A Phase 2/3, Randomized, Double-blind, Placebo- and Active-controlled, Parallel-group, Multicenter Protocol to Evaluate the Efficacy and Safety of Guselkumab in Participants With Moderately to Severely Active Crohn's Disease
Phase: PHASE2
Conditions: Crohn's Disease
Sponsor: Janssen Research & Development, LLC

CONFIDENTIAL – FOIA Exemptions Apply in U.S.
1
Status: Approved, Date: 12 July 2022
Janssen Research & Development*
Clinical Protocol
Protocol Title
A Phase 2/3, Randomized, Double-blind, Placebo- and Active-controlled, Parallel-group, 
Multicenter Protocol to Evaluate the Efficacy and Safety of Guselkumab in Participants 
with Moderately to Severely Active Crohn's Disease
GALAXI
Short Title
A Study of the Efficacy and Safety of Guselkumab in Participants
with Moderately to Severely Active Crohn's Disease
Protocol CNTO1959CRD3001; Phase 2/3
AMENDMENT 5 
CNTO 1959 (guselkumab)
*Janssen Research & Development is a global organization that operates through different legal entities in
various countries. Therefore, the legal entity acting as the sponsor for Janssen Research & Development
studies may vary, such as, but not limited to Janssen Biotech, Inc.; Janssen Products, LP; Janssen Biologics,
BV; Janssen-Cilag International NV; Janssen, Inc; Janssen Pharmaceutica NV; Janssen Sciences Ireland
UC; 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.
US sites of this study will be conducted under US Food & Drug Administration IND regulations 
(21 CFR Part 312).
EudraCT NUMBER:         2017-002195-13
Status:
Approved
Date:
12 July 2022
Prepared by:
Janssen Research & Development, LLC  
EDMS number:
EDMS-ERI-136754231, 7.0
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.
NCT03466411

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
2
Status: Approved, Date: 12 July 2022
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document
Date
Amendment 5
12 July 2022
Amendment 4
21 July 2021
Amendment 3
20 October 2020
Amendment 2
13 November 2019
Amendment 1
10 December 2018
Original Protocol
06 December 2017
Amendment 5 (12 July 2022)
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union. 
Minor changes, such as those made for editorial purposes, or to correct grammatical or 
typographical errors, are not described.
Overall Rationale for the Amendment:
After review of the Phase 2 (GALAXI 1) Week 48 database lock (DBL) results, the Sponsor 
engaged in negotiations with Health Authorities regarding the Phase 3 study endpoints and 
analyses. Following negotiations with health authorities, the co-primary endpoints in the original 
GALAXI Phase 3 studies were modified for the United States (US) and other countries/territories
throughout the world as applicable, creating Global co-primary endpoints.  As other health 
authorities preferred the Week 12 co-primary endpoints be retained, these endpoints are now 
labeled as Regional co-primary endpoints.
Protocol Amendment 5 now contains two modules within the Endpoints and Hypothesis 
Section 3.2.2 for the Phase 3 studies (GALAXI 2 and GALAXI 3). The first module refers to the 
Global Endpoints and Hypotheses where the co-primary endpoints have been modified to 
composite endpoints that reflect short-term and long-term efficacy of guselkumab versus placebo. 
These co-primary endpoints are also consistent with the recent STRIDE guidelines that support a 
treatment goal of early clinical response prior to achievement of clinical and endoscopic long-term 
goals (Turner 2021). The major secondary endpoints have also been adjusted to incorporate 
evaluation of long-term efficacy of guselkumab versus placebo as well as ustekinumab. 
The second module in the Endpoints and Hypothesis Section 3.2.2 refers to Regional Endpoints 
and Hypotheses where the original co-primary endpoints have been retained for the Phase 3 
studies. The original major secondary endpoints, including those to assess long-term efficacy, have 
also been retained. Consistent with the Global approach, corticosteroid-free clinical remission at 
Week 48 and endoscopic response at Week 48 have been added to the Regional major secondary 
endpoints to evaluate the long-term efficacy of guselkumab vs. placebo. Finally, a composite 
endpoint of clinical remission at Week 48 and endoscopic response at Week 48 in the same 
NCT03466411

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
3
Status: Approved, Date: 12 July 2022
participant has been added to the Global and Regional major secondary endpoints. This composite 
endpoint is also consistent with the STRIDE guidelines where improvement in both clinical and 
endoscopic long-term outcomes should be targeted in the same participant (Turner 2021).
In addition, the sample size required to appropriately power the Global co-primary endpoints and 
the Regional co-primary endpoints, as well as key Regional major secondary endpoints to 
demonstrate the long-term efficacy of guselkumab versus placebo, was reassessed based on the 
Week 48 DBL results from the Phase 2 (GALAXI 1) study and was reduced from the original size. 
Based on this assessment, a total Phase 3 sample size of approximately 980 participants 
(approximately 490 participants in each Phase 3 study) will provide adequate power and an 
adequate number of participants to assess the safety of guselkumab in Crohn’s disease. The 
reduced sample size provides the opportunity to obtain appropriate scientific data while reducing 
the number of participants exposed to placebo. Of note, the decision to reduce the sample size was 
not based on knowledge of any data from the Phase 3 GALAXI studies, as these studies are still 
blinded and will remain blinded to the Sponsor until the Week 48 database lock.
The changes made to the clinical protocol CNTO1959CRD3001 as part of Protocol Amendment 5
are listed below, including the rationale of each change and a list of all applicable sections. 
Changes made in previous protocol amendments are listed in Section 10.15, Appendix 15: Protocol 
Amendment History.
Section Number
and Name
Description of Change
Brief Rationale
CCI
NCT03466411

NCT03466411

NCT03466411

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
6
Status: Approved, Date: 12 July 2022
Section Number
and Name
Description of Change
Brief Rationale
10.3. Appendix 3
The paragraph after item 1.b.6 was moved to 
follow item 2.d.2 and modified slightly. 
To clarify that the paragraph applies 
to both primary non-responders and to 
secondary non-responders. 
10.12. Appendix 12
Updated guidelines on anticipated events.
To align with current protocol 
guidelines.
Throughout the 
protocol
Minor grammatical, formatting, or spelling 
errors and inconsistency were corrected.
Minor errors were noted.
NCT03466411

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 12 July 2022
TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................................... 2
TABLE OF CONTENTS ............................................................................................................................... 7
LIST OF IN-TEXT TABLES AND FIGURES.............................................................................................. 11
1.
PROTOCOL SUMMARY ................................................................................................................... 12
1.1.
Synopsis......................................................................................................................................... 12
1.2.
Schema .......................................................................................................................................... 24
1.3.
Schedule of Activities (SoA)........................................................................................................... 25
2.
INTRODUCTION................................................................................................................................ 39
2.1.
Study Rationale.............................................................................................................................. 39
2.1.1.
Unmet Need in Crohn’s Disease ................................................................................................ 40
2.1.2.
Rationale for Targeting IL-23 in Crohn’s Disease ...................................................................... 40
2.1.2.1.
Preclinical Evidence Implicating IL-23 as a Target in Crohn’s Disease .................................. 40
2.1.2.2.
Clinical Evidence Establishing Proof of Concept for Targeting IL-23 in Crohn’s 
Disease.................................................................................................................................... 40
2.1.2.2.1.
Clinical Experience with IL-12/23-Targeted Therapy (Ustekinumab) in Crohn’s 
Disease ................................................................................................................................ 41
2.1.2.2.2.
Clinical Experience with IL-23-Targeted Therapy in Crohn’s Disease................................. 41
2.1.3.
Overall Rationale for Guselkumab in Crohn’s Disease .............................................................. 42
2.2.
Background .................................................................................................................................... 42
2.2.1.
Guselkumab Clinical Experience................................................................................................ 42
2.2.2.
Guselkumab Nonclinical Studies ................................................................................................ 43
2.3.
Benefit-Risk Assessment ............................................................................................................... 45
2.3.1.
Guselkumab................................................................................................................................ 45
2.3.2.
Active Comparator: Ustekinumab............................................................................................... 46
3.
OBJECTIVES AND ENDPOINTS ..................................................................................................... 46
3.1.
Phase 2 Dose-Ranging Study (GALAXI 1) .................................................................................... 46
3.1.1.
Objectives ................................................................................................................................... 46
3.1.2.
Endpoints.................................................................................................................................... 47
3.1.3.
Hypothesis .................................................................................................................................. 47
3.2.
Phase 3 Dose-Confirming Studies (GALAXI 2 and GALAXI 3) ..................................................... 48
3.2.1.
Objectives ................................................................................................................................... 48
3.2.2.
Endpoints and Hypotheses......................................................................................................... 48
3.2.2.1.
Global Endpoints and Hypotheses .......................................................................................... 48
3.2.2.2.
Regional Endpoints and Hypotheses ...................................................................................... 50
3.2.2.3.
Definition of Endpoints............................................................................................................. 51
4.
STUDY DESIGN ................................................................................................................................ 51
4.1.
Overall Design................................................................................................................................ 51
4.1.1.
Phase 2 Dose-Ranging Study (GALAXI 1): Induction and Maintenance ................................... 55
4.1.1.1.
Overview of Phase 2 Study Design and Dose Decision for Phase 3...................................... 55
4.1.1.2.
Treatment Groups ................................................................................................................... 56
4.1.1.3.
Endpoints and Evaluations...................................................................................................... 58
4.1.2.
Phase 3 Dose-Confirming Studies (GALAXI 2 and GALAXI 3): Induction and 
Maintenance ............................................................................................................................... 58
4.1.2.1.
Overview of Phase 3 Design ................................................................................................... 58
4.1.2.2.
Treatment Groups ................................................................................................................... 59
4.1.2.3.
Endpoints and Evaluations...................................................................................................... 61
4.1.3.
Long-Term Extension for GALAXI 1, 2, and 3............................................................................ 61
4.1.3.1.
Treatment Adjustment for Inadequate Response.................................................................... 62
4.1.3.2.
Self-Administration of Study Intervention (or Administration by Caregiver) at Home ............. 63
4.1.3.3.
Concomitant and Prohibited Therapies for Crohn’s Disease .................................................. 64
NCT03466411

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
8
Status: Approved, Date: 12 July 2022
4.1.3.4.
Endpoints and Evaluations...................................................................................................... 64
4.2.
Scientific Rationale for Study Design............................................................................................. 64
4.2.1.
Use of Placebo- and Active-Control ........................................................................................... 64
4.2.2.
Biomarker and DNA Collection................................................................................................... 65
4.2.3.
Patient-Reported Outcomes on Health-Related Quality of Life.................................................. 66
4.2.4.
Medical Resource Utilization and Health Economics Data Collection ....................................... 66
4.2.5.
Study-Specific Ethical Design Considerations ........................................................................... 66
4.3.
Justification for Dose...................................................................................................................... 66
4.3.1.
Guselkumab................................................................................................................................ 66
4.3.1.1.
Phase 2 Dose-Ranging Study (GALAXI 1).............................................................................. 66
4.3.1.1.1.
Induction Dose Regimens.................................................................................................... 67
4.3.1.1.2.
Maintenance Dose Regimens.............................................................................................. 68
4.3.1.2.
Phase 3 Dose-Confirming Studies (GALAXI 2 and GALAXI 3)............................................... 69
4.3.1.3.
Long-Term Extension (Week 48 to Week 240) for GALAXI 1, 2, and 3.................................. 69
4.3.2.
Ustekinumab............................................................................................................................... 69
4.4.
End of Study Definition................................................................................................................... 70
5.
STUDY POPULATION ...................................................................................................................... 70
5.1.
Inclusion Criteria ............................................................................................................................ 70
5.2.
Exclusion Criteria ........................................................................................................................... 75
5.3.
Lifestyle Considerations................................................................................................................. 79
5.4.
Screen Failures .............................................................................................................................. 80
6.
STUDY INTERVENTION................................................................................................................... 81
6.1.
Study Interventions Administered .................................................................................................. 81
6.1.1.
Combination Products ................................................................................................................ 82
6.2.
Preparation/Handling/Storage/Accountability ................................................................................ 82
6.2.1.
Guselkumab................................................................................................................................ 82
6.2.2.
Ustekinumab............................................................................................................................... 83
6.2.3.
Accountability.............................................................................................................................. 83
6.3.
Measures to Minimize Bias: Randomization and Blinding............................................................. 84
6.4.
Study Intervention Compliance...................................................................................................... 86
6.5.
Concomitant Therapy..................................................................................................................... 86
6.5.1.
Concomitant Medications ........................................................................................................... 87
6.5.1.1.
Oral Corticosteroids Tapering.................................................................................................. 88
6.5.2.
Prohibited Concomitant Medications .......................................................................................... 88
6.5.3.
Vaccinations (Including COVID-19)............................................................................................ 89
6.6.
Dose Modification........................................................................................................................... 89
6.7.
Intervention After the End of the Study.......................................................................................... 89
7.
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ............................................................................................... 90
7.1.
Discontinuation of Study Intervention ............................................................................................ 90
7.2.
Participant Discontinuation/Withdrawal From the Study................................................................ 92
7.2.1.
Withdrawal From the Use of Research Samples ....................................................................... 93
7.3.
Lost to Follow-up............................................................................................................................ 93
8.
STUDY ASSESSMENTS AND PROCEDURES ............................................................................... 94
8.1.
Efficacy Assessments .................................................................................................................... 97
8.2.
Safety Assessments..................................................................................................................... 100
8.2.1.
Electrocardiogram..................................................................................................................... 100
8.2.2.
Physical Examination................................................................................................................ 100
8.2.3.
Height and Weight .................................................................................................................... 100
8.2.4.
Vital Signs................................................................................................................................. 100
8.2.5.
Infections .................................................................................................................................. 101
8.2.6.
Tuberculosis Evaluation(s) ....................................................................................................... 101
8.2.6.1.
Initial Tuberculosis Evaluation............................................................................................... 101
8.2.6.2.
Ongoing Tuberculosis Evaluation.......................................................................................... 102
NCT03466411

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 12 July 2022
8.2.7.
Allergic Reaction....................................................................................................................... 103
8.2.8.
Adverse Events Temporally Related to Infusion ...................................................................... 103
8.2.9.
Injection-Site Reaction.............................................................................................................. 104
8.2.10.
Columbia-Suicide Severity Rating Scale (C-SSRS)................................................................. 104
8.2.11.
Clinical Safety Laboratory Assessments .................................................................................. 105
8.2.12.
Immunogenicity Assessments (Antibodies to Guselkumab and Ustekinumab) ....................... 106
8.2.13.
Concomitant Medication Review .............................................................................................. 106
8.3.
Adverse Events and Serious Adverse Events ............................................................................. 106
8.3.1.
Time Period and Frequency for Collecting Adverse Event and Serious Adverse Event 
Information................................................................................................................................ 107
8.3.2.
Follow-up of Adverse Events and Serious Adverse Events ..................................................... 107
8.3.3.
Regulatory Reporting Requirements for Serious Adverse Events ........................................... 108
8.3.4.
Pregnancy................................................................................................................................. 108
8.3.5.
Events of Special Interest......................................................................................................... 108
8.4.
Treatment of Overdose ................................................................................................................ 108
8.5.
Pharmacokinetics......................................................................................................................... 109
8.6.
Pharmacodynamics...................................................................................................................... 109
8.7.
Genetics ....................................................................................................................................... 110
8.8.
Biomarkers ................................................................................................................................... 110
8.8.1.
Serum-based Biomarkers......................................................................................................... 110
8.8.2.
Whole Blood-based Biomarkers ............................................................................................... 111
8.8.3.
Biopsy-based Biomarkers......................................................................................................... 111
8.8.3.1.
Optional Week 4 Biopsy Substudy ........................................................................................ 111
8.8.4.
Fecal Biomarkers...................................................................................................................... 111
8.9.
Medical Resource Utilization and Health Economics .................................................................. 112
9.
STATISTICAL CONSIDERATIONS................................................................................................ 112
9.1.
Statistical Hypotheses.................................................................................................................. 112
9.1.1.
Phase 2 Dose-Ranging Study (GALAXI 1)............................................................................... 112
9.1.2.
Phase 3 Dose-Confirming Studies (GALAXI 2 and GALAXI 3)................................................ 112
9.2.
Sample Size Determination ......................................................................................................... 112
9.2.1.
Assumptions for Phase 2 Study ............................................................................................... 112
9.2.2.
Assumptions for Phase 3 Studies............................................................................................. 114
9.2.2.1.
Global Endpoints ................................................................................................................... 114
9.2.2.2.
Regional Endpoints ............................................................................................................... 115
9.2.3.
Power and Sample Size Calculations....................................................................................... 116
9.2.3.1.
Phase 2 Dose-Ranging Study (GALAXI 1)............................................................................ 116
9.2.3.2.
Phase 3 Dose-Confirming Studies (GALAXI 2 and GALAXI 3)............................................. 117
9.2.3.2.1.
Global Endpoints................................................................................................................ 117
9.2.3.2.2.
Regional Endpoints ............................................................................................................ 118
9.3.
Populations for Analyses.............................................................................................................. 118
9.4.
Statistical Analyses ...................................................................................................................... 120
9.4.1.
Endpoints.................................................................................................................................. 120
9.4.1.1.
Phase 2 Dose-Ranging Study (GALAXI 1)............................................................................ 120
9.4.1.2.
Phase 3 Dose-Confirming Studies (GALAXI 2 and GALAXI 3)............................................. 121
9.4.1.2.1.
Global Endpoints................................................................................................................ 121
9.4.1.2.2.
Regional Endpoints ............................................................................................................ 122
9.4.1.2.3.
Exploratory Endpoints ........................................................................................................ 123
9.4.2.
Phase 2 (GALAXI 1) Efficacy Analyses.................................................................................... 126
9.4.2.1.
Population for Efficacy Analysis ............................................................................................ 126
9.4.2.2.
Primary Endpoint Analysis..................................................................................................... 127
9.4.2.3.
Major Secondary Endpoint Analysis...................................................................................... 128
9.4.2.4.
Other Efficacy Endpoint Analyses ......................................................................................... 129
9.4.3.
Phase 3 (GALAXI 2 and GALAXI 3) Efficacy Analyses............................................................ 129
9.4.3.1.
Population for Efficacy Analysis ............................................................................................ 129
9.4.3.2.
Primary Endpoint Analysis..................................................................................................... 129
9.4.3.2.1.
Global Primary Endpoint Analysis...................................................................................... 129
9.4.3.2.2.
Regional Primary Endpoint Analysis.................................................................................. 130
NCT03466411

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
10
Status: Approved, Date: 12 July 2022
9.4.3.2.3.
Analysis Methods Applicable to both Global and Regional Co-primary Endpoints ........... 130
9.4.3.3.
Major Secondary Endpoint Analysis...................................................................................... 131
9.4.3.3.1.
Global Major Secondary Endpoint Analyses...................................................................... 131
9.4.3.3.2.
Regional Major Secondary Endpoint Analyses.................................................................. 132
9.4.3.4.
Exploratory Efficacy Endpoint Analyses................................................................................ 133
9.4.4.
Safety Analyses ........................................................................................................................ 133
9.4.5.
Other Analyses ......................................................................................................................... 134
9.5.
Interim Analysis............................................................................................................................ 136
9.5.1.
Dose Selection Analysis for Phase 2 (GALAXI 1) .................................................................... 136
9.5.2.
Data Monitoring Committee...................................................................................................... 137
10.
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .......................... 138
10.1.
Appendix 1: Abbreviations and Trademarks................................................................................ 138
10.2.
 of Corticosteroids or 6-
MP/AZA/MTX and Corticosteroid Dependence ........................................................................... 140
10.3.
Appendix 3: Definition of Inadequate Initial Response, Loss of Response, or Intolerance 
to TNF Antagonist Therapies (Infliximab, Adalimumab, or Certolizumab Pegol) or 
Vedolizumab ................................................................................................................................ 142
10.4.
Appendix 4: Definition of Exposure to Ustekinumab.................................................................... 146
10.5.
Appendix 5: Tuberculin Skin Testing ........................................................................................... 149
10.6.
Appendix 6: Contraceptive and Barrier Guidance and Collection of Pregnancy Information...... 150
10.7.
Appendix 7: Hepatitis B Virus (HBV) Screening with HBV DNA Testing..................................... 153
10.8.
Appendix 8: Regulatory, Ethical, and Study Oversight Considerations....................................... 154
10.8.1.
Regulatory and Ethical Considerations .................................................................................... 154
10.8.2.
Financial Disclosure.................................................................................................................. 157
10.8.3.
Informed Consent Process ....................................................................................................... 157
10.8.4.
Data Protection ......................................................................................................................... 158
10.8.5.
Long-Term Retention of Samples for Additional Future Research .......................................... 159
10.8.6.
Committees Structure............................................................................................................... 159
10.8.7.
Publication Policy/Dissemination of Clinical Study Data .......................................................... 159
10.8.8.
Data Quality Assurance............................................................................................................ 161
10.8.9.
Data Collection ......................................................................................................................... 161
10.8.10.
Source Documents ................................................................................................................... 162
10.8.11.
Monitoring ................................................................................................................................. 162
10.8.12.
On-Site Audits........................................................................................................................... 163
10.8.13.
Record Retention...................................................................................................................... 163
10.8.14.
Study and Site Closure............................................................................................................. 164
10.9.
Appendix 9: Guideline Algorithm for Monitoring, Assessment, and Evaluation of Abnormal 
Liver Tests in Participants With No Underlying Liver Disease..................................................... 165
10.10.
Appendix 10: Crohn’s Disease Activity Index .............................................................................. 169
10.11.
Appendix 11: Adverse Events: Definitions and Procedures for Recording, Evaluating, 
Follow-up, and Reporting............................................................................................................. 170
10.11.1.
Adverse Event Definitions and Classifications ......................................................................... 170
10.11.2.
Attribution Definitions................................................................................................................ 171
10.11.3.
Severity Criteria ........................................................................................................................ 172
10.11.4.
Special Reporting Situations .................................................................................................... 172
10.11.5.
Procedures ............................................................................................................................... 173
10.11.6.
Product Quality Complaint Handling......................................................................................... 174
10.11.7.
Contacting Sponsor Regarding Safety ..................................................................................... 175
10.12.
Appendix 12: Anticipated Events ................................................................................................. 176
10.13.
Appendix 13
177
10.14.
Appendix 14: Guidance on Study Conduct During a Major Disruption Event.............................. 181
10.15.
Appendix 15: Protocol Amendment History ................................................................................. 183
11.
REFERENCES................................................................................................................................. 228
INVESTIGATOR AGREEMENT ............................................................................................................... 230
CCI
CCI
NCT03466411

NCT03466411

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
12
Status: Approved, Date: 12 July 2022
1.
PROTOCOL SUMMARY
1.1.
Synopsis
A Phase 2/3, Randomized, Double-blind, Placebo- and Active-controlled, Parallel-group, Multicenter 
Protocol to Evaluate the Efficacy and Safety of Guselkumab in Participants with Moderately to Severely 
Active Crohn's Disease
Protocol number: CNTO1959CRD3001
EudraCT Number: 2017-002195-13
OVERVIEW OF PROTOCOL
The clinical development program for guselkumab in Crohn’s disease is designed to evaluate the safety and 
efficacy of guselkumab compared with placebo and an active control (ustekinumab) and will be conducted 
under this single 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 Crohn’s disease who have demonstrated an inadequate 
response or failure to tolerate previous conventional therapy or biologic therapy. 
Under this protocol, there are 3 separate studies: a 48-week Phase 2 dose-ranging study (ie, GALAXI 1) 
and 2 identical 48-week Phase 3 confirmatory studies (ie, GALAXI 2 and GALAXI 3). Participants who 
complete the 48-week Phase 2 or Phase 3 studies may be eligible to enter the long-term extension (LTE 
[Week 48 to Week 252]) and receive approximately 4 additional years of treatment. The overall Phase 2/3 
development program will enroll approximately 1,340 participants with a total duration for each participant 
of up to approximately 5 years.
OBJECTIVES AND HYPOTHESES
Phase 2 Dose-Ranging Study (GALAXI 1)
Objectives

Primary Objectives

To evaluate the clinical efficacy of guselkumab in participants with Crohn’s disease

To evaluate the safety of guselkumab

Secondary Objectives

To evaluate the dose-response of guselkumab to inform dose selection for the Phase 3 portion of 
this protocol

To evaluate the efficacy of guselkumab on endoscopic improvement

To evaluate the pharmacokinetics (PK), immunogenicity, and pharmacodynamics (PD) of 
guselkumab therapy, including changes in C-reactive protein (CRP) and fecal calprotectin 

Other Objectives

To evaluate the impact of guselkumab on health-related quality of life (HRQOL) and health 
economics outcome measures

To evaluate the efficacy of guselkumab on histologic improvement

To evaluate the impact of treatment with guselkumab on intestinal mucosal gene expression 
profiles and cellular composition associated with Crohn’s disease
Hypothesis
The primary hypothesis for GALAXI 1 is that guselkumab is superior to placebo in inducing a reduction 
from baseline in the Crohn’s Disease Activity Index (CDAI) score in participants with moderately to 
severely active Crohn’s disease.
NCT03466411

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
13
Status: Approved, Date: 12 July 2022
Phase 3 Dose-Confirming Studies (GALAXI 2 and GALAXI 3)
GALAXI 2 and GALAXI 3 are identical studies and have the same objectives and hypotheses, as described 
below.
Objectives

Primary Objectives

To evaluate the clinical and endoscopic efficacy of guselkumab in participants with Crohn’s 
disease

To evaluate the safety of guselkumab

Secondary Objectives

To evaluate the impact of guselkumab on HRQOL

To evaluate the PK, immunogenicity, and PD of guselkumab therapy, including changes in CRP 
and fecal calprotectin

Other Objectives

To evaluate the impact of guselkumab on health economics outcome measures

To evaluate the efficacy of guselkumab on histologic improvement

To evaluate the impact of treatment with guselkumab on intestinal mucosal gene expression 
profiles and cellular composition associated with Crohn’s disease
Hypothesis
The protocol will contain two modules for co-primary and major secondary endpoints. The first module 
will be referred to as Global and will apply to the US and other countries/territories around the world where 
the co-primary endpoints have been modified as below. The second module will be referred to as Regional 
and will apply to those countries/territories who will retain the original protocol Week 12 co-primary 
endpoints.
Global Hypotheses
The co-primary hypotheses will be tested within each of GALAXI 2 and GALAXI 3 separately.  
The co-primary hypotheses are that guselkumab is superior to placebo in achieving:

clinical response at Week 12 and clinical remission at Week 48

clinical response at Week 12 and endoscopic response at Week 48
Regional Hypotheses 
The co-primary hypotheses will be tested within each of GALAXI 2 and GALAXI 3 separately.  
The co-primary hypotheses are that guselkumab is superior to placebo in achieving:

clinical remission at Week 12 

endoscopic response at Week 12 
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OVERALL DESIGN
Under this protocol, there are 3 separate studies: a 48-week Phase 2 dose-ranging study (ie, GALAXI 1) 
and 2 identical 48-week Phase 3 confirmatory studies (ie, GALAXI 2 and GALAXI 3). All 3 studies will 
be conducted using a treat-through study design, ie, participants are randomized to treatment regimens at 
Week 0 and will remain on that treatment regimen through at least Week 48 of each study, unless otherwise 
indicated.
In the Phase 2 dose-ranging study (ie, GALAXI 1), the safety and efficacy of guselkumab dose regimens 
spanning a wide induction and maintenance dose range will be evaluated to support the selection of 
induction and maintenance dose regimens for confirmatory evaluation in Phase 3. It is estimated that 250 
to 500 participants may be required to select the dose regimens that will be evaluated in Phase 3. Therefore, 
the first 250 participants in GALAXI 1 will be enrolled into an Initial Dose Decision Cohort. Since data 
from more participants may be required to inform the dose decision, the sponsor may elect to continue
enrollment and newly enrolled participants (ie, starting from participant #251) will be randomized into a 
Transition Cohort while the data from the Initial Dose Decision Cohort are being collected and analyzed. 
If the decision is made to proceed with enrollment into the Transition Cohort, it is anticipated that a 
maximum of approximately 250 additional participants will be enrolled into GALAXI 1 (ie, 250 in the 
Initial Dose Decision Cohort and up to 250 in the Transition Cohort) prior to the dose decision. If a dose
decision for Phase 3 is not made by the time the 500th patient is randomized, enrollment will be paused 
until a decision for Phase 3 dosing, or a decision to terminate the development program, is made.
This is an operationally seamless protocol in countries where the local health authorities have approved a 
seamless transition. In the countries that have approved a seamless transition, there will be no break in 
enrollment between the Phase 2 and Phase 3 studies if enrollment continues into the Transition Cohort and 
a dose decision can be made before 500 patients are randomized. Transition from the Phase 2 portion to the 
Phase 3 portion of the protocol will occur once the dose decision for Phase 3 has been made and 
implemented. In countries where the local health authority requires additional regulatory approval prior to 
initiating the Phase 3 studies, enrollment will pause until approval is received. In all countries, all 
participants randomized after the dose decision has been implemented will be part of the Phase 3 studies.
In the Phase 3 dose-confirming studies (ie, GALAXI 2 and GALAXI 3), the safety and efficacy of the 
selected guselkumab dose regimens will be evaluated. GALAXI 2 and GALAXI 3 are identical from a 
study design perspective. The goal of conducting two replicate studies is to achieve independent 
confirmation of clinical efficacy in two independent samples of patients, which is required by some health 
authorities. A target of approximately 490 participants will be enrolled in each of the Phase 3 studies, for a 
total target sample size of approximately 980 participants in the Phase 3 portion of the protocol.
Participants who complete the 48-week Phase 2 or Phase 3 studies may be eligible to enter the LTE to 
receive approximately 4 additional years of treatment.
Target Population
The target population in all 3 studies under this protocol will consist of participants ≥18 years of age at the 
time of informed consent with moderately to severely active Crohn’s disease (of at least 3 months’ 
duration). Participants must have colitis, ileitis, or ileocolitis previously confirmed by radiography, 
histology, and/or endoscopy.
Active Disease Criteria
At baseline, participants must have active Crohn’s disease, defined as follows:
1.
Clinically active Crohn’s disease
2.
Endoscopic evidence of ileocolonic Crohn’s disease
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Status: Approved, Date: 12 July 2022
EFFICACY EVALUATIONS AND ENDPOINTS
Efficacy evaluations will include the following:

Crohn’s Disease Activity Index (CDAI)

PRO-2 (the unweighted CDAI components of the total number of liquid or very soft stools and the 
abdominal pain score)

Endoscopic assessments based on the presence and absence of mucosal ulcerations and the Simple 
Endoscopic Score for Crohn’s Disease (SES-CD)

Histologic assessments based on the Global Histology Activity Score

Inflammatory PD markers including CRP and fecal calprotectin

Fistula assessment 

HRQOL outcome measures including Inflammatory Bowel Disease Questionnaire, Patient-Reported 
Outcomes Measurement Information System (PROMIS)-29, PROMIS Fatigue Short Form 7a, and 
5-level EuroQol five dimensions instrument

Health economics outcome measures including the Work Productivity and Activity Impairment 
Questionnaire in Crohn’s disease

Exploratory patient-reported symptom measures including Bristol Stool Form Scale, Abdominal Pain 
– Numerical Rating Scale, Patient’s Global Impression of Severity of Crohn’s Disease, and Patient’s 
Global Impression of Change of Severity of Crohn’s Disease
Endpoints in the Phase 2 Study (GALAXI 1)
The primary endpoint and major secondary endpoints evaluate the short-term efficacy of guselkumab versus 
placebo. These endpoints are described below.

Primary Endpoint

Change from baseline in the CDAI score at Week 12.

Major Secondary Endpoints

Clinical remission at Week 12 (defined as CDAI score <150).

Clinical response at Week 12 (defined as ≥100-point reduction from baseline in CDAI score or 
CDAI score <150).

PRO-2 remission at Week 12 (defined as an abdominal pain [AP] mean daily score at or below 1 
[ie, AP≤1] AND a stool frequency [SF] mean daily score at or below 3 [SF≤3], and no worsening 
of AP or SF from baseline).

Clinical-biomarker response at Week 12 (clinical response based on CDAI score and ≥50% 
reduction from baseline in CRP or fecal calprotectin).

Endoscopic response at Week 12 (defined as at least 50% improvement from baseline in the SES-
CD score or SES-CD score ≤2).
Endpoints in the Phase 3 Studies (GALAXI 2 and GALAXI 3)
GALAXI 2 and GALAXI 3 have the same primary and major secondary endpoints, whether Global or 
Regional.
Global Co-primary Endpoints
The Global co-primary endpoints are:

clinical response at Week 12 and clinical remission at Week 48  

clinical response at Week 12 and endoscopic response at Week 48
For these endpoints, comparisons will be made within each study between each guselkumab dose 
(guselkumab 
 and placebo.  
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Status: Approved, Date: 12 July 2022
Global Major Secondary Endpoints  
The Global major secondary endpoints are grouped into 3 categories based on timepoint and comparator; 
note that these are grouped for the purpose of categorization but are not presented in the order of testing in 
the multiplicity-controlled testing procedure (the specific order for the testing procedure will be provided 
in the statistical analysis plan).
The following Global major secondary endpoints evaluate the short-term efficacy of guselkumab versus 
placebo in each study: 

Clinical response at Week 4

Clinical remission at Week 12

Endoscopic response at Week 12

Fatigue response at Week 12 

Clinical remission at Week 12 and endoscopic response at Week 12

Endoscopic remission (Global definition) at Week 12 
The following long-term endpoints evaluate guselkumab versus placebo in each study:

Clinical response at Week 12 and corticosteroid-free clinical remission at Week 48 

Clinical response at Week 12 and endoscopic remission (Global definition) at Week 48
The following long-term endpoints evaluate guselkumab versus ustekinumab:

Clinical remission at Week 48

Endoscopic response at Week 48

Clinical remission at Week 48 and endoscopic response at Week 48

Endoscopic remission (Global definition) at Week 48

Deep remission (Global definition) at Week 48
Regional Co-primary Endpoints
The Regional co-primary endpoints are:

clinical remission at Week 12

endoscopic response at Week 12 
For these endpoints, comparisons will be made within each study between the combined guselkumab 
induction dose group and placebo.
Regional Major Secondary Endpoints
The Regional major secondary endpoints are grouped into 3 categories based on timepoint and comparator; 
note that these are grouped for the purpose of categorization but are not presented in the order of testing in 
the multiplicity-controlled testing procedure (the specific order for the testing procedure will be provided 
in the statistical analysis plan).
The following Regional major secondary endpoints evaluate the short-term efficacy of guselkumab versus 
placebo: 

PRO-2 remission at Week 12 

Fatigue response at Week 12

Endoscopic remission (Regional definition) at Week 12
The following long-term endpoints evaluate guselkumab versus placebo:

Corticosteroid-free clinical remission at Week 48

Endoscopic response at Week 48
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Status: Approved, Date: 12 July 2022
The following long-term endpoints evaluate guselkumab versus ustekinumab:

Endoscopic remission (Regional definition) at Week 48 

Clinical remission at Week 48 

Endoscopic response at Week 48

Durable clinical remission at Week 48

PRO-2 remission at Week 48 

Clinical remission at Week 48 and endoscopic response at Week 48 

Corticosteroid-free remission at Week 48
PHARMACOKINETIC EVALUATIONS
Serum samples will be analyzed to determine concentrations of guselkumab and ustekinumab using 
validated, specific, and sensitive methods by or under the supervision of the sponsor.
IMMUNOGENICITY EVALUATIONS
Serum samples will be screened for antibodies binding to guselkumab or ustekinumab and the titer of 
confirmed positive samples will be reported as applicable. Other analyses may be performed to further 
characterize the immunogenicity of guselkumab or ustekinumab.  
PHARMACODYNAMIC AND BIOMARKER EVALUATIONS
Inflammatory PD markers (CRP and fecal calprotectin) will be evaluated. Biomarker assessments will be 
made to examine the biologic response to treatment and to identify biomarkers that are relevant to 
guselkumab or ustekinumab treatment and/or Crohn’s disease. Assessments will include the evaluation of 
relevant biomarkers in serum, whole blood, stool, and ileocolonic biopsy samples.
PHARMACOGENOMIC (DNA) EVALUATIONS
A pharmacogenomic blood sample will be collected from participants who consent to this component of 
the protocol to allow for pharmacogenomic research as necessary where local regulations permit. 
Participation in pharmacogenomic research is optional. Deoxyribonucleic acid (DNA) samples will be 
analyzed for identification of genetic factors that may be associated with clinical response.
MEDICAL RESOURCE UTILIZATION AND HEALTH ECONOMICS EVALUATIONS
Medical resource utilization, including but not limited to Crohn’s disease-related hospitalizations and 
surgeries, will be collected in the studies. The Work Productivity and Activity Impairment Questionnaire 
in Crohn’s Disease will also be utilized to evaluate work productivity.
SAFETY EVALUATIONS
Safety evaluations conducted at each study visit will include the assessment of adverse events (AEs; at the 
visit and those occurring between evaluation visits), a tuberculosis evaluation and other infection 
assessment, clinical laboratory blood tests (complete blood count and serum chemistries), vital signs (as 
defined in the Schedule of Activities), suicidality assessment, concomitant medication review, and 
observations for injection-site reactions, reactions temporally associated with an infusion, and/or allergic 
reactions.
STATISTICAL METHODS
Sample Size Calculation
Taking into account a mixed biologic therapy failure or intolerance (BIO-Failure)/conventional therapy 
failure or intolerance (CON-Failure) population in this program, sample size assumptions for the overall 
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Status: Approved, Date: 12 July 2022
randomized population were based on the ratio of an approximate 25% to 50% of participants in the 
CON-Failure patient population.
Phase 2 Dose-Ranging Study (GALAXI 1)
The sample size is based on statistical power considerations (for both the Initial Dose Decision Cohort and 
the Total Phase 2 Population) and the objective of selecting induction and maintenance dose regimens for 
confirmatory evaluation in Phase 3.
Assuming the mean CDAI reductions from baseline at Week 12 of approximately 105 to 115 in the 
guselkumab high 
 induction dose group versus approximately 45 to 50 in the placebo group with a 
common standard deviation of 100, for the Initial Dose Decision Cohort, 50 participants per treatment group 
(with 250 participants in total) will provide greater than 80% power to detect a treatment difference between 
guselkumab high 
 induction dose group and placebo using a 2-sample t-test at the α=0.05 (2-sided) level. 
For the Total Phase 2 Population, based on the minimum number of participants (70 per treatment group 
and 350 in total), the power is greater than 90% for the change from baseline in the CDAI score at Week 12, 
and greater than 85% for clinical remission at Week 12 assuming clinical remission rates of approximately 
12% to 15% for placebo and approximately 35% to 40% for the guselkumab high 
 induction dose at 
Week 12.
Phase 3 Dose-Confirming Studies (GALAXI 2 and GALAXI 3)
GALAXI 2 and GALAXI 3 are separate studies and will have separate type I error control at the 2-sided 
0.05 significance level. 
The power for the key endpoints in these Phase 3 studies (ie, Global co-primary endpoints, Regional co-
primary endpoints, Regional endpoints of corticosteroid-free clinical remission at Week 48 and endoscopic 
response at Week 48 [which are meant to demonstrate the long-term efficacy of guselkumab versus 
placebo]), as well as the adequate number of participants needed to assess the safety of guselkumab in 
Crohn's disease, were considered in determining the appropriate sample size for these Phase 3 studies. 
Based on this, a total sample size of approximately 980 participants (approximately 490 participants per 
study, consisting of 140 participants in each of the two guselkumab treatment groups, 70 participants in the 
placebo treatment group, and 140 participants in the ustekinumab group) will provide at least 90% power 
for these key endpoints in each study.
Global Co-primary Endpoints:
For   the co-primary endpoint of clinical response at Week 12 and clinical remission at Week 48: In 
each of the Phase 3 studies, assuming a rate of 8% to 10% for placebo and a minimum of a 40% difference 
between guselkumab and placebo based on Phase 2 (GALAXI 1) results, 140 participants in each 
guselkumab dose group and 70 participants in the placebo group will provide >99% power for this endpoint 
at the 0.05 (2-sided) alpha level.
For the co-primary endpoint of clinical response at Week 12 and endoscopic response at Week 48: In 
each of the Phase 3 studies, assuming a rate of approximately 2% to 5% for placebo and a minimum of a 
30% difference between guselkumab and placebo based on Phase 2 (GALAXI 1) results, 140 participants 
in each guselkumab dose group and 70 participants in the placebo group will provide >99% power for this 
endpoint at the 0.05 (2-sided) alpha level.
C
CI
C
CI
C
CI
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Status: Approved, Date: 12 July 2022
Regional Co-primary Endpoints:
For the co-primary endpoint of clinical remission at Week 12: In each of the Phase 3 studies, assuming 
a clinical remission at Week 12 rate of approximately 10% to 15% for placebo and a 35-40% difference 
between guselkumab and placebo based on Phase 2 (GALAXI 1) results, 280 participants in the combined 
guselkumab induction dose group and 70 participants in the placebo group, respectively, will provide 
greater than 99% power for clinical remission at Week 12 at an overall Type 1 error rate controlled at 0.05 
(2-sided). 
For the co-primary endpoint of endoscopic response at Week 12: In each of the Phase 3 studies, 
assuming an endoscopic response at Week 12 rate of approximately 10% to 13% for placebo and a 20% to 
25% difference between guselkumab and placebo based on Phase 2 (GALAXI 1) results, 280 participants 
in the combined guselkumab induction dose group and 70 participants in the placebo group, respectively, 
will provide approximately 95% power for endoscopic response at Week 12 at an overall Type 1 error rate 
controlled at 0.05 (2-sided).  
Statistical Analyses for Phase 2 Dose-Ranging Study (GALAXI 1)
Primary Efficacy Analysis
The primary efficacy analysis is based on the Full Analysis Set, defined as all participants who are 
randomized and who have received at least 1 dose of study intervention in GALAXI 1. The primary 
endpoint of the change from baseline in the CDAI score at Week 12 will be analyzed using a Mixed Model 
for Repeated Measures (MMRM) approach.
Major Secondary Efficacy Analyses
The major secondary endpoints of clinical remission (either based on CDAI or on PRO-2), clinical response, 
and clinical-biomarker response at Week 12 will be compared between each guselkumab dose group and 
the placebo group using the Cochran-Mantel-Haenszel (CMH) test (2-sided) stratified by baseline CDAI 
score (≤300 or >300) and BIO-Failure status (Yes/No), at a significance level of 0.05. Endoscopic response 
at Week 12 will be compared between each guselkumab dose group and the placebo group using the CMH
test (2-sided) stratified by SES-CD score (≤12 or >12) and BIO-Failure status (Yes/No), at a significance 
level of 0.05. 
A multiple testing procedure to control the Type 1 error at α=0.05 (2-sided) over the primary and major 
secondary endpoints will be prespecified in the Phase 2 SAP.
Statistical Analyses for Phase 3 Dose-Confirming Studies (GALAXI 2 and GALAXI 3)
GALAXI 2 and GALAXI 3 have identical study designs, objectives, and endpoints. Efficacy analyses 
within each study will be based on the Primary Analysis Set for that study, which includes all randomized 
participants who received at least 1 (partial or complete) dose of study intervention and satisfied the SES-
CD eligibility criteria adopted in Protocol Amendment 3 (ie, screening SES-CD score ≥6 [or ≥4 for 
participants with isolated ileal disease]).
Primary Efficacy Analysis
Global Primary Analysis
For testing of the Global co-primary endpoints, the efficacy of each dose of guselkumab versus placebo 
will be compared. A CMH test (2-sided) stratified by baseline CDAI score (≤300 or >300), baseline SES-
CD score (≤12 or >12), BIO-Failure status (Yes/No), and baseline corticosteroid use (Yes/No) will be used.
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Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 12 July 2022
Immunogenicity Analyses
The incidence and titers of antibodies to guselkumab and ustekinumab will be summarized respectively for 
all participants who receive a dose of guselkumab or ustekinumab and have appropriate samples for 
detection of antibodies to guselkumab or ustekinumab (ie, participants with at least 1 sample obtained after 
their first dose of guselkumab or ustekinumab).
Biomarker Analyses
Changes in serum protein analytes and whole blood ribonucleic acid (RNA) obtained over time will be 
summarized by treatment group. Associations between baseline levels and changes from baseline in select 
markers and response to treatment will be explored. RNA analyses will be summarized in a separate 
technical report.
Pharmacokinetic/Pharmacodynamic Analyses
The relationship between serum guselkumab concentrations and efficacy measures will be analyzed 
graphically. If any visual trend is observed, a suitable population PK/PD model may be developed to 
describe the exposure-response relationship. The results of the population PK/PD analysis will be presented 
in a separate technical report.
Medical Resource Utilization and Health Economics Analyses
Medical resource utilization and health economics, including work productivity, will be summarized by 
treatment group. 
Safety Analyses
Safety analyses will include summaries of AEs and laboratory parameters. These summaries will be based 
on participants who received at least 1 dose of study intervention in each respective study.
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Status: Approved, Date: 12 July 2022
1.2.
Schema
Figure 1:
Overview of the GALAXI Phase 2/3 Protocol
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Clinical Protocol CNTO1959CRD3001 Amendment 5
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Status: Approved, Date: 12 July 2022
Table 3:
SoA – Week 48 to Week 240 (Long-Term Extension) for Eligible Participants Who Have Completed Week 48 of GALAXI 1, GALAXI 2, or 
GALAXI 3
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Status: Approved, Date: 12 July 2022
Table 3:
SoA – Week 48 to Week 240 (Long-Term Extension) for Eligible Participants Who Have Completed Week 48 of GALAXI 1, GALAXI 2, or 
GALAXI 3
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Status: Approved, Date: 12 July 2022
Table 3:
SoA – Week 48 to Week 240 (Long-Term Extension) for Eligible Participants Who Have Completed Week 48 of GALAXI 1, GALAXI 2, or 
GALAXI 3
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Status: Approved, Date: 12 July 2022
Table 4:
SoA – Study Intervention Discontinuation (SID) Visit and the Final Efficacy and Safety (FES) Follow-Up Visit for GALAXI 1, GALAXI 2, or 
GALAXI 3: (a) Participants to Complete SID and/or FES Visits, Plus Additional Study Visits
(a) Participants should complete the SID and/or the FES visits, and additional study visits, as outlined below
SID a
FES b
Additional 
Visit
Required
Notes
Participant terminates study participation at any time during the study
X
Evaluations for SID should be completed prior to 
participant terminating study participation.
Participant discontinues study intervention at or prior to the Week 12 visit
X
X
Week 12
(see Table 2)
Discontinuation prior to Week 12: A video 
ileocolonoscopy at Week 12 is not required if 
already completed at the SID visit prior to 
Week 12.
Discontinuation at Week 12: A video 
ileocolonoscopy is required at Week 12 (or can 
be performed as part of the SID visit after 
Week 12).
Participant discontinues study intervention after Week 12 and up to the Week 48 visit
X
X
Discontinuation after Week 12 (visit and 
ileocolonoscopy) and before Week 44: A video 
ileocolonoscopy (with biopsy samples) is optional 
(or can be performed as part of the SID visit).
Discontinuation at Week 44 or Week 48: A video 
ileocolonoscopy (with biopsy samples) is required 
(or can be performed as part of SID visit).  
Participant completes the 48-week study but does not enter the LTE at Week 48
X
Week 48
(see Table 2)
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Status: Approved, Date: 12 July 2022
Table 4:
SoA – Study Intervention Discontinuation (SID) Visit and the Final Efficacy and Safety (FES) Follow-Up Visit for GALAXI 1, GALAXI 2, or 
GALAXI 3: (a) Participants to Complete SID and/or FES Visits, Plus Additional Study Visits
Participant discontinues study intervention after Week 48 and up to Week 240
X
X
Discontinuation after Week 48 and before 
Week 96: The video ileocolonoscopy at the SID 
visit is optional for participants who discontinue 
after Week 48, since these participants would have 
completed the procedure as part of the Week 48 
visit.
Discontinuation after Week 96 and before 
Week 144: The video ileocolonoscopy at the SID 
visit is optional for participants who discontinue 
after Week 96, since these participants would have 
completed the procedure as part of the Week 96 
visit.  
Discontinuation after Week 144 and before 
Week 192: The video ileocolonoscopy at the SID 
visit is optional for participants who discontinue 
after Week 144, since these participants would 
have completed the procedure as part of the 
Week 144 visit.  
Discontinuation after Week 192 and before 
Week 240: The video ileocolonoscopy at the SID 
visit is optional for participants who discontinue 
after Week 192, since these participants would 
have completed the procedure as part of the 
Week 192 visit.
Participant completes LTE participation at Week 240
X
Week 240
(see Table 3)
The FES should occur around Week 248 or 252 
(ie, approximately 16 weeks after the last study 
intervention administration at Week 232 [for 
 
