Conditions: Giant Cell Arteritis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 53
Healthy volunteers: no

Brief summary:
The primary purpose of this study is to evaluate the efficacy of guselkumab compared to placebo, in combination with a 26-week glucocorticoid (GC) taper regimen, in adult participants with new-onset or relapsing giant cell arteritis (GCA).

Detailed description:
Giant cell arteritis (GCA) is a non-necrotizing granulomatous systemic vasculitis of unknown etiology affecting medium-sized and large arteries usually accompanied or preceded by systemic inflammation. Guselkumab is a monoclonal antibody (mAb) that binds to the p19 sub-unit of human interleukin (IL)-23 with high affinity and blocks binding of extracellular IL-23 to cell surface IL-23 receptor, inhibiting IL 23 specific intracellular signaling and subsequent activation and cytokine production. It is used in treatment of psoriatic arthritis, generalized pustular psoriasis, erythrodermic psoriasis. The study consists of a screening period (less than or equal to \[\<=\] 6 weeks), double-blind treatment period (48 weeks), and safety follow-up period (12 weeks). Participants who complete the Week 52 visit and are assessed to be in glucocorticoid (GC)-free remission, may have the option to participate in the long-term extension (LTE) period of the study for up to 12 months. This study will evaluate the efficacy, safety, Pharmacokinetics (PK), and immunogenicity of guselkumab in combination with a 26-week GC taper regimen for the treatment of active new-onset or relapsing GCA in adult participants. The total duration of the study is up to 66 weeks for the main study and for participants that continue in the LTE period, the total study duration will be up to 112 weeks.

Arms:
arm 1: Participants will receive guselkumab subcutaneously (SC) every 4 weeks from Week 0 through Wweek 48. This will be in combination with a protocol specified 26-week GC taper. Participants of the long-term extension (LTE) period will continue to receive subcutaneous (SC) injections every 4 weeks starting at Week 52 (LTE Week 0) through Week 100 (LTE Week 48) or until the participants have a Giant cell arteritis (GCA) flare, or the participants discontinues treatment due to unblinding after the Week 60 DBL for the Main study, or until a decision is made not to continue clinical development in this GCA population, whichever occurs first. arm 2: Participants will receive matching placebo SC every 4 weeks from Week 0 through Week 48. This will be in combination with a protocol-specified 26-week GC taper. Participants of the LTE period will continue to receive SC injections every 4 weeks starting at Week 52 (LTE Week 0) through Week 100 (LTE Week 48) or until the participants have a GCA flare, or the participants discontinues treatment due to unblinding after the Week 60 DBL for the Main study, or until a decision is made not to continue clinical development in this GCA population, whichever occurs first.

Interventions: intervention 1: Guselkumab intervention 2: Placebo
Intervention descriptions: intervention 1: Guselkumab will be administered subcutaneously. intervention 2: Matching placebo will be administered subcutaneously.

Protocol document:
Prot_000.pdf: 
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
1
Status: Approved, Date: 25 May 2022
Janssen Research & Development*
Clinical Protocol
A Phase 2, Multicenter, Randomized, Placebo-controlled, Double-blind, Proof-of-Concept Study to
Evaluate Guselkumab for the Treatment of Participants with New-onset or Relapsing Giant Cell Arteritis
THEIA
A Proof-of-Concept Study of Guselkumab in the Treatment of Subjects with New-onset or
Relapsing Giant Cell Arteritis
Protocol CNTO1959GCA2001; Phase 2
Amendment 5
Guselkumab (CNTO1959)
*Janssen Research & Development is a global organization that operates through different legal entities in
various countries/territories. Therefore, the legal entity acting as the sponsor for Janssen Research &
Development studies may vary, such as, but not limited to Janssen Biotech, Inc.; Janssen Products, LP;
Janssen Biologics, BV; Janssen-Cilag International NV; Janssen, Inc; Janssen Pharmaceutica NV; Janssen
Sciences Ireland UC; Janssen Biopharma Inc., or Janssen Research & Development, LLC. The term
“sponsor” is used throughout the protocol to represent these various legal entities; the sponsor is identified
on the Contact Information page that accompanies the protocol.
United States (US)sites of this study will be conducted under US Food & Drug Administration
Investigational New Drug (IND) regulations (21 CFR Part 312).
Regulatory Agency Identifier Number(s)
Registry  
ID
EudraCT  
2020-000622-26
Status: 
Approved
Document Date: 
25 May 2022
Prepared by: 
Janssen Research & Development, LLC
EDMS Number: 
EDMS-ERI-204602737, 7.0
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory
requirements.
Confidentiality Statement
The information provided herein contains Company trade secrets, commercial or financial information that the Company
customarily holds close and treats as confidential.  The information is being provided under the assurance that the recipient will
maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or otherwise.
NCT04633447


Guselkumab (CNTO1959) 
Clinical Protocol CNTO1959GCA2001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
2
Status: Approved, Date: 25 May 2022
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document 
Date
Amendment 5 
25 May 2022
Amendment 4 
17 Sep 2021
Amendment 3 
09 Jul 2021
Amendment 2 
18Dec 2020
Amendment 1 
09 Jul 2020
Original Protocol 
12 May 2020
Overall Rationale for the Amendment:  The sponsor decided to no longer pursue a treatment regimen
that includes IV induction doses. Newly enrolled participants will now be treated with a full subcutaneous
(SC) dosing regimen. Sample size reduced while maintaining sufficient statistical power. Updated
inclusion/exclusion criteria.
Section Number
and Name
Description of Change 
Brief Rationale
1.1. Synopsis; 1.2. Schema. 1.3. Schedule of
activities (SoA); 4.1.Overall Design; 4.2.
Scientific Rationale for Study Design; 4.3
Justification of Dose; 6.1. Study interventions
administered; 6.2.
Preparation/Handling/Storage/Accountability;
6.4. Study Intervention Compliance
Change in treatment regimen:
removal of IV induction dosing of
study intervention. Newly enrolled
participants will receive SC
dosing of study intervention
throughout the study. Added
rationale for SC only treatment
regimen.
Updated Figure 1 (Schematic
Overview of Main Study)
Updated Schedule of Activities
Removed Section 4.3.1. Induction
Dose Regimen, and 4.3.2.
Maintenance Dose Regimen
As dose regimen for newly
enrolled participants is
guided by scientific
rationale and based on
emerging data, IV
induction dosing followed
by SC maintenance dosing
is no longer being pursued
as a dosing regimen for
GCA. SC only treatment
regimen is also more
convenient for participants.
1.1. Synopsis; 4.1. Overall design; 6.3.
Measures to Minimize Bias: Randomization
and Blinding; ; 9.2. Sample size
determination; 9.5. Interim Analyses
Sample size reduced from
approximately 60 to
approximately 51. Removal of
Interim analyses.
Sample size was reduced to
ensure timely completion
of the study while
maintaining sufficient
statistical power.
Reduction of sample size
to 51 negates the need for
interim analysis at n=45
participants to inform the
future development
planning of guselkumab for
the treatment of GCA. Data
from the week 28 DBL will
be used instead.
1.3. Schedule of Activities ; 8.9. Exploratory
FDG-PET/CT Imaging
Added clarification on utilization
of FDGPET/CT scan as
exploratory endpoint.
Protocol clarification.
2.2. Background; 2.3.3. Benefit-Risk
Assessment for Study Participation
Updated paragraph on clinical
studies with guselkumab.
Removed content related to IV
dosing.
Update with current
available information.


Guselkumab (CNTO1959) 
Clinical Protocol CNTO1959GCA2001 Amendment 5
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Status: Approved, Date: 25 May 2022
Section Number 
and Name
Description of Change 
Brief Rationale
4.1. Overall Design  
Clarifying that Flare visit can be 
combined with a regular visit and
that PET/CT scan can be
performed on another day.
Protocol clarification.
5.1. Inclusion criteria 
Criterion 4 modified to also allow 
GCA confirmation by 
angiography or cross-sectional 
imaging (ultrasound, MRI, CT, 
PET). 
Based on feedback from
investigators, EULAR
recommendations and
ACR/VF guidelines for
management of GCA.
5.1. Inclusion criteria 
Criterion 14: Updated TB 
screening criteria.
New sponsor standard.
5.2. Exclusion criteria 
Criterion 4 and 19 expanded  to 
exclude individuals with high risk 
of venous thromboembolism 
(VTE). 
GCA is associated with an
increased risk ofVTE.
Two  participants in this
study reported venous
thromboembolisms during
the IV induction period.
Both participants had
individual risk factors that
may have contributed to
their risk ofvenous
thrombosis.
5.4. Screen failures 
Clarified that for participants that 
are rescreened, PET/CT scans
obtained during the first screening
do not have to be repeated if
performed in a reasonable period
of time before randomization after
consultation with the sponsor.
Added that individuals who were
screen fails due to a trial
suspension may be rescreened a
second time with sponsor
approval.
Protocol clarification.
6.8.1. Permitted therapy; 8. Study 
Assessments and Procedures 
Modified language to clarify when 
to start tapering glucocorticoids. 
Protocol clarification to
increase compliance to
protocol-defined GC taper
regimen.
7.1. Discontinuation of Study Intervention  
Added that study assessments may 
be reduced if participants 
discontinue treatment and 
continue in the study. 
Protocol clarification to
avoid oversampling and
collection of data that is
not in the interest of the
study or the participant.
8. Study Assessments and Procedures 
Removed details related to sample 
collection for PK analysis.
Diagnostic confirmation of GCA:
Editorial changes and cross-
referred to inclusion criterion 4
Protocol clarification
8.2.2. Vital signs 
Added language that bilateral 
measurement  of blood pressure 
and pulse is required for the first 
measurement only per visit.
Subsequent measurements can be
performed on a single arm
(unilateral).
Protocol clarifications to
reduce burden on the
participants.


Guselkumab (CNTO1959) 
Clinical Protocol CNTO1959GCA2001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
4
Status: Approved, Date: 25 May 2022
Section Number 
and Name
Description of Change 
Brief Rationale
8.2.9. Adverse Events Temporally 
Associated with Infusion 
Removed Section. 
Study agent is not
administered through IV
infusion anymore.
8.3.7. Adverse event of special interest 
Added Venous thromboembolism 
(VTE) as AESI.
Expedite reporting ofVTE.
8.4. Pharmacokinetics (8.4.1. 
Evaluations) 
Removed that PK samples should 
be drawn  from a different arm  
than the IV infusion line if study 
agent is administered at that visit.
Study agent is not
administered through IV
infusion anymore.
9.3. Analysis Sets 
Updated population definition for 
immunogenicity analysis set.
Protocol clarification
9.4.5. Safety analyses 
The number and proportion of 
participants with injection-site 
reactions by treatment intervention
will be analysed for all visits at
which participants received SC
injections.
Modified due to change in
dosing regimen.
Title page; Appendix 3: Regulatory, Ethical, 
and Study Oversight Considerations 
(Investigator Responsibilities; Regulatory 
Approval/Notification; Country/Territory 
Selection; Privacy of Personal Data)
Updated “country” to 
“country/territory” 
To align with the latest
template per Asia Pacific
(APAC) Market
Referencing Guidance
Throughout the protocol 
Minor grammatical, formatting, or 
spelling changes were made.
Minor errors were noted.


Guselkumab (CNTO1959) 
Clinical Protocol CNTO1959GCA2001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 25 May 2022
TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................................... 2
TABLE OF CONTENTS ............................................................................................................................... 5
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 7
1. 
PROTOCOL SUMMARY..................................................................................................................... 8
1.1. 
Synopsis........................................................................................................................................... 8
1.2. 
Schema.......................................................................................................................................... 11
1.3. 
Schedule of Activities (SoA)........................................................................................................... 14
1.4. 
Schedule of Activities (SoA) –Long-Term Extension.................................................................... 18
2. 
INTRODUCTION................................................................................................................................ 21
2.1. 
Study Rationale.............................................................................................................................. 21
2.1.1. 
Unmet Need in Giant Cell Arteritis.............................................................................................. 22
2.1.2. 
Rationale for Targeting IL-23 in Giant Cell Arteritis.................................................................... 23
2.2. 
Background.................................................................................................................................... 24
2.3. 
Benefit/Risk.................................................................................................................................... 26
2.3.1. 
Risks for Study Participation....................................................................................................... 26
2.3.2. 
Benefits for Study Participation .................................................................................................. 30
2.3.3. 
Benefit-Risk Assessment for Study Participation ....................................................................... 30
3. 
OBJECTIVE AND ENDPOINTS........................................................................................................ 32
4. 
STUDY DESIGN ................................................................................................................................ 36
4.1. 
Overall Design................................................................................................................................ 36
4.2. 
Scientific Rationale for Study Design............................................................................................. 38
4.2.1. 
Participant Input into Design....................................................................................................... 39
4.2.2. 
Study-Specific Ethical Design Considerations ........................................................................... 39
4.3. 
Justification for Dose...................................................................................................................... 40
4.4. 
End of Study Definition................................................................................................................... 41
5. 
STUDY POPULATION ...................................................................................................................... 42
5.1. 
Inclusion Criteria............................................................................................................................ 42
5.2. 
Exclusion Criteria........................................................................................................................... 47
5.3. 
Lifestyle Considerations................................................................................................................. 53
5.4. 
Screen Failures.............................................................................................................................. 54
5.5. 
Criteria for Temporarily Delaying [Enrollment/Randomization/Administration of Study
Intervention Administration] ........................................................................................................... 54
6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY............................................................ 55
6.1. 
Study Interventions Administered .................................................................................................. 55
6.1.1. 
Combination Products ................................................................................................................ 55
6.2. 
Preparation/Handling/Storage/Accountability ................................................................................ 56
6.3. 
Measures to Minimize Bias: Randomization and Blinding............................................................. 57
6.4. 
Study Intervention Compliance...................................................................................................... 58
6.5. 
Dose Modification........................................................................................................................... 58
6.6. 
Continued Access to Study Intervention After the End of the Study ............................................. 58
6.7. 
Treatment of Overdose .................................................................................................................. 58
6.8. 
Concomitant Therapy..................................................................................................................... 59
6.8.1. 
Permitted Therapy...................................................................................................................... 59
6.8.2. 
Prohibited Therapies................................................................................................................... 62
6.8.3. 
Rescue Medication ..................................................................................................................... 63
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL............................................................................................... 64
7.1. 
Discontinuation of Study Intervention ............................................................................................ 64


Guselkumab (CNTO1959) 
Clinical Protocol CNTO1959GCA2001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 25 May 2022
7.2. 
Participant Discontinuation/Withdrawal From the Study................................................................ 66
7.2.1. 
Withdrawal from the Use of Research Samples......................................................................... 67
7.3. 
Lost to Follow-up............................................................................................................................ 67
8. 
STUDY ASSESSMENTS AND PROCEDURES ............................................................................... 68
8.1. 
Efficacy Assessments .................................................................................................................... 70
8.1.1. 
GCA Disease Signs and Symptoms........................................................................................... 70
8.1.2. 
Physician's Global Assessment of Disease Activity (PhGA)...................................................... 71
8.1.3. 
C-Reactive Protein and Erythrocyte Sedimentation Rate .......................................................... 71
8.1.4. 
Patient’s Global Assessment of Disease Activity (PGA) ............................................................ 71
8.1.5. 
Pain Assessment........................................................................................................................ 71
8.1.6. 
FACIT-fatigue ............................................................................................................................. 72
8.1.7. 
Short Form 36 (SF-36)................................................................................................................ 72
8.2. 
Safety Assessments....................................................................................................................... 72
8.2.1. 
Physical Examinations................................................................................................................ 73
8.2.2. 
Vital Signs................................................................................................................................... 73
8.2.3. 
Electrocardiograms..................................................................................................................... 73
8.2.4. 
Clinical Safety Laboratory Assessments .................................................................................... 74
8.2.5. 
Pregnancy Testing...................................................................................................................... 74
8.2.6. 
Columbia-Suicide Severity Rating Scale.................................................................................... 74
8.2.7. 
Concomitant Medication Review ................................................................................................ 76
8.2.8. 
Injection-Site Reactions.............................................................................................................. 76
8.2.9. 
Hypersensitivity Reactions.......................................................................................................... 76
8.2.10. 
Infections .................................................................................................................................... 76
8.2.11. 
Tuberculosis Evaluations............................................................................................................ 77
8.3. 
Adverse Events, Serious Adverse Events, and Other Safety Reporting ....................................... 78
8.3.1. 
Time Period and Frequency for Collecting Adverse Event and Serious Adverse Event
Information.................................................................................................................................. 79
8.3.2. 
Method of Detecting Adverse Events and Serious Adverse Events .......................................... 79
8.3.3. 
Follow-up of Adverse Events and Serious Adverse Events ....................................................... 80
8.3.4. 
Regulatory Reporting Requirements for Serious Adverse Events ............................................. 80
8.3.5. 
Pregnancy................................................................................................................................... 80
8.3.6. 
Disease-Related Events and Disease-Related Outcomes not Qualifying as Adverse
Events or Serious Adverse Events............................................................................................. 80
8.3.7. 
Adverse Events of Special Interest............................................................................................. 80
8.4. 
Pharmacokinetics........................................................................................................................... 81
8.4.1. 
Evaluations ................................................................................................................................. 81
8.4.2. 
Analytical Procedures................................................................................................................. 81
8.4.3. 
Pharmacokinetic Parameters ..................................................................................................... 81
8.5. 
Pharmacogenomics ....................................................................................................................... 81
8.6. 
Biomarkers..................................................................................................................................... 82
8.7. 
Immunogenicity Assessments ....................................................................................................... 83
8.7.1. 
Evaluations ................................................................................................................................. 83
8.7.2. 
Analytical Procedures................................................................................................................. 83
8.8. 
Medical Resource Utilization and Health Economics .................................................................... 83
8.9. 
Exploratory FDG-PET/CT Imaging ................................................................................................ 83
8.10. 
Digital Health –Actigraphy Measurements.................................................................................... 84
9. 
STATISTICAL CONSIDERATIONS.................................................................................................. 85
9.1. 
Statistical Hypothesis..................................................................................................................... 85
9.2. 
Sample Size Determination ........................................................................................................... 85
9.3. 
Analysis Sets.................................................................................................................................. 86
9.4. 
Statistical Analyses ........................................................................................................................ 86
9.4.1. 
General Considerations.............................................................................................................. 86
9.4.2. 
Primary Endpoint ........................................................................................................................ 86
9.4.3. 
Secondary Endpoints.................................................................................................................. 87
9.4.4. 
Tertiary/Exploratory Endpoints ................................................................................................... 88
9.4.5. 
Safety Analyses.......................................................................................................................... 88


Guselkumab (CNTO1959) 
Clinical Protocol CNTO1959GCA2001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
7
Status: Approved, Date: 25 May 2022
9.4.6. 
Other Analyses ........................................................................................................................... 90
9.5. 
Interim Analyses............................................................................................................................. 93
9.6. 
Data Monitoring Committee ........................................................................................................... 93
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ............................ 94
10.1. 
Appendix 1: Abbreviations ............................................................................................................. 94
10.2. 
Appendix 2: Clinical Laboratory Tests ........................................................................................... 96
10.3. 
Appendix 3: Regulatory, Ethical, and Study Oversight Considerations......................................... 97
10.4. 
Appendix 4: Adverse Events, Serious Adverse Events, Product Quality Complaints, and
Other Safety Reporting: Definitions and Procedures for Recording, Evaluating, Follow-up,
and Reporting............................................................................................................................... 109
10.5. 
Appendix 5: Revised American College of Rheumatology Criteria for Diagnosis of GCA .......... 114
10.6. 
Appendix 6: Hepatitis B Virus (HBV) Screening with HBV DNA Testing..................................... 115
10.7. 
Appendix 7: Contraceptive and Barrier Guidance ....................................................................... 116
10.8. 
Appendix 8: Protocol Defined 26-Week Glucocorticoid Taper .................................................... 119
10.9. 
Appendix 9: Liver Safety: Suggested Actions and Follow-up Assessments................................ 121
10.10. Appendix 10: Glucocorticoid Conversion Table........................................................................... 126
10.11. Appendix 11: Guidance on Study Conduct during the COVID-19 Pandemic.............................. 127
10.12. Appendix 12: Protocol Amendment History................................................................................. 129
11. REFERENCES................................................................................................................................. 139
INVESTIGATOR AGREEMENT............................................................................................................... 142
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1: 
Predicted Guselkumab Exposure Margins for the Dosing Regimen to be Evaluated in
the Study................................................................................................................................... 24
Table 2: 
Power to Detect Difference in Proportions of Participants Achieving Glucocorticoid-
free Remission between the Guselkumab and Placebo Intervention Groups at Week
28 .............................................................................................................................................. 85
Table 3: 
Protocol Defined 26-Week Glucocorticoid Taper# .................................................................. 119
FIGURES
Figure 1: Schematic Overview of Main Study.......................................................................................... 12
Figure 2: Schematic Overview of the Long-Term Extension (LTE) Period.............................................. 13


Guselkumab (CNTO1959) 
Clinical Protocol CNTO1959GCA2001 Amendment 5
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Status: Approved, Date: 25 May 2022
1. 
PROTOCOL SUMMARY
1.1. 
Synopsis
A Phase 2, Multicenter, Randomized, Placebo-controlled, Double-blind, Proof-of-Concept Study to
Evaluate Guselkumab for the Treatment of Participants with New-onset or Relapsing Giant Cell Arteritis
DESCRIPTION OF COMPOUND
Guselkumab (CNTO1959) is a fully human immunoglobulin G1 lambda (IgG1λ) monoclonal antibody
(mAb) that binds to human interleukin (IL)-23 with high specificity and affinity.
OBJECTIVES AND ENDPOINTS
Primary objectives:
 
To evaluate the efficacy of guselkumab compared to placebo, in combination with a 26-week
glucocorticoid (GC)taper regimen, in adult participants with new-onset or relapsing giant cell arteritis
(GCA).
Secondary Objectives:
 
To evaluate the efficacy of guselkumab compared to placebo, in combination with a 26-week GC taper
regimen, in adult participants with new-onset or relapsing GCA as measured by alternative definitions
of GC free remission, GC-sparing effects, and prevention of disease flares.
 
To evaluate the safety of guselkumab, in combination with a 26-week GC taper regimen, in adult
participants with new-onset or relapsing GCA.
 
To evaluate the pharmacokinetics (PK) and immunogenicity of guselkumab, in combination with a
26-week GC taper regimen, in adult participants with new-onset or relapsing GCA.
Exploratory objectives:
 
To explore the longer-term efficacy of guselkumab compared to placebo, in combination with a
26-week GC taper regimen, in adult participants with new-onset or relapsing GCA.
 
To evaluate the changes in immune-markers to guselkumab compared to placebo, in combination with
a 26-week GC taper regimen, in adult participants with new-onset or relapsing GCA.
 
To explore the changes in pharmacodynamic markers and arterial vessel wall inflammation following
administration of guselkumab in adult participants with new-onset or relapsing GCA.
 
To explore changes in participant reported Clinical Outcome Assessments, pain and fatigue, and
physician reported outcomes and digital health parameters following administration of guselkumab in
adult participants with new-onset or relapsing GCA.
Exploratory objectives for the Long-Term Extension (LTE) Period:
 
To evaluate long-term efficacy of guselkumab in adult participants with new-onset or relapsing GCA.
 
To evaluate the continued safety of guselkumab in adult participants with new-onset or relapsing GCA.
 
To evaluate the PK and immunogenicity of guselkumab, in adult participants with new-onset or
relapsing GCA.
 
To explore the changes in pharmacodynamic (PD) markers and arterial vessel wall inflammation
following administration of guselkumab in adult participants with new-onset or relapsing GCA in the
LTE period.


Guselkumab (CNTO1959) 
Clinical Protocol CNTO1959GCA2001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 25 May 2022
 
To explore changes in participant reported Clinical Outcome Assessments, pain and fatigue, and
physician reported outcomes following administration of guselkumab in adult participants with new-
onset or relapsing GCA in the LTE period.
HYPOTHESIS
The primary hypothesis is that guselkumab treatment with a 26-week GC taper is superior to placebo with
a 26-week GC taper in participants with new-onset or relapsing GCA as assessed by the proportion of
participants achieving GC-free remission at Week 28.
OVERALL DESIGN
This is a randomized, double-blind, placebo-controlled, parallel, multicenter, interventional Phase 2 Proof-
of-Concept study evaluating the efficacy, safety, PK, and immunogenicity of guselkumab for the treatment
of active new-onset or relapsing GCA in adult participants.
NUMBER OF PARTICIPANTS
A target of approximately 51 participants will be enrolled in this study. Participants will be randomly
assigned into 2 treatment groups in a 2:1 ratio for guselkumab versus placebo.
INTERVENTION GROUPS AND DURATION
Participants in the study will be on background GC, supplied by the clinical study site.
In addition to remaining on the standard-of-care noted above, participants will be randomized with a 2:1
ratio to 1 of 2 treatment groups as described below:
 
Guselkumab: Participants will receive guselkumab 200 mg SC every 4 weeks from Week 0 through
Week 48.
 
Placebo: Participants will receive placebo SC every 4 weeks from Week 0 through Week 48.
Participants who complete the Week 52 visit and are assessed to be in GC-free remission, may have the
option to participate in the LTE period of the study for up to 12 months.
Participants of the LTE period will continue to receive SC injections every  4 weeks (either active or
placebo) starting at Week 52 (LTE Week 0) through Week 100 (LTE Week 48) or until the participants
have a GCA flare, or the participants discontinues treatment due to unblinding after the Week 60 DBL for
the Main study, or until a decision is made not to continue clinical development in this GCA population,
whichever occurs first.
EFFICACY EVALUATIONS
Investigator assessments and patient-reported outcomes of efficacy include the following:
 
GCA disease signs and symptoms
 
Physician’s global assessment of disease activity
 
C-reactive protein and erythrocyte sedimentation rate
 
Patient’s global assessment of disease activity
 
Pain assessment
 
Functional assessment of chronic illness therapy-fatigue
 
Short form 36


Guselkumab (CNTO1959) 
Clinical Protocol CNTO1959GCA2001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 25 May 2022
PHARMACOKINETIC EVALUATIONS
Venous blood samples will be collected for measurement of serum concentrations of guselkumab and
antibodies to guselkumab (Section 8.7) at the timepoints shown in the Schedule of Activities (SoA,
Section 1.3).
Venous blood samples will be collected, and each serum sample will be divided into 3 aliquots (1 each for
PK, anti-guselkumab antibodies, and a back-up).
IMMUNOGENICITY EVALUATIONS
Serum samples for detection of antibodies to guselkumab will be collected and evaluated according to the
SoA. Additionally, serum samples should also be collected at the final visit from participants who were
withdrawn from the study.
Serum samples will be screened for antibodies binding to guselkumab and the titer of confirmed positive
samples will be reported. Other analyses may be performed to verify the stability of antibodies to
guselkumab and/or further characterize the immunogenicity of guselkumab.
BIOMARKER EVALUATIONS
Biomarker assessments will be made to examine the biologic response to treatment and to identify
biomarkers that are relevant to guselkumab treatment, GCs and GCA, where local regulations permit.
Assessments will include the evaluation of relevant biomarkers in serum, whole blood, and peripheral blood
mononuclear cells collected as specified in the SoA, where local regulations permit.
PHARMACOGENOMIC (DEOXYRIBONUCLEIC ACID [DNA]) EVALUATIONS
Participation in pharmacogenomic research is optional. A pharmacogenomic (DNA) blood sample will be
collected from participants who consent separately to this component of the study to allow for
pharmacogenomic research, where local regulations permit.
SAFETY EVALUATIONS
Key safety assessments include adverse events, clinical laboratory tests (hematology and chemistry), vital
signs, monitoring for injection-site and hypersensitivity reactions, suicidality assessment, and early
detection of active tuberculosis.
STATISTICAL METHODS
Approximately 51 participants are planned to be enrolled into the study. The assumptions for the sample
size and power calculation were based on the data from the Actemra Phase 3 GCA study. The GC-free
remission rates at Week 28 are assumed to be 40% for placebo and 80% for guselkumab treatment arm.
Based on these assumptions, 51 participants are planned to be randomized in a 2:1 ratio to either the
guselkumab group or the placebo group. These sample sizes provide the study with 82% power to detect a
difference in the primary endpoint between the 2 treatment groups.
For purposes of analysis, the following populations are defined:
 
Enrolled: All participants who signed the informed consent form.
 
Full Analyses Set: All participants who were randomized in the study and received at least one
administration of study intervention.
 
Safety Analysis Set: All participants who received at least one dose ofstudy intervention.
 
Immunogenicity Analysis Set: All participants who received at least 1 administration of guselkumab
and have at least one sample obtained after their first dose of guselkumab.


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Status: Approved, Date: 25 May 2022
 
PK Analysis Set: All participants who received at least 1 administration of guselkumab and have at
least one valid blood sample drawn for PK analysis.
 
PD Analysis Set: All participants who received at least 1 administration of study intervention and have
at least one post-dose sample collection.
Data primarily will be summarized using descriptive statistics. Continuous variables will be summarized
using the number of observations, mean, standard deviation, median, interquartile range, minimum and
maximum, as appropriate. Categorical values will be summarized using the number of observations and
percentages as appropriate. Median time will be reported for time to event variables. In addition, graphical
data displays (eg, line plots) and participant listings may also be used to summarize/present the data.
For continuous endpoints, Mixed-Effect Model Repeated Measure model and Analysis of Covariance will
be used for analysis. For binary endpoints, a Cochran-Mantel-Haenszel test stratified by new-onset and
relapsing GCA, and the baseline prednisone dose (≤30 mg/day or >30 mg/day) will be used to analyze data.
For time to first event data, Kaplan-Meier curves and Cox proportional hazards regression will be used to
analyze the data. In addition, treatment differences and their associated 90% confidence intervals will be
presented.
In general, all statistical tests will be performed at a 2-sided significance level of α=0.10. No multiplicity
adjustment will be made for the secondary endpoints being tested and nominal p values will be reported.
1.2. 
Schema
An overview of the main study design  is presented in Figure 1. Participants in glucocorticoid
(GC)-free remission at Week 52 of the main study have the option to continue treatment in the
LTE period. The Week 52 visit of the main study will be Week 0 of the LTE period.
An overview of the long-term extension (LTE) period is presented in Figure 2.




Guselkumab (CNTO1959) 
Clinical Protocol CNTO1959GCA2001 Amendment 5
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Status: Approved, Date: 25 May 2022
Figure 2: 
Schematic Overview of the Long-Term Extension (LTE) Period








Guselkumab (CNTO1959) 
Clinical Protocol CNTO1959GCA2001 Amendment 5
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17
Status: Approved, Date: 25 May 2022
Schedule of Activities From Screening through Week 60
Period  
Screeninga 
-6 to -1 
Blinded Active Treatment Period
Safety Follow-up
Study Week  
0 
4 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48 
52g 
60
Flare
Visitq 
Early
Termination
Visitb
Study Day (post D1
window ±7 days)
-42 to -1 
1 
28 
56 
84 
112 140 
168 
196 
224 
252 
280 
308 336 364 420 
Study Procedurec
to excess radiation. FDG PET/CT scan is being obtained as part ofexploratory endpoint and results should not be used in determining disease status at the associated week 52
visit.
i. Chest radiograph (posterior anterior and lateral views, or per country regulations where applicable) must be obtained within 12 weeks before the Week 0 visit. Note: A chest CT
scan is also acceptable if obtained instead of a chest radiograph outside of the protocol.
j. 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. In this study, the C SSRS is a physician
administered questionnaire and should be administered by certified, trained, and delegated principal investigator or subinvestigator only.
k. At screening participants will be provided with an Actigraphy watch to be able to capture a baseline profile. Participants who will not prove eligible will return their Actigraphy
watch to the study site.  Participants may decline actigraphy measurements in case the participant is at risk for withdrawal of consent or if this assessment is a reason for participant
not wanting to join the study.
l. Every attempt should be made to collect biomarker samples (as per schedule) during a flare but before a GC dose increase.
m. An optional whole blood pharmacogenomic (DNA) sample will be collected from those participants who sign a separate consent form (where local regulations permit). The
pharmacogenomic sample should be collected at the specified time point, however if necessary, it may be collected at a later time point without constituting a protocol deviation.
n. Minimum criteria for the availability of documentation supporting the eligibility criteria are described in Source Documentation in Section 10.3. Check clinical status again before
first dose of study medication
o. Urine pregnancy testing is required for female participants of childbearing potential only (Section 8.2.5). If more frequent pregnancy testing is required by local regulations, these
are allowed to be taken locally.
p. Investigators/site staffare recommended to contact the participant by telephone weekly to verify that correct steroid dose is taken.
q. In case a participant is diagnosed as having a flare during a study visit or shortly before a planned study visit, the Flare visit and regular visit can be combined. Overlapping
procedures and assessments need only be performed once. The FDG PET/CT scan can be scheduled separately from other  assessments.
r. A tuberculin skin test is additionally required if the QuantiFERON TB test is not approved/registered in the country in which this study is being conducted.
Abbreviations: CRP=C reactive protein; CT=computed tomography; C SSRS=Columbia Suicide Severity Rating Scale; D1=Day 1; DNA=deoxyribonucleic acid;
ECG=electrocardiogram; ESR=erythrocyte sedimentation rate; FACIT=Functional Assessment of Chronic Illness Therapy; FDG=fluorodeoxyglucose; GC=glucocorticoid;
GCA=Giant cell arteritis; HIV=human immunodeficiency virus; LTE=long term extension; PBMC=peripheral blood mononuclear cell; PET=positron emission tomography;
PGA=Patient's Global Assessment of Disease Activity; PhGA=Physician's Global Assessment of Disease Activity; PRO=patient reported outcome; SF 36=short form 36;
SC=subcutaneous; TB=tuberculosis; Term= termination.






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Status: Approved, Date: 25 May 2022
Schedule of Activities from Week 52 Main Study until End of LTE Period
Period  
LTE Treatment Period 
LTE Safety Follow-up
Study Week  
52k 
56 
60 
64 
68 
72 
76 
80 
84 
88 
92 
96 
100 
104 
112
LTE
Flare
Visitm
LTE Early
Termination Visita
LTE Week  
0 
4 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48 
52 
60 
Study Day (window ±7
days)
364 392 420 448 476 504 
532 560 588 616 644 672 700 
728 
784
d. Clinical Assessor’s assessment of GCA signs and symptoms as specified in Section 8.1.1.
e. FDG PET/CT scan in the LTE is to be performed at Study Week 104 (LTE Week 52)or timepoint of flare if earlier. If a participant has a GCA flare prior to Study Week 104 (LTE
Week 52), an attempt should be made to perform the FDG PET/CT imaging within 1 week from identification of GCA flare by the principal investigator during the LTE period. If
a participant has a GCA flare within 1 month (or other timeframe in accordance with local country regulations) of FDG PET/CT imaging for the Study Week 52 timepoint of the
main study, the FDG PET/CT scan should not be performed. Participants may decline to obtain the LTE FDG PET/CT. FDG PET/CT scan is being obtained as part of exploratory
endpoint and results should not be used in determining disease status at the associated Study Week 104 (LTE Week 52)visit.
f. In this study, the C SSRS is a physician administered questionnaire and should be administered by the certified, trained, and delegated principal investigator or subinvestigator
only.
g. Minimum criteria for the availability of documentation supporting the eligibility criteria are described in Source Documentation in Section 10.3. Check clinical status again before
first dose of study medication
h. Urine pregnancy testing is required for female participants of childbearing potential only (Section 8.2.5). If more frequent pregnancy testing is required by local regulations, these
are allowed to be taken locally.
i. For visits where study intervention will be administered, 1 blood sample should be collected prior to study intervention administration, if applicable, for evaluation of serum
concentration of guselkumab and/or antibodies to guselkumab.
j. The investigator is expected to re review the informed consent with the participant to ensure that the participant understands the purpose of, as well as the study procedures and
required visits associated with the LTE period.
k. Participants who are eligible and willing to participate in the LTE study will continue with LTE Week 0 activities after completing Week 52 assessments of the main study.
l. PGA, Pain assessment, FACIT Fatigue, and SF 36 should be performed before any laboratory/safety tests, procedures, or other evaluations (PhGA and assessment of GCA disease
signs and symptoms). Event driven PROs will be applicable for participants developing a GCA flare. C SSRS should be completed after all PROs and before any other tests,
procedures, or other consultations.
m. In case a participant is diagnosed as having a flare during a study visit or shortly before a planned study visit  the Flare visit and regular visit can be combined.  Overlapping
procedures and assessments need only be performed once. The FDG PET/CT scan can be scheduled separately from other  assessments.
Abbreviations: CRP=C reactive protein; CT=computed tomography; C SSRS=Columbia Suicide Severity Rating Scale; ESR=erythrocyte sedimentation rate;
FDG=fluorodeoxyglucose; GC=glucocorticoid; GCA=Giant cell arteritis; LTE=long term extension; PET=positron emission tomography; PRO=patient reported outcome.
SC=subcutaneous.


