at Week 24 or 
Week 48 and cross over to open-label guselkumab treatment will be censored at cross over for the 
time to disease recurrence endpoint.
Estimands and Estimators
Estimand of Clinical Remission without Disease Recurrence at Week 48
Treatment: 
Experimental: Guselkumab 
 at Week 0 and then 
 at Week 8, then
 
thereafter through the end of the total study period. 
Control: Matched placebo 
at Weeks 0 and 8 and then 
thereafter through the end of 
the total study period. 
i.
Population: Participants with recent (<49 days) qualifying surgery and no evidence of 
active Crohn’s disease postoperatively. 
ii.
Variable (endpoint): 
A binary variable of clinical remission without disease recurrence at Week 48 (as defined by 
Rutgeerts score smaller than i2 and CDAI < 150 without disease recurrence) or experiencing 
ICEs 1-4 presented below. 
iii. 
ICEs and corresponding strategies: 
The following are the ICEs considered for this study: 
1) A CD-related surgery (with the exception of minor procedures such as drainage of a 
superficial abscess or seton placement, etc.) 
2) A prohibited change in CD medication 
3) Discontinuation of study intervention due to lack of efficacy or an AE of worsening CD 
4) Cross over to open-label guselkumab
5) Discontinuation of study intervention due to COVID-19 related reasons (excluding 
COVID-19 infection) 
6) Discontinuation of study intervention due to reasons other than those in ICE 3 or 4 
Intercurrent events in categories 1-4 will be handled by the composite 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 1-4 is an unfavorable 
outcome. For participants experiencing ICEs in category 5 and 6, the treatment policy strategy will 
be used and considers the occurrence of ICE category 5 and 6 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 and 6.  
iv.
Population-level summary: Difference in proportions of the binary variable of clinical 
remission without disease recurrence, as described above, between guselkumab group and 
the placebo group. 
CCI
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Estimators 
The analysis of the first secondary endpoint 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. 
To compare the guselkumab versus placebo group for the first secondary endpoint, the CMH chi-
square test (2-sided) will be used. 
After accounting for the ICE strategies, missing data will be imputed by multiple imputation. 
Estimand of Disease Recurrence 
Treatment: 
Experimental: Guselkumab 
 at Week 0 and then 
 at Week 8, then 
 
thereafter through the end of the total study period. 
Control: Matched placebo 
at Weeks 0 and 8 and then 
thereafter through the end of 
the total study period. 
i.
Population: Participants with recent (<49 days) qualifying surgery and no evidence of 
active Crohn’s disease postoperatively. 
ii.
Variable (endpoint): The time to disease recurrence (as defined above) or experiencing 
ICE 1-3 presented below.  
iii.
ICEs and corresponding strategies: 
1) A CD-related surgery (with the exception of minor procedures such as drainage of a 
superficial abscess or seton placement, etc.) 
2) A prohibited change in CD medication 
3) Discontinuation of study intervention due to lack of efficacy or an AE of worsening CD 
4) Discontinuation of study intervention due to COVID-19 related reasons (excluding 
COVID-19 infection) 
5) Discontinuation of study intervention due to - reasons other than those in ICE 3 or 4 
Intercurrent events in categories 1 to 3 will be handled by the composite strategy. This estimand 
acknowledges that having an ICE in categories 1 to 3 is an unfavorable outcome. For participants 
experiencing ICEs in category 4 and 5, the treatment policy strategy will be used and considers
the occurrence of ICE category 4 and 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 4 and 
5. 
iv.
Population-level summary:  Difference in the time to disease recurrence (as defined 
above) or experiencing ICE 1-3 presented above between guselkumab group and the 
placebo group. 
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. 
CCI
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The log-rank test will be used to compare disease recurrence distribution between the two 
treatment groups. The Kaplan-Meier method will be used to estimate the distribution of disease 
recurrence for each treatment. The treatment effect (hazard ratio) and its two-sided 95% confidence 
intervals are to be estimated using Cox regression model with treatment and stratification factors. 
Participants who have not achieved disease recurrence during the main study period at the database 
lock will be censored at the last visit. Participants without any post-baseline follow-up will be 
censored at randomization. 
The other secondary endpoints include:

Abdominal pain free (abdominal pain [AP] score = 0) at Week 48

Time-to-recurrence of symptoms

Steroid-free clinical remission at Week 48
These endpoints will be analyzed in a similar way as endoscopic recurrence (binary endpoint) or 
time to disease recurrence (time to event endpoint). Type I error will be controlled over the primary 
and secondary endpoints hierarchically. Further details will be included in SAP. 
9.4.4.
Other/Exploratory Endpoints 
The other/exploratory endpoints include but are not limited to the endpoints described in Section
3. A complete list of the other endpoints will be provided in the SAP. The testing of these endpoints 
will not be controlled for multiplicity and nominal p-values will be provided.
Other endpoints include:

Change in PROMIS-Fatigue Short Form 7a score over 48 weeks

Abdominal pain (AP score = 0) at each post baseline visit through Week 152

Time to a flare of abdominal pain

Clinical remission (CDAI <150) at each post baseline visit

Change in PROMIS-Fatigue SF 7a at each post baseline visit through Week 152

Change in PROMIS-29 score, both overall score and individual domain scores at each post 
baseline visit through Week 152

Change from baseline in the WPAI at each post baseline visit through Week 152

The number of participants not on corticosteroids and without disease recurrence at each post 
baseline visit through Week 152

The number of participants not on corticosteroids and without endoscopic or disease
recurrence at each post baseline visit through Week 152

Endoscopic recurrence prior to or at Week 24

Histologic score (as measured by Geboes scale/RHI/GHAS) at Week 48 ileocolonoscopy

The number of participants with Geboes score over 3.1 at Week 48 ileocolonoscopy
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
The number of participants with Geboes score of 2.0 or less at Week 48 ileocolonoscopy

Clinical remission (CDAI <150) at Week 24 after initiation of guselkumab SC induction

Clinical response (CDAI decrease of <100 points or CDAI <150) 24 weeks after initiation of 
guselkumab SC induction

Disease recurrence (using definition described in Section 9.4.3) at Week 152  

Fecal calprotectin recurrence, defined by calprotectin of >200 μg/g with a 100 μg/g increase 
over baseline

The change from baseline in fecal calprotectin concentration at all postbaseline visits through 
Week 152

The change from baseline in CRP concentration at all postbaseline visits through Week 152
An additional exploratory analysis for risk factors of endoscopic and disease recurrence will be 
performed. A sensitivity analysis of the primary endpoint will be performed using a Rutgeerts 
score of > i3 as the definition for endoscopic recurrence.
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 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 AE 
or a SAE.
The following analyses of AEs will be used to assess the safety in participants:

Frequency and type of AEs.

Frequency and type of SAEs.

Frequency and type of related AEs as assessed by the investigator.

Frequency and type of AEs leading to discontinuation of study intervention.

Frequency and type of infections, including serious infections.

Frequency and type of injection site reactions.
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Clinical Laboratory Tests
The following summaries of clinical laboratory tests will be used to assess participant safety:
Laboratory parameters and change from baseline in laboratory parameters (hematology and 
chemistry).
Summary of maximum National Cancer Institute Common Terminology Criteria for Adverse 
Events toxicity grade for post-baseline laboratory values (hematology and chemistry). 
Listings of participants with any abnormal post-baseline laboratory values of National Cancer 
Institute Common Terminology Criteria for Adverse Events grade ≥2 will also be provided.
Suicidal Ideation and Behavior
Suicidal ideation and behavior based on the C-SSRS and AEs will be summarized descriptively.
9.4.6.
Other Analyses
9.4.6.1.
Pharmacokinetic Analyses
The analyses are based on the 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.
9.4.6.2.
Pharmacogenomic Analyses
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.
9.4.6.3.
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
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or sponsor after the cutoff date will not be analyzed, and therefore, excluded from the biomarker
analysis.
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.
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.
9.4.6.4.
Immunogenicity Analyses 
The analyses are based on the 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 of guselkumab).
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.
9.4.6.5.
Pharmacokinetic/Pharmacodynamic Analyses 
The relationship between serum guselkumab concentrations and efficacy measures will be 
analyzed graphically. If any visual trend is observed, additional analysis may be conducted if 
deemed necessary.
9.5.
Interim Analysis
Not applicable.
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10.
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1.
Appendix 1: Abbreviations
Abbreviation
Definition
6-MP
6-mercaptopurine
AE
adverse event
ALP
alkaline phosphatase
ANCOVA
analysis of covariance
ANOVA
analysis of variance
ALT
alanine transferase
AP
abdominal pain
AST
aspartate transaminase
AZA
Azathioprine
BCG
Bacille Calmette-Guérin
CD
Crohn’s disease
CDAI
Crohn’s Disease Activity Index
CI
confidence interval
CRP
C-reactive protein
C-SSRS
Columbia Suicide Severity Rating Scale
DBL
database lock
eCRF
electronic case report form
ET
early termination
EU
European Union
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GHAS
Global Histology Activity Index
GI
Gastrointestinal
HBV
hepatitis B virus
HCV
hepatitis C virus
HIV
human immunodeficiency virus
HRT
hormone replacement therapy
IB
Investigator Brochure
IBD
inflammatory bowel disease
ICE
intercurrent event
ICF
informed consent form
IEC
Independent Ethics Committee
IgG
immunoglobulin G
IGRA
interferon gamma release assay
IL
Interleukin
INR
International Normalized Ratio
IQ
Interquartile
IRB
Institutional Review Board
IWRS
interactive web response system
LTE
long-term extension
mAb
monoclonal antibody
MMRM
mixed model for repeated measures
MTX
Methotrexate
OTC
over the counter
PCC
Protocol Clarification Communication
PD
pharmacodynamic(s)
PFS
prefilled syringe
PK
pharmacokinetic(s)
C
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POCD
postoperative Crohn’s disease
PQC
Product Quality Complaint
PRO
patient-reported outcome(s) (paper or electronic as appropriate for this study)
PROMIS
Patient-Reported Outcomes Measurement System
RHI
Robarts histopathology index
SAE
serious adverse event
SAP
Statistical Analysis Plan
SD
standard deviation
SES-CD
Simple Endoscopic Score – Crohn’s Disease
SF
stool frequency
SI
International Units
SoA
Schedule of Activities
SUSAR
suspected unexpected serious adverse reactions
TB
tuberculosis
TNF
tumor necrosis factor
UC
ulcerative colitis
ULN
upper limit of normal
US
United States
WPAI
Work Productivity Activity Index
CCI
C
CI
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10.3.
Appendix 3: Regulatory, Ethical, and Study Oversight Considerations
10.3.1.
Regulatory and Ethical Considerations
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the 
protocol, current International Conference on Harmonisation (ICH) guidelines on Good Clinical 
Practice (GCP), and applicable regulatory and country- or territory-specific requirements.
Good Clinical Practice is an international ethical and scientific quality standard for designing, 
conducting, recording, and reporting studies that involve the participation of human participants. 
Compliance with this standard provides public assurance that the rights, safety, and well-being of 
study participants are protected, consistent with the principles that originated in the Declaration of 
Helsinki, and that the study data are credible.
Protocol Clarification Communications
If text within a final approved protocol requires clarification (eg, current wording is unclear or 
ambiguous) that does not change any aspect of the current study conduct, a protocol clarification 
communication (PCC) may be prepared. The PCC Document will be communicated to the 
Investigational Site, Site Monitors, Local Trial Managers, Clinical Trial Managers, and/or Contract 
Research Organizations who will ensure that the PCC explanations are followed by the 
investigators.
The PCC Document may be shared by the sites with Independent Ethics Committees/Institutional 
Review Boards (IECs/IRBs) per local regulations.
The PCC Documents must NOT be used in place of protocol amendments, but the content of the 
PCC Document must be included in any future protocol amendments.
Protocol Amendments
Neither the investigator nor the sponsor will modify this protocol without a formal amendment by 
the sponsor. All protocol amendments must be issued by the sponsor, and signed and dated by the 
investigator. Protocol amendments must not be implemented without prior IEC/IRB approval, or 
when the relevant competent authority has raised any grounds for non-acceptance, except when 
necessary to eliminate immediate hazards to the participants, in which case the amendment must 
be promptly submitted to the IEC/IRB and relevant competent authority. Documentation of 
amendment approval by the investigator and IEC/IRB must be provided to the sponsor. When the 
change(s) involve only logistic or administrative aspects of the study, the IEC/IRB (where 
required) only needs to be notified.
In situations where a departure from the protocol is unavoidable during the study, the investigator 
or other physician in attendance will contact the appropriate sponsor representative listed in the 
Contact Information page(s), which will be provided as a separate document. Except in emergency 
situations, this contact must be made before implementing any departure from the protocol. In all 
cases, contact with the sponsor must be made as soon as possible to discuss the situation and agree 
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on an appropriate course of action. The data recorded in the CRF and source documents will reflect 
any departure from the protocol, and the source documents will describe this departure and the 
circumstances requiring it.
Regulatory Approval/Notification
This protocol and any amendment(s) must be submitted to the appropriate regulatory authorities 
in each respective country/territory, if applicable. A study may not be initiated until all local 
regulatory requirements are met.
Required Prestudy Documentation
The following documents must be provided to the sponsor before shipment of study intervention
to the study site:

Protocol and amendment(s), if any, signed and dated by the principal investigator

A copy of the dated and signed (or sealed, where appropriate per local regulations), written 
IEC/IRB approval of the protocol, amendments, ICF, any recruiting materials, and if 
applicable, participant compensation programs. This approval must clearly identify the 
specific protocol by title and number and must be signed (or sealed, where appropriate per 
local regulations) by the chairman or authorized designee.

Name and address of the IEC/IRB, including a current list of the IEC/IRB members and their 
function, with a statement that it is organized and operates according to GCP and the 
applicable laws and regulations. If accompanied by a letter of explanation, or equivalent, from 
the IEC/IRB, a general statement may be substituted for this list. If an investigator or a 
member of the study site personnel is a member of the IEC/IRB, documentation must be 
obtained to state that this person did not participate in the deliberations or in the vote/opinion 
of the study.

Regulatory authority approval or notification, if applicable

Signed and dated statement of investigator (eg, Form FDA 1572), if applicable

Documentation of investigator qualifications (eg, curriculum vitae)

Completed investigator financial disclosure form from the principal investigator, where 
required

Signed and dated clinical trial agreement, which includes the financial agreement

Any other documentation required by local regulations
The following documents must be provided to the sponsor before enrollment of the first 
participant:

Completed investigator financial disclosure forms from all subinvestigators

Documentation of subinvestigator qualifications (eg, curriculum vitae)

Name and address of any local laboratory conducting tests for the study, and a dated copy of 
current laboratory normal ranges for these tests, if applicable
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
Local
laboratory 
documentation 
demonstrating 
competence 
and 
test 
reliability 
(eg, accreditation/license), if applicable
Independent Ethics Committee or Institutional Review Board
Before the start of the study, the investigator (or sponsor where required) will provide the IEC/IRB 
with current and complete copies of the following documents (as required by local regulations):

Final protocol and, if applicable, amendments

Sponsor-approved ICF (and any other written materials to be provided to the participants)

IB (or equivalent information) and amendments/addenda

Sponsor-approved participant recruiting materials

Information on compensation for study-related injuries or payment to participants for 
participation in the study, if applicable

Investigator's curriculum vitae or equivalent information (unless not required, as documented 
by the IEC/IRB)

Information regarding funding, name of the sponsor, institutional affiliations, other potential 
conflicts of interest, and incentives for participants

Any other documents that the IEC/IRB requests to fulfill its obligation
This study will be undertaken only after the IEC/IRB has given full approval of the final protocol, 
amendments (if any, excluding the ones that are purely administrative, with no consequences for 
participants, data or study conduct, unless required locally), the ICF, applicable recruiting 
materials, and participant compensation programs, and the sponsor has received a copy of this 
approval. This approval letter must be dated and must clearly identify the IEC/IRB and the 
documents being approved.
During the study the investigator (or sponsor where required) will send the following documents 
and updates to the IEC/IRB for their review and approval, where appropriate:

Protocol amendments (excluding the ones that are purely administrative, with no 
consequences for participants, data or study conduct)

Revision(s) to ICF and any other written materials to be provided to participants

If applicable, new or revised participant recruiting materials approved by the sponsor

