Conditions: Colitis, Ulcerative
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 214
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate the clinical efficacy and safety of combination therapy with guselkumab and golimumab in participants with moderately to severely active ulcerative colitis (UC).

Detailed description:

Arms:
arm 1: Participants will receive guselkumab Dose 1 as intravenous (IV) infusion and Dose 2 as subcutaneous (SC) injection; and golimumab Dose 1 and Dose 2 as SC injection and placebo to maintain the blind. arm 2: Participants will receive guselkumab Dose 1 as IV infusion, Dose 2 as SC injection and placebo to maintain the blind. arm 3: Participants will receive golimumab Dose 1 and Dose 2 as SC injection and placebo to maintain the blind.

Interventions: intervention 1: Guselkumab Dose 1 intervention 2: Guselkumab Dose 2 intervention 3: Golimumab Dose 1 intervention 4: Golimumab Dose 2 intervention 5: Placebo
Intervention descriptions: intervention 1: Guselkumab Dose 1 will be administered as IV infusion. intervention 2: Guselkumab Dose 2 will be administered as SC injection. intervention 3: Golimumab Dose 1 will be administered as SC injection. intervention 4: Golimumab Dose 2 will be administered as SC injection. intervention 5: Placebo will be administered.

Protocol document:
Prot_000.pdf: 
1
Status: Approved,  Date: 7 March 2019
Janssen Research & Development *
Clinical Protocol
Protocol Title
A Phase 2a Randomized, Double-blind, Active-controlled, Parallel-group, Multicenter, 
Proof-of-concept Clinical Study to Evaluate the Efficacy and Safety of Combination 
Therapy With Guselkumab and Golimumab in Participants With Moderately to Severely 
Active Ulcerative Colitis  
VEGA
Short Title
A Proof-of-concept Study of the Efficacy and Safety of Combination Therapy With Guselkumab
and Golimumab in Participants With Moderately to Severely Active Ulcerative Colitis
Protocol CNTO1959UCO2002; Phase 2a
Amendment 2
TREMFYA®  (guselkumab)
SIMPONI®  (golimumab)
*Janssen Research & Development is a global organization that operates through different legal entities in
various countries. Therefore, the legal entity acting as the sponsor for Janssen Research & Development
studies may vary, such as, but not limited to Janssen Biotech, Inc.; Janssen Products, LP; Janssen
Biologics, BV; Janssen-Cilag International NV; Janssen, Inc; Janssen Pharmaceutica NV; Janssen
Sciences Ireland UC; or Janssen Research & Development, LLC. The term “sponsor” is used throughout
the protocol to represent these various legal entities; the sponsor is identified on the Contact Information
page that accompanies the protocol.
US sites of this study will be conducted under US Food & Drug Administration IND regulations 
(21 CFR Part 312).
EudraCT NUMBER:          2018-001510-15
Status:
Approved
Date:
7 March 2019
Prepared by:
Janssen Research & Development, LLC  
EDMS number:
EDMS-ERI-155505739, 3.0
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory 
requirements. 
Confidentiality Statement
The information in this document contains trade secrets and commercial information that are privileged or confidential and 
may not be disclosed unless such disclosure is required by applicable law or regulations. In any event, persons to whom the 
information is disclosed must be informed that the information is privileged or confidential and may not be further disclosed 
by them. These restrictions on disclosure will apply equally to all future information supplied to you that is indicated as 
privileged or confidential.
NCT03662542


TREMFYA (guselkumab)
SIMPONI  (golimumab)
Clinical Protocol CNTO1959UCO2002 Amendment 2
2
Approved, Date: 7 March 2019
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document
Date
Amendment 2
07 March 2019
Amendment 1
24 Sep 2018
Original Protocol
21 June 2018
Amendment 2- 07 March 2019
Overall Rationale for the Amendment: The overall reason for the amendment is to update the 
procedure for single cell isolation to be collected from all participants during mucosal biopsy sample 
collection and to collect peripheral blood mononuclear cells (PBMCs) from whole blood. Additional 
clarifications were made throughout the protocol based on feedback from health authorities, ethics 
committees, and investigative sites.
The changes to the protocol are outlined in the table below. Additions to the text are indicated by 
underline; deletion of text is shown in strikethrough. 
Section Number
and Name
Description of Change
Brief Rationale
1.3. Schedule of 
Activities
8.8.4 Mucosal 
Biopsy (RNA, 
Histology, and 
Single Cell 
Isolation)
The following footnote from Table 1 (footnote u.)
and from Table 2 (footnote l.) was modified: 
Mucosal biopsy samples will be collected from all 
participants during endoscopy for RNA expression 
analysis, and histologic assessment, and single cell 
isolation. Additional biopsy samples for single cell 
isolation will be collected from a subset of 
approximately 75 participants at pre defined study 
sites capable of performing biopsy collection 
procedure for single cell isolation.
Footnote v. on Table 1 was modified:
The screening biopsy samples for histology, RNA 
analyses, and single cell isolation (at selected study 
sites) will be collected from all participants during 
the screening endoscopy performed within 2 weeks 
of the baseline (W0) visit.
The section was modified as follows:
Mucosal biopsy samples will be collected from all 
participants during endoscopy at the times specified 
in the SoA for RNA expression analysis, and 
histologic assessment, and single cell isolation. Total 
RNA will be isolated and used for differential gene 
expression analyses to identify mRNA or microRNA 
expression patterns that are relevant to guselkumab 
or golimumab treatment and/or UC, and to evaluate 
markers that can predict therapeutic response. The 
biopsy samples collected will also be used for the 
The protocol was updated to collect
mucosal biopsy samples from all 
participants for single cell isolation. 


TREMFYA (guselkumab)
SIMPONI  (golimumab)
Clinical Protocol CNTO1959UCO2002 Amendment 2
3
Approved, Date: 7 March 2019
Section Number
and Name
Description of Change
Brief Rationale
histologic and immunohistochemical assessment of 
disease and healing. Additional biopsy samples will 
be collected from a subset of up to approximately 75 
participants at selected study sites capable of 
performing biopsy collection procedure for single 
cell isolation. Protein and gene expression will be 
measured at higher resolution in various immune cell 
populations isolated from these biopsy samples.
1.1. Synopsis
1.3. Schedule of 
Activities
1.3. Schedule of 
Activities; 10.1. 
Appendix 1: 
Abbreviations and 
Trademarks
4.2.2. DNA and 
Biomarker 
Collection
Peripheral blood mononuclear cells (PBMCs) was 
added to the subsection of “Pharmacodynamic and 
Biomarker Evaluations.”
Whole blood (PBMC) collection was added to the 
SoA under Pharmacodynamics and Biomarkers in 
Table 1 and Table 2. Whole blood (PBMCs) will be 
collected at screening, Week 4 (only those who 
consent to participate in the optional endoscopy and 
biopsy sub-study), and Week 12 during the 
combination phase and at Week 38 and the early 
termination visit during the monotherapy phase.
The following footnote from Table 1 (footnote w.) 
and Table 2 (footnote m.) was modified:
Serum biomarkers and whole blood RNA and
PBMCs will be measured in collected from all 
participants to evaluate the molecular effects of each 
study intervention in UC.
Footnote p. on Table 1 was modified:
Only those participants who consent to participate in 
the optional endoscopy and biopsy sub-study will 
undergo Week 4 endoscopy and mucosal biopsy 
collection and whole blood PBMC collection.
The following footnote was added to Table 1
(footnote cc.) and Table 2 (footnote q.):
Whole blood (PBMC) samples are to be collected 
ideally within ±2 days of the endoscopy visit.
The following abbreviation was added to Table 1 
and Table 2 of the SoA, and to the Abbreviation list 
in Appendix 1:
PBMC= peripheral blood mononuclear cell
The following was added as the second to last 
sentence in the bullet for Optional Week 4 
endoscopy and biopsy sub-study:
Whole blood (PBMCs) will also be collected. 
The protocol was updated to include 
procedures and timing for whole 
blood collection for PBMC isolation. 


TREMFYA (guselkumab)
SIMPONI  (golimumab)
Clinical Protocol CNTO1959UCO2002 Amendment 2
4
Approved, Date: 7 March 2019
Section Number
and Name
Description of Change
Brief Rationale
4.2.5 Study-Specific 
Ethical Design 
Considerations; 8. 
Study Assessments 
and Procedures
8.8.5 Whole blood 
(PBMCs)
The maximum total blood volume to be collected 
from each participant in the study was updated from 
approximately 310 mL to approximately 350 mL. 
Section 8.8.5 was added to describe the collection of 
whole blood (PBMCs) and the subsequent 
subsection was renumbered accordingly:
Whole blood samples will be collected from all 
participants as specified in the SoA. Peripheral blood 
mononuclear cells (PBMCs) will be isolated and 
used for single cell isolation. Protein and gene 
expression that are relevant to study intervention 
and/or UC will be measured at higher resolution in 
PBMCs isolated from whole blood. To match with 
single cell analysis in colonic biopsies, whole blood 
samples will also be obtained at Week 4 from 
participants who agree to participate in the optional 
endoscopy and biopsy sub-study.
1.1. Synopsis, 
Statistical Methods; 
9.4.2 Safety 
Analyses 
The first sentence in the subsection of “Safety 
Analyses” in the Synopsis and in section 9.4.2 was 
modified:
Safety data, including but not limited to, AEs, 
serious adverse events (SAEs), infections, serious 
infections, and changes in laboratory assessments,
and changes in vital signs will be summarized.
To clarify that vital signs will be 
collected as indicated on the SoA 
but will not be summarized. 
1.3. Schedule of 
Activities
The following footnote was added to the line item 
for “Injection-site evaluation” in both Table 1
(footnote bb.) and Table 2 (footnote p.):
An injection-site reaction is any adverse reaction at 
any SC study intervention injection site. Injection 
sites will be evaluated for reactions and any 
injection-site reaction should be recorded as an 
adverse event.
To clarify how injection-site 
reactions should be recorded if 
noted.  
4.2.3. Patient-
Reported Outcomes 
on Health-Related 
Quality of Life
The following sentence was added to the paragraph:
Patient-reported outcomes will only be collected in 
countries where translations of the evaluations are 
available.
Translations of the PRO evaluations 
are currently available in all 
participating countries. However, in 
the event that additional sites are 
needed in additional countries, it is 
possible that translations of the PRO 
evaluation may not be available. 
5.1. Inclusion 
Criteria; 
Appendix 2:
Definition of 
Inadequate 
Response to or 
Intolerance of 
Appendix 2, Definition of Inadequate Response to or 
Intolerance of Corticosteroids or AZA/6-MP and
Corticosteroid Dependence, was added to the 
protocol. The subsequent appendices were 
renumbered accordingly. 
Inclusion criterion #5 a., b., and c., remain the same 
This appendix was inadvertently not 
included in the prior version of the 
protocol. 


TREMFYA (guselkumab)
SIMPONI  (golimumab)
Clinical Protocol CNTO1959UCO2002 Amendment 2
5
Approved, Date: 7 March 2019
Section Number
and Name
Description of Change
Brief Rationale
Corticosteroids or 
AZA/6-MP and
Corticosteroid 
Dependence
but were updated to include the statement “as 
defined in Appendix 2 (Section 10.2)” for each. 
5.1. Inclusion 
Criteria
8.2.12.1 Initial 
Tuberculosis 
Evaluation
Inclusion Criterion #11 d. was modified:
Within 8 weeks prior to the first administration of 
study intervention, has a negative QuantiFERON®-
TB test result. For the purposes of this study, an 
indeterminate QuantiFERON® TB test result is 
exclusionary as outlined in Section 8.2.12. For a 
participant with an indeterminate QuantiFERON®-
TB test, the test may be repeated once. If the result is 
indeterminate on repeat testing, the participant is 
considered a screen failure as outlined in Section 
8.2.12.1.
The last sentence of the second paragraph was 
modified as follows:
For the purposes of this study, participants with an 
indeterminate QuantiFERON® TB test result are 
excluded. For a participant with an indeterminate 
QuantiFERON®-TB test, the test may be repeated 
once. If the result is indeterminate on repeat testing, 
the participant is considered a screen failure.
To clarify the retesting procedure for 
the QuantiFERON-TB test with 
respect to participant eligibility
during screening.
5.1. Inclusion 
Criteria
Inclusion Criterion #17 was modified: 
Be willing and able to adhere to all specified 
requirements, including but not limited to 
completion of required assessments, adherence to 
visit schedule, and compliance with the lifestyle 
restrictions as specified in this protocol.
Added specific examples of what 
may be considered critical barriers 
for a potential study participant to be 
eligible for enrollment.
5.1. Inclusion 
Criteria
Inclusion Criterion #20 was added:
Each participant must sign a separate ICF if he or 
she agrees to participate in the optional Week 4 
endoscopy and biopsy sub-study. In regions where 
the legal age of consent is older than 18 years, 
informed consent must be obtained from and signed 
by both the participant and his or her legally 
acceptable representative. Refusal to give consent 
for the optional Week 4 endoscopy and biopsy sub-
study does not exclude a participant from 
participation in the study.
The inclusion criterion for 
participants to sign a separate ICF 
for the optional Week 4 endoscopy 
and biopsy sub-study was 
inadvertently not included in the 
prior version of the protocol.
5.2. Exclusion 
Criteria
Exclusion Criterion #11 was modified:
Has a stool culture or other examination positive for 
an enteric pathogen, including Clostridium difficile
toxin, in the previous within 4 months before the 
first administration of study intervention, unless a 
repeat examination is negative and there are no signs 
To clarify the timeframe of a 
positive test for an enteric pathogen 
is within 4 months before the first 
administration of study intervention,
which aligns with footnote l. in 
Table 1 of the SoA. 


TREMFYA (guselkumab)
SIMPONI  (golimumab)
Clinical Protocol CNTO1959UCO2002 Amendment 2
6
Approved, Date: 7 March 2019
Section Number
and Name
Description of Change
Brief Rationale
of ongoing infection with that pathogen.
5.2. Exclusion 
Criteria
Exclusion Criterion #31 was deleted:
31. Has previously undergone allergy 
immunotherapy for prevention of anaphylactic 
reactions (eg, venom immunotherapy).
This exclusion criterion was 
included in the original protocol in 
error and is not relevant for 
guselkumab or golimumab.
7.1. Discontinuation 
of Study 
Intervention
The following sentences were removed from 
Criterion #7 under the section entitled "A 
participant's study treatment must be discontinued
under the following conditions:”
The participant has a serious adverse reaction that is 
related to an injection or an infusion, including an 
injection-site or infusion reaction, resulting in 
bronchospasm with wheezing and/or dyspnea that 
requires ventilatory support OR that results in 
symptomatic hypotension with a decrease in systolic 
blood pressure >40 mm Hg or blood pressure <90/60 
mm Hg. This may include events of National Cancer 
Institute Common Terminology Criteria for Adverse 
Events (NCI CTCAE) toxicity grade ≥3. In general, 
discontinuation of study intervention administration 
must be considered for participants who develop a 
severe injection site or infusion reaction.
The first statement on NCI-CTCAE 
criteria was removed because 
grading of adverse events is not 
being performed in this study.
The second statement on injection 
site reactions was removed because 
injection site or infusion reactions 
are not mandatory discontinuation 
requirements.
7.1. Discontinuation 
of Study 
Intervention
The following criterion was relocated from Criterion 
#4 in the section entitled “Discontinuation of a 
participant’s study intervention must be strongly 
considered under the following conditions” to 
become Criterion #14 in the section entitled "A 
participant's study treatment must be discontinued
under the following conditions":
The investigator believes that for safety or 
tolerability reasons, it is in the best interest of the 
participant to discontinue study intervention.
Relocation of the specified statement 
is necessary because the criterion is 
clearly indicative of the need to 
mandate discontinuation.
7.1. Discontinuation 
of Study 
Intervention
The following note was added to Criterion 2 under 
“Discontinuation of a participant’s study 
intervention must be strongly considered under the 
following conditions”:
The participant develops a serious infection,
including but not limited to sepsis or pneumonia.
Note: Any serious infection should be discussed 
with the medical monitor or designee, and study 
intervention should be withheld until the clinical 
assessment is complete.
To clarify that study intervention 
should be withheld until a clinical 
assessment is complete for any 
serious infection. 
7.1. Discontinuation 
of Study 
Intervention
The following criterion was relocated from #7 in the 
section entitled "A participant's study treatment must 
be discontinued under the following conditions" to 
become criterion #6 in the section entitled 
“Discontinuation of a participant’s study 
Relocation of the specified criterion 
was necessary since injection site or 
infusion reactions are not mandatory 
discontinuation requirements.


TREMFYA (guselkumab)
SIMPONI  (golimumab)
Clinical Protocol CNTO1959UCO2002 Amendment 2
7
Approved, Date: 7 March 2019
Section Number
and Name
Description of Change
Brief Rationale
intervention must be strongly considered under the 
following conditions:”
The participant develops a severe injection-site or 
infusion reaction.
8. Study 
Assessments and 
Procedures
The following sentence was added to the second 
paragraph of the subsection “Screening Phase”:
Participants will be instructed to complete a daily 
Mayo diary for 7 days immediately before each visit 
and bring them to every visit for data collection and 
review by the investigator/study coordinator.
The following sentence was added to the third 
paragraph of the subsection “Screening Phase”:
Participants will complete the BSFS as a daily diary 
entry from Week 0 through Week 12.
The fourth paragraph of the subsection “Screening 
Phase” was deleted:
Participants will be instructed to complete Mayo and 
BSFS diaries 7 days immediately before each visit 
and bring them to every visit for data collection and 
review by the investigator/study coordinator. Bristol 
Stool Form Scale diaries are required only during the 
combination comparison phase of the study (ie, 
through Week 12). 
To clarify that the diary for the 
Bristol Stool Form Scale will only 
need to be completed from Week 0 
through Week 12. 
8. Study 
Assessments and 
Procedures
The following sentence was added to the fifth 
paragraph of the subsection “Screening Phase”:
Histology results from the polypectomy must be 
available to confirm absence of colonic mucosal 
dysplasia before first administration of study 
intervention (Section 5.1, Exclusion Criterion #8).
To clarify Exclusion Criterion #8 
that absence of colonic mucosal 
dysplasia must be confirmed before 
first administration of study 
intervention. 
8.1.6. PROMIS-29
The following sentences were added to the 
paragraph: 
Norm-based scores have been calculated for each 
domain on the PROMIS measures, with a score of 
50 representing the mean or average of the reference 
population. On symptom-oriented domains of 
PROMIS-29 (anxiety, depression, fatigue, pain 
interference, and sleep disturbance), higher scores 
represent worse symptomatology. On the function-
oriented domains (physical functioning and social 
role), higher scores represent better functioning.
To clarify how the PROMIS-29 is 
scored and how the scores should be 
interpreted.
8.2.9 
Hypersensitivity 
Reactions
The third paragraph was modified:
Participants who experience serious adverse 
reactions related to an injection or infusion should
The text was updated to align with 
the changes made to the 
discontinuation criteria regarding 
hypersensitivity reactions in 


TREMFYA (guselkumab)
SIMPONI  (golimumab)
Clinical Protocol CNTO1959UCO2002 Amendment 2
8
Approved, Date: 7 March 2019
Section Number
and Name
Description of Change
Brief Rationale
must strongly be considered to be discontinued from 
further study intervention administrations.
The fourth paragraph was modified:
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 or blood pressure <90/60 mm Hg 
will not be permitted to receive must be discontinued 
from additional study intervention administration 
(see Section 7).
The first sentence of the fifth paragraph was 
modified:
Participants who experience reactions suggestive of 
serum sickness (resulting in symptoms such as 
myalgia and/or arthralgia with fever and/or rash that 
are not representative of signs and symptoms of 
other recognized clinical syndromes) occurring 1 to 
14 days after administration of study intervention, 
should must be discontinued from further study 
intervention administration.
Section 7 and to clarify when study 
intervention must be discontinued or 
must be strongly considered to be 
discontinued for hypersensitivity
reactions.
8.3.5 Events of 
Special Interest
10.9 Appendix 9: 
Adverse Events: 
Definitions and 
procedures for 
Recording, 
Evaluating, Follow-
up, and Reporting
The first sentence of the section was modified as 
follows:
Any newly identified malignancy or case of active 
TB occurring after the first study intervention 
administration(s) in subjects participating in this 
clinical study must be reported by the investigator to 
the sponsor or designee within 24 hours after being 
made aware of the event, according to the 
procedures in Appendix 9 (Section 10.9), Adverse 
Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting for SAEs.
The following sentence was added as the first 
sentence to the subsection for “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.
To specify the time period in which 
investigators or site personnel must 
report an event of special interest 
and special reporting situations. 
Section 10.6, 
Appendix 6: 
Regulatory, Ethical, 
and Study Oversight 
Considerations
The subsection for “Investigator Responsibilities”
was revised as follows:
The investigator is responsible for ensuring that the 
study is performed in accordance with the protocol, 
current ICH guidelines on Good Clinical Practice 
(GCP), the latest version of the Declaration of 
Clarification to specify that 
investigators are required to comply 
with the principles of Declaration of 
Helsinki.


TREMFYA (guselkumab)
SIMPONI  (golimumab)
Clinical Protocol CNTO1959UCO2002 Amendment 2
9
Approved, Date: 7 March 2019
Section Number
and Name
Description of Change
Brief Rationale
Helsinki, and applicable regulatory and country-
specific requirements.
Throughout the 
protocol
Minor grammatical, formatting, or spelling changes 
were made.
Minor errors were noted.


TREMFYA (guselkumab)
SIMPONI  (golimumab)
Clinical Protocol CNTO1959UCO2002 Amendment 2
10
Approved, Date: 7 March 2019
TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................................... 2
TABLE OF CONTENTS ............................................................................................................................. 10
LIST OF IN-TEXT TABLES AND FIGURES.............................................................................................. 13
1.
PROTOCOL SUMMARY ................................................................................................................... 14
1.1.
Synopsis......................................................................................................................................... 14
1.2.
Schema .......................................................................................................................................... 19
1.3.
Schedule of Activities (SoA)........................................................................................................... 20
2.
INTRODUCTION................................................................................................................................ 28
2.1.
Study Rationale.............................................................................................................................. 28
2.1.1.
Rationale for Use of Guselkumab in Ulcerative Colitis............................................................... 29
2.1.1.1.
Nonclinical Evidence Implicating IL-23 as a Target in Ulcerative Colitis................................. 29
2.1.1.2.
Clinical Evidence Establishing Proof-of-Concept for IL-23 Targeted Therapy in 
Ulcerative Colitis...................................................................................................................... 29
2.1.2.
Rationale for Combined Use of Guselkumab and Golimumab in Ulcerative Colitis................... 30
2.2.
Background .................................................................................................................................... 31
2.2.1.
Nonclinical Development ............................................................................................................ 31
2.2.1.1.
Guselkumab............................................................................................................................. 31
2.2.1.2.
Golimumab .............................................................................................................................. 33
2.2.1.3.
Combination of Guselkumab and Golimumab......................................................................... 34
2.2.2.
Clinical Development.................................................................................................................. 34
2.2.2.1.
Current Status of Guselkumab Development.......................................................................... 34
2.2.2.2.
Current Status of Golimumab Development............................................................................ 35
2.3.
Benefit/Risk Assessment ............................................................................................................... 35
3.
OBJECTIVES AND ENDPOINTS ..................................................................................................... 37
3.1.
Objectives ...................................................................................................................................... 37
3.1.1.
Primary Objectives...................................................................................................................... 37
3.1.2.
Secondary Objectives................................................................................................................. 37
3.1.3.
Exploratory Objectives................................................................................................................ 38
3.2.
Endpoints ....................................................................................................................................... 38
3.2.1.
Primary Endpoint ........................................................................................................................ 38
3.2.2.
Major Secondary Endpoint ......................................................................................................... 38
3.2.3.
Other Efficacy Endpoints ............................................................................................................ 38
3.2.4.
Exploratory Endpoints................................................................................................................. 40
3.3.
Hypothesis ..................................................................................................................................... 40
4.
STUDY DESIGN ................................................................................................................................ 40
4.1.
Overall Design................................................................................................................................ 40
4.2.
Scientific Rationale for Study Design............................................................................................. 42
4.2.1.
Blinding, Control, Study Phase/Periods, Intervention Groups.................................................... 42
4.2.2.
DNA and Biomarker Collection................................................................................................... 42
4.2.3.
Patient-Reported Outcomes on Health-Related Quality of Life.................................................. 43
4.2.4.
Medical Resource Utilization Collection ..................................................................................... 43
4.2.5.
Study-Specific Ethical Design Considerations ........................................................................... 43
4.3.
Justification for Dose...................................................................................................................... 44
4.3.1.
Guselkumab................................................................................................................................ 44
4.3.2.
Golimumab ................................................................................................................................. 45
4.3.3.
Guselkumab and Golimumab Combination................................................................................ 45
4.4.
End of Study Definition................................................................................................................... 45
5.
STUDY POPULATION ...................................................................................................................... 45
5.1.
Inclusion Criteria ............................................................................................................................ 46


TREMFYA (guselkumab)
SIMPONI  (golimumab)
Clinical Protocol CNTO1959UCO2002 Amendment 2
11
Approved, Date: 7 March 2019
5.2.
Exclusion Criteria ........................................................................................................................... 50
5.3.
Lifestyle Considerations................................................................................................................. 54
5.4.
Screen Failures .............................................................................................................................. 55
6.
STUDY INTERVENTION................................................................................................................... 56
6.1.
Study Interventions Administered .................................................................................................. 56
6.2.
Preparation/Handling/Storage/Accountability ................................................................................ 56
6.2.1.
Accountability.............................................................................................................................. 57
6.3.
Measures to Minimize Bias: Randomization and Blinding............................................................. 57
6.4.
Study Intervention Compliance...................................................................................................... 59
6.5.
Concomitant Therapy..................................................................................................................... 60
6.5.1.
Concomitant Medications ........................................................................................................... 60
6.5.1.1.
Oral Corticosteroids Tapering.................................................................................................. 60
6.5.2.
Prohibited Concomitant Medications .......................................................................................... 61
6.6.
Dose Modification........................................................................................................................... 62
6.7.
Intervention After the End of the Study.......................................................................................... 62
7.
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ............................................................................................... 62
7.1.
Discontinuation of Study Intervention ............................................................................................ 62
7.2.
Participant Discontinuation/Withdrawal From the Study................................................................ 64
7.2.1.
Withdrawal From the Use of Research Samples ....................................................................... 65
7.3.
Lost to Follow-up............................................................................................................................ 65
8.
STUDY ASSESSMENTS AND PROCEDURES ............................................................................... 66
8.1.
Efficacy Assessments .................................................................................................................... 68
8.1.1.
Mayo Score and Partial Mayo Score.......................................................................................... 69
8.1.2.
Ulcerative Colitis Endoscopic Index of Severity (UCEIS)........................................................... 70
8.1.3.
C-Reactive Protein...................................................................................................................... 70
8.1.4.
Fecal Calprotectin....................................................................................................................... 70
8.1.5.
Inflammatory Bowel Disease Questionnaire............................................................................... 70
8.1.6.
PROMIS-29 ................................................................................................................................ 70
8.1.7.
PROMIS Fatigue 7-items Short Form......................................................................................... 71
8.1.8.
Bristol Stool Form Scale ............................................................................................................. 71
8.1.9.
Patient’s Global Impression of Change (PGIC) of Severity of Ulcerative Colitis........................ 71
8.2.
Safety Assessments....................................................................................................................... 71
8.2.1.
Physical Examination.................................................................................................................. 71
8.2.2.
Height and Weight ...................................................................................................................... 72
8.2.3.
Vital Signs................................................................................................................................... 72
8.2.4.
Electrocardiogram....................................................................................................................... 72
8.2.5.
Clinical Safety Laboratory Assessments .................................................................................... 72
8.2.6.
Columbia-Suicide Severity Rating Scale (C-SSRS)................................................................... 73
8.2.7.
Concomitant Medication Review ................................................................................................ 75
8.2.8.
Injection-Site Reactions.............................................................................................................. 75
8.2.9.
Hypersensitivity Reactions.......................................................................................................... 75
8.2.10.
Adverse Events Temporally Associated With Infusion............................................................... 75
8.2.11.
Infections .................................................................................................................................... 76
8.2.12.
Tuberculosis Evaluations............................................................................................................ 76
8.2.12.1.
Initial Tuberculosis Evaluation................................................................................................. 76
8.2.12.2.
Ongoing Tuberculosis Evaluation............................................................................................ 76
8.3.
Adverse Events and Serious Adverse Events ............................................................................... 77
8.3.1.
Time Period and Frequency for Collecting Adverse Event and Serious Adverse Event 
Information.................................................................................................................................. 78
8.3.2.
Follow-up of Adverse Events and Serious Adverse Events ....................................................... 78
8.3.3.
Regulatory Reporting Requirements for Serious Adverse Events ............................................. 78
8.3.4.
Pregnancy................................................................................................................................... 78
8.3.5.
Events of Special Interest........................................................................................................... 79
8.4.
Treatment of Overdose .................................................................................................................. 79


TREMFYA (guselkumab)
SIMPONI  (golimumab)
Clinical Protocol CNTO1959UCO2002 Amendment 2
12
Approved, Date: 7 March 2019
8.5.
Pharmacokinetics and Immunogenicity ......................................................................................... 79
8.5.1.
Evaluations ................................................................................................................................. 79
8.5.2.
Analytical Procedures................................................................................................................. 80
8.5.3.
Pharmacokinetic Parameters and Evaluations........................................................................... 80
8.5.4.
Immunogenicity Assessments .................................................................................................... 80
8.6.
Pharmacodynamics........................................................................................................................ 81
8.7.
Genetics ......................................................................................................................................... 81
8.8.
Biomarkers ..................................................................................................................................... 81
8.8.1.
Serum ......................................................................................................................................... 81
8.8.2.
Whole Blood (RNA) .................................................................................................................... 82
8.8.3.
Fecal ........................................................................................................................................... 82
8.8.4.
Mucosal Biopsy (RNA, Histology, and Single Cell Isolation)...................................................... 82
8.8.4.1.
Optional Week 4 Endoscopy and Biopsy Sub-study............................................................... 82
8.8.5.
Whole Blood (PBMCs)................................................................................................................ 82
8.8.6.
Negative Response Signature.................................................................................................... 82
8.9.
Medical Resource Utilization.......................................................................................................... 83
9.
STATISTICAL CONSIDERATIONS.................................................................................................. 83
9.1.
Statistical Hypotheses.................................................................................................................... 83
9.2.
Sample Size Determination ........................................................................................................... 84
9.3.
Populations for Analyses................................................................................................................ 84
9.4.
Statistical Analyses ........................................................................................................................ 85
9.4.1.
Efficacy Analyses........................................................................................................................ 85
9.4.1.1.
Population for Efficacy Analysis .............................................................................................. 85
9.4.1.2.
Primary Endpoint Analyses ..................................................................................................... 85
9.4.1.3.
Major Secondary Endpoint Analyses ...................................................................................... 85
9.4.1.4.
Other Efficacy Endpoint Analyses ........................................................................................... 86
9.4.1.5.
Exploratory Endpoint Analyses................................................................................................ 86
9.4.2.
Safety Analyses .......................................................................................................................... 86
9.4.3.
Other Analyses ........................................................................................................................... 87
9.5.
Interim Analysis.............................................................................................................................. 88
9.5.1.
Data Monitoring Committee........................................................................................................ 89
10.
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ............................ 90
10.1.
Appendix 1: Abbreviations and Trademarks.................................................................................. 90
10.2.
Appendix 2: Definition of Inadequate Response to or Intolerance of Corticosteroids or 
AZA/6 MP and Corticosteroid Dependence................................................................................... 92
10.3.
Appendix 3: Tuberculin Skin Testing ............................................................................................. 93
10.4.
Appendix 4: Contraceptive and Barrier Guidance and Collection of Pregnancy Information........ 94
10.5.
Appendix 5: Hepatitis B Virus (HBV) Screening with HBV DNA Testing....................................... 97
10.6.
Appendix 6: Regulatory, Ethical, and Study Oversight Considerations......................................... 98
REGULATORY AND ETHICAL CONSIDERATIONS .......................................................................... 98
FINANCIAL DISCLOSURE ................................................................................................................ 101
INFORMED CONSENT PROCESS ................................................................................................... 101
DATA PROTECTION ......................................................................................................................... 102
LONG-TERM RETENTION OF SAMPLES FOR ADDITIONAL FUTURE RESEARCH.................... 103
COMMITTEES STRUCTURE ............................................................................................................ 103
PUBLICATION POLICY/DISSEMINATION OF CLINICAL STUDY DATA......................................... 103
DATA QUALITY ASSURANCE .......................................................................................................... 105
CASE REPORT FORM COMPLETION ............................................................................................. 105
SOURCE DOCUMENTS .................................................................................................................... 106
MONITORING .................................................................................................................................... 106
ON-SITE AUDITS............................................................................................................................... 107
RECORD RETENTION ...................................................................................................................... 107
STUDY AND SITE CLOSURE ........................................................................................................... 108
10.7.
Appendix 7: Liver Safety: Suggested Actions and Follow-up Assessments................................ 109
10.8.
Appendix 8: Mayo Score.............................................................................................................. 110


TREMFYA (guselkumab)
SIMPONI  (golimumab)
Clinical Protocol CNTO1959UCO2002 Amendment 2
13
Approved, Date: 7 March 2019
10.9.
Appendix 9: Adverse Events: Definitions and Procedures for Recording, Evaluating, 
Follow-up, and Reporting............................................................................................................. 111
ADVERSE EVENT DEFINITIONS AND CLASSIFICATIONS............................................................ 111
ATTRIBUTION DEFINITIONS............................................................................................................ 112
SEVERITY CRITERIA ........................................................................................................................ 112
SPECIAL REPORTING SITUATIONS ............................................................................................... 113
PROCEDURES .................................................................................................................................. 113
CONTACTING SPONSOR REGARDING SAFETY........................................................................... 114
PRODUCT QUALITY COMPLAINT HANDLING................................................................................ 115
10.10.
Appendix 10: Anticipated Events ................................................................................................. 116
10.11.
Appendix 11: Protocol Amendment History ................................................................................. 117
11.
REFERENCES................................................................................................................................. 120
INVESTIGATOR AGREEMENT ............................................................................................................... 124
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1:
SoA - Combination Comparison Phase (ie, through Week 12) ................................................ 20
Table 2:
SoA- Monotherapy Phase (ie, after Week 12).......................................................................... 25
Table 3:
Recommended Tapering Schedule for Oral Corticosteroids.................................................... 61
Table 4:
Power to Detect a Treatment Effect of the Combination Therapy Versus Both 
Guselkumab Monotherapy and Golimumab Monotherapy Based on the Proportion of 
Participants Achieving Clinical Response at Week 12 ............................................................. 84
FIGURES
Figure 1:
Schematic Overview of Study CNTO1959UCO2002 ............................................................... 19


TREMFYA (guselkumab)
SIMPONI  (golimumab)
Clinical Protocol CNTO1959UCO2002 Amendment 2
14
Approved, Date: 7 March 2019
1.
PROTOCOL SUMMARY
1.1.
Synopsis
A Phase 2a Randomized, Double-blind, Active-controlled, Parallel-group, Multicenter, Proof-of-concept 
Clinical Study to Evaluate the Efficacy and Safety of Combination Therapy With Guselkumab and 
Golimumab in Participants With Moderately to Severely Active Ulcerative Colitis
Protocol number: CNTO1959UCO2002
EudraCT Number: 2018-001510-15
Guselkumab (CNTO 1959 or TREMFYA®) is a fully human immunoglobulin G1 lambda monoclonal 
antibody (mAb) that binds to the p19 subunit of human interleukin (IL)-23 with high specificity and 
affinity. The binding of guselkumab to IL-23 blocks the binding of extracellular IL-23 to the cell surface 
IL-23 receptor, inhibiting IL-23-specific intracellular signaling and subsequent activation and cytokine 
production. Guselkumab is currently approved in the United States, European Union, Canada, and several 
other countries for the treatment of moderate to severe plaque psoriasis. In addition, guselkumab is also 
being evaluated in psoriatic arthritis (PsA) and Crohn’s disease globally.
Golimumab (CNTO 148 or SIMPONI®) is a fully human anti-tumor necrosis factor alpha (TNFα) mAb 
that binds to TNFα with high affinity. This interaction prevents the binding of TNFα to its receptors, 
thereby inhibiting the biological activity of TNFα. Golimumab is approved for treatment of moderately to 
severely active ulcerative colitis (UC) in over 90 countries worldwide. Additionally, golimumab is 
approved for 1 or more of the following indications around the world: rheumatoid arthritis (RA), PsA, 
ankylosing spondylitis (AS), nonradiographic axial spondyloarthritis (nr-Axial SpA), and polyarticular 
juvenile idiopathic arthritis (pJIA).
OBJECTIVES AND ENDPOINTS
This study will consist of 2 distinct phases: a 12-week combination comparison phase followed by a 
26-week monotherapy phase.
Objectives
Primary Objectives
Combination Comparison Phase

To evaluate the clinical efficacy of combination therapy with guselkumab and golimumab in 
participants with moderately to severely active UC.

To evaluate the safety of combination therapy with guselkumab and golimumab in participants with 
moderately to severely active UC.
Secondary Objectives
Combination Comparison Phase

To evaluate the effect of combination therapy with guselkumab and golimumab on endoscopic
improvement.

To evaluate the impact of combination therapy with guselkumab and golimumab on disease-specific 
health-related quality of life (HRQOL), including fatigue.

To evaluate the efficacy of combination therapy with guselkumab and golimumab by negative 
response signature status at baseline.


TREMFYA (guselkumab)
SIMPONI  (golimumab)
Clinical Protocol CNTO1959UCO2002 Amendment 2
15
Approved, Date: 7 March 2019

To evaluate the pharmacokinetics (PK), immunogenicity, and pharmacodynamics (PD) of 
combination therapy with guselkumab and golimumab, including changes in C-reactive protein 
(CRP), fecal calprotectin, and other PD biomarkers.
Monotherapy Phase

To evaluate the clinical efficacy of combination therapy followed by guselkumab monotherapy.

To evaluate the safety of combination therapy followed by guselkumab monotherapy.

To evaluate the effect of combination therapy followed by guselkumab monotherapy on endoscopic 
improvement. 

To evaluate the impact of combination therapy followed by guselkumab monotherapy on disease-
specific HRQOL, including fatigue.

To evaluate the efficacy of combination therapy followed by guselkumab monotherapy by negative 
response signature status at baseline.

To evaluate the PK, immunogenicity, and PD of combination therapy followed by guselkumab
monotherapy, including changes in CRP, fecal calprotectin, and other PD biomarkers.
Exploratory Objectives

To explore the effect of combination therapy on patient-reported outcome (PRO) instruments (eg, 
Bristol Stool Form Scale [BSFS] and Patient’s Global Impression of Change [PGIC] of Severity of 
UC).
Endpoints
Primary Endpoint

Clinical response at Week 12, defined as a decrease from baseline in the Mayo score ≥30% and ≥3 
points with either a decrease in rectal bleeding subscore (RBS) ≥1 or a RBS of 0 or 1.
Major Secondary Endpoint

Clinical remission at Week 12, defined as a Mayo score ≤ 2 with no individual subscore >1. 
Note: Other remission definitions may be considered and will be fully described in the Statistical Analysis 
Plan (SAP).
Hypothesis
Combination therapy with guselkumab and golimumab will result in a rate of clinical response at 
Week 12 that is superior to both monotherapy arms.
OVERALL DESIGN
This is a Phase 2a, randomized, double-blind, active-controlled, parallel-group, multicenter, interventional
proof-of-concept (POC) clinical study designed to evaluate the efficacy and safety of combination therapy 
with guselkumab and golimumab in adults with moderately to severely active UC. The target population 
is men or women 18 to 65 years old with moderately to severely active UC, as defined by a Mayo score of 
6 to 12, inclusive, at baseline, including an endoscopy subscore ≥2 as obtained during the central review 
of the video endoscopy. Participants must be naïve to TNF antagonists and have failed or not tolerated 
conventional therapy with oral or intravenous (IV)
corticosteroids or immunomodulators 
(6-mercaptopurine [6-MP] or azathioprine [AZA]). 


TREMFYA (guselkumab)
SIMPONI  (golimumab)
Clinical Protocol CNTO1959UCO2002 Amendment 2
16
Approved, Date: 7 March 2019
Immunomodulators (6-MP, AZA, and methotrexate [MTX]) must be discontinued for at least 2 weeks 
before the first dose of study intervention. For participants who are receiving oral corticosteroids at 
baseline, the investigator must begin tapering the daily dose of corticosteroids at Week 6. All participants 
will be evaluated for clinical worsening of UC throughout the study. In general, doses of concomitant 
therapies for UC should remain stable through Week 38 (except for oral corticosteroid tapering beginning 
at Week 6), and concomitant therapies for UC should not be initiated unless considered medically 
necessary by the investigator. Initiation of prohibited therapies will result in discontinuation of study 
intervention.
Endoscopy with central read is planned for screening/baseline, Week 12, and Week 38. Consenting 
participants will have an additional endoscopy at Week 4, which will also be assessed by a central reader. 
Efficacy, PK and PD parameters, biomarkers, and safety will be assessed according to the Schedule of 
Activities (SoA). A pharmacogenomic blood sample will be collected from participants who consent to 
this component of the protocol (where local regulations permit). Participation in pharmacogenomic 
research is optional.
An interim analysis is planned to inform future clinical development. Database locks (DBLs) are planned 
at Weeks 12 and 38, and a final DBL is planned after all participants complete the safety follow-up visit. 
An independent Data Monitoring Committee (DMC) will be commissioned for this study. 
NUMBER OF PARTICIPANTS
A target of 210 participants will be enrolled in this study with 70 participants planned per intervention 
group.
INTERVENTION GROUPS AND DURATION
This study will consist of 2 distinct phases: a 12-week combination comparison phase followed by a 26-
week monotherapy phase. At Week 0, a target of 210 participants will be randomized in a 1:1:1 ratio to 
either combination therapy with guselkumab and golimumab, guselkumab monotherapy, or golimumab 
monotherapy, stratified by the concomitant use of corticosteroids at baseline (Y/N). Participants 
randomized to combination therapy will receive guselkumab monotherapy after Week 12. Participants 
randomized to a monotherapy group will continue on their originally randomized monotherapy after 
Week 12. The combination therapy arm will employ the same dose regimens of guselkumab and 
golimumab being used in the respective monotherapy intervention groups to facilitate scientific 
interpretation of the results. The following is a description of the 3 intervention groups:

Combination therapy: guselkumab 200 mg IV and golimumab 200 mg subcutaneous (SC) at 
Week 0; golimumab 100 mg SC at Weeks 2, 6, and 10; guselkumab 200 mg IV at Weeks 4 and 8 
followed by guselkumab 100 mg SC q8w

Guselkumab monotherapy: guselkumab 200 mg IV at Weeks 0, 4, and 8 followed by guselkumab 
100 mg SC q8w

Golimumab monotherapy: golimumab 200 mg SC injection at Week 0, followed by golimumab 
100 mg at Week 2 and then golimumab 100 mg every 4 weeks (q4w)
In addition, placebo administrations (IV or SC) will be given, as appropriate, to maintain the blind 
throughout the duration of the study.
Overall participant duration will be up to 58 weeks total (screening: up to 8 weeks; treatment duration: 38 
weeks [12 weeks for the combination comparison phase; 26 weeks for the monotherapy phase]; safety 
follow-up: approximately 16 weeks after the last administration of study intervention at Week 34). The 
end of the study will be defined as when the last participant completes his or her final safety follow-up 
visit.  