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Status: Approved, Date: 25 May 2022
2. 
INTRODUCTION
Guselkumab (CNTO1959) is a fully human immunoglobulin G1 lambda (IgG1λ) monoclonal
antibody (mAb) that binds to human interleukin (IL)-23 with high specificity and affinity. The
binding of guselkumab to the IL-23p19 subunit blocks the binding of extracellular IL-23 to the
cell surface IL-23 receptor, 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 has been approved for the treatment of adults with moderate to severe plaque
psoriasis (PsO) in the United States (US), European Union, Canada, Japan and several other
countries worldwide. In addition, guselkumab has been approved for the treatment of psoriatic
arthritis (PsA), generalized pustular PsO, erythrodermic PsO, and palmoplantar pustulosis in
Japan.
Guselkumab is currently being developed in other diseases including for the treatment of patients
with PsA, hidradenitis suppurativa (HS), familial adenomatous polyposis, Crohn’s disease, Lupus
Nephritis (LN)and ulcerative colitis (UC). Phase 3 studies in PsA, a Phase 2/3 program in Crohn’s
disease, a Phase 2b/3 study in UC, and Phase 2 studies in HS and LN are currently ongoing or
planned globally.
For the most comprehensive nonclinical and clinical information regarding guselkumab, refer to
the latest version of the Investigator’s Brochure (IB) and Addenda for guselkumab.
The term “study intervention” throughout the protocol, refers to study drug, as defined in
Section 6.1, Study Interventions Administered.
The term “sponsor” used throughout this document refers to the entities listed in the Contact
Information page(s), which will be provided as a separate document.
2.1. 
Study Rationale
Giant cell arteritis (GCA) is a non-necrotizing granulomatous systemic vasculitis of unknown
etiology affecting medium-sized and large arteries usually accompanied or preceded by systemic
inflammation. GCA has 2 disease components: vessel wall inflammation inducing arterial
stenosis/occlusion and a systemic inflammation leading to polymyalgias, anemia, failure-to-thrive,
and malaise (Weyand 2003). Prototypic vessel wall inflammation preferentially affects the upper
extremity and extracranial branches of the aorta causing blindness, stroke, aortic arch syndrome,
aortic aneurysm, or dissection (Weyand 2003; Evans 1995). Histologically, GCA is characterized
by an infiltration of the media with lymphocytes, macrophages, and giant cells (Ciccia 2017).
Inflammation may show a segmental infestation pattern in which inflammatory and non-
inflammatory vascular segments are located side by side. It is the most common primary form of
vasculitis in the US and Europe and occurs predominantly in individuals aged 50 years or over
with the mean age of onset of approximately 70 years of age (Salvarani 2004). The onset of GCA
symptoms may be abrupt, but in most instances, symptoms develop gradually over a period of
several weeks. Women are affected 2-3 times as often as men (Nesher 2014; Waldman 2013).


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Status: Approved, Date: 25 May 2022
Clinically, patients with GCA suffer from symptoms including headaches, scalp tenderness or
pain, jaw/tongue/limb claudication, symptoms of polymyalgia rheumatica (PMR) and visual
impairment. In many patients a systemic inflammatory response may also occur with symptoms
including fever, weight loss and fatigue (González-Gay2019). Typically C-reactive protein (CRP)
and erythrocyte sedimentation rate (ESR) are increased, and anemia, thrombocytosis and mild
transaminitis are common features of GCA. Establishing a firm early diagnosis for GCA can be
challenging, as patients present with a variety of symptoms and there are no conclusive diagnostic
markers for GCA. Histological analysis of temporal artery biopsy tissue and temporal artery
ultrasound are used to confirm GCA diagnosis.  Delayed diagnosis and treatment can lead to
significant complications including permanent visual loss due to anterior optic ischemic
neuropathy or retinal artery occlusion. Other serious GCA complications include cerebrovascular
strokes, infarction of the tongue and scalp necrosis (Waldman 2013).
Glucocorticoids (GCs) are the treatment of choice starting with an initial high dose of prednisone
at 40-60 mg/day for most cases followed by a tapered lowering of dose. Glucocorticoid treatment
with intravenous (IV) methylprednisolone 500 to 1000 mg/day for 3 days may be considered in
patients with vision loss (transient or permanent), diplopia, transient ischemic attacks, or stroke.
2.1.1. 
Unmet Need in Giant Cell Arteritis
Major unmet needs in GCA include non-invasive diagnostic tests, optimization of GC use to avoid
GC  related complications, identification of more targeted treatments, and identification of
prognostic factors.
Despite an often-rapid improvement of symptoms following initial GC treatment, most patients
develop serious adverse side effects related to long-term use of GCs, including GC-induced
diabetes, arterial hypertension, osteoporosis, cataracts, infection, and psychosis (Baig 2019). In
fact, an estimated 86% of patients treated with long-term GC  therapy suffered from these GC-
related complications within 10 years (Ness 2013).
Glucocorticoid tapering is typically started when symptomatology resolves and inflammatory
markers normalize, with the goal to reduce the risks of long-term GC use. Tapering can result in
either complete weaning off of GC or finding a low stable maintenance dose, however disease
relapse is common (50% to 80%) during GC taper (Hachulla 2001; Weyand 2000). While the
general view is that GC treatment can be reasonably stopped after 2 years, patients oftentimes
require GC therapy for much longer (Hayreh 1997). Furthermore, a significant proportion (~25%)
of patients do not achieve permanent remission (Proven 2003).
Due to the frequent complications of prolonged GC  treatment, there is a need to develop
GC-sparing maintenance therapies for GCA.
Tocilizumab (anti-IL6) is the only biologic approved for GCA. Its use is often limited to patients
who fail GCs due to limited efficacy or safety concerns. Additionally, IL-6 receptor blockade with
tocilizumab abrogates the hepatic synthesis of acute-phase reactants and renders CRP and ESR
measurement unreliable for the purpose of monitoring disease activity in GCA in clinical practice
(Prieto-González 2017).


Guselkumab (CNTO1959) 
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Status: Approved, Date: 25 May 2022
Significant opportunity remains for the development of new treatment options for GCA that
provide greater sustained GC-free remission with a favorable safety profile in newly diagnosed
and relapsing GCA patients. A safe and efficacious alternative to GCs is an urgent unmet need in
GCA and is a niche that guselkumab may fill given its well-characterized safety profile and durable
responses in other indications where it has been shown to be effective.
2.1.2. 
Rationale for Targeting IL-23 in Giant Cell Arteritis
IL-23 responses occur mainly in two types of tissue: microbiome rich barrier surfaces (gut and
skin) (Furie 2009)and sterile interfaces subject to dynamic biomechanical loading. The latter is
directly relevant to GCA as sites include the aorta (as well as entheses and eye). In contrast to
adaptive immune responses, resident IL-23R+ cells are present within tissue in the resting, healthy
state. In animal models and/or explants from human tissues, exposure to IL-23 results in immediate
activation of these cells and a robust onset of tissue inflammation which exactly phenocopies the
pathognomonic anatomical specificity of human disease in conditions such as aortitis, PsO,
PsA/enthesitis, uveitis and (with additional manipulations) inflammatory bowel disease
(Hayreh 1997; Baig 2019). These insights have underscored the clinical success of guselkumab in
several disease areas.
Aortitis is therefore within the domain of broader systemic inflammatory disorders in which IL-23
is known to be important. This is further emphasized by the observation that enthesopathic arthritis
is associated with aortitis. Enthesopathic arthritis is also associated with both clinical and
subclinical intestinal inflammation, whilst aortitis (specifically, Takayasu’s arteritis) has been
reported to associate with inflammatory bowel disease (Deng 2010). Strong evidence of the role
of IL-23 in aortitis comes from its ability to directly drive aortic root inflammation upon
experimental expression of the cytokine where it acts on local IL-23 responsive cells resident in
this structure (Hayreh 1997). This understanding of aortitis is consistent with the role of IL-23 at
other sites of high biomechanical stress, such as the entheseal structures where similar IL-23
responsive cells are present.  Furthermore, the IL-23 driven aortic inflammation bears strong
histopathological resemblance to Takayasu’s Arteritis (a large vessel vasculitis predominantly
affecting the aorta). Despite GCA having a different phenotype than Takayasu’s, it can also be
associated with a widespread aortitis and there is even a diagnostic entity of “large vessel GCA”
(Hachulla 2001; Evans 1995; Conway 2018). Whereas both the precise location of IL-23R+ cells
and the exact location of skeletal enthesitis is related to the presence of tensile collagenous fibers,
GCA is well known to develop in the part of the artery which has an internal elastic lamina. This
may reflect an analogous predilection for IL-23 responses to be focused upon such biomechanical
fibers as well as the lamina being a potential target for adaptive immune responses. In GCA, the
temporal artery is also IL-23 responsive, and IL-23 is expressed by local inflammatory cells
(Ciccia 2017).
As well as these anatomical and structural implications, further evidence for the involvement of
IL-23 comes from the presence of IL-23 driven Th17 cells in GCA. These cells are expanded in
GCA and cytokines in the IL-23 pathway, including IL-17, IL-6, IL-21 are elevated. Indeed
pro-inflammatory cytokines including IL-6 and IL-23 that induce Th17 cells are elevated in GCA.
T cell lines from GCA patients have been tested for their inflammation-inducing capacity and a T


Guselkumab (CNTO1959) 
Clinical Protocol CNTO1959GCA2001 Amendment 5
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 25 May 2022
cell subset analysis revealed a strong bias towards the enrichment of Th17 and Th17/Th1 cells
(Deng 1995), including the detection of IL-17+ T cells in the vascular tissue of GCA patients. The
relevance of these cells is further highlighted by the effects of therapeutics on this biology.
Currently, GCs are the standard of care for GCA and are highly effective in normalizing
pro-inflammatory cytokines including IL-6, IL-17, IL-23 and Th17 cell levels in blood and lesional
tissue, providing rationale for testing guselkumab in GCA (Weyand 2011). The pathogenesis of
GCA is incompletely understood and clinical trials with targeted therapies provide an opportunity
to test the relevance of specific pathways that may be driving vascular inflammation, including
IL-23.
Taken together, these observations supply firm scientific evidence to suggest a role for IL-23 in
driving the pathogenesis of large vessel vasculitides such as GCA. These results suggest that
reducing IL-23-mediated inflammation with guselkumab may improve the signs and symptoms of
new-onset and relapsing GCA.
2.2. 
Background
Nonclinical Studies
A full nonclinical development program was conducted with guselkumab in support of initial
global submissions and approvals. This program included general toxicology and toxicokinetic
studies in support of first-in-human dosing, studies in support of Phase 2 and Phase 3 clinical
development, and developmental and reproductive toxicologystudies. A comprehensive overview
of nonclinical data is presented in Section 3 of the guselkumab IB.
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 in this Phase 2 clinical study in GCA.
Details regarding the proposed dose regimen and dose rationale are described in Section 4.3 of this
protocol.
To place the selected clinical dosing for guselkumab in GCA patients into perspective relative to
the existing preclinical data, the predicted human exposure at steady-state (based on the dose tested
in this protocol, ie, 200 mg SC every 4 weeks) was compared with the exposure at the NOAEL in
cynomolgus monkeys following weekly SC administration in the 24-week arm of the subchronic
toxicology study. These data are presented in Table 1.
Table 1: 
Predicted Guselkumab Exposure Margins for the Dosing Regimen to be Evaluated in the
Study
Guselkumab Predicted Exposure Margins at 200 mg SC Dosing
Parameters 
Mean Cmax 
(µg/mL) 
Mean AUC
(µg.day/mL)
Cynomolgus Monkey Exposure at the NOAEL (50 mg/kg/week)
Following 24 Weekly SC Doses
993a 
5412b


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Clinical Protocol CNTO1959GCA2001 Amendment 5
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Status: Approved, Date: 25 May 2022
Table 1: 
Predicted Guselkumab Exposure Margins for the Dosing Regimen to be Evaluated in the
Study
Human Predicted SC Exposure 
30c 
134d
Predicted Exposure Margine 
33.1 
40.4
Abbreviations: AUC=area under the curve; Cmax=maximum serum concentration; NOAEL=no observed adverse effect level;
SC=subcutaneous
a. Highest observed concentration following the twenty fourth 50 mg/kg dose (SC)
b. AUC from Day 161 through 168 (1 week after the last 50 mg/kg dose).
c. Highest predicted concentration at steady state following SC administration.
d. Predicted human AUC at steady state following 200 mg SC every 4 weeks administration. Each value was divided by 4 to
obtain the AUC over one week, which in turn corresponds to the AUC interval for cynomolgus monkeys. Simulation of
human pharmacokinetic exposure was based on a body weight of 70 kg.
e. Exposure margins represent the ratio between guselkumab exposure metrics in the cynomolgus monkey compared with those
predicted in humans.
From a nonclinical perspective, the risk to GCA patients at the selected guselkumab dose regimen
is considered low based on no adverse findings observed in cynomolgus monkeys. As shown in
Table 1, the predicted exposure margins for the selected SC dose (200 mg SC every 4 weeks)
relative to the exposures at the NOAEL in cynomolgus monkeys are approximately 33- to 40-fold
for mean area under the curve and mean Cmax, respectively, which is considered adequate to
support the long-term SC dosing in the guselkumab GCA Phase 2 study. Further supportive clinical
data for the selected guselkumab doses in terms of safety are described in Section 4.3.
Clinical Studies
Guselkumab has demonstrated efficacy in PsO and has received marketing approval in several
countries and regions globally for the treatment of adults with moderate to severe plaque PsO,
including in the US, Canada, European Union, Latin America, and the Asia Pacific region. The
approved guselkumab dose for PsO is 100 mg by SC injection at Weeks 0, 4, and every 8 weeks
thereafter. In addition, guselkumab has been approved for the treatment of PsA  in multiple
countries, and for generalized pustular PsO, erythrodermic PsO, and palmoplantar pustulosis in
Japan.
This protocol represents the first study of guselkumab in participants with GCA.
Phase 3 development is ongoing globally in PsA, and a seamless global Phase 2/3 clinical program
is ongoing in Crohn’s disease, a global Phase 2b/3 program is ongoing in ulcerative colitis, and
there are several Phase 2 studies with guselkumab in other indications.
 
The Phase 2 study of the Phase 2/3 guselkumab Crohn’s disease program evaluated the
induction dose regimens up to a maximum dose of 1200 mg IV every 4 weeks given 3 times.
 
The ongoing Phase 3 studies of the Phase 2/3 guselkumab Crohn's disease program are
evaluating an induction dose of 200 mg IV every 4 weeks given 3 times and a maintenance
dose of 100 mg SC every 8 weeks or 200 mg SC every 4 weeks.


Guselkumab (CNTO1959) 
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Status: Approved, Date: 25 May 2022
 
In the Phase 2b/3 guselkumab UC program induction doses up to 400 mg IV every 4 weeks
and maintenance doses up to 200 mg SC every 4 weeks were evaluated. For the Phase 3
induction part of the study, 200 mg IV at Week 0, 4, and 8 was chosen for induction regimen.
 
A Phase 2 HS study evaluated the induction dose regimen of 1200 mg IV every 4 weeks given
3 times, as well as a maintenance dose range from 100 mg SC every 8 weeks to 200 mg SC
every 4 weeks.
 
In a Phase 2 LN study and Phase 2 systemic Sclerosis study, guselkumab doses of 400 mg IV
at Weeks 0, 4, and 8 followed by guselkumab 200 mg SC every 4 weeks are being evaluated.
 
A Phase 2a proof-of-concept study with a guselkumab and golimumab combination in UC
which includes a guselkumab monotherapy arm (guselkumab 200 mg IV at Weeks 0, 4, and
8 followed by guselkumab 100 mg SC every 8 weeks) has been completed.
Details about these guselkumab clinical development programs across various indications are
provided in Section 4 of the latest version of the guselkumab IB.
Through the IB cutoff date of 12 July  2021, an estimated 703 healthy participants,
4,068participants with PsO, 109 participants with rheumatoid arthritis (RA), 1,471 participants
with PsA, 182 participants with palmoplantar pustulosis, 230 participants with Crohn’s disease,
175 participants with HS, 540 participants with UC, and 51 participants with familial adenomatous
polyposis have been exposed to guselkumab. Overall, an estimated 7,827 participants have been
exposed to guselkumab in the clinical development program.
The largest clinical experience to date with guselkumab has been in plaque PsO. The safety profile
of guselkumab in participants with moderate to severe plaque PsO is based on data from the Phase
2 study CNTO1959PSO2001 and Phase 3 studies CNTO1959PSO3001, CNTO1959PSO3002,
CNTO1959PSO3003, CNTO1959PSO3006, and CNTO1959PSO3009. Of the 2,711 guselkumab
treated participants, 2,255 participants were exposed for at least 1 year, 1,516 were exposed for at
least 2 years, and 692 participants were exposed for 3 years. The Phase 2 and 3 plaque PsO studies
included a substantial proportion of participants ≥45 years of age. Out of 2,711 participants, a total
of 1,174 (43.3%) patients between the age of 45 and <65 years and 165 (6.1%) patients ≥65 years
of age received guselkumab. No overall differences in safety or efficacy were observed between
older and younger patients who received guselkumab in clinical studies.
2.3. 
Benefit/Risk
2.3.1. 
Risks for Study Participation
Potential Risks of 
Clinical Significance 
Summary of Data/
Rationale for Risk  
Mitigation Strategy
Risks Due to Study Intervention Guselkumab
Clinical worsening of
GCA related to rapid GC
taper
The benefit-risk of guselkumab in
treatment of GCA has not been
established.
Participants are receiving investigational agent
with standard-of-care GCs that are tapered down
(Section 6.5). Participants that are unable to taper


Guselkumab (CNTO1959) 
Clinical Protocol CNTO1959GCA2001 Amendment 5
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Status: Approved, Date: 25 May 2022
Potential Risks of
Clinical Significance
Summary of Data/
Rationale for Risk  
Mitigation Strategy
GCs (GC dependent) for their GCA will not be
permitted to participate in the study (Section 5.2).
Participants that experience a flare will be
allowed to use rescue GCs as needed
(Section 6.8.3).
Participants may discontinue study intervention if
it is not in their best interest or if they need to
initiate certain protocol-prohibited medications in
Section 6.8and Section 7.1).
Serious infections and
reactivation of latent
infections
Available animal and human data
suggest that blockade of IL-23
may be associated with an
increased infection risk. Infections
have been identified as adverse
reactions 
of 
guselkumab,
including respiratory infections,
herpes simplex, tinea infections,
and gastroenteritis.
Participants with a history of, or ongoing, chronic,
or recurrent infectious disease, evidence of active
or untreated latent opportunistic infections
including tuberculosis (TB), will be excluded
from the study (Section 5.2).
Participants receiving a live viral or bacterial
vaccination within 12 weeks of first study
intervention will be excluded from the study. In
addition, participants must agree not to receive a
live viral or live bacterial vaccination during the
study and for 12 weeks after receiving the last
dose of study intervention (Section 5.2).
Participants will be instructed to seek medical
attention if they develop signs or symptoms
suggestive of an infection, and investigators are
instructed in the protocol to monitor for signs or
symptoms 
of 
infections, 
including 
TB
(Sections 8.2.10 and 8.2.10).
A participant’s study intervention must be
discontinued if an opportunistic infection
including TB develops, and study intervention
must be interrupted if the participant develops a
serious infection, including but not limited to
sepsis or pneumonia, and continuation or
discontinuation of study intervention should be
discussed and decided with the medical monitor
or designee (Section 7.1).
Hypersensitivity
reactions, 
including
serious hypersensitivity
reactions.
Serious hypersensitivity reactions
including anaphylaxis have been
reported 
in 
postmarketing
experience with guselkumab in
PsO  patients. Hypersensitivity,
including anaphylaxis, urticaria
Participants with known allergy, hypersensitivity,
or intolerance to guselkumab or its excipients will
be excluded from the study.
Sites are instructed that before any administration
of study intervention, appropriately trained


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and rash have been identified as
ADRs for guselkumab.
personnel, and medications (eg, injectable
epinephrine) 
must be available to treat
hypersensitivity reactions, including anaphylaxis.
In addition, all participants must be observed
carefully for signs and symptoms of a
hypersensitivity reaction (eg, urticaria, pruritis,
angioedema, wheezing, dyspnea, or hypotension)
(Section 8.2.8).
Any participant who develops a serious
hypersensitivity reaction such as anaphylaxis
must discontinue study intervention (Section 7.1).
Malignancy  
The preponderance of preclinical
data suggests that blockade of
endogenous IL-23 would not be
detrimental and may in fact be
beneficial 
in 
tumor
immunosurveillance 
and 
host
protection; however, a risk of
malignancy cannot be excluded.
Participants with a current malignancy or a
history of malignancy within 5 years prior to
screening (with exceptions noted in Section 5.2)
will be excluded from the study.
Participants 
who 
have 
a 
history 
of
lymphoproliferative 
disease, 
including
lymphoma; a history of monoclonal gammopathy
of undetermined significance or signs and
symptoms 
suggestive 
of 
possible
lymphoproliferative 
disease, 
such 
as
lymphadenopathy or splenomegaly will be
excluded from the study (Section 5.2).
During the conduct of the study, participants will
undergo regular clinical monitoring including
routine safety labs and inquiring of any adverse
events (AEs) to assess for any changes in health
status that may indicate a possible malignancy.
Participants who develop a malignancy during the
study (with the exception of no more than 2
localized basal cell skin cancers that are treated
with no evidence of recurrence or residual
disease) will be discontinued from study
intervention (Section 7.1).
Liver injury  
A serious adverse event (SAE) of
‘toxic hepatitis’ was reported in
the ongoing Phase 2/3 guselkumab
Crohn’s disease program in a
participant 
who 
received
guselkumab 1200 mg IV at Weeks
0, 4, and 8, and 200 mg SC at
Week 12. 
Based 
on 
the
hepatocellular pattern of injury,
During the conduct of the study, liver function
tests will be monitored at regular intervals in
accordance 
with 
regulatory 
guidance
(Section 10.9) (FDA 2009). In addition, the
induction doses in this study will be lower and
will not exceed 400 mg IV.
Participants with marked liver enzyme elevations
or symptoms or signs of liver dysfunction (eg,


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temporal relationship of the event
to guselkumab exposure, and the
exclusion of alternative etiologies,
this event may represent drug-
induced liver injury possibly
related 
to 
guselkumab.
Transaminase increases have been
identified as an adverse reaction of
guselkumab. In PsA studies
transaminase 
increases 
were
observed with a higher incidence
with a maintenance dose of
100 mg every 4 weeks compared
to100 mg every 8 weeks.
jaundice), 
should 
undergo 
a 
thorough
investigation for possible causes of liver injury. A
participant must have their study intervention
discontinued if the participant has severe liver test
abnormalities that are not transient and are not
explained by other etiologies (Section 7.1).
Immunosuppression 
Although guselkumab has been
studied 
with 
other
immunosuppressives 
in 
other
diseases, 
there 
may 
be an
increased risk of infection or
malignancy.
In order to minimize the theoretical increased risk
of infection or malignancy with the combination
of guselkumab with immunosuppressive therapy,
the baseline dose of oral GCs on study entry is
limited to ≤60 mg/day prednisone or equivalent,
which must be tapered starting at Week 1.
Additionally, participants are also excluded from
the study if they have received a variety of
immunomodulatory therapies if received within a
protocol defined timeframe from first study
intervention (Section 5.1 and 5.2).
Risks Due to Study Procedures
Risks associated with 
fluorodeoxyglucose 
(FDG)- 
positron 
emission 
tomography 
(PET)/computed 
tomography 
(CT) 
imaging 
include 
radiation exposure and
risk of allergic reaction
to the tracer.
These risks are well recognized,
with radiation exposure for a
PET/CT scan being lower than if
both scans were to be done
separately, and the risk of serious
complications like an allergic
reaction is very rare.
Trained and experienced physicians will be
performing the procedure during this study,
participant 
preparation 
and 
precautionary
measures will be taken to reduce tracer uptake in
normal tissues (fasting, well pre-hydrated, limited
activity and kept warm).
A low-dose protocol will be used for
fluorodeoxyglucose 
positron 
emission
tomography/computed 
tomography
(FDG-PET/CT) scanning which results in an
estimated average effective radiation dose
between 9 and 15 mSv when a full body CT
(approximately 2-8mSv) is used and a fixed dose
of 10mCi*  of FDG (approximately 7 mSv) is
administered. All participants will be limited to
two FDG-PET/CT scans over the course of the
main study (Grayson 2018; Willowson 2012).


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In the long-term extension (LTE) period, 1
additional FDG-PET/CT scan will be performed
at Week 104 (LTE Week 52) or if a participant
has a flare. If a participant has a GCA flare prior
to LTE Week 52, an attempt should be made to
perform the FDG-PET/CT imaging within 1 week
from identification of GCA flare by the principal
investigator during the LTE period. In case of a
flare occurring within 1 month of the Week 52
main study FDG-PET/CT scan  (or other
timeframe in accordance with local country
regulations), the FDG-PET/CT scan will not be
performed.
* 
In countries where local regulations require adjustment of the dose this should be done in consultation with the
sponsor.
More detailed information about the known and expected benefits and risks of guselkumab may
be found in the IB.
2.3.2. 
Benefits for Study Participation
There is no established benefit to participants of receiving study intervention. There is evidence
that inflammation associated with increased IL-17 pathway activity mediated by IL-23 may be
involved in the pathogenesis of GCA. Given the scientific rationale for IL-23 blockade and that
ustekinumab may provide benefit in the treatment of GCA (Section 2.1.2), participants may
experience an improvement in disease status during treatment with guselkumab. Participants in the
study will also help in furthering development of this drug to treat GCA and increased
understanding of GCA. Thus, the knowledge gained from this study has the potential to benefit
many more patients suffering with GCA, and thus offers potential public health benefits.
Participants may also experience some benefit from the participation in a clinical study irrespective
of receiving study treatment, due to regular visits and assessments monitoring their overall health.
2.3.3. 
Benefit-Risk Assessment for Study Participation
Guselkumab has undergone extensive nonclinical and clinical development as summarized in the
latest version of the IB and described briefly in Section 2.2. The collective efficacy and safety
results of the Phase 1, Phase 2, and Phase 3 clinical studies in healthy volunteers and patients with
plaque PsO and PsA established a favorable benefit-risk profile for guselkumab in the treatment
of plaque PsO  and PsA. There is a global regulatory approval for the plaque PsO  and PsA
indications. In Japan, guselkumab has also been studied and received regulatory approval for the
treatment of erythrodermic PsO, generalized pustular PsO, and palmoplantar pustulosis. This
clinical experience provided support for the ongoing development of guselkumab in other
inflammatory diseases such as Crohn’s disease, UC, lupus nephritis and systemic sclerosis.


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Although at present there are no clinical results for guselkumab in the treatment of GCA, current
available scientific data suggests IL-23 may play an important role in the pathogenesis of GCA
(Section 2.1.2) and inhibition of IL-23 cytokines will be helpful in controlling GCA while being
able to taper GCs. In addition, a phase 2 study evaluating secukinumab in GCA (Venhoff 2021),
provided evidence that targeting IL-17 is efficacious.  The secukinumab data is particularly
relevant for guselkumab since secukinumab targets IL-17 which is connected with  the IL-23
pathway that is targeted by guselkumab. A 26-week GC taper is considered the standard in clinical
trials in GCA, and combined with a rescue GC therapy option provides an appropriate mitigation
for potential GCA flares.
The guselkumab dose to be evaluated (ie, 200 mg SC every 4 weeks) in this protocol is higher than
the approved dose regimen of guselkumab in PsO and PsA. Based on the data from nonclinical
toxicology studies (Section 2.2), the predicted exposure margins during the treatment period
relative to the exposure at the NOAEL identified in cynomolgus monkey are adequate to support
the proposed clinical doses (Section 4.3).
The guselkumab dose to be evaluated in this protocol is 200 mg SC every 4 weeks from Week 0
to Week 48 for the main study (see Sections 4.2, Scientific Rationale for Study Design and
Section 4.3, Justification for Dose). Based on a population pharmacokinetics (PK) analyses in
patients with PsO or PsA, age (≥65 years)was not found to have significant impact on guselkumab
apparent clearance following SC administration; therefore, guselkumab PK exposure in elderly
participants is not expected to be substantially different from the non-elderly.
Potential risks of guselkumab, including those of serious infection and malignancy, and the risk of
tapering participants of GCs are being addressed via judicious inclusion/exclusion criteria,
frequent study visits to allow for close monitoring of patient safety, guidelines for participant
management (including monitoring of clinical laboratory tests and treatment discontinuation
criteria), detailed description of allowed and prohibited concomitant medications, and
comprehensive medical monitoring of data by the sponsor during the conduct of the studies. In
addition, a comprehensive safety monitoring plan with oversight from an independent Data
Monitoring Committee (DMC) will be implemented to ensure the safety of guselkumab in
participants with new-onset or relapsing GCA (Section 9.6).
In summary, the collective preclinical and clinical evidence for the anti-IL-23 mechanism of action
in GCA, and the benefit-risk profile of guselkumab established to date in PsO and other immune
mediated diseases, provide a strong scientific and clinical rationale for pursuing development of
guselkumab in patients with GCA and for the investigation of guselkumab in this Phase 2 program.
Taking into account the measures taken to minimize risk to participants in this study, the potential
risks associated with guselkumab are justified by the potential benefits that may be provided to
participants with GCA.


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3. 
OBJECTIVE AND ENDPOINTS
Objectives 
Endpoints
Primary
To evaluate the efficacy of guselkumab 
compared to placebo, in combination 
with a 26-week glucocorticoid (GC)
taper regimen, in adult participants with
new-onset or relapsing giant cell
arteritis (GCA).
The proportion of participants achieving GC-free
remission at Week 28
Secondary
To evaluate the efficacy of guselkumab 
compared to placebo, in combination  
with a 26-week GC  taper regimen, in
adult participants with new-onset or 
relapsing GCA  as measured by 
alternative definitions of GC  free 
remission, GC-sparing effects, and 
prevention of disease flares.
The proportion of participants achieving GC-free
remission from Week 28by visit through Week 52
The proportion of participants achieving GC-free
remission 
and 
normalization 
of erythrocyte
sedimentation rate (ESR) at Week 28 and by visit
through Week 52
The proportion of participants achieving GC-free
remission and normalization of C-reactive protein
(CRP)at Week 28 and by visit through Week 52
The proportion of participants achieving GC-free
remission and normalization of both ESR and CRP at
Week 28 and by visit through Week 52
The cumulative GC  dose through week 28 and
through Week 52
The time to first GCA disease flare or discontinuation
of study intervention due to AE of worsening of GCA
through Week 28 and through Week 52
The number of GCA disease flares or discontinuation
of study intervention due to AE of worsening of GCA
through Week 28 and through Week 52
To evaluate the safety of guselkumab, in
combination with a 26-week GC  taper
Number/proportion of participants with treatment-
emergent adverse events (TEAEs)through Week 60


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Objectives 
Endpoints
regimen, in adult participants with new- 
onset or relapsing GCA. 
Number/proportion of participants with TEAEs by
system organ class with a frequency threshold of 5%
or more through Week 60
Number/proportion of participants with treatment-
emergent serious adverse events (SAEs) through
Week 60
Number/proportion of participants with clinically
significant abnormalities in vital signs, laboratory
safety tests through Week 60
To evaluate the PK and immunogenicity
of guselkumab, in combination with a
26-week GC  taper regimen, in adult
participants with new-onset or relapsing
GCA.
Mean 
(standard 
deviation 
[SD]) 
serum
concentrations of guselkumab through Week 52 in
participants receiving active study intervention.
Number/proportion of participants with antibodies to
guselkumab in participants receiving active study
intervention.
Exploratory
To explore the longer-term efficacy of 
guselkumab compared to placebo, in 
combination with a 26-week GC  taper
regimen, in adult participants with new-
onset or relapsing GCA.
Proportion of participants in sustained remission
through Week 52
To evaluate the changes in immune- 
markers to guselkumab compared to
placebo, in combination with a 26-week 
GC taper regimen, in adult participants
with new-onset or relapsing GCA.
Change from baseline in CRP through Week 52
Change from baseline in ESR through Week 52
To 
explore 
the 
changes 
in 
pharmacodynamic (PD) markers and 
arterial 
vessel 
wall 
inflammation 
following administration of guselkumab 
in adult participants with new-onset or
relapsing GCA. 
Assessment of IL-23 pathway  related and disease
related biomarkers in serum, whole blood, and
peripheral blood mononuclear cell (PBMC) through
Week 52.
Large-Vessel Imaging (fluorodeoxyglucose positron
emission 
tomography/computed 
tomography
[FDG-PET/CT]) changes from baseline at Week 52
(or flare)


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Objectives 
Endpoints
To explore changes in participant 
reported 
Clinical 
Outcome 
Assessments, pain and fatigue, and 
physician reported outcomes and digital 
health 
parameters 
following 
administration of guselkumab in adult 
participants with new-onset or relapsing
GCA. 
Change from baseline on electronic patient-reported
outcome (ePRO): Patient's Global Assessment of
Disease 
Activity 
(PGA), 
Pain 
Assessment,
Functional Assessment of Chronic Illness Therapy
(FACIT)-Fatigue and short form-36 (SF-36) by visit
through Week 52
Change from baseline on clinician reported outcome:
Physician's Global Assessment of Disease Activity
(PhGA)by visit through Week 52
Change from baseline in Actigraphy Watch collected
continuous data on physical activity, mobility, and
sleep by visit through Week 52
Exploratory Objectives for the Long-Term Extension (LTE) period
To evaluate long-term efficacy of 
guselkumab in adult participants with 
new-onset or relapsing GCA  
The proportion of participants achieving GC-free
remission from Week 52 (LTE Week 0) through
Week 104 by visit (LTE Week 52)
The time to first GCA disease flare from Week 52
(LTE week 0) through Week 104 (LTE Week 52).
To evaluate the continued safety of 
guselkumab in adult participants with 
new-onset or relapsing GCA. 
Number/proportion of participants with TEAEs or
SAEs from Week 52 (LTE Week 0) through Week
112 (LTE Week 60)
Number/proportion of participants with clinically
significant abnormalities in vital signs and laboratory
safety tests from Week 52 (LTE Week 0) through
Week 112 (LTE Week 60)
To evaluate the PK and immunogenicity 
of guselkumab, in adult participants 
with new-onset or relapsing GCA. 
Mean (SD) serum concentrations of guselkumab
from Week 52 through Week 104 (LTE Week 52) in
participants receiving active study intervention.
Number/proportion of participants with antibodies to
guselkumab in participants receiving active study
intervention


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Objectives 
Endpoints
To explore the changes in PD markers 
and arterial vessel wall inflammation 
following administration of guselkumab 
in adult participants with new-onset or 
relapsing GCA in the LTE period. 
Assessment of IL-23 pathway related and disease
related biomarkers in serum and whole blood at Week
104 (LTE Week 52)
Large-Vessel Imaging (FDG-PET/CT) changes from
baseline and Week 52 at Week 104 (LTE Week 52)
or flare
To explore changes in participant 
reported 
Clinical 
Outcome 
Assessments, pain and fatigue, and 
physician reported outcomes following 
administration of guselkumab in adult 
participants with new-onset or relapsing 
GCA in the LTE period. 
Change from baseline on electronic patient-reported
outcome (ePRO): Patient's Global Assessment of
Disease 
Activity 
(PGA), 
Pain 
Assessment,
Functional Assessment of Chronic Illness Therapy
(FACIT)-Fatigue and short form-36 (SF-36) at Week
76 (LTE Week 24), Week 104 (LTE Week 52) or
Flare visit.
Change from baseline on clinician reported outcome:
Physician's Global Assessment of Disease Activity
(PhGA) at Week 76 (LTE Week 24) Week 104 (LTE
Week 52) or Flare visit.
Refer to Section 8for evaluations related to endpoints.
Definitions of Efficacy Endpoints:
Remission of GCA: No signs or symptoms of GCA and adherence to the 26-week taper without
GCA flare.
GCA Flare: For participants in GCA remission, flare is defined as the recurrence of signs and
symptoms of GCA, with or without elevation of inflammatory markers, and the necessity for an
increase in GC dose for GCA.
Having CRP/ESR elevations in isolation without clinical signs and symptoms attributable to GCA,
does not qualify as flare, unless the investigator decided to increase the GC  dose (see
Section 6.8.3).
Sustained remission of GCA:No signs and symptoms of GCA through Week 52, and completion
of the protocol defined GC  taper, and not having required GC rescue therapy at any time by
Week 52.