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 of the IEC/IRB
For all protocol amendments (excluding the ones that are purely administrative, with no 
consequences for participants, data or study conduct), the amendment and applicable ICF revisions 
must be submitted promptly to the IEC/IRB for review and approval before implementation of the 
change(s).
At least once a year, the IEC/IRB will be asked to review and reapprove this study, where required.
At the end of the study, the investigator (or sponsor where required) will notify the IEC/IRB about 
the study completion (if applicable, the notification will be submitted through the head of 
investigational institution).
Other Ethical Considerations
For study-specific ethical design considerations, refer to Section 4.2.2.
10.3.2.
Financial Disclosure
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information in accordance with local regulations to allow the sponsor to submit complete and 
accurate financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the study and 
for 1 year after completion of the study.
Refer to Required Prestudy Documentation (above) for details on financial disclosure.
10.3.3.
Informed Consent Process Form
Each participant (or a legally acceptable representative) must give consent according to local 
requirements after the nature of the study has been fully explained. The ICF(s) must be signed 
before performance of any study-related activity. The ICF(s) and assent form that is/are used must 
be approved by both the sponsor and by the reviewing IEC/IRB and be in a language that the 
participant can read and understand. The informed consent must be in accordance with principles 
that originated in the Declaration of Helsinki, current ICH and GCP guidelines, applicable 
regulatory requirements, and sponsor policy.
Before enrollment in the study, the investigator or an authorized member of the study site personnel 
must explain to potential participants or their legally acceptable representatives the aims, methods, 
reasonably anticipated benefits, and potential hazards of the study, and any discomfort 
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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 for the treatment 
of his or her disease. Participants will be told that alternative treatments are available if they refuse 
to take part and that such refusal will not prejudice future treatment. Finally, they will be told that 
the investigator will maintain a participant identification register for the purposes of long-term 
follow up if needed and that their records may be accessed by health authorities and authorized 
sponsor personnel without violating the confidentiality of the participant, to the extent permitted 
by the applicable law(s) or regulations. By signing the ICF the participant or legally acceptable 
representative is authorizing such access, which includes permission to obtain information about 
his or her survival status. It also denotes that the participant agrees to allow his or her study 
physician to recontact the participant for the purpose of obtaining consent for additional safety 
evaluations, and subsequent disease-related treatments, if needed.  The physician may also 
recontact the participant for the purpose of obtaining consent to collect information about his or 
her survival status.
The participant or legally acceptable representative will be given sufficient time to read the ICF 
and the opportunity to ask questions. After this explanation and before entry into the study, consent 
must be appropriately recorded by means of either the participant's or his or her legally acceptable 
representative's personally dated signature. After having obtained the consent, a copy of the ICF 
must be given to the participant.
If the participant or legally acceptable representative is unable to read or write, an impartial witness 
must be present for the entire informed consent process (which includes reading and explaining all 
written information) and must personally date and sign the ICF after the oral consent of the 
participant or legally acceptable representative is obtained.
Participants who are rescreened are required to sign a new ICF.
Where local regulations require, a separate ICF may be used for the required DNA component of 
the study.
Participants who are unable to comprehend the information provided can be enrolled only after 
obtaining consent of a legally acceptable representative.
10.3.4.
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. 
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Sponsor personnel whose responsibilities require access to personal data agree to keep the identity 
of participants confidential.
The informed consent obtained from the participant (or his or her legally acceptable representative) 
includes information about, and where required per applicable regulations, explicit consent for the 
processing of personal data and for the investigator/institution to allow direct access to his or her 
original medical records (source data/documents) for study-related monitoring, audit, IEC/IRB 
review, and regulatory inspection. The informed consent also provides information to address the 
lawful transfer of the data to other entities and to other countries/territories.
The participant has the right to request through the investigator access to his or her personal data 
and the right to request rectification of any data that are not correct or complete, or make requests 
concerning his or her personal data in accordance with applicable data protection law. Reasonable 
steps will be taken to respond to such a request, taking into consideration the nature of the request, 
the conditions of the study, and the applicable laws and regulations.
In the event of a data security breach, the sponsor will apply measures to adequately manage and 
mitigate possible adverse effects taking into consideration the nature of the data security breach as 
necessary to address other obligations such as notifying appropriate authorities in accordance with 
applicable data protection law.
Exploratory PD, biomarker, PK, and 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.
10.3.5.
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 CD, 
to understand differential intervention responders, and to develop tests/assays related to 
guselkumab and CD. The research may begin at any time during the study or during 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.
10.3.6.
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 biomarker research data, 
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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 the goals of this study and will not use it for other purposes without 
the sponsor's prior written consent.
The investigator understands that the information developed in the study will be used by the 
sponsor in connection with the continued development of guselkumab, and thus may be disclosed 
as required to other clinical investigators or regulatory agencies. To permit the information derived 
from the clinical studies to be used, the investigator is obligated to provide the sponsor with all 
data obtained in the study.
The results of the study will be reported in a Clinical Study Report generated by the sponsor and 
will contain data from all study sites that participated in the study as per protocol. Recruitment 
performance or specific expertise related to the nature and the key assessment parameters of the 
study will be used to determine a coordinating investigator for the study. Results of 
pharmacogenomic or biomarker analyses performed after the Clinical Study Report has been 
issued will be reported in a separate report and will not require a revision of the Clinical Study 
Report.
Study participant identifiers will not be used in the 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 interim results of clinical studies as required by law. The 
disclosure of the study results will be performed after the end of study in order to ensure the 
statistical analyses are relevant.
10.3.7.
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, and periodic monitoring visits by the sponsor, and direct 
transmission of clinical laboratory data from a central laboratory into the sponsor's data base. 
Written instructions will be provided for collection, handling, storage, and shipment of samples.
Guidelines for eCRF completion will be provided and reviewed with study site personnel before 
the start of the study.
The sponsor may 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.
10.3.8.
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 
electronic 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
the eCRF in English. The eCRF must be completed as soon as possible after a participant visit and 
the forms must be available for review at the next scheduled monitoring visit.
All participative measurements (eg, pain scale information or other questionnaires) will be 
completed by the same individual who made the initial baseline determinations whenever possible.
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If necessary, queries will be generated in the eDC tool. If corrections to a eCRF are needed after 
the initial entry into the eCRF, this can be done in either of the following ways:

Investigator and study site personnel can make corrections in the eDC tool at their own 
initiative or as a response to an auto query (generated by the eDC tool).

Sponsor or sponsor delegate can generate a query for resolution by the investigator and study 
site personnel.
10.3.9.
Source Documents
At a minimum, source documents consistent in the type and level of detail with that commonly 
recorded at the study site as a basis for standard medical care must be available for the following: 
participant identification, eligibility, and study identification; study discussion and date of signed 
informed consent; dates of visits; results of safety and efficacy parameters as required by the 
protocol; record of all AEs and follow-up of AEs; concomitant medication; intervention
receipt/dispensing/return records; study intervention administration information; and date of study 
completion and reason for early discontinuation of study intervention or withdrawal from the 
study, if applicable.
The author of an entry in the source documents must be identifiable. 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 study participants into source 
records cannot be overridden by site staff or investigators.
Specific details required as source data for the study and source data collection methods will be 
reviewed with the investigator before the study and will be described in the monitoring guidelines 
(or other equivalent document).
The minimum source documentation requirements for Section 5.1, Inclusion Criteria and 
Section 5.2, Exclusion Criteria that specify a need for documented medical history are as follows:

Referral letter from treating physician or

Complete history of medical notes at the site

Discharge summaries
Inclusion and exclusion criteria not requiring documented medical history must be verified at a 
minimum by participant interview or other protocol required assessment (eg, physical 
examination, laboratory assessment) and documented in the source documents.
An eSource system may be utilized, which contains data traditionally maintained in a hospital or 
clinic record to document medical care (eg, electronic source documents) as well as the clinical 
study-specific data fields as determined by the protocol. This data is electronically extracted for 
use by the sponsor. If eSource is utilized, references made to the 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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10.3.10.
Monitoring
The sponsor will use a combination of monitoring techniques (central, remote, or on-site 
monitoring) to monitor this study.
The sponsor will perform on-site monitoring visits as frequently as necessary. The monitor will 
record dates of the visits in a study site visit log that will be kept at the study site. The first post-
initiation visit will be made as soon as possible after enrollment has begun. At these visits, the 
monitor may 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.
10.3.11.
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 must immediately notify the sponsor if he or she has been 
contacted by a regulatory agency concerning an upcoming inspection.
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10.3.12.
Record Retention
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all CRF and 
all source documents that support the data collected from each participant, as well as all study 
documents as specified in ICH/GCP Section 8, Essential Documents for the Conduct of a Clinical 
Trial, and all study documents as specified by the applicable regulatory requirement(s). The 
investigator/institution will take measures to prevent accidental or premature destruction of these 
documents.
Essential documents must be retained until at least 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing applications 
in an ICH region or until at least 2 years have elapsed since the formal discontinuation of clinical 
development of the investigational product. These documents will be retained for a longer period 
if required by the applicable regulatory requirements or by an agreement with the sponsor. It is the 
responsibility of the sponsor to inform the investigator/institution as to when these documents no 
longer need to be retained.
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.
10.3.13.
Study and Site Start and Closure
The first subject screened is considered the first act of recruitment and the study start date.
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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10.4.
Appendix 4: Adverse Events, Serious Adverse Events, Product Quality 
Complaints, and Other Safety Reporting: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting
10.4.1.
Adverse Event Definitions and Classifications
Adverse Event
An AE is any untoward medical occurrence in a clinical study participant administered a 
pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have 
a causal relationship with the intervention. An AE can therefore be any unfavorable and unintended 
sign (including an abnormal finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational or non-investigational) product, whether or not related to that medicinal 
(investigational or non-investigational) product. (Definition per International Council on 
Harmonisation [ICH])
This includes any occurrence that is new in onset or aggravated in severity or frequency from the 
baseline condition, or abnormal results of diagnostic procedures, including laboratory test 
abnormalities.
Note: The sponsor collects AEs starting with the signing of the ICF (refer to All Adverse Events
under Section 8.5.1, Time Period and Frequency for Collecting Adverse Events and Serious 
Adverse Events Information, for time of last AE recording).
For combination products with a device constituent, AEs include those resulting from insufficient 
or inadequate instructions for use, deployment, implantation, installation, or operation, or any 
malfunction of the device. It includes any AE resulting from use error or from intentional misuse 
of the investigational device.
Serious Adverse Event
A SAE based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human 
Use is any untoward medical occurrence that at any dose:

Results in death

Is life-threatening
(The participant was at risk of death at the time of the event. It does not refer to an event that 
hypothetically might have caused death if it were more severe.)

Requires inpatient hospitalization or prolongation of existing hospitalization

Results in persistent or significant disability/incapacity

Is a congenital anomaly/birth defect

Is a suspected transmission of any infectious agent via a medicinal product

Is Medically Important*
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*Medical and scientific judgment must be exercised in deciding whether expedited reporting 
is also appropriate in other situations, such as important medical events that may not be 
immediately life threatening or result in death or hospitalization but may jeopardize the 
participant or may require intervention to prevent one of the other outcomes listed in the 
definition above. These should usually be considered serious.
If a serious and unexpected AE occurs for which there is evidence suggesting a causal relationship 
between the study intervention and the event (eg, death from anaphylaxis), the event must be 
reported as a serious and unexpected suspected adverse reaction even if it is a component of the 
study endpoint (eg, all-cause mortality).
For combination products with a device constituent, SAEs include adverse device effects that 
resulted in any of the consequences characteristic of an SAE. An unanticipated serious adverse 
device effect is a serious adverse device effect which by its nature, incidence, severity or outcome 
has not been identified in the current version of the risk analysis report (see Section 2.3. Benefit-
Risk Assessment).
Unlisted (Unexpected) Adverse Event/Reference Safety Information
An AE is considered unlisted if the nature or severity is not consistent with the applicable product 
reference safety information. For guselkumab, the expectedness of an AE will be determined by 
whether or not it is listed in the IB.
10.4.2.
Attribution Definitions
Assessment of Causality
The causal relationship to study intervention is assessed by the Investigator. The following 
selection must be used to assess all AEs.
Related
There is a reasonable causal relationship between study intervention administration and the AE.
Not Related
There is not a reasonable causal relationship between study intervention administration and the 
AE.
The term "reasonable causal relationship" means there is evidence to support a causal relationship.
10.4.3.
Severity Criteria 
An assessment of severity grade will be made using the following general categorical descriptors:
Mild: Awareness of symptoms that are easily tolerated, causing minimal discomfort and not 
interfering with everyday activities.
Moderate: Sufficient discomfort is present to cause interference with normal activity.
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Severe: Extreme distress, causing significant impairment of functioning or incapacitation. 
Prevents normal everyday activities.
The investigator must use clinical judgment in assessing the severity of events not directly 
experienced by the participant (eg, laboratory abnormalities).
10.4.4.
Special Reporting Situations
Safety events of interest on a sponsor study intervention in an interventional study that may require 
expedited reporting or safety evaluation include, but are not limited to:

Overdose of a sponsor study intervention (see Section 6.7)

Suspected abuse/misuse of a sponsor study intervention

Accidental or occupational exposure to a sponsor study intervention

Unexpected therapeutic or clinical benefit from use of a sponsor study intervention

Medication error, intercepted medication error, or potential medication error involving a 
Johnson & Johnson medicinal product (with or without patient exposure to the Johnson & 
Johnson medicinal product, eg, product name confusion, product label confusion, intercepted 
prescribing or dispensing errors)

Exposure to a sponsor study intervention from breastfeeding

Reporting of participant pregnancy or participant partner(s) pregnancy
Special reporting situations must be recorded in the eCRF. Any special reporting situation that 
meets the criteria of an SAE must be recorded on the SAE page of the eCRF.
10.4.5.
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
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
Local sponsor's name and 24-hour contact telephone number (for medical personnel only)

Site number

Participant number

Any other information that is required to do an emergency breaking of the blind
Serious Adverse Events
All SAEs that have not resolved by the end of the study, or that have not resolved upon the 
participant's discontinuation from the study, must be followed until any of the following occurs:

The event resolves

The event stabilizes

The event returns to baseline, if a baseline value/status is available

The event can be attributed to agents other than the study intervention or to factors unrelated 
to study conduct

It becomes unlikely that any additional information can be obtained (participant or health care 
practitioner refusal to provide additional information, lost to follow-up after demonstration of 
due diligence with follow-up efforts)
Any event requiring hospitalization (or prolongation of hospitalization) that occurs during 
participation in the study must be reported as an SAE, except hospitalizations for the following:

Hospitalizations not intended to treat an acute illness or AE (eg, social reasons such as pending 
placement in long-term care facility)

Surgery or procedure planned before entry into the study (must be documented in the eCRF). 
Note: Hospitalizations that were planned before the signing of the ICF, and where the 
underlying condition for which the hospitalization was planned has not worsened, will not be 
considered SAEs. Any AE that results in a prolongation of the originally planned 
hospitalization is to be reported as a new SAE.
The cause of death of a participant in a study within 12 weeks of the last dose of study intervention, 
whether or not the event is expected or associated with the study intervention, is considered an 
SAE.
Information regarding SAEs will be transmitted to the sponsor using an SAE reporting form, which 
must be completed and signed by a physician from the study site, and transmitted in a secure 
manner to the sponsor within 24 hours. The initial and follow-up reports of an SAE should be 
made by facsimile (fax). Telephone reporting should be the exception and the reporter should be 
asked to complete the appropriate form(s) first.
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10.4.6.
Product Quality Complaint Handling
Definition
A product quality complaint (PQC) is defined as any suspicion of a product defect related to 
manufacturing, labeling, or packaging, ie, any dissatisfaction relative to the identity, quality, 
durability, reliability, or performance of a distributed product, including its labeling, drug delivery 
system, or package integrity. A PQC may have an impact on the safety and efficacy of the product.
In addition, it includes any technical complaints, defined as any complaint that indicates a potential 
quality issue during manufacturing, packaging, release testing, stability monitoring, dose 
preparation, storage or distribution of the product or the drug delivery system.
This definition includes any PQC related to a device constituent in a combination product, 
including those used in the administration of the study intervention or the comparator. A device 
deficiency is an inadequacy of a device with respect to its identity, quality, durability, reliability, 
safety, or performance. Device deficiencies include malfunctions, use errors, and inadequate 
labeling.
Procedures
All initial PQCs must be reported to the sponsor by the study site personnel within 24 hours after 
being made aware of the event.
A sample of the suspected product should be maintained under the correct storage conditions until 
a shipment request is received from the sponsor.
10.4.7.
Contacting Sponsor Regarding Safety, Including Product Quality
The names (and corresponding telephone numbers) of the individuals who must 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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10.5.
Appendix 5: Contraceptive Guidance
Participants must follow contraceptive measures as outlined in Section 5.1, Inclusion Criteria. 
Pregnancy information will be collected and reported as noted in Section 8.5.5, Pregnancy and 
Appendix 4: Adverse Events, Serious Adverse Events, Product Quality Complaints, and Other 
Safety Reporting: Definitions and Procedures for Recording, Evaluating, Follow-up, and 
Reporting.
Definitions
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below).
Woman Not of Childbearing Potential

premenarchal
A premenarchal state is one in which menarche has not yet occurred.

postmenopausal
A postmenopausal state is defined as >45 years of age with amenorrhea for at least 12 months 
or any age with amenorrhea for at least 6 months and a serum follicle-stimulating hormone 
[FSH] level >40 IU/L). If there is a question about menopausal status in women on hormone 
replacement therapy (HRT), the woman will be required to use one of the   
non-estrogen-containing hormonal highly effective contraceptive methods if she wishes to 
continue HRT during the study.

permanently sterile (for the purpose of this study)

Permanent sterilization methods include hysterectomy, or bilateral salpingectomy, or 
bilateral oophorectomy.

Has congenital abnormalities resulting in sterility.
Note: If the childbearing potential changes after start of the study (eg, a premenarchal woman 
experiences menarche) or the risk of pregnancy changes (eg, a woman who is not heterosexually 
active becomes active), a woman must begin a highly effective method of contraception, as 
described throughout the inclusion criteria.
If reproductive status is questionable, additional evaluation should be considered.
Contraceptive (birth control) use by men or women must be consistent with local regulations 
regarding the acceptable methods of contraception for those participating in clinical studies.
Typical use failure rates may differ from those when used consistently and correctly. Use must be 
consistent with local regulations regarding the use of contraceptive methods for participants in 
clinical studies.
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Examples of Contraceptives 
EXAMPLES OF CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE:
USER INDEPENDENT
Highly Effective Methods That Are User Independent Failure rate of <1% per year when used 
consistently and correctly.

Implantable progestogen-only hormone contraception associated with inhibition of ovulationb

Intrauterine device (IUD)

Intrauterine hormone-releasing system (IUS)

Bilateral tubal occlusion

Azoospermic partner (vasectomized or due to medical cause)
(Vasectomized partner is a highly effective contraceptive method provided that the partner is the 
sole sexual partner of the woman of childbearing potential and the absence of sperm has been 
confirmed. If not, additional highly effective method of contraception should be used. 
Spermatogenesis cycle is approximately 74 days.)
USER DEPENDENT
Highly Effective Methods That Are User Dependent Failure rate of <1% per year when used 
consistently and correctly.

Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulationb
oral
intravaginal
transdermal
injectable

Progestogen-only hormone contraception associated with inhibition of ovulationb
oral
injectable

Sexual abstinence
(Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study intervention. 
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study 
and the preferred and usual lifestyle of the participant.)
NOT ALLOWED AS SOLE METHOD OF CONTRACEPTION DURING THE STUDY (not 
considered to be highly effective - failure rate of 1% per year)

Progestogen-only oral hormonal contraception where inhibition of ovulation is not the primary 
mode of action.

Male or female condom with or without spermicidec

Cap, diaphragm, or sponge with spermicide

A combination of male condom with either cap, diaphragm, or sponge with spermicide (double-
barrier methods)c

Periodic abstinence (calendar, symptothermal, post-ovulation methods)

Withdrawal (coitus-interruptus)

Spermicides alone

Lactational amenorrhea method (LAM)
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a) Typical use failure rates may differ from those when used consistently and correctly. Use should be 
consistent with local regulations regarding the use of contraceptive methods for participants in 
clinical studies.
b) Hormonal contraception may be susceptible to interaction with the study intervention, which may 
reduce the efficacy of the contraceptive method. In addition, consider if the hormonal contraception 
may interact with the study intervention.
c) Male condom and female condom should not be used together (due to risk of failure with friction).
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10.6.
Appendix 6: Hepatitis B Virus (HBV) Screening with HBV DNA Testing
Participants must undergo screening for hepatitis B virus (HBV). At a minimum, this includes 
testing for HBsAg (HBV surface antigen), anti-HBs (HBV surface antibody), and anti-HBc total 
(HBV core antibody total): 

Participants who test negative for all HBV screening tests (ie, HBsAg-, anti-HBc-, and anti-
HBs-) are eligible for this protocol. 

Participants who test negative for surface antigen (HBsAg-) and test positive for core antibody 
(antiHBc+) and surface antibody (anti-HBs+) are eligible for this protocol. 

Participants who test positive only for surface antibody (anti-HBs+) are eligible for this 
protocol. 

Participants who test positive for surface antigen (HBsAg+) are NOT eligible for this 
protocol, regardless of the results of other hepatitis B tests. 