dosing] or Week 236 [for 
 dosing]).
Abbreviations:  FES=final efficacy and safety (follow-up visit); LTE=long-term extension; 
 SID=study intervention discontinuation (visit). 
Footnotes:
a.
The SID visit should be completed at the time of SID.
b.
The FES visit should be completed approximately 16 weeks after the last study intervention administration.
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Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 12 July 2022
2.
INTRODUCTION
Guselkumab (CNTO 1959 or TREMFYA®) is a fully human immunoglobulin G1 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 IL-23 blocks the binding of extracellular 
IL-23 to the cell surface IL-23 receptor, inhibiting IL-23-specific intracellular signaling and 
subsequent activation and cytokine production. In this manner, guselkumab inhibits the biologic
activity of IL-23 in all in vitro assays examined.
For the most comprehensive nonclinical and clinical information regarding guselkumab, refer to 
Section 2.2 in this protocol and the latest version of the guselkumab Investigator’s Brochure (IB).
Note: The term “sponsor” used throughout this document refers to the entities listed in the Contact 
Information page(s), which will be provided as a separate document. The term “study intervention” 
is used throughout this document in place of “study agent” or “study drug.”
2.1.
Study Rationale
There is a high unmet need for new treatment options in Crohn’s disease that are safe and effective, 
especially new therapies that can provide improved long-term efficacy (ie, sustained remission)
over currently available therapies.
The clinical development program for guselkumab in Crohn’s disease is designed to evaluate the 
safety and efficacy of guselkumab compared with placebo and an active control (ustekinumab) 
and will be conducted under this single 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 Crohn’s disease who 
have demonstrated an inadequate response or failure to tolerate previous conventional therapy or 
biologic therapy. 
Under this protocol, there are 3 separate studies: a 48-week Phase 2 dose-finding study (ie, 
GALAXI 1) and 2 identical 48-week Phase 3 confirmatory studies (ie, GALAXI 2 and 
GALAXI 3). Participants who complete the 48-week Phase 2 or Phase 3 studies may be eligible 
to enter the long-term extension (LTE [Week 48 to Week 252]) and receive approximately 4 
additional years of treatment. The overall Phase 2/3 development program will enroll 
approximately 1,340 participants with a total duration for each participant of up to approximately 
5 years.
An overview of the protocol design and supportive rationale is described in Section 4.
The clinical and scientific rationale in support of the overall development program is described in 
Section 2.1.
Relevant background information on the clinical and nonclinical development of guselkumab is 
summarized in Section 2.2.
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2.1.1.
Unmet Need in Crohn’s Disease
Currently, there are 3 classes of biologic agents approved for the treatment of moderately to 
severely active Crohn’s disease: tumor necrosis factor (TNF) antagonist therapies (infliximab, 
adalimumab, certolizumab), integrin inhibitors (natalizumab and vedolizumab), and IL-12/23 
inhibitors (ustekinumab). Although the introduction of biologic agents has significantly improved 
the clinical management of patients with moderately to severely active Crohn’s disease, a sizable 
proportion of the target patient population is non-responsive or will lose response over time. A 
review of the available data for approved biologic agents highlighted the unmet need in achieving 
and maintaining long-term remission, especially among patients who have previously failed 
biologic treatments. In all-treated patients (ie, all patients who were randomized at Week 0 of the 
studies evaluated), the estimated rates of clinical remission at 1 year in the biologic therapy failure
or intolerance (BIO-Failure) population is around 20%, and ranges from 20% to 50% in the 
conventional therapy failure or intolerance (CON-Failure) population.13
In summary, there remains considerable unmet medical need for new treatment options, especially 
therapies with novel mechanisms of action that have the potential to raise the efficacy bar and 
maximize the proportion of patients who achieve and maintain clinical remission.
2.1.2.
Rationale for Targeting IL-23 in Crohn’s Disease
2.1.2.1.
Preclinical Evidence Implicating IL-23 as a Target in Crohn’s Disease
Genetic and animal model studies have explored the contribution of IL-12 and IL-23 in driving 
the pathophysiology of Crohn’s disease. The results indicate that IL-23 plays a predominant role 
in inflammatory bowel disease (IBD) and emerging evidence suggests that blocking IL-23 alone 
may be a more effective strategy than blocking both IL-12 and IL-23. 
Initial observations from genetic and animal model data suggest that Crohn’s disease is mediated 
by IL-12 and/or IL-23, potentially through the Th1 and Th17 pathways they induce, respectively.16
However, increasing evidence suggests a predominant role for IL-23 in Crohn’s disease. Genome-
wide association studies identified polymorphisms in the interleukin-23 receptor gene that are 
associated with Crohn’s disease.1 The role of IL-23 in driving intestinal inflammation has been 
shown in several mouse models. Mice treated with anti-IL-23 antibodies exhibited attenuated 
inflammation,16 and mice with a genetic deletion of the p19 subunit of IL-23 are protected in 
several models of intestinal inflammation.11
2.1.2.2.
Clinical Evidence Establishing Proof of Concept for Targeting IL-23 in 
Crohn’s Disease
The potential therapeutic role of IL-23 in Crohn’s disease was first established by clinical studies 
of IL-12/23p40 antagonists (briakinumab18 and ustekinumab8). Ustekinumab (STELARA®) was 
recently approved for the treatment of moderately to severely active Crohn’s disease (STELARA 
Summary of Product Characteristics [SmPC]22; STELARA US Prescribing Information23). While 
these programs demonstrated that blockade of both IL-12 and IL-23 is effective in treating Crohn’s 
disease, they could not ascertain the relative contributions of the 2 cytokines.
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More recent studies of 2 anti-IL-23 antagonists, risankizumab (previously BI-655066)7,9 and 
brazikumab (formerly MEDI2070, AMG 139),20 reported Phase 2 results demonstrating efficacy 
of IL-23 blockade in participants with moderately to severely active Crohn’s disease. The 
magnitude of efficacy observed in each of these studies suggests the potential for improved 
efficacy compared with ustekinumab (anti-IL-12/23), recognizing the limitations of cross-study 
comparisons as well as the comparatively small size of the IL-23 Phase 2 studies.
2.1.2.2.1.
Clinical Experience with IL-12/23-Targeted Therapy (Ustekinumab) in 
Crohn’s Disease
The ustekinumab Phase 3 program in Crohn’s disease included two 8-week studies evaluating the 
efficacy and safety of ustekinumab 
induction, and one maintenance study 
evaluating the efficacy and safety of ustekinumab 
maintenance, for a total 
duration of 52 weeks of treatment. Ustekinumab was evaluated in the full spectrum of biologic-
eligible patients with Crohn’s disease, ie, those who were conventional therapy failures and those 
who were biologic therapy failures. After a single ustekinumab 
 induction dose at 
Week 0, approximately 21% and 40% of BIO-Failure and CON-Failure participants, respectively 
(versus approximately 7% and 20% of placebo-treated participants, respectively), achieved clinical 
remission at Week 8 (as evaluated by the Crohn’s Disease Activity Index [CDAI]).8 Among 
participants who responded to ustekinumab 
 induction and were rerandomized to receive 
ustekinumab 
 maintenance 
, approximately 
53% and 49% of participants were in clinical remission at Week 52, respectively, compared with 
36% of participants who received placebo maintenance.8
2.1.2.2.2.
Clinical Experience with IL-23-Targeted Therapy in Crohn’s Disease
Recent Phase 2 studies of 2 IL-23 mAbs, risankizumab7,9 and brazikumab,20 demonstrated their 
efficacy in improving clinical signs and symptoms, reducing inflammatory biomarkers, and 
improving endoscopic findings in participants primarily with biologic-refractory Crohn’s disease. 
Cross-study comparisons of clinical remission rates with the IL-23 blockers suggest the potential 
for improved efficacy compared with ustekinumab. It is notable that the induction doses used in 
the studies of both risankizumab (200 and 
 at Weeks 0, 4, 8) and brazikumab 
 
 at Weeks 0, 4) were considerably higher than approved ustekinumab dosing 
 at 
Week 0). A cross-compound meta-analysis suggests that the risankizumab dosing, in particular, 
may be at the higher end of the dose-response curve (see Section 4.3, Justification for Dose). 
Furthermore, the Phase 2 study with risankizumab also suggested the potential that response rates 
may not reach maximum until after 6 months of treatment. With doses of 
 
 for up to 6 months, clinical remission rates of approximately 50% were observed in all-
treated patients,9 substantially higher than remission rates previously reported for other agents, 
including ustekinumab, in similar study populations at similar follow-up time points. Of those 
participants who were in remission at 6 months and who continued risankizumab maintenance 
treatment 
 approximately 70% were in remission at 1 year.6
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2.1.3.
Overall Rationale for Guselkumab in Crohn’s Disease
In summary, the collective genetic and preclinical evidence implicates the prominent role of 
selectively targeting IL-23 in modulating the underlying pathophysiology of IBD. The available 
clinical experience of 2 IL-23 antagonists and the established evidence from an approved IL-12/23 
antagonist (ustekinumab) have demonstrated proof of mechanism and proof of concept, 
respectively, for targeting IL-23 in the treatment of Crohn’s disease. Together, the available 
evidence provide support for investigating guselkumab in the treatment of Crohn’s disease.
2.2.
Background
2.2.1.
Guselkumab Clinical Experience
This protocol represents the first studies of guselkumab in patients with Crohn’s disease.
This section provides a summary of the sponsor’s assessment of how the overall clinical 
experience with guselkumab across various indications supports the investigation of guselkumab 
in Crohn’s disease. Details about these guselkumab clinical development programs across various 
indications are provided in Section 4 of the latest version of the guselkumab IB.
Through the cutoff date of 30 June 2017, 2,805 subjects have been exposed to guselkumab across 
all indications in completed and ongoing studies, including 185 healthy subjects, 2,336 subjects 
with psoriasis, 129 subjects with psoriatic arthritis (PsA), and 155 subjects in other indications.
The largest clinical experience to date with guselkumab has been in plaque psoriasis, primarily 
based on dosing at 
 in the Phase 2 and Phase 3 clinical development program
(n=1,748); but also at doses up to 
 in a small number of participants (n=10) during 
Phase 1 clinical development. The safety profile of guselkumab in participants with moderate to 
severe plaque psoriasis based on data from the Phase 2 study (CNTO1959PSO2001) and 3 Phase 3 
studies (CNTO1959PSO3001, CNTO1959PSO3002, and CNTO1959PSO3003) is described in 
Section 4.4 of the latest version of the guselkumab IB. Briefly, of the 1,748 guselkumab-treated 
participants in the Phase 2 and Phase 3 studies, 1,393 participants were exposed for at least 
6 months and 728 participants were exposed for at least 1 year. The LTEs of the Phase 3 studies 
(CNTO1959PSO3001 and CNTO1959PSO3002) are ongoing and will evaluate the safety and 
efficacy of guselkumab through up to 5 years of follow-up.
The totality of the safety data available to date show that guselkumab, administered 
 at doses 
of 
in participants with plaque psoriasis, is well-tolerated and has a safety profile 
comparable to placebo over 16 weeks, and safety remained favorable when referenced versus 
active comparator (adalimumab) over 1 year. Additional safety data in other indications (in 
participants who also receive concomitant immunomodulators as background therapy) at 
guselkumab doses as high as 
 (Phase 2 rheumatoid arthritis study; n=54) did not 
identify any clinically significant safety signals through 1 year. Finally, a limited number of 
healthy participants (n=30) received single doses of 
guselkumab between 
 and up 
to 
. Of the 6 participants in the 
 dose group, the highest dose received was 
 in 1 participant. No clinically significant safety signals were identified.
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Status: Approved, Date: 12 July 2022
being an immunomodulatory mAb and include malignancy and hypersensitivity, as well as liver 
injury, based on an event of potential drug-induced liver injury (DILI) that occurred in a single 
participant at the highest Phase 2 induction dose administered. Since there is limited clinical 
information available for the higher dose regimens of guselkumab (as proposed in this protocol), 
safety will be evaluated in an initial cohort of 25 patients by an independent Data Monitoring 
Committee (DMC). Details about the evaluation of this initial cohort and the decision to continue 
or modify the protocol are outlined in Section 9.5.2 and in the DMC charter. The early safety 
evaluation of the initial cohort will ensure acceptable safety for continued study of the proposed 
Phase 2 and Phase 3 dose regimens in larger numbers of patients, and the ongoing unblinded safety 
assessments by the DMC throughout the Phase 2 and 3 studies will ensure patient safety in the 
overall development program. Since the initiation of the GALAXI protocol, higher doses of 
guselkumab (up to 
 have been administered in two clinical studies (a Phase 1 PK 
study in healthy Japanese participants and a Phase 2 study in participants with hidradenitis 
suppurativa).
2.3.2.
Active Comparator: Ustekinumab
Ustekinumab (STELARA) is the active comparator in this protocol. Ustekinumab is a human IgG1
kappa mAb that binds with high affinity and specificity to the p40 subunit common to both human 
IL-12 and human IL-23.
Ustekinumab is an approved treatment for moderately to severely active Crohn’s disease in adult 
patients in several countries including the US, Canada, and the EU; submissions for regulatory 
approval of the Crohn’s disease indication are currently under review in a number of countries 
globally.
The proposed induction and maintenance dosing of ustekinumab in this protocol is consistent with 
the currently approved country labels globally and is consistent with the dose regimens evaluated 
in the ustekinumab Phase 3 clinical development program in Crohn’s disease that established the 
efficacy and safety of ustekinumab in patients with moderately to severely active Crohn’s disease.
Additional details about the dose selection rationale for ustekinumab are provided in Section 4.3.2.
The general benefits and risks of ustekinumab are presented in the country-specific prescribing 
information where ustekinumab is approved; for countries where ustekinumab is not yet approved, 
investigators should refer to the latest version of the ustekinumab IB.
3.
OBJECTIVES AND ENDPOINTS
3.1.
Phase 2 Dose-Ranging Study (GALAXI 1)
3.1.1.
Objectives
Primary Objectives

To evaluate the clinical efficacy of guselkumab in participants with Crohn’s disease

To evaluate the safety of guselkumab
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Secondary Objectives

To evaluate the dose-response of guselkumab to inform dose selection for the Phase 3 portion 
of this protocol

To evaluate the efficacy of guselkumab on endoscopic improvement

To evaluate the PK, immunogenicity, and pharmacodynamics (PD) of guselkumab therapy, 
including changes in C-reactive protein (CRP) and fecal calprotectin
Other Objectives

To evaluate the impact of guselkumab on health-related quality of life (HRQOL) and health 
economics outcome measures

To evaluate the efficacy of guselkumab on histologic improvement

To evaluate the impact of treatment with guselkumab on intestinal mucosal gene expression 
profiles and cellular composition associated with Crohn’s disease
3.1.2.
Endpoints
The primary endpoint and major secondary endpoints evaluate the short-term efficacy of 
guselkumab versus placebo. These endpoints are described below. Note: the final ordering of the 
major secondary endpoints will be provided in the Phase 2 Statistical Analysis Plan (SAP).
Primary Endpoint
Change from baseline in the CDAI score at Week 12.  
Major Secondary Endpoints

Clinical remission at Week 12 (defined as CDAI score <150).

Clinical response at Week 12 (defined as ≥100-point reduction from baseline in CDAI score 
or CDAI score <150).

PRO-2 remission at Week 12 (defined as an AP mean daily score at or below 1 [AP≤1] AND 
an SF mean daily score at or below 3 [SF≤3], and no worsening of AP or SF from baseline).

Clinical-biomarker response at Week 12 (clinical response based on CDAI score and ≥50%
reduction from baseline in CRP or fecal calprotectin).

Endoscopic response at Week 12 (defined as at least 50% improvement from baseline in the 
Simple Endoscopic Score for Crohn’s Disease [SES-CD] or SES-CD score ≤2). 
A complete list of the efficacy endpoints is provided in Section 9.4.1.1.
3.1.3.
Hypothesis
The primary hypothesis for GALAXI 1 is that guselkumab is superior to placebo in inducing a 
reduction from baseline in CDAI score in participants with moderately to severely active Crohn's 
disease.
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3.2.
Phase 3 Dose-Confirming Studies (GALAXI 2 and GALAXI 3)
GALAXI 2 and GALAXI 3 are identical studies and have the same objectives and endpoints, as 
described below.
3.2.1.
Objectives
Primary Objectives

To evaluate the clinical and endoscopic efficacy of guselkumab in participants with Crohn’s 
disease

To evaluate the safety of guselkumab
Secondary Objectives

To evaluate the impact of guselkumab on HRQOL

To evaluate the PK, immunogenicity, and PD of guselkumab therapy, including changes in 
CRP and fecal calprotectin
Other Objectives

To evaluate the impact of guselkumab on health economics outcome measures

To evaluate the efficacy of guselkumab on histologic improvement

To evaluate the impact of treatment with guselkumab on intestinal mucosal gene expression 
profiles and cellular composition associated with Crohn’s disease
3.2.2.
Endpoints and Hypotheses
The primary and major secondary endpoints and hypotheses found in Section 3.2.2.1 refer to the 
Global endpoints and hypotheses for the US and other countries/territories throughout the world 
as applicable. The primary and major secondary endpoints and hypotheses found in Section 3.2.2.2
refer to the Regional endpoints and hypotheses for other health authorities that preferred the 
Week 12 co-primary endpoints were retained. The definitions associated with the endpoints will 
be provided in Section 3.2.2.3.
3.2.2.1.
Global Endpoints and Hypotheses
Co-primary Endpoints
The Global co-primary endpoints are:

Clinical response at Week 12 and clinical remission at Week 48  

Clinical response at Week 12 and endoscopic response at Week 48
For these endpoints, comparisons will be made within each study between each guselkumab dose 
(guselkumab 
 and 
placebo.  
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Major Secondary Endpoints  
The Global major secondary endpoints are grouped into 3 categories based on timepoint and 
comparator; note that these are grouped for the purpose of categorization but are not presented in 
the order of testing in the multiplicity-controlled testing procedure (the specific order for the 
testing procedure will be provided in the statistical analysis plan).
The following Global major secondary endpoints evaluate the short-term efficacy of guselkumab 
versus placebo in each study:

Clinical response at Week 4

Clinical remission at Week 12

Endoscopic response at Week 12

Fatigue response at Week 12 

Clinical remission at Week 12 and endoscopic response at Week 12

Endoscopic remission (Global definition) at Week 12 
The following long-term endpoints evaluate guselkumab versus placebo in each study:

Clinical response at Week 12 and corticosteroid-free clinical remission at Week 48 

Clinical response at Week 12 and endoscopic remission (Global definition) at Week 48
The following long-term endpoints evaluate guselkumab versus ustekinumab:

Clinical remission at Week 48

Endoscopic response at Week 48

Clinical remission at Week 48 and endoscopic response at Week 48

Endoscopic remission (Global definition) at Week 48

Deep remission (Global definition) at Week 48
A list of the exploratory endpoints can be found in Section 9.4.1.2.
Global Hypotheses
The co-primary hypotheses will be tested within each of GALAXI 2 and GALAXI 3 separately.  
The co-primary hypotheses are that guselkumab is superior to placebo in achieving:

clinical response at Week 12 and clinical remission at Week 48

clinical response at Week 12 and endoscopic response at Week 48
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3.2.2.2.
Regional Endpoints and Hypotheses
Co-primary Endpoints
The Regional co-primary endpoints are:

Clinical remission at Week 12

Endoscopic response at Week 12 
For these endpoints, comparisons will be made within each study between the combined 
guselkumab induction dose group and placebo.
Major Secondary Endpoints
The Regional major secondary endpoints are grouped into 3 categories based on timepoint and 
comparator; note that these are grouped for the purpose of categorization but are not presented in 
the order of testing in the multiplicity-controlled testing procedure (the specific order for the 
testing procedure will be provided in the statistical analysis plan):
The following Regional major secondary endpoints evaluate the short-term efficacy of guselkumab 
versus placebo: 

PRO-2 remission at Week 12 

Fatigue response at Week 12

Endoscopic remission (Regional definition) at Week 12
The following long-term endpoints evaluate guselkumab versus placebo:

Corticosteroid-free clinical remission at Week 48

Endoscopic response at Week 48
The following long-term endpoints evaluate guselkumab versus ustekinumab:

Endoscopic remission (Regional definition) at Week 48 

Clinical remission at Week 48 

Endoscopic response at Week 48

Durable clinical remission at Week 48

PRO-2 remission at Week 48

Clinical remission at Week 48 and endoscopic response at Week 48 
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
Corticosteroid-free remission at Week 48
A list of the exploratory endpoints can be found in Section 9.4.1.2.
Regional Hypotheses
The co-primary hypotheses will be tested within each of GALAXI 2 and GALAXI 3 separately.  
The co-primary hypotheses are that guselkumab is superior to placebo in achieving:

clinical remission at Week 12 

endoscopic response at Week 12 
3.2.2.3.
Definition of Endpoints
Definitions:

Clinical response: ≥100-point reduction from baseline in CDAI score or CDAI score 
<150

Clinical remission: CDAI <150

Endoscopic response: at least 50% improvement from baseline in the SES-CD or SES-
CD score ≤2 

Corticosteroid-free clinical remission at Week 48: CDAI score <150 at Week 48 and not 
receiving corticosteroids at Week 48 

Fatigue response: an improvement of ≥ 7 points in PROMIS Fatigue Short Form 7a.

Durable clinical remission: CDAI <150 for ≥80% of all visits between Week 12 and Week 
48 [ie, at least 8 of 10 visits]), which must include Week 48

PRO-2 remission: AP mean daily score at or below 1 [AP≤1] AND SF mean daily score 
at or below 3 [SF≤3], and no worsening of AP or SF from baseline
Global Definitions:

Endoscopic remission: SES-CD ≤4 with at least a 2-point reduction from baseline and no 
subscore greater than 1 in any individual subcomponent

Deep remission: Clinical remission and endoscopic remission (Global definition)
Regional Definitions:

Endoscopic remission: SES-CD score ≤2

Deep remission: Clinical remission and endoscopic remission (Regional definition)
4.
STUDY DESIGN
4.1.
Overall Design
The clinical development program for guselkumab in Crohn’s disease will be conducted under this 
single protocol: a Phase 2/3, randomized, double-blind, placebo- and active-controlled 
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(ustekinumab), parallel-group, multicenter protocol to evaluate the safety and efficacy of 
guselkumab in participants with moderately to severely active Crohn’s disease who have 
demonstrated an inadequate response or failure to tolerate previous conventional therapy or 
biologic therapy.
An overview of this clinical development program is presented in Figure 1 and described briefly 
below. Under this protocol, there are 3 separate studies: a 48-week Phase 2 dose-ranging study (ie,
GALAXI 1) and 2 identical 48-week Phase 3 confirmatory studies (ie, GALAXI 2 and 
GALAXI 3). All 3 studies will be conducted using a treat-through study design, ie, participants 
are randomized to treatment regimens at Week 0 and will remain on that treatment regimen through 
at least Week 48 of each study, unless otherwise indicated.
In the Phase 2 dose-ranging study (ie, GALAXI 1), the safety and efficacy of guselkumab dose 
regimens spanning a wide induction and maintenance dose range will be evaluated to support the 
selection of induction and maintenance dose regimens for confirmatory evaluation in Phase 3. It 
is estimated that 250 to 500 participants may be required to select the dose regimens that will be 
evaluated in Phase 3 (GALAXI 2 and GALAXI 3). Therefore, the first 250 participants in 
GALAXI 1 will be enrolled into an Initial Dose Decision Cohort; an interim analysis (IA) primarily 
based on this cohort will occur once these participants reach Week 12 (or terminate study 
participation prior to Week 12), as described in Section 9.5.1. Since data from more participants 
may be required to inform the dose decision, the sponsor may elect to continue enrollment and 
newly enrolled participants (ie, starting from participant #251) will be randomized into a 
Transition Cohort while data from the Initial Dose Decision Cohort are being collected and 
analyzed. The purpose of the Transition Cohort will be to continue accruing safety and efficacy
data on the Phase 2 dose regimens without interrupting the study, thereby increasing the size of 
the overall safety database as well as possibly contributing additional information in making a dose 
decision should there be uncertainty on dose selection based on the results from the Initial Dose 
Decision Cohort. If the decision is made to proceed with enrollment into the Transition Cohort, it 
is anticipated that a maximum of approximately 250 additional participants will be enrolled into 
GALAXI 1 (ie, 250 in the Initial Dose Decision Cohort and up to 250 in the Transition Cohort) 
prior to the dose decision. If a dose decision for Phase 3 is not made by the time the 500th patient 
is randomized, enrollment will be paused until a decision for Phase 3 dosing, or a decision to 
terminate the development program, is made.
This is an operationally seamless protocol in countries where the local health authorities have 
approved a seamless transition. In the countries that have approved a seamless transition, there 
will be no break in enrollment between the Phase 2 and Phase 3 studies if enrollment continues 
into the Transition Cohort and a dose decision can be made before 500 patients are randomized. 
Transition from the Phase 2 portion to the Phase 3 portion of the protocol will occur once the dose
decision for Phase 3 has been made and implemented. In countries where the local health authority 
requires additional regulatory approval prior to initiating the Phase 3 studies, enrollment will pause 
until approval is received. In all countries, all participants randomized after the dose decision has 
been implemented will be part of the Phase 3 studies. 
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In the Phase 3 dose-confirming studies (ie, GALAXI 2 and GALAXI 3), the safety and efficacy of 
the selected guselkumab dose regimens will be evaluated. A target of approximately 490 
participants will be enrolled in each of the Phase 3 studies, for a total target sample size of 
approximately 980 participants in the Phase 3 portion of the protocol. Participants impacted by
major disruptions may be replaced (see Section 10.14, Appendix 14).
Participants who complete the 48-week Phase 2 or Phase 3 studies may be eligible to enter the
LTE to receive approximately 4 additional years of treatment.
The overall GALAXI Phase 2/3 protocol will enroll a total of approximately 1,340 participants, 
with a total duration for each participant of up to approximately 5 years.
Target Population
The target population in all 3 studies under this protocol will consist of men or women ≥18 years 
of age at the time of informed consent with moderately to severely active Crohn’s disease (of at 
least 3 months’ duration). Participants must have colitis, ileitis, or ileocolitis previously confirmed 
by radiography, histology, and/or endoscopy.
Active Disease Criteria
At baseline, participants must have active Crohn’s disease, defined as follows:
1. Clinically active Crohn’s disease
a.
CDAI score ≥220 but ≤450
AND EITHER
b.
Mean daily SF count >3, based on the unweighted CDAI component of the number of 
liquid or very soft stools 
OR
c.
Mean daily AP score >1, based on the unweighted CDAI component of AP
AND
2. Endoscopic evidence of ileocolonic Crohn’s disease
A SES-CD score ≥6 (or ≥4 for participants with isolated ileal disease), as assessed by central 
endoscopy reading at the screening endoscopy, based on the presence of ulceration in at least 
1 of the 5 ileocolonic segments, resulting in the following specified ulceration component 
scores:
a.
a minimum score of 1 for the component of “size of ulcers”
AND
b.
a minimum score of 1 for the component of “ulcerated surface”.
Of note, before the implementation of Amendment 3, where the minimum SES-CD score was 
≥3 based on the presence of ulceration, within each of the studies, a maximum of 10% of the 
total enrolled population could include participants who had baseline scores for SES-CD <4 
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(ie, for participants with isolated ileal disease), or SES-CD <7 (ie, for participants with colonic 
or ileocolonic disease).
Medication History Criteria
In addition, a broad participant population eligible for systemic therapy will be evaluated in this 
protocol and will include participants who have demonstrated an inadequate response or failed to 
tolerate previous conventional therapy or biologic therapy. 
Detailed eligibility criteria for prior exposure to conventional therapy or biologic therapy are 
described in Appendix 2 (Section 10.2) and Appendix 3 (Section 10.3), respectively, and are 
summarized below.
Note that participants with prior exposure to IL-12/23 or IL-23 agents are ineligible for entry into 
this protocol, with the exception of participants who have had limited exposure to and who have 
not demonstrated failure or intolerance to ustekinumab, as described in Appendix 4 (Section 10.4). 

Conventional therapy failure or intolerance (CON-Failure)
Participants must have demonstrated an inadequate response to, or have failed to tolerate, at 
least 1 of the following conventional Crohn’s disease therapies: oral corticosteroids (including 
prednisone, budesonide, and beclomethasone dipropionate) or the immunomodulators 
azathioprine (AZA), 6-mercaptopurine (6-MP) or methotrexate (MTX). Participants who have 
demonstrated corticosteroid dependence (ie, an inability to successfully taper corticosteroids 
without a return of the symptoms of Crohn’s disease) are also eligible. Participants may be 
naïve to biologic therapy (ie, a TNF antagonist or vedolizumab or ustekinumab) or may have 
been exposed to biologic therapy but have not demonstrated inadequate response or 
intolerance.
Within each of the studies, an approximate 25% to 50% of the total enrolled population will 
be participants who are CON-Failures.

Biologic therapy failure or intolerance (BIO-Failure) 
Participants must have demonstrated an inadequate response to, or have failed to tolerate, at 
least 1 or more biologic therapies (ie, TNF antagonists or vedolizumab) at a dose approved 
for the treatment of Crohn’s disease. Inadequate response is defined as: Primary non-response 
(ie, no initial response) or Secondary non-response (ie, response initially but subsequently lost 
response). Participants who have demonstrated an inadequate response to, or have failed to 
tolerate ustekinumab are not eligible.
The use of concomitant and prohibited therapies is described in Section 6.5. In general, 
concomitant therapies should maintain stable dosing (except for steroid tapering) and new 
concomitant therapies should not be initiated unless considered medically necessary by the 
investigator. Corticosteroids will be tapered beginning at Week 12. Initiation of prohibited 
therapies will result in study intervention discontinuation (SID). Finally, in the event of persistent 
inadequate response or clinically significant Crohn’s disease worsening, discontinuation of study 
intervention should be strongly considered, as described in Section 7.1.
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Evaluations
Throughout the 3 studies, efficacy, PK, biomarkers, and safety will be assessed at time points 
indicated in the appropriate Schedule of Activities (Section 1.3).
An overview of the endpoints for the 3 studies is presented in Section 3 and full details are 
presented in Section 9.4.1.
A pharmacogenomic blood sample will be collected from participants who consent to this 
component of the protocol (where local regulations permit; Section 1.3). Participation in 
pharmacogenomic research is optional. Deoxyribonucleic acid (DNA) samples will be analyzed 
for identification of genetic factors that may be associated with clinical response.
An external independent DMC, with defined roles and responsibilities as governed by a DMC 
charter, will assess the safety of participants across the 3 studies. The DMC’s initial responsibility 
will be careful review of the safety data from the first 25 participants randomized and treated in 
GALAXI 1. After that, ongoing safety data reviews will continue as specified in the DMC charter. 
After each review, the DMC will make recommendations to the sponsor about the continuation of 
the studies (Section 9.5.2).
4.1.1.
Phase 2 Dose-Ranging Study (GALAXI 1): Induction and Maintenance
4.1.1.1.
Overview of Phase 2 Study Design and Dose Decision for Phase 3
At Week 0, participants will be randomized in a 1:1:1:1:1 ratio to receive 1 of 3 dose regimens of 
guselkumab, ustekinumab, or placebo. Participants will be allocated to a treatment group using a 
permuted block randomization with baseline CDAI score (≤300 or >300) and prior BIO-Failure 
status (Yes/No) as the stratification variables. An approximate 25% to 50% of the total enrolled 
population will be CON-Failure participants. In addition, a maximum of 10% of the total enrolled 
population will have baseline scores for SES-CD <4 (ie, for participants with isolated ileal 
disease), or SES-CD <7 (ie, for participants with colonic or ileocolonic disease). Allocation to 
treatment group will be performed using a central randomization center by means of an interactive 
web response system (IWRS).
As described in Section 4.1, it is anticipated that up to 500 participants may be enrolled into 
GALAXI 1 (ie, 250 in the Initial Dose Decision Cohort and up to 250 in the Transition Cohort) 
prior to the dose decision for Phase 3. If a dose decision for Phase 3 is not made by the time the 
500th patient is randomized, enrollment will be paused until a decision for Phase 3 dosing, or a 
decision to terminate the development program, is made.
Interim analyses are planned at Week 12 (and at Week 24, if necessary) after all participants from 
the Initial Dose Decision Cohort have either completed the Week 12 (or Week 24) visit or 
terminated study participation prior to the Week 12 (or Week 24) visit to inform the dose decision 
for Phase 3. At the time of each IA, all available data from both the Initial Dose Decision Cohort 
and the Transition Cohort will be analyzed, including any data beyond Week 12. Additional data 
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The use of concomitant and prohibited therapies is described in Section 6.5. In general, 
concomitant therapies should maintain stable dosing (except for steroid tapering) and new 
concomitant therapies should not be initiated, unless considered medically necessary by the 
investigator. Corticosteroids will be tapered beginning at Week 12. Initiation of prohibited 
therapies will result in SID. Finally, in the event of persistent inadequate response or clinically 
significant Crohn’s disease worsening, discontinuation of study intervention should be strongly 
considered, as described in Section 7.
All participants who complete the Week 48 evaluations may be eligible to enter the LTE and 
continue to receive study intervention for approximately 4 additional years (Week 48 to 
Week 252), as described in Section 4.1.3.
4.1.1.3.
Endpoints and Evaluations
The primary endpoint is change from baseline in the CDAI score at Week 12. The major secondary 
endpoints are clinical remission at Week 12, clinical response at Week 12, PRO-2 remission at 
Week 12, endoscopic response at Week 12, and clinical-biomarker response at Week 12. Analyses 
of these endpoints will be based on comparisons between each guselkumab group and the placebo
group. Additional analyses of endpoints at other time points, including comparisons of guselkumab 
with ustekinumab at Week 48, will also be performed.
Efficacy, PK, and PD parameters, biomarkers, and safety will be assessed according to the 
Schedule of Activities (Section 1.3).
Database locks (DBLs) are planned for Week 12 and Week 48. Additional DBLs (eg, Week 24) 
may be added as necessary and will be specified in the SAP.
4.1.2.
Phase 3 Dose-Confirming Studies (GALAXI 2 and GALAXI 3): 
Induction and Maintenance
4.1.2.1.
Overview of Phase 3 Design
GALAXI 2 and GALAXI 3 are identical studies from a study design perspective. The purpose of 
conducting two replicate studies is to achieve independent confirmation of clinical efficacy in two 
independent samples of patients, which is required by some health authorities. At Week 0, a target
of approximately 980 participants will be randomly allocated to GALAXI 2 (n=approximately 
490) or GALAXI 3 (n=approximately 490), using a permuted block randomization with baseline 
CDAI score (≤300 or >300), baseline SES-CD score (≤12 or >12), prior BIO-Failure status 
(Yes/No), and baseline corticosteroid use (Yes/No) as the stratification variables. Within each 
stratum, participants in each study will be randomized in a 2:2:2:1 ratio to receive 1 of 2 dose 
regimens of guselkumab, ustekinumab, or placebo, respectively. Within each study (GALAXI 2 
and GALAXI 3), an approximate 25% to 50% of the total enrolled population will be participants 
who are CON-Failures. Allocation to treatment groups will be performed using a central 
randomization center by means of an IWRS.
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All participants who complete the Week 48 evaluations may be eligible to enter the LTE and 
continue to receive approximately 4 additional years of treatment, as described in Section 4.1.3.
4.1.2.3.
Endpoints and Evaluations
Both GALAXI 2 and GALAXI 3 have the same co-primary and major secondary endpoints, 
whether Global or Regional.
Within each study, the Global co-primary endpoints are:

clinical response at Week 12 and clinical remission at Week 48

clinical response at Week 12 and endoscopic response at Week 48
Within each study, the Regional co-primary endpoints are:

clinical remission at Week 12

endoscopic response at Week 12
For the Global co-primary endpoints, comparisons will be made within each study between each
guselkumab dose group and placebo. For the Regional co-primary endpoints, comparisons will be 
made within each study between the combined guselkumab induction dose group and placebo, as 
the guselkumab induction dose is the same up to Week 12. All major secondary endpoints are 
listed in Section 3.2.2. Other efficacy endpoints are described in Section 9.4.1.2.
Efficacy, PK, and PD parameters, biomarkers, and safety will be assessed according to the 
Schedule of Activities (Section 1.3).
A DBL is planned for the Phase 3 Week 48 dataset. Additional DBLs may be added if necessary 
and will be specified in the SAP.
4.1.3.
Long-Term Extension for GALAXI 1, 2, and 3
The LTE will be conducted for approximately 4 years, from Week 48 through Week 252.
At Week 48 of GALAXI 1, GALAXI 2, or GALAXI 3, all participants who, in the opinion of the 
investigator, will continue to benefit from treatment (ie, based on Week 48 clinical and endoscopic 
evaluations) are eligible to enter the LTE to receive approximately 4 additional years of treatment, 
during which time the longer-term efficacy and safety of guselkumab will be evaluated. All 
participants will be assessed according to the Schedule of Activities (Section 1.3). The final
efficacy and safety follow-up (FES) visit of the LTE will occur at approximately Week 248 or 252
(ie, approximately 16 weeks after their last study intervention administration at Week 232 [for 
 
dosing] or Week 236 [for 
 dosing]).
Participants who are not eligible to enter the LTE at Week 48 are to return for an FES visit 
16 weeks after their last study intervention administration.
During the LTE, all participants will continue to receive the same treatment regimen (ie, 
guselkumab, ustekinumab, or placebo) that they were receiving at the end of GALAXI 1, 
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GALAXI 2, or GALAXI 3. The first study intervention administration in the LTE will occur at 
Week 48 and the last study intervention administration will occur at Week 236. Treatment 
adjustment for inadequate response is permitted between Week 52 and Week 80 of the LTE, as 
described in Section 4.1.3.1.
Beginning at Week 48, at the discretion of the investigator and participant, and after appropriate 
and documented training, participants may self-administer study intervention at the investigative 
site. A caregiver may also be trained to administer study intervention. After receiving training at 
Week 48, participants who are eligible for self- (or caregiver) administration of study intervention 
will be supplied with study intervention for at-home administration and will have their first at-
home administration at Week 52. Participants who are unable or unwilling to have study 
intervention administered away from the investigative site will continue administration at the 
investigative site. See Section 4.1.3.2 for further details.
All participants will continue to receive active or placebo study intervention administration in the 
LTE in a blinded fashion until study unblinding, which will occur after the Week 48 DBL and the 
Week 48 analyses have been completed for the Phase 2 study (for participants entering the LTE 
from GALAXI 1) or for the Phase 3 studies (for participants entering the LTE from GALAXI 2 or
GALAXI 3).
After study unblinding, all participants who are on active treatment (ie, guselkumab or
ustekinumab) will continue to receive their assigned active treatment for the remaining duration 
of the LTE through Week 236. Participants who are on placebo will be discontinued from study 
intervention upon study unblinding and will have an FES visit at that time.
 
 
 
 
 
 
4.1.3.1.
Treatment Adjustment for Inadequate Response
Participants from all treatment groups (ie, guselkumab, ustekinumab, and placebo) who meet 
inadequate response criteria between Week 52 (ie, the first visit at which treatment adjustment is 
permitted) and Week 80 (ie, the last visit at which treatment adjustment is permitted) will be 
eligible for a single treatment adjustment (ie, the first-time inadequate response criteria are met).
Inadequate response is defined as not being in clinical response AND having a CDAI score of at 
least 220 points. 
Clinical response is defined as a reduction from baseline (ie, Week 0) in the CDAI score of 
≥100 points or being in clinical remission (CDAI <150).
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CDAI assessments may be conducted at
visits between Weeks 52 and 80 (inclusive) to support 
the evaluation of CDAI response status. Participants who meet inadequate response criteria, and 
who are not already receiving the highest guselkumab 
 maintenance dose regimen, are eligible 
to receive treatment adjustment as described below. 
Participants (who are receiving placebo, ustekinumab, or the lower 
 maintenance dose of 
guselkumab) will be eligible to receive a single, blinded, treatment adjustment to the highest 
guselkumab 
 maintenance dose as defined in the Phase 2 or the Phase 3 portion of the protocol
in which they are enrolled. Participants who are already receiving the highest guselkumab 
 
maintenance dose will receive a single, blinded, sham treatment adjustment. Participants who have
received treatment adjustments will remain on their new treatment regimen through Week 92. At 
Week 96, the benefit of treatment adjustment will be evaluated. Continued participation in the 
remaining duration of the LTE will be decided on investigator’s clinical judgment of the results of 
the Week 96, 144, and 192 clinical and endoscopic evaluations. Discontinuation of study 
intervention should be considered in participants with persistent unsatisfactory response or 
clinically significant worsening Crohn’s disease where continuation of the study intervention is 
not in the best interest of the participant.
4.1.3.2.
Self-Administration of Study Intervention (or Administration by 
Caregiver) at Home
Study intervention will be administered at the investigative site by a health care professional (HCP) 
through Week 44.
Beginning at Week 48, at the discretion of the investigator and participant, and after appropriate 
and documented training, participants may self-administer study intervention at the investigative 
site according to regional/local regulations and instruction. A caregiver may also be trained to
administer study intervention.
After receiving training at Week 48, participants who are eligible for self- (or caregiver) study 
intervention administration will be supplied with study intervention for at-home administration 
and will have their first at-home administration at Week 52. Participants will record all at-home 
study intervention administrations on a diary card. Participants will also be instructed to contact 
the investigator promptly in the event of any signs of an allergic reaction, infection, or bleeding. 
Finally, participants will continue to have study visits and assessments at the investigative sites 
approximately 
through Week 240, as outlined in Section 1.3.
Participants who are unable or unwilling to have injections administered away from the site will 
be required to return to the site for administration of study intervention injection(s). Participants 
will continue to have study visits and assessments at the investigative site approximately 
(if 
receiving 
 dosing per protocol) or 
(if receiving 
 dosing per protocol) through 
Week 240, as outlined in Section 1.3.
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4.1.3.3.
Concomitant and Prohibited Therapies for Crohn’s Disease
During the LTE, all concomitant therapies for Crohn’s disease may be adjusted at the discretion 
of the investigator.
At any time during the study, the initiation of prohibited therapies for Crohn’s disease will result 
in discontinuation of study intervention administration.
For further details please refer to Section 6.5.
4.1.3.4.
Endpoints and Evaluations
Through Week 252, the longer-term efficacy and safety of guselkumab will be evaluated. In 
addition, the benefit of treatment adjustment will be evaluated based on descriptive analysis of 
various efficacy endpoints (to be specified in the SAP).
Efficacy, PK parameters, biomarkers, and safety will be assessed according to the Schedule of 
Activities (Section 1.3).
Phase 2 LTE database locks are planned at Week 96 (to evaluate the durability of efficacy 
evaluations and the benefit of dose adjustment) and at the final efficacy and safety visit in the LTE.
Phase 3 LTE database locks are planned at the final efficacy and safety visit in the LTE. Additional 
DBLs for Phase 2 and Phase 3 LTE may be added if necessary. 
4.2.
Scientific Rationale for Study Design
4.2.1.
Use of Placebo- and Active-Control
The inclusion of both placebo and active controls in the same protocol has several advantages. A 
short-term placebo-control period facilitates the evaluation of the efficacy and safety of a new 
treatment compared with placebo within a timeframe for which the use of placebo in participants 
with active disease is considered clinically acceptable in support of scientific research. The use of 
an active comparator control can alleviate the concern over the extended use of placebo and can 
also provide an opportunity to evaluate comparative efficacy and safety in a randomized-controlled 
setting in addition to comparison to placebo. There is significant clinical value to determine 
whether a new treatment option will provide similar or greater benefit to patients compared with 
an approved treatment option. 
Ustekinumab was selected as the active comparator because it targets an overlapping mechanism 
of action (ie, both IL-12/23 blockade) and the preclinical evidence suggests the potential for 
improved efficacy with more specific targeting of IL-23. Further, the proposed dosing of 
ustekinumab in this protocol is the highest currently approved induction-maintenance dose 
regimen and was one of the dose regimens evaluated in the ustekinumab Phase 3 clinical 
development program in Crohn’s disease. Therefore, the inclusion of ustekinumab as an active 
comparator in this program will provide a valuable and relevant benchmark for comparison with 
guselkumab. For additional information on the ustekinumab dose rationale, see Section 4.3.2.
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Ustekinumab is included as an active-reference arm in the Phase 2 study to collect data that will 
inform treatment effect size and sample size assumptions for the Phase 3 studies. Ustekinumab is 
included in the 2 Phase 3 studies as an active comparator control arm to enable the randomized-
controlled evaluation of the long-term efficacy and safety of the 2 guselkumab dose regimens 
compared with ustekinumab in addition to comparison to placebo through approximately 1 year 
(ie, Week 48) of treatment. 
4.2.2.
Biomarker and DNA Collection
Biomarker samples will be collected to evaluate the cellular and molecular mechanism of action 
of guselkumab and ustekinumab, or help to explain interindividual variability in clinical outcomes,
or may help to identify population subgroups that respond differently to either intervention. Serum 
biomarkers will be collected (where local regulations permit) from whole blood in all participants 
to assess PD markers associated with the response to guselkumab and ustekinumab. Whole blood 
samples will be collected from all participants to assess the effect of study intervention on 
ribonucleic acid (RNA) expression profiles. Ileocolonic biopsies will also be obtained from all 
participants pretreatment during screening and post-treatment at Weeks 12, 48, 96, 144, 192 and 
240 to assess cellular and molecular changes within the intestinal mucosal tissue. The goal of the 
biomarker analyses is to further define the mechanism of action of the selective blockade of IL-23 
with guselkumab compared with dual blockade of IL-12/23 with ustekinumab in Crohn’s disease, 
and to aid in evaluating the intervention-clinical response relationship. 
Two optional substudies are planned:

Optional Week 4 ileocolonoscopy substudy: The optional ileocolonoscopy substudy will be 
performed at Week 4 in a subset of participants who consent to participate and will include 
endoscopic assessment and intestinal biopsy. This substudy will target approximately 200 
study participants. Exploratory analyses of intestinal mucosal tissue obtained by biopsy at 
Week 4 will be performed to delineate the mechanisms of action of guselkumab and 
ustekinumab by establishing a sequence of molecular and cellular effects beginning at an early 
time point. In addition, data collected at Week 4 will be explored for correlation with clinical 
efficacy observations at later time points.