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HYPOTHESIS
The primary hypothesis is that guselkumab treatment with a 26-week GC taper is superior to
placebo with a 26-week GC taper in participants with new-onset or relapsing GCA as assessed by
the proportion of participants achieving GC-free remission at Week 28.
4. 
STUDY DESIGN
4.1. 
Overall Design
This is a randomized, double-blind, placebo-controlled, parallel, multicenter, interventional
Phase 2 Proof-of-Concept study evaluating the efficacy, safety, PK, and immunogenicity of
guselkumab for the treatment of active new-onset or relapsing GCAin adult participants.
A target of approximately 51 participants will be enrolled in this study. Participants will be
randomly assigned into 2 treatment groups in a 2:1 ratio ofguselkumab versus placebo.
 Group 1: Guselkumab (200 mg SC every 4 weeks)
Participants will receive guselkumab 200 mg SC every 4 weeks at Week 0 through Week
48.
 Group 2: Placebo
Participants will receive placebo SC every 4 weeks at Week 0 through Week 48.
Participant randomization will be stratified by new-onset and relapsing GCA (relapsing
preferentially limited to 70% to ensure some enrollment of new-onset GCA but may be increased
depending on the rate of enrollment of relapsing versus new-onset GCA), and by baseline GC dose
(≤30 mg/day or >30 mg/day).
The placebo comparator (in addition to standard-of-care background therapy of GCs) will be used
in this study through Week 48 of the Main study to allow for blinded, placebo-controlled
evaluation of the long-term efficacy and safety of guselkumab in participants with GCA.
Participants on placebo that continue into the LTE will continue to receive placebo until the
participant reaches Week 100 (LTE Week 48) or experiences a GCA flare, or until unblinding of
the study due to completion of the main study, whichever occurs first.
The total duration of the study is up to 66 weeks for the main study: a screening period of
≤6 weeks, a 48-week main study treatment period, and a 12-week safety follow-up period after
the last dose (a final efficacy visit 4 weeks after the last dose and a safety follow-up visit 12 weeks
after the last dose). Participants that continue in the LTE period may continue in the study for a
total duration of 112 weeks.
Participants that experience a flare should have a Flare visit with assessments performed according
to the SoA preferably within 1 week of having the flare. In case a participant is diagnosed as having
a flare during a study visit or  shortly before a planned study visit,  the Flare visit and regular visit
can be combined. Overlapping procedures and assessments need only be performed once. The


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FDG-PET/CT scan can be scheduled separately from other  assessments. In case of subsequent
flares, a Flare visit should be performed according to the SoA with the exception of the FDG-
PET/CT scan. Depending on the circumstances, reduced assessments may  be considered in
consultation with the sponsor.
Efficacy, safety, PK, immunogenicity, and biomarkers will be assessed according to the Schedule
of Activities (SoA; Section 1.3). An optional pharmacogenomic blood sample will be collected
from participants who consent to the collection of these samples (where local regulations permit).
The primary efficacy analysis will be performed after all participants have completed Week 28
efficacy assessments (or discontinued). Additional secondary endpoints will be completed at
Week 28 and Week 52. Three planned database locks (DBLs) will occur, at Week 28 and at
Week 60 for the main study and a final DBL lock when the last participant completes last visit in
the LTE period. The study will be double-blind until all participants have completed the main
study and  associated Week 60 DBL has occurred.
An independent DMC will be commissioned for this study. Refer to Sections 9.6 (Data Monitoring
Committee) and for the Committees Structure in Section 10.3.
Long-term Extension Treatment Period (Week 52 to Week 112; optional for eligible
participants)
Participants who complete the Week 52 visit and are assessed to be in GC-free remission, may
have the option to participate in the LTE period of the study.
If a participant is in GC-free remission at Week 48, the participant will be informed of the
possibility to participate in the LTE period and continue to receive study intervention. Study
intervention will continue to be blinded, meaning that a participant will continue to receive the
treatment that had been allocated to that participant (placebo or guselkumab) in the main study.
After the Week 52 evaluations, if the participant is eligible and has consented for the LTE, the
participants will continue to receive SC study intervention every 4 weeks starting at Week 52 (LTE
Week 0) under this protocol’s study extension until participants reach Week 100 (LTE Week 48)
or until a participant experiences a GCA flare, or the participants discontinues treatment due to
unblinding after the Week 60 DBL for the Main study, or until the Sponsor makes a decision not
to continue this study, whichever occurs first. Participants who continue treatment as part of the
study extension will be intermittently evaluated per the protocol for efficacy, PK, and safety. The
LTE period is followed by a 12-week safety follow-up period after the last dose (a final efficacy
visit 4 weeks after the last dose and a safety follow-up visit 12 weeks after the last dose).
Participants that experience a flare should have have a Flare visit with assessments performed
according to the SoA preferably within 1 week of having the flare and an early termination visit
approximately 12 weeks after the last dose. In case a participant is diagnosed as having a flare
during a study visit or  shortly before a planned study visit,  the Flare visit and regular visit can be
combined.  Overlapping procedures and assessments need only be performed once. The FDG-
PET/CT scan can be scheduled separately from other  assessments.


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After the Week 60 DBL, the study will be unblinded to treatment. Any participants in the LTE that
are on placebo will be informed and administration of study intervention will be discontinued. The
participants may still continue in the study until Week 112 or until the end of the safety follow-up
period in case they experienced a GCA flare.
A diagram of the study design is provided in Section 1.2.
4.2. 
Scientific Rationale for Study Design
A double-blind, placebo-controlled study was selected where participants would be randomized to
guselkumab or placebo in addition to the standard-of-care background therapy. This study design
was selected as a true placebo comparator group is unethical for this serious disease condition.
Therefore, placebo and experimental treatments will be added to a standard-of-care regimen of
GCs.
With this standard-of-care regimen, participants will enter on GCs (not exceeding 60 mg/day
prednisone or its equivalent) and will be tapered off their GCs by Week 26 to minimize
confounding treatment effects of GCs on efficacy endpoints and to determine GC-sparing effects
of study intervention in order to reduce the risks of long-term GC use. Similar GC  tapering
regimens have been used in some recent GCA  studies (Unizony 2013; Stone 2017), and are
currently used in ongoing investigational studies for GCA.
For participants who will be treated with guselkumab, an IV induction dose regimen  of
guselkumab was originally  chosen, followed by SC doses as this follows the typical
induction-maintenance treatment paradigm, that has been used to treat multiple immune-mediated
disease under investigation with guselkumab including CD, HS, UC, and LN. This was expected
to ensure target inhibition of IL-23 in the large vessel walls in this proof-of-relevance study. New
insights based on results from these ongoing internal studies as well as data from external studies
with therapeutics that have been evaluated for treatment of GCA, suggest that IV induction dose
regimens may not be needed and that SC onlydose regimens are expected to be sufficient to ensure
target inhibition of IL-23 in GCA (discussed in section 4.3). Per Amendment 5, newly enrolled
participants will start study intervention on a SC dose regimen.
Additional details on doses and dose justification are described in Section 4.3.
Blinding, Control, Study Phase/Periods, Intervention Groups
A placebo control will be used to establish the frequency and magnitude of changes in clinical
endpoints that may occur in the absence of active intervention. Randomization will be used to
minimize bias in the assignment of participants to intervention groups, to increase the likelihood
that known and unknown participant attributes (eg, demographic and baseline characteristics) are
evenly balanced across intervention groups, and to enhance the validity of statistical comparisons
across intervention groups. Blinded intervention will be used to reduce potential bias during data
collection and evaluation of clinical endpoints.


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Deoxyribonucleic acid (DNA) and Biomarker Collection
Optional pharmacogenomic samples may be obtainedfrom participants only when specific consent
is provided by signing the optional genetic research informed consent form (ICF). It is recognized
that genetic variation can be an important contributory factor to interindividual differences in
intervention distribution and response and can also serve as a marker for disease susceptibility and
prognosis. Pharmacogenomic research may help to explain interindividual variability in clinical
outcomes and may help to identify population subgroups that respond differently to an
intervention. The goal of the pharmacogenomic component is to collect DNA to allow the
identification of genetic factors that may influence the PK, PD, efficacy, safety, or tolerability of
guselkumab and to identify genetic factors associated with GCA or the response to guselkumab
treatment.
Biomarker samples (where local regulations permit) will be collected to evaluate cellular and
molecular mechanism of action of guselkumab  or help to explain interindividual variability in
clinical outcomes or may help to identify population subgroups that respond differently to a
treatment. The goal of the biomarker analyses is to further define the mechanism of action of
selective blockade of IL-23 with  guselkumab  in GCA and aid in evaluating the intervention-
clinical response relationship. Biomarker samples may be used to help address emerging issues
and to enable the development of safer, more effective, and ultimately individualized therapies.
Collection of biomarker samples, including samples from the optional pharmacogenomic
collection, will only occur where local regulations permit and may not occur at all clinical sites.
4.2.1. 
Participant Input into Design
An advisory board of GCA patients and several GCA patient interviews were used to consult
patients on the study design and conduct. Participants provided insights on the protocol design,
where they perceived barriers to participation, and how the clinical study experience could be
improved for patients. In particular, feedback was received about preference of repeat imaging
over repeat temporal artery biopsy for GCA, there were reservations about a 1:1 randomization
ratio versus a 2:1 ratio, and the highest-ranking patient concerns were continued fatigue affecting
their daily lives and the fear of losing sight. Additionally, there was feedback on some of the
inclusion/exclusion criteria and the SoA.
Improvements to willingness to participate likely to impactrecruitment strategy included provision
of logistical support with study site visits (transportation, home study visits) and access to the
medication after the trial, which were considered to make trial participation more attractive.
4.2.2. 
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 primary ethical concern is that although the medication has shown to have efficacy in humans
in other diseases, efficacy has not been shown in GCA, and response to medication in GCA is
theoretical at this time.
The total blood volume to be collected is considered to be an acceptable amount of blood to be
collected over this time period from the population in this study based upon the standard of the
American Red Cross standard.
4.3. 
Justification for Dose
The dose regimen of 200 mg SC every 4 weeks will be evaluated for this Phase 2 POC study in
participants with active new-onset or relapsing GCA.
This dose regimen was selected based on the objective of determining the maximum efficacy of
guselkumab for treatment of GCA, the approved dose regimen for PsO  and PsA, the ongoing
investigation for induction and maintenance therapy in Crohn’s disease, UC, LN, and systemic
sclerosis, the available safety information from relevant preclinical and clinical studies and the
results from clinical studies from other approved and/or emerging GCA therapeutics.
In previous versions of the protocol (prior to amendment 5), a guselkumab dose regimen consisting
of an IV induction regimen (400 mg at weeks 0, 4 and 8) followed by a SC maintenance regimen
of 200 mg every 4 weeks starting from Week 12 had been chosen for this POC study based on
evidence available at time of initial protocol development and outlined in protocol versions 1-4.
Based on scientific rationale and emerging data, it is now considered that an IV induction dose
regimen of guselkumab would not be necessary for the treatment of GCA. The  dose regimen of
200 mg SC every 4 weeks starting at Week 0 is anticipated to provide sufficient drug exposure to
treat GCA. Results from a Phase 2 trial with secukinumab, an anti-IL-17A monoclonal antibody,
reveal that a SC regimen targeting IL-17 can be effective at treating GCA (Venhoff 2021).  These
data are particularly relevant since IL-17 is an inflammatory cytokine within the IL-23 pathway.
The SC dose regimen in this study is also supported by the results of the phase 3 tocilizumab data
(Stone 2017), which demonstrated that a beneficial effect on GCA can be obtained without the use
of an IV induction dose regimen and at doses that are similar to those utilized for inflammatory
arthritis.
Furthermore, the lowest IV induction dose regimen (200 mg of guselkumab at Week 0, 4  and 8)
was shown to be efficacious in  Phase 2 dose ranging studies for Crohn’s disease (GALAXI
[Sandborn 2022]) and Ulcerative Colitis (QUASAR [Dignass 2022]). This lowest IV dose regimen
was therefore selected for further evaluation in the ongoing Phase 3 studies for these two IBD
populations (see also Section 2.2). In addition, the CRP reduction associated with guselkumab was
not found to be dose dependent in these trials (Sandborn  2022). This is pertinent for GCA as
systemic markers of inflammation, CRP and ESR, are utilized to follow disease activity in GCA.
These data suggest that an IV induction regimen would not add incremental value to the treatment
of GCA with guselkumab.
In population PK analyses for guselkumab PsA or PsO studies, age was not found to have
significant impact on guselkumab apparent clearance following SC administration in participants
with PsA (range: 19 to 74 years; 38 [5.1%] participants ≥65 years old and 13 [1.74%] participants


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≥70 years old) or PsO (range: 18-82 years; 70 [4.8%] participants ≥65 years old and 4 [0.3%]
participants ≥75 years old) (Population Pharmacokinetics Analysis 2016; Population
Pharmacokinetics Analysis 2019). As a monoclonal antibody, guselkumab PK exposure in elderly
participants is not expected to be substantially higher than that in the non-elderly.
With respect to safety of the SC dose regimens, the predicted exposure margins for the 200 mg SC
every 4 weeks dose regimen relative to the NOAEL of 50 mg/kg/week in cynomolgus monkeys
are approximately 33 to 40, as shown in Table 1, which are considered adequate to support the
long-term SC dosing (for chronic maintenance) in the guselkumab GCA clinical development
programs. Guselkumab is approved for the treatment of plaque PsO and PsA with a good long-
term clinical safety profile (with data generated primarily at 100 mg SC every 8 weeks), and dose
regimens up  to 200 mg SC every 4 weeks are being investigated in clinical trials with no new
safety concerns identified to date.
The available clinical safety data, along with acceptable safety margins and other studies
evaluating similar dose regimens, make it reasonable to study GCA with this dose regimen  of
200 mg of guselkumab SC every 4 weeks.  This dose regimen is anticipated to provide sufficient
drug exposure for the treatment of GCA. In addition, the SC administration will be more
convenient for study participants.
4.4. 
End of Study Definition
End of Study Definition
The end of study is considered as the last visit for the participant in the study. The final data from
the study site will be sent to the sponsor (or designee) after completion of the final participant visit
at that study site, in the time frame specified in the Clinical Trial Agreement.
Study Completion Definition
A participant will be considered to have completed the main study if the participant has completed
study treatment through Week 48of the main study phase, and the 12-week safety follow-up for
the main study (Week 60) or, if a participant continued onto the LTE period, has completed main
study Week 52 visit. For the LTE period, a participant will be considered having completed the
study ifthe participant has completed study treatment through Week 100 (LTE Week 48) and the
12-week safety follow-up for the LTE period (Week 112 [LTE Week 60]).


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5. 
STUDY POPULATION
Screening for eligible participants will be performed within 6 weeks before administration of the
study intervention. Refer to Section 5.4 for conditions under which the repeat of any screening
procedures is allowed.
The inclusion and exclusion criteria for enrolling participants in this study are described below. If
there is a question about these criteria, the investigator must consult with the appropriate sponsor
representative and resolve any issues before enrolling a participant in the study. Waivers are not
allowed. The inclusion and exclusion criteria will be evaluated by the sponsor prior to enrollment
of participants.
For a discussion of the statistical considerations of participant selection, refer to Section 9.2.
5.1. 
Inclusion Criteria
Each potential participant must satisfy all the following criteria to be enrolled in the study:
1. 
Male or female (according to their reproductive organs and functions assigned by
chromosomal complement)
2. 
At least 50 years of age, inclusive
3. 
Diagnosis of GCA according to the revised American College of Rheumatology
criteria (Salehi-Abari 2016):
 Age at onset of disease ≥50 years, AND
 No criteria excluding GCA (ENT and eye inflammation, kidney, skin and
peripheral nervous system involvement, lung infiltration, lymphadenopathies, stiff
neck and digital gangrene or ulceration), AND
 Presence of 3 points (p) or more out of 11 with at least one point from domain I
Domain I criteria:
 new onset localized headache (1p)
 sudden onset of visual disturbances (1p)
 unequivocal symptoms of PMR defined as shoulder and/or hip girdle pain
associated with inflammatory morning stiffness (2p)
 jaw claudication (1p)
 abnormal temporal artery (up to 2p)
Domain II criteria:
 Unexplained fever and/or anemia (1p)
 History or current ESR ≥50 mm/hour* (1p)
 GCA compatible pathology (vascular and/or perivascular fibrinoid necrosis
along with leucocyte infiltration (1p) /and granuloma (1p)
* If historic ESR is unavailable, a history of CRP ≥ 24.5 mg/L (2.45 mg/dL) is required.
The CRP value was derived from published data both from GCA and RA patients
(Hayreh 1997; Paulus 1999; Wolfe 1997).


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4. 
4.1 
Criterion modified per Amendment 1
4.2 
Criterion modified per Amendment 4
4.3 
Criterion modified per Amendment 5.
 Temporal artery biopsy revealing features of GCA either at time of diagnosis or
at other timepoint during disease history
OR,
 Evidence of cranial GCA either at time of diagnosis or at other timepoint during
disease history by cranial doppler-ultrasound, cranial Magnetic Resonance Imaging
or Magnetic Resonance Angiography, or other imaging modality upon agreement
with the sponsor.
OR
Evidence of GCA by angiography or cross-sectional imaging (ultrasound, MRI,
CT, PET).
5. 
Have new onset or relapsing GCA
New onset: diagnosis of GCA within 6 weeks of first study intervention*
Relapsing GCA: diagnosis of GCA >6 weeks before first study intervention and in the
meantime achieved remission (absence of signs and symptoms attributable to GCA and
normalization of ESR (<30 mm/hr) and CRP (<10 mg/L or <1 mg/dL) included)
including previous treatment with ≥40 mg/day prednisolone (or equivalent) for
≥2 weeks.
* The 6-week time window must be calculated from the date of suspected GCA
diagnosis. Suspected diagnosis is defined as the date when GC therapy was initiated to
treat suspected GCA.
6. 
Criterion modified per Amendment 2
6.1. Have active GCA within 6 weeks of first study intervention
Active GCA: presence of signs and symptoms of GCA (Domain I, see
Section 10.5) and elevated ESR ≥ 30 mm/hr, or CRP ≥ 10 mg/L (or 1 mg/dL),
attributed to active GCA.
ESR ≥ 30 mm/hour or CRP ≥ 10 mg/L (or 1 mg/dL) is not required if active GCA
has been confirmed by a positive temporal artery biopsy or ultrasound or other
imaging modality (see inclusion criterion 4) within 6 weeks of first study
intervention


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Concomitant or previous medical therapies received
7. 
At screening, receiving oral GC  treatment with a minimum dose of 20 mg/day and
maximum dose of 60 mg/day (prednisone or equivalent) for the treatment of active
GCA.
8. 
Clinically stable GCA disease on a GC dose between 20 and 60 mg/day (prednisone or
equivalent) at randomization such that the participant is able to safely participate in the
protocol defined prednisone taper regimen, in the opinion of the investigator.
Contraception
9. 
A woman must be:
Not of childbearing potential
OR
Of childbearing potential and
Practicing a highly effective method of contraception (failure rate of <1% per year when
used consistently and correctly) and agrees to remain on a highly effective method while
receiving study intervention and until 12 weeks after last dose - the end of relevant
systemic exposure.
Definitions of childbearing potential and examples of highly effective methods of
contraception are located in Section 10.7.
10. 
A woman of childbearing potential must have a negative urine pregnancy test at
screening and at Week 0 prior to administration of study intervention.
11. 
A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted
reproduction during the study and for at least 12 weeks after receiving the last
administration of study intervention.
12. 
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
during the study and for at least 12 weeks after receiving the last administration of study
intervention.
13. 
A male participant must agree not to donate sperm for the purpose of reproduction or
plan to father a child during the study and for a minimum of 12 weeks after receiving
the last dose of study intervention.


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14. 
Criterion modified per Amendment 5
14.1. Are considered eligible according to the following TB screening criteria:
a) Have no history active TB before screening.
b) have no history of untreated latent TB. An exception is made for participants who
satisfy one of the following criteria:
 are currently receiving treatment for latent TB,
OR
 will initiate treatment for latent TB before the first administration of study
intervention,
Note: For participants with a history of treated latent TB, there must be documentation
of having completed appropriate treatment prior to the first administration of study
intervention. It is the responsibility of the investigator to verify the adequacy of previous
anti-TB treatment and provide appropriate documentation.
c) Have no signs or symptoms suggestive of active TB upon medical history and/or
physical examination.
d) Have had no recent close contact with a person with active TB. An exception is
made if such participants are referred to a physician specializing in TB to determine
if treatment is warranted or not. This evaluation must be adequately documented
and, if treatment is recommended, the participant must be receiving appropriate
treatment prior to the first administration of study intervention.
e) Within 2 months before the first administration of study intervention, have a
negative QuantiFERON-TB test result, or have a newly identified positive
QuantiFERON-TB test result (see Laboratory Manual) in which active TB has been
ruled out and for which appropriate treatment for latent TB has been initiated before
the first administration of study intervention. Within 2 months before the first
administration of study intervention, a negative tuberculin skin test, or a newly
identified positive tuberculin skin test in which active TB has been ruled out and for
which appropriate treatment for latent TB has been initiated before the first
administration of study intervention, is additionally required if the QuantiFERON-
TB test is not approved/registered in that country or the tuberculin skin test is
mandated by local health authorities.
A suspected false-positive initial QuantiFERON-TB test must be repeated. If repeat
testing is NOT positive, the participant must be referred to a physician specializing in
TB to determine if the initial test can be considered a false-positive. This evaluation
must be adequately documented prior to the first administration of study intervention.
If repeat testing is positive, however, it will be considered a true-positive and the
participant is only eligible if active TB has been ruled out and appropriate treatment for
latent TB has been initiated as described above.
A participant whose first QuantiFERON-TB test result is indeterminate should have the
test repeated. If the second QuantiFERON-TB test result is also indeterminate, the
participant may be enrolled without treatment for latent TB, if active TB is ruled out,
their chest radiograph shows no abnormality suggestive of TB (active or old, inactive


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TB), and the participant has no additional risk factors for TB as determined by the
investigator. This determination must be promptly reported to the sponsor’s medical
monitor and recorded in the participant’s source documents and initialed by the
investigator.
NOTE: The QuantiFERON-TB test and the tuberculin skin test are not required at
screening for participants with a history of latent TB and ongoing treatment for latent
TB or documentation of having completed adequate treatment as described above;
participants with documentation of having completed adequate treatment as described
above are not required to initiate additional treatment for latent TB.
f) Have a chest radiograph (both posterior-anterior and lateral views, or per country
regulations where applicable), taken within 3 months before the first administration
of study intervention and read by a qualified radiologist (or pulmonologist in
accordance with local regulations), with no evidence of current, active TB or old,
inactive TB. A chest CT scan is also acceptable if obtained instead of a chest
radiograph outside of the protocol.
15. 
Have screening laboratory test results within the following parameters, if one or more
of the laboratory parameters is out of range, a single retest of laboratory values is
permitted:
*For ALT/AST values >2 upper limit of normal (ULN) participants can only be included
if bilirubin is normal.
a. Hemoglobin  
≥9 g/dL 
SI:≥90 mmol/L
b. White blood cells 
≥3.0×103/µL 
SI: ≥3.0 GI/L
c. Neutrophils 
≥1.5×103/µL 
SI: ≥1.5 GI/L
d. Platelets 
≥100×103/µL  
SI: ≥100 GI/L
e. Serum creatinine 
≤1.8mg/dL 
SI:≤159 μmol/L
f. Aspartate aminotransferase (AST) 
≤3 × ULN*
g. Alanine aminotransferase (ALT) 
≤3 × ULN*
General
16. 
Criterion modified per Amendment 3
16.1. Must sign an ICF indicating that the participant understands the purpose of, and
procedures required for, the study and is willing to participate in the study.
17. 
Criterion modified per Amendment 3
17.1. Must sign a separate ICF  if the participant agrees to provide an optional DNA
sample for research (where local regulations permit). Refusal to give consent for the
optional DNA research sample does not exclude a participant from participation in the
study.


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18. 
Must be willing and able to adhere to all specified requirements, including but not
limited to completion of the required assessments, adherence to the visit schedule, and
compliance with the lifestyle restrictions as specified in this protocol.
Inclusion criterion for LTE period
19. 
Participants are eligible for participation in the LTE period of the study if the participant:
1. Has completed Week 52 visit of the main study, AND
 has no signs and symptoms of active GCA, AND
 completed treatment study intervention according to the protocol, AND
 completed 26-week protocol defined GC-taper without the need to use rescue
medication for GCA, AND
 has not experienced a GCA flare through Week 52
2. Has not had any study intervention-related SAE or severe AE
3. Is able and willing to continue (blinded) treatment with study intervention
5.2. 
Exclusion Criteria
Any potential participant who meets any of the following criteria will be excluded from
participating in the study:
Coexisting Medical Conditions or Past Medical History
1. 
Has any known severe or uncontrolled GCA complications (aortic, thoracic or
abdominal aneurysm, history of myocardial infarction or stroke due to GCA, significant
or permanent and complete visual loss in at least 1 eye due to GCA)
2. 
Criterion modified per Amendment 3
Has any rheumatic disease other than GCA such as Takayasu's Arteritis, granulomatosis
with polyangiitis (Wegener's), RA, systemic lupus erythematosus that could interfere
with assessment of GCA
3. 
Has a current diagnosis or signs or symptoms of severe, progressive, or uncontrolled
renal, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic,
hematologic, rheumatologic, psychiatric, or metabolic disturbances, (or, in the
investigators opinion, has any other concomitant medical condition that places the
participant at risk by participating in this study).
4. 
Criterion modified per Amendment 5:


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4.1a. Has or has had any major ischemic event, within 12 weeks of first study
intervention
4.1b. Has a personal history of arterial thrombosis or venous thromboembolism
(including deep venous thrombosis [DVT] and Pulmonary Embolism [PE])
5. 
Has a history of lymphoproliferative disease, including lymphoma; a history of
monoclonal gammopathy of undetermined significance; or signs and symptoms
suggestive of possible lymphoproliferative disease, such as lymphadenopathy or
splenomegaly
6. 
Has any comorbidities requiring 3 or more courses of systemic GCs within 12 months
of first study intervention, AND,
 inability, in the opinion of the investigator, to withdraw GC  therapy through
protocol-defined taper regimen due to suspected or established adrenal
insufficiency,
    OR,
 currently on systemic chronic GC therapy for reasons other than GCA and be GC
dependent and have the potential to flare due to GC tapering (eg, unstable asthma,
unstable COPD)
7. 
Has a history of, or ongoing, chronic or recurrent infectious disease, including but not
limited to chronic renal infection, chronic chest infection (eg, bronchiectasis), recurrent
urinary tract infection (recurrent pyelonephritis or chronic non remitting cystitis),
fungal infection (eg, mucocutaneous candidiasis, but excluding fungal infections of the
nail beds), or open, draining, or infected skin wounds or ulcers
8. 
Has or has had a serious infection (eg, sepsis, pneumonia, or pyelonephritis), or has
been hospitalized or received IV antibiotics for an infection during the 2 months before
first study intervention
9. 
A potential participant with the following features will be excluded from participating
in the study protocol
 During the 6 weeks prior to baseline, have had ANY of (a) confirmed SARS-CoV-2
(Coronavirus Disease 2019; COVID-19) infection (test positive), OR (b) suspected
SARS-CoV-2 infection (clinical features without documented test results), OR (c)
close contact with a person with known or suspected SARS-CoV-2 infection
 Exception: may be included with a documented negative result for a validated
SARS-CoV-2 test
(i) obtained at least 2 weeks after conditions (a), (b), (c) above (timed from
resolution of key clinical features if present, eg, fever, cough, dyspnea)


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AND
(ii) with absence of ALL conditions (a), (b), (c) above during the period between
the negative test result and the baseline study visit
 NOTES on COVID-related exclusion:
1. If a participant is excluded due to recent COVID-19-related features, the
reason for screen failure should be documented in the case report form under
the exclusion criterion of having a condition for which participation would
not be in the participant’s interest or could confound study assessments.
2. The field of COVID-related testing (for presence of, and immunity to, the
SARS-CoV-2 virus) is rapidly evolving. Additional testing may be
performed as part of screening and/or during the study if deemed necessary
by the investigator and in accordance with current regulations / guidance
from authorities / standards of care.
10. 
Has or has had a nontuberculous mycobacterial infection or clinically significant
opportunistic infection (eg, cytomegalovirus, pneumocystosis, invasive aspergillosis)
11. 
Has a history of latent or active granulomatous infection, including histoplasmosis or
coccidioidomycosis, before screening. Refer to inclusion criterion 14 for information
regarding eligibility with a history of latent TB
12. 
Has a history of an infected joint prosthesis or has received antibiotics for a suspected
infection of a joint prosthesis within 6 months of first study intervention, if that
prosthesis has not been removed or replaced
13. 
Has a history of or is infected with human immunodeficiency virus (HIV [positive
serology for HIV antibody]); tests positive for hepatitis B virus (HBV) infection (refer
to Section 10.6); has antibodies to hepatitis C virus (HCV) at screening
14. 
Has experienced a recent single dermatomal herpes zoster eruption within the past
4 months. Has ever had multi-dermatomal herpes zoster (defined as appearance of
lesion outside the primary or adjacent dermatome) or central nervous system zoster
infection
15. 
Currently has a malignancy or has a history of malignancy within 5 years before
screening (with the exception of a non-melanoma skin cancer that has been adequately
treated with no evidence of recurrence for at least 3 months before the first study
intervention administration or cervical carcinoma in situ that has been treated with no
evidence of recurrence for at least 3 months before the first study intervention)
Note: premalignant lesions should be discussed with the sponsor medical monitor


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16. 
Has a transplanted organ (with exception of a corneal transplant >3 months before the
first study intervention)
17. 
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:
 Ideation level 4: Some intent to act, no plan; OR
 Ideation level 5: Specific plan and intent; OR
 Any of the following suicidal behaviors:
 Actual suicide attempts
 Interrupted attempts
 Aborted attempts
 Preparatory actions
AND
is confirmed to be at risk by the investigator based on an evaluation by a mental health
professional. The final decision on excluding a participant will be made at the judgment
of the investigator.
In addition, participants with C-SSRS ratings of Ideation level 1 
3 (ie, Wish to be
Dead, Non-Specific Active Suicidal Thoughts, Active Suicidal Ideation with Any
Methods (Not Plan) without Intent to Act), or non-suicidal self-injurious behavior who
are determined to be at risk by the investigator may also not be randomized.
18. 
Has known allergies, hypersensitivity, or intolerance to guselkumab or its excipients
19. 
Criterion modified per Amendment 5
19.1. Has had a fracture of the hip or leg, major trauma or spinal cord injury, hip or
knee replacement within 8 weeks before screening; had major surgery (eg, requiring
general anesthesia and hospitalization), within 8 weeks before screening, or has not
fully recovered from major surgery, or has major surgery planned during the time the
participant is expected to participate in the study (48 weeks). Note: Participants with
planned surgical procedures to be conducted under local anesthesia may participate
20. 
Has a history of drug or alcohol abuse according to the Diagnostic and Statistical
Manual of Mental Disorders, 5th edition, within 1 year before screening
Concomitant or previous medical therapies received
21. 
Criterion modified per Amendment 1


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21.1. Has received within 90 days, or 5 half-lives (whichever is greater), or failed
treatment with  any investigational or approved biologic agent or Janus kinase
inhibitor prior to first study intervention, including but not limited to:
 IL-23 inhibitor therapy (including but not limited to guselkumab,
risankizumab, tildrakizumab, brazikumab, mirikizumab, ustekinumab)
 tocilizumab (Actemra)
 sirukumab, sarilumab, mavrilimumab, abatacept, belimumab
 TNFα-inhibitors (including infliximab, adalimumab, etanercept,
certolizumab, golimumab)
 IL-12/23 inhibitors (ustekinumab)
 IL-17 inhibitors (secukinumab, ixekizumab, brodalumab)
 JAK-inhibitors (including tofacitinib, baricitinib, upadacitinib)
OR,
Received the following therapy within  6 months, or 5 half-lives (whichever is
greater):
 natalizumab, visilizumab
OR,
Received the following therapy within 12 months, or 5 half-lives (whichever is
greater):
 rituximab, alemtuzumab
Note: Not listed biologic agents should be discussed and agreed with the sponsor
medical monitor
22. 
Criterion modified per Amendment 2
22.1. Has been treated with:
Within 6 months of study intervention:
 Any cytotoxic agents (cyclophosphamide, chlorambucil, nitrogen
mustard, or other alkylating agents)
 Intravenous immunoglobulin (IVIG), apheresis therapy (plasmapheresis
or leukopheresis)
Within 3 months of first study intervention or at least 5 half-lives (whichever is
greater):
 Hydroxychloroquine, cyclosporine A, azathioprine, tacrolimus,
sirolimus, sulfasalazine, leflunomide with cholestyramine washout or
mycophenolate mofetil/mycophenolic acid
Within 6 weeks of first study intervention:


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 Intramuscular, intra-articular, intrabursal, epidural, intra-lesional or IV
GCs
 Any complementary therapies, including traditional/Chinese medicines,
herbs, ointments, or procedures (eg, acupuncture), that have the
potential to activate (eg, echinacea) or inhibit (eg, Tripterygium
wilfordii Hook F) the immune system
 Any complementary therapies, including traditional/Chinese medicines
and herbs, that have the potential to interact with antithrombotic agents
(eg, St. John’s Wort) in those taking antithrombotic agents
Any questions or concerns with the use of these therapies should be discussed with
the study sponsor and/or medical monitor.
23. 
Criterion modified per Amendment 4
23.1. Has started Methotrexate (MTX) within 12 weeks of first study intervention. If
started MTX >12 weeks prior to first study intervention MTX must have been at a stable
dose for minimally 4 weeks and must not be receiving more than 25 mg oral or SC
MTX per week
24. 
Has chronic continuous use of systemic GCs for >4 years or inability, in the opinion of
the investigator, to withdraw GC treatment through protocol-defined taper regimen due
to suspected or established adrenal insufficiency
25. 
Has received an investigational intervention (including investigational vaccines) within
3 months or 5 half-lives (whichever is longer) or used an invasive investigational
medical device within 3 months of the first study intervention or is currently enrolled
in an investigational study
26. 
Bacille Calmette-Guérin (BCG) vaccination within 12 months or any other live
bacterial or live viral vaccination within 12 weeks of randomization
27. 
Has taken any prohibited or restricted medications as noted in Section 6.8, Concomitant
Therapy before the first study intervention
General
28. 
Has donated blood (volume ≥450 mL) within 60 days prior to screening
29. 
Is unable or unwilling to undergo multiple venipunctures because of poor tolerability
or lack of easy access to veins
30. 
Lives in an institution on court or authority order


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31. 
Currently participating or intends to participate in any other study using an
investigational agent or procedure during the conduct of this study
32. 
Is an employee of the investigator or study site, with direct involvement in the proposed
study or other studies under the direction of that investigator or study site, as well as
family members of the employees or the investigator.
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 the participant no longer meets all eligibility criteria, then the participant should be
excluded from participation in the study. Section 5.4 describes options for retesting. The required
source documentation to support meeting the enrollment criteria is noted in Section 10.3.
5.3. 
Lifestyle Considerations
Potential participants must be willing and able to adhere to the following lifestyle restrictions
during the study to be eligible for participation:
1. 
Refer to Section 6.8for 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 during the study and
for 12 weeks after receiving the last dose of study intervention
4. 
Must agree not to receive a BCG vaccination during the study and for 12 months after
receiving the last dose of study intervention
5. 
Must not receive guselkumab outside of this protocol or participate in any other clinical
study with an investigational agent while in this study and must terminate study
participation if they do. A participant who intends to participate in any other clinical
study with an investigational agent should complete the appropriate visit(s) as described
in Section 1.3 before the participant terminates study participation
6. 
Must be willing and able to complete study related questionnaires and document clinical
symptoms, AEs, etc


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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.
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 up to 6 weeks. In such cases, the first abnormal test result will not
constitute a screen failure. If a laboratory abnormality occurs, the site is encouraged to wait for all
laboratory tests to be completed to ensure other laboratory tests do not need to be repeated, as only
1 retest of laboratory tests is allowed. A screening laboratory test(s) analyzed by the central
laboratory may be repeated more than once in the event of suspected error in sample collection or
analysis as long as the result is obtained within the screening period.
Rescreening
Individuals who do not meet the criteria for participation in this study (screen failure) may be
rescreened 1 time. Rescreened participants will be assigned a new participant number, undergo the
informed consent process, and then start a new screening phase. Previous TB evaluation results
(including the QuantiFERON-TB test and chest radiograph) from the first screening event may be
used if they meet the specified protocol criteria as described in Section 5.1. Medical Monitor
approval is required prior to the study site obtaining a new informed consent for rescreening. In
addition, individuals who were screen fails due to a trial suspension may be rescreened a second
time with sponsor approval.
FDG-PET/CT results from the first screening event do not have to be repeated when performed
within a reasonable period of time before randomization and after consultation of the Sponsor.
5.5. 
Criteria for Temporarily Delaying
[Enrollment/Randomization/Administration of Study Intervention
Administration]
This section is not applicable for this protocol.


