A Phase 3, Open-label, Multicenter Study to Evaluate the Safety and Efficacy of Guselkumab in Participants With Moderately to Severely Active Crohn's Disease
Phase: PHASE3
Conditions: Crohns Disease
Sponsor: Janssen Pharmaceutical K.K.

CONFIDENTIAL – FOI A Exemption s Appl y i n U.S. 
1
Status: Approved,  Date:  11 December 2020
Janssen Pharmaceutical K.K.*
Clinical Protocol
Protocol Title
A Phase 3, Open-label, Multicenter Study to Evaluate the Safety and Efficacy of
Guselkumab in Participants With Moderately to Severely Active Crohn’s Disease
Protocol CNTO1959CRD3003; Phase 3
AMENDMENT 1
CNTO1959 (guselkumab)
*This study is being conducted by Janssen Pharmaceutical K.K. in Japan. The term “sponsor” is used
throughout the protocol to represent Janssen Pharmaceutical K.K.
Status: 
Approved
Date: 
11 December 2020
Prepared by: Janssen Pharmaceutical K.K.
EDMS number: 
EDMS-ERI-203665726, 2.0
GCP Compliance:  This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory
requirements. 
Confidentiality Statement
The information provided herein contains Company trade secrets, commercial or financial information that the Company
customarily holds close and treats as confidential.  The information is being provided under the assurance that the recipient
will maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or
otherwise.
NCT04397263

 
CNTO1959 (guselkumab)  
Clinical Protocol CNTO1959CRD3003 Amendment 1 
CONFIDENTIA L – FOI A Exemption s Appl y i n U.S. 
 
 
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Status: Approved,  Date:  11 December 2020
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document 
Date
Amendment 1 
11 December 2020
Original Protocol 
6 March 2020
Amendment 1 (11 December 2020)
Overall Rationale for the Amendment:  To revise the inclusion criteria around SES-CD scores in align
with the amendment of GALAXI program.
Section Number, 
Name
Description of Change 
Brief Rationale
1.1, Synopsis 
4.1, overall design 
Participants who have a concurrent or history of 
SB disease activity confirmed by radiography, 
imaging and/or endoscopy may be eligible to 
participate in the substudy for additional SB
assessment by device-assisted enteroscopy.
To clarify the imaging data are
acceptable to confirm a concurrent
or history of SB disease.
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, and 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. 
1.3, Table 2, 3 
8.2.6, Tuberculosis 
Evaluation(s) 
If TB is suspected at any time during the study, a 
chest radiograph or chest CT, and QuantiFERON- 
TB or T-SPOT test should be performed.  
To clarify that chest CT is also
acceptable for the test method to
assess TB during the study 
1.3, Table 2, 4 
The required timing of the endoscopy was 
clarified, and it should be scheduled as close as
possible to the designated visit 
Clarification
1.3, Table 2 
Delete the following footnote. 
 
a. If a participant discontinues study intervention 
prior to the Week 12 visit, the participant should 
complete the evaluations as detailed under the 
Study Intervention Discontinuation (SID) visit at 
the time of SID. In addition, the participant should
All tests specified at Week 12 is no
longer necessary for a participant
who discontinues study
intervention prior to the Week 12
visit if SID and FES are performed
as per protocol. 

 
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Status: Approved,  Date:  11 December 2020
Section Number, 
Name
Description of Change 
Brief Rationale
return for the Week 12 visit and complete all
evaluations specified at Week 12 (except the
endoscopy if already completed at the SID visit)
and have a final efficacy and safety (FES) visit
approximately 12 weeks after their last study
intervention administration. See Table 4 for
additional details .
1.3, Table 3  
Weight measurement was added at q4w visit 
timing in the LTE. 
To have sufficient data to precisely
calculate CDAI in the LTE
Stool samples required for last efficacy visit q48w 
visit must be obtained before the start of the bowel 
preparation
To clarify the timing of stool
sample collection
5.1, Inclusion 
Criteria 
Have endoscopic evidence of active ileocolonic 
CD as assessed by central endoscopy reading at the 
screening endoscopy (Schedule of ActivitiesSoA, 
Table 14), defined as a screening SES-CD score 
≥36 (or ≥4 for participants with isolated ileal 
disease), based on the presence of ulceration in 
anyat 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”.
OR
Have endoscopic evidence of active SB CD as
assessed by central endoscopy reading at the
screening device assisted enteroscopy (Schedule of
ActivitiesSoA, Table 14), defined as a screening
modified SES-CD score ≥5, based on the presence
of ulceration in any 1 of the 3 segments including
terminal ileum, proximal ileum and jejunum.
Inclusion criteria for endoscopic
evidence in Guselkumab Crohn’s
disease phase 3 study (GALAXI
2/3) have been revised based on
foreign Health Authority feedback
and Phase 2 (GALAXI 1) results. 
The inclusion criteria for this study
should be aligned accordingly in
order to make the study population
of this study consistent with
GALAXI program.
 
Typos for table reference is also
corrected.
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 85-week screening period
To align with designated screening
period allowance
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: 
Clarification

 
CNTO1959 (guselkumab)  
Clinical Protocol CNTO1959CRD3003 Amendment 1 
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Status: Approved,  Date:  11 December 2020
Section Number, 
Name
Description of Change 
Brief Rationale
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.
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
6.5.1, Concomitant 
Medications 
A phrase was deleted from the following 
subsection:
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 loss of response to treatment for Crohn’s
disease (eg, stress doses of corticosteroids for
surgery, asthma, adrenocortical insufficiency).
Clarification
8, Study assessments 
and procedures 
electrocardiogram (ECG) and vital signs (blood 
pressure, pulse rate, respiratory rate, and axillary 
body temperature) should be performed first 
Amended to allow other models of
body temperature measurements in
addition to axillary
8.2.11, Columbia-
Suicide Severity
Rating Scale (C-
SSRS)
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
To clarify the C-SSRS should be
performed before any other study
procedure
10.2, Appendix 2:
Clinical Laboratory
Tests
FSH was added 
Omitted from the previous version
10.3, Appendix 3:
Regulatory, Ethical,
and Study Oversight
Considerations
Following section was deleted:
LONG TERM RETENTION OF SAMPLES FOR
ADDITIONAL FUTURE RESEARCH 
Samples collected in this study may be stored for
up to 15 years (or according to local regulations)
for additional research. Samples will only be used
to understand guselkumab, to understand Crohn’s
No additional sample retention is
currently planned for future
research

 
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Status: Approved,  Date:  11 December 2020
Section Number, 
Name
Description of Change 
Brief Rationale
disease, to understand differential intervention
responders, and to develop tests/assays related to
guselkumab and Crohn’s disease. The research
may begin at any time during the study or the
poststudy 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,
Withdrawal From the Study).
10.4, Appendix 4: 
Adverse Events: 
Definitions and
Procedures for 
Recording, 
Evaluating, Follow-
up, and Reporting 
Following sentence was deleted: 
 
• Unexpected therapeutic or clinical benefit from
use of a sponsor study intervention
This is not intended to be reported
in a clinical study
10.6, Appendix 6: 
Liver Safety: 
Suggested Actions 
and Follow-up 
Assessments 
Added a sentence to the first paragraph of text in 
the Appendix (below the algorithm): 
A hepatologist consultation should be considered if
clinically indicated for the diagnosis and
management of potential DILI.
Added at the request of a Health
Authority, to ensure that
investigators will perform
appropriate follow-up in the
evaluation and management of
cases of potential drug-induced
liver injury.
Throughout the 
protocol 
Minor grammatical, formatting, and/or spelling 
changes were made.
Minor errors were noted. 

 
CNTO1959 (guselkumab)  
Clinical Protocol CNTO1959CRD3003 Amendment 1 
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Status: Approved,  Date:  11 December 2020
TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................................. 2 
TABLE OF CONTENTS .......................................................................................................................... 6 
LIST OF IN-TEXT TABLES AND FIGURES ............................................................................................ 8 
1. 
PROTOCOL SUMMARY ................................................................................................................ 9 
1.1. 
Synopsis ..................................................................................................................................... 9 
1.2. 
Schema .................................................................................................................................... 13
1.3. 
Schedule of Activities (SoA) ...................................................................................................... 14
2. 
INTRODUCTION .......................................................................................................................... 23
2.1. 
Study Rationale......................................................................................................................... 23
2.2. 
Background............................................................................................................................... 25
2.3. 
Benefit-Risk Assessment .......................................................................................................... 26
2.3.1. 
Risks of Study Participation.................................................................................................... 26
2.3.2. 
Benefits of Study Participation ............................................................................................... 30
2.3.3. 
Benefit-Risk Assessment for Study Participation .................................................................... 30
3. 
OBJECTIVES AND HYPOTHESIS ............................................................................................... 30
4. 
STUDY DESIGN ........................................................................................................................... 30
4.1. 
Overall Design .......................................................................................................................... 30
4.2. 
Scientific Rationale for Study Design ......................................................................................... 32
4.2.1. 
Study-Specific Ethical Design Considerations ........................................................................ 32
4.3. 
Justification for Dose ................................................................................................................. 32
4.4. 
End of Study Definition .............................................................................................................. 32
5. 
STUDY POPULATION ................................................................................................................. 33
5.1. 
Inclusion Criteria ....................................................................................................................... 33
5.2. 
Exclusion Criteria ...................................................................................................................... 38
5.3. 
Lifestyle Considerations ............................................................................................................ 42
5.4. 
Screen Failures ......................................................................................................................... 43
6. 
STUDY INTERVENTION .............................................................................................................. 44
6.1. 
Study Intervention(s) Administered ............................................................................................ 44
6.2. 
Preparation/Handling/Storage/Accountability ............................................................................. 44
6.3. 
Measures to Minimize Bias: Randomization and Blinding .......................................................... 46
6.4. 
Study Intervention Compliance .................................................................................................. 46
6.5. 
Concomitant Therapy ................................................................................................................ 46
6.5.1. 
Concomitant Medications ....................................................................................................... 46
6.5.1.1. 
Oral Corticosteroids Tapering ............................................................................................. 47
6.5.2. 
Prohibited Concomitant Medications ...................................................................................... 48
6.6. 
Dose Modification ..................................................................................................................... 48
6.7. 
Intervention After the End of the Study ...................................................................................... 48
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL ........................................................................................... 49
7.1. 
Discontinuation of Study Intervention ........................................................................................ 49
7.2. 
Participant Discontinuation/Withdrawal From the Study ............................................................. 51
7.3. 
Lost to Follow-up ....................................................................................................................... 51
8. 
STUDY ASSESSMENTS AND PROCEDURES ............................................................................ 52
8.1. 
Efficacy Assessments ............................................................................................................... 54
8.2. 
Safety Assessments .................................................................................................................. 55
8.2.1. 
Physical Examinations ........................................................................................................... 55
8.2.2. 
Vital Signs ............................................................................................................................. 55

 
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Status: Approved,  Date:  11 December 2020
8.2.3. 
Electrocardiograms ................................................................................................................ 56
8.2.4. 
Height and Weight ................................................................................................................. 56
8.2.5. 
Infections ............................................................................................................................... 56
8.2.6. 
Tuberculosis Evaluation(s) ..................................................................................................... 56
8.2.6.1. 
Initial Tuberculosis Evaluation ............................................................................................. 56
8.2.6.2. 
Ongoing Tuberculosis Evaluation ........................................................................................ 57
8.2.7. 
Hepatitis B monitoring ............................................................................................................ 58
8.2.8. 
Allergic Reaction .................................................................................................................... 58
8.2.9. 
Adverse Events Temporally Related to Infusion ..................................................................... 58
8.2.10. 
Injection-Site Reaction ........................................................................................................... 58
8.2.11. 
Columbia-Suicide Severity Rating Scale (C-SSRS) ................................................................ 59
8.2.12. 
Clinical Safety Laboratory Assessments ................................................................................. 60
8.2.13. 
Concomitant Medication Review ............................................................................................ 61
8.3. 
Adverse Events and Serious Adverse Events ............................................................................ 61
8.3.1. 
Time Period and Frequency for Collecting Adverse Event and Serious Adverse Event
Information ............................................................................................................................ 61
8.3.2. 
Follow-up of Adverse Events and Serious Adverse Events ..................................................... 62
8.3.3. 
Regulatory Reporting Requirements for Serious Adverse Events ........................................... 62
8.3.4. 
Pregnancy ............................................................................................................................. 62
8.3.5. 
Adverse Events of Special Interest ......................................................................................... 62
8.4. 
Treatment of Overdose ............................................................................................................. 63
8.5. 
Pharmacokinetics ...................................................................................................................... 63
8.5.1. 
Evaluations ............................................................................................................................ 63
8.5.2. 
Analytical Procedures ............................................................................................................ 63
8.6. 
Pharmacodynamics................................................................................................................... 63
8.7. 
Genetics ................................................................................................................................... 64
8.8. 
Biomarkers ............................................................................................................................... 64
8.9. 
Immunogenicity Assessments ................................................................................................... 64
9. 
STATISTICAL CONSIDERATIONS .............................................................................................. 64
9.1. 
Statistical Hypotheses ............................................................................................................... 64
9.2. 
Sample Size Determination ....................................................................................................... 65
9.3. 
Populations for Analyses ........................................................................................................... 65
9.4. 
Statistical Analyses ................................................................................................................... 65
9.4.1. 
General Considerations ......................................................................................................... 65
9.4.2. 
Safety Analyses ..................................................................................................................... 65
9.4.3. 
Other Analyses ...................................................................................................................... 66
9.5. 
Interim Analysis......................................................................................................................... 67
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ........................... 68
10.1. 
Appendix 1: Abbreviations ......................................................................................................... 68
10.2. 
Appendix 2: Clinical Laboratory Tests........................................................................................ 70
10.3. 
Appendix 3: Regulatory, Ethical, and Study Oversight Considerations ....................................... 71
REGULATORY AND ETHICAL CONSIDERATIONS ....................................................................... 71
FINANCIAL DISCLOSURE .............................................................................................................. 74
INFORMED CONSENT PROCESS ................................................................................................. 74
DATA PROTECTION ...................................................................................................................... 75
COMMITTEES STRUCTURE .......................................................................................................... 75
PUBLICATION POLICY/DISSEMINATION OF CLINICAL STUDY DATA ......................................... 75
DATA QUALITY ASSURANCE ........................................................................................................ 77
CASE REPORT FORM COMPLETION ........................................................................................... 77
SOURCE DOCUMENTS ................................................................................................................. 78
MONITORING ................................................................................................................................. 78
ON-SITE AUDITS............................................................................................................................ 79
RECORD RETENTION ................................................................................................................... 79
STUDY AND SITE START AND CLOSURE .................................................................................... 80
10.4. 
Appendix 4: Adverse Events: Definitions and Procedures for Recording, Evaluating,
Follow-up, and Reporting .......................................................................................................... 81