TREMFYA (guselkumab)
SIMPONI  (golimumab)
Clinical Protocol CNTO1959UCO2002 Amendment 2
17
Approved, Date: 7 March 2019
EFFICACY EVALUATIONS
Efficacy evaluations will include the following:

Mayo score and Partial Mayo score

Ulcerative Colitis Endoscopic Index of Severity (UCEIS)

Inflammatory PD markers including CRP and fecal calprotectin

Patient-reported outcome measures to assess HRQOL outcomes and fatigue (ie, Inflammatory Bowel 
Disease Questionnaire [IBDQ], Patient-Reported Outcomes Measurement Information System 
[PROMIS]-29, and PROMIS Fatigue 7-item Short Form [7a])

Exploratory patient-reported symptom measures including BSFS and PGIC of Severity of UC
PHARMACOKINETIC AND IMMUNOGENICITY EVALUATIONS
Serum samples will be analyzed to determine concentrations of guselkumab and golimumab and detection 
of anti-guselkumab and anti-golimumab antibodies, respectively, using validated, specific, and sensitive 
immunoassay methods by or under the supervision of the sponsor. 
PHARMACODYNAMIC AND BIOMARKER EVALUATIONS
Biomarker assessments will be made to examine the biologic response to treatment and to identify 
biomarkers that are relevant to guselkumab and/or golimumab in the treatment of UC. Assessments will 
include the evaluation of relevant biomarkers in serum, stool, whole blood, and mucosal biopsy samples
(RNA [ribonucleic acid], peripheral blood mononuclear cells (PBMCs), histology, and single cell 
isolation).
PHARMACOGENOMIC (DNA) EVALUATIONS
A pharmacogenomic whole blood sample of approximately 5 mL will be collected (where local 
regulations permit) for genetic analyses as specified in the SoA. Only participants who sign the consent 
form to participate in the genetic assessment will have whole blood deoxyribonucleic acid (DNA)
samples collected. Participation in the pharmacogenomic sub-study is optional.
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 (TB) evaluation and other infection 
assessment, clinical laboratory blood tests (hematology and chemistry), vital signs, suicidality assessment, 
concomitant medication review, observations for injection-site reactions, AEs temporally associated with 
infusion, and/or hypersensitivity reactions.
STATISTICAL METHODS
Sample Size Determination
A sample size of 210 participants (70 per intervention group) was determined by the power to detect a 
significant difference in the proportion of participants in clinical response at Week 12 (primary endpoint) 
between the combination therapy and both monotherapies using a 1-sided chi-square test with 0.1 
significance level for each comparison. The study is sized such that the combination therapy has
approximately 80% power based on simulations to achieve both comparisons to monotherapy for the 
primary endpoint. The proportion of participants in clinical response at Week 12 is assumed to be 75% for 
the combination therapy, which is based on the additive effect from both monotherapies (20% 
improvement from each monotherapy relative to a historical placebo response of 35%). 


TREMFYA (guselkumab)
SIMPONI  (golimumab)
Clinical Protocol CNTO1959UCO2002 Amendment 2
18
Approved, Date: 7 March 2019
Efficacy Analyses
All randomized participants who receive at least 1 dose of study intervention will be included in the 
efficacy analyses. Participants will be analyzed according to the treatment group to which they were 
randomized regardless of the treatment they received.
For testing of the primary endpoint, the efficacy of combination therapy versus each monotherapy will be 
compared. For both statistical comparisons of the primary endpoint, a Cochran-Mantel-Haenszel (CMH)
chi-square test stratified by concomitant use of corticosteroids at baseline (Y/N) will be used. The testing 
will be done simultaneously at the 1-sided 0.1 level of significance for each comparison. The study will 
be considered positive if the combination therapy group is significantly different from both monotherapy 
groups for the primary endpoint. 
If both tests of the primary endpoint are positive, a CMH chi-square test (1-sided) stratified by 
concomitant use of corticosteroids at baseline (Y/N) will be used to compare the efficacy of the 
combination therapy to each monotherapy for the major secondary endpoint. The testing will be done 
simultaneously at the 1-sided 0.1 level of significance for each comparison.
Analyses for other efficacy endpoints will be performed with no adjustments made for multiple 
comparisons and nominal p-values will be provided.
Safety Analyses
Safety data, including but not limited to, AEs, serious adverse events (SAEs), infections, serious 
infections, and changes in laboratory assessments will be summarized. Treatment-emergent AEs will be 
summarized by treatment group and Medical Dictionary for Regulatory Activities (MedDRA) system 
organ class and preferred terms.
Other Analyses
Pharmacokinetic Analyses 
Serum guselkumab and golimumab concentrations over time will be summarized for each treatment 
group using descriptive statistics.
Population PK modeling may be conducted when appropriate. If these population PK analyses are 
conducted, the results of these analyses will be presented in a separate report.
Immunogenicity Analyses 
The incidence of antibodies to guselkumab and to golimumab will be summarized for all participants who 
receive at least 1 dose of guselkumab or golimumab and have appropriate samples for detection of 
antibodies to guselkumab and to golimumab (ie, participants with at least 1 sample obtained after their 
first dose of guselkumab or golimumab, respectively).
Pharmacokinetic/Pharmacodynamic Analyses
The relationship between serum concentrations of guselkumab and golimumab and the efficacy measures
and/or relevant biomarker(s) may be explored graphically when appropriate. Additional analysis may be 
conducted if deemed necessary.
Biomarkers Analyses
Changes in serum protein analytes, fecal biomarkers, and biopsy and whole blood RNA obtained over 
time will be summarized by treatment group. Associations between baseline levels and changes from 
baseline in select markers and response to treatment will be explored. Biomarker analyses will be 
summarized in a separate technical report.


TREMFYA (guselkumab)
SIMPONI  (golimumab)
Clinical Protocol CNTO1959UCO2002 Amendment 2
19
Approved, Date: 7 March 2019
Pharmacogenomic Analyses
Genetic (DNA) analyses will be conducted only in participants who sign the consent form to participate in 
the pharmacogenomic sub-study. These analyses are considered exploratory and will be summarized in a 
separate technical report.
1.2.
Schema
Figure 1:
Schematic Overview of Study CNTO1959UCO2002






TREMFYA (guselkumab)
SIMPONI  (golimumab)
Clinical Protocol CNTO1959UCO2002 Amendment 2
22
Approved, Date: 7 March 2019
Table 1:
SoA - Combination Comparison Phase (ie, through Week 12)
Phase
Screening
Treatment
Week
Within 8 
weeks
W0
W2
W4
W6e
W8
W10
W12f
Study Proceduresa,b,c,d
Bowel Disease Questionnaire; IV=intravenous; PBMC= peripheral blood mononuclear cell; PK=pharmacokinetic; PGIC=Patient’s Global 
Impression of Change (of Severity of UC); PRO=patient-reported outcome; PROMIS=Patient-Reported Outcomes Measurement 
Information System; RNA=ribonucleic acid; SC=subcutaneous; TB=tuberculosis; UC=ulcerative colitis; W=Week.
a.
Screening should occur within 8 weeks before the W0 visit. Visit dates are based on the participant’s original 
randomization date; visit windows are as follows: day of the scheduled visit ±4 days (ie, plus or minus 4 days). 
b.
All assessments are to be completed before study intervention administration, unless otherwise specified; PRO 
assessments should be completed first. At the screening visit, the C-SSRS should be completed as the first assessment 
after signing informed consent and before any other tests, procedures, or other consultations. When blood samples are to 
be collected for safety, PK, efficacy, and biomarkers evaluations at the same time point, the order of blood draws will be 
samples for CRP, hematology and chemistry, PK/immunogenicity, serum biomarkers, whole blood DNA (for those 
participating in the optional pharmacogenomic sub-study at Week 0), and whole blood RNA.
c.
Participants who discontinue study intervention (but have not terminated study participation) before W12 visit should 
complete the W12 assessments at the time of discontinuation and a safety follow-up visit (see Table 2) approximately 
16 weeks after their last study intervention administration.
d.
Subjects who terminate their study participation before the W12 visit should complete the W12 assessments at the time 
of termination (which will serve as the early termination visit).
e.
For participants who are receiving oral corticosteroids, the investigator must begin tapering the daily dose of 
corticosteroids at W6.
f.
Participants randomized to combination therapy will receive guselkumab monotherapy after W12.  Participants 
randomized to a monotherapy group will continue on their originally randomized monotherapy after W12.
g.
Must be signed before first study-related activity.
h.
The required source documentation to support meeting the enrollment criteria are noted in Appendix 6 [Section 10.6], 
Regulatory, Ethical, and Study Oversight Considerations. Check clinical status again before first dose of study 
intervention.
i.
All participants will undergo QuantiFERON®-TB testing. If the QuantiFERON®-TB test is not approved/registered in the 
country in which this protocol is being conducted or the tuberculin skin test is mandated by local health authorities, a 
negative tuberculin skin test result (see Appendix 3 [Section 10.3]) is also required. In Ukraine, while the 
QuantiFERON®-TB test is not approved/registered, it is accepted, and a tuberculin skin test is not required.
j.
Chest radiograph (posterior-anterior and lateral views, or per country regulations where applicable) must be obtained 
within 3 months before the W0 visit. Note: A chest CT scan is also acceptable in place of a chest radiograph.
k.
Must be performed before any study intervention administration for female participants of childbearing potential. 
l.
Stool studies for enteric pathogens may be performed at either the central or local laboratory and must include a stool 
culture and Clostridium difficile toxin assay. These tests must be performed during screening or have been performed 
during the current episode of disease exacerbation (as long as the stool studies were performed within 4 months before 
the first administration of study intervention). Additional testing (eg, ova and parasites or Escherichia coli O157:H7 


TREMFYA (guselkumab)
SIMPONI  (golimumab)
Clinical Protocol CNTO1959UCO2002 Amendment 2
23
Approved, Date: 7 March 2019
Table 1:
SoA - Combination Comparison Phase (ie, through Week 12)
Phase
Screening
Treatment
Week
Within 8 
weeks
W0
W2
W4
W6e
W8
W10
W12f
Study Proceduresa,b,c,d
assessments) may be performed at the investigator’s clinical discretion. 
m.
Participants should be instructed to bring their diaries to each study visit for review.
n.
Endoscopy findings will be assessed by the investigator (ie, local endoscopist) during the procedure and a video of the 
endoscopy must be submitted to the central reader. 
o.
The screening endoscopy must be performed within 2 weeks of the baseline (W0) visit. The interval from the endoscopy 
procedure to the availability of the Mayo endoscopy subscore is approximately 4 days; therefore, the screening 
endoscopy must be performed at least 4 days before the baseline (W0) visit. The Mayo endoscopy subscore obtained 
during the central review of the video endoscopy will be used to determine eligibility (ie, Mayo endoscopy subscore ≥2) 
and to calculate the baseline Mayo score. A full colonoscopy will replace a sigmoidoscopy if screening for polyps or 
dysplasia is required. At least 48 hours must elapse between a colonoscopy with polypectomy and the W0 visit.
p.
Only those participants who consent to participate in the optional endoscopy and biopsy sub-study will undergo Week 4 
endoscopy and mucosal biopsy collection and whole blood PBMC collection.
q.
If TB is suspected at any time, a chest radiograph (or chest CT scan if obtained instead) and QuantiFERON®-TB test 
should be performed. In countries where the QuantiFERON®-TB test is not registered/approved or the tuberculin skin 
test is mandated by local health authorities, TB skin testing (see Appendix 3 [Section 10.3]) should also be performed. 
Note: In Ukraine, while the QuantiFERON®-TB test is not approved/registered, it is accepted and a tuberculin skin test is 
not required. 
r.
Temperature, pulse/heart rate, respiratory rate, and blood pressure. At a study intervention administration visit, vital 
signs should be obtained before, approximately every 30 minutes during, and twice (at approximately 30-minute 
intervals) after completion of the IV infusion(s), or before and approximately 30 minutes after the SC injection, or if the 
participant reports any symptoms.
s.
At the screening visit, the C-SSRS should be completed as the first assessment after signing informed consent and before 
any other tests, procedures, or other consultations. For subsequent visits, the C-SSRS should be completed after all PROs 
and before any other tests, procedures, or other consultations.
t.
For all visits where study intervention will be administered, 1 blood sample should be collected prior to study 
intervention administration for evaluation of serum concentrations and/or antibodies to interventions. In addition, for IV 
infusion-related visits (ie, Weeks 0, 4, and 8), another blood draw should be taken approximately 60 minutes after 
completion of the infusion for serum concentration measurement. All reasonable attempts should be made to collect 
samples at the scheduled timepoints and record the actual dates and times of PK sample collections.
u.
Mucosal biopsy samples will be collected from all participants during endoscopy for RNA expression analysis,
histologic assessment, and single cell isolation.
v.
The screening biopsy samples for histology, RNA analyses, and single cell isolation will be collected from all 
participants during the screening endoscopy performed within 2 weeks of the baseline (W0) visit. 
w.
Serum biomarkers and whole blood RNA and PBMCs will be collected from all participants to evaluate the molecular 


TREMFYA (guselkumab)
SIMPONI  (golimumab)
Clinical Protocol CNTO1959UCO2002 Amendment 2
24
Approved, Date: 7 March 2019
Table 1:
SoA - Combination Comparison Phase (ie, through Week 12)
Phase
Screening
Treatment
Week
Within 8 
weeks
W0
W2
W4
W6e
W8
W10
W12f
Study Proceduresa,b,c,d
effects of each study intervention in UC.
x.
Fecal biomarkers (including microbiome) and associated products will be collected from all participants to evaluate the 
association between microbial activities, study intervention, and/or UC.
y.
Whole blood for genetic analyses will be collected (where local regulations permit) only from participants who sign a 
separate ICF to participate in the optional pharmacogenomic sub-study. The pharmacogenomic (DNA) sample should be 
collected at the specified time point; however, if necessary it may be collected later without constituting a protocol 
deviation.
z.
For the baseline (W0) visit, the IV study intervention should be administered first. The SC study intervention should be 
administered approximately 30 minutes after the IV study intervention infusion is complete.
aa.
Certain laboratory abnormalities require re-testing and potential discontinuation of study intervention (See Sections 8.2.5
and 7.1, respectively).
bb.
An injection-site reaction is any adverse reaction at any SC study intervention injection site. Injection sites will be 
evaluated for reactions and any injection-site reaction should be recorded as an adverse event.
cc.
Whole blood (PBMC) samples are to be collected ideally within ±2 days of the endoscopy visit.






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Table 2:
SoA- Monotherapy Phase (ie, after Week 12)
Phase
Treatment
Early 
Termc,e
Safety
Follow-
Upd,e
Week
W14
W16
W18
W22
W24
W26
W30
W32
W34
W38
Study Procedurea,b
l.
Mucosal biopsy samples will be collected from all participants during endoscopy for RNA expression analysis, histologic assessment, and single cell isolation.
m.
Serum biomarkers and whole blood RNA and PBMCs will be collected from all participants to evaluate the molecular effects of each study intervention in UC.
n.
Fecal biomarkers (including microbiome) and associated products analysis will be collected from all participants to evaluate the association between microbial 
activities, study intervention, and/or UC.
o.
Certain laboratory abnormalities require re-testing and potential discontinuation of study intervention (See Sections 8.2.5 and 7.1, respectively).
p.
An injection-site reaction is any adverse reaction at any SC study intervention injection site. Injection sites will be evaluated for reactions and any injection-site 
reaction should be recorded as an adverse event.
q.
Whole blood (PBMC) samples are to be collected ideally within ±2 days of the endoscopy visit.


TREMFYA (guselkumab)
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2.
INTRODUCTION
Guselkumab (CNTO 1959 or TREMFYA®) is a fully human immunoglobulin G (IgG)1 lambda
monoclonal antibody (mAb) that binds to the p19 subunit of human interleukin (IL)-23 with high 
specificity and affinity. The binding of guselkumab to IL-23 blocks the binding of extracellular
IL-23 to the cell surface IL-23 receptor, inhibiting IL-23-specific intracellular signaling and 
subsequent activation and cytokine production. In this manner, guselkumab inhibits the 
biological activity of IL-23 in all in vitro assays examined.
Guselkumab is currently approved in the United States (US), European Union (EU), Canada, and 
several other countries for the treatment of moderate to severe plaque psoriasis. Clinical 
programs in non-plaque form psoriasis (generalized pustular psoriasis [GPP], erythrodermic 
psoriasis [EP], and palmoplantar pustulosis [PPP]) are being conducted in Japan only and Japan 
recently approved guselkumab for the treatment of patients with psoriasis, GPP, EP, and 
psoriatic arthritis (PsA). In addition, guselkumab is also being evaluated in PsA and Crohn’s 
disease globally. 
Golimumab (CNTO 148 or SIMPONI®) is a fully human anti-tumor necrosis factor alpha 
(TNFα) mAb that binds to TNFα with high affinity. This interaction prevents the binding of 
TNFα to its receptors, thereby inhibiting the biological activity of TNFα. The overall anti-TNFα 
activity results in limited production or activity of inflammatory cytokines, thereby providing 
therapeutic benefit in various chronic inflammatory disorders, including ulcerative colitis (UC).
Golimumab has demonstrated an acceptable benefit/risk profile and is approved for treatment of 
moderately to severely active UC in over 90 countries worldwide. Additionally, golimumab is 
approved for 1 or more of the following indications around the world:  rheumatoid arthritis (RA), 
PsA, ankylosing spondylitis (AS), nonradiographic axial spondyloarthritis (nr-Axial SpA), and 
polyarticular juvenile idiopathic arthritis (pJIA).
For the most comprehensive nonclinical and clinical information regarding guselkumab and 
golimumab, refer to the latest versions of the Investigator’s Brochure (IB) for guselkumab and 
golimumab, respectively.
Note: The term “sponsor” used throughout this document refers to the entities listed in the 
Contact Information page(s), which will be provided as a separate document. The term “study 
intervention” is used throughout this document in place of “study agent” or “study drug.”
2.1.
Study Rationale
Ulcerative colitis is an inflammatory disorder which involves the surface mucosa, the crypt 
epithelium, and submucosa of the colon.57 Clinically, patients with UC suffer from diarrhea, 
rectal bleeding, weight loss, abdominal pain, fever, and may also display prominent 
extraintestinal manifestations, commonly colitic arthritis, and AS.57 The goals of UC treatment in 
general are the induction and maintenance of remission of symptoms to provide an improved 
quality of life, reduction in need for long-term corticosteroids, and minimization of cancer risk.24
Biologic agents, most notably the anti-TNFα class, have revolutionized the clinical management 


TREMFYA (guselkumab)
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of inflammatory bowel disease (IBD [UC and Crohn’s disease]), yet many patients either fail to 
respond or lose their initial response to treatment highlighting the significant unmet medical need 
for more effective therapies.10,24,35 Biologic therapies used as monotherapies have short-term 
remission rates of <20%.10,24,35 A therapeutic approach of targeting multiple pathogenic pathways 
may be required to achieve higher rates of clinical remission. Emerging evidence suggests that 
targeting both TNFα and IL-23 pathways may result in greater clinical efficacy (Section 2.1.2). 
Given the well-established scientific and clinical rationale for each monotherapy in IBD, the 
unmet medical need for more efficacious therapies in UC specifically, and the expected clinical 
benefit of combination therapy, this Phase 2a proof-of-concept (POC) clinical study will evaluate 
the efficacy and safety of short-term (ie, approximately 12 weeks) combination therapy with 
guselkumab and golimumab compared to either guselkumab or golimumab alone in the treatment 
of patients with moderately to severely active UC.
2.1.1.
Rationale for Use of Guselkumab in Ulcerative Colitis
2.1.1.1.
Nonclinical Evidence Implicating IL-23 as a Target in Ulcerative 
Colitis
The involvement of the IL-12/23 pathway in the pathogenesis of IBD is well established. 
Genome-wide association studies have implicated several genetic loci in the IL-12/23 pathway 
that are associated with susceptibility to UC and Crohn’s disease, including the IL-23 receptor, 
the IL-12B subunit, Janus kinase (JAK) 2, and signal transducer and activator of transcription 3 
genes.4,9,12,28 Early nonclinical studies showed that treatment with an anti-IL-12/23p40 mAb 
abrogated or prevented disease in murine models of intestinal inflammation.29,34 Subsequent 
studies dissecting the roles of IL-12p35, IL-12/23p40, and IL-23p19 demonstrated a key role for 
IL-23 in mediating local intestinal inflammation relative to systemic inflammation driven by 
IL-12.18,65 The role of IL-23 in driving intestinal inflammation has been further evaluated in 
several murine colitis models. Mice treated with anti-IL-23p19 antibodies exhibit attenuated 
inflammation31 and mice with a genetic deletion of the p19 subunit of IL-23 are protected in 
several models of intestinal inflammation.26,69 These data suggest that the efficacy obtained with 
IL-12/23p40 blockade may be through the inhibition of IL-23 and provide a strong rationale for 
inhibiting only IL-23 in IBD. 
2.1.1.2.
Clinical Evidence Establishing Proof-of-Concept for IL-23 Targeted 
Therapy in Ulcerative Colitis
Clinical POC has been established for anti-IL-23 mAbs in both Crohn’s disease and 
UC.14,15,46,47,49 In a recently reported Phase 2 study, mirikizumab (anti-IL-23 mAb) demonstrated 
efficacy in the induction treatment for patients with moderately to severely active UC, as 
assessed by multiple measures including clinical response.46 Overall AE frequencies were similar 
for mirikizumab and placebo-treated patients. There are several ongoing and planned studies in 
UC with anti-IL-12/23 and anti-IL-23 specific mAbs, including: 


TREMFYA (guselkumab)
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
ustekinumab (Phase 3, ClinicalTrials.gov Identifier: NCT02407236)

mirikizumab (Phase 3, ClinicalTrials.gov Identifier: NCT03518086 and NCT03524092;
Phase 2, ClinicalTrials.gov Identifier: NCT02589665)

risankizumab (Phase 3, ClinicalTrials.gov Identifier: NCT03398148 and NCT03398135)
The therapeutic role of anti-IL-23 in Crohn’s disease was first established by clinical studies of 
IL-12/23p40 antagonists (briakinumab39 and ustekinumab15). Ustekinumab, an IL-12/23p40 
antagonist, is approved for the treatment of moderate to severe Crohn’s disease (STELARA 
United States Prescribing Information [USPI]56, Summary of Product Characteristics [SmPC]55).
While these programs demonstrated that blockade of both IL-12 and IL-23 is effective in treating 
Crohn’s disease, they could not determine the relative contributions specific to the blockade of 
each of the 2 cytokines. Two other anti-IL-23 mAbs, risankizumab (BI 655066)13,14,16 and 
brazikumab (MEDI2070, AMG-139)49,50 have reported Phase 2 results demonstrating the 
efficacy of IL-23 blockade in subjects with moderate to severe Crohn’s disease. Further, Phase 3 
Crohn’s disease programs are underway for risankizumab (ClinicalTrials.gov Identifier: 
NCT03105128) and guselkumab (Phase 2b/3, ClinicalTrials.gov Identifier: NCT03466411).
Given the similarities in the biology and treatment of Crohn’s disease and UC, as well as the 
efficacy and safety of anti-IL-23 treatment demonstrated to date in both Crohn’s disease and UC,
there is strong rationale for the clinical development of guselkumab in UC.
2.1.2.
Rationale for Combined Use of Guselkumab and Golimumab in 
Ulcerative Colitis
The purpose of this combination Phase 2a POC study is to provide critical data that will inform 
potential future studies for combination use of an anti-IL-23 intervention and an anti-TNFα
intervention in UC.
As described in Section 2.1, there remains a high unmet need in the IBD patient population with 
many patients failing to achieve clinical response or clinical remission with current treatments. 
Addressing this unmet need may require targeting multiple pathogenic mechanisms through 
combination therapies. Combination therapy is already well accepted in the clinical management 
of IBD; studies show that patients treated with a combination of infliximab and azathioprine
(AZA) are more likely to achieve corticosteroid-free remission than those treated with either 
monotherapy alone.7,38 More recently, sponsors and independent investigators have initiated 
studies in IBD evaluating combinations of anti-TNFα agents with other biologic agents for 
periods up to 12 months.6,25,58 Specifically, there is an ongoing open-label study to evaluate the 
efficacy and safety of combination therapy with vedolizumab, adalimumab, and methotrexate 
(MTX)
for 26 weeks in subjects with Crohn's disease
(ClinicalTrials.gov Identifier: 
NCT02764762).58 There are also case series describing treatment successes of combination 
therapy with vedolizumab plus ustekinumab or various anti-TNFα agents in patients with UC 
and Crohn’s disease for periods up to 12 months.6,19,25


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Collectively, human genetics, nonclinical animal models and clinical data in IBD patients have 
validated the involvement of both TNFα and IL-23 signaling pathways in IBD pathogenesis and 
the role of monotherapies targeting these proteins in the treatment of IBD. However, as observed 
with anti-TNFα therapies, it is anticipated that a population of patients may not fully respond to 
anti-IL-23 therapy alone. In addition to addressing patients not fully responsive to monotherapy, 
there may be benefit to treating the patient population as a whole upfront with 2 agents versus
monotherapy alone. Accordingly, this study will evaluate the effect of short-term treatment with 
both agents (ie, approximately 12 weeks), in a manner similar to ongoing evaluations in IBD.58
In support of this combination therapy approach, the sponsor has generated positive efficacy data 
from anti-TNFα/anti-IL-23 combination treatment in a nonclinical colitis model and evaluated 
the molecular impact of monotherapy versus combination therapy on the human disease using a 
network genomics approach (Section 2.2.1). 
2.2.
Background
2.2.1.
Nonclinical Development
Full nonclinical development programs were conducted with guselkumab and golimumab in 
support of global submissions and approvals for both products. These included general 
toxicology and toxicokinetic (TK) studies in support of first-in-human dosing, studies in support 
of Phase 2 and Phase 3 clinical development, and developmental and reproductive toxicology 
studies. A comprehensive overview of the guselkumab and golimumab nonclinical data is 
presented in the guselkumab IB and the golimumab IB, respectively.
This section provides a summary of the sponsor's assessment of how the overall nonclinical data 
support the safety of the proposed dosing for guselkumab and golimumab in this Phase 2a 
program in UC. Details regarding the proposed clinical dose regimen and dose rationale are 
described in Section 4.3 of this protocol.
2.2.1.1.
Guselkumab
Pharmacology
Primary pharmacodynamic (PD) studies determined guselkumab target binding interactions, 
epitope mapping, in vitro mechanism of action, functional effects of neutralization, species 
cross-reactivity, and in vivo neutralization of human IL-23 in mice. Guselkumab was shown to 
bind and neutralize IL-23, and to be pharmacologically active in guinea pigs and the non-human 
primate. Guselkumab does not bind to or neutralize IL-23 in the rat or mouse. The cynomolgus 
monkey was selected to be the pharmacologically relevant toxicology species for guselkumab, 
and the guinea pig was selected as the species to assess fertility. 
In accordance with the provisions of the International Conference on Harmonisation (ICH) S7A
guidance document22, safety pharmacology evaluations (cardiovascular [CV], respiratory, central 
nervous system) were incorporated into the design of the Good Laboratory Practice (GLP)
repeat-dose toxicity study in cynomolgus monkeys. Additionally, a CV safety pharmacology 
study was conducted in cynomolgus monkeys.


TREMFYA (guselkumab)
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Pharmacokinetics
The pharmacokinetic (PK) profile of guselkumab has been characterized in cynomolgus 
monkeys in (1) single-dose studies in which monkeys received a single intravenous (IV) and 
subcutaneous (SC) administration; (2) a 5-week/24-week study in which monkeys received 
repeated weekly IV and/or SC doses of guselkumab (followed by a 3-month recovery); and (3) 
an enhanced prenatal and postnatal developmental (ePPND) study in which pregnant females
were administered repeated weekly SC doses of guselkumab. The PK profile was also
characterized in guinea pigs that received repeated SC doses of guselkumab twice a week. The 
results showed that guselkumab behaves as a typical IgG-based therapeutic mAb. The TK results 
from all toxicology studies conducted in guinea pigs and monkeys demonstrated adequate and 
sustained drug exposure in the circulation to support the safety evaluation in animal species. In 
addition, the TK results also demonstrated cross-placenta distribution of circulating guselkumab 
to the fetus and no measurable excretion of guselkumab into milk. Only a small percentage 
(2.2%) of monkeys (2 of 90) were positive for anti-guselkumab antibodies and exhibited 
accelerated total systemic clearance of drug after IV administration or apparent total systemic 
clearance of drug after extravascular administration, and/or accelerated decrease in serum 
guselkumab concentrations. One of 24 (4.2%) infants from guselkumab-treated females in the 
ePPND study was also found to be positive for anti-guselkumab antibodies.
Toxicology
The guselkumab toxicology program evaluated the potential for sub-chronic and chronic toxicity, 
reproductive and developmental toxicity, tissue cross-reactivity (TCR), serum compatibility, and 
hemolytic potential using the cynomolgus monkey and guinea pig, the only pharmacologically 
relevant species. During the conduct of the initial non-GLP and GLP TCR assays, cytoplasmic 
binding of guselkumab to skeletal and cardiac myocytes was observed in both cynomolgus 
monkey and human tissues. As a result of the unusual binding, a CV safety pharmacology study 
with guselkumab was conducted in cynomolgus monkeys to evaluate any potential adverse 
effects of guselkumab on cardiac function. In the cynomolgus monkey, potential for toxicity was 
assessed in a GLP repeat-dose (5-week/24-week plus 3-month drug-free period) study conducted 
in 2 separate phases in different sets of animals. Developmental toxicity was evaluated in an 
ePPND toxicity study in cynomolgus monkeys. Effects of guselkumab on fertility and early 
embryonic development were evaluated in guinea pigs initially in non-GLP male and female 
fertility studies, and then in GLP male and female fertility studies. No adverse effects of 
guselkumab were observed in nonclinical toxicology studies. The guselkumab CV safety 
pharmacology and sub-chronic and chronic toxicity studies demonstrated that the No Observed 
Adverse Effect Level (NOAEL) for guselkumab in cynomolgus monkeys was at least 
50 mg/kg/week. In the ePPND study, the NOAEL for both maternal and developmental 
outcomes in cynomolgus monkeys was also 50 mg/kg/week.  In guinea pig fertility studies, the 
NOAEL was 100 mg/kg (administered twice-weekly). In all cases, doses were the highest 
administered in the respective test systems. 


TREMFYA (guselkumab)
SIMPONI  (golimumab)
Clinical Protocol CNTO1959UCO2002 Amendment 2
33
Approved, Date: 7 March 2019
2.2.1.2.
Golimumab
Pharmacology
In accordance with the provisions of the ICH S7A guidance document22, safety pharmacology 
evaluations (CV, respiratory, central nervous system) were incorporated into the design of the 
GLP repeat-dose toxicity study in cynomolgus monkeys. No adverse effects were observed 
following single or repeated IV or SC dosing up to 50 mg/kg twice-weekly or in 6-month old 
cynomolgus monkey infants exposed to golimumab during a GLP pre- and postnatal 
development study.
Pharmacokinetics
The cynomolgus monkey was chosen as it was the only pharmacologically relevant species for 
golimumab PK and toxicology studies.
The PK profile of golimumab displayed dose-proportional PK with respect to maximum 
observed concentration and area under the serum concentration versus time curve. Following SC 
administration, maximum observed concentration was observed 1 to 3 days after administration 
with an absolute bioavailability of 77% or higher. Terminal elimination half-life (t1/2) was similar 
following IV and SC administration and ranged from 0.39 to 8.84 days. As with other IgG1s, 
golimumab can be transported through the placental barrier and expose the fetus when 
golimumab is administered to pregnant cynomolgus monkeys. An embryo-fetal development 
study in cynomolgus monkeys demonstrated a substantial exposure to golimumab in both 
maternal and fetal circulation in response to twice-weekly SC administration of golimumab at 
doses of 25 mg/kg or 50 mg/kg. By the end of the second trimester (gestation day 100) the 
maternal serum concentration ranged from 1 to 99 times that of fetal serum concentration. 
Development of antibodies to golimumab was frequently observed in monkeys, especially 
following limited dosing at ≤10 mg/kg. Animals with shorter serum t1/2 of golimumab produced 
antibodies to golimumab earlier than animals with longer t1/2 values. It was expected that 
antibody to golimumab induction was less likely in human subjects because golimumab is a 
human IgG and thus should be less immunogenic to humans than to monkeys.
Toxicology
Nonclinical IV and SC toxicology studies were conducted in cynomolgus monkeys up to 
6 months in duration. In addition, an embryo-fetal development study evaluating the maternal 
and fetal effects following maternal treatment during the period of organogenesis, a prenatal and 
postnatal development study evaluating the maternal and neonatal effects following maternal 
treatment during the fetal and lactation periods, and a study in young cynomolgus monkeys to 
provide safety information to support use in pediatric subjects was conducted. Chronic toxicity 
and reproductive and developmental toxicity of an anti-mouse TNFα mAb (cV1q) were also 
assessed to provide additional supportive data for the development of anti TNFα mAb therapies. 
An in vitro human TCR study was also conducted. No signs of toxicity considered golimumab-
related were observed in any of these studies, except in 1 animal treated with golimumab at the 
lowest dose of 25 mg/kg IV that developed a disseminated histoplasmosis infection. This finding 
may have been due to a reactivation of a latent infection and was not unexpected based upon an 


TREMFYA (guselkumab)
SIMPONI  (golimumab)
Clinical Protocol CNTO1959UCO2002 Amendment 2
34
Approved, Date: 7 March 2019
increased incidence of opportunistic infections (including histoplasmosis) in patients treated with 
anti-TNFα agents.
2.2.1.3.
Combination of Guselkumab and Golimumab
While the sponsor has not performed combination toxicology studies, anti-TNFα and anti-IL-23 
antibodies have been administered concomitantly to mice in a nonclinical model of colitis to 
evaluate the efficacy and molecular impact of the combination therapy on intestinal 
inflammation. Multiple dose combinations of anti-TNFα and anti-IL-23 antibodies have been 
tested in the agonist anti-CD40 murine model of innate colitis. In this acute model of intestinal 
inflammation mice received a single dose of antibodies (day -1) and were sacrificed 7 days after 
the induction of inflammation (day 0). Mice were weighed daily to monitor disease-associated 
wasting and colon tissue collected to assess intestinal inflammation. In the highest dose 
combination of 500 µg anti-TNFα and 500 µg anti-IL-23, no animals died and all animals 
showed improvement in weight and histological inflammation scores compared to diseased 
control-treated (phosphate buffered saline or isotype injected) animals. 
In summary, combination of anti-TNFα and anti-IL-23 antibodies administered to mice in a 
nonclinical model of colitis showed improvement in weight and histological inflammation scores 
in the absence of any acute toxicity. Neither guselkumab nor golimumab presented any apparent 
overlapping toxicities detectable in nonclinical toxicology studies that could be expected to be 
potentiated when administered in combination, and the probability of PK or PD interaction in the 
combination is considered low.
2.2.2.
Clinical Development
2.2.2.1.
Current Status of Guselkumab Development
Guselkumab is a human mAb directed against the p19 subunit of IL-23 and thus specifically 
targets IL-23. A growing body of literature suggests that the IL-23 pathway contributes to the 
chronic inflammation underlying the pathophysiology of many immune-mediated diseases,37,59
including psoriasis, PsA, and IBD. Susceptibility to psoriasis, PsA, and IBD has been shown to 
be associated with genetic polymorphisms in IL-23/IL-23 receptor components.5,12,30,33,36
The clinical development program for guselkumab includes studies in patients with psoriasis 
(including plaque psoriasis, GPP, EP, PPP), PsA, and RA. Clinical data from these studies 
indicate that guselkumab administered IV or SC was generally well tolerated. Additional 
information on these studies is provided in the guselkumab IB.
To date, guselkumab has been approved in the US, EU, Canada, and several other countries for 
the treatment of moderate to severe plaque psoriasis (TREMFYA USPI63, SmPC62).
While this is the first clinical study conducted with guselkumab in UC to date, other anti-IL-23 
mAbs have been studied in UC and Crohn’s disease by other sponsors (Section 2.1.1.2), and the 
sponsor
is also conducting a guselkumab Phase 2b/3 program in Crohn’s disease
(ClinicalTrials.gov Identifier: NCT03466411).


TREMFYA (guselkumab)
SIMPONI  (golimumab)
Clinical Protocol CNTO1959UCO2002 Amendment 2
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Approved, Date: 7 March 2019
2.2.2.2.
Current Status of Golimumab Development
Golimumab is a human anti-TNFα mAb and is being, or has been studied, in the treatment of the 
following clinical indications: RA, PsA, AS, nr-Axial SpA, sarcoidosis, uveitis, and asthma in 
adults; UC and type 1 diabetes in adults and children; and pJIA in children. Additional 
information on these studies is provided in the golimumab IB.
To date, golimumab is approved for the treatment of moderately to severely active UC in adult 
patients in over 90 countries worldwide. Golimumab is also approved for at least 1 of the 
following indications in adults: RA, PsA, AS, and nr-Axial SpA. In addition, golimumab is also 
approved for use in children with pJIA in over 30 countries including the EU.
The golimumab development program in adult UC consisted of 1 IV induction study 
(C0524T16)42, 1 SC induction study (C0524T17)44, and 1 SC maintenance study (C0524T18)45.
C0524T16 and C0524T17 were both 6-week induction studies with identical study designs; the 
primary differences were the dose regimens and routes of administration. More information on 
these studies can be found in the golimumab IB.
2.3.
Benefit/Risk Assessment
Given the well-established scientific and clinical rationale for each monotherapy in IBD 
(Section 2.1), the high unmet medical need in UC, and the expected clinical benefit of 
combination therapy, this Phase 2a POC clinical study will evaluate the efficacy and safety of 
short-term combination therapy with guselkumab and golimumab compared to guselkumab or 
golimumab alone in the treatment of patients with moderately to severely active UC. 
Importantly, all participants will have the benefit of receiving active treatment in this study as 
there is no placebo treatment arm. Although guselkumab is an experimental treatment in IBD, 
clinical POC has been established for anti-IL-23 mAbs in both UC and Crohn’s disease.
14,15,46,47,49 In a recently reported Phase 2 study, mirikizumab (anti-IL-23 mAb) demonstrated 
efficacy in the induction treatment for patients with moderately to severely active UC, as 
assessed by multiple measures including clinical response.46 Overall AE frequencies were similar 
for mirikizumab and placebo-treated patients. 
The safety profiles of guselkumab and golimumab are well characterized due to large clinical 
programs leading to their respective approvals (guselkumab – psoriasis and golimumab – RA, 
PsA, AS, nr-Axial SpA, and UC). Based on the available data and the safety measures in this 
protocol, the overall benefit/risk assessment for using the selected dose regimens for 
combination therapy, guselkumab, and golimumab in this study is deemed acceptable based on 
the below considerations.
For guselkumab, the main risk, as described in Section 5 of the guselkumab IB, is infection. 
Other potential safety concerns, also described in greater detail in the guselkumab IB, are based 
on guselkumab being an immunomodulatory mAb and include malignancy and hypersensitivity. 
The approved dose regimen of guselkumab in psoriasis (100 mg SC at Week 0 and Week 4, and 
then every 8 weeks [q8w]) has been demonstrated to have a favorable safety profile, and dose 
regimens as high as 200 mg SC q8w have been shown to have favorable safety in a 6-month


TREMFYA (guselkumab)
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Clinical Protocol CNTO1959UCO2002 Amendment 2
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Approved, Date: 7 March 2019
Phase 2 trial in RA.53 A higher guselkumab dose regimen was selected for this study compared 
to what is approved for psoriasis over the induction period (Week 0 to Week 12), because 
historically, doses during the induction period (up to 12 weeks) in IBD have been higher than 
those used in psoriasis for mAbs approved for both indications to achieve the desired efficacy in 
IBD (STELARA USPI56, SmPC55; HUMIRA USPI21, SmPC20). The proposed guselkumab dose 
for this protocol is the lowest of the 3 induction doses being evaluated in the ongoing 
guselkumab Phase2b/3 program in Crohn’s disease (200 mg, 600 mg, 1200 mg IV). Additional 
details about the dose selection rationale for guselkumab are provided in Section 4.3.1.
The anti-TNF class of agents has been extensively studied and has a well-defined safety profile. 
Known risks for anti-TNF agents such as golimumab include infections, including serious 
infections, tuberculosis (TB), and opportunistic infections. Other known risks include, but are not 
limited to, lymphoma, leukemia, lupus-like syndrome, and demyelinating disorders (SIMPONI 
USPI52, SmPC51). The dose regimen of golimumab in this protocol is consistent with the 
currently approved dose, and is consistent with the dose regimens evaluated in the golimumab 
Phase 3 clinical development program in UC that established the efficacy and safety of 
golimumab in patients with moderately to severely active UC. 
Given the risk of serious infections associated with the anti-TNF class and combination biologic 
use, the eligibility criteria and screening assessments of this study are designed to exclude 
subjects with chronic/active infections or a predisposition to infections. Measures to ensure the 
early detection of TB, such as chest radiograph and QuantiFERON®-TB test, are outlined in 
Section 8.2.12 and participants with a history of latent or active TB are excluded from this study.
Subjects older than 65 years of age are excluded from the study due to immunosenescence, 
which is defined as the state of dysregulated immune function that contributes to an increased 
susceptibility of the elderly to infection.8,41 In contrast to the reported longer duration RA 
combination biologics studies (ie, up to 1 year),17,67,68 the combination comparison phase of this 
study in UC is of relatively short duration (ie, approximately 12 weeks), meaning that 
participants randomized to the combination therapy intervention group will only receive 3 doses 
of guselkumab and 4 doses of golimumab that overlap. To reduce the risks associated with 
immunosuppression, immunomodulators (6-MP, AZA, and MTX) must be discontinued for at 
least 2 weeks before the first administration of study intervention. Additionally, participants 
taking more than 20 mg of prednisone or equivalent are excluded from the study, and there will 
be mandatory oral corticosteroid tapering beginning at Week 6. Participants will be closely 
monitored for signs and symptoms of infection during and after treatment. During the 
combination comparison phase, clinic visits are scheduled biweekly. Furthermore, safety will be 
monitored in the first 25 participants, randomized to any intervention group and treated on an 
ongoing basis, for any potential safety concerns that would result in a pause in dosing by an 
independent Data Monitoring Committee (DMC). Details about the evaluation of this initial 
cohort and subsequent DMC reviews are outlined in Section 9.5.1. Safety evaluations will 
include AEs, clinical laboratory tests (hematology and chemistry), vital signs and physical 
examinations, a screening electrocardiogram (ECG), hypersensitivity reactions, AEs temporally
associated with infusion, injection-site reactions, and early detection of active TB. The safety 
follow-up period for this study is 16 weeks after the last dose of study intervention.