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6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY
6.1. 
Study Interventions Administered
Participants in the study will be on background GC (see also Section 5.1, inclusion criterion 7 and
inclusion criterion 8), supplied by the clinical study site. The GC dose tapering is described in
Section 6.8.1 and a tapering schedule is provided in Section 10.8.
In addition to remaining on the standard-of-care noted above, participants will be randomized with
a 2:1 ratio to 1 of 2 treatment groups as described below:
 
Guselkumab: Participants will receive guselkumab 200 mg SC every 4 weeks, Week 0 through
Week 48.
 
Placebo: Participants will receive placebo SC every 4 weeks Week 0 through Week 48.
Participants will remain on their assigned treatment through Week 48. Participants will receive 2
SC injections (either active or placebo) at each SC dosing visit. Participants of the LTE period will
continue to receive SC injections every 4 weeks (either active or placebo) starting at Week 52
(LTE Week 0) through Week 100 (LTE Week 48) or until the participants have a GCA flare or the
participants discontinues treatment due to unblinding after the Week 60 DBL for the Main study,
or until a decision is made not to continue clinical development in this GCA population, whichever
occurs first.
Since multiple SC injections are administered at visits, 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 placebo for guselkumab will be manufactured and provided under the
responsibility of the sponsor. Refer to the guselkumab IB for a list of excipients.
Detailed instructions on the administration of study intervention will be provided in the Site
Investigational Product Procedures Manual (sIPPM).
For details on rescue medications, refer to Section 6.8.3. For a definition of study intervention
overdose, refer to Section 6.7.
6.1.1. 
Combination Products
 
For this protocol, the term combination product refers to the single integral drug-device
combination
 
The sponsor-manufactured combination product for use in this study is the PFS assembled
with an UltraSafe Plus™ Passive Needle Guard (PFS-U). Additional details on the PFS-U are
provided in Section 6.2 and the guselkumab IB
 
All combination product deficiencies (including failure, malfunction, improper or inadequate
design, manufacturer error, use error, and inadequate labeling) shall be documented and


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reported by the investigator throughout the study. For studies using a combination product,
these deficiencies will be reported as product quality complaints (PQC) (see Section 10.4 in
Appendix 10: Adverse Events, Serious Adverse Events, Product Quality Complaints, and
Other Safety Reporting: Definitions and Procedures for Recording, Evaluating, Follow-up,
and Reporting)and appropriately managed by the sponsor.
6.2. 
Preparation/Handling/Storage/Accountability
Preparation/Handling/Storage
For SC administrations, guselkumab will be supplied as a 100 mg/mL sterile solution in a single-
use prefilled syringe (PFS) assembled in an UltraSafe Plus™ Passive Needle Guard (PFS-U). For
SC administration, placebo for guselkumab will be supplied as a 1 mL sterile solution in a single-
use PFS assembled in a PFS-U.
Guselkumab and placebo for guselkumab should be clear and colorless to light yellow solution
that may contain small translucent particles. Do not use guselkumab or placebo for guselkumab if
the liquid is cloudy or discolored or has large particles. Protection from light is not required during
the preparation and administration of the study intervention material but avoid direct exposure to
sunlight. Aseptic technique must be used during the preparation and administration of the study
intervention material.
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 drug accountability form. All study intervention will be
stored and disposed of according to the sponsor's instructions.
Accountability
The investigator is responsible for ensuring that all study intervention received at the site is
inventoried and accounted for throughout the study.
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


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dispensed again, even  to the same participant. Study intervention may not be relabeled or
reassigned for use by other participants. The investigator agrees neither to dispense the study
intervention from, nor store it at, any site other than the study sites agreed upon with the sponsor.
Further guidance and information for the final disposition of unused study interventions are
provided in the sIPPM.
6.3. 
Measures to Minimize Bias: Randomization and Blinding
Intervention Allocation - Procedures for Randomization and Stratification
Central randomization will be implemented in this study. Participants will be randomly assigned
to 1 of 2 intervention groups 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 new-onset and relapsing GCA and
baseline GC use (≤30 mg/day or >30 mg/day). The interactive web response system (IWRS) will
assign a unique intervention code, which will dictate the intervention assignment and matching
study intervention kit for the participant. The requestor must use his or her own user identification
and personal identification number when contacting the IWRS  and will then give 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, reference number, and storage conditions. The label will not
identify the study intervention in the container. However, if it is necessary for a participant's safety,
the study blind may be broken, and the identity of the study intervention ascertained. The study
intervention number will be entered in the eCRF when the study intervention is administered. The
study interventions will be identical in appearance and will be packaged in identical containers.
The investigator will not be provided with randomization codes. The codes will be maintained
within the IWRS, which has the functionality to allow the investigator to break the blind for an
individual participant.
Data that may potentially unblind the intervention assignment (ie, study intervention serum
concentrations, anti-guselkumab antibodies, study intervention preparation/accountability data,
intervention allocation, biomarker, or other specific laboratory data) will be handled with special
care to ensure that the integrity of the blind is maintained and the potential for bias is minimized.
This can include making special provisions, such as segregating the data in question from view by
the investigators, clinical team, or others as appropriate until the time of DBL and unblinding.
Under normal circumstances, the blind should not be broken until all participants have completed
the Main study and the Week 60 database is finalized. Otherwise, the blind should be broken only
if specific emergency intervention/course of action would be dictated by knowing the intervention
status of the participant. In such cases, the investigator may, in an emergency, determine the
identity of the intervention by contacting 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.


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Telephone contact with the sponsor or its designee will be available 24 hours per day, 7 days per
week. In the event the blind is broken, the sponsor must be informed as soon as possible. The date
and reason for the unblinding must be documented in the appropriate section of the CRF 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.
Participants who have had their intervention assignment unblinded should continue to return for
scheduled evaluations.
In general, randomization codes will be disclosed fully only if the study is completed, and the
clinical database is closed. However, as a DBL at Week 28 is specified, the randomization codes
and, if required, the translation of randomization codes into intervention and control groups will
be disclosed to those authorized. At the Week 28 DBL, the data will be unblinded for analysis to
limited sponsor personnel while participants are still participating in the study. Identification of
sponsor personnel who will have access to the unblinded participant-level data will be documented
prior to unblinding. Investigative study sites and participants will remain blinded to initial
treatment assignment until after the Week 60 database is locked.
6.4. 
Study Intervention Compliance
When study intervention is administered by qualified staff, the details of each administration will
be recorded in the eCRF. For SC injections, this will include date and time of SC injection.
Compliance with the treatment schedule is strongly encouraged.
6.5. 
Dose Modification
No study intervention dose adjustment will be permitted through the study.
6.6. 
Continued Access to Study Intervention After the End of the Study
Local regulations on continued access will always take precedence. Plans for continued access
stated in this protocol may change if new information on the benefit-risk profile of guselkumab
becomes available during the study or program.
At the end of their participation in the main study, participants who have completed the study and
are benefiting from the study intervention, as determined by being in GC-free remission for GCA
at Week 52, may be offered the opportunity to enter the LTE period to continue treatment for up
to 12 months.
If analyses performed prior to the first participant’s entry  into the LTE or during the LTE
demonstrate an unfavorable benefit: risk profile or safety concerns arise, the study (and LTE) may
be stopped.
6.7. 
Treatment of Overdose
For this study, any dose of guselkumab greater than 10% above the dose at a single dosing visit
specified in this protocol will be considered an overdose. The sponsor does not recommend


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specific treatment for an overdose. In the event of overdosage, monitor the participant for any signs
or symptoms of adverse reactions and administer appropriate symptomatic treatment immediately.
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 as well as the duration of the overdosing in the CRF
 
Discuss with the medical monitor if one or additional serum sample for PK analysis will be
required and at what timepoints
Decisions regarding dose interruptions will be made by the investigator in consultation with the
medical monitor based on the clinical evaluation of the participant.
6.8. 
Concomitant Therapy
Prestudy therapies including specific GCA therapies administered up to 60 days before first dose
of study intervention must be recorded at screening.
Concomitant therapies including specific GCA therapies must be recorded throughout the study
beginning with start of the screening to the final safety follow-up visit. Concomitant therapies
should also be recorded beyond the final safety follow-up visit only in conjunction with SAEs that
meet the criteria outlined in SAEs that meet the criteria outlined in Section 8.3.1.
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, or other specific categories of interest) different from the study
intervention must be recorded in the eCRF. Recorded information will include a description of the
type of therapy, duration of use, dosing regimen, 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.
Any questions or concerns with the use of concomitant therapies should be discussed with the
study sponsor and/or medical monitor. The sponsor must be notified in advance (or as soon as
possible thereafter) of any instances in which prohibited therapies are administered.
6.8.1. 
Permitted Therapy
Therapy to Prevent and Treat GC-Induced Osteopenia/Osteoporosis
Participants are recommended to receive oral calcium and 25-hydroxy vitamin D supplementation
unless contraindicated (calcium 1000 to 1200 mg and vitamin D 600 800 IU daily in divided
doses). Unless contraindicated, bisphosphonate therapy (eg, alendronate 70 mg weekly or
zoledronate 5 mg annually) may also be administered at the discretion of the investigator for the
prevention of GC-induced osteoporosis (Buckley 2017). Participants with documented


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osteoporosis will be treated with approved drugs for osteoporosis according to local practice or
clinical guidelines (eg, National Osteoporosis Foundation).
Methotrexate
Methotrexate may be used if started >12 weeks prior to the first study administration, but the dose
must remain stable for minimally 4  weeks prior to study agent administration and not exceed
25 mg/week of oral or SC MTX. During the study the MTX dose should stay stable, but may be
reduced or discontinued if necessary for safety reasons or if, in the opinion of the investigator, it
is no longer required to treat the participant’s GCA after Week 28. Folic acid should be taken
concomitantly with MTX according to the local practice.
Anti-Platelet or Anti-Coagulation Therapy
Participants may be treated with anti-platelet therapy (including but not limited to aspirin,
clopidogrel, ticlopidine) or anti-coagulation therapy  (including but not limited to warfarin)
according to the local practice at the discretion of the investigator.
Lipid Lowering Therapy
Use of lipid-lowering agents in participants with elevated lipids is strongly encouraged at any time
during the study in conjunction with the investigator’s clinical judgment and any applicable
professional treatment guidelines.
Anti-Hypertensive Therapy
Participants are permitted to receive stable doses (>2 weeks prior to first study agent
administration) of anti-hypertensive treatment according to the local practice at the discretion of
the investigator. Participants should not initiate anti-hypertensive therapy between randomization
and 4 weeks after the last dose of study intervention, unless discussed and agreed with the sponsor
medical monitor.
Non-steroidal Anti-inflammatory Drugs
Non-steroidal anti-inflammatory drugs (NSAIDs) and other regularly administered analgesics
should not be adjusted for at least 2 weeks prior to the first administration of the study intervention
and through 4 weeks after the last dose of study intervention, and they may be changed only if the
participant develops unacceptable side effects. Participants are permitted to receive the usual
marketed doses approved in the country in which the study is being conducted. NSAIDs, including
aspirin or selective cyclooxygenase-2 (COX-2) inhibitors, and other analgesics (including
injectable NSAIDs, analgesics or other pain-relieving agents) that are used on an “as needed” basis
would generally not be considered to constitute stable dosing. Participants using them in specific
situations (eg, prior to an activity) may be considered stable but these situations should be
discussed with the medical monitor or sponsor prior to enrollment into the study.
Topical Medications
Regular use of topical medications is permitted. “As needed” use of topical NSAIDs, analgesics,
or other pain-relieving agents is permitted, but not within 48 hours prior to study visit. “As needed”


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use of topical GCs is permitted if involving a limited BSA (≤20%), but not within 48hours prior
to a study visit.
Oral Glucocorticoids and Protocol-Defined 26-Week Taper for GCA
Participants must be receiving this medication at screening and be on a stable dose equivalent to
an average daily dose between 20 and 60 mg/day prednisone (or equivalent), for at least 2 weeks
prior to the first study intervention dose. Participants that are on GC other than prednisone or
prednisolone during screening should preferably be switched to prednisone or prednisolone to
follow the GC taper in Section 10.8. If the participant continues on GC other than prednisone or
prednisolone, the Investigator should contact the Sponsor to ensure that the taper is appropriately
adjusted for the GC equivalency compared with prednisone (see Section 10.10). Participants are
required to be receiving at least 20 mg/day prednisone (or equivalent) at screening and
randomization.
A protocol specified 26-Week open-label GC  tapering schedule is provided in Section 10.8.
Adherence to this schedule is required. Participants will remain on the GC dose they were on at
baseline for one week (Week 0). Participant should adhere to the tapering schedule that
corresponds to their entry dose of glucocorticoid (section 10.8) through Week 26 unless they
require use of rescue GC therapy for GCA disease flare. Reason(s) for not tapering GCs should be
documented.
Additional considerations of oral GC use during the study are as follows:
 
If a participant is unable to follow the protocol specified GC taper due to worsening GCA
disease activity requiring an increase in GC dose (GCA flare), further GC dose decreases will
be suspended, and/or their oral GC dose may be temporarily increased (ie, GC rescue, see
section 6.8.3) if deemed necessary by the investigator
 
If a participant is receiving rescue GCs, and thus no longer follows the protocol specified GC
tapering schedule, Investigators are to continue to provide GC as per standard medical care
for GCA
 
It is recommended that participants be educated about and monitored for symptoms of GC
adrenal insufficiency/deficiency (eg, Addisonian symptoms such as fatigue, muscle weakness,
decreased appetite, nausea, vomiting, joint and muscle pain) by study staff during periods of
GC tapering, as appropriate. Investigators should monitor participants at the regular study
visits for any signs and symptoms of Addisonian crisis
 
If a participant is unable to follow the protocol specified GC  taper due to requirement for
increased GC for management of adrenal insufficiency, the participant can make use of the
rescue GC therapy (see Section 6.8.3).
Glucocorticoids for Conditions Other than GCA
Glucocorticoids administered by bronchial or nasal inhalation for treatment of stable concomitant
respiratory conditions may be given as needed. Otic, ocular, topical or other routes of mucosal
delivery of GCs are allowed throughout the study.


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Non-live vaccines, including COVID-19 vaccines
It is recommended that participants are up-to-date on age-appropriate vaccinations prior to
screening as per routine local medical guidelines. When considering use of locally-approved
COVID-19 vaccines in study participants, follow applicable local labelling, guidelines, and
standards of care for patients receiving immune-targeted therapy.
For study participants receiving a locally-approved COVID-19 vaccine, in order to help identify
acute reactions potentially related to COVID-19 vaccine, it is recommended where possible that
vaccine and study drug be administered on different days, separated by as large an interval as is
practical within the protocol.
6.8.2. 
Prohibited Therapies
Use of additional investigational or approved biologic or non-biologic immunosuppressant or
immunomodulatory agents, other than those explicitly allowed in the inclusion/exclusion criteria
(see Sections 5.1 and 5.2), are prohibited including but not limited to, the following:
 biologic agents (eg, Actemra or other anti-IL-6(R), anti-IL-23, anti-IL-12, anti-IL-17, anti-
TNF therapy, mavrilimumab)
 Janus kinase inhibitors (eg, tofacitinib, upadacitinib)
 cell-depleting therapies (eg, abatacept, rituximab, alemtuzumab)
 cytotoxic alkylating agents (eg, chlorambucil, cyclophosphamide)
 new start of MTX
 IV immunoglobulin
 apheresis therapy
 other investigational agents
Oral Glucocorticoids
Use of oral GCs for GCA other than for the protocol-defined taper, is prohibited during the study,
with the exception of use for GC rescue therapy (see Section 6.8.3).
The use of oral GCs (or other systemic GCs) for indications other than GCA during the study
should be limited to only situations for which, in the opinion of the treating physician, there are no
adequate alternatives. This should be discussed with the medical monitor or designee prior to
providing these and may require discontinuation of study drug.
Intramuscular, Intra-articular, Intrabursal, Epidural, Intra-lesional or IV Glucocorticoids
Intramuscular, intra-articular, intrabursal, epidural, intra-lesional, or IV GCs are prohibited from
6 weeks prior to first study intervention until end of study and are also prohibited when used as
chronic continuous systemic GCs for >4 years.


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Complementary Therapies
The use of complementary therapies (eg, herbs, ointments, traditional Chinese medicine,
acupuncture) that have the potential to activate or inhibit the immune system is prohibited
(see Section 5.2). In addition, use of complementary therapies that have the potential to interact
with antithrombotic agents is prohibited in those taking antithrombotic agents.
The use of other complementary therapies is strongly discouraged; in individual cases, use may be
permitted following discussion with the study sponsor and/or medical monitor.
As these lists cannot be exhaustive, please consult the medical monitor to discuss prior to starting
any new therapies not specifically mentioned in inclusion or exclusion criteria or the list of
permitted medications.
6.8.3. 
Rescue Medication
The study site will supply GC rescue medication that will be obtained locally.
Participants who develop a GCA flare or are unable to adhere to the protocol-defined 26-week
open-label GC tapering regimen because of ongoing disease activity should stop the protocol-
defined GC taper and be given open-label rescue therapy with GCs at the discretion of the
investigator. When considering use of rescue GC, a careful assessment should be made by the
investigator whether the symptoms are related to a GCA flare (failure of taper) or are more likely
due to non-inflammatory symptoms which could represent adrenal insufficiency or other
comorbidities.
The participant may continue to receive blinded study agent administrations and continue in the
studyif it is in the best interest for the participant in the opinion of the investigator. Treatment with
GC and/or other GCA medication will be at the discretion of the investigator for the further
duration of the study. If other GCA medication is required, the medical monitor or designee should
be contacted and treatment with study intervention should be discontinued. A wash-out period of
12 weeks is recommended before starting treatment with biologic therapies.
The date and time of rescue medication administration as well as the name and dosage regimen of
the rescue medication must be recorded.
Participants who require rescue therapy for their GCA disease during the protocol-defined GC
taper and up to Week 28 will be deemed non-responders in the primary endpoint analysis.


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7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL
7.1. 
Discontinuation of Study Intervention
A participant’s study intervention must be discontinued if:
 
The participant withdraws consent to receive study intervention
 
The investigator believes that for safety reasons or tolerability reasons (eg, AE) it is in the
best interest of the participant to discontinue study intervention
 
The participant becomes pregnant within the study period (see Section 10.7)
 
The participant develops an opportunistic infection (this does not include candidiasis that is
limited to the mouth)
 
The participant becomes ineligible according to the following TB screening criteria:
 
A diagnosis of active TB is made
 
A participant has symptoms suggestive of active TB based on follow-up assessment
questions and/or physical examination, or has had recent close contact with a person with
active TB, and cannot or will not continue to undergo additional evaluation
 
A participant undergoing evaluation has a chest radiograph with evidence of current
active TB and/or a positive QuantiFERON-TB test result (and/or a positive tuberculin
skin test result in countries in which the QuantiFERON-TB test is not approved/registered
or the tuberculin skin test is mandated by local health authorities), unless active TB can
be ruled out and appropriate treatment for latent TB can be initiated prior to the next study
intervention administration and continued to completion (see also Section 8.2.11).
Indeterminate QuantiFERON-TB test results should be handled as described in
Section 8.2.11. Participants with persistently indeterminate QuantiFERON-TB test
results may continue without treatment for latent TB if active TB is ruled out, their chest
radiograph shows no abnormality suggestive of TB (active or old, inactive TB) and the
participant has no additional risk factors for TB as determined by the investigator. This
determination must be promptly reported to the medical monitor or designee and recorded
in the participant's source documents and initialed by the investigator
 A participant receiving treatment for latent TB discontinues this treatment prematurely or
is noncompliant with the therapy
 
The participant has a serious adverse reaction that is related to an injection 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
 
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


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The participant has a malignancy including squamous cell skin cancer. Consideration may be
given to allowing participants who develop ≤2 basal cell skin cancers that are adequately
treated with no evidence of residual disease to continue to receive study intervention
 
Participant requires dialysis
 
Noncompliance with study drug administration defined as multiple episodes of missing the
window in which to receive study intervention
 
The participant has severe liver test abnormalities that are not transient and are not explained
by other etiologies, as described in Section 10.9.
 
In the LTE period, the study intervention must be discontinued if a participant experiences a
GCA flare. Participants that experience a flare should have a Flare visit with assessments
performed according to the SoA preferably within 1 week of having the flare and an early
termination visit approximately 12 weeks after the last dose.
 
After the study has been unblinded at the Week 60 DBL, participants in the LTE will be
unblinded to treatment. Study treatment of participants on placebo will be discontinued. They
may continue in the study for their planned visits as per the schedule of events until Week 112
or, in case of a GCA flare, until the early termination visit.
Discontinuation of a participant’s study intervention should be considered under the
following conditions:
 
Worsening of GCA based on visual symptoms related to GCA
 
If the participant initiates treatment with prohibited therapies for GCA, the medical monitor
or designee should be contacted to discuss possible discontinuation of study intervention
 
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.
 
Discontinuation of study treatment should be considered for participants who report suicidal
Ideation level 4 (some intent to act, no plan), Ideation level 5 (specific plan and intent), or any
suicidal behavior (actual suicide attempts, interrupted attempts, aborted attempts, or
preparatory actions) on a postbaseline (after Week 0) 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
continue with treatment if agreed to by the medical monitor or designee. Discussion of such
participants with the medical monitor or designee is required
 
The participant develops a severe injection-site reaction, but not meeting criteria specified
above.
A participant will not be automatically withdrawn from the study if he or she must discontinue
treatment before the end of the treatment regimen. If a participant discontinues study intervention
for any reason before the end of the main study phase, they may continue for their planned visits
as per the schedule of events, but without study intervention administration. Depending on the
reason for study treatment discontinuation, assessments may be reduced in consultation with the


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Sponsor. Study intervention assigned to the participant who discontinued study intervention may
not be assigned to another participant.
7.2. 
Participant Discontinuation/Withdrawal From the Study
A participant will be withdrawn from the study for any of the following reasons:
 Lost to follow-up
 Withdrawal of consent
 Death
When a participant withdraws before study  completion, the reason for withdrawal is to be
documented in the CRF and in the source document. Participants who terminate their study
participation before final planned study visit, should receive an early termination visit
approximately 12 weeks after the last administration of study intervention (unless consent is
withdrawn) as specified in the SoA (Sections 1.3 and 1.4). If the reason for withdrawal from the
study is withdrawal ofconsent, then no additional assessments are allowed.
Withdrawal of Consent
A participant declining to return for scheduled visits does not necessarily constitute withdrawal of
consent. Alternate follow-up mechanisms that the participant agreed to when signing the consent
form apply as local regulations permit.
Prior to a participant withdrawing consent for follow-up, the investigator should offer the
participant an opportunity for one of the alternative reduced follow-up mechanisms described
below as well as the opportunity to decline actigraphy assessment described in Section 8.10.
Withdrawal of consent should be an infrequent occurrence in clinical studies (Rodriguez 2015),
therefore, prior to the start of the study the sponsor and the investigator should discuss and reach
a clear understanding of what constitutes withdrawal of consent in the context of the available
reduced follow-up mechanisms listed.
Circumstances for Reduced Follow-up
In the situation where a participant may be at risk for withdrawal of consent and is unable to return
for scheduled visits at the protocol-defined frequency, the investigator may consider options for
reduced follow-up. These may include (as local regulations permit):
Less frequent clinical visits
 Telephone, email, letter, social media, fax, or other contact with:
 
participant
 
relatives of the participant
 
participant’s physicians (general or specialist)
 Review of any available medical records


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Details regarding these contacts must be properly documented in source records including
responses by participants.
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 Section 10.3). 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
To reduce the chances of a participant being deemed lost to follow-up, prior to randomization
attempts should be made to obtain contact information from each participant, eg, home, work, and
mobile telephone numbers and email addresses for both the participant as well as appropriate
family members.
A participant will be considered lost to follow-up if the participant repeatedly fails to return for
scheduled visits and is unable to be contacted by the study site. A participant cannot be deemed
lost to follow-up until all reasonable efforts made by the study-site personnel to contact the
participant are deemed futile. The following actions must be taken if a participant fails to return to
the study site for a required study visit:
 
The study-site personnel must attempt to contact the participant to reschedule the missed visit
as soon as possible, to counsel the participant on the importance of maintaining the assigned
visit schedule, to ascertain whether the participant wishes to or should continue in the study
 
Before a participant is deemed lost to follow up, the investigator or designee must make every
reasonable effort to regain contact with the participant (where possible, 3 telephone calls,


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emails, fax, and, if necessary, a certified letter to the participant’s last known mailing address,
or local equivalent methods). These contact attempts should be documented in the
participant’s medical records
 
Should the participant continue to be unreachable, they will be considered to have withdrawn
from the study
 
Should a study site close, eg, for operational, financial, or other reasons, and the investigator
cannot reach the participant to inform them, their contact information will be transferred to
another study site.
8. 
STUDY ASSESSMENTS AND PROCEDURES
Overview
The SoA summarizes the frequency and timing of efficacy, PK, immunogenicity, biomarker/PD,
pharmacogenomic, and safety measurements applicable to this study.
All visit-specific PRO assessments should be conducted/completed before any tests, procedures,
or other consultations (only exception is urine pregnancy test) to prevent influencing participant
perceptions. All PROs should be completed independently by study participants. It is
recommended that PROs be completed in the following sequence: PGA, pain assessment, SF-36,
FACIT-fatigue and C-SSRS  (except at screening where the C-SSRS is performed as first
assessment after signing informed consent). It is recommended that clinician-reported outcome
procedures be performed in the following sequence: GCA signs and symptoms assessment and
PhGA. Clinician-reported outcome assessments should be performed by an adequately trained
assessor (see Section 8.1 for details).
Laboratory samples: All samples (including for safety, efficacy, and PD/biomarkers) should be
obtained after the PRO assessments but prior to study intervention administration.
Screening Phase
The screening phase is up to 6 weeks duration  before randomization. After written informed
consent has been obtained, all screening evaluations (eg, laboratory test results, medical history,
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. The C-SSRS should be completed as
the first assessment after signing informed consent and before any other tests, procedures, or other
consultations. Participants who meet all the inclusion and none of the exclusion criteria can be
enrolled in the study. Every effort should be made to adhere to the SoA (Sections 1.3 and 1.4) for
each participant. The collection ofAEs will start at the time informed consent is obtained.
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 (Section 8.2.11). Procedures conducted as part of the participant’s
routine clinical management (eg, chest radiograph taken up to 3 months prior to baseline) and
obtained prior to signing of informed consent may be utilized for screening or baseline purposes
provided the procedure meets the protocol-defined criteria.


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All screening evaluations establishing participant eligibility will be performed and reviewed by
the investigator before a participant can be randomized.
A diagnostic confirmation of GCA according to inclusion criterion 4 is required, if one has not
been done this must be performed prior to allowing the participant to complete the full screening.
A de-identified copy of the pathology or imaging report will be required to be provided for study
entry confirmation.
Documentation (historical or local laboratory testing) of unequivocally positive biochemical test
values (as defined in the laboratory’s reference range) should be provided for the following: CRP
and ESR by Westergren.
All participants should be receiving GC  treatment at screening between 20 and 60 mg/day
prednisone or equivalent. GC treatment must be initiated at screening for new-onset or relapsing
GCA participants not currently receiving treatment, and with a dose based upon investigator
clinical decision. An increase in GC dose during screening may be required for some participants
to stabilize their disease activity prior to randomization. Participants are required to have clinically
stable GCA disease at randomization and be able to participate in the GC taper regimen in the
opinion of the investigator. At Baseline (Randomization), doses must be within 20-60 mg
prednisone or equivalent for the starting dose when the protocol-specified GC taper is initiated. At
Week 0 participants will remain on their baseline GC dose that week, and will follow the GC
protocol defined taper regimen from Week 1 as described in Section 6.8.1 and in Section 10.8.
The total blood volume to be collected from each participant will not exceed 300 mL. In addition,
repeat or unscheduled samples may be taken for safety reasons or for technical issues with the
samples.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the eCRF or laboratory
requisition form.
Refer to the SoA (Sections 1.3 and 1.4)for the timing and frequency of all sample collections.
Instructions for the collection, handling, storage, and shipment of samples are found in the
Laboratory Manual that will be provided. Collection, handling, storage, and shipment of samples
must be under the specified, and where applicable, controlled temperature conditions as indicated
in the Laboratory Manual.
Study-Specific Materials
The investigator will be provided with the following supplies:
 
Investigator Site File (includes clinical study protocol and guselkumab IB)
 
Study sIPPM
 
Sample ICFs


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Laboratory Manual and Laboratory kits
 
IWRS Manual
 
eCRF completion instructions
 
ePRO equipment (tablet device questionnaires, completion instructions)
 
Imaging manual
 
Actigraphy watch and instruction for use
 
Patient recruitment materials
8.1. 
Efficacy Assessments
Investigator assessments, inflammatory PD markers, physician’s global assessment and PROs of
efficacy are included in this section. Specific assessments will be collected as noted in Sections 1.3
and 1.4.
 
The PRO instruments will be provided in the local language in accordance with local
guidelines
 
The PRO instruments must be available for regulators and for IRB/ERC submissions
 
The PRO and adverse event data will not be reconciled with one another
If a participant develops a GCA flare (as per Investigator clinical decision and in accordance with
the GCA Flare definition), the participant should be further assessed by the investigator following
the Flare Visit assessments as noted in Sections 1.3 and 1.4.
If a participant has a GCA flare, an attempt will be made to collect event-driven PRO assessments,
preferably before a GC dose increase, if possible.
8.1.1. 
GCA Disease Signs and Symptoms
Efficacy of guselkumab in GCA will be assessed from the presence of GCA activity including
investigator assessment of signs and symptoms of GCA.
Evaluation of clinical signs and symptoms by the dedicated Clinical Assessor at every study visit
according to the SoA will include the following (Hellmich 2020).
Key symptoms
 
Persistent localized headache, often in the temporal area, consistent with GCA
 
Constitutional symptoms (eg, fatigue/malaise) could be considered features of a flare only if
they occur in combination with elevated ESR and/or CRP.
 
Jaw and/or tongue claudication
 
Acute visual symptoms such as amaurosis fugax, acute visual loss, diplopia


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Symptoms of PMR such as recent discreet proximal musculoskeletal symptoms including
aching and stiffness about the upper arms, posterior neck, pelvic girdle, and/or lumbar region
often associated with morning stiffness, gelling, and/or functional limitations
 
Limb claudication, myocardial and cerebrovascular symptoms
Key signs on clinical examination
 
Tenderness and / or thickening of the superficial temporal arteries with or without reduced
pulsation
 
Scalp tenderness
 
Bruits (particularly in the axilla)
 
Reduced pulses/blood pressure of the upper limbs
 
Pathological findings during ophthalmologic examination including anterior ischemic optic
neuropathy, oculomotor cranial nerve palsy/palsies, central retinal artery occlusion, branch
retinal artery occlusion and/or choroidal ischemia.
8.1.2. 
Physician's Global Assessment of Disease Activity (PhGA)
The physician’s global assessment independent of participants’ assessment of the patients GCA
activity is recorded on a 10-cm visual analog scale (VAS) with verbal anchors “No GCA” on the
far-left side of the scale and “Very  severe GCA” on the far right of the scale. The baseline
measurement for the PhGA is defined as the closest measurement taken prior to the initiation of
the Week 0 administration.
8.1.3. 
C-Reactive Protein and Erythrocyte Sedimentation Rate
C-reactive protein and ESR have been demonstrated to be useful as a marker of inflammation in
participants with GCA. In participants with GCA, elevated CRP and ESR have been associated
with more active disease (van der Geest 2015).
Samples for the measurement of CRP  and ESR will be collected from all participants at visits
indicated in the SoA (Sections 1.3 and 1.4). C-reactive protein will be assayed using a validated,
CRP assay and ESR will be assessed using the Westergren method.
8.1.4. 
Patient’s Global Assessment of Disease Activity (PGA)
The patient’s global assessment of their GCA disease activity is recorded on a 10-cm VAS with
verbal anchors on how their GCA feels today are “very poor” on the far-left side of the scale and
“very well” on the far right of the scale. The baseline measurement for the PGA is defined as the
closest measurement taken prior to the initiation of the Week 0 administration.
8.1.5. 
Pain Assessment
Participants will be asked to rate the severity of their average pain now on 10-cm VAS  with
anchors ranging from 0, “no pain” to 10, “the worst pain imaginable”. The baseline measurement
for the pain assessment is defined as the closest measurement taken prior to the initiation of the
Week 0 administration.