 
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Status: Approved,  Date:  11 December 2020
ADVERSE EVENT DEFINITIONS AND CLASSIFICATIONS ........................................................... 81
ATTRIBUTION DEFINITIONS ......................................................................................................... 82
SEVERITY CRITERIA ..................................................................................................................... 82
SPECIAL REPORTING SITUATIONS ............................................................................................. 82
PROCEDURES ............................................................................................................................... 83
CONTACTING SPONSOR REGARDING SAFETY.......................................................................... 84
PRODUCT QUALITY COMPLAINT HANDLING .............................................................................. 84
10.5. 
Appendix 5: Contraceptive and Barrier Guidance and Collection of Pregnancy Information ........ 86
10.6. 
Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments ................................ 88
10.7. 
Appendix 7: Definitions of Inadequate Response to or Intolerance of Corticosteroids or 6-
MP/AZA and Corticosteroid Dependence .................................................................................. 92
10.8. 
Appendix 8: Definition of Inadequate Initial Response, Loss of Response, or Intolerance
to TNF Antagonist Therapies (Infliximab or Adalimumab) Vedolizumab ..................................... 93
10.9. 
Appendix 9: Definition of Minimal Exposure to Ustekinumab ...................................................... 97
10.10. Appendix 10: Crohn’s Disease Activity Index ........................................................................... 100
10.11. Appendix 11: Hepatitis B Virus (HBV) Screening with HBV DNA Testing ................................. 101
10.12. Appendix 12: Protocol Amendment History .............................................................................. 102
11. REFERENCES ........................................................................................................................... 103
INVESTIGATOR AGREEMENT .......................................................................................................... 104
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1: 
SoA – Screening Activities ................................................................................................... 14
Table 2: 
SoA – Week 0 to Week 48 ................................................................................................... 16
Table 3: 
SoA – Week 48 until the end of study of Long-Term Extension for eligible participants
who have completed Week 48.............................................................................................. 19
Table 4: 
SoA – Study Intervention Discontinuation (SID) Visit and the Final Efficacy and Safety
(FES) Follow-Up Visit ........................................................................................................... 21
Table 5: 
Recommended Tapering Schedule for Oral Corticosteroids .................................................. 48
Table 6: 
Eligibility based on hepatitis B virus test results .................................................................. 101
FIGURES
Figure 1: Schematic Overview of the Study ......................................................................................... 13

 
CNTO1959 (guselkumab)  
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Status: Approved,  Date:  11 December 2020
1. 
PROTOCOL SUMMARY
1.1. 
Synopsis
A Phase 3, Open-label, Multicenter Study to Evaluate the Safety and Efficacy of Guselkumab in
Participants With Moderately to Severely Active Crohn’s Disease
Guselkumab (CNTO 1959) is a fully human immunoglobulin G (IgG)1 lambda monoclonal antibody (mAb)
that binds to human interleukin (IL)-23 with high 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
biological activity of IL-23 in all in vitro assays examined.
OBJECTIVES AND HYPOTHESIS
Primary Objective
 
To evaluate the safety of guselkumab in participants with Crohn’s disease (CD)
Secondary Objectives
 
To evaluate the efficacy of guselkumab in participants with CD
 
To evaluate the pharmacokinetics (PK), immunogenicity, and pharmacodynamics (PD) of guselkumab,
including changes in C-reactive protein (CRP) and fecal calprotectin
Exploratory Objective
 
To assess the efficacy of guselkumab on small bowel (SB) lesions
Hypothesis
The primary objective is to evaluate the safety of guselkumab in participants with CD. No hypothesis testing
will be performed in this study.
OVERALL DESIGN
This is a Phase 3, open-label, multicenter study to evaluate the safety and efficacy of guselkumab in
participants with moderately to severely active CD who have demonstrated an inadequate response or failed
to tolerate the previous conventional therapy (ie, 6-mercaptopurine [6-MP], azathioprine [AZA], or
corticosteroids [CON-failure. Refer to Section 10.7 Appendix 7]) or biologic therapy (ie, TNFα antagonists
or vedolizumab [BIO-failure. Refer to Section 10.8 Appendix 8]). 
Participants will receive following guselkumab treatment in an open-label fashion;
 
Weeks 0, 4, and 8: Guselkumab 200 mg intravenous (IV) administration (induction)
 
Every 4 weeks (q4w) after Week 8 until the end of the study: Guselkumab 200 mg subcutaneous (SC)
administration (maintenance)
The study will be conducted in 3 phases: a maximum 8-week screening phase, a 48-week treatment phase
followed by long-term extension (LTE) phase, and a posttreatment follow up visit (12 weeks after the
participant's last dose of study intervention to collect any adverse events since the last study visit). The
duration of individual participation will be approximately 68 weeks if a participant ends the study
participation at the end of treatment phase and does not enter the LTE.
At-home self-administration can begin after the Week 48 visit at the discretion of the investigator and
participant, and upon completion of at least 3 training sessions starting from Week 48. All participants who

 
CNTO1959 (guselkumab)  
Clinical Protocol CNTO1959CRD3003 Amendment 1 
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Status: Approved,  Date:  11 December 2020
are willing to perform at-home self-administration will be requested to record at-home administration
medication diary.
Long-term extension will be continued until the time when guselkumab is approved for CD indication in
Japan and marketed guselkumab becomes available at the study site (up to around 3 years at maximum in
addition to a 48-week treatment phase depending on the timing of approval of guselkumab for CD in Japan)
or discontinuation of the clinical development of guselkumab for CD, and all participants who will be
continuing the treatment at the time of marketing approval of guselkumab for CD or discontinuation of the
clinical development of guselkumab for CD will be asked to come to the study site, and complete their
safety and efficacy assessments.
Participants who have a concurrent or history of SB disease activity confirmed by radiography, imaging
and/or endoscopy may be eligible to participate in the substudy for additional SB assessment by device-
assisted enteroscopy.
Key safety assessments will include the monitoring of adverse events (AEs), vital sign measurements, and
clinical laboratory tests including inflammatory biomarkers. Key efficacy assessments include Crohn’s
Disease Activity Index (CDAI) and its components, endoscopic assessments by either ileocolonoscopy or
device-assisted enteroscopy (if a participant agrees to perform additional SB assessment).
NUMBER OF PARTICIPANTS
The study will target to enroll a total of approximately 25 participants.
INTERVENTION GROUPS AND DURATION
Participants will receive guselkumab 200 mg IV induction doses at Weeks 0, 4, and 8 (total of 3 IV doses),
followed by guselkumab 200 mg SC maintenance doses as q4w starting at Week 12 through Week 44.
During LTE, participants will continue to receive the same study intervention regimen that they were
receiving at the end of maintenance, with the first dose in the LTE being administered at Week 48.
EFFICACY EVALUATIONS
Efficacy evaluations will include the following:
 
CDAI including patient-reported outcome (PRO)-2 score (the unweighted CDAI components of the
total number of liquid or very soft stools and the abdominal pain [AP] score)
 
Endoscopic assessments of the intestinal mucosa based on the presence and absence of mucosal
ulcerations and the simple endoscopic score for Crohn’s Disease (SES-CD) and/or modified SES-CD
PHARMACOKINETIC EVALUATIONS
Serum samples will be analysed to determine concentrations of guselkumab using validated, specific, and
sensitive method by or under the supervision of the sponsor.
PHARMACODYNAMIC AND BIOMARKER EVALUATIONS
Inflammatory PD markers (CRP and fecal calprotectin) will be evaluated to assess the disease activities of
CD for the participants throughout the study. Biomarker data may be used to examine the biologic response
to treatment and to identify biomarkers that are relevant to guselkumab treatment.
IMMUNOGENICITY EVALUATIONS
Serum samples will be screened for antibodies binding to guselkumab and the titer of confirmed positive
samples will be reported. Neutralizing antibodies will be assessed for positive samples. Other analyses may
be performed to further characterize the immunogenicity of guselkumab.

 
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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
assessments, clinical laboratory blood tests (complete blood count and serum chemistries), vital signs (as
defined in the Schedule of Activities [SoA]), suicidality assessment, concomitant medication review, and
observations for injection-site reactions, reactions temporally associated with an infusion, and/or allergic
reactions.
STATISTICAL METHODS
There will be 3 analysis plans supporting this protocol: one for the analysis based on Week 24 database
lock (including efficacy and safety analysis through Week 24), second one for the analysis based on
Week 48 database lock (including full data through Week 48 except LTE), and last one for the analysis
based on the entire study result including LTE.
No statistical hypothesis testing based on any endpoint is planned in this study, thus the sample size was
not calculated based on statistical considerations. The objective of the study is to assess the safety of
guselkumab in the Japanese patients with moderately to severely active CD together with
CNTO1959CRD3001 study, and the sample size was chosen to achieve this objective and provide
additional safety information as much as possible.
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.
Safety Analysis
Safety analyses will include summaries of AEs, vital signs, and laboratory parameters. These analyses will
be based on participants who received at least 1 dose of guselkumab.
Efficacy analysis
Efficacy analyses will be based on the Full Analysis Set, which is defined as all enrolled participants who
had at least 1 dose of guselkumab in the study.
Efficacy analysis for SB assessment will only be performed among the participants who have assessment
data at both baseline and Week 48 (or at the end of LTE period).
Pharmacokinetic Analysis
Pharmacokinetic analysis will be performed based on the population which includes all participants who
received at least 1 dose of guselkumab and have at least 1 observed postdose PK data. Descriptive statistics
of the serum guselkumab concentrations will be calculated at each sampling time point. These
concentrations will be summarized over time.
Immunogenicity analysis
The incidence and titers of antibodies to guselkumab will be summarized for all participants who received
at least 1 dose of guselkumab and have at least 1 observed postdose immunogenicity data. The incidence
of neutralizing antibodies to guselkumab will be summarized for participants who are positive for
antibodies to guselkumab and have samples evaluable for neutralizing antibodies to guselkumab.

 
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Pharmacokinetic/Pharmacodynamic Analyses
The relationship between serum guselkumab concentrations and biomarker and/or efficacy measures may
be analysed graphically.

 
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1.2. 
Schema
Figure 1: 
Schematic Overview of the Study

 
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Status: Approved,  Date:  11 December 2020
Table 4: 
SoA – Study Intervention Discontinuation (SID) Visit and the Final Efficacy and Safety (FES) Follow-Up Visit
(a) Participants should complete the SID and/or the FES visits, and additional study visits, as outlined below
 
SIDa 
FESb 
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 after Week 0 and up to the Week 48 visit 
X 
X 
 
Participant completes the 48-week study but does not enter the LTE at Week 48 
 
X
Week 48
(see Table 2)
 
Participant discontinues study intervention after Week 48 until the end of study 
X 
X 
Video endoscopy should be performed at SID visit
at the end of the study. If video endoscopy were
performed within 48 weeks before the SID visit,
the test is not necessary to be repeated.
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 12 weeks after the last study intervention administration.

 
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2. 
INTRODUCTION
Guselkumab (CNTO 1959) is a fully human immunoglobulin G (IgG)1 lambda monoclonal
antibody (mAb) that binds to human interleukin (IL)-23 with high 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.
Guselkumab has been approved for the treatment of adults with moderate to severe plaque
psoriasis (PsO) in the United States, European Union (EU), Canada, Japan, and a number of other
countries worldwide. In addition, guselkumab has been approved for the treatment of psoriatic
arthritis (PsA), generalized pustular psoriasis, erythrodermic psoriasis, and palmoplantar
pustulosis (PPP) in Japan.
Guselkumab is currently being developed for other diseases including treatment of patients with
PsA (globally), hidradenitis suppurativa (HS), familial adenomatous polyposis (FAP), Crohn’s
disease (CD), and ulcerative colitis (UC). Phase 3 studies in PsA, a Phase 2/3 program in CD, and
a Phase 2b/3 program in UC are ongoing globally.
For the most comprehensive nonclinical and clinical information regarding guselkumab, refer to
the latest version of the Investigator's Brochure (IB)5 for guselkumab.
The term “study intervention” throughout the protocol, refers to guselkumab.
The term "sponsor" used throughout this document refers to the entities listed in the ‘Protocol
Supplementary Information’, which will be provided as a separate document.
2.1. 
Study Rationale
There is a high unmet need for new treatment options in CD that are safe and effective, especially
new therapies that can provide improved long-term efficacy (ie, sustained remission) over
currently available therapies.
Sponsor is currently conducting the clinical development program to evaluate the safety and
efficacy of guselkumab compared with placebo and an active control (ustekinumab): a Phase 2/3,
randomized, double-blind, placebo- and active-controlled (ustekinumab), parallel-group,
multicenter protocol to evaluate the safety and efficacy of guselkumab in participants with
moderately to severely active CD who have demonstrated an inadequate response or failure to
tolerate previous conventional therapy or biologic therapy (Program name: GALAXI, Study
number: CNTO1959CRD3001).
Under the 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 156]) and receive approximately 2 years of
additional treatment. The overall Phase 2/3 development program will enroll approximately 2,000

 
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participants with a total duration for each participant of up to approximately 3 years. For Phase 2
study, interim analysis has been completed and the study is still ongoing as per protocol. The Phase
3 studies have been initiated using the following dose regimens that were selected based on the
interim analysis of Phase 2 study:
 
Guselkumab Regimen 1 – Induction: 200 mg IV at Weeks 0, 4, and 8; followed by
Maintenance: 200 mg SC every 4 weeks (q4w; ie, at Weeks 12, 16, 20, 24, 28, 32, 36, 40, and
44)
 
Guselkumab Regimen 2 – Induction: 200 mg IV at Weeks 0, 4, and 8; followed by
Maintenance: 100 mg SC every 8 weeks (q8w; ie, at Weeks 16, 24, 32, and 40)
Based on the preclinical evidence and clinical experience targeting IL-23 in CD, guselkumab could
be a potential therapeutic option for patients with CD who have demonstrated an inadequate
response or failure to tolerate previous conventional therapy or biologic therapy.
Since CD is a chronic inflammatory disease requiring long-term therapy, the safety, especially
under long-term treatments, in addition to the efficacy would be the critical factor. The primary
objective of the study is to assess the safety of guselkumab in patients with CD in Japan. Although
the safety of guselkumab in patients with CD will also be assessed in GALAXI program comparing
to the entire study results and available data of guselkumab for other diseases, this study is planned
to complement the existing safety database by enrolling additional participants exposed to
guselkumab in Japan.
In addition to the secondary objectives to assess the efficacy, PK, and immunogenicity of
guselkumab in participants with CD, an exploratory objective of this study is to assess the efficacy
of guselkumab on small bowel (SB) disease. Crohn’s disease is categorized with the part of
intestinal lesion into 3 types: the ileal-type, colonic-type, and ileocolonic-type6,16 and it is known
that more ileal-type of CD were identified in Asian countries compared to Western countries.17
Recent research revealed that patients who achieved the SB improvement had lower rate of relapse,
hospitalization, and Crohn’s related surgery compared with those who had not.13 The research also
found that antitumor necrosis factor (TNF) therapy might not be as effective in SB lesions as in
colonic lesions, therefore there would be a high unmet need for effective treatment for SB lesions
in patients with CD.13 While no clinical efficacy data of either guselkumab or other anti-IL-23
antibodies on the SB lesions are available to date, there are some case reports to support the
potential clinical efficacy of ustekinumab, an anti-IL-12/23 antibody on SB lesions as well as
stenosis.9,18 Of note, it is reported that the several major leukocytes inducing the tissue
inflammation related to the IL-17/23 pathway such as cluster of differentiation (CD)103+CD11b+
dendritic cells (DCs) and T helper 17 (Th17) cells are specially localized in the small intestine
rather than in colon in the mouse intestine.7 These scientific backgrounds and evidences are
considered to provide a rationale to investigate the effect of guselkumab on SB lesions.