Participants who test positive only for core antibody (anti-HBc+) must undergo further testing 
for the presence of hepatitis B virus deoxyribonucleic acid (HBV DNA) test. 
o
If the HBV DNA test is negative, the participant is eligible for this protocol. 
o
If the HBV DNA test is positive, the participant is NOT eligible for this protocol. 
o
In the event the HBV DNA test cannot be performed, the participant is NOT eligible
for this protocol.
These eligibility criteria based on HBV test results are also represented in table below. For 
participants who are eligible with surface antigen (HBsAg) negative, core antibody (anti-HBc) 
and/or surface antibody (anti-HBs) positive, and HBV DNA test is negative, HBV DNA 
quantitation should be monitored according to local guidelines.
Eligibility Based on Hepatitis B Virus (HBV) Test Results
Hepatitis B Test Result
STATUS
Hepatitis B surface 
antigen (HBs-Ag)
Hepatitis B surface 
antibody (anti-HBs)
Hepatitis B core 
antibody (anti-HBc 
total)
negative
negative
negative
ELIGIBLE
negative
(+)
negative
negative
(+)
(+)
(+)
negative or (+)
negative or (+)
NOT ELIGIBLE
negative
negative
(+)
Requires testing for 
presence of HBV DNA*
* If HBV DNA is detectable, the participant is not eligible for this protocol. If HBV DNA testing cannot be performed, 
or there is evidence of chronic liver disease, the participant is not eligible for this protocol.
For participants who are not eligible for this protocol due to HBV test results, consultation with a 
physician with expertise in the treatment of HBV infection is recommended. 
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10.7.
Appendix 7: Liver Safety: Suggested Actions and Follow-up Assessments
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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 below), then gamma-glutamyl transferase, anti-mitochondrial 
antibody (AMA) 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 
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10.8.
Appendix 8: Study Conduct During a Natural Disaster/Major Disruption/
Pandemic
It is recognized that the COVID-19 pandemic may have an impact on the conduct of this clinical 
study due to, for example, isolation or quarantine of participants and  study site personnel; travel 
restrictions/limited access to public places, including hospitals; study site personnel being 
unavailable, isolated, or reassigned to critical tasks. 
The sponsor is providing options for study related participant management in the event of 
disruption to the conduct of the study. This guidance does not supersede any local or government 
requirements or the clinical judgement of the investigator to protect the health and well-being of 
participants and site staff. If, at any time, a participant’s travel to the study site is considered to be 
dangerous, study participation may be interrupted, and study follow-up conducted. If it becomes 
necessary to discontinue participation in the study, the procedures outlined in the protocol for 
discontinuing study intervention will be followed.
If, as a result of the COVID-19 pandemic, scheduled visits cannot be conducted in person at the 
study site, they will be performed to the extent possible remotely/virtually or delayed until such 
time that on-site visits can be resumed. At each contact, participants will be interviewed to collect 
safety data. Key efficacy endpoint assessments should be performed if required and as feasible. 
Participants will also be questioned regarding general health status to fulfill any physical 
examination requirement. 
Every effort should be made to adhere to protocol-specified assessments for participants on study 
intervention, including follow up. Modifications to protocol-required assessments may be 
permitted 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 CRF.
If the participant has tested positive for COVID-19, the investigator should contact the sponsor’s 
responsible medical officer to discuss plans for administration of study intervention, performing 
study assessments, and follow-up. Modifications made to the study conduct as a result of the 
infection should be summarized in the clinical study report.
ADDITIONAL ELEMENTS, WHERE APPLICABLE: 

Certain protocol-mandated visits to the study site may not be possible during the COVID-19 
pandemic. Therefore, temporary measures may be implemented if considered appropriate by 
the Sponsor and investigator to maintain continuity of patient care and study integrity. Certain 
measures, such as those listed below, may be necessary and should be instituted in accordance 
with applicable (including local) laws, regulations, guidelines, and procedures:

remote (eg, by phone/telemedicine) or in-person, off-site (eg, in-home) interactions 
between site staff (or designees) and patients for study procedures eg, those related to 
safety monitoring/efficacy evaluation/study intervention storage and administration 
(including training where pertinent)
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
procurement of study intervention by patients (or designee) or shipment of study 
intervention from the study site directly to patients for at-home administration (including 
the potential for patient self-administration of study intervention)

laboratory assessments using a suitably accredited local laboratory; for selected measures 
(eg, urine pregnancy), home testing may be employed

Missed assessments/visits will be captured in the clinical trial management system for
protocol deviations. Discontinuations of study interventions and withdrawal from the study 
should be documented with the prefix “COVID-19-related” in the eCRF. 

other relevant study data elements impacted by the pandemic should also be documented 
as “COVID-19-related” in eCRFs and/or other study systems, as directed by detailed 
Sponsor guidance. These may include missed/delayed/modified study visits or 
assessments/dosing, and instances where temporary measures such as those above are 
implemented. 

The study intervention may be delivered directly to the participants from a courier, if 
necessary, as permitted by local requirements and/or regulations if approved by the 
Independent Ethics Committee (IEC)/Institutional Review Board (IRB) (see Section 6.1). 
Details regarding delivery are provided in the study manual.  The participant has the 
ability to opt-in or opt-out of using this service throughout the duration of the trial 
according to the protocol Schedule of Activities (SoA). 

The Sponsor will evaluate the totality of impact of COVID-19 on collection of key study data 
and additional data analyses will be outlined in study SAP(s). 
Precaution: for those who may carry a higher risk for severe COVID-19 illness (eg, those aged 
over 65 years), follow guidance from local health authorities when weighing the potential benefits 
and risks of enrolling in the study, and during participation in the study.
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10.9.
Appendix 9: Clinical Disease Activity Index
CCI
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11.
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SAP_001.pdf: 
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
1
Status: Approved, Date: 30 November 2023
Janssen Research & Development
Statistical Analysis Plan
A Randomized, Double-blind, Placebo-controlled Study Evaluating the Safety and Efficacy 
of Guselkumab for the Treatment of Participants with Crohn’s Disease After Surgical 
Resection
Protocol CNTO1959CRD3007; Phase 3
CNTO1959 (guselkumab)
Status:
Approved
Date:
30 November 2023
Prepared by:
Janssen Research & Development, LLC
Document No.:
EDMS-RIM-1164638, 3.0
Compliance: The study described in this report was performed according to the principles of Good Clinical Practice (GCP). 
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 
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NCT05784129


CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959CRD3007
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
2
Status: Approved, Date: 30 November 2023
TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
VERSION HISTORY..................................................................................................................................... 4
1.
INTRODUCTION.................................................................................................................................. 5
1.1.
Objectives and Endpoints ................................................................................................................ 5
1.2.
Study Design.................................................................................................................................... 8
1.2.1.
Overall Design .............................................................................................................................. 8
1.2.2.
Schematic Overview of the Study............................................................................................... 12
1.2.3.
Randomization and Blinding....................................................................................................... 13
2.
STATISTICAL HYPOTHESES.......................................................................................................... 14
3.
SAMPLE SIZE DETERMINATION.................................................................................................... 14
4.
POPULATIONS (ANALYSIS SETS) FOR ANALYSIS..................................................................... 17
5.
STATISTICAL ANALYSES............................................................................................................... 17
5.1.
General Considerations ................................................................................................................. 17
5.1.1.
Visit Windows ............................................................................................................................. 18
5.2.
Participant Disposition.................................................................................................................... 18
5.3.
Primary Endpoint(s) Analysis......................................................................................................... 19
5.3.1.
Definition of Endpoint.................................................................................................................. 19
5.3.2.
Estimand..................................................................................................................................... 19
5.3.2.1.
Primary Estimand .................................................................................................................... 19
5.3.2.2.
Supplementary Estimands for the Primary Endpoint............................................................... 21
5.3.2.2.1.
All ICEs Composite .............................................................................................................. 21
5.3.3.
Analysis Methods........................................................................................................................ 21
5.3.3.1.
Estimator (Analysis) of the Primary Estimand......................................................................... 21
5.3.3.2.
Estimator (Analysis) for the Supplementary Estimands of the Primary Endpoint ................... 22
5.3.3.2.1.
All ICEs Composite .............................................................................................................. 22
5.3.4.
Subgroup Analyses..................................................................................................................... 22
5.3.5.
Sensitivity Analyses.................................................................................................................... 23
5.3.5.1.
Tipping Point Analysis ............................................................................................................. 23
5.3.5.2.
Modified Endoscopic Recurrence............................................................................................ 23
5.4.
Secondary Endpoint(s) Analysis .................................................................................................... 24
5.4.1.
Key Confirmatory Secondary Endpoint(s) .................................................................................. 24
5.4.1.1.
Definition of Endpoint(s) .......................................................................................................... 24
5.4.1.2.
Estimand(s).............................................................................................................................. 25
5.4.1.2.1.
Estimand of Clinical Remission without Disease Recurrence at Week 48 .......................... 25
5.4.1.2.2.
Estimand of Time to Disease Recurrence ........................................................................... 26
5.4.1.2.3.
Estimand of Abdominal Pain Free at Week 48 .................................................................... 27
5.4.1.2.4.
Estimand of Time-to-Recurrence of Symptoms................................................................... 28
5.4.1.2.5.
Estimand of Steroid Free Clinical Remission at Week 48 ................................................... 29
5.4.1.3.
Analysis Methods .................................................................................................................... 29
5.5.
Other Endpoint(s) Analysis ............................................................................................................ 32
5.5.1.
Definition of Endpoints................................................................................................................ 32
5.5.2.
Analysis Methods........................................................................................................................ 33
5.6.
Other Exploratory Analyses ........................................................................................................... 35
5.6.1.
Risk Factor of Endoscopic Recurrence and Disease Recurrence ............................................. 35
5.6.2.
Cross over .................................................................................................................................. 36
5.6.2.1.
Definition of Endpoints............................................................................................................. 36
5.6.2.2.
Analysis Methods .................................................................................................................... 36
5.7.
Safety Analyses ............................................................................................................................. 36
5.7.1.
Extent of Exposure ..................................................................................................................... 36
NCT05784129


CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959CRD3007
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
3
Status: Approved, Date: 30 November 2023
5.7.2.
Adverse Events........................................................................................................................... 37
5.7.3.
Additional Safety Assessments .................................................................................................. 38
5.7.3.1.
Clinical Laboratory Tests......................................................................................................... 38
5.7.3.2.
Other Safety Parameters......................................................................................................... 40
5.7.3.2.1.
The Columbia Suicide Severity Rating Scale ...................................................................... 40
5.8.
Other Analyses............................................................................................................................... 41
5.8.1.
Pharmacokinetics ....................................................................................................................... 41
5.8.1.1.
Serum Guselkumab Concentrations ....................................................................................... 41
5.8.1.2.
Pharmacokinetic Data Handling Rules.................................................................................... 42
5.8.1.3.
Relationship between Pharmacokinetic Concentration and Efficacy ...................................... 42
5.8.1.4.
Population Pharmacokinetic Analysis ..................................................................................... 42
5.8.2.
Immunogenicity........................................................................................................................... 43
5.8.2.1.
Immunogenicity Analysis ......................................................................................................... 43
5.8.2.2.
Other Immunogenicity Analyses.............................................................................................. 43
5.8.3.
Pharmacodynamics and Biomarkers.......................................................................................... 43
5.8.4.
Health Economics....................................................................................................................... 44
5.8.4.1.
Medical Resource Utilization and Health Economics Data, Associated with Medical 
Encounters............................................................................................................................... 44
5.8.4.2.
Work Productivity and Activity Impairment-General Health .................................................... 44
5.8.5.
Definition of Subgroups .............................................................................................................. 45
6.
SUPPORTING DOCUMENTATION .................................................................................................. 47
6.1.
Appendix 1 List of Abbreviations.................................................................................................... 47
6.2.
Appendix 2 Changes to Protocol-Planned Analyses ..................................................................... 48
6.3.
Appendix 3 Demographics and Baseline Characteristics.............................................................. 49
6.4.
Appendix 4 Protocol Deviations and Quality Tolerance Limits (QTL)............................................ 50
6.5.
Appendix 5 Prior and Concomitant Medications............................................................................ 51
6.6.
Appendix 6 Medical History ........................................................................................................... 53
6.7.
Appendix 7 Intervention Compliance ............................................................................................. 54
6.8.
Appendix 8 Adverse Events of Special Interest............................................................................. 55
6.9.
Appendix 9 Medications of Special Interest................................................................................... 56
6.10.
Appendix 10 Laboratory Toxicity Grading...................................................................................... 58
6.11.
Appendix 11 Imputation Rule......................................................................................................... 65
6.12.
Appendix 12 CDAI.......................................................................................................................... 66
6.12.1.
Partial CDAI Score Calculation Logic ......................................................................................... 66
6.12.2.
CDAI Score Calculation Logic .................................................................................................... 66
6.12.3.
CDAI Score Calculation.............................................................................................................. 68
6.13.
Appendix 13: Liver Safety: Suggested Actions and Follow-up Assessments................................ 69
NCT05784129


CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959CRD3007
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
4
Status: Approved, Date: 30 November 2023
VERSION HISTORY
SAP Version History Summary
SAP Version
Approval Date
Change
Rationale
1.0
10/27/2023
Not Applicable
Initial release
2.0
11/14/2023
Include pharmacokinetics and 
immunogenicity
Include additional data points for
CSR
3.0
11/30/2023
Administrative
Correction to version number 
(internal) 
NCT05784129


CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959CRD3007
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
5
Status: Approved, Date: 30 November 2023
1.
INTRODUCTION
A Randomized, Double-blind, Placebo-controlled Study Evaluating the Safety and Efficacy of 
Guselkumab for the Treatment of Participants with Crohn’s Disease After Surgical Resection: 
PROGRESS 
Janssen made an internal business decision to discontinue the PROGRESS study. This decision is 
not related to any efficacy or safety concerns. Only four subjects were enrolled, and the originally 
planned statistical analyses are no longer applicable. 
We will report data collected on those four patients including:

Baseline characteristics: demographics, medical history of interest, date of CD diagnosis, 
Montreal classification, prior gastrointestinal surgeries, prior CD medications, qualifying 
surgery information, corticosteroid use

Efficacy assessments: Rutgeerts score, CDAI score, fistula assessment, fecal calprotectin, 
CRP, medical resource utilization

Safety assessments: adverse events, concomitant and prohibited medications, hematology, 
clinical chemistry

Pharmacokinetics and immunogenicity: serum guselkumab concentration, antibody status 
(titer and neutralizing antibodies status)
Below are the originally planned statistical analyses for reference.
This SAP contains definitions of the analysis sets, derived variables, and statistical methods for all 
planned analyses for the main study period database lock and the Week 156 database lock. The 
term “study intervention” throughout this SAP refers to placebo and guselkumab.
1.1.
Objectives and Endpoints
The primary and secondary objectives and endpoints are listed below.
Objectives
Endpoints
Primary

To evaluate the efficacy of guselkumab 
treatment versus placebo in preventing 
endoscopic recurrence of CD in participants 
after surgery

Endoscopic recurrence prior to or at Week 48 (as defined 
by modified Rutgeerts score ≥ i2a in the neo-terminal 
ileum, anastomotic site, or its equivalent elsewhere in 
the gastrointestinal (GI) tract [eg colonic ulceration])
Secondary

To evaluate clinical remission without 
disease recurrence in participants treated 
with guselkumab versus placebo after 
surgery

Clinical remission (CDAI < 150) without disease 
recurrence at Week 48 (as defined in Section 5.4.1.1)

To 
evaluate 
disease 
recurrence 
in 
participants treated with guselkumab versus 
placebo after surgery

Time-to-disease recurrence (as defined by CDAI/event 
driven criteria as described in Section 5.4.1.1) at the 
main study database lock, which will incorporate all 
available follow-up of enrolled participants at the time 
that the last participant dosed has completed the Week 
48 study procedures, including the ileocolonoscopy
NCT05784129


CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959CRD3007
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
6
Status: Approved, Date: 30 November 2023
Objectives
Endpoints

To evaluate symptoms such as stool
frequency and abdominal pain scores in 
guselkumab versus placebo after surgery

Abdominal pain free (abdominal pain [AP] score = 0) at 
Week 48

Time-to-recurrence of symptoms, defined as time to 
attaining an AP mean daily score >1 (and also >1 point 
higher than baseline) along with stool frequency (SF) 
mean daily score >3 (and also >3 higher per day than 
baseline) for 2 consecutive weeks through Week 48

To evaluate the safety and PK of guselkumab 
in participants with CD in the postoperative 
period

Frequency and type of AEs and serious adverse events 
(SAEs)

Describe serum guselkumab concentrations over time

The evaluate the efficacy of guselkumab in 
limiting 
steroid 
use 
and 
maintaining 
remission in the postoperative period

Steroid free clinical remission at Week 48, defined as 
CDAI <150 and no corticosteroids within 30 days
Other

To evaluate fatigue and other patient 
reported outcomes in guselkumab versus 
placebo after surgery

Change in Patient-Reported Outcomes Measurement 
Information System (PROMIS)-Fatigue Short Form 7a 
score over 48 weeks

Change in PROMIS-Fatigue SF 7a at each post baseline 
visit through Week 152

Change in PROMIS-29 score, both overall score and 
individual domain scores at each post baseline visit 
through Week 152

Change from baseline in the WPAI at each post baseline 
visit through Week 152

Abdominal pain (AP score = 0) at each post baseline 
visit through Week 152

To evaluate steroid use and healthcare 
utilization 
in 
participants 
within 
the 
postoperative period

The number of participants not on corticosteroids and 
without disease recurrence at each post baseline visit 
through Week 152

The number of participants not on corticosteroids and 
who have not experienced endoscopic or disease 
recurrence at each post baseline visit through Week 152

To evaluate histologic status in CD patients 
after surgery

Histologic 
score 
(as 
measured 
by 
Geboes 
scale/RHI/GHAS) at Week 48 ileocolonoscopy

The number of participants with Geboes score of 2.0 or 
less at Week 48 ileocolonoscopy

The number of participants with Geboes score over 3.1 
at Week 48 ileocolonoscopy

To evaluate the efficacy and safety of open-
label 
guselkumab 
SC 
induction 
and 
maintenance treatment in the cross over 
population after postoperative endoscopic or 
disease recurrence of CD has occurred

Clinical remission (CDAI < 150) at 24 weeks after 
initiation of guselkumab SC induction

Clinical response (CDAI decrease of <100 points or 
CDAI <150) at 24 weeks after initiation of guselkumab 
SC induction

Endoscopic remission (SES-CD of 3 or less) at 24 weeks 
after guselkumab SC induction
NCT05784129


CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959CRD3007
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
7
Status: Approved, Date: 30 November 2023
Objectives
Endpoints

Endoscopic remission (modified Rutgeerts score <i2a) 
at 24 weeks after guselkumab SC induction

To evaluate the efficacy of guselkumab 
treatment versus placebo in changes to 
inflammatory biomarkers after surgery

The change from baseline in CRP concentration at all 
postbaseline visits through Week 152

The change from baseline in fecal calprotectin 
concentration at all postbaseline visits through Week 
152

Fecal calprotectin recurrence, defined by calprotectin of 
>200 μg/g with a 100 μg/g increase over baseline

To evaluate the clinical efficacy of 
guselkumab treatment 

Disease recurrence (using CDAI/Event-driven definition 
as described in Section 9.4.3) at Week 152

Clinical remission (CDAI <150) at each post baseline 
visit

Time to a flare of abdominal pain

To evaluate the endoscopic efficacy of 
guselkumab treatment

Endoscopic remission (SES-CD of 3 or less) at Week 24, 
Week 48, Week 152

Endoscopic recurrence (modified Rutgeerts score >i2a) 
at Week 24, Week 152
Key: AE = adverse event; AP = abdominal pain; CD = Crohn’s disease; CDAI = Crohn’s disease activity index; 
CRP = C-reactive protein; GI = gastrointestinal; PROMIS = Patient-Reported Outcomes Measurement Information 
System; SC = subcutaneous; SAE = serious adverse event; SES-CD = Simple Endoscopic Score - Crohn’s disease; 
SF = stool frequency
Efficacy endpoints definitions are as follows:

Endoscopic Recurrence prior to or at Week 48: modified Rutgeerts score ≥ i2a in the 
neo-terminal ileum, anastomotic site, or its equivalent elsewhere in the gastrointestinal (GI) 
tract [eg colonic ulceration].