Optional pharmacogenomic substudy: 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, identify markers associated with disease susceptibility and prognosis, and may help 
to identify population subgroups that respond differently to an intervention. The goal of the 
pharmacogenomic component is to collect DNA to allow for the identification of genetic 
factors that may influence the PK, PD, efficacy, safety, or tolerability of guselkumab and to 
identify genetic factors associated with Crohn’s disease or the response to guselkumab or 
ustekinumab treatment. The focus of this analysis will be the evaluation of genetic single 
nucleic polymorphisms (SNPs) associated with Crohn’s disease and response to treatment 
with guselkumab.
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4.2.3.
Patient-Reported Outcomes on Health-Related Quality of Life
Patient-reported outcome (PRO) evaluations (ie, Inflammatory Bowel Disease Questionnaire
[IBDQ], PROMIS-29, PROMIS Fatigue 7-item Short Form, 5-level EuroQol 5 dimensions 
[EQ-5D-5L] instrument) will be used to assess the benefits of guselkumab treatment on disease-
specific and general HRQOL. Patient-reported outcome evaluations are only being collected in 
countries where translations of the evaluations are available. See Section 8.1 for more details.
4.2.4.
Medical Resource Utilization and Health Economics Data Collection
Medical resource utilization evaluations, including but not limited to Crohn’s disease-related 
hospitalizations and Crohn’s disease-related surgeries, will be collected for evaluation of the health 
economics of guselkumab treatment. Additionally, the impact of guselkumab treatment on work 
productivity will be assessed using the Work Productivity and Activity Impairment Questionnaire
in Crohn’s Disease (WPAI-CD).
4.2.5.
Study-Specific Ethical Design Considerations
Potential participants will be fully informed of the risks and requirements of the study and, during 
the study, participants will be given any new information that may affect their decision to continue
participation. They will be told that their consent to participate in the study is voluntary and may 
be withdrawn at any time with no reason given and without penalty or loss of benefits to which 
they would otherwise be entitled. Only participants who are fully able to understand the risks, 
benefits, and potential adverse events (AEs) of the study and provide their consent voluntarily will 
be enrolled.
The total blood volume to be collected from each participant in each study (maximum of 
approximately 500 mL over approximately 252 weeks) is far less than the American Red Cross 
standard limit for whole blood donation (approximately 475 mL q8w) and is, therefore, considered 
an acceptable amount of blood to be collected over this time period. For more details regarding 
blood collection, see Blood Sample Collection in Section 8.
4.3.
Justification for Dose
4.3.1.
Guselkumab
This section provides the rationale for the guselkumab dose regimens to be evaluated in the 
guselkumab Phase 2 dose-ranging study (GALAXI 1) and Phase 3 dose-confirming studies 
(GALAXI 2 and GALAXI 3) in participants with moderately to severely active Crohn’s disease.
4.3.1.1.
Phase 2 Dose-Ranging Study (GALAXI 1)
The following guselkumab dose regimens will be evaluated through Week 48 of GALAXI 1:

Guselkumab Regimen 1 – Induction:
 at Weeks 0, 4, 8; followed by Maintenance: 
 (ie, at Weeks 12, 16, 20, 24, 28, 32, 36, 40, and 44)

Guselkumab Regimen 2 – Induction: 
 at Weeks 0, 4, 8; followed by Maintenance: 
(ie, at Weeks 12, 16, 20, 24, 28, 32, 36, 40, and 44)
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No treatment adjustments are planned for any of the treatment groups from Week 0 through 
Week 48 of GALAXI 1, except for 
 induction placebo nonresponders who will cross over to 
receive the ustekinumab dose regimen being evaluated in this study (ie, 
 at Week 12 
followed by 
 from Week 20). Participants randomized to placebo 
 who are 
responders at Week 12 will continue to receive 
 placebo through Week 44.
4.3.1.2.
Phase 3 Dose-Confirming Studies (GALAXI 2 and GALAXI 3)
Based on the Phase 2 data, 2 guselkumab dose regimens (ie, 
) 
were selected for confirmatory evaluation in Phase 3.
The goal was to select a single induction dose regimen from the induction dose range evaluated 
(ie,
 to 
 at Week 0, Week 4, and Week 8) in the Phase 2 dose-ranging
study based on the totality of the efficacy, safety, and exposure-response data at the time of dose 
decision. The goal of selecting a single induction regimen to be evaluated in the Phase 3 dose-
confirming studies was based on the consideration that a sufficient amount of information would 
be available to establish an optimal induction dose regimen. In this scenario, the selected induction 
dose regimen was to be paired with 2 maintenance dose regimens selected from the range of 
exposures obtained from the guselkumab 
 dose regimens evaluated in Phase 2 (ie, between 
 
. As described in Section 4.1.2, the goal of selecting a single induction 
dose regimen to be paired with 2 maintenance dose regimens was achieved.
No treatment adjustments are planned for any of the treatment groups from Week 0 through 
Week 48 of GALAXI 2 and GALAXI 3, except for 
 induction placebo nonresponders who will 
cross over to receive the ustekinumab dose regimen being evaluated in this study (ie, 
 
at Week 12 followed by 
 from Week 20). Participants randomized to placebo 
 
who are responders at Week 12 will continue to receive 
 placebo through Week 44.
4.3.1.3.
Long-Term Extension (Week 48 to Week 240) for GALAXI 1, 2, and 3
Participants will continue on their assigned guselkumab maintenance dose during the LTE of 
GALAXI 1, GALAXI 2, and GALAXI 3. Participants who experience inadequate response 
between Week 52 through Week 80 while on the lower of the 2 maintenance dose regimens being 
evaluated in the applicable study will be eligible for a single dose adjustment and will receive the 
higher maintenance dose until the end of the LTE to assess if they can regain clinical response.
4.3.2.
Ustekinumab
Ustekinumab (STELARA) is approved in many countries (including the US, EU, Canada, and 
Japan) for the treatment of Crohn’s disease and is included in this study as an active comparator 
for comparisons with guselkumab after Week 12. The ustekinumab dosages selected for the study 
were found to be safe and effective in the pivotal Phase 3 studies of ustekinumab in patients with 
Crohn’s disease.8,22 All participants enrolled in the ustekinumab group will receive a single 
 
induction dose of approximately 
 (based on weight tiers), which is the approved induction 
dose for patients with Crohn’s disease. From Week 8, participants will receive a maintenance dose 
regimen of 
 Of note, the ustekinumab 
 regimen was chosen for the maintenance 
dose regimen as opposed to the every-12-weeks regimen as it more reliably demonstrated efficacy 
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across a range of clinical endpoints, especially with more stringent measures of efficacy such as 
sustained remission, in the pivotal ustekinumab Crohn’s disease maintenance study (IM-UNITI). 
Evaluating the 
 regimen would, therefore, provide participants randomized to ustekinumab
with the best chance for the highest levels of efficacy, thus allowing the fairest comparison for 
testing the superiority of guselkumab to ustekinumab.
4.4.
End of Study Definition
For each of the 3 studies conducted under this protocol, the studies are considered completed when 
the last participant completes the last scheduled study assessment shown in the Schedule of 
Activities (Section 1.3) or if a decision has been made by the sponsor not to pursue an indication 
in Crohn’s disease and appropriate follow-up has been completed. The final data from the study 
site will be sent to the sponsor (or designee) after completion of the final participant assessment at 
that study site, in the time frame specified in the Clinical Trial Agreement.
5.
STUDY POPULATION
A target of approximately 1,340 participants combined will be enrolled under the GALAXI 
protocol and will be randomized into the Phase 2 study (GALAXI 1) or one of the two Phase 3 
studies (GALAXI 2 or GALAXI 3).
Screening for eligible participants will be performed within approximately 5 weeks before 
administration of the study intervention. Refer to Section 5.4, Screen Failures, for conditions under 
which repeating any screening procedures are allowed.
The inclusion and exclusion criteria for enrolling participants in this study are described in the
following 2 subsections. If there is a question about the inclusion or exclusion criteria below, the 
investigator must consult with the appropriate sponsor representative or designee 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.
5.1.
Inclusion Criteria
Each potential participant must satisfy all of the following criteria to be enrolled in the protocol: 
1.
Be male or female (according to their reproductive organs and functions assigned by 
chromosomal complement) ≥18 years of age.
2.
Have Crohn’s disease or fistulizing Crohn’s disease of at least 3 months duration (defined as 
a minimum of 12 weeks), with colitis, ileitis, or ileocolitis, confirmed at any time in the past 
by radiography, histology, and/or endoscopy.
3.
Have clinically active Crohn’s disease, defined as a baseline CDAI score ≥220 but ≤450 and 
either:
a.
Mean daily SF count >3, based on the unweighted CDAI component of the number of 
liquid or very soft stools 
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OR
b.
Mean daily AP score >1, based on the unweighted CDAI component of AP
4.
Criterion modified per Amendment 1.
4.1. Criterion modified per Amendment 3.
4.2. Criterion modified per Amendment 5.
4.3. Have endoscopic evidence of active ileocolonic Crohn’s disease as assessed by central 
endoscopy reading at the screening endoscopy (Schedule of Activities, Table 4), defined as a 
screening SES-CD score ≥6 (or ≥4 for participants with isolated ileal disease), based on the 
presence of ulceration in at least 1 of the 5 ileocolonic segments, resulting in the following 
specified ulceration component scores:
a.
a minimum score of 1 for the component of “size of ulcers”
AND
b.
a minimum score of 1 for the component of “ulcerated surface”. 
Of note, before the implementation of Amendment 3, where the minimum SES-CD score was 
≥3 based on the presence of ulceration, within each of the studies, a maximum of 10% of the 
total enrolled population could include participants who had baseline scores for SES-CD <4 
(ie, for participants with isolated ileal disease) or SES-CD <7 (ie, for participants with colonic 
or ileocolonic disease). 
Note: Adenomatous polyps should be removed before the first administration of study agent. 
Histopathology for polyps or for any biopsies performed during the screening ileocolonoscopy 
due to concern or surveillance for malignancy should be negative for malignancy and 
dysplasia (low-grade, high-grade, or “indefinite dysplasia in reactive atypia”) prior to the first 
dose of study intervention. Please refer to Exclusion Criterion #20 regarding metaplasia. 
Concomitant or previous medical therapies received
5.
Criterion modified per Amendment 4.
5.1. Criterion modified per Amendment 5.
5.2. Prior or current medication for Crohn’s disease must include at least 1 of the following, 
and must fulfill additional criteria as described in Appendix 2 (Section 10.2), Appendix 
3 (Section 10.3), and Appendix 4 (Section 10.4), as applicable:
a. Current treatment with oral corticosteroids (including budesonide and beclomethasone 
dipropionate) and/or immunomodulators (AZA, 6-MP, MTX)
OR
b. History of failure to respond to, or tolerate, at least 1 of the following therapies:  oral 
corticosteroids (including budesonide
and beclomethasone dipropionate) or 
immunomodulators (AZA, 6-MP, MTX).
OR
c. History of corticosteroid dependence (ie, an inability to successfully taper 
corticosteroids without a return of the symptoms of Crohn’s disease).
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OR
d. Has previously demonstrated lack of initial response (ie, primary nonresponders), 
responded initially but then lost response with continued therapy (ie, secondary 
nonresponders), or were intolerant to 1 or more biologic agents with at least the 
minimum dose approved for the treatment of Crohn's disease (ie, infliximab, 
adalimumab, certolizumab pegol, vedolizumab, or approved biosimilars for these 
agents, see Appendix 3 [Section 10.3]).
Note: Participants meeting criteria 5a-c may also be naïve to biologic therapy (ie, a TNF 
antagonist or vedolizumab or ustekinumab) or may have been exposed to these biologic 
therapies but have not demonstrated inadequate response or intolerance. Participants with 
prior exposure to IL-12/23 or IL-23 agents are ineligible for entry into this protocol, with 
the exception of participants who have had exposure to ustekinumab at its approved 
labeled dosage AND have met the required washout criterion AND have not demonstrated 
failure or intolerance to ustekinumab (per Exclusion Criterion 7, Appendix 4
[Section 10.4]).  
6.
Adhere to the following requirements for concomitant medication for the treatment of Crohn's 
disease. The following medications are permitted provided that doses meeting the 
requirements listed below are stable or have been discontinued prior to baseline within the 
timeframes specified below:
a.
Oral 5-aminosalicylic acid (5-ASA) compounds on stable doses for at least 2 weeks; 
or if recently discontinued, must have been stopped for at least 2 weeks. 
b.
Oral corticosteroids at a prednisone-equivalent dose at or below 
day, or 
/day of budesonide, or 
/day beclomethasone dipropionate, and on stable 
dosing for at least 2 weeks; or if recently discontinued, must have been stopped for at 
least 2 weeks.
c.
Conventional immunomodulators (ie, AZA, 6-MP, or MTX) for at least 12 weeks and 
have been on a stable dose for at least 4 weeks; or if recently discontinued, must have 
been stopped for at least 4 weeks.
d.
If receiving antibiotics as a primary treatment of Crohn's disease, doses must be stable 
for at least 3 weeks; or if recently discontinued, must have been stopped for at least 
3 weeks.
e.
If receiving enteral nutrition as a primary treatment for Crohn’s disease, must have 
been receiving for at least 2 weeks; or if recently discontinued, must have been stopped 
for at least 2 weeks.
Screening laboratory tests
7.
Have screening laboratory test results within the following parameters, and if 1 or more of the 
laboratory parameters is out of range, a single retest of laboratory values is permitted during 
the approximately 5-week screening period:
a.
Hemoglobin ≥8.0 g/dL. 
b.
White blood cells (WBCs) ≥3.5 x 103/µL.
c.
Neutrophils ≥1.5 x 103/µL.
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d.
Platelets ≥100 x 103/µL.
e.
Serum creatinine ≤1.5 mg/dL.
f.
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations 
must be ≤2 times the upper limit of normal (ULN) range for the laboratory conducting 
the test.
g.
Direct (conjugated) bilirubin <1.0 mg/dL.
Tuberculosis
8.
Criterion modified per Amendment 3.
8.1. Criterion modified per Amendment 5.
8.2. Are considered eligible according to the following tuberculosis (TB) screening criteria: 
a.
Have no history of latent or active TB prior to screening. An exception is made for 
participants who have a history of latent TB AND who satisfy one of the following 
criteria:
o
currently receiving treatment for latent TB
o
will initiate treatment for latent TB prior to the first administration of study 
intervention 
OR
o
have documentation of having completed appropriate treatment for latent TB within 
5 years prior to the first administration of study intervention. It is the responsibility 
of the investigator to verify the adequacy of previous anti-tuberculosis treatment and 
provide appropriate documentation.
b.
Have no signs or symptoms suggestive of active TB upon medical history and/or 
physical examination. 
c.
Have had no recent close contact with a person with active TB or, if there has been 
such contact, will be referred to a physician specializing in TB to undergo additional 
evaluation and, if warranted, receive appropriate treatment for latent TB prior to or 
simultaneously with the first administration of study intervention.
d.
Criterion modified per Amendment 3.
8.d.1. Criterion modified per Amendment 5.
8.d.2. Within 8 weeks prior to the first administration of study intervention, have a 
negative QuantiFERON®-TB test result (or T-SPOT® Test for sites in Japan where local 
regulations permit), or have a newly identified positive QuantiFERON-TB test (or 
T-SPOT Test for sites in Japan) in which active TB has been ruled out and for which 
appropriate treatment for latent TB has been initiated either prior to or simultaneously 
with the first study intervention administration (see Section 8.2.6). Indeterminate or 
suspected false positive results should be handled as outlined in Section 8.2.6.
Note: A negative tuberculin skin test result (see Appendix 5 [Section 10.5]) is additionally 
required if the QuantiFERON-TB test is not approved/registered in the country in which 
this protocol is being conducted. In Ukraine, while the QuantiFERON-TB test is not 
approved/registered, it is acceptable, and an additional tuberculin skin test is not required.
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The QuantiFERON-TB test (or T-SPOT test for sites in Japan where local regulations 
permit) and the tuberculin skin test are not required at screening for participants with a 
history of latent TB, if active TB has been ruled out, and if appropriate treatment has been 
initiated/completed as described above in Inclusion Criterion 8a.
e.
Criterion modified per Amendment 3.
8.e.1. Have a chest radiograph (both posterior-anterior and lateral views, or per 
local/country
regulations where applicable),
taken ≤12 weeks before the first 
administration of study intervention and read by a qualified radiologist or qualified 
pulmonologist according to local clinical practice, with no evidence of current, active TB 
or old, inactive TB. A chest CT scan is also acceptable if obtained instead of a chest 
radiograph outside of the protocol.
Contraception
Contraceptive (birth control) use by men or women should be consistent with local regulations 
regarding the acceptable methods of contraception for those participating in clinical studies.
Typical use failure rates may differ from those when used consistently and correctly. Use should 
be consistent with local regulations regarding the use of contraceptive methods for participants in 
clinical studies.
9.
A female participant of childbearing potential must have a negative urine pregnancy test result 
at screening and baseline.
10. Before randomization, a female participant must be (as defined in Appendix 6 [Section 10.6], 
Contraceptive and Barrier Guidance and Collection of Pregnancy Information):
a.
Not of childbearing potential
b.
Of childbearing potential and: 
o
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 16 weeks after last dose (ie, the 
end of relevant systemic exposure). Examples of highly effective methods of 
contraception are located in Appendix 6 (Section 10.6), Contraceptive and Barrier 
Guidance and Collection of Pregnancy Information; 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.
11. A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted 
reproduction during the study and for a period of 16 weeks after the last administration of 
study intervention.
12. During the study and for at least 16 weeks after the last administration of study intervention, 
a male participant
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a.
who is sexually active with a female of childbearing potential must agree to use a 
barrier 
method 
of 
contraception 
(eg, 
condom 
with 
spermicidal 
foam/gel/film/cream/suppository).
b.
who is sexually active with a pregnant female must use a condom. 
c.
must agree not to donate sperm for the purpose of reproduction. 
General
13. Criterion modified per Amendment 1.
13.1. Criterion modified per Amendment 2.
13.2. Be willing and able to adhere to all specified requirements, including but not limited to 
completion of assessments, adherence to visit schedule, and compliance with the lifestyle 
restrictions (Section 5.3), etc, as specified in this protocol.
14. Must sign an informed consent form (ICF) indicating that he or she understands the purpose 
of, and procedures required for, the study and is willing to participate in the study.
15. Must sign a separate ICF if he or she agrees to provide an optional DNA sample for research 
(where local regulations permit). Refusal to give consent for the optional DNA research 
sample does not exclude a participant from participation in the study.
5.2.
Exclusion Criteria
Any potential participant who meets any of the following criteria will be excluded from 
participating in the protocol:
1. Has complications of Crohn’s disease, such as symptomatic strictures or stenoses, short gut 
syndrome, or any other manifestation, that might be anticipated to require surgery, could 
preclude the use of the CDAI to assess response to therapy, or would possibly confound the 
ability to assess the effect of treatment with guselkumab or ustekinumab.
2. Currently has or is suspected to have an abscess. Recent cutaneous and perianal abscesses are 
not exclusionary if drained and adequately treated at least 3 weeks before baseline, or 8 weeks 
before baseline for intra-abdominal abscesses, provided that there is no anticipated need for 
any further surgery. Participants with active fistulas may be included if there is no anticipation 
of a need for surgery and no abscesses are currently identified.
3. Criterion modified per Amendment 3.
3.1. Has had any kind of bowel resection within 6 months, or any other intra-abdominal or 
other major surgery within 12 weeks before baseline. 
4. Has a draining (ie, functioning) stoma or ostomy. 
5. Criterion modified per Amendment 4. 
5.1. Has a stool culture or other examination positive for an enteric pathogen, including 
Clostridioides difficile (formerly known as Clostridium difficile) toxin, in the previous 4 
months, unless a repeat examination is negative and there are no signs of ongoing infection 
with that pathogen.
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Concomitant or previous medical therapies received
6. Criterion modified per Amendment 3.
6.1. Criterion modified per Amendment 4.
6.2. Criterion modified per Amendment 5.
6.3. Has received any of the following prescribed medications or therapies within the specified 
period: 
a.
 corticosteroids received within 3 weeks of baseline
b. Cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil received within 8 
weeks of baseline
c. 6-thioguanine received within 4 weeks of baseline
d. Biologic agents: 
1) Anti-TNF therapy (eg, infliximab, etanercept, certolizumab
pegol, 
adalimumab, golimumab) received within 8 weeks of baseline
2) Vedolizumab received within 12 weeks of baseline
3) Ustekinumab received within 16 weeks of baseline
Note: A shorter washout duration for anti-TNF agents, ustekinumab or vedolizumab 
is acceptable if undetectable drug levels of the biologic can be demonstrated.
Undetectable levels are defined as levels below the quantification limit using approved 
commercial testing.
4) Other immunomodulatory biologic agents, including approved and 
investigational biologic agents, received within 12 weeks of baseline or within 
5 half-lives of baseline, whichever is longer.
e. Any investigational intervention received within 4 weeks of baseline or within 5 
half-lives of baseline, whichever is longer. (Refer to Exclusion Criterion 6.d.4 for 
investigational biologic agents.)
f. Nonautologous stem cell therapy (eg, Prochymal), natalizumab, efalizumab, or 
biologic agents that deplete B- or T-cells (eg, rituximab, alemtuzumab, or 
visilizumab) received within 12 months of baseline. 
g. Treatment with apheresis (eg, Adacolumn apheresis) or total parenteral nutrition 
for Crohn’s disease within 3 weeks of baseline.  
7. Criterion modified per Amendment 5.
7.1. Has previously received a biologic agent targeting IL-12/23 or IL-23, including but not 
limited to briakinumab, brazikumab, guselkumab, mirikizumab (formerly LY3074828), 
and risankizumab.
Exception: Participants who have had exposure to ustekinumab at its approved labeled dosage 
AND have met the required washout criterion AND have not demonstrated failure or 
intolerance to ustekinumab (criteria specified in Appendix 4 [Section 10.4]) are not excluded 
from this protocol provided that other inclusion criteria have been satisfied and no other 
exclusion criteria are met.
C
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Infections or predisposition to infections:
8. Has a history of, or ongoing, chronic or recurrent infectious disease, including but not limited 
to, chronic renal infection, chronic chest infection (eg, bronchiectasis), recurrent urinary tract 
infection (eg, recurrent pyelonephritis or chronic non-remitting cystitis), or open, draining, or 
infected skin wounds or ulcers.
9. Has current signs or symptoms of a clinically significant infection. Established non-serious 
infections (eg, acute upper respiratory tract infection, simple urinary tract infection) need not 
be considered exclusionary at the discretion of the investigator.
10. Has a history of serious infection (eg, hepatitis, sepsis, pneumonia, or pyelonephritis), 
including any infection requiring hospitalization or IV antibiotics, during the 8 weeks before 
baseline. 
11. Has evidence of a herpes zoster infection within 8 weeks before baseline.
12. Has a history of latent or active granulomatous infection, including histoplasmosis or 
coccidioidomycosis, prior to screening. Participants with radiographic evidence of possible 
prior histoplasmosis or coccidioidomycosis will be excluded.
13. Has a chest radiograph within 12 weeks prior to the first administration of study intervention
that shows an abnormality suggestive of a malignancy or current active infection, including 
TB.
14. Has or has had a nontuberculous mycobacterial infection or clinically significant opportunistic 
infection (eg, cytomegalovirus colitis, pneumocystosis, invasive aspergillosis).
15. Participants must undergo screening for human immunodeficiency virus (HIV). Any 
participant who has a history of HIV antibody positivity, or tests positive for HIV at screening, 
is not eligible for this study. 
16. Criterion revised per Amendment 1.
16.1. Criterion revised per Amendment 4.
16.2. Participants who are seropositive for antibodies to hepatitis C virus (HCV), unless they 
satisfy one of the following conditions: 
a. Have a history of successful treatment (defined as being negative for HCV RNA at 
least 12 weeks after completing antiviral treatment) and have a negative HCV RNA 
test result at screening, OR 
b. While seropositive have a negative HCV RNA test result at least 12 weeks prior to 
screening and a negative HCV RNA test result at screening.
17. Tests positive for hepatitis B virus (HBV) infection (Appendix 7 [Section 10.7]).
Note: For participants who are not eligible for this study due to HIV, HCV, HBV, or TB test 
results, consultation with a physician with expertise in the treatment of those infections is 
recommended. 
18. Has received, or is expected to receive, any live virus or bacterial vaccination within 12 weeks 
before the first administration of study intervention. For Bacille Calmette-Guérin (BCG)
vaccine, see Exclusion Criterion 19.
19. Has had a BCG vaccination within 12 months of screening.
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Malignancy or increased potential for malignancy
20. Criterion modified per Amendment 5.
20.1. Currently has a malignancy or has a history of malignancy within 5 years before 
screening (with the exception of a nonmelanoma skin cancer that has been adequately treated 
with no evidence of recurrence for at least 3 months [defined as a minimum of 12 weeks]
before the first study intervention administration or cervical carcinoma in situ that has been 
treated with no evidence of recurrence for at least 3 months before the first study intervention
administration).
Note: Premalignant conditions (eg, gastric or esophageal metaplasia) should be discussed with 
the sponsor for eligibility determination.
21. Has a known history of lymphoproliferative disease, including lymphoma, or signs and 
symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy, 
hepatomegaly, or splenomegaly, or monoclonal gammopathy of undetermined significance.
Coexisting medical conditions or past medical history
22. Has a history of severe, progressive, or uncontrolled renal, genitourinary, hepatic, hematologic, 
endocrine, cardiac, vascular, pulmonary, rheumatologic, neurologic, psychiatric, or metabolic 
disturbances, or signs and symptoms thereof.
23. Has a transplanted organ (with exception of a corneal transplant >12 weeks before screening). 
24. Is unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack 
of adequate venous access.
25. Is known to have had a history of drug or alcohol abuse according to Diagnostic and Statistical 
Manual of Disorders (5th edition) (DSM-V) criteria within 12 months before baseline.
26. Has unstable suicidal ideation or suicidal behavior in the last 6 months that may be defined as 
a Columbia-Suicide Severity Rating Scale (C-SSRS) rating at screening of: Suicidal Ideation 
with Intention to Act (“Ideation level 4”), Suicidal Ideation with Specific Plan and Intent 
(“Ideation level 5”), or suicidal behavior (actual suicide attempt, 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.
27. Has known allergies, hypersensitivity, or intolerance to guselkumab or ustekinumab or any of 
their excipients (see guselkumab IB and ustekinumab IB).
28. Is a woman who is pregnant, or breastfeeding, or planning to become pregnant while enrolled 
in this study or within 16 weeks after the last administration of study intervention. 
29. Is a man who plans to father a child while enrolled in this study or within 16 weeks after the 
last administration of study intervention. 
General
30. Is currently enrolled in or intends to participate in any other study using an investigational 
agent or procedure during participation in this study. 
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31. Criterion modified per Amendment 5.
31.1. Has any condition for which, in the opinion of the investigator or sponsor, 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.
32. 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.
33. Has previously undergone allergy immunotherapy for prevention of anaphylactic reactions (eg, 
venom immunotherapy).
Infections or predisposition to infections:
34. Coronavirus Disease 2019 (COVID-19) infection
During the 6 weeks prior to baseline, have had ANY of (a) confirmed severe acute respiratory 
syndrome coronavirus 2 (SARS-CoV-2) 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
(i)
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
(ii)
with absence of ALL conditions (a), (b), (c) above during the period 
between the negative test result and the baseline study visit 
Note on the COVID-related exclusion: 

The field of COVID-related testing (for presence of, and immunity to, the SARS-CoV-2 
virus) is rapidly evolving. Additional testing may be performed as part of screening and/or 
during the study if deemed necessary by the investigator and in accordance with current 
regulations / guidance from authorities / standards of care. 
Precaution: for those who may carry a higher risk for severe COVID-19 illness (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. 
NOTE: Investigators should ensure that all study enrollment criteria have been met at screening. 
If a participant's clinical status changes (including any available laboratory results or receipt of 
additional medical records) after screening but before the first dose of study intervention is given 
such that he or she no longer meets all eligibility criteria, then the participant should be excluded 
from participation in the study. Section 5.4, Screen Failures, describes options for retesting. The 
required source documentation to support meeting the enrollment criteria are noted in 
Appendix 10.8, Regulatory, Ethical, and Study Oversight Considerations.
5.3.
Lifestyle Considerations
Potential participants must be willing and able to adhere to the following lifestyle restrictions 
during the course of the study to be eligible for participation:
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1.
Lifestyle consideration modified per Amendment 4.
1.1. Refer to Section 6.5, Concomitant Therapy, for details regarding prohibited and restricted 
therapy during the study.
It is recommended that participants are up-to-date on all age-appropriate vaccinations prior 
to screening per routine local medical guidelines. For study participants who received 
locally approved (including emergency-use-authorized) COVID-19 vaccine(s) recently 
prior to study entry, follow applicable local vaccine labeling, guidelines, and standards of 
care for patients receiving immune-targeted therapy when determining an appropriate 
interval between vaccination and study enrollment (see also Section 6.5.3 Vaccinations 
[Including COVID-19]).
2.
Agree to follow all requirements that must be met during the study as noted in the inclusion 
and exclusion criteria (eg, contraceptive requirements).
3.
Must not receive guselkumab or ustekinumab outside of this protocol or participate in any 
other clinical study with an investigational agent while in this study and must terminate study 
participation if they do. A participant who intends to participate in any other clinical study 
with an investigational agent should undergo a SID visit before he or she terminates study 
participation.
4.
Must agree not to receive a live virus or live bacterial vaccination during the study and for 
12 weeks after receiving the last dose of study intervention.
5.
Lifestyle consideration modified per Amendment 4.
5.1. Must agree not to receive a BCG vaccination during the study and for 16 weeks after 
receiving the last dose of study intervention.
6.
Participants who require treatment for latent TB must complete the appropriate course of TB 
therapy.
7.
Must be willing and able to complete a daily diary to document clinical symptoms, AEs, etc.
5.4.
Screen Failures
Participant Identification, Enrollment, and Screening Logs
The investigator agrees to complete a participant identification and enrollment log to permit easy 
identification of each participant during and after the study. This document will be reviewed by 
the sponsor or designee study site contact for completeness.
The participant identification and enrollment log will be treated as confidential and will be filed 
by the investigator in the study file. To ensure participant confidentiality, no copy will be made. 
All reports and communications relating to the study will identify participants by participant 
identification and date of birth (as allowed by local regulations). In cases where the participant is 
not randomized into the study, the date seen and date of birth (as allowed by local regulations) will 
be used.
Completion of screening and randomization procedures within the specified screening window of 
approximately 5 weeks is required.
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If any delay leads to the expiration of time-specific assessments (eg, TB, chest radiograph, stool 
analysis, ileocolonoscopy), the participant will be considered a screen failure because he/she will 
not meet eligibility criteria, and the expired assessments (along with the non-time-specific 
laboratory tests) will have to be repeated on rescreening.
Additional criteria for retesting and rescreening are outlined below.
Retesting
Retesting of abnormal laboratory values that may lead to exclusion will be allowed once. Retesting 
can occur at an unscheduled visit during the screening phase, as long as this is done within the 
specified screening window of approximately 5 weeks.
Rescreening
Participants who do not meet the criteria for participation in this study (screen failure) may be 
rescreened. Participants who are rescreened will be assigned a new participant number, undergo 
the informed consent process, and then start a new screening phase including the collection and 
testing of new laboratory specimens. Previous TB evaluation results (including the QuantiFERON-
TB test [or TSPOT test for sites in Japan where local regulations permit] and chest radiograph) 
and stool study results, and ileocolonoscopy results from the first screening event may be used if 
they meet the specified protocol criteria as described in Section 5.1.  Medical Monitor approval is 
required prior to the study site obtaining a new informed consent for rescreening.
6.
STUDY INTERVENTION
6.1.
Study Interventions Administered
In both the Phase 2 and Phase 3 portions of the protocol:

All participants will receive 2 IV infusions at Week 0 (1 active + 1 placebo OR 2 placebo) 
and 1 IV infusion at Weeks 4, 8, and 12 (either active or placebo). 

All participants will receive 1 
 injection (either active or placebo) at Week 8 and up to 3 
 injections (either active or placebo) at each visit from Week 12 to Week 140. 
 study intervention (including the flush) should be administered over a period of not 
less than 1 hour, and not more than 2 hours. The infusion (including the flush) should be completed 
within 6 hours of preparation. 
At Week 0, the guselkumab/placebo in dextrose IV infusion (including the flush with dextrose) 
should be administered first. The IV infusion administration line set will be changed (ie, use a new 
line set) prior to the administration of the ustekinumab/placebo in saline IV infusion, followed by 
the flush with saline.
At Week 4, only guselkumab/placebo in dextrose IV infusion is administered (including the flush 
with dextrose).
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At Week 8, the guselkumab/placebo in dextrose IV infusion (including the flush with dextrose) 
should be administered first, followed by 
 injection with ustekinumab/placebo investigational 
product (IP).
At Week 12, the ustekinumab/placebo in saline IV infusion (including the flush with saline) should 
be administered first, followed by 
 injection with guselkumab/placebo IP.
At Week 12 and beyond, multiple 
 injections may be administered within the administration 
visit. Each injection of study intervention should be given at a different location of the body.
Detailed instructions on the preparation and administration of study intervention will be provided 
in the site Investigational Product Procedures Manual (IPPM).
Guidelines for study intervention administration affected by the COVID-19 pandemic are found 
in Section 10.14.
6.1.1.
Combination Products
 
 
 
 
 
 
 
 
 
 
 
 
 
6.2.
Preparation/Handling/Storage/Accountability
6.2.1.
Guselkumab
Guselkumab and placebo for guselkumab will be supplied to the study sites. All guselkumab and 
placebo for guselkumab must be stored at controlled temperatures ranging from 36°F to 46°F (2°C 
to 8°C) and protected from exposure to light. The sterile product does not contain preservatives 
and is designed for single use only. It should be clear to slightly yellow and may contain tiny white 
or clear particles. Do not use if the liquid is cloudy or discolored or has large particles. Protection 
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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.
Further details regarding the preparation and storage of guselkumab and placebo will be provided 
in the site IPPM.
6.2.2.
Ustekinumab
All ustekinumab must be stored at controlled temperatures ranging from 36°F to 46°F (2°C to 
8°C), not frozen, and protected from light. Vigorous shaking of the product should be avoided.
Prior to administration, the product should be inspected visually for particulate matter and 
discoloration. If discoloration (other than a slight yellow color), visible opaque particles, or other 
foreign particles are observed in the solution, the product should not be used.
Aseptic procedures must be used during the preparation and administration of the study
intervention material. Exposure to direct sunlight should be avoided during preparation and 
administration.
The needle cover on the 
 contains dry natural rubber (a derivative of latex), which may cause 
allergic reactions in individuals sensitive to latex.
Further details regarding the preparation and storage of ustekinumab and placebo will be provided 
in the site IPPM.
6.2.3.
Accountability
The investigator is responsible for ensuring that all study intervention received at the site is 
inventoried and accounted for throughout the study. The study intervention administered to the 
participant must be documented on the intervention accountability form. All study intervention 
will be stored and disposed of according to the sponsor's instructions. The dispensing of study 
intervention to the participant, and the return of study intervention from the participant, must be 
documented on the intervention accountability form. Participants must be instructed to return all 
original containers, whether empty or containing study intervention.
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 or designee’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 containing 
hazardous liquids should be disposed of immediately in a safe manner and therefore will not be 
retained for intervention accountability purposes. The immediate destruction of these drug supplies 
should be documented in the drug accountability records on site.
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Study intervention should be dispensed under the supervision of the investigator or a qualified 
member of the study site personnel, or by a hospital/clinic pharmacist. Study intervention will be 
supplied only to participants participating in the study. Returned study intervention must not be 
dispensed again, even to the same participant. Study intervention may not be reassigned for use by 
other participants. The investigator agrees not to dispense the study intervention from, or store it 
at, any site other than the study sites agreed upon with the sponsor.
6.3.
Measures to Minimize Bias: Randomization and Blinding
Randomization will be used to minimize bias in the assignment of participants to treatment groups, 
to increase the likelihood that known and unknown participant attributes (eg, demographic and 
baseline characteristics) are evenly balanced across treatment groups, and to enhance the validity 
of statistical comparisons across treatment groups. Blinded treatment will be used to reduce 
potential bias during data collection and evaluation of clinical endpoints.
Intervention Allocation
Central randomization will be implemented in GALAXI 1. Participants will be randomly assigned 
to 1 of 5 treatment groups (1:1:1:1:1 ratio), based on a computer-generated randomization schedule 
prepared before the studies by or under the supervision of the sponsor. The randomization will be 
balanced by using randomly permuted blocks and will be stratified by baseline CDAI score (≤300 
or >300) and BIO-Failure status (Yes/No). The IWRS will assign a unique treatment code, which 
will dictate the treatment assignment and matching study intervention kit(s) for the participant. 
The requestor must use his or her own user identification and personal identification number when 
contacting the IWRS and will then be given the relevant participant details to uniquely identify the 
participant.
Central randomization will also be implemented in GALAXI 2 and GALAXI 3. Participants will 
be randomly assigned to GALAXI 2 (n=approximately 490) or GALAXI 3 (n=approximately 
490), using a permuted block randomization with baseline CDAI score (≤300 or >300), baseline 
SES-CD score (≤12 or >12), prior BIO-Failure status (Yes/No), and baseline corticosteroid use 
(Yes/No) as the stratification variables. Within each stratum, participants in each study will then 
be randomized in a 2:2:2:1 ratio to receive 1 of 2 dose regimens of guselkumab, ustekinumab, or 
placebo, respectively, based on a computer-generated randomization schedule prepared before the 
studies by or under the supervision of the sponsor. The IWRS will assign a unique treatment code, 
which will dictate the treatment assignment and matching study intervention kit(s) for the 
participant. The requestor must use his or her own user identification and personal identification 
number when contacting the IWRS and will then be given the relevant participant details to 
uniquely identify the participant.
Blinding
To maintain the study blind, the study intervention container will have a label containing the 
protocol name, medication number, and reference number. The medication number will be entered 
in the electronic case report form (eCRF) when the study intervention is dispensed. Each active 
study intervention and its matching placebo will be identical in appearance.
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The investigator will not be provided with randomization codes. The codes will be maintained 
within the IWRS, which has the functionality to allow the investigator to break the blind for an 
individual participant.
Data that may potentially unblind the treatment assignment (ie, study intervention serum 
concentrations, antibodies to study intervention) 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 study unblinding.
The post-baseline results of CRP and fecal calprotectin tests performed by the central laboratory 
will be blinded to the investigative sites. If an investigative site requests these data, it will be 
provided to them after the Week 48 analyses of both Phase 3 studies have been completed.
All participants will continue to receive active or placebo study intervention administration in the 
LTE in a blinded fashion until study unblinding, which will occur after the Week 48 DBL and the 
Week 48 analyses have been completed for the Phase 2 study (for participants entering the LTE 
from GALAXI 1) or for the Phase 3 studies (for participants entering the LTE from GALAXI 2 or 
GALAXI 3). 
In GALAXI 1, the sponsor will remain blinded until the Week 48 DBL. However, a limited number 
of sponsor personnel will become unblinded at the Week 12 DBL for a dosing decision after the 
first 250 randomized participants have either completed the Week 12 visit or have terminated study 
participation before Week 12. If a dosing decision cannot be made, a subsequent DBL will occur 
after the first 250 randomized participants have either completed the Week 24 visit or have 
terminated study participation before Week 24. At the time of each analysis, selected sponsor
personnel will be unblinded for all randomized participants from the Initial Dose Decision Cohort 
and for any available participants from the Transition Cohort. After the Week 48 DBL when all 
randomized participants (including both the Initial Dose Decision Cohort and the Transition 
Cohort) have either completed the Week 48 visit or have terminated study participation before 
Week 48, the treatment assignment information will be unblinded for all participants and released 
to the sponsor for analysis.
In GALAXI 2 or GALAXI 3, when all randomized participants in that study have either completed 
the Week 48 visit or have terminated study participation before Week 48, the treatment assignment 
information will be unblinded for all participants in that study and released to the sponsor for 
analysis. The sponsor will remain blinded until after the Week 48 DBL has occurred.
Identification of sponsor personnel who will have access to the unblinded participant-level data at 
the time of each DBL will be documented before unblinding. 
Under normal circumstances, the investigator blind should not be broken unless specific 
emergency treatment/course of action would be dictated by knowing the treatment status of the 
participant. In such cases, the investigator may in an emergency determine the identity of the 
treatment via the IWRS. It is recommended that the investigator contact the sponsor or its designee,
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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. If 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 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.
Additionally, a given participant’s treatment assignment may be unblinded to the sponsor, the 
Independent Ethics Committee/Institutional Review Board (IEC/IRB), and site personnel to fulfill 
regulatory reporting requirements for suspected unexpected serious adverse reactions (SUSARs). 
If a participant is unblinded by the site, the information must be entered in the appropriate section 
of the eCRF and in the participant's source documents. 
Participants who have had their treatment assignment unblinded by the investigator will not be 
eligible to receive further study intervention, but should complete evaluations specified in the 
appropriate Schedule of Activities for participants who discontinue study intervention 
(Section 1.3). 
A separate code break procedure will be available for use by J&J Global Medical Safety group to 
allow for unblinding of individual participants to comply with specific requests from regulatory or 
health authorities.
6.4.
Study Intervention Compliance
When study intervention is administered as an IV infusion or 
 injection by qualified staff, the 
details of each administration will be recorded in the eCRF. For IV infusions, this will include date 
and start and stop times of the IV infusion and volume infused; for 
 injections, this will include 
date and time of 
 injection.
Throughout the study, the investigator or designated study research personnel will be responsible 
for providing additional instruction to re-educate any participant who is not compliant with taking 
study intervention.
Compliance with the treatment schedule is strongly encouraged. Study site personnel will keep a 
log of all study intervention dispensed and will compare the amount of study intervention 
dispensed with the amount returned. Additional details may be provided in the site IPPM that is 
provided separately.
6.5.
Concomitant Therapy
Prestudy therapies administered up to 30 days before the first administration of study intervention
must be recorded on the eCRF. Any COVID-19 vaccines administered, regardless of timing, must 
be recorded on the eCRF. Concomitant therapies must be recorded throughout the study, from 
signing of the informed consent to the last study visit. 
All therapies (prescription or over the counter medications, including vaccines, vitamins, herbal 
supplements; non-pharmacologic therapies such as electrical stimulation, acupuncture, special 
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diets, exercise regimens) different from the study intervention must be recorded in the eCRF. 
Recorded information will include a description of the type of therapy, treatment period, dosage, 
route of administration, and indication. Modification of an effective preexisting therapy should not 
be made for the explicit purpose of entering a participant into the study. 
6.5.1.
Concomitant Medications
Participants who are receiving oral 5-ASA compounds, oral corticosteroids, conventional 
immunomodulators (ie, AZA, 6-MP, or MTX), antibiotics, and/or enteral nutrition for the 
treatment of Crohn’s disease at baseline should maintain a stable dose for the specified period 
before baseline, as defined in the Inclusion Criteria (Section 5.1). 
In general, participants who are receiving these medications for Crohn’s disease at baseline (ie, 
Week 0) of all 3 studies should maintain a stable dose through Week 48, with the exception of oral 
corticosteroids. Therapies can only be discontinued or reduced in dose after Week 0 if investigator 
judgment requires it because of toxicity or other medical necessity; even if the toxicity resolves, 
the therapy should not be restarted. Corticosteroids must be maintained at baseline doses through 
Week 12, and all participants must begin tapering corticosteroids at Week 12, unless medically 
not feasible (see further details in Section 6.5.1.1, Oral Corticosteroids Tapering).
Week 0 through Week 48
From Week 0 through Week 48 of each study, enrolled participants should not initiate any of the 
following concomitant Crohn’s disease-specific medical therapies:

Oral or rectal 5-ASA compounds.