 
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2.2. 
Background
Nonclinical Studies
A comprehensive overview of the nonclinical development program for guselkumab to support
the initiation of the study has been completed and the information is available in Section 3 of the
latest version of the guselkumab IB.5
Details regarding the proposed dose regimen and dose rationale are described in Section 6.1 and
Section 4.3. Guselkumab dosing regimens of induction and maintenance to be tested in this study
are within the range of dosing regimens investigated in the GALAXI program.
Clinical Studies
Guselkumab has been approved for the treatment of adults with moderate to severe plaque
psoriasis (PsO) in the United States, EU, Canada, Japan and a number of other countries worldwide.
In addition, guselkumab has been approved for the treatment of psoriatic arthritis (PsA),
generalized pustular psoriasis, erythrodermic psoriasis, and PPP in Japan. 
Guselkumab is currently being developed in other diseases including for the treatment of patients
with PsA (globally), HS, FAP, CD and UC. Global phase 3 development programs are ongoing as
Phase 3 studies in PsA, a Phase 2/3 program in CD and a Phase 2b/3 program in UC.
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 CD. Details about these guselkumab clinical development programs across various indications
are provided in Section 4 of the latest version of the guselkumab IB.5 
Through the cutoff date of 12 July 2019, an estimated 203 healthy subjects, 3,454 subjects with
PsO, 109 subjects with RA, 1,136 subjects with PsA, 182 subjects with PPP, 151 subjects with
CD, 149 subjects with HS, 29 subjects with UC, and 3 subjects with FAP have been exposed to
guselkumab. Overall, an estimated 5,416 subjects have been exposed to guselkumab in the clinical
development program.
The largest clinical experience to date with guselkumab has been in plaque psoriasis. The safety
profile of guselkumab in subjects with moderate to severe plaque psoriasis is based on data from
the Phase 2 study CNTO1959PSO2001 and Phase 3 studies CNTO1959PSO3001,
CNTO1959PSO3002, CNTO1959PSO3003, CNTO1959PSO3006, and CNTO1959PSO3009. Of
the 2,711 guselkumab-treated subjects, 2,255 subjects were exposed for at least 1 year,
1,516 subjects were exposed for at least 2 years, and 692 subjects and were exposed for 3 years.
Long-term extensions of 2 of the studies (CNTO1959PSO3001 and CNTO1959PSO3002) are
ongoing and will continue through up to 5 years of follow-up.
For CD program, interim analysis of phase 2 of CNTO1959CRD3001 study has been completed
and the study is still ongoing as per protocol. The phase 3 of CNTO1959CRD3001 studies have
been initiated after interim analysis of phase 2 part of the study.

 
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CNTO1959CRD1002 was conducted as a Phase 1, randomized, double-blind, placebo-controlled
study to assess safety, tolerability, and PK of guselkumab after single IV administrations up to
1,200 mg of guselkumab in Japanese healthy male subjects. No new safety concerns were observed
in this study. When the PK of guselkumab following a single IV dose was compared between
non-Japanese healthy subjects (CNTO1959PSO1001 Study, Part1) and Japanese healthy subjects
(CNTO1959CRD1002 Study), the distribution range of weight-corrected clearance (CL) and
volume of distribution at the terminal phase (Vz) mostly overlapped between Japanese and
non-Japanese, while uncorrected CL and Vz were slightly lower in Japanese subjects. There was
no substantial difference in PK characteristics in terms of elimination/distribution between races
(Japanese and non-Japanese) when guselkumab is given in IV formulation. Furthermore, when
guselkumab is given in SC formulation as a single dose or multiple dose (SD:10-300 mg, MD:
100 mg at Weeks 0, 4, and q8w thereafter) in Japanese and non-Japanese patients with psoriasis,
there was no substantial difference between Japanese and non-Japanese in terms of serum
guselkumab concentration or PK parameters (CNTO1959PSO1001 part2, CNTO1959PSO1002,
CNTO1959PSO3001, CNTO1959PSO3002, CNTO1959PSO3004 and CNTO1959PSO3005
study).
2.3. 
Benefit-Risk Assessment
More detailed information about the known and expected benefits and risks of guselkumab may
be found in the IB.
2.3.1. 
Risks of Study Participation
Potential Risks of Clinical 
Significance 
Summary of Data/
Rationale for Risk 
Mitigation Strategy
Clinical worsening of CD  
The benefit-risk of guselkumab in
the treatment of moderately to
severely active CD has not been
established.
 
During the study, participants
will be permitted to continue
treatment of CD with certain
concomitant medications
(Section 6.5).
 
Participants will discontinue
study intervention if it is not in
their best interest or if they
need to initiate protocol-
prohibited medications
including certain biologics
(Section 6.5.2 and Section 7.1).
 
Disease activities will
continuously be evaluated
throughout the study with
Crohn’s Disease Activity Index
(CDAI) diary as well as
inflammatory biomarkers such
as CRP and fecal calprotectin. 
Potential Risks Due to Study Intervention Guselkumab
Serious infections and reactivation 
of latent infections 
Available animal and human data 
suggest that blockade of IL-23 may 
be associated with an increased 
infection risk.  
 
Participants with a history of,
or ongoing, chronic or
recurrent infectious disease,
includin  g HIV, Hepatitis B or

 
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C, will be excluded from the
study. Similarly, participants
with evidence of active or
untreated latent TB will be
excluded from the study
(Section 5.2).
 
Participants who have received
a live viral or bacterial
vaccination within 12 weeks of
baseline will be excluded from
the study. In addition,
participants must agree not to
receive a live viral or live
bacterial vaccination during the
study and for 12 weeks after
receiving the last dose of study
intervention (Section 5.2).
 
Participants will be instructed
to seek medical attention if
they develop signs or
symptoms suggestive of an
infection, and investigators are
instructed in the protocol to
monitor for signs or symptoms
of infections, including
tuberculosis (Section 8.2.5 and
Section 8.2.6). 
 
Discontinuation of a
participant’s study intervention
must be strongly considered if
the participant develops a
serious infection, including but
not limited to sepsis or
pneumonia. In addition, any
serious infection should be
discussed with the medical
monitor or designee, and study
intervention should be withheld
until the clinical assessment is
complete (Section 7.1). 
Hypersensitivity reactions, 
including serious hypersensitivity 
reactions. 
Serious hypersensitivity reactions 
including anaphylaxis have been 
reported in postmarketing 
experience with guselkumab in 
psoriasis patients. 
 
Participants with known
allergy, hypersensitivity, or
intolerance to guselkumab or its
excipients will be excluded
from the study.
 
Sites are instructed that before
any administration of study
intervention, appropriately
trained personnel and
medications (eg, injectable
epinephrine) must be available
to treat hypersensitivity
reactions, including
anaphylaxis. In addition, all
participants must be observed
carefully for signs and
symptoms of a hypersensitivity 

 
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reaction (eg, urticaria, pruritis,
angioedema, wheezing,
dyspnea, or hypotension)
(Section 8.2.8).
 
Any participant who develops a
serious hypersensitivity
reaction such as anaphylaxis
must discontinue study
intervention (Section 7.1).
Malignancy 
The preponderance of preclinical 
data suggests that blockade of 
endogenous IL-23 would not be 
detrimental and may in fact be 
beneficial in tumor 
immunosurveillance and host 
protection; however, a risk of 
malignancy cannot be excluded. 
 
Those participants who
currently have a malignancy or
have a history of malignancy
within 5 years prior to
screening (with exceptions
noted in Section 5.2) will be
excluded from the study.
Additionally, participants who
have a history of
lymphoproliferative disease,
including lymphoma; a history
of monoclonal gammopathy of
undetermined significance or
signs and symptoms suggestive
of possible lymphoproliferative
disease, such as
lymphadenopathy or
splenomegaly will be excluded
from the study (Section 5.2). 
 
During the conduct of the
study, participants will undergo
regular clinical monitoring
including routine safety labs to
assess for any changes in health
status that may indicate a
possible malignancy.
 
Participants who develop a
malignancy during the study
(with the exception of no more
than 2 localized basal cell skin
cancers that are treated with no
evidence of recurrence or
residual disease) will be
discontinued from study
intervention (Section 7.1).
Liver injury 
A serious adverse event (SAE) of 
‘toxic hepatitis’ was reported in the 
ongoing Phase 2/3 guselkumab CD 
program in a participant who 
received guselkumab 1200 mg IV 
at Weeks 0, 4, and 8, and 200 mg 
SC at Week 12. Based on the 
hepatocellular pattern of injury, 
temporal relationship of the event 
to guselkumab exposure, and the 
exclusion of alternative etiologies, 
this event may represent drug- 
 
During the conduct of the
study, liver function tests will
be monitored at regular
intervals in accordance with
regulatory guidance.4 In
addition, the induction doses
evaluated in this clinical
program will be lower and will
not exceed 200 mg IV. 
 
Participants with marked liver
enzyme elevations or
symptoms or signs of liver
dysfunction (eg, jaundice),

 
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induced liver injury possibly related 
to guselkumab. 
should undergo a thorough
investigation for possible
causes of liver injury. A
participant must have their
study intervention discontinued
if the participant has severe
liver test abnormalities that are
not transient and are not
explained by other etiologies
(Section 7.1). 
Immunosuppression 
It is unknown if guselkumab in 
combination with other 
immunosuppressives increases the 
risk of diseases associated with 
immunosuppression, such as 
infections or malignancy. 
 
In order to minimize the
theoretical increased risk of
infection or malignancy with
the combination of guselkumab
with immunosuppressive
therapy, the baseline dose of
oral corticosteroids on study
entry is limited to ≤40 mg
prednisone or its equivalent per
day which must be tapered
from Week 12. Furthermore,
participants receiving
azathioprine (AZA) or
6-mercaptopurine (6-MP) must
have been taking them for
≥12 weeks and been on a stable
dose for at least 4 weeks before
baseline. Additionally,
participants are also excluded
from the study if they have
received cyclosporine,
mycophenolate mofetil,
tacrolimus, or sirolimus within
8 weeks, anti-TNF therapy
within 8 weeks, vedolizumab
within 16 weeks, or
ustekinumab within 16 weeks
prior to the first dose of study
intervention. Further detail
regarding concomitant
medications is provided in
Section 5.1 and Section 5.2.
 
During study participation, the
use of immunomodulators
other than AZA or 6-MP (eg,
cyclosporine) as well as
biologic immunomodulators
(eg, anti-TNFs, vedolizumab)
is prohibited. Participants
initiating these treatments will
be discontinued from further
study intervention
administration.
Risks Due to Study Procedures
Risks associated with the
endoscopy procedure including
These risks are well recognized, but
are rare.1,11 Risk of increase in
 
Trained and experienced
endoscopists will be

 
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bleeding, colonic perforation, 
serum amylase elevation and 
pancreatitis 
serum amylase elevation or 
pancreatitis are reported for device 
assisted enteroscopy.12 
performing the procedure
during this study.
 
Risk of increase in serum
amylase elevation or
pancreatitis may not be
relevant to this study because
the scope is not planned to be
inserted through the mouth.
2.3.2. 
Benefits of Study Participation 
The efficacy and safety of guselkumab in the treatment of CD has not been established. The
well-established scientific and clinical rationale for IL-23 blockade in the treatment of CD supports
the clinical evaluation of guselkumab in this disease population. 
2.3.3. 
Benefit-Risk Assessment for Study Participation
Based on the available data and the proposed safety measures described in Section 2.3.1, the
sponsor contends that the benefit-risk of the selected dose regimens of guselkumab to be
investigated in this protocol is acceptable.
3. 
OBJECTIVES AND HYPOTHESIS
Primary Objective
 
To evaluate the safety of guselkumab in participants with CD
Secondary Objectives
 
To evaluate the efficacy of guselkumab in participants with CD
 
To evaluate the PK, immunogenicity, and pharmacodynamics (PD) of guselkumab, including
changes in C-reactive protein (CRP) and fecal calprotectin
Exploratory Objective
 
To assess the efficacy of guselkumab on SB lesions
Refer to Section 8, Study Assessments and Procedures for evaluations related to endpoints.
HYPOTHESIS
The primary objective is to evaluate the safety of guselkumab in participants with CD. No
hypothesis testing will be performed in this study.
4. 
STUDY DESIGN 
4.1. 
Overall Design
This is a Phase 3, open-label, multicenter study to evaluate the safety and efficacy of guselkumab
in participants with moderately to severely active CD who have demonstrated an inadequate
response or failed to tolerate the previous conventional therapy (ie, 6-mercaptopurine [6-MP],
azathioprine [AZA], or corticosteroids [CON-failure. Refer to Section 10.7 Appendix 7]) or

 
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biologic therapy (ie, TNFα antagonists, vedolizumab) [BIO-failure. Refer to Section 10.8
Appendix 8].
Participants will receive following guselkumab treatment in an open-label fashion;
 
Weeks 0, 4, and 8: Guselkumab 200 mg IV administration (induction)
 
Every 4 weeks after Week 8 until the end of the study: Guselkumab 200 mg SC administration
(maintenance)
The study will be conducted in 3 phases: a maximum 8-week screening phase, a 48-week treatment
phase followed by LTE phase, and a posttreatment follow up visit (12 weeks after the participant's
last dose of study intervention to collect any adverse events since the last study visit). The duration
of individual participation will be approximately 68 weeks if a participant ends the study
participation at the end of treatment phase and does not enter the LTE.
At-home self-administration can begin after the Week 48 visit at the discretion of the investigator
and participant, and upon completion of at least 3 training sessions starting from Week 48. All
participants who are willing to perform at-home self-administration will be requested to record
at-home administration medication diary and will continue to have study visits and assessments at
the investigative sites approximately q8w through the end of the study, as outlined in Section 1.3.
Details of instruction of at-home administration will be described in a separate document (Training
guide for Investigators for Use of Prefilled syringe).
Long-term extension will be continued until the time when guselkumab is approved for CD
indication in Japan and marketed guselkumab becomes available at the study site (up to around 3
years at maximum in addition to a 48-week treatment phase depending on the timing of approval
of guselkumab for CD in Japan) or discontinuation of the clinical development of guselkumab for
CD, and all participants who will be continuing the treatment at the time of marketing approval of
guselkumab for CD or discontinuation of the clinical development of guselkumab for CD will be
asked to come to the study site, and complete their safety and efficacy assessments.
Participants who have a concurrent or history of SB disease activity confirmed by radiography,
imaging and/or endoscopy may be eligible to participate in the substudy for additional SB
assessment by device-assisted enteroscopy.
Key safety assessments will include the monitoring of adverse events, vital sign measurements,
and clinical laboratory tests including inflammatory biomarkers. Key efficacy assessments include
Crohn’s Disease Activity Index (CDAI) and its components, endoscopic assessments by either
ileocolonoscopy or device-assisted enteroscopy (if a participant agrees to perform additional SB
assessment; refer to Section 8.1, Efficacy Assessments).
There will be 3 database locks planned for this study to assess the safety and efficacy data of
guselkumab in Japanese participants with CD:
 
The first database lock will be at Week 24 after all participants have either completed the
Week 24 or terminated study participation prior to Week 24.