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Based on the prospect of clinical efficacy with the study interventions being evaluated, the well
characterized safety profiles of guselkumab and golimumab, and the safety measures in place, 
the overall benefit/risk of participation in this clinical study is deemed acceptable.
3.
OBJECTIVES AND ENDPOINTS
This study will consist of 2 distinct phases: a 12-week combination comparison phase followed 
by a 26-week monotherapy phase.
3.1.
Objectives
3.1.1.
Primary Objectives
Combination Comparison Phase

To evaluate the clinical efficacy of combination therapy with guselkumab and golimumab in 
participants with moderately to severely active UC.

To evaluate the safety of combination therapy with guselkumab and golimumab in 
participants with moderately to severely active UC.
3.1.2.
Secondary Objectives
Combination Comparison Phase

To evaluate the effect of combination therapy with guselkumab and golimumab on 
endoscopic improvement.

To evaluate the impact of combination therapy with guselkumab and golimumab on disease-
specific health-related quality of life (HRQOL), including fatigue.

To evaluate the efficacy of combination therapy with guselkumab and golimumab by 
negative response signature status at baseline.

To evaluate the PK, immunogenicity, and PD of combination therapy with guselkumab and 
golimumab, including changes in C-reactive protein (CRP), fecal calprotectin, and other PD 
biomarkers.
Monotherapy Phase

To evaluate the clinical efficacy of combination therapy followed by guselkumab 
monotherapy.

To evaluate the safety of combination therapy followed by guselkumab monotherapy.

To evaluate the effect of combination therapy followed by guselkumab monotherapy on 
endoscopic improvement. 

To evaluate the impact of combination therapy followed by guselkumab monotherapy on 
disease-specific HRQOL, including fatigue.


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
To evaluate the efficacy of combination therapy followed by guselkumab monotherapy by 
negative response signature status at baseline.

To evaluate the PK, immunogenicity, and PD of combination therapy followed by 
guselkumab monotherapy, including changes in CRP, fecal calprotectin, and other PD 
biomarkers.
3.1.3.
Exploratory Objectives

To explore the effect of combination therapy on patient-reported outcome (PRO)
instruments (eg, Bristol Stool Form Scale [BSFS] and Patient’s Global Impression of 
Change [PGIC] of Severity of UC).
3.2.
Endpoints
3.2.1.
Primary Endpoint

Clinical response at Week 12, defined as a decrease from baseline in the Mayo score ≥30% 
and ≥3 points with either a decrease in rectal bleeding subscore (RBS) ≥1 or a RBS of 0 
or 1.
3.2.2.
Major Secondary Endpoint

Clinical remission at Week 12, defined as a Mayo score ≤ 2 with no individual subscore >1. 
Note: Other remission definitions may be considered and will be fully described in the Statistical 
Analysis Plan (SAP).
3.2.3.
Other Efficacy Endpoints
Combination Comparison Phase (ie, through Week 12)

Endoscopic healing at Week 12 (Mayo endoscopic subscore of 0 or 1).

Normalization of endoscopic appearance of the mucosa (Mayo endoscopic subscore of 0). 

Histologic healing at Week 12.

Mucosal healing at Week 12 (Composite Mayo endoscopic healing and histologic healing).

Change from baseline in the total score of the Inflammatory Bowel Disease Questionnaire 
(IBDQ) at Weeks 6 and 12.

A >20-point improvement in the IBDQ score at Weeks 6 and 12.

Change from baseline in the 7 domains and the abdominal pain numerical rating scale of 
Patient-Reported Outcomes Measurement Information System (PROMIS)-29 at Weeks 6 
and 12. 

Fatigue response at Weeks 6 and 12 (based on the PROMIS Fatigue Short Form 7a; to be 
defined in the SAP).

Clinical response, clinical remission, and endoscopic healing at Week 12 by negative 
response signature status at baseline. 

Change from baseline in the Mayo score at Week 12. 


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
Change from baseline in the partial Mayo score through Week 12.

Change from baseline in CRP through Week 12.

Change from baseline in fecal calprotectin concentration through Week 12.

Normalization of CRP concentration at Week 12 among participants with abnormal CRP 
concentration at baseline.

Normalization of fecal calprotectin concentration at Week 12 among participants with 
abnormal fecal calprotectin concentration at baseline.

Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score at Weeks 0 and 12 by the 
level of Mayo endoscopy score at the corresponding visit.

Change from baseline in the UCEIS score at Week 12. 

UCEIS score ≤4 at Week 12.

UC-related emergency department visits, hospitalizations, and surgeries through Week 12.
Monotherapy Phase (ie, after Week 12)

Clinical remission at Week 38.

Clinical response at Week 38.

Maintenance of clinical response at Week 38 among participants who achieved clinical 
response at Week 12.

Endoscopic healing at Week 38.

Normalization of endoscopic appearance of the mucosa at Week 38. 

Histologic healing at Week 38.

Mucosal healing at Week 38.

Clinical remission and not receiving concomitant corticosteroids at Week 38.

Maintenance of clinical remission at Week 38 among participants who achieved clinical 
remission at Week 12.

Change from baseline in the total score of the IBDQ at Weeks 24 and 38.

A >20-point improvement in the IBDQ score at Weeks 24 and 38. 

Change from baseline in the 7 domains and the abdominal pain numerical rating scale of
PROMIS-29 at Weeks 24 and 38.

Fatigue response at Weeks 24 and 38.

Clinical response, clinical remission, and endoscopic healing at Week 38 by negative 
response signature status at baseline.

Change from baseline in the Mayo score at Week 38.

Change from baseline in the partial Mayo score through Week 38.

Change from baseline in CRP through Week 38.


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
Change from baseline in fecal calprotectin concentration through Week 38.

Normalization of CRP concentration at Week 38 among participants with abnormal CRP 
concentration at baseline.

Normalization of fecal calprotectin concentration at Week 38 among participants with 
abnormal fecal calprotectin concentration at baseline.

UCEIS score at Week 38 by the level of Mayo endoscopy score at Week 38.

Change from baseline in the UCEIS score at Week 38.

UCEIS score ≤4 at Week 38.

UC-related emergency department visits, hospitalizations, and surgeries through Week 38.
3.2.4.
Exploratory Endpoints

BSFS score over time.

The distribution of the PGIC of Severity of UC over time.
Refer to Section 8, Study Assessments and Procedures for evaluations related to endpoints.
3.3.
Hypothesis
Combination therapy with guselkumab and golimumab will result in a rate of clinical response at 
Week 12 that is superior to both monotherapy arms.
4.
STUDY DESIGN
4.1.
Overall Design
This is a Phase 2a, randomized, double-blind, active-controlled, parallel-group, multicenter,
interventional POC clinical study designed to evaluate the efficacy and safety of combination 
therapy with guselkumab and golimumab in adults with moderately to severely active UC. The 
target population is men or women 18 to 65 years old with moderately to severely active UC, as 
defined by a Mayo score of 6 to 12, inclusive, at baseline, including an endoscopy subscore ≥2 as 
obtained during the central review of the video endoscopy. Participants must be naïve to TNF 
antagonists and have failed or not tolerated conventional therapy with oral or IV corticosteroids 
or immunomodulators (6-mercaptopurine [6-MP] or AZA). 
This study will consist of 2 distinct phases: a 12-week combination comparison phase followed 
by a 26-week monotherapy phase. At Week 0, a target of 210 participants will be randomized in 
a 1:1:1 ratio to either combination therapy with guselkumab and golimumab, guselkumab 
monotherapy, or golimumab monotherapy, stratified by the concomitant use of corticosteroids at 
baseline (Y/N). Participants randomized to combination therapy will receive guselkumab 
monotherapy after Week 12. Participants randomized to a monotherapy group will continue on 
their originally randomized monotherapy after Week 12. The combination therapy arm will 
employ the same dose regimens of guselkumab and golimumab being used in the respective 
monotherapy intervention groups to facilitate scientific interpretation of the results. The 
following is a description of the 3 intervention groups:


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
Combination therapy: guselkumab 200 mg IV and golimumab 200 mg SC at Week 0; 
golimumab 100 mg SC at Weeks 2, 6, and 10; guselkumab 200 mg IV at Weeks 4 and 8 
followed by guselkumab 100 mg SC q8w

Guselkumab monotherapy: guselkumab 200 mg IV at Weeks 0, 4, and 8 followed by 
guselkumab 100 mg SC q8w

Golimumab monotherapy: golimumab 200 mg SC injection at Week 0, followed by 
golimumab 100 mg at Week 2 and then golimumab 100 mg every 4 weeks (q4w)
In addition, placebo administrations (IV or SC) will be given, as appropriate, to maintain the 
blind throughout the duration of the study. Refer to Study Intervention (Section 6) for additional 
details.
Immunomodulators (6-MP, AZA, and MTX) must be discontinued for at least 2 weeks before 
the first dose of study intervention. For participants who are receiving oral corticosteroids at 
baseline, the investigator must begin tapering the daily dose of corticosteroids at Week 6. All 
participants will be evaluated for clinical worsening of UC throughout the study. The use of 
concomitant and prohibited therapies is described in Section 6.5. In general, doses of 
concomitant therapies for UC should remain stable through Week 38 (except for mandatory oral 
corticosteroid tapering beginning at Week 6), and concomitant therapies for UC should not be 
initiated unless considered medically necessary by the investigator. Initiation of prohibited 
therapies will result in discontinuation of study intervention.
Endoscopy with central read is planned for screening/baseline, Week 12, and Week 38. 
Consenting participants will have an additional endoscopy at Week 4, which will also be 
assessed by a central reader. Efficacy, PK and PD parameters, biomarkers, and safety will be 
assessed according to the Schedule of Activities (SoA) (Section 1.3). A pharmacogenomic blood 
sample will be collected from participants who consent to this component of the protocol (where 
local regulations permit). Participation in pharmacogenomic research is optional.
Overall participant duration will be up to 58 weeks total (screening: up to 8 weeks; treatment 
duration: 38 weeks [12 weeks for the combination comparison phase; 26 weeks for the 
monotherapy phase]; safety follow-up: approximately 16 weeks after the last administration of 
study intervention at Week 34). An interim analysis is planned to inform future clinical 
development (see details in Section 9.5). Database locks (DBLs) are planned at Weeks 12 and 
38, and a final DBL is planned after all participants complete the safety follow-up visit. The end 
of the study will be defined as when the last participant completes his or her final safety follow-
up visit. 
An independent DMC will be commissioned for this study, refer to Section 9.5.1 for more details 
on the DMC. 
A diagram of the study design is provided in Section 1.2, Schema.


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4.2.
Scientific Rationale for Study Design
This type of parallel-group study design is consistent with the design of other combination 
therapy studies.7,11,38,58 The combination therapy arm will employ the same dose regimens of 
guselkumab and golimumab that are being used in the respective monotherapy treatment arms 
which will allow the contribution of each monotherapy to the combination to be assessed relative 
to each monotherapy alone. The target population (ie, men or women 18 to 65 years old with 
moderately to severely active UC who are naïve to TNF antagonists and have failed or not 
tolerated conventional therapy) is considered appropriate given the study interventions being 
evaluated. For example, the inclusion of patients who previously failed TNF antagonists is not 
considered clinically appropriate for this study design since they could be randomized to the 
golimumab monotherapy treatment arm. 
This study will consist of 2 distinct phases: a 12-week combination comparison phase followed 
by a 26-week monotherapy phase. The duration of the combination comparison phase (ie, 
approximately 12 weeks) is thought to provide sufficient time to evaluate the effect of 
combination therapy compared to monotherapy, while minimizing the potential risks associated 
with longer duration combination therapy. The 12-week duration of the combination comparison 
phase is important because if combination therapy merely shifted late responders to an earlier 
response, but did not increase the total fraction of responders, then combination therapy would 
provide limited benefit to patients with UC. Moreover, Week 12 efficacy endpoints are being 
used to evaluate other anti-IL-23 mAbs.1,46 Participants randomized to a monotherapy group will 
continue in the monotherapy phase based on their original randomized treatment group, with 
participants in the combination therapy arm receiving guselkumab monotherapy after Week 12. 
The duration of 26 weeks for the monotherapy phase is thought to provide sufficient time to 
evaluate response in all 3 intervention groups.
4.2.1.
Blinding, Control, Study Phase/Periods, Intervention Groups
Two monotherapy controls will be used to determine the sensitivity of the clinical endpoints in 
this study. Randomization will be used to minimize bias in the assignment of participants to 
intervention groups, to increase the likelihood that known and unknown participant attributes 
(eg, demographic and baseline characteristics) are evenly balanced across intervention groups, 
and to enhance the validity of statistical comparisons across intervention groups. Blinded 
intervention will be used to reduce potential bias during data collection and evaluation of clinical 
endpoints.
4.2.2.
DNA and Biomarker Collection
Biomarker samples will be collected to evaluate the cellular and molecular mechanism of action 
of guselkumab and golimumab, or help to explain interindividual variability in clinical outcomes, 
or may help to identify population subgroups that respond differently to either intervention. 
Serum, whole blood, and fecal samples will be collected from all participants to assess PD 
markers associated with the response to guselkumab and golimumab. Mucosal biopsies will also 
be obtained from all participants pre-treatment during screening and post-treatment at Weeks 12 
and 38 to assess cellular and molecular changes within the intestinal mucosal tissue. The goal of 
the biomarker analyses is to further define the mechanism of action of guselkumab and 


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golimumab combination treatment or monotherapy with either agent in UC, and to aid in 
evaluating the intervention-clinical response relationship. 
Two optional sub-studies are planned:

Optional Week 4 endoscopy and biopsy sub-study: Only those participants who consent 
to participate in the optional sub-study will undergo Week 4 endoscopy assessment and
biopsy collection. Exploratory analyses of intestinal mucosal tissue obtained by biopsy at 
Week 4 will be performed to delineate the mechanisms of action of guselkumab and/or
golimumab by establishing a sequence of molecular and cellular effects beginning at an 
early time point. Whole blood (PBMCs) will also be collected. In addition, data collected at 
Week 4 will be explored for correlation with clinical efficacy observations at later time 
points.

Optional pharmacogenomic sub-study: It is recognized that genetic variation can be an 
important contributory factor to interindividual differences in intervention distribution and 
response and can also serve as a marker for disease susceptibility and prognosis. 
Pharmacogenomic research may help to explain interindividual variability in clinical 
outcomes, identify markers associated with disease susceptibility and prognosis, and may 
help to identify population subgroups that respond differently to an intervention. The goal of 
the pharmacogenomic component is to collect deoxyribonucleic acid (DNA) to allow for the 
identification of genetic factors that may influence the PK, PD, efficacy, safety, or 
tolerability of guselkumab and/or golimumab and to identify genetic factors associated with 
UC or the response to guselkumab and/or golimumab treatment. 
4.2.3.
Patient-Reported Outcomes on Health-Related Quality of Life
Patient-reported outcome (PRO) evaluations (ie, IBDQ, PROMIS-29, PROMIS Fatigue 7-item 
Short Form, and PGIC of Severity of UC) will be used to assess the benefits of guselkumab and 
golimumab treatment on disease-specific and general HRQOL. Patient-reported outcomes will 
only be collected in countries where translations of the evaluations are available. See Section 8.1
for more details.
4.2.4.
Medical Resource Utilization Collection
Medical resource utilization evaluations, including but not limited to UC-related emergency 
department visits, hospitalizations, and surgeries, will be collected for future evaluation of the 
health economics of guselkumab and golimumab treatment.
4.2.5.
Study-Specific Ethical Design Considerations
Potential participants will be fully informed of the risks and requirements of the study and, during 
the study, participants will be given any new information that may affect their decision to continue 
participation. They will be told that their consent to participate in the study is voluntary and may be 
withdrawn at any time with no reason given and without penalty or loss of benefits to which they 
would otherwise be entitled. Only participants who are fully able to understand the risks, benefits, 
and potential AEs of the study, and provide their consent voluntarily will be enrolled.


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The total blood volume to be collected from each participant in this study (maximum of 
approximately 350 mL over approximately 58 weeks) is far less than the American Red Cross 
standard limit for whole blood donation (approximately 475 mL q8w) and is, therefore, 
considered an acceptable amount of blood to be collected over this time. For more details 
regarding blood collection, see Blood Sample Collection in Section 8.
4.3.
Justification for Dose
4.3.1.
Guselkumab
The planned guselkumab dose is 200 mg IV at Weeks 0, 4, and 8 followed by 100 mg SC q8w. 
The approved psoriasis dose of guselkumab is 100 mg administered by SC injection at Week 0, 
Week 4, and q8w thereafter and dose regimens as high as 200 mg SC q8w have been shown to 
have favorable safety in a 6-month Phase 2 trial in RA. The sponsor selected a higher dose of 
guselkumab for this Phase 2a POC study in UC compared to what is approved for psoriasis over 
the induction period of Week 0 to Week 12 because, historically, doses in IBD have been higher 
than those in psoriasis for mAbs approved for both indications (STELARA USPI56, SmPC55; 
HUMIRA USPI21, SmPC20).
Regarding the safety of this higher IV guselkumab dose, single doses of guselkumab as high as 
10 mg/kg, with the highest single dose tested being 987 mg, have been previously studied in a 
Phase 1 plaque psoriasis study in a limited number of participants. Additionally, guselkumab IV 
doses of up to 50 mg/kg weekly for 5 weeks and guselkumab SC doses of up to 50 mg/kg weekly 
for 24 weeks were well tolerated in cynomolgus monkeys, and did not result in any clinical or 
anatomic findings (Section 2.2.1.1). These data suggest an acceptable exposure margin between 
the predicted guselkumab exposures at the proposed dose regimen compared to those observed in 
toxicology studies; the estimated safety margin is approximately 19- to 26-fold for the 200 mg 
IV dosing.
This guselkumab dose regimen was further chosen to align with the dose regimens being tested 
in the guselkumab Phase 2b/3 Crohn’s disease program while minimizing the potential safety 
risk in the combination setting (see Section 4.3.3). This is deemed to be a reasonable selection 
given the shared biology and the similar response to treatments between Crohn’s disease and 
UC. Specifically, this guselkumab dose regimen corresponds to the lowest dose regimen planned 
to be evaluated in the dose-ranging portion of the Phase 2b/3 Crohn’s disease program. Dose 
selection for the latter program was based on several considerations, including dose-response 
data from studies of guselkumab in plaque psoriasis, and published information on risankizumab 
(another anti-IL-23 mAb) in plaque psoriasis and Crohn’s disease, and on the relative dosing 
requirements for anti-IL-23 mAbs in plaque psoriasis versus Crohn’s disease. Specifically, in 
Crohn’s disease, the 200 mg IV induction dose of risankizumab achieved clinical response and 
remission rates of 32% and 17% respectively at Week 8, approximating rates observed with 
STELARA at the approved dose in comparable patient populations.14 A maintenance regimen of 
100 mg SC q8W anchored at the approved psoriasis dose will be studied following the 200 mg 
IV induction therapy. The posology of other biologics in Crohn’s disease suggests that once the 


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disease inflammatory burden is reduced, the drug exposures required to maintain efficacy may be 
lower than the exposures attained with initial induction doses. 
4.3.2.
Golimumab
The planned golimumab dose is the approved dose for UC (SIMPONI USPI52, SmPC51). It is the 
highest approved golimumab dose across indications and the safety profile is well established: 

200 mg initially administered by SC injection at Week 0, followed by 100 mg at 
Week 2 and then 100 mg q4w.
4.3.3.
Guselkumab and Golimumab Combination
The objective of this Phase 2a study is to establish the POC for a combination treatment 
approach in UC by demonstrating clinically relevant benefit of guselkumab combined with 
golimumab as compared to monotherapy alone with either treatment. To achieve this objective,
over the first 12 weeks, the combination therapy arm will employ the same dose regimens of 
guselkumab and golimumab that are being used in the respective monotherapy intervention 
groups which allows the contribution of each monotherapy to the combination to be assessed 
relative to each monotherapy alone. From Week 12, the same dose regimen of guselkumab that 
is being used in the monotherapy intervention group will be followed to see how well it performs 
as a maintenance therapy following combination induction treatment.
In nonclinical toxicology studies, neither guselkumab or golimumab present any apparent 
overlapping toxicities that could be expected to be potentiated when administered in 
combination. Moreover, the probability of PK or PD interaction in the combination is considered 
low. Guselkumab is a human IgG1λ mAb that binds IL-23 p19 while golimumab is a human 
IgG1κ mAb that binds to soluble and transmembrane bioactive forms of TNFα. Both are likely 
degraded into small peptides and amino acids via catabolic pathways typically associated with 
endogenous IgG metabolism, which has large capacity. Given the acceptable nonclinical and 
clinical safety profiles for guselkumab and golimumab and the short duration in the combination
comparison phase (approximately 12 weeks), potential safety risk in the combination setting is 
considered to be manageable with careful monitoring and early intervention (including 
pre-defined stopping rule Section 2.3 and Section 7).
4.4.
End of Study Definition
The study is considered completed when the last participant completes the last scheduled study 
assessment shown in the SoA (Section 1.3) and appropriate follow-up has been completed. The 
final data from the study site will be sent to the sponsor (or designee) after completion of the 
final participant assessment at that study site, in the time frame specified in the Clinical Trial 
Agreement.
5.
STUDY POPULATION
Screening for eligible participants will be performed within 8 weeks before administration of the 
study intervention. Refer to Section 5.4, Screen Failures for conditions under which the repeat of 
any screening procedures are allowed.


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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.
Male or female, 18 to 65 years old (inclusive).
2.
Has a confirmed clinical diagnosis of UC at least 3 months before screening.
3.
Has moderately to severely active UC, defined as a baseline (Week 0) Mayo score of 6 
to 12, inclusive, using the Mayo endoscopy subscore obtained during the central review 
of the video endoscopy.
4.
Has a screening endoscopy with ≥2 endoscopy subscore of the Mayo score as obtained 
during the central review of the video endoscopy.
Concomitant or previous medical therapies received
5.
Must be naïve to TNF antagonists and have a prior or current UC medication history 
that includes at least 1 of the following:
a.
Inadequate response to or failure to tolerate current treatment with oral 
corticosteroids or immunomodulators (6-MP or AZA)
as defined in 
Appendix 2 (Section 10.2).
OR
b.
History of failure to respond to, or tolerate, at least 1 of the following 
therapies: oral or IV corticosteroids or immunomodulators (6-MP or AZA) as 
defined in Appendix 2 (Section 10.2).
OR
c.
History of corticosteroid dependence (ie, an inability to successfully taper 
corticosteroids without a return of the symptoms of UC) as defined in 
Appendix 2 (Section 10.2).
6.
Before the first administration of study intervention, the following conditions must be 
met:
a.
If receiving oral 5-aminosalicylic acid (5-ASA) compounds, the dose must 
have been stable for at least 2 weeks.
b.
If receiving oral corticosteroids other than budesonide or beclomethasone
dipropionate, the dose must be ≤20 mg/day prednisone or its equivalent and 
must have been stable for at least 2 weeks.


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c.
If receiving budesonide or beclomethasone dipropionate, the dose must have 
been stable for at least 2 weeks.
d.
If oral 5-ASA compounds or oral corticosteroids have been recently 
discontinued, they must have been stopped for at least 2 weeks.
7.
The following medications/therapies must have been discontinued before the first 
administration of study intervention:
a.
Immunomodulators (6-MP, AZA, or MTX) for at least 2 weeks.
b.
Vedolizumab for at least 18 weeks.
c.
Tofacitinib and other inhibitors of JAKs for at least 4 weeks or 5 half-lives, 
whichever is longer.
d.
Cyclosporine, mycophenolate mofetil, tacrolimus, or sirolimus for at least 
4 weeks.
e.
6-thioguanine must have been discontinued for at least 4 weeks.
f.
Rectal corticosteroids (ie, corticosteroids administered to the rectum or 
sigmoid colon via foam or enema or suppository) for at least 2 weeks.
g.
Rectal 5-ASA compounds (ie, 5-ASAs administered to the rectum or sigmoid 
colon via foam or enema or suppository) for at least 2 weeks.
h.
Parenteral corticosteroids for at least 2 weeks.
i.
Total parenteral nutrition or enteral nutrition for at least 2 weeks.
j.
Antibiotics for the primary treatment of UC (eg, ciprofloxacin, metronidazole, 
or rifaximin) for at least 2 weeks.
8.
A participant ≥45 years of age must either have had a full colonoscopy to assess for the 
presence of adenomatous polyps within 5 years before the first administration of study 
intervention or a full colonoscopy to assess for the presence of adenomatous polyps at 
the screening visit. The adenomatous polyps must be removed before the first 
administration of study intervention.
9.
A participant who has had extensive colitis for ≥8 years, or disease limited to the left 
side of the colon for ≥10 years, must either have had a full colonoscopy to assess for the 
presence of dysplasia within 1 year before the first administration of study intervention
or a full colonoscopy to assess for the presence of malignancy at the screening visit.
Screening laboratory tests
10.
Has screening laboratory test results within the following parameters:
a.
Hemoglobin ≥8.0 g/dL (International System of Units [SI]: ≥80.0 g/L)
b.
White blood cell count (WBC) ≥3 × 103/µL (SI: ≥3.0 × 109/L)
c.
Neutrophils ≥1.5 × 103/µL (SI: ≥1.5 × 109/L)
d.
Platelets ≥100 × 103/µL (SI: ≥100 × 109/L)


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e.
Serum creatinine ≤1.5 mg/dL (SI: ≤133 µmol/L)
f.
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 
concentrations must be within 2 times the upper limit of the normal range 
(ULN) for the laboratory conducting the test.
Tuberculosis
11.
Is considered eligible according to the following TB screening criteria:
a.
Has no history of latent or active TB before screening. 
b.
Has no signs or symptoms suggestive of active TB upon medical history and/or 
physical examination.
c.
Has had no recent close contact with a person with active TB.
d.
Criterion modified per Amendment 2. 
d.1. Within 8 weeks prior to the first administration of study intervention, has a 
negative QuantiFERON®-TB test result.
For a participant with an 
indeterminate QuantiFERON®-TB test, the test may be repeated once. If the 
result is indeterminate on repeat testing, the participant is considered a screen 
failure as outlined in Section 8.2.12.1.   
Note: A negative tuberculin skin test result (see Appendix 3 [Section 10.3]) is 
required if the QuantiFERON®-TB test is not approved/registered in the 
country in which this protocol is being conducted. In Ukraine, while the 
QuantiFERON®-TB test is not approved/registered, it is accepted and a 
tuberculin skin test is not required.
e.
Has a chest radiograph (both posterior-anterior and lateral views, or per 
country regulations where applicable), taken within 12 weeks before the first 
administration of study intervention and read by a qualified radiologist, with no 
evidence of current, active TB or old, inactive TB.
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.
12.
A woman of childbearing potential must have a negative highly sensitive serum 
(-human chorionic gonadotropin) pregnancy test result at screening and a negative 
urine pregnancy test result at Week 0.
13.
Before randomization, a woman must be (as defined in Appendix 4 [Section 10.4],
Contraceptive and Barrier Guidance and Collection of Pregnancy Information):


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a.
Not of childbearing potential
OR
b.
Of childbearing potential and:
o
If heterosexually active, practicing a highly effective method of 
contraception (failure rate of <1% per year when used consistently and 
correctly) and agrees to remain on a highly effective method while 
receiving study intervention and until 6 months after last dose (ie, the end 
of relevant systemic exposure). Examples of highly effective methods of 
contraception are located in Appendix 4 (Section 10.4), Contraceptive and 
Barrier Guidance and Collection of Pregnancy Information; however, the 
method selected must meet local/regional regulations/guidelines for highly 
effective contraception. 
Note: If a participant’s childbearing potential changes after start of the study (eg, a 
premenarchal woman experiences menarche) or the risk of pregnancy changes (eg, 
a woman who is not heterosexually active becomes active), a woman must begin 
using a highly effective method of contraception, as described above.
14.
A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted 
reproduction during the study and for 6 months after the last study intervention.
15.
A man who is sexually active with a woman of childbearing potential and who has not 
had a vasectomy must agree to use a barrier method of birth control, eg, either condom 
with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap 
(diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
16.
A male participant must agree not to donate sperm for the purpose of reproduction 
during the study and for a minimum of 6 months after receiving the last dose of study 
intervention.
General
17.
Criterion modified per Amendment 2.
17.1. Be willing and able to adhere to all specified requirements, including but not 
limited to completion of required assessments, adherence to visit schedule, and 
compliance with the lifestyle restrictions as specified in this protocol.
18.
Each participant must sign an informed consent form (ICF) indicating that he or she 
understands the purpose of and procedures required for the study and is willing to 
participate in the study. In regions where the legal age of consent is older than 18 years, 
informed consent must be obtained from and signed by both the participant and his or 
her legally acceptable representative.
19.
Each participant must sign a separate ICF if he or she agrees to provide optional DNA 
samples for research where local regulations permit. In regions where the legal age of 
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both the participant and his or her legally acceptable representative. Refusal to give 
consent for the optional DNA samples does not exclude a participant from participation 
in the study.
20.
Each participant must sign a separate ICF if he or she agrees to participate in the 
optional Week 4 endoscopy and biopsy sub-study. In regions where the legal age of 
consent is older than 18 years, informed consent must be obtained from and signed by 
both the participant and his or her legally acceptable representative. Refusal to give 
consent for the optional Week 4 endoscopy and biopsy sub-study does not exclude a 
participant from participation in the study
5.2.
Exclusion Criteria
Any potential participant who meets any of the following criteria will be excluded from 
participating in the study:
1.
Has severe extensive colitis as evidenced by:
a.
Current hospitalization for the treatment of UC.
OR
b.
Investigator judgment that the participant is likely to require a colectomy 
within 12 weeks of baseline.
OR
c.
Symptom complex at screening or baseline visits that includes at least 4 of the 
following:
1)
Diarrhea with ≥6 bowel movements/day with macroscopic blood in stool
2)
Focal severe or rebound abdominal tenderness
3)
Persistent fever (≥37.5°C)
4)
Tachycardia (>100 beats/minute)
5)
Anemia (hemoglobin <8.5 g/dL)
2.
Has UC limited to the rectum only or to <20 cm of the colon.
3.
Presence of a stoma.
4.
Presence or history of a fistula.
5.
Require, or required within the 2 months before screening, surgery for active 
gastrointestinal bleeding, peritonitis, intestinal obstruction, or intra-abdominal or 
pancreatic abscess requiring surgical drainage, or other conditions possibly confounding 
the evaluation of benefit from study intervention treatment.


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6.
Presence of symptomatic colonic or small bowel obstruction, confirmed by objective 
radiographic or endoscopic evidence of a stricture with resulting obstruction (dilation of 
the colon or small bowel proximal to the stricture on barium radiograph or an inability 
to traverse the stricture at endoscopy).
7.
History of extensive colonic resection (eg, less than 30 cm of colon remaining) that 
would prevent adequate evaluation of the effect of study intervention on clinical disease 
activity.
8.
History of colonic mucosal dysplasia. Participants will not be excluded from the study 
because of a pathology finding of “indefinite for dysplasia with reactive atypia.”
9.
Presence on screening endoscopy of adenomatous colonic polyps, if not removed before 
study entry, or history of adenomatous colonic polyps that were not removed.
10.
Diagnosis of indeterminate colitis, microscopic colitis, ischemic colitis, or Crohn’s 
disease or clinical findings suggestive of Crohn’s disease.
11.
Criterion modified per Amendment 2.
11.1. Has a stool culture or other examination positive for an enteric pathogen, 
including Clostridium difficile toxin, within 4 months before the first administration of 
study intervention, unless a repeat examination is negative and there are no signs of 
ongoing infection with that pathogen.
Concomitant or previous medical therapies received
12.
Has received the following prescribed medications or therapies:
a.
A biologic therapy targeted at IL-12 and/or IL-23 (eg, ustekinumab, 
briakinumab, guselkumab, mirikizumab, tildrakizumab, brazikumab,
or 
risankizumab).
b.
A biologic therapy targeted at TNF (eg, golimumab, infliximab, etanercept,
adalimumab, or certolizumab pegol). 
c.
Natalizumab within 12 months of first study intervention administration. 
d.
Agents that deplete B or T cells (eg, rituximab, alemtuzumab) within 12 
months of first study intervention administration, or continue to manifest 
depletion of B or T cells more than 12 months after completion of therapy with 
lymphocyte-depleting agents.
e.
Any investigational drug within 4 weeks before first administration of study 
intervention or within 5 half-lives of the investigational agent, whichever is 
longer.
f.
Apheresis (eg, Adacolumn or Cellsorba apheresis) within 2 weeks before the 
first administration of study intervention.


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Infections or predisposition to infections
13.
Has a history of latent or active granulomatous infection, including histoplasmosis or 
coccidioidomycosis, before screening. Refer to Inclusion Criterion 11 for information 
regarding eligibility with a history of latent TB.
14.
Has a history of, or ongoing, chronic or recurrent infectious disease, including but not 
limited to, chronic renal infection, chronic chest infection (eg, bronchiectasis), sinusitis, 
recurrent urinary tract infection (eg, recurrent pyelonephritis, recurrent cystitis), an 
open, draining, or infected skin wound, or an ulcer.
15.
Has a chest radiograph within 3 months before the first administration of study 
intervention that shows an abnormality suggestive of a malignancy or current active 
infection, including TB.
16.
Has a history of being human immunodeficiency virus (HIV) antibody-positive, or tests 
positive for HIV at screening.
17.
Is seropositive for antibodies to hepatitis C virus (HCV) without a history of successful 
treatment, defined as being negative for HCV ribonucleic acid (RNA) at least 24 weeks 
after completing antiviral treatment.
18.
Tests positive for hepatitis B virus (HBV) infection (see Appendix 5 [Section 10.5], 
Hepatitis B Virus Screening with HBV DNA Testing).
Note: For participants who are not eligible for this study due to HIV, HCV, and HBV 
test results, consultation with a physician with expertise in the treatment of those 
infections is recommended.
19.
Has had a Bacille Calmette-Guérin (BCG) vaccination within 12 months or any other 
live bacterial or live viral vaccination within 12 weeks before baseline. 
20.
Has or has had a nontuberculous mycobacterial infection or clinically significant 
opportunistic infection (eg, cytomegalovirus colitis, pneumocystosis, invasive 
aspergillosis).
21.
Has had a clinically significant infection (eg, hepatitis, sepsis, pneumonia, 
pyelonephritis), has been hospitalized for an infection, or has been treated with 
parenteral antibiotics for an infection within 2 months before first administration of 
study intervention. Treated and resolved infections not considered clinically significant 
at the discretion of the investigator need not be exclusionary (eg, acute upper respiratory 
tract infection, uncomplicated urinary tract infection).
22.
Has current signs or symptoms of a clinically significant infection. Ongoing infections 
not considered clinically significant at the discretion of the investigator need not be 
exclusionary (eg, acute upper respiratory tract infection, uncomplicated urinary tract 


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infection).
23.
Has evidence of a herpes zoster infection ≤8 weeks before baseline.
Malignancy or increased potential for malignancy
24.
Has any known malignancy or has a history of malignancy (with the exception of basal 
cell carcinoma; squamous cell carcinoma in situ of the skin; or cervical carcinoma in 
situ that has been treated with no evidence of recurrence; or squamous cell carcinoma of 
the skin that has been treated with no evidence of recurrence within 5 years before 
screening).
25.
Presence or history of lymphoproliferative disease including lymphoma, or signs and 
symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy 
of unusual size or location (eg, nodes in the posterior triangle of the neck, 
infraclavicular, epitrochlear, or periaortic areas), or clinically significant hepatomegaly 
or splenomegaly, or monoclonal gammopathy of undetermined significance.
Coexisting medical conditions or past medical history
26.
Has known allergies, hypersensitivity, or intolerance to guselkumab or golimumab or 
their excipients (refer to the respective guselkumab and golimumab IBs).
27.
Has severe, progressive, or uncontrolled renal, hepatic, hematologic, endocrine, 
pulmonary, cardiac, neurologic, psychiatric, or cerebral disease, or signs or symptoms 
thereof.
28.
Has a history of, or concurrent congestive heart failure including medically controlled, 
asymptomatic congestive heart failure.
29.
Has a history of a demyelinating disorder such as multiple sclerosis or optic neuritis. 
30. 
Has a transplanted organ (with the exception of a corneal transplant performed >12 
weeks before screening).
31.
Criterion deleted per Amendment 2.
32.
Has a history of drug or alcohol abuse according to the Diagnostic and Statistical 
Manual of Mental Disorders, 5th edition (DSM-V), within 1 year before screening.
33.
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 


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ratings of Wish to be Dead (“Ideation level 1”), Non-Specific Active Suicidal Thoughts 
(“Ideation level 2”), Active Suicidal Ideation with Any Methods (Not Plan) without 
Intent to Act (“Ideation level 3”), or non-suicidal self-injurious behavior who are 
determined to be at risk by the investigator may not be randomized.
34.
Has poor tolerability of venipuncture or lacks adequate venous access for required blood 
sample collections during the study period.
35.
Is a woman who is pregnant, or breast-feeding, or planning to become pregnant, or is a 
man who plans to father a child while enrolled in this study or within 6 months after the 
last dose of study intervention.
General
36.
Is currently participating or intends to participate in any other study using an 
investigational agent or procedure during participation in this study.
37.
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.
38.
Is an employee of the investigator or study site, with direct involvement in the proposed 
study or other studies under the direction of that investigator or study site, as well as 
family members of the employees or the investigator.
NOTE: Investigators should ensure that all study enrollment criteria have been met at screening. 
If a participant's clinical status changes (including any available laboratory results or receipt of 
additional medical records) after screening but before the first dose of study intervention is given 
such that he or she no longer meets all eligibility criteria, then the participant should be excluded 
from participation in the study. Section 5.4, Screen Failures, describes options for retesting. The 
required source documentation to support meeting the enrollment criteria are noted in 
Appendix 6 [Section 10.6], 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.
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 agree not to receive a live virus or live bacterial vaccination, including a BCG 
vaccination, during the study and for 12 months after receiving study intervention for 
BCG vaccination or 12 weeks after receiving the last administration of study 


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intervention for other live vaccines.
4.
Must not receive guselkumab or golimumab 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 complete the Week 12 visit or 
early termination visit as described in Section 1.3 before he or she terminates study 
participation.
5.
Must be willing and able to complete daily diaries 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 not 
randomized into the study, the date seen and age at initial informed consent will be used.
Completion of screening and randomization procedures within the specified 8-week window is 
required. If any delay leads to the expiration of time-specific assessments (eg, TB, chest 
radiograph, 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.
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 8 weeks.
Rescreening
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened 1 time. Rescreened participants should be assigned a new participant number, 
undergo the informed consent process, and then start a new screening phase.


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6.
STUDY INTERVENTION
6.1.
Study Interventions Administered

All participants will receive an IV infusion of either guselkumab or placebo at Weeks 0, 4, 
and 8. 

All participants will receive 1 SC injection of either guselkumab or placebo at Weeks 16, 24, 
and 32.

All participants will receive 2 SC injections of either golimumab or placebo at Week 0, and 
1 SC injection of either golimumab or placebo at Weeks 2, 6, 10, 14, 18, 22, 26, 30, and 34.
For the baseline (W0) visit, the IV study intervention should be administered first. The SC study 
intervention should be administered approximately 30 minutes after the IV study intervention 
infusion is complete. If multiple SC injections are administered within the administration visit, 
each injection of study intervention should be given at a different location of the body. 
Study intervention administration must be captured in the source documents and the electronic 
case report form (eCRF).
Guselkumab and golimumab and the corresponding placebo for each intervention will be 
manufactured and provided under the responsibility of the sponsor. Refer to the respective IBs
for a list of excipients. Detailed instructions on the administration of study intervention will be 
provided in the site Investigational Product Procedures Manual (IPPM) and Investigation 
Product Preparation Instructions (IPPI).
Guselkumab
Guselkumab will be supplied as a 100 mg/mL sterile liquid in a single dose prefilled syringe 
(PFS) assembled in an UltraSafe Plus™ Passive Needle Guard (PFS-U). Placebo for guselkumab 
will be supplied as a 1 mL sterile liquid in a single dose PFS assembled in a PFS-U. The single 
dose PFS-U will support both IV preparations and SC administrations.
Golimumab
Golimumab for SC injection will be supplied as a 100 mg/mL sterile liquid in a single-use PFS. 
Placebo for golimumab for SC injection will be supplied as a 1 mL sterile liquid in a single-use 
PFS. 
6.2.
Preparation/Handling/Storage/Accountability
Guselkumab, placebo for guselkumab, golimumab, and placebo for golimumab will be supplied 
to the study sites. All study interventions must be stored according to the labeled storage 
condition, 2°C to 8°C (36°F to 46°F), and protected from exposure to light. Do not freeze the 
study interventions. The products are designed for single-use only. 
Guselkumab 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 


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particles. Golimumab should be clear to slightly opalescent and colorless to light yellow. Do not 
use golimumab if the solution is discolored or cloudy, or if foreign particles are present. 
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 IPPM and IPPI for additional guidance on study intervention preparation, 
handling, and storage.
6.2.1.
Accountability
The investigator is responsible for ensuring that all study intervention received at the site is 
inventoried and accounted for throughout the study. The study intervention administered to the 
participant must be documented on the intervention accountability form. All study intervention 
will be stored and disposed of according to the sponsor's instructions. 
Study intervention must be handled in strict accordance with the protocol and the container label, 
and must be stored at the study site in a limited-access area or in a locked cabinet under 
appropriate environmental conditions. Unused study intervention must be available for 
verification by the sponsor's study site monitor during on-site monitoring visits. The return to the 
sponsor of unused study intervention will be documented on the intervention return form. When 
the study site is an authorized destruction unit and study intervention supplies are destroyed on-
site, this must also be documented on the intervention return form.
Potentially hazardous materials such as used ampules, needles, syringes, and vials containing 
hazardous liquids should be disposed of immediately in a safe manner and therefore will not be 
retained for intervention accountability purposes. 
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.
6.3.
Measures to Minimize Bias: Randomization and Blinding
Randomization will be used to minimize bias in the assignment of participants to treatment 
groups, to increase the likelihood that known and unknown participant attributes (eg, 
demographic and baseline characteristics) are evenly balanced across treatment groups, and to 
enhance the validity of statistical comparisons across treatment groups. Blinded treatment will be 
used to reduce potential bias during data collection and evaluation of clinical endpoints.
Intervention Allocation
Central randomization will be implemented in this study. Participants will be randomly assigned 
to 1 of 3 intervention groups (1:1:1 ratio), based on a computer-generated randomization 


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schedule prepared before the studies by or under the supervision of the sponsor. The 
randomization will be balanced by using randomly permuted blocks and will be stratified by
concomitant use of corticosteroids at baseline (Y/N). The interactive web response system 
(IWRS) will assign a unique treatment code, which will dictate the treatment assignment and 
matching study intervention kit(s) for the participant. The requestor must use his or her own user 
identification and personal identification number when contacting the IWRS, and will then be 
given the relevant participant details to uniquely identify the participant.
Blinding
To maintain the study blind, the study intervention container will have a label containing the 
study name, study intervention number, and reference number. The study intervention number 
will be entered in the eCRF when the study intervention is dispensed. Each active study 
intervention and its matching placebo will be identical in appearance.
The investigator will not be provided with randomization codes. The codes will be maintained 
within the IWRS, which has the functionality to allow the investigator to break the blind for an 
individual participant.
Data that may potentially unblind the treatment assignment (eg, study intervention serum 
concentrations, antibodies to study intervention) will be handled with special care to ensure that 
the integrity of the blind is maintained and the potential for bias is minimized. This can include 
making special provisions, such as segregating the data in question from view by the 
investigators, clinical team, or others as appropriate until the study unblinding.
The post-baseline results of CRP and fecal calprotectin tests performed by the central laboratory 
will be blinded to the study sites. If a study site requests these data, it will be provided to them 
after the final safety analyses have been completed.
Treatment assignment blinding will be maintained for study sites, site monitors, and participants
until the final safety DBL and analyses are completed. 
In this study, the full sponsor unblinding will occur after the Week 38 DBL. However, a planned 
interim analysis will occur after the first 30% to 60% of randomized participants have either 
completed the Week 12 visit or have terminated study participation before Week 12. At the time 
of this interim analysis, a limited number of sponsor personnel (except for site monitors, who 
have interactions with the investigative sites) will become unblinded to only those first 30% to 
60% of randomized participants. The purpose and analytical details for this interim analysis are 
provided in Section 9.5. After all 210 randomized participants have either completed the 
Week 12 visit or have terminated study participation before Week 12, the Week 12 DBL will 
occur and the data for participants will be unblinded and released for analysis to a limited 
number of sponsor personnel (except for site monitors, who have interactions with the 
investigative sites). A subsequent Week 38 DBL will occur when all 210 randomized 
participants have either completed the Week 38 visit or have terminated study participant before 
Week 38. Following the Week 38 DBL, the treatment assignment information will be unblinded 
to the sponsor for all participants and released to the sponsor for analysis. The final safety DBL


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will occur when all randomized participants have either completed the final safety visit or have
terminated study participation. Additional DBLs may occur as needed.
Identification of sponsor personnel who will have access to the unblinded participant-level data 
at the time of each DBL will be documented before unblinding. 
Under normal circumstances, the investigator blind should not be broken unless specific 
emergency treatment/course of action would be dictated by knowing the treatment status of the 
participant. In such cases, the investigator may in an emergency determine the identity of the 
treatment via the IWRS. It is recommended that the investigator contact the sponsor or its 
designee, if possible, to discuss the particular situation before breaking the blind. Telephone 
contact with the sponsor or its designee will be available 24 hours per day, 7 days per week. If 
the blind is broken, the sponsor must be informed as soon as possible. The date and reason for 
the unblinding must be documented in the appropriate section of the eCRF and in the source 
document. The documentation received from the IWRS indicating the code break must be 
retained with the participant's source documents in a secure manner.
Additionally, a given participant’s treatment assignment may be unblinded to the sponsor, the 
Independent Ethics Committee/Institutional Review Board (IEC/IRB), and site personnel to 
fulfill regulatory reporting requirements for suspected unexpected serious adverse reactions 
(SUSARs). If a participant is unblinded by the site, the information must be entered in the 
appropriate section of the eCRF and in the participant's source documents. 
Participants who have had their treatment assignment unblinded by the investigator will not be 
eligible to receive further study intervention, but should complete evaluations specified in the 
appropriate SoA (Section 1.3) for participants who discontinue study intervention.
A separate code break procedure will be available for use by J&J Global Medical Safety group to 
allow for unblinding of individual participants to comply with specific requests from regulatory 
or health authorities.
6.4.
Study Intervention Compliance
When study intervention is administered as an IV infusion or 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. Additional details may be provided in the site IPPM and 
IPPI that is provided separately.
Compliance with the treatment schedule is strongly encouraged. 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.