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8.1.6. 
FACIT-fatigue
The FACIT-fatigue version 4.0 is a 13-item questionnaire formatted for self-administration that
assesses patient-reported fatigue and its impact upon daily activities and function over the past
7 days. Participants will be asked to answer each question using a 5-point Likert-type scale (0 Not
at all; 1 A little bit; 2 Somewhat; 3 Quite a bit; and 4 Very much). The interpretation of FACIT-
fatigue scores is such that a higher score indicates less fatigue, with a range of possible scores of
0-52, with 0 being the worst possible score and 52 the best (Lai 2011).
8.1.7. 
Short Form 36 (SF-36)
The Medical Outcome Study health measure entitled the 36-item Short-Form Version 2 acute (SF-
36v2 acute) health survey questionnaire was developed as part of the Rand Health Insurance
Experiment and consists of 8 multi-item scales.
 
Limitations in physical functioning due to health problems.
 
Limitations in usual role activities due to physical health problems.
 
Bodily pain.
 
General mental health (psychological distress and well-being).
 
Limitations in usual role activities due to personal or emotional problems.
 
Limitations in social functioning due to physical or mental health problems.
 
Vitality (energy and fatigue).
 
General health perception.
These scales are scored from 0 to 100 with higher scores indicating better health. Another
algorithm yields 2 summary scores, the Physical Component Score and Mental Component Score.
These summary scores are also scaled with higher scores indicating better health) (Ware 1994).
The concepts measured by the SF-36 are not specific to any age, disease, or treatment group,
allowing comparison of relative burden of different diseases and the relative benefit of different
treatments)(Ware 1992).
8.2. 
Safety Assessments
Details regarding the Independent DMC are provided in Committees Structure in Section 9.6.
Adverse events will be reported and followed by the investigator as specified in Section 8.3 and
Section 10.4.
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 condition is reached.
The study will include the following evaluations of safety and tolerability according to the time
points provided in the SoA (Sections 1.3 and 1.4).


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8.2.1. 
Physical Examinations
Physical Examination
Physical examinations will be performed by the investigator or designated physician, nurse
practitioner or physician assistant as specified in the SoA  (Sections 1.3 and 1.4). Any new,
clinically significant finding (in the opinion of the investigator) must be captured as an AE. In
addition, resolution of any abnormal findings during the study will be noted in the source document
and in the eCRF.
The full physical examination will be performed including: the head and neck, chest, abdomen,
and extremities, as well as including examinations based on the individual’s medical history and
manifestations of GCA.
Specific assessment of GCA related signs and symptoms will be performed by a clinical assessor
as described in Section 8.1.1 and at timepoints specified in the SoA (Section 1.3 and 1.4).
Assessment of the participants for safety may  require some physical examination by an
investigator.
Heightand Weight
Height and weight will be measured as specified in the SoA (Sections 1.3 and 1.4 [only weight]).
Participants will be instructed to remove shoes and outdoor apparel and gear prior to this
measurement.
8.2.2. 
Vital Signs
Temperature, pulse/heart rate, respiratory rate and blood pressure will be assessed at each visit.
At study intervention SC administration visits, vital signs should be obtained before the SC
injection, and ifthe participant reports any symptoms after study intervention administration.
Blood pressure and pulse/heart rate measurements will be tested in both arms using a completely
automated device. Manual techniques will be used only if an automated device is not available.
Bilateral measurement  of blood pressure and pulse is required for the first measurement only per
visit. Subsequent measurements can be performed on a single arm (unilateral).
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).
8.2.3. 
Electrocardiograms
A 12-lead electrocardiogram (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


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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.
8.2.4. 
Clinical Safety Laboratory Assessments
Blood samples for blood chemistry, hematology, coagulation, serology, and other safety laboratory
assessments 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 panels will be performed by the central laboratory (see Section 10.2) unless
otherwise specified or approved by the medical monitor or designee:
 
Hematology assessments
 
Blood chemistry assessments
 
Coagulation assessment (screening only)
 
Serology assessment (screening only)
 
QuantiFERON-TB test or TB skin test (screening only; performed locally).
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.
8.2.5. 
Pregnancy Testing
Urine pregnancy testing will be done for women of childbearing potential only (performed
locally), see definition in Section 10.7. Additional urine pregnancy tests may be performed, if
applicable, 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.
8.2.6. 
Columbia-Suicide Severity Rating Scale
No signal of suicidal ideation and behavior has been observed in the clinical trials of guselkumab
to date. However, in light of reports concerning suicidal ideation and behavior in patients with
plaque PsO  treated with an IL-17R antagonist (brodalumab), the C-SSRS will be used as a
screening tool to prospectively evaluate suicidal ideation and behavior among study participants
(Rodriguez 2019).
The C-SSRS measures 5 possible levels of suicidal ideation and 4 possible suicidal behaviors, as
well as non-suicidal self-injurious behavior. The C-SSRS is an investigator-administered
questionnaire (Mundt 2013; Posner 2011). Two versions of the C-SSRS will be used in this study,
the Lifetime version and the Since Last Contact version. The Lifetime version will be conducted
during the screening visit and the Since Last Contact version will be conducted at all other visits.


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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 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. 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
Ideation level 4 or 5 (ie, Suicidal Ideation with Intention to Act, Suicidal Ideation with Specific
Plan and Intent), 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 Ideation level 1-3 (ie, Wish to be Dead, Non-Specific Active
Suicidal Thoughts, Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act)
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 C-SSRS 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 level 4 (some intent to act, no plan), Ideation level 5 (specific plan and
intent), or any suicidal behavior (actual suicide attempts, interrupted attempts, aborted attempts,
or preparatory actions) on a postbaseline (after Week 0) 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


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the medical monitor or designee. Discussion of such participants with the medical monitor or
designee is required (see Section 7.1). The final decision on suitability for continuing in the study
will be made by the investigator.
Any C-SSRS findings, which in the opinion of the investigator are new or considered to be a
worsening and clinically significant, should be reported on the AE eCRF (see Section 10.4).
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 AE at a SC study intervention injection-site. Participants should
be monitored for the occurrence of injection-site reactions for at least 30 minutes following SC
injections. Injection sites will be evaluated for reactions and any injection-site reaction will be
recorded as an AE. Participants in the LTE period will not be actively monitored for injection-site
reactions but will be asked to report injection-site reactions to the investigator.
8.2.9. 
Hypersensitivity Reactions
Before any administration of study intervention at the study site, appropriately trained personnel,
and medications (eg, antihistamines, injectable epinephrine) must be available to treat
hypersensitivity reactions, including anaphylaxis. All participants must be observed carefully for
signs and symptoms of a hypersensitivity reaction (eg, urticaria, pruritis, angioedema, wheezing,
dyspnea, or hypotension). Potential cases of anaphylaxis should be assessed according to
Sampson’s Criteria (Sampson 2006).
Hypersensitivity reactions including anaphylaxis should preferably  be managed conform the
standard operating procedures (SOPs) of the site. If the site does not have SOPs, the following
guidance should be used (Muraro 2014).
In the case of a severe allergic reaction (eg, anaphylaxis), SC aqueous epinephrine, corticosteroids,
respiratory assistance, and other proper resuscitative measures are essential and must be available
when study intervention is being administered. Participants who experience serious adverse
reactions related to an injection should be discontinued from further study intervention
administrations.
8.2.10. 
Infections
Investigators are required to evaluate participants for any signs or symptoms of infection at
scheduled visits. Study intervention administration should not be given to a participant with a
clinically significant, active infection. If a participant develops a serious infection, including but
not limited to sepsis or pneumonia, discontinuation of study intervention must be strongly
considered (see Section 7.1). Any serious infection should be discussed with the medical monitor
or designee, and study intervention should be withheld until the clinical assessment is complete.


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8.2.11. 
Tuberculosis Evaluations
8.2.11.1. 
Initial TB 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 to screen for latent
TB if they believe, based on their judgment, that the use of both tests is clinically indicated to
evaluate a participant who is 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 for the
purposes of eligibility for this 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 test result must undergo an
evaluation to rule out active TB and initiate appropriate treatment for latent TB. Appropriate
treatment for latent TB is defined according to local country guidelines for immunocompromised
patients. If no local country guidelines for immunocompromised patients exist, US guidelines
should be followed, or the participant will be excluded from the study.
A participant whose first QuantiFERON-TB test result is indeterminate should have the test
repeated. In the event that the second QuantiFERON-TB test result is also indeterminate, the
participant may be enrolled without treatment for latent TB if active TB is ruled out, their chest
radiograph shows no abnormality suggestive of TB (active or old, inactive TB) and the participant
has no additional risk factors for TB as determined by the investigator. This determination must
be promptly reported to the medical monitor or designee and recorded in the participant's source
documents and initialed by the investigator.
8.2.11.2. 
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:
 
Persistent fever?
 
Unintentional weight loss?
 
Night sweats?”


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“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 newly identified positive QuantiFERON-TB test result must undergo an
evaluation to rule out active TB and initiate appropriate treatment for latent TB. Appropriate
treatment for latent TB is defined according to local country guidelines for immunocompromised
patients. If no local country guidelines for immunocompromised patients exist, US guidelines
should be followed, or the participant will be excluded from the study. If the QuantiFERON-TB
test result is indeterminate, the test should be repeated. Participants should be encouraged to return
for all subsequent scheduled study visits according to the protocol. Participants who discontinue
treatment for latent TB prematurely or who are noncompliant with therapy must immediately
discontinue further administration of study intervention and be encouraged to return for all
subsequent scheduled study visits according to the SoA (Sections 1.3 and 1.4).
8.3. 
Adverse Events, Serious Adverse Events, and Other Safety Reporting
Timely, accurate, and complete reporting and analysis of safety information, including AEs, SAEs,
and PQCs, from clinical studies are crucial for the protection of participants, investigators, and the
sponsor, and are mandated by regulatory agencies worldwide. The sponsor has established SOPs
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 SOPs.
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, surrogate,
or the participant’s legally acceptable representative) for the duration of the study.
For study intervention that meets the definition of a combination product, malfunctions or
deficiencies of a device constituent will be reported as PQC.


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For further details on AEs and SAEs (Definitions and Classifications; Attribution Definitions;
Severity Criteria; Special Reporting Situations; Procedures) as well as PQCs, refer to Section 10.4.
8.3.1. 
Time Period and Frequency for Collecting Adverse Event and Serious
Adverse Event Information
All Adverse Events
All AEs and special reporting situations, whether serious or non-serious, will be reported from the
time a signed and dated ICF is obtained until completion of the participant’s last study-related
procedure, which may include contact for follow-up of safety.
Serious Adverse Events
All SAEs, as well as PQCs, 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.
Any possible Hy’s law case (AST or ALT ≥3×ULN together with total bilirubin ≥2×ULN or INR
>1.5) is considered an important medical event and must be reported to the sponsor in an expedited
manner using the Serious Adverse Event Form and Safety Report form of the eCRF, even before
all other possible causes of liver injury have been excluded (INR criterion is not applicable to
participants receiving anticoagulants).
Serious adverse events, including those spontaneously reported to the investigator by the final
safety visit, must be reported using the SAE form and Safety Report Form of the eCRF. The
sponsor will evaluate any safety information that is spontaneously reported by an investigator
beyond the time frame specified in the protocol.
Information regarding SAEs will be transmitted to the sponsor using the SAE Form and Safety
Report Form of the eCRF, 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 transmitted electronically or (in case of technical issues) by facsimile (fax). Telephone reporting
should be the exception and the reporter should be asked to complete the appropriate form(s) first.
8.3.2. 
Method of Detecting Adverse Events and Serious Adverse Events
Care will be taken not to introduce bias when detecting AEs or SAEs. Open-ended and nonleading
verbal questioning of the participant is the preferred method to inquire about AE occurrence.
Solicited Adverse Events
Solicited AEs are predefined local at the injection site and systemic events for which the participant
is specifically questioned.
Unsolicited Adverse Events
Unsolicited AEs are all AEs for which the participant is not specifically questioned.


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8.3.3. 
Follow-up of Adverse Events and Serious Adverse Events
The investigator is obligated to perform or arrange for the conduct of supplemental measurements
and evaluations as medically indicated to elucidate the nature and causality of the adverse event,
serious adverse event, or PQC as fully as possible. This may include additional laboratory tests or
investigations, histopathological examinations, or consultation with other health care
professionals.
Adverse events, including pregnancy, will be followed by the investigator as specified in
Section 10.4.
8.3.4. 
Regulatory Reporting Requirements for Serious Adverse Events
The sponsor assumes responsibility for appropriate reporting of AEs to the regulatory authorities.
The sponsor will also report to the investigator (and the head of the investigational institute where
required) all suspected unexpected serious adverse reactions (SUSARs). The investigator (or
sponsor where required) must report SUSARs to the appropriate Independent Ethics
Committee/Institutional Review Board (IEC/IRB) that approved the protocol unless otherwise
required and documented by the IEC/IRB. A SUSAR will be reported to regulatory authorities
unblinded. Participating investigators and IEC/IRB will receive a blinded SUSAR summary,
unless otherwise specified.
8.3.5. 
Pregnancy
All initial reports of pregnancy in female participants or partners of male participants must be
reported to the sponsor by the study-site personnel within 24 hours of their knowledge of the event
using the appropriate pregnancy notification form. Abnormal pregnancy outcomes
(eg, spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are
considered SAEs and must be reported using a serious adverse event reporting form.
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the
infant will be required (see Sections 10.7 and 10.4).
8.3.6. 
Disease-Related Events and Disease-Related Outcomes not
Qualifying as Adverse Events or Serious Adverse Events
The cause of death of a participant in a study within 12 weeks of the last dose of study intervention,
whether or not the event is expected or associated with the study intervention, is considered an
SAE.
8.3.7. 
Adverse Events of Special Interest
Any newly identified malignancy, case of active TB, or venous thromboembolism occurring after
the first study intervention administration(s) in participants in this clinical study must be reported
by the investigator to the sponsor or designee within 24 hours after being made aware of the event,
according to the procedures in Section 10.4. Investigators are also advised that active TB is
considered a reportable disease in most countries. These events are to be considered serious only
if they meet the definition of an SAE.


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8.4. 
Pharmacokinetics
8.4.1. 
Evaluations
Venous blood samples will be collected for measurement of serum concentrations of guselkumab
and antibodies to guselkumab  (Section 8.7) at the timepoints shown in the SoA (Sections 1.3
and 1.4).
Venous blood samples will be collected, and each serum sample will be divided into 3 aliquots
(1 each for PK, anti-guselkumab antibodies, and a back-up).
Samples collected for analyses of guselkumab serum concentration and antibodies to guselkumab
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. Additional information about the collection, handling, and
shipment of biological samples can be found in the Laboratory Manual.
8.4.2. 
Analytical Procedures
Serum  samples will be analyzed to determine guselkumab concentrations using a validated,
specific, and sensitive immunoassay method by the sponsor or under the supervision of the
sponsor. The sponsor, or its designee, under conditions in which the participants’ identity remains
blinded, will assay these samples.
8.4.3. 
Pharmacokinetic Parameters
If feasible, the total systemic clearance and volume of distribution of guselkumab may be estimated
using a nonlinear mixed-effects modeling approach.
8.5. 
Pharmacogenomics
Participation in pharmacogenomic research is optional. A pharmacogenomic (DNA) blood sample
will be collected from participants who consent separately to this component of the study to allow
for pharmacogenomic research, where local regulations permit.
Genetic (DNA) variation may be an important contributory factor to interindividual variability in
drug response and associated clinical outcomes. Genetic factors may also serve as markers for
disease susceptibility and prognosis and may identify population subgroups that respond
differently to an intervention.
The optional pharmacogenomic samples may also be analyzed for identification of genetic factors
that may be associated with clinical response. This research may consist of the analysis of 1 or
more candidate genes, assessment of single nucleotide polymorphisms, or analysis of the entire
genome (as appropriate) in relation to guselkumab intervention and/or GCA. Whole blood samples
of approximately 6 mL will be collected for genetic analyses as specified in the SoA (Sections 1.3
and 1.4).


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8.6. 
Biomarkers
Biomarker assessments will be made to examine the biologic response to treatment and to identify
biomarkers that are relevant to guselkumab treatment, GCs and GCA, where local regulations
permit. Assessments will include the evaluation of relevant biomarkers in serum, whole blood, and
PBMCs collected as specified in the SoA (Sections 1.3 and 1.4), where local regulations permit.
Data collected from these samples will be used for exploratory research that will include the
following objectives:
1. To understand the molecular effects of guselkumab
2. To understand GCA pathogenesis
3. To understand why individual participants may respond differently to guselkumab
4. To understand the impact of treatment with guselkumab on vascular or systemic inflammation
5. To develop diagnostic tests to identify GCA populations that may be responsive or non-
responsive to treatment with guselkumab
Serum-based Biomarkers
Blood samples for serum-based biomarker analyses will be collected from all participants. Serum
will be analyzed for levels of specific proteins, and other inflammation-related molecules and/or
disease-associated serologies relevant to GCA and GCA pathogenesis and treatment and response
to guselkumab.
Whole Blood-based Biomarkers
Whole blood will be collected by venipuncture from participants for ribonucleic acid (RNA)
expression analysis, where local regulations permit. Total RNA will be isolated and used for
differential gene expression analyses to identify gene expression  patterns that are relevant to
guselkumab treatment and/or GCA, and to evaluate markers that can predict clinical response.
Transcriptome studies will be conducted using microarray, and/or alternative equivalent
technologies, which facilitates the simultaneous measurement of the relative abundances of
multiple RNA species resulting in a transcriptome profile for each blood sample. This will enable
the evaluation of changes in transcriptome profiles that may correlate with biological response
relating to GCA and/or the action of guselkumab.
Whole blood will also be collected and processed for PBMC isolation and cryopreserved for later
analysis. Analysis may include but is not limited to flow cytometric assessment of cell populations,
single cell transcriptomics, or functional assessment of cells in response to guselkumab treatment.
Stopping Analysis
Biomarker analyses are dependent upon the availability of appropriate biomarker assays and
clinical response rates. Biomarker analysis may be deferred or not performed, if during or at the
end of the study, it becomes clear that the analysis will not have sufficient scientific value for
biomarker evaluation, or if there are not enough samples or responders to allow for adequate


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biomarker evaluation. In the event the study is terminated early or shows poor clinical efficacy,
completion of biomarker assessments is based on justification and intended utility of the data.
8.7. 
Immunogenicity Assessments
8.7.1. 
Evaluations
Serum samples for detection of antibodies to guselkumab will be collectedand evaluatedaccording
to the SoA (Sections 1.3 and 1.4). Additionally, serum samples should also be collected at the final
visit from participants who were withdrawn from the study.
Serum samples will be screened for antibodies binding to guselkumab and the titer of confirmed
positive samples will be reported. Other analyses may be performed to verify the stability of
antibodies to guselkumab and/or further characterize the immunogenicity of guselkumab.
8.7.2. 
Analytical Procedures
The detection and characterization of antibodies to guselkumab will be performed using a validated
assay method by or under the supervision of the sponsor. Antibodies may be further characterized
and/or evaluated for their ability to neutralize the activity of the study intervention(s).
8.8. 
Medical Resource Utilization and Health Economics
This section is not applicable for this protocol.
8.9. 
Exploratory FDG-PET/CT Imaging
18F-FDG (FDG) PET imaging is a non-invasive functional imaging modality  that provides
tomographic images and can be used to obtain quantitative parameters concerning the metabolic
activity of target tissues of inflammatory diseases (Ito 2020). Computerized tomography scanning
(CT) uses a combined X-ray transmission source and detector system rotating around the
participant to generate tomographic images. CT allows not only attenuation correction but also the
visualization of morphological and anatomical structures with a high spatial resolution.
Anatomical and morphological information derived from CT can be used to improve the
localization, extent and characterization of large vessel inflammation detected by FDG-PET.
The combined FDG-PET/CT imaging modality has been used as a non-invasive way to assess
inflammatory disease activity in the arterial wall in large vessel vasculitis including GCA by
visualizing enhanced glycolytic activity of inflammatory cells (Grayson 2018). This imaging
methodology has been further standardized by an international joint working group via a consensus
paper on FDG-PET/CT imaging in LLV (Sampson 2006).
In this study, FDG-PET/CT scans of the body will be performed in all participants according to
the SoA (Sections 1.3 and 1.4). FDG-PET/CT is to be performed during screening prior to Week
0, and at Week 52 (or timepoint of flare if earlier). FDG-PET/CT scan is being obtained as part of
exploratory endpoint and week 52 FDG-PET/CT should not be used in determining disease status
of participants for the associated week 52 visit. If a participant has a flare prior to Week 52, an
attempt will be made to perform the FDG-PET/CT imaging at that flare timepoint, preferably


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within 1 week from identification of GCA flare by the principal investigator. In the LTE period,
another FDG-PET/CT scan is to be performed at Week 104 (LTE Week 52) or timepoint of flare
if earlier, preferably within 1 week from identification of GCA flare by the principal investigator.
FDG-PET/CT scan is being obtained as part of exploratory endpoint and week 104 (LTE Week
52) FDG-PET/CT should not be used in determining disease status of participants for the
associated week 104 (LTE Week 52) visit. A participant may decline the LTE PET/CT as noted in
footnote e of the LTE SoA. If the participant has a GCA flare within 1 month of the Week 52 main
study FDG-PET/CT scan (or other timeframe in accordance with local country regulations), the
FDG-PET/CT scan will not be performed.
Participant preparation for an FDG-PET/CT scan includes instructions to consume a carbohydrate-
sparse meal on the day prior, and to be in fasting condition prior to imaging (details are provided
in a separate FDG-PET/CT Imaging Manual).
Study independent central imaging assessment will be used to analyze all FDG-PET/CT scans
included in this study. The central imaging assessment of imaging will be blinded to the clinical
data. FDG-PET/CT scan interpretation will determine whether findings are consistent with active
or inactive vasculitis based upon assessment of vascular FDG uptake.
8.10. Digital Health –Actigraphy Measurements
Digital health has emerged as one of the important advancements that may help to objectively
capture patient well-being. Wearable devices equipped with powerful sensors and self-reporting
mobile apps are becoming handy in keeping continuous track of patient symptoms and providing
useful insights on disease progression, clinical response, or complications.
The use of remote sensing technology for data collection will enable to compare the actigraphy
measures obtained in placebo versus guselkumab treated participants to better understand the
underlying differences from the treatment effects. Digital sensing technologies will provide
valuable data that supplements clinical data streams such as clinical endpoints, PROs, objective
measures from clinical laboratory and biomarker assessments to better characterize the disease
status and well-being of patients with GCA when treated with guselkumab. To enable this work
stream, we will use an actigraph device from actigraph corporation.
Actigraphy data, including physical activity, mobility, and sleep parameters, will be captured as
specified in the SoA (Sections 1.3 and 1.4). A wrist-worn actigraph device validated against
polysomnography to assess sleep-related variables will be used.
Each participant will be dispensed a single actigraph device (wristwatch) at screening with
instructions for use. Participants will be asked to continuously wear the device preferably on the
non-dominant wrist from screening until Week 52, and bring the actigraph device to each clinic
visit, during which the data from the device will be downloaded as needed. Sites and participants
will not have access to data generated from the use of the device during the study. All devices will
be collected at the Week 52 visit and inventoried.


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Participants may decline actigraphy measurements in case the participant is at risk for withdrawal
of consent or if this assessment is a reason for participants not wanting to join the 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 Statistical Analysis Plan (SAP).
9.1. 
Statistical Hypothesis
The primary hypothesis is that guselkumab treatment with a 26-week GC taper is superior to
placebo with a 26-week GC taper in participants with new-onset or relapsing GCA as assessed by
the proportion of participants achieving GC-free remission at Week 28.
9.2. 
Sample Size Determination
Approximately 51 participants are planned to be enrolled into the study. The assumptions for the
sample size and power calculation were based on the data from the Actemra Phase 3 GCA study.
In the Actemra Phase 3 study, the proportions of participants in GC-free remission at Week 28
were estimated to be approximately 38% and 74% for placebo (+26-week GC taper) and Actemra
qw (+26-week GC-taper), respectively, for a treatment difference of 36% (Stone 2017).
Based on the data above, the GC-free remission rates at Week 28 are assumed to be 40% for
placebo and 80% for guselkumab treatment arm. Based on these assumptions, with approximately
51 participants planned to be randomized in a 2:1 ratio to either the guselkumab group (N 34) or
the placebo group  (N 17). These sample sizes provide the study with 82% power to detect a
difference in the primary endpoint between the 2 treatment groups.
Table 2 shows the power to detect a difference in proportions of participants in GC-free remission
between the guselkumab and placebo intervention groups at Week 28under various assumptions.
More participants may be enrolled to compensate for higher than anticipated attrition.
Table 2: 
Power to Detect Difference in Proportions of Participants Achieving Glucocorticoid-free
Remission between the Guselkumab and Placebo Intervention Groups at Week 28
Placebo (n = 17) 
Guselkumab (n = 34) 
Power (%)
35% 
70% 
68
75% 
81
80%  
90
40%  
75% 
69
80%  
82
85%  
91
Notes:
• The power calculation is based on two-sample Z test with continuity correction (pooled variance) under the
normal distribution approximation.
• Power calculation is based on a 2-sided significance level of 0.10.
• Total sample size is 51.


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9.3. 
Analysis Sets
For purposes of analysis, the following populations are defined:
Population 
Description
Enrolled 
All participants who signed the informed consent form (ICF).
Full Analyses 
Set 
All participants who were randomized in the study and received at least one administration of
study intervention.
Safety Analysis 
Set
All participants who received at least one dose of study intervention.
Immunogenicity 
Analysis Set 
All participants who received at least 1 administration of guselkumab and have at least one
sample obtained after their first dose of guselkumab
PK Analysis Set 
All participants who received at least 1 administration of guselkumab and have at least one
valid blood sample drawn for PK analysis.
PD Analysis Set 
All participants who received at least 1 administration of study intervention and have at least
one post-dose sample collection.
9.4. 
Statistical Analyses
The SAP will be finalized prior to the DBL at Week 28. and it will include a more technical and
detailed description of the statistical analyses described in this section. This section is a summary
of the planned statistical analyses of the most important endpoints including primary and key
secondary endpoints.
9.4.1. 
General Considerations
Data primarily will be summarized using descriptive statistics. Continuous variables will be
summarized using the number of observations, mean, SD, median, interquartile range, minimum
and maximum, as appropriate. Categorical values will be summarized using the number of
observations and percentages as appropriate. Median time will be reported for time to event
variables. In addition, graphical data displays (eg, line plots) and participant listings may also be
used to summarize/present the data.
For continuous endpoints, Mixed-Effect Model Repeated Measure model and Analysis of
Covariance will be used for analysis. For binary endpoints, Cochran-Mantel-Haenszel test
stratified by new-onset and relapsing GCA, and the baseline prednisone dose (≤30 mg/day or >30
mg/day) will be used to analyze data. For time to first event data, Kaplan-Meier curves and Cox
proportional hazards regression will be used to analyze the data. In addition, treatment differences
and their associated 90% confidence intervals will be presented.
In general, all statistical tests will be performed at a 2-sided significance level of α 0.10. No
multiplicity adjustment will be made for the secondary endpoints being tested and nominal p
values will be reported.
9.4.2. 
Primary Endpoint
Definition of Primary Endpoint
The primary endpoint is the proportion of participants achieving GC-free remission at Week 28
(ie, meeting remission definition and not on GC for GCA at Week 28).


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Estimand: The estimand, based on the primary objective above, is defined by the following 5
components based on the composite strategy which assesses the treatment effects not only based
on the variable measurements, but also based on intercurrent events:
 
Population: adult participants 50 years or older with active new-onset or relapsing GCA
 
Variable: GC-free remission at Week 28
 
Treatment:
 
Guselkumab in addition to 26-weeks GC-taper
 
Placebo in addition to 26-weeks GC-taper
 
Intercurrent Events:discontinuation of study intervention due to lack ofefficacy or an AE
of worsening of GCA, or initiation of a protocol-prohibited medication or therapy  during
the study  that could improve GCA, or initiation of GC rescue therapy
 
Population level summary: difference in proportion of GC-free remission at Week 28
between the guselkumab group and the placebo group
Primary Endpoint Analysis
Analyses of the primary efficacy endpoint (GC-free remission at Week 28) will include data from
all randomized participants who received at least one administration of study intervention based
on their assigned intervention group, regardless of the actual intervention received and have
baseline data (Full Analyses Set population).
In this primary analysis, the number and proportion of participants who achieve GC-free remission
at Week 28 will be summarized for each treatment group. Participants who experienced
intercurrent events prior to Week 28 will be considered as not achieving the endpoint. In addition,
participants with missing data at Week 28 will also be considered as not achieving the endpoint.
To address the primary  objective, Cochran-Mantel-Haenszel chi-square statistic stratified by
new-onset and relapsing GCA, and the baseline prednisone dose (≤30 mg/day or >30 mg/day)
at a 2-sided significance level of 0.10 will be used. Difference in  response rates between  the
2 treatment groups and the corresponding 90% CI will be presented.
Subgroup analysis (based on demographics, baseline characteristics, new-onset vs relapsing, GC
dose at baseline [≤30 mg/day or >30 mg/day])will be performed for the primary endpoint.
9.4.3. 
Secondary Endpoints
Secondary Endpoints:
 
The proportion of participants achieving GC-free remission from Week 28 by visit through
Week 52
 
The proportion of participants achieving GC-free remission and normalization of ESR at
Week 28 and by visit through Week 52
 
The proportion of participants achieving GC-free remission and normalization of CRP at
Week 28 and by visit through Week 52


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The proportion of participants achieving GC-free remission and normalization of both ESR
and CRP at Week 28 and by visit through Week 52
 
The cumulative GC dose through Week 28 and through Week 52
 
The time to first GCA disease flare or discontinuation of study intervention due to AE of
worsening of GCA through Week 28 and through Week 52
 
The number of GCA disease flares or discontinuation of study intervention due to AE of
worsening of GCA through Week 28 and through Week 52
Secondary Endpoint Analyses
The Full Analyses Set population will be used for analysis and participants will be counted in the
intervention group assigned, regardless of the study intervention received.
The details of the analysis of the secondary endpoints will be included in the SAP.
9.4.4. 
Tertiary/Exploratory Endpoints
Other Efficacy Endpoints
 
Proportion of participants in sustained remission through Week 52.
Sustained remission through Week 52 is defined as: No signs and symptoms of GCA through
Week 52, and completion of the protocol defined GC taper, and not having required GC rescue
therapy at any time by Week 52.
 
Change from baseline in CRP through Week 52
 
Change from baseline in ESR through Week 52
Clinical Outcome Assessments
 
Change from baseline in PGA by visit through Week 52
 
Change from baseline in Pain Assessment by visit through Week 52
 
Change from baseline in SF-36 individual domains by visit through Week 52
 
Change from baseline in FACIT-fatigue score by visit through Week 52
 
Change from baseline in PhGA by visit through Week 52.
Further details of tertiary/exploratory endpoints analyses and analyses for efficacy during the LTE
will be provided in the SAP.
9.4.5. 
Safety Analyses
All safety analyses will be analyzed using the Safety Analysis Set population (refer to Section 9.3
for definition).
Adverse Events
The verbatim terms used in the CRF by investigators to identify AEs will be coded using the
Medical Dictionary for Regulatory Activities. Any AE occurring at or after the initial


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administration of study intervention through the end of the study is considered to be treatment
emergent. All reported TEAEs 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. In addition, comparisons between intervention groups will be provided if
appropriate.
The following analyses of AEs will be used to assess the safety of participants in the main study:
 
Number and proportion of participants with TEAEs by treatment intervention through
Week 60
 
Number and proportion of participants with TEAEs by system organ class and preferred term
with a frequency threshold of 5% or more by treatment intervention through Week 60
 
Number and proportion of participants with treatment-emergent SAEs by treatment
intervention through Week 60
 
Number and proportion of participants with reasonably related TEAEs as assessed by
investigator by treatment intervention through Week 60
 
Number and proportion of participants with infections, serious infections, and infections
requiring oral or parenteral antimicrobial treatment through Week 60
 
Number and proportion of participants with TEAEs leading to discontinuation  of study
intervention by treatment intervention through Week 60
 
Number and proportion of participants with TEAEs temporally associated with an IV infusion
by treatment intervention through Week 8
 
Number and proportion of participants with injection-site reactions by treatment intervention.
Summaries, listings, datasets, or participant narratives may be provided through Week 28 and
Week 60 by treatment intervention, for the above AEs, deaths, and severe AEs.
Similar safety analyses from Week 52 (LTE Week 0) through Week 112 (LTE Week 60) will be
performed for participants in the LTE period.
Clinical Laboratory Tests
Laboratory data will be summarized by type of laboratory test over time and by treatment
intervention.  National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-
CTCAE) grades (specified in the SAP) will be used in the summary of laboratory data. Descriptive
statistics will be calculated for each laboratory analyte at baseline and for observed values and
changes from baseline at each scheduled time point.
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 postbaseline laboratory values
(hematology and chemistry)


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Listings of participants with any abnormal postbaseline laboratory values of NCI-CTCAE
Grade ≥2 will also be provided
Columbia-Suicide Severity Rating Scale
Suicide-related thoughts and behaviors based on the C-SSRS will be summarized descriptively by
treatment group.
Vital Signs
Descriptive statistics of temperature, pulse/heart rate, respiratory rate, and blood pressure (systolic
and diastolic) values and changes from baseline will be summarized at each scheduled time point.
The percentage of participants with values beyond clinically important limits will be summarized.
Weight
Descriptive statistics of changes from baseline will be summarized at each scheduled time point.
9.4.6. 
Other Analyses
Pharmacokinetic Analyses
The PK evaluable population is defined as all the participants who received at least 1 complete
dose of guselkumab and had at least 1 valid blood sample drawn for PK analysis after their first
dose of guselkumab.
Serum guselkumab concentrations will be summarized over time for all participants who receive
at least 1 dose of guselkumab. Descriptive statistics will be calculated at each sampling timepoint.
All serum concentrations below the lowest quantifiable concentration or missing data will be
labeled as such in the concentration database. Concentrations below the lowest quantifiable
concentration will be treated as zero in the summary statistics. Pharmacokinetic data may also be
displayed graphically.
If feasible, population PK analysis of serum concentration-time data may be performed using
nonlinear mixed-effects modeling. Details will be provided in a separate technical report.
Immunogenicity Analyses
The incidence and titers ofantibodies to guselkumab will be summarized for all participants who
receive at least 1 dose of guselkumab and have appropriate samples for detection of antibodies to
guselkumab (ie, participants with at least 1 sample obtained after their first dose ofguselkumab).
A listing of participants who are positive for antibodies to guselkumab will be provided. The
maximum titers of antibodies to guselkumab will be summarized for participants who are positive
for antibodies to guselkumab.
The incidence of neutralizing antibodies (NAbs) to  will be summarized for participants who are
positive for antibodies to guselkumab and have samples evaluable for NAbs to guselkumab.