 
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 
The second database lock will be at Week 48 after all participants have either completed the
Week 48 or terminated study participation prior to Week 48.
 
The final database lock will be planned at the end of study period including LTE.
A target of 25 participants will be enrolled in this study.
A diagram of the study design is provided in Section 1.2, Schema.
4.2. 
Scientific Rationale for Study Design
The primary objective of the study is to assess the safety of guselkumab in patients with CD in
Japan. Although the safety of guselkumab in patients with CD will also be assessed in GALAXI
program, this study is planned to complement the existing safety database for CD by enrolling
additional participants exposed to guselkumab in Japan.
4.2.1. 
Study-Specific Ethical Design Considerations
Potential participants will be fully informed of the risks and requirements of the study and, during
the study, participants will be given any new information that may affect their decision to continue
participation. They will be told that their consent to participate in the study is voluntary and may
be withdrawn at any time with no reason given and without penalty or loss of benefits to which
they would otherwise be entitled. Only participants who are fully able to understand the risks,
benefits, and potential adverse events of the study, and provide their consent voluntarily will be
enrolled.
The total blood volume of approximately 210 mL will be collected through Week 48, and
additional blood sampling of up to approximately 90 mL per year will be required if a participant
is willing to enter LTE phase. This amount of blood sampling is considered to be acceptable with
reference to the blood donation rule by the Japanese Red Cross Society. 
4.3. 
Justification for Dose
The induction dose selected for this study (200 mg IV at Weeks 0, 4 and 8) is identical to what is
selected for phase 3 part of CNTO1959CRD3001 study based on the interim analysis result of
phase 2 part of CNTO1959CRD3001 study and will be used to confirm the induction safety of
guselkumab in participants with moderately and severely active CD. The maintenance dose
selected for this study (200 mg SC q4w) is the highest dosing regimen to be tested in the phase 3
part of CNTO1959CRD3001 study to accumulate the safety data with potential highest
maintenance dosing regimen. Of note, guselkumab 200 mg q4w regimen is also being tested in the
phase 2 part of CNTO1959CRD3001 study.
4.4. 
End of Study Definition
End of Study Definition
The end of study is considered as the last scheduled study assessment shown in the SoA for the
last participant in the study. All participants who will be continuing the treatment at the time of
marketing approval of guselkumab for CD will be asked to come to the study site and complete
their safety and efficacy assessment. The final data from the study site will be sent to the sponsor

 
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(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
The inclusion and exclusion criteria for enrolling participants in this study are described below. If
there is a question about these criteria, the investigator must consult with the appropriate sponsor
representative and resolve any issues before enrolling a participant in the study. Waivers are not
allowed. 
5.1. 
Inclusion Criteria
Each potential participant must satisfy all of the following criteria to be enrolled in the study: 
1. 
Be man or woman (according to their reproductive organs and functions assigned by
chromosomal complement) ≥18 years of age.
2. 
Have CD or fistulizing CD 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 CD, defined as:
a. Mean daily stool frequency (SF) count >3, based on the unweighted CDAI
component of the number of liquid or very soft stools
OR
b. Mean daily abdominal pain (AP) score >1, based on the unweighted CDAI
component of AP
4. 
Criterion modified per Amendment 1.
4.1. Have endoscopic evidence of active ileocolonic CD as assessed by central
endoscopy reading at the screening endoscopy (SoA, Table 1), 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”.
OR

 
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Have endoscopic evidence of active SB CD as assessed by central endoscopy reading
at the screening device assisted enteroscopy (SoA, Table 1), defined as a screening
modified SES-CD score ≥5, based on the presence of ulceration in any 1 of the 3
segments including terminal ileum, proximal ileum and jejunum.
Concomitant or previous medical therapies received
5. 
Prior or current medication for CD must include at least 1 of the following, and must
fulfill additional criteria as described in Section 10.7 (Appendix 7) and Section 10.8
(Appendix 8), as applicable:
a. Current treatment with oral corticosteroids (including budesonide) and/or
immunomodulators (AZA, 6-MP)
OR
b. History of failure to respond to, or tolerate, at least 1 of the following therapies:
oral corticosteroids (including budesonide) or immunomodulators (AZA, 6-
MP).
OR
c. History of corticosteroid dependence (ie, an inability to successfully taper
corticosteroids without a return of the symptoms of CD).
OR
d. Has previously demonstrated lack of initial response (ie, primary
nonresponders), responded initially but then lost response with continued
therapy (ie, secondary nonresponders), or were intolerant to 1 or more biologic
agents at a dose approved for the treatment of CD (ie, infliximab, adalimumab,
vedolizumab, or approved biosimilars for these agents).
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 limited 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).
6. 
Adhere to the following requirements for concomitant medication for the treatment of
CD. The following medications are permitted provided that doses meeting the

 
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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 40 mg/day, or
9 mg/day of budesonide, 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) 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 CD, 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 CD, 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. 
Criterion modified per Amendment 1.
7.1. 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 8-week screening period:
a. Hemoglobin ≥8.0 g/dL.
b. White blood cells (WBCs) ≥3.5 × 103/μL.
c. Neutrophils ≥1.5 × 103/μL.
d. Platelets ≥100 × 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.

 
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Tuberculosis
8. 
Is 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. Within 8 weeks prior to the first administration of study intervention, have a
negative QuantiFERON-TB or T-SPOT test result, or have a newly identified
positive QuantiFERON-TB or T-SPOT test 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 borderline results should be handled as outlined
in Section 8.2.6.
Note: The QuantiFERON-TB or T-SPOT 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. Have a chest radiograph (both posterior-anterior and lateral views) taken ≤12
weeks before the first administration of study intervention and read by a
qualified physician to read radiogram (eg, a radiologist or pulmonologist), with
no evidence of current, active TB or old, inactive TB. Chest computerized

 
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tomography (CT) may also be performed if deemed appropriate by the
investigator.
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 first dose administration, a female participant must be:
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
12 weeks after last dose (ie, the end of relevant systemic exposure). 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 12 weeks after the last administration
of study intervention.
12. 
During the study and for at least 12 weeks after the last administration of study
intervention, a male participant
a. who is sexually active with a woman 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 woman must use a condom.

 
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c. must agree not to donate sperm for the purpose of reproduction.
General
13. 
Be willing and able to adhere to all specified requirements including but not limited to
completion of assessments, adherence to visit schedule, compliance with the lifestyle
restrictions, 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.
5.2. 
Exclusion Criteria
Any potential participant who meets any of the following criteria will be excluded from
participating in the study: 
1. 
Has complications of CD, 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 or other instruments to assess response to therapy,
or would possibly confound the ability to assess the effect of treatment with
guselkumab.
2. 
Currently has or is suspected to have an abscess. Recent cutaneous and perianal
abscesses are not exclusionary if drained and adequately treated at least 3 weeks before
baseline, or 8 weeks before baseline for intra-abdominal abscesses, provided that there
is no anticipated need for any further surgery. Participants with active fistulas may be
included if there is no anticipation of a need for surgery and no abscesses are currently
identified.
3.  
Criterion modified per Amendment 1.
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. 
Has a stool culture or other examination positive for an enteric pathogen, including
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.
Concomitant or previous medical therapies received
6. 
Criterion modified per Amendment 1.

 
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6.1. Has received any of the following prescribed medications or therapies within the
specified period:
a. IV corticosteroids received within 3 weeks of baseline
b. Cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil received within
8 weeks of baseline
c. 6-thioguanine received within 4 weeks of baseline
d. Biologic agents:
1. Anti-TNF therapy (eg, infliximab, etanercept, certolizumab pegol,
adalimumab, golimumab) received within 8 weeks of baseline
2. Vedolizumab received within 16 weeks of baseline
3. Ustekinumab received within 16 weeks of baseline
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 CD within 3 weeks of baseline.
7. 
Has previously received a biologic agent targeting IL-12/23 or IL-23, including but not
limited to briakinumab, brazikumab, guselkumab, mirikizumab, and risankizumab.
Exception: Participants who have had limited exposure to ustekinumab at its approved
labeled dosage AND have met the required washout criterion AND have not
demonstrated failure or intolerance to ustekinumab.
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

 
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urinary tract infection (eg, recurrent pyelonephritis or chronic nonremitting cystitis), or
open, draining, or infected skin wounds or ulcers.
9. 
Has current signs or symptoms of a clinically significant infection. Established
nonserious 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. 
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 6 months 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 prior
to screening and a negative HCV RNA test result at screening.
17. 
Participants who tests positive for hepatitis B virus (HBV) infection.
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.

 
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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.
Malignancy or increased potential for malignancy
20. 
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).
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

 
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Intent to Act (“Ideation level 3”) or nonsuicidal self-injurious behavior who are
determined to be at risk by the investigator may not be enrolled.
27. 
Known allergies, hypersensitivity, or intolerance to guselkumab or its excipients (refer
to the IB5).
28. 
Is a woman who is pregnant, or breastfeeding, or planning to become pregnant while
enrolled in this study or within 12 weeks after the last administration of study
intervention.
29. 
Is a man who plans to father a child while enrolled in this study or within 12 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.
31. 
Has any condition for which, in the opinion of the investigator, participation would not
be in the best interest of the participant (eg, compromise the well-being) or that could
prevent, limit, or confound the protocol-specified assessments.
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).
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. The required source documentation to support meeting the
enrollment criteria are noted in Section 10.3 Appendix 3, 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:
1. Refer to Section 6.5, Concomitant Therapy for details regarding prohibited and restricted
therapy during the study.

 
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2. Agree to follow all requirements that must be met during the study as noted in the inclusion
and exclusion criteria (eg, contraceptive requirements).
3. Must not receive guselkumab outside of this protocol or participate in any other clinical
study with an investigational agent while in this study, and must terminate study
participation if they do. A participant who intends to participate in any other clinical study
with an investigational agent should undergo a study intervention discontinuation (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. Must agree not to receive a BCG vaccination during the study and for 12 months 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 study-site contact for completeness.
The participant identification and enrollment log will be treated as confidential and will be filed
by the investigator in the study file. To ensure participant confidentiality, no copy will be made.
All reports and communications relating to the study will identify participants by participant
identification and age at initial informed consent. In cases where the participant is screen failure,
the date seen and age at initial informed consent will be used.
Completion of screening within the specified screening window of approximately 8 weeks is
required.
If any delay leads to the expiration of time-specific assessments (eg, TB, chest radiograph, stool
analysis, endoscopy), 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.

 
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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 8 weeks.
Rescreening
Individuals who do not meet the criteria for participation in this study (screen failure) may be
rescreened one 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, T-SPOT test, chest radiograph, and chest CT) and stool study results, and
endoscopy results from the first screening event may be used if they meet the specified protocol
criteria as described in Section 5.1. Sponsor’s approval is required prior to the study site obtaining
a new informed consent for rescreening.
6. 
STUDY INTERVENTION
6.1. 
Study Intervention(s) Administered
Participants will receive guselkumab 200 mg IV induction doses at Weeks 0, 4, and 8 (total of 3
IV doses), followed by guselkumab 200 mg SC maintenance doses as q4w starting at Week 12
through Week 44.
During LTE, participants will continue to receive the same study intervention regimen that they
were receiving at the end of maintenance, with the first dose in the LTE being administered at
Week 48.
Intravenous 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.
Since 2 SC injections by using 100 mg/mL prefilled syringe (PFS) are administered at visits, each
injection of study intervention should be given at a different location of the body. Recommended
locations are abdomen and/or thigh.
Study intervention administration must be captured in the source documents and the case report
form (eCRF).
Guselkumab will be manufactured and provided under the responsibility of the sponsor. 
6.2. 
Preparation/Handling/Storage/Accountability
Preparation/Handling/Storage
Guselkumab will be manufactured and provided under the responsibility of the Sponsor. Refer to the
guselkumab IB5 for a list of excipients. Guselkumab will be supplied as a 100 mg/mL sterile liquid
in a single dose PFS assembled in an UltraSafe Plus™ Passive Needle Guard (PFS-U).

 
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All study interventions must be stored according to the labeled storage condition, 2°C to 8°C and
protected from exposure to light. Do not freeze the study interventions. The products are designed
for single-use only.
Guselkumab should be clear and colorless to light yellow solution that may contain small translucent
particles. Do not use guselkumab if the liquid is cloudy or discolored or has large particles. Protection
from light is not required during the preparation and administration of the study intervention
material; avoid direct exposure to sunlight. Aseptic procedures must be used during the preparation
and administration of the study intervention material.
Refer to the site Investigational Product Procedures Manual (IPPM) and Investigational Product
Procedure Instructions (IPPI) for additional guidance on study intervention preparation, handling,
and storage.
Accountability
The investigator is responsible for ensuring that all study intervention received at the site is
inventoried and accounted for throughout the study. The dispensing of study intervention to the
participant, and the return of study intervention from the participant (if applicable), must be
documented on the intervention accountability form. Participants must be instructed to return all
original containers, whether empty or containing study intervention. All study intervention will be
stored and disposed of according to the sponsor's instructions. Study-site personnel must not
combine contents of the study intervention containers.
Study intervention must be handled in strict accordance with the protocol and the container label,
and must be stored at the study site in a limited-access area or in a locked cabinet under appropriate
environmental conditions. Unused study intervention must be available for verification by the
sponsor's study site monitor during on-site monitoring visits. The return to the sponsor of unused
study intervention will be documented on the intervention return form. When the study site is an
authorized destruction unit and study intervention supplies are destroyed on-site, this must also be
documented on the intervention return form.
Potentially hazardous materials containing hazardous liquids, such as used ampules, needles,
syringes and vials should be disposed of immediately in a safe manner and therefore will not be
retained for intervention accountability purposes. The immediate destruction of these drug supplies
should be documented in the drug accountability records on site.
Study intervention should be dispensed under the supervision of the investigator or a qualified
member of the study-site personnel, or by a hospital/clinic pharmacist. Study intervention will be
supplied only to participants participating in the study. Returned study intervention must not be
dispensed again, even to the same participant. Study intervention may not be relabeled or
reassigned for use by other participants. The investigator agrees neither to dispense the study
intervention from, nor store it at, any site other than the study sites agreed upon with the sponsor.
Further guidance and information for the final disposition of unused study interventions are
provided in the IPPI.

 
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6.3. 
Measures to Minimize Bias: Randomization and Blinding
As this is an open study, randomization and blinding procedures are not applicable. Central readers
to assess the endoscopic data will be blinded to participant information including medical
background, study site and visit.
6.4. 
Study Intervention Compliance
When study intervention is administered as an IV infusion or SC 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 SC injections, this will include
date and time of SC 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. If participants administer study intervention at home in the
LTE, participants will be instructed to record all at-home study intervention administrations on a
diary card. Participants will also be instructed to contact the study site promptly of any issues of
the product quality are found prior to the administration of the study intervention. Participants who
are unable or unwilling or missed to have injections administered away from the site should contact
the study site and follow the instruction of the study site.  In this case, participants will be required
to return to the site for administration of study intervention if deemed appropriate. Additional
details may be provided in the site IPPM that is provided separately.
6.5. 
Concomitant Therapy
6.5.1. 
Concomitant Medications
Participants who are receiving oral 5-ASA compounds, oral corticosteroids, conventional
immunomodulators (ie, AZA or 6-MP), antibiotics, and/or enteral nutrition for the treatment of
CD 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 CD at baseline (ie, Week 0) should
maintain a stable dose through Week 48, with the exception of oral corticosteroids. Therapies can
only be discontinued or reduced in dose after Week 0 if 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).