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6.5.
Concomitant Therapy
Prestudy therapies administered up to 30 days before the first administration of study 
intervention must be recorded on the eCRF. Concomitant therapies must be recorded throughout 
the study, from signing of the informed consent to the last study visit.
All therapies (prescription or over-the-counter medications, including vaccines, vitamins, herbal 
supplements; non-pharmacologic therapies such as electrical stimulation, acupuncture, special 
diets, exercise regimens) different from the study intervention must be recorded in the eCRF. 
Recorded information will include a description of the type of therapy, treatment period, dosage, 
route of administration, and indication. Modification of an effective pre-existing therapy should 
not be made for the explicit purpose of entering a participant into the study.
6.5.1.
Concomitant Medications
Immunomodulators (6-MP, AZA, and MTX) must be discontinued 2 weeks prior to the first dose 
of study intervention, as defined in the Inclusion Criteria (Section 5.1). Participants who are 
receiving oral 5-ASA compounds or oral corticosteroids for the treatment of UC 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 UC at 
baseline (ie, Week 0) should maintain a stable dose through Week 38, 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. Oral corticosteroids must be maintained at 
baseline doses through Week 6, and all participants must begin tapering oral corticosteroids at 
Week 6, unless medically not feasible (see further details in Section 6.5.1.1, Oral Corticosteroids 
Tapering).
Enrolled participants should not initiate any of the following concomitant UC-specific medical 
therapies:

Oral or rectal 5-ASA compounds.

Oral, parenteral, or rectal corticosteroids, including budesonide and beclomethasone 
dipropionate.

Antibiotics as a primary treatment for UC. 

Total parenteral nutrition or enteral nutrition as a treatment for UC.
If the above medical therapies are initiated or medication doses are changed based on medical 
necessity as assessed by the investigator, participants should continue to attend all study visits 
and have all assessments. While this does not represent a deviation from the study protocol and 
the participants may remain on their assigned therapy, it may be considered a treatment failure. 
Treatment failures due to UC medication changes will be defined in the SAP.
6.5.1.1.
Oral Corticosteroids Tapering
At Week 6, all participants who were taking oral corticosteroids at Week 0 must begin tapering 
corticosteroids. This tapering is mandatory, unless not medically feasible, and should follow the 


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recommended schedule shown in Table 3. 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).
Table 3:
Recommended Tapering Schedule for Oral Corticosteroids
Recommended Tapering Schedule for Oral Corticosteroids (Other than Oral Budesonide and Oral 
Beclomethasone dipropionate)
Dose >15 mg/day prednisone or 
equivalent:
Taper daily dose by 5 mg/week until receiving 10 mg/day, then 
continue tapering by 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 by
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 and Oral Beclomethasone dipropionate
Participants receiving oral budesonide or oral beclomethasone dipropionate should have their daily dose tapered
according to local clinical practice until 0 mg/day
6.5.2.
Prohibited Concomitant Medications
Participants who initiate the following treatments during study participation will have their study 
intervention discontinued:

Immunomodulatory agents (including, but not limited to, 6-MP, AZA, MTX, tofacitinib,
6-thioguanine, cyclosporine, mycophenolate mofetil, tacrolimus, and sirolimus). 

Immunomodulatory biologic agents (including, but not limited to, TNF antagonists, 
ustekinumab, vedolizumab, abatacept, anakinra). 

Experimental IBD medications (including, but not limited to, upadacitinib, filgotinib, 
ozanimod, etrolizumab, brazikumab, mirikizumab, risankizumab) or other investigational 
therapies. 

Thalidomide or related agents. 
The sponsor or designee must be notified in advance (or as soon as possible thereafter) of any 
instances in which prohibited therapies are administered.
As protection of human research participants is paramount, it is recognized that initiating such 
therapies may rarely be required due to medical necessity. However, initiation of these
prohibited medications should be documented as a deviation from the study protocol, and 
participants will be discontinued from receiving further study intervention (Section 7). 


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Participants who discontinue study intervention administration should complete the appropriate
visit(s) as described in Section 1.3.
Note: Participants must not receive guselkumab or golimumab outside of the protocol or
participate in any other clinical study with an investigational agent while in this study, and must 
terminate study participation if they do. Prior to termination of study participation, participants 
should complete the appropriate visit(s) as described in Section 1.3.
6.6.
Dose Modification
No dose adjustment of study intervention will be permitted during the study.
6.7.
Intervention After the End of the Study
This protocol is designed to provide participants with up to approximately 38 weeks of 
treatment.
Participants will be instructed that study intervention will not be made available to them after 
they have completed/discontinued study intervention and that they should return to their primary 
physician to determine standard of care.
7.
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
If a participant discontinues study intervention or withdraws from the study before the end of the 
study, assessments should be obtained as specified in the SoA (Section 1.3).
7.1.
Discontinuation of Study Intervention
A participant who discontinues study intervention will not be automatically withdrawn from the 
study (see Section 7.2).
A participant's study intervention must be discontinued under the following conditions:
1.
The 
participant 
initiates 
treatment 
with 
prohibited 
concomitant 
medication(s) 
(Section 6.5.2).
2.
The participant has a colectomy.
3.
The participant becomes pregnant or plans a pregnancy within the study period. Refer to 
Appendix 4 (Section 10.4), Contraceptive and Barrier Guidance and Collection of 
Pregnancy Information.
4.
The participant (or the participant’s legally acceptable representative) withdraws consent for 
administration of study intervention.
5.
The participant develops an opportunistic infection.


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6.
The participant is deemed ineligible according to the following TB screening criteria:

A diagnosis of active TB is made.

A participant has symptoms suggestive of active TB based on follow-up assessment 
questions and/or physical examination, or has had recent close contact with a person 
with active TB, and cannot or will not continue to undergo additional evaluation.
A participant undergoing evaluation has a chest radiograph with evidence of current 
active TB and/or a positive or indeterminate QuantiFERON®-TB test result (and/or a 
positive tuberculin skin test result in countries in which the QuantiFERON®-TB test is 
not approved/registered or the tuberculin skin test is mandated by local health 
authorities). 
Note: In Ukraine, while the QuantiFERON®-TB test is not approved/registered, it is 
accepted and a tuberculin skin test is not required.
7.
Criterion modified per Amendment 2. 
7.1. The participant has a serious adverse reaction that is related to an injection or an 
infusion, including an injection-site or infusion reaction, resulting in bronchospasm with 
wheezing and/or dyspnea that requires ventilatory support OR that results in symptomatic 
hypotension with a decrease in systolic blood pressure >40 mm Hg or blood pressure 
<90/60 mm Hg.
8.
The participant has a reaction resulting in myalgia and/or arthralgia with fever and/or rash 
(suggestive of serum sickness and not representative of signs and symptoms of other 
recognized clinical syndromes) occurring 1 to 14 days after an injection of study 
intervention. These may be accompanied by other events including pruritus, facial, hand, or 
lip edema, dysphagia, urticaria, sore throat, and/or headache.
9.
The participant has severe hepatic function abnormalities, as described in Section 8.2.5 and 
Appendix 7 (Section 10.7).
10. The participant is diagnosed with 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 participant develops congestive heart failure.
12. The participant is diagnosed with a demyelinating disorder. 
13. The participant develops symptoms suggestive of a lupus-like syndrome and is positive for 
antibodies against double-stranded DNA. 
14. 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 UC based on signs, symptoms, and/or 
laboratory values. If the participant experiences AEs consistent with clinically significant 
worsening of UC at any time during the study, these events should be evaluated by the 
investigator and the study medical monitor to decide on discontinuation of study 


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intervention. Discontinuation of study intervention should be considered in participants with 
clinically significant worsening of UC where continuation of the study intervention is not in 
the best interest of the participant.
2.
Criterion modified per Amendment 2. 
2.1. The participant develops a serious infection, including but not limited to sepsis or
pneumonia.
Note: Any serious infection should be discussed with the medical monitor or designee, and 
study intervention should be withheld until the clinical assessment is complete.
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 (actual 
suicide attempt, interrupted suicide attempt, aborted suicide attempt, or preparatory 
behaviors for making a suicide attempt) on a post-baseline C-SSRS assessment. If a 
participant can be adequately treated with psychotherapy and/or pharmacotherapy based on 
an evaluation by a mental health professional, then the participant, at the discretion of the 
investigator, may be continued with treatment if agreed to by the medical monitor or 
designee. Discussion of such participants with the medical monitor or designee is required
(see Section 8.2.6).
4.
Criterion deleted per Amendment 2. 
5.
The participant has hematology abnormalities as described below:

Two sequential absolute neutrophil counts <0.75 × 103/µL (SI: <0.75 × 109 /L)

Two sequential absolute lymphocyte counts <0.5 × 103/µL (SI: <0.5 × 109/L)

Two sequential hemoglobin values <8.0 g/dL (SI: <80.0g/L) or a decrease of >30% 
from baseline

Two sequential platelet counts <75 × 103/µL (SI: <75 × 109/L)
Note: These laboratory abnormalities should be discussed with the medical monitor or 
designee, and study intervention should be withheld until the clinical assessment is 
complete.
6.
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 (Section 1.3). If the reason for 
withdrawal from the study is withdrawal of consent, every effort should be made to conduct the 
early termination assessments, as indicated in the SoA, prior to terminating study participation. 
After termination of study participation, no additional assessments are allowed.
7.2.
Participant Discontinuation/Withdrawal From the Study
Participant discontinuation/withdrawal from the study is defined as no longer following up for 
study visits. It is different from discontinuation from study intervention, as described in 
Section 7.1. 
A participant will be withdrawn from the study for any of the following reasons:


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
Lost to follow-up (see Section 7.3)

Withdrawal of consent

Death

Sponsor decision (eg, participating in any other clinical study with an investigational agent)
Participants who terminate study participation will not be required to return for any follow-up 
assessments; however, these participants should complete the safety and efficacy evaluations 
specified in the SoA (Section 1.3) at the time they terminate study participation. No additional 
evaluations are performed after a participant’s withdrawal from the study.
When a participant withdraws before completing the study, the reason for withdrawal is to be 
documented in the eCRF and in the source document. Study intervention assigned to the 
withdrawn participant may not be assigned to another participant. Additional participants will 
not be entered.
7.2.1.
Withdrawal From the Use of Research Samples
A participant who withdraws from the study will have the following options regarding the 
optional research samples:

The collected samples will be retained and used in accordance with the participant's original 
separate informed consent for optional research samples.

The participant may withdraw consent for optional research samples, in which case the 
samples will be destroyed and no further testing will take place. To initiate the sample 
destruction process, the investigator must notify the sponsor study site contact of withdrawal 
of consent for the optional research samples and to request sample destruction. The sponsor 
study site contact will, in turn, contact the biomarker representative to execute sample 
destruction. If requested, the investigator will receive written confirmation from the sponsor 
that the samples have been destroyed.
Withdrawal From the Optional Research Samples While Remaining in the Main Study
The participant may withdraw consent for optional research samples while remaining in the 
study. In such a case, the optional research samples will be destroyed. The sample destruction 
process will proceed as described above.
Withdrawal From the Use of Samples in Future Research
The participant may withdraw consent for use of samples for research (refer to Long-Term 
Retention of Samples for Additional Future Research in Appendix 6 [Section 10.6], Regulatory, 
Ethical, and Study Oversight Considerations). In such a case, samples will be destroyed after 
they are no longer needed for the clinical study. Details of the sample retention for research are 
presented in the main ICF and in the separate ICF for optional research samples.
7.3.
Lost to Follow-up
If a participant is lost to follow-up, every reasonable effort must be made by the study site 
personnel to contact the participant and determine the reason for discontinuation/withdrawal. 


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Such efforts should include repeated telephone calls, certified letters, and email requests. The 
measures taken to follow up must be documented. Refer to Section 7.2, Participant 
Discontinuation/Withdrawal From the Study.
8.
STUDY ASSESSMENTS AND PROCEDURES
Overview
The SoA (Section 1.3) summarizes the frequency and timing of efficacy, PK, immunogenicity, 
biomarker (PD), pharmacogenomic, medical resource utilization, and safety measurements 
applicable to this study.
All visit-specific PRO assessments should be conducted/completed before any tests, procedures, 
or other consultations to prevent influencing participant perceptions.
Blood collections for PK and PD assessments should be kept as close to the specified time as 
possible. Other measurements may be done earlier than specified time points if needed. Actual 
dates and times of assessments will be recorded in the source documentation.  
For women of childbearing potential only, 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.
Medical resource utilization data will be collected. Refer to Section 8.9, Medical Resource 
Utilization for details.
At their last study visit, each study participant will be invited to complete an IEC/IRB approved 
Experience Survey, to share his/her experience as a volunteer in this study. The responses will be 
collected by an external party and provided anonymously to the sponsor.
Screening Phase
After written informed consent has been obtained and within 8 weeks before randomization, all 
screening evaluations (eg, laboratory test results, clinical data, and concomitant medication data) 
that establish participant eligibility will be performed by the principal investigator or designee to 
confirm that the participant satisfies all inclusion criteria and does not violate any exclusion 
criteria. Participants who meet all of the inclusion and none of the exclusion criteria can be 
enrolled in the study. Every effort should be made to adhere to the SoA (Section 1.3) for each 
participant. The collection of AEs will start at the time informed consent is obtained. 
Diaries will be provided to each participant to record concomitant medications, stool production, 
and episodes of rectal bleeding. A Mayo diary will be completed from recall at screening and 
will be used to calculate a partial Mayo score (Section 8.1.1) to assess the participant’s eligibility 
for further screening and to train the participant on the use of the diary. Participants with a partial 
Mayo score ≥3 can proceed with endoscopy. Participants will be instructed to complete a daily 
Mayo diary for 7 days immediately before each visit and bring them to every visit for data 
collection and review by the investigator/study coordinator.


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Bristol Stool Form Scale diaries will also be provided to participants to classify the form (or 
consistency) of their stools during the combination comparison phase of the study 
(Section 8.1.8). Participants will complete the BSFS as a daily diary entry from Week 0 through 
Week 12.
The screening endoscopy must be performed within 2 weeks (and at least 4 days) before the 
baseline (Week 0) visit. Participants who are identified as being at increased risk for colon 
cancer (Section 5.1, Inclusion Criterion #9) or for adenomatous polyps (Section 5.1, Inclusion 
Criterion #8) will undergo a full colonoscopy instead of a sigmoidoscopy to allow screening for 
dysplasia or to assess for the presence of adenomatous polyps, respectively. Any screening 
colonoscopy for malignancy should include surveillance biopsies consistent with local practice. 
At least 48 hours must elapse between a colonoscopy with polypectomy and the Week 0 visit. 
Histology results from the polypectomy must be available to confirm absence of colonic mucosal 
dysplasia before first administration of study intervention (Section 5.2, Exclusion Criterion #8).
Women of childbearing potential must have a negative serum pregnancy test result at screening 
and a negative urine pregnancy test result at the Week 0 visit. Participants must be reminded that 
they are required to use a highly effective method of contraception during the study (as described 
in Section 5.1, Inclusion Criterion 13) and must continue taking such precautions for 6 months
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 8.2.12) and their medical history assessment 
must include specific questions about a history of TB or known occupational or other personal 
exposure to individuals with active TB. The participant should be asked about past testing for 
TB, including chest radiograph results and responses to tuberculin skin or other TB testing. A 
participant’s eligibility according to TB screening criteria is described in Section 5.1, Inclusion 
Criterion 11.
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 biomarkers evaluations at the same time point, the order of blood draws will be 
samples for CRP, hematology and chemistry, PK/immunogenicity, serum biomarkers, whole 
blood DNA (for those participating in the optional pharmacogenomic sub-study at Week 0), and 
whole blood RNA.
The maximum total blood volume to be collected from each participant in the study will be 
approximately 350 mL over approximately 58 weeks. This total may vary due to:

whether or not the participant consents to take part in the optional pharmacogenomic 
sub-study (5 mL).


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
repeat or unscheduled samples taken for safety reasons or technical issues with the samples.

regional or country-specific variation in blood collection systems.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded on the laboratory requisition 
form. Refer to the SoA (Section 1.3) for the timing and frequency of all sample collections.
Instructions for the collection, handling, storage, and shipment of samples are found in the 
Laboratory Manual.
Study-Specific Materials
The investigator will be provided with the following supplies:

Investigator Site File (includes protocol and IBs)

IPPM

IPPI

Laboratory Manual 

eCRF completion instructions

Patient recruitment materials

Sample ICFs

IWRS Manual

Biopsy Manual

ePRO equipment

Endoscopy kit

Imaging Manual

Lab kits
8.1.
Efficacy Assessments
Efficacy evaluations will include the following:

Mayo score and Partial Mayo score

Ulcerative Colitis Endoscopic Index of Severity (UCEIS)

Inflammatory PD markers including CRP and fecal calprotectin

Patient-reported outcome measures to assess HRQOL outcomes and fatigue (ie, IBDQ, 
PROMIS-29, and PROMIS Fatigue 7-item Short Form [7a])

Exploratory patient-reported symptom measures including BSFS and PGIC of Severity of 
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The SoA summarizes the frequency and timing of efficacy measurements applicable to this study
(Section 1.3).
8.1.1.
Mayo Score and Partial Mayo Score
The Mayo score (see Appendix 8 [Section 10.8]) was developed from the criteria of Truelove 
and Witts64 for mild, moderate, and severe UC and from the criteria of Baron et al3 for grading 
endoscopic appearance. The Mayo score is calculated as the sum of 4 subscores (stool frequency, 
rectal bleeding, physician's global assessment, and endoscopy findings) each with a score range 
of 0 (normal activity) to 3 (severe activity) and a total score range of 0 to 12 points. A score of 3 
to 5 points indicates mildly active disease, a score of 6 to 10 points indicates moderately active 
disease, and a score of 11 to 12 points indicates severely active disease. The endoscopic findings 
will be assessed by the investigator (ie, local endoscopist) during the endoscopy procedure and 
by the central reader reviewing a video of the endoscopy. Participant eligibility at baseline will 
be based on the final reported endoscopic subscore as determined by the following process:

If the local endoscopist and the central reader agree on the endoscopic subscore, the agreed 
score will be the final reported endoscopic subscore.  

If there is a discrepancy between the local endoscopist and the central reader subscores, the 
video endoscopy will be submitted to a second central reader (designated for adjudication). 
The median score of the 3 completed reads (ie, local read, central read 1, and central read 2 
designated for adjudication) will be the final reported endoscopic subscore.
Specific details will be provided in the imaging charter.
Mayo scores are calculated using the following: 
1.
The stool frequency and rectal bleeding data from the most recent consecutive 3-day period 
within the 1 week before the visit. The average of the 3-day period will be used to calculate 
the stool frequency and RBSs for the visit. Days on which the following conditions are met 
should be excluded from the calculation:
a.
The day on which medications for constipation, diarrhea, or irregularity were taken.  
(For participants maintained on a stable dose of bulking or stool-softening agents 
throughout the study, the days on which these agents are taken should not be excluded 
from consideration in calculating the Mayo score.)
b.
The day(s) of a procedure or preparation for a procedure (eg, enemas, other laxatives, a 
clear liquid diet) that would affect bowel frequency and/or blood content of the stool.
c.
The 48 hours after the use of antimotility agents (ie, diphenoxylate hydrochloride with 
atropine sulfate, loperamide, or other opioids).
d.
The 48 hours immediately following a colonoscopy.
2.
The physician’s global assessment.
3.
The results of a sigmoidoscopy or colonoscopy.
The partial Mayo score is the Mayo score without the endoscopy subscore and ranges from 0 to 
9 points.


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If 1 or more of the 4 Mayo subscores is missing at a specific visit, but not all 4 subscores are 
missing, the last available Mayo subscore will be carried forward to compute a full Mayo score 
and a partial Mayo score at that visit. If all 4 subscores are missing at a specific visit, the Mayo 
score and partial Mayo score will be considered missing at that visit.
8.1.2.
Ulcerative Colitis Endoscopic Index of Severity (UCEIS)
The UCEIS is an index that provides an overall assessment of endoscopic severity of UC, based 
on mucosal vascular pattern, bleeding, and ulceration.61 The score ranges from 3 to 11, with a 
higher score indicating more severe disease by endoscopy. The UCEIS score will be assessed 
only by the central video readers for all endoscopies.
8.1.3.
C-Reactive Protein
C-reactive protein has been demonstrated to be useful as a marker of inflammation in subjects 
with IBD. In subjects with UC, elevated CRP has been associated with severe clinical activity, an 
elevated sedimentation rate, and active disease as detected by colonoscopy.54,66 Serum samples 
for the measurement of CRP will be collected from all participants at visits indicated in the SoA
(Section 1.3). C-reactive protein will be assayed using a validated, high sensitivity CRP assay.
8.1.4.
Fecal Calprotectin
Fecal calprotectin has been demonstrated to be a sensitive and specific marker in identifying 
intestinal inflammation and response to treatment in participants with IBD, especially in UC.2
Stool samples for calprotectin concentrations will be collected from all participants at visits as 
indicated in the SoA (Section 1.3).
Assays for fecal calprotectin concentration will be performed by the central laboratory using a 
validated method. Additional tests may also be performed on the stool samples for additional 
markers that are related to intestinal inflammation and treatment response such as the 
microbiome.
8.1.5.
Inflammatory Bowel Disease Questionnaire
The IBDQ23 is a validated, 32-item, self-reported questionnaire for participants with IBD that 
will be used to evaluate the disease-specific HRQOL across 4 dimensional scores: bowel
symptoms (loose stools, abdominal pain), systemic functions (fatigue, altered sleep pattern), 
social function (work attendance, need to cancel social events), and emotional function (anger, 
depression, irritability). Scores range from 32 to 224, with higher scores indicating better 
outcomes.
8.1.6.
PROMIS-29
The PROMIS-29 is a validated general health profile instrument that is not disease-specific. It is 
a collection of short forms containing 4 items for each of 7 domains (depression, anxiety, 
physical function, pain interference, fatigue, sleep disturbance, and ability to participate in social 
roles and activities). PROMIS-29 also includes an overall average pain intensity 0-10 numeric 
rating scale. Norm-based scores have been calculated for each domain on the PROMIS 
measures, with a score of 50 representing the mean or average of the reference population. On 


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symptom-oriented domains of PROMIS-29 (anxiety, depression, fatigue, pain interference, and 
sleep disturbance), higher scores represent worse symptomatology. On the function-oriented 
domains (physical functioning and social role), higher scores represent better functioning.  
8.1.7.
PROMIS Fatigue 7-items Short Form
The PROMIS Fatigue Short Form 7a contains 7 items evaluating fatigue-related symptoms (ie, 
tiredness, exhaustion, mental tiredness, and lack of energy) and associated impacts on daily 
activities (ie, activity limitations related to work, self-care, and exercise). PROMIS Fatigue Short 
Form 7a has a recall period of past 7 days. Compared to the fatigue scale of PROMIS-29, 
PROMIS Fatigue Short Form 7a provides additional information to evaluate severity of fatigue.
8.1.8.
Bristol Stool Form Scale
The BSFS is a medical aid to classify the form (or consistency) of human feces into 
7 categories.27 It has been used as a research tool to evaluate the effectiveness of treatments for 
various diseases of the bowel (eg, irritable bowel syndrome). Participants will complete the 
BSFS as a daily diary entry from Week 0 through Week 12.
8.1.9.
Patient’s Global Impression of Change (PGIC) of Severity of 
Ulcerative Colitis
Participants’ perceived change (improvement or deterioration) in the severity of their UC will be 
assessed using the PGIC. Participants will rate how their UC has changed since the beginning of 
the study using a 7-point scale ranging from “a lot better now” to “a lot worse now” with a 
neutral center point (“neither better nor worse”). 
8.2.
Safety Assessments 
Details regarding the independent DMC are provided in Section 9.5.1.
Adverse events will be reported and followed by the investigator as specified in Section 8.3, 
Adverse Events and Serious Adverse Events and Appendix 9 (Section 10.9), Adverse Events: 
Definitions and Procedures for Recording, Evaluating, Follow-Up, and Reporting.
Any clinically relevant changes occurring during the study must be recorded on the Adverse 
Event section of the eCRF.
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 (Section 1.3):
8.2.1.
Physical Examination
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 exam should be performed as specified in the SoA. 


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Total body skin examination will be performed to evaluate for any suspected malignant skin 
lesions including basal cell carcinoma, squamous cell carcinoma, and melanoma.
8.2.2.
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.
8.2.3.
Vital Signs
Temperature, pulse/heart rate, respiratory rate, and blood pressure will be assessed. 
Blood pressure and pulse/heart rate measurements will be assessed with a completely automated 
device. Manual techniques will be used only if an automated device is not available.
If feasible, blood pressure and pulse/heart rate measurements should be preceded by at least 5 
minutes of rest in a quiet setting without distractions (eg, television, cell phones).
At a study intervention administration visit, vital signs should be obtained before, approximately
every 30 minutes during, and twice (at approximately 30-minute intervals) after completion of 
the IV infusion(s), or before and approximately 30 minutes after the SC injection, or if the 
participant reports any symptoms.
8.2.4.
Electrocardiogram
A 12-lead ECG will be performed at screening.
During the collection of the ECG, participants should be in a quiet setting without distractions 
(eg, television, cell phones). Participants should rest in a supine position for at least 5 minutes 
before ECG collection and should refrain from talking or moving arms or legs. If blood sampling 
or vital sign measurement is scheduled for the same time point as ECG recording, the procedures 
should be performed in the following order: ECG(s), vital signs, blood draw.
8.2.5.
Clinical Safety Laboratory Assessments
Blood samples for serum chemistry and hematology will be collected as noted in Section 1.3. 
The investigator must review the laboratory results, document this review, and record any 
clinically relevant changes occurring during the study in the adverse event section of the eCRF. 
The laboratory reports must be filed with the source documents.
The following tests will be performed by the central laboratory unless otherwise specified or 
approved by the medical monitor or designee:

Hematology assessments will include but are not limited to the following: hemoglobin, 
hematocrit, platelet count, total and differential WBC count.
Mandatory Re-Testing
The following hematology abnormalities require monitoring and re-testing (ideally within 
3-5 days):


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Absolute neutrophil count <1.2 × 103/µL (SI: <1.2 × 109/L)

Absolute lymphocyte count <0.5 × 103/µL (SI: <0.5 × 109/L)

Any single hemoglobin value <8.0 g/dL (SI: <80.0 g/L), or any decrease in hemoglobin 
>2.0 g/dL (SI: >20.0 g/L) from baseline

Platelet count <100 × 103/µL (SI: <100 × 109/L)
The medical monitor or designee and the clinical site will be notified if these abnormal 
laboratory values are identified in any participant during the conduct of the study.

Blood chemistry assessments will include but are not limited to the following: chemistry 
panel (total and direct bilirubin, ALT, AST, alkaline phosphatase, albumin, total protein, 
calcium, phosphate, sodium, potassium, chloride, blood urea nitrogen/urea, and creatinine).
A medical monitor or designee and the clinical site will be notified if pre-specified abnormal 
laboratory values defined in the Laboratory Manual are identified in any participant during 
the conduct of the study. 

Serology: HIV antibody, HBV antibodies and surface antigen, and HCV antibody.

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. See Appendix 7 (Section 10.7; Liver 
Safety: Suggested Actions and Follow-up Assessments) for additional information on 
monitoring and assessment of abnormal liver function tests.

Pregnancy testing: Female participants of childbearing potential will undergo a serum 
β-human chorionic gonadotropin pregnancy test at screening, and a urine pregnancy test
before each study intervention administration, at the early termination visit, and the safety 
follow-up visit. 
8.2.6.
Columbia-Suicide Severity Rating Scale (C-SSRS)
The C-SSRS defines 5 subtypes of suicidal ideation and 4 possible suicidal behaviors, as well as 
non-suicidal self-injurious behavior and completed suicide. It will be used as a screening tool to 
prospectively evaluate suicidal ideation and behavior in this study, as part of a comprehensive 
evaluation of safety. The C-SSRS is an investigator-administered questionnaire.32,40 Two 
versions of it will be used in this study: the ‘Baseline/Screening’ version of the C-SSRS will be 
conducted during the screening visit and the ‘Since Last Visit’ version of the C-SSRS will be 
completed at all other visits through the end of the study.
The investigator or trained study-site personnel will interview the participant and complete the 
C-SSRS. The C-SSRS will be provided in the local languages in accordance with local 
guidelines.
At screening, the C-SSRS will be the first assessment performed after signing informed consent,
before any other study procedure. At all subsequent visits, the C-SSRS will be performed 


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according to the assessment schedule and should be performed after other PROs but before any 
other study procedures. Participants will be interviewed by the investigator or trained study-site 
personnel in a private, quiet place. 
At the conclusion of each assessment, the trained personnel administering the C-SSRS will 
determine the level of suicidal ideation or behavior, if any. They will then determine the next 
course of action if any level of suicidal ideation or behavior is reported. The participant should 
not be released from the site until the C-SSRS has been reviewed by the investigator and the 
participant’s risk has been assessed and follow-up determined, as appropriate.
At screening (within the last 6 months) and Week 0, participants with a C-SSRS rating of 
Suicidal Ideation with Intention to Act (“Ideation level 4”), Suicidal Ideation with Specific Plan 
and Intent (“Ideation level 5”), or suicidal behavior (actual suicide attempt, interrupted suicide 
attempt, aborted suicide attempt, or preparatory behaviors for making a suicide attempt), must be 
determined to not be at risk by the investigator based on an evaluation by a mental health 
professional (eg, psychiatrist, psychologist, or appropriately trained social worker or nurse) in 
order to be randomized.
Participants with C-SSRS ratings of Wish to be Dead (“Ideation level 1”), Non-Specific Active 
Suicidal Thoughts (“Ideation level 2”), Active Suicidal Ideation with Any Methods (Not Plan) 
without Intent to Act (“Ideation level 3”) or non-suicidal self-injurious behavior must be 
determined not to be at risk by the investigator in order to be randomized in the study. Any 
questions regarding eligibility of such participants should be discussed with the medical monitor 
or designee.
For each assessment after Week 0, the following actions should be taken, if applicable:

No suicidal ideation or behaviors (including self-injurious behavior without suicidal intent): 
No further action is needed.

Suicidal ideation levels 1-3 or non-suicidal self-injurious behavior: Participant risk is 
assessed by the investigator.

Suicidal ideation levels 4 or 5 or any suicidal behavior: Participant risk assessed and referral 
to a mental health professional.
Interruption or the discontinuation of study treatment should be considered for any participant 
who reports Suicidal Ideation with Intention to Act (“Ideation level 4”), Suicidal Ideation with 
Specific Plan and Intent (“Ideation level 5”), or suicidal behavior (actual suicide attempt, 
interrupted suicide attempt, aborted suicide attempt, or preparatory behaviors for making a 
suicide attempt) on a post-baseline C-SSRS assessment and who is deemed to be at risk by the 
investigator based upon evaluation by a mental health professional. If a participant can be 
adequately treated with psychotherapy and/or pharmacotherapy then the participant, at the 
discretion of the investigator, may be continued with treatment if agreed to by the medical 
monitor or designee. Discussion of such participants with the medical monitor or designee is 
required (see Section 7.1, Discontinuation of Study Intervention). 


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Any C-SSRS finding, which in the opinion of the investigator is new or considered to be a 
worsening and clinically significant, should be reported on the AE eCRF (see Appendix 9
[Section 10.9], Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow-
up, and Reporting).
8.2.7.
Concomitant Medication Review
Concomitant medications will be reviewed at each visit.
8.2.8.
Injection-Site Reactions
An injection-site reaction is any adverse reaction at a SC study intervention injection site. 
Injection sites will be evaluated for reactions and any injection-site reaction will be recorded as 
an AE.
8.2.9.
Hypersensitivity Reactions
Before any SC injection or IV infusion of study intervention, appropriately trained personnel and 
medications must be available to treat hypersensitivity reactions, including anaphylaxis. All 
participants must be observed carefully for signs and symptoms of a hypersensitivity reaction 
(eg, urticaria, pruritis, angioedema, wheezing, dyspnea, or hypotension). 
In the case of anaphylaxis, injectable epinephrine (intramuscular), 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 must
strongly be considered to 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 or blood pressure 
<90/60 mm Hg must be discontinued from additional study intervention administration (see 
Section 7).
Participants who experience reactions suggestive of serum sickness (resulting in symptoms such 
as myalgia and/or arthralgia with fever and/or rash that are not representative of signs and 
symptoms of other recognized clinical syndromes) occurring 1 to 14 days after administration of 
study intervention, must be discontinued from further study intervention administration. Note 
that these signs and symptoms may be accompanied by other events including pruritus, facial, 
hand, or lip edema, dysphagia, urticaria, sore throat, and/or headache.
8.2.10.
Adverse Events Temporally Associated With 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 


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interrupted 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.
8.2.11.
Infections
Study intervention should not be administered to a participant with a clinically significant, active 
infection. Investigators are required to evaluate participants for any signs or symptoms of 
infection at scheduled visits (see SoA, Section 1.3). If a participant develops a serious infection, 
including but not limited to sepsis or pneumonia, discontinuation of study intervention must be 
strongly considered.
8.2.12.
Tuberculosis Evaluations
8.2.12.1.
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 results and responses to tuberculin skin or other TB testing. Investigators have 
the option to use both the QuantiFERON®-TB test and the tuberculin skin test (refer to 
Appendix 3 [Section 10.3]) to screen for latent TB if they believe, based on their judgment, that 
the use of both tests is clinically indicated in order to evaluate a participant who has high risk of 
having latent TB. If either the QuantiFERON®-TB test or the tuberculin skin test is positive, the 
participant is considered to have latent TB infection and is excluded from the study.
Participants with a negative QuantiFERON®-TB test result (and a negative tuberculin skin test 
result in countries in which the QuantiFERON®-TB test is not approved/registered or the 
tuberculin skin is mandated by local health authorities) are eligible to continue with pre-
randomization procedures. Participants with a newly identified positive QuantiFERON®-TB (or 
tuberculin skin) test result are excluded from the study and must undergo an evaluation to rule 
out active TB and initiate appropriate treatment for latent TB. Appropriate treatment for latent 
TB is defined according to local country guidelines for immunocompromised patients. If no local 
country guidelines for immunocompromised patients exist, US guidelines must be followed. For 
a participant with an indeterminate QuantiFERON®-TB test, the test may be repeated once. If the 
result is indeterminate on repeat testing, the participant is considered a screen failure.
8.2.12.2.
Ongoing Tuberculosis Evaluation
Early Detection of Active Tuberculosis 
To aid in the early detection of TB reactivation or new TB infection during study participation, 
participants must be evaluated for signs and symptoms of active TB at scheduled visits (refer to 
the SoA in Section 1.3) or by telephone contact approximately every 8 to 12 weeks. The 
following series of questions is suggested for use during the evaluation: 

“Have you had a new cough of >14 days’ duration or a change in a chronic cough?”

“Have you had any of the following symptoms:


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
Persistent fever?

Unintentional weight loss?

Night sweats?”

“Have you had close contact with an individual with active TB?” (If there is uncertainty as 
to whether a contact should be considered “close,” a physician specializing in TB should be 
consulted.)
If the evaluation raises suspicion that a participant may have TB reactivation or new TB 
infection, an immediate and thorough investigation should be undertaken, including, where 
possible, consultation with a physician specializing in TB. 
Investigators should be aware that TB reactivation in immunocompromised participants may 
present as disseminated disease or with extrapulmonary features. Participants with evidence of 
active TB should be referred for appropriate treatment.
Participants who experience close contact with an individual with active TB during the conduct 
of the study must have a repeat chest radiograph, a repeat QuantiFERON®-TB test, a repeat 
tuberculin skin test in countries in which the QuantiFERON®-TB test is not approved/registered 
or the tuberculin skin test is mandated by local health authorities, and, if possible, referral to a 
physician specializing in TB to determine the participant’s risk of developing active TB and 
whether treatment is warranted. Study intervention administration should be interrupted during 
the investigation. A positive QuantiFERON®-TB test or tuberculin skin test result should be 
considered detection of latent TB. Participants with a positive or indeterminate 
QuantiFERON®-TB test or positive tuberculin skin test must immediately discontinue further 
administration of study intervention and be encouraged to return for scheduled study visits 
according to the SoA (Section 1.3).
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.
Anticipated events will be recorded and reported as described in Appendix 10 (Section 10.10).
For further details on AEs and SAEs (Definitions and Classifications; Attribution Definitions; 
Severity Criteria; Special Reporting Situations; Procedures) as well as product quality 
complaints, refer to Appendix 9 (Section 10.9 ), Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-Up, and Reporting.


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8.3.1.
Time Period and Frequency for Collecting Adverse Event and Serious 
Adverse Event Information
All Adverse Events
All AEs and special reporting situations, whether serious or non-serious, will be reported from 
the time a signed and dated ICF is obtained until completion of the participant's last study-related 
procedure, which may include contact for follow-up of safety. Serious adverse events, including 
those spontaneously reported to the investigator within 16 weeks after the last dose of study 
intervention, must be reported using the Serious Adverse Event Form. The sponsor will evaluate 
any safety information that is spontaneously reported by an investigator beyond the time frame 
specified in the protocol.
Serious Adverse Events
All SAEs occurring during the study must be reported to the appropriate sponsor contact person 
by study-site personnel within 24 hours of their knowledge of the event.
Information regarding SAEs will be transmitted to the sponsor using the Serious Adverse Event 
Form, which must be completed and signed by a physician from the study site, and transmitted to 
the sponsor within 24 hours. The initial and follow-up reports of a SAE should be made by 
facsimile (fax).
8.3.2.
Follow-up of Adverse Events and Serious Adverse Events
Adverse events, including pregnancy, will be followed by the investigator as specified in 
Appendix 9 (Section 10.9), 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 adverse events to the regulatory 
authorities. The sponsor will also report to the investigator (and the head of the investigational 
institute where required) all SUSARs. The investigator (or sponsor where required) must report 
SUSARs to the appropriate IEC/IRB that approved the protocol unless otherwise required and 
documented by the IEC/IRB. A SUSAR will be reported to regulatory authorities unblinded. 
Participating investigators and IEC/IRB will receive a blinded SUSAR summary, unless 
otherwise specified. 
8.3.4.
Pregnancy
All initial reports of pregnancy in female participants or partners of male participants must be 
reported to the sponsor 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 (see Section 7).


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Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the 
infant will be required (see Appendix 4 [Section 10.4], Contraceptive and Barrier Guidance and 
Collection of Pregnancy Information and Appendix 9 [Section 10.9], Adverse Events: 
Definitions and Procedures for Recording, Evaluating, Follow-Up, and Reporting).
8.3.5.
Events of Special Interest
Any newly identified malignancy or case of active TB occurring after the first study intervention 
administration(s) in subjects participating in this clinical study must be reported by the 
investigator to the sponsor or designee within 24 hours after being made aware of the event, 
according to the procedures in Appendix 9 (Section 10.9), Adverse Events: Definitions and 
Procedures for Recording, Evaluating, Follow-Up, and Reporting for SAEs. Investigators are 
also advised that active TB is considered a reportable disease in most countries. These events are 
to be considered serious only if they meet the definition of an SAE.
8.4.
Treatment of Overdose
For this study, any dose of study intervention greater than the highest dose at a single dosing visit 
specified in this protocol will be considered an overdose. The sponsor does not recommend 
specific intervention for an overdose.
In the event of an overdose, the investigator or treating physician should:

Contact the Medical Monitor immediately.