Clinical remission without disease recurrence at Week 48: Clinical remission without 
disease recurrence is a composite endpoint defined by the following:

CDAI < 150 at Week 48 and.

No endoscopic recurrence as defined by Rutgeerts score < i2 by Week 48 and

Have not experienced a disease recurrence as defined below.

Disease recurrence: Disease Recurrence is a composite endpoint defined by the following:

A ≥ 70-point increase from baseline in CDAI score at beyond 8 weeks after 
randomization; and a CDAI score of ≥ 200 and evidence of endoscopic recurrence. 
Endoscopic recurrence is defined as a modified Rutgeerts score of ≥ i2a at the anastomotic 
site or its equivalent elsewhere in the GI tract, unless a stool test for C. difficile toxin or 
other enteric pathogen is positive.

In event of a positive test for enteric pathogen including C. difficile toxin, the underlying 
infection should be treated and if ileocolonoscopy has not yet been performed, it should 
only be done when the infection has resolved, and if disease recurrence threshold is still 
met.
NCT05784129


CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959CRD3007
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
8
Status: Approved, Date: 30 November 2023

OR initiation of a physician-prescribed corticosteroids, or an increase in the dose of 
steroids already being taken (by greater than 5 mg/day), for over one week for the 
treatment of CD and evidence of endoscopic recurrence as described above, unless a stool 
test for C. difficile toxin or other enteric pathogen is positive.

OR a new draining external fistula.

OR the reopening and draining of a previously existing external fistula.

OR developing a new internal fistula.

OR developing a new perianal abscess.

OR developing a new intra-abdominal abscess more than three months after the date of 
the index surgery.
Participants who have confirmed endoscopic recurrence at Week 24 or Week 48 and cross 
over to open-label guselkumab treatment will be censored at cross over for the time to disease 
recurrence endpoint.
Time-to-disease recurrence at the main study database lock, which will incorporate all 
available follow-up of enrolled participants at the time that the last participant dosed has 
completed the Week 48 study procedures, including the ileocolonoscopy.

Abdominal pain free at Week 48: abdominal pain [AP] score = 0.

Time-to-recurrence of symptoms: defined as time to attaining an AP mean daily score >1 
(and also >1 point higher than baseline) along with stool frequency (SF) mean daily score >3 
(and also >3 higher per day than baseline) for 2 consecutive weeks through Week 48.

Steroid free clinical remission at Week 48: defined as CDAI <150 and no corticosteroids 
within 30 days.
Specific primary, secondary, and exploratory endpoints, along with definitions, are provided in 
Section 5, Statistical Analyses, and the study protocol.
1.2.
Study Design
1.2.1.
Overall Design
This is a Phase 3, multicenter, randomized, placebo-controlled, prospective double-blind study 
designed to evaluate the efficacy and safety of 
 guselkumab in preventing the recurrence of 
active CD in patients who have recently undergone a surgical resection for CD. A diagram of the 
study design is provided in Section 1.2.2, Schema.
The target population is male or female participants (minimum age 18) with a diagnosis of CD 
who have a qualifying surgery (eg, ileocolonic resection) a maximum of 49 days before 
randomization. Participants will be excluded if they have a short segment of bowel affected 
(ie, less than 10 cm) for fibrostenotic disease and they had their first surgery more than 10 years 
after diagnosis of CD. There is no requirement that participants have failed prior biologics.
NCT05784129
CC
I


CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959CRD3007
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
9
Status: Approved, Date: 30 November 2023
Participants will have a baseline CDAI <200 and will be eligible regardless of prior biologic use. 
Participants who are low risk for recurrent CD (ie, participants whose qualifying surgery was their 
first in >10 years since their diagnosis of CD and was performed for fibrostenotic stricturing 
disease involving <10 cm of the intestine) will be excluded. Participants must be able to undergo 
randomization no later than 49 days after surgery. 
A target of approximately 370 participants will be enrolled from approximately 150 sites. The 
target population consists of participants with CD who have undergone a recent (<49 days) 
ileocolonic resection with ileocolonic anastomosis for CD, without evidence of active disease 
postoperatively. Participants must not have had their qualifying surgery for the purpose of 
resecting known dysplasia.
Randomization will occur in a 1:1 ratio with participants receiving either:

Arm 1 (Guselkumab): Guselkumab 
 at Week 0 and then 
 at Week 8, 
then 
thereafter through the end of the total study period.

Arm 2 (Placebo): Matched placebo 
 at Week 0 and then 
 thereafter through the 
end of the total study period.
Randomization will be stratified by clinical remission status at baseline (CDAI < 150, 
CDAI > 150), region (North America, Western Europe, rest of world) and number of prior 
surgeries (1 surgery versus > 1 surgery, with the qualifying surgery counting as 1 surgery).
A Week 48 video ileocolonoscopy will be performed between Weeks 48 and 51 and participants 
with endoscopic recurrence confirmed by a central reader will cross over to open-label treatment 
with guselkumab SC induction. An optional video ileocolonoscopy can be performed at Week 24 
and cross over will occur at the discretion of the principal investigator if there is only endoscopic 
recurrence without disease recurrence. If participants meet criteria for disease recurrence after 
Week 8 they will also cross over to open-label treatment.
Participants who discontinue study intervention early will return for an early termination visit at 
least 12 weeks after study intervention discontinuation, which will also serve as their final safety 
visit. This visit will include a video ileocolonoscopy at the time of discontinuation, except those 
participants who have already had demonstrated endoscopic recurrence in a study 
ileocolonoscopy. 
Database Locks and Maintenance of the Blind
The first database lock (DBL) is the main study DBL. It will occur when all participants have 
completed the Week 48 visit assessments, or have terminated study participation prior to Week 48, 
and will include all assessments performed as of that date (even those beyond Week 48). The final 
DBL will occur after the last participant completes the final safety visit at Week 156. Additional 
DBLs may be added between Weeks 48 and 156, as warranted.
NCT05784129
CCI
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CCI
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CCI


CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959CRD3007
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
10
Status: Approved, Date: 30 November 2023
The study blind will be maintained for the investigative sites, site monitors, and study participants 
until after the final participant has completed their Week 156 visit. In the event of an emergency, 
the investigator may also unblind a participant’s treatment if such knowledge would change the 
participants’ clinical care. The sponsor will remain blinded to the original treatment assignments 
until after the main study DBL has occurred. 
Study Length 
After the screening period, the total study duration is 156 weeks, with the final dose of study 
intervention given at Week 144 and the final efficacy visit at Week 152 followed by the final safety 
visit at Week 156. The end of the study is defined as when all participants have completed the 
Week 156 visit assessments, or have terminated study participation prior to Week 156 and had 
their last follow-up assessment (12 weeks after the last dose of study intervention or at early 
termination visit). 
The main study period is defined as when the last randomized participant has completed the 
Week 48 assessments at which point the main study database lock will occur. Participant follow-up 
for the main study period will vary depending upon when they enrolled in the trial (estimated to 
be from 12 to 30 months, based upon an anticipated accrual time of 18 months, but with an upper 
limit of 36 months [total study treatment duration], should accrual time exceed 18 months).
Standard immunomodulators (MTX, AZA, and 6-MP) or IV/oral corticosteroids should not be 
initiated (or increased in dose) unless medically necessary as rescue therapy as this will impact the 
efficacy analyses in this study and will be considered treatment failure. If initiated as rescue 
therapy, these treatments should be discontinued or tapered off as soon as medically tolerable and 
appropriate; however, participants can (and should) continue to receive study intervention and 
attend all study visits despite initiation (or increasing dose) of any of these CD related medications, 
except for those described as prohibited medications below.
It is recognized that some participants will have been steroid dependent prior to their surgery and 
may be unable to safely complete tapering of their steroid therapy prior to randomization.
However, as participants enter the study without residual active CD, participants who enter the 
study on steroids should initiate, or continue, tapering of corticosteroids for CD without any delay 
upon study entry at Week 0, unless medically inappropriate. Corticosteroid tapering should follow 
the below-recommended schedule (Table 1), without exceeding the prescribed magnitude or rate 
of tapering unless due to medical necessity (eg, participant experiencing corticosteroid-related side 
effects).
If a participant experiences worsening in his/her disease activity while tapering corticosteroids, 
further dose decreases may be suspended, and the oral corticosteroid dose may be temporarily 
increased if deemed necessary by the investigator, to attempt to return to response. For participants 
whose corticosteroid taper is interrupted on this basis, investigators should resume tapering as soon 
as possible thereafter.
NCT05784129






CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959CRD3007
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
13
Status: Approved, Date: 30 November 2023
1.2.3.
Randomization and Blinding
Randomization will be used to minimize bias in the initial 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, 
stratification by known potentially relevant baseline characteristics that may affect study outcomes 
will also be used to avoid chance imbalance of these relevant variables among treatment groups. 
Blinded intervention will be used to reduce potential bias during data collection and evaluation of 
clinical endpoints.
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 2 intervention groups in a 1:1 ratio 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 clinical remission
status at baseline (CDAI < 150, CDAI ≥150), region (North America, Western Europe, rest of 
world) and number of prior surgeries (1 surgery versus > 1 surgery, with the qualifying surgery 
counting as 1 surgery). The IWRS will assign a unique intervention code, which will dictate the 
intervention assignment and matching study intervention kit for 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 8-week intervals 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.
At the Week 48 DBL (main study DBL), data will be unblinded for analysis to the sponsor only. 
Treatment assignment will remain blinded to the study sites and participants until the 
last participant completes the Week 156 evaluations.
NCT05784129


CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959CRD3007
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
14
Status: Approved, Date: 30 November 2023
Under normal circumstances, the investigator blind should not be broken until the Week 156 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 
for participants who discontinue study intervention.
2.
STATISTICAL HYPOTHESES
The primary hypothesis is that guselkumab is superior to placebo in preventing endoscopic 
recurrence prior to or at Week 48.
3.
SAMPLE SIZE DETERMINATION
A sample size of 370 participants (185 participants assigned to guselkumab and 185 assigned to 
placebo) will allow to have at least 90% power to detect 20% differences between guselkumab 
(30%) and placebo (50%) for endoscopic recurrence rate (primary endpoint) at Week 48, assuming 
a 2-sided alpha level of 0.05.
This also will allow at least 90% power to detect 17% differences between guselkumab (37%) and 
placebo (20%) for clinical remission without disease recurrence at Week 48, assuming a 2-sided 
alpha level of 0.05. This also will allow 90% power to detect 10% differences between guselkumab 
(10%) and placebo (20%) for disease recurrence at the main database lock, all available follow-up 
of all participants will be used to examine disease recurrence at the time of the primary database 
lock. 
Endoscopic Recurrence
Assumptions for endoscopic recurrence prior to or at Week 48 were based on previous studies, as 
described in Table 2.
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Table 2:
Endoscopic Recurrence, Placebo Group
Reference*
Endoscopic 
Recurrence definition
Sample Size
Placebo rate
Timepoint
Regueiro 2016
Rutgeerts > i2
150
60%
76 weeks
Yamamoto 2007
Rutgeerts > i2
20
70%
52 weeks
Marteau 2006
Rutgeerts > i2
47
64%
24 weeks
Rutgeerts 2005
Rutgeerts > i2
33
78.8% 
52 weeks
Hanauer 2004
Rutgeerts > i2
40
64% 
104 weeks
Lochs 2000
Rutgeerts > i2
166
50% 
72 weeks
Ewe 1999
Rutgeerts > i2
40
70% 
52 weeks
Hellers 1999
Rutgeerts > i2
66
58% 
52 weeks
* References are provided in the protocol.
Based on these data above, the endoscopic recurrence rates are assumed to be 50% for placebo and 
30% for guselkumab.
To accommodate other potential scenarios, power was calculated based on different assumptions 
as listed in Table 3.
Table 3:
Power to Detect a Treatment Effect Based on Different Scenarios in Endoscopic Recurrence
Event rate at Week 48 for 
endoscopic recurrence in 
placebo group
Event rate at Week 
48 for endoscopic 
recurrence in 
guselkumab group
Difference to be detected
Power
50%
30%
20%
97.7%
50%
25%
25%
99.9%
50%
35%
15%
83.3%
45%
25%
20%
98.3%
40%
20%
20%
98.9%
60%
30%
30%
>99.9%
Clinical Remission without Disease Recurrence
Based on data from PREVENT (20% for placebo, and 36.7 for Infliximab), the rates of clinical 
remission without disease recurrence are assumed to be 20% for placebo and 37% for guselkumab.
To accommodate other potential scenarios, power was calculated based on different assumptions 
as listed in Table 4:
Table 4:
Power to Detect a Treatment Effect Based on Different Scenarios in Clinical Remission without 
Disease Recurrence
Event rate at Week 48 for 
clinical remission without 
disease recurrence in 
placebo group
Event rate at Week 
48 for clinical 
remission without 
disease recurrence in 
guselkumab group
Difference to be detected
Power
20%
35%
15%
90.0%
20%
36%
16%
93.1%
20%
37%
17%
95.4%
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Disease Recurrence
Assumptions for disease recurrence were based on previous studies, as described in Table 5. 
Table 5:
Disease Recurrence, Placebo Group
Reference*
Disease Recurrence definition
Sample 
Size
Placebo rate
Timepoint
Regueiro 2016
CDAI > 200 and 70 point increase
150
20%
76 weeks
Ng 2009
Symptoms related to CD associated 
with endo, lab or radiologic findings
99
28%
52 weeks
Yamamoto 2007
CDAI > 150
20
35%
52 weeks
Rutgeerts 2005
CDAI > 250 or need for rescue 
medical therapy
40
37.5%
54 weeks
Prantera 2002
CDAI >150, confirmed by 
endoscopy
22
10.5%
52 weeks
Lochs 2000
CDAI >250 or CDAI > 200 with a 
60 point increase
166
31.4%
72 weeks
Hellers 1999
CDAI > 200
66
31%
52 weeks
Ewe 1999
CDAI > 200, rise of 60 points
40
28%
52 weeks
Olaison 1992
CDAI > 150 or HBI >4
42
37%
52 weeks
* References are provided in the protocol.
For this endpoint, all follow-up data available at the primary DBL, including beyond one year 
when available, will be used. Based on this, as well as these data above, the disease recurrence 
rates are assumed to be 20% for placebo and 10% for guselkumab.
To accommodate other potential scenarios, power was calculated based on different assumptions 
as listed in Table 6.
Table 6:
Power to Detect a Treatment Effect Based on Different Scenarios in Disease Recurrence
Event rate at Week 48 
for disease recurrence in 
placebo group
Event rate at Week 48 
for disease recurrence in 
guselkumab group
Difference to be detected
Power
20%
10%
10%
90.0%
8%
12%
98.5%
25%
15%
10%
80.9%
10%
15%
99.7%
30%
15%
15%
98.5%
Accrual time used here is 18 months, total time used here is 30 months. It is expected median 
follow-up time available at the time of, and thus incorporated in, the main database lock is 
approximately 18 months. Assuming non-uniform accrual pattern: 25% of participants will be 
enrolled in the first 6 months, 35% of participants will be enrolled in the next 6 months, and 40% 
will be enrolled in the last 6 months. Assuming dropout rate is 15% annually. Average duration of 
follow-up is expected to be approximately 20 months.
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4.
POPULATIONS (ANALYSIS SETS) FOR ANALYSIS
Analysis Sets
Description
Randomized
The randomized analysis set includes all participants who were 
randomized in the study.
Full Analysis Set (FAS)
All randomized participants.
Participants in the FAS will be analyzed according to their 
randomized study intervention regardless of the study intervention 
they actually received.
Safety Analysis Set
All randomized participants who receive at least 1 dose of study 
intervention.
Participants in the Safety Analysis Set will be analyzed according 
to the study intervention they actually received.
Pharmacokinetics Analysis Set
All randomized participants who receive at least 1 dose of study 
intervention and have at least one valid blood sample drawn 
postbaseline for PK analysis. 
Participants in the PK Analysis Set will be analyzed according to 
the study intervention they actually received.
Immunogenicity Analysis Set
All participants who received at least 1 dose of study intervention 
and have appropriate samples for anti-drug antibody detection. 
Participants in the Immunogenicity Analysis Set will be analyzed 
according to the study intervention they actually received.
5.
STATISTICAL ANALYSES
5.1.
General Considerations

Unless otherwise specified, for each study, data from all investigational centers/sites will be 
pooled for analysis

Study Day 1 refers to the day of the first study intervention administration. All efficacy and 
safety assessments at all visits will be assigned a day relative to this day.
Study day for a visit is defined as:

Visit date - (date of Study Day 1) +1, if visit date is ≥ date of Study Day 1

Visit date - date of Study Day 1, if visit date < date of Study Day 1
There is no 'Study Day 0'.

Baseline assessment is defined as the last available assessment collected prior to the first study 
intervention.

Descriptive statistics (ie, N, mean, median, SD, IQ range, minimum and maximum) will be 
used to summarize continuous variables. Counts and percentages will be used to summarize 
categorical variables. Graphical data displays (eg, line plots) may also be used to summarize 
the data.
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
The following conventions will be applied for reporting descriptive statistics of all continuous 
parameters. For presentation, the mean and median will be presented to 1 decimal greater than 
the original data, SD will be 2 decimal places greater than the original data, and the minimum 
and maximum will have the same number of decimal places as the original data. 