 
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Week 0 through Week 48
From Week 0 through Week 48, enrolled participants should not initiate any of the following
concomitant CD-specific medical therapies:
 
Oral or rectal 5-ASA compounds.
 
Immunomodulators (ie, AZA or 6-MP).
 
Oral, parenteral, or rectal corticosteroids, including budesonide.
 
Antibiotics as a primary treatment for CD. 
 
Parenteral or enteral nutrition as a treatment for CD.
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 therapy, 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, participants may transiently use (ie, for <4 weeks) increased
doses of corticosteroids for reasons other than treatment for CD (eg, stress doses of corticosteroids
for surgery, asthma, adrenocortical insufficiency).
During LTE (after Week 48 till the end of study):
Concomitant therapies for CD including 5-ASAs, corticosteroids, antibiotics, and
immunomodulators (ie, AZA or 6-MP), and/or total parenteral or enteral nutrition may be
administered and changed at the discretion of the investigator.
6.5.1.1. 
Oral Corticosteroids Tapering
At Week 12, all participants who were taking corticosteroids at Week 0 must begin tapering
corticosteroids. This tapering is mandatory, unless not medically feasible, and should follow the
recommended schedule shown in Table 5. If participants experience worsening of their disease
activity while tapering corticosteroids, further dose decreases may be suspended, and/or their oral
corticosteroid dose may be temporarily increased if deemed necessary by the investigator. The oral
corticosteroid dose, however, may not be increased above the Week 0 dose unless due to medical
necessity. For participants whose corticosteroid taper is interrupted, investigators are encouraged
to resume tapering within 4 weeks. Tapering may exceed this schedule only if warranted by
medical necessity (eg, participant experiencing corticosteroid-related side effects).

 
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Table 5: 
Recommended Tapering Schedule for Oral Corticosteroids
Recommended Tapering Schedule for Oral Corticosteroids (Other than Budesonide)
Dose >15 mg/day prednisone or 
equivalent 
Taper daily dose by 5 mg/week until receiving 10 mg/day, then
continue tapering at 2.5 mg/week until 0 mg/day
Dose 11 to 15 mg/day prednisone or 
equivalent 
Taper daily dose to 10 mg/day for 1 week, then continue at
2.5 mg/week until 0 mg/day
Dose ≤10 mg/day prednisone or 
equivalent:
Taper daily dose by 2.5 mg/week until 0 mg/day
Recommended Tapering Schedule for Oral Budesonide
Participants receiving budesonide should have their daily dose tapered by 3 mg every 3 weeks until 0 mg/day
6.5.2. 
Prohibited Concomitant Medications
Participants who initiate the following treatments during study participation will have their study
intervention discontinued: 
 
Immunomodulatory agents other than AZA or 6-MP (including, but not limited to, 
6-thioguanine, cyclosporine, mycophenolate mofetil, tacrolimus, and sirolimus).
 
Immunomodulatory biologic agents (including, but not limited to, TNF antagonists,
natalizumab, ustekinumab, rituximab, vedolizumab). 
 
Experimental CD medications (including, but not limited to, upadacitinib, filgotinib,
ozanimod, etrolizumab, brazikumab, mirikizumab, risankizumab, GS-5745). 
 
Thalidomide or related agents.
The sponsor must be notified in advance (or as soon as possible thereafter) of any instances in
which prohibited therapies are administered.
6.6. 
Dose Modification
No treatment/dose adjustment of study drug will be permitted throughout the study period.
6.7. 
Intervention After the End of the Study
This protocol is designed to provide participants with approximately 48 weeks of treatment plus
up to approximately 3 additional years of treatment in the LTE depending on the timing of approval
of guselkumab for CD.
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
7.1. 
Discontinuation of Study Intervention
A participant's study treatment must be discontinued under the following conditions:
1. The participant initiates treatment with prohibited therapies for CD (Section 6.5.2). 
2. The participant has a CD-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 CD-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.
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 or chest CT with evidence of
current active TB and/or a positive QuantiFERON-TB test or T-SPOT test result, 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). Indeterminate QuantiFERON-TB test or borderline T-SPOT test results
should be handled as described in Section 8.2.6. Participants with persistently
indeterminate QuantiFERON-TB test results or borderline T-SPOT test may continue
without treatment for latent TB if active TB is ruled out, their chest radiograph or chest
CT 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 and recorded in the participant's source
documents and initialed by the investigator.
 
A participant receiving treatment for latent TB discontinues this treatment prematurely or
is noncompliant with the therapy.
7. The participant has a serious adverse reaction that is related to an injection 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.

 
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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. 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. Persistent inadequate response or worsening of CD or experience AEs consistent with
clinically significant worsening of CD at any time during the study.
These events must be evaluated by the investigator. A consultation with the Sponsor may also
be considered, at the investigator's discretion. Discontinuation of study intervention must be
considered in participants with clinically significant worsening of CD 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 postbaseline 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 Sponsor. Discussion of such participants with Sponsor is required.
4. 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 SoA. If the reason for discontinuation
of study intervention is withdrawal of consent, every effort should be made to conduct the SID
visit assessments, as indicated in the SoA, prior to terminating study participation. After
termination of study participation, no additional assessments are allowed.

 
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7.2. 
Participant Discontinuation/Withdrawal From the Study
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
specified for the SID visit in the appropriate SoA (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 study completion, the reason for withdrawal is to be
documented in the eCRF and in the source document. If the reason for withdrawal from the study
is withdrawal of consent, then no additional assessments are allowed.
Withdrawal of Consent
A participant declining to return for scheduled visits does not necessarily constitute withdrawal of
consent. Alternate follow-up mechanisms that the participant agreed to when signing the consent
form apply as local regulations permit.
7.3. 
Lost to Follow-up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for
scheduled visits and is unable to be contacted by the study site. A participant cannot be deemed
lost to follow-up until all reasonable efforts made by the study-site personnel to contact the
participant are deemed futile. The following actions must be taken if a participant fails to return to
the study site for a required study visit:
 
The study-site personnel must attempt to contact the participant to reschedule the missed visit
as soon as possible, to counsel the participant on the importance of maintaining the assigned
visit schedule, to ascertain whether the participant wishes to or should continue in the study.
 
Before a participant is deemed lost to follow up, the investigator or designee must make every
reasonable effort to regain contact with the participant where possible, 3 telephone calls, e-
mails, fax, and, if necessary, a certified letter to the participant’s last known mailing address,
or local equivalent methods. These contact attempts should be documented in the participant’s
medical records.
 
Should the participant continue to be unreachable, they will be considered to have withdrawn
from the study.

 
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8. 
STUDY ASSESSMENTS AND PROCEDURES
Overview
The SoA summarizes the frequency and timing of efficacy, PK, immunogenicity, and safety
measurements applicable to this study.
If multiple assessments are scheduled for the same timepoint, it is recommended that procedures
be performed in the following sequence: electrocardiogram (ECG) and vital signs (blood pressure,
pulse rate, respiratory rate, and body temperature) should be performed first, and then blood draws
for PK or laboratory measurements. Blood collections for PK and PD assessments should be
completed as outlined in the SoA (Section 1.3). Other measurements may be done earlier than
specified timepoints if needed. Actual dates and times of assessments will be recorded in the source
documentation.
Additional serum or urine pregnancy tests may be performed, as determined necessary by the
investigator or required by local regulation, to establish the absence of pregnancy at any time
during the participation in the study.
Screening Phase
At the screening visit, written informed consent must be obtained from the participant for this
program by the principal investigator or designee before performing any protocol-specific
procedure. Procedures to be performed at the screening visit are outlined in the SoA (Section 1.3).
The CDAI diary will be completed by participants during the screening period. 
A minimum of 7 days of stool frequency and abdominal pain data during the screening period is
required.
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 Criteria [Section 5.1]) and must continue
taking such precautions for 12 weeks after receiving the last administration of study intervention.
The method(s) of contraception used by each participant must be documented. 
Participants must undergo testing for TB (Section 8.2.6) 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 or chest CT results.
Participants with a negative QuantiFERON-TB test or T-SPOT test result are eligible to continue
with registration procedures.
Participants with a newly identified positive QuantiFERON-TB or T-SPOT test result must
undergo an evaluation to rule out active TB and initiate appropriate treatment for latent TB.

 
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Appropriate treatment for latent TB is defined according to local country guidelines for
immunocompromised patients.
A participant whose first QuantiFERON-TB test result is indeterminate or T-SPOT test result is
borderline should have the test repeated. If the second QuantiFERON-TB or T-SPOT test result is
also indeterminate or borderline, the participant may be enrolled without treatment for latent TB
if his/her chest radiograph or chest CT 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 Sponsor.
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 SoA (Section 1.3). The date and
time of collection will be recorded. When blood samples are to be collected for safety, PK, efficacy,
and biomarker at the same time point, the order of blood draws will be samples for CRP, chemistry,
hematology, and PK/Immunogenicity.
The total blood volume of approximately 210 mL will be collected through Week 48, and
additional blood sampling of up to approximately 90 mL per year will be required if a participant
is willing to enter LTE phase. Repeat or unscheduled samples taken for safety reasons or technical
issues with the samples.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the eCRF or laboratory
requisition form. Refer to the SoA 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
The investigator will be provided with the following supplies:
 
Investigator Site File (includes protocol and IB5)
 
IPPM and IPPI
 
Central Laboratory Manual 
 
eCRF completion instructions
 
Patient recruitment materials
 
ICF
 
Participant Diary Card including CDAI (including PRO-2)

 
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 
Training guide for Investigators for Use of Prefilled syringe
 
Endoscopy kit
 
Imaging Manual (for ileocolonoscopy and device assisted enteroscopy)
 
Laboratory kits
8.1. 
Efficacy Assessments
Efficacy evaluations will include the following:
 
CDAI including PRO-2 score (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/or modified SES-CD
The CDAI will be assessed by collecting information on 8 different CD-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 or
device assisted enteroscopy (see SB assessment) in all participants. A video endoscopic
examination will be performed at Screening, Week 48, every 48 weeks after Week 48 (Optional),
and at the end of the study. Video endoscopies will be assessed by a central facility that will be
blinded to clinical characteristics of participants and study visit. A video endoscopic examination
can be completed at the location where it can be visualized. The SES-CD score will be used to
evaluate Endoscopic Improvement.3,15 The SES-CD is based on the evaluation of 4 endoscopic
components (presence/size of ulcers, proportion of mucosal surface covered by ulcers, proportion
of mucosal surface affected by any other lesions, and presence/type of narrowing/strictures) across
5 ileocolonic segments. Each endoscopic component is scored from 0 to 3 for each segment,
resulting in a total score of up to 15 for each component, except for the narrowing component
which can only attain a maximum total score of 11 because by definition, the presence of a
narrowing that cannot be passed can be only observed once. In summary, an overall total SES-CD
score is derived from the sum of all the component scores and can range from 0 to 56). Endoscopic
healing, which is traditionally defined as the resolution (absence) of mucosal ulcers in response to
a therapeutic intervention, will also be assessed.
Small bowel (SB) assessment will be performed optionally in participants who agree to participate
in the SB assessment study and are deemed appropriate for their participation to SB assessment
judged by the investigator. Participants who are eligible only with SB lesions should undergo SB
assessment at Week 48 and at the end of study. Modalities to be used for the study are follows;
 
Because of the difficulties attempting to push a slim, flexible instrument through the soft and
lengthy SB, conventional colonoscopy cannot reach the proximal ileum and jejunum. Device-

 
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assisted enteroscopy12 including single-balloon endoscopy (SBE) and double-balloon
endoscopy (DBE) are developed to overcome this issues and the usage of a balloon would
grip the intestinal wall and prevent subsequent loop formation, allowing further advancement
of scopes. Device-assisted enteroscopy is widely used to establish the diagnosis of CD,
particularly if a patient complains of symptoms such as abdominal pain but ileocolonoscopy
up to terminal ileum fails to establish a definite diagnosis of CD.6 Modified SES-CD15 will be
used to evaluate endoscopic improvement in SB lesions. While 3 endoscopic components
except for presence/type of narrowing/strictures for the evaluation of modified SES-CD is the
same as that for original SES-CD, 3 SB segments of the SB will be applied to calculate
modified SES-CD score instead of 5 ileocolonic segments for original SES-CD score; terminal
ileum (≤10 cm from ileocecal valve), proximal ileum (10-300 cm from the ileocecal valve)
and jejunum (SB proximally beyond the section defined as the proximal ileum), ranging from
0-27. Endoscopic lesions were defined as no mucosal activity (Modified SES-CD=0), mild
disease (1≤Modified SES-CD<5) and ulcerative disease (Modified SES-CD≥5) and
endoscopic healing is defined as modified SES-CD <5.14
8.2. 
Safety Assessments
Adverse events will be reported and followed by the investigator as specified in Section 8.3,
Adverse Events and Serious Adverse Events and Section 10.4 Appendix 4, Adverse Events:
Definitions and Procedures for Recording, Evaluating, Follow-Up, and Reporting.
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 provided in the SoA.
8.2.1. 
Physical Examinations
Physical examinations will be performed as specified in the SoA. While assessment of the
participants for safety and efficacy requires some physical examination by an investigator at all
visits, a more complete, detailed physical examination will be performed at specified visits.
8.2.2. 
Vital Signs
Temperature, pulse/heart rate, respiratory rate, blood pressure will be assessed.
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 SC 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 study intervention at home will be trained to
perform self-evaluation for injection-site reactions and reporting of AEs after administering study

 
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interventions at home. Vital signs will only be assessed at the study site when study participants
receive study intervention administration at the study site.
8.2.3. 
Electrocardiograms
A 12-lead ECG will be performed at screening.
During the collection of ECGs, participants should be in a quiet setting without distractions (eg,
television, cell phones). Participants should rest in a supine position for at least 5 minutes before
ECG collection and should refrain from talking or moving arms or legs. If blood sampling or vital
sign measurement is scheduled for the same time point as ECG recording, the procedures should
be performed in the following order: ECG(s), or vital signs first, and then blood draw.
8.2.4. 
Height and Weight
Height and weight will be measured as specified in the SoA. Participants will be instructed to
remove shoes and outdoor apparel and gear prior to these measurements.
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. 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 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 and/or CT results. If either the QuantiFERON-TB test or T-SPOT test is positive,
the participant is considered to have latent TB infection for the purposes of eligibility for this study.
Participants with a negative QuantiFERON-TB (or T-SPOT if performed) test result are eligible
to continue with screening procedures. Participants with a newly identified positive
QuantiFERON-TB (or T-SPOT if performed) test result must undergo an evaluation to rule out
active TB and initiate appropriate treatment for latent TB. Appropriate treatment for latent TB is
defined according to local country guidelines for immunocompromised patients.  Otherwise, the
participant will be excluded from the study. 
A participant whose first QuantiFERON-TB test result is indeterminate or T-SPOT test result is
borderline should have the test repeated. In the event that the second QuantiFERON-TB test or T-
SPOT test result is also indeterminate or borderline, the participant may be enrolled without
treatment for latent TB if active TB is ruled out, their chest radiograph or chest CT shows no
abnormality suggestive of TB (active or old, inactive TB) and the participant has no additional risk

 
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factors for TB as determined by the investigator. This determination must be promptly reported to
the Sponsor and recorded in the participant's source documents and initialed by the investigator.
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 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 or chest CT, a repeat QuantiFERON TB or T-SPOT
test, 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.
Study intervention administration should be interrupted during the investigation. A positive
QuantiFERON-TB test or T-SPOT test result should be considered detection of latent TB. If the
QuantiFERON-TB test result is indeterminate or T-SPOT test result is borderline, the test should
be repeated. Participants should be encouraged to return for all subsequent scheduled study visits
according to the protocol. Participants who discontinue treatment for latent TB prematurely or who
are noncompliant with therapy must immediately discontinue further administration of study
intervention and be encouraged to return for all subsequent scheduled study visits according to the
SoA.