Closely monitor the participant for AE/SAE and laboratory abnormalities.

Document the quantity of the excess dose in the eCRF.
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the participant.
8.5.
Pharmacokinetics and Immunogenicity 
Serum samples will be used to evaluate the PK of guselkumab and golimumab and antibodies to 
guselkumab and to golimumab, respectively, at the timepoints presented in the SoA 
(Section 1.3). Serum collected for PK and/or immunogenicity may additionally be used to 
evaluate safety or efficacy aspects that address concerns arising during or after the study period, 
for further characterization of immunogenicity, or for the evaluation of relevant biomarkers. 
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 and golimumab will be evaluated (ie, 
no antibodies to guselkumab and golimumab will be evaluated), 1 venous blood sample of 
sufficient volume should be collected. Each serum sample will be divided into 3 aliquots: 1 for 
serum concentration of guselkumab, 1 for serum concentration of golimumab, and a back-up. 


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At visits where serum concentration of guselkumab and golimumab and antibodies to 
guselkumab and golimumab will be evaluated, 1 venous blood sample of sufficient volume 
should be collected. Each serum sample will be divided into 5 aliquots: 1 for serum 
concentration of guselkumab, 1 for serum concentration of golimumab, 1 for antibodies to 
guselkumab, 1 for antibodies to golimumab, and a back-up. The exact dates and times of blood 
sample collection must be recorded in the laboratory requisition form.
Additional information about the collection, handling, and shipment of biological samples can be 
found in the Laboratory Manual.
8.5.2.
Analytical Procedures
Pharmacokinetics
Serum samples will be analyzed to determine concentrations of guselkumab and golimumab
using respective validated, specific, and sensitive immunoassay methods by or under the 
supervision of the sponsor. The sponsor, or its designee, under conditions in which the 
participants’ identities remains blinded, will assay these samples. 
Immunogenicity
The detection and characterization of anti-guselkumab and anti-golimumab antibodies will be 
performed using respective validated assay methods by or under the supervision of the sponsor. 
All samples collected for detection of anti-guselkumab and anti-golimumab antibodies will also 
be evaluated for guselkumab and golimumab serum concentrations to enable interpretation of the 
antibody data.
8.5.3.
Pharmacokinetic Parameters and Evaluations
Parameters
Serum samples will be used to evaluate various guselkumab and golimumab PK parameters 
based on blood drawn from all participants according to the SoA (Section 1.3). A population PK 
analysis approach may also be used to derive PK parameters when appropriate.
Pharmacokinetic/Pharmacodynamic Evaluations
The relationship between serum concentrations of guselkumab and golimumab and efficacy 
measures or relevant biomarker(s) may be examined when appropriate.  
8.5.4.
Immunogenicity Assessments
Serum samples will be screened for antibodies binding to guselkumab and to golimumab, 
respectively, and the titer of confirmed positive samples will be reported. Other analyses may be 
performed to further characterize the immunogenicity of guselkumab and golimumab.


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8.6.
Pharmacodynamics
Pharmacodynamic markers will be evaluated using blood and fecal samples collected at visits as 
indicated in the SoA (Section 1.3). Post-baseline PD test results will not be released to the 
investigators by the central laboratory. 
8.7.
Genetics
Genetic variation may be important contributory factors to interindividual differences in drug 
disposition, response, and clinical outcomes. Genetic (DNA) factors may also serve as markers 
for disease susceptibility and prognosis and may identify population subgroups that respond 
differently to a drug. DNA samples will be analyzed for identification of genetic factors to better 
understand the molecular effects of guselkumab and/or golimumab treatment and/or UC, and to 
evaluate markers that can predict clinical response. Genetic (DNA) research may consist of the 
analysis of 1 or more candidate genes or analysis of the entire genome (as appropriate) in relation 
to treatment(s) and/or UC.
A pharmacogenomic whole blood sample of approximately 5 mL will be collected (where local 
regulations permit) for genetic analyses as specified in the SoA (Section 1.3). Only participants
who sign the consent form to participate in the genetic assessment will have whole blood DNA 
samples collected. Participation in the pharmacogenomic sub-study is optional.
8.8.
Biomarkers
Biomarker assessments will be made to examine the biologic response to treatment and to 
identify biomarkers that are relevant to guselkumab and/or golimumab in the treatment of UC. 
Combination TNFand IL-23 blockade will be compared to the selective inhibition of TNFor 
IL-23. Assessments will include the evaluation of relevant biomarkers in serum, whole blood, 
stool, and mucosal biopsy samples collected as specified in the SoA (Section 1.3). Data collected 
from these samples will be used for exploratory research that will include the following 
objectives:
1.
To understand the molecular effects of guselkumab and golimumab combination treatment 
or monotherapy of either agent.
2.
To understand UC pathogenesis.
3.
To understand why an individual participant may respond differently to guselkumab or 
golimumab.
4.
To develop tests for guselkumab, golimumab and/or UC.
Instructions for the collection and shipment of biomarker samples will be found in the 
Laboratory Manual.
8.8.1.
Serum
Serum samples for biomarker analyses will be obtained from all participants as specified in the
SoA. Analysis of serum samples for biomarkers may include proteins associated with 
proinflammatory and anti-inflammatory effects, the recruitment and proliferation of cells 
associated with inflammation and repair, and markers associated with tissue injury or repair.


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8.8.2.
Whole Blood (RNA)
Whole blood samples will be collected from all participants as specified in the SoA. Total RNA 
will be isolated and used for differential gene expression analyses to identify mRNA or 
microRNA expression patterns that are relevant to guselkumab, golimumab, and/or UC. Analysis 
will also be conducted to identify markers that can predict clinical response.
8.8.3.
Fecal 
Fecal samples will be collected from all participants as specified in the SoA. Microbiome and 
associated products analysis will be conducted to evaluate the association between inflammatory 
proteins, microbial activities and guselkumab, golimumab, and/or UC. The relationships between 
microbiome, metabolites, and biomarkers in other tissue samples will also be assessed.
8.8.4.
Mucosal Biopsy (RNA, Histology, and Single Cell Isolation)
Mucosal biopsy samples will be collected from all participants during endoscopy at the times
specified in the SoA for RNA expression analysis, histologic assessment, and single cell 
isolation. Total RNA will be isolated and used for differential gene expression analyses to 
identify mRNA or microRNA expression patterns that are relevant to guselkumab or golimumab 
treatment and/or UC, and to evaluate markers that can predict therapeutic response. The biopsy 
samples collected will also be used for the histologic and immunohistochemical assessment of 
disease and healing. Protein and gene expression will be measured at higher resolution in various 
immune cell populations isolated from these biopsy samples.
8.8.4.1.
Optional Week 4 Endoscopy and Biopsy Sub-study
Mucosal biopsies will be obtained at Week 4 only from participants who agree to participate in 
the optional sub-study. This optional sub-study is included to investigate early onset of action at 
Week 4 and to assess whether data collected at Week 4 correlate with clinical efficacy at later 
time points. The endoscopic assessment will also be conducted for this time point. The 
endoscopy subscores will be used to calculate full Mayo scores for this timepoint (see 
Section 8.1.1).
8.8.5.
Whole Blood (PBMCs)
Whole blood samples will be collected from all participants as specified in the SoA. Peripheral 
blood mononuclear cells (PBMCs) will be isolated and used for single cell isolation. Protein and 
gene expression that are relevant to study intervention and/or UC will be measured at higher 
resolution in PBMCs isolated from whole blood. To match with single cell analysis in colonic 
biopsies, whole blood samples will also be obtained at Week 4 from participants who agree to 
participate in the optional endoscopy and biopsy sub-study.
8.8.6.
Negative Response Signature 
The negative response signature is a predictive gene expression signature, initially discovered 
from colon biopsies collected at baseline from a subset of participants in the ACT 1 infliximab
UC study43, refined in the PURSUIT golimumab UC study44, and prospectively evaluated for 
prediction of mucosal healing in an open-label study of 103 UC subjects treated with golimumab


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(PROgECT).60 Using machine learning approaches, it was found that this length-13 gene 
signature predicted anti-TNFα nonresponse by mucosal healing with good accuracy, identifying 
63% of mucosal healing nonresponders with a negative predictive value of 0.87. The signature 
had similar negative predictive value in a Phase 2a study of a JAK inhibitor in UC suggesting 
that it may be mechanism agnostic.48 Efficacy of guselkumab and golimumab combination 
treatment or monotherapy treatment will be evaluated by negative response signature status at 
baseline (see Sections 3.1.2 and Section 3.2.3).
8.9.
Medical Resource Utilization 
Medical resource utilization, including but not limited to UC-related emergency department 
visits, hospitalizations, and surgeries, will be collected in this study.
9.
STATISTICAL CONSIDERATIONS
Statistical analysis will be done by the sponsor or under the authority of the sponsor. A general
description of the statistical methods to be used to analyze the efficacy and safety data is outlined 
below. Specific details will be provided in the SAP.
Descriptive statistics (eg, mean, median, standard deviation [SD], interquartile range, minimum, 
and maximum) will be used to summarize continuous variables. Counts and percentages will be 
used to summarize categorical variables. Graphical data displays (eg, line plots) may also be 
used to summarize data.
Analyses suitable for categorical data (eg, chi-square tests, Cochran-Mantel-Haenszel [CMH]
chi-square tests, or logistic regression, as appropriate) will be used to compare the proportions of 
participants achieving selected endpoints (eg, clinical response). In cases of rare events, the 
Fisher’s exact test will be used for treatment comparisons. Continuous response parameters will 
be compared using an analysis of variance (ANOVA) or analysis of covariance (ANCOVA), 
unless otherwise specified. If the normality assumption is in question, an ANOVA or ANCOVA
on the van der Waerden normal scores will be used.
Unless otherwise specified, the analysis of endpoints related to the endoscopy subscore, 
including the Mayo score, will be based on the final reported endoscopic subscore as defined in 
Section 8.1.1.
All statistical testing will be performed at a significance level of 0.1 (1-sided) unless otherwise 
specified. Nominal p-values will be displayed for all treatment comparisons.
9.1.
Statistical Hypotheses
The primary hypothesis is that guselkumab and golimumab combination therapy is superior to 
both monotherapy arms as assessed by the proportion of participants achieving clinical response 
at Week 12.


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9.2.
Sample Size Determination
A sample size of 210 participants (70 per intervention group) was determined by the power to 
detect a significant difference in the proportion of participants in clinical response at Week 12 
(primary endpoint) between the combination therapy and both monotherapies using a 1-sided 
chi-square test with 0.1 significance level for each comparison. The study is sized such that the
combination therapy has approximately 80% power (based on simulations) to achieve both 
comparisons to monotherapy for the primary endpoint.
The assumptions for the sample size calculations were based on data from the past golimumab 
programs conducted by the sponsor in participants with UC who were naïve to biologic therapy. 
The proportion of participants in clinical response at Week 12 is expected to be 55% for 
golimumab compared to 51% observed at Week 6 in study C0524T17 (PURSUIT), as the 
PURSUIT program suggested that the response rate might increase slightly with further 
treatment. This was also confirmed in study CNTO148UCO2001 (PROgECT).60 The tested dose 
of guselkumab is assumed to have the same clinical response rate as golimumab at Week 12. The 
proportion of participants in clinical response at Week 12 is assumed to be 75% for the 
combination therapy, which is based on the additive effect from both monotherapies (20% 
improvement from each monotherapy relative to a historical placebo response of 35%). The 
different combinations of clinical response rate assumptions and associated power are displayed 
in Table 4.
Table 4:
Power to Detect a Treatment Effect of the Combination Therapy Versus Both Guselkumab
Monotherapy and Golimumab Monotherapy Based on the Proportion of Participants Achieving 
Clinical Response at Week 12
Golimumab
(n=70)
Guselkumab
(n=70)
Combination Therapy
(n=70)
Power
50%
50%
70%
79%
50%
55%
70%
66%
55%
60%
75%
69%
55%
55%
75%
81%
55%
60%
80%
90%
60%
60%
80%
85%
9.3.
Populations for Analyses
For purposes of analysis, the following populations are defined:
Population
Description
Randomized Analysis Set
All participants who are randomized
Full Analysis Set
All randomized participants who receive at least 1 dose of study intervention
Safety Analysis Set
All randomized participants who receive at least 1 dose of study intervention
PK Analysis Set
All randomized participants who receive at least 1 dose of study intervention
and have at least 1 valid blood sample drawn for PK analysis


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9.4.
Statistical Analyses
9.4.1.
Efficacy Analyses
9.4.1.1.
Population for Efficacy Analysis
Unless otherwise noted, efficacy analyses will be based on the Full Analysis Set, which is 
defined as all randomized participants who receive at least 1 dose of study intervention. 
Participants will be analyzed according to the treatment group to which they were randomized 
regardless of the treatment they received. 
9.4.1.2.
Primary Endpoint Analyses 
The primary endpoint is clinical response at Week 12 defined as a decrease from baseline in the 
Mayo score ≥30% and ≥3 points with either a decrease in RBS ≥1 or a RBS of 0 or 1. The 
endoscopy subscore will be based on the final reported endoscopy subscore. 
Participants who have a colectomy or ostomy, or have protocol-prohibited medication changes 
(to be detailed in the SAP), or who have discontinued study intervention due to unsatisfactory 
therapeutic effect or an AE of worsening UC, before the Week 12 visit will be considered not to 
be in clinical response at Week 12, regardless of the actual Mayo score. 
Participants with a missing Mayo score (ie, all 4 Mayo subscores are missing) or who do not 
return for evaluation at Week 12 will be considered not to be in clinical response at Week 12.
For testing of the primary endpoint, the efficacy of combination therapy versus each 
monotherapy will be compared. For both statistical comparisons of the primary endpoint, a CMH
chi-square test stratified by concomitant use of corticosteroids at baseline (Y/N) will be used. 
The testing will be done simultaneously at the 1-sided 0.1 level of significance for each 
comparison. 
The study will be considered positive if the combination therapy group is significantly different 
from both monotherapy groups for the primary endpoint. 
To examine the robustness of the primary endpoint analysis, sensitivity analyses of the primary 
endpoint will be conducted using different missing data approaches; these analyses will be 
described in the SAP. 
Subgroup analyses of the primary endpoint will be performed based on demographic and 
baseline disease characteristics, and baseline concomitant UC medication use and history of
UC-related medications. Additional subgroup analyses of other endpoints (eg, clinical remission)
may be considered and will be described in the SAP.
9.4.1.3.
Major Secondary Endpoint Analyses
The major secondary endpoint is clinical remission at Week 12 defined as Mayo score ≤ 2 with 
no individual subscore >1. Note: Other remission definitions may be considered and will be fully 
described in the SAP.


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Participants who meet 1 or more treatment failure rules (as specified for the primary endpoint) 
before Week 12 will be considered not to be in clinical remission at Week 12.
Participants with a missing Mayo score (ie, all 4 Mayo subscores are missing) or who do not 
return for evaluation at Week 12 will be considered not to be in clinical remission at Week 12.
If both tests of the primary endpoint are positive, a CMH chi-square test (1-sided) stratified by 
concomitant use of corticosteroids at baseline (Y/N) will be used to compare the efficacy of the 
combination therapy to each monotherapy for the major secondary endpoint. The testing will be 
done simultaneously at the 1-sided 0.1 level of significance for each comparison.
9.4.1.4.
Other Efficacy Endpoint Analyses
Pairwise comparisons of the combination therapy with each monotherapy will be made for the 
endpoints specified in Section 3.2.3 with details that are to be specified in the SAP.
All statistical testing will be performed at the 1-sided 0.1 significance level. No adjustments for 
multiple comparisons will be made for these other efficacy endpoints and nominal p-values will 
be presented. 
9.4.1.5.
Exploratory Endpoint Analyses
Exploratory analyses will be conducted for BSFS scores over time and the distribution of PGIC 
of UC severity over time (details will be provided in the SAP).
9.4.2.
Safety Analyses
Safety data, including but not limited to, AEs, SAEs, infections, serious infections, changes in 
laboratory assessments will be summarized. Treatment-emergent AEs will be summarized by 
treatment group and Medical Dictionary for Regulatory Activities (MedDRA) system organ class 
and preferred terms. Details will be specified in the SAP.
Adverse Events
The verbatim terms used in the eCRF by investigators to identify AEs will be coded using the 
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 AEs
which are treatment-emergent will be included in the analysis. For each AE, the percentage of 
participants who experience at least 1 occurrence of the given event will be summarized by 
intervention group. 
The following analyses of AEs will be used to assess the safety of participants:

Frequency and type of AEs.

Frequency and type of SAEs.

Frequency and type of reasonably related AEs as assessed by the investigator.

Frequency and type of AEs leading to discontinuation of study intervention.


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
Frequency and type of infections, including serious infections and infections requiring oral 
or parenteral antimicrobial treatment.

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 adverse event, 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 NCI-CTCAE toxicity grade for post-baseline laboratory values 
(hematology and chemistry). 
Listings of participants with any abnormal post-baseline laboratory values of NCI-CTCAE 
grade ≥2 will also be provided.
Suicidal Ideation and Behavior
Suicidal ideation and behavior based on the C-SSRS and AEs will be summarized descriptively.
9.4.3.
Other Analyses
Pharmacokinetic Analyses 
Serum guselkumab and golimumab concentrations over time will be summarized for the PK 
Analysis Set. Descriptive statistics, including arithmetic mean, SD, median, interquartile range, 
minimum, and maximum will be calculated at each nominal sampling timepoint. 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.
Participants will be excluded from the PK analysis if their data do not allow for accurate 
assessment of the PK (eg, incomplete administration of the study intervention; missing time of 
study intervention administration). Detailed rules for the analysis will be specified in the SAP.
Population PK modeling may be conducted when appropriate. If these population PK analyses 
are conducted, the results of these analyses will be presented in a separate report.
Immunogenicity Analyses 
The incidence of antibodies to guselkumab and to golimumab will be summarized for all 
participants who receive at least 1 dose of guselkumab or golimumab and have appropriate 
samples for detection of antibodies to guselkumab and to golimumab (ie, participants with at 
least 1 sample obtained after their first dose of guselkumab or golimumab, respectively).


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A listing of participants who are positive for antibodies to guselkumab and to golimumab will be 
provided, respectively. The maximum titers of antibodies to guselkumab and to golimumab will 
be summarized for participants who are positive for antibodies to guselkumab and to golimumab, 
respectively. 
The incidence of neutralizing antibodies to guselkumab and to golimumab will be summarized 
for participants who are positive for antibodies to guselkumab and to golimumab and have 
samples evaluable for neutralizing antibodies to guselkumab and to golimumab, respectively.
Pharmacokinetic/Pharmacodynamic Analyses
The relationship between serum concentrations of guselkumab and golimumab and the efficacy 
measures and/or relevant biomarker(s) may be explored graphically when appropriate.
Additional analysis may be conducted if deemed necessary.
Biomarkers Analyses
Planned biomarker analyses may be deferred if emerging study data show no likelihood of 
providing useful scientific information. Any biomarker samples received by the contract vendor 
or sponsor after the cutoff date will not be analyzed, and therefore, will be excluded from the 
biomarker analysis.
Changes in serum protein analytes, fecal biomarkers, and biopsy and whole blood RNA obtained 
over time will be summarized by treatment group. Associations between baseline levels and 
changes from baseline in select markers and response to treatment will be explored. Biomarker
analyses will be summarized in a separate technical report.
The biomarker analyses will characterize the effects of guselkumab and/or golimumab to identify 
biomarkers relevant to treatment, and to determine if these biomarkers can predict response to 
guselkumab or golimumab. Results of serum, stool, whole blood, and mucosal biopsy analyses 
will be reported in separate technical reports.
Pharmacogenomic Analyses
Genetic (DNA) analyses will be conducted only in participants who sign the consent form to 
participate in the pharmacogenomic sub-study. These analyses are considered exploratory and 
will be summarized in a separate technical report. 
Medical Resource Utilization Analyses
Medical resource utilization data will be descriptively summarized by intervention group.
9.5.
Interim Analysis
For the purpose of future clinical development planning, there will be 1 interim analysis for this 
study. Depending on the enrollment rate, the sponsor anticipates that the interim analysis will 
take place when 30% to 60% of randomized participants have either completed their Week 12 
visit or have terminated their study participation before Week 12. No database locks are planned 
for interim analyses unless otherwise stated.


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A limited number of sponsor personnel will review the interim data. As this interim analysis does 
not affect the conduct or completion of the study, it will not require multiplicity adjustment for 
the final analysis.
9.5.1.
Data Monitoring Committee
An external independent DMC will be established and will meet periodically to review interim 
unblinded safety data to ensure the continuing safety of the participants enrolled in the study. 
The DMC will consist of 2 physicians and a statistician. The DMC responsibilities, authorities, 
and procedures will be documented in a separate DMC charter.
The DMC’s initial responsibility will be careful review of the safety data from the first 
25 participants randomized to any intervention group and treated. Similar to conduct of a Phase 1 
study, the safety of these first 25 participants will be monitored on an ongoing basis for any 
potential safety concerns that would result in a pause in dosing. Detailed guidance for the DMC 
regarding these reviews will be provided in the DMC charter. Once the 25th participant is 
randomized, the DMC will perform a review of unblinded safety tables. If no new safety 
concerns are identified during this initial review period, then the subsequent DMC reviews will 
include monthly reports of all SAEs in enrolled participants as well as review of unblinded safety 
tables at least every 3 months. After each safety review, the DMC will make recommendations 
regarding the continuation of the study.


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10.
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1.
Appendix 1: Abbreviations and Trademarks
5-ASA
5-aminosalicylic acid
6-MP
6-mercaptopurine
AE
adverse event
ALT
alanine aminotransferase
ANCOVA
analysis of covariance
ANOVA
analysis of variance 
ARC
Anticipated Event Review Committee
AS
ankylosing spondylitis
AST
aspartate aminotransferase
AZA
azathioprine
BCG
Bacille Calmette-Guérin
BSFS
Bristol Stool Form Scale
CMH
Cochran-Mantel-Haenszel
CRP
C-reactive protein
CV
cardiovascular
DBL
database lock
DMC
Data Monitoring Committee
DNA
deoxyribonucleic acid
ECG
electrocardiogram
eCRF
electronic case report form 
EP
erythrodermic psoriasis
ePPND
enhanced prenatal and postnatal development
EU
European Union
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GLP
Good Laboratory Practice
GPP
generalized pustular psoriasis
HBV
hepatitis B virus
HCV
hepatitis C virus
HIV
human immunodeficiency virus
HRQOL
health-related quality of life
HRT
hormonal replacement therapy
IB
Investigator’s Brochure
IBD
inflammatory bowel disease
IBDQ
Inflammatory Bowel Disease Questionnaire
ICF
informed consent form
ICH
International Conference on Harmonisation
ICMJE
International Committee of Medical Journal Editors
IEC
Independent Ethics Committee
IgG
immunoglobulin G
IL
interleukin
IPPI
Investigation Product Preparation Instructions
IPPM
Investigational Product Procedures Manual
IRB
Institutional Review Board
IV
intravenous
IWRS
interactive web response system
JAK
Janus kinase
mAb
monoclonal antibody
MedDRA
Medical Dictionary for Regulatory Activities
MTX
methotrexate
NCI-CTCAE
National Cancer Institute Common Terminology Criteria for Adverse Events
NOAEL
No Observed Adverse Effect Level
nr-Axial SpA
nonradiographic axial spondyloarthritis
PBMC
peripheral blood mononuclear cell


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PD
pharmacodynamic
PFS
prefilled syringe
PFS-U
PFS assembled in an UltraSafe Plus™ Passive Needle Guard
PGIC
Patient’s Global Impression of Change (of Severity of Ulcerative Colitis)
pJIA
polyarticular juvenile idiopathic arthritis
PK
pharmacokinetic
POC
proof-of-concept
PPP
palmoplantar pustulosis
PQC
product quality complaint
PRO
patient-reported outcomes
PROMIS
Patient-Reported Outcomes Measurement Information System
PsA
psoriatic arthritis
q4w
every 4 weeks
q8w
every 8 weeks
RA
rheumatoid arthritis
RBS
rectal bleeding subscore
RNA
ribonucleic acid
SAE
serious adverse event
SAP
Statistical Analysis Plan
SC
subcutaneous
SD
standard deviation
SmPC
Summary of Product Characteristics
SoA
Schedule of Activities
SUSAR
suspected unexpected serious adverse reaction
t1/2
half-life
TB
tuberculosis
TCR
tissue cross-reactivity
TK
toxicokinetic
TNFα
tumor necrosis factor alpha 
UC
ulcerative colitis
UCEIS
Ulcerative Colitis Endoscopic Index of Severity
ULN
upper limit of normal
US
United States
USPI
United States Prescribing Information
WBC
white blood cell
Definitions of Terms
Data collection 
system (DCS)
Includes data collected via electronic case report forms (eCRFs) and ancillary systems such 
as the Interactive Web Response System (IWRS), patient-reported outcome (PRO) tablets, 
laboratory database and imaging database.
Electronic source 
system
Contains data traditionally maintained in a hospital or clinic record to document medical 
care or data recorded in a CRF as determined by the protocol. Data in this system may be 
considered source documentation.


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10.2.
Appendix 2: Definition of Inadequate Response to or Intolerance of 
Corticosteroids or AZA/6 MP and Corticosteroid Dependence
CORTICOSTEROIDS
Subjects have failed to respond to corticosteroids if they have had evidence of an initial inadequate 
response, recurrent disease, or a relapse despite receiving at least 0.75 mg/kg/day or >40 mg/day of 
prednisone (or corticosteroid equivalent, given orally or intravenously) for 2 weeks; or ≥9 mg/day of 
budesonide or ≥5 mg/day of beclomethasone dipropionate given orally for at least 4 weeks.
Subjects are intolerant of corticosteroids if:

They have developed clinically significant adverse events (eg, osteonecrosis or osteoporosis, 
psychosis, uncontrolled diabetes) unresponsive to dose reduction that, in the judgment of the 
investigator, precluded the use of corticosteroids to treat ulcerative colitis (UC). 
OR

They have a medical condition that precludes the use of corticosteroids as a treatment for UC.
Subjects 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): 
Subjects 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 subject with whole blood 
thioguanine nucleotide levels >200 pmole/8 x 108 RBCs. 
OR

The highest tolerated dosage due to leukopenia, elevated liver enzymes, or nausea. 
Subjects are intolerant of 6-MP or AZA if: 

They have developed clinically significant adverse events (eg, pancreatitis, arthritis accompanied by 
high fever and/or rash, leukopenia, or persistently elevated liver enzymes) unresponsive to dose 
reduction that, in the judgment of the investigator, precluded the use of 6-MP or AZA to treat UC 
within the past 5 years.
OR

They have a medical condition that precludes the use of 6-MP or AZA. 


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10.3.
Appendix 3: Tuberculin Skin Testing
Administering the Mantoux Tuberculin Skin Test
The Mantoux tuberculin skin test (CDC, 2000) is the standard method of identifying persons infected with 
Mycobacterium tuberculosis. Multiple puncture tests (Tine and Heaf) should not be used to determine whether a 
person is infected because the amount of tuberculin injected intradermally cannot be precisely controlled.  
Tuberculin skin testing is both safe and reliable throughout the course of pregnancy. The Mantoux tuberculin test is 
performed by placing an intradermal injection of 0.1 mL of tuberculin into the inner surface of the forearm. The test 
must be performed with tuberculin that has at least the same strength as either 5 tuberculin units (TU) of standard 
purified protein derivative (PPD)-S or 2 TU of PPD-RT 23, Statens Seruminstitut, as recommended by the World 
Health Organization. PPD strengths of 1 TU or 250 TU are not acceptable (Menzies, 2000). Using a disposable 
tuberculin syringe with the needle bevel facing upward, the injection should be made just beneath the surface of the 
skin. This should produce a discrete, pale elevation of the skin (a wheal) 6 mm to 10 mm in diameter. To prevent 
needle-stick injuries, needles should not be recapped, purposely bent or broken, removed from disposable syringes, 
or otherwise manipulated by hand. After they are used, disposable needles and syringes should be placed in 
puncture-resistant containers for disposal. Institutional guidelines regarding universal precautions for infection 
control (eg, the use of gloves) should be followed. A trained health care worker, preferably the investigator, should 
read the reaction to the Mantoux test 48 to 72 hours after the injection. Participants should never be allowed to read 
their own tuberculin skin test results. If a participant fails to show up for the scheduled reading, a positive reaction 
may still be measurable up to 1 week after testing. However, if a participant who fails to return within 72 hours has a 
negative test, tuberculin testing should be repeated. The area of induration (palpable raised hardened area) around 
the site of injection is the reaction to tuberculin. For standardization, the diameter of the induration should be 
measured transversely (perpendicular) to the long axis of the forearm. Erythema (redness) should not be measured.  
All reactions should be recorded in millimeters, even those classified as negative.
Interpreting the Tuberculin Skin Test Results
In the US and many other countries, the most conservative definition of positivity for the tuberculin skin test is 
reserved for immunocompromised patients, and this definition is to be applied in this study to maximize the 
likelihood of detecting latent TB, even though the participants may not be immunocompromised at baseline.
In the US and Canada, an induration of 5 mm or greater in response to the intradermal tuberculin skin test is 
considered to be a positive result and evidence for either latent or active TB.
In countries outside the US and Canada, country-specific guidelines for immunocompromised patients should be 
consulted for the interpretation of tuberculin skin test results. If no local country guidelines for 
immunocompromised patients exist, US guidelines must be followed. 
Treatment of Latent Tuberculosis
Local country guidelines for immunocompromised patients should be consulted for acceptable antituberculous 
treatment regimens for latent TB. If no local country guidelines for immunocompromised patients exist, US 
guidelines must be followed.
References
Centers for Disease Control and Prevention.  Core curriculum on tuberculosis:  What the clinician should know 
(Fourth Edition).  Atlanta, GA:  Department of Health and Human Services; Centers for Disease Control and 
Prevention; National Center for HIV, STD, and TB Prevention; Division of Tuberculosis Elimination; 2000:25-86. 
Menzies RI.  Tuberculin skin testing.  In:  Reichman LB, Hershfield ES (eds). Tuberculosis, a comprehensive 
international approach.  2nd ed.  New York, NY:  Marcel Dekker, Inc; 2000:279-322.


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10.4.
Appendix 4: Contraceptive and Barrier Guidance and Collection of 
Pregnancy Information
Participants must follow contraceptive measures as outlined in Section 5.1, Inclusion Criteria. 
Pregnancy information will be collected and reported as noted in Section 8.3.4, Pregnancy and 
Appendix 10.9 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 non-estrogen-containing hormonal highly effective contraceptive methods if she 
wishes to continue HRT during the study.

permanently sterile
Permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral 
tubal occlusion/ligation procedures, and bilateral oophorectomy.
Note: If the childbearing potential changes after start of the study (eg, a premenarchal woman 
experiences menarche) or the risk of pregnancy changes (eg, a woman who is not heterosexually 
active becomes active), a woman must begin a highly effective method of contraception, as 
described throughout the inclusion criteria.
If reproductive status is questionable, additional evaluation should be considered.
As noted in Inclusion Criterion 13, study participants who are women of childbearing potential 
must be practicing a highly effective method of contraception and remain on a highly effective 
method while receiving study intervention and until 6 months after last dose. Examples of highly 
effective methods of contraception are provided below; however, the method selected must meet 
local/regional regulations/guidelines for highly effective contraception.


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Examples of Contraceptives
EXAMPLES OF CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE:
USER INDEPENDENT
Highly Effective Methods That Are User Independent Failure rate of <1% per year when used consistently 
and correctly.

Implantable progestogen-only hormone contraception associated with inhibition of ovulationb

Intrauterine device (IUD)

Intrauterine hormone-releasing system (IUS)

Bilateral tubal occlusion

Vasectomized partner
(Vasectomized partner is a highly effective contraceptive method provided that the partner is the sole sexual 
partner of the woman of childbearing potential and the absence of sperm has been confirmed. If not, 
additional highly effective method of contraception should be used. Spermatogenesis cycle is approximately 
74 days.)
USER DEPENDENT
Highly Effective Methods That Are User Dependent Failure rate of <1% per year when used consistently 
and correctly.

Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of 
ovulationb

oral

intravaginal

transdermal

injectable

Progestogen-only hormone contraception associated with inhibition of ovulationb

oral

injectable

Sexual abstinence
(Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of risk associated with the study intervention. The reliability of sexual 
abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle 
of the participant.)
NOT ALLOWED AS SOLE METHOD OF CONTRACEPTION DURING THE STUDY (not considered 
to be highly effective - failure rate of 1% per year)

Progestogen-only oral hormonal contraception where inhibition of ovulation is not the primary mode of 
action.

Male or female condom with or without spermicidec

Cap, diaphragm, or sponge with spermicide

A combination of male condom with either cap, diaphragm, or sponge with spermicide (double-barrier 
methods)c

Periodic abstinence (calendar, symptothermal, post-ovulation methods)

Withdrawal (coitus-interruptus)

Spermicides alone

Lactational amenorrhea method (LAM)
a) Typical use failure rates may differ from those when used consistently and correctly. Use should be 
consistent with local regulations regarding the use of contraceptive methods for participants in clinical 
studies.
b) Hormonal contraception may be susceptible to interaction with the study intervention, which may reduce the 
efficacy of the contraceptive method. In addition, consider if the hormonal contraception may interact with 
the study intervention.
c) Male condom and female condom should not be used together (due to risk of failure with friction).


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Pregnancy during the study
All initial reports of pregnancy in female participants or partners of male participants must be 
reported to the sponsor or designee by the study-site personnel within 24 hours of their 
knowledge of the event using the appropriate pregnancy notification form. Abnormal pregnancy 
outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic 
pregnancy) are considered serious adverse events and must be reported using the Serious 
Adverse Event Form. Any participant who becomes pregnant during the study must discontinue 
further study intervention.
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the 
infant will be required.




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10.6.
Appendix 6: 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), the latest version of the 
Declaration of Helsinki, and applicable regulatory and country-specific requirements.
Good Clinical Practice is an international ethical and scientific quality standard for designing, 
conducting, recording, and reporting studies that involve the participation of human participants. 
Compliance with this standard provides public assurance that the rights, safety, and well-being of 
study participants are protected, consistent with the principles that originated in the Declaration 
of Helsinki, and that the study data are credible.
Protocol Amendments
Neither the investigator nor the sponsor will modify this protocol without a formal amendment 
by the sponsor. All protocol amendments must be issued by the sponsor, and signed and dated by 
the investigator. Protocol amendments must not be implemented without prior IEC/IRB 
approval, or when the relevant competent authority has raised any grounds for non-acceptance, 
except when necessary to eliminate immediate hazards to the participants, in which case the 
amendment must be promptly submitted to the IEC/IRB and relevant competent authority. 
Documentation of amendment approval by the investigator and IEC/IRB must be provided to the 
sponsor. When the change(s) involve only logistic or administrative aspects of the study, the 
IEC/IRB (where required) only needs to be notified.
During the course of the study, in situations where a departure from the protocol is unavoidable, 
the investigator or other physician in attendance will contact the appropriate sponsor 
representative listed in the Contact Information page(s), which will be provided as a separate 
document. Except in emergency situations, this contact should be made before implementing any 
departure from the protocol. In all cases, contact with the sponsor must be made as soon as 
possible to discuss the situation and agree on an appropriate course of action. The data recorded 
in the Data Collection System (DCS) and source documents will reflect any departure from the 
protocol, and the source documents will describe this departure and the circumstances requiring 
it.
Regulatory Approval/Notification
This protocol and any amendment(s) must be submitted to the appropriate regulatory authorities 
in each respective country, if applicable. A study may not be initiated until all local regulatory 
requirements are met.
Required Prestudy Documentation
The following documents must be provided to the sponsor 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 Food and Drug Administration [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)

Investigator's Brochure (or equivalent information) and amendments/addenda

Sponsor-approved participant recruiting materials


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
Information on compensation for study-related injuries or payment to participants for 
participation in the study, if applicable

Investigator's curriculum vitae or equivalent information (unless not required, as 
documented by the IEC/IRB)

Information regarding funding, name of the sponsor, institutional affiliations, other potential 
conflicts of interest, and incentives for participants

Any other documents that the IEC/IRB requests to fulfill its obligation
This study will be undertaken only after the IEC/IRB has given full approval of the final 
protocol, amendments (if any, excluding the ones that are purely administrative, with no 
consequences for participants, data or study conduct, unless required locally), the ICF, applicable 
recruiting materials, and participant compensation programs, and the sponsor has received a copy 
of this approval. This approval letter must be dated and must clearly identify the IEC/IRB and 
the documents being approved.
Approval for the collection of optional samples for research and for the corresponding ICF must 
be obtained from the IEC/IRB. Approval for the protocol can be obtained independent of this 
optional research component.
During the study the investigator (or sponsor where required) will send the following documents 
and updates to the IEC/IRB for their review and approval, where appropriate:

Protocol amendments (excluding the ones that are purely administrative, with no 
consequences for participants, data or study conduct)

Revision(s) to ICF and any other written materials to be provided to participants

If applicable, new or revised participant recruiting materials approved by the sponsor

Revisions to compensation for study-related injuries or payment to participants for 
participation in the study, if applicable

New edition(s) of the IB and amendments/addenda

Summaries of the status of the study at intervals stipulated in guidelines of the IEC/IRB (at 
least annually)

Reports of 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


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
Development Safety Update Report and Line Listings, where applicable

Any other requirements of the IEC/IRB
For all protocol amendments (excluding the ones that are purely administrative, with no 
consequences for participants, data or study conduct), the amendment and applicable ICF 
revisions must be submitted promptly to the IEC/IRB for review and approval before 
implementation of the change(s).
At least once a year, the IEC/IRB will be asked to review and reapprove this study, where 
required.
At the end of the study, the investigator (or sponsor where required) will notify the IEC/IRB 
about the study completion (if applicable, the notification will be submitted through the head of 
investigational institution).
Country Selection
This study will only be conducted in those countries where the intent is to launch or otherwise 
help ensure access to the developed product if the need for the product persists, unless explicitly 
addressed as a specific ethical consideration in Section 4.2.5, Study-Specific Ethical Design 
Considerations.
Other Ethical Considerations
For study-specific ethical design considerations, refer to Section 4.2.5.
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 


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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.
A participant may be rescreened 1 time. Participants who are rescreened are required to sign a 
new ICF.
Completion of screening and randomization procedures within the specified screening window 
of approximately 8 weeks is required. If any delay leads to the expiration of time-specific 
assessments (eg, TB, chest radiograph, 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.
Participants will be asked for consent to provide optional samples for research (where local 
regulations permit). After informed consent for the study is appropriately obtained, the 
participant will be asked to sign and personally date a separate ICF indicating agreement to 
participate in the optional research component. Refusal to participate in the optional research will 
not result in ineligibility for the study. A copy of this signed ICF will be given to the participant.
DATA PROTECTION
Privacy of Personal Data
The collection and processing of personal data from participants enrolled in this study will be 
limited to those data that are necessary to fulfill the objectives of the study.
These data must be collected and processed with adequate precautions to ensure confidentiality 
and compliance with applicable data privacy protection laws and regulations. Appropriate 
technical and organizational measures to protect the personal data against unauthorized 
disclosures or access, accidental or unlawful destruction, or accidental loss or alteration must be 
put in place. Sponsor personnel whose responsibilities require access to personal data agree to 
keep the identity of participants confidential.


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The informed consent obtained from the participant includes explicit consent for the processing 
of personal data and for the investigator/institution to allow direct access to his or her original 
medical records (source data/documents) for study-related monitoring, audit, IEC/IRB review, 
and regulatory inspection. This consent also addresses the transfer of the data to other entities 
and to other countries.
The participant has the right to request through the investigator access to his or her personal data 
and the right to request rectification of any data that are not correct or complete. Reasonable 
steps will be taken to respond to such a request, taking into consideration the nature of the 
request, the conditions of the study, and the applicable laws and regulations.
Exploratory DNA, biomarker, PK, and immunogenicity 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.
LONG-TERM RETENTION OF SAMPLES FOR ADDITIONAL FUTURE RESEARCH
Samples collected in this study may be stored for up to 15 years (or according to local 
regulations) for additional research. The start of the storage period is defined as last participant 
last visit. Samples will only be used to understand guselkumab and golimumab, to understand
UC, to understand differential intervention responders, and to develop tests/assays related to 
guselkumab and golimumab and UC. The research may begin at any time during the study or the 
post-study storage period. 
Stored samples will be coded throughout the sample storage and analysis process and will not be 
labeled with personal identifiers. Participants may withdraw their consent for their samples to be 
stored for research (refer to Section 7.2.1, Withdrawal From the Use of Research Samples).
COMMITTEES STRUCTURE
Data Monitoring Committee
Details regarding the DMC are presented in Section 9.5.1.
PUBLICATION POLICY/DISSEMINATION OF CLINICAL STUDY DATA
All information, including but not limited to information regarding guselkumab and golimumab
or the sponsor's operations (eg, patent application, formulas, manufacturing processes, basic 
scientific data, prior clinical data, formulation information) supplied by the sponsor to the 
investigator and not previously published, and any data, including pharmacogenomic or 
exploratory biomarker research data, generated as a result of this study, are considered 
confidential and remain the sole property of the sponsor. The investigator agrees to maintain this 
information in confidence and use this information only to accomplish this study, and will not 
use it for other purposes without the sponsor's prior written consent.


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


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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.
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
Data for each study participant will be collected in the eCRF or ancillary data collection systems 
such as the IWRS, PRO tablets, laboratory database, and imaging database. Case report forms 
are prepared and provided by the sponsor for each participant in electronic format. Collectively, 
all data collection via eCRFs and ancillary systems will comprise what is referred to in this 
protocol as the DCS.
All DCS entries, corrections, and alterations must be made by the investigator or authorized 
study-site personnel. 
The investigator must verify that all data entries in the eCRF are accurate and correct.
Study data will be transcribed by study-site personnel from source documentation to an eCRF or 
the appropriate ancillary DCS, as applicable. Study-specific data from each source will be 
transmitted in a secure manner to the sponsor.
Worksheets may be used as source documentation to capture data and facilitate completion of the 
eCRF or entry of data into the applicable ancillary data system. Data must be entered into the 
DCS in English. The eCRF must be completed as soon as possible after a participant visit and the 
forms should be available for review at the next scheduled monitoring visit.
Necessary eCRF or ancillary data modifications can only be made by the investigator or 
appropriate site personnel using eCRF system functionality and/or ancillary data revision 
procedures. All data changes will be recorded in an audit trail.