The following intervention groups will be presented through Week 48, unless otherwise 
stated:

Placebo

Guselkumab
Partial dates for adverse events will be imputed as described in Appendix 11.
5.1.1.
Visit Windows
As participants do not always adhere to the protocol visit schedule, the following rules are applied 
to assign actual visits to analysis visits. All post-baseline visits up to and including Week 56 will 
have a visit window of ± 10 days counting from Week 0 as Day 1. If a study visit occurs outside 
this window, the Sponsor should be consulted about how the participant should resume his or her 
normal dose schedule. If a participant has 2 or more actual visits in 1 visit window, the visit closest 
to the target day will be used as the protocol visit for that visit window. The other additional visit(s) 
will not be used in the summaries or analyses but they can be used for determination of clinically 
important endpoints. If 2 actual visits are equidistant from the target day within a visit window, 
the later visit is used.
All assignments will be made in chronological order. Once a visit date is assigned to a visit 
window, it will no longer be used for a later time point except for the endpoint. 
5.2.
Participant Disposition
The number of participants screened, the number of participants screen failed, primary reason for 
screen failure and the number of participants re-screened will be presented. In addition, the number 
of participants who were randomized will be given. 
The number of participants included in the analysis sets by intervention group will be presented. 
Percentages will be based on the number of participants in the RAS. In addition, the distribution 
of participants by region, country and site ID will be presented for the Full Analysis Set. 
The number and frequency of participants in the following disposition categories will be 
summarized by the intervention group based on the Full Analysis Set:

Participants who received study intervention

Participants who completed the study intervention through Week 48

Participants discontinuing study intervention prior to Week 48 and reasons for discontinuation 

Participants discontinuing study intervention prior to Week 156 and reasons for 
discontinuation 

Participants who terminated study participation prior to Week 156 and reasons for termination
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A listing of participants who prematurely discontinued study intervention or prematurely
discontinued the study and the primary reason for discontinuation will be presented. The listing 
will identify the visits completed and when the study intervention or study was discontinued. 
Listings of participants will be provided for the following categories:

Participants who discontinued study intervention prior to Week 48

Participants who terminated study participation

Participants who were randomized yet did not receive study intervention

Participants who were unblinded prior to Week 48 
Study assessment of compliance will be summarized and listed by randomized treatment group.
This will include the number of participants who missed at least one scheduled CDAI assessment, 
at least one scheduled endoscopy assessment, or at least one missed study agent administration
due to any reason or due to COVID-19-related events.
5.3.
Primary Endpoint(s) Analysis
5.3.1.
Definition of Endpoint
The primary endpoint is endoscopic recurrence prior to or at Week 48 as defined by modified 
Rutgeerts score ≥ i2a in the neo-terminal ileum, anastomotic site, or its equivalent elsewhere in the 
GI tract (eg, colonic ulceration).
Rutgeerts score
Score
Endoscopic Findings
i0
No lesions
i1
< 5 aphthous lesions
i2
> 5 aphthous lesions with normal mucosa between the lesions or skip areas of larger 
lesions or lesions confined to the ileocolonic anastomosis (ie, < 1 cm in length)
i2a
Lesions confined to the ileocolonic anastomosis (including anastomotic stenosis)
i2b
More than 5 aphthous ulcers or larger lesions, with normal mucosa in-between, in the 
neoterminal ileum (with or without anastomotic lesions)
i3
Diffuse aphthous ileitis with diffusely inflamed mucosa
i4
Large ulcers with diffuse mucosal inflammation or nodules or stenosis in the neoterminal 
ileum
5.3.2.
Estimand
5.3.2.1.
Primary Estimand
An estimand is a precise definition of the primary targeted treatment effect defined by the 
following 5 attributes: Study Intervention, population, variable (endpoint), intercurrent events 
(ICEs) and corresponding strategies, and population-level summary.
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Primary Trial Objective: To evaluate the efficacy of guselkumab treatment prior to or at 
Week 48 compared with placebo in preventing endoscopic recurrence of CD in participants after 
surgery.
Estimand Scientific Question of Interest: What is the proportion of participants developing 
endoscopic recurrence prior to or at Week 48, and thus considered to have benefited from 
guselkumab versus placebo?
Study intervention:

Experimental: Guselkumab 
 at Week 0 and then 
 at Week 8, then 
 
thereafter through the end of the total study period.

Control: Matched placebo 
 at Weeks 0 and 8 and then
 thereafter through the 
end of the total study period.
Population: Participants with recent (<49 days) qualifying surgery and no evidence of active 
Crohn’s disease postoperatively.
Variable: A binary recurrence variable (recurrence/no recurrence) where recurrence is defined as 
Endoscopic Recurrence prior to or at Week 48 (as defined by modified Rutgeerts score greater 
than or equal to i2a in the neo-terminal ileum, anastomotic site, or its equivalent elsewhere in the 
GI tract (eg, colonic ulceration)) or experiencing intercurrent events (ICEs) 1-4 presented below.
Summary Measure (Population-level summary): Difference in proportions of the binary 
recurrence variable of endoscopic recurrence, as described above, between guselkumab group and 
the placebo group.
Intercurrent events and their corresponding strategies:
The ICEs considered for this study are listed in Table 7:
Table 7:
Intercurrent Events and Corresponding Analysis Strategies for Endoscopic Recurrence prior to 
or at Week 48
Intercurrent Events (between baseline and Week 48)
Analysis Strategy for Intercurrent Events
1.
A CD-related surgery (with the exception of minor 
procedures such as drainage of a superficial abscess or 
seton placement, etc.)
2.
A prohibited change in CD medication
3.
Discontinuation of study intervention due to lack of 
efficacy or an AE of worsening CD 
4.
Cross over to open-label guselkumab
Composite Strategy: Participants are considered 
endoscopic recurrence if they experience any of these 
ICEs, prior to Week 48, as reflected in the variable 
definition.
5.
Discontinuation of study intervention due to COVID-19 
related reasons (excluding COVID-19 infection)
6.
Discontinuation of study intervention due to reasons 
other than those in ICE 3 or 5
Treatment Policy: ICE5 and ICE6 will be ignored, 
and any data observed after the associated ICE event 
will be used for the analysis.
Abbreviation: AE=adverse event; CD=Crohn's disease; COVID-19= Coronavirus disease 2019; ICE=intercurrent 
event
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Intercurrent events in categories 1-4 will be handled by the composite 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 1-4 is an unfavorable 
outcome. For participants experiencing ICEs in category 5 and 6, the treatment policy strategy will 
be used and considers the occurrence of ICE category 5 and 6 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 and 6. 
5.3.2.2.
Supplementary Estimands for the Primary Endpoint
5.3.2.2.1.
All ICEs Composite 
In this supplementary estimand, all ICEs defined above for the primary estimand are addressed by 
the composite strategy. The supplementary estimand for the primary endpoint acknowledges that 
having an ICE is an unfavorable outcome. Besides the strategy change, other components of the 
supplementary estimand are the same as those for the primary estimand with the exception of the 
Variable, which is described as follows: 
Supplementary Estimand of Endoscopic Recurrence prior to or at Week 48
Variable (endpoint): A binary recurrence variable (recurrence/no recurrence) where recurrence 
is defined as Endoscopic Recurrence prior to or at Week 48 (as defined by modified Rutgeerts 
score greater than or equal to i2a in the neo-terminal ileum, anastomotic site, or its equivalent 
elsewhere in the GI tract (eg, colonic ulceration)) or experiencing intercurrent events (ICEs) 1-6
presented in Table 7.
5.3.3.
Analysis Methods
5.3.3.1.
Estimator (Analysis) of the Primary Estimand
The analyses will be based on the Full Analysis Set (FAS), which includes all randomized 
participants. Participants will be analyzed according to the intervention group to which they were 
randomized regardless of the study intervention they actually received.
To compare the guselkumab versus placebo group for the primary endpoint, the Cochran Mantel 
Haenszel chi-square test (2-sided) will be used with stratification of clinical remission status at 
baseline (CDAI < 150, CDAI ≥ 150), region (North America, Western Europe, rest of world) and 
number of prior surgeries (1 surgery versus > 1 surgery, with the qualifying surgery counting as 
1 surgery). The study will be considered successful if the test of the primary endpoint is positive 
at the 0.05 significance level.
After accounting for the ICE strategies, missing data will be imputed by multiple imputation. 
Multiple imputation will be used for imputing missing data under the assumption that the data are 
MAR. The analysis will impute the missing Rutgeerts score at Week 48 using the analysis method 
and ancillary variables as described in Table 8. The responses at Week 48 will be derived from the 
imputed datasets and combined for analysis. 
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Table 8:
Multiple Imputation Methods for Rutgeerts Score at Week 48
Variable
MI specification
Analysis method/Summary statistics
Rutgeerts score at 
Week 48
Multiple imputation with 
monotone regression of 
total scores
MIdataset1 (N=200, Seed=5748941)

Imputation variables: Rutgeerts score at Week 48

Ancillary variables: Treatment group, and history of 
primary non-response to at least one approved ADT 
(Yes, No), clinical remission status at baseline (CDAI 
< 150, CDAI ≥ 150), region (North America, Western 
Europe, rest of world) and number of prior surgeries (1 
surgery versus > 1 surgery, with the qualifying surgery 
counting as 1 surgery)
The number and percentage of participants who experienced any ICE prior to Week 48 will be 
summarized by the type of ICE. 
5.3.3.2.
Estimator (Analysis) for the Supplementary Estimands of the Primary 
Endpoint
5.3.3.2.1.
All ICEs Composite
The same estimator used for the primary estimand will be used for the supplementary estimand,
with the exception that the treatment policy no longer applies to ICE5 and ICE6, as all ICEs are 
addressed by the composite strategy. After accounting for the ICE strategies, participants whose 
endoscopic recurrence status is missing for the primary endpoint will be considered to having 
endoscopic recurrence. 
5.3.4.
Subgroup Analyses
To evaluate the consistency of the primary analyses, subgroup analyses based on demographics 
(eg, age, sex, race, body weight, region), baseline characteristics (CD duration, involved 
gastrointestinal areas, number of CD related prior surgeries, CDAI score), baseline CD-related 
concomitant medication usage and biologic history (oral corticosteroids, oral 5-ASA compounds, 
immunomodulators(6-MP, AZA, or MTX), oral corticosteroids and immunomodulators, oral 
corticosteroids or immunomodulators prior biologic use), and potential risk factors for recurrence 
of active CD (number of risk factors for recurrence of active CD, the qualifying surgery was the 
patient’s second intra-abdominal operation for CD in the past 10 years, the qualifying surgery was 
the patient’s third (or more) intra-abdominal operation for CD, the qualifying surgery was 
performed for a penetrating complication of CD (ie, an intra-abdominal abscess, internal fistula, 
sinus tracts or intestinal perforation), the patient has any history of perianal fistulizing CD provided 
that this has not been active in the 3 months prior to study start, the patient is a cigarette smoker),
the patient has Kono-S (antimesenteric functional end-to-end handsewn), the patient has 
mesenterectomy will be performed if sufficient data are available in the subgroup.
For subgroup analyses, the analysis sets are based on the FAS. Subgroup analyses will be 
performed when the number of participants in each subgroup permits. The following subgroup 
analyses will be performed:
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1.
The consistency of treatment effect for the primary endpoint will be evaluated for the 
subgroups defined in Section 5.8.5, using the primary estimand:
For each of the subgroups identified in Section 5.8.5, the rate (risk) difference of guselkumab 
vs placebo group and the associated p-values and 95% confidence intervals will be provided 
using forest plots. The difference in proportions, p-values and confidence intervals will be 
provided based on the same model specified in Section 5.3.3.1.
2.
Using the primary estimand, an analysis of the primary endpoint will be performed for each 
region, country, and investigator site. This analysis will be descriptive and statistical testing 
will not be applied.
5.3.5.
Sensitivity Analyses
The following sensitivity analyses will be based on varying assumptions of the missing data, and 
different definition for the primary endpoint of endoscopic recurrence.
5.3.5.1.
Tipping Point Analysis 
Tipping point sensitivity analyses will be conducted to explore the potential impact of missing data 
and to show the robustness of the conclusion based on the primary analysis. The analysis finds a 
(tipping) point in this spectrum of assumptions, at which conclusions change from being favorable 
to the experimental intervention to being unfavorable. After such a tipping point is determined, 
clinical judgment can be applied as to the plausibility of the assumptions underlying this tipping 
point. The tipping point can be identified when the result is no longer statistically significant. 
The Tipping Point Analysis will be applied to primary endpoint and will use the primary estimand, 
after accounting for ICEs. For participants with missing data for the endpoint, the endoscopic 
recurrence (recurrence/no recurrence) will be imputed in an increasing manner by participant level 
for each intervention group. Specifically, for each participant, a recurrence/no recurrence status 
will be imputed starting with the scenario where all participants have recurrence up to the scenario 
where all participants have no recurrence. This would include all possible scenarios of recurrence
status for all missing data allowing assumptions about the missing outcomes to vary independently, 
including scenarios where participants randomized to the Guselkumab group have worse outcomes 
than participants on placebo. For each scenario, the adjusted intervention difference 
(with CMH weight) in proportion of participants achieving the primary endpoint between the 
Guselkumab group and placebo group and the corresponding p-values will be provided. 
5.3.5.2.
Modified Endoscopic Recurrence
This sensitivity analysis will evaluate the primary endpoint in a similar fashion. Same ICE strategy 
and similar estimand and estimators will be used, with exception that 

The definition of endoscopic recurrence: endoscopic recurrence prior to or at Week 48 as 
defined by modified Rutgeerts score i2b or above in the neo-terminal ileum, anastomotic site, 
or its equivalent elsewhere in the GI tract (eg, colonic ulceration).

Variable (endpoint): A binary recurrence variable (recurrence/no recurrence) where 
recurrence is defined as Endoscopic Recurrence prior to or at Week 48 (as defined by modified 
Rutgeerts score greater than i3) or experiencing intercurrent events (ICEs) 1-4.
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5.4.
Secondary Endpoint(s) Analysis
5.4.1.
Key Confirmatory Secondary Endpoint(s)
The following are the first secondary endpoint and second secondary endpoint:

Clinical remission without disease recurrence at Week 48

Time to disease recurrence
The analyses of the first secondary endpoint will be performed after the test of the primary 
endpoint. The analyses of second secondary endpoint will be performed after the test of the primary 
endpoint and the first secondary endpoint.
5.4.1.1.
Definition of Endpoint(s)
Clinical remission without disease recurrence is a composite endpoint defined by the following:

CDAI < 150 at Week 48 and

No endoscopic recurrence as defined by Rutgeerts score < i2a by Week 48 and

Have not experienced a disease recurrence as defined below
Disease recurrence is a composite endpoint defined by the following:

A ≥ 70-point increase from baseline in CDAI score at beyond 8 weeks after randomization; 
and a CDAI score of ≥ 200 and evidence of endoscopic recurrence. Endoscopic recurrence is 
defined as a modified Rutgeerts score of ≥ i2a at the anastomotic site or its equivalent 
elsewhere in the GI tract, unless a stool test for C. difficile toxin or other enteric pathogen is 
positive

In event of a positive test for enteric pathogen including C. difficile toxin, the underlying 
infection should be treated and if ileocolonoscopy has not yet been performed, it should only 
be done when the infection has resolved, and if disease recurrence threshold is still met

OR initiation of a physician-prescribed corticosteroids, or an increase in the dose of steroids 
already being taken (by greater than 5 mg/day), for over one week for the treatment of CD 
and evidence of endoscopic recurrence as described above, unless a stool test for C. difficile 
toxin or other enteric pathogen is positive

OR a new draining external fistula

OR the reopening and draining of a previously existing external fistula

OR developing a new internal fistula

OR developing a new perianal abscess

OR developing a new intra-abdominal abscess more than three months after the date of the 
index surgery
Participants who have confirmed endoscopic recurrence without disease recurrence at Week 24 or 
Week 48 and cross over to open-label guselkumab treatment will be censored at cross over for the 
time to disease recurrence endpoint.
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Abdominal pain free at Week 48 is defined as abdominal pain (AP) score = 0 at Week 48
Time-to-recurrence of symptoms is defined as time to attaining an AP mean daily score >1 (and 
also >1 point higher than baseline) along with stool frequency (SF) mean daily score >3 (and also 
>3 higher per day than baseline) for 2 consecutive weeks through Week 48. Participants who cross 
over to open-label guselkumab treatment and do not have recurrence of symptoms will be censored 
at cross over for the time to recurrence of symptoms endpoint.
Steroid free clinical remission at Week 48 is defined as CDAI <150 and no corticosteroids within 
30 days.
5.4.1.2.
Estimand(s)
5.4.1.2.1.
Estimand of Clinical Remission without Disease Recurrence at 
Week 48
Objective: To evaluate clinical remission without disease recurrence in participants treated with 
guselkumab versus placebo after surgery.
Estimand Scientific Question of Interest: What is the proportion of participants achieving 
clinical remission without disease recurrence at Week 48, and thus considered to have benefited 
from guselkumab versus placebo?
Study intervention:

Experimental: Guselkumab 
 at Week 0 and then 
 Week 8, then
 
thereafter through the end of the total study period.

Control: Matched placebo 
at Weeks 0 and 8 and then
 thereafter through the 
end of the total study period.
Population: Participants with recent (<49 days) qualifying surgery and no evidence of active 
Crohn’s disease postoperatively.
Variable: A binary variable of clinical remission without disease recurrence at Week 48 (as 
defined by Rutgeerts score smaller than i2 and CDAI <150 without disease recurrence) or 
experiencing ICEs 1-4 presented below.
Summary Measure (Population-level summary): Difference in proportions of the binary 
variable of clinical remission without disease recurrence, as described above, between guselkumab 
group and the placebo group.
Intercurrent events and their corresponding strategies:
The ICEs considered for this study are listed in Table 9:
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Table 9:
Intercurrent Events and Corresponding Analysis Strategies for Clinical Remission without 
Disease Recurrence at Week 48
Intercurrent Events (between baseline and Week 48)
Analysis Strategy for Intercurrent Events
1.
A CD-related surgery (with the exception of minor 
procedures such as drainage of a superficial abscess or 
seton placement, etc.)
2.
A prohibited change in CD medication (details in 
Appendix 9 Medications of Special Interest)
3.
Discontinuation of study intervention due to lack of 
efficacy or an AE of worsening CD 
4.
Cross over to open-label guselkumab
Composite Strategy: Participants are considered 
not achieving clinical remission without disease 
recurrence if they experience any of these ICEs, 
prior to Week 48, as reflected in the variable 
definition.
5.
Discontinuation of study intervention due to COVID-19 
related reasons (excluding COVID-19 infection)
6.
Discontinuation of study intervention due to reasons 
other than those in ICE 3 or 5
Treatment Policy: ICE5 and ICE6 will be 
ignored, and any data observed after the 
associated ICE event will be used for the analysis.
Abbreviation: AE=adverse event; CD=Crohn's disease; COVID-19= Coronavirus disease 2019; ICE=intercurrent 
event
Intercurrent events in categories 1-4 will be handled by the composite 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 1-4 is an unfavorable 
outcome. For participants experiencing ICEs in category 5 and 6, the treatment policy strategy will 
be used and considers the occurrence of ICE category 5 and 6 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 and 6. 
5.4.1.2.2.
Estimand of Time to Disease Recurrence
Objective: To evaluate disease recurrence in participants treated with guselkumab versus placebo 
after surgery
Estimand Scientific Question of Interest: What is the difference in time to disease recurrence at 
the main database lock, and thus considered to have benefited from guselkumab versus placebo?
Study intervention:

Experimental: Guselkumab 
 at Week 0 and then 
 at Week 8, then 
 
thereafter through the end of the total study period.