 
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8.2.7. 
Hepatitis B monitoring
For participants who are eligible with surface antigen (HbsAg) negative, core antibody (anti-HBc)
and/or surface antibody (anti-HBs) positive, and HBV deoxy ribonucleic acid (DNA) test is
negative, HBV DNA quantitation should be monitored at least every 3 months or shorter.
8.2.8. 
Allergic Reaction
Before any SC injection or IV 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), SC 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.
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.
8.2.9. 
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.
8.2.10. 
Injection-Site Reaction
An injection-site reaction is any adverse reaction at a SC study intervention injection site. Injection
sites will be evaluated for reactions and any injection-site reaction will be recorded as an AE.

 
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8.2.11. 
Columbia-Suicide Severity Rating Scale (C-SSRS)
The C-SSRS defines 5 subtypes of suicidal ideation and 4 possible suicidal behaviors, as well as
nonsuicidal 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.8,10 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 study period up to Week 48. During LTE, C-SSRS will be completed
every 8 weeks.
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
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 enrolled.
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 nonsuicidal self-injurious behavior must be determined
not to be at risk by the investigator in order to be enrolled. Any questions regarding eligibility of
such participants should be discussed with Sponsor.
For each assessment after Week 0, the following actions should be taken, if applicable:
 
No suicidal ideation or behaviors (including self-injurious behavior without suicidal intent):
No further action is needed.
 
Suicidal ideation levels 1-3 or nonsuicidal self-injurious behavior: Participant risk is assessed
by the investigator.

 
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 
Suicidal ideation levels 4 or 5 or any suicidal behavior: Participant risk assessed and referral
to a mental health professional.
Interruption or the discontinuation of study 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
postbaseline 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 Sponsor. Discussion of such participants with
Sponsor 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. 
8.2.12. 
Clinical Safety Laboratory Assessments
Blood samples for serum chemistry, hematology, and stool sample will be collected at scheduled
study visits according to the SoA. The investigator must review the laboratory results, document
this review, and record any clinically relevant changes occurring during the study in the adverse
event section of the eCRF.
The following tests will be performed by the central laboratory unless otherwise specified or
approved by Sponsor.
 
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).
Sponsor 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. 
 Inflammatory biomarkers such as CRP and fecal calprotectin will also be included to assess
the disease activities of CD for the participants.
 
Serology: HIV antibody, HBV antibodies and surface antigen, and HCV antibody.
 
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 the separate
instruction for additional information on monitoring and assessment of abnormal liver
function tests.

 
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 
Pregnancy testing: Female participants of childbearing potential will undergo a urine
pregnancy test at screening before study intervention administration, at a SID visit, and at the
FES visit.
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
information; all clinical studies conducted by the sponsor or its affiliates will be conducted in
accordance with those procedures.
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, surrogate,
or the participant's legally acceptable representative) for the duration of the study.
For further details on adverse events and serious adverse events (Definitions and Classifications;
Attribution Definitions; Severity Criteria; Special Reporting Situations; Procedures) as well as
product quality complaints, refer to Section 10.4 Appendix 4, 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 adverse events and special reporting situations, whether serious or nonserious, 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 12 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.
Serious Adverse Events
All serious adverse events occurring during the study must be reported to the appropriate sponsor
contact person by study-site personnel within 24 hours of their knowledge of the event.
Information regarding serious adverse events will be transmitted to the sponsor using the Serious
Adverse Event Form, which must be completed and signed by a physician from the study site, and
transmitted to the sponsor within 24 hours. The initial and follow-up reports of a serious adverse
event should be made by facsimile (fax).

 
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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
Section 10.4 Appendix 4, Adverse Events: Definitions and Procedures for Recording, Evaluating,
Follow-up, and Reporting.
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 suspected unexpected serious adverse reactions (SUSARs). The investigator (or
sponsor where required) must report SUSARs to the appropriate Independent Ethics
Committee/Institutional Review Board (IEC/IRB) that approved the protocol unless otherwise
required and documented by the IEC/IRB. 
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: 
 
AEs related to symptoms of CD
 
AEs related to worsening or progression of CD
These anticipated events are exempt from expedited reporting as individual single cases to Health
Authorities, except where local regulations require expedited reporting of all SUSARs. However,
if based on an aggregate review, it is determined that an anticipated event is possibly related to
study intervention, the sponsor will report these events in an expedited manner.
8.3.4. 
Pregnancy
All initial reports of pregnancy in female participants or partners of male participants must be
reported to the sponsor by the study-site personnel within 24 hours of their knowledge of the event
using the appropriate pregnancy notification form. Abnormal pregnancy outcomes (eg,
spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are
considered 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.
8.3.5. 
Adverse Events of Special Interest
Any newly identified malignancy or case of active TB occurring after the first study intervention
administration(s) in participants participating in this clinical study must be reported by the
investigator to the sponsor or designee within 24 hours after being made aware of the event 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.

 
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8.4. 
Treatment of Overdose
For this study, any dose of study intervention greater than the highest dose at a single 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 Sponsor 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 Sponsor based on the clinical evaluation of the participant.
8.5. 
Pharmacokinetics
Serum samples will be used to evaluate the PK of guselkumab. Guselkumab concentration will be
evaluated on blood drawn from all participants according to the SoA. Additionally, serum samples
should also be collected at the final visit from participants who discontinued study intervention or
were withdrawn from the study. These samples will be tested by the sponsor or sponsors designee.
Serum collected for PK may additionally be used to evaluate safety or efficacy aspects that address
concerns arising during or after the study period or for the evaluation of relevant biomarkers.
Additional blood sampling may be considered when patient experienced serious adverse event.
Genetic analyses will not be performed on these serum samples. Participant confidentiality will be
maintained.
8.5.1. 
Evaluations
At visits where only serum concentration of guselkumab will be evaluated (ie, no antibodies to
guselkumab will be evaluated), 1 venous blood sample of sufficient volume should be collected,
and each serum sample should be divided into 2 aliquots (1 for serum concentration of guselkumab,
and a back-up). At visits where serum concentration of guselkumab and antibodies to guselkumab
will be evaluated, 1 venous blood sample of sufficient volume should be collected, and each serum
sample will be divided into 3 aliquots (1 each for serum concentration of guselkumab, antibodies
to guselkumab, and a back-up).
8.5.2. 
Analytical Procedures
Serum samples will be analysed to determine concentrations of guselkumab using validated,
specific, and sensitive method by or under the supervision of the sponsor.
8.6. 
Pharmacodynamics
C-reactive protein (CRP) and fecal calprotectin will be evaluated using blood and stool samples
collected at visits as indicated in the SoA (Section 1.3).

 
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8.7. 
Genetics
Pharmacogenomics are not evaluated in this study.
8.8. 
Biomarkers
No specific biomarkers other than serum or fecal inflammatory markers will be evaluated in this
study.
8.9. 
Immunogenicity Assessments
Serum samples will be screened for antibodies binding to guselkumab and the titer of confirmed
positive samples will be reported. Neutralizing antibodies will be assessed for positive samples.
Other analyses may be performed to further characterize the immunogenicity of guselkumab.
Antibodies to guselkumab will be evaluated on blood drawn from all participants according to the
SoA. Additionally, serum samples should also be collected at the final visit from participants who
discontinued study intervention or were withdrawn from the study. These samples will be tested
by the sponsor or sponsor's designee.
Serum samples will be used to evaluate the immunogenicity of anti-guselkumab antibodies.
Samples collected for immunogenicity analyses may additionally be used to evaluate safety or
efficacy aspects that address concerns arising during or after the study period. Genetic analyses
will not be performed on these serum samples. Participant confidentiality will be maintained.
Analytical Procedures 
The detection and characterization of antibodies to guselkumab will be performed using a validated
assay method by or under the supervision of the sponsor. 
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 analyse the efficacy and safety data is outlined
below. Specific details will be provided in the Statistical Analysis Plan (SAP). 
There will be 3 analysis plans supporting this protocol: one for the analysis based on Week 24
database lock (including efficacy and safety analysis through Week 24), second one for the
analysis based on Week 48 database lock (including full data through Week 48 except LTE), and
last one for the analysis based on the entire study result including LTE.
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.
9.1. 
Statistical Hypotheses
No statistical hypothesis testing is planned in this study. 

 
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9.2. 
Sample Size Determination
As no statistical hypothesis testing based on any endpoint is planned in this study, the sample size
was not calculated based on statistical considerations. The objective of the study is to assess the
safety of guselkumab in the Japanese patients with moderately to severely active CD together with
CNTO1959CRD3001 study, and the sample size was chosen to achieve this objective and provide
additional safety information as much as possible.
9.3. 
Populations for Analyses
For purposes of analysis, the following populations are defined:
Population 
Description
Enrolled 
All participants who sign the ICF
Full Analysis Set 
All enrolled participants who receive at least 1 dose of guselkumab.
Safety 
All enrolled participants who receive at least 1 dose of guselkumab. 
PK 
All enrolled participants who receive at least 1 complete dose of guselkumab and have at
least 1 valid blood sample drawn for PK analysis after their first dose of guselkumab.
Immunogenicity 
All enrolled participants who receive at least 1 dose of guselkumab and have at least 1
observed postdose immune response data.
9.4. 
Statistical Analyses
9.4.1. 
General Considerations
Unless otherwise noted, efficacy analyses will be based on the Full Analysis Set, which is defined
as all enrolled participants who had at least 1 dose of guselkumab in the study.
Efficacy analysis for SB assessment will only be performed among the participants who have
assessment data at both baseline and Week 48 (or at the end of LTE period).
9.4.2. 
Safety Analyses
All safety analyses will be made on the Safety Population.
Adverse Events
The verbatim terms used in the eCRF by investigators to identify adverse events will be coded
using the Medical Dictionary for Regulatory Activities (MedDRA). Treatment-emergent AEs are
AEs with onset during the intervention phase or that are a consequence of a pre-existing condition
that has worsened since baseline. All reported treatment-emergent adverse events will be included
in the analysis. For each adverse event, the percentage of participants who experience at least
1 occurrence of the given event will be summarized.
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.

 
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 
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 postbaseline laboratory values (hematology and chemistry).
Listings of participants with any abnormal postbaseline laboratory values of National Cancer
Institute Common Terminology Criteria for Adverse Events grade ≥2 will also be provided.
9.4.3. 
Other Analyses
Pharmacokinetic Analyses 
Pharmacokinetic analysis will be performed based on the PK analysis set.
Descriptive statistics, including arithmetic mean, SD, CV%, median, interquartile range, minimum,
and maximum of the serum guselkumab concentrations will be calculated at each nominal
sampling time point. These concentrations will be summarized over time.
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.
The data will be excluded from the PK analysis if their data do not allow for accurate assessment
of the PK (eg, incomplete administration of the study intervention; missing time of study
intervention administration). Detailed rules for the analysis will be specified in the SAP.
Population PK modeling may be conducted when appropriate. If population PK analysis is
conducted, the results of the modeling analysis will be presented in a separate report.
Immunogenicity Analyses
Immunogenicity analysis will be performed based on the immunogenicity analysis set.
The incidence and maximum titers of antibodies to guselkumab will be summarized for
participants who are positive for antibodies to guselkumab.

 
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A listing of participants who are positive for antibodies to guselkumab will be provided. 
The incidence of neutralizing antibodies to guselkumab will be summarized for participants who
are positive for antibodies to guselkumab and have samples evaluable for neutralizing antibodies
to guselkumab.
Pharmacokinetic/Pharmacodynamic Analyses
The relationship between serum guselkumab concentrations and biomarkers and/or efficacy
measures might be analysed graphically.
9.5. 
Interim Analysis
There are 2 interim analysis planned at Week 24 database lock as well as Week 48 database lock
before final database lock. Details will be described in analysis plan.

 
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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. 
Appendix 1: Abbreviations
5-ASA 
5-aminosalicylic acid 
6-MP 
6-mercaptopurine
AE 
adverse event
Alk P 
alkaline phosphatase
ALT 
alanine aminotransferase
AMA 
anti-mitochondrial antibody 
ANA 
antinuclear antibody 
AP 
abdominal pain
ASMA 
anti-smooth muscle antibody 
AST 
aspartate aminotransferase
AZA 
Azathioprine
BCG 
Bacille Calmette-Guérin
BIO-Failure 
biologic therap y failure or intolerance
BMI 
bod y mass index
CBC 
complete blood count
CD 
Crohn’s disease
CDAI 
Crohn’s Disease Activit y Index
CHF 
congestive heart failure
CL 
Clearance
CMV 
Cytomegalovirus
CON-Failure 
conventional therap y failure or intolerance
CRP 
C-reactive protein
C-SSRS 
Columbia-Suicide Severit y Ratin  g Scale
CT 
computerized tomography 
CV 
coefficient of variation
DCs 
dendritic cells
DILI 
dru  g induced liver injury 
DM 
diabetes mellitus
DNA 
deoxyribonucleic acid 
ECG 
Electrocardiogram
eCRF 
electronic case report form
eDC 
electronic data capture
EBV 
Epstein-Barr virus
ERCP 
endoscopic retrograde cholangiopancreatography 
ESR 
erythrocyte sedimentation rate
EU 
European Union
FDA 
Food and Dru  g Administration
FES 
Final Efficac y and Safety 
FSH 
follicle stimulatin  g hormone
GCP 
Good Clinical Practice
GGT 
gamma-glutamyl transferase
HAV 
hepatitis A virus
HBsAg 
hepatitis B surface antigen
HBV 
hepatitis B virus
HBV DNA 
hepatitis B virus deoxyribonucleic acid 
HCV 
hepatitis C virus
HEV 
hepatitis E virus
HIV 
human immunodeficienc y virus
HRT 
hormonal replacement therapy 
IB 
Investigator’s Brochure
ICF 
informed consent form
ICH 
International Conference on Harmonisation
ICMJE 
International Committee of Medical Journal Editors
IEC 
Independent Ethics Committee