Immunomodulators (ie, AZA, 6-MP, or MTX).

Oral, parenteral, or rectal corticosteroids, including budesonide and beclomethasone 
dipropionate.

Antibiotics as a primary treatment for Crohn’s disease.

Total parenteral nutrition or enteral nutrition as a treatment for Crohn’s disease.
If the above medical therapies are initiated or medication doses are changed based on medical 
necessity as assessed by the investigator, participants should continue to attend all study visits and 
have all assessments. While this does not represent a deviation from the study protocol and the 
participants may remain on their assigned therapy (guselkumab, ustekinumab, or placebo), it may 
be considered a treatment failure. Treatment failures will be defined in the SAP.
Week 12 and through Week 48
From Week 12 through Week 48 of each study, participants may transiently use (ie, for <4 weeks) 
increased doses of corticosteroids for reasons other than treatment for Crohn’s disease (eg, stress 
doses of corticosteroids for surgery, asthma, adrenocortical insufficiency).
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
Thalidomide or related agents.
The sponsor or designee must be notified in advance (or as soon as possible thereafter) of any 
instances in which prohibited therapies are administered.
As protection of human research participants is paramount, it is recognized that initiating such 
therapies may rarely be required due to medical necessity. However, initiation of these prohibited 
medications should be documented as a deviation from the study protocol, and participants will be 
discontinued from receiving further study intervention (Section 7). Participants who discontinue 
study intervention administration should complete a SID visit and an FES visit as described in 
Section 1.3.
Note: Participants must not receive guselkumab or ustekinumab outside of the protocol or 
participate in any other clinical study with an investigational agent while in this study and must 
terminate study participation if they do. Prior to termination of study participation, participants 
should complete evaluations for a SID visit as described in Section 1.3.
6.5.3.
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 participants receiving 
immune-targeted therapy.
For study participants receiving a locally approved (including emergency-use-authorized) 
COVID-19 vaccine, in order to help identify acute reactions potentially related to the COVID-19 
vaccine, it is recommended that, where possible, vaccine and study intervention be administered 
on different days, separated by as large an interval as is practical within the protocol. 
Refer to Section 5.3 for additional vaccination details.
6.6.
Dose Modification
No treatment/dose adjustment will be permitted through Week 48. After that time point, 
treatment/dose modification will be allowed as described in Section 4.1.3.1.
6.7.
Intervention After the End of the Study
This protocol is designed to provide participants with up to approximately 5 years of treatment (ie, 
48-week treatment under the Phase 2 or Phase 3 studies plus approximately 4 additional years of 
treatment in the LTE).
After completing the LTE, participants will be instructed that study intervention will not be made 
available to them as part of this protocol and that they should return to their treating physician for 
guidance.
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7.
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
A participant will be considered to have completed the study if he or she has completed 
assessments through the FES visit as specified in the Schedule of Activities (Section 1.3).
If a participant discontinues study intervention or withdraws from the study before the end of the 
study, assessments should be obtained as specified in the Schedule of Activities (Section 1.3).
7.1.
Discontinuation of Study Intervention
A participant who discontinues study intervention will not be automatically withdrawn from the 
study (see Section 7.2).
A participant's study treatment must be discontinued under the following conditions:
1. The
participant initiates treatment with prohibited therapies for Crohn’s disease
(Section 6.5.2).
2. The participant has a Crohn’s disease-related surgery that represents a lack of efficacy of study 
intervention or that will preclude the future ability to assess efficacy using the CDAI or other 
instruments required for demonstration of efficacy endpoints.
Note: Other permitted Crohn’s disease-related surgeries (eg, to resolve long-standing 
complications such as strictures or for symptomatic nonhealing fistulas, in participants 
experiencing improvement on study intervention) other than minor procedures (eg, placement 
of a seton or cutaneous drainage of an abscess) should be postponed until after the FES visit, 
unless necessary to ensure participant well-being and/or safety.
3. The participant becomes pregnant or plans a pregnancy within the study period. Refer to 
Appendix 6 (Section 10.6), Contraceptive and Barrier Guidance and Collection of Pregnancy 
Information.
4. The participant (or the participant’s representative) withdraws consent for administration of 
study intervention.
5. The participant develops a systemic opportunistic infection.
6. The participant is deemed ineligible according to the following TB screening criteria:

A diagnosis of active TB is made.

A participant has symptoms suggestive of active TB based on follow-up assessment 
questions and/or physical examination or has had recent close contact with a person with 
active TB and cannot or will not continue to undergo additional evaluation.

A participant undergoing evaluation has a chest radiograph with evidence of current
active TB and/or a positive QuantiFERON-TB (or T-SPOT for sites in Japan where local 
regulations permit) test result (and/or a positive tuberculin skin test result in countries in 
which the QuantiFERON-TB test is not approved/registered or the tuberculin skin test is 
mandated by local health authorities), unless active TB can be ruled out and appropriate 
treatment for latent TB can be initiated prior to the next study intervention administration 
and continued to completion (see also Section 8.2.6, Section 10.5, and Section 10.6). 
Indeterminate QuantiFERON-TB (or borderline T-SPOT for sites in Japan) test results 
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should be handled as described in Section 8.2.6. Participants with persistently 
indeterminate QuantiFERON-TB (or borderline T-SPOT for sites in Japan) test results 
may continue without treatment for latent TB if active TB is ruled out, their chest 
radiograph shows no abnormality suggestive of TB (active or old, inactive TB) and the 
participant has no additional risk factors for TB as determined by the investigator. This 
determination must be promptly reported to the sponsor’s or designee’s medical monitor 
and recorded in the participant's source documents and initialed by the investigator.
Note: In Ukraine, while the QuantiFERON-TB test is not approved/registered, it is 
acceptable, and an additional tuberculin skin test is not required.

A participant receiving treatment for latent TB discontinues this treatment prematurely 
or is noncompliant with the therapy.
7. Criterion revised per Amendment 1.
7.1. The participant has a serious adverse reaction that is related to an injection or an infusion, 
including an injection-site or infusion reaction, resulting in bronchospasm with wheezing 
and/or dyspnea that requires ventilatory support OR that results in symptomatic 
hypotension with a decrease in systolic blood pressure >40 mm Hg or blood pressure 
<90/60 mm Hg. 
8. The participant has a reaction resulting in myalgia and/or arthralgia with fever and/or rash 
(suggestive of serum sickness and not representative of signs and symptoms of other 
recognized clinical syndromes) occurring 1 to 14 days after an injection of study intervention. 
These may be accompanied by other events including pruritus, facial, hand, or lip edema, 
dysphagia, urticaria, sore throat, and/or headache.
9. The participant has severe liver test abnormalities that are not transient and are not explained 
by other etiologies, as described in Section 8.2.11 and Appendix 9 (Section 10.9). Such 
abnormalities would include: 

ALT or AST >8 x ULN 

ALT or AST >5 x ULN for more than 2 weeks 

ALT or AST >3 x ULN and (TBL >2 x ULN or international normalized ratio [INR] >1.5) 

ALT or AST >3 x ULN and symptoms of hepatitis (eg, fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness, fever, rash) and/or eosinophilia (>5%)
10. The participant has a malignancy including squamous cell skin cancer. Consideration may be 
given to allowing participants who develop ≤2 basal cell skin cancers that are adequately 
treated with no evidence of residual disease to continue to receive study intervention.
11. The investigator believes that for safety or tolerability reasons, it is in the best interest of the 
participant to discontinue study intervention.
Discontinuation of a participant’s study intervention must be strongly considered under 
the following conditions: 
1. Criterion revised per Amendment 1.
1.1. Persistent inadequate response or worsening of Crohn’s disease:
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a.
The participant has a change from baseline in the CDAI score <70 points and has a 
CDAI score >220 at both Week 20 and Week 24.
OR
b.
The participant experiences AEs consistent with clinically significant worsening of 
Crohn’s disease at any time during the study.
These events must be evaluated by the investigator. A consultation with the study medical 
monitor may also be considered, at the investigator's discretion. Discontinuation of study 
intervention must be considered in participants with clinically significant worsening of 
Crohn’s disease where continuation of the study intervention is not in the best interest of the 
participant.
2. The participant develops a serious infection, including but not limited to sepsis or pneumonia.
3. 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.
4. Criterion revised per Amendment 1.
4.1. The participant develops a severe injection-site or infusion reaction. 
If a participant discontinues study intervention for any reason before the end of the treatment 
period, assessments should be obtained as specified in the Schedule of Activities (Section 1.3). If 
the reason for discontinuation of study intervention is withdrawal of consent, every effort should 
be made to conduct the SID visit assessments, as indicated in the Schedule of Activities, prior to 
terminating study participation. After termination of study participation, no additional assessments 
are allowed.
7.2.
Participant Discontinuation/Withdrawal From the Study
Participant discontinuation/withdrawal from the study is defined as no longer following up for 
study visits. It is different from discontinuation from study intervention, as described in 
Section 7.1.
A participant will be withdrawn from the study for any of the following reasons:

Withdrawal of consent

Lost to follow-up (see Section 7.3)

Sponsor decision (eg, participating in any other clinical study with an investigational agent)

Death
Participants who terminate study participation will not be required to return for any follow-up 
assessments; however, these participants should complete the safety and efficacy evaluations 
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specified for the SID visit in the appropriate Schedule of Activities (Table 4) at the time they 
terminate study participation. No additional evaluations are performed after participant’s 
withdrawal from the study.
When a participant withdraws before completing the study, the reason for withdrawal is to be 
documented in the eCRF and in the source document. Study intervention assigned to the withdrawn 
participant may not be assigned to another participant. Participants who withdraw will not be 
replaced.
7.2.1.
Withdrawal From the Use of Research Samples
A participant who withdraws from the study will have the following options regarding the optional 
research samples:

The collected samples will be retained and used for research activities in accordance with the 
participant’s original separate informed consent for optional research samples.

The participant may withdraw consent for optional research samples, in which case the 
samples will be destroyed and no further testing will take place. To initiate the sample 
destruction process, the investigator must notify the sponsor study site contact of withdrawal 
of consent for the optional research samples and to request sample destruction. If requested, 
the investigator will receive written confirmation from the sponsor that the samples have been 
destroyed.
Withdrawal from the Optional Research Samples While Remaining in the Main Study
The participant may withdraw consent for optional research samples while remaining in the study. 
In such a case, the optional research samples will be destroyed. The sample destruction process 
will proceed as described above.
Withdrawal from the Use of Samples in Future Research
The participant may withdraw consent for use of samples for future research (refer to Appendix 8
[Section 10.8], Long-Term Retention of Samples for Additional Future Research). In such a case, 
samples will be destroyed after they are no longer needed for the clinical study. Details of the 
sample retention for research are presented in the main ICF and in the separate ICF for optional 
research samples.
7.3.
Lost to Follow-up
If a participant is lost to follow-up, every reasonable effort must be made by the study site 
personnel to contact the participant and determine the reason for discontinuation/withdrawal
before considering the participant to be lost to follow-up. Such efforts should include repeated 
telephone calls, certified letters, and email requests. The measures taken to follow up must be 
documented. Refer to Section 7.2, Participant Discontinuation/Withdrawal From the Study.
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8.
STUDY ASSESSMENTS AND PROCEDURES
Overview
The Schedule of Activities (Section 1.3) summarizes the frequency and timing of efficacy, PK, 
immunogenicity, biomarker (PD), pharmacogenomic, medical resource utilization, health 
economic, and safety measurements applicable to this study.
Except at the screening visit, all visit-specific PRO assessments should be conducted/completed 
before any tests, procedures, or other consultations to prevent influencing participant perceptions.
Blood collections for PK and PD assessments should be completed as outlined in the Schedule of 
Activities (Section 1.3). Other measurements may be done earlier than specified time points if 
needed. Actual dates and times of assessments will be recorded in the source documentation.  
For women of childbearing potential only, additional pregnancy tests may be performed, as 
determined necessary by the investigator or required by local regulation, to establish the absence 
of pregnancy at any time during the participation in the study.
Medical resource utilization and health economics data will be collected. Refer to Section 8.9, 
Medical Resource Utilization and Health Economics for details.
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 Schedule of 
Activities (Section 1.3).
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 urine 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 10) and must continue taking 
such precautions for 16 weeks after receiving the last administration of study intervention. The 
method(s) of contraception used by each participant must be documented. 
Participants must undergo testing for TB (Section 8.2.6 and Appendix 5 [Section 10.5]) 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.
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Participants with a negative QuantiFERON-TB (or T-SPOT for sites in Japan where local 
regulations permit) test result (and a negative tuberculin skin test result in countries in which the 
QuantiFERON-TB [or T-SPOT for sites in Japan] test is not approved/registered or the tuberculin 
skin is mandated by local health authorities) are eligible to continue with prerandomization 
procedures. Note: A negative tuberculin skin test is additionally required if the QuantiFERON-TB
(or T-SPOT for sites in Japan) test is not approved/registered in the country in which this protocol 
is being conducted. In Ukraine, while the QuantiFERON-TB test is not approved/registered, it is 
acceptable, and an additional tuberculin skin test is not required.
Participants with a newly identified positive QuantiFERON-TB (or tuberculin skin) test (or 
T-SPOT test for sites in Japan where local regulations permit) result must undergo an evaluation 
to rule out active TB and initiate appropriate treatment for latent TB. Appropriate treatment for 
latent TB is defined according to local country guidelines for immunocompromised patients. If no 
local country guidelines for immunocompromised patients exist, US guidelines must be followed, 
or the participant will be excluded from the study.
A participant whose first QuantiFERON-TB (or T-SPOT for sites in Japan where local regulations 
permit) test result is indeterminate should have the test repeated. If the second QuantiFERON-TB 
(or T-SPOT for sites in Japan) test result is also indeterminate, the participant may be enrolled 
without treatment for latent TB if his/her chest radiograph shows no abnormality suggestive of TB 
(active or old, inactive TB) and the participant has no additional risk factors for TB as determined 
by the investigator and medical monitor.
An assessment of all screening laboratory test 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.
Blood Sample Collection
Blood samples should be collected at the visits indicated in the Schedule of Activities
(Section 1.3). The date and time of collection will be recorded. When blood samples are to be 
collected for safety, PK, efficacy, biomarkers, and pharmacogenomic evaluations at the same time 
point, the order of blood draws will be samples for CRP, chemistry/lipids, hematology, 
PK/Immunogenicity, serum biomarkers, pharmacogenomics, and RNA expression.
The maximum total blood volume to be collected from each participant in each study (GALAXI 1, 
GALAXI 2, or GALAXI 3) will be approximately 500 mL over approximately 252 weeks 
(Table 8). This total may vary due to:

whether or not the participant consents to take part in the optional pharmacogenomics study 
(10 mL)

which final visit the participant completes (SID [23 mL] versus FES [12 mL])

repeat or unscheduled samples taken for safety reasons or technical issues with the samples

regional or country-specific variation in blood collection systems
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Table 8:
Volume of Blood to be Collected from Each Participant per Study
Study Period or Type of Sample
Approximate Total Volume of Blood (mL)
Screening through Week 48
216
Pharmacogenomics sample a
10
Week 52 through Week 96
92
Week 100 through Week 144
69
Week 148 through Week 240 
94
Final visit (SID or FES)
23 or 12 b
Approximate Total c,d
500
a. Sample to be collected only from participants who have consented to provide an optional pharmacogenomics (DNA) 
sample for research.
b. A participant’s final visit will be either a study intervention discontinuation (SID) visit (23 mL) or a final efficacy and 
safety follow-up (FES) visit (12 mL).
c. Repeat or unscheduled samples may be taken for safety reasons or technical issues with the samples.
d. May differ slightly due to regional or country-specific variation in blood collection systems.
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 Schedule of Activities (Section 1.3) for the timing and frequency of 
all sample collections.
Instructions for the collection, handling, and shipment of samples are found in the Laboratory 
Manual.
Study-Specific Materials
Supplies provided to the investigator will include:

Investigator Site File (includes protocol and IB)

IPPM

Central Laboratory Manual 

eCRF completion instructions

Patient recruitment materials

ICF

Participant Diary Card including CDAI (including PRO-2), Bristol Stool Form Scale (BSFS), 
and Abdominal Pain – Numerical Rating Scale (AP-NRS)

IWRS Manual

Biopsy Manual

ePRO equipment
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
Endoscopy kit

Imaging Manual

Laboratory kits
8.1.
Efficacy Assessments
Efficacy evaluations will include the following:

CDAI

PRO-2 (the unweighted CDAI components of the total number of liquid or very soft stools 
and the AP score)

Endoscopic assessments of the intestinal mucosa based on the presence and absence of 
mucosal ulcerations and the SES-CD, and histologic assessments based on the Global
Histology Activity Score (GHAS), Robarts histopathology index (RHI), and Geboes scores

Inflammatory PD markers including CRP and fecal calprotectin

Fistula assessment

Patient-reported outcome (PRO) measures to assess HRQOL outcomes (ie, IBDQ, PROMIS-
29, and PROMIS Fatigue 7-item Short Form [7a], and EQ-5D-5L), and health economics 
outcomes (ie, WPAI-CD)

Exploratory patient-reported symptom measures including BSFS, AP-NRS, Patient’s Global
Impression of Severity (PGIS) of Crohn’s Disease, and Patient’s Global Impression of Change 
(PGIC) of Severity of Crohn’s Disease
The CDAI (Appendix 10 [Section 10.10]) will be assessed by collecting information on 8 different 
Crohn’s disease-related variables2: extraintestinal manifestations, abdominal mass, weight, 
hematocrit, total number of liquid or very soft stools, AP/cramping, use of antidiarrheal drug(s) 
and/or opiates, and general well-being. The last 4 variables are scored over 7 days by the 
participant on a diary card that participants are to complete on a daily basis. The PRO-2 includes 
the unweighted CDAI components of the total number of liquid or very soft stools and the AP
score.
Endoscopic assessments of the intestinal mucosa will be evaluated during ileocolonoscopy in 
all participants. A video ileocolonoscopic examination will be performed at screening, Week 12, 
Week 48, Week 96, Week 144, Week 192, and Week 240. An optional substudy involving a 
Week 4 evaluation will be performed in consenting participants in addition to the above-specified 
evaluations. (See Biopsy Manual for more information.) Video endoscopies will be assessed by a 
central facility that will be blinded to treatment group and visit. A complete video endoscopic 
examination does not require assessment of the terminal ileum if it cannot be visualized. The SES-
CD score will be used to evaluate Endoscopic Improvement.4 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 
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narrowing component which can only attain a maximum total score of 11 because by definition, 
the presence of a narrowing that cannot be passed can be only observed once. In summary, an 
overall total SES-CD score is derived from the sum of all the component scores and can range 
from 0 to 56. Endoscopic healing, which is traditionally defined as the resolution (absence) of 
mucosal ulcers in response to a therapeutic intervention, will also be assessed.
Histologic assessments will be performed using biopsy samples collected during ileocolonoscopy. 
Biopsy samples will be collected at screening, Week 12, Week 48, Week 96, Week 144, 
Week 192, and Week 240 from each of 3 predefined anatomic locations: the terminal ileum, 
splenic flexure, and rectum, as clinically feasible. An optional substudy involving a Week 4 
evaluation will be performed in consenting participants in addition to the above-specified 
evaluations. The biopsy samples collected post-baseline will be obtained near where the screening 
biopsy samples were collected from each of the 3 predefined locations, as clinically feasible. 
Histologic assessments will be conducted by a central reader who is blinded to treatment groups 
and visit. The GHAS will be used to evaluate histologic improvements and healing.5 Additional 
histologic assessments (including RHI and Geboes scores) will also be implemented. Analyses 
will be specified in the SAP.
Fistula assessment will be performed in all participants on an ongoing basis throughout the 
duration of the studies. All participants will be assessed for fistulas at baseline. For participants 
with fistulizing disease, fistula closure will be assessed during the studies. Enterocutaneous fistulas 
(eg, perianal and abdominal) will be considered no longer draining (ie, closed) when there is 
absence of drainage despite gentle compression. Rectovaginal fistulas will be considered closed 
based on either physical examination or absence of relevant symptoms (eg, passage of rectal 
material or flatus from the vagina).
Patient-reported outcome measures will be evaluated at visits as indicated in the Schedule of 
Activities (Section 1.3):

The IBDQ is a validated, 32-item, self-reported questionnaire for participants with IBD to 
evaluate PROs across 4 dimensions: bowel symptoms (loose stools, AP), systemic symptoms 
(fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), 
and emotional function (anger, depression, irritability).12 Scores range from 32 to 224, with 
higher scores indicating better outcomes. 

The PROMIS-29 is a validated general health profile instrument that is not disease-specific.
It is a collection of short forms containing 4 items for each of 7 domains (depression, anxiety, 
physical function, pain interference, fatigue, sleep disturbance, and ability to participate in 
social roles and activities). PROMIS-29 also includes an overall average pain intensity 0-10 
numeric rating scale (NRS).

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, self-care, and exercise). PROMIS Fatigue Short Form 7a has a recall period of past 
7 days. Compared with the fatigue scale of PROMIS-29, PROMIS Fatigue Short Form 7a 
provides additional information to evaluate severity of fatigue. 
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
The EQ-5D-5L is a validated instrument consisting of the EuroQol five dimensions 
descriptive system (EQ-5D) and the EuroQol visual analog scale (EQ-VAS). The descriptive 
system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, 
anxiety/depression). Each dimension has 5 levels: no problems, slight problems, moderate 
problems, severe problems, and extreme problems. The respondent is asked to indicate his/her 
health state by checking the most appropriate statement in each of the 5 dimensions. The EQ-
VAS records the respondent’s self-rated health on a 20-cm vertical, visual analog scale with 
endpoints labeled ‘the best health you can imagine’ and ‘the worst health you can imagine’. 
The respondents mark an “X” on the scale to indicate their health TODAY and then write the 
number marked on the scale in the box. 

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 to determine employment status, 
hours missed from work due to Crohn’s disease, hours missed from work for other reasons, 
hours worked, the degree to which Crohn’s disease affected work productivity while at work, 
and the degree to which Crohn’s disease affected activities outside of work. Four scores are 
derived: percentage of absenteeism, percentage of presenteeism (reduced productivity while 
at work), an overall work impairment score that combines absenteeism and presenteeism, and 
percentage of impairment in activities performed outside of work. Higher scores indicate 
greater impairment.
Exploratory patient-reported symptom measures will be evaluated at visits as indicated in the 
Schedule of Activities (Section 1.3):

The BSFS is a medical aid to classify the form (or consistency) of human feces into 
7 categories.15 It has been used as a research tool to evaluate the effectiveness of treatments 
for various diseases of the bowel (eg, irritable bowel syndrome [IBS]). Participants will 
complete the BSFS as a daily diary entry from Week 0 through Week 48.

The AP-NRS is an 11-point (0-10) scale that will be used to evaluate AP. The score of 0 
represents “no AP” and the score of 10 represents the “worst possible AP” with greater scores 
indicating greater pain severity and intensity. Participants will complete the AP-NRS as a 
daily diary entry from Week 0 through Week 48, selecting only one number that best reflects 
their pain at its worst.

PGIS of Crohn’s Disease: Participants will rate their Crohn’s disease activity at baseline and 
each visit using a 5-point scale (“None”, “Mild”, “Moderate”, “Severe”, and “Very Severe”). 
The PGIS will be used as an anchor to establish and or validate response criteria of other 
clinical endpoints.

PGIC of Severity of Crohn’s Disease: Participants’ perceived change (improvement or 
deterioration) in the severity of their Crohn’s disease will be assessed using the PGIC. 
Participants will rate how their Crohn’s disease has changed since the beginning of the study 
using a 7-point scale ranging from “a lot better now” to “a lot worse now” with a neutral center 
point (“neither better nor worse”). The PGIC will be used as an anchor to establish and or 
validate response criteria of other clinical endpoints.
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8.2.
Safety Assessments
Details regarding the Independent Data Monitoring Committee are provided in Section 9.5.2.
Adverse events will be reported and followed by the investigator as specified in Section 8.3, 
Adverse Events and Serious Adverse Events and Appendix 11 (Section 10.11, Adverse Events: 
Definitions and Procedures for Recording, Evaluating, Follow-Up, and Reporting).
Any clinically relevant changes occurring during the study must be recorded in the Adverse Event 
section of the eCRF.
Any clinically significant abnormalities persisting at the end of the study/early withdrawal will be 
followed by the investigator until resolution or until a clinically stable endpoint is reached. 
The study will include the following evaluations of safety and tolerability according to the time 
points specified in the Schedule of Activities (Section 1.3):
8.2.1.
Electrocardiogram
A 12-lead electrocardiogram (ECG) will be performed at screening.
During the collection of ECGs, participants should be in a quiet setting without distractions (eg, 
television, cell phones). Participants should rest in a supine position for at least 5 minutes before 
ECG collection and should refrain from talking or moving arms or legs. If blood sampling or vital 
sign measurement is scheduled for the same time point as ECG recording, the procedures should 
be performed in the following order: ECG(s), vital signs, blood draw.
8.2.2.
Physical Examination
Physical examinations will be performed as specified in the Schedule of Activities. While 
assessment of the participants for safety and efficacy requires some physical examination by an
investigator at all visits, a more complete, detailed physical examination will be performed at 
specified visits.
8.2.3.
Height and Weight
Height and weight will be measured as specified in the Schedule of Activities. Participants will be 
instructed to remove shoes and outdoor apparel and gear prior to these measurements.
8.2.4.
Vital Signs
Through Week 48, vital signs (including temperature, pulse/heart rate, respiratory rate, and blood 
pressure) will be obtained before and approximately every 30 minutes during every IV infusion, 
and for 1 hour at approximately 30-minute intervals after completion of the final IV infusion. Vital 
signs should be obtained before and approximately 30 minutes after the final 
 injection.
After Week 48, study participants receiving study intervention administration at the study site will 
have vital signs assessed at these visits as described above.
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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 injection-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.
8.2.5.
Infections
Study intervention administration should not be given to a participant with a clinically important, 
active infection. Investigators are required to evaluate participants for any signs or symptoms of 
infection at scheduled visits (see Schedule of Activities, Section 1.3). If a participant develops a 
serious infection, including but not limited to sepsis or pneumonia, discontinuation of study 
treatment (ie, no further study intervention administrations) must be considered.
8.2.6.
Tuberculosis Evaluation(s)
8.2.6.1.
Initial Tuberculosis Evaluation
Participants must undergo testing for TB (refer to Appendix 5 [Section 10.5]) and their medical 
history assessment must include specific questions about a history of TB or known occupational 
or other personal exposure to individuals with active TB. The participant should be asked about 
past testing for TB, including chest radiograph results and responses to tuberculin skin or other TB 
testing. Investigators have the option to use both the QuantiFERON-TB (or T-SPOT for sites in 
Japan where local regulations permit) test and the tuberculin skin test to screen for latent TB if 
they believe, based on their judgment, that the use of both tests is clinically indicated to evaluate 
a participant who has high risk of having latent TB. If either the QuantiFERON-TB (or T-SPOT 
for sites in Japan) test or the tuberculin skin test is positive, the participant is considered to have 
latent TB infection for the purposes of eligibility for this study. See below for suspected false 
positive initial testing.
Participants with a negative QuantiFERON-TB (or T-SPOT for sites in Japan where local 
regulations permit) test result (and a negative tuberculin skin test result in countries in which the 
QuantiFERON-TB test is not approved/registered or the tuberculin skin is mandated by local 
health authorities) are eligible to continue with prerandomization procedures. Participants with a 
newly identified positive QuantiFERON-TB (or tuberculin skin) test (or T-SPOT test for sites in 
Japan) result must undergo an evaluation to rule out active TB and initiate appropriate treatment 
for latent TB. Appropriate treatment for latent TB is defined according to local country guidelines 
for immunocompromised patients. If no local country guidelines for immunocompromised 
patients exist, US guidelines must be followed, or the participant will be excluded from the study. 
A participant whose first QuantiFERON-TB test result is indeterminate should have the test 
repeated. In the event that the second QuantiFERON-TB test result is also indeterminate, the 
participant may be enrolled without treatment for latent TB if active TB is ruled out, their chest 
radiograph shows no abnormality suggestive of TB (active or old, inactive TB) and the participant 
has no additional risk factors for TB as determined by the investigator. For sites in Japan, a 
participant whose first T-SPOT test result (where local regulations permit) is borderline should 
have the test repeated. In the event that the second T-SPOT (for sites in Japan) test result is also 
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borderline, the participant may be enrolled without treatment for latent TB if active TB is ruled 
out, their chest radiograph shows no abnormality suggestive of TB (active or old, inactive TB), 
and the participant has no additional risk factors for TB as determined by the investigator. This 
determination must be promptly reported to the sponsor’s or designee’s medical monitor and 
recorded in the participant's source documents and initialed by the investigator.
A suspected false-positive initial QuantiFERON-TB test must be repeated. If repeat testing is NOT 
positive, the participant should be referred to a physician specializing in TB to determine if the 
initial test can be considered a false-positive. This evaluation should 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.
8.2.6.2.
Ongoing Tuberculosis Evaluation
Early Detection of Active Tuberculosis 
To aid in the early detection of TB reactivation or new TB infection during study participation, 
participants must be evaluated for signs and symptoms of active TB at scheduled visits (refer to 
the Schedule of Activities in Section 1.3) or by telephone contact approximately every 8 to 12 
weeks. The following series of questions is suggested for use during the evaluation: 

“Have you had a new cough of >14 days’ duration or a change in a chronic cough?”

“Have you had any of the following symptoms:

Persistent fever?

Unintentional weight loss?

Night sweats?”

“Have you had close contact with an individual with active TB?” (If there is uncertainty as to 
whether a contact should be considered “close,” a physician specializing in TB should be 
consulted.)
If the evaluation raises suspicion that a participant may have TB reactivation or new TB infection, 
an immediate and thorough investigation should be undertaken, including, where possible, 
consultation with a physician specializing in TB. 
Investigators should be aware that TB reactivation in immunocompromised participants may 
present as disseminated disease or with extrapulmonary features. Participants with evidence of 
active TB should be referred for appropriate treatment.
Participants who experience close contact with an individual with active TB during the conduct of 
the study must have a repeat chest radiograph, a repeat QuantiFERON-TB (or T-SPOT for sites in 
Japan where local regulations permit) test, a repeat tuberculin skin test in countries in which the 
QuantiFERON-TB test is not approved/registered or the tuberculin skin test is mandated by local 
health authorities, and, if possible, referral to a physician specializing in TB to determine the 
participant’s risk of developing active TB and whether treatment for latent TB is warranted.
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Study intervention administration should be interrupted during the investigation. A positive 
QuantiFERON-TB (or T-SPOT for sites in Japan where local regulations permit) test or tuberculin 
skin test result should be considered detection of latent TB. If the QuantiFERON-TB (or T-SPOT 
for sites in Japan) test result is indeterminate, the test should be repeated. Participants should be 
encouraged to return for all subsequent scheduled study visits according to the protocol. 
Participants who discontinue treatment for latent TB prematurely or who are noncompliant with 
therapy must immediately discontinue further administration of study intervention and be
encouraged to return for all subsequent scheduled study visits according to the Schedule of 
Activities (Section 1.3).
8.2.7.
Allergic Reaction
Before any 
 injection or 
 infusion, appropriately trained personnel and medications must be 
available to treat allergic reactions, including anaphylaxis. All participants must be observed 
carefully for symptoms of an allergic reaction (eg, urticaria, itching, hives). If a mild or moderate 
allergic reaction is observed, acetaminophen, nonsteroidal anti-inflammatory drugs, and/or 
diphenhydramine may be administered.
In the case of a severe allergic reaction (eg, anaphylaxis), 
 aqueous epinephrine, corticosteroids,
respiratory assistance, and other proper resuscitative measures are essential and must be available 
at the study site where the injections or infusions are being administered.
Participants who experience serious adverse reactions related to an injection or infusion should be 
discontinued from further study intervention administrations.
Participants who experience reactions following an injection or infusion that result in 
bronchospasm with wheezing and/or dyspnea that requires ventilatory support, or symptomatic 
hypotension with a decrease in systolic blood pressure greater than 40 mm Hg will not be permitted 
to receive additional study intervention (see Section 7 and Table 4).
Participants who experience reactions suggestive of serum sickness-like reactions (resulting in 
symptoms such as myalgia and/or arthralgia with fever and/or rash that are not representative of 
signs and symptoms of other recognized clinical syndromes) occurring 1 to 14 days after an 
injection of study intervention, should be discontinued from further study intervention 
administrations. Note that these symptoms may be accompanied by other events including pruritus, 
facial, hand, or lip edema, dysphagia, urticaria, sore throat, and/or headache.
8.2.8.
Adverse Events Temporally Related to Infusion
Any AE (except laboratory abnormalities) that occurs during or within 1 hour after the IV infusion 
of study intervention will be carefully evaluated.  Minor infusion-related AEs may be managed by 
slowing the rate of the IV infusion and/or treating with antihistamines and/or acetaminophen 
(paracetamol) as clinically indicated. If an IV infusion of study intervention is stopped because of 
an AE that, in the opinion of the investigator, is not severe or does not result in a serious adverse 
event (SAE), the infusion may be restarted with caution.
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8.2.9.
Injection-Site Reaction
An injection-site reaction is any adverse reaction at a 
 study intervention injection site. Injection 
sites will be evaluated for reactions and any injection-site reaction will be recorded as an AE.
8.2.10.
Columbia-Suicide Severity Rating Scale (C-SSRS)
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.17,19 Two versions 
of it will be used in this study: the ‘Baseline/Screening’ version of the C-SSRS will be conducted 
during the screening visit and the ‘Since Last Visit’ version of the C-SSRS will be completed at 
all other visits through the end of the study.
The investigator or trained study site personnel will interview the participant and complete the 
C-SSRS. The C-SSRS will be provided in the local languages in accordance with local guidelines.
At screening, the C-SSRS will be the first assessment performed, before any other study procedure. 
At all subsequent visits, the C-SSRS will be performed according to the assessment schedule and 
should be performed after other PROs but before any other study procedure. Participants will be 
interviewed by the investigator or trained study site personnel in a private, quiet place. 
At the conclusion of each assessment, the trained personnel administering the C-SSRS will 
determine the level of suicidal ideation or behavior, if any. They will then determine the next 
course of action if any level of suicidal ideation or behavior is reported. The participant should not 
be released from the site until the C-SSRS has been reviewed by the investigator and the 
participant’s risk has been assessed and follow-up determined, as appropriate.
At screening (within the last 6 months) and Week 0, participants with a C-SSRS rating of 
Suicidal Ideation with Intention to Act (“Ideation level 4”), Suicidal Ideation with Specific Plan 
and Intent (“Ideation level 5”), or suicidal behavior (actual suicide attempt, interrupted suicide 
attempt, aborted suicide attempt, or preparatory behaviors for making a suicide attempt), must be 
determined to not be at risk by the investigator based on an evaluation by a mental health 
professional (eg, psychiatrist, psychologist, or appropriately trained social worker or nurse) in 
order to be randomized.
Participants with C-SSRS ratings of Wish to be Dead (“Ideation level 1”), Non-Specific Active 
Suicidal Thoughts (“Ideation level 2”), Active Suicidal Ideation with Any Methods (Not Plan) 
without Intent to Act (“Ideation level 3”) or non-suicidal self-injurious behavior must be 
determined not to be at risk by the investigator in order to be randomized. Any questions regarding 
eligibility of such participants should be discussed with the medical monitor or designee.
For each assessment after Week 0, the following actions should be taken, if applicable:

No suicidal ideation or behaviors (including self-injurious behavior without suicidal intent): 
No further action is needed.
CC
I
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
Suicidal ideation levels 1-3 or non-suicidal self-injurious behavior: Participant risk is assessed 
by the investigator.

Suicidal ideation levels 4 or 5 or any suicidal behavior: Participant risk assessed and referral 
to a mental health professional.
Interruption or the discontinuation of study treatment should be considered for any participant who 
reports Suicidal Ideation with Intention to Act (“Ideation level 4”), Suicidal Ideation with Specific 
Plan and Intent (“Ideation level 5”), or suicidal behavior (actual suicide attempt, interrupted suicide 
attempt, aborted suicide attempt, or preparatory behaviors for making a suicide attempt) on a post-
baseline C-SSRS assessment and who is deemed to be at risk by the investigator based upon 
evaluation by a mental health professional. If a participant can be adequately treated with 
psychotherapy and/or pharmacotherapy then the participant, at the discretion of the investigator, 
may be continued with treatment if agreed to by the medical monitor or designee. Discussion of 
such participants with the medical monitor or designee is required (see Section 7.1, 
Discontinuation of Study Intervention). 
Any C-SSRS finding, which in the opinion of the investigator is new or considered to be a 
worsening and clinically significant, should be reported on the AE eCRF (see Appendix 11
[Section 10.11], Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow-
up, and Reporting).
8.2.11.
Clinical Safety Laboratory Assessments
Blood samples for serum chemistry and hematology will be collected as noted in Section 1.3. The 
investigator must review the laboratory results, document this review, and record any clinically 
relevant changes occurring during the study in the AE section of the eCRF. The laboratory reports 
must be filed with the source documents.
The following tests will be performed by the central laboratory unless otherwise specified or 
approved by the medical monitor.

Hematology assessments will include but are not limited to the following: hemoglobin, 
hematocrit, platelet count, total and differential WBC count.

Blood chemistry assessments will include but are not limited to the following: chemistry 
panel (total and direct bilirubin, ALT, AST, alkaline phosphatase, albumin, total protein, 
calcium, phosphate, sodium, potassium, chloride, blood urea nitrogen /urea, and creatinine).
A medical monitor or delegate and the clinical site will be notified if prespecified abnormal 
laboratory values defined in the Laboratory Manual are identified in any participant during 
the conduct of the study. 

Serology: HIV antibody, HBV antibodies and surface antigen, and HCV antibody. For 
participants who are eligible with 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. Additional details are 
provided in Section 10.7 (Appendix 7).
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
Abnormal liver function tests: If laboratory testing for a participant who is enrolled in the 
study and receiving study intervention reveals an increase of serum aminotransferases (ALT 
or AST) to >3 x ULN and an increase of bilirubin to >2 x ULN, study intervention should be 
suspended immediately. In addition, laboratory tests for ALT, AST, alkaline phosphatase, and 
total bilirubin should be confirmed by a retest within 24 hours if possible, but no later than 72 
hours following notification of test results. Additional clinical and laboratory studies may be 
performed to evaluate the underlying etiology of abnormal findings. See Appendix 9 
(Section 10.9; Guideline Algorithm for Monitoring, Assessment, and Evaluation of Abnormal 
Liver Tests in Participants With No Underlying Liver Disease) for additional information on 
monitoring and assessment of abnormal liver function tests. Also refer to Section 8.3.1, Time 
Period and Frequency for Collecting Adverse Event and Serious Adverse Event Information.

Pregnancy testing: Female participants of childbearing potential will undergo a urine 
pregnancy test at screening before each study intervention administration, at a SID visit, and 
at the FES visit.
8.2.12.
Immunogenicity Assessments (Antibodies to Guselkumab and 
Ustekinumab)
Serum samples will be screened for antibodies binding to guselkumab or ustekinumab and the titer 
of confirmed positive samples will be reported as applicable. Other analyses may be performed to 
further characterize the immunogenicity of guselkumab or ustekinumab.  Antibodies to 
guselkumab or ustekinumab will be evaluated on blood drawn from all participants according to 
the Schedule of Activities (Section 1.3). Additionally, samples should also be collected at the final 
visit for participants who terminate from the study. These samples will be tested by the sponsor or 
sponsor’s designee. Genetic analyses will not be performed on these serum samples. Participant 
confidentiality will be maintained.
Evaluations
At visits where antibodies to study intervention will be evaluated in addition to serum 
concentration of study intervention, 1 venous blood sample of sufficient volume should be 
collected. Each serum sample will be divided into 3 aliquots (1 each for serum concentration of 
study intervention, antibodies to study intervention, and a back-up).
Analytical Procedures
The detection and characterization of antibodies to guselkumab and ustekinumab will be 
performed using validated assay methods by or under the supervision of the sponsor.
8.2.13.
Concomitant Medication Review
Concomitant medications will be reviewed at each visit.
8.3.
Adverse Events and Serious Adverse Events
Timely, accurate, and complete reporting and analysis of safety information 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 
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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.
Anticipated events will be recorded and reported as described in Appendix 12 (Section 10.12).
For further details on AEs and SAEs (Definitions and Classifications; Attribution Definitions; 
Severity Criteria; Special Reporting Situations; Procedures) as well as product quality complaints
(PQCs), refer to Appendix 11 (Section 10.11), Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-Up, and Reporting.
8.3.1.
Time Period and Frequency for Collecting Adverse Event and Serious 
Adverse Event Information
All Adverse Events
All AEs and special reporting situations, whether serious or non-serious, will be reported from the 
time a signed and dated ICF is obtained until completion of the participant’s last study-related 
procedure, which may include contact for follow-up of safety.
Serious Adverse Events
All SAEs occurring during the study must be reported to the appropriate sponsor or designee 
contact person by study site personnel within 24 hours of their knowledge of the event.
Information regarding SAEs will be transmitted to the sponsor or designee using the Serious 
Adverse Event Form, which must be completed and reviewed by a physician from the study site 
and transmitted to the sponsor or designee within 24 hours.
Serious adverse events, including those spontaneously reported to the investigator within 16 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.
Any possible Hy’s law case (AST or ALT ≥3xULN together with bilirubin ≥2xULN or INR >1.5) 
is considered an important medical event and must be reported to the sponsor in an expedited 
manner using the Serious Adverse Event Form, even before all other possible causes of liver injury 
have been excluded (INR criterion is not applicable to participants receiving anticoagulants). 
8.3.2.
Follow-up of Adverse Events and Serious Adverse Events
Adverse events, including pregnancy, will be followed by the investigator as specified in 
Appendix 11 (Section 10.11), Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting.
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8.3.3.
Regulatory Reporting Requirements for Serious Adverse 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 SUSARs. The investigator (or sponsor where required) must report SUSARs to the 
appropriate IEC/IRB that approved the protocol unless otherwise required and documented by the 
IEC/IRB. A SUSAR will be reported to regulatory authorities unblinded. Participating 
investigators and IEC/IRB will receive a blinded SUSAR summary, unless otherwise specified.
8.3.4.
Pregnancy
All initial reports of pregnancy in female participants or partners of male participants must be 
reported to the sponsor or designee by the study site personnel within 24 hours of their knowledge 
of the event using the appropriate pregnancy notification form. Abnormal pregnancy outcomes 
(eg, spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are 
considered SAEs and must be reported using the Serious Adverse Event Form. Any participant 
who becomes pregnant during the study must discontinue further study intervention (see Section 7
and Table 4).
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the 
infant will be required (Section 10.6, Section 10.11).
8.3.5.
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 10.11 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.
8.4.
Treatment of Overdose
For this study, any dose of study intervention greater than the highest dose at a single dosing visit 
specified in this protocol will be considered an overdose. The sponsor does not recommend 
specific intervention for an overdose.
In the event of an overdose, the investigator or treating physician should:

Contact the Medical Monitor immediately.

Closely monitor the participant for AE/SAE and laboratory abnormalities.

Document the quantity of the excess dose in the eCRF.
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the participant.
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8.5.
Pharmacokinetics
Serum samples will be used to evaluate the PK of guselkumab and ustekinumab. Samples collected 
for the analyses of serum concentrations of guselkumab and ustekinumab may additionally be used 
to evaluate safety or efficacy aspects that address concerns arising during or after the study period, 
or for the evaluation of relevant biomarkers. Genetic analyses will not be performed on these serum 
samples. Participant confidentiality will be maintained.
Evaluations
At visits where only serum concentration of study intervention will be evaluated (ie, no antibodies 
to study intervention will be evaluated), 1 venous blood sample of sufficient volume should be 
collected, and each serum sample should be divided into 2 aliquots (1 for serum concentration of 
study intervention, and a back-up). At visits where serum concentration of study intervention and 
antibodies to study intervention will be evaluated, 1 venous blood sample of sufficient volume 
should be collected. Each serum sample will be divided into 3 aliquots (1 each for serum 
concentration of study intervention, antibodies to study intervention, and a back-up).
Analytical Procedures
Serum samples will be analyzed to determine concentrations of guselkumab and ustekinumab 
using respective validated, specific, and sensitive methods by or under the supervision of the 
sponsor’s respective assay methods.
Pharmacokinetic Parameters
Serum samples will be used to evaluate various guselkumab PK parameters based on blood drawn 
from all participants according to the Schedule of Activities.
8.6.
Pharmacodynamics
Inflammatory PD markers will be evaluated using blood samples collected at visits as indicated in 
the Schedule of Activities (Section 1.3). Post-baseline PD test results will not be released to the 
investigators by the central laboratory. 