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SOURCE DOCUMENTS
At a minimum, source documents consistent in the type and level of detail with that commonly 
recorded at the study site as a basis for standard medical care must be available for the following: 
participant identification, eligibility, and study identification; study discussion and date of signed 
informed consent; dates of visits; results of safety and efficacy parameters as required by the 
protocol; record of all AEs and follow-up of AEs; concomitant medication; intervention 
receipt/dispensing/return records; study intervention administration information; and date of 
study completion and reason for early discontinuation of study intervention or withdrawal from 
the study, if applicable. 
The author of an entry in the source documents should be identifiable.
Specific details required as source data for the study and source data collection methods will be 
reviewed with the investigator before the study and will be described in the monitoring 
guidelines (or other equivalent document).
The minimum source documentation requirements for Section 5.1, Inclusion Criteria and 
Section 5.2, Exclusion Criteria that specify a need for documented medical history are as 
follows:

Referral letter from treating physician or

Complete history of medical notes at the site

Discharge summaries
Inclusion and exclusion criteria not requiring documented medical history must be verified at a 
minimum by participant interview or other protocol required assessment (eg, physical 
examination, laboratory assessment) and documented in the source documents.
An electronic source (eSource) system may be utilized, which contains data traditionally 
maintained in a hospital or clinic record to document medical care (eg, electronic source 
documents) as well as the clinical study-specific data fields as determined by the protocol. This 
data is electronically extracted for use by the sponsor. If eSource is utilized, references made to 
the eCRF in the protocol include the eSource system but information collected through eSource 
may not be limited to that found in the eCRF.
MONITORING
The sponsor will use a combination of monitoring techniques (central, remote, and 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, as allowed by 
local regulation. The first post-initiation visit will be made as soon as possible after enrollment 
has begun. At these visits, the monitor will compare the data entered into the applicable DCS 
component (as defined in the monitoring guidelines) with the source documents 
(eg, hospital/clinic/physician’s office medical records). The nature and location of all source 


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documents will be identified to ensure that all sources of original data required to complete the 
applicable DCS component 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 development of the investigational product. These documents will be 


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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 CLOSURE
Study Termination
The sponsor reserves the right to close the study site or terminate the study at any time for any 
reason at the sole discretion of the sponsor. Study sites will be closed upon study completion. A 
study site is considered closed when all required documents and study supplies have been 
collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to:

Failure of the investigator to comply with the protocol, the requirements of the IEC/IRB or 
local health authorities, the sponsor's procedures, or GCP guidelines

Inadequate recruitment of participants by the investigator

Discontinuation of further study intervention development


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10.7.
Appendix 7: Liver Safety: Suggested Actions and Follow-up Assessments
Abbreviations
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; CRF=case report form; EOT=end 
of treatment (end of intervention); GGT=gamma-glutamyltransferase; INR=international normalized ratio; LT/LFT=liver 
tests/liver function tests; Tbili=total bilirubin; ULN=upper limit of normal.


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10.8.
Appendix 8: Mayo Score
Mayo scoring system for assessment of ulcerative colitis activity
Stool frequencya
0 = Normal number of stools for this patient
1 = 1-2 stools more than normal
2 = 3-4 stools more than normal
3 = 5 or more stools more than normal
Rectal bleedingb
0 = No blood seen
1 = Streaks of blood with stool less than half the time
2 = Obvious blood with stool most of the time
3 = Blood alone passed
Findings of endoscopy
0 = Normal or inactive disease
1 = Mild disease (erythema, decreased vascular pattern, mild friability)
2 = Moderate disease (marked erythema, absent vascular pattern, friability, erosions)
3 = Severe disease (spontaneous bleeding, ulceration)
Physician’s global assessmentc
0 = Normal
1 = Mild disease
2 = Moderate disease
3 = Severe disease
a At the screening visit, each person indicates the number of stools he/she passed in a 24-hour period when in 
remission or before his/her UC diagnosis, thereby serving as his/her own control to establish the degree of 
abnormality of stool frequency.
b The daily bleeding score represents the most severe bleeding of the day.
c The physician’s global assessment acknowledges the 3 other criteria, the patient’s recall of abdominal 
discomfort and general sense of well-being, and other observations, such as physical findings and the 
patient’s performance status.


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10.9.
Appendix 9: 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 non-investigational) product. An adverse event does not 
necessarily have a causal relationship with the intervention. An adverse event can therefore be 
any unfavorable and unintended sign (including an abnormal finding), symptom, or disease 
temporally associated with the use of a medicinal (investigational or non-investigational) 
product, whether or not related to that medicinal (investigational or non-investigational) product. 
(Definition per International 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.


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Unlisted (Unexpected) Adverse Event/Reference Safety Information
An adverse event is considered unlisted if the nature or severity is not consistent with the 
applicable product reference safety information. For guselkumab and golimumab, the 
expectedness of an adverse event will be determined by whether or not it is listed in the IB for 
guselkumab or for golimumab, respectively. 
Adverse Event Associated With the Use of the Intervention
An adverse event is considered associated with the use of the intervention if the attribution is 
possible, probable, or very likely by the definitions listed below (see Attribution Definitions).
ATTRIBUTION DEFINITIONS
Not Related
An adverse event that is not related to the use of the intervention.
Doubtful
An adverse event for which an alternative explanation is more likely, eg, concomitant 
treatment(s), concomitant disease(s), or the relationship in time suggests that a causal 
relationship is unlikely.
Possible
An adverse event that might be due to the use of the intervention. An alternative explanation, 
eg, concomitant treatment(s), concomitant disease(s), is inconclusive. The relationship in time is 
reasonable; therefore, the causal relationship cannot be excluded.
Probable
An adverse event that might be due to the use of the intervention. The relationship in time is 
suggestive (eg, confirmed by dechallenge). An alternative explanation is less likely, 
eg, concomitant treatment(s), concomitant disease(s).
Very Likely
An adverse event that is listed as a possible adverse reaction and cannot be reasonably explained 
by an alternative explanation, eg, concomitant treatment(s), concomitant disease(s). The 
relationship in time is very suggestive (eg, it is confirmed by dechallenge and rechallenge).
SEVERITY CRITERIA 
An assessment of severity grade will be made using the following general categorical 
descriptors:
Mild: Awareness of symptoms that are easily tolerated, causing minimal discomfort and not 
interfering with everyday activities.
Moderate: Sufficient discomfort is present to cause interference with normal activity.


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Severe: Extreme distress, causing significant impairment of functioning or incapacitation. 
Prevents normal everyday activities.
The investigator 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

Accidental or occupational exposure to a sponsor study intervention

Any failure of expected pharmacologic action (ie, lack of effect) of a sponsor study 
intervention

Unexpected therapeutic or clinical benefit from use of a sponsor study intervention

Medication error involving a sponsor product (with or without participant/patient exposure 
to the sponsor study intervention, eg, name confusion)

Exposure to a sponsor study intervention from breastfeeding
Special reporting situations should be recorded in the eCRF. Any special reporting situation that 
meets the criteria of a serious adverse event should be recorded on the serious adverse event page 
of the eCRF.
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


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
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 staff only)

Site number

Participant number

Any other information that is required to do an emergency breaking of the blind
Serious Adverse Events
All serious adverse events that have not resolved by the end of the study, or that have not 
resolved upon discontinuation of the participant's participation in the study, must be followed 
until any of the following occurs:

The event resolves

The event stabilizes

The event returns to baseline, if a baseline value/status is available

The event can be attributed to agents other than the study intervention or to factors unrelated 
to study conduct

It becomes unlikely that any additional information can be obtained (participant or health 
care practitioner refusal to provide additional information, lost to follow-up after 
demonstration of due diligence with follow-up efforts)
Suspected transmission of an infectious agent by a medicinal product will be reported as a 
serious adverse event. Any event requiring hospitalization (or prolongation of hospitalization) 
that occurs during the course of a participant's participation in a study must be reported as a 
serious adverse event, except hospitalizations for the following:

Hospitalizations not intended to treat an acute illness or adverse event (eg, social reasons 
such as pending placement in long-term care facility)

Surgery or procedure planned before entry into the study (must be documented in the 
eCRF). Note: Hospitalizations that were planned before the signing of the ICF, and where 
the underlying condition for which the hospitalization was planned has not worsened, will 
not be considered serious adverse events. Any adverse event that results in a prolongation of 
the originally planned hospitalization is to be reported as a new serious adverse event.
The cause of death of a participant in a study within 16 weeks of the last dose of study 
intervention, whether or not the event is expected or associated with the study intervention, is 
considered a serious adverse event.
CONTACTING SPONSOR REGARDING SAFETY
The names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding safety issues or questions regarding the study are listed in the Contact Information 
page(s), which will be provided as a separate document.


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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.
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 Contact Information page(s), which will be 
provided as a separate document.


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10.10. Appendix 10: Anticipated Events 
Anticipated Event
An anticipated event is an adverse event (serious or non-serious) that commonly occurs as a 
consequence of the underlying disease or condition under investigation (disease-related) or 
background regimen.
For the purposes of this study the following events will be considered anticipated events: 
Adverse Events Associated with the Study Population

Adverse events related to symptoms of UC

Adverse events related to worsening or progression of UC
Reporting of Anticipated Events
All adverse events will be recorded in the eCRF regardless of whether considered to be 
anticipated events and will be reported to the sponsor as described under All Adverse Events in 
Section 8.3.1, Time Period and Frequency for Collecting Adverse Event and Serious Adverse 
Event Information. Any anticipated event that meets serious adverse event criteria will be 
reported to the sponsor as described under Serious Adverse Events in Section 8.3.1, Time Period 
and Frequency for Collecting Adverse Event and Serious Adverse Event Information. These 
anticipated events are exempt from expedited reporting as individual single cases to Health 
Authorities. 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.
Anticipated Event Review Committee (ARC) 
An Anticipated Event Review Committee (ARC) will be established to perform reviews of pre-
specified anticipated events at an aggregate level. The ARC is a safety committee within the 
sponsor’s organization that is independent of the sponsor’s study team. The ARC will meet to aid 
in the recommendation to the sponsor’s study team as to whether there is a reasonable possibility 
that an anticipated event is related to the study intervention.
Statistical Analysis
Details of statistical analysis of anticipated events, including the frequency of review and 
threshold to trigger an aggregate analysis of anticipated events will be provided in a separate 
Anticipated Events Safety Monitoring Plan (ASMP).


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10.11. Appendix 11: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents.
Amendment 1 - 24 Sep 2018
Overall Rationale for the Amendment: The overall reason for the amendment is to incorporate health
authority feedback on additional safety precautions. In addition, revisions were made to improve clarity 
and consistency in the protocol. 
Section number
and Name
Description of Change
Brief Rationale
1.3 Schedule of 
Activities; 4.2.5 
Study-Specific 
Ethical Design 
Considerations; 8 
Study Assessments 
and Procedures
The protocol was revised to collect hematology and 
chemistry (including liver biochemistry) laboratory 
test results from every 4 weeks to every 2 weeks 
(Weeks 0, 2, 4, 6, 8, 10, and 12) during the 
combination comparison phase and from every 8 
weeks to every visit (Weeks 14, 16, 18, 22, 24, 26, 
30, 32, 34, and 38) during the monotherapy phase. 
The maximum total blood volume to be collected 
from each participant in the study was revised from 
approximately 265 mL to approximately 310 mL. 
Hematology and chemistry 
(including liver biochemistry) tests 
will be collected more frequently to 
enhance safety monitoring. 
8.2.5 Clinical Safety 
Laboratory 
Assessments
The following criteria for retesting were added under 
Hematology assessments in Section 8.2.5:
Mandatory Re-testing
The following hematology abnormalities require 
monitoring and re-testing (ideally within 3-5 days):
-
Absolute neutrophil count <1.2 × 103
cells/µL (SI: <1.2 × 109 cells/L)
-
Absolute lymphocyte count <0.5 × 103
cells/µL (SI: <0.5 × 109 cells/L)
-
Any single hemoglobin value <8.0 g/dL (SI: 
<80.0 g/L), or any decrease in hemoglobin 
>2.0 g/dL (SI: >20.0 g/L) from baseline
-
Platelet count <100 × 103 cells/µL (SI: <100 
× 109 cells/L)
The medical monitor or designee and the clinical site 
will be notified if these abnormal laboratory values 
are identified in any participant during the conduct 
of the study.
Monitoring and retesting for certain 
laboratory abnormalities were added 
to the protocol as a safety 
precaution.
7.1 Discontinuation 
of Study 
Intervention
The following criteria and note were added to the list 
of conditions for which discontinuation of a 
participants’ study intervention must be strongly 
considered: 
5. The participant has hematology abnormalities as 
described below:
-
Two sequential absolute neutrophil counts 
<0.75 × 103 cells/µL (SI: <0.75 × 109
cells/L)
-
Two sequential absolute lymphocyte counts 
Discontinuation criteria for 
cytopenia (including lymphopenia 
and neutropenia) were added as a 
safety precaution. 


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Section number
and Name
Description of Change
Brief Rationale
<0.5 × 103 cells/µL (SI: <0.5 × 109 cells/L)
-
Two sequential hemoglobin values <8.0 g/dL
(SI: <80.0g/L) or a decrease of >30% from 
baseline
-
Two sequential platelet counts <75 × 103
cells/µL (SI: <75 × 109 cells/L)
Note: These laboratory abnormalities should be 
discussed with the medical monitor or designee, and 
study intervention should be withheld until the 
clinical assessment is complete.
1.3 Schedule of 
Activities
The following footnote was added to Hematology 
and chemistry on Table 1 and Table 2 of the 
Schedule of Activities: Certain laboratory 
abnormalities require re-testing and potential 
discontinuation of study intervention (See Sections 
8.2.5 and 7.1, respectively).
Footnote was added to direct 
investigators to Sections 8.2.5 and 
7.1 for laboratory values that may 
require retesting or potential 
discontinuation of study 
intervention, respectively. 
7.1 Discontinuation 
of Study 
Intervention
The description of the first criterion under 
discontinuation of a participant’s study intervention 
must be strongly considered under the following 
conditions was revised to say: 
1. Persistent inadequate response or worsening of 
UC based on signs, symptoms, and/or laboratory 
values.
The description was clarified for 
investigators to strongly consider 
discontinuation based on signs, 
symptoms, and/or laboratory values 
for persistent inadequate response or 
worsening of UC.
1.3 Schedule of 
Activities; 6.1 Study 
Interventions 
Administered 
The following was added as a footnote to Week 0, 
Administer study intervention on Table 1 of the 
Schedule of Activities and to Section 6.1: 
For the baseline (W0) visit, the IV study intervention 
should be administered first. The SC study 
intervention should be administered approximately 
30 minutes after the IV study intervention infusion is 
complete. 
Clarify when the IV and SC study 
interventions should be administered 
at Week 0. 
5.1 Inclusion 
Criteria
Inclusion criterion #7b was revised to discontinue 
vedolizumab from at least 8 weeks to at least 
18 weeks before the first administration of study 
intervention:
7 b. Vedolizumab for at least 18 weeks.
The washout period for vedolizumab 
was revised to 18 weeks to be 
consistent with the serum half-life of 
vedolizumab.
5.1 Inclusion 
Criteria; 5.2 
Exclusion Criteria; 8 
Study Assessments; 
10.3 Appendix 3: 
Contraceptive and 
Barrier Guidance 
and Collection of 
Pregnancy 
Information
For the following inclusion criteria, the time frame 
for precautions for reproduction was revised from 
16 weeks to 6 months:
13 b. If heterosexually active, practicing a highly 
effective method of contraception (failure rate of 
<1% per year when used consistently and correctly) 
and agrees to remain on a highly effective method 
while receiving study intervention and until 6 
months after last dose (ie, the end of relevant 
systemic exposure). 
14. A woman must agree not to donate eggs (ova, 
oocytes) for the purposes of assisted reproduction 
during the study and for 6 months after the last study 
intervention.
16. A male participant must agree not to donate 
sperm for the purpose of reproduction during the 
study and for a minimum of 6 months after receiving 
the last dose of study intervention.
The time frame for participants to 
use a highly effective method of 
contraception and to continue taking 
precautions after receiving the last 
administration of study intervention 
was revised from 16 weeks to 
6 months to align with the longest 
duration defined for SIMPONI.


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Section number
and Name
Description of Change
Brief Rationale
The following exclusion criterion revised the 
timeframe for precautions for reproduction from 
16 weeks to 6 months:
35. Is a woman who is pregnant, or breast-feeding, 
or planning to become pregnant, or is a man who 
plans to father a child while enrolled in this study or 
within 6 months after the last dose of study 
intervention.
5.2 Exclusion 
Criteria
Exclusion criterion #1c.4) was revised from >90 
beats/minute to >100 beats/minute:
1 c. 4) Tachycardia (>100 beats/minute)
The exclusion criterion for 
tachycardia was increased to >100 
beats/minute since the normal adult 
heart rate has been considered 
historically to range from 60 to 100 
beats per minute, with sinus 
tachycardia being defined as a sinus 
rhythm with a rate exceeding 100 
beats per minute.
5.2 Exclusion 
Criteria
Exclusion criteria #12c and #12d were modified to 
include a time frame:
12 c. Natalizumab within 12 months of first study 
intervention administration. 
12 d. Agents that deplete B or T cells (eg, rituximab, 
alemtuzumab) within 12 months of first study 
intervention administration, or continue to manifest 
depletion of B or T cells more than 12 months after 
completion of therapy with lymphocyte-depleting 
agents.  
A time frame of 12 months was 
specified for patients who previously 
received natalizumab or agents that 
deplete B or T cells. 
6.5.1 Concomitant 
Medications
Conventional immunomodulators (ie, 6-MP, AZA, 
or MTX) were removed from the list of concomitant 
UC-specific medical therapies that enrolled 
participants should not initiate.
Conventional immunomodulators 
are listed under prohibited 
concomitant medications; therefore, 
participants who initiate 6-MP, 
AZA, or MTX during the study will 
have their study intervention 
discontinued.
7.1 Discontinuation 
of Study 
Intervention
The following criterion was added to the list of 
conditions for which a participant's study treatment 
intervention must be discontinued:
13. The participant develops symptoms suggestive 
of a lupus-like syndrome and is positive for 
antibodies against double-stranded DNA. 
This criterion was added as a safety 
precaution.
Throughout the 
protocol
Minor grammatical, formatting, or spelling changes 
were made.
Minor errors were noted


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11.
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SAP_001.pdf: 
1
Approved, Date: 24 February 2021
Janssen Research & Development
Statistical Analysis Plan
A Phase 2a Randomized, Double-blind, Active-controlled, Parallel-group, Multicenter, 
Proof-of-concept Clinical Study to Evaluate the Efficacy and Safety of Combination 
Therapy with Guselkumab and Golimumab in Participants with Moderately to Severely 
Active Ulcerative Colitis
VEGA
Protocol CNTO1959UCO2002; Phase 2a
CNTO1959 (guselkumab); CNTO148 (golimumab)  
Status:
Approved
Date:
24 February 2021
Prepared by:
Janssen Research & Development, LLC  
Document No.: EDMS-RIM-346041
Compliance: The study described in this report was performed according to the principles of Good Clinical Practice (GCP). 
Confidentiality Statement
The information in this document contains trade secrets and commercial information that are privileged or confidential and 
may not be disclosed unless such disclosure is required by applicable law or regulations. In any event, persons to whom the 
information is disclosed must be informed that the information is privileged or confidential and may not be further disclosed 
by them. These restrictions on disclosure will apply equally to all future information supplied to you that is indicated as 
privileged or confidential.
NCT03662542


CNTO1959 (guselkumab); CNTO148 (golimumab)  (VEGA)
Statistical Analysis Plan CNTO1959UCO2002
2
Approved, Date: 24 February 2021
TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
LIST OF TABLES ......................................................................................................................................... 4
ABBREVIATIONS ........................................................................................................................................ 5
1.
INTRODUCTION.................................................................................................................................. 7
1.1.
Trial Objectives ................................................................................................................................ 7
1.2.
Trial Design ...................................................................................................................................... 8
1.3.
Statistical Hypotheses for Trial Objectives..................................................................................... 10
1.4.
Sample Size Justification ............................................................................................................... 10
1.5.
Randomization and Blinding .......................................................................................................... 11
2.
GENERAL ANALYSIS DEFINITIONS .............................................................................................. 13
2.1.
Visit Windows................................................................................................................................. 13
2.2.
Analysis Sets.................................................................................................................................. 13
2.2.1.
Randomized Analysis Set........................................................................................................... 13
2.2.2.
Efficacy Analysis Set(s) .............................................................................................................. 13
2.2.3.
Safety Analysis Set..................................................................................................................... 13
2.2.4.
Pharmacokinetics Analysis Set .................................................................................................. 13
2.2.5.
Immunogenicity Analysis Set...................................................................................................... 14
2.3.
Definition of Subgroups.................................................................................................................. 14
2.4.
Study Day and Relative Day .......................................................................................................... 15
2.5.
Baseline ......................................................................................................................................... 15
2.6.
Imputation Rules for Missing AE Date/Time of Onset/Resolution ................................................. 15
3.
INTERIM ANALYSIS AND DATA MONITORING COMMITTEE REVIEW....................................... 16
4.
SUBJECT INFORMATION................................................................................................................ 17
4.1.
Demographics and Baseline Characteristics ................................................................................. 17
4.2.
Disposition Information................................................................................................................... 18
4.3.
Treatment Compliance................................................................................................................... 18
4.4.
Extent of Exposure......................................................................................................................... 18
4.5.
Protocol Deviations ........................................................................................................................ 18
4.6.
Prior and Concomitant Medications ............................................................................................... 19
5.
EFFICACY ......................................................................................................................................... 19
5.1.
General Method of Analysis........................................................................................................... 19
5.2.
Analysis Specifications................................................................................................................... 20
5.2.1.
Level of Significance................................................................................................................... 20
5.3.
Primary Efficacy Endpoint.............................................................................................................. 20
5.3.1.
Definition..................................................................................................................................... 20
5.3.1.1.
Mayo Score, Partial Mayo Score, and Modified Mayo Score.................................................. 20
5.3.2.
Primary Estimand (Estimand 1).................................................................................................. 22
5.3.3.
Analysis Methods for the Primary Estimand (Estimand 1) ......................................................... 24
5.3.3.1.
Main Estimator (Analysis) for the Primary Estimand............................................................... 24
5.3.3.2.
Subgroup Analyses ................................................................................................................. 24
5.3.3.3.
Sensitivity Analyses................................................................................................................. 24
5.3.4.
Supplementary Estimands.......................................................................................................... 25
5.3.4.1.
Estimand 2............................................................................................................................... 25
5.3.4.2.
Estimand 3............................................................................................................................... 25
5.3.5.
Estimators (Analyses) for the Supplementary Estimands .......................................................... 26
5.3.5.1.
Estimator (Analysis) for Estimand 2 ........................................................................................ 26
5.3.5.2.
Estimator (Analysis) for Estimand 3 ........................................................................................ 26
5.4.
Major Secondary Endpoint............................................................................................................. 26
5.4.1.
Definition..................................................................................................................................... 26


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Statistical Analysis Plan CNTO1959UCO2002
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5.4.2.
Main Estimand (Estimand 4) ...................................................................................................... 27
5.4.3.
Analysis Methods for the Main Estimand (Estimand 4).............................................................. 27
5.4.3.1.
Main Estimator (Analysis) for the Main Estimand.................................................................... 27
5.4.3.2.
Subgroup Analyses ................................................................................................................. 27
5.4.4.
Supplementary Estimands.......................................................................................................... 27
5.4.4.1.
Estimand 5............................................................................................................................... 27
5.4.4.2.
Estimand 6............................................................................................................................... 28
5.4.5.
Estimators (Analyses) for the Supplementary Estimands .......................................................... 28
5.4.5.1.
Estimator (Analysis) for Estimand 5 ........................................................................................ 28
5.4.5.2.
Estimator (Analysis) for Estimand 6 ........................................................................................ 28
5.5.
Other Efficacy Endpoints................................................................................................................ 28
5.5.1.
Definitions ................................................................................................................................... 31
5.5.1.1.
Clinical Endpoints .................................................................................................................... 31
5.5.1.1.1.
Modified Mayo Response..................................................................................................... 31
5.5.1.1.2.
Symptomatic remission........................................................................................................ 31
5.5.1.1.3.
Endoscopic healing .............................................................................................................. 31
5.5.1.1.4.
Endoscopic normalization (i.e. normalization of endoscopic appearance of mucosa 
in protocol)............................................................................................................................ 31
5.5.1.1.5.
Clinical remission by alternative definitions ......................................................................... 31
5.5.1.1.6.
Histologic healing ................................................................................................................. 31
5.5.1.1.7.
Mucosal healing ................................................................................................................... 32
5.5.1.1.8.
Histologic remission ............................................................................................................. 32
5.5.1.1.9.
Histologic-endoscopic mucosal healing ............................................................................... 32
5.5.1.1.10.
Deep histologic-endoscopic mucosal healing...................................................................... 32
5.5.1.1.11.
Geboes Scores..................................................................................................................... 32
5.5.1.1.12.
Roberts Histologic Index (RHI)-based histologic remission................................................. 32
5.5.1.1.13.
Nancy Histologic Index (NHI)-based histologic remission ................................................... 32
5.5.1.1.14.
Ulcerative Colitis Endoscopic Index of Severity (UCEIS) .................................................... 32
5.5.1.2.
Inflammatory Biomarkers......................................................................................................... 33
5.5.1.2.1.
C-Reactive Protein ............................................................................................................... 33
5.5.1.2.2.
Fecal Calprotectin ................................................................................................................ 33
5.5.1.3.
HRQoL Endpoints.................................................................................................................... 33
5.5.1.3.1.
Inflammatory Bowel Disease Questionnaire (IBDQ)............................................................ 33
5.5.1.3.2.
PROMIS-29.......................................................................................................................... 33
5.5.1.3.3.
PROMIS Fatigue 7-items Short Form .................................................................................. 33
5.5.2.
Estimands ................................................................................................................................... 34
5.5.3.
Estimators (Analyses) for Estimands.......................................................................................... 34
5.6.
Exploratory Endpoints.................................................................................................................... 35
5.6.1.
Definitions ................................................................................................................................... 36
5.6.1.1.
Bristol Stool Form Scale.......................................................................................................... 36
5.6.1.2.
Patient’s Global Impression of Change (PGIC) of Severity of Ulcerative Colitis..................... 36
5.6.2.
Estimands ................................................................................................................................... 36
5.6.3.
Estimators (Analyses) for Estimands.......................................................................................... 37
6.
SAFETY............................................................................................................................................. 38
6.1.
Adverse Events .............................................................................................................................. 38
6.2.
Clinical Laboratory Tests................................................................................................................ 39
6.3.
Other Safety Parameters ............................................................................................................... 40
6.3.1.
Suicidal Ideation and Behavior ................................................................................................... 40
7.
PHARMACOKINETICS/PHARMACODYNAMICS ........................................................................... 40
7.1.
Pharmacokinetics........................................................................................................................... 40
7.1.1.
Serum Guselkumab and Golimumab Concentrations ................................................................ 40
7.1.1.1.
Data Handling Rules................................................................................................................ 41
7.1.2.
PK vs Efficacy............................................................................................................................. 41
7.1.3.
Population PK Analysis............................................................................................................... 42
7.2.
Immunogenicity.............................................................................................................................. 42
7.2.1.
Antibodies to Guselkumab and to Golimumab ........................................................................... 42


CNTO1959 (guselkumab); CNTO148 (golimumab)  (VEGA)
Statistical Analysis Plan CNTO1959UCO2002
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Approved, Date: 24 February 2021
7.2.1.1.
Neutralized Antibodies to Guselkumab and to Golimumab..................................................... 42
7.2.2.
Antibody vs PK/Efficacy/Safety .................................................................................................. 42
7.3.
Pharmacokinetic/Pharmacodynamic Relationships....................................................................... 43
8.
BIOMARKERS................................................................................................................................... 43
9.
MEDICAL RESOURCE UTILIZATION AND HEALTH ECONOMICS.............................................. 43
REFERENCES............................................................................................................................................ 45
ATTACHMENTS......................................................................................................................................... 46
LIST OF TABLES
Table 1: 
Power to Detect a Treatment Effect of the Combination Therapy Versus Both 
Guselkumab Monotherapy and Golimumab Monotherapy Based on the Proportion of 
Participants Achieving Clinical Response at Week 12 ............................................................. 11
Table 2:  Demographic and Baseline Characteristics Variables................................................................. 17
Table 3: Multiple Imputation Methods ......................................................................................................... 26
Table 4: Dosing Window ............................................................................................................................. 41


CNTO1959 (guselkumab); CNTO148 (golimumab)  (VEGA)
Statistical Analysis Plan CNTO1959UCO2002
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ABBREVIATIONS
5-ASA
5-aminosalicyclic acid
6-MP
6-mercaptopurine
AE
adverse event
ALT
alanine aminotransferase
ANCOVA
analysis of covariance
AST
aspartate aminotransferase
AZA
azathioprine
BSFS
bristol stool form scale
BMI
body mass index
CI
confidence interval
CMH
cochran-mantel-haenszel
CRP
c-reactive protein
CV
coefficient of variation
DBL
database lock
DMC
data monitoring committee
eCRF
electronic case report form 
FAS
full analysis set
FCS
full conditional specification
GCP
good clinical practice
HRQOL
health-related quality of life
IAP
interim analysis plan
IBD
inflammatory bowel disease
IBDQ
inflammatory bowel disease questionnaire
IEC
independent ethics committee
IQ
interquartile
IRB
institutional review board
IV
intravenous
IWRS
interactive web response system
LLOQ
lower limit of quantification
LSmeans
least squares means 
MedDRA
medical dictionary for regulatory activities
MTX
methotrexate
MI
multiple imputation
MMRM
mixed-effect model repeated measure
MAR
missing data random
NAbs
neutralizing antibodies
NCI-CTCAE
national cancer institute common terminology criteria for adverse events
NHI
Nancy Histologic Index
NONMEM
nonlinear mixed-effects modeling
NA
North America
PD
pharmacodynamic
PGIC
patient’s global impression of change (of severity of Ulcerative Colitis)
PGA
physician’s global assessment
PK
pharmacokinetic
POC
proof-of-concept
PRO
patient-reported outcomes
PROMIS
patient-reported outcomes measurement information system
q4w
every 4 weeks
q8w
every 8 weeks
RBS
rectal bleeding subscore
RHI
Roberts Histologic Index
RNA
ribonucleic acid
SAE
serious adverse event
SAP
Statistical Analysis Plan
SC
Subcutaneous
SD
standard deviation


CNTO1959 (guselkumab); CNTO148 (golimumab)  (VEGA)
Statistical Analysis Plan CNTO1959UCO2002
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Approved, Date: 24 February 2021
SI
système internationale
SoA
schedule of activities
SUSAR
suspected unexpected serious adverse reaction
t1/2
half-life
TF
treatment failure
TNF
tumor necrosis factor
UC
ulcerative colitis
UCEIS
Ulcerative Colitis endoscopic index of severity
ULN
upper limit of normal
US
United States
WBC
white blood cell


CNTO1959 (guselkumab); CNTO148 (golimumab)  (VEGA)
Statistical Analysis Plan CNTO1959UCO2002
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Approved, Date: 24 February 2021
1.
INTRODUCTION
The protocol CNTO1959UCO2002 is a Phase 2a clinical trial designed to evaluate the efficacy 
and safety of combination therapy with guselkumab and golimumab in participants with 
moderately to severely active ulcerative colitis (UC). This study is comprised of 2 distinct phases: 
a 12-week combination comparison phase followed by a 26-week monotherapy phase. This 
Statistical Analysis Plan (SAP) contains definitions of analysis sets, derived variables, and 
statistical methods for all planned analyses for protocol CNTO1959UCO2002.
1.1.
Trial Objectives
Primary Objectives
Combination Comparison Phase

To evaluate the clinical efficacy of combination therapy with guselkumab and golimumab in 
participants with moderately to severely active UC.

To evaluate the safety of combination therapy with guselkumab and golimumab in participants
with moderately to severely active UC.
Secondary Objectives
Combination Comparison Phase

To evaluate the effect of combination therapy with guselkumab and golimumab on endoscopic
improvement.

To evaluate the impact of combination therapy with guselkumab and golimumab on disease-
specific health-related quality of life (HRQoL), including fatigue.

To evaluate the efficacy of combination therapy with guselkumab and golimumab by negative 
response signature status at baseline.

To evaluate the pharmacokinetic (PK), immunogenicity, and pharmacodynamics (PD) of 
combination therapy with guselkumab and golimumab, including changes in C-reactive 
protein (CRP), fecal calprotectin, and other PD biomarkers.
Monotherapy Phase

To evaluate the clinical efficacy of combination therapy followed by guselkumab 
monotherapy.

To evaluate the safety of combination therapy followed by guselkumab monotherapy.

To evaluate the effect of combination therapy followed by guselkumab monotherapy on 
endoscopic improvement. 

To evaluate the impact of combination therapy followed by guselkumab monotherapy on 
disease specific HRQoL, including fatigue.


CNTO1959 (guselkumab); CNTO148 (golimumab)  (VEGA)
Statistical Analysis Plan CNTO1959UCO2002
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Approved, Date: 24 February 2021

To evaluate the efficacy of combination therapy followed by guselkumab monotherapy by 
negative response signature status at baseline.

To evaluate the PK, immunogenicity, and PD of combination therapy followed by guselkumab 
monotherapy, including changes in CRP, fecal calprotectin, and other PD biomarkers.
Exploratory Objectives

To explore the effect of combination therapy on patient-reported outcome (PRO) instruments 
(e.g., Bristol Stool Form Scale [BSFS] and Patient’s Global Impression of Change [PGIC] of 
Severity of UC).
1.2.
Trial Design
This is a Phase 2a, randomized, double-blind, active-controlled, parallel-group, multicenter,
interventional proof-of-concept (POC) clinical study designed to evaluate the efficacy and safety 
of combination therapy with guselkumab and golimumab in adults with moderately to severely 
active UC. The target population is men or women 18 to 65 years old with moderately to severely 
active UC, as defined by a Mayo score of 6 to 12, inclusive, at baseline, including an endoscopy 
subscore ≥2 as obtained during the central review of the video endoscopy. Participants must be 
naïve to tumor necrosis factor (TNF) antagonists and have failed or not tolerated conventional 
therapy with oral or intravenous (IV) corticosteroids or immunomodulators (6-mercaptopurine [6-
MP] or azathioprine [AZA]). 
This study will consist of 2 distinct phases: a 12-week combination comparison phase followed 
by a 26-week monotherapy phase. At Week 0, a target of 210 participants will be randomized in 
a 1:1:1 ratio to either combination therapy with guselkumab and golimumab, guselkumab 
monotherapy, or golimumab monotherapy, stratified by corticosteroid use at baseline (yes, no). 
Participants randomized to combination therapy will receive guselkumab monotherapy after Week 
12. Participants randomized to a monotherapy group will continue on their originally randomized 
monotherapy after Week 12. The combination therapy arm will employ the same dose regimens 
of guselkumab and golimumab being used in the respective monotherapy intervention groups to 
facilitate scientific interpretation of the results. The following is a description of the 3 intervention 
groups:

Combination therapy (N = 70): guselkumab 200 mg IV and golimumab 200 mg 
subcutaneous (SC) at Week 0; golimumab 100 mg SC at Weeks 2, 6, and 10; guselkumab 200 
mg IV at Weeks 4 and 8 followed by guselkumab 100 mg SC q8w

Guselkumab monotherapy (N = 70): guselkumab 200 mg IV at Weeks 0, 4, and 8 followed 
by guselkumab 100 mg SC q8w

Golimumab monotherapy (N = 70): golimumab 200 mg SC injection at Week 0, followed 
by golimumab 100 mg at Week 2 and then golimumab 100 mg every 4 weeks (q4w)
In addition, placebo administrations (IV or SC) will be given, as appropriate, to maintain blinding
throughout the duration of the study. Refer to Protocol Section 6 for additional details. A diagram 
of the study design is provided in Figure 1.


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Figure 1:
Schematic Overview of Study CNTO1959UCO2002
Immunomodulators (6-MP, AZA, and methotrexate [MTX]) must be discontinued for at least 2 
weeks before the first dose of study intervention. For participants who are receiving oral 
corticosteroids at baseline, the investigator must begin tapering the daily dose of corticosteroids at 
Week 6. The use of concomitant and prohibited therapies is described in Protocol Section 6.5. In 
general, doses of concomitant therapies for UC should remain stable through Week 38 (except for
mandatory oral corticosteroid tapering beginning at Week 6), and concomitant therapies for UC 
should not be initiated unless considered medically necessary by the investigator. Initiation of 
prohibited therapies will result in discontinuation of study intervention.
All participants will be evaluated for clinical worsening of UC throughout the study. Endoscopy 
with central read is planned for screening/baseline, Week 12, and Week 38. Consenting 
participants will have an additional endoscopy at Week 4, which will also be assessed by a central 
reader. Efficacy, PK and PD parameters, biomarkers, and safety will be assessed according to the 
Schedule of Activities (SoA) (Protocol Section 1.3). A pharmacogenomic blood sample will be 
collected from participants who consent to this component of the protocol (where local regulations 
permit). Participation in pharmacogenomic research is optional.
Overall participant duration will be up to 58 weeks total (screening: up to 8 weeks; treatment 
duration: 38 weeks [12 weeks for the combination comparison phase; 26 weeks for the 
monotherapy phase]; safety follow-up: approximately 16 weeks after the last administration of 
study intervention at Week 34).


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An interim analysis (IA) was performed in April 2020 to inform future clinical development
planning after the first 126 randomized participants (i.e., 60% of the planned sample size) who 
received at least one administration of studyintervention (complete or partial) completed the Week 
12 assessments or terminated study participation prior to the Week 12 visit. The details regarding 
this IA are provided in the Interim Analysis Plan (IAP). 
There are 3 planned database locks (DBLs) for this study, respectively, at Week 12, at Week 38, 
and at end of the study.  The end of the study is defined as when the last participant completes his 
or her final safety follow-up visit.  The first DBL will occur when all participants randomized in 
this study have either completed the Week 12 assessments or terminated study participation prior 
to the Week 12 visit (referred to as Week 12 DBL hereafter).  The second DBL will occur when 
all participants randomized in this study have either completed the Week 38 assessments or 
terminated study participation prior to the Week 38 visit (referred to as Week 38 DBL hereafter). 
The third DBL will occur at end of study when all participants randomized in this study have either 
completed their final safety follow-up visit or have terminated study participation [referred to as 
Final Safety DBL hereafter]. 
The primary endpoint of this study is clinical response at Week 12 (refer to Section 5.3 for endpoint
definition and analyses). The major secondary endpoint is clinical remission at Week 12 
(Section 5.4 – definitions and analyses methods).  The primary and major secondary endpoints 
will be analyzed at the Week 12 DBL.
An external independent data monitoring committee (DMC) will be commissioned for this study
to monitor the safety of the study in an unblinded fashion on a regular basis and whenever deemed 
necessary.  Refer to the DMC charter for more details on the DMC.
1.3.
Statistical Hypotheses for Trial Objectives
The primary endpoint of this study is clinical response at Week 12 (refer to Section 5.3 for endpoint
definition and analyses).
The primary hypothesis is that guselkumab and golimumab combination therapy is superior to 
both monotherapy arms as assessed by the proportion of participants achieving clinical response 
at Week 12.
The study will be considered positive if both comparisons of guselkumab and golimumab 
combination therapy versus guselkumab monotherapy therapy and guselkumab and golimumab 
combination therapy versus golimumab monotherapy therapy achieve the statistical significance 
at the 2-sided significance level of 0.2 for the primary endpoint.
1.4.
Sample Size Justification
A sample size of 210 participants (70 per intervention group) was determined by the power to 
detect a significant difference in the proportion of participants in clinical response at Week 12 
(primary endpoint) between the combination therapy and both monotherapies using a 1-sided chi-
square test with 0.1 significance level for each comparison. The study is sized such that the


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combination therapy has approximately 80% power (based on simulations) to achieve both 
comparisons to monotherapy for the primary endpoint. 
The assumptions for the sample size calculations were based on data from the past golimumab 
programs conducted by the sponsor in participants with UC who were naïve to biologic therapy. 
The proportion of participants in clinical response at Week 12 is expected to be 55% for 
golimumab compared to 51% observed at Week 6 in study C0524T17 (PURSUIT), as the 
PURSUIT program suggested that the response rate might increase slightly with further treatment. 
This was also confirmed in study CNTO148UCO2001 (PROgECT)13. The tested dose of 
guselkumab is assumed to have the same clinical response rate as golimumab at Week 12. The 
proportion of participants in clinical response at Week 12 is assumed to be 75% for the 
combination therapy, which is based on the additive effect from both monotherapies (20% 
improvement from each monotherapy relative to a historical placebo response of 35%). The 
different combinations of clinical response rate assumptions and associated power are displayed 
in Table 1.
Table 1: 
Power to Detect a Treatment Effect of the Combination Therapy Versus Both Guselkumab 
Monotherapy and Golimumab Monotherapy Based on the Proportion of Participants 
Achieving Clinical Response at Week 12
Golimumab
(n=70)
Guselkumab
(n=70)
Combination Therapy
(n=70)
Power
50%
50%
70%
79%
50%
55%
70%
66%
55%
60%
75%
69%
55%
55%
75%
81%
55%
60%
80%
90%
60%
60%
80%
85%
1.5.
Randomization and Blinding
Randomization will be used to minimize bias in the assignment of participants to treatment groups, 
to increase the likelihood that known and unknown participant attributes (e.g., demographic and 
baseline characteristics) are evenly balanced across treatment groups, and to enhance the validity 
of statistical comparisons across treatment groups. Blinded treatment will be used to reduce 
potential bias during data collection and evaluation of clinical endpoints.
Intervention Allocation
Central randomization will be implemented in this study. Participants will be randomly assigned 
to 1 of 3 intervention groups (1:1:1 ratio), based on a computer-generated randomization schedule 
prepared before the study by or under the supervision of the sponsor. The randomization will be 
balanced by using randomly permuted blocks and will be stratified by corticosteroid use at baseline 
(yes, no). The interactive web response system (IWRS) will assign a unique treatment code, which 
will dictate the treatment assignment and matching study intervention kit(s) for the participant. 


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The requestor must use his or her own user identification and personal identification number when 
contacting the IWRS and will then be given the relevant participant details to uniquely identify the 
participant.
Blinding
To maintain the study blind, the study intervention container will have a label containing the study 
name, study intervention number, and reference number. The study intervention number will be 
entered in the electronic case report form (eCRF) when the study intervention is dispensed. Each 
active study intervention and its matching placebo will be identical in appearance.
Data that may potentially unblind the treatment assignment (e.g., study intervention serum 
concentrations, antibodies to study intervention) will be handled with special care to ensure that 
the integrity of the blind is maintained and the potential for bias is minimized. This can include 
making special provisions, such as segregating the data in question from view by the investigators, 
clinical team, or others as appropriate until the study unblinding.
The post-baseline results of CRP and fecal calprotectin tests performed by the central laboratory 
will be blinded to the study sites. If a study site requests these data, it will be provided to them 
after the analyses based on the Final Safety DBL have been completed.
Treatment assignment blinding will be maintained for study sites, site monitors, and participants
until the analyses based on the Final Safety DBL are completed. The full sponsor unblinding will 
occur after the Week 38 DBL. A limited number of sponsor personnel were unblinded to the IA 
data (only those randomized participants who were included in the IA; the treatment assignment 
for the remaining participants remained blinded) for data analyses and review. The sponsor 
personnel who were unblinded to the IA data were documented in the IA unblinding plan. In 
addition, a limited number of sponsor personnel will become unblinded at the Week 12 DBL for 
data analyses and review. Identification of sponsor personnel who will have access to the 
unblinded data and at what level (treatment group-level or participant-level) will be documented 
in the unblinding plan before unblinding occurs at the Week 12 DBL. 
The investigator will not be provided with randomization codes. The codes will be maintained 
within the IWRS, which has the functionality to allow the investigator to break the blind for an 
individual participant.
Under normal circumstances, the investigator blind should not be broken unless specific 
emergency treatment/course of action would be dictated by knowing the treatment status of the 
participant. In such cases, the investigator may in an emergency determine the identity of the 
treatment via the IWRS. It is recommended that the investigator contact the sponsor or its designee, 
if possible, to discuss the particular situation before breaking the blind. Telephone contact with the 
sponsor or its designee will be available 24 hours per day, 7 days per week. If the blind is broken, 
the sponsor must be informed as soon as possible. The date and reason for the unblinding must be 
documented in the appropriate section of the eCRF and in the source document. The 
documentation received from the IWRS indicating the code break must be retained with the 
participant's source documents in a secure manner.