 
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IgG 
immunoglobulin G
IgM 
immunoglobulin M
IL 
Interleukin
INR 
international normalized ratio
IPPI 
Investigational Product Procedure Instructions
IPPM 
Investigational Product Procedures Manual
IRB 
Institutional Review Board 
IUS 
intrauterine hormone-releasin  g system
IUD 
intrauterine device
IV 
Intravenous
LAM 
lactational amenorrhea method 
LKM(1) 
liver kidney microsomal antibody (type 1)
LT 
laborator y tests
LTE 
long-term extension
mAb 
monoclonal antibody 
MedDRA 
Medical Dictionar y for Regulator y Activities
MRCP 
magnetic resonance cholangiopancreatography 
MRI 
magnetic resonance imaging 
NSAID 
nonsteroidal anti-inflammator y drug(s)
OTC 
over the counter
pANCA 
(perinuclear) anti-neutrophil cytoplasmic antibody 
PD 
Pharmacodynamic
PK 
pharmacokinetic(s)
PPP 
palmoplantar pustulosis
PQC 
Product Qualit y Complaint
PRO 
patient-reported outcome(s) (paper or electronic as appropriate for this study)
PsA 
psoriatic arthritis
PsO 
plaque psoriasis
PT 
prothrombin time
PTT 
partial thromboplastin time
q4w 
ever y 4 weeks
q8w 
ever y 8 weeks
RNA 
ribonucleic acid 
SAE 
serious adverse event
SAP 
Statistical Analysis Plan
SB 
small bowel
SC 
Subcutaneous
SD 
standard deviation
SES-CD 
Simple Endoscopic Score for Crohn’s Disease 
SF 
stool frequency 
SID 
stud y intervention discontinuation (visit)
SoA 
Schedule of Activities
SUSAR 
suspected unexpected serious adverse reaction
TB 
Tuberculosis
Th17 
T helper 17
TIBC 
Total iron bindin  g capacity 
TNF 
tumor necrosis factor 
TOC 
Table of Contents
UC 
Ulcerative colitis
ULN 
upper limit of normal
Vz 
volume of distribution durin  g terminal phase
WBC 
white blood cell (count)
WOCBP 
woman of childbearin  g potential

 
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10.3. 
Appendix 3: Regulatory, Ethical, and Study Oversight Considerations
REGULATORY AND ETHICAL CONSIDERATIONS
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the
protocol, current ICH guidelines on Good Clinical Practice (GCP), and applicable regulatory and
country-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 nonacceptance, except when
necessary to eliminate immediate hazards to the participants, in which case the amendment must
be promptly submitted to the IEC/IRB and relevant competent authority. Documentation of
amendment approval by the investigator and IEC/IRB must be provided to the sponsor. When the
change(s) involve only logistic or administrative aspects of the study, the IEC/IRB (where
required) only needs to be notified.
During the course of the study, in situations where a departure from the protocol is unavoidable,
the investigator or other physician in attendance will contact the appropriate sponsor representative
listed in the Protocol Supplementary Information, which will be provided as a separate document.
Except in emergency situations, this contact should be made before implementing any departure
from the protocol. In all cases, contact with the sponsor must be made as soon as possible to discuss
the situation and agree on an appropriate course of action. The data recorded in the eCRF and
source documents will reflect any departure from the protocol, and the source documents will
describe this departure and the circumstances requiring it.
Regulatory Approval/Notification
This protocol and any amendment(s) must be submitted to the appropriate regulatory authorities
in each respective country, if applicable. A study may not be initiated until all local regulatory
requirements are met.
Required Prestudy Documentation
The following documents must be provided to the sponsor before shipment of study intervention
to the study site:

 
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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 before enrollment of the first
participant:
 
Completed investigator financial disclosure forms from all subinvestigators
 
Documentation of subinvestigator qualifications (eg, curriculum vitae)
 
Name and address of any local laboratory conducting tests for the study, and a dated copy of
current laboratory normal ranges for these tests, if applicable
 
Local laboratory documentation demonstrating competence and test reliability
(eg, accreditation/license), if applicable
Independent Ethics Committee or Institutional Review Board
Before the start of the study, the investigator (or sponsor where required) will provide the IEC/IRB
with current and complete copies of the following documents (as required by local regulations):
 
Final protocol and, if applicable, amendments
 
Sponsor-approved ICF (and any other written materials to be provided to the participants)
 
IB (or equivalent information) and amendments/addenda
 
Sponsor-approved participant recruiting materials
 
Information on compensation for study-related injuries or payment to participants for
participation in the study, if applicable

 
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 
Investigator's curriculum vitae or equivalent information (unless not required, as documented
by the IEC/IRB)
 
Information regarding funding, name of the sponsor, institutional affiliations, other potential
conflicts of interest, and incentives for participants
 
Any other documents that the IEC/IRB requests to fulfill its obligation
This study will be undertaken only after the IEC/IRB has given full approval of the final protocol,
amendments (if any, excluding the ones that are purely administrative, with no consequences for
participants, data or study conduct, unless required locally), the ICF, applicable recruiting
materials, and participant compensation programs, and the sponsor has received a copy of this
approval. This approval letter must be dated and must clearly identify the IEC/IRB and the
documents being approved.
During the study the investigator (or sponsor where required) will send the following documents
and updates to the IEC/IRB for their review and approval, where appropriate:
 
Protocol amendments (excluding the ones that are purely administrative, with no
consequences for participants, data or study conduct)
 
Revision(s) to ICF and any other written materials to be provided to participants
 
If applicable, new or revised participant recruiting materials approved by the sponsor
 
Revisions to compensation for study-related injuries or payment to participants for
participation in the study, if applicable
 
New edition(s) of the IB and amendments/addenda
 
Summaries of the status of the study at intervals stipulated in guidelines of the IEC/IRB (at
least annually)
 
Reports of 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
 
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).
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At the end of the study, the investigator (or sponsor where required) will notify the IEC/IRB about
the study completion (if applicable, the notification will be submitted through the head of
investigational institution).
Other Ethical Considerations
For study-specific ethical design considerations, refer to Section 4.2.1.
FINANCIAL DISCLOSURE
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial
information in accordance with local regulations to allow the sponsor to submit complete and
accurate financial certification or disclosure statements to the appropriate regulatory authorities.
Investigators are responsible for providing information on financial interests during the course of
the study and for 1 year after completion of the study.
Refer to Required Prestudy Documentation (above) for details on financial disclosure.
INFORMED CONSENT PROCESS
Each participant must give written consent according to local requirements after the nature of the
study has been fully explained. The ICF(s) must be signed before performance of any study-related
activity. The ICF(s) that is/are used must be approved by both the sponsor and by the reviewing
IEC/IRB and be in a language that the participant can read and understand. The informed consent
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.
Participants will be informed that their participation is voluntary and that they may withdraw
consent to participate at any time. They will be informed that choosing not to participate will not
affect the care the participant will receive. Finally, they will be told that the investigator will
maintain a participant identification register for the purposes of long-term follow up if needed and
that their records may be accessed by health authorities and authorized sponsor personnel without
violating the confidentiality of the participant, to the extent permitted by the applicable law(s) or
regulations. By signing the ICF the participant is authorizing such access. It also denotes that the
participant agrees to allow his or her study physician to recontact the participant for the purpose
of obtaining consent for additional safety evaluations, and subsequent disease-related treatments,
if needed. 
The participant will be given sufficient time to read the ICF and the opportunity to ask questions.
After this explanation and before entry into the study, consent should be appropriately recorded
by means of the participant's personally dated signature. After having obtained the consent, a copy
of the ICF must be given to the participant.
Participants who are rescreened are required to sign a new ICF.

 
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If the participant is unable to read or write, an impartial witness should be present for the entire
informed consent process (which includes reading and explaining all written information) and
should personally date and sign the ICF after the oral consent of the participant is obtained.
DATA PROTECTION
Privacy of Personal Data
The collection and processing of personal data from participants enrolled in this study will be
limited to those data that are necessary to fulfill the objectives of the study.
These data must be collected and processed with adequate precautions to ensure confidentiality
and compliance with applicable data privacy protection laws and regulations. Appropriate
technical and organizational measures to protect the personal data against unauthorized disclosures
or access, accidental or unlawful destruction, or accidental loss or alteration must be put in place.
Sponsor personnel whose responsibilities require access to personal data agree to keep the identity
of participants confidential.
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 research is not conducted under standards appropriate for the return of data to
participants. In addition, the sponsor cannot make decisions as to the significance of any findings
resulting from exploratory research. Therefore, exploratory research data will not be returned to
participants or investigators, unless required by law or local regulations. Privacy and
confidentiality of data generated in the future on stored samples will be protected by the same
standards applicable to all other clinical data.
COMMITTEES STRUCTURE
No data monitoring committee is employed in this study.
PUBLICATION POLICY/DISSEMINATION OF CLINICAL STUDY DATA
All information, including but not limited to information regarding guselkumab or the sponsor's
operations (eg, patent application, formulas, manufacturing processes, basic scientific data, prior
clinical data, formulation information) supplied by the sponsor to the investigator and not
previously published, and any data, including exploratory research data, generated as a result of
this study, are considered confidential and remain the sole property of the sponsor. The investigator

 
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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 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 exploratory
analyses performed after the Clinical Study Report has been issued will be reported in a separate
report and will not require a revision of the Clinical Study Report. 
Study participant identifiers will not be used in publication of results. Any work created in
connection with performance of the study and contained in the data that can benefit from copyright
protection (except any publication by the investigator as provided for below) shall be the property
of the sponsor as author and owner of copyright in such work.
Consistent with Good Publication Practices and International Committee of Medical Journal
Editors (ICMJE) guidelines, the sponsor shall have the right to publish such primary (multicenter)
data and information without approval from the investigator. The investigator has the right to
publish study site-specific data after the primary data are published. If an investigator wishes to
publish information from the study, a copy of the manuscript must be provided to the sponsor for
review at least 60 days before submission for publication or presentation. Expedited reviews will
be arranged for abstracts, poster presentations, or other materials. If requested by the sponsor in
writing, the investigator will withhold such publication for up to an additional 60 days to allow for
filing of a patent application. In the event that issues arise regarding scientific integrity or
regulatory compliance, the sponsor will review these issues with the investigator. The sponsor will
not mandate modifications to scientific content and does not have the right to suppress information.
For multicenter study designs and 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 ICMJE Recommendations
for the Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals, which
state that the named authors must have made a significant contribution to the conception or design
of the work; or the acquisition, analysis, or interpretation of the data for the work; and drafted the
work or revised it critically for important intellectual content; and given final approval of the
version to be published; and agreed to be accountable for all aspects of the work in ensuring that

 
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questions related to the accuracy or integrity of any part of the work are appropriately investigated
and resolved.
Registration of Clinical Studies and Disclosure of Results
The sponsor will register and disclose the existence of and the results of clinical studies as required
by law. The disclosure of the final study results will be performed after the end of study in order
to ensure the statistical analyses are relevant.
DATA QUALITY ASSURANCE
Data Quality Assurance/Quality Control
Steps to be taken to ensure the accuracy and reliability of data include the selection of qualified
investigators and appropriate study sites, review of protocol procedures with the investigator and
study-site personnel before the study, periodic monitoring visits by the sponsor, and direct
transmission of clinical laboratory data from a central laboratory into the sponsor's data base.
Written instructions will be provided for collection, handling, storage, and shipment of samples. 
Guidelines for eCRF completion will be provided and reviewed with study-site personnel before
the start of the study. 
The sponsor will review eCRF for accuracy and completeness during on-site monitoring visits and
after transmission to the sponsor; any discrepancies will be resolved with the investigator or
designee, as appropriate. After upload of the data into the study database they will be verified for
accuracy and consistency with the data sources. 
CASE REPORT FORM COMPLETION
Case report forms are prepared and provided by the sponsor for each participant in electronic
format. All data relating to the study must be recorded in eCRF. All eCRF entries, corrections, and
alterations must be made by the investigator or authorized study-site personnel. The investigator
must verify that all data entries in the eCRF are accurate and correct.
The study data will be transcribed by study-site personnel from the source documents onto an
eCRF, if applicable.  Study-specific data will be transmitted in a secure manner to the sponsor.
Worksheets may be used for the capture of some data to facilitate completion of the eCRF. Any
such worksheets will become part of the participant's source documents. Data must be entered into
eCRF in English. The eCRF must be completed as soon as possible after a participant visit and the
forms should be available for review at the next scheduled monitoring visit.
If necessary, queries will be generated in the electronic data capture (eDC) tool. If corrections to
a eCRF are needed after the initial entry into the eCRF, this can be done in either of the following
ways:
 
Investigator and study-site personnel can make corrections in the eDC tool at their own
initiative or as a response to an auto query (generated by the eDC tool).

 
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 
Sponsor or sponsor delegate can generate a query for resolution by the investigator and study-
site personnel.
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 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.
MONITORING
The sponsor will use a combination of monitoring techniques central, remote, or on-site monitoring
to monitor this study.
The sponsor will perform on-site monitoring visits as frequently as necessary. The monitor will
record dates of the visits in a study site visit log that will be kept at the study site. The first
postinitiation visit will be made as soon as possible after enrollment has begun. At these visits, the
monitor will compare the data entered into the eCRF with the source documents

 
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(eg, hospital/clinic/physician’s office medical records). The nature and location of all source
documents will be identified to ensure that all sources of original data required to complete the
eCRF are known to the sponsor and study-site personnel and are accessible for verification by the
sponsor study-site contact. If electronic records are maintained at the study site, the method of
verification must be discussed with the study-site personnel. 
Direct access to source documents (medical records) must be allowed for the purpose of verifying
that the recorded data are consistent with the original source data. Findings from this review will
be discussed with the study-site personnel. The sponsor expects that, during monitoring visits, the
relevant study-site personnel will be available, the source documents will be accessible, and a
suitable environment will be provided for review of study-related documents. The monitor will
meet with the investigator on a regular basis during the study to provide feedback on the study
conduct.
In addition to on-site monitoring visits, remote contacts can occur. It is expected that during these
remote contacts, study-site personnel will be available to provide an update on the progress of the
study at the site.
Central monitoring will take place for data identified by the sponsor as requiring central review.
ON-SITE AUDITS
Representatives of the sponsor's clinical quality assurance department may visit the study site at
any time during or after completion of the study to conduct an audit of the study in compliance
with regulatory guidelines and company policy. These audits will require access to all study
records, including source documents, for inspection. Participant privacy must, however, be
respected. The investigator and study-site personnel are responsible for being present and available
for consultation during routinely scheduled study-site audit visits conducted by the sponsor or its
designees. 
Similar auditing procedures may also be conducted by agents of any regulatory body, either as part
of a national GCP compliance program or to review the results of this study in support of a
regulatory submission. The investigator should immediately notify the sponsor if he or she has
been contacted by a regulatory agency concerning an upcoming inspection.
RECORD RETENTION
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all eCRF
and all source documents that support the data collected from each participant, as well as all study
documents as specified in ICH/GCP Section 8, Essential Documents for the Conduct of a Clinical
Trial, and all study documents as specified by the applicable regulatory requirement(s). The
investigator/institution will take measures to prevent accidental or premature destruction of these
documents.
Essential documents must be retained until at least 2 years after the last approval of a marketing
application in an ICH region and until there are no pending or contemplated marketing applications
in an ICH region or until at least 2 years have elapsed since the formal discontinuation of clinical