CRP has been demonstrated to be useful as a marker of inflammation in patients with IBD. 
In Crohn’s disease, elevated CRP concentrations have been associated with severe clinical 
activity, elevated sedimentation rate, and active disease as detected by colonoscopy.21 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.3 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. 
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8.7.
Genetics
A pharmacogenomic blood sample will be collected from participants who consent separately to 
this component of the study to allow for pharmacogenomic research, as necessary where local 
regulations permit. Participation in pharmacogenomic research is optional.
Genetic (DNA) variation may be an important contributory factor to interindividual variability in 
drug response and associated clinical outcomes. Genetic factors may also serve as markers for 
disease susceptibility and prognosis and may identify population subgroups that respond 
differently to an intervention.
DNA samples will be analyzed for identification of genetic factors that may be associated with 
clinical response. This research may consist of the analysis of 1 or more candidate genes, 
assessment of SNPs, or analysis of the entire genome (as appropriate) in relation to guselkumab 
or ustekinumab intervention and/or Crohn’s disease. Whole blood samples of approximately 
10 mL will be collected for genetic analyses as specified in the Schedule of Activities 
(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 or ustekinumab treatment and/or Crohn’s disease. 
Assessments (detailed below) will include the evaluation of relevant biomarkers in serum, whole 
blood, stool, and ileocolonic biopsy samples collected as specified in the Schedule of Activities, 
where local regulations permit. 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 and ustekinumab
2.
To understand Crohn’s disease pathogenesis
3.
To understand why an individual may respond differently to guselkumab or ustekinumab
4.
To understand the impact of treatment with guselkumab or ustekinumab on intestinal mucosal 
inflammation in participants with moderately to severely active Crohn’s disease
5.
To develop diagnostic tests to identify Crohn’s disease populations that may be responsive or 
non-responsive to treatment with guselkumab or ustekinumab
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.
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 
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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 not be limited to IL-17A and IL-22. Proprietary algorithms and standard 
statistical techniques, such as analysis of variance (ANOVA) and analysis of covariance 
(ANCOVA), will be used to identify individual proteins exhibiting statistically significantly 
different changes in their levels between samples and/or between groups of samples. This will 
enable the evaluation of changes in proteome profiles that may correlate with biologic response 
relating to Crohn’s disease or the mechanism of action of guselkumab.
8.8.2.
Whole Blood-based Biomarkers
Whole blood samples will be collected from all participants to assess the effect of study 
intervention on RNA expression profiles where local regulations permit. Whole blood analyses 
may also examine RNA expression associated with the pathogenesis of Crohn’s disease.
Transcriptome studies may be conducted using microarray, and/or alternative equivalent 
technologies, which facilitates the simultaneous measurement of the relative abundances of 
thousands of RNA species resulting in a transcriptome profile for each blood sample. This will 
enable the evaluation of changes in transcriptome profiles that may correlate with biologic
response relating to Crohn’s disease or the action of guselkumab.
The same samples may also be used to confirm findings by application of alternative technologies.
8.8.3.
Biopsy-based Biomarkers
Mucosal biopsy samples will be collected during ileocolonoscopy to study the effect of study 
intervention on the histological assessment of disease and healing. Biopsies will also be analyzed 
for exploratory gene and protein expression analysis where local regulations permit. Ileocolonic 
biopsy analyses may also examine gene and protein expression associated with the pathogenesis 
of Crohn’s disease.
8.8.3.1.
Optional Week 4 Biopsy Substudy
Ileocolonic biopsies will be obtained at Week 4 only from participants who agree to participate in 
the optional substudy. This optional substudy is included to investigate the mechanism of action
of guselkumab and ustekinumab, and to assess whether data collected at Week 4 correlate with 
clinical efficacy at later time points. The endoscopic assessment will also be conducted for this 
time point. Approximately 200 study participants are defined for the Week 4 ileocolonoscopy 
substudy to provide sufficient power to support exploratory analyses.
8.8.4.
Fecal Biomarkers
Fecal samples will be collected from all participants as specified in the Schedule of Activities.
Where local regulations permit, microbiome and associated products analysis will be conducted to 
evaluate the association between inflammatory proteins, microbial activities and guselkumab, 
ustekinumab, and/or Crohn’s disease. The relationships between microbiome, metabolites, and 
biomarkers in other tissue samples will also be assessed.
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8.9.
Medical Resource Utilization and Health Economics
Medical resource utilization, including but not limited to Crohn’s disease-related hospitalizations 
and surgeries, will be collected in the studies. The WPAI-CD will also be utilized to evaluate work 
productivity (Section 8.1).
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 are outlined 
below. Specific details will be provided in the SAP. There will be 2 SAPs supporting this protocol:
one for the Phase 2 study (ie, GALAXI 1) and one for the Phase 3 studies (ie, GALAXI 2 and 
GALAXI 3). A separate SAP will cover the LTE. In addition, an IA plan for Phase 2 will provide 
specific details for the dose selection analysis.
Descriptive statistics (eg, mean, median, standard deviation [SD], interquartile range, minimum, 
and maximum) will be used to summarize continuous variables. Counts and percentages will be 
used to summarize categorical variables. Graphical data displays (eg, line plots) may also be used 
to summarize data.
Analyses suitable for categorical data (eg, chi-square tests, Cochran-Mantel-Haenszel [CMH]
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 efficacy endpoints that are collected at 
multiple post baseline time points will be compared using a MMRM model. Continuous endpoints 
that are measured only at a single time point will be compared using an ANCOVA.
All statistical testing will be performed at a significance level of 0.05 (2-sided) unless otherwise 
specified. For endpoints that are not multiplicity-controlled, nominal p-values will be displayed.
9.1.
Statistical Hypotheses
9.1.1.
Phase 2 Dose-Ranging Study (GALAXI 1)
The primary hypothesis is that guselkumab is superior to placebo as assessed by the reduction from 
baseline in CDAI at Week 12.
9.1.2.
Phase 3 Dose-Confirming Studies (GALAXI 2 and GALAXI 3)
Refer to Section 3.2.2 for the co-primary and major secondary hypotheses. 
9.2.
Sample Size Determination
9.2.1.
Assumptions for Phase 2 Study
Data from several sources informed the underlying assumptions for sample size determination in 
Phase 2, as summarized below. These include the ustekinumab Crohn’s disease Phase 3 program 
consisting 
of 
3 
studies
(ie, 
CNTO1275CRD3001, 
CNTO1275CRD3002, 
and 
CNTO1275CRD3003), a program conducted by the sponsor in participants with Crohn’s disease 
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Status: Approved, Date: 12 July 2022
Clinical response at Week 12 and Endoscopic response at Week 48
The placebo rate for the endpoint of clinical response at Week 12 and endoscopic response at Week 
48 was derived by the randomized placebo arm from the Phase 2 (GALAXI 1)Week 48 DBL 
results. In GALAXI 1, 1 out of 55 (1.8%) placebo participants (meeting the GALAXI Phase 3 
eligibility criteria) were in clinical response at Week 12 and subsequently achieved endoscopic 
response at Week 48. Therefore, a placebo rate of 2% to 5% is assumed. Guselkumab rates were 
derived by the guselkumab arms in the Phase 2 (GALAXI 1) Week 48 DBL results. For the 
combined guselkumab group, 61 out of 165 (37.0%) participants randomized at Week 0 achieved 
clinical response at Week 12 and endoscopic response at Week 48. The overall treatment 
difference versus placebo was 35%. Based on these results, a difference of 30% to 35% between 
guselkumab and placebo is assumed. 
9.2.2.2.
Regional Endpoints
The assumptions for the original co-primary endpoints were also re-evaluated based on the 
GALAXI 1 (Phase 2) Week 48 DBL.
Clinical remission at Week 12
The placebo rate for the endpoint of clinical remission at Week 12 was derived from the 
randomized placebo arm from the Phase 2 (GALAXI 1) Week 48 DBL. In GALAXI 1, 6 out of 
55 (10.9%) placebo participants (meeting the GALAXI Phase 3 eligibility criteria) were in clinical 
remission at Week 12. Therefore, a placebo rate of 10% to 15% is assumed. Guselkumab rates 
were derived from the guselkumab arms in the Phase 2 (GALAXI 1) Week 48 DBL. For the 
combined guselkumab group, 86 out of 165 (52.1%) participants randomized at Week 0 achieved 
clinical remission at Week 12. The overall treatment difference versus placebo was 41%.  Based 
on these results, a difference of 35% to 40% between guselkumab and placebo is assumed. 
Endoscopic response at Week 12
The placebo rate for the endpoint of endoscopic response at Week 12 was derived from the 
randomized placebo arm from the Phase 2 (GALAXI 1) Week 48 DBL. In GALAXI 1, 7 out of 
55 (12.7%) placebo participants (meeting the GALAXI Phase 3 eligibility criteria) were in 
endoscopic response at Week 12. Therefore, a placebo rate of 10% to 13% is assumed. 
Guselkumab rates were derived from the guselkumab arms in the Phase 2 (GALAXI 1) Week 48 
DBL. For the combined guselkumab group, 57 out of 165 (34.5%) participants randomized at 
Week 0 achieved endoscopic response at Week 12. The overall treatment difference versus placebo 
was 22%.  Based on these results, a difference of 20% to 25% between guselkumab and placebo 
is assumed.
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9.2.3.
Power and Sample Size Calculations
9.2.3.1.
Phase 2 Dose-Ranging Study (GALAXI 1)
Power for Phase 2 was evaluated for the 2 analysis populations described below, using a 2-sample 
t-test (at the 0.05 level of significance) to detect a significant difference in the change from baseline 
in the CDAI score at Week 12 between the guselkumab high 
 induction dose and placebo. 
Assuming the mean CDAI reductions from baseline at Week 12 of approximately 105 to 115 in 
the guselkumab high
 induction dose group versus approximately 45 to 50 in the placebo group 
with a common SD of 100:
For the Initial Dose Decision Cohort: 50 participants in the guselkumab high 
 induction dose 
group and 50 participants in the placebo group will provide greater than 80% power to detect a 
treatment difference between guselkumab and placebo at a Type 1 error rate controlled at α=0.05 
(2-sided) (Table 9). With 5 dose groups, the total sample size for the Initial Dose Decision Cohort 
is 250 participants.
For the Total Phase 2 Population: It is anticipated that 100 to 250 participants will be enrolled 
into the Transition Cohort by the time a dose decision is made for Phase 3. Thus, the sample size 
for the total Phase 2 study is expected to range from a minimum of 350 participants (70 per dose 
group) up to a maximum of 500 participants (100 per dose group). The power, based on the 
minimum number of participants, is greater than 90% for the change from baseline in the CDAI 
score at Week 12 and greater than 85% for clinical remission at Week 12 (Table 9).
Table 9:
Power to Detect a Treatment Effect of Guselkumab Versus Placebo Based on Mean 
Change in CDAI and Proportion of Participants Achieving Clinical Remission at Week 12
Change in CDAI at Week 12*
Clinical remission at Week 12
Initial Dose Decision Cohort
Placebo
(n=50)
Guselkumab
(n=50)
Power
Placebo
(n=50)
Guselkumab
(n=50)
Power
45
95
70%
12%
30%
52%
45
105
84%
12%
35%
73%
50
105
78%
15%
35%
57%
50
115
89%
15%
40%
76%
Total Phase 2 Population
(minimal sample size)
Placebo
(n=70)
Guselkumab
(n=70)
Power
Placebo
(n=70)
Guselkumab
(n=70)
Power
45
95
83%
12%
30%
69%
45
105
94%
12%
35%
87%
50
105
90%
15%
35%
73%
50
115
97%
15%
40%
89%
*SD=100.
C
CI
C
CI
C
CI
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9.2.3.2.
Phase 3 Dose-Confirming Studies (GALAXI 2 and GALAXI 3)
GALAXI 2 and GALAXI 3 are separate studies and will have separate type I error control at the 
2-sided 0.05 significance level. 
The power for the key endpoints in these Phase 3 studies (ie, Global co-primary endpoints, 
Regional co-primary endpoints, Regional endpoints of corticosteroid-free clinical remission at 
Week 48 and endoscopic response at Week 48 [which are meant to demonstrate the long-term 
efficacy of guselkumab versus placebo]), as well as the number of participants necessary to assess 
the safety of guselkumab, were considered in determining the appropriate sample size for these 
Phase 3 studies. Based on this, a total sample size of approximately 980 participants 
(approximately 490 participants per study, consisting of 140 participants in each of the two 
guselkumab treatment groups, 70 participants in the placebo treatment group, and 140 participants 
in the ustekinumab group) will provide at least 90% power for these key endpoints in each study.
9.2.3.2.1.
Global Endpoints
For the co-primary endpoint of clinical response at Week 12 and clinical remission at 
Week 48: In each of the Phase 3 studies, assuming a rate of 8% to 10% for placebo and a 40% to 
45% difference between guselkumab and placebo based on Phase 2 (GALAXI 1) results, 140 
participants in each guselkumab dose group and 70 participants in the placebo group will provide 
>99% power for this endpoint at the 0.05 (2-sided) alpha level (Table 10).
For the co-primary endpoint of clinical response at Week 12 and endoscopic response at 
Week 48: In each of the Phase 3 studies, assuming a rate of approximately 2% to 5% for placebo 
and a 30% to 35% difference between guselkumab and placebo based on Phase 2 (GALAXI 1) 
results, 140 participants in each guselkumab dose group and 70 participants in the placebo group 
will provide >99% power for this endpoint at the 0.05 (2-sided) alpha level (Table 10).
Table 10: 
Power to Detect a Treatment Effect of Guselkumab versus Placebo for Global Co-primary 
Endpoints
Clinical Response at Week 12 and Clinical Remission at Week 48
Placebo (n=70)
Guselkumab (n=140)
Power
8%
10%
8%
10%
48%
50%
53%
55%
>99%
>99%
>99%
>99%
Clinical Response at Week 12 and Endoscopic Response at Week 48
Placebo (n=70)
Guselkumab (n=140)
Power
2%
5%
2%
5%
32%
35%
37%
40%
>99%
>99%
>99%
>99%
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9.2.3.2.2.
Regional Endpoints
Note that the 2 guselkumab dose groups will receive identical induction intervention, therefore, 
for short-term comparisons between guselkumab and placebo, the 2 guselkumab dose groups will 
be combined to compare to placebo. This comparison is applicable for all short-term endpoints, 
including regional co-primary endpoints, major secondary endpoints and exploratory endpoints. It 
will be referred to as the combined guselkumab induction dose group throughout the protocol.
For the co-primary endpoint of clinical remission at Week 12: In each of the Phase 3 studies, 
assuming a clinical remission at Week 12 rate of approximately 10% to 15% for placebo and a 
35% to 40% difference between guselkumab and placebo based on Phase 2 (GALAXI 1) Week 48 
DBL, 280 participants in the combined guselkumab induction dose group and 70 participants in 
the placebo group, respectively, will provide greater than 99% power for clinical remission at 
Week 12 at an overall Type 1 error rate controlled at 0.05 (2-sided) (Table 11). 
For the co-primary endpoint of endoscopic response at Week 12: In each of the Phase 3 studies, 
assuming an endoscopic response at Week 12 rate of approximately 10% to 13% for placebo and 
a 20% to 25% difference between guselkumab and placebo based on Phase 2 (GALAXI 1) Week 
48 DBL, 280 participants in the combined guselkumab induction dose group and 70 participants 
in the placebo group, respectively, will provide approximately 95% power for endoscopic response 
at Week 12 at an overall Type 1 error rate controlled at 0.05 (2-sided) (Table 11).  
Table 11:
Power to Detect a Treatment Effect of Guselkumab Versus Placebo for the Regional Co-
primary Endpoints at Week 12 
Co-Primary Endpoint of Clinical Remission at Week 12
Placebo (n=70)
Guselkumab (n=280)
Power
10%
45%
>99%
10%
50%
>99%
15%
50%
>99%
15%
55%
>99%
Co-Primary Endpoint of Endoscopic Response at Week 12
Placebo (n=70)
Guselkumab (n=280)
Power
10%
30%
97%
13%
33%
95%
10%
35%
>99%
13%
38%
>99%
9.3.
Populations for Analyses
For purposes of analysis, the following populations are defined for Phase 2 (Table 12) and Phase 3 
(Table 13) studies. Note: Additional analysis populations may be defined in the SAP:
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Table 12:
Populations for Analyses for Phase 2 Study
Population
Description
Randomized Analysis Set
All participants who are randomized
Full Analysis Set
All participants who are randomized and receive at least 1 dose of study 
intervention.
Safety Analysis Set
All participants who are randomized and received at least 1 dose of study 
intervention (including a partial dose).
Table 13: 
Populations for Analyses for Phase 3 Studies
Analysis Sets
Description
Randomized
The randomized analysis set includes all participants who were randomized in 
the study.
Primary Analysis Set (PAS)
The Primary analysis set (PAS) includes all randomized participants who 
received at least 1 (partial or complete) dose of study intervention and satisfied 
the SES-CD eligibility criteria adopted in Protocol Amendment 3 (ie, 
screening SES-CD score ≥6 (or ≥4 for participants with isolated ileal disease)).
Primary Safety Analysis Set 
The Primary Safety analysis set includes all randomized participants who 
received at least 1 (partial or complete) dose of study intervention and satisfied 
the SES-CD eligibility criteria adopted in Protocol Amendment 3 (ie, 
screening SES-CD score ≥6 (or ≥4 for participants with isolated ileal disease)). 
Primary Pharmacokinetics 
Analysis Set (PPK)
The Primary guselkumab PK analysis set (GPPK) is defined as all randomized 
participants who received at least 1 (partial or complete) dose of guselkumab 
and satisfied the SES-CD eligibility criteria adopted in Protocol Amendment 3 
(ie, screening SES-CD score ≥6 [or ≥4 for participants with isolated ileal 
disease]) and have at least 1 valid post-baseline blood sample drawn for PK 
analysis.
The Primary ustekinumab PK analysis set (UPPK) is defined as all 
randomized participants who received at least 1 (partial or complete) dose of 
ustekinumab and satisfied the SES-CD eligibility criteria adopted in Protocol 
Amendment 3 (ie, screening SES-CD score ≥6 [or ≥4 for participants with 
isolated ileal disease]) and have at least 1 valid post-baseline blood sample 
drawn for PK analysis.
Primary Immunogenicity 
Analysis Set (PIM)
The Primary guselkumab Immunogenicity analysis set (GPIM) is defined as 
all participants who received at least 1 (partial or complete) dose of 
guselkumab and satisfied the SES-CD eligibility criteria adopted in Protocol 
Amendment 3 (ie, screening SES-CD score ≥6 [or ≥4 for participants with 
isolated ileal disease]) and have appropriate samples for detection of 
antibodies to guselkumab (ie, participants with at least 1 sample obtained after 
their first dose of guselkumab).
The Primary ustekinumab Immunogenicity analysis set (UPIM) is defined as 
all participants who received at least 1 (partial or complete) dose of 
ustekinumab and satisfied the SES-CD eligibility criteria adopted in Protocol 
Amendment 3 (ie, screening SES-CD score ≥6 [or ≥4 for participants with 
isolated ileal disease]) and have appropriate samples for detection of 
antibodies to ustekinumab (ie, participants with at least 1 sample obtained after 
their first dose of ustekinumab).
  
Note: Additional analysis sets used for supportive analyses (eg, those that include all treated participants, including 
those participants who do not meet the SES-CD entry criteria) will be identified and described in the SAP.
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9.4.
Statistical Analyses
9.4.1.
Endpoints
9.4.1.1.
Phase 2 Dose-Ranging Study (GALAXI 1)
For the primary and major secondary endpoints, comparisons of each guselkumab group with the 
placebo group will be made. Note that the final ordering of the major secondary endpoints 
will be provided in the Phase 2 SAP.
Primary Endpoint
Change from baseline in the CDAI score at Week 12.  
Major Secondary Endpoints

Clinical remission at Week 12 (defined as CDAI score <150).

Clinical response at Week 12 (defined as ≥100-point reduction from baseline in CDAI score 
or CDAI score <150).

PRO-2 remission at Week 12 (defined as an AP mean daily score at or below 1 [AP≤1] AND 
an SF mean daily score at or below 3 [SF≤3], and no worsening of AP or SF from baseline).

Clinical-biomarker response at Week 12 (clinical response based on CDAI score and ≥50% 
reduction from baseline in CRP or fecal calprotectin).

Endoscopic response at Week 12 (defined as at least 50% improvement from baseline in SES-
CD score or SES-CD score ≤2).
Exploratory Endpoint(s)
Short-term Efficacy
The short-term endpoints for Phase 2 are the same as those for Phase 3 (refer to Section 9.4.1.2).
In addition, the following endpoints will be assessed:

Fatigue response at Week 12 (based on PROMIS Fatigue Short Form 7a; to be defined in the 
SAP).

Change in SES-CD score from baseline at Week 12, endoscopic response at Week 12, 
endoscopic remission at Week 12, and endoscopic healing at Week 12, among participants 
with baseline SES-CD ≥4 (ie, for participants with isolated ileal disease) or SES-CD ≥6 (ie, 
for participants with colonic or ileocolonic disease). 
The comparisons for these endpoints will be of each guselkumab group with the placebo group.
Long-term Efficacy
The long-term endpoints for Phase 2 are the same as those for Phase 3 (refer to Section 9.4.1.2). 
In addition, clinical remission and PRO-2 remission at Week 24 will be assessed based on the 
following:

among participants in clinical response at Week 12
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
among participants in clinical remission (or PRO-2 remission) at Week 12

by CRP level (CRP ≤5 mg/L, >5 mg/L to ≤10 mg/L, and >10 mg/L) at Week 12

by fecal calprotectin level (fecal calprotectin <250 µg/g, ≥250 µg/g) at Week 12
The comparisons for these endpoints will be of each guselkumab group with the ustekinumab 
group.
Endpoints (short-term and long-term) based on the following measures will also be defined in the 
Phase 2 SAP:

AP-NRS

BSFS

Change from baseline in PGIS

PGIC

Assessments for histologic improvement and histologic healing
9.4.1.2.
Phase 3 Dose-Confirming Studies (GALAXI 2 and GALAXI 3)
GALAXI 2 and GALAXI 3 are identical studies and have the same endpoints, as described 
below.
9.4.1.2.1.
Global Endpoints
Co-primary Endpoints
The Global co-primary endpoints are:

Clinical response at Week 12 and clinical remission at Week 48

Clinical response at Week 12 and endoscopic response at Week 48
For these endpoints, comparisons will be made within each study between each guselkumab dose 
(guselkumab 
 and 
placebo.  
Major Secondary Endpoints  
The Global major secondary endpoints are grouped into 3 categories based on timepoint and 
comparator; note that these are grouped for the purpose of categorization but are not presented in 
the order of testing in the multiplicity-controlled testing procedure (the specific order for the 
testing procedure will be provided in the statistical analysis plan).
The Global major secondary endpoints below evaluate the short-term efficacy of guselkumab 
versus placebo in each study:

Clinical response at Week 4
CCI
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
Clinical remission at Week 12

Endoscopic response at Week 12

Fatigue response at Week 12

Clinical remission at Week 12 and endoscopic response at Week 12

Endoscopic remission (Global definition) at Week 12
Note that the 2 guselkumab dose groups will receive identical induction intervention, therefore, 
for short-term comparisons between guselkumab and placebo, the 2 guselkumab dose groups will 
be combined to compare to placebo. 
The following long-term endpoints evaluate guselkumab versus placebo in each study:

Clinical response at Week 12 and corticosteroid-free clinical remission at Week 48 

Clinical response at Week 12 and endoscopic remission (Global definition) at Week 48
These following long-term endpoints evaluate guselkumab versus ustekinumab:

Clinical remission at Week 48

Endoscopic response at Week 48

Clinical remission at Week 48 and endoscopic response at Week 48

Endoscopic remission at Week 48

Deep remission (Global definition) at Week 48
9.4.1.2.2.
Regional Endpoints
Co-primary Endpoints
The Regional co-primary endpoints are:

Clinical remission at Week 12 

Endoscopic response at Week 12 
For these endpoints, comparisons will be made within each study between the combined 
guselkumab induction dose group and placebo.
Major Secondary Endpoints
The Regional major secondary endpoints are grouped into 3 categories based on timepoint and 
comparator; note that these are grouped for the purpose of categorization but are not presented in 
the order of testing in the multiplicity-controlled testing procedure (the specific order for the 
testing procedure will be provided in the statistical analysis plan).
The following Regional major secondary endpoints evaluate the short-term efficacy of guselkumab 
versus placebo: 
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
PRO-2 remission at Week 12 

Fatigue response at Week 12

Endoscopic remission (Regional definition) at Week 12
The following long-term endpoints evaluate guselkumab versus placebo:

Corticosteroid-free clinical remission at Week 48

Endoscopic response at Week 48
The following long-term endpoints evaluate guselkumab versus ustekinumab:

Endoscopic remission (Regional definition) at Week 48 

Clinical remission at Week 48 

Endoscopic response at Week 48

Durable clinical remission at Week 48

PRO-2 remission at Week 48 

Clinical remission at Week 48 and endoscopic response at Week 48 

Corticosteroid-free clinical remission at Week 48
9.4.1.2.3.
Exploratory Endpoints
Exploratory endpoints include but are not limited to the endpoints below. A complete list of the 
exploratory endpoints will be provided in the SAP.  The Regional and Global co-primary and 
major secondary endpoints are not the same. If a Global major secondary is not listed as a Regional 
major secondary endpoint, it will be considered exploratory for the Regional endpoints. If a 
Regional major secondary is not listed as a Global major secondary endpoint, it will be considered 
exploratory for the Global endpoints. Exploratory endpoints that include a component of 
endoscopic remission are specified as the Global and/or Regional definition of endoscopic 
remission.  
Short-term Efficacy vs. Placebo
The following endpoints will be assessed, and the comparisons within each study will be of the 
combined guselkumab induction dose group with placebo. 

Change in CDAI score from baseline at all post-baseline visits through Week 12

Clinical remission at all post-baseline visits through Week 12

Clinical response at all post-baseline visits through Week 12
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
Clinical-biomarker response (clinical response and ≥50% reduction from baseline in CRP or 
fecal calprotectin) at Week 12

PRO-2 remission at all post-baseline visits through Week 12

Abdominal pain score (daily average based on the CDAI assessment) ≤1 at all post-baseline 
visits through Week 12, among participants with daily average AP score >1 at baseline

Number of liquid or very soft stools (daily average based on the CDAI assessment) ≤3 at all 
post-baseline visits through Week 12, among participants with daily average number of liquid 
or very soft stools >3 at baseline

Change in SES-CD score from baseline at Week 12

Endoscopic healing (defined as the absence of mucosal ulcerations) at Week 12

Fistula response at all post-baseline visits through Week 12, defined as a ≥50% reduction from 
baseline in the number of draining fistulas, among participants with 1 or more fistulas at 
baseline

Complete fistula response at all post-baseline visits through Week 12, among participants with 
1 or more fistulas at baseline

Change in CRP at all post-baseline visits through Week 12

Normalization of CRP concentrations at Week 8 and Week 12, among participants with 
elevated CRP at baseline

Change in fecal calprotectin from baseline at Week 8 and Week 12

Fecal calprotectin concentration of ≤250 µg/g at Week 8 and Week 12, fecal calprotectin ≤100 
µg/g at Weeks 8 and 12, and fecal calprotectin ≤50 µg/g at Weeks 8 and 12 among participants 
with fecal calprotectin >250 µg/g at baseline

Change from baseline in IBDQ score (including IBDQ domains) at Week 8 and Week 12

IBDQ remission (based on IBDQ ≥170) at Week 8 and Week 12

IBDQ response (≥16-point improvement from baseline) at Week 8 and Week 12

Change from baseline in the 7 domains and the pain NRS score of PROMIS-29 at Week 8 and 
Week 12

Responses in the 7 domains and the pain NRS score of PROMIS-29 (to be defined in the SAP) 
at Week 8 and Week 12

Change from baseline in the PROMIS Fatigue Short Form 7a total score at Week 8 and 
Week 12

Change from baseline in the EQ-5D dimensions and EQ-VAS at Week 8 and Week 12

Change from baseline in each of 4 impairments from WPAI-CD at Week 8 and Week 12

Crohn’s disease-related hospitalizations and/or Crohn’s disease-related surgeries through 
Week 12
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Long-Term Efficacy vs Placebo 
The following endpoints will be assessed, and the comparisons will be for each guselkumab group 
with the placebo group. 

Clinical response at Week 12 and deep remission (Global definition) at Week 48

Clinical response at Week 12 and clinical response at Week 48 (Sustained response)

Clinical response at Week 12 and 90-day steroid free clinical remission at Week 48 

Clinical remission at Week 12 and clinical remission at Week 48 (Sustained remission) 

Deep remission (Regional definition) at Week 48
Long-Term Efficacy vs Ustekinumab 
The following endpoints will be assessed, and the comparisons will be for each guselkumab group 
with the ustekinumab group.

Corticosteroid-free (90-days) clinical remission at Week 48 (defined as CDAI <150 at 
Week 48 and not receiving corticosteroids for at least 90 days prior to Week 48)

Change in CDAI score from baseline at all post-baseline visits from Week 16 to Week 48

Clinical remission (CDAI score <150) at all post-baseline visits from Week 16 to Week 48

Clinical remission at Week 12 and clinical remission at Week 48 (Sustained remission)

Clinical response at all post-baseline visits from Week 16 to Week 48

PRO-2 remission (AP ≤1 and SF ≤3 and no worsening of AP or SF from baseline) at all post-
baseline visits from Week 16 to 48

Abdominal pain score (daily average based on the CDAI assessment) ≤1 at all post-baseline 
visits from Week 16 to Week 48, among participants with daily average AP score >1 at 
baseline

Number of liquid or very soft stools (daily average based on the CDAI assessment) ≤3 at all 
post-baseline visits from Week 16 to Week 48, among participants with daily average number 
of liquid or very soft stools >3 at baseline

Fistula response at all post-baseline visits from Week 16 to 48, defined as a ≥50% reduction 
from baseline in the number of draining fistulas among participants with 1 or more fistulas at 
baseline

Complete fistula response at all post-baseline visits from Week 16 to 48 among participants 
with 1 or more fistulas at baseline

Change in SES-CD score from baseline at Week 48

Endoscopic healing (defined as the absence of mucosal ulcerations) at Week 48

Change in CRP from baseline at all post-baseline visits from Week 16 to Week 48

Normalization of CRP concentrations at Week 24 and Week 48 among participants with 
elevated CRP at baseline
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
Change in fecal calprotectin from baseline at Week 24 and Week 48

Fecal calprotectin concentration ≤250 µg/g at Week 24 and Week 48, and fecal calprotectin 
≤100 µg/g at Weeks 24 and 48, among participants with fecal calprotectin >250 µg/g at 
baseline

Clinical-biomarker response (clinical response and ≥50% reduction from baseline in CRP or 
fecal calprotectin) at Week 24 and Week 48

Clinical response and normalization of CRP concentration and fecal calprotectin 
concentration ≤250 µg/g at Week 24 and Week 48, among participants with elevated CRP or 
fecal calprotectin >250 µg/g at baseline

Change in IBDQ score and domain scores from baseline at Week 24 and Week 48

IBDQ remission (based on IBDQ ≥170) at Week 24 and Week 48

IBDQ response (≥16-point improvement from baseline) at Week 24 and Week 48

Change from baseline in the 7 domains and the pain NRS score of PROMIS-29 at Week 24 
and Week 48 

Responses in the 7 domains and the pain NRS score of PROMIS-29 (to be defined in the SAP) 
at Week 24 and Week 48

Change from baseline in the PROMIS Fatigue Short Form 7a total score at Weeks 24 and 48

Fatigue response (defined as an improvement of ≥ 7 points in PROMIS Fatigue Short Form 
7a) at Week 24

Change from baseline in the EQ-5D dimensions and EQ-VAS at Week 24 and Week 48

Change from baseline in each of 4 impairment percentages from WPAI-CD at Week 24 and 
Week 48

Crohn’s disease-related hospitalizations through Week 48 and Crohn’s disease-related 
surgeries through Week 48
Endpoints (short-term and long-term) based on the following measures will be defined in the 
Phase 3 SAP:

AP-NRS

BSFS

Assessments for histologic improvement and histologic healing
Refer to Study Assessments and Procedures (Section 8) for evaluations related to endpoints.
9.4.2.
Phase 2 (GALAXI 1) Efficacy Analyses
9.4.2.1.
Population for Efficacy Analysis
Unless otherwise noted, efficacy analyses will be based on the Full Analysis Set, which is defined 
as all randomized participants who had at least 1 study intervention administration in GALAXI 1 
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9.4.2.3.
Major Secondary Endpoint Analysis
The major secondary endpoints are:

Clinical remission at Week 12 (defined as CDAI score <150)

Clinical response at Week 12 (defined as ≥100-point reduction from baseline in CDAI score 
or CDAI score <150)

PRO-2 remission at Week 12 (defined as an AP mean daily score at or below 1 [AP≤1] AND 
an SF mean daily score at or below 3 [SF≤3], and no worsening of AP or SF from baseline)

Clinical-biomarker response at Week 12 (clinical response based on CDAI score and ≥50% 
reduction from baseline in CRP or fecal calprotectin)

Endoscopic response at Week 12 (defined as at least 50% improvement from baseline in SES-
CD score or SES-CD score ≤2)
Participants who meet 1 or more treatment failure rules (as specified for the primary endpoint) 
before Week 12 will be considered not to be in clinical remission or clinical response, either based 
on CDAI or PRO-2. For endoscopic response, the same treatment failure rules apply, except for a 
modification of the “certain changes in concomitant Crohn’s disease medications” rule, which will 
only consider prohibited medications as treatment failure. Details will be provided in the Phase 2 
SAP.
The CDAI score will be calculated for a visit if at least 4 of the 8 components are available at that 
visit. When at least 4 of the 8 components are available, any missing components will be imputed 
by carrying forward the last available components. The clinical response or remission endpoints 
will be determined based on these imputed CDAI scores. If the CDAI score cannot be calculated 
(ie, <4 components available) at a visit, the CDAI score will be considered missing for that visit. 
Participants who do not return for evaluation or have a missing CDAI score at Week 12 will be 
considered not to be in clinical remission or clinical response as measured by the CDAI score. 
Participants who do not return for evaluation or have missing AP or SF scores at Week 12 will not 
be considered to have achieved clinical remission, as measured by PRO-2. Participants with a 
nonevaluable or missing endoscopy will be considered not in endoscopic response. The details for 
handling missing segments in the SES-CD score will be described in the Phase 2 SAP.
The major secondary endpoints of clinical remission (either based on CDAI or PRO-2), clinical 
response, and clinical-biomarker response at Week 12 will be compared between each guselkumab 
dose group and the placebo group using the CMH test (2-sided) stratified by baseline CDAI score 
(≤300 or >300) and BIO-Failure status (Yes/No), at a significance level of 0.05. Endoscopic 
response at Week 12 will be compared between each guselkumab dose group and the placebo 
group using the CMH test (2-sided) stratified by SES-CD score (≤12 or >12) and BIO-Failure 
status (Yes/No), at a significance level of 0.05.
Details of the multiplicity control of these major secondary endpoints will be specified in the 
Phase 2 SAP.
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9.4.2.4.
Other Efficacy Endpoint Analyses
Pairwise comparisons of each guselkumab treatment group with the placebo treatment group or
the ustekinumab treatment group will be made for certain endpoints (as specified in 
Section 9.4.1.1), with details that are to be specified in the Phase 2 SAP.
The treatment failures rules are the same as those specified for the primary endpoint except for the 
following addition:

Protocol-specified recommendation for discontinuation of study intervention at Week 24 due 
to lack of efficacy.
No adjustments for multiple comparisons will be made and nominal p-values will be presented.
9.4.3.
Phase 3 (GALAXI 2 and GALAXI 3) Efficacy Analyses
In this protocol, the co-primary and major secondary endpoints, as well as all other endpoints, are 
the same in GALAXI 2 and GALAXI 3. Each study will control the overall Type I error rate at the 
0.05 level of significance (2-sided).
9.4.3.1.
Population for Efficacy Analysis
Unless otherwise noted, efficacy analyses within each study will be based on the Primary Analysis 
Set for that study, which includes all randomized participants who received at least 1 (partial or 
complete) dose of study intervention and satisfied the SES-CD eligibility criteria adopted in 
Protocol Amendment 3 (ie, screening SES-CD score ≥6 [or ≥4 for participants with isolated ileal 
disease]). Participants will be analyzed according to the treatment group to which they were 
randomized regardless of the treatment they received.
9.4.3.2.
Primary Endpoint Analysis
9.4.3.2.1.
Global Primary Endpoint Analysis
The Global co-primary endpoints in each Phase 3 study are:

clinical response at Week 12 and clinical remission at Week 48

clinical response at Week 12 and endoscopic response at Week 48
For testing of the co-primary endpoints, the efficacy of each dose of guselkumab versus placebo 
will be compared. A CMH test (2-sided) stratified by baseline CDAI score (≤300 or >300), 
baseline SES-CD score (≤12 or >12), BIO-Failure status (Yes/No), and baseline corticosteroid use 
(Yes/No) will be used. Additional analysis considerations are provided in Section 9.4.3.2.3.
To control the Type I error at the 2-sided 0.05 significance level, a fixed sequence testing approach 
will be used for the co-primary endpoints for each study. Specifically, the sequential testing will 
begin with the guselkumab 
 group with the following 2 co-
primary endpoints tested sequentially:  
CCI
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
clinical response at Week 12 and clinical remission at Week 48 

clinical response at Week 12 and endoscopic response at Week 48
Followed by the guselkumab 
 group with the same co-
primary endpoints tested sequentially:

clinical response at Week 12 and clinical remission at Week 48 

clinical response at Week 12 and endoscopic response at Week 48
Each study will be considered positive if the guselkumab 
 
group is significantly different from the placebo group for both of the co-primary endpoints. 
9.4.3.2.2.
Regional Primary Endpoint Analysis
The co-primary endpoints in each Phase 3 study are:

clinical remission at Week 12

endoscopic response at Week 12 
For testing of the co-primary endpoints, the efficacy of the induction dose of guselkumab versus 
placebo will be compared. As such, within each study, the two guselkumab groups that are 
randomized to receive identical guselkumab induction treatment through Week 12 will be 
combined for these comparisons. To control the Type I error at the 2-sided 0.05 significance level, 
a fixed sequence testing approach will be used with the 2 co-primary endpoints tested 
sequentially:

clinical remission at Week 12

endoscopic response at Week 12 
A CMH test (2-sided) stratified by baseline CDAI score (≤300 or >300), baseline SES-CD score 
(≤12 or >12), BIO-Failure status (Yes/No), and baseline corticosteroid use (Yes/No) will be used.
Additional analysis considerations are provided in Section 9.4.3.2.3.
9.4.3.2.3.
Analysis Methods Applicable to both Global and Regional Co-primary 
Endpoints
Participants who have any of the following events before the Week 12 visit (for short-term 
endpoints) or before the Week 48 visit (for long-term endpoints) will be considered as treatment 
failures, and will not be considered to have achieved the endpoint: 

Specified changes in concomitant Crohn’s disease medications (to be detailed in the Phase 3 
SAP)

A Crohn’s disease-related surgery (except drainage of an abscess or seton placement)

Discontinuation of study intervention due to lack of efficacy or due to an AE of worsening 
Crohn’s disease (NOTE: For all endpoints [including major secondary and other endpoints] 
assessed at Week 24 and beyond, this includes discontinuation of study intervention at 
Week 24 due to Week 20/24 non-responder criteria)   
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The CDAI score will be calculated for a visit if at least 4 of the 8 components are available at that 
visit. When at least 4 of the 8 components are available, any missing components will be imputed 
by carrying forward the last available components. If the CDAI score cannot be calculated (ie, < 4 
components available) at a visit, the CDAI score will be considered missing for that visit. 
Participants who do not return for evaluation or have a missing CDAI score at Week 12 and/or 
Week 48 will not be considered to have achieved the Global co-primary endpoint of clinical 
response at Week 12 and clinical remission at Week 48. Likewise, participants who do not return 
for evaluation or have a missing CDAI score at Week 12 will not be considered to have achieved 
the Regional co-primary endpoint of clinical remission at Week 12.  
The total SES-CD score at a visit will be calculated based on all segments scored at the visit. If the 
total SES-CD score cannot be calculated (ie, no segment is scored) at a visit, the total SES-CD 
score will be considered missing. Participants who do not return for evaluation or who have a 
missing SES-CD score at Week 48 or a missing CDAI score at Week 12 will not be considered to 
have achieved the Global co-primary endpoint of clinical response at Week 12 and endoscopic 
response at Week 48. Similarly, participants who do not return for evaluation or who have a 
missing SES-CD score at Week 12 will not be considered to have achieved the Regional co-
primary endpoint of endoscopic response at Week 12.
Treatment failure rules will overrule the missing data rules. The statistical analysis plan (SAP) will 
provide details on analysis rules for the data impacted by any major disruption.
To examine the robustness of the co-primary endpoint analyses, sensitivity analyses of the 
co-primary endpoints will be conducted using different missing data approaches; these analyses 
will be described in the Phase 3 SAP. 
Subgroup analyses of the co-primary endpoints will be performed based on demographic and 
baseline disease characteristics and baseline use and history of Crohn’s disease medications 
(including BIO-Failure status).
9.4.3.3.
Major Secondary Endpoint Analysis
9.4.3.3.1.
Global Major Secondary Endpoint Analyses
The Global major secondary endpoints are grouped into 3 categories as listed in Section 9.4.1.2.1
(note that these are grouped for the purpose of categorization but are not presented in the order of 
testing in the testing procedure). 
The major secondary endpoints in the first category evaluate the short-term efficacy of the 
combined guselkumab induction dose group versus placebo; the major secondary endpoints in the 
second category evaluate the long-term efficacy of each guselkumab dose group versus placebo; 
and the major secondary endpoints in the third category evaluate the long-term efficacy of each 
guselkumab dose group vs. ustekinumab. For all 3 sets of comparisons, the CMH test (2-sided) 
stratified by baseline CDAI score (≤300 or >300), baseline SES-CD (≤12 or >12), BIO-Failure 
status (Yes/No), and baseline corticosteroid use (Yes/No) will be used. 
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Participants who meet 1 or more treatment failure rules before a visit will be considered not to 
have achieved any of the major secondary endpoints from that visit onward. The treatment failure 
rules and missing data rules will follow the principles of the rules specified for the co-primary 
endpoints. Additional analysis considerations will be specified in the SAP.  
A Global testing procedure to control the Type-I error at the 2-sided 0.05 significance level for the 
co-primary endpoints and the major secondary endpoints will be performed for each study 
separately. Each study will be tested with a separate testing procedure, but some tests of each 
guselkumab group vs. ustekinumab within each studies’ testing procedure may be based on data 
pooled across studies.  An overview is described below, and more details are specified in the SAP. 
The testing procedure begins with sequential tests (within each Phase 3 study) of superiority of 
each guselkumab dose group compared with placebo relative to the co-primary endpoints at the 2-
sided 0.05 significance level for each study. If any of these tests of the co-primary endpoints within 
a study is not significant (ie, p>0.05), all subsequent p-values in the testing hierarchy will be 
considered nominal. The major secondary endpoints will be grouped into tiers for testing. Within 
each tier, the Hochberg procedure will be used. 10 The testing procedure will start with Tier 1. If 
all p-values in a tier are less than 0.05, all tests will be declared significant, and the procedure will 
move onto the next tier. If at least one p-value is greater than 0.05 in a tier, formal testing will stop, 
and other endpoints within the same tier could still be declared as significant if they meet the 
Hochberg thresholds, but all p-values in subsequent tiers would be considered as nominal.
9.4.3.3.2.
Regional Major Secondary Endpoint Analyses 
The Regional major secondary endpoints are listed in Section 9.4.1.2.2.
Within each study, the major secondary endpoints of clinical remission at Week 12 as measured 
by PRO-2, fatigue response at Week 12, and endoscopic remission at Week 12 will be compared 
between the combined guselkumab induction dose group and the placebo group using the 
CMH test (2-sided) stratified by baseline CDAI score (≤300 or >300), baseline SES-CD (≤12 or 
>12), BIO-Failure status (Yes/No), and baseline corticosteroid use (Yes/No). 
The major secondary endpoints of endoscopic response at Week 48 and corticosteroid-free clinical 
remission at Week 48 will be compared between each guselkumab dose group and the placebo 
group using the CMH test (2-sided) stratified by baseline CDAI score (≤300 or >300), baseline 
SES-CD (≤12 or >12), BIO-Failure status (Yes/No), and baseline corticosteroid use (Yes/No). For 
these comparisons, clinical non-responders at Week 12 will be considered non-responders.
The major secondary endpoints of clinical remission at Week 48 (either based on CDAI or PRO-
2), endoscopic response at Week 48, endoscopic remission at Week 48, clinical remission at Week 
48 and endoscopic response at Week 48, durable clinical remission at Week 48, and corticosteroid-
free remission at Week 48 will be compared between each guselkumab dose group and the 
ustekinumab group using the CMH test (2-sided) stratified by baseline CDAI score (≤300 or 
>300), baseline SES-CD (≤12 or >12), BIO-Failure status (Yes/No), and baseline corticosteroid 
use (Yes/No).
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Participants who meet 1 or more treatment failure rules before a visit will be considered not to 
have achieved any of the major secondary endpoints from that visit onward. The treatment failure 
rules and the missing data rules will follow the principles of the rules specified for the co-primary 
endpoints. Additional analysis considerations will be specified in the SAP.  
A Regional testing procedure to control the Type-I error at the 2-sided 0.05 significance level for 
the co-primary endpoints and major secondary endpoints will be performed for each study 
separately.  This testing procedure is separate from the Global testing procedure. An overview is 
described below, and more details are specified in the SAP.
The testing procedure begins with sequential tests (within each Phase 3 study) of superiority of the 
combined guselkumab induction dose group compared with placebo relative to the co-primary 
endpoints at the 2-sided 0.05 significance level for each study. If either of the tests of the co-
primary endpoints within a study is not significant (ie, p>0.05), all subsequent p-values in the 
testing hierarchy will be considered nominal. The major secondary endpoints will be grouped into 
tiers for testing. Within each tier, the Hochberg procedure will be used. 10 The testing procedure 
will start with Tier 1. If all p-values in a tier are less than 0.05, all tests will be declared significant, 
and the procedure will move onto the next tier. If at least one p-value is greater than 0.05 in a tier, 
formal testing will stop, and other endpoints within the same tier could still be declared as 
significant if they meet the Hochberg thresholds, but all p-values in subsequent tiers would be 
considered as nominal. 
9.4.3.4.
Exploratory Efficacy Endpoint Analyses
Exploratory efficacy endpoints defined in Section 9.4.1.2.3 will be analyzed based on the timepoint 
(short-term, long-term) and comparator (placebo, ustekinumab) as described in Section 9.4.3.3. 
Within each study, the endpoints defined at Week 12 will be compared between the combined 
guselkumab induction dose group and the placebo group. The endpoints defined at Week 48 will 
be compared between each guselkumab dose group and the placebo group, or between each 
guselkumab dose group and the ustekinumab group, as specified in Section 3. Details will be 
provided in the Phase 3 SAP.
All statistical testing will be performed at the 2-sided 0.05 significance level. No adjustments for 
multiple comparisons will be made for these other efficacy endpoints and nominal p-values will 
be presented.
9.4.4.
Safety Analyses
Adverse Events
The verbatim terms used in the eCRF by investigators to identify AEs will be coded using the 
Medical Dictionary for Regulatory Activities. Treatment-emergent AEs are AEs with onset during 
the intervention phase or that are a consequence of a preexisting condition that has worsened since 
baseline. 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.
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The following analyses of AEs will be used to assess the safety of participants:

Frequency and type of AEs.