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Other immunogenicity analyses may be performed to further characterize the immune responses
that are generated.
Biomarkers/Pharmacodynamic Analyses
The biomarker analyses will characterize the effects of guselkumab to identify PD markers and
biomarkers relevant to treatment, and to determine if these markers can predict response to
guselkumab. Changes in serum analytes, RNA levels in whole blood and in single cells from
PBMC, and leukocyte subset counts and frequencies in PBMC over time will be summarized by
interventiongroup, in separate technical reports. Associations between baseline levels and changes
from baseline in select markers and clinical response on primary and major secondary endpoints
in Sections 9.4.2 and 9.4.3 will be explored and summarized in separate technical reports.
Planned biomarker analyses may be deferred if emerging study data show no likelihood of
providing useful scientific information. Any biomarker samples received by the contract vendor
or sponsor after the cutoff date will not be analyzed, and therefore, excluded from the biomarker
analysis.
Pharmacokinetic/Pharmacodynamic Analyses
The relationship between serum concentrations of guselkumab and the efficacy measures and/or
relevant PD endpoints may be explored graphically when appropriate.
Pharmacogenomic Analyses
Genetic (DNA) analyses will be conducted only in participants who sign the consent form to
participate in the pharmacogenomic substudy. DNA samples will be used for research related to
guselkumab, GCs, or GCA. They may also be used to develop tests/assays related to guselkumab,
GCs and GCA. Pharmacogenomic research may consist of the analysis of one or more candidate
genes or of the analysis of genetic markers throughout the genome (as appropriate) in relation to
guselkumab, GCs or GCA clinical endpoints. These analyses are considered exploratory and will
be summarized in a separate technical report.
Exploratory FDG-PET/CT Imaging Analyses
FDG-PET/CT scans will be qualitatively assessed for FDG uptake in 9 arterial territories (carotid
arteries, subclavian  arteries, brachiocephalic artery, ascending aorta, aortic arch, descending
thoracic aorta, and the abdominal aorta). The degree of arterial uptake will be visually assessed
relative to liver uptake as: 0  no uptake; 1  less than liver; 2  same as liver; 3  greater than
liver. To assess the qualitative inflammatory burden byarterial FDG uptake across multiple arterial
regions, a summary score (hereafter termed PET Vascular Activity Score [PETVAS]) will be
created by adding the qualitative scores in specific arterial territories (Grayson 2018).
Large-Vessel Imaging (FDG-PET/CT) changes from baseline in PETVAS at Week 52 (or flare)
and Week 104 (LTE Week 52) (or flare), if applicable will be summarized per participant and by
treatment intervention. Correlation of PETVAS score with clinical features and laboratory tests,
and additional semi-quantitative assessments and analyses may also be explored. These analyses
are considered exploratory and will be summarized in a separate technical report.


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Digital Health - Actigraphy Analyses
The raw data sampled by Actiwatch sensors will be transformed into the following derived digital
health endpoints, assessing the changes from baseline in on physical activity, mobility, and sleep
components by visit through Week 52, including but not limited to the following:
 
Activity
 
Total activity counts
 
Average activity (counts/minute)
 
Maximum activity (counts/minute)
 
Time above sedentary
 
Mean daily activity
 
Activity threshold analysis
 
Daily peak activity
 
Sleep
 
Total sleep time
 
Onset latency
 
Sleep efficiency
 
Wake time after sleep onset
 
Percent (%) wake
 
Number of wake bouts (number of awakenings)
 
Average wake bout
 
Fragmentation index
 
Mobility
 
Immobile time within the given interval
 
Percentage immobile time within the given interval
 
Number of immobile bouts
 
Average duration of immobile bouts
 
Mobile time within the given interval
 
Percentage mobile time within the given interval
 
Number of mobile bouts
 
Average duration of mobile bouts
 
Number of immobile bouts of ≥1-minute duration, within the given interval
 
Percentage of immobile bouts that are ≥1-minute duration
 
Fragmentation index


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Additional actigraphy digital health endpoints may be derived using emerging algorithms.
Associations between baseline measurements and changes from baseline in selected measurements
and clinical response on primary and secondary endpoints in Sections 9.4.2 and 9.4.3 may be
explored. All Actigraphy data related analyses are considered exploratory and will be summarized
in a separate technical report.
9.5. 
Interim Analyses
No interim analyses are planned for this study.
9.6. 
Data Monitoring Committee
An independent DMC will be established as noted in Committees Structure in Section 10.3. The
DMC will monitor safety data on an ongoing basis until all participants complete the study or
terminate the study. The main focus of the DMC will be on reviewing interim unblinded safety
data, but the DMC may also review efficacy data needed to ensure the full benefit: risk profile for
guselkumab.
The DMC will consist of at least one external and one internal clinical physician with relevant
therapeutic expertise (rheumatology) and one internal statistician, not related to the study team.
The content of the safety summaries, the DMC’s role and responsibilities, the general procedures
(including communications), and their recommendations on the study conduct are defined and
documented in the DMC charter, which will be finalized prior to the first DMC review.
In addition, during the study, the sponsor's study responsible physician (or designee) will regularly
review blinded safety data from the sites and notify the DMC and appropriate sponsor personnel
of any issues.


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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Abbreviations
AE 
adverse event
ALT  
alanine aminotransferase
AST  
aspartate aminotransferase
BCG  
Bacille Calmette-Guérin
CRF  
case report form(s) (paper or electronic as appropriate for this study)
CRP  
C-reactive protein
CT  
computed tomography
DBL 
database lock
DCS  
data collection systems
DILI 
drug induced liver injury
DMC  
Data Monitoring Committee
DNA  
deoxyribonucleic acid
ECG  
electrocardiogram
C-SSRS  
Columbia-Suicide Severity Rating Scale
eDC  
electronic data capture
ESR  
erythrocyte sedimentation rate
FACIT  
Functional Assessment of Chronic Illness Therapy
FDG  
fluorodeoxyglucose
GC  
glucocorticoid
GCA  
Giant cell arteritis
GCP  
Good Clinical Practice
HBsAg 
hepatitis B surface antigen
HBV  
hepatitis B virus
HCV  
hepatitis C virus
HIV  
human immunodeficiency virus
HRT  
hormonal replacement therapy
HS  
Hidradenitis suppurativa
IB  
investigator’s brochure
ICF  
informed consent form
ICH  
International Council on Harmonisation
IEC  
Independent Ethics Committee
Ig 
immunoglobin
INR  
international normalized ratio
IRB  
Institutional Review Board
IV  
intravenous
IWRS  
interactive web response system
LN  
Lupus Nephritis
LTE  
long-term extension
MTX  
methotrexate
NOAEL 
no-observed-adverse-effect level
NSAID  
non-steroidal anti-inflammatory drug
p 
Point(s)
PBMC  
peripheral blood mononuclear cell
PETVAS  
PET Vascular Activity Score
PD 
pharmacodynamic(s)
PET  
positron emission tomography
PFS  
prefilled syringe
PFS-U 
UltraSafe Plus™ Passive Needle Guard
PGA  
Patient's Global Assessment of Disease Activity
PhGA  
Physician's Global Assessment of Disease Activity
PK 
pharmacokinetic(s)
PMR  
polymyalgia rheumatica


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PQC  
Product Quality Complaint
PRO  
patient-reported outcome(s) (paper or electronic as appropriate for this study)
PsA  
psoriatic arthritis
PsO  
psoriasis
PT  
prothrombin time
PTT  
Partial thromboplastin time
q4w  
every 4 weeks
q8w  
every 8 weeks
RA  
rheumatoid arthritis
RBC  
red blood cell
RNA  
ribonucleic acid
SAE 
serious adverse event
SAP  
Statistical analysis plan
SC 
subcutaneous
SD 
standard deviation
SF-36 
short-form 36
sIPPM  
Site Investigational Product Procedures Manual
SoA  
Schedule of Activities
SUSAR  
suspected unexpected serious adverse reaction
TB  
tuberculosis
TEAE  
treatment-emergent adverse event
UC  
ulcerative colitis
US  
United States
ULN  
upper limit of normal
VAS  
Visual Analog Scale
Definitions of Terms
PRO  
Reports directly from the patient without interpretation by clinician or anybody else.


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10.2. Appendix 2: Clinical Laboratory Tests
The following tests will be performed according to the SoAby the central laboratory:
Protocol-Required Safety Laboratory Assessments
Laboratory
Assessments
Parameters
Hematology  
Platelet count
Red blood cell (RBC)
count
Hemoglobin
Hematocrit
RBC Indices: 
MCV  
MCH  
% Reticulocytes 
White Blood Cell count
with Differential:
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
Note: A white blood cell evaluation may include any abnormal cells, which will then
be reported by the laboratory. A RBC evaluation may include abnormalities in the
RBC count, RBC parameters, or RBC morphology, which will then be reported by
the laboratory. In addition, any other abnormal cells in a blood smear will also be
reported.
Clinical 
Chemistry  
Sodium  
Potassium  
Chloride 
Bicarbonate 
Blood urea nitrogen (BUN) 
Creatinine 
Glucose  
AST/Serum glutamic-oxaloacetic 
ALT/Serum glutamic-oxaloacetic 
Gamma-glutamyltransferase 
Total bilirubin, reflex test indirect
bilirubin if abnormal
Alkaline phosphatase
Creatine phosphokinase (CPK)
Lactic acid dehydrogenase (LDH)
Uric acid
Calcium
Phosphate
Albumin
Total protein
Cholesterol
Triglycerides
Magnesium
Note: Details of liver chemistry stopping criteria and required actions and follow-up
are given in Section 10.9, Appendix 9: Liver Safety.
Potential Hy’s Law case (ALT or AST ≥3×ULN together with Tbili ≥2×ULN or INR
>1.5) reporting requirements are defined in Section 8.3.
Other Tests 
 
Urine Pregnancy Testing for women of childbearing potential only (performed
locally)
 
Serology (HIV antibody, hepatitis B surface antigen [HBsAg], and Hepatitis B,
surface antibody [anti-HBs], Hepatitis B core antibody [anti-HBc], hepatitis C
virus antibody, and HBV DNA, screening only)
 
Coagulation (prothrombin time [PT], partial thromboplastin time [PTT], INR),
at screening only
 
CRP and ESR (Westergren method). ESR will be performed locally


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10.3. Appendix 3: Regulatory, Ethical, and Study Oversight Considerations
REGULATORY AND ETHICAL CONSIDERATIONS
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the
protocol, current international council for harmonization (ICH) guidelines on Good Clinical
Practice (GCP), and applicable regulatory and country- or territory-specific requirements.
Good Clinical Practice is an international ethical and scientific quality standard for designing,
conducting, recording, and reporting studies that involve the participation of human participants.
Compliance with this standard provides public assurance that the rights, safety, and well-being of
study participants are protected, consistent with the principles that originated in the Declaration of
Helsinki, and that the study data are credible.
Protocol Clarification Communications
If text within a final approved protocol requires clarification (eg, current wording is unclear or
ambiguous) that does not change any aspect of the current study conduct, a protocol clarification
communication (PCC) may be prepared. The PCC Document will be communicated to the
Investigational Site, Site Monitors, Local Trial Managers (LTMs), Clinical Trial Managers
(CTMs), and/or Contract Research Organizations (CROs) who will ensure that the PCC
explanations are followed by the investigators.
The PCC Document may be shared by the sites with Independent Ethics Committees/Institutional
Review Boards (IECs/IRBs) per local regulations.
The PCC Documents must NOT be used in place of protocol amendments, but the content of the
PCC Document must be included in any future protocol amendments.
Protocol Amendments
Neither the investigator nor the sponsor will modify this protocol without a formal amendment by
the sponsor. All protocol amendments must be issued by the sponsor and signed and dated by the
investigator. Protocol amendments must not be implemented without prior IEC/IRB approval, or
when the relevant competent authority has raised any grounds for non-acceptance, except when
necessary to eliminate immediate hazards to the participants, in which case the amendment must
be promptly submitted to the IEC/IRB and relevant competent authority. Documentation of
amendment approval by the investigator and IEC/IRB must be provided to the sponsor. When the
change(s) involves only logistic or administrative aspects of the study, the IEC/IRB (where
required) only needs to be notified.
In situations where a departure from the protocol is unavoidable during the study, the investigator
or other physician in attendance will contact the appropriate sponsor representative listed in the
Contact Information page(s), which will be provided as a separate document. Except in emergency
situations, this contact should be made before implementing any departure from the protocol. In


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


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Local laboratory documentation demonstrating competence and test reliability
(eg, accreditation/license), if applicable
Independent Ethics Committee or Institutional Review Board
Before the start of the study, the investigator (or sponsor where required) will provide the IEC/IRB
with current and complete copies of the following documents (as required by local regulations):
 
Final protocol and, if applicable, amendments
 
Sponsor-approved ICF (and any other written materials to be provided to the participants)
 
IB (or equivalent information) and amendments/addenda
 
Sponsor-approved participant recruiting materials
 
Information on compensation for study-related injuries or payment to participants for
participation in the study, if applicable
 
Investigator’s curriculum vitae or equivalent information (unless not required, as documented
by the IEC/IRB)
 
Information regarding funding, name of the sponsor, institutional affiliations, other potential
conflicts of interest, and incentives for participants
 
Any other documents that the IEC/IRB requests to fulfill its obligation
This study will be undertaken only after the IEC/IRB has given full approval of the final protocol,
amendments (if any, excluding the ones that are purely administrative, with no consequences for
participants, data, or study conduct, unless required locally), the ICF, applicable recruiting
materials, and participant compensation programs, and the sponsor has received a copy of this
approval. This approval letter must be dated and must clearly identify the IEC/IRB and the
documents being approved.
Approval for the collection of optional samples for pharmacogenomics and for the corresponding
ICF must be obtained from the IEC/IRB. Approval for the protocol can be obtained independent
of this optional pharmacogenomic 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


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Summaries of the status of the study at intervals stipulated in guidelines of the IEC/IRB (at
least annually)
 
Reports of AEs that are serious, unlisted/unexpected, and associated with the study
intervention
 
New information that may adversely affect the safety of the participants or the conduct of the
study
 
Deviations from or changes to the protocol to eliminate immediate hazards to the participants
 
Report of deaths of participants under the investigator’s care
 
Notification if a new investigator is responsible for the study at the site
 
Development Safety Update Report and Line Listings, where applicable
 
Any other requirements of the IEC/IRB
For all protocol amendments (excluding the ones that are purely administrative, with no
consequences for participants, data, or study conduct), the amendment and applicable ICF
revisions must be submitted promptly to the IEC/IRB for review and approval before
implementation of the change(s).
At least once a year, the IEC/IRB will be asked to review and reapprove this study, where required.
At the end of the study, the investigator (or sponsor where required) will notify the IEC/IRB about
the study completion (if applicable, the notification will be submitted through the head of
investigational institution).
Country/Territory Selection
This study will only be conducted in those countries/territories 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 4.2.2., Study-Specific Ethical
Design Considerations.
Other Ethical Considerations
For study-specific ethical design considerations, refer to Section 4.2.2.
FINANCIAL DISCLOSURE
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial
information in accordance with local regulations to allow the sponsor to submit complete and
accurate financial certification or disclosure statements to the appropriate regulatory authorities.
Investigators are responsible for providing information on financial interests during the study and
for 1 year after completion of the study.
Refer to Required Prestudy Documentation (above) for details on financial disclosure.


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DATA PROTECTION
Privacy of Personal Data
The collection and processing of personal data from participants enrolled in this study will be
limited to those data that are necessary to fulfill the objectives of the study.
These data must be collected and processed with adequate precautions to ensure confidentiality
and compliance with applicable data privacy protection laws and regulations. Appropriate
technical and organizational measures to protect the personal data against unauthorized disclosures
or access, accidental or unlawful destruction, or accidental loss or alteration must be put in place.
Sponsor personnel whose responsibilities require access to personal data agree to keep the identity
of participants confidential.
The informed consent obtained from the participant includes explicit consent for the processing of
personal data and for the investigator/institution to allow direct access to his or her original medical
records (source data/documents) for study-related monitoring, audit, IEC/IRB review, and
regulatory inspection. This consent also addresses the transfer of the data to other entities and to
other countries/territories.
The participant has the right to request through the investigator access to his or her personal data
and the right to request rectification of any data that are not correct or complete. 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, PD/biomarker, PK, and immunogenicity  research is not conducted under
standards appropriate for the return of data to participants. In addition, the sponsor cannot make
decisions as to the significance of any findings resulting from exploratory research. Therefore,
exploratory research data will not be returned to participants or investigators, unless required by
law or local regulations. Privacy and confidentiality of data generated in the future on stored
samples will be protected by the same standards applicable to all other clinical data.
INFORMED CONSENT PROCESS
Each participant must give written consent according to local requirements after the nature of the
study has been fully explained. The ICF(s) must be signed before performance of any study-related
activity. The ICF(s) that is/are used must be approved by both the sponsor and by the reviewing
IEC/IRB and be in a language that the participant can read and understand. The informed consent
should be in accordance with principles that originated in the Declaration of Helsinki, current ICH
and GCP guidelines, applicable regulatory requirements, and sponsor policy.
Before enrollment in the study, the investigator or an authorized member of the study-site
personnel must explain to potential participants the aims, methods, reasonably anticipated benefits,
and potential hazards of the study, and any discomfort participation in the study may entail.
Participants will be informed that their participation is voluntary and that they may withdraw
consent to participate at any time. They will be informed that choosing not to participate will not
affect the care the participant will receive. Finally, they will be told that the investigator will


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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, which includes
permission to obtain information about his or her survival status. It also denotes that the participant
agrees to allow his or her study physician to recontact the participant for the purpose of obtaining
consent for additional safety evaluations, and subsequent disease-related treatments, if needed.
The physician may also recontact the participant for the purpose of obtaining consent to collect
information about his or her survival status.
The participant will be given sufficient time to read the ICF and the opportunity to ask questions.
After this explanation and before entry into the study, consent should be appropriately recorded by
means of the participant’s personally dated signature. After having obtained the consent, a copy of
the ICF must be given to the participant.
Participants who are rescreened and required to sign a new ICF.
Participants will be asked for consent to provide optional samples for research (where local
regulations permit). After informed consent for the study is appropriately obtained, the participant
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.
Where local regulations require, a separate ICF may be used for the required DNA component of
the study.
LONG-TERM RETENTION OF SAMPLES FOR ADDITIONAL FUTURE RESEARCH
Samples collected in this study may be stored for up to 15 years (or according to local regulations)
for additional research. Samples will only be used to understand guselkumab treatment, GCs, to
understand GCA, to understand differential intervention responders, and to develop tests/assays
related to guselkumab treatment, GCs and GCA. 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).
COMMITTEES STRUCTURE
Data Monitoring Committee
A DMC will be established to review interim data. This committee will consist of at least one
medical expert in the relevant therapeutic area and at least one statistician; committee membership
responsibilities, authorities, and procedures will be documented in its charter. The committee will
meet periodically to review interim data. After the review, the DMC will make recommendations
regarding the continuation of the study.


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PUBLICATION POLICY/DISSEMINATION OF CLINICAL STUDY DATA
All information, including but not limited to information regarding guselkumab or the sponsor’s
operations (eg, patent application, formulas, manufacturing processes, basic scientific data, prior
clinical data, formulation information) supplied by the sponsor to the investigator and not
previously published, and any data, including exploratory biomarker, imaging, digital health
research data, generated as a result of this study, are considered confidential and remain the sole
property of the sponsor. The investigator agrees to maintain this information in confidence and use
this information only to accomplish this study and will not use it for other purposes without the
sponsor’s prior written consent.
The investigator understands that the information developed in the study will be used by the
sponsor in connection with the continued development ofguselkumab, and thus may be disclosed
as required to other clinical investigators or regulatory agencies. To permit the information derived
from the clinical studies to be used, the investigator is obligated to provide the sponsor with all
data obtained in the study.
The results of the study will be reported in a Clinical Study Report generated by the sponsor and
will contain data from all study sites that participated in the study as per protocol. Recruitment
performance or specific expertise related to the nature and the key assessment parameters of the
study will be used to determine a coordinating investigator for the study. Results of exploratory
biomarker, imaging, digital health 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 guidelines, the sponsor shall have the right to publish such primary (multicenter) data and
information without approval from the investigator. The investigator has the right to publish study
site-specific data after the primary data are published. If an investigator wishes to publish
information from the study, a copy of the manuscript must be provided to the sponsor for review
at least 60 days before submission for publication or presentation. Expedited reviews will be
arranged for abstracts, poster presentations, or other materials. If requested by the sponsor in
writing, the investigator will withhold such publication for up to an additional 60 days to allow for
filing of a patent application. In the event that issues arise regarding scientific integrity or
regulatory compliance, the sponsor will review these issues with the investigator. The sponsor will
not mandate modifications to scientific content and does not have the right to suppress information.
For multicenter study designs and substudy approaches, secondary results generally should not be
published before the primary endpoints of a study have been published. Similarly, investigators
will recognize the integrity of a multicenter study by not submitting for publication data derived
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submitted for publication, within 18months after the study end date, or the sponsor confirms there
will be no multicenter study publication. Authorship of publications resulting from this study will
be based on the guidelines on authorship, such as those described in the International Committee
of Medical Journal Editors Recommendations for the Conduct, Reporting, Editing and Publication
of Scholarly Work in Medical Journals, which state that the named authors must have made a
significant contribution to the conception or design of the work; or the acquisition, analysis, or
interpretation of the data, for the work; and drafted the work or revised it critically for important
intellectual content; and given final approval of the version to be published; and agreed to be
accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity
of any part of the work are appropriately investigated and resolved.
Registration of Clinical Studies and Disclosure of Results
The sponsor will register and disclose the existence of and the results of clinical studies as required
by law. The disclosure of the final study results will be performed after the end of study in order
to ensure the statistical analyses are relevant.
DATA QUALITY ASSURANCE
Data Quality Assurance/Quality Control
Steps to be taken to ensure the accuracy and reliability of data include the selection of qualified
investigators and appropriate study sites, review of protocol procedures with the investigator and
study-site personnel before the study, periodic monitoring visits by the sponsor, and direct
transmission of clinical laboratory data from a central laboratory into the sponsor’s data base.
Written instructions will be provided for collection, handling, storage, and shipment of samples.
Guidelines for CRF completion will be provided and reviewed with study-site personnel before
the start of the study. The sponsor may review the CRF 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 from each study participant will be captured in an eCRF or ancillary data collection systems
(DCS) such as the IWRS, PRO tablets, laboratory database, and imaging database. Electronic
CRFs prepared by the sponsor are provided to the site for each participant. If the site is required to
enter data directly into an ancillary DCS, the applicable system will be prepared by the ancillary
data provider and provided to the site for each participant.
Case report forms are prepared and provided by the sponsor for each participant in electronic CRF.
All data relating to the study must be recorded in the CRF. All CRF 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 CRF are accurate and correct.


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The study data will be transcribed by study-site personnel from the source documents onto an
electronic CRF, or the ancillary DCS, if applicable. Study-specific data 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 entry in the applicable DCS
must be completed as soon as possible after a participant visit and the data should be available for
review at the next scheduled monitoring visit. The investigator must verify that all data entries in
the eCRF are accurate and correct.
All participative measurements (eg, pain scale information or other questionnaires) will be
completed by the same individual who made the initial baseline determinations whenever possible.
If necessary, queries will be generated in the electronic data capture (eDC) tool. If corrections to
a CRF are needed after the initial entry into the CRF, this can be done in either of the following
ways:
 Investigator and study-site personnel can make corrections in the eDC tool at their own
initiative or as a response to an auto query (generated by the eDC tool).
 Sponsor or sponsor delegate can generate a query for resolution by the investigator and study-
site personnel.
SOURCE DOCUMENTS
At a minimum, source documents consistent in the type and level of detail with that commonly
recorded at the study site as a basis for standard medical care must be available for the following:
participant identification, eligibility, and study identification; study discussion and date of signed
informed consent; dates of visits; results of safety and efficacy parameters as required by the
protocol; record of all AEs and follow-up of AEs; concomitant medication; intervention
receipt/dispensing/return records; study intervention administration information; and date of study
completion and reason for early discontinuation of study intervention or withdrawal from the
study, if applicable.
The author of an entry in the source documents should be identifiable. Given that patient-reported
outcomes (PROs) are reports of a patient's health condition that come directly from the patient,
without interpretation by a clinician or anyone else, the responses to PRO measures entered by
study participants into source records cannot be overridden by site staff or investigators.
Specific details required as source data for the study and source data collection methods will be
reviewed with the investigator before the study and will be described in the monitoring guidelines
(or other equivalent document).
The following data will be added into the electronic device and will be considered source data:
 
Clinical Outcome Assessments/PROs
 
Physician global assessment of disease activity


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GCA signs and symptoms assessment may be considered source, if collected through
electronic device.
The minimum source documentation requirements for Section 5.1 and Section 5.2 that specify a
need for documented medical history are as follows:
 Referral letter from treating physician or
 Complete history of medical notes at the site
 Discharge summaries
Inclusion and exclusion criteria not requiring documented medical history must be verified at a
minimum by participant interview or other protocol required assessment (eg, physical
examination, laboratory assessment) and documented in the source documents.
An 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 CRF in the protocol include the
eSource system, but information collected through eSource may not be limited to that found in the
CRF.
MONITORING
The sponsor will use a combination of monitoring techniques central, remote, or on-site monitoring
to monitor this study.
The sponsor will perform on-site monitoring visits as frequently as necessary. The monitor will
record dates of the visits in a study site visit log that will be kept at the study site. The first post-
initiation visit will be made as soon as possible after enrollment has begun. At these visits, the
monitor will compare the data entered into the CRF with the source documents
(eg, hospital/clinic/physician’s office medical records). At these visits, the monitor may compare
data entered into the CRF with the source documents (eg, hospital/clinic/physician’s office medical
records); a sample may be reviewed. The nature and location of all source documents will be
identified to ensure that all sources of original data required to complete the CRF 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.


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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 CRF and
all source documents that support the data collected from each participant, as well as all study
documents as specified in ICH/GCP Section 8, Essential Documents for the Conduct of a Clinical
Trial, and all study documents as specified by the applicable regulatory requirement(s). The
investigator/institution will take measures to prevent accidental or premature destruction of these
documents.
Essential documents must be retained until at least 2 years after the last approval of a marketing
application in an ICH region and until there are no pending or contemplated marketing applications
in an ICH region or until at least 2 years have elapsed since the formal discontinuation of clinical
development of the investigational product. These documents will be retained for a longer period
if required by the applicable regulatory requirements or by an agreement with the sponsor. It is the
responsibility of the sponsor to inform the investigator/institution as to when these documents no
longer need to be retained.
If the responsible investigator retires, relocates, or for other reasons withdraws from the
responsibility of keeping the study records, custody must be transferred to a person who will accept
the responsibility. The sponsor must be notified in writing of the name and address of the new
custodian. Under no circumstance shall the investigator relocate or dispose of any study documents
before having obtained written approval from the sponsor.
If it becomes necessary for the sponsor or the appropriate regulatory authority to review any
documentation relating to this study, the investigator/institution must permit access to such reports.


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


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10.4. Appendix 4: Adverse Events, Serious Adverse Events, Product Quality
Complaints, and Other Safety Reporting: Definitions and Procedures for
Recording, Evaluating, Follow-up, and Reporting
ADVERSE EVENT DEFINITIONS AND CLASSIFICATIONS
Adverse Event
An adverse event is any untoward medical occurrence in a clinical study participant administered
a pharmaceutical (investigational or non-investigational) product. An adverse event does not
necessarily have a causal relationship with the intervention. An adverse event can therefore be any
unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally
associated with the use of a medicinal (investigational or non-investigational) product, whether or
not related to that medicinal (investigational or non-investigational) product. (Definition per
International Council for Harmonisation [ICH]).
This includes any occurrence that is new in onset or aggravated in severity or frequency from the
baseline condition, or abnormal results of diagnostic procedures, including laboratory test
abnormalities.
Note:  The sponsor collects AEs starting with the signing of the ICF (refer to Section 8.3.1).
For combination products with a device constituent, adverse events include those resulting from
insufficient or inadequate instructions for use, deployment, implantation, installation, or operation,
or any malfunction of the device. It includes any adverse event resulting from use error or from
intentional misuse of the investigational device.
Serious Adverse Event
A SAE based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for Human
Use is any untoward medical occurrence that at any dose:
 
Results in death
 
Is life-threatening
(The participant was at risk of death at the time of the event. It does not refer to an event that
hypothetically might have caused death if it were more severe.)
 
Requires inpatient hospitalization or prolongation of existing hospitalization
 
Results in persistent or significant disability/incapacity
 
Is a congenital anomaly/birth defect
 
Is a suspected transmission of any infectious agent via a medicinal product
 
Is Medically Important*
*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


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participant or may require intervention to prevent one of the other outcomes listed in the
definition above. These should usually be considered serious.
For combination products with a device constituent, serious adverse events include adverse device
effects that resulted in any of the consequences characteristic of a serious adverse event. An
unanticipated serious adverse device effect is a serious adverse device effect which by its nature,
incidence, severity, or outcome has not been identified in the current version of the risk analysis
report (see Section 2.3. Benefit-Risk Assessment).
Unlisted (Unexpected) Adverse Event/Reference Safety Information
An adverse event is considered unlisted if the nature or severity is not consistent with the applicable
product reference safety information. For guselkumab, the expectedness of an adverse event will
be determined by whether or not it is listed in the IB.
ATTRIBUTION DEFINITIONS
Assessment of Causality
The causal relationship to study intervention  is determined by the investigator. The following
selection should be used to assess all AE.
Related
There is a reasonable causal relationship between study intervention administration and the AE.
The term “reasonable causal relationship” means there is evidence to support a causal relationship.
Not Related
There is no reasonable causal relationship between study intervention administration and the AE.
SEVERITY CRITERIA
An assessment of severity grade will be made using the following general categorical descriptors:
Mild: Awareness of symptoms that are easily tolerated, causing minimal discomfort, and not
interfering with everyday activities.
Moderate: Sufficient discomfort is present to cause interference with normal activity.
Severe: Extreme distress, causing significant impairment of functioning or incapacitation.
Prevents normal everyday activities.
The investigator should use clinical judgment in assessing the severity of events not directly
experienced by the participant (eg, laboratory abnormalities).
SPECIAL REPORTING SITUATIONS
Safety events of interest on a sponsor study intervention that may require expedited reporting or
safety evaluation include, but are not limited to:


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Overdose of a sponsor study intervention
 
Suspected abuse/misuse of a sponsor study intervention
 
Accidental or occupational exposure to a sponsor study intervention
 
Medication error, intercepted medication error or potential medication error involving a
Johnson & Johnson medicinal product (with or without patient exposure to the Johnson &
Johnson medicinal product, eg, product name confusion, product label confusion, intercepted
prescribing, or dispensing errors)
 
Exposure to a sponsor study intervention from breastfeeding
Special reporting situations should be recorded in the eCRF. Any special reporting situation that
meets the criteria of a SAE should be recorded on the SAE page of the eCRF.
PROCEDURES
All Adverse Events
All AEs, regardless of seriousness, severity, or presumed relationship to study intervention, must
be recorded using medical terminology in the source document and the eCRF. Whenever possible,
diagnoses should be given when signs and symptoms are due to a common etiology (eg, cough,
runny nose, sneezing, sore throat, and head congestion should be reported as "upper respiratory
infection"). Investigators must record in the eCRF their opinion concerning the relationship of the
adverse event to study therapy. All measures required for adverse event management must be
recorded in the source document and reported according to sponsor instructions.
For all studies with an outpatient phase, including open-label studies, the participant must be
provided with a "wallet (study) card" and instructed to carry this card with them for the duration
of the study indicating the following:
 
Study number
 
Statement, in the local language(s), that the participant is participating in a clinical study
 
Investigator’s name and 24-hour contact telephone number
 
Local sponsor’s name and 24-hour contact telephone number (for medical personnel only)
 
Site number
 
Participant number
 
Any other information that is required to do an emergency breaking of the blind
Serious Adverse Events
All SAEs that have not resolved by the end of the study, or that have not resolved upon the
participant’s discontinuation from participation in the study, must be followed until any of the
following occurs:
 
The event resolves


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The event stabilizes
 
The event returns to baseline, if a baseline value/status is available
 
The event can be attributed to agents other than the study intervention or to factors unrelated
to study conduct
 
It becomes unlikely that any additional information can be obtained (participant or health care
practitioner refusal to provide additional information, lost to follow-up after demonstration of
due diligence with follow-up efforts)
Any event requiring hospitalization (or prolongation of hospitalization) that occurs during
participation in the study must be reported as a SAE, 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 CRF).
Note: Hospitalizations that were planned before the signing of the ICF, and where the
underlying condition for which the hospitalization was planned has not worsened, will not be
considered SAEs. Any adverse event that results in a prolongation of the originally planned
hospitalization is to be reported as a new SAE
The cause of death of a participant in a study within 12 weeks of the last dose of study intervention,
whether or not the event is expected or associated with the study intervention, is considered a SAE.
Disease progression should not be recorded as an adverse event or SAE term; instead, signs and
symptoms of clinical sequelae resulting from disease progression/lack of efficacy will be reported
if they fulfill the SAE definition (refer to Adverse Event Definitions and Classifications in this
section).
Expected progression of disease should not be considered an adverse event (or SAE). However, if
determined by the investigator to be more likely related to the study intervention than the
underlying disease, the clinical signs or symptoms of progression and the possibility that the study
intervention is enhancing disease progression, should be reported per the usual reporting
requirements.
Information regarding serious adverse events will be transmitted to the sponsor using a serious
adverse event reporting form, which must be completed and signed by a physician from the study
site and transmitted in a secure manner to the sponsor within 24 hours. The initial and follow-up
reports of a serious adverse event should be made by facsimile (fax). Telephone reporting should
be the exception and the reporter should be asked to complete the appropriate form(s) first.


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


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10.5. Appendix 5: Revised American College of Rheumatology Criteria for
Diagnosis of GCA
2016 Revised American College of Rheumatology criteria for diagnosis of Giant Cell
(Temporal) Arteritisa, (Salehi-Abari 2016).
Entry Criteria
 
Age at onset ≥50 years old
 
Absence of exclusion criteriab
Domain I Criteria
 
New onset localized headachec
1p
 
Sudden onset of visual disturbancesc
1p
 
Polymyalgia Rheumatica (PMR) 
2p
 
Jaw Claudicationc 
1p
 
Abnormal temporal arteryd
up to 2p
Domain II
 
Unexplained fever and/or anaemia 
1p
 
ESR ≥50 mm/houre 
1p
 
Compatible pathologyf
up to 2p
a
In the presence of 3 points (p)or more out of 11 with at least one point belonging to domain I
along with all entry criteria, the diagnosis of Giant cell arteritis can be established;
b
Exclusion criteria are including: ENT and eye inflammation, kidney, skin and peripheral
nervous system involvement, lung infiltration, lymphadenopathies, stiff neck and digital
gangrene or ulceration;
c
No other etiologies can better explain any one of the criteria;
d
Enlarged and/or pulseless temporal artery: 1.p./tender temporal artery: 1.p;
e
It must be ignored in the presence of PMR;
f
Vascular and/or perivascular fibrinoid necrosis along with leucocyte infiltration: 1.p. /and
granuloma: 1.p.