 
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development of the investigational product. These documents will be retained for a longer period
if required by the applicable regulatory requirements or by an agreement with the sponsor. It is the
responsibility of the sponsor to inform the investigator/institution as to when these documents no
longer need to be retained.
If the responsible investigator retires, relocates, or for other reasons withdraws from the
responsibility of keeping the study records, custody must be transferred to a person who will accept
the responsibility. The sponsor must be notified in writing of the name and address of the new
custodian. Under no circumstance shall the investigator relocate or dispose of any study documents
before having obtained written approval from the sponsor.
If it becomes necessary for the sponsor or the appropriate regulatory authority to review any
documentation relating to this study, the investigator/institution must permit access to such reports.
STUDY AND SITE START AND CLOSURE
First Act of Recruitment
The first site open is considered the first act of recruitment and it becomes the study start date.
Study Termination
The sponsor reserves the right to close the study site or terminate the study at any time for any
reason at the sole discretion of the sponsor. Study sites will be closed upon study completion. A
study site is considered closed when all required documents and study supplies have been collected
and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable cause and
sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or investigator may include but are not
limited to:
 
Failure of the investigator to comply with the protocol, the requirements of the IEC/IRB or
local health authorities, the sponsor's procedures, or GCP guidelines
 
Inadequate recruitment of participants by the investigator
 
Discontinuation of further study intervention development

 
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10.4. 
Appendix 4: Adverse Events: Definitions and Procedures for Recording,
Evaluating, Follow-up, and Reporting
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 noninvestigational) 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 noninvestigational) product, whether or not related
to that medicinal (investigational or noninvestigational) product. (Definition per International
Conference on Harmonisation [ICH])
This includes any occurrence that is new in onset or aggravated in severity or frequency from the
baseline condition, or abnormal results of diagnostic procedures, including laboratory test
abnormalities.
Note: The sponsor collects 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).
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*
*Medical and scientific judgment should be exercised in deciding whether expedited reporting is
also appropriate in other situations, such as important medical events that may not be immediately
life threatening or result in death or hospitalization but may jeopardize the participant or may
require intervention to prevent one of the other outcomes listed in the definition above. These
should usually be considered serious.
If a serious and unexpected adverse event occurs for which there is evidence suggesting a causal
relationship between the study intervention and the event (eg, death from anaphylaxis), the event

 
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must be reported as a serious and unexpected suspected adverse reaction even if it is a component
of the study endpoint (eg, all-cause mortality). 
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, the expectedness of an adverse event will
be determined by whether or not it is listed in the IB. 
ATTRIBUTION DEFINITIONS
Assessment of Causality
The causal relationship to study treatment is determined by the Investigator. The following
selection should be used to assess all adverse events (AE).
Related
There is a reasonable causal relationship between study treatment administration and the AE.
Not Related
There is not a reasonable causal relationship between study treatment administration and the AE.
The term "reasonable causal relationship" means there is evidence to support a causal relationship.
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).
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

 
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 
Accidental or occupational exposure to a sponsor study intervention
 
Any failure of expected pharmacologic action (ie, lack of effect) of a sponsor study
intervention
 
Medication error, intercepted medication error, or potential medication error involving a
Johnson & Johnson medicinal product (with or without patient exposure to the Johnson &
Johnson medicinal product, eg, product name confusion, product label confusion, intercepted
prescribing or dispensing errors)
 
Exposure to a sponsor study intervention from breastfeeding
Special reporting situations should be recorded in the eCRF. 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.
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 name and 24-hour contact telephone number (for medical personnel only)
 
Site number
 
Participant number
 
Any other information that is required to do an emergency breaking of the blind
Serious Adverse Events
All 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:

 
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 
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)
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, the hospitalization for
device assisted enteroscopy at screening, and where the underlying condition for which the
hospitalization was planned has not worsened, will not be considered SAE. 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, whether or not the event is expected or associated
with the study intervention, is considered a serious adverse event.
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 ’Protocol Supplementary
Information, which will be provided as a separate document.
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, or reliability of a product, including its labeling or package integrity. A PQC may have
an impact on the safety and efficacy of the product. 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.

 
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Procedures
All initial PQCs must be reported to the sponsor by the study-site personnel within 24 hours after
being made aware of the event.
If the defect is combined with a serious adverse event, the study-site personnel must report the
PQC to the sponsor 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). 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 Protocol Supplementary Information, which will
be provided as a separate document.

 
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10.5. 
Appendix 5: 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 4 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 (FSH) level (>40 IU/L or mIU/mL) in the
postmenopausal range may be used to confirm a postmenopausal state in women not using
hormonal contraception or hormonal replacement therapy (HRT), however in the absence of
12 months 
of 
amenorrhea, 
a 
single 
FSH 
measurement 
is 
insufficient.
If there is a question about menopausal status in women on HRT, the woman will be required
to use one of the nonestrogen-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.
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.
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.
 Intrauterine device (IUD)

 
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 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
 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 condom with or without spermicide
 Diaphragm
 A combination of male condom with diaphragm
 Periodic abstinence (calendar, symptothermal, postovulation methods)
 Withdrawal (coitus-interruptus)
 Lactational amenorrhea method (LAM)
a) Typical use failure rates may differ from those when used consistently and correctly.
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. 

 
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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 alkaline phosphatase (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.

 
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10.7. 
Appendix 7: Definitions of Inadequate Response to or Intolerance of
Corticosteroids or 6-MP/AZA and Corticosteroid Dependence 
CORTICOSTEROIDS
Participants have failed to respond to corticosteroids if they have had evidence of an initial inadequate
response, recurrent disease, or a relapse despite receiving at least 0.75 mg/kg/day or ≥40 mg/day of
prednisone (or corticosteroid equivalent, given orally or intravenously) for 2 weeks; or ≥9 mg/day of
budesonide 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 CD. 
OR
 
They have a medical condition that precludes the use of corticosteroids as a treatment for CD.
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) or AZATHIOPRINE (AZA)
Participants have failed to respond to 6-MP or AZA if they have had evidence of an initial inadequate
response, recurrent disease, or a relapse despite receiving: 
 
At least 3 months of therapy with 1 mg/kg/day of 6-MP or 2 mg/kg/day of AZA
OR
 
A lower dosage of 6-MP or AZA when country 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 or AZA 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. 
Participants are intolerant of 6-MP or AZA if: 
 
They have developed clinically significant adverse events (eg, pancreatitis, arthritis accompanied by
high fever and/or rash, leukopenia, or persistently elevated liver enzymes) unresponsive to dose
reduction that, in the judgment of the investigator, precluded the use of 6-MP or AZA to treat CD
within the past 5 years.
OR
 
They have a medical condition that precludes the use of 6-MP or AZA.

 
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10.8. 
Appendix 8: Definition of Inadequate Initial Response, Loss of Response,
or Intolerance to TNF Antagonist Therapies (Infliximab or Adalimumab)
Vedolizumab
The criteria for inadequate initial response, response followed by loss of response, or intolerance to
infliximab, adalimumab, or vedolizumab are described in items I, II, and III, below.
1. 
Inadequate initial response to current or prior therapy with infliximab, adalimumab or
vedolizumab (primary nonresponse) 
Eligible participants must satisfy criteria a, b, and c.
a. 
Have received induction doses of:
1) Infliximab (2 or 3 doses of  5 mg/kg)
or
2) Adalimumab (at a dose of 160 mg followed by a dose  80 mg or at a dose of 80 mg followed
by a dose  40 mg)
or
3) Vedolizumab (3 or 4 doses of 300 mg)
AND
b. 
Did not initially respond to these induction doses of infliximab, adalimumab or vedolizumab as
evidenced by the presence of at least 1 of the following signs or symptoms related to persistence
of CD, 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 CD
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 CD must have occurred 2 weeks after receiving the last induction
dose of infliximab, adalimumab 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 or vedolizumab therapy. This benchmark
acknowledges that the CDAI is not routinely recorded in clinical practice.
It is acknowledged that previous treatment decisions could have been made based on evaluation
of other measures that may be indicative of worsening disease (eg, elevations of inflammatory
markers including but not limited to CRP or fecal calprotectin,  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 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.
AND
c. 
Have documentation available to the investigator that meets the following 2 requirements:

 
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1) Provide the dates and doses of the failed infliximab, adalimumab or vedolizumab induction
therapy.
2) Documents that the participant had persistence of disease activity following infliximab,
adalimumab 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 or vedolizumab (secondary nonresponse)
Eligible participants must satisfy criteria a, b, c, d.
a. 
Initially responded to induction therapy
AND
b. 
Have received at least 2 maintenance doses of:
1) Infliximab (at a dose of 5 mg/kg)
or
2) Adalimumab (at a dose of 40 mg)
or
3) Vedolizumab (at a dose of 300 mg)
AND
c. 
Have or had at least 1 of the following signs or symptoms related to recurrence of CD, 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 CD
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 CD must have occurred 2 weeks after receiving the last
maintenance dose of infliximab, adalimumab 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 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 or vedolizumab
maintenance therapy.
2) Documents that the participant had recurrence of disease activity despite infliximab,
adalimumab or vedolizumab maintenance therapy.

 
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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).
3. 
Current or prior intolerance to therapy with infliximab, adalimumab 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 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 or
vedolizumab
AND
c) 
Was considered related to the infusion/administration of infliximab, adalimumab or
vedolizumab.
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

 
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AND
b) Occurred >24 hours and <15 days after infusion/administration of infliximab,
adalimumab or vedolizumab
AND
c) 
Was considered related to the infusion/administration of infliximab, adalimumab or
vedolizumab.
3) 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 SC injection of adalimumab
AND
c) 
Was considered related to the injection.
b. 
Have documentation available to the investigator that meets the following 2 requirements:
1) Provides the date of discontinuation of infliximab, adalimumab or vedolizumab. 
2) Documents that the participant had intolerance to infliximab, adalimumab 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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10.9. 
Appendix 9: Definition of Minimal Exposure to Ustekinumab
Participants who have had limited 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 (~6 mg/kg IV)
b. 
No more than one maintenance dose of ustekinumab (90 mg SC) 8 weeks after the single
induction dose
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 CD
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 CD; AND
b. 
Provide the date of discontinuation of ustekinumab for the treatment of CD; 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 CD 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 CD.  Participants who meet these criteria are ineligible to enter this protocol.
Evidence of inadequate response to ustekinumab that had precluded continuation of previous
treatment with ustekinumab for CD:
 
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 CD
 
Lack of improvement or worsening in a draining fistula or development of a new draining fistula

 
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 
Lack of improvement or worsening in rectal bleeding
 
Initiation or increase in antidiarrheal medication
These signs and symptoms of CD 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 CD:
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)
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

 
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 
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 SC injection of ustekinumab.
 
AND
c. 
Was considered related to the SC injection of ustekinumab.

 
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10.10. Appendix 10: Crohn’s Disease Activity Index
CCI

 
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10.12. Appendix 12: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located
directly before the Table of Contents (TOC).

 
CNTO1959 (guselkumab)  
Clinical Protocol CNTO1959CRD3003 Amendment 1 
CONFIDENTIAL – FOIA Exemptions Apply in U.S.  
 
 
103
Status: Approved,  Date:  11 December 2020
11. 
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Cooperative Crohn’s Disease Study. Gastroenterology. 1976;70(3):439-444
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Daperno M, D'Haens G, Van Assche G, et al. Development and validation of a new, simplified endoscopic
activity score for Crohn's disease: the SES-CD. Gastrointest Endosc. 2004; 60(4):505-512.
4. 
Food and Drug Administration. Guidance for Industry Drug-Induced Liver Injury: Premarketing Clinical
Evaluation. July 2009 Drug Safety. https://www.fda.gov/media/116737/download. Accessed 10 December
2019.
5. 
Investigator's Brochure: CNTO1959 (guselkumab) Edition 10. Janssen &Janssen (17 December 2019).
6. 
Matsuoka K, Kobayashi T, Ueno F, Matsui T, Hirai F, Inoue N, et al. Evidence-based clinical practice
guidelines for inflammatory bowel disease. J Gastroenterol. 2018;53:305–353.
7. 
Mowat AM, Agace WW. Regional specialization within the intestinal immune system. Nature reviews.
2014;14(10):667-685.
8. 
Mundt, JC, Greist, JH, Jefferson, JW, et al. Prediction of suicidal behavior in clinical research by lifetime
suicidal ideation and behavior ascertained by the electronic Columbia-Suicide Severity Rating Scale. J Clin
Psych. 2013; 74(9):887-893.
9. 
Murate K, Nakamura M, Fujishiro M. A Case Where Administration of Ustekinumab Maintained the Intestinal
Patency After Balloon Dilation for Small Intestinal Stenosis Caused by Crohn’s Disease. Inflamm Bowel Dis.
November 2019;25(Number II):e140.
10. Posner, K, Brown, GK, Stanley, B, et al. The Columbia-Suicide Severity Rating Scale: Initial validity and
internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry.
2011;168(12):1266-1277.
11. Rabeneck L, Paszat LF, Hilsden RJ, et al. Bleeding and perforation after outpatient colonoscopy and their risk
factors in usual clinical practice. Gastroenterology. 2008;135(6):1899-1906.
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assisted enteroscopy: Technical matters, indication, limits and complications. World J Gastrointest Endosc.
2012;4(10):453-461.
13. Takenaka K, Fujii T, Suzuki K, Shimizu H, Motobayashi M, Hibiya S, et al. Small Bowel Healing Detected by
Endoscopy in Patients With Crohn’s Disease After Treatment With Antibodies Against Tumor Necrosis
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14. Takenaka K, Ohtsuka K, Kitazume Y, Matsuoka K, Nagahori M, Fujii T, et al. Utility of Magnetic Resonance
Enterography For Small Bowel Endoscopic Healing in Patients With Crohn’s Disease Am J Gastroenterol.
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15. Takenaka K, Ohtsuka K, Kitazume Y, Nagahori M, Fujii T, Saito E, et al. Correlation of the Endoscopic and
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CNTO1959 (guselkumab)  
Clinical Protocol CNTO1959CRD3003 Amendment 1 
CONFIDENTIAL – FOIA Exemptions Apply in U.S.  
 
 
104
Status: Approved,  Date:  11 December 2020
INVESTIGATOR AGREEMENT
I have read this protocol and agree that it contains all necessary details for carrying out this study. I will
conduct the study as outlined herein and will complete the study within the time designated.
I will provide copies of the protocol and all pertinent information to all individuals responsible to me who
assist in the conduct of this study. I will discuss this material with them to ensure that they are fully informed
regarding the study intervention, the conduct of the study, and the obligations of confidentiality.
Principal (Site) Investigator: 
Name (typed or printed): 
Institution and Address: 
Telephone Number: 
Signature: 
 
Date: 
  
 
(Day Month Year)
 
Sponsor's Responsible Medical Officer: 
Name (typed or printed): 
Institution: 
Janssen Pharmaceutical K.K.
Signature: 
electronic signature appended at the end of the protocol
Date: 
  
 
(Day Month Year)
 
Note: If the address or telephone number of the investigator changes during the course of the study, written
notification will be provided by the investigator to the sponsor, and a protocol amendment will not be required.
PPD

Signature
User 
Date 
Reason
10-Dec-2020
23:49:25
(GMT)
Document Approval
PPD