Frequency and type of SAEs.

Frequency and type of reasonably related AEs as assessed by the investigator.

Frequency and type of AEs leading to discontinuation of study intervention.

Frequency and type of infections.

Frequency and type of AEs temporally associated with infusion. 

Frequency and type of injection-site reactions.
Summaries, listings, datasets, or participant narratives may be provided, as appropriate, for those 
participants who die, who discontinue intervention due to an AE, or who experience a severe or a 
serious AE.
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.
9.4.5.
Other Analyses
Pharmacokinetic Analyses
Descriptive statistics of the serum guselkumab and ustekinumab 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 will be used to 
evaluate guselkumab PK parameters. The influence of important covariates on the population PK 
parameter estimates may be evaluated. Details will be provided in a population PK analysis plan 
and the results of the population PK analysis will be presented in a separate technical report.
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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 SAPs.
Immunogenicity Analyses
The incidence and titers of antibodies to guselkumab and ustekinumab will be summarized 
respectively for all participants who receive a dose of guselkumab or ustekinumab and have 
appropriate samples for detection of antibodies to guselkumab or ustekinumab (ie, participants 
with at least 1 sample obtained after their first dose of guselkumab or ustekinumab).
A listing of participants who are positive for antibodies to guselkumab or ustekinumab will be 
provided. The maximum titers of antibodies to guselkumab or ustekinumab will be provided for 
participants who are positive for antibodies to guselkumab or ustekinumab.
The incidence of neutralizing antibodies to guselkumab or ustekinumab will be summarized for 
participants who are positive for antibodies to guselkumab or ustekinumab and have samples 
evaluable for neutralizing antibodies to guselkumab or ustekinumab.
Biomarkers Analyses
Planned biomarker analyses may be deferred if emerging study data show no likelihood of 
providing useful scientific information. Any biomarker samples received by the contract vendor 
or sponsor after the cutoff date will not be analyzed, and therefore, excluded from the biomarker 
analysis.
Changes in serum protein analytes and whole blood RNA obtained over time will be summarized 
by treatment group where local regulations permit. Associations between baseline levels and 
changes from baseline in select markers 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, stool, and ileocolonic biopsy analyses will be reported in separate 
technical reports.
Pharmacokinetic/Pharmacodynamic Analyses
The relationship between serum guselkumab concentrations and efficacy measures will be 
analyzed graphically. If any visual trend is observed, a suitable population PK/PD model may be 
developed to describe the exposure-response relationship. Details will be provided in a population 
PK/PD analysis plan and results of the population PK/PD analysis will be presented in a separate 
technical report.
Medical Resource Utilization and Health Economics Analyses
Medical resource utilization and health economics, including work productivity, will be 
summarized by treatment group.
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9.5.
Interim Analysis
An IA is planned for the Phase 2 study (GALAXI 1) to support the selection of induction and 
maintenance guselkumab dose regimens that will be evaluated in Phase 3. Moreover, the IA will 
help to inform the hypothesis testing order of the major secondary endpoints in the Phase 3 studies. 
This IA will be referred to as the dose selection analysis.
No IA is planned for the Phase 3 studies.
9.5.1.
Dose Selection Analysis for Phase 2 (GALAXI 1)
The IA for the Phase 2 study (dose selection analysis) will occur after the first 250 randomized 
participants (ie, the Initial Dose Decision Cohort) in GALAXI 1 have either completed the 
Week 12 visit or terminated study participation prior to the Week 12 visit. The objective is to select
2 guselkumab dose regimens for continued development in Phase 3. The selection of the 
guselkumab dose regimens will be based on the analyses of key efficacy endpoints, dose-response 
analysis, safety, and PK data (further details to be provided in the Phase 2 Dose Selection Analysis 
Plan). In addition, the Phase 2 data through Week 48 will help to refine the assumptions for 
endoscopy endpoints, and to inform the testing procedure and the final ordering of the major 
secondary endpoints in Phase 3. Statistical analyses will be primarily based on data from the Initial 
Dose Decision Cohort (ie, the first 250 randomized participants) in GALAXI 1, but will also 
include data from the Transition Cohort. All available data from both cohorts will be analyzed, 
including any data beyond Week 12.
A Dose Selection Committee, composed of sponsor management representatives from Clinical, 
Safety, Biostatistics, and Clinical Pharmacology who are not associated with study conduct, will 
be responsible for deciding on the dose regimens of guselkumab to be evaluated in Phase 3.
The Dose Selection Committee will have access to the unblinded safety and efficacy summary 
tables and figures, but it will not have access to individual participant treatment assignment, with 
the exception of a listing of SAEs, AEs leading to discontinuation of study intervention, and 
maximum post-baseline toxicity values for the purpose of safety evaluation.
In general, individual participant treatment assignment will remain blinded to the sponsor. 
However, to support the dose selection process, a limited number of sponsor personnel will be 
unblinded to individual participant treatment assignment. Those sponsor personnel will not have 
contact with the investigative sites. Details of which sponsor personnel will be unblinded to 
individual participant treatment assignments will be specified prior to unblinding.  
Investigative sites and site monitors will remain blinded to individual participant treatment 
assignments.
If a dose selection cannot be made at the Week 12 IA, further evaluation will be conducted at the
Week 24 IA, which would occur when all participants in the Initial Dose Decision Cohort (n=250) 
have reached Week 24 or terminated study participation prior to Week 24. For both the Week 12 
IA and the Week 24 IA, all available data for both the Initial Dose Decision Cohort and the 
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Transition Cohort will be analyzed. Additional data transfers and analyses may be performed if
needed to enable the dose decision for Phase 3.
Since the sponsor does not plan to stop the trial early for efficacy, there is no alpha spending 
penalty for the IA.
The Dose Selection Analysis Plan will describe the analyses to be performed, the prespecified dose 
selection criteria, and other operational plans in greater detail.
9.5.2.
Data Monitoring Committee
An external independent DMC will be established and will meet periodically to review interim 
unblinded safety data from the Phase 2 and Phase 3 studies to ensure the continuing safety of the 
participants enrolled in this program. This DMC may also participate in the IA (see Section 9.5.1). 
The DMC will consist of a gastroenterologist familiar with the treatment of the adult IBD 
population, a physician familiar with the safety profile of guselkumab, and a statistician. The DMC
responsibilities, authorities, and procedures will be documented in a separate DMC charter.
The DMC’s initial responsibility will be careful review of the safety data from the first 25 
participants randomized and treated in GALAXI 1. Based on the planned randomization ratio, this 
first 25 participants should include approximately 5 participants in each of the highest guselkumab 
dosing groups (
 
 similar to the cohort size for each dose in a typical single or 
multiple ascending dose Phase 1 study. Also similar to conduct of a Phase 1 study, the safety of 
these first 25 participants will be monitored on an ongoing basis for any potential safety concerns 
that would result in a pause in dosing. Detailed guidance for the DMC regarding these reviews 
will be provided in the DMC charter. Once the 25th participant is randomized, the DMC will 
additionally perform a review of unblinded safety tables.  In the event that the number of patients 
in either the 
 group or the 
 group for this review is less than 5, then the DMC will 
conduct another review of unblinded safety tables 1 month later, when at least 5 patients will have 
been treated in both the 
 and 
 groups. If no new safety concerns are identified 
during this initial review period, then the subsequent DMC reviews will include monthly reports 
of all SAEs in enrolled participants as well as review of unblinded safety tables at least every 4 
months. After each safety review, the DMC will make recommendations regarding the 
continuation of the study.
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10.
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1.
Appendix 1: Abbreviations and Trademarks
5-ASA
5-aminosalicylic acid
6-MP
6-mercaptopurine
AE
adverse event
ALT
alanine aminotransferase
ANCOVA
analysis of covariance
ANOVA
analysis of variance
AP
abdominal pain
AP-NRS
abdominal pain – numerical rating scale
AST
aspartate aminotransferase
AUC
area under the serum concentration versus time curve
AZA
azathioprine
BCG
Bacille Calmette-Guérin
BIO-Failure
biologic therapy failure or intolerance
BSFS
Bristol Stool Form Scale
CDAI
Crohn’s Disease Activity Index
CMH
Cochran-Mantel-Haenszel
CON-Failure
conventional therapy failure or intolerance
COVID-19
Coronavirus Disease 2019
CRP
C-reactive protein
CSR
Clinical Study Report
C-SSRS
Columbia-Suicide Severity Rating Scale
DBL
database lock
DCS
data collection system
DMC
Data Monitoring Committee
DNA
deoxyribonucleic acid
ECG
electrocardiogram
eCRF
electronic case report form
EQ-5D
EuroQol five dimensions descriptive system
EQ-5D-5L
5-level EuroQol five dimensions instrument (consisting of the EuroQol five dimensions 
descriptive system [EQ-5D] and the EuroQol Visual Analog Scale [EQ-VAS])
EQ-VAS
EuroQol visual analog scale
EU
European Union
FDA
Food and Drug Administration (US)
FES
Final Efficacy and Safety
GCP
Good Clinical Practice
GHAS
Global Histology Activity Score
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HIV
human immunodeficiency virus
HBV DNA
hepatitis B virus deoxyribonucleic acid
HCP
healthcare professional
HRQOL
health-related quality of life
HRT
hormonal replacement therapy
IA
interim analysis
IB
Investigator’s Brochure
IBD
inflammatory bowel disease
IBDQ
Inflammatory Bowel Disease Questionnaire
ICF
informed consent form
ICH
International Council for Harmonisation
ICMJE
International Committee of Medical Journal Editors
IEC
Independent Ethics Committee
IL
interleukin
INR
international normalized ratio
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10.2.
Appendix 2: Definitions of Inadequate Response to or Intolerance of 
Corticosteroids or 6-MP/AZA/MTX and Corticosteroid Dependence 
CORTICOSTEROIDS
Participants have failed to respond to corticosteroids if they have had evidence of an initial inadequate 
response, recurrent disease, or a relapse despite receiving at least 
 of 
prednisone (or corticosteroid equivalent, given orally or intravenously) for 2 weeks; or 
 of 
budesonide or 
 of beclomethasone dipropionate given orally for at least 4 weeks. Evidence of 
CON-Failure must be documented in the participant’s source documentation. 
Participants are intolerant of corticosteroids if:

They have developed clinically significant adverse events (eg, osteonecrosis or osteoporosis, 
psychosis, uncontrolled diabetes) unresponsive to dose reduction that, in the judgment of the 
investigator, precluded the use of corticosteroids to treat Crohn’s disease. 
OR

They have a medical condition that precludes the use of corticosteroids as a treatment for Crohn’s 
disease.
Participants are corticosteroid dependent if they have failed to successfully taper their corticosteroid (ie, 
had a flare of disease) within 3 months of starting therapy, or if a relapse occurs within 3 months after 
stopping corticosteroids or if they are unable to discontinue these agents without flare within 3 months after 
starting them.
6-MERCAPTOPURINE (6-MP), AZATHIOPRINE (AZA), OR METHOTREXATE 
(MTX)
Participants have failed to respond to 6-MP, AZA, OR MTX if they have had evidence of an initial 
inadequate response, recurrent disease, or a relapse despite receiving: 

At least 3 months of therapy with 
 of 6-MP,
 of AZA, or 
week 
(intramuscular or 
 of MTX.
OR

A lower dosage of 6-MP, AZA, or MTX when country or local guidelines specify a different treatment 
regimen. (In such an event, the country or local guidelines needs to be included in the source 
document).
OR

The dosage of 6-MP, AZA, or MTX confirmed to be therapeutic for the participant with whole blood 
thioguanine nucleotide levels >200 pmol/8 x 108 red blood cells. 
OR

The highest tolerated dosage due to leukopenia, elevated liver enzymes, or nausea. 
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Participants are intolerant of 6-MP, AZA, or MTX if: 

They have developed clinically significant adverse events (eg, pancreatitis, arthritis accompanied by 
high fever and/or rash, leukopenia, or persistently elevated liver enzymes) unresponsive to dose 
reduction that, in the judgment of the investigator, precluded the use of 6-MP, AZA, or MTX to treat 
Crohn’s disease.
OR

They have a medical condition that precludes the use of 6-MP, AZA, or MTX.
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10.3.
Appendix 3: Definition of Inadequate Initial Response, Loss of Response, 
or Intolerance to TNF Antagonist Therapies (Infliximab, Adalimumab, or 
Certolizumab Pegol) or Vedolizumab
The criteria for inadequate initial response, response followed by loss of response, or intolerance to 
infliximab, adalimumab, certolizumab pegol, or vedolizumab are described in items 1, 2, and 3, below.
1.
Inadequate initial response to current or prior therapy with infliximab, adalimumab, 
certolizumab pegol (primary non-response), or vedolizumab (primary non-response) 
Eligible participants must satisfy criteria a, b, and c.
a.
Have received, at minimum, a locally approved induction dose, for example:
1)
Infliximab (2 or 3 doses of 
or
2)
Adalimumab (at a dose of 
followed by a dose
 or at a dose of 
 followed 
by a dose 
or
3)
Certolizumab pegol (2 or 3 doses of 
or
4)
Vedolizumab (at least 2 and up to 4 doses of 
AND
b.
Did not initially respond to these induction doses of infliximab, adalimumab, certolizumab pegol, 
or vedolizumab, as evidenced by the presence of at least 1 of the following signs or symptoms 
related to persistence of Crohn’s disease, as assessed by a treating physician:
1)
Lack of improvement or worsening in stool frequency
2)
Lack of improvement or worsening in daily abdominal pain
3)
Occurrence, lack of improvement, or worsening of fever thought to be related to Crohn’s 
disease
4)
Lack of improvement or worsening in a draining fistula or development of a new draining 
fistula
5)
Lack of improvement or worsening in rectal bleeding
6)
Initiation or increase in antidiarrheal medication
These signs and symptoms of Crohn’s disease must have occurred 2 weeks after receiving the 
last induction dose of infliximab, adalimumab, certolizumab pegol, or vedolizumab, and are 
offered only as a benchmark of the minimally acceptable criteria required to designate a 
participant as having had an inadequate initial response to infliximab, adalimumab, certolizumab 
pegol, or vedolizumab therapy. This benchmark acknowledges that the CDAI is not routinely 
recorded in clinical practice.
AND
c.
Have documentation available to the investigator that meets the following 2 requirements:
1)
Provide the dates and doses of the failed infliximab, adalimumab, certolizumab pegol, or 
vedolizumab induction therapy.
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2)
Documents that the participant had persistence of disease activity following infliximab, 
adalimumab, certolizumab pegol, or vedolizumab induction therapy.
Examples of acceptable documents include medical records, letter provided by a referring 
physician, or other “reason for referral” documents (eg, insurance authorization form).
2.
Initial response followed by loss of response to current or prior therapy with infliximab, 
adalimumab, certolizumab pegol, or vedolizumab (secondary non-response)
Eligible participants must satisfy criteria a, b, c, d.
a.
Initially responded to induction therapy
AND
b.
Have received, at minimum, 2 doses of a locally approved maintenance dose, for example:
1)
Infliximab (at a dose of 
or
2)
Adalimumab (at a dose of 
or
3)
Certolizumab pegol (at a dose of 
or
4)
Vedolizumab (at a dose of 
 or 
AND
c.
Have or had at least 1 of the following signs or symptoms related to recurrence of Crohn’s disease, 
as assessed by a treating physician:
1)
Worsening in stool frequency
2)
Worsening in daily abdominal pain
3)
Occurrence or worsening in fever thought to be related to Crohn’s disease
4)
Recurring drainage from a previously nondraining fistula or development of a new draining 
fistula
5)
Worsening in rectal bleeding
6)
Initiation or increase in antidiarrheal medication
These signs and symptoms of Crohn’s disease must have occurred 2 weeks after receiving the 
last maintenance dose of infliximab, adalimumab, certolizumab pegol, or vedolizumab, and are 
offered only as a benchmark of the minimally acceptable criteria required to designate a participant
as having lost response to infliximab, adalimumab, certolizumab pegol, or vedolizumab therapy.  
This benchmark acknowledges that the CDAI is not routinely recorded in clinical practice.
AND
d.
Have documentation available to the investigator that meets the following 2 requirements:
1)
Provide the dates and doses of the failed infliximab, adalimumab, certolizumab pegol, or 
vedolizumab maintenance therapy.
2)
Documents that the participant had recurrence of disease activity despite infliximab, 
adalimumab, certolizumab pegol, or vedolizumab maintenance therapy.
C
C
C
C
C
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Examples of acceptable documents include medical records, letter provided by a referring 
physician, or other “reason for referral” documents (eg, insurance authorization form).
If the above evidence is not sufficient to be considered for primary or secondary non-response, 
this may also be determined based on evaluation of other measures that may be indicative of 
worsening disease (eg, elevations of inflammatory markers including but not limited to CRP or 
fecal calprotectin, and/or evidence of disease flare based on clinical imaging modalities including 
but not limited to ileocolonoscopy, CT, and MRI). Under these circumstances, documentation of 
these specified measures of worsening disease activity can be accepted as evidence of loss of 
response or inadequate response to prior biologic treatment. However, investigators should note 
that participants must meet protocol-specified criteria for active disease (ie, clinical and 
endoscopic) during the current screening period, as described in Section 5.1, to be eligible for 
enrollment.
3.
Current or prior intolerance to therapy with infliximab, adalimumab, certolizumab pegol, or 
vedolizumab
Eligible participants must satisfy criteria A and B.
a.
Have had an adverse reaction that meets 1 of the following 3 criteria:  1) significant acute 
infusion/administration reaction; 2) significant delayed infusion/administration reaction (for 
example, delayed hypersensitivity or serum sickness-like reaction); or 3) significant injection-site 
reaction.  Definitions of these 3 criteria are provided below.  Adverse reactions also must have 
followed 1 dose of infliximab, adalimumab, certolizumab pegol, or vedolizumab, and, in the 
treating physician’s opinion, precluded continued use of the therapy.
1)
A significant acute infusion/administration reaction is defined as an adverse reaction that 
was:
a)
Manifested through 1 of the following symptoms.
o
Fever greater than 100F (37.8C)
o
Chills or rigors
o
Itching
o
Rash
o
Flushing
o
Urticaria or angioedema
o
Breathing difficulties (dyspnea, chest paint or tightness, shortness of breath, 
wheezing, stridor)
o
Clinical hypotension (pallor, diaphoresis, faintness, syncope), blood pressure less 
than 90 mm Hg systolic and 60 mm Hg diastolic, or a systemic or orthostatic drop 
in systolic blood pressure of greater than 20 mm Hg
AND
b)
Occurred 24 hours after infusion/administration of infliximab, adalimumab, 
certolizumab pegol, or vedolizumab
AND
c)
Was considered related to the infusion/administration of infliximab, adalimumab, 
certolizumab pegol, or vedolizumab.
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2)
A significant delayed infusion/administration reaction is defined as an adverse reaction that:
a)
Was manifested through 1 or more of the following symptoms:
o
Myalgias
o
Arthralgias
o
Fever greater than 100F (37.8C)
o
Malaise
o
Rash
AND
b)
Occurred >24 hours and <15 days after infusion/administration of infliximab, 
adalimumab, certolizumab pegol, or vedolizumab
AND
c)
Was considered related to the infusion/administration of infliximab, adalimumab, 
certolizumab pegol, or vedolizumab.
3)
A significant injection-site reaction is defined as an adverse reaction that:
d)
Was manifested through 1 or more of the following symptoms:
o
Significant bruising
o
Erythema
o
Hemorrhage
o
Irritation
o
Pain
o
Pruritus
o
“Injection-site reaction”
AND
o
Occurred within 24 hours of an 
 injection of adalimumab or certolizumab pegol.
AND
o
Was considered related to the injection.
b.
Have documentation available to the investigator that meets the following 2 requirements:
1)
Provides the date of discontinuation of infliximab, adalimumab, certolizumab pegol, or 
vedolizumab.  
2)
Documents that the participant had intolerance to infliximab, adalimumab, certolizumab 
pegol, or vedolizumab.
Examples of acceptable documents include medical records, letter provided by a referring 
physician, or other “reason for referral” documents (eg, insurance authorization form).
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10.4.
Appendix 4: Definition of Exposure to Ustekinumab
Participants who have had exposure to ustekinumab at its approved labeled dosage AND have met the 
required washout criterion AND have not demonstrated failure or intolerance to ustekinumab as defined 
further below are eligible for entry into this protocol.
Participants who have had exposure to ustekinumab as an investigational agent (ie, exposure to ustekinumab 
from participation in prior ustekinumab clinical studies) or exposure to ustekinumab as an off-label 
treatment at their physician’s discretion are ineligible for entry into this protocol.
Participants with prior exposure to other anti-IL-12/23 (ie, briakinumab) or anti-IL-23 (ie, including but not 
limited to risankizumab, brazikumab, and mirikizumab) agents are ineligible for entry into this protocol.
Participants MUST meet all of criteria 1, 2, and 3 below to qualify for entry into this protocol as 
having had minimal exposure to ustekinumab, and provided that all other entry criteria as described 
in Sections 5.1 and 5.2 have been satisfied.
1.
The criteria for minimal exposure to ustekinumab at its approved label dosage is defined as 
follows:
a.
No more than one induction dose of ustekinumab 
AND EITHER
b.
No more than one maintenance dose of ustekinumab 
 after the single 
induction dose
OR
c. 
More than one maintenance dose with sponsor approval
Note: Discussion with sponsor must occur to confirm participant did not have inadequate response 
or intolerance as referenced in #3 below.
2.
The required washout period from ustekinumab is defined as followed:
Participants must have been discontinued from ustekinumab for at least 16 weeks prior to the Week 0 
dosing visit of this protocol
3.
The following documentation to confirm the discontinuation of ustekinumab treatment for 
Crohn’s disease for reasons other than inadequate response or intolerance MUST be provided:
Examples of acceptable documents include medical records, letter provided by a referring physician, 
or other “reason for referral” documents (eg, insurance authorization / denial notifications) that:
a.
Provide the dates and doses of ustekinumab for the treatment of Crohn’s disease; AND
b.
Provide the date of discontinuation of ustekinumab for the treatment of Crohn’s disease; AND
c.
Indicate the participant had discontinued ustekinumab treatment for reasons other than inadequate 
response and/or intolerance (eg, loss of insurance); AND
d.
Indicate the participant did not discontinue ustekinumab treatment for Crohn’s disease due to 
inadequate response and/or intolerance. See further details under the NOTE section below for 
evidence indicative of inadequate response and/or intolerance.
NOTE:
The following is considered evidence of inadequate response and/or intolerance to ustekinumab treatment 
for Crohn’s disease.  Participants who meet these criteria are ineligible to enter this protocol.
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Evidence of inadequate response to ustekinumab that had precluded continuation of previous 
treatment with ustekinumab for Crohn’s disease:

Lack of improvement or worsening in stool frequency

Lack of improvement or worsening in daily abdominal pain

Occurrence, lack of improvement, or worsening of fever thought to be related to Crohn’s disease

Lack of improvement or worsening in a draining fistula or development of a new draining fistula

Lack of improvement or worsening in rectal bleeding

Initiation or increase in antidiarrheal medication
These signs and symptoms of Crohn’s disease are offered only as a benchmark and acknowledges that the 
CDAI is not routinely recorded in clinical practice.
Evidence of intolerance to ustekinumab that had precluded continuation of previous treatment with 
ustekinumab for Crohn’s disease:
Have had an adverse reaction that meets 1 of the following 3 criteria: 1) significant acute 
infusion/administration reaction; 2) significant delayed infusion/administration reaction (for example, 
delayed hypersensitivity or serum sickness-like reaction); or 3) significant injection-site reaction.  
Definitions of these 3 criteria are provided below.

A significant acute infusion/administration reaction is defined as an adverse reaction that was:
a.
Manifested through 1 of the following symptoms.
o
Fever greater than 100F (37.8C)
o
Chills or rigors
o
Itching
o
Rash
o
Flushing
o
Urticaria or angioedema
o
Breathing difficulties (dyspnea, chest paint or tightness, shortness of breath, wheezing, 
stridor)
o
Clinical hypotension (pallor, diaphoresis, faintness, syncope), blood pressure less than 
90 mm Hg systolic and 60 mm Hg diastolic, or a systemic or orthostatic drop in systolic 
blood pressure of greater than 20 mm Hg
AND
b.
Occurred 24 hours after infusion/administration of ustekinumab
AND
c.
Was considered related to the infusion/administration of ustekinumab

A significant delayed infusion/administration reaction is defined as an adverse reaction that:
a.
Was manifested through 1 or more of the following symptoms:
o
Myalgias
o
Arthralgias
o
Fever greater than 100F (37.8C)
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o
Malaise
o
Rash
AND
b.
Occurred >24 hours and <15 days after infusion/administration of ustekinumab
AND
c.
Was considered related to the infusion/administration of ustekinumab

A significant injection-site reaction is defined as an adverse reaction that:
a.
Was manifested through 1 or more of the following symptoms:
o
Significant bruising
o
Erythema
o
Hemorrhage
o
Irritation
o
Pain
o
Pruritus
o
“Injection-site reaction”
AND
b.
Occurred within 24 hours of an 
 injection of ustekinumab.
AND
c.
Was considered related to the 
 injection of ustekinumab.
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10.5.
Appendix 5: Tuberculin Skin Testing
Administering the Mantoux Tuberculin Skin Test
The Mantoux tuberculin skin test (CDC, 2000) is the standard method of identifying persons infected with 
Mycobacterium tuberculosis. Multiple puncture tests (Tine and Heaf) should not be used to determine whether a 
person is infected because the amount of tuberculin injected intradermally cannot be precisely controlled.  Tuberculin 
skin testing is both safe and reliable throughout the course of pregnancy. The Mantoux tuberculin test is performed 
by placing an intradermal injection of 0.1 mL of tuberculin into the inner surface of the forearm. The test must be 
performed with tuberculin that has at least the same strength as either 5 tuberculin units (TU) of standard purified 
protein derivative (PPD)-S or 2 TU of PPD-RT 23, Statens Seruminstitut, as recommended by the World Health 
Organization. PPD strengths of 1 TU or 250 TU are not acceptable (Menzies, 2000). Using a disposable tuberculin 
syringe with the needle bevel facing upward, the injection should be made just beneath the surface of the skin. This 
should produce a discrete, pale elevation of the skin (a wheal) 6 mm to 10 mm in diameter. To prevent needle-stick 
injuries, needles should not be recapped, purposely bent or broken, removed from disposable syringes, or otherwise 
manipulated by hand. After they are used, disposable needles and syringes should be placed in puncture-resistant 
containers for disposal. Institutional guidelines regarding universal precautions for infection control (eg, the use of 
gloves) should be followed. A trained health care worker, preferably the investigator, should read the reaction to the 
Mantoux test 48 to 72 hours after the injection. Participants should never be allowed to read their own tuberculin skin 
test results. If a participant fails to show up for the scheduled reading, a positive reaction may still be measurable up 
to 1 week after testing. However, if a participant who fails to return within 72 hours has a negative test, tuberculin 
testing should be repeated. The area of induration (palpable raised hardened area) around the site of injection is the 
reaction to tuberculin. For standardization, the diameter of the induration should be measured transversely 
(perpendicular) to the long axis of the forearm. Erythema (redness) should not be measured.  All reactions should be 
recorded in millimeters, even those classified as negative.
Interpreting the Tuberculin Skin Test Results
In the US and many other countries, the most conservative definition of positivity for the tuberculin skin test is 
reserved for immunocompromised patients, and this definition is to be applied in this study to maximize the likelihood 
of detecting latent TB, even though the participants may not be immunocompromised at baseline.
In the US and Canada, an induration of 5 mm or greater in response to the intradermal tuberculin skin test is considered 
to be a positive result and evidence for either latent or active TB.
In countries outside the US and Canada, country-specific guidelines for immunocompromised patients should be 
consulted for the interpretation of tuberculin skin test results. If no local country guidelines for immunocompromised 
patients exist, US guidelines must be followed. 
Treatment of Latent Tuberculosis
Local country guidelines for immunocompromised patients should be consulted for acceptable antituberculous 
treatment regimens for latent TB. If no local country guidelines for immunocompromised patients exist, US guidelines 
must be followed.
References
Centers for Disease Control and Prevention.  Core curriculum on tuberculosis:  What the clinician should know 
(Fourth Edition).  Atlanta, GA:  Department of Health and Human Services; Centers for Disease Control and 
Prevention; National Center for HIV, STD, and TB Prevention; Division of Tuberculosis Elimination; 2000:25-86. 
Menzies RI.  Tuberculin skin testing.  In:  Reichman LB, Hershfield ES (eds). Tuberculosis, a comprehensive 
international approach.  2nd ed.  New York, NY:  Marcel Dekker, Inc; 2000:279-322.
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10.6.
Appendix 6: Contraceptive and Barrier Guidance and Collection of 
Pregnancy Information
Participants must follow contraceptive measures as outlined in Section 5.1, Inclusion Criteria. 
Pregnancy information will be collected and reported as noted in Section 8.3.4 (Pregnancy), and 
Appendix 10.11 Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow-
up, and Reporting.
Definitions
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below).
Woman Not of Childbearing Potential

premenarchal
A premenarchal state is one in which menarche has not yet occurred.

postmenopausal
A postmenopausal state is defined as no menses for 12 months without an alternative medical 
cause. A high follicle stimulating hormone level (>40 IU/L or mIU/mL) in the postmenopausal 
range may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormone-replacement therapy (HRT), however in the absence of 12 months 
of amenorrhea, a single follicle stimulating hormone measurement is insufficient. If there is a 
question about menopausal status in women on HRT, the woman will be required to use one 
of the non-estrogen-containing hormonal highly effective contraceptive methods if she wishes 
to continue HRT during the study.

permanently sterile
Permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal 
occlusion/ligation procedures, and bilateral oophorectomy.
Note: If the childbearing potential changes after start of the study (eg, a premenarchal woman 
experiences menarche) or the risk of pregnancy changes (eg, a woman who is not heterosexually 
active becomes active), a woman must begin a highly effective method of contraception, as 
described throughout the inclusion criteria.
If reproductive status is questionable, additional evaluation should be considered.
As noted in Inclusion Criterion 10, study participants who are women of childbearing potential 
must be practicing a highly effective method of contraception and remain on a highly effective 
method while receiving study intervention and until 16 weeks after last dose. Examples of highly 
effective methods of contraception are provided below; however, the method selected must meet 
local/regional regulations/guidelines for highly effective contraception.
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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

Vasectomized partner
(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)
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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Pregnancy during the study
All initial reports of pregnancy in female participants or partners of male participants must be 
reported to the sponsor or designee by the study site personnel within 24 hours of their knowledge 
of the event using the appropriate pregnancy notification form. Abnormal pregnancy outcomes 
(eg, spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are 
considered serious adverse events and must be reported using the Serious Adverse Event Form. 
Any participant who becomes pregnant during the study must discontinue further study 
intervention.
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the 
infant will be required.
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10.8.
Appendix 8: Regulatory, Ethical, and Study Oversight Considerations
10.8.1.
Regulatory and Ethical Considerations
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the 
protocol, current International Council for Harmonisation (ICH) guidelines on Good Clinical 
Practice (GCP), the latest version of the Declaration of Helsinki, and applicable regulatory and 
country-specific requirements.
Good Clinical Practice is an international ethical and scientific quality standard for designing, 
conducting, recording, and reporting studies that involve the participation of human participants. 
Compliance with this standard provides public assurance that the rights, safety, and well-being of 
study participants are protected, consistent with the principles that originated in the Declaration of 
Helsinki, and that the study data are credible.
Protocol 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 or designee. 
When the change(s) involve only logistic or administrative aspects of the study, the IEC/IRB 
(where required) only needs to be notified.
During the course of the study, in situations where a departure from the protocol is unavoidable, 
the investigator or other physician in attendance will contact the appropriate sponsor designee. 
Except in emergency situations, this contact should be made before implementing any departure 
from the protocol. In all cases, contact with the sponsor or designee must be made as soon as 
possible to discuss the situation and agree on an appropriate course of action. The data recorded in 
the Data Collection System (DCS) and source documents will reflect any departure from the 
protocol, and the source documents will describe this departure and the circumstances requiring it.
Regulatory Approval/Notification
This protocol and any amendment(s) must be submitted to the appropriate regulatory authorities 
in each respective country, if applicable. A study may not be initiated until all local regulatory 
requirements are met.
Required Prestudy Documentation
The following documents must be provided to the sponsor or designee before shipment of study 
intervention to the study site:
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
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 or designee before enrollment of the 
first participant:

Completed investigator financial disclosure forms from all subinvestigators

Documentation of subinvestigator qualifications (eg, curriculum vitae)

Name and address of any local laboratory conducting tests for the study, and a dated copy of 
current laboratory normal ranges for these tests, if applicable

Local 
laboratory 
documentation 
demonstrating 
competence 
and 
test 
reliability 
(eg, accreditation/license), if applicable
Independent Ethics Committee or Institutional Review Board
Before the start of the study, the investigator (or sponsor where required) will provide the IEC/IRB 
with current and complete copies of the following documents (as required by local regulations):

Final protocol and, if applicable, amendments

Sponsor-approved ICF (and any other written materials to be provided to the participants)

Investigator's Brochure (or equivalent information) and amendments/addenda

Sponsor-approved participant recruiting materials
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
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 or designee has received a copy 
of this approval. This approval letter must be dated and must clearly identify the IEC/IRB and the 
documents being approved.
Approval for the collection of optional samples for research and for the corresponding ICF must 
be obtained from the IEC/IRB. Approval for the protocol can be obtained independent of this 
optional research component.
During the study the investigator (or sponsor where required) will send the following documents 
and updates to the IEC/IRB for their review and approval, where appropriate:

Protocol amendments (excluding the ones that are purely administrative, with no 
consequences for participants, data or study conduct)

Revision(s) to ICF and any other written materials to be provided to participants

If applicable, new or revised participant recruiting materials approved by the sponsor

Revisions to compensation for study-related injuries or payment to participants for 
participation in the study, if applicable

New edition(s) of the Investigator's Brochure and amendments/addenda

Summaries of the status of the study at intervals stipulated in guidelines of the IEC/IRB (at 
least annually)

Reports of adverse events that are serious, unlisted/unexpected, and associated with the study 
intervention

New information that may adversely affect the safety of the participants or the conduct of the 
study

Deviations from or changes to the protocol to eliminate immediate hazards to the participants

Report of deaths of participants under the investigator's care
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
Notification if a new investigator is responsible for the study at the site

Development Safety Update Report and Line Listings, where applicable

Any other requirements of the IEC/IRB
For all protocol amendments (excluding the ones that are purely administrative, with no 
consequences for participants, data or study conduct), the amendment and applicable ICF revisions 
must be submitted promptly to the IEC/IRB for review and approval before implementation of the 
change(s).
At least once a year, the IEC/IRB will be asked to review and reapprove this study, where required.
At the end of the study, the investigator (or sponsor where required) will notify the IEC/IRB about 
the study completion (if applicable, the notification will be submitted through the head of 
investigational institution).
Country Selection
This study will only be conducted in those countries where the intent is to launch or otherwise help 
ensure access to the developed product if the need for the product persists, unless explicitly 
addressed as a specific ethical consideration in Section 4.2.5, Study-Specific Ethical Design 
Considerations.
Other Ethical Considerations
For study-specific ethical design considerations, refer to Section 4.2.5.
10.8.2.
Financial Disclosure
Investigators and subinvestigators will provide the sponsor or designee with sufficient, accurate 
financial information in accordance with local regulations to allow the sponsor to submit complete 
and accurate financial certification or disclosure statements to the appropriate regulatory 
authorities. Investigators are responsible for providing information on financial interests during 
the course of the study and for 1 year after completion of the study.
Refer to Required Prestudy Documentation (above) for details on financial disclosure.
10.8.3.
Informed Consent Process
Each participant must give written consent according to local requirements after the nature of the 
study has been fully explained. The ICF(s) must be signed before performance of any study-related 
activity. The ICF(s) that is/are used must be approved by both the sponsor or designee and by the 
reviewing IEC/IRB and be in a language that the participant can read and understand. The informed 
consent should be in accordance with principles that originated in 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 the aims, methods, reasonably anticipated benefits, and 
potential hazards of the study, and any discomfort participation in the study may entail. 
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Participants will be informed that their participation is voluntary and that they may withdraw 
consent to participate at any time. They will be informed that choosing not to participate will not 
affect the care the participant will receive. Finally, they will be told that the investigator will 
maintain a participant identification register for the purposes of long-term follow-up if needed and 
that their records may be accessed by health authorities and authorized sponsor or designee 
personnel without violating the confidentiality of the participant, to the extent permitted by the 
applicable law(s) or regulations. By signing the ICF the participant is authorizing such access. It 
also denotes that the participant agrees to allow his or her study physician to recontact the 
participant for the purpose of obtaining consent for additional safety evaluations, and subsequent 
disease-related treatments, if needed.
The participant will be given sufficient time to read the ICF and the opportunity to ask questions. 
After this explanation and before entry into the study, consent should be appropriately recorded 
by means of the participant's personally dated signature. After having obtained the consent, a copy 
of the ICF must be given to the participant.
A participant may be rescreened 1 time. Participants who are rescreened are required to sign a new 
ICF.
Completion of screening and randomization procedures within the specified approximately 5-week 
window is required. If a participant is approaching the completion of that period, the medical 
monitor can be contacted to discuss eligibility. 
If any delay leads to the expiration of time-specific assessments (eg, TB, chest radiograph, stool 
analysis), the participant will be considered a screen failure because he/she will not meet eligibility 
criteria, and the expired assessments (along with the non-time-specific laboratory tests) will have 
to be repeated on rescreening. 
Participants will be asked for consent to provide optional samples for research (where local 
regulations permit). After informed consent for the study is appropriately obtained, the participant 
will be asked to sign and personally date a separate ICF indicating agreement to participate in the 
optional research component. Refusal to participate in the optional research will not result in 
ineligibility for the study. A copy of this signed ICF will be given to the participant.
10.8.4.
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 includes explicit consent for the processing of 
personal data and for the investigator/institution to allow direct access to his or her original medical 
records (source data/documents) for study-related monitoring, audit, IEC/IRB review, and 
regulatory inspection. This consent also addresses the transfer of the data to other entities and to 
other countries.
The participant has the right to request through the investigator access to his or her personal data 
and the right to request rectification of any data that are not correct or complete. Reasonable steps 
will be taken to respond to such a request, taking into consideration the nature of the request, the 
conditions of the study, and the applicable laws and regulations.
Exploratory DNA, biomarker, PK, and immunogenicity tests are only for research. They will not 
be used for medical care of the participant or to make a diagnosis about the participant’s health.  
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. 
10.8.5.
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. The start of the storage period is defined as last participant last visit. 
Samples will only be used to understand guselkumab and ustekinumab, to understand Crohn’s 
disease, to understand differential intervention responders, and to develop diagnostic tests to 
identify Crohn’s disease populations that may be responsive or non-responsive to treatment with 
guselkumab or ustekinumab. The research may begin at any time during the study or the post-
study storage period. 
Stored samples will be coded throughout the sample storage and analysis process and will not be 
labeled with personal identifiers. Participants may withdraw their consent for their samples to be 
stored for research (refer to Section 7.2.1, Withdrawal from the Use of Research Samples).
10.8.6.
Committees Structure
Data Monitoring Committee
Details regarding the DMC are presented in Section 9.5.2.
10.8.7.
Publication Policy/Dissemination of Clinical Study Data
All information, including but not limited to information regarding guselkumab or the sponsor's 
operations (eg, patent application, formulas, manufacturing processes, basic scientific data, prior 
clinical data, formulation information) supplied by the sponsor to the investigator and not 
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previously published, and any data, including pharmacogenomic or exploratory biomarker 
research data, generated as a result of this study, are considered confidential and remain the sole 
property of the sponsor. The investigator agrees to maintain this information in confidence and use 
this information only to accomplish this study and will not use it for other purposes without the 
sponsor's prior written consent.
The investigator understands that the information developed in the study will be used by the 
sponsor in connection with the continued development of guselkumab, and thus may be disclosed 
as required to other clinical investigators or regulatory agencies. To permit the information derived 
from the clinical studies to be used, the investigator is obligated to provide the sponsor with all 
data obtained in the study.
The results of the study will be reported in a Clinical Study Report (CSR) generated by the sponsor
and will contain data from all study sites that participated in the study 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 and exploratory biomarker analyses performed after the CSR has been issued 
will be reported in a separate report and will not require a revision of the CSR. 
Study participant identifiers will not be used in publication of results. Any work created in 
connection with performance of the study and contained in the data that can benefit from copyright 
protection (except any publication by the investigator as provided for below) shall be the property 
of the sponsor as author and owner of copyright in such work.
Consistent with Good Publication Practices and International Committee of Medical Journal 
Editors guidelines, the sponsor shall have the right to publish such primary (multicenter) data and 
information without approval from the investigator. The investigator has the right to publish study 
site-specific data after the primary data are published. If an investigator wishes to publish 
information from the study, a copy of the manuscript must be provided to the sponsor for review 
at least 60 days before submission for publication or presentation. Expedited reviews will be 
arranged for abstracts, poster presentations, or other materials. If requested by the sponsor in 
writing, the investigator will withhold such publication for up to an additional 60 days to allow for 
filing of a patent application. In the event that issues arise regarding scientific integrity or 
regulatory compliance, the sponsor will review these issues with the investigator. The sponsor will 
not mandate modifications to scientific content and does not have the right to suppress information. 
For multicenter study designs and substudy approaches, secondary results generally should not be 
published before the primary endpoints of a study have been published. Similarly, investigators 
will recognize the integrity of a multicenter study by not submitting for publication data derived 
from the individual study site until the combined results from the completed study have been 
submitted for publication, within 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 International Committee 
of Medical Journal Editors Recommendations for the Conduct, Reporting, Editing and Publication 
of Scholarly Work in Medical Journals, which state that the named authors must have made a 
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significant contribution to the conception or design of the work; or the acquisition, analysis, or 
interpretation of the data for the work; and drafted the work or revised it critically for important 
intellectual content; and given final approval of the version to be published; and agreed to be 
accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity 
of any part of the work are appropriately investigated and resolved.
Registration of Clinical Studies and Disclosure of Results
The sponsor will register and disclose the existence of and the results of clinical studies as required 
by law.
10.8.8.
Data Quality Assurance
Data Quality Assurance/Quality Control
Steps to be taken to ensure the accuracy and reliability of data include the selection of qualified 
investigators and appropriate study sites, review of protocol procedures with the investigator and 
study site personnel before the study, periodic monitoring visits by the sponsor or designee, 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 or designee will review eCRF for accuracy and completeness during on-site 
monitoring visits and after transmission to the sponsor; any discrepancies will be resolved with the 
investigator or designee, as appropriate. After upload of the data into the study database they will 
be verified for accuracy and consistency with the data sources.
10.8.9.
Data Collection
Data for each study participant will be collected in the eCRF or ancillary data collection systems 
such as the IWRS, patient-reported outcome (PRO) tablets, laboratory database, and imaging 
database. Case report forms are prepared and provided by the sponsor for each participant in eCRF. 
Collectively, all data collection via eCRFs and ancillary systems will comprise what is referred to 
in this protocol as the DCS.
All DCS 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.
Study data will be transcribed by study site personnel from source documentation to an eCRF or 
the appropriate ancillary DCS, as applicable. Study-specific data from each source will be 
transmitted in a secure manner to the sponsor.
Worksheets may be used as source documentation to capture data and facilitate completion of the 
eCRF or entry of data into the applicable ancillary data system. Data must be entered into the DCS
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in English. The eCRF must be completed as soon as possible after a participant visit and the forms 
should be available for review at the next scheduled monitoring visit.
Necessary eCRF or ancillary data modifications can only be made by the investigator or 
appropriate site personnel using eCRF system functionality and/or ancillary data revision 
procedures. All data changes will be recorded in an audit trail.
10.8.10.
Source Documents
At a minimum, source documents consistent in the type and level of detail with that commonly 
recorded at the study site as a basis for standard medical care must be available for the following: 
participant identification, eligibility, and study identification; study discussion and date of signed 
informed consent; dates of visits; results of safety and efficacy parameters as required by the 
protocol; record of all adverse events and follow-up of adverse events; concomitant medication; 
intervention receipt/dispensing/return records; study intervention administration information; and 
date of study completion and reason for early discontinuation of study intervention or withdrawal 
from the study, if applicable. 
The author of an entry in the source documents should be identifiable.
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 electronic source (eSource) system may be utilized, which contains data traditionally 
maintained in a hospital or clinic record to document medical care (eg, electronic source 
documents) as well as the clinical study-specific data fields as determined by the protocol. These 
data are electronically extracted for use by the sponsor. If eSource is utilized, references made to 
the eCRF in the protocol include the eSource system but information collected through eSource 
may not be limited to that found in the eCRF.
10.8.11.
Monitoring
The sponsor designee will perform on-site monitoring visits as frequently as necessary. This will 
include blinded site monitors who will perform the majority of source data verification and 
unblinded site monitors who will specifically review drug preparation and dispensation. The 
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monitor will record dates of the visits in a study site visit log that will be kept at the study site, as 
allowed by local regulation. The first post-initiation visit will be made as soon as possible after 
enrollment has begun. At these visits, the monitor will compare the data entered into the applicable 
DCS component (as defined in the monitoring guidelines) 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 
applicable DCS component are known to the sponsor or designee 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 or designee 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 or designee as requiring 
central review.
10.8.12.
On-Site Audits
Representatives of the sponsor's (or sponsor designee’s) clinical quality assurance department may 
visit the study site at any time during or after completion of the study to conduct an audit of the 
study in compliance with regulatory guidelines and company policy. These audits will require 
access to all study records, including source documents, for inspection. Participant privacy must, 
however, be respected. The investigator and study site personnel are responsible for being present 
and available for consultation during routinely scheduled study site audit visits conducted by the 
sponsor or its designees. 
Similar auditing procedures may also be conducted by agents of any regulatory body, either as part 
of a national GCP compliance program or to review the results of this study in support of a 
regulatory submission. The investigator should immediately notify the sponsor or designee if he 
or she has been contacted by a regulatory agency concerning an upcoming inspection.
10.8.13.
Record Retention
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all eCRF 
and all source documents that support the data collected from each participant, as well as all study 
documents as specified in ICH/GCP Section 8, Essential Documents for the Conduct of a Clinical 
Trial, and all study documents as specified by the applicable regulatory requirement(s). The 
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investigator/institution will take measures to prevent accidental or premature destruction of these 
documents.
Essential documents must be retained until at least 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing applications 
in an ICH region or until at least 2 years have elapsed since the formal discontinuation of clinical 
development of the investigational product. These documents will be retained for a longer period 
if required by the applicable regulatory requirements or by an agreement with the sponsor. It is the 
responsibility of the sponsor to inform the investigator/institution as to when these documents no 
longer need to be retained.
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 or designee.
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.
10.8.14.
Study and Site Closure
Study Termination
The sponsor reserves the right to close the study site or terminate the study at any time for any 
reason at the sole discretion of the sponsor. Study sites will be closed upon study completion. A 
study site is considered closed when all required documents and study supplies have been collected 
and a study site closure visit has been performed.
The investigator may initiate study site closure at any time, provided there is reasonable cause and 
sufficient notice is given in advance of the intended termination.
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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3.
If total bilirubin (Tbili) is >2xULN, request fractionation to document the fraction that is direct 
bilirubin and to rule out indirect hyperbilirubinemia indicative of Gilbert’s syndrome, 
hemolysis or other causes of indirect hyperbilirubinemia. Complete blood count (CBC) with 
white blood count (WBC) and eosinophil count platelet count, international normalized ratio 
(INR), and total protein and albumin (compute globulin fraction) should also be documented.  
If INR is abnormal, prothrombin time (PT), partial thromboplastin time (PTT) 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.
4. 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 M (anti-HAV IgM), anti-HAV total, hepatitis B surface antigen (HBsAg), anti-
HBs,  anti-HB core total,  anti-HB core IgM, anti-hepatitis C virus (anti-HCV), anti-hepatitis 
E virus IgM (anti-HEV IgM) (even if has not traveled to an endemic area for hepatitis E), 
Epstein-Barr virus (EBV) and Cytomegalovirus (CMV) screen.