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10.7. Appendix 7: Contraceptive and Barrier Guidance
Participants must follow contraceptive measures as outlined in Section 5.1, Inclusion Criteria.
Pregnancy information will be collected and reported as noted in Sections 8.3.5, Pregnancy and
10.4, Adverse Events, Serious Adverse Events, Product Quality Complaints, and Other Safety
Reporting: Definitions and Procedures for Recording, Evaluating, Follow-up, and Reporting.
Definitions
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming postmenopausal unless
permanently sterile (see below).
Woman Not of Childbearing Potential
 premenarchal
A premenarchal state is one in which menarche has not yet occurred.
 postmenopausal
A postmenopausal state is defined as no menses for 12 months without an alternative medical
cause. A high follicle stimulating hormone level (>40 IU/L or mIU/mL) in the postmenopausal
range may be used to confirm a postmenopausal state in women not using hormonal
contraception or hormonal replacement therapy (HRT), however in the absence of 12 months
of amenorrhea, a single follicle stimulating hormone measurement is insufficient. If there is a
question about menopausal status in women on HRT, the woman will be required to use one
of the non-estrogen-containing hormonal highly effective contraceptive methods if she wishes
to continue HRT during the study.
 permanently sterile
Permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal
occlusion/ligation procedures, and bilateral oophorectomy.
Note: If the childbearing potential changes after start of the study (eg, a premenarchal woman
experiences menarche) or the risk of pregnancy changes (eg, a woman who is not heterosexually
active becomes active), a woman must begin a highly effective method of contraception, as
described throughout the inclusion criteria.
If reproductive status is questionable, additional evaluation should be considered.
Contraceptive (birth control) use by men or women should be consistent with local regulations
regarding the acceptable methods of contraception for those participating in clinical studies.
Typical use failure rates may differ from those when used consistently and correctly. Use should
be consistent with local regulations regarding the use of contraceptive methods for participants in
clinical studies.


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


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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 SAEs 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.
b) Hormonal contraception may be susceptible to interaction with the study intervention, which may
reduce the efficacy of the contraceptive method. In addition, consider if the hormonal contraception
may interact with the study intervention.
c) Male condom and female condom should not be used together (due to risk of failure with friction).


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10.8. Appendix 8: Protocol Defined 26-Week Glucocorticoid Taper
Table 3: 
Protocol Defined 26-Week Glucocorticoid Taper#
Week  
Initial prednisone+ dose at Randomization (*)
60-50 mg 
49-40 mg 
39-30 mg 
29-20 mg
Daily dose 
(mg/day) 
Daily dose 
(mg/day) 
Daily dose 
(mg/day) 
Daily dose
(mg/day)
  0** 
60-50 
49-40 
39-30 
29-20
1 
50 
40 
30 
20
2 
40 
35 
25 
20
3 
35 
30 
20 
17.5
4 
30 
25 
20 
17.5
5 
25 
20 
17.5 
17.5
6 
20 
17.5 
17.5 
15
7 
17.5 
15 
15 
15
8 
15 
15 
15 
15
9 
12.5 
12.5 
12.5 
12.5
10 
12.5 
12.5 
12.5 
12.5
11 
10 
10 
10 
10
12 
10 
10 
10 
10
13 
9 
9 
9 
9
14 
8 
8 
8 
8
15 
7 
7 
7 
7
16 
6 
6 
6 
6
17 
6 
6 
6 
6
18 
5 
5 
5 
5
19 
5 
5 
5 
5
20 
4 
4 
4 
4
21 
4 
4 
4 
4
22 
3 
3 
3 
3
23 
3 
3 
3 
3
24 
2 
2 
2 
2
25 
1 
1 
1 
1
26 
0 
0 
0 
0
27 
0 
0 
0 
0
28 
Primary Endpoint Assessment Week 28
* Individual participants will be receiving different doses of prednisone (or equivalent) at
specified time points, depending on their initial GC dose at randomization. Therefore, the
tapering schedule indicates the required decrease in prednisone dose on a weekly basis, with
the specific week varying by individual participant.


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** The first week (Week 0) after randomization the participant will take their initial GC dose,
and per Week 1 start with their taper in accordance with this table and their initial starting
dose.
+ If the participant continues on GC other than prednisone or prednisolone, the Investigator
should contact the Sponsor to ensure that the taper is appropriately adjusted for the GC
equivalency compared with prednisone, using the Appendix 10 conversion table to convert
the Prednisone Taper doses to the equivalent alternate glucocorticoid.
# In countries where not all required tablet strengths are available to comply with the lower
doses of the protocol-defined taper, where authorized (ie, HA and Ethics Committee
approval in place), small variations in daily steroid dose of up to 0.5 mg/day are allowed to
make the taper feasible. Sites that are impacted by this should reach out to the sponsor
clinical team for further guidance before any participants start their taper. If tablets need to
be cut in half or in quarters this should preferably be performed by site staff.


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10.9. Appendix 9: Liver Safety: Suggested Actions and Follow-up Assessments
Guideline Algorithm for Monitoring, Assessment & Evaluation of Abnormal
Liver Tests in Participants with no Underlying Liver Disease
Abbreviations: ALT = alanine transaminase; AST = aspartate transaminase, INR = international normalized ratio;
SAE = serious adverse event; ULN = upper limit of normal, Tbili = Total bilirubin
Abbreviations: ALT = alanine transaminase; AST = aspartate transaminase, Tbili = total bilirubin; INR = international
normalized ratio; SAE = serious adverse event; ULN = upper limit of normal, Tbili = Total bilirubin
aIn participants whose liver function tests (ALT or AST) are ≥5× ULN, medication should be interrupted until a decrease in liver
function test is noted.
Liver Chemistry Increased Monitoring Algorithm with Continued Study Intervention for
Participants with ALT or AST ≥3× ULN but <8× ULN


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In those cases of liver function tests (ALT or AST) ≥5× ULN where a potential etiology other than
guselkumab is identified, the study intervention may be interrupted for an extended period
(>2 weeks) until a thorough assessment is performed by the investigator and Sponsor prior to the
restart of study intervention. If liver function tests remain ≥5× ULN for 2 weeks and are considered
related to study intervention, investigational treatment will be discontinued.


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Phase 3-4 liver chemistry stopping criteria are designed to assure participant safety and to evaluate
liver event etiology.
Liver Chemistry Stopping Criteria
ALT /AST- 
absolute
ALT or AST 8 × ULN
ALT /AST 
Increase 
ALT or AST 5 ×ULN but <8×ULN persists for 2 weeks
ALT or AST 3 ×  ULN but <5×ULN persists for 4 weeks
Bilirubin1, 2 
ALT or AST 3 × ULN and total bilirubin 2×ULN (or at least a doubling
of direct bilirubin in known Gilbert’s syndrome)
INR2 
ALT or AST 3 × ULN and international normalized ratio (INR) >1.5, if
INR measured
Cannot 
Monitor 
ALT or AST 5 × ULN but <8×ULN and cannot be monitored weekly for
2 weeks
ALT or AST 3 × ULN but <5×ULN and cannot be monitored weekly for
4 weeks
Symptomatic3 ALT or AST 3 × ULN associated with symptoms (new or worsening)
believed to be related to liver injury or hypersensitivity
Suggested Actions, Monitoring and Follow up Assessments
Actions 
Follow Up Assessments
 Immediately discontinue study intervention  
 Report the event to the sponsor within  
24 hours 
 Complete the [CRF as per CRF completion 
guidelines] and complete an SAE data 
collection tool if the event also met the
criteria for an SAE2
 Perform follow-up assessments as described 
in the Follow up Assessment column
 Monitor the participant until liver chemistry 
test abnormalities resolve, stabilize, or 
return to baseline (see MONITORING) 
MONITORING: 
If ALT[or AST]- 3×ULN AND total 
bilirubin 2×ULN (or at least a doubling of 
direct bilirubin in known Gilbert’s
syndrome) or INR >1.5 (if measured):
 Repeat liver chemistry tests (include ALT,
aspartate transaminase [AST], alkaline
phosphatase, total and direct bilirubin and 
INR) and perform liver event follow-up 
assessments within 24 hours 
 Viral hepatitis serology4
 Obtain blood sample for pharmacokinetic
(PK) analysis after the most recent dose5
 Obtain a serum creatine phosphokinase
(CPK) and lactate dehydrogenase (LDH)
 Fractionate bilirubin
 Obtain complete blood count with
differential to assess eosinophilia
 Record the appearance or worsening of
clinical symptoms of liver injury, or
hypersensitivity [CRF as per CRF
completion guidelines]
 Record use of concomitant medications
(including acetaminophen, herbal
remedies, recreational drugs, and other
over-the-counter medications)
 Record alcohol use on the [Relevant
Substance use tobacco CRF as per CRF
completion guidelines]
If ALT 3×ULN AND total bilirubin
2×ULN (or at least a doubling of direct
bilirubin in known Gilbert’s syndrome)
or INR >1.5 (if measured) obtain the


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 Monitor participant twice weekly until liver
chemistry test abnormalities resolve,
stabilize, or return to baseline
 A specialist or hepatology consultation is
recommended
For all other criteria
 Repeat liver chemistry tests (include ALT,
AST, alkaline phosphatase, total bilirubin
and INR) and perform liver chemistry
follow-up assessments within 24 to 72
hours
 Monitor participants weekly until liver
chemistry abnormalities resolve, stabilize, or
return to baseline
RESTART
 Do not restart/rechallenge participant with
study intervention.
following in addition to the assessments
listed above:
 Anti-nuclear antibody, anti-smooth
muscle antibody, Type 1 anti-liver kidney
microsomal antibodies, and quantitative
total immunoglobulin G (IgG) or gamma
globulins
 Liver imaging (ultrasound, magnetic
resonance, or computerized tomography)
to evaluate liver disease; complete [CRF
as per CRF completion guidelines]
 Liver biopsy may be discussed with local
specialist if available, for instance:
 In patients when serology raises the
possibility of autoimmune hepatitis
(AIH)
 In patients when suspected DILI
progresses or fails to resolve on
withdrawal of study intervention
 In patients with acute or chronic
atypical presentation: hepatic vascular
disorder, chronic hepatitis fibrosis,
micro vesicular statosis
 If liver biopsy conducted complete (CRF
as per CRF completion guidelines).
1. Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not
immediately available, stop study intervention if ALT [or AST] 3×ULN and total bilirubin 2×ULN.
Additionally, if serum bilirubin fractionation testing is unavailable, record the absence/presence of detectable
urinary bilirubin on dipstick which is indicative of direct bilirubin elevations suggesting liver injury.
2. All events of ALT [or AST] 3×ULN and total bilirubin 2×ULN (or at least a doubling of direct bilirubin for
known Gilbert's syndrome) or ALT [or AST] 3×ULN and INR >1.5 may indicate severe liver injury (possible
‘Hy’s Law’) and must be reported to sponsor in an expedited manner and as an SAE if SAE criteria met
(excluding studies of hepatic impairment or cirrhosis). The INR stated threshold value will not apply to
participants receiving anticoagulants.
3. New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right upper
quadrant pain or tenderness, or jaundice) or hypersensitivity (such as fever, rash, or eosinophilia).
4. Includes: hepatitis A immunoglobulin M (IgM) antibody; HBsAgG and HBcAB; hepatitis C RNA;
cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, heterophile
antibody or monospot testing); and hepatitis E IgM antibody. In those with underlying chronic hepatitis B at
study entry (identified by positive hepatitis B surface antigen) quantitative hepatitis B DNA and hepatitis delta
antibody. If hepatitis delta antibody assay cannot be performed, it can be replaced with a polymerase chain
reaction (PCR) of hepatitis D RNA virus (where needed) [Le Gal, 2005].
5. Record the date/time of the PK blood sample draw and the date/time of the last dose of study intervention prior
to the PK blood sample draw on the CRF. If the date or time of the last dose is unclear, provide the participant’s
best approximation. If the date/time of the last dose cannot be approximated OR a PK sample cannot be collected
in the time period indicated above, do not obtain a PK sample. Instructions for sample handling and shipping are
in the Study Reference Manual.


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Liver Chemistry Increased Monitoring Criteria and Actions with Continued Study
Intervention
Criterion 
Actions
ALT or AST3xULN and <5xULN
and total bilirubin <2xULN or
INR<1.5, withoutsymptoms believed
to be related to liver injury or
hypersensitivity, and who can be
monitored weekly for 4 weeks
 Notify the Sponsor within 24 hours of learning of
the abnormality to discuss participant safety
 Participant must return weekly for repeat liver
chemistry tests (ALT, AST, alkaline phosphatase,
total bilirubin) until the abnormalities resolve,
stabilize, or return to baseline
 If at any time, the participant meets liver
chemistry stopping criteria, proceed as described
in Section 7.1.
 If, after 4 weeks of monitoring, ALT or
AST<3xULN and total bilirubin <2xULN,
monitor participants twice monthly until liver
chemistry tests resolve, stabilize, or return to
baseline.




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10.11. Appendix 11: Guidance on Study Conduct during the COVID-19 Pandemic
It is recognized that the Coronavirus Disease 2019 (COVID-19) pandemic may have an impact on
the conduct of this clinical study due to, for example, isolation/quarantine of participants and
study-site personnel; travel restrictions/limited access to public places, including hospitals; study
site personnel being unavailable, isolated, or reassigned to critical tasks.
The sponsor is providing options for study -related participant management in the event of
disruption to the conduct of the study. This guidance does not supersede any local or government
guidelines or requirements or the clinical judgement of the investigator to protect the health and
well-being of participants and site staff. If at any time a participant’s travel to the study site is
considered to be dangerous, study intervention  may be interrupted. If it becomes necessary to
discontinue participation in the study, the procedures outlined in the protocol for discontinuing
study intervention will be followed.
If, as a result of the COVID-19 pandemic, scheduled visits cannot be conducted in person at the
study site, they will be performed to the extent possible remotely/virtually or delayed until such
time that on-site visits can be resumed. At each contact, participants will be interviewed to collect
safety data. Key efficacy endpoint assessments should be performed if required and as feasible.
Participants will also be questioned regarding general health status to fulfill any physical
examination requirement.
Every effort should be made to adhere to protocol-specified assessments for participants on study
intervention, including follow up. Modifications to protocol-required assessments may be
permitted using the examples contained in this appendix, after consultation between the participant
and investigator, and with the agreement of the sponsor (see below).
The sponsor will continue to monitor the conduct and progress of the clinical study, and any
changes will be communicated to the sites and to the health authorities according to local guidance.
If a participant has tested positive for COVID-19, the investigator should contact the sponsor’s
responsible medical officer to discuss plans for administration of study intervention, performing
study assessments, and follow-up. Modifications made to the study conduct as a result of the
COVID-19 pandemic should be summarized in the clinical study report.
ADDITIONAL ELEMENTS, WHERE APPLICABLE:
 
Certain protocol-mandated visits to the study site may not be possible during the COVID-19
outbreak. Therefore, temporary measures may be implemented if considered appropriate by
the Sponsor and Investigator to maintain continuity of patient care and study integrity. Certain
measures, such as those listed below, may be necessary and should be instituted in accordance
with applicable (including local) laws, regulations, guidelines, and procedures:
 
remote (eg, by phone / telemedicine) or in-person, off-site (eg, in-home) interactions
between site staff (or designees) and patients for study procedures eg, those related to
safety monitoring / efficacy evaluation / study drug storage and administration (including
training where pertinent)


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laboratory assessments using a suitably accredited local laboratory; for selected measures
(eg, urine pregnancy), home testing may be employed
 
other procedures may be conducted at an appropriate facility
 
Missed assessments/visits will be captured in the clinical trial management system for
protocol deviations.  Discontinuations of study interventions and withdrawal from the study
should be documented with the prefix “COVID-19-related” in the case report form (CRF).
 
other relevant study data elements impacted by the pandemic should also be documented
/ labeled as “COVID-19-related” in CRFs and / or other study systems, as directed by
detailed Sponsor guidance. These may include missed / delayed / modified study visits /
assessments / dosing, and instances where temporary measures such as those above are
implemented
 
The Sponsor will evaluate the totality of impact of COVID-19 on collection of key study data
and additional data analyses will be outlined in study SAP(s).
 
NOTES on COVID-related exclusion:
1. If a patient is excluded due to recent COVID-19-related features, the reason for screen
failure should be documented in the case report form under the exclusion criterion of
having a condition for which participation would not be in the participant’s interest or
could confound study assessments.
2. The field of COVID-related testing (for presence of, and immunity to, the
SARS-CoV-2 virus) is rapidly evolving. Additional testing may be performed as part
of screening and/or during the study if deemed necessary by the investigator and in
accordance with current regulations / guidance from authorities / standards of care.
 
Precaution: for those who may carry a higher risk for severe COVID-19 illness (eg, those aged
over 65 years), follow guidance from local health authorities when weighing the potential
benefits and risks of enrolling in the study, and during participation in the study.


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10.12. Appendix 12: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located
directly before the Table of Contents. A summary of previous amendments is provided below.
Amendment 4 (17 September 2021)
Overall Rationale for the Amendment: This clinical study has been experiencing slow enrollment of
participants and 2 participants had withdrawn consent during screening. Based on feedback from the study
sites, the actigraphy watch appeared to be a hurdle for participants to participate in the trial. As actigraphy
is an exploratory endpoint, the study team is introducing the possibility for participants to decline this
assessment to increase enrollment rates. Additional assessments were also adjusted to increase enrollment
rates.
Section Number
and Name
Description of Change 
Brief Rationale
1.3. Schedule of Activities (SoA); 
7.2. Participant 
Discontinuation/Withdrawal From 
the Study; 8.10. Digital Health –
Actigraphy Measurements 
Footnote ‘m’: Added that participants
have the opportunity to decline use of
the actigraphy watch.
Statement revised to allow for a
participant withdrawing consent the
opportunity to decline actigraphy
assessment/ measurements.
Based on feedback from
participants and site, actigraphy
assessments have been made
optional to minimize burden on
participants.
1.3. Schedule of Activities (SoA) 
Timepoints for weight assessment was
changed.
Timepoints for efficacy assessments
were changed:
 All assessments under early
termination visits were deleted
 Assessments for Physician’s
Global Assessment for
Disease Activity (PhGA),
Patient’s Global Assessment
of Disease Activity (PGA),
Pain Assessment, FACIT-
Fatigue, and SF-36 were
deleted for Week 12, 20, 36
and 44.
 Assessment for ESR/CRP were
deleted for early termination
visit.
Timepoints for pharmacokinetics and
immunogenicity changed:
 Assessments at Week 20, 24, 40
and 60 were deleted
Timepoints for biomarker assessments
were changed:
 Assessments for serum
biomarkers and whole blood
(PAXgene) were deleted for
Week 8, 12, 20, 40, and early
termination visit and PBMC
sample collection was deleted
for Week 12 and Flare visit.
Assessments were reduced to
decrease potential burden to
participants.


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Section Number 
and Name
Description of Change 
Brief Rationale
1.4. Schedule of Activities (SoA)– 
Long Term Extension  
 Timepoints for weight 
assessment was changed 
 C-SSRS assessment was deleted 
under timepoints: Week 100 
(LTE Week 48), Week 112 
(LTE Week 60), and early 
termination visit in LTE 
period; added under Week 104
(LTE Week 52).
 All efficacy assessments under
early termination visits were
deleted
 Assessments for Clinical
Assessor’s GCA Disease
Assessment S&S, Physician’s
Global Assessment of Disease
Activity (PhGA), Patient’s
Global Assessment of Disease
Activity (PGA), Pain
Assessment, FACIT-Fatigue,
and SF-36 were deleted for
Week 112 (LTE Week 60).
 Assessment for ESR/CRP was
deleted on Week 112 (LTE
Week 60) and early
termination visit in the LTE
period.
 Serum biomarkers and whole
blood (PAXgene) were
deleted.
Adjustments made in 12 week
safety follow up visit and early
termination visit to to reduce
participant burden. Serum
biomarkers and whole blood
removed to reduce participant
burden.
4.1. Overall design  
 Clarification of visit in Safety 
Follow-up period in main 
study. Adding timing of the 
Flare visit. 
 Clarification of visit in Safety
Follow-up period in LTE
period of the study. Adding
the follow-up visits after
participants experience a Flare
(timing of Flare visit and early
termination visit).
For participants in the placebo arm,
they can maystill continue in the study
until Week 112.
Clarification of visits to be
scheduled after flare or study
discontinuation during LTE
period according to SoA.
1.1. Synopsis; 1.4. Schedule of
Activities (SoA)–Long Term
Extension; 4.1. Overall Design; 6.1.
Study Interventions Administered;
8.9 Exploratory FDG-PET/CT
imaging
Under Intervention Groups and
Duration, GC rescue medication was
deleted.
Footnote ‘c’: GC rescue medication
was deleted.
Footnote ‘e’ updated to include the
following regarding a GCA flare, “or
other timeframe in accordance with
local country regulations”
Removal of redundant text.
Harmonize footnote with
wording in body of protocol.
Reduce assessments.


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Section Number 
and Name
Description of Change 
Brief Rationale
Footnote ‘e’ amended to add the ability
of participants to decline PET-CT that
is obtained in the LTE.
2.3.1. Risks for Study Participation 
Table was updated for infections and 
transaminase increases identified as 
adverse reactions of guselkumab as 
well as hypersensitivity. 
Added language as a rationale
for the existing exclusion and
discontinuation criteria and
safety assessments in the study.
3. Objective and Endpoints 
Exploratory objective (LTE): The 
endpoints for the participant and 
clinician-reported assessments was 
revised to remove Week 112 (LTE
Week 60) or ET visit.
Focus follow up safety and
early termination visit on safety
assessments.
1.1. Synopsis; 3. Objective and 
Endpoints 
Moved Secondary Objective ‘To 
evaluate the changes in immune- 
markers to guselkumab compared to 
placebo, in combination with a 26- 
week GC taper regimen, in adult 
participants with new-onset or 
relapsing GCA’ to Exploratory 
objectives.
Objective is degraded to
Exploratory, Immune-markers
ESR and CRP are non-specific
markers of inflammation and
changes in these markers alone
(without signs and symptoms of
GCA) may have other causes.
3. Objective and Endpoints; 9.4.3. 
Secondary Endpoints 
Modified endpoint to include ‘or 
discontinuation of study intervention 
due to AE of worsening of GCA’ to the 
objectives ‘time to first GCA disease 
Flare’ and ‘number of GCA disease 
flares’ 
Objectives broadened to
include participants that have
worsening of GCA without
classification as having a Flare,
for example for participants
that have not reached the status
“in remission”
5.1. Inclusion Criteria 
Criteria 4 amended to add that both 
temporal artery biopsy revealing
features of GCA and evidence of
cranial GCA can be obtained either at
time of diagnosis or at any time point
during disease history
Protocol clarification
5.2. Exclusion Criteria; 6.8.1. 
Permitted Therapy  
Criteria 23 amended to include new  
text: ‘stable dose for minimally 4 
weeks’.
The duration of stable methotrexate
dosage (if used) was revised from 6 to
4 weeks. Maximum dose was increased
to 25mg oral or SC methotrexate and
15 mg SC was deleted
To align with standard of care
in GCA.
7.1. Discontinuation of Study 
Intervention 
Treatment discontinuation criteria text 
relocated to clarify that study 
intervention discontinuation is required 
if GCA flare occurs during LTE period. 
Protocol clarification.
Discontinuation of study
intervention should not be
‘considered’ and therefore
should be mentioned in the first
section. The description of the
follow-up visits was incorrect
and is already described
elsewhere in the protocol.
8. Study Assessments and 
Procedures 
Total blood volume to be collected 
from each participant was reduced from 
450 mL to 300 mL. 
Total volume is lower due to
reduced assessments
implemented in this
amendment


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Section Number 
and Name
Description of Change 
Brief Rationale
8.1.1. GCA Disease signs and 
symptoms 
Removed text “new-onset” and 
changed ‘findings’ to ‘signs’
Minor clarification
8.2.2. Vital signs 
Reduce number of assessments 
required with SC administration in 
absence of symptoms
Reduce patient burden and
align with other protocols.
3. Objective and Endpoints; 9.4.3. 
Secondary Endpoints 
Moved ‘Supportive Secondary 
Endpoints’ to ‘Exploratory endpoints’
Protocol clarification
10.7. Appendix 7: Contraceptive 
and Barrier Guidance 
Bilateral tubal occlusion was deleted 
from Examples of Contraceptives. 
Clarification of categorization
of bilateral tubal occlusion.
Throughout the protocol 
Minor grammatical, formatting, or 
spelling changes were made.
Minor errors were noted.
Amendment 3 (09 July 2021)
Overall Rationale for the Amendment: To add a long-term extension (LTE) period to the study for
evaluating the long-term effectiveness of guselkumab, and to offer participants who are still in remission at
Week 52, the opportunity to continue to be treated with the study intervention until they become
non-responsive.
Section Number 
and Name
Description of Change 
Brief Rationale
1.1. Synopsis 
Deleted ‘a generalized linear model with logit link 
for binary repeated measurement data and/or’ for 
binary endpoint analysis. 
To clarify that logistic regression
will be used as sensitivity analysis
for the primary endpoint only, and
that the primary endpoint and major
secondary endpoint will use
Cochran-Mantel-Haenszel test.
To align with changes made to
Section. 9.4.1. General
Considerations during Amendment
2.
1.2. Schema 
The schematic overview of study was updated to 
indicate start of follow-up period from Week 48 
onwards.
To correctly align with the
protocol.
1.2. Schema 
The study design for the LTE period was added. 
To accommodate information for
the LTE period of the study.
1.3. Schedule of 
Activities (SoA)
Footnote‘s’ for Week 52 visit was added. 
1.4. Schedule of 
Activities (SoA) – 
Long-Term
Extension
The schedule of activities for the LTE period was
added.
1.1. Synopsis; 
3. Objective And 
[Endpoints And/Or
Estimands]
The exploratory objective and endpoints for the
LTE period were added.
2.3.1. Risks for 
Study Participation; 
8.9. Exploratory 
FDG-PET/CT 
Imaging 
 The details on additional fluorodeoxyglucose-
positron emission tomography/computed
tomography scan in the LTE period were
added.
 Added a note that FDG-dose may be modified
in consultation with the sponsors in countries
where local regulations require this.
4.1. Overall Design  
 The duration of the LTE period was added.


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Section Number 
and Name
Description of Change 
Brief Rationale
 The count of DBL for the study was changed
from 2 to 3 and information on DBL for the
LTE period was defined.
 The study design for the LTE period was
added.
4.4. End of Study 
Definition
The definition of study completion was modified.
5.1. Inclusion 
Criteria (#19)
Inclusion criteria for the LTE period was added.
1.1. Synopsis; 
6.1. Study 
Intervention(s)
Administered
The period for SC injection in participants of the
LTE period was added.
1.1. Synopsis; 
1.2. Schema;
6.6. Continued
Access to Study
Intervention After
the End of the Study
The option to enter the LTE period was mentioned.
7.1. Discontinuation 
of Study 
Intervention
The conditions for discontinuation of study
intervention in the LTE period were added.
9.4.4. 
Tertiary/Exploratory 
Endpoint(s) 
The following text was modifiedas ‘Further
details of tertiary/exploratory endpoints analyses
and analyses for efficacy during the LTEwill be
provided in the SAP’.
1.3. Schedule of 
Activities (SoA) 
(Footnote l)
Footnote was updated to define that the C-SSRS is 
physician administerd.
To provide clarity to the protocol.
1.2. Schema; 
2.3.1. Risks for 
Study Participation; 
4.1 Overall Design;
4.4. End of Study
Definition;
6.6. Continued
Access to Study
Intervention After
the End of the
Study;
9.4.5. Safety
Analyses
The terms ‘main’ or ‘main study’ were added. 
To distinguish the study
information for Main study and the
LTE period.
1.1. Synopsis; 6.1. 
Study 
Intervention(s) 
Administered
Sentence revised to include "or the participants
discontinues treatment due to unblinding after the
Week 60 DBL for the Main study"
4.1. Overall Design; 
4.4. End of Study 
Definition; 
7.1. Discontinuation 
of Study
Intervention
The term ‘double-blind treatment period’ or 
‘double-blind phase’ was changed to ‘main study 
treatment period’ or ‘main study phase’. 
To avoid the suggestion that
participants will be unblinded after
completing treatment in the main
study.
4.4. End of Study 
Definition; 
The pronouns ‘he or she’ was replaced with ‘the 
participant’. 
To adhere with the current
standards for gender inclusivity.


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Section Number 
and Name
Description of Change 
Brief Rationale
5.1. Inclusion
Criteria (#16 and
#17);
5.2. Exclusion
Criteria (Note);
5.3. Lifestyle
Considerations;
7.3. Lost to
Follow-up
5.2. Exclusion 
Criteria (#2) 
The term ‘PMR’ was removed. 
To avoid confusion, as PMR is also
a symptom of GCA and listed in
the revised ACR diagnostic criteria.
6.3. Measures to 
Minimize Bias: 
Randomization and 
Blinding
Subheading Blinding: Sentence was revised to 
clarify main study with a database finalization at 
Week 60. 
To distinguish the study
information for main study and the
LTE period.
6.8.1. Permitted 
Therapy (Anti- 
Hypertensive 
Therapy, Non-
steroidal Anti-
inflammatory
Drugs)
Week 52 was changed to ‘4 weeks after the last 
dose of study intervention’ for anti-hypertensive 
therapy and non-steroidal anti-inflammatory drugs.
To make the timelines applicable
for both the main study as the LTE.
6.8.1. Permitted 
Therapy (Non-live 
vaccines, including
COVID-19
vaccines)
Information on non-live vaccines including 
COVID-19 vaccines was added. 
To provide guidance on the use of
COVID-19 vaccine.
8.2.8. Injection-Site 
Reactions 
Information around reporting of injection-site 
reactions for LTE participants was added. 
To allow for short dosing visits on
days where minimal assessments
are performed in the LTE period.
8.3.1. Time Period 
and Frequency for 
Collecting Adverse 
Event and Serious
Adverse Event
Information; 10.2.
Appendix 2: Clinical
Laboratory Tests
Instructions for investigators on reporting cases of 
biochemical Hy’s law was included in the protocol
body.
To provide clarity to the protocol.
9.4.5. Safety 
Analyses 
The safety analyses was defined for participants in 
the LTE period.
To encompass the LTE period.
9.4.6. Other 
Analyses 
The analyses of large-vessel imaging changes from
baseline in PETVAS was summaries per
participant and by treatment intervention was
updated to include Week 104 participants.
9.6. Data Monitoring 
Committee 
The monitoring of safety data by DMC was
extended until study completion (or termination).
10.3 Appendix 3: 
Regulatory, Ethical, 
and Study Oversight 
Considerations
(Regulatory and
Ethical
Considerations)
Added text on protocol clarification 
communications. 
To account for potential use of a
‘Protocol Clarification
Communication.


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Section Number 
and Name
Description of Change 
Brief Rationale
10.9. Appendix 9: 
Liver Safety: 
Suggested Actions 
and Follow-up 
Assessments 
 
Appendix replaced with latest version with 
updated definition for Hy’s Law  
 
Section title was updated to remove [and 
Study Intervention Rechallenge Guidelines] 
 
Stopping criteria and follow-up assessments 
added 
 
Update to align with current
standards
 
Removal of not applicable
language between brackets
 
Adding pages that were
missing.
10.10. Appendix 10: 
Glucocorticoid 
Conversion Table
The value of betamethasone was changed from 0.6 
to 0.75 
Protocol clarification to promote
consistency between sites
10.11. Appendix 11: 
Guidance on Study 
Conduct during the 
COVID-19 
Pandemic 
 
Section was updated 
 
Information on direct-to-patient shipments is 
removed 
 
Information on exclusion criteria is removed. 
 
To align with the latest template
 
Direct-to-patients shipments is
not applicable for the study
 
To avoid duplication, because
COVID-19 exclusion criteria
have been incorporated in
protocol Section 5.2 with
Protocol Amendment 2.
Throughout the 
protocol 
Minor grammatical and formatting changes were 
made.
Minor errors were noted.
Amendment 2 (18 December 2020)
Overall Rationale for the Amendment: The primary driver for this amendment is to add clarifying
language to Section 10.8, Appendix 8, Protocol Defined 26-Week Glucocorticoid Taper to allow for more
flexibility to execute the protocol-defined 26-week steroid taper. This flexibility is needed to accommodate
the use of tablet strengths other than 1 mg prednisone equivalent to achieve required doses if these tablets
are not locally available. Other changes are made in response to feedback acquired from the Health
Authorities (HA), Ethics Committees, and Investigators.
Section Number 
and Name
Description of Change 
Brief Rationale
1.1. Synopsis;
3. Objective and
[Endpoints and/or
Estimands];
10.3. Appendix 3:
Regulatory, Ethical,
and Study Oversight
Considerations
(Source Documents)
Replaced ‘Health-Related Quality of Life’ by
‘Clinical Outcome Assessments’.
To better describe the
questionnaires performed in the
study. To clarify that only the
SF-36 falls under the definition of
Health-Related Quality of Life and
the other questionnaires are better
described as ‘Clinical Outcome
Assessments.
9.4.4.
Tertiary/Exploratory
Endpoint(s)
Replaced ‘Health-Related Quality of Life and
Fatigue’ by ‘Clinical Outcome Assessments’.
1.1. Synopsis
(Statistical
Methods);
9.3. Analysis Sets
Definition for Pharmacokinetic Analysis Set was
updated.
To align with the standard
definition in statistical analysis plan
and for consistency within the
protocol.
1.1. Synopsis;
9.4.1. General
Considerations
Deleted ‘nominal’ and clarified that statistical tests
will be performed at a 2-sided significance level.
Added the terms ‘secondary’ to clarify that
multiplicity adjustment will not be done for
Protocol clarification and update to
align with statistical analysis plan.