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Additionally, a given participant’s treatment assignment may be unblinded to the sponsor, the 
Independent Ethics Committee/Institutional Review Board (IEC/IRB), and site personnel to fulfill 
regulatory reporting requirements for suspected unexpected serious adverse reactions (SUSARs). 
If a participant is unblinded for this reason, the information must be entered in the appropriate 
section of the eCRF and in the participant's source documents. 
Participants who have had their treatment assignment unblinded by the investigator will not be 
eligible to receive further study intervention but should complete evaluations specified in the 
appropriate SoA (Protocol Section 1.3) for participants who discontinue study intervention.
A separate code break procedure will be available for use by the J&J Global Medical Safety group 
to allow for unblinding of individual participants to comply with specific requests from regulatory 
or health authorities.
2.
GENERAL ANALYSIS DEFINITIONS
2.1.
Visit Windows
Unless otherwise specified, actual scheduled visits will be used for over time summaries and 
listings with no visit windows applied.
2.2.
Analysis Sets
2.2.1.
Randomized Analysis Set
The randomized analysis set includes all participants who are randomized in the study. Participants 
in the Randomized Analysis Set will be analyzed according to the randomized study intervention 
regardless of the study intervention they actually received.
2.2.2.
Efficacy Analysis Set(s)
Unless otherwise specified, all efficacy analyses will be based on the Full Analysis Set (FAS), 
which includes all randomized participants who receive at least 1 (partial or complete) dose of 
study intervention. Participants in FAS will be analyzed according to the randomized study 
intervention regardless of the study intervention they actually received.
2.2.3.
Safety Analysis Set
The safety analysis set includes all randomized participants who receive at least 1 (partial or 
complete) dose of study intervention. Participants in the Safety Analysis Set will be analyzed 
according to the study intervention they actually received.
2.2.4.
Pharmacokinetics Analysis Set
The PK analysis set includes all randomized participants who receive at least 1 (complete) dose of 
study intervention (golimumab or guselkumab) and have at least 1 valid blood sample drawn for 
PK analysis after their first dose of study intervention (golimumab or guselkumab). Participants in 
the Pharmacokinetics Analysis Set will be analyzed according to the study intervention they 
actually received.


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2.2.5.
Immunogenicity Analysis Set
The immunogenicity analysis set is defined as all participants who receive at least 1 (partial or 
complete) dose of guselkumab and/or golimumab and have appropriate samples for detection of 
antibodies to guselkumab and/or to golimumab (ie, participants with at least 1 sample obtained 
after their first dose of guselkumab or golimumab, respectively). Participants in the 
Immunogenicity Analysis Set will be analyzed according to the study intervention they actually 
received.
2.3.
Definition of Subgroups
The primary endpoint will be evaluated for subgroups based on demographics and baseline UC 
clinical disease characteristics, UC-related concomitant medication usage, and UC-related 
medication history.
Demographics

Gender (male, female)

Race (Caucasian, non-Caucasian)

Baseline age (≤ median age, > median age) 

Baseline body weight (≤ 1st quartile, >1st quartile and ≤ 2nd quartile, >2nd quartile and ≤ 3rd 
quartile, >3rd quartile) 

Baseline body mass index (BMI) (≤ 1st quartile, >1st quartile and ≤ 2nd quartile, >2nd quartile 
and ≤ 3rd quartile, >3rd quartile) 

Tobacco use status (non-user, prior user, current user)

Region 

Eastern Europe: Poland, Russia, Ukraine 

Latin America: Argentina, Mexico, Brazil

Rest of World: United States, Germany, Australia
Baseline UC clinical disease characteristics

UC disease duration (≤ 5 years, > 5 years to ≤ 15 years, > 15 years)

Extent of disease (limited, extensive)

Severity of UC disease (moderately active: 6 ≤ Mayo score ≤ 10, severely active: Mayo score 
>10)

Severity of endoscopic disease (moderate: endoscopic subscore = 2, severe: endoscopic
subscore = 3)

CRP (≤3 mg/L, > 3 mg/L)

CRP (≤ 1st quartile, >1st quartile and ≤ 2nd quartile, >2nd quartile and ≤ 3rd quartile, >3rd 
quartile)

Fecal calprotectin (≤250 mg/kg, > 250 mg/kg)


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
Fecal calprotectin (≤ 1st quartile, > 1st quartile and ≤ 2nd quartile, > 2nd quartile and ≤ 3rd 
quartile, > 3rd quartile)
Baseline UC-related concomitant medications 

Oral 5-aminosalicylic acid [5-ASA] compounds (receiving, not receiving)

Oral corticosteroids including budesonide and beclomethasone dipropionate (receiving, not 
receiving) 

Participants taking conventional immunomodulators (6-MP/AZA/MTX) during Screening but 
discontinuing it prior to Week 0

Participants taking Vedolizumab during Screening but discontinuing it prior to Week 0
UC-related medication history

Refractory or intolerant to 6-MP/AZA (yes, no)

Refractory, dependent or intolerant to oral or IV corticosteroids (yes, no)

Refractory, dependent, or intolerant to oral or IV corticosteroids, but not refractory or 
intolerant to 6-MP/AZA (yes, no)

Refractory, dependent or intolerant to oral or IV corticosteroids, and refractory or intolerant 
to 6-MP/AZA (yes, no)

Refractory or intolerant to Vedolizumab (yes, no)

Vedolizumab experienced (yes, no)

Refractory or intolerant to Tofacitinib (yes, no)

Tofacitinib experienced (yes, no)
2.4.
Study Day and Relative Day
Study Day 1 refers to the date of the first study intervention administration. All efficacy and safety 
assessments at all visits will be assigned a day relative to this date.
Study day for a visit is defined as:

Visit date - (date of Study Day 1) +1, if visit date is ≥date of Study Day 1

Visit date - date of Study Day 1, if visit date < date of Study Day 1
There is no 'Study Day 0'.
2.5.
Baseline 
Baseline is defined as the last observation prior to or on the day of the first study intervention, 
unless otherwise specified.
2.6.
Imputation Rules for Missing AE Date/Time of Onset/Resolution
Partial adverse event (AE) onset dates will be imputed as follows:


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
If the onset date of an adverse event is missing day only, it will be set to:

First day of the month that the AE occurred, if month/year of the onset of AE is different 
than the month/year of the date of the first study intervention administration

The day of the first study intervention administration, if the month/year of the onset of 
AE is the same as month/year of the first study intervention administration and 
month/year of the AE resolution date is later

The day of the first study intervention administration or day of AE resolution date, 
whichever is earliest, if month/year of the onset of AE and month/year of the first study 
intervention administration date and month/year of the AE resolution date are same

If the onset date of an adverse event is missing both day and month, it will be set to the earliest 
of:

January 1 of the year of onset, as long as the year is the same or after the year of the first 
study intervention administration

Month and day of the first study intervention administration, if this date is the same year 
that the AE occurred

Last day of the year if the year of the AE onset is prior to the year of the first study 
intervention administration

Completely missing onset dates will not be imputed.
Partial AE resolution dates not marked as ongoing will be imputed as follows:

If the resolution date of an adverse event is missing day only, it will be set to the earliest of 
the last day of the month of occurrence of resolution or the day of the date of death, if the 
death occurred in that month.

If the resolution date of an adverse event is missing both day and month, it will be set to the 
earliest of December 31 of the year or the day and month of the date of death, if the death 
occurred in that year.

Completely missing resolution dates will not be imputed.
AE onset/resolution dates with missing times will be imputed as follows:

A missing time of onset of an adverse event will be set to:

00:01 as long as the onset date is after the study intervention start date

The time of the study intervention start date if this is the same day the AE occurred.

The missing time of resolution of an adverse event will be set to 23:59.
If a missing time is associated with a partial or missing date, the date will be imputed first prior to 
imputing the time.
3.
INTERIM ANALYSIS AND DATA MONITORING COMMITTEE REVIEW
For the purpose of future clinical development planning, an IA was performed in April 2020 after 
the first 126 randomized participants (i.e., 60% of the planned sample size) completed their Week 
12 visit or terminated their study participation before Week 12. 


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An external DMC has been established and are meeting periodically to review interim unblinded 
safety data to ensure the continuing safety of the participants enrolled in the study. The DMC 
consists of 2 physicians and a statistician. The DMC responsibilities, authorities, and procedures 
are documented in a separate DMC charter.
4.
SUBJECT INFORMATION
The number of participants in each analysis set will be summarized by treatment group and overall
for this study. In addition, the distribution of participants by region, country and site ID will be 
presented.
Descriptive statistics (mean, standard deviation (SD), median, interquartile (IQ) range, minimum 
and maximum) will be provided for continuous variables. Frequency distributions will be provided 
for categorical variables. No formal statistical analyses for treatment comparisons will be 
performed.
4.1.
Demographics and Baseline Characteristics
Table 2 presents a list of the demographic and baseline characteristics variables that will be 
summarized by treatment group and overall for the FAS (Section 2.2.2).
Table 2:  Demographic and Baseline Characteristics Variables
Continuous Variables:
Summary Type
Age (years)
Descriptive statistics (N, mean, 
standard deviation [SD], median 
and range [minimum and 
maximum], and IQ range).
Weight (kg)
Height (cm)
BMI (kg/m2)
UC Disease Duration (years)
Mayo score
Partial Mayo score
Modified Mayo score
Mayo subscores (rectal bleeding subscore, stool frequency subscore)
CRP (mg/L)
Fecal Calprotectin (mg/kg)
Categorical Variables
Sex (male, female)
Frequency distribution with the 
number and percentage of 
participants in each category.
Racea (American Indian or Alaska Native, Asian, Black or African 
American, Native Hawaiian or other Pacific Islander, White, Not 
Reported, Multiple)
Ethnicity (Hispanic or Latino, not Hispanic or Latino, Not Reported)
Regionb (Eastern Europe, Latin America, Rest of World)
UC Disease Duration (≤ 5 years, > 5 and ≤15 years, > 15 years)
Mayo Endoscopy Subscore (moderate: subscore = 2, severe: subscore = 3)
Extent of disease (limited, extensive)
Severity of UC disease (moderately active: 6 ≤ Mayo score ≤10, severely 
active: Mayo score > 10)
Abnormal CRP (> 3 mg/L)
Abnormal fecal calprotectin (> 250 mg/kg)
Tobacco use status (non-user, prior user, current user)
(randomization stratification factor) Corticosteroid use (yes, no) 
a  If multiple race categories are indicated, the Race is recorded as 'Multiple'.


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b Eastern Europe: Poland, Russia, Ukraine; Latin America: Argentina, Mexico, Brazil; Rest of World: United States, 
Germany, Australia
4.2.
Disposition Information
Participants who discontinued study intervention early, along with the reasons for discontinuation
of study intervention (including those due to COVID-19 related events), will be summarized by 
treatment group and overall based on the FAS (Section 2.2.2). In addition, participants who 
terminated study participation early, along with the reasons for termination of study participation
(including those due to COVID-19 related events), will be summarized by treatment group and 
overall based on the FAS.
A list of participants who discontinued study intervention early (including those due to COVID-
19 related events) and a list of participants who terminated study participation early (including 
those due to COVID-19 related events) will also be provided.
4.3.
Treatment Compliance
The number of participants receiving each scheduled study intervention will be summarized by 
treatment group for the FAS (Section 2.2.2). Compliance with randomized study intervention
versus actual received study intervention will be presented in a summary table for the FAS.
In addition, a listing of participants who were assigned treatment but were never treated and a 
listing of participants who were unblinded during the study will be provided.
4.4.
Extent of Exposure
The number and percentage of participants who receive study intervention will be summarized by 
treatment group for the Safety Analysis Set (Section 2.2.3). The cumulative dose of guselkumab 
and golimumab received will be summarized by treatment group based on the Safety Analysis Set.  
In addition, the number of administrations of study intervention and average duration of follow-
up in weeks will be summarized by treatment group for all participants in the Safety Analysis Set
as part of the AE tables.  
The distribution of participants by study intervention lot will also be summarized by treatment 
group for the Safety Analysis Set.
4.5.
Protocol Deviations
Participants with a major protocol deviation will be summarized by treatment group based on the 
FAS (Section 2.2.2). Major protocol deviations will be categorized as study intervention 
administration deviations, study entry criteria not met, prohibited concomitant medications 
deviations, withdrawal criteria met but not withdrawn, or other (including a sub-category for 
COVID-19 related deviations). 
In addition, participants who did not meet study entry criteria will be further summarized by 
category (UC disease criteria, Medication criteria, Laboratory criteria, Medical history criteria,
and other) based on the FAS. Further, participants who had study intervention administration 


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deviations will be further summarized by category identified prior to unblinding (e.g., received 
wrong study intervention administration, missed study intervention administration, received study 
intervention administration outside of protocol specified window).  
A listing of participants who had a major protocol deviation (including COVID-19 related 
deviations), a more detailed listing of participants who did not meet study entry criteria (by 
category), and a more detailed listing of participants who had a study intervention administration 
deviations will be provided. A listing of participants with minor protocol deviations related to 
COVID-19 will also be provided.
4.6.
Prior and Concomitant Medications
Summaries of UC medication history (participants who took medications for UC and their length 
of exposure prior to the study), UC-related non-biologic medication history (ie, history of response 
to or intolerance of corticosteroids and immunomodulators [ie, 6-MP/AZA]), UC-related biologic 
medication history (ie, vedolizumab), and prior use of JAK inhibitors (ie, tofacitinib) will be 
provided by treatment group based on the FAS (Section 2.2.2 ). 
UC-specific baseline medications (ie, 5-ASA and corticosteroids) will be summarized by treatment 
group based on the FAS. Baseline medications are defined as any therapy used at baseline prior to
the first dose of study intervention.
UC-specific concomitant medications that are permitted and taken during the trial (i.e., oral 5-ASA
and oral corticosteroids) will be summarized by treatment group based on the FAS. Concomitant 
medications are defined as any therapy used on or after the first dose of study intervention, 
including those that started before and are continued after the first dose of study intervention.
A listing of concomitant medications for COVID-19 infections will be provided.
5.
EFFICACY
5.1.
General Method of Analysis
Descriptive statistics (i.e., mean, median, SD, IQ range, minimum, and maximum) will be used to 
summarize continuous variables. Counts and percentages will be used to summarize categorical 
variables. Graphical data displays (e.g., line plots) may also be used to summarize the data.
Analyses suitable for categorical data (e.g., chi-square tests, Cochran-Mantel-Haenszel [CMH]
chi-square tests, or logistic regression, as appropriate) will be used to compare the proportions of 
participants achieving selected endpoints (e.g., clinical response) in treatment groups. In cases of 
rare events, Fisher’s exact test will be used for treatment comparisons. Continuous response 
parameters will be compared using a Mixed-Effect Model Repeated Measure (MMRM) model
unless otherwise specified. If the normality assumption is in question, an appropriate 
transformation may be implemented before fitting the MMRM model.  In cases of small sample 
size, t-test will be used for treatment comparisons.


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5.2.
Analysis Specifications
5.2.1.
Level of Significance
A 2-sided significance level of 0.2 (equivalent to the 1-sided 0.1 level specified in the protocol) 
will be used for all hypothesis testing and no adjustments for multiple comparisons will be made.
Nominal p-values will be presented.
5.3.
Primary Efficacy Endpoint
The primary efficacy endpoint is clinical response at Week 12.
5.3.1.
Definition
Clinical response: A decrease from baseline in the Mayo score (Section 5.3.1.1) ≥30% and ≥3 
points, with either a decrease in the rectal bleeding subscore (RBS) ≥1 or a RBS of 0 or 1. 
5.3.1.1.
Mayo Score, Partial Mayo Score, and Modified Mayo Score
The Mayo score was developed from the criteria of Truelove and Witts14 for mild, moderate, and 
severe UC and from the criteria of Baron et al2for grading endoscopic appearance. The Mayo score 
consists of the following 4 subscores:

Stool frequency

Rectal bleeding

Findings of endoscopy

Physician’s global assessment (PGA)
Each subscore is rated on a scale from 0 to 3, indicating normal to severe activity, as defined in
Attachment 1.
The Mayo score is calculated as the sum of the 4 subscores (stool frequency, rectal bleeding, PGA, 
and endoscopy findings) and ranges from 0 to 12 points. A score of 3 to 5 points indicates mildly 
active disease, a score of 6 to 10 points indicates moderately active disease, and a score of 11 to 
12 points indicates severely active disease. 
The partial Mayo score, which is the Mayo score without taking into account the findings of 
endoscopy, is calculated as the sum of stool frequency, rectal bleeding, and PGA subscores, and 
may take on values from 0 to 9.
The modified Mayo score, which is the Mayo score without the PGA subscore, is calculated as 
the sum of the stool frequency, rectal bleeding, and endoscopy subscores, and may take on values 
from 0 to 9.
Due to the requirement for endoscopy findings for the evaluation of the Mayo score, it is not 
feasible to evaluate the Mayo score at each scheduled visit in the study. Therefore, the Mayo score 
will be evaluated at Weeks 0, 12 and 38, and the partial Mayo score will be evaluated at the other 


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study visits. The modified Mayo score can be derived from the Mayo score and is not a separate 
evaluation.
Mayo Rectal Bleeding and Stool Frequency Subscores
The eCRFs capture seven days of rectal bleeding data and the number of stools per day prior to 
each visit at which the Mayo score or partial Mayo score is collected. Data from 3 of these 7 days 
are used to calculate the Mayo rectal bleeding and stool frequency subscores; sites are instructed 
to check the boxes next to the 3 days which are used (see below for information on what days the 
sites are instructed to use). 
The Mayo rectal bleeding subscore is calculated as the average rectal bleeding number for the 
three days based on the criteria in Attachment 1.
The Mayo stool frequency subscore is calculated as follows: The absolute stool number is the 
average of the daily stool number over the three days. At the screening visit, each person indicates 
the number of stools he/she passed in a 24-hour period when in remission or before his/her UC 
diagnosis. The stool frequency subscore will be calculated based on the criteria in Attachment 1
by subtracting the number of stools when in remission or prior to UC from the absolute stool 
number.
Instructions on which 3 days to use in the calculation of the Mayo rectal bleeding and stool 
frequency subscores: Sites are directed to use the most recent 3 consecutive days within the 7 
days prior to the visit and are directed to exclude the following:

The day medications were taken for constipation, diarrhea or irregularity

The day of a procedure or preparation for procedure (e.g. enema, other laxatives, or clear 
liquid diet) that would affect stool frequency and/or blood content of the stool

The 48 hours after the use of antimotility agents (e.g. diphenoxylate hydrochloride with 
atropine sulfate or loperamide)

The 48 hours immediately following a colonoscopy
If 3 consecutive days are not available, the sites are instructed to choose 2 consecutive days and 
the closest nonconsecutive day. If 2 consecutive days are not available, then 3 nonconsecutive days 
closest to the visit should be chosen. If 3 days (within the 7 days prior to the indicated visit) that 
meet the criteria defined above are not available, then the absolute stool number, stool frequency 
subscore, and rectal bleeding subscore cannot be calculated and will be missing in the eCRF.
Mayo Endoscopy Subscore
The endoscopic findings will be based on the criteria of the Mayo endoscopy subscore described 
in Attachment 1. The endoscopic findings will be assessed by the investigator (ie, local 
endoscopist) during the endoscopy procedure and by the central reader reviewing a video of the 
endoscopy. The endoscopy may be either a colonoscopy or sigmoidoscopy. A full colonoscopy 
will replace a sigmoidoscopy if screening for polyps or dysplasia is required. The central reader 


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will also perform a friability assessment (yes, no) for each endoscopy, except for those with an 
assessed endoscopy subscore of 0, which requires that no friability is present.
Participant eligibility at baseline will be based on the final reported endoscopic subscore as 
determined by the following process:

If the local endoscopist and the central reader agree on the endoscopic subscore, the agreed 
score will be the final reported endoscopic subscore.  

If there is a discrepancy between the local endoscopist and the central reader scores, the video 
endoscopy will be submitted to a second central reader (designated for adjudication) who is 
blinded to the scores of the local and the first central reader. From the scores of the 3 readers 
(i.e., local reader, central reader, second central reader designated for adjudication), the score 
with which 2 readers agree will be reported as the final reported endoscopic subscore. If the 
scores of the 3 readers (ie, local reader, central reader, second central reader designated for 
adjudication) are all different, then the median score of the 3 scores will be the final reported 
endoscopic subscore.
Further details are provided in the imaging charter.
Unless otherwise specified, the analysis of endpoints that include the Mayo endoscopy 
subscore will be based on the final reported endoscopic subscore. If the final reported 
endoscopic score is not available, the corresponding central endoscopy score (central read 1) will 
be used, if available. If the central endoscopy score (central read 1) is also missing, then the local 
endoscopy score will be used, if available. If the local endoscopy score is not available, then the 
endoscopy subscore for the analysis will be left missing.
Mayo Physician’s Global Assessment Subscore
The physician’s global assessment acknowledges the 3 other Mayo subscores, the patient’s recall 
of abdominal discomfort and general sense of well-being, and other observations, such as physical 
findings and the patient’s performance status.
5.3.2.
Primary Estimand (Estimand 1)
The primary estimand (Estimand 1), i.e. a precise definition of the primary targeted treatment 
effect, is defined by the following 5 attributes:
Treatment by Week 12:
Experimental:
o
Combination Therapy: Guselkumab 200 mg IV q4w (Weeks 0, 4, 8) AND
Golimumab 200 mg SC (Week 0) and 100 mg SC q4w (Weeks 2, 6, 10) 
Controls:
o
Golimumab Monotherapy: Golimumab 200 mg SC (Week 0) and 100 mg SC q4w 
(Weeks 2, 6, 10)


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o
Guselkumab Monotherapy: Guselkumab 200 mg IV q4w (Weeks 0, 4, 8)
Population:
Participants 18 -65 years old with moderately to severely active UC, as defined by a Mayo score 
of 6 to 12, inclusive, at baseline, including an endoscopy subscore ≥2 as obtained during the 
central review of the video endoscopy.
Variable (Endpoint):
Clinical response at Week 12 (Section 5.3.1). Participants who have intercurrent events in 
categories 1-3 (defined below) prior to Week 12 visit will be considered not to have achieved 
clinical response at Week 12.
Intercurrent Events and Corresponding Strategies:
The following are the intercurrent events (ICEs) for this study:
1. An ostomy or colectomy (partial or total)
2. A protocol-prohibited change in concomitant UC medication(s) (described in Attachment 
2)
3. Discontinuation of study intervention due to lack of efficacy or due to an AE of worsening 
of UC
4. Discontinuation of study intervention due to COVID-19 related reasons (excluding 
COVID-19 infection)
5. Discontinuation of study intervention for reasons other than lack of efficacy or an AE of 
worsening of UC or COVID-19-related reasons (this would include COVID-19 infections)
ICEs in categories 1-3 will be handled with the composite strategy. ICE category 4 will be 
handled by the hypothetical strategy (as if participants would have not experienced this 
intercurrent event), and ICE category 5 will be handled by the treatment policy strategy. This 
estimand acknowledges that having an ICE in categories 1-3 is an unfavorable outcome. 
Participants experiencing ICEs 1-3 will be considered not to have achieved clinical response at 
Week 12. For participants experiencing ICE 4, data at all visits after an ICE will be set to missing. 
For participants experiencing ICE 5, their observed clinical response status at Week 12 (if 
available) will be used. For participants experiencing multiple ICEs, ICEs in categories 1-3 will
override ICEs 4 and 5. 
Population-level summary:
The difference in proportion of participants achieving clinical response at Week 12 between 
combination therapy and each monotherapy.


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5.3.3.
Analysis Methods for the Primary Estimand (Estimand 1)
5.3.3.1.
Main Estimator (Analysis) for the Primary Estimand
The primary endpoint, defined in Section 5.3.1, will be analyzed based on the Primary Estimand 
(Section 5.3.2). After accounting for the ICEs for the primary estimand (Estimand 1), participants 
who are missing any or all of the Mayo subscores that comprise the primary endpoint at Week 12 
will be considered not to be in clinical response at Week 12 (i.e. nonresponder imputation).
In the primary analysis, data from all participants in the FAS (Section 2.2.2) will be analyzed 
according to the randomized study intervention regardless of the study intervention they actually 
received. The treatment difference between combination therapy versus each monotherapy will be 
tested using a 2-sided CMH chi-square test stratified by corticosteroid use at baseline (yes, no) at 
the 0.2 significance level. The magnitude of the treatment difference will be estimated by the 
difference in the proportion of participants achieving clinical response at Week 12 between the 
combination therapy group and each monotherapy group with a 2-sided 80% confidence interval 
(CI) calculated based on Wald statistic.
The study will be considered positive if the combination therapy group is significantly different 
from both monotherapy groups at the 2-sided significance level of 0.2 for the primary endpoint.
5.3.3.2.
Subgroup Analyses
Subgroup analyses will be performed (if the number of participants within each subgroup level 
permits) based on demographic and baseline disease characteristics, baseline concomitant UC 
medication use, and history of UC-related medications specified in Section 2.3. Note that, for 
subgroup analyses, the analysis sets are the individual subgroups of the FAS.  A forest plot will be 
produced for all subgroups. Odds ratio of the combination therapy group versus each monotherapy 
group and the associated 80% CI from a logistic regression model will be provided for each of 
subgroups. The logistic regression model will include treatment group and corticosteroid use at 
baseline (yes, no) as the factors.  For subgroup analyses of corticosteroid use at baseline (yes, no), 
treatment group will be the only the factor in the model. The primary estimand (Estimand 1) will 
be used for these subgroup analyses.
5.3.3.3.
Sensitivity Analyses
For the primary estimand (Estimand 1), after accounting for the ICEs, the proportion of 
participants with missing clinical response status at Week 12 is expected to be quite small. Despite 
the expectation of a very small percentage of missing data at Week 12, the following sensitivity 
analysis will be performed using a tipping point analysis with exhaustive scenarios. 
The following method will be utilized to vary the imputation of clinical response status at Week 
12 for missing data after the intercurrent event rules have been applied. For participants with 
missing data at Week 12, the clinical response status will be imputed in an increasing manner by 
participant level for each study intervention. Specifically, for each participant, a responder/non-
responder status will be imputed starting with the scenario where all participants are non-
responders up to the scenario where all participants are responders. This would include all possible 


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scenarios of responder status for all missing data. For each scenario, an analysis same as described 
above in Section 5.3.3.1 for the primary analysis for the primary estimand will be performed.
5.3.4.
Supplementary Estimands
Two supplementary estimands (Estimands 2 and 3) are considered to support the primary estimand
for the primary endpoint (Estimand 1).  
5.3.4.1.
Estimand 2
In this supplementary estimand for the primary endpoint (Estimand 2), all ICEs (Section 5.3.2) 
will be addressed by the composite strategy.  
The attributes of this supplementary estimand are the same as those for the primary estimand 
(Estimand 1) with the exception of the Variable (Endpoint) and strategy for ICEs, which is 
described as follows:  
Variable (Endpoint): Clinical response at Week 12.  Participants who have any ICE in categories 
1-5 (listed in Section 5.3.2) prior to the Week 12 visit will be considered not to have achieved 
clinical response at Week 12, regardless of the observed data.
5.3.4.2.
Estimand 3
In this supplementary estimand for the primary endpoint (Estimand 3), all ICEs (Section 5.3.2) 
will be addressed by the hypothetical strategy.  
The attributes of this supplementary estimand are the same as those for the primary estimand
(Estimand 1) with the exception of the Variable (Endpoint) and strategy for ICEs, which is 
described as follows:  
Variable (Endpoint): Clinical response at Week 12. Participants who have any ICE in categories 
1-5 (listed in Section 5.3.2) prior to the Week 12 visit will be considered to have missing clinical 
response status at Week 12, regardless of the observed data.
This supplementary estimand uses a hypothetical strategy that considers the clinical response
status at Week 12 after the ICE to be the same as for other participants in the same study 
intervention who had not yet experienced the ICE. The hypothetical strategy attempts to estimate 
the treatment effect if the randomized treatment is taken as specified in the protocol. As such, any 
clinical response status observed after an ICE is excluded in order to ensure results reflect 
participant experience on randomized treatment only. Therefore, utilizing the hypothetical 
estimand allows for an analysis of participants under the scenario when they are compliant with 
the investigative therapy, and thus, is justified clinically since it attempts to eliminate the 
potentially confounding effects due to ICEs.


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5.3.5.
Estimators (Analyses) for the Supplementary Estimands
5.3.5.1.
Estimator (Analysis) for Estimand 2
For the supplementary analysis of the primary endpoint based on Estimand 2, after accounting for 
the ICEs for this supplementary estimand, participants who have a missing clinical response status 
at Week 12 will be considered not to be in clinical response at Week 12 (i.e. nonresponder 
imputation).
In this supplementary analysis, data from all participants in the FAS (Section 2.2.2) will be 
analyzed according to the randomized study intervention regardless of the study intervention they 
actually received. The analysis method is same as that for the main estimator (analysis) for the 
primary estimand (Estimand 1).  Refer to Section 5.3.3.1 for details.
5.3.5.2.
Estimator (Analysis) for Estimand 3
For the supplementary analysis of the primary endpoint based on Estimand 3, after accounting for 
the ICEs for this supplementary estimand, the missing status of clinical response at Week 12 will 
be imputed using multiple imputation (MI) as described in Table 3, under the assumption that the 
data are missing at random (MAR) for all participants in the FAS.  The MI will be performed on 
each Mayo subscore with missing data and then the clinical response status at Week 12 will be 
derived from such imputed Mayo subscores.
Table 3: Multiple Imputation Methods
Endpoints
MI specification
Analysis method/Summary statistics
Clinical Response 
at Week 12
Multiple imputation with 
full conditional specification
(FCS) regression of 
subscores
MIMayoData1 (N=200, Seed=4362478)

Imputation variables: 4 Mayo subscores from Week 0 
– 12 (after accounting for ICEs)

Ancillary variables: Treatment group, corticosteroid 
use at baseline (yes, no)
In this supplementary analysis, data from all participants in the FAS will be analyzed according to 
the randomized study intervention regardless of the study intervention they actually received. For 
each of the N imputation datasets, the treatment difference between combination therapy versus 
each monotherapy will be tested using a 2-sided CMH chi-square test stratified by corticosteroid
use at baseline (yes, no). The analysis results from all the imputation datasets will be combined 
according to Rubin10, and the p-value for testing the treatment difference will be obtained.
5.4.
Major Secondary Endpoint
The major secondary endpoint is clinical remission at Week 12.
5.4.1.
Definition
Clinical remission: the Mayo score ≤ 2 with no individual subscore >1.


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5.4.2.
Main Estimand (Estimand 4)
The attributes and strategies for the ICEs that were used for the primary estimand (Estimand 1, 
defined in Section 5.3.2) will also be used for the main estimand (Estimand 4) for the major 
secondary endpoint.
5.4.3.
Analysis Methods for the Main Estimand (Estimand 4)
5.4.3.1.
Main Estimator (Analysis) for the Main Estimand
The major secondary endpoint will be analyzed based on the Main Estimand (Section 5.4.2). After 
accounting for the ICEs for the main estimand, participants who have a missing clinical remission 
status at Week 12 will be considered not to be in clinical remission at Week 12 (i.e. nonresponder 
imputation).
In this analysis for the major secondary endpoint, data from all participants in the FAS will be 
analyzed according to the randomized study intervention regardless of the study intervention they 
actually received. The treatment difference between combination therapy versus each 
monotherapy will be tested using a CMH chi-square test stratified by corticosteroid use at baseline 
(yes, no). The magnitude of the treatment difference will be estimated by the difference in the 
proportion of participants achieving clinical remission at Week 12 between combination therapy 
and each monotherapy with a 2-sided 80% CI calculated based on Wald statistic.
The testing of the major secondary endpoints will occur at a 2-sided significance level of 0.2 
regardless of the significance of the primary endpoint. No adjustment for multiple comparisons 
will be made and nominal p-values will be presented.
5.4.3.2.
Subgroup Analyses
Subgroup analyses will be performed (if the number of participants within each subgroup level 
permits) based on demographic and baseline disease characteristics, baseline concomitant UC 
medication use, and history of UC-related medications specified in Section 2.3. Note that, for 
subgroup analyses, the analysis sets are the individual subgroups of the FAS.  A forest plot will be 
produced for all subgroups. Odds ratio of the combination therapy group versus each monotherapy 
group and the associated 80% CI from a logistic regression model will be provided for each of 
subgroups. The logistic regression model will include treatment group and corticosteroid use at 
baseline (yes, no) as the factors.  For subgroup analyses of corticosteroid use at baseline (yes, no), 
treatment group will be the only the factor in the model. The main estimand (Estimand 4) will be 
used for these subgroup analyses.
5.4.4.
Supplementary Estimands
Two supplementary estimands (Estimands 5 and 6) are considered to support the main estimand 
for the major secondary endpoint (Estimand 4).  
5.4.4.1.
Estimand 5
In this supplementary estimand for the major secondary endpoint (Estimand 5), all ICEs 
(Section 5.3.2) will be addressed by the composite strategy.  


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The attributes and strategies for the ICEs that were used for Estimand 2 for the primary endpoint 
(Section 5.3.4.1) will also be used for this supplementary estimand for the major secondary 
endpoint (Estimand 5).
5.4.4.2.
Estimand 6
In this supplementary estimand for the major secondary endpoint (Estimand 6), all ICEs 
(Section 5.3.2) will be addressed by the hypothetical strategy.  
The attributes and strategies for the ICEs that were used for Estimand 3 for the primary endpoint 
(Section 5.3.4.2) will also be used for this supplementary estimand for the major secondary 
endpoint (Estimand 6).
5.4.5.
Estimators (Analyses) for the Supplementary Estimands
5.4.5.1.
Estimator (Analysis) for Estimand 5
For the supplementary analysis of the major secondary endpoint based on Estimand 5, after 
accounting for the ICEs for this supplementary estimand, participants who have a missing clinical 
remission status at Week 12 will be considered not to be in clinical remission at Week 12 (i.e. 
nonresponder imputation).
In this supplementary analysis for the major secondary endpoint, data from all participants in the 
FAS (Section 2.2.2) will be analyzed according to the randomized study intervention regardless of 
the study intervention they actually received. The analysis method is same as that for the main 
estimator (analysis) for the primary estimand (Estimand 1).  Refer to Section 5.3.3.1 for details. 
5.4.5.2.
Estimator (Analysis) for Estimand 6
For the supplementary analysis of the major secondary endpoint based on Estimand 6, after 
accounting for the ICEs for this supplementary estimand, the missing status of clinical remission
at Week 12 will be imputed using MI. For participants with missing status of clinical remission at 
Week 12, their clinical remission status at Week 12 will be derived from the imputed Mayo
subscores in MIMayoData1 that has been created in Section 5.3.5.2.
The analysis method based on this supplementary estimand (Estimand 6) for the major secondary 
endpoint is same as the analysis method based on the supplementary estimand (Estimand 3) for 
the primary endpoint.  Refer to Section 5.3.5.2 for details.
5.5.
Other Efficacy Endpoints
In addition to the primary and major secondary endpoints, other efficacy endpoints related to 
disease status, HRQoL outcomes (including fatigue), and inflammatory biomarkers will also be 
analyzed. This section outlines the definitions (Section 5.5.1 ) and analyses (Section 5.5.2) of the 
other efficacy endpoints.
Clinical Endpoints

Clinical response at Week 38


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
Clinical response at Week 38 by clinical response status at Week 12

Clinical remission at Week 38

Clinical remission at Week 38 by clinical remission status at Week 12

Clinical remission at Week 38 by clinical response status at Week 12

Change from baseline in Mayo score at Weeks 12 and 38. 

Change from baseline in partial Mayo score by visit through Week 38.

Change from baseline in modified Mayo score at Weeks 12 and 38.

Change from baseline in Mayo subscores by visit through Week 38.

Modified Mayo response at Weeks 12 and 38

Modified Mayo response at Week 38 by modified Mayo response status at Week 12

Symptomatic remission by visit through Week 38

Endoscopic healing at Weeks 12 and 38

Endoscopic healing at Week 38 by endoscopic healing status at Week 12

Endoscopic normalization at Weeks 12 and 38. 

Endoscopic normalization at Weeks 38 by endoscopic normalization status at Week 12

Clinical response, clinical remission, and endoscopic healing at Weeks 12 and 38 by negative 
response signature status at baseline. 

Clinical remission by alternative definitions:

Clinical remission (UNIFI definition) at Weeks 12 and 38

Clinical remission (UNIFI definition) at Week 38 by clinical remission (UNIFI 
definition) status at Week 12

Clinical remission (Health Authority definition 1) at Weeks 12 and 38

Clinical remission (Health Authority definition 1) at Week 38 by clinical remission 
(Health Authority definition 1) status at Week 12

Clinical remission (Health Authority definition 2) by visit at Weeks 12 and 38

Clinical remission (Health Authority definition 2) at Week 38 by clinical remission 
(Health Authority definition 2) status at Week 12

Histologic healing at Weeks 12 and 38

Mucosal healing at Weeks 12 and 38

Histologic remission at Weeks 12 and 38

Histologic-endoscopic mucosal healing at Weeks 12 and 38

Deep histologic-endoscopic mucosal healing at Weeks 12 and 38

Geboes total score, high activity subscore, and low activity subscore at Weeks 0, 12, and 38

Roberts Histologic Index (RHI)-based histologic remission at Weeks 12 and 38


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
Nancy Histologic Index (NHI)-based histologic remission at Weeks 12 and 38

Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score at Weeks 0, 12, and 38 by the 
level of Mayo endoscopy score at the corresponding visit

Change from baseline in UCEIS score at Weeks 12 and 38

UCEIS score ≤4 at Weeks 12 and 38

Clinical remission and not receiving concomitant corticosteroids at Week 12

Clinical response and not receiving concomitant corticosteroids at Week 12

Clinical remission and not receiving concomitant corticosteroids at Week 38

Clinical response and not receiving concomitant corticosteroids at Week 38

Clinical remission and not receiving concomitant corticosteroids at Week 38 by status of 
clinical remission and not receiving concomitant corticosteroids at Week 12

Clinical response and not receiving concomitant corticosteroids at Week 38 by status of 
clinical response and not receiving concomitant corticosteroids at Week 12

ICEs (listed in Section 5.3.2) prior to Week 12 and prior to Week 38

Mayo score missing at Week 12 by reason causing missing (including COVID-19 related) and 
at Week 38 by reason causing missing (including COVID-19 related)

Endoscopy subscore missing at Week 12 by reason causing missing (including COVID-19 
related) and at Week 38 by reason causing missing (including COVID-19 related)
Inflammatory Biomarkers (CRP and Fecal Calprotectin)

Change from baseline in CRP by visit through Week 38

Change from baseline in CRP by visit through Week 38 among participants with abnormal 
CRP concentration at baseline

Change from baseline in fecal calprotectin concentration by visit through Week 38

Change from baseline in fecal calprotectin concentration by visit through Week 38 among 
participants with abnormal fecal calprotectin concentration at baseline

Normalization of CRP concentration by visit through Week 38 among participants with 
abnormal CRP concentration at baseline

Normalization of fecal calprotectin concentration by visit through Week 38 among 
participants with abnormal fecal calprotectin concentration at baseline
HRQoL Endpoints

Change from baseline in the total score of the Inflammatory Bowel Disease Questionnaire 
(IBDQ) by visit through Week 38

A >20-point improvement from baseline in the IBDQ score by visit through Week 38

Change from baseline in the 7 domain scores (norm-based) and the abdominal pain intensity 
score of Patient-Reported Outcomes Measurement Information System (PROMIS)-29 by visit 
through Week 38


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
A ≥ 5-point improvement from baseline in PROMIS-29 domain scores (norm-based) and pain 
intensity score by visit through Week 38

Change from baseline in the PROMIS Fatigue Short Form 7a total score by visit through Week
38

Fatigue response (≥ 5-point improvement) based on the PROMIS Fatigue Short Form 7a by 
visit through Week 38
5.5.1.
Definitions
5.5.1.1.
Clinical Endpoints
5.5.1.1.1.
Modified Mayo Response 
Modified Mayo response is defined as a decrease from baseline in modified Mayo score ≥ 30% 
and ≥ 2 points, with either a decrease in the RBS ≥ 1 or a RBS of 0 or 1.
5.5.1.1.2.
Symptomatic remission
Symptomatic remission is defined as a stool frequency subscore of 0 or 1, where the stool 
frequency subscore has not increased from baseline, and a rectal bleeding subscore of 0.
5.5.1.1.3.
Endoscopic healing
Endoscopic healing (i.e., improvement in the endoscopic appearance of the mucosa) is defined as 
an endoscopy subscore of 0 or 1 with no friability present on the endoscopy.
5.5.1.1.4.
Endoscopic normalization (i.e. normalization of endoscopic 
appearance of mucosa in protocol)
Endoscopic normalization is defined as an endoscopic subscore of 0 with no friability present on 
the endoscopy.
5.5.1.1.5.
Clinical remission by alternative definitions 
Clinical Remission (UNIFI definition) is defined as an absolute stool number ≤3, a rectal 
bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the 
endoscopy. 
Clinical Remission (Health Authority definition 1) is defined as a stool frequency subscore of 
0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability
present on the endoscopy, where the stool frequency subscore has not increased from baseline.
Clinical Remission (Health Authority definition 2) is defined as a stool frequency subscore of 
0, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present
on the endoscopy.
5.5.1.1.6.
Histologic healing
Histologic healing is defined as 0 - < 5% neutrophils in epithelium and no crypt destruction, and 
no erosion, ulceration, or granulation tissue according to the Geboes grading system3
(Attachment 3).