If patient is immunosuppressed, test for HCV RNA and HEV RNA.

If HBsAg or anti-HB core IgM or anti-HB core IgG positive, also get HBV DNA to detect 
active HepB, 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.
5.
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: Total protein and 
albumin (estimate globulin fraction and obtain quantitative immunoglobulins if elevated), 
antinuclear antibody (ANA), anti-liver kidney microsomal antibody type 1 (anti-LKM1), anti-
liver-kidney microsomal antibodies (anti-LKM antibodies), anti-smooth muscle antibodies 
(ASMA), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). If the pattern 
of laboratory abnormalities is not hepatocellular, but cholestatic or a mixed pattern (see 
definitions in table above), then gamma-glutamyl transferase (GGT), anti-mitochondrial 
antibody (AMA) and anti-neutrophil cytoplasmic antibody (pANCA) 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 
(TIBC) 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.
6.
A liver biopsy should be considered if autoimmune hepatitis remains a competing etiology 
and if immunosuppressive therapy is contemplated.
A liver biopsy may be considered:

if there is unrelenting rise in liver biochemistries or signs of worsening liver function 
despite stopping the suspected offending agent.
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
if peak ALT level has not fallen by >50% at 30-60 days after onset in cases of 
hepatocellular DILI, or if peak Alk P has not fallen by >50% at 180 days in cases of 
cholestatic DILI despite stopping the suspected offending agent.

in cases of DILI where continued use or re-exposure to the implicated agent is expected.

if liver biochemistry abnormalities persist beyond 180 days to evaluate for the presence 
of chronic liver diseases and chronic DILI.
7.
If pertinent, copies of hospital discharge summary, radiology, pathology and autopsy reports 
should be obtained.
Abbreviations
AlkP
alkaline phosphatase
ALT
alanine aminotransferase
AST
aspartate aminotransferase
AMA
anti-mitochondrial antibody
ANA
antinuclear antibody
Anti-LKM1
anti-liver kidney microsomal antibody type 1
ASMA
anti-smooth muscle antibodies
AST
aspartate aminotransferase
BMI
body mass index
CBC 
complete blood count
CHF
congestive heart failure
CMV
cytomegalovirus 
CRP
C-reactive protein
CT
computerized tomography
DM
diabetes mellitus
DNA
deoxyribonucleic acid
EBV
Epstein-Barr virus
ERCP
endoscopic retrograde cholangiopancreatography
ESR
erythrocyte sedimentation rate
EOI
end of intervention
GGT
gamma-glutamyltransferase
HAV 
hepatitis A virus 
HBsAg
hepatitis B surface antigen
HCV
hepatitis C virus
HepB
hepatitis B virus
HEV
hepatitis E virus
IgM
immunoglobin M
INR
international normalized ratio
LT/LFT
liver tests/liver function tests
MRI
magnetic resonance imaging
MRCP
magnetic resonance cholangiopancreatography
NSAID
nonsteroidal anti-inflammatory drug
OTC
over the counter
PT
prothrombin time
PTT
partial thromboplastin time
RNA
ribonucleic acid
Tbili
total bilirubin
TIBC
total iron binding capacity
ULN
upper limit of normal
WBC
white blood count
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10.10. Appendix 10: Crohn’s Disease Activity Index
CCI
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10.11. Appendix 11: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
10.11.1.
Adverse Event Definitions and Classifications
Adverse Event
An adverse event is any untoward medical occurrence in a clinical study participant administered 
a medicinal (investigational or non-investigational) product. An adverse event does not necessarily 
have a causal relationship with the intervention. An adverse event 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 for 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 adverse events starting with the signing of the ICF (refer to All Adverse 
Events under Section 8.3.1, Time Period and Frequency for Collecting Adverse Events and Serious 
Adverse Events Information, for time of last adverse event recording).
For combination products with a device constituent, adverse events include those resulting from 
insufficient or inadequate instructions for use, deployment, implantation, installation, or operation, 
or any malfunction of the device. It also includes any adverse event resulting from use error or 
from intentional misuse of the investigational device.
Serious Adverse Event
A serious adverse event based on ICH and EU Guidelines on Pharmacovigilance for Medicinal 
Products for Human Use is any untoward medical occurrence that at any dose:

Results in death

Is life-threatening
(The participant was at risk of death at the time of the event. It does not refer to an event that 
hypothetically might have caused death if it were more severe.)

Requires inpatient hospitalization or prolongation of existing hospitalization

Results in persistent or significant disability/incapacity

Is a congenital anomaly/birth defect

Is a suspected transmission of any infectious agent via a medicinal product

Is Medically Important*
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*Medical and scientific judgment should be exercised in deciding whether expedited reporting is 
also appropriate in other situations, such as important medical events that may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the participant or may 
require intervention to prevent one of the other outcomes listed in the definition above. These 
should usually be considered serious.
For combination products with a device constituent, serious adverse events include adverse device 
effects that resulted in any of the consequences characteristic of a serious adverse event. 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 adverse event is considered unlisted if the nature or severity is not consistent with the applicable 
product reference safety information. For guselkumab and for ustekinumab, the expectedness of 
an adverse event will be determined by whether or not it is listed in the IB for guselkumab or for 
ustekinumab, respectively.
Adverse Event Associated With the Use of the Intervention
An adverse event is considered associated with the use of the intervention if the attribution is 
possible, probable, or very likely by the definitions listed below (see Attribution Definitions).
10.11.2.
Attribution Definitions
Not Related
An adverse event that is not related to the use of the intervention.
Doubtful
An adverse event for which an alternative explanation is more likely, eg, concomitant treatment(s), 
concomitant disease(s), or the relationship in time suggests that a causal relationship is unlikely.
Possible
An adverse event that might be due to the use of the intervention. An alternative explanation, 
eg, concomitant treatment(s), concomitant disease(s), is inconclusive. The relationship in time is 
reasonable; therefore, the causal relationship cannot be excluded.
Probable
An adverse event that might be due to the use of the intervention. The relationship in time is 
suggestive (eg, confirmed by dechallenge). An alternative explanation is less likely, 
eg, concomitant treatment(s), concomitant disease(s).
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Very Likely
An adverse event that is listed as a possible adverse reaction and cannot be reasonably explained 
by an alternative explanation, eg, concomitant treatment(s), concomitant disease(s). The 
relationship in time is very suggestive (eg, it is confirmed by dechallenge and rechallenge).
10.11.3.
Severity Criteria
An assessment of severity grade will be made using the following general categorical descriptors: 
Mild: Awareness of symptoms that are easily tolerated, causing minimal discomfort and not 
interfering with everyday activities.
Moderate: Sufficient discomfort is present to cause interference with normal activity.
Severe: Extreme distress, causing significant impairment of functioning or incapacitation. 
Prevents normal everyday activities.
The investigator should use clinical judgment in assessing the severity of events not directly 
experienced by the participant (eg, laboratory abnormalities).
10.11.4.
Special Reporting Situations
Special reporting situations must be reported by the investigator or site staff personnel to the 
sponsor or designee within 24 hours after being made aware of the event. Safety events of interest 
on a sponsor study intervention in an interventional study that may require expedited reporting or 
safety evaluation include, but are not limited to:  

Overdose of a sponsor study intervention

Suspected abuse/misuse of a sponsor study intervention

Accidental or occupational exposure to a sponsor study intervention

Any failure of expected pharmacologic action (ie, lack of effect) of a sponsor study 
intervention

Unexpected therapeutic or clinical benefit from use of a sponsor study intervention

Medication error involving a sponsor product (with or without participant/patient exposure to 
the sponsor study intervention, eg, name confusion)

Exposure to a sponsor study intervention from breastfeeding
Special reporting situations should be recorded in the eCRF. Any special reporting situation that 
meets the criteria of a serious adverse event should be recorded on the serious adverse event page 
of the eCRF.
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10.11.5.
Procedures
All Adverse Events
All adverse events, 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 adverse event to study therapy. All measures required for adverse event 
management must be recorded in the source document and reported according to sponsor
instructions.
For all studies with an outpatient phase, including open-label studies, the participant must be 
provided with a "wallet (study) card" and instructed to carry this card with them for the duration 
of the study indicating the following: 

Study number

Statement, in the local language(s), that the participant is participating in a clinical study

Investigator's name and 24-hour contact telephone number

Local sponsor's or designee’s name and 24-hour contact telephone number (for medical staff 
only)

Site number

Participant number

Any other information that is required to do an emergency breaking of the blind
Serious Adverse Events
All serious adverse events that have not resolved by the end of the study, or that have not resolved 
upon discontinuation of the participant's participation in the study, must be followed until any of 
the following occurs:

The event resolves

The event stabilizes

The event returns to baseline, if a baseline value/status is available

The event can be attributed to agents other than the study 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)
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Suspected transmission of an infectious agent by a medicinal product will be reported as a serious 
adverse event. Any event requiring hospitalization (or prolongation of hospitalization) that occurs 
during the course of a participant's participation in a study must be reported as a serious adverse 
event, except hospitalizations for the following:

Hospitalizations not intended to treat an acute illness or adverse event (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 serious adverse events. Any adverse event that results in a prolongation of the 
originally planned hospitalization is to be reported as a new serious adverse event.
The cause of death of a participant in a study within 16 weeks of the last dose of study intervention, 
whether or not the event is expected or associated with the study intervention, is considered a 
serious adverse event.
10.11.6.
Product Quality Complaint Handling
A product quality complaint (PQC) is defined as any suspicion of a product defect related to 
manufacturing, labeling, or packaging, ie, any dissatisfaction relative to the identity, quality, 
durability, 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. Timely, accurate, 
and complete reporting and analysis of PQC information from studies are crucial for the protection 
of participants, investigators, and the sponsor, and are mandated by regulatory agencies 
worldwide. The sponsor has established procedures in conformity with regulatory requirements 
worldwide to ensure appropriate reporting of PQC information; all studies conducted by the 
sponsor or its affiliates will be conducted in accordance with those procedures.
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 or designee by the study site personnel within 24 
hours after being made aware of the event.
If the defect is combined with a serious adverse event, the study site personnel must report the 
PQC to the sponsor designee according to the serious adverse event reporting timelines (refer to 
Section 8.3.1, Time Period and Frequency for Collecting Adverse Event and Serious Adverse 
Event Information). 
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A sample of the suspected product should be maintained for further investigation if requested by 
the sponsor.
Contacting Sponsor Regarding Product Quality
The names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding product quality issues are listed in the Contact Information page(s), which will be 
provided as a separate document.
10.11.7.
Contacting Sponsor Regarding Safety
The names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding safety issues or questions regarding the study are listed in the Contact Information 
page(s), which will be provided as a separate document.
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10.12. Appendix 12: Anticipated Events
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.
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10.13. Appendix 13:
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Table 14:
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Table 14:
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10.14. Appendix 14: Guidance on Study Conduct During a Major Disruption Event
It is recognized that the events causing major disruption such as COVID-19 pandemic, war, or 
natural disaster 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, relocated, 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 
guidelines or requirements or the clinical judgment 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 at unacceptable safety risk, 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 major disruption on scheduled visits cannot be conducted in person at the study 
site, the study visit 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. 
Related to the COVID-19 pandemic, if a participant has tested positive for COVID-19, the 
investigator should contact the sponsor’s medical officer or designee to discuss plans for
administration of study intervention, performing study assessments, and follow-up. 
The sponsor will continue to monitor the conduct and progress of the clinical study, and any 
changes will be communicated to the sites and to the health authorities according to local guidance. 
Modifications made to the study conduct as a result of the major disruption, should be summarized 
in the Clinical Study Report.
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ADDITIONAL ELEMENTS, WHERE APPLICABLE:

Certain protocol-mandated visits to the study site may not be possible during the major 
disruption events. Therefore, temporary measures may be implemented if considered 
appropriate by the sponsor and investigator to maintain continuity of participant 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:
o
remote (eg, by phone / telehealth) or in-person, off-site (eg, in-home) interactions 
between site staff (or designees) and participants for study procedures, eg, those related 
to safety monitoring / efficacy evaluation / study intervention storage and 
administration (including training where pertinent)
o
procurement of study intervention by participants (or designee) or shipment of study 
intervention from the study site directly to participants for at-home administration 
(including the potential for self-administration of study intervention)
o
laboratory assessments using a suitably accredited local laboratory; for selected 
measures (eg, urine pregnancy), home testing may be employed
o
other procedures, eg, imaging, may be conducted at an appropriate facility

Missed assessments/visits will be captured in the clinical trial management system for protocol 
deviations. Discontinuations of study interventions and withdrawal from the study should be 
documented in the case report form (CRF). 
o
other relevant study data elements impacted by the major disruption, should also be 
documented in CRFs and / or other study systems, as directed by detailed sponsor 
guidance. These may include missed / delayed / modified study visits / assessments / 
dosing, and instances where temporary measures such as those above are implemented.  

The sponsor will evaluate the totality of impact of major disruption events on collection of key 
study data and additional data analyses will be outlined in study SAP(s). 
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Status: Approved, Date: 12 July 2022
Section Number
and Name
Description of Change
Brief Rationale

Stool sample (fecal calprotectin): Stool samples 
required for the Week 96, 144, 192, and 240 visits
must be obtained before the start of the bowel 
preparation for the video ileocolonoscopy that is 
scheduled for the visit. 

CRP: To be collected 
 from Week 48 to 
Week 96, and q16w from Week 96 to Week 144240.

Study intervention serum concentration: Study 
intervention serum concentration will be collected 
 from Week 48 to Week 96, and q16w from 
Week 96 to Week 144240. 

Ileocolonoscopy biopsy sample collections for 
histology: Ileocolonoscopy biopsy sample will only
be collected at Weeks 96, 144, 192, and 240 (not 
Week 144).

Crohn’s disease-related hospitalizations and 
surgeries: Hospitalization for ileocolonoscopy at 
Weeks 96, 144, 192, and 240 is not included in this 
category.
[Whole blood sample collection for RNA analysis row 
deleted]
Whole blood sample and collection for RNA analysis 
(where local regulations permit)
[q16w visit column]: X
[q48w visit column]: X
Whole blood for RNA analysis will be collected 
from all participants in the study to assess the RNA 
transcriptome related to both Crohn’s disease and 
response to guselkumab and ustekinumab.
[Serum biomarkers row edited to show that samples will 
not be collected at the q16w visit; “X” removed from 
q16w visit column]
[Stool sample (microbiome; where local regulations 
permit) row deleted]
Stool sample (microbiome; where local regulations 
permit)
[q16w visit column]: X
[q48w visit column]: X
[Footnotes in Table 3 were revised:] 
b: (Third sentence) Upon study unblinding, study 
intervention administration will continue for all 
participants on active treatment through 
Week 144240.
c: The 
 visits include scheduled visits at Weeks 56, 
72, 88, 104, 120, and 136, 152, 168, 184, 200, 216, 
and 232.
d: The q16w visits include scheduled visits at 
Weeks 64, 80, 112, and 128, 160, 176, 208, and 224. 
e: The q48w visits occur at Weeks 96, and Week 144, 
192, and 240.
Schedule of 
Activities (SoA); 
Table 4
[The following row headers and notes were revised to 
show updated study timepoints for the extended LTE:]
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Section Number
and Name
Description of Change
Brief Rationale
Participant discontinues study intervention after Week 48 
and up to Week 144240: 
Discontinuation after Week 48 and before Week 96:
The video ileocolonoscopy at the SID visit is 
optional for participants who discontinue after 
Week 48, since these participants would have 
completed the procedure as part of the Week 48 
visit.
Discontinuation after Week 96 and before 
Week 144: The video ileocolonoscopy at the SID 
visit is optional for participants who discontinue 
after Week 96, since these participants would have 
completed the procedure as part of the Week 96 
visit.  
Discontinuation after Week 144 and before 
Week 192: The video ileocolonoscopy at the SID 
visit is optional for participants who discontinue 
after Week 144, since these participants would have 
completed the procedure as part of the Week 144 
visit.  
Discontinuation after Week 192 and before 
Week 240: The video ileocolonoscopy at the SID 
visit is optional for participants who discontinue 
after Week 192, since these participants would have 
completed the procedure as part of the Week 192 
visit.
Participant completes LTE participation at Week 
144240: 
Week 144240 (see Table 3)
The FES should occur around Week 156248 or 252
(ie, approximately 16 weeks after the last study 
intervention administration at Week 140232 [for 
dosing] or 236 [for 
 dosing]).
Schedule of 
Activities (SoA); 
Table 5
[The note in the Patient-Reported Outcomes (PROs) row 
was edited]
PRO assessments for efficacy (PGIC, PGIS, IBDQ, 
PROMIS-29, PROMIS Fatigue Short Form 7a, and 
EQ-5D-5L) and health economics (WPAI-CD) should be 
administered before the C-SSRS and before any clinical 
procedures or tests are performed. The IBDQ, PROMIS-
29, and WPAI-CD assessments should be performed if a 
participant discontinues in the LTE.  
4.1.1. Phase 2 Dose-
Ranging Study 
(GALAXI 1): 
Induction and 
Maintenance; 4.1.2. 
Phase 3 Dose-
Confirming Studies 
(GALAXI 2 and 
GALAXI 3): 
Induction and 
Maintenance; 4.1.3. 
Long-Term 
[Edited subheaders]
4.1.1. Phase 2 Dose-Ranging Study (GALAXI 1): 
Induction and Maintenance
4.1.2. Phase 3 Dose-Confirming Studies (GALAXI 2 and 
GALAXI 3): Induction and Maintenance
4.1.3. Long-Term Extension for GALAXI 1, 2, and 3
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Section Number
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Description of Change
Brief Rationale
Extension for 
GALAXI 1, 2, and 
3 
4.1.1.2. Treatment 
Groups
All participants who complete the Week 48 evaluations 
may be eligible to enter the LTE and continue to receive 
study intervention for approximately 24 additional years 
(Week 48 to Week 156252), as described in 
Section 4.1.3.
4.1.3. Long-Term 
Extension for 
GALAXI 1, 2, and 
3
The LTE will be conducted for approximately 24 years, 
from Week 48 through Week 156252.
At Week 48 of GALAXI 1, GALAXI 2, or GALAXI 3, 
all participants who, in the opinion of the investigator, 
will continue to benefit from treatment (ie, based on 
Week 48 clinical and endoscopic evaluations) are 
eligible to enter the LTE to receive approximately 24
additional years of treatment, during which time the 
longer-term efficacy and safety of guselkumab will be 
evaluated. All participants will be assessed according to 
the Schedule of Activities (Section 1.3). The final 
efficacy and safety follow-up (FES) visit of the LTE will 
occur at approximately Week 156248 or 252 (ie, 
approximately 16 weeks after their last study 
intervention administration at Week 140232 [for 
 
dosing] or Week 236 [for 
 dosing]).
[Paragraph 4] During the LTE, all participants will 
continue to receive the same treatment regimen (ie, 
guselkumab, ustekinumab, or placebo) that they were 
receiving at the end of GALAXI 1, GALAXI 2, or 
GALAXI 3. The first study intervention administration in 
the LTE will occur at Week 48 and the last study 
intervention administration will occur at Week 140236. 
Treatment adjustment for inadequate response is 
permitted between Week 52 and Week 80 of the LTE, as 
described in Section 4.1.3.1. 
[Paragraph 7] After study unblinding, all participants 
who are on active treatment (ie, guselkumab or 
ustekinumab) will continue to receive their assigned 
active treatment for the remaining duration of the LTE 
through Week 140236. Participants who are on placebo 
will be discontinued from study intervention upon study 
unblinding and will have an FES visit at that time. 
4.1.3.1. Treatment 
Adjustment for 
Inadequate 
Response
…[Paragraph 5, 2nd to last sentence] Continued 
participation in the remaining duration of the LTE will 
be decided on investigator’s clinical judgment of the 
results of the Week 96, 144, and 192 clinical and 
endoscopic evaluations.
4.1.3.2. Self-
Administration of 
Study Intervention 
(or Administration 
…[Paragraph 3, last sentence] Finally, participants will 
continue to have study visits and assessments at the 
investigative sites approximately 
 through 
Week 144240, as outlined in Section 1.3.
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Section Number
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Brief Rationale
by Caregiver) at 
Home
…[Paragraph 4, last sentence] Participants will continue 
to have study visits and assessments at the investigative 
site approximately 
 (if receiving 
 dosing per 
protocol) or 
 (if receiving 
 dosing per protocol) 
through Week 144240, as outlined in Section 1.3.
4.2.1. Endpoints and 
Evaluations
[Paragraph 1, 1st sentence] Through Week 156252, the 
longer-term efficacy and safety of guselkumab will be 
evaluated. 
[Paragraph 3] Database locks are planned at Weeks 96 
(to evaluate the durability of efficacy evaluations and the 
benefit of dose adjustment); Weeks 144 and 192, and 
when the final participant has completed the FES visit in 
the LTE (to provide longer-term safety and efficacy 
data). Additional DBLs may be added if necessary and 
will be specified in the Phase 3 SAP.
4.2.3. Biomarker 
and DNA 
Collection
[Paragraph 1, 4th sentence] Ileocolonic biopsies will also 
be obtained from all participants pretreatment during 
screening and post-treatment at Weeks 12, 48, and 96, 
144, 192 and 240 to assess cellular and molecular 
changes within the intestinal mucosal tissue.
4.2.6. Study-
Specific Ethical 
Design 
Considerations
[Paragraph 2, 1st sentence] The total blood volume to be 
collected from each participant in each study (maximum 
of approximately 500400 mL over approximately 156252
weeks) is far less than the American Red Cross standard 
limit for whole blood donation (approximately 475 mL 
 and is, therefore, considered an acceptable amount 
of blood to be collected over this time period. 
4.3.1.3. Long-Term 
Extension (Week 48 
to Week 240) for 
GALAXI 1, 2, and 
3
Long-Term Extension (Week 48 to Week 144240) for 
GALAXI 1, 2, and 3
Participants will continue on their assigned guselkumab 
maintenance dose during the LTE of GALAXI 1, 
GALAXI 2, and GALAXI 3. Participants who 
experience inadequate response between Week 52 
through Week 80 while on the lower of the 2 
maintenance dose regimens being evaluated in the 
applicable respective study will be eligible for a single 
dose adjustment and will receive the higher maintenance 
dose until the end of the LTE to assess if they can regain 
clinical response.
6.5.1. Concomitant 
Medications
[Subhead 3] During treatment phase of LTE (ie, 
Week 48 through Week 144240):
6.7. Intervention 
After the End of the 
Study
[Paragraph 1] This protocol is designed to provide 
participants with up to approximately 35 years of 
treatment (ie, 48-week treatment under the Phase 2 or 
Phase 3 studies plus approximately 24 additional years of 
treatment in the LTE).
8. Study 
Assessments and 
Procedures
[Blood Sample Collection subsection, 2nd paragraph] 
The maximum total blood volume to be collected from 
each participant in each study (GALAXI 1, GALAXI 2, 
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Section Number
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Description of Change
Brief Rationale
(ii) with absence of ALL conditions (a), (b), (c) above 
during the period between the negative test result and the 
baseline study visit 
Note on the COVID-related exclusion: 
•
The field of COVID-related testing (for presence of, 
and immunity to, the SARS-CoV-2 virus) is rapidly 
evolving. Additional testing may be performed as part of 
screening and/or during the study if deemed necessary by 
the investigator and in accordance with current 
regulations / guidance from authorities / standards of 
care. 
Precaution: for those who may carry a higher risk for 
severe COVID-19 illness (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.
5.3. Lifestyle 
Considerations
[Lifestyle Consideration 1 modified:] 
1.1. Refer to Section 6.5, Concomitant Therapy, for
details regarding prohibited and restricted therapy during 
the study.
It is recommended that participants are up-to-date on all 
age-appropriate vaccinations prior to screening per 
routine local medical guidelines. For study participants 
who received locally approved (including emergency-
use-authorized) COVID-19 vaccine(s) recently prior to 
study entry, follow applicable local vaccine labeling, 
guidelines, and standards of care for patients receiving 
immune-targeted therapy when determining an 
appropriate interval between vaccination and study 
enrollment (see also Section 6.5.3 Vaccinations 
[Including COVID-19]).
6.1. Study 
Interventions 
Administered
Guidelines for study intervention administration affected 
by the COVID-19 pandemic are found in Section 10.14.
6.5. Concomitant 
Therapy
Prestudy therapies administered up to 30 days before the 
first administration of study intervention must be 
recorded on the eCRF. Any COVID 19 vaccines 
administered, regardless of timing, must be recorded on 
the eCRF. Concomitant therapies must be recorded 
throughout the study, from signing of the informed 
consent to the last study visit.
6.5.3. 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 
participants receiving immune-targeted therapy.
For study participants receiving a locally approved 
(including emergency-use-authorized) COVID-19 
vaccine, in order to help identify acute reactions 
potentially related to the COVID-19 vaccine, it is 
recommended that, where possible, vaccine and study 
intervention be administered on different days, separated 
by as large an interval as is practical within the protocol.
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Section Number
and Name
Description of Change
Brief Rationale
a. Have a history of successful treatment (defined as 
being negative for HCV RNA at least 6 months
12 weeks after completing antiviral treatment) 
and have a negative HCV RNA test result at 
screening, OR
b. While seropositive have a negative HCV RNA 
test result at least 6 months 12 weeks prior to 
screening and a negative HCV RNA test result 
at screening.
below) regarding HCV 
retesting in treated and 
untreated patients.
EASL Clinical Practice 
Guidelines: Management of 
hepatitis C virus infection 
Journal of Hepatology 2014 
vol. 60 j 392–420
Burgess, Sarah V et al. 
Concordance of sustained 
virologic response at weeks 4, 
12 and 24 post-treatment of 
hepatitis C in the era of new 
oral direct-acting antivirals: A 
concise review. Annals of 
hepatology vol. 15,2 (2016): 
154-9. 
doi:10.5604/16652681.1193693
The American Association for 
the Study of Liver Diseases and 
the Infectious Diseases Society 
of America Present HCV 
Guidance: Recommendations 
for Testing, Managing, and 
Treating Hepatitis C Last 
Updated: January 21, 2021 
www.hcvguidelines.org
5.3. Lifestyle 
Considerations
[Lifestyle Consideration 5:] 
5.1. Must agree not to receive a BCG vaccination during 
the study and for 126 weeksmonths after receiving the 
last dose of study intervention. 
To use ustekinumab half-life 
to determine the washout 
period.
8.2.11. Clinical 
Safety Laboratory 
Assessments
[Abnormal liver function tests paragraph, final sentence 
added.] 
See Appendix 9 (Section 10.9; Guideline Algorithm for 
Monitoring, Assessment, and Evaluation of Abnormal 
Liver Tests in Participants With No Underlying Liver 
Disease) for additional information on monitoring and 
assessment of abnormal liver function tests. Also refer to 
Section 8.3.1, Time Period and Frequency for Collecting 
Adverse Event and Serious Adverse Event Information.
Reference to Section 8.3.1. 
added for clarification. 
8.3.1. Time Period 
and Frequency for 
Collecting Adverse 
Event and Serious 
Adverse Event 
Information
All Adverse Events
All AEs and special reporting situations, whether serious 
or non-serious, will be reported from the time a signed 
and dated ICF is obtained until completion of the 
participant’s last study-related procedure, which may 
include contact for follow-up of safety. Serious adverse 
events, including those spontaneously reported to the 
investigator within 16 weeks after the last dose of study 
intervention, must be reported using the Serious Adverse 
Event Form. The sponsor will evaluate any safety 
information that is spontaneously reported by an 
investigator beyond the time frame specified in the 
protocol.
Administrative additions 
made for SAE monitoring.
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Clinical Protocol CNTO1959CRD3001 Amendment 5
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Status: Approved, Date: 12 July 2022
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Brief Rationale
from insufficient or inadequate instructions for 
use, deployment, implantation, installation, or 
operation, or any malfunction of the device. It 
includes any adverse event resulting from use error 
or from intentional misuse of the investigational 
device.
Paragraph 3 (under Serious Adverse Event 
subhead): 
For combination products with a device 
constituent, serious adverse events include adverse 
device effects that resulted in any of the 
consequences characteristic of a serious adverse 
event. 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).
10.11.6, Product 
Quality Complaint 
Handling
Text was revised/added:
A product quality complaint (PQC) is defined as 
any suspicion of a product defect related to 
manufacturing, labeling, or packaging, ie, any 
dissatisfaction relative to the identity, quality, 
durability, or reliability, of a 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. Timely, 
accurate, and complete reporting and analysis of 
PQC information from studies are crucial for the 
protection of participants, investigators, and the 
sponsor, and are mandated by regulatory agencies 
worldwide. The sponsor has established 
procedures in conformity with regulatory 
requirements worldwide to ensure appropriate 
reporting of PQC information; all studies 
conducted by the sponsor or its affiliates will be 
conducted in accordance with those procedures. 
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 
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Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 12 July 2022
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Brief Rationale
power for endoscopic response at Week 12 at the 
α=0.05 (2-sided) level.
9.2.2.2, Phase 3 
Dose-Confirming 
Studies (GALAXI 2 
and GALAXI 3)
Paragraph 3 was revised to add the co-primary 
endpoint: 
Therefore, the sample sizes for each of these 
studies were determined by the power to detect a 
significant difference in clinical remission at Week 
12 and endoscopic response at Week 12 (co-
primary endpoints) between the combined 
guselkumab induction dose group and placebo.
Paragraph 4 was revised and new fifth paragraph 
was added for co-primary endpoints:
For the co-primary endpoint of clinical 
remission at Week 12: In each of the Phase 3 
studies, assuming a clinical remission rate of 
approximately 12% to 15% for placebo and a 
minimum of a 20% difference between 
guselkumab and placebo, 440 participants in the 
combined guselkumab induction dose group and 
110 participants in the placebo group, respectively, 
will provide greater than 99% power for clinical 
remission at Week 12 at an overall Type 1 error 
rate controlled at a 0.05 (2-sided) alpha level 
(Table 10). If 2 guselkumab induction doses are 
chosen, based on the same assumptions 220 
participants in each guselkumab induction dose 
group and 110 participants in the placebo group, 
respectively, will provide power ≥98%.  
For the co-primary endpoint of endoscopic 
response at Week 12: In each of the Phase 3 
studies, assuming an endoscopic response rate of 
approximately 10% to 13% for placebo and a 
minimum of a 15% difference between 
guselkumab and placebo, 440 participants in the 
combined guselkumab induction dose group and 
110 participants in the placebo group, respectively, 
will provide approximately 94% power for 
endoscopic response at Week 12 at an overall 
Type 1 error rate controlled at a 0.05 (2-sided) 
alpha level (Table 10). If 2 guselkumab induction 
doses are chosen, based on the same assumptions 
220 participants in each guselkumab induction 
dose group and 110 participants in the placebo 
group, respectively, will provide approximately 
89% power.  
To add text for the co-primary 
endpoints, and to delete (in 
Section 9.2.2.2) hypothetical 
statements that were part of the 
protocol before the Phase 3 dose 
groups were chosen (these 
statements are no longer applicable 
because only 1 induction dose was 
chosen for the Phase 3 studies). 
Table 10
Table 10 was revised to add power calculations for 
the co-primary endpoint of endoscopic response at 
Week 12 and for an additional major secondary 
endpoint. The table title was also updated. 
9.4.3.2, Primary 
Endpoint Analysis
Text was revised to incorporate the second co-
primary endpoint: 
The co-primary endpoints in each Phase 3 study 
are clinical remission at Week 12 and endoscopic 
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Clinical Protocol CNTO1959CRD3001 Amendment 5
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Status: Approved, Date: 12 July 2022
Section Number, 
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Brief Rationale
response at Week 12. Clinical remission is defined 
as a CDAI score <150 points. Endoscopic 
response is defined as at least 50% improvement 
from baseline in SES-CD score or SES-CD score 
≤2.
Participants who have any of the following events 
before the Week 12 visit will be considered as 
treatment failures, and will not be considered to 
have achieved clinical remission at Week 12 or 
endoscopic response at Week 12:
•
Specified changes in concomitant Crohn’s 
disease medications (to be detailed in the 
Phase 3 SAP)
•
A Crohn’s disease-related surgery (except 
drainage of an abscess or seton placement)
•
Discontinuation of study intervention due to 
lack of efficacy or due to an AE of worsening 
Crohn’s disease
The CDAI score will be calculated for a visit if at 
least 4 of the 8 components are available at that 
visit. When at least 4 of the 8 components are 
available, any missing components will be 
imputed by carrying forward the last available 
components. If the CDAI score cannot be 
calculated (ie, < 4 components available) at a visit, 
the CDAI score will be considered missing for that 
visit. Participants who do not return for evaluation 
or have a missing CDAI score at Week 12 will not 
be considered to have achieved clinical remission 
at Week 12. The total SES-CD score at a visit will 
be calculated based on all segments scored at the 
visit. If the total SES-CD score cannot be 
calculated (ie, no segment is scored) at a visit, the 
total SES-CD score will be considered missing. 
The details for handling missing segments in the 
SES-CD score will be described in the Phase 3 
SAP. Participants who do not return for evaluation 
or who have a missing SES-CD score at Week 12 
will not be considered to have achieved 
endoscopic response at Week 12. Treatment 
failure rules will overrule the missing data rules.  
For testing of the co-primary endpoints, the 
efficacy of the induction dose of guselkumab 
versus placebo will be compared. As such, within 
each study, the two guselkumab groups that are 
randomized to receive identical guselkumab 
induction treatment through Week 12 will be 
combined for this these comparisons. A CMH chi-
square test (2-sided) stratified by baseline CDAI 
score (≤300 or >300), baseline SES-CD score (≤12 
or >12), BIO-Failure status (Yes/No), and baseline 
corticosteroid use (Yes/No) will be used.
Each study will be considered positive if the 
combined guselkumab induction dose group (ie, 
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CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 12 July 2022
Section Number, 
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Description of Change
Brief Rationale
Treatment Group 1 and Treatment Group 2 that 
received the same guselkumab induction treatment 
through Week 8) for that study is significantly 
different from the placebo group for both of the 
co-primary endpoints. 
To examine the robustness of the co-primary 
endpoint analyses, sensitivity analyses of the 
co-primary endpoints will be conducted using 
different missing data approaches; these analyses 
will be described in the Phase 3 SAP. 
Subgroup analyses of the co-primary endpoints
will be performed based on demographic and 
baseline disease characteristics and baseline use 
and history of Crohn’s disease medications 
(including BIO-Failure status). 
Synopsis; 
9.4.3.3, Major 
Secondary Endpoints
For the Phase 3 studies, endoscopic response at 
Week 12 was deleted, and endoscopic remission at 
Week 12 and endoscopic remission at Week 48 
were added, as major secondary endpoints: 
•
Clinical remission at Week 48
•
Endoscopic response at Week 48
•
Durable clinical remission at Week 48 (defined 
as CDAI score <150 for ≥80% of all visits 
between Week 12 and Week 48 [ie, at least 8 
of 10 visits], which must include Week 48)
•
Corticosteroid-free clinical remission at 
Week 48 (defined as CDAI score <150 at 
Week 48 and not receiving corticosteroid at 
Week 48)
•
PRO-2 remission at Week 12 (defined as an 
AP mean daily score at or below 1 [AP≤1]
AND an SF mean daily score at or below 3 [, 
ie, AP≤1 and SF≤3], and no worsening of AP 
or SF from baseline)
•
PRO-2 remission at Week 48
•
Endoscopic response at Week 12 (defined as at 
least 50% improvement from baseline in SES
CD score or SES CD score ≤2)
•
Endoscopic response at Week 48
•
Endoscopic remission (defined as SES-CD 
score ≤2) at Week 12 
•
Endoscopic remission at Week 48
•
Fatigue response at Week 12 (based on the 
PROMIS Fatigue Short Form 7a; to be defined 
in the SAP)
Participants who meet 1 or more treatment failure 
rules before a visit will be considered not to have 
achieved any of the major secondary endpoints be 
in clinical remission or fatigue response from that 
visit onward. …
In Section 9.4.3.3, the following paragraph was 
also deleted: 
To align the treatment failure rules 
among different efficacy endpoints.
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CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 12 July 2022
Section Number, 
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Brief Rationale
For endoscopic endpoints, the same treatment 
failure rules apply, except for a modification of the 
“certain changes in concomitant Crohn’s disease 
medications” rule, which will only consider 
prohibited medications as treatment failure. Details 
will be provided in the Phase 3 SAP.
In Section 9.4.3.3, the following paragraphs were 
also edited: 
Within each study, the major secondary endpoints 
of clinical remission at Week 12 as measured by 
PRO-2, fatigue response at Week 12, and
endoscopic remission response at Week 12 will be 
compared between the combined guselkumab 
induction dose group and the placebo group using 
the CMH chi-square test (2 sided) stratified by 
baseline CDAI score (≤300 or >300), baseline 
SES-CD (≤12 or >12), BIO-Failure status 
(Yes/No), and baseline corticosteroid use 
(Yes/No).
The major secondary endpoints related to clinical 
remission at Week 48 (either based on CDAI or 
PRO-2), endoscopic response at Week 48, and 
endoscopic remission at Week 48 will be 
compared between each guselkumab dose group 
and the ustekinumab group using the CMH chi-
square test (2-sided) stratified by baseline CDAI 
score (≤300 or >300), baseline SES-CD (≤12 or 
>12), BIO-Failure status (Yes/No), and baseline 
corticosteroid use (Yes/No). 
Synopsis; 
3.2.1, Objectives
The first primary objective was edited to include 
endoscopic efficacy and the first secondary 
objective was deleted: 
Primary Objectives
•
To evaluate the clinical and endoscopic
efficacy of guselkumab in participants with 
Crohn’s disease 
•
To evaluate the safety of guselkumab
Secondary Objectives
•
To evaluate the efficacy of guselkumab on 
endoscopic improvement
•
To evaluate the impact of guselkumab on 
HRQOL
•
To evaluate the PK, immunogenicity, and PD 
of guselkumab therapy, including changes in 
CRP and fecal calprotectin
Synopsis; 
3.2.3, Hypothesis
Endoscopic response at Week 12 was added to the 
primary hypothesis: 
The primary hypothesis for both GALAXI 2 and 
GALAXI 3 is that guselkumab is superior to 
placebo in achieving clinical remission at Week 12 
and endoscopic response at Week 12 in 
participants with moderately to severely active 
Crohn's disease.
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CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
204
Status: Approved, Date: 12 July 2022
Section Number, 
Name
Description of Change
Brief Rationale
based on the presence of ulceration in any at 
least 1 of the 5 ileocolonic segments, resulting 
in the following specified ulceration 
component scores: 
a. a minimum score of 1 for the component of 
“size of ulcers”
AND
b. a minimum score of 1 for the component of 
“ulcerated surface”.
Of note, before the implementation of 
Amendment 3, where the minimum SES-CD score 
was ≥3 based on the presence of ulceration, within 
each of the studies, a maximum of 10% of the total 
enrolled population will be could include
participants who had have baseline scores for 
SES-CD <4 (ie, for participants with isolated ileal 
disease), or SES-CD <7 (ie, for participants with 
colonic or ileocolonic disease).
4.1.2.1, Overview of 
Phase 3 Design
The second-last sentence in the following 
paragraph was deleted: 
GALAXI 2 and GALAXI 3 are identical studies 
from a study design perspective. The purpose of 
conducting two replicate studies is to achieve 
independent confirmation of clinical efficacy in 
two independent samples of patients, which is 
required by some health authorities. At Week 0, a  
target of 1,540 participants will be randomly 
allocated to GALAXI 2 (n=770) or GALAXI 3 
(n=770), using a permuted block randomization 
with baseline CDAI score (≤300 or >300), baseline 
SES-CD score (≤12 or >12), prior BIO-Failure 
status (Yes/No), and baseline corticosteroid use 
(Yes/No) as the stratification variables. Within 
each stratum, participants in each study will be 
randomized in a 2:2:2:1 ratio to receive 1 of 2 dose 
regimens of guselkumab, ustekinumab, or placebo, 
respectively. Within each study (GALAXI 2 and 
GALAXI 3), a minimum of 25% and a maximum 
of 50% of the total enrolled population will be 
participants who are CON-Failures. In addition, a 
maximum of 10% of the total enrolled population 
will have baseline scores for SES CD <4 (ie, for 
participants with isolated ileal disease) or SES CD 
<7 (ie, for participants with colonic or ileocolonic 
disease). Allocation to treatment groups will be 
performed using a central randomization center by 
means of an IWRS.
This sentence is no longer 
necessary because of the change in 
SES-CD criteria. 
9.4.1.1, Phase 2 
Dose-Ranging Study 
(GALAXI 1)
9.4.1.2, Phase 3 
Dose-Confirming 
The following bullet was moved from the list of 
Other Endpoints (Short-Term Efficacy) for the 
Phase 3 studies to equivalent list for the Phase 2 
study: 
•
Change in SES-CD score from baseline at 
Week 12, endoscopic response at Week 12, 
This analysis is no longer 
applicable for the Phase 3 studies 
because of the change to SES-CD 
enrollment criteria for the Phase 3 
studies (but is still valid for the 
Phase 2 study).
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CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
206
Status: Approved, Date: 12 July 2022
Section Number, 
Name
Description of Change
Brief Rationale
1.3, Table 1
The Note for Chest radiograph item was edited: 
Chest radiograph (posterior-anterior and lateral 
views) must may be obtained within 12 weeks 
before the Week 0 visit. 
To clarify that the time frame for 
obtaining this screening activity is 
required, not optional.
The Note for Stool studies item was edited: 
Stool studies for enteric pathogens may be 
performed at screening at either the central or a 
local laboratory and must include a stool culture 
and Clostridium difficile toxin assay. Although 
stool studies may be processed at either the central 
or local laboratory, the central laboratory is 
preferred when available. Stool studies must have 
been performed within 4 months before Week 0. 
Additional testing, such as ova and parasites or 
Escherichia coli O157:H7 assessment, may be 
performed at the investigator’s clinical discretion.
To clarify that central laboratory 
processing is preferred and to 
confirm the timing of screening 
stool studies. 
1.3, Table 2
“Review medical history” row added to the SoA 
for Week 0 to Week 48.
Added as a double-check at 
Week 0 before participant 
randomization. 
Note added to the Randomization row: 
Randomization should be performed 
approximately 5 weeks after screening/informed 
consent signing.
Added as a reminder from the 
Screening SoA (Table 1).
1.3, Table 3
Clarification was added to Footnote a:
a. Week 48 study procedures outlined in the SoA 
for Week 0 to Week 48 (Table 2) must be 
performed prior to study intervention 
administration. In participants who are 
considered appropriate for self-administration 
at home after being trained, at-home 
administration can begin after the Week 48 
visit according to regional/local regulations 
and instructions.
Clarification
1.3, Table 4
A Note was added to the item about participant 
discontinuation after Week 12 but up to Week 48:
Discontinuation after Week 12 (visit and 
ileocolonoscopy) and before Week 44: A video 
ileocolonoscopy (with biopsy samples) is optional (or 
can be performed as part of SID visit).
Discontinuation at Week 44 or Week 48: A video 
ileocolonoscopy (with biopsy samples) is required (or 
can be performed as part of SID visit).  
To clarify (depending on the time 
point) when video ileocolonoscopy 
is required for participants who 
discontinue study intervention after 
Week 12 but before Week 48.
1.3, Table 5
Two rows were added under the 
Pharmacodynamic and Biomarkers subsection of 
Table 5: 
Ileocolonoscopy biopsy sample collections for 
histology 
To clarify that ileocolonoscopy 
biopsy sample collections are 
required as part of a Study 
Intervention Discontinuation (SID) 
visit.
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CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 12 July 2022
Section Number, 
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Description of Change
Brief Rationale
Ileocolonoscopy biopsy sample collections for 
exploratory RNA and protein assessments 
(where local regulations permit)
4.1.2.2, Figure 3
A note was added to Figure 3:
Note: This schematic only illustrates the dosing for 
the treatment groups. It does not provide a 
complete illustration of all blinding (placebo) 
administrations.
This note was added as 
clarification and parallels the note 
in the Phase 2 schematic (Figure 
2). 
5.1, Inclusion 
Criteria
Inclusion Criterion 8e: 
e.1 Have a chest radiograph (both posterior-
anterior and lateral views, or per local/country 
regulations where applicable), taken ≤12 weeks 
before the first administration of study 
intervention and read by a qualified radiologist 
or qualified pulmonologist according to local 
clinical practice, with no evidence of current, 
active TB or old, inactive TB. A chest CT scan 
is also acceptable if obtained instead of a chest 
radiograph outside of the protocol.
Clarification
5.2, Exclusion 
Criteria
Exclusion Criterion 3:
“Requiring general anesthesia” was removed as an 
example of other major surgery:
3. Has had any kind of bowel resection within 6 
months, or any other intra-abdominal or other 
major surgery (eg, requiring general 
anesthesia) within 12 weeks, before baseline.
The example was removed to 
prevent confusion because general 
anesthesia may be administered for 
less invasive surgeries that would 
not be exclusionary.
Exclusion Criterion 6.d.4:
Clarification was added for other 
immunomodulatory biologic agents: 
6. Has received any of the following prescribed 
medications or therapies within the specified 
period:
…d.
Biologic agents:
…4)
Other immunomodulatory biologic agents, 
including approved and investigational biologic 
agents, received within 12 weeks of baseline or 
within 5 half-lives of baseline, whichever is 
longer.
Clarification
Exclusion Criterion 6.e:
A clarification was added to the EC regarding 
investigational interventions: 
e. Any investigational intervention received 
within 4 weeks of baseline or within 5 half-
lives of baseline, whichever is longer. (Refer to 
Exclusion Criterion 6.d.4 for investigational 
biologic agents.)
Clarification
Exclusion Criterion 6.g:
Clarification
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CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 12 July 2022
Section number
and Name
Description of Change
Brief Rationale
6.1, Study 
Interventions 
Administered
Last paragraph: 
Detailed instructions on the preparation and 
administration of study intervention will be 
provided in the site Investigational Product 
Procedures Manual (IPPM). Of note, instructions 
on the preparation and administration of study 
intervention in the Phase 3 portion of the protocol 
will be finalized and provided to investigative sites 
when the Phase 3 dose decision is made and 
implemented.
Text was deleted because the IPPM 
already includes instructions for the 
dose regimens in Phase 2 and 
Phase 3.
2.3.1, Benefit-Risk 
Assessment, 
Guselkumab
Fourth paragraph:
… Other potential safety concerns, also described 
in greater detail in the guselkumab IB, are based on 
guselkumab being an immunomodulatory mAb and 
include malignancy and hypersensitivity, as well as 
liver injury, based on an event of potential drug-
induced liver injury (DILI) that occurred in a single 
participant at the highest Phase 2 induction dose 
administered. 
Text was revised to indicate that 
information was added to the IB 
regarding the potential safety 
concern of liver injury. 
7.1, Discontinuation 
of Study 
Intervention
Item 9 was revised: 
6.
The participant has severe hepatic function
liver test abnormalities that are not transient 
and are not explained by other etiologies, as 
described in Section 8.2.1.1 and Appendix 9 
(Section 10.9). Such abnormalities would 
include the following:  