Control: Matched placebo 
 at Weeks 0 and 8 and then 
 thereafter through the 
end of the total study period.
Population: Participants with recent (<49 days) qualifying surgery and no evidence of active 
Crohn’s disease postoperatively.
Variable: The time to disease recurrence (as defined above) or experiencing ICE 1-3 presented 
below.
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Summary Measure (Population-level summary): Difference in the time to disease recurrence 
(as defined above) or experiencing ICE 1-3 presented below between guselkumab group and the 
placebo group.
Intercurrent events and their corresponding strategies:
The following are the ICEs considered for this study:
Table 10:
Intercurrent Events and Corresponding Analysis Strategies for Disease Recurrence at Main 
Database Lock
Intercurrent Events (between baseline and main database 
lock)
Analysis Strategy for Intercurrent Events
1.
A CD-related surgery (with the exception of minor 
procedures such as drainage of a superficial abscess or 
seton placement, etc.)
2.
A prohibited change in CD medication (details in 
Appendix 9 Medications of Special Interest)
3.
Discontinuation of study intervention due to lack of 
efficacy or an AE of worsening CD 
Composite Strategy: Participants are considered 
having disease recurrence if they experience any 
of these ICEs, prior to main database lock, as 
reflected in the variable definition.
4.
Discontinuation of study intervention due to COVID-19 
related reasons (excluding COVID-19 infection)
5.
Discontinuation of study intervention due to reasons 
other than those in ICE 3 or 4
Treatment Policy: ICE4 and ICE5 will be 
ignored, and any data observed after the 
associated ICE event will be used for the analysis.
Abbreviation: AE=adverse event; CD=Crohn's disease; COVID-19= Coronavirus disease 2019; ICE=intercurrent 
event
Intercurrent events in categories 1 to 3 will be handled by the composite strategy. This estimand 
acknowledges that having an ICE in categories 1 to 3 is an unfavorable outcome. For participants 
experiencing ICEs in category 4 and 5, the treatment policy strategy will be used and considers 
the occurrence of ICE category 4 and 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 4 and 
5.
5.4.1.2.3.
Estimand of Abdominal Pain Free at Week 48
Objective: To evaluate abdominal pain scores in guselkumab versus placebo after surgery.
Estimand Scientific Question of Interest: What is the proportion of participants achieving 
abdominal pain free at Week 48, and thus considered to have benefited from guselkumab versus 
placebo?
Study intervention:

Experimental: Guselkumab 
 at Week 0 and then 
 at Week 8, then
 
thereafter through the end of the total study period.

Control: Matched placebo 
at Weeks 0 and 8 and then 
 thereafter through the 
end of the total study period.
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Population: Participants with recent (<49 days) qualifying surgery and no evidence of active 
Crohn’s disease postoperatively.
Variable: A binary variable of abdominal pain free at Week 48 (abdominal pain [AP] score = 0) 
or experiencing ICEs 1-4 in Table 9.
Summary Measure (Population-level summary): Difference in proportions of the binary 
variable of abdominal pain free, as described above, between guselkumab group and the placebo 
group.
Intercurrent events and their corresponding strategies:
The same ICEs and corresponding strategies that are specified for primary endpoint of endoscopic 
recurrence prior to or at Week 48 will be used.
5.4.1.2.4.
Estimand of Time-to-Recurrence of Symptoms
Objective: To evaluate symptoms such as stool frequency and abdominal pain scores in 
guselkumab versus placebo after surgery.
Estimand Scientific Question of Interest: What is the difference in time to symptoms at the main 
database lock, and thus considered to have benefited from guselkumab versus placebo?
Study intervention:

Experimental: Guselkumab 
 at Week 0 and then
 at Week 8, then 
 
thereafter through the end of the total study period.

Control: Matched placebo 
 at Weeks 0 and 8 and then 
 thereafter through the 
end of the total study period.
Population: Participants with recent (<49 days) qualifying surgery and no evidence of active 
Crohn’s disease postoperatively.
Variable: The time to symptoms (defined as time to attaining an AP mean daily score >1 (and 
also >1 point higher than baseline) along with stool frequency (SF) mean daily score >3 (and also 
>3 higher per day than baseline) for 2 consecutive weeks through Week 48) or experiencing 
ICE 1-3 in Table 10.
Summary Measure (Population-level summary): Difference in the time to symptoms (as 
defined above) or experiencing ICE 1-3 presented in Table 10 between guselkumab group and the 
placebo group.
Intercurrent events and their corresponding strategies:
The same ICEs and corresponding strategies that are specified for second secondary endpoint of 
time to disease recurrence will be used.
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and ancillary variables as described in Table 11. The responses at Weeks 48 will be derived from 
the imputed datasets and combined for analysis. 
Table 11:
Multiple Imputation Methods for CDAI at Weeks 48
Variable
MI specification
Analysis method/Summary statistics
CDAI score at 
Week 48
Multiple imputation 
with monotone 
regression of total 
scores
MIdataset1 (N=200, Seed=5748941)

Imputation variables: CDAI at Week 48

Ancillary variables: Treatment group, baseline Rutgeerts 
score, history of primary non-response to at least one 
approved ADT (Yes, No), clinical remission status at 
baseline (CDAI < 150, CDAI ≥ 150), region (North 
America, Western Europe, rest of world) and number of 
prior surgeries (1 surgery versus > 1 surgery, with the 
qualifying surgery counting as 1 surgery)
Estimators of Disease Recurrence
Summaries of median survival time and interquartile range of survival time by treatment group 
will be provided. The log-rank test will be used to compare disease recurrence distribution between 
the two treatment groups. The Kaplan-Meier method will be used to estimate the distribution of 
disease recurrence for each treatment. The treatment effect (hazard ratio) and its two-sided 95% 
confidence intervals are to be estimated using Cox regression model with treatment and 
stratification factors. Participants who have not achieved disease recurrence during the main study 
period at the database lock will be censored at the last visit. Participants without any post-baseline 
follow-up will be censored at randomization. 
Estimators of Abdominal Pain Free at Week 48
Summaries of the proportion of participants that achieve abdominal pain free by treatment group 
will be provided. To compare the guselkumab versus placebo group for the first secondary
endpoint, the CMH chi-square test (2-sided) will be used with stratification of clinical remission 
status at baseline (CDAI < 150, CDAI ≥ 150), region (North America, Western Europe, rest of 
world) and number of prior surgeries (1 surgery versus > 1 surgery, with the qualifying surgery 
counting as 1 surgery). 
After accounting for the ICE strategies, missing data will be imputed by multiple imputation.
Multiple imputation will be used for imputing missing data under the assumption that the data are 
MAR. The analysis will impute the missing Rutgeerts score at Week 48 using the analysis method 
and ancillary variables as described in Table 12. The responses at Weeks 48 will be derived from 
the imputed datasets and combined for analysis.
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Table 12:
Multiple Imputation Methods for AP Score at Weeks 48
Variable
MI specification
Analysis method/Summary statistics
AP score at 
Week 48
Multiple imputation 
with monotone 
regression of total 
scores
MIdataset1 (N=200, Seed=5748941)

Imputation variables: AP score at Week 48

Ancillary variables: Treatment group, baseline Rutgeerts score,
history of primary non-response to at least one approved ADT 
(Yes, No), clinical remission status at baseline (CDAI < 150, 
CDAI ≥ 150), region (North America, Western Europe, rest of 
world) and number of prior surgeries (1 surgery versus > 1 
surgery, with the qualifying surgery counting as 1 surgery)
Estimators of Recurrence of Symptoms
Summaries of median survival time and interquartile range of survival time by treatment group 
will be provided. The log-rank test will be used to compare disease recurrence distribution between 
the two treatment groups. The Kaplan-Meier method will be used to estimate the distribution of 
disease recurrence for each treatment. The treatment effect (hazard ratio) and its two-sided 95% 
confidence intervals are to be estimated using Cox regression model with treatment and 
stratification factors. Participants who have not achieved disease recurrence during the main study 
period at the database lock will be censored at the last visit. Participants without any post-baseline 
follow-up will be censored at randomization. 
Estimators of Steroid Free Clinical Remission at Week 48
Summaries of the proportion of participants that achieve steroid free clinical remission by 
treatment group will be provided. To compare the guselkumab versus placebo group for the first 
secondary endpoint, the CMH chi-square test (2-sided) will be used with stratification of clinical 
remission status at baseline (CDAI < 150, CDAI ≥ 150), region (North America, Western Europe, 
rest of world) and number of prior surgeries (1 surgery versus > 1 surgery, with the qualifying 
surgery counting as 1 surgery). 
After accounting for the ICE strategies, missing data will be imputed by multiple imputation.
Multiple imputation will be used for imputing missing data under the assumption that the data are 
MAR. The analysis will impute the missing Rutgeerts score at Week 48 using the analysis method 
and ancillary variables as described in Table 13. The responses at Weeks 48 will be derived from 
the imputed datasets and combined for analysis. 
Table 13:
Multiple Imputation Methods for CDAI at Weeks 48
Variable
MI specification
Analysis method/Summary statistics
CDAI score at 
Week 48
Multiple 
imputation with 
monotone 
regression of total 
scores
MIdataset1 (N=200, Seed=5748941)

Imputation variables: CDAI at Week 48

Ancillary variables: Treatment group, baseline Rutgeerts score, 
history of primary non-response to at least one approved ADT 
(Yes, No), clinical remission status at baseline (CDAI < 150, 
CDAI ≥ 150), region (North America, Western Europe, rest of 
world) and number of prior surgeries (1 surgery versus > 1 
surgery, with the qualifying surgery counting as 1 surgery)
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Type I error will be controlled over the primary and secondary endpoints hierarchically. The 
sequence of tests will be:
1.
Endoscopic recurrence prior to or at Week 48 
2.
Clinical remission without disease recurrence at Week 48
3.
Time-to-disease recurrence
4.
Abdominal pain free at Week 48
5.
Time-to-recurrence of symptoms
6.
Steroid free clinical remission at Week 48
5.5.
Other Endpoint(s) Analysis
5.5.1.
Definition of Endpoints

Change in PROMIS-Fatigue Short Form 7a score over one year

Abdominal pain (AP score = 0) at each post baseline visit through Week 152

Time to a flare of abdominal pain (AP score >1).

Clinical remission (CDAI <150) at each post baseline visit

Change in PROMIS-Fatigue SF 7a at each post baseline visit through Week 152

Change in PROMIS-29 score, both overall score and individual domain scores at each post 
baseline visit through Week 152

Change from baseline in the WPAI at each post baseline visit through Week 152

The number of participants not on corticosteroids and without disease recurrence at each post 
baseline visit through Week 152

The number of participants not on corticosteroids and without endoscopic or disease
recurrence at each post baseline visit through Week 152

Endoscopic recurrence prior to or at Week 24

Histologic score (as measured by Geboes scale/RHI/GHAS) at Week 48 ileocolonoscopy

The number of participants with Geboes score over 3.1 at Week 48 ileocolonoscopy

The number of participants with Geboes score of 2.0 or less at Week 48 ileocolonoscopy

Clinical remission (CDAI <150) at Week 24 after initiation of guselkumab 
induction

Clinical response (CDAI decrease of <100 points or CDAI <150) 24 weeks after initiation of 
guselkumab SC induction

Disease recurrence (using definition described in Section 5.4.1) at Week 152

Fecal calprotectin recurrence, defined by calprotectin of >200 with a 100 μg/g increase over 
baseline

The change from baseline in fecal calprotectin concentration at all postbaseline visits through 
Week 152
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
The change from baseline in CRP concentration at all postbaseline visits through Week 152

Endoscopic remission (SES-CD of 3 or less) at Week 24, Week 48, Week 152

Endoscopic recurrence (modified Rutgeerts score >i2a) at Week 24, Week 152
PRO Instruments

PROMIS-29
The Patient-Reported Outcomes Measurement Information System (PROMIS)-29 is a 
validated general health profile instrument that is not disease-specific (Hayes 2018). 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 an activities). They assess all domains over the past seven days except for Physical 
Function which has no timeframe specified. PROMIS-29 also includes an overall average pain 
intensity 0-10 numeric rating scale. The raw score of each domain is converted into a 
standardized score with a mean of 50 and a standard deviation (SD) of 10 (T-Score). The 
standardized T-score is reported as the final score for each participant. Pain Intensity is 
presented as raw responses (0-10). Norm-based scores have been calculated for each domain 
on the PROMIS measures, with a score of 50 representing the mean or average of the reference 
population. On symptom-oriented domains of PROMIS-29 (anxiety, depression, fatigue, pain 
interference, and sleep disturbance), higher scores represent worse symptomatology. On the 
function-oriented domains (physical functioning and social role), higher scores represent 
better functioning.

PROMIS Fatigue-7a
The PROMIS Fatigue 7-items Short Form (PROMIS Fatigue Short Form 7a) contains 7 items 
evaluating fatigue-related symptoms (ie, tiredness, exhaustion, mental tiredness, and lack of 
energy) and associated impacts on daily activities (ie, activity limitations related to work, 
selfcare, and exercise) (Ameringer 2016). PROMIS Fatigue Short Form 7a has a recall period 
of past 7 days. Compared to the fatigue scale of PROMIS-29, PROMIS Fatigue Short Form 
7a provides additional information to evaluate severity of fatigue. The raw total score is 
converted into a standardized score with a mean of 50 and a SD of 10 (T-Score). The 
standardized T-score is reported as the final score for each participant.

Work Productivity and Activity Index for Crohn’s disease (WPAI-CD)
The WPAI-CD is a validated instrument created as a patient-reported quantitative assessment 
of the amount of absenteeism, presenteeism, and daily activity impairment attributable to CD 
(Reilly 2008). The WPAI-CD consists of 6 questions to determine employment status, hours 
missed from work due to CD, hours missed from work for other reasons, hours worked, the 
degree to which CD affected work productivity while at work, and the degree to which CD 
affected activities outside of work. Higher scores indicate greater impairment.
5.5.2.
Analysis Methods
Unless otherwise specified, the exploratory endpoints listed and defined in Section 5.5.1 will be 
analyzed based on the FAS according to the randomized intervention group regardless of the 
intervention actually received. 
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All exploratory endpoints will be tested regardless of the significance of the primary and secondary 
endpoints; the testing of these endpoints will not be controlled for multiplicity. Nominal p-values 
will be presented.
Descriptive statistics (ie, N, mean, median, SD, IQ range, minimum, and maximum) will be used 
to summarize continuous variables. Frequency counts and percentages will be used to summarize 
categorical variables. Graphical data displays (eg, line plots) may also be used to summarize the 
data.
Binary Endpoints
The intercurrent events captured for binary endpoints specified in Section 5.3.2 will be applied to 
each of the above binary endpoints. Participants with ICEs in categories 1-4 will be considered to 
have unfavored outcome. For participants experiencing an ICE 5 and ICE 6, their observed values 
will be used, if available.
Participants with any missing data for an endpoint after accounting for the ICEs will be imputed 
as having unfavored outcome. Binary endpoints will be summarized with the number and 
frequency of participants who achieve the endpoint by treatment group. Treatment comparisons 
will be performed using CMH chi-square test stratified by clinical remission status at baseline 
(CDAI < 150, CDAI ≥150), region (North America, Western Europe, rest of world) and number 
of prior surgeries (1 surgery versus > 1 surgery, with the qualifying surgery counting as 1 surgery). 
In case of rare events, the Fisher’s exact test will be used for treatment comparisons.
Time-to-event Endpoints
The ICEs captured for time-to-event endpoints specified in Section 5.4.1 will be applied to each 
of the above time-to-event endpoints. Participants with ICEs in categories 1-3 will be considered 
to have unfavored outcome. For participants experiencing an ICE 4 and ICE 5, their observed 
values will be used, if available.
Time-to-event endpoints will be summarized with median survival time and interquartile range of 
survival time by treatment group. Kaplan-Meier curves will be provided for time-to-event 
endpoints as well. Treatment comparisons will be performed using the log-rank test stratified by 
clinical remission status at baseline (CDAI < 150, CDAI ≥150), region (North America, Western 
Europe, rest of world) and number of prior surgeries (1 surgery versus > 1 surgery, with the 
qualifying surgery counting as 1 surgery).
Continuous Endpoints
The ICEs specified as following will be applied to each of the above continuous endpoints, ie, if a 
participant has an ICE in categories 1-4, last available values will be assigned from the point of 
ICE onward (i.e., no change from baseline). For participants experiencing an ICE 5 or ICE 6, their 
observed values will be used, if available. Note that the application of ICE categories 1-4 overrides 
that of ICE 6 and ICE 6. This means that for a participant with an ICE in categories 1-4 baseline 
values will be assigned from the point of ICE onward (ie, no change from baseline), regardless of 
whether the participant has had an ICE 5 or ICE 6.
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To account for the missing data for continuous endpoints of change from baseline measured at 
more than one post-baseline visit (after applying the ICEs), a Mixed-Effect Model Repeated 
Measures (MMRM) will be used, under the assumption of missing at random (MAR), to test the 
difference between treatment groups. In MMRM, missing data will not be imputed, but rather 
missing data will be accounted for through correlation of repeated measures in the model. 
Additionally, if the MMRM normality assumption is in question, an appropriate transformation 
may be implemented before fitting the MMRM model.
The explanatory variables of the MMRM model will include treatment group, visit, applicable 
baseline score, clinical remission status at baseline (CDAI < 150, CDAI ≥150), region (North 
America, Western Europe, rest of world) and number of prior surgeries (1 surgery versus 
> 1 surgery, with the qualifying surgery counting as 1 surgery), an interaction term of visit with 
treatment group, and an interaction term of visit with applicable baseline score.
An unstructured covariance matrix for repeated measures within a participant will be used. The 
F test will use Kenward-Roger’s approximation for degree of freedom. In case of lack of 
convergence, empirical structured covariances will be used in the following order until 
convergence is reached: 1) Toeplitz, 2) first order Autoregressive Moving Average.
The treatment difference between treatment groups will be estimated by the difference in the least 
squares means (LSmeans). The 95% 2-sided CI for the differences in LSmeans and p-values will 
be calculated based on the MMRM.
5.6.
Other Exploratory Analyses
5.6.1.
Risk Factor of Endoscopic Recurrence and Disease Recurrence
The analyses to identify risk factor of endoscopic recurrence and disease recurrence will be based 
on safety analysis set (based on actual intervention received).
All variables in interest will be included in univariate analysis. Univariate logistic regression 
model will be applied for endoscopic recurrence and univariate Cox proportional regression model 
will be applied for disease recurrence. The variables that are significantly (p value < 0.1) associated 
with each endpoint will be included in a full multivariable model for each endpoint. Stepwise 
selection, based on AIC, will be used to find the subset of variables to form a reduced multivariable 
model with only significant variable for each endpoint.
Variables in interest are listed as below:

Second intra-abdominal operation for CD in the past 10 years

Qualifying surgery was the patient’s >3 intra-abdominal operation for CD

Qualifying surgery was performed for a penetrating complication of CD

Any history of perianal fistulizing CD provided that this has not been active in the 3 months 
before study start
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
Cigarette smoker

Kono-S anastomosis

Mesenteric resection

CD duration before first surgery (< 1 year, 1-10 yrs, > 10 years)

Location of CD (Montreal L1 vs L2 vs L3 v L4)

Crohn’s phenotype: B3 (penetrating) vs other phenotypes
5.6.2.
Cross over
The testing of these endpoints will not be controlled for multiplicity and nominal p-values will be 
provided.
5.6.2.1.
Definition of Endpoints

Clinical remission (CDAI < 150) at 24 weeks after initiation of guselkumab SC induction

Clinical response (CDAI decrease of <100 points or CDAI <150) at 24 weeks after initiation 
of guselkumab SC induction

Endoscopic remission (SES-CD of 3 or less) at 24 weeks after guselkumab SC induction

Endoscopic remission (modified Rutgeerts score <i2a) at 24 weeks after guselkumab SC 
induction
5.6.2.2.
Analysis Methods
Unless otherwise specified, the exploratory endpoints listed and defined in Section 5.6.2 will be 
analyzed based on the cross over participants. 
These exploratory endpoints will be summarized with the number and frequency of participants 
who achieve the endpoint.
Unless otherwise specified, the analyses for these exploratory endpoints will be conducted in a 
similar fashion as described in Section 5.5.2.
5.7.
Safety Analyses
All safety analyses will be based on the safety analysis set based on actual intervention received, 
unless otherwise specified.
For all continuous safety variables, descriptive statistics by intervention group will include the N, 
mean, standard deviation, median, minimum, and maximum. Categorical variables will be 
summarized by intervention group using frequency counts and percentages.
5.7.1.
Extent of Exposure
The exposure data will be summarized through Week 48 and Week 152. The number and 
percentage of subjects who receive study agents will be summarized by treatment group for the
safety analysis set. Descriptive statistics will be presented for the following parameters:
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
Number of study agent 
through Week 48.