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5.5.1.1.7.
Mucosal healing
Mucosal healing is a combination of histologic healing (Section 5.5.1.1.6) and endoscopic healing 
(Section 5.5.1.1.3).
5.5.1.1.8.
Histologic remission
Histologic remission is defined as absence of neutrophils from the mucosa (both lamina propria 
and epithelium), no crypt destruction, and no erosions, ulcerations or granulation tissue according 
to the Geboes grading system3 (Attachment 3).
5.5.1.1.9.
Histologic-endoscopic mucosal healing 
Histologic-endoscopic 
mucosal 
healing 
is 
a 
combination
of 
histologic 
remission
(Section 5.5.1.1.8) and endoscopic healing (Section 5.5.1.1.3).
5.5.1.1.10.
Deep histologic-endoscopic mucosal healing
Deep histologic-endoscopic mucosal healing is a combination of histologic remission
(Section 5.5.1.1.8) and endoscopic normalization (Section 5.5.1.1.4).
5.5.1.1.11.
Geboes Scores
The Geboes total score, a continuous histology score, is calculated as the sum of all Geboes 
Grades (Attachment 3) and may take on values from 0 to 22. 
The Geboes high activity subscore, a continuous histology score, is calculated as the sum of 
Geboes Grades 3, 4, and 5 and may take on values from 0 to 10. 
The Geboes low activity subscore, a continuous histology score, is calculated as the sum of 
Geboes Grades 0, 1, 2A and 2B and may take on values from 0 to 12. 
5.5.1.1.12.
Roberts Histologic Index (RHI)-based histologic remission
RHI-based histologic remission is defined as RHI ≤3 with sub-scores of 0 for lamina propria 
neutrophils and neutrophils in the epithelium according to the Robarts Histologic Index7
(Attachment 4).
5.5.1.1.13.
Nancy Histologic Index (NHI)-based histologic remission
NHI-based histologic remission is defined as NHI ≤1 according to the Nancy Histologic Index6
(Attachment 5).
5.5.1.1.14.
Ulcerative Colitis Endoscopic Index of Severity (UCEIS)
The UCEIS (Attachment 6) is an index that provides an overall assessment of endoscopic severity 
of UC, based on mucosal vascular pattern, bleeding, and ulceration12. The score ranges from 3 to 
11, with a higher score indicating more severe disease by endoscopy. The UCEIS score will be 
assessed only by the central video readers for all endoscopies.


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5.5.1.2.
Inflammatory Biomarkers
5.5.1.2.1.
C-Reactive Protein
C-reactive protein (CRP) has been demonstrated to be useful as a marker of inflammation in 
participants with IBD. In subjects with UC, elevated CRP has been associated with more severe 
clinical activity, an elevated sedimentation rate, and active disease as detected by colonoscopy11,15.
5.5.1.2.2.
Fecal Calprotectin
Fecal calprotectin has been demonstrated to be a sensitive and specific marker in identifying 
intestinal inflammation and response to treatment in participants with IBD, especially in UC1.
Assays for fecal calprotectin concentration will be performed by the central laboratory using a 
validated method. Additional tests may also be performed on the stool samples for additional 
markers that are related to intestinal inflammation and treatment response such as the microbiome.
5.5.1.3.
HRQoL Endpoints
5.5.1.3.1.
Inflammatory Bowel Disease Questionnaire (IBDQ)
The IBDQ4 is a validated, 32-item, self-reported questionnaire for participants with IBD that will 
be used to evaluate the disease-specific HRQOL across 4 dimensional scores: bowel symptoms
(loose stools, abdominal pain), systemic function (fatigue, altered sleep pattern), social function
(work attendance, need to cancel social events), and emotional function (anger, depression, 
irritability). Scores range from 32 to 224, with higher scores indicating better outcomes.
The individual IBDQ dimensions will be calculated when no more than 1 item is missing in the 
dimension. If an item is missing, it will be estimated using the average value across the non-
missing items. If any of the 4 dimensions of the IBDQ cannot be calculated, then the total IBDQ 
score cannot be calculated and will be missing for that visit.
5.5.1.3.2.
PROMIS-29
The PROMIS-29 is a validated general health profile instrument that is not disease-specific. It is 
a collection of short forms containing 4 items for each of 7 domains (depression, anxiety, physical 
function, pain interference, fatigue, sleep disturbance, and ability to participate in social roles and 
activities). PROMIS-29 also includes an overall average pain intensity 0-10 numeric rating scale.
Norm-based scores have been calculated for each domain on the PROMIS measures, with a score 
of 50 representing the mean or average of the reference population. On symptom-oriented domains 
of PROMIS-29 (anxiety, depression, fatigue, pain interference, and sleep disturbance), higher 
scores represent worse symptomatology. On the function-oriented domains (physical functioning 
and social role), higher scores represent better functioning.
5.5.1.3.3.
PROMIS Fatigue 7-items Short Form
The PROMIS Fatigue Short Form 7a contains 7 items evaluating fatigue-related symptoms (ie, 
tiredness, exhaustion, mental tiredness, and lack of energy) and associated impacts on daily 
activities (ie, activity limitations related to work, self-care, and exercise). PROMIS Fatigue Short 


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Form 7a has a recall period of past 7 days. Compared to the fatigue scale of PROMIS-29, PROMIS 
Fatigue Short Form 7a provides additional information to evaluate severity of fatigue.
Fatigue response is defined as a ≥ 5-point improvement in the PROMIS Fatigue Short Form 7a.
5.5.2.
Estimands 
Unless otherwise specified, the attributes and strategies for the ICEs that were used for the primary 
estimand of the primary endpoint (Estimand 1, Section 5.3.2) will also be used for the estimand 
for each of the other endpoints (Section 5.5).
ICE categories 1-3 will be handled by the composite strategy. ICE category 4 will be handled by 
the hypothetical strategy (as if participants would have not experienced this intercurrent event), 
and ICE category 5 will be handled by the treatment policy strategy. To be more specific,

Participants with an ICE in category 1-3 prior to a visit will be considered, at that visit and all 
subsequent visits, as not having achieved the binary endpoints for binary endpoints and as 
having no change from baseline (i.e., the baseline value will be assigned) for continuous 
endpoints.  

Participants with an ICE 4 will have their observed data set to missing at all visits after the ICE 
4.  

Participants with an ICE 5 will have their observed data used after the ICE 4 used, if available.  

For participants experiencing multiple ICEs, ICEs in categories 1-3 will override ICEs 4 and 
5.
5.5.3.
Estimators (Analyses) for Estimands 
Unless otherwise specified, the other endpoints presented in Section 5.5 will be analyzed based on 
the FAS (Section 2.2.2) according to randomized study intervention regardless of the study 
intervention actually received. 
Descriptive statistics (i.e., mean, median, SD, IQ range, minimum, and maximum) will be used to 
summarize continuous endpoints and counts and percentages will be used to summarize binary 
endpoints by visit. 
Treatment comparisons between combination therapy versus each monotherapy will be performed 
by visit through Week 38. All statistical testing will be performed at the 2-sided significance level
of 0.2. No adjustment for multiple comparisons will be made for these other endpoints. Nominal 
p-values will be presented.
Binary Endpoints
After accounting for the ICEs, participants with missing status for a binary endpoint will be 
considered not to have achieved the associated binary endpoint (i.e. nonresponder imputation).


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Binary endpoints will be summarized with the number and frequency of participants who achieve 
the endpoint by treatment group. Treatment comparisons (combination therapy versus each 
monotherapy) will be performed using analyses suitable for categorical data (e.g., a CMH chi-
square test stratified by corticosteroid use at baseline, as appropriate) to compare the proportion of 
participants achieving the endpoints. In case of rare events, the Fisher’s exact test will be used for 
treatment comparisons.
Continuous Endpoints
For continuous endpoints that are assessed only at one post-baseline visit (e.g., change from 
baseline in Mayo score and change from baseline in modified Mayo score at the Week 12 DBL), 
the missing data after accounting for ICEs will be imputed by the MI methods as described in 
Table 3. The MI will be performed on each Mayo subscore with missing data and then the Mayo 
scores will be derived from such imputed subscores. These endpoints will be compared between
combination therapy versus each monotherapy using an analysis of covariance (ANCOVA) with 
treatment group, corticosteroid use at baseline (yes, no), and baseline score as the explanatory
factors.
For continuous endpoints that are assessed at more than one post-baseline visit, to account for the 
missing data after the ICEs have been accounted for, a MMRM will be used, under the assumption 
of MAR, to test the treatment difference between combination therapy versus each monotherapy. 
In MMRM, missing data will not be imputed, but rather missing data will be accounted for through 
correlation of repeated measures in the MMRM model. If the MMRM normality assumption is in 
question, an appropriate transformation may be implemented before fitting the MMRM model.
The explanatory variables of the MMRM model will include treatment group, corticosteroid use 
at baseline (yes, no), visit, respective baseline score, and an interaction term of visit with treatment 
group. An unstructured covariance matrix for repeated measures within a subject will be used. The 
F-test will use Kenward-Roger’s approximation for degree of freedom. In case of lack of 
convergence, empirical structured covariances will be used in the following order until 
convergence is reached: 1) Toeplitz; 2) first order Autoregressive Moving Average. The treatment 
difference between combination therapy and each monotherapy will be estimated by the difference 
in the least squares means (LSmeans). The 80% CI for the difference in LSmeans and p-values 
will be calculated based on the MMRM.
5.6.
Exploratory Endpoints
Exploratory endpoints include:

Change from baseline in average daily number of BSFS types 6 and 7 stools by visit through 
Week 12

Change from baseline in average daily number of BSFS types 5, 6, and 7 stools by visit 
through Week 12

A ≥2 reduction in average daily number of BSFS types 6 and 7 stools by visit through Week 
12


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
A ≥2 reduction in average daily number of BSFS types 5, 6, and 7 stools by visit through 
Week 12

Proportion of participants in each category of Patient’s Global Impression of Change (PGIC)
of Severity of UC by visit through Week 38

A ≥ 1-point improvement in PGIC by visit through Week 38

A ≥ 2-point improvement in PGIC by visit through Week 38
5.6.1.
Definitions
5.6.1.1.
Bristol Stool Form Scale
The BSFS is a medical aid to classify the form (or consistency) of human feces into 7 categories5. 
It has been used as a research tool to evaluate the effectiveness of treatments for various diseases 
of the bowel (e.g., irritable bowel syndrome). Participants will complete the BSFS as a daily diary 
entry from Week 0 through Week 12.
Average number of BSFS types 6 and 7 stools per day is defined as: the sum of number of BSFS 
types 6 and 7 stools in previous 7 days in a dairy card ÷ total days assessment performed.  Similarly, 
average number of BSFS types 5, 6 and 7 stools per day is defined as: the sum of number of BSFS 
types 5, 6 and 7 stools in previous 7 days in a dairy card ÷ total days assessment performed. 
Average number of BSFS stools per day at a scheduled visit will not be calculated if total days of 
assessment is less than 5 within the previous 7 days prior to a scheduled visit.
5.6.1.2.
Patient’s Global Impression of Change (PGIC) of Severity of 
Ulcerative Colitis
Participants’ perceived change (improvement or deterioration) in the severity of their UC will be 
assessed using the PGIC. Participants will rate how their UC has changed since the beginning of 
the study using a 7-point scale ranging from “a lot better now” to “a lot worse now” with a neutral 
center point (“neither better nor worse”). 
5.6.2.
Estimands 
Unless otherwise specified, the attributes and strategies for the ICEs that were used for the primary 
estimand of the primary endpoint (Estimand 1, Section 5.3.2) will also be used for the estimand 
for each exploratory efficacy endpoint (Section 5.6).
ICE categories 1-3 will be handled by the composite strategy. ICE category 4 will be handled by 
the hypothetical strategy (as if participants would have not experienced this intercurrent event), 
and ICE category 5 will be handled by the treatment policy strategy. To be specific,

Participants with an ICE in category 1-3 prior to a visit will be considered, at that visit and all 
subsequent visits, as not having achieved the binary endpoints for binary endpoints and as 
having no change from baseline (i.e., the baseline value will be assigned) for continuous 
and ordinal endpoints.  


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o
PGIC has no baseline data. When PGIC is analyzed as an ordinal endpoint, participants 
with an ICE in category 1-3 prior to a visit will be considered to have a UC severity 
change of “neither better, nor worse (no change)” from that visit onwards.

Participants with an ICE 4 will have their observed data set to missing at all visits after the ICE 
4.  

Participants with an ICE 5 will have their observed data used after the ICE 4 used, if available.  

For participants experiencing multiple ICEs, ICEs in categories 1-3 will override ICEs 4 and 
5.
5.6.3.
Estimators (Analyses) for Estimands
Unless otherwise specified, exploratory endpoints presented in Section 0 will be analyzed based 
on the FAS (Section 2.2.2) according to randomized study intervention regardless of the study 
intervention actually received. 
Descriptive statistics (i.e., mean, median, SD, IQ range, minimum, and maximum) will be used to 
summarize continuous endpoints and counts and percentages will be used to summarize binary 
endpoints by visit. 
Treatment comparisons between combination therapy versus each monotherapy will be performed 
by visit through Week 38. No adjustment for multiple comparisons will be made for these other 
endpoints. Nominal p-values will be presented.
Binary Endpoints
After accounting for the ICEs, participants with missing status for a binary endpoint will be 
considered not to have achieved the associated binary endpoint (i.e. nonresponder imputation).
Treatment comparisons (combination therapy versus each monotherapy) will be performed using 
analyses suitable for categorical data (e.g., a CMH chi-square test stratified by corticosteroid use 
at baseline, as appropriate) to compare the proportion of participants achieving the endpoints.  In 
case of rare events, the Fisher’s exact test will be used for treatment comparisons.
Continuous Endpoints
After accounting for the ICEs, to account for the missing data for continuous endpoints, a MMRM 
as described in Section 5.5.3 will be used, under the assumption of MAR, to test the treatment 
comparison between combination therapy versus each monotherapy. In MMRM, missing data will 
not be imputed, but rather missing data will be accounted for through correlation of repeated 
measures in the model. If the normality assumption is in question, an appropriate transformation 
may be implemented before fitting the MMRM model.
Ordinal Endpoints


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After accounting for the ICEs, treatment comparisons (combination therapy versus each 
monotherapy) will be performed using a CMH chi-square test (Row Mean Scores) stratified by 
corticosteroid use at baseline (yes, no).
6.
SAFETY
Safety data, including but not limited to, AEs, serious adverse events (SAEs), infections, serious 
infections, and changes in laboratory assessments will be summarized through Week 12 and 
through Week 38. Treatment-emergent AEs will be summarized by treatment group and Medical 
Dictionary for Regulatory Activities (MedDRA) system organ class and preferred terms.
Unless otherwise specified, safety analyses will be provided for participants in the Safety Analysis 
Set, which includes all randomized participants who received at least 1 dose of study intervention, 
according to the study intervention that they actually received, regardless of the study intervention
they were randomized to. No formal statistical comparisons are planned.
6.1.
Adverse Events
The verbatim terms used in the eCRF by investigators to identify AEs will be coded using the 
Medical Dictionary for Regulatory Activities (MedDRA). Treatment-emergent AEs (TEAEs) 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 AEs which are treatment-emergent will be included 
in the analysis. For each AE, the count and percentage of participants who experience at least 
1 occurrence of the given event will be summarized by intervention group. 
The following analyses of TEAEs will be used to assess the safety of participants:

Frequency and type of AEs

Frequency and type of SAEs

Frequency and type of reasonably related AEs as assessed by the investigator

Frequency and type of AEs leading to discontinuation of study intervention

Frequency and type of infections (including COVID-19 infections)

Frequency and type of serious infections 

Frequency and type of infections requiring oral or parenteral antimicrobial treatment

Frequency and type of AEs temporally associated with infusion

Frequency and type of injection-site reactions
Since safety should be assessed relative to exposure and follow-up, all AE summary tables will 
summarize the average weeks of follow-up and average exposure (number of administrations) for 
each treatment group.
In addition to the summary tables, a by-subject listing will be provided for deaths that occurred 
during the study and, respectively, for the following TEAEs:


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1.
SAEs
2.
AEs that led to permanent discontinuation of study intervention
3.
Serious infections including TB
4.
COVID-19 infections
5.
Anaphylactic reactions or serum sickness reactions
6.
Malignancies
6.2.
Clinical Laboratory Tests
Routine laboratory data for hematology and clinical chemistry will be collected at study visits from 
Week 0 through Week 38 according to SoA in the Protocol Section 1.3. The following laboratory 
assessments will be collected:  
1.
Hematology: hemoglobin, hematocrit, platelet count, total and differential white blood cell 
count (WBC) count. 
2.
Chemistry: total and direct bilirubin, alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), alkaline phosphatase, albumin, total protein, calcium, phosphate, 
sodium, potassium, chloride, blood urea nitrogen (BUN), and creatinine.
The following summaries of clinical laboratory tests will be provided for participants in the Safety 
Analysis Set (Section 2.2.3):
1. Summary of laboratory parameters and change from baseline in laboratory parameters over 
time
2. Plots of laboratory parameters and changes from baseline in selected clinical laboratory 
parameters over time
3. Summary of maximum NCI-CTCAE toxicity grade for postbaseline laboratory values
4. Shift tables for maximum NCI-CTCAE toxicity grade for selected laboratory parameters 
(hematology: hemoglobin, platelets, total WBC, absolute lymphocytes, and absolute 
neutrophils; chemistry: ALT, AST, and alkaline phosphatase) from baseline to corresponding 
postbaseline laboratory values
5. Summary of maximum postbaseline measurement for ALT, AST, alkaline phosphatase and 
total bilirubin relative to ULN  
6. Summary of maximum postbaseline elevated liver function tests (AST or ALT > 5xULN)
7. Patterns of change in ALT and AST will be assessed by summarizing the number of 
participants with only one ALT/AST > 1 ULN or ≥ 3 ULN or ≥ 5 ULN; with 2 or more 
consecutive ALT/AST measurements >1 ULN or ≥ 3 ULN or ≥ 5 ULN; with 2 or more non-
consecutive ALT/AST measurements
8. Summary of laboratory data missed or collected outside window due to COVID-19 Pandemic 
The baseline value for a participant is the value closest to but prior to the first dose of study agent.  
In addition, change from baseline is defined to be the assessment at the postbaseline visit minus 
the assessment at baseline.  There will be no imputation for missing laboratory values.


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Clinical laboratory test values are to be graded based on National Cancer Institute Common 
Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 (Attachment 7). The 
laboratory tests not included in Attachment 7 will not be presented in the corresponding tables or 
listings.
Listings of participants with any abnormal post-baseline laboratory values of NCI-CTCAE grade 
≥2 and maximum postbaseline elevated liver function tests (AST or ALT > 5xULN) will also be 
provided.
6.3.
Other Safety Parameters
6.3.1.
Suicidal Ideation and Behavior
The Columbia-Suicide Severity Rating Scale (C-SSRS) will be used as a screening tool to 
prospectively evaluate suicidal ideation and behavior in this study, as part of a comprehensive 
evaluation of safety. The C-SSRS is an investigator-administered questionnaire that defines 5
subtypes of suicidal ideation and 4 possible suicidal behaviors, as well as self-injurious behavior 
with no suicidal intent and completed suicide, and is a fully-structured subject self-report 
questionnaire, including standardized questions, follow-up prompts, error handling routines, and 
scoring conventions8,9. 
The baseline is defined as the most severe/maximum score at screening and Week 0. Suicidal 
ideation and behavior will be summarized by the most severe/maximum post baseline outcome. A
shift table from baseline to post-baseline will also be provided.  Participants with positive (i.e., 
score > 0) ideation and behavior will be presented in a data listing.
7.
PHARMACOKINETICS/PHARMACODYNAMICS
7.1.
Pharmacokinetics
PK analyses will be based on the PK Analysis Set (Section 2.2.4). Participants will be analyzed 
according to the study intervention that they actually received, regardless of the treatments they 
are randomized to. No imputation for missing data will be performed.
7.1.1.
Serum Guselkumab and Golimumab Concentrations
Blood samples for determining the serum guselkumab and golimumab concentrations will be 
drawn from all participants according to the Schedule of Activities in the Protocol. Unless 
otherwise mentioned, serum guselkumab and golimumab concentration summaries will be 
provided by study intervention at each visit through Week 12 and through Week 38. Descriptive 
statistics of the serum guselkumab and golimumab concentrations will be calculated by treatment 
group at each sampling time point when appropriate, including n, arithmetic mean, SD, coefficient 
of variation (%CV), median, interquartile range, range (minimum and maximum). PK data may 
be displayed graphically. The following analyses will be performed as appropriate:

Summary of serum guselkumab and golimumab concentrations at each visit by study 
intervention


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
Proportion of participants without detectable serum guselkumab and golimumab concentration 
(below the lower limit of quantification [< LLOQ]) at each visit by study intervention

Summary of serum guselkumab and golimumab concentrations at each visit by study 
intervention and baseline body weight (quartiles)

Plot of median serum guselkumab and golimumab concentrations over time by study 
intervention

Plot of median serum guselkumab and golimumab concentrations over time by study 
intervention and baseline body weight (≤median, > median)
7.1.1.1.
Data Handling Rules
Unless otherwise specified, the following data handling rules will apply to PK analyses:

A concentration not quantifiable (< LLOQ) will be treated as 0 in the summary statistics and 
shown as ‘< LLOQ’ in the data listings. 

The data from a participant who meets 1 of the following dosing deviation criteria will be 
excluded from the by-visit data analyses from that point onwards:
o
Discontinued guselkumab or golimumab administrations.
o
Skipped a guselkumab or golimumab administration.
o
Received an incomplete/ incorrect dose.
o
Received an incorrect study agent.
o
Received an additional guselkumab or golimumab dose.
In addition, if a participant has an administration outside of dosing windows (Table 4), the sample
data collected at that visit and after that visit prior to the next administration will be excluded from 
the by-visit data analyses. 
Table 4: Dosing Window
Visit
Window
Week 0 through Week 38
± 4 days from scheduled visit day
Final Safety and Efficacy Follow-up visits
± 7 days from scheduled visit day
7.1.2.
PK vs Efficacy 
The relationship between serum guselkumab and/or golimumab concentrations and efficacy 
endpoints may be explored, e.g.: 
1. The relationship between serum guselkumab and golimumab concentrations (quartiles) and 
clinical response, clinical remission, change in Mayo score, symptomatic remission, and 
endoscopic healing status at Week 12 and Week 38 may be explored by treatment group. 


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2. The relationship between serum guselkumab and golimumab concentrations (quartiles) and 
change from baseline in CRP concentration (mg/L) and Fecal Calprotectin concentration 
(mg/kg) at Week 12 and Week 38 may be explored by treatment group.
7.1.3.
Population PK Analysis
When appropriate, population PK analysis will be performed using serum guselkumab 
concentration-time data in PK analysis set with the nonlinear mixed-effects modeling (NONMEM) 
approach. Population PK analysis for golimumab may also be explored when appropriate. Details 
will be provided in a separate document.
7.2.
Immunogenicity 
Immunogenicity analyses will be based on the Immunogenicity Analysis Set (Section 2.2.5).
Participants will be analyzed according to the study intervention that they actually received. No 
imputation for missing data will be performed.
7.2.1.
Antibodies to Guselkumab and to Golimumab
Blood samples will be collected to examine the formation of antibodies to guselkumab and/or to 
golimumab at the specified visits as shown in the SoA (Protocol Section 1.3). Serum samples will 
also be collected at the final visit from participants who terminate study participation early. 
The antibodies to guselkumab and/or to golimumab status (positive at any time, negative) and peak
titers will be summarized by treatment group through Week 12 and through Week 38.
A listing of participants who are positive for antibodies to guselkumab and/or to golimumab will 
be provided. The sample antibodies status, the titer, and the neutralizing antibodies status will be 
listed by visit. This listing will also provide information regarding dose administered, injection-
site reactions and/or reactions temporally associated with infusion, guselkumab and/or golimumab 
serum concentration, partial Mayo score, and Mayo score for all visits. In addition, a list of 
antibodies to guselkumab and/or to golimumab status in participants who discontinued study agent 
early will be provided.
7.2.1.1.
Neutralized Antibodies to Guselkumab and to Golimumab
The incidence of neutralizing antibodies (NAbs) to guselkumab and/or to golimumab will be 
summarized through Week 12 and through Week 38 for participants who are positive for 
antibodies to guselkumab and/or to golimumab, respectively, and have samples evaluable for 
NAbs to guselkumab and/or to golimumab.
7.2.2.
Antibody vs PK/Efficacy/Safety
To explore the relationship between antibodies to guselkumab status and to golimumab status and
serum guselkumab and serum golimumab concentrations, and efficacy and safety, the following 
analyses may be performed as appropriate:  

Plots of median trough serum guselkumab concentrations over time by antibodies to 
guselkumab status 


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
Plots of median trough serum golimumab concentrations over time by antibodies to 
golimumab status 

Summary of clinical response, clinical remission, change in Mayo score, and endoscopic 
healing, all at Week 12 and Week 38, by antibodies to guselkumab and to golimumab status 
if sufficient participants have antibodies

Summary of injection-site reactions by antibodies to guselkumab and to golimumab status

Summary of AEs temporally associated with infusion by antibodies to guselkumab 
7.3.
Pharmacokinetic/Pharmacodynamic Relationships
If data permit, the relationships between serum guselkumab and serum golimumab concentration 
and efficacy may be analyzed graphically. If any visual trend is observed, a suitable population 
PK/PD model may be developed to describe the exposure-response relationship. Details will be 
given in a population PK/PD analysis plan and results of the population PK/PD analysis will be 
presented in a separate technical document.
8.
BIOMARKERS
The biomarker analyses will characterize the effects of guselkumab and/or golimumab to identify 
biomarkers relevant to treatment, and to determine if these biomarkers can predict response to 
guselkumab or golimumab. Results of serum, stool, whole blood, and mucosal biopsy analyses 
will be reported in separate technical reports.
Changes in serum protein analytes, fecal biomarkers, and biopsy and whole blood RNA obtained 
over time will be summarized by study intervention. Associations between baseline levels and 
changes from baseline in selected markers and response to treatment will be explored. Biomarker
analyses will be summarized in a separate technical report.
9.
MEDICAL RESOURCE UTILIZATION AND HEALTH ECONOMICS
Medical resource utilization evaluations, including but not limited to UC-related emergency 
department visits, hospitalizations, and surgeries are collected in this study. The following is a list 
of the endpoints to be analyzed:

Proportion of participants having any UC-related ER/hospitalizations/surgeries through Week 
12 and though Week 38 (final safety follow-up)

Proportion of participants with a UC-related hospitalization through Week 12 and though 
Week 38 (final safety follow-up)

Proportion of participants with a UC-related surgery through Week 12 and though Week 38
The health economics data will be analyzed based on the FAS (Section 2.2.2) according to
randomized study intervention regardless of the study intervention actually received.
The ICEs in categories 1 - 5 specified in Section 5.3.2 will not be used. No imputation will be 
performed for missing data and the missing values will remain as missing.


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Treatment comparisons will be performed. Nominal p-values will be reported. These endpoints 
will not be adjusted for multiplicity. 
Binary endpoints will be summarized with the number and frequency of participants by treatment 
group. Treatment comparisons (combination therapy versus each monotherapy) will be performed 
using a CMH chi-square test stratified by corticosteroid use at baseline (yes, no).  In case of rare 
events, the Fisher’s exact test will be used for treatment comparisons.


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Abraham BP and Kane S. Fecal Markers: Calprotectin and Lactoferrin.  Gastroenterol Clin N Am.  
2012;41:483-495.
2.
Baron JH, Connell AM, Lennard-Jones JE. Variation between observers in describing mucosal appearances in 
proctocolitis. Brit Med J. 1964;1:89-92. 
3.
Geboes K, Riddell R, Öst A, et al. A reproducible grading scale for histological assessment of inflammation in 
ulcerative colitis. Gut. 2000;47:404-409
4.
Irvine EJ, Feagan B, Rochon J, et al. Quality of life:  a valid and reliable measure of therapeutic efficacy in the 
treatment of inflammatory bowel disease. Canadian Crohn’s Relapse Prevention Trial Study Group. 
Gastroenterology. 1994;106(2):287-296. 
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Lewis SJ, Heaton KW. Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol. 
1997;32(9):920–924.
6.
Marchal‐Bressenot A, Salleron J, Boulagnon‐Rombi C, Bastien C, Cahn V, Cadiot G, et al. Development and 
validation of the Nancy histological index for UC. Gut 2017;66(1):43‐9.
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Mosli MH, Feagan BG, Zou G, Sandborn WJ, D'Haens G, Khanna R, et al. Development and validation of a 
histological index for UC. Gut 2017;66(1):50‐8.
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.
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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.
10. Rubin DB, Multiple Imputations for Nonresponse in Surveys. New York: John Wiley & Sons. 1987
11. Solem CA, Loftus EV, Tremaine WJ, et al. Correlation of C-reactive protein with clinical, endoscopic, 
histologic, and radiographic activity in inflammatory bowel disease. Inflamm Bowel Dis. 2005;11(8):707-712.
12. Travis SP, Schnell D, Krzeski P, et al. Developing an instrument to assess the endoscopic severity of ulcerative 
colitis: the Ulcerative Colitis Endoscopic Index of Severity (UCEIS). Gut. 2012;61:535-542. 
13. Telesco S, Greenbaum L, Zhang H, et al. Prediction of Non-Response to Anti-TNF Therapy in Ulcerative 
Colitis: Implications for Patient Stratification for IBD Trials and Novel Treatment Paradigms. Gastroenterology. 
2017;152(5):S984-S985
14. Truelove SC, Witts LJ. Cortisone in ulcerative colitis: final report on a therapeutic trial. Brit Med J. 
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Inflamm Bowel Dis. 2004;10(5):661-665.


CNTO1959 (guselkumab); CNTO148 (golimumab)  (VEGA)
Statistical Analysis Plan CNTO1959UCO2002
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Approved, Date: 24 February 2021
ATTACHMENTS
Attachment 1: MAYO SCORE .................................................................................................................... 47
Attachment 2: PROHIBITED CHANGES IN UC MEDICATIONS (ICE 2) .................................................. 48
Attachment 3: GRADING CRITERIA FOR THE HISTOLOGICAL EVALUATION OF DISEASE 
ACTIVITY IN ULCERATIVE COLITIS ...................................................................................... 50
Attachment 4: ROBARTS HISTOLOGIC INDEX ........................................................................................ 51
Attachment 5: NANCY HISTOLOGIC INDEX............................................................................................. 52
Attachment 6: UCEIS.................................................................................................................................. 53
Attachment 7: NCI-CTCAE GRADING CRITERIA FOR HEMATOLOGY AND CHEMISTRY 
LABORATORY TESTS [CTCAE VERSION 5.0] ...................................................................... 54


CNTO1959 (guselkumab); CNTO148 (golimumab)  (VEGA)
Statistical Analysis Plan CNTO1959UCO2002
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Attachment 1: MAYO SCORE
Mayo scoring system for assessment of ulcerative colitis activity
Stool frequencya
0 = Normal number of stools for this patient
1 = 1-2 stools more than normal
2 = 3-4 stools more than normal
3 = 5 or more stools more than normal
Rectal bleedingb
0 = No blood seen
1 = Streaks of blood with stool less than half the time
2 = Obvious blood with stool most of the time
3 = Blood alone passed
Findings of endoscopy
0 = Normal or inactive disease
1 = Mild disease (erythema, decreased vascular pattern, mild friability)
2 = Moderate disease (marked erythema, absent vascular pattern, friability, erosions)
3 = Severe disease (spontaneous bleeding, ulceration)
Physician’s global assessmentc
0 = Normal
1 = Mild disease
2 = Moderate disease
3 = Severe disease
a At the screening visit, each person indicates the number of stools he/she passed in a 24-hour period when in 
remission or before his/her UC diagnosis, thereby serving as his/her own control to establish the degree of 
abnormality of stool frequency.
b The daily bleeding score represents the most severe bleeding of the day.
c The physician’s global assessment acknowledges the 3 other criteria, the patient’s recall of abdominal discomfort 
and general sense of well-being, and other observations, such as physical findings and the patient’s performance 
status.


CNTO1959 (guselkumab); CNTO148 (golimumab)  (VEGA)
Statistical Analysis Plan CNTO1959UCO2002
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Attachment 2: PROHIBITED CHANGES IN UC MEDICATIONS (ICE 2)
The following are the protocol-prohibited changes in UC medication(s):
(i) Restricted or prohibited medications
-
Initiation of restricted or prohibited medications or therapies as defined in the protocol (see 
Protocol Section 6.5.2), except for antibiotics used to treat UC, TPN, and apheresis
(ii) Oral corticosteroids
Over the Combination Comparison Phase (Through Week 12)
-
Initiation of oral corticosteroids (including budesonide and beclomethasone dipropionate)
due to worsening of disease after the baseline visit for participants who were not 
receiving oral corticosteroids at baseline
-
Increase in the dose of oral corticosteroids (including budesonide and beclomethasone 
dipropionate) above the baseline dose, as specified below, due to worsening of disease 
i.
Oral corticosteroids > 5 mg/day (prednisone equivalent)
ii. Oral budesonide > 3 mg/day
iii. Oral beclomethasone dipropionate > 5 mg/day
-
Any switch among oral budesonide, oral beclomethasone dipropionate or other oral 
corticosteroids (excluding prednisone equivalent changes) due to worsening of disease
Over the Monotherapy Phase (After Week 12 Through Week 38)
-
Initiation of oral corticosteroids (including budesonide and beclomethasone dipropionate) 
due to worsening of disease that lasts for more than 7 days after the Week 26 visit (i.e., 
approximately 90 days prior to Week 38) for participants who were not receiving oral 
corticosteroids at baseline
-
Increase in the dose of oral corticosteroids (including budesonide and beclomethasone 
dipropionate) above the baseline dose, as specified below, due to worsening of disease for 
more than 7 days after the Week 26 visit (i.e., approximately 90 days prior to Week 38).
i.
Oral corticosteroids > 5 mg/day (prednisone equivalent)
ii. Oral budesonide > 3 mg/day
iii. Oral beclomethasone dipropionate > 5 mg/day
-
Initiation of oral corticosteroids (including budesonide and beclomethasone dipropionate) 
due to reasons other than worsening of disease that lasts for more than 28 days after the 
Week 26 visit (i.e., approximately 90 days prior to Week 38) for participants who were 
not receiving oral corticosteroids at baseline
-
Increase in the dose of oral corticosteroids (including budesonide and beclomethasone 
dipropionate) above the baseline dose, as specified below, due to reasons other than 
worsening of disease for more than 28 days after the Week 26 visit (i.e., approximately 90 
days prior to Week 38)
i.
Oral corticosteroids > 5 mg/day (prednisone equivalent)
ii. Oral budesonide > 3 mg/day


CNTO1959 (guselkumab); CNTO148 (golimumab)  (VEGA)
Statistical Analysis Plan CNTO1959UCO2002
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iii. Oral beclomethasone dipropionate > 5 mg/day
-
Any switch among oral budesonide, oral beclomethasone dipropionate or other oral 
corticosteroids (excluding prednisone equivalent changes) due to worsening of disease
(iii) 5-ASA compounds
-
Initiation of oral or rectal 5-ASA compounds due to worsening of disease
-
Increase above baseline in the dosage of oral 5-ASA compounds due to worsening of 
disease
-
Change from one oral 5-ASA compound to another 5-ASA compound due to worsening of 
disease


CNTO1959 (guselkumab); CNTO148 (golimumab)  (VEGA)
Statistical Analysis Plan CNTO1959UCO2002
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Approved, Date: 24 February 2021
Attachment 3: GRADING CRITERIA FOR THE HISTOLOGICAL EVALUATION OF DISEASE 
ACTIVITY IN ULCERATIVE COLITIS


CNTO1959 (guselkumab); CNTO148 (golimumab)  (VEGA)
Statistical Analysis Plan CNTO1959UCO2002
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Approved, Date: 24 February 2021
Attachment 4: ROBARTS HISTOLOGIC INDEX
Component 
Chronic inflammatory infiltrate
0=No increase
1=Mild but unequivocal increase
2=Moderate increase
3=Marked increase
Lamina propria neutrophils
0=None
1=Mild but unequivocal increase
2=Moderate increase
3=Marked increase
Neutrophils in epithelium
0=None
1=<5% crypts involved
2=<50% crypts involved
3=>50% crypts involved
Erosion or ulceration
0=No erosion, ulceration or granulation tissue
1=Recovering epithelium+adjacent inflammation
1=Probable erosion-focally stripped
2=Unequivocal erosion
3=Ulcer or granulation tissue
RHI = 1 x chronic inflammatory infiltrate level (4 levels)
        + 2 x lamina propria neutrophils (4 levels)
        + 3 x neutrophils in epithelium (4 levels)
        + 5 x erosion or ulceration (4 levels)


CNTO1959 (guselkumab); CNTO148 (golimumab)  (VEGA)
Statistical Analysis Plan CNTO1959UCO2002
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Approved, Date: 24 February 2021
Attachment 5: NANCY HISTOLOGIC INDEX


CNTO1959 (guselkumab); CNTO148 (golimumab)  (VEGA)
Statistical Analysis Plan CNTO1959UCO2002
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Approved, Date: 24 February 2021
Attachment 6: UCEIS
The UCEIS is an index that provides an overall assessment of endoscopic severity of UC based 
upon mucosal vascular pattern, bleeding, and ulceration. The score ranges from 3 to 11. The 
UCEIS score will be assessed only by the central readers for all endoscopies received.
UCEIS descriptors and definitions: 
Descriptor (score most 
severe lesions)
Likert scale anchor points 
Definition
Vascular pattern
Normal (1)
Normal vascular pattern with
arborisation of capillaries clearly defined, 
or with blurring or patchy loss of capillary 
margins
Patchy obliteration (2)
Patchy obliteration of vascular pattern
Obliterated (3)
Complete obliteration of vascular pattern
Bleeding
None (1)
No visible blood
Mucosal (2)
Some spots or streaks of coagulated blood 
on the surface of the mucosa ahead of the 
scope, which can be washed away
Luminal mild (3)
Some free liquid blood in the Lumen 
Luminal moderate or severe (4)
Frank blood in the lumen ahead of 
endoscope or visible oozing from mucosa 
after washing intraluminal blood, or visible 
oozing from a haemorrhagic mucosa
Erosions and ulcers
None (1) 
Normal mucosa, no visible erosions or 
ulcers
Erosions (2) 
Tiny (# 5mm) defects in the mucosa, of a 
white or yellow color with a flat edge
Superficial ulcer (3) 
Larger (> 5 mm) defects in the mucosa, 
which are discrete fibrincovered ulcers in 
comparison with erosions, but remain 
superficial
Deep ulcer (4)
Deeper excavated defects in the mucosa, 
with a slightly raised edge


CNTO1959 (guselkumab); CNTO148 (golimumab)  (VEGA)
Statistical Analysis Plan CNTO1959UCO2002
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Approved, Date: 24 February 2021
Attachment 7: NCI-CTCAE GRADING CRITERIA FOR HEMATOLOGY AND CHEMISTRY 
LABORATORY TESTS [CTCAE VERSION 5.0]
Hematology Tests
Criteria
Test
Direction
1
2
3
4
Hemoglobin (g/dL)
Increase
>0 - 2 x ULN
>2 - 4 x ULN
>4 x ULN
Hemoglobin (g/dL)
Decrease
<LLN - 10.0 
<10.0 - 8.0 
<8.0 
Lymphocytes (/mm3)
Increase
>4000 -
20,000
>20,000
Lymphocytes (/mm3)
Decrease
<LLN - 800
<800 - 500
<500 - 200
<200
Neutrophils (/mm3)
Decrease
<LLN - 1500 
<1500 - 1000 
<1000 - 500
<500
Platelets (/mm3)
Decrease
<LLN - 75,000
<75,000 -
50,000
<50,000 -
25,000
<25,000
Total WBC count (/mm3)
Increase
>100,000
Total WBC count (/mm3)
Decrease
<LLN - 3000
<3000 - 2000
<2000 - 1000
<1000 
Chemistry Tests
Criteria
Test
Direction
1
2
3
4
ALT
Increase
>ULN - 3.0 x 
ULN if 
baseline was 
normal; 1.5 -
3.0 x baseline if 
baseline was 
abnormal
>3.0 - 5.0 x 
ULN if 
baseline was 
normal; >3.0 -
5.0 x baseline 
if baseline was 
abnormal
>5.0 - 20.0 x 
ULN if 
baseline was 
normal; >5.0 -
20.0 x 
baseline if 
baseline was 
abnormal
>20.0 x ULN 
if baseline was 
normal; >20.0 
x baseline if 
baseline was 
abnormal
AST
Increase
>ULN - 3.0 x 
ULN if 
baseline was 
normal; 1.5 -
3.0 x baseline if 
baseline was 
abnormal
>3.0 - 5.0 x 
ULN if 
baseline was 
normal; >3.0 -
5.0 x baseline 
if baseline was 
abnormal
>5.0 - 20.0 x 
ULN if 
baseline was 
normal; >5.0 -
20.0 x 
baseline if 
baseline was 
abnormal
>20.0 x ULN 
if baseline was 
normal; >20.0 
x baseline if 
baseline was 
abnormal
Albumin (g/L)
Decrease
<LLN - 30
<30 - 20
<20
Alkaline Phosphatase
Increase
>ULN - 2.5 x 
ULN if 
baseline was 
normal; 2.0 -
2.5 x baseline if 
baseline was 
abnormal
>2.5 - 5.0 x 
ULN if 
baseline was 
normal; >2.5 -
5.0 x baseline 
if baseline was 
abnormal
>5.0 - 20.0 x 
ULN if 
baseline was 
normal; >5.0 -
20.0 x 
baseline if 
baseline was 
abnormal
>20.0 x ULN 
if baseline was 
normal; >20.0 
x baseline if 
baseline was 
abnormal
Bilirubin (total)
Increase
>ULN - 1.5 x 
ULN if 
baseline was 
normal; > 1.0 -
1.5 x baseline if 
baseline was 
abnormal
>1.5 - 3.0 x 
ULN if 
baseline was 
normal; >1.5 -
3.0 x baseline 
if baseline was 
abnormal
>3.0 - 10.0 x 
ULN if 
baseline was 
normal; >3.0 -
10.0 x 
baseline if 
baseline was 
abnormal
>10.0 x ULN 
if baseline was 
normal; >10.0 
x baseline if 
baseline was 
abnormal
Corrected Calcium 
(mmol/L)
Increase
>ULN - ≤2.9
>2.9 - 3.1
>3.1 - 3.4
>3.4


CNTO1959 (guselkumab); CNTO148 (golimumab)  (VEGA)
Statistical Analysis Plan CNTO1959UCO2002
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Approved, Date: 24 February 2021
Chemistry Tests
Criteria
Test
Direction
1
2
3
4
Corrected Calcium 
(mmol/L)
Decrease
<LLN – 2.0
<2.0 - 1.75
<1.75 - 1.5
<1.5
Creatinine
Increase
>ULN - 1.5 x 
ULN
>1.5 - 3.0 x 
baseline; >1.5 
- 3.0 x ULN
>3.0 x 
baseline; >3.0 
- 6.0 x ULN
>6.0 x ULN
Glucose (mmol/L)
Decrease
<LLN - 3.0
<3.0 - 2.2
<2.2 - 1.7
<1.7
Potassium (mmol/L)
Increase
>ULN - 5.5
>5.5 - 6.0
>6.0 - 7.0
>7.0
Potassium (mmol/L)
Decrease
<LLN - 3.0
<3.0 - 2.5
<2.5
Sodium (mmol/L)
Increase
>ULN - 150
>150 - 155
>155 - 160
>160
Sodium (mmol/L)
Decrease
<LLN - 130
125 - 129
120 - 124
<120