ALT or AST >8 x ULN 

ALT or AST >5 x ULN for more than 
2 weeks 

ALT or AST >3 x ULN and (total 
bilirubin >2 x ULN or international 
normalized ratio [INR] >1.5) 

ALT or AST >3 x ULN and symptoms of 
hepatitis (eg, fatigue, nausea, vomiting, 
right upper quadrant pain or tenderness, 
fever, rash, and/or eosinophilia [>5%]) 
This item was revised to clarify the 
criteria for discontinuation of study 
intervention due to liver test 
abnormalities. 
8.2.11, Clinical 
Safety Laboratory 
Assessments

Abnormal liver function tests: If laboratory 
testing for a subject who is enrolled in the 
study and receiving study intervention reveals 
an increase of serum aminotransferases (ALT 
or AST) to >3 x ULN and an increase of 
bilirubin to >2 x ULN, study intervention
should be suspended immediately. In 
addition, laboratory tests for ALT, AST, 
alkaline phosphatase, and total bilirubin 
should be confirmed by a retest within 24 
hours if possible, but no later than 72 hours 
following notification of test results. 
Additional clinical and laboratory studies may 
be performed to evaluate the underlying 
A sentence was added to clarify 
that additional testing may be 
requested, and the appendix 
number was corrected.
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CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 12 July 2022
Section number
and Name
Description of Change
Brief Rationale
etiology of abnormal findings. See Appendix 
9 (Section 10.9; Guideline Algorithm for 
Monitoring, Assessment, and Evaluation of 
Abnormal Liver Tests in Participants With 
No Underlying Liver Disease) for additional 
information on monitoring and assessment of 
abnormal liver function tests.
10.9, Appendix 9
Updated Appendix.
This Appendix was updated with 
the most current version. The 
updated Appendix provides 
detailed guidance regarding 
additional tests and evaluations to 
be obtained in the setting of 
specific patterns of liver enzyme 
abnormalities.
Throughout the 
protocol
Minor grammatical, formatting, or spelling changes 
were made. 
Minor errors were noted.
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CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
214
Status: Approved, Date: 12 July 2022
Amendment 1 10 December 2018
Overall Rationale for the Amendment: The primary rationale for the amendment is to update 
the endoscopic inclusion criterion to more accurately define the contemporaneous Crohn’s 
disease patient population based on the observed patient characteristics from this ongoing 
protocol and other protocols conducted by the sponsor. Additional clarifications were made 
throughout the protocol based on feedback from health authorities, ethics committees, and 
investigative sites.
The changes to the protocol are outlined in the table below and are indicated with an underline.
Section number
and Name
Description of Change
Brief Rationale
Section 1.1, 
Synopsis, Overall 
Design; Section 4.1, 
Overall Design
Since data from more participants may be required 
to inform the dose decision, the sponsor may elect 
to continue enrollment and newly enrolled 
participants (ie, starting from participant #251) will 
be randomized into a Transition Cohort while the 
data from the Initial Dose Decision Cohort are 
being collected and analyzed.
Clarification of participant 
enrollment in the Phase 2 
(GALAXI 1) study. The sponsor 
may elect to pause or to continue 
enrollment of participants into the 
transition cohort, depending on the 
sponsor’s assessment of whether 
additional data are needed to inform 
the dose decision. 
Section 1.1, 
Synopsis, Overall 
Design; Section 4.1, 
Overall Design
This is an operationally seamless protocol in 
countries where the local health authorities have 
approved a seamless transition. In the countries 
that have approved a seamless transition, there will 
be no break in enrollment between the Phase 2 and 
Phase 3 studies if enrollment continues into the 
Transition Cohort and a dose decision can be made 
before 500 patients are randomized. Transition 
from the Phase 2 portion to the Phase 3 portion of 
the protocol will occur once the dose decision for 
Phase 3 has been made and implemented. In 
countries where the local health authority requires 
additional regulatory approval prior to initiating 
the Phase 3 studies, enrollment will pause until 
approval is received.  In all countries, all 
participants randomized after the dose decision has 
been implemented will be part of the Phase 3 
studies.
Clarification to acknowledge that 
this protocol will be conducted 
based on the original operationally 
seamless design, in countries where 
this design is approved by the local 
health authority if enrollment 
continues into the Transition 
Cohort; and to acknowledge that in 
a number of countries, the local 
health authority requires a non-
seamless transition and requires a 
separate approval prior to the 
initiation of the Phase 3 studies.
NCT03466411

NCT03466411

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
216
Status: Approved, Date: 12 July 2022
Section number
and Name
Description of Change
Brief Rationale
weeks before the Week 0 visit to 
support randomization.
Section 1.3, 
Schedule of 
Activities, Table 1, 
Table 2, Table 3; 
Section 8.8.3, 
Biopsy-based 
Biomarkers
Ileocolonoscopy biopsy sample collections for 
histology 
and
Ileocolonoscopy biopsy sample collections for 
exploratory RNA and protein assessments (where 
local regulations permit).
Mucosal biopsy samples will be collected during 
ileocolonoscopy to study the effect of study 
intervention on the histological assessment of 
disease and healing. Biopsies will also be analyzed 
for exploratory gene and protein expression 
analysis where local regulations permit. 
Ileocolonic biopsy analyses may also examine 
gene and protein expression associated with the 
pathogenesis of Crohn’s disease.
Clarification on the collection of 
ileocolonoscopy biopsy samples for 
RNA and protein analysis to be 
executed only in applicable 
countries where local regulations 
permit, since not all countries 
permit this testing on biopsy 
samples. 
Section 1.3, 
Schedule of 
Activities, Table 1, 
Table 2, Table 3
Fecal biomarkers and microbiome moved from 
Efficacy Assessments to Pharmacodynamics and 
Biomarkers in Table 1 and Table 2. Microbiome 
moved from Efficacy Assessments to 
Pharmacodynamics and Biomarkers in Table 3.
Fecal biomarkers and microbiome 
analyses are considered part of the 
pharmacodynamics and biomarkers 
analyses.
Section 1.3, 
Schedule of 
Activities, Table 1, 
Table 2, Table 3, 
Table 4b; Section 
4.2.2, Biomarker 
and DNA 
Collection; Section 
8.8, Biomarkers; 
Section 8.8.1, 
Serum-based 
Biomarkers; Section 
8.8.2, Whole Blood-
based Biomarkers; 
Section 8.8.3, 
Biopsy-based 
Biomarkers; Section 
8.8.4, Fecal 
Biomarkers; Section 
9.4.5, Other 
Analyses, 
Biomarker Analyses
The following content was added:
Where local regulations permit.
Clarification that whole blood 
samples for RNA analysis, serum 
biomarkers, and fecal biomarkers 
and microbiome will only be 
collected in applicable countries 
where local regulations permit, 
since not all countries permit the 
collection and/or testing of these 
samples.
Section 1.3, 
Schedule of 
Activities, Table 2 
Optional Week 4: Only those participants who 
consent to participate in the optional substudy will 
undergo Week 4 video ileocolonoscopy and biopsy 
collection. Participation in the optional Week 4 
substudy will target approximately 200 study 
participants.
Clarification on the number of 
study participants for the Week 4 
substudy. The enrollment target is 
approximately 200 participants. 
Additional study participants will 
be accepted into the substudy if 
they consent.
NCT03466411

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
217
Status: Approved, Date: 12 July 2022
Section number
and Name
Description of Change
Brief Rationale
Section 4.2.2, 
Biomarker and 
DNA Collection
Section 8.8.3.1 
Optional Week 4 
Biopsy Substudy
This substudy will target approximately 200 study 
participants. 
Approximately 200 study participants are defined 
for the Week 4 ileocolonoscopy substudy to provide 
sufficient power to support exploratory analyses.
Section 1.3, 
Schedule of 
Activities, Table 3 
Section 8.2.4, Vital 
Signs
Includes temperature, pulse/heart rate, respiratory 
rate, and blood pressure. Must be obtained prior to 
and approximately 30 minutes after the final 
 
injection. For study participants receiving study 
intervention administration at the study site, vital 
signs will be assessed during the visit. For study 
participants who are trained to self-inject or have a 
caregiver who is trained to administer the study 
intervention at home, vital signs will only be 
assessed at the study site when these participants 
receive study intervention at the study site.
Through Week 48, vital signs (including 
temperature, pulse/heart rate, respiratory rate, and 
blood pressure) will be obtained before and 
approximately every 30 minutes during every 
 
infusion, and for 1 hour at approximately 30-
minute intervals after completion of the final 
 
infusion. Vital signs should be obtained before and 
approximately 30 minutes after the final 
 
injection. 
After Week 48, study participants receiving study 
intervention administration at the study site will 
have vital signs assessed at these visits as 
described above.
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 injection-site reactions and 
reporting of adverse events 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.
No change to the originally planned 
assessments. Clarifications 
provided to indicate how study 
participants who will receive at-
home study intervention 
administration will have their vital 
signs assessed at the study site vs at 
home.
Section 1.3, 
Schedule of 
Activities, Table 3
The following was added as a note to the injection-
site evaluation line item:
An injection-site reaction is any adverse reaction at 
any 
 study intervention injection site. Injection 
sites will be evaluated for reactions and any 
injection-site reaction will be recorded as an AE.
This content is included in Table 2 
and was inadvertently omitted from 
Table 3 in the original protocol.
Section 1.3, 
Schedule of 
Activities, Table 3
The following was added as a note to the stool 
sample (fecal calprotectin) line item:
Stool samples required for the Week 96 visit must be 
obtained before the start of the bowel preparation for 
This content is included in Table 2 
and was inadvertently omitted from 
Table 3 in the original protocol.
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NCT03466411

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
218
Status: Approved, Date: 12 July 2022
Section number
and Name
Description of Change
Brief Rationale
the video ileocolonoscopy that is scheduled for the 
visit.
Section 1.3, 
Schedule of 
Activities, Table 3
Section 4.1.3.1, 
Treatment 
Adjustment for 
Inadequate 
Response
Footnote i added:
CDAI assessments may be conducted at 
 visits 
between Weeks 52 and 80 (inclusive) to support 
the evaluation of CDAI response status. 
Participants who meet inadequate response criteria, 
and who are not already receiving the highest 
guselkumab 
 maintenance dose regimen, are 
eligible to receive treatment adjustment per
protocol Section 4.1.3.1.
The following paragraph was added:
CDAI assessments may be conducted at 
 visits 
between Weeks 52 and 80 (inclusive) to support 
the evaluation of CDAI response status. 
Participants who meet inadequate response criteria, 
and who are not already receiving the highest 
guselkumab 
 maintenance dose regimen, are 
eligible to receive treatment adjustment as 
described below.
Clarification on the assessment of 
CDAI response status between 
Weeks 52 and 80 (inclusive). No 
change to the originally planned
assessments. Clarifications are 
provided to indicate that study sites 
can perform CDAI response status 
evaluation at 
 visits to 
determine if participants meet 
inadequate response criteria to 
pursue the protocol-specified 
treatment adjustment.
Section 1.3, 
Schedule of 
Activities, Table 4a
Participant discontinues study intervention at or
prior to the Week 12 visit
The following notes were added:
Discontinuation prior to Week 12: A video 
ileocolonoscopy at Week 12 is not required if 
already completed at the SID visit prior to 
Week 12.
Discontinuation at Week 12: A video 
ileocolonoscopy is required at Week 12 (or can be 
performed as part of SID visit after Week 12).
No change to the originally planned 
assessments. Clarifications are 
provided to indicate the timing of 
discontinuation and the 
corresponding requirement to 
perform the video ileocolonoscopy.
Section 1.3, 
Schedule of 
Activities, Table 4a, 
Table 4b
The following note was added:
The video ileocolonoscopy at the SID visit is 
optional for participants who discontinue after 
Week 48, since these participants would have 
completed the procedure as part of the Week 48 
visit.
The requirement of the video 
ileocolonoscopy for participants 
who discontinue study intervention 
after Week 48 is modified from 
“required” to “optional”. Study 
participants will have completed 
the procedure already at Week 48, 
and the endoscopy endpoints 
planned at Week 96 are considered 
exploratory. Therefore, to limit the 
number of unnecessary procedures 
in study participants who will be 
discontinuing study intervention 
after Week 48, the sponsor 
considers it important for study 
participants to be given the option 
to have this procedure, or not, as 
part of the discontinuation visit 
after Week 48.
Section 2.2.1, 
Guselkumab 
Clinical Experience; 
Section 2.2.2, 
The following sentence was added:
Since the initiation of the GALAXI protocol, 
higher doses of guselkumab (up to 
 
The description of available clinical 
experience with guselkumab in 
other study populations, at the dose 
range under study in the GALAXI 
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NCT03466411

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
219
Status: Approved, Date: 12 July 2022
Section number
and Name
Description of Change
Brief Rationale
Guselkumab 
Nonclinical Studies; 
Section 2.3.1, 
Guselkumab; 
Section 4.3.1.1.1, 
Induction Dose 
Regimens
have been administered in two clinical studies (a 
Phase 1 PK study in healthy Japanese participants 
and a Phase 2 study in participants with 
hidradenitis suppurativa). 
protocol, is included to provide 
additional background information 
to investigators. 
Section 2.3.1, 
Guselkumab
Since there is limited clinical information available 
for the higher dose regimens of guselkumab (as 
proposed in this protocol), safety will be evaluated 
in an initial cohort of 25 patients by an independent 
Data Monitoring Committee (DMC).
The description of available clinical 
experience with guselkumab in 
other study populations, at the dose 
range under study in the GALAXI 
protocol, is included to provide 
additional background information 
to investigators. 
Section 4.1, Overall 
Design; Section 5.1, 
Inclusion Criteria
Endoscopic evidence of ileocolonic Crohn’s 
disease
A SES-CD score ≥3, as assessed by central 
endoscopy reading at the screening endoscopy, 
based on the presence of any ulceration in any 1 of 
the 5 ileocolonic segments, resulting in the 
following specified ulceration component scores:
a. a minimum score of 1 for the component of 
“size of ulcers”
AND
b. a minimum score of 1 for the component of 
“ulcerated surface”.
Within each of the studies, a maximum of 10% of 
the total enrolled population will be participants 
who have baseline scores for SES-CD <4 (ie, for 
participants with isolated ileal disease), or SES-CD 
<7 (ie, for participants with colonic or ileocolonic 
disease).
Based on the scoring mechanism of 
the SES-CD, there are various 
endoscopic presentations of 
moderately to severely active 
Crohn’s disease that would meet 
the originally specified protocol 
criteria (ie, achieving a minimum 
SES-CD score ≥3), and would also 
maintain consistency with the 
originally specified protocol criteria 
that were established after scientific 
consultation with several major 
health authorities. 
Therefore, the endoscopic inclusion 
criterion has been revised to enroll 
study participants with any 
evidence of ulceration in any 1 of 
the 5 ileocolonic segments. The 
revised criterion is intended to more 
accurately define the 
contemporaneous Crohn’s disease 
patient population with moderately 
to severely active disease based on 
the observed patient characteristics 
from this ongoing protocol and 
other protocols conducted by the 
sponsor.
Section 4.1.1.2, 
Treatment Groups, 
Phase 2 Dose-
Ranging Study 
(GALAXI 1), 
Figure 2
The following note was added to Figure 2, design 
schematic of the Phase 2 (GALAXI 1) study:
Note: This schematic only illustrates the dosing for 
the treatment groups. It does not provide a 
complete illustration of all blinding (placebo) 
administrations.
Clarification is provided to indicate 
that the specified dosing only 
accounts for the planned treatment 
groups. The schematic is not 
intended to provide a complete 
account of both the assigned 
treatment administrations as well as 
the blinding (placebo) 
administrations. 
NCT03466411

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
220
Status: Approved, Date: 12 July 2022
Section number
and Name
Description of Change
Brief Rationale
Section 4.2.3, 
Patient-Reported 
Outcomes on 
Health-Related 
Quality of Life
Patient-reported outcome (PRO) evaluations (ie, 
IBDQ, PROMIS-29, PROMIS Fatigue 7-item 
Short Form, 5-level EuroQol 5 dimensions [EQ-
5D-5L] instrument) will be used to assess the 
benefits of guselkumab treatment on disease-
specific and general HRQOL. Patient-reported 
outcome evaluations are only being collected in 
countries where translations of the evaluations are 
available. See Section 8.1 for more details.
Clarification is provided to indicate 
that PROs will be only be done in 
those countries where the PRO is 
available in the local language.
Section 5.1, 
Inclusion Criteria
Criterion #13: 
Be willing and able to adhere to all specified 
requirements, including but not limited to 
completion of required assessments, adherence to 
visit schedule, compliance with lifestyle 
restrictions (Section 5.3), etc as specified in this 
protocol.
Added specific examples of what 
may be considered critical barriers 
for a potential study participant to 
be eligible for enrollment into the 
protocol.
Section 5.2, 
Exclusion Criteria
Criterion #16: 
Participants who are seropositive for antibodies to 
hepatitis C virus (HCV), unless they satisfy one of 
the following conditions:
have a history of successful treatment (defined 
as being negative for HCV RNA at least 6 
months after completing antiviral treatment) and 
have a negative HCV RNA test result at 
screening, OR 
while seropositive have a negative HCV RNA 
test result at least 6 months prior to screening
and a negative HCV RNA test result at 
screening.
The objective of the HCV exclusion 
criteria is to identify participants 
with HCV infections who should 
not be enrolled into the protocol.
The original specified criterion is 
not consistent with current practice 
and has been updated based on 
current HCV screening and 
treatment guidelines.
Section 5.2, 
Exclusion Criteria
Criterion #33 was added:
7.
Has 
previously 
undergone 
allergy 
immunotherapy for prevention of anaphylactic 
reactions (eg, venom immunotherapy).
This exclusion criterion was 
inadvertently omitted from the 
original protocol.
Section 5.4, Screen 
Failures
Rescreening
Participants who do not meet the criteria for 
participation in this study (screen failure) may be 
rescreened 1 time. Participants who are rescreened 
will be assigned a new participant number, 
undergo the informed consent process, and then 
start a new screening phase, including the 
collection and testing of new laboratory specimens. 
Previous TB evaluation results (including the 
QuantiFERON-TB test and chest radiograph) and 
stool study results, and ileocolonoscopy results 
from the first screening event may be used if they 
meet the specified protocol criteria as described in 
Section 5.1.  Medical Monitor approval is required 
prior to the study site obtaining a new informed 
consent for rescreening.
Clarifications are provided 
regarding rescreening requirements, 
including specifications of which 
screening tests need to be 
performed again during rescreening 
and which screening test results 
from the previous screening event 
may be considered acceptable, 
provided that these previous tests 
were conducted in accordance with 
the protocol and meet the specified 
criteria.
NCT03466411

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
221
Status: Approved, Date: 12 July 2022
Section number
and Name
Description of Change
Brief Rationale
Section 6.1, Study 
Interventions 
Administered
In both the Phase 2 and Phase 3 portions of the 
protocol:

All participants will receive 2 
 infusions at 
Week 0 (either active or placebo) and 1 
 
infusion at Weeks 4, 8, and 12 (either active or 
placebo). 

All participants will receive 1 
 injection 
(either active or placebo) at Week 8 and up to 
3 
 injections (either active or placebo) at 
each visit from Week 12 to Week 140.
 study intervention (including the flush)
should be administered over a period of not less 
than 1 hour, and not more than 2 hours. The 
infusion (including the flush) should be completed 
within 6 hours of preparation. 
At Week 0, the guselkumab/placebo in dextrose 
 
infusion (including the flush with dextrose) should 
be administered first. The 
 infusion 
administration line set will be changed (ie, use a 
new line set) prior to the administration of the 
ustekinumab/placebo in saline 
 infusion, 
followed by the flush with saline.
At Week 4, only guselkumab/placebo in dextrose 
 infusion is administered.
At Weeks 8 and 12, the guselkumab/placebo in 
dextrose 
 infusion (including the flush with 
dextrose) should be administered first, followed by 
the 
 injection(s) with active 
(guselkumab/placebo or ustekinumab/placebo) or 
placebo investigational product (IP).
At Week 12 and beyond, multiple 
 injections 
may be administered within the administration 
visit. Each injection of study intervention should 
be given at a different location of the body.
Detailed instructions on the preparation and 
administration of study intervention will be 
provided in the site Investigational Product 
Procedures Manual (IPPM). Of note, instructions 
on the preparation and administration of study 
intervention in the Phase 3 portion of the protocol 
will be finalized and provided to investigative sites 
when the Phase 3 dose decision is made and 
implemented.
Clarifications are provided 
regarding 
 study 
intervention administration 
procedures for specific study visits. 
These clarifications are intended to 
provide a high-level summary only, 
and investigators and site staff are 
to refer to the IPPM for further 
details.
Section 6.2.2, 
Ustekinumab
The following sentence was added:
The needle cover on the 
 contains dry natural 
rubber (a derivative of latex), which may cause 
allergic reactions in individuals sensitive to latex.
This statement was inadvertently 
omitted from the original protocol. 
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NCT03466411

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
222
Status: Approved, Date: 12 July 2022
Section number
and Name
Description of Change
Brief Rationale
Section 6.2.3,
Accountability
The following sentence was removed:
Study site personnel must not combine contents of 
the study intervention containers. 
Clarification is provided regarding 
IP preparation. The protocol-
specified IP preparation method 
requires the pooling of multiple 
vials and syringes.
Section 6.3, 
Measures to 
Minimize Bias: 
Randomization and 
Blinding
The following paragraph was deleted and replaced 
with the paragraph below:
[Deleted] Treatment assignment blinding will be 
maintained for investigative sites, site monitors, 
and participants until the Week 48 DBL and 
analyses are completed for both Phase 3 studies.
[Replacement] All participants will continue to 
receive active or placebo study intervention 
administration in the LTE in a blinded fashion until 
study unblinding, which will occur after the Week 
48 DBL and the Week 48 analyses have been 
completed for the Phase 2 study (for participants 
entering the LTE from GALAXI 1) or for the 
Phase 3 studies (for participants entering the LTE 
from GALAXI 2 or GALAXI 3). 
The original text was incorrect in 
stating that all 3 studies under the 
protocol will be fully blinded until 
the Phase 3 study Week 48 DBL.
Section 7.1, 
Discontinuation of 
Study Intervention, 
The following sentences were removed or 
relocated from Criterion #7 under the section 
entitled " A participant's study treatment must be 
discontinued under the following conditions:”
The participant has a serious adverse reaction that 
is related to an injection or an infusion, including 
an injection-site or infusion reaction, resulting in 
bronchospasm with wheezing and/or dyspnea that 
requires ventilatory support OR that results in 
symptomatic hypotension with a decrease in 
systolic blood pressure >40 mm Hg or blood 
pressure <90/60 mm Hg. This may include events 
of National Cancer Institute Common Terminology 
Criteria for Adverse Events (NCI CTCAE) toxicity 
grade ≥3. In general, discontinuation of study 
intervention administration must be considered for 
participants who develop a severe injection site or 
infusion reaction.
Removal of the CTCAE statement 
was necessary because grading of 
adverse events is not being 
performed in this study.
Relocation of the specified 
statement is necessary because 
injection-site or infusion reactions 
are not mandatory discontinuation 
requirements.
Section 7.1, 
Discontinuation of 
Study Intervention
The following criterion was relocated from 
Criterion #1 in the section entitled 
“Discontinuation of a participant’s study 
intervention must be strongly considered under the 
following conditions” to become Criterion #11 in 
the section entitled "A participant's study treatment 
must be discontinued under the following 
conditions".
The investigator believes that for safety or 
tolerability reasons, it is in the best interest of the 
participant to discontinue study intervention.
Relocation of the specified 
statement is necessary because the 
criterion is clearly indicative of the 
need to mandate discontinuation.
NCT03466411

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
223
Status: Approved, Date: 12 July 2022
Section number
and Name
Description of Change
Brief Rationale
Section 7.1, 
Discontinuation of 
Study Intervention
Criterion #1:
Discontinuation of a participant’s study 
intervention must be strongly considered under 
the following conditions: 
8.
Persistent inadequate response or worsening of 
Crohn’s disease:
f.
The participant has a change from 
baseline in the CDAI score <70 
points and has a CDAI score >220 at 
both Week 20 and Week 24.
OR
g.
The participant experiences AEs 
consistent with clinically significant 
worsening of Crohn’s disease at any 
time during the study.
These events must be evaluated by the 
investigator. A consultation with the study 
medical monitor may also be considered, at the 
investigator's discretion. Discontinuation of 
study intervention must be considered in 
participants 
with 
clinically 
significant 
worsening 
of 
Crohn’s 
disease 
where 
continuation of the study intervention is not in 
the best interest of the participant.
Clarifications were provided to 
ensure that discontinuation of study 
intervention is strongly considered 
by the investigator and that the 
investigator may also consult with 
the study medical monitor if 
necessary.
Section 7.1, 
Discontinuation of 
Study Intervention, 
The following criterion was relocated from #7 in 
the section entitled "A participant's study treatment 
must be discontinued under the following 
conditions" to become #4 in the section entitled 
“Discontinuation of a participant’s study 
intervention must be strongly considered under the 
following conditions”:
The participant develops a severe injection-site or 
infusion reaction.
Relocation of the specified criterion 
was necessary since injection-site 
or infusion reactions are not 
mandatory discontinuation 
requirements.
Section 8.1, 
Efficacy 
Assessments
Histologic assessments will be performed using 
biopsy samples collected during ileocolonoscopy. 
Biopsy samples will be collected at screening, 
Week 12, Week 48, and Week 96 from each of 3 
predefined anatomic locations: the terminal ileum, 
splenic flexure, and rectum, as clinically feasible. 
An optional substudy involving a Week 4 
evaluation will be performed in consenting 
participants in addition to the above-specified 
evaluations. The biopsy samples collected post-
baseline will be obtained near where the screening 
biopsy samples were collected from each of the 3 
predefined locations, as clinically feasible. 
Histologic assessments will be conducted by a 
central reader who is blinded to treatment groups 
and visit. The Global Histology Activity Score 
(GHAS) will be used to evaluate histologic 
Text clarified to acknowledge the 
collection of the specified 
ileocolonic biopsy samples may not 
be always clinically feasible.
NCT03466411

CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959CRD3001 Amendment 5
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
224
Status: Approved, Date: 12 July 2022
Section number
and Name
Description of Change
Brief Rationale
improvements and healing.5 Analyses will be 
specified in the SAP.
Section 8.3.5, 
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 10.11 for 
serious adverse events. 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.
Clarification to specify the time 
period in which investigators or site 
staff personnel must report an event 
of special interest and special 
reporting situations.
Section 10.11, 
Appendix 11 
Adverse Events: 
Definitions and 
Procedures for 
Recording, 
Evaluating, Follow-
up, and Reporting
The following was added as the first sentence 
under Special Reporting Situation:
Special reporting situations must be reported by the 
investigator or site staff personnel to the sponsor or 
designee within 24 hours after being made aware 
of the event.
Clarification to specify the time 
period in which investigators or site 
staff personnel must report an event 
of special interest and special 
reporting situations.
Section 1.1, 
Synopsis, Primary 
Efficacy Analysis 
Section 9.4.2.2, 
Primary Endpoint 
Analysis
Section 9.4.2.3, 
Major Secondary 
Endpoint Analysis 
The primary efficacy analysis is based on the Full 
Analysis Set, defined as all participants who are 
randomized and who have received at least 1 dose 
of study intervention in GALAXI 1. The primary 
endpoint of the change from baseline in the CDAI 
score at Week 12 will be analyzed using a Mixed 
Effect Repeated Measures Model (MMRM) 
approach.
The CDAI score will be calculated for a visit if at 
least 4 of the 8 components are available at 
Week 12. When at least 4 of the 8 components are 
available, any missing components will be imputed 
by carrying forward the last available components. 
If the CDAI score cannot be calculated (ie, <4 
components available) at a visit, the CDAI score 
will be considered missing for that visit. The 
missing data handling rules for the CDAI score 
will be described in the Phase 2 SAP.
The change from baseline in CDAI will be 
analyzed using a Mixed Effect Repeated Measures 
Model (MMRM) approach. Further details will be 
described in the Phase 2 SAP. A multiple testing 
procedure will be used to control the Type 1 error 
at α=0.05 (2-sided) over the comparisons of 
guselkumab with placebo (to be defined in the 
Phase 2 SAP).
The CDAI score will be calculated for a visit if at 
least 4 of the 8 components are available at that 
visit. When at least 4 of the 8 components are 
Text was updated to reflect planned 
alternate approaches to handling
missing data to align with 
regulatory guidelines on missing
data handling, and to indicate that 
additional details will be provided 
in the SAP.
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Section number
and Name
Description of Change
Brief Rationale
Section 9.4.3.2, 
Primary Endpoint 
Analysis 
Section 9.4.3.3, 
Major Secondary 
Endpoint Analysis
available, any missing components will be imputed 
by carrying forward the last available components. 
The clinical response or remission endpoints will 
be determined based on these imputed CDAI 
scores. If the CDAI score cannot be calculated (ie, 
<4 components available) at a visit, the CDAI 
score will be considered missing for that visit. 
Participants who do not return for evaluation or 
have a missing CDAI score at Week 12 will be 
considered not to be in clinical remission or 
clinical response as measured by the CDAI score. 
Participants who do not return for evaluation or 
have missing AP or SF scores at Week 12 will not 
be considered to have achieved clinical remission, 
as measured by PRO-2. Participants with a 
nonevaluable or missing endoscopy will be 
considered not in endoscopic response. The details 
for handling missing segments in the SES-CD 
score will be described in the Phase 2 SAP.
The CDAI score will be calculated for a visit if at 
least 4 of the 8 components are available at that 
visit. When at least 4 of the 8 components are 
available, any missing components will be imputed 
by carrying forward the last available components. 
If the CDAI score cannot be calculated (ie, <4 
components available) at a visit, the CDAI score 
will be considered missing for that visit. 
Participants who do not return for evaluation or 
have a missing CDAI score at Week 12 will not be 
considered to have achieved clinical remission at 
Week 12. Treatment failure rules will overrule the 
missing data rules.
The CDAI score will be calculated for a visit if at 
least 4 of the 8 components are available at that 
visit. When at least 4 of the 8 components are 
available, any missing components will be imputed 
by carrying forward the last available components. 
The clinical remission endpoints will be 
determined based on these imputed CDAI scores. 
If the CDAI score cannot be calculated (ie, <4 
components available) at a visit, the CDAI score 
will be considered missing for that visit. 
Participants who do not return for evaluation or 
have a missing CDAI score at any visit will be 
considered not to be in clinical remission based on 
CDAI for that visit. Participants who do not return 
for evaluation or have missing AP or SF scores at 
the analysis time point will not be considered to 
have achieved clinical remission, as measured by 
PRO-2 for that analysis time point. Participants 
with a nonevaluable or missing endoscopy will be 
considered to be not in endoscopic response. The 
details for handling missing segments in the SES-
CD score will be described in the SAP. In addition, 
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Section number
and Name
Description of Change
Brief Rationale
Section 10.3, 
Appendix 3: 
Definition of 
Inadequate Initial 
Response, Loss of 
Response, or 
Intolerance to TNF 
Antagonist 
Therapies 
(Infliximab, 
Adalimumab, or 
Certolizumab Pegol) 
or Vedolizumab
The following content was added to Appendix 3:
It is also acknowledged that previous treatment 
decisions could have been made based on 
evaluation of other measures that may be indicative 
of worsening disease (eg, elevations of 
inflammatory markers including but not limited to 
CRP or fecal calprotectin, etc, and/or evidence of 
disease flare based on clinical imaging modalities 
including but not limited to ileocolonoscopy, CT, 
MRI).  Under these circumstances, documentations 
of these specified measures of worsening disease 
activity can be accepted as evidence of inadequate 
response to prior biologic treatment. However, 
investigators should note that participants must 
meet protocol-specified criteria for active disease 
(ie, clinical and endoscopic) during the current 
screening period as described in Section 5.1 to be 
eligible for enrollment.
Based on current clinical practice, 
clarifications are provided to 
acknowledge that additional 
measures of worsening disease 
activity indicative of inadequate 
response to previous biologic 
treatments may be acceptable.
Section 10.5, 
Appendix 5: 
QuantiFERON®-
TB Gold Testing
Appendix 5 was removed and Appendices 6 
through 13 were renumbered accordingly.
Appendix 5 QuantiFERON®-TB 
Gold Testing was removed since 
most of this information is already 
included in the Site Laboratory 
Manual and is not necessary to be 
included in the protocol.
Section 10.8, 
Appendix 8: 
Regulatory, Ethical, 
and Study Oversight 
Considerations
Investigator Responsibilities subsection was 
revised as follows:
The investigator is responsible for ensuring that the 
study is performed in accordance with the protocol, 
current ICH guidelines on Good Clinical Practice 
(GCP), the latest version of the Declaration of 
Helsinki, and applicable regulatory and country-
specific requirements.
Clarification to specify that 
investigators are required to comply 
with the principles of Declaration 
of Helsinki as requested by a health 
authority. 
Throughout the 
protocol
Minor grammatical, formatting, or spelling 
changes were made.
Minor errors were noted.
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11.
REFERENCES
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Feagan BG, Sandborn WJ, D’Haens G, et al. Induction therapy with the selective interleukin-23 inhibitor 
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Feagan BG, Sandborn WJ, Gasink C, et al. Ustekinumab as induction and maintenance therapy for Crohn’s 
disease. N Engl J Med. 2016; 375(20):1946-1960.
9.
Feagan BG, Sandborn WJ, Panés J, et al. Efficacy and safety of re-induction treatment with the selective 
IL-23 inhibitor risankizumab in patients with moderate-to-severe Crohn’s disease. United European 
Gastroenterol J. 2016; 4(6):806.
10. Hochberg Y. A sharper Bonferroni procedure for multiple tests of significance. Biometrika. 1988; 
75(4):800-802.
11. Hue S, Ahern P, Buonocore S, et al. Interleukin-23 drives innate and T cell-mediated intestinal 
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12. Irvine EJ, Feagan B, Rochon J, et al. Quality of life:  a valid and reliable measure of therapeutic efficacy in 
the treatment of inflammatory bowel disease. Canadian Crohn’s Relapse Prevention Trial Study Group.  
Gastroenterology. 1994; 106(2):287-296.
13. Kamm MA, Ng SC, De Cruz P, Allen P, Hanauer SB. Practical application of anti-TNF therapy for luminal 
Crohn’s disease. Inflamm Bowel Dis. 2011; 17:2366–2391.
14. Krueger JG, Ferris LK, Menter A, et al. Anti-IL-23A mAb BI 655066 for treatment of moderate-to-severe 
psoriasis: Safety, efficacy, pharmacokinetics, and biomarker results of a single-rising-dose, randomized, 
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20. Sands BE, Chen J, Feagan BG, et al. Efficacy and safety of MEDI2070, an antibody against Interleukin 23, 
in patients with moderate to severe Crohn’s disease: a Phase 2a study. Gastroenterology (2017); 153(1):77-
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24. Turner D, Ricciuto A, Lewis A, et al. STRIDE-II: An update on the selecting therapeutic targets in 
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25. Zhuang Y, Calderon C, Marciniak SJ, et al. First-in-human study to assess guselkumab (anti-IL-23 mAb) 
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Status: Approved,  Date: 27 April 2020
Janssen Research & Development *
Clinical Protocol
COVID-19 Appendix
Protocol Title
A Phase 2/3, Randomized, Double-blind, Placebo- and Active-controlled, Parallel-group, 
Multicenter Protocol to Evaluate the Efficacy and Safety of Guselkumab 
in Participants with Moderately to Severely Active Crohn's Disease
GALAXI
[A Study of the Efficacy and Safety of Guselkumab in Participants
with Moderately to Severely Active Crohn's Disease]
Protocol CNTO1959CRD3001; Phase 2/3
CNTO 1959 (guselkumab)
*Janssen Research & Development is a global organization that operates through different legal entities in 
various countries. Therefore, the legal entity acting as the sponsor for Janssen Research & Development 
studies may vary, such as, but not limited to Janssen Biotech, Inc.; Janssen Products, LP; Janssen Biologics, 
BV; Janssen-Cilag International NV; Janssen, Inc; Janssen Pharmaceutica NV; Janssen Sciences Ireland
UC; Janssen Biopharma Inc.; or Janssen Research & Development, LLC. The term “sponsor” is used 
throughout the protocol to represent these various legal entities; the sponsor is identified on the Contact 
Information page that accompanies the protocol.
United States (US) sites of this study will be conducted under US Food & Drug Administration
Investigational New Drug (IND) regulations (21 CFR Part 312).]
Status:
Approved  
Date:
27 April 2020
Prepared by:
Janssen Research & Development, LLC
EDMS number:
EDMS-RIM-38072
THIS APPENDIX APPLIES TO ALL CURRENT APPROVED VERSIONS OF 
PROTOCOL CNTO1959CRD3001
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.
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Status: Approved,  Date: 27 April 2020
COVID-19 APPENDIX
GUIDANCE ON STUDY CONDUCT DURING THE COVID-19 PANDEMIC
It is recognized that the Coronavirus Disease 2019 (COVID-19) pandemic may have an impact on 
the conduct of this clinical study due to, for example, self-isolation/quarantine by participants and 
study-site personnel; travel restrictions/limited access to public places, including hospitals; study 
site personnel being reassigned to critical tasks.
In alignment with recent health authority guidance, the sponsor is providing options for 
study-related participant management in the event of disruption to the conduct of the study. This 
guidance does not supersede any local or government guidelines or requirements or the clinical 
judgement of the investigator to protect the health and well-being of participants and site staff. If,
at any time, a participant’s safety is considered to be at unacceptable risk, study intervention will 
be discontinued, and study follow-up will be conducted.
Scheduled visits that cannot be conducted in person at the study site will be performed to the extent 
possible remotely/virtually or delayed until such time that on-site visits can be resumed. At each 
contact, participants will be interviewed to collect safety data. Key efficacy endpoint assessments 
should be performed if required and as feasible. Participants will also be questioned regarding 
general health status to fulfill any physical examination requirement. 
Every effort should be made to adhere to protocol-specified assessments for participants on study 
intervention, including follow-up. Modifications to protocol-required assessments may be 
permitted via COVID-19 Appendix after consultation between the participant and investigator, 
and with the agreement of the sponsor (see below). 
The sponsor will continue to monitor the conduct and progress of the clinical study, and any 
changes will be communicated to the sites and to the health authorities according to local guidance.
If a participant has tested positive for COVID-19, the investigator should contact the sponsor’s 
responsible medical officer to discuss plans for study intervention and follow-up. Modifications 
made to the study conduct as a result of the COVID-19 pandemic should be summarized in the 
clinical study report.
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Status: Approved,  Date: 27 April 2020
ADDITIONAL ELEMENTS, WHERE APPLICABLE:

Certain protocol-mandated visits to the study site may not be possible during the COVID-19 
outbreak. Therefore, temporary measures may be implemented if considered appropriate by 
the sponsor and investigator to maintain continuity of participant 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:
o
remote (eg, by phone / telemedicine) or in-person, off-site (eg, in-home) interactions 
between site staff (or designees) and participants for study procedures, eg, those related 
to safety monitoring / efficacy evaluation / study intervention storage and 
administration (including training where pertinent)
o
procurement of study intervention by participants (or designee) or shipment of study 
intervention from the study site directly to participants for at home administration 
(including the potential for self-administration of study intervention)
o
laboratory assessments using a suitably accredited local laboratory; for selected 
measures (eg, urine pregnancy), home testing may be employed
o
other procedures, eg, imaging, may be conducted at an appropriate facility

Missed assessments/visits will be captured in the clinical trial management system for protocol 
deviations. Discontinuations of study interventions and withdrawal from the study should be 
documented with the prefix “COVID-19-related” in the case report form (CRF). 
o
other relevant study data elements impacted by the pandemic should also be 
documented / labeled as “COVID-19-related” in CRFs and / or other study systems, as 
directed by detailed sponsor guidance. These may include missed / delayed / modified 
study visits / assessments / dosing, and instances where temporary measures such as 
those above are implemented.  

The sponsor will evaluate the totality of impact of COVID-19 on collection of key study data 
and additional data analyses will be outlined in study SAP(s). 

Exclusion: a potential participant with the following features will be excluded from 
participating in the study protocol:
o
During the 6 weeks prior to baseline, have had ANY of (a) confirmed SARS-CoV-2 
(COVID-19) infection (test positive), OR (b) suspected SARS-CoV-2 infection 
(clinical features without documented test results), OR (c) close contact with a person 
with known or suspected SARS-CoV-2 infection 

Exception: may be included with a documented negative result for a validated 
SARS-CoV-2 test
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(i) 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
(ii) with absence of ALL conditions (a), (b), (c) above during the period 
between the negative test result and the baseline study visit 

NOTES on COVID-related exclusion:
1. If a participant is excluded due to recent COVID-19-related features, the reason for 
screen failure should be documented in the CRF under the exclusion criterion of having 
a condition for which participation would not be in the participant’s interest or could 
confound study assessments. 
2. The field of COVID-related testing (for presence of, and immunity to, the SARS-
CoV-2 virus) is rapidly evolving. Additional testing may be performed as part of 
screening and/or during the study if deemed necessary by the investigator and in 
accordance with current regulations / guidance from authorities / standards of care. 

Precaution: for those who may carry a higher risk for severe COVID-19 illness (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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