Number of study agent 
through Week 152.
For cross over population, additional descriptive statistic will be presented for the following 
parameter:

Number of study agent 
 from cross over through cross over + Week 24.
5.7.2.
Adverse Events
The verbatim terms used in the CRF by investigators to identify adverse events will be coded using 
the Medical Dictionary for Regulatory Activities (MedDRA). Any AE occurring at or after the 
initial administration of study intervention through Week 48 and Week 156, is considered to be 
treatment emergent. If the event occurs on the day of the initial administration of study 
intervention, and either event time or time of administration are missing, then the event will be 
assumed to be treatment emergent. If the event date is recorded as partial or completely missing, 
then the event will be considered as treatment emergent unless it is known to be prior to the first 
administration of study intervention based on partial onset date or resolution date. All reported 
treatment-emergent adverse events will be included in the analysis. For each adverse event, the 
number and percentage of participants who experience at least 1 occurrence of the given event will 
be summarized by intervention group. Average duration of study participation follow-up in weeks 
will be presented for each summary of AEs. The duration of follow-up in weeks will be defined 
as [(study discontinuation) – (date of first study intervention) + 1]/7 (including the SFU period 
after the last study intervention), if participants discontinued study intervention prematurely. The 
duration of follow-up in weeks will be defined as [(date of Visit 48) – (date of first study 
intervention) + 1]/7, if participants completed study intervention through Week 48. The duration 
of follow-up in weeks will be defined as [(date of Visit 156) – (date of first study 
intervention) + 1]/7, if participants completed study intervention through Week 156. To account 
for differences in follow-up times, adverse events will also be summarized using events per 
100 participant years of follow-up. 
The following summaries will be provided for treatment-emergent adverse events:

Overall summary of AEs, presenting frequencies and types of AEs

Summary of AEs by system organ class (SOC) and preferred term (PT)

Summary of SAEs by SOC and PT

Summary of related to study intervention AEs (as assessed by the investigator) by system 
organ class and preferred term

A related AE is defined as any event with a relationship to study intervention of ‘related’ 
on the AE eCRF page or if the relationship to study intervention is missing.

Summary of AEs leading to discontinuation of study intervention by SOC and PT

Frequency and type of AEs associated with the SMQ Opportunistic Infections (narrow)
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
Summary of maximum post-baseline measurement through Week 48 and through Week 156
for ALT, AST, alkaline phosphatase, and total bilirubin relative to ULN among participants 
taking immunomodulators at baseline.

Summary of maximum post-baseline elevated liver function tests through Week 48 and 
through Week 156 by the following categories for ALT, AST, alkaline phosphatase, and total 
bilirubin relative to ULN:

> 1 to ≤ 3 x ULN

> 3 to ≤ 5 x ULN

> 5 to ≤ 10 x ULN

> 10 to ≤ 20 x ULN

> 20 x ULN

Summary of potential Hy’s Law case (ALT or AST ≥3 x ULN and total bilirubin ≥2 x ULN 
or INR >1.5) through Week 48 and through Week 156.

Box plots of observed laboratory values and change from baseline in laboratory parameters 
(hematology and chemistry) through Week 48 and through Week 156 will be provided.
Listings of participants with any abnormal post-baseline laboratory values of NCI-CTCAE grade 
≥ 2, participants with maximum post-baseline elevated liver function tests (AST or ALT >5xULN) 
and participants with potential Hy’s Law case (ALT or AST ≥3 x ULN and total bilirubin 
≥2 x ULN or INR >1.5), will also be provided by study intervention group, participant, and visit. 
There will be no imputation for missing laboratory values.
Any laboratory values given as <X.X in the database will be imputed with the value of the number 
without the sign for the descriptive statistics and the calculation of changes from baseline, eg. a 
value of <2.2 will be imputed as 2.2 for the calculations. 
5.7.3.2.
Other Safety Parameters
5.7.3.2.1.
The Columbia Suicide Severity Rating Scale 
The Columbia-Suicide Severity Rating Scale (C-SSRS) will be used as a screening tool to 
prospectively evaluate suicidal ideation and behavior in this study, as part of a comprehensive 
evaluation of safety. The C-SSRS is an investigator-administered questionnaire that defines 
five subtypes of suicidal ideation and 4 possible suicidal behaviors, as well as non-suicidal 
self-injurious behavior and completed suicide.
The baseline is defined as the most severe/maximum score at screening and Week 0. Suicidal 
ideation and behavior based on the electronic Clinical Outcome Assessment (eCoA) C-SSRS 
findings ≥ 1 and on any C-SSRS finding reported on the AE CRF, which in the opinion of the 
investigator is new or considered to be a worsening and clinically significant, will be summarized.
Number of participants with treatment-emergent events of suicidal ideation, suicidal behavior, or 
self-injurious behavior without suicidal intent by worst severity through Week 48 and through 
Week 156 by ideation/ behavior level will be presented. In addition, summary of change from 
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baseline to postbaseline worst severity in suicidal ideation, suicidal behavior, or self-injurious 
behavior without suicidal intent through Week 48 and through Week 156 will be included. 
Furthermore, participants with positive postbaseline (C-SSRS findings > 0) ideation and behavior 
through Week 48 and through Week 156 will be presented in a data listing. 
5.8.
Other Analyses
5.8.1.
Pharmacokinetics
PK analyses will be performed on the PK Analysis Set.
5.8.1.1.
Serum Guselkumab Concentrations
Blood samples for determining the serum guselkumab concentration will be drawn from all 
participants according to the Schedule of Activities in the Protocol. 
Descriptive statistics of the serum guselkumab concentrations will be calculated by intervention 
group at each visit, including n, arithmetic mean, SD, median, coefficient of variation (%CV), 
interquartile range, range (minimum and maximum).
The following analyses will be performed:

Summary of serum guselkumab concentrations by visit through Week 48 (or up to the time of 
cross over if applicable)

Summary of serum guselkumab concentrations by visit through Week 152 (or up to the time 
of cross over if applicable)

Proportion of participants without detectable serum guselkumab concentration (below the 
lower limit of quantification) at each visit through Week 48 (or up to the time of cross over if 
applicable)

Proportion of participants without detectable serum guselkumab concentration (below the 
lower limit of quantification) at each visit through Week 152 (or up to the time of cross over 
if applicable)

Summary of serum guselkumab concentrations at each visit by baseline body weight (using 
quartiles) through Week 48 (or up to the time of cross over if applicable)

Summary of serum guselkumab concentrations at each visit by baseline body weight (using 
quartiles) through Week 152 (or up to the time of cross over if applicable)
For patients who had a cross over, additional analyses will be performed:

Summary of serum guselkumab concentrations by visit from cross over through the end of 
study (including the PK at cross over visit)

Proportion of participants without detectable serum guselkumab concentration (below the 
lower limit of quantification) at each visit from cross over through the end of study (including 
the PK at cross over visit)

Summary of serum guselkumab concentrations at each visit by baseline body weight (using 
quartiles) from cross over through the end of study (including the PK at cross over visit)
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5.8.1.2.
Pharmacokinetic Data Handling Rules
Unless otherwise specified, the following data handling rules will apply to PK analyses:

Participants will be analyzed according to the intervention that they actually received. 

All serum concentration summaries for a particular time point will include data obtained from 
treated participants at the timepoint of interest without imputing any missing data. 

A concentration not quantifiable (below the lower limit of quantification) will be treated as 0 
in the summary statistics and shown as the lower limit of quantification (< LLOQ) in the data 
listings. 

The data from a participant who meets any of the following dosing deviation criteria will be 
excluded from the by-visit data analyses from that point onwards:
−
Discontinued study intervention.
−
Skipped a study intervention administration.
−
Received an incomplete / incorrect dose.
−
Received an incorrect study intervention.
−
Received an additional dose.
Additional samples excluded from the analysis are described as follows:

Pre-dose samples collected after the study intervention administration at the time of visit

Pre-dose samples collected before the study intervention administration at Week 0, 4, and 8 
that were outside of the visit window +/- 4 days

Samples collected before the study intervention administration after Week 8 through Week 48 
that were outside of the visit window +/- 7 days. 
5.8.1.3.
Relationship between Pharmacokinetic Concentration and Efficacy
To explore the relationship between guselkumab serum concentrations and the efficacy endpoints, 
the analyses of the primary and secondary efficacy endpoints by trough concentrations, using 
quartiles, at Week 16, Week 24 and Week 48 will be presented graphically. 
Additional relationships between the serum concentrations and the exploratory efficacy endpoints 
may be explored graphically.
5.8.1.4.
Population Pharmacokinetic Analysis
If sufficient data are available, then population PK analysis using serum concentration-time data 
of guselkumab will be performed using nonlinear mixed-effects modeling. Details will be given 
in a population PK analysis plan and the results of the analysis will be presented in a separate 
report.
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Status: Approved, Date: 30 November 2023
5.8.2.
Immunogenicity
5.8.2.1.
Immunogenicity Analysis
Unless otherwise mentioned, summaries of immunogenicity to guselkumab will be provided based 
on the Immunogenicity Analysis Set.
Serum samples will be screened for antibodies binding to guselkumab and the titer of confirmed 
positive samples will be reported. 
The incidence and titers of antibodies to guselkumab will be summarized through Week 48 and 
through Week 152 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 study intervention). The maximum titers of antibodies to guselkumab will 
be provided for participants who are positive for antibodies to guselkumab. These analyses will 
also be performed by baseline immunomodulator use (Yes, No).
Separate listings of participants who are positive for antibodies to guselkumab will be provided. 
The listing will contain intervention group, visit, serum guselkumab concentration at the visit, dose 
administered, baseline immunomodulators use (Yes or No), CDAI score at the visit, modified 
Rutgeerts score, SES-CD score at the visit, 
-site reactions, and antibody status (titer and 
neutralizing antibodies status) for all visits, and cross over status (Yes or No). In addition, a list of 
antibodies to guselkumab status in participants who discontinued study intervention early will be 
provided.
The incidence of neutralizing antibodies (NAbs) to guselkumab will be summarized for 
participants who are positive for antibodies to guselkumab and have samples evaluable for NAbs 
to guselkumab.
5.8.2.2.
Other Immunogenicity Analyses
To explore the relationship of antibodies to guselkumab status with serum guselkumab
concentrations, and efficacy and safety, the following analyses may be performed as appropriate:

Summary of median trough serum guselkumab concentrations over time by antibodies to 
guselkumab status

Summary of primary and secondary efficacy endpoints by antibodies to guselkumab if 
sufficient participants have antibodies to guselkumab

Summary of 
-site reactions by antibodies to guselkumab status
5.8.3.
Pharmacodynamics and Biomarkers
Changes in serum protein analytes and whole blood ribonucleic acid (RNA) obtained over time 
will be summarized by study intervention group. Associations between baseline levels and changes 
from baseline in select markers and response to study intervention will be explored. The biomarker 
analyses will characterize the effects of guselkumab to identify biomarkers relevant to study 
intervention, and to determine if these biomarkers can predict response to guselkumab. 
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Inflammatory pharmacodynamics markers (CRP and fecal calprotectin) will be evaluated and are 
discussed in further detail in Appendix 6.3. Analyses of serum biomarkers, whole blood RNA, 
peripheral blood mononuclear cells, stool biomarkers, and endoscopic biopsy will be reported in 
separate technical reports.
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.
5.8.4.
Health Economics
The data collected will be used to conduct exploratory economic analyses based on the FAS. The 
summaries of health economics will be performed for the main study period.
5.8.4.1.
Medical Resource Utilization and Health Economics Data, Associated 
with Medical Encounters
Medical resource utilization and health economics data associated with medical encounters, will 
be collected in the CRF throughout the study. 
1.
Proportion of participants having any CD-related ER/hospitalizations and/or surgeries through 
Week 48. 
2.
Summary of duration of CD-related medical care encounters, including surgeries, and other 
selected procedures (inpatient and outpatient) (total days length of stay, including duration by 
wards; eg, intensive care unit)
3.
Time to first CD-related ER/hospitalization and/or surgeries through Week 48.
4.
Summary of duration of hospitalization (total days length of stay, including duration by wards; 
eg, intensive care unit)
5.
Proportion of participants having any ER/hospitalizations and/or surgeries through Week 48
6.
Time to first ER/hospitalization and/or surgeries through Week 48
7.
Proportion of participants with a CD-related surgery through Week 48 
8.
Time to first CD-related surgery through Week 48 
9.
Summary of diagnostic and therapeutic tests and procedure by type through Week 48
5.8.4.2.
Work Productivity and Activity Impairment-General Health 
For the endpoints listed below, analysis will be based on the data as observed and the attributes
and strategies for the ICEs will only be applied to Work Productivity and Activity Impairment
Questionnaire-General Health (WPAI-CD) endpoint:
1.
Change from baseline in the WPAI at each post baseline visit through Week 152 
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WPAI-CD
The WPAI-CD is a validated instrument created as a patient-reported quantitative assessment of 
the amount of absenteeism, presenteeism, and daily activity impairment attributable to Crohn’s 
disease. The WPAI-CD consists of 6 questions: 
Q1) currently employed (working for pay)? (yes, no) If No, skip to Q6.
Q2) hours missed from work in the past 7 days due to Crohn’s disease, 
Q3) hours missed in the past 7 days from work for other reasons, 
Q4) hours worked in the past 7 days, 
Q5 the degree to which Crohn’s disease affected work productivity while at work in the past 7 
days, 
Q6) the degree to which Crohn’s disease affected activities outside of work in the past 7 days. 
Four scores are derived. 
1.
percentage of absenteeism: 100*Q2/(Q2+Q4)
2.
percentage of presenteeism (reduced productivity while at work): 100*Q5/10
3.
an 
overall 
work 
impairment 
score 
that 
combines 
absenteeism 
and 
presenteeism: 100*{Q2/(Q2+Q4) + [(1-Q2/(Q2+Q4)) * (Q5/10)]}
4.
percentage of impairment in activities performed outside of work: 100* Q6/10
Higher scores indicate greater impairment.
Note that for participants with answer=’No’ to Q1, only the 4th score (ie, percent activity 
impairment outside work due to CD) can be calculated.
5.8.5.
Definition of Subgroups
The following subgroups will be evaluated for the primary endpoint in this study:
1.
Demographics:
a.
Age at baseline (≤ median age, > median age)
b.
Sex (male, female)
c.
Race (Caucasian, non-Caucasian)
d.
Weight at baseline (≤ median body weight, > median body weight)
e.
Center location [Americas (Canada, USA), APAC (Australia, South Korea, Taiwan),
EMEA (Austria, Belgium, Czech Republic, France, Germany, Hungary, Israel, Italy, 
Netherlands, Poland, UK, Serbia, Spain), LATAM (Argentina, Brazil, Mexico)]
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2.
Baseline disease characteristics:
a.
CD duration (5 years, > 5 years to 15 years, or > 15 years)
b.
Involved gastrointestinal areas (ileum, colon, ileum & colon)
c.
number of CD-related prior surgeries (0, 1-2, >2)
d.
CDAI score (<150, ≥ 150)
3.
Baseline CD-related concomitant medication usage and tumor necrosis factor (anti-TNF) 
history:
a.
Oral corticosteroids (receiving, not receiving)
b.
Oral corticosteroids and (6-MP, AZA, or MTX) (receiving, not receiving)
c.
Oral corticosteroids or (6-MP, AZA, or MTX) (receiving, not receiving) 
d.
Prior biologic use (Yes, No)
4.
Risk factors for recurrence of active CD:
a.
Number of risk factors for recurrence of active CD (1, >1)
b.
The qualifying surgery was the patient’s second intra-abdominal operation for CD in the 
past 10 years (Yes, No)
c.
The qualifying surgery was the patient’s third (or more) intra-abdominal operation for 
CD (Yes, No)
d.
The qualifying surgery was performed for a penetrating complication of CD (ie, an intra-
abdominal abscess, internal fistula, sinus tracts or intestinal perforation) (Yes, No)
e.
The patient has any history of perianal fistulizing CD provided that this has not been 
active in the 3 months prior to study start (Yes, No)
f.
Smoking statue (Y, N)
g.
The patient has Kono-S (antimesenteric functional end-to-end handsewn) (Yes, No)
h.
The patient has mesenterectomy (Yes, No)
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6.
SUPPORTING DOCUMENTATION
6.1.
Appendix 1 List of Abbreviations
ADA
anti-drug antibody
AE
adverse event
ALT/SGPT
alanine aminotransferase
ANCOVA
analysis of covariance
AST/SGOT
aspartate aminotransferase
ATC
anatomic and therapeutic class
AUC
area under the curve
BMI
body mass index
BSA
body surface area
CI
confidence interval
CL
total systemic clearance
Cmax
maximum concentration
CRF
case report form
CSR
Clinical Study Report
CTCAE
Common Terminology Criteria for Adverse Events
CV
coefficient of variation
DMC
Data Monitoring Committee
DPS
Data Presentation Specifications
ECG
Electrocardiogram
eCRF
electronic case report form
F (%)
absolute SC bioavailability
FAS
full analysis set
FDA
Food and Drug Administration
iARBM
Integrated Analytical Risk-Based Monitoring
ICH
International Conference on Harmonisation
IQ
Interquartile
IVRS
interactive voice response system
IWRS
interactive web response system
LLOQ
lower limit of quantification
LOCF
last observation carried forward
MedDRA
Medical Dictionary for Regulatory Activities
MRD
minimum required dilution
Nab
neutralizing antibodies
PD
pharmacodynamic(s)
PI
principal investigator
PK
pharmacokinetic(s)
PP
per protocol
QTL
Quality Tolerance Limit
SAE
serious adverse event
SAP
Statistical Analysis Plan
SD
standard deviation
SMQs
standardised MedDRA queries
TEAE
treatment-emergent adverse event
Tmax
time to maximum concentration
US NCI
United States National Cancer Institute
V
volume distribution
Vz
volume of distribution based on terminal phase
Vz/F
apparent volume of distribution based on terminal phase after extravascular administration
WHO
World Health Organization
WHO-DD
World Health Organization Drug Dictionary
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6.2.
Appendix 2 Changes to Protocol-Planned Analyses
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6.3.
Appendix 3 Demographics and Baseline Characteristics
Table 14 and Table 15 present the list of the demographic and baseline Crohn’s disease variables 
that will be summarized by treatment group, and overall for the FAS.
Table 14:
Demographic Variables
Continuous Variables
Summary Type
Age (years)
Frequency distribution with the 
number and percentage of 
participants in each category.
Weight (kg)
Height (cm)
BMI (kg/m2)
Categorical Variables
Sex (male, female, unknown, undifferentiated)
Racea (American Indian or Alaska Native, Asian (Japanese or Other 
Asian), Black or African American, Native Hawaiian or other Pacific 
Islander, White, Multiple)
Ethnicity (Hispanic or Latino, not Hispanic or Latino)
Region (North America, Western Europe, rest of world)
Tobacco or nicotine use (non-user, prior user, current user)
Alcohol use (never used, current user, former user) 
aIf multiple race categories are indicated, the Race is recorded as 'Multiple'
Table 15:
Baseline Disease Characteristic Variables
Continuous Variables
Summary Type
Crohn’s disease duration (years)
Descriptive statistics (N, mean, 
standard deviation [SD], median 
and range [minimum and 
maximum], and IQ range).
CDAI score
PRO-2 score (weighted sum of AP and SF subscores of CDAI)
Days from surgery to randomization
IBDQ
CRP
Fecal Calprotectin
Categorical Variables
Frequency distribution with the 
number and percentage of 
participants in each category.
Crohn’s disease complications (Intra-abdominal abscess, sinus 
tracts/perforations, fistula, structuring complications of CD, total or sub-
total colectomy, partial bowel resection, perianal surgery, other CD related 
surgery, total parenteral nutrition) 
Involved GI areas (Ileum, Colon, Ileum and Colon)
Previous ADTs (1, 2, > 2)
Primary nonresponse to at least one approved ADT (yes, no)
Secondary nonresponse to at least one approved ADT (yes, no)
Intolerance to at least one approved ADT (yes, no)
PRO-2 score [Stool frequency ≥ 4 and Abdominal pain ≥ 2, Stool 
frequency ≥ 4 and Abdominal pain < 2, Stool frequency < 4 and 
Abdominal pain ≥ 2]
Fecal calprotectin > 250 mg/kg
CRP >3 mg/L
Fecal calprotectin > 250 mg/kg and CRP >3 mg/L
aIf multiple race categories are indicated, the Race is recorded as 'Multiple'
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6.4.
Appendix 4 Protocol Deviations and Quality Tolerance Limits (QTL)
In general, the following list of major protocol deviations (PDs) may have the potential to impact 
participants’ rights, safety or well-being, or the integrity and/or result of the clinical study. 
Participants with major protocol deviations will be identified prior to database lock.
The following categories will be considered as major PDs:

Received wrong treatment or incorrect dose

Entered but did not satisfy criteria

Received a disallowed concomitant treatment 

Developed withdrawal criteria but not withdrawn

Other 

Didn’t cross over when met the cross over criteria

Cross over when not met the cross over criteria
Participants with a major protocol deviation through Week 48 will be summarized by category
based on the FAS. A listing of participants who have major protocol deviations will be provided. 
Participants having irregularities in study intervention administration will be summarized in more 
detail using sub-categories identified prior to unblinding (eg, participant receives study 
intervention administration outside of protocol window). In addition, participants with study 
intervention administration irregularities will be listed.
A listing of participants with protocol deviations related to COVID-19 by center and by category
(major PD, minor PD) will be provided.
Quality Tolerance Limit (QTL) parameters and thresholds are defined and will be monitored in 
this study. QTL parameters will be summarized. More details are described in the Integrated 
Analytical Risk-Based Monitoring (iARBM) Plan.
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6.5.
Appendix 5 Prior and Concomitant Medications
Prior and Concomitant medications will be coded using the [World Health Organization Drug 
Dictionary (WHO-DD)]. Prior medications are defined as any therapy used before the day of 
first dose (partial or complete) of study intervention. Concomitant medications are defined as any 
therapy used on or after the same day as the first dose of study intervention, including those that 
started before and continue on after the first dose of study intervention.
Summaries of CD concomitant medications will be presented by ATC term and intervention group. 
Prior medications will be summarized by ATC term and intervention.
Summaries of CD medication history for the FAS will be summarized by treatment group:

Summary of Concomitant Medications for CD at Baseline

Participants with 1 or more concomitant medications for CD (n, %)

Aminosalicylates (n, %)

Antibiotics (n, %)

Corticosteroids (including budesonide and beclomethasone dipropionate) (n, %)

Corticosteroids P.Eq dose (excluding budesonide and beclomethasone dipropionate) 
(mg/day)

Budesonide dose (mg/day)

Beclomethasone dirpropionate dose (mg/day)

Corticosteroids (duration of use)

Immunomodulators (6-MP/AZA/MTX) (duration of use)

Biologics (Infliximab, Adalimumab, Certolizumab Pegol, Vedolizumab, Ustekinumab, 
Risankizumab, biosimilars of Infliximab and Adalimumab)

Summary of TNF Antagonist Therapy History by Number of TNF Antagonists (1, 2, 3) 
Received

Participants with inadequate initial response, loss of response, or intolerance to TNF 
antagonist

Participants with inadequate initial response to TNF antagonist

Participants with response followed by loss of response to TNF antagonist

Participants with intolerance to TNF antagonist

Summary of Biologic Therapy History by Biologic (Infliximab, Adalimumab, Certolizumab 
Pegol, Vedolizumab, Ustekinumab, Risankizumab, biosimilars of Infliximab and 
Adalimumab)

Participants with inadequate initial response, loss of response or intolerance to biologic 
therapy

Participants with inadequate initial response to biologic therapy
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
Participants with response followed by loss of response to biologic therapy

Participants with intolerance to biologic therapy

Summary of CD-related Non-biologic Medication History (History of Response to or 
Intolerance of Corticosteroids or 6-MP/AZA/MTX)

Participants with inadequate response, intolerance, or dependence 

Participants with inadequate response

Participants intolerant

Participants dependent

Summary of CD-related Biologic Medication History

Primary response, secondary nonresponse, or intolerance to
o
At least one anti-TNF
o
≥ 2 anti-TNFs
o
Anti-TNF only
o
Ustekinumab
o
Ustekinumab only
o
Ustekinumab and at least one other biologic
o
Vedolizumab
o
Vedolizumab only
o
Vedolizumab and at least one other biologic
o
Risa
o
Risa only
o
Risa and at least one other biologic
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6.6.
Appendix 6 Medical History
A summary of medical history of interest, as well as a summary of CD history and CD conditions 
of interest, and smoking status will be summarized for the FAS.
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6.7.
Appendix 7 Intervention Compliance
Randomized treatment versus actual treatment will be summarized using the FAS. 
The doses in mg will be calculated based on administered volume (the actual volume administered 
after accounting for priming and flushing) as follows:

For Placebo: 

For induction dosing at Week 0:
o
 1: dose [mg] = (administered volume [mL]/1 mL) x 0 mg 
o
 2: dose [mg] = (administered volume [mL]/1 mL) x 0 mg

For maintenance dosing starting at Week 8 then 
 through Week 144:
o
 1: dose [mg] = (administered volume [mL]/1 mL) x 0 mg 

For Guselkumab: 

For induction dosing at Week 0:
o
1: dose [mg] = (administered volume [mL]/1 mL) x 100 mg 
o
 2: dose [mg] = (administered volume [mL]/1 mL) x 100 mg

For maintenance dosing starting at Week 8 then 
through Week 144:
o
 1: dose [mg] = (administered volume [mL]/1 mL) x 100 mg 
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6.8.
Appendix 8 Adverse Events of Special Interest
Any newly identified:

clinically significant infection - tuberculosis (TB) events, invasive fungal infections, and 
hepatitis B reactivation 

newly identified malignancy

hypersensitivity reaction

congestive heart failure

demyelinating disorders

lupus-like syndrome
after the first study intervention administration are considered as AESI.

Malignancy will be identified as AEs where the preferred perm is featured in the global 
Standardized MedDRA Queries (SMQ) dataset is SMQ=’MALIGNANCIES (SMQ)’ and 
SUB_SMQ1=’MALIGNANT TUMOURS (SMQ)’
The following AEs will be identified and summarized as described in Section 5.7.2:

Drug-related hepatic disorders will be identified by SMQs (narrow) MedDRA version 24.1 or 
current available version:

Select AE terms from dictionary with smq = “HEPATIC DISORDERS (SMQ)” and 
sub_smq1=”DRUG RELATED HEPATIC DISORDERS -
COMPREHENSIVE 
SEARCH (SMQ)” and scope=”NARROW”
Identification of other AEs:

AEs associated with anaphylaxis/serum sickness 

AEs with one of the following dictionary-derived term in ADAE ADaM dataset, variable 
ADAE.AEDECOD: 
o
ANAPHYLACTIC REACTION 
o
ANAPHYLACTIC SHOCK 
o
ANAPHYLACTOID REACTION 
o
ANAPHYLACTOID SHOCK 
o
TYPE I HYPERSENSITIVITY 
o
“SERUM SICKNESS”
o
“SERUM SICKNESS-LIKE REACTION”
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CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959CRD3007
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
56
Status: Approved, Date: 30 November 2023
6.9.
Appendix 9 Medications of Special Interest
The following will be considered as prohibited changes in CD medications for the ICE category 2 
for all estimands:
1.
Prohibited medications initiated after Week 0:

Immunomodulatory agents except for AZA, 6-MP, or MTX (including, but not limited to, 
6-thioguanine, cyclosporine, mycophenolate mofetil, tacrolimus, and sirolimus).

Advanced therapy agents (including, but not limited to, additional TNFα antagonists, antiIL23 
medications, natalizumab, ustekinumab, vedolizumab, rituximab). 

All experimental vaccines and medications, including those for CD (including, but not limited 
to upadacitinib, filgotinib, ozanimod, etrolizumab, and andecaliximab). 

Thalidomide or related agents. 

Total or partial parenteral nutrition

IV and intramuscular corticosteroids

Oral corticosteroids dose at a prednisone-equivalent dose above 20 mg/day, or 6 mg/day of 
budesonide, or 5 mg/day beclomethasone dipropionate. 

Live vaccines

Participants must not receive guselkumab outside of the protocol or participate in any other 
clinical study with an investigational agent while in this study. Prior to termination of study 
participation, participants should complete evaluations for an ED visit.
2.
Corticosteroids initiated or doses changed based on medical necessity as assessed by the 
investigator:

Initiation of oral corticosteroids (including budesonide and beclomethasone dipropionate) due 
to worsening of CD.

Increase in the dose of oral corticosteroids (including budesonide and beclomethasone 
dipropionate) above the baseline dose due to worsening of CD. 

Initiation of oral corticosteroids (including budesonide and beclomethasone dipropionate) due 
to reasons other than worsening CD for more than 28 days cumulatively between Week 0 and 
Week 48.

Increase in the dose of oral corticosteroids (including budesonide and beclomethasone 
dipropionate) above the baseline dose due to reasons other than worsening of CD for more 
than 28 days cumulatively between Week 0 and Week 48. 
3.
Immunomodulator agents initiated from Week 0 through Week 48 or doses changed based on 
medical necessity as assessed by the investigator:

Initiation of oral 6-MP/AZA due to worsening of CD.

Initiation of oral, subcutaneous, or intramuscular MTX due to worsening of CD.

Increase in the dose of oral 6-MP/AZA above the baseline dose due to worsening of CD.
NCT05784129


CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959CRD3007
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
57
Status: Approved, Date: 30 November 2023

Increase in the dose of oral, subcutaneous, or intramuscular MTX above the baseline dose due 
to worsening of CD (within the same route).

Any switch between 6-MP/AZA and MTX due to worsening of CD.
4.
Antibiotics

Initiation or change of antibiotics due to worsening CD.
NCT05784129


CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959CRD3007
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
58
Status: Approved, Date: 30 November 2023
6.10.
Appendix 10 Laboratory Toxicity Grading
The grading scale use for lab assessments is based on ‘Common Terminology Criteria for Adverse 
Events (CTCAE) v5.0’.
If a laboratory value falls within the grading as specified below but also within the local laboratory 
normal limits, the value is considered to be normal and will be reset to grade 0.
Pre-baseline measurements will use the same grading ranges as applied to baseline measurements. 
In case a test has two sets of ranges – one for baseline normal and one for baseline abnormal, the 
one for baseline normal will be applied for all measurements taken pre-baseline and on baseline.
Text in gray italic in the table is present in the grading scale, but is not applied by Janssen when 
grading lab data.
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CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959CRD3007
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
65
Status: Approved, Date: 30 November 2023
6.11.
Appendix 11 Imputation Rule

Partial AE onset dates will be imputed as follows:
If the onset date of an adverse event is missing day only, it will be set to:

First day of the month that the AE occurred, if month/year of the onset of AE is different than 
the month/year of the study intervention start.

The day of study intervention start, if the month/year of the onset of AE is the same as 
month/year of the study intervention start and month/year of the AE resolution date is 
different.

The day of study intervention start or day of AE resolution date, whichever is earliest, if 
month/year of the onset of AE and month/year of the study intervention start date and 
month/year of the AE resolution date are same.
If the onset date of an adverse event is missing both day and month, it will be set to the earliest of:

January 1 of the year of onset, as long as this date is on or after the study intervention start 
date.

Month and day of the study intervention start date, if this date is the same year that the AE 
occurred.

Last day of the year if the year of the AE onset is prior to the year of the study intervention 
start date.
Completely missing onset dates will not be imputed.

Partial AE resolution dates not marked as ongoing will be imputed as follows:

If the resolution date of an adverse event is missing day only, it will be set to the earliest 
of the last day of the month of occurrence of resolution or the day of the date of death, if 
the death occurred in that month.

If the resolution date of an adverse event is missing both day and month, it will be set to 
the earliest of December 31 of the year or the day and month of the date of death, if the 
death occurred in that year.
Completely missing resolution dates will not be imputed.

AE onset/resolution dates with missing times will be imputed as follows:

A missing time of onset of an adverse event will be set to the earlier of:
o
00:01 as long as the onset date is after the study intervention start date
o
The time of the study intervention start if this is the same day the AE occurred.

The missing time of resolution of an adverse event will be set to 23:59.
If a missing time is associated with a partial or missing date, the date will be imputed first 
prior to imputing the time.
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CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959CRD3007
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
66
Status: Approved, Date: 30 November 2023
6.12.
Appendix 12 CDAI
6.12.1.
Partial CDAI Score Calculation Logic

Pre-Calculation Logic
Step 1: Determine if a Partial CDAI total score can be calculated. 
Sufficient CDAI Daily Diary data/components. CDAI score components are defined as:

CDAI Daily Diary (participant diary) components:
1.
Number of liquid or soft stools each day for seven days
2.
Abdominal pain each day for seven days
3.
General well-being each day for seven days
4.
Fever (Yes/No)
5.
Anti-diarrhea medication (Yes/No)
For CDAI Daily Diary components, if there is not enough data in the previous 7 days (a 
minimum of 4 days of eligible diary data), then Partial CDAI total score cannot be 
calculated.
6.12.2.
CDAI Score Calculation Logic

Pre-Calculation Logic
Step 1: Determine if a CDAI total score can be calculated. 
Sufficient CDAI Daily Diary data/components AND CDAI Site Form completion for the 
current visit is required to calculate a total CDAI Score. CDAI score components are defined 
as:

CDAI Daily Diary (participant diary) components:
6.
Number of liquid or soft stools each day for seven days
7.
Abdominal pain each day for seven days
8.
General well-being each day for seven days
9.
Fever (Yes/No)
10. Anti-diarrhea medication (Yes/No)

CDAI Site Form (site worksheet) components:
1.
Manifestations (arthritis/arthralgia, iritis/uveitis, erythema nodosum/pyoderma 
gangrenosum/aphthous stomatitis, anal fissure, fistula or abscess and other fistula)
2.
Abdominal mass evaluation
3.
Hematocrit
4.
Weight
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CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959CRD3007
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
67
Status: Approved, Date: 30 November 2023
For CDAI Daily Diary components, if there is not enough data in the previous 7 days (a 
minimum of 4 days of eligible diary data), then CDAI total score cannot be calculated. 
For CDAI Site Form components, if the CDAI Site Form has not been completed (and 
synced) on the tablet for the current visit, then CDAI score cannot be calculated. 
Step 2: Determine if there is missing data for the CDAI Evening Diary components:

For the current visit’s CDAI Site Form, if the site user enters bowel preparation and video
ileocolonoscopy dates (required if they answered, ‘Yes’ to “Has the participant had a 
video ileocolonoscopy since their last site visit?”) (CDAI Site Form questions ebf0226f-
b3a0-433a-82a7-aefd0e510c93_Question 
and 
422e412e-1189-4b32-bcef-
b7481d90dec9_Question), then any diary entries (if in the previous 7 days) between and 
including those 2 dates entered should be ineligible for the current calculation.

A minimum of 4 days of diary data entry is required for components from the participant's 
CDAI Evening Diary in the 7 days prior to the current visit activation date.
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CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959CRD3007
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
68
Status: Approved, Date: 30 November 2023
6.12.3.
CDAI Score Calculation
Has the participant had a video ileocolonoscopy since the last site visit? Yes/no
If yes, 
Date of video ileocolonoscopy:
Date of the start of the bowel preparation:
DISEASE ACTIVITY INDEX
         SUM
XFACTOR
        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
Sum general well-being ratings (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 or 
opiate medications for diarrhea at least once:
x
30
=
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)
NCT05784129


CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959CRD3007
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
69
Status: Approved, Date: 30 November 2023
6.13.
Appendix 13: Liver Safety: Suggested Actions and Follow-up 
Assessments
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CNTO1959 (guselkumab)
Statistical Analysis Plan CNTO1959CRD3007
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
71
Status: Approved, Date: 30 November 2023
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 below), then gamma-glutamyl transferase, anti-mitochondrial 
antibody (AMA) and anti-neutrophil cytoplasmic antibody should also be tested. If there is an 
indication by history or elevated baseline LTs that there may be an underlying chronic liver 
disease possibly exacerbated by exposure to the study intervention in the clinical trial or 
making the participant more susceptible to DILI, test iron/total iron binding capacity and 
ferritin (hemochromatosis), and alpha-1-antitrypsin level. If patient is <50 years of age, 
ceruloplasmin should also be tested to screen for Wilson’s disease. If patient is sick enough 
to be hospitalized and is under age 50, a slit lamp examination to detect Kayser-Fleischer rings 
and a 24-hour urine collection for copper should be measured. Consider serum ethanol and/or 
acetaminophen level and urine drug screen as clinically appropriate.
NCT05784129