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Section Number 
and Name
Description of Change 
Brief Rationale
secondary endpoints and nominal p values will be
reported.
1.3. Schedule of 
Activities (SoA) 
Updated footnote j to include direction for baseline 
use of fluorodeoxyglucose - positron emission 
tomography/computed tomography scan. 
To provide clarification to align
with inclusion criterion 4 and to
avoid excess radiation exposure of
participants.
1.3. Schedule of 
Activities (SoA) 
Added footnote r: Recommended additional 
optional telephone contact with participant to 
verify correct tapering of steroid intake.
To increase compliance to
protocol-defined taper.
2.1.1. Unmet Need 
in Giant Cell 
Arteritis
Split sentence and added the word ‘often’ in first 
sentence to 5th  paragraph. 
To accommodate an HA request for
clarification.
2.2. Background 
Update the number of participants exposed to 
guselkumab in the clinical development program. 
To accommodate updates from the
latest edition (edition 11) of
Investigator’s Brochure.
4.2. Scientific 
Rationale for Study 
Design  
Indicated that the biomarker sample collection was 
restricted by local regulations. 
To accommodate potential country
specific restrictions for biomarker
sample collection (such as samples
for pharmacogenomic research).
5.1. Inclusion 
Criteria 
Modified inclusion criterion 6 to accommodate 
update to criterion 4 from amendment 1.
Updated to provide clarification.
5.2. Exclusion 
Criteria 
Modified exclusion criterion 22 to include “Within 
3 months of first study intervention or at least 5 
half-lives (whichever is greater)” for 
hydroxychloroquine, cyclosporine A, azathioprine, 
tacrolimus, sirolimus, sulfasalazine, leflunomide 
with cholestyramine washout or mycophenolate
mofetil/mycophenolic acid.
To accommodate an HA request,
safety measure, and protocol
clarification, because wash-out
period of 6 weeks may not always
be sufficient.
6.8.2. Prohibited 
therapies 
Added ‘use of’ and ‘for GCA’ to oral 
glucocorticoids (GCs). 
Updated to provide clarification
(limited use for other indications
was not prohibited).
6.8.2. Prohibited 
therapies 
Added ‘until end of study” to intramuscular, 
intra-articular, intrabursal, epidural, intra-lesional,
or IV GCs subsection.
Updated to provide clarification.
6.8.3. Rescue 
Medication  
Languages changed from “the participant should 
continue” to “the participant may continue” plus 
added additional explanation on the follow-up 
procedures. 
Updated to allow the investigator to
decide whether a participant that
has a flare should continue on study
agent given there are alternative
treatments other than GC such as
tocilizumab.
Additionally, updated to
accommodate an HA request.
Deleted the paragraph on the posttreatment phase. 
To avoid duplication and because
the paragraph should not be part of
the Section 6.8.3. Rescue
Medication.
7.1. Discontinuation 
of Study 
Intervention 
Clarification of discontinuation criterion regarding 
TB: replacement of “is deemed ineligible” by
“becomes ineligible”.
To correct the language.
7.1. Discontinuation 
of Study 
Intervention; 
10.2. Appendix 2: 
Clinical Laboratory 
Tests;
 
Removed the liver function tests results that will 
lead to discontinuation but instead and refer 
only to the Section 10.9 which now contains 
both alanine aminotransferase (ALT) and 
aspartate aminotransferase (AST) evaluations. 
 To not duplicate criteria for
treatment discontinuation that
are presented and updated in
Section 10.9 to avoid
misinterpretation.


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Section Number 
and Name
Description of Change 
Brief Rationale
10.9. Appendix 9: 
Liver Safety: 
Suggested Actions 
and Follow-up 
Assessments [and 
Study Intervention 
Rechallenge 
Guidelines] 
 
Included the evaluation of AST in the note 
section of clinical chemistry. 
 
The Algorithm was updated. Added footnote to 
Section 10.9 to clarify that in this trial the study 
intervention should be interrupted in case of 
ALT or AST ≥5× ULN and <8× ULN until a 
decrease in liver function test is noted or new 
results require to permanently discontinue 
treatment. 
 To ensure consistency between
Section 10.2 and 10.9 and align
with liver function test related
discontinuation criteria
previously specified in
Section 7.1. that were selected
for this study.
 Footnote was added to
Section 10.9 to accommodate
an HA request.
8.2.10. 
Hypersensitivity 
Reactions
Added the assessment criteria for potential cases of 
anaphylaxis guidance.
To accommodate an HA request.
8.2.10. 
Hypersensitivity 
Reactions
Added the guidance around the management of 
hypersensitivity reactions. 
To accommodate an Ethics
Committee request.
9.4.1. General 
Considerations 
Deleted ‘a generalized linear model with logit link 
for binary repeated measurement data and/or’ for 
binary endpoint analysis. 
To clarify that logistic regression
will be used as sensitivity analysis
for the primary endpoint only, and
that the primary endpoint and major
secondary endpoint will use
Cochran-Mantel-Haenszel test.
9.4.5. Safety 
analysis 
Definition of treatment emergent adverse event 
adjusted: “day of last dose plus 12 weeks” replaced 
by “end of the study”. 
To be aligned with the programmed
definition of treatment emergent
adverse events.
10.4. Appendix 4: 
Adverse Events, 
Serious Adverse
Events, Product
Quality Complaints,
and Other Safety
Reporting:
Definitions and
Procedures for
Recording,
Evaluating, Follow-
up, and Reporting
(Attribution
Definitions)
Corrected definition of Not Related Adverse 
Events. 
Updated to correct error in
language.
10.8. Appendix 8: 
Protocol Defined 
26-Week 
Glucocorticoid 
Taper 
Additional language was added to provide 
flexibility to the taper regimen. 
To accommodate tapering with
tablets strength >1 mg if these are
not available locally. Small
variations in tapering regimen are
not considered clinically relevant as
long as steroid taper is gradual and
reaches 0 in Week 26.
11. References 
Added new literature references #23 and 35 
(guidance document on the management of 
hypersensitivity reactions and anaphylaxis).
To support information added in
Section 8.2.10.
Throughout the 
protocol 
The word ‘subject’ was replaced by ‘participant’. 
To conform with the company
standard naming convention.
Minor grammatical, formatting, or spelling changes 
were made.
Minor errors were noted.


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Amendment 1 (09 July 2020)
Overall Rationale for the Amendment: The imaging requirements for confirmation of diagnosis
(Inclusion Criterion #4) were expanded to increase the eligibility of sites to participate in this study. Next
to temporal artery biopsy and doppler-ultrasound, imaging techniques using Magnetic Resonance
(Magnetic Resonance Imaging and Magnetic Resonance Angiography) are allowed to confirm giant cell
arteritis (GCA) diagnosis. In addition, the protocol has been updated with respect to the conditions and
analyses 
of 
the 
fluorodeoxyglucose-positron emission tomography/computed tomography
(FDG-PET/CT)-imaging, according to the imaging protocol and analyses plan that has become available
after finalization of the initial protocol.
Section number 
and Name
Description of Change 
Brief Rationale
1.3 Schedule of 
Activities 
PROs added to Week 44 
PROs were inadvertently omitted at
this timepoint.
1.3 Schedule of 
Activities 
Additional serum sample for biomarkers added to 
visit Week 40 and extra sample for Whole blood 
(PAXgene) added to visit Week 8 and Week 40. 
These timepoints have been
identified as high interest for
understanding of the disease and of
mechanism of action of the
compound.
2.3.1 Risks for 
Study Participation  
Adjusted the estimated radiation dose and removed 
statement that CT scan will be limited to the torso. 
More details on the exact PET/CT
procedure have become available
requiring an update of the protocol
text.
5.1 Inclusion 
Criteria 
Expanded acceptable imaging modality for 
inclusion criterion #4. 
Allow additional imaging
modalities that are readily available
at sites as long as focus remains on
cranial manifestations of GCA.
5.2 Exclusion 
Criteria 
Reworded Exclusion criterion #21 
To describe more clearly under
which conditions certain previous
therapies are not allowed. Changed
based on feedback from sites.
8.9 Exploratory 
FDG-PET/CT 
Imaging 
Removed the word ‘upper’ 
More details on the exact procedure
have become available requiring an
update of the protocol text.
8.9 Exploratory 
FDG-PET/CT
Imaging
Changed wording on fasting condition 
Clarification
9.4.6 Other 
Analyses 
Adjusted procedure for exploratory FDG-PET/CT 
Imaging Analyses 
More details on the exact procedure
have become available requiring an
update of the protocol text.
1.1 Synopsis 
1.3 Schedule of 
Activities 
8.4.1 Evaluations
Added text to clarify that pharmacokinetic (PK) 
sample should be drawn from a different line than 
the IV administration line 
To prevent potential aberrant data
due to sampling from the same line
as the IV administration.
Appendix 10.2 
Removed ‘HCV RNA (if applicable)’ template text Not applicable in this study.
Throughout the 
protocol 
Minor grammatical, formatting, or spelling changes 
were made.
Minor errors were noted


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11. 
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Status: Approved, Date: 25 May 2022
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Guselkumab (CNTO1959) 
Clinical Protocol CNTO1959GCA2001 Amendment 5
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142
Status: Approved, Date: 25 May 2022
INVESTIGATOR AGREEMENT
I have read this protocol and agree that it contains all necessary details for carrying out this study. I will
conduct the study as outlined herein and will complete the study within the time designated.
I will provide copies of the protocol and all pertinent information to all individuals responsible to me who
assist in the conduct of this study. I will discuss this material with them to ensure that they are fully informed
regarding the study intervention, the conduct of the study, and the obligations of confidentiality.
Coordinating Investigator (where required):
Name (typed or printed):
Institution and Address:
Signature: 
Date:
(Day Month Year)
Principal (Site) Investigator:
Name (typed or printed):
Institution and Address:
Telephone Number:
Signature: 
Date:
(Day Month Year)
Sponsor's Responsible Medical Officer:
Name (typed or printed): 
Institution: 
Janssen Research & Development
Signature: electronic signature appended at the end of the protocol 
Date:
(Day Month Year)
Note: If the address or telephone number of the investigator changes during the study, written notification will be
provided by the investigator to the sponsor, and a protocol amendment will not be required.
PPD


Signature
User 
Date 
Reason
25-May-2022
17:02:29
(GMT)
Document Approval
PPD

SAP_001.pdf: 
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
1
Status: Approved, Date: 10 October 2023
Janssen Research & Development
Statistical Analysis Plan
A Proof-of-Concept Study of Guselkumab in the Treatment of Subjects with New-onset or 
Relapsing Giant Cell Arteritis
Protocol CNTO1959GCA2001; Phase 2
CNTO1959 (Guselkumab)
Status:
Approved
Date:
10 October 2023 
Prepared by:
Janssen Research & Development, LLC
Document No.: EDMS-RIM-1153377, 1.0
Compliance: The study described in this report was performed according to the principles of Good Clinical Practice (GCP). 
Confidentiality Statement
The information provided herein contains Company trade secrets, commercial or financial information that the Company 
customarily holds close and treats as confidential. The information is being provided under the assurance that the recipient 
will maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or 
otherwise.
NCT04633447


CNTO1959 (Guselkumab)
Statistical Analysis Plan CNTO1959GCA2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
2
Status: Approved, Date: 10 October 2023
TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
1.
INTRODUCTION.................................................................................................................................. 4
1.1.
Objectives and Endpoints ................................................................................................................ 4
1.2.
Study Design.................................................................................................................................... 7
2.
STATISTICAL HYPOTHESES.......................................................................................................... 10
3.
SAMPLE SIZE DETERMINATION....................................................................................................10
4.
POPULATIONS (ANALYSIS SETS) FOR ANALYSIS.....................................................................11
5.
STATISTICAL ANALYSES............................................................................................................... 12
5.1.
General Considerations ................................................................................................................. 12
5.1.1.
Visit Windows ............................................................................................................................. 13
5.1.2.
Pooling Algorithm for Analysis Centers ...................................................................................... 13
5.1.3.
Reference Date, Study Day and Relative Day ...........................................................................13
5.2.
Participant Dispositions.................................................................................................................. 13
5.3.
Primary Endpoint Analysis ............................................................................................................. 14
5.3.1.
Definition of Endpoint.................................................................................................................. 14
5.3.2.
Estimand..................................................................................................................................... 15
5.3.2.1.
Primary Estimand .................................................................................................................... 16
5.3.2.2.
Supplementary Estimand ........................................................................................................ 17
5.3.2.2.1.
Supplementary Estimand 1 (Hypothetical Strategy Estimand)............................................ 17
5.3.2.2.2.
Supplementary Estimand 2 (Treatment Policy Estimand) ................................................... 17
5.3.3.
Analysis Methods for the Primary Estimand...............................................................................17
5.3.4.
Supplementary Estimand Analyses............................................................................................ 18
5.3.4.1.
Supplementary Analysis 1 (Supplementary Estimand 1, Hypothetical Strategy 
Estimand)................................................................................................................................. 18
5.3.4.2.
Supplementary Analysis 2 (Supplementary Estimand 2, Treatment Policy Estimand)........... 18
5.3.4.3.
Supplementary Analysis 3 (Supplementary Estimand 2, Treatment Policy Estimand 
[Sensitivity Analysis])............................................................................................................... 19
5.3.4.4.
Supplementary Analysis 4 (Supplementary Estimand 2, Treatment Policy Estimand)........... 19
5.3.5.
Per Protocol Analysis.................................................................................................................. 19
5.4.
Secondary Endpoints Analysis ...................................................................................................... 19
5.4.1.
Secondary Endpoints.................................................................................................................. 19
5.4.1.1.
Definition of Endpoints............................................................................................................. 20
5.4.1.1.1.
GC-free Remission at Each Timepoint from Week 28 through Week 52 ............................ 20
5.4.1.1.2.
GC-free Remission and Normalization of ESR at Week 28 and from Week 28 
through Week 52 by Visit ..................................................................................................... 20
5.4.1.1.3.
GC-free Remission and Normalization of CRP at Week 28 and from Week 28 
through Week 52 by Visit ..................................................................................................... 20
5.4.1.1.4.
Cumulative GC Dose ........................................................................................................... 21
5.4.1.1.5.
Time to First GCA Disease Flare or Discontinuation of Study Intervention due to AE 
of Worsening of GCA ...........................................................................................................21
5.4.1.1.6.
Number of GCA Disease Flares or Discontinuation of Study Intervention due to AE 
of Worsening of GCA ...........................................................................................................21
5.4.1.2.
Estimands................................................................................................................................ 21
5.4.1.3.
Analysis Methods .................................................................................................................... 22
5.4.1.3.1.
Binary Endpoints (Secondary Endpoints 1 - 4)....................................................................23
5.4.1.3.2.
Continuous Endpoint (Secondary Endpoints 5, 7)...............................................................23
5.4.1.3.3.
Time to First Event Endpoint................................................................................................ 23
5.5.
Exploratory Endpoints Analysis for the Main Study.......................................................................24
5.5.1.
Definition of Endpoints................................................................................................................ 26
5.5.1.1.
Sustained Remission through Week 52 Following Induction of Remission at Week 8........... 26


CNTO1959 (Guselkumab)
Statistical Analysis Plan CNTO1959GCA2001
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Status: Approved, Date: 10 October 2023
5.5.1.2.
Sustained Remission from Week 28 through Week 52 by Visit Following Induction of 
Remission at Week 8............................................................................................................... 26
5.5.1.3.
Normalization of CRP and ESR............................................................................................... 26
5.5.1.4.
Patient’s Global Assessment of Disease Activity (PGA) .........................................................26
5.5.1.5.
Pain Severity Assessment....................................................................................................... 27
5.5.1.6.
SF-36....................................................................................................................................... 27
5.5.1.7.
FACIT-fatigue .......................................................................................................................... 28
5.5.1.8.
Physician’s Global Assessment of Disease Activity (PhGA)................................................... 28
5.5.1.9.
Analysis Methods .................................................................................................................... 28
5.6.
Exploratory Endpoints Analysis for the LTE Period ....................................................................... 29
5.6.1.
Definition of Endpoints................................................................................................................ 30
5.6.1.1.
GC-free Remission at Each Timepoint from Week 52 through Week 104.............................. 30
5.6.2.
Analysis Methods........................................................................................................................ 30
5.7.
Safety Analyses ............................................................................................................................. 30
5.7.1.
Extent of Exposure ..................................................................................................................... 31
5.7.2.
Adverse Events........................................................................................................................... 31
5.7.3.
Additional Safety Assessments .................................................................................................. 33
5.7.3.1.
Clinical Laboratory Tests......................................................................................................... 33
5.7.3.2.
Vital Signs and Physical Examination Findings.......................................................................34
5.7.3.3.
Columbia-Suicide Severity Rating Scale.................................................................................34
5.8.
Other Analyses............................................................................................................................... 36
5.8.1.
Pharmacokinetics ....................................................................................................................... 36
5.8.1.1.
Data Handling Guidelines........................................................................................................ 36
5.8.2.
Immunogenicity........................................................................................................................... 37
5.8.2.1.
Participant ADA Classifications ............................................................................................... 37
5.8.2.2.
Immunogenicity Analyses........................................................................................................ 38
5.8.3.
Pharmacokinetic/Pharmacodynamic Relationships ................................................................... 39
5.8.4.
Biomarkers.................................................................................................................................. 39
5.8.5.
Pharmacogenomic Analyses ...................................................................................................... 40
5.8.6.
Exploratory FDG-PET/CT Imaging Analyses ............................................................................. 40
5.8.7.
Digital Health - Actigraphy Analyses .......................................................................................... 40
5.8.8.
Definition of Subgroups .............................................................................................................. 40
5.9.
Interim Analyses............................................................................................................................. 42
5.9.1.
Data Monitoring Committee (DMC) or Other Review Board ...................................................... 42
6.
SUPPORTING DOCUMENTATION ..................................................................................................43
6.1.
Appendix 1 List of Abbreviations.................................................................................................... 43
6.2.
Appendix 2 Demographics and Baseline Characteristics..............................................................44
6.3.
Appendix 3 Protocol Deviations ..................................................................................................... 46
6.4.
Appendix 4 Prior and Concomitant Medications............................................................................47
6.5.
Appendix 5 Medical History of Interest .......................................................................................... 48
6.6.
Appendix 6 Laboratory Toxicity Grading........................................................................................ 49
6.7.
Appendix 7 COVID-19 Related Summaries...................................................................................50
6.8.
Appendix 8 Protocol-prohibited Concomitant Medications/Therapies ........................................... 51


CNTO1959 (Guselkumab)
Statistical Analysis Plan CNTO1959GCA2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 10 October 2023
1.
INTRODUCTION
This Statistical Analysis Plan (SAP) contains definitions of analysis sets, derived variables, and 
addresses the statistical methods for all planned analyses of efficacy, safety, tolerability, 
pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity of guselkumab. This SAP 
incorporates all analyses through the Week 28 database lock (DBL), through the Week 60 DBL
for the main study, and a final DBL when the last participant completes last visit in the long-term 
extension (LTE) period for the CNTO1959GCA2001 study.
1.1.
Objectives and Endpoints
Objectives
Endpoints
Primary
To evaluate the efficacy of guselkumab 
compared to placebo, in combination with a 
26-week GC taper regimen, in adult
participants with new-onset or relapsing
GCA.
The proportion of participants achieving 
GC-free remission at Week 28
Secondary
To evaluate the efficacy of guselkumab 
compared to placebo, in combination with a 
26-week GC taper regimen, in adult
participants with new-onset or relapsing GCA
as measured by alternative definitions of GC
free remission, GC-sparing effects, and
prevention of disease flares.
The proportion of participants achieving 
GC-free remission from Week 28 by visit 
through Week 52
The proportion of participants achieving 
GC-free remission and normalization of 
erythrocyte sedimentation rate (ESR) at 
Week 28 and by visit through Week 52
The proportion of participants achieving 
GC-free remission and normalization of 
C-reactive protein (CRP) at Week 28 and by
visit through Week 52
The proportion of participants achieving 
GC-free remission and normalization of both 
ESR and CRP at Week 28 and by visit 
through Week 52
The cumulative GC dose through Week 28 
and through Week 52
The time to first GCA disease flare or 
discontinuation of study intervention due to 
AE of worsening of GCA through Week 28 
and through Week 52 


CNTO1959 (Guselkumab)
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Status: Approved, Date: 10 October 2023
Objectives
Endpoints
The number of GCA disease flares or 
discontinuation of study intervention due to 
AE of worsening of GCA through Week 28 
and through Week 52
To evaluate the safety of guselkumab, in 
combination with a 26-week GC taper 
regimen, in adult participants with new- onset 
or relapsing GCA.
Number/proportion of participants with 
treatment- emergent adverse events (TEAEs) 
through Week 60
Number/proportion of participants with 
TEAEs by system organ class with a 
frequency threshold of 5% or more through 
Week 60
Number/proportion of participants with 
treatment- emergent serious adverse events 
(SAEs) through Week 60
Number/proportion of participants with 
clinically significant abnormalities in vital 
signs, laboratory safety tests through Week 60
To evaluate the PK and immunogenicity of 
guselkumab, in combination with a 26-week 
GC taper regimen, in adult participants with 
new-onset or relapsing GCA.
Mean (standard deviation [SD]) serum 
concentrations of guselkumab through 
Week 52 in participants receiving active study 
intervention.
Number/proportion of participants with 
antibodies to guselkumab in participants 
receiving active study intervention.
Exploratory
To explore the longer-term efficacy of 
guselkumab compared to placebo, in 
combination with a 26-week GC taper 
regimen, in adult participants with new-onset 
or relapsing GCA.
Proportion of participants in sustained 
remission through Week 52
To evaluate the changes in immune- markers 
to guselkumab compared to placebo, in 
combination with a 26-week GC taper 
regimen, in adult participants with new-onset 
or relapsing GCA.
Change from baseline in CRP through 
Week 52
Change from baseline in ESR through 
Week 52
To explore the changes in pharmacodynamic 
(PD) markers and arterial vessel wall 
inflammation following administration of 
guselkumab in adult participants with 
new-onset or relapsing GCA.
Assessment of IL-23 pathway related and 
disease related biomarkers in serum, whole 
blood and peripheral blood mononuclear cell 
(PBMC) through Week 52.


CNTO1959 (Guselkumab)
Statistical Analysis Plan CNTO1959GCA2001
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Status: Approved, Date: 10 October 2023
Objectives
Endpoints
Large-Vessel Imaging (fluorodeoxyglucose 
positron emission tomography/computed 
tomography [FDG-PET/CT]) changes from 
baseline at Week 52 (or flare)
To explore changes in participant reported 
Clinical Outcome Assessments, pain and 
fatigue, and physician reported outcomes
Change from baseline on electronic 
patient-reported outcome (ePRO): Patient's 
Global Assessment of Disease Activity 
(PGA), Pain Assessment, Functional 
Assessment of Chronic Illness Therapy 
(FACIT)-Fatigue and short form-36 (SF-36) 
by visit through Week 52
Change from baseline on clinician reported 
outcome: Physician's Global Assessment of 
Disease Activity (PhGA) by visit through 
Week 52
To explore digital health parameters 
following administration of guselkumab in 
adult participants with new-onset or relapsing 
GCA.
Change from baseline in Actigraphy Watch 
collected continuous data on physical activity, 
mobility, and sleep by visit through Week 52
Exploratory Objectives for the Long-Term Extension (LTE) period
To evaluate long-term efficacy of guselkumab 
in adult participants with new-onset or 
relapsing GCA
The proportion of participants achieving 
GC-free remission from Week 52 (LTE 
Week 0) through Week 104 by visit (LTE 
Week 52) 
The time to first GCA disease flare from 
Week 52 (LTE week 0) through Week 104 
(LTE Week 52).
To evaluate the continued safety of 
guselkumab in adult participants with 
new-onset or relapsing GCA.
Number/proportion of participants with 
TEAEs or SAEs from Week 52 (LTE 
Week 0) through Week 112 (LTE Week 60)
Number/proportion of participants with 
clinically significant abnormalities in vital 
signs and laboratory safety tests from 
Week 52 (LTE Week 0) through Week 112 
(LTE Week 60)
To evaluate the PK and immunogenicity of 
guselkumab, in adult participants with new-
onset or relapsing GCA.
Mean (SD) serum concentrations of 
guselkumab from Week 52 through Week 104 
(LTE Week 52) in participants receiving 
active study intervention.
Number/proportion of participants with 
antibodies to guselkumab in participants 
receiving active study intervention


CNTO1959 (Guselkumab)
Statistical Analysis Plan CNTO1959GCA2001
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Status: Approved, Date: 10 October 2023
Objectives
Endpoints
To explore the changes in PD markers and 
arterial vessel wall inflammation following 
administration of guselkumab in adult 
participants with new-onset or relapsing GCA 
in the LTE period.
Assessment of IL-23 pathway related and 
disease related biomarkers in serum and 
whole blood at Week 104 (LTE Week 52)
Large-Vessel Imaging (FDG-PET/CT) 
changes from baseline and Week 52 at 
Week 104 (LTE Week 52) or flare
To explore changes in participant reported 
Clinical Outcome Assessments, pain and 
fatigue, and physician reported outcomes 
following administration of guselkumab in 
adult participants with new-onset or relapsing 
GCA in the LTE period.
Change from baseline on electronic 
patient-reported outcome (ePRO): Patient's 
Global Assessment of Disease Activity 
(PGA), Pain Assessment, Functional 
Assessment of Chronic Illness Therapy 
(FACIT)-fatigue and short form-36 (SF-36) at 
Week 76 (LTE Week 24), Week 104 (LTE 
week 52) and or Flare visit. 
Change from baseline on clinician reported 
outcome: Physician's Global Assessment of 
Disease Activity (PhGA) at Week 76 (LTE 
Week 24) week 104 (LTE Week 52) and or 
Flare visit.
1.2.
Study Design
CNTO1959GCA2001 is a randomized, double-blind, placebo-controlled, parallel, multicenter,
interventional
Phase 2 Proof-of-Concept study evaluating the efficacy, safety, PK, and
immunogenicityof guselkumab for the treatment of active new-onset or relapsing GCA in adult
participants.
Main Study Treatment Period (Through up to Week 60)
A target of approximately 51 participants will be enrolled in this study. Participants will be
randomly assigned into 2 study intervention groups with a 2:1 ratio for guselkumab versus placebo.
!
Group 1: Guselkumab (200 mg SC every 4 weeks)
Participants will receive guselkumab 200 mg SC every 4 weeks at Week 0 through 
Week 48 in the Main study.
!
Group 2: Placebo
Participants will receive placebo SC every 4 weeks at Week 0 through Week 48.
Participant randomization will be stratified by baseline disease status (new-onset and relapsing
GCA; relapsing preferentially limited to 70% to ensure some enrollment of new-onset GCA but 
may be increased depending on the rate of enrollment of relapsing versus new-onset GCA), and by
baseline GC dose (≤30 mg/day or >30 mg/day).


CNTO1959 (Guselkumab)
Statistical Analysis Plan CNTO1959GCA2001
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Status: Approved, Date: 10 October 2023
The placebo comparator (in addition to standard-of-care background therapy of GCs) will be used
in this study through Week 48 of the Main study to allow for blinded, placebo-controlled evaluation
of the long-term efficacy and safety of guselkumab in participants with GCA. Participants on 
placebo that continue into the LTE will continue to receive placebo until the participant reaches
Week 100 (LTE Week 48) or experiences a GCA flare, or until unblinding of the study due to 
completion of the main study, whichever occurs first.
The total duration of the study is up to 66 weeks of the main study: a screening period of ≤6 week,
a 48-week main study treatment period, and a 12-week safety follow-up period after the last dose (a 
final efficacy visit 4 weeks after the last dose and a safety follow-up visit 12 weeks after the last 
dose). Participants that continue in the LTE period may continue in the study for a total duration 
of 112 weeks.).
Participants who develop a GCA flare should stop the protocol-defined GC taper and be given 
rescue therapy with GCs at the discretion of the investigator.
Efficacy, safety, PK, immunogenicity, and biomarkers will be assessed according to the Schedule
of Activities of the protocol. An optional pharmacogenomic blood sample will be collected from 
participants who consent to the collection of these samples (where local regulations permit).
The primary efficacy analysis will be performed after all participants have completed Week 28
efficacy assessments (or discontinued). Additional secondary endpoints will be completed at
Week 28 and Week 52. Three planned database locks (DBLs) will occur, at Week 28 and
at Week 60 for the main study and a final DBL lock when the last participant completes last visit 
in the LTE period. The study will be double-blind until all participants have completed the main 
study and associated Week 60 DBL has occurred.
Participants who complete the Week 52 visit and are assessed to be in GC-free remission, may
have the option to participate in a long-term extension (LTE) study. Participants not entering LTE 
will be followed to Week 60 and are deemed having completed the main study.
An overview of the main study design is presented in Figure 1.


CNTO1959 (Guselkumab)
Statistical Analysis Plan CNTO1959GCA2001
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Status: Approved, Date: 10 October 2023
Figure 1:
Schematic Overview of the Study
Long-term Extension Treatment Period (Week 52 to Week 112; optional for eligible 
participants)
Participants who complete the Week 52 visit and are assessed to be in GC-free remission, may 
have the option to participate in the LTE period of the study.
If a participant is in GC-free remission at Week 48, the participant will be informed of the
possibility to participate in the LTE period and continue to receive study intervention. Study
intervention will continue to be blinded, meaning that a participant will continue to receive the
treatment that had been allocated to that participant (placebo or guselkumab) in the main study.
After the Week 52 evaluations, if the participant is eligible and has consented for the LTE, the
participants will continue to receive SC study intervention every 4 weeks starting at Week 52 (LTE 
Week 0) under this protocol’s study extension until participants reach Week 100 (LTE Week 48)
or until a participant experiences a GCA flare requiring GC rescue medication, or the participants 
discontinue study intervention due to unblinding after the Week 60 DBL for the Main study, or 
until the Sponsor makes a decision not to continue this study, whichever occurs first. Participants 
who continue treatment as part of the study extension will be intermittently evaluated per the 
protocol for efficacy, PK, and safety. The LTE treatment period is followed by a 12-week safety 
follow-up period after the last dose (a final efficacy visit 4 weeks after the last dose and a safety 
follow-up visit 12 weeks after the last dose). Participants that experience a flare should have a 
Flare visit with assessments performed according to the SoA of the protocol preferably within 1 
week of having the flare and an early termination visit approximately 12 weeks after the last dose.
In case a participant is diagnosed as having a flare during a study visit or shortly before a planned 
study visit, the Flare visit and regular visit can be combined. Overlapping procedures and 


CNTO1959 (Guselkumab)
Statistical Analysis Plan CNTO1959GCA2001
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Status: Approved, Date: 10 October 2023
assessments need only be performed once. The FDG-PET/CT scan can be scheduled separately 
from other assessments.
After the Week 60 DBL, the study will be unblinded to treatment. Any participants in the LTE that 
are on placebo will be informed and administration of study intervention will be discontinued. The 
participants may still continue in the study until Week 112 or until the end of the safety follow-up 
period in case they experienced a GCA flare.
An overview of the long-term extension (LTE) period is presented in Figure 2.
Figure 2:
Schematic Overview of the Long-Term Extension (LTE) Period
2.
STATISTICAL HYPOTHESES
The primary hypothesis is that guselkumab treatment with a 26-week GC taper is superior to
placebo with a 26-week GC taper in participants with new-onset or relapsing GCA as assessed by
the proportion of participants achieving GC-free remission at Week 28.
3.
SAMPLE SIZE DETERMINATION
Approximately 51 participants are planned to be randomized into the study. The assumptions for
the sample size and power calculation were based on the data from the Actemra Phase 3 GCA
study. In the Actemra Phase 3 study, the proportions of participants in GC-free remission at
Week 28 were estimated to be approximately 38% and 74% for placebo (+26-week GC taper) and
Actemra qw (+26-week GC-taper), respectively, for a treatment difference of 36%.
Based on the data above, the GC-free remission rates at Week 28 are assumed to be 40% for
placebo and 80% for guselkumab treatment arm. Based on these assumptions, 51 participants are
planned to be randomized in a 2:1 ratio to either the guselkumab group (N=34) or the placebo


CNTO1959 (Guselkumab)
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group (N=17). These sample sizes provide the study with 82% power to detect a difference in the
primary endpoint between the 2 study intervention groups.
Table 1 shows the power to detect a difference in proportions of participants in GC-free remission
between the guselkumab and placebo intervention groups at Week 28 under various assumptions.
Table 1:
Power to Detect Difference in Proportions of Participants Achieving Glucocorticoid-free
Remission between the Guselkumab and Placebo Intervention Groups at Week 28
Placebo (n = 17)
Guselkumab (n = 34)
Power (%)
35%
70%
68
75%
81
80%
90
40%
75%
69
80%
82
85%
91
Notes:
!
The power calculation is based on two-sample Z test with continuity correction (pooled variance) under the
normal distribution approximation.
!
Power calculation is based on a 2-sided significance level of 0.10.
!
Total sample size is 60.
4.
POPULATIONS (ANALYSIS SETS) FOR ANALYSIS
For purposes of analysis, the following populations are defined:
Analysis Sets
Description
Enrolled Analysis Set
All participants who signed the ICF
Randomized Analysis Set
The randomized analysis set includes all participants who 
were randomized in the study.
Full Analysis Set (FAS)
The full analysis set (FAS) includes all randomized
participants who received at least 1 administration of study 
intervention.
Per Protocol (PP)
The per protocol analysis set (PP) includes a subset of 
participants in the full analysis set (FAS) who were in general 
compliance with the protocol. General compliance is defined 
as having no major protocol deviations that could have an 
impact on the efficacy assessment per clinical judgement. 
This analysis will be used for the primary endpoint.
Participants will be excluded from this analysis as below: 
! who did not meet the inclusion criteria 3, 4, 6, 8 in the 
protocol;
! who met the exclusion criteria 1, 6, 22, 24 in the protocol;


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Analysis Sets
Description
! who discontinued study intervention for reasons other than 
lack of efficacy or an AE of worsening of GCA, or missed 
at least two scheduled study agent administrations prior to 
Week 28. 
Participants who did not completed all scheduled study 
intervention administration due to intercurrent events 
(discontinued the study intervention due to lack of efficacy or 
an AE of worsening of GCA, or participants who started 
prohibited medications or therapy during the study that
could improve GCA, or received a rescue medication for a 
GCA flare) will be included in the per protocol analysis and 
the data handling rules for these intercurrent events specified 
in Section 5.3.2 and Section 5.3.3 will be applied. 
Safety Analysis Set
The safety analysis set includes all participants who received 
at least 1 dose of study intervention.
Pharmacokinetics Analysis Set
All participants who received at least 1 administration of 
guselkumab and have at least one valid post-dose blood 
sample drawn for PK analysis.
Immunogenicity Analysis Set
All participants who received at least 1 administration of 
guselkumab and have at least one post-dose sample 
collection.
Pharmacodynamic Analysis Set
All participants who received at least 1 administration of
study intervention and have at least one post-dose sample
collection.
Full Analysis Set with Subjects 
Participating in the Long-Term 
Extension
All participants who were in the FAS and received at least 1 
injection at or beyond Week 52.
Safety Analysis Set with
Subjects Participating in the 
Long-Term Extension
All participants who were in the safety analysis set and 
received at least 1 injection at or beyond Week 52.
5.
STATISTICAL ANALYSES
5.1.
General Considerations
Unless specified otherwise, efficacy data summaries will be provided by intervention group for 
the FAS. Data primarily will be summarized using descriptive statistics. Continuous variables will 
be summarized using the number of observations, mean, SD, median, interquartile range,
minimum and maximum, as appropriate. Categorical values will be summarized using the number 
of observations and percentages as appropriate. Median time will be reported for time to event
variables. In addition, graphical data displays (eg, line plots) and participant listings may also be
used to summarize/present the data. Statistical comparisons will be made between the guselkumab 
intervention group and the placebo intervention group.


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In general, all statistical tests will be performed at a 2-sided significance level of α=0.10.
No multiplicity adjustment will be made for the secondary endpoints being tested and nominal 
p-values will be reported.
The baseline measurement is defined as the closest measurement taken prior to or at the time of 
the first study agent administration date unless otherwise specified.
5.1.1.
Visit Windows
Unless otherwise specified, nominal visits will be used for all by visit analyses. The study visits 
scheduled after randomization should occur at the time delineated in the Schedule of Activities of 
the protocol.
5.1.2.
Pooling Algorithm for Analysis Centers
No pooling algorithm will be performed.
5.1.3.
Reference Date, Study Day and Relative Day
The Reference Date is the date of the first study agent administration. If the date of the first study 
agent administration is missing or the first study agent administration is not done, then the 
Reference Date equals the corresponding visit date (eg, Week 0 visit date). If the corresponding 
visit date is also missing, then the Reference Date equals the randomization date.
Study Day 1 or Day 1 refers to the reference date (there is no Study Day 0). All efficacy and safety
assessments at all visits will be assigned a day relative to this date.
5.2.
Participant Dispositions
Screened participants and reason for screen failures will be summarized overall.
The number of participants in the following disposition categories will be summarized throughout 
the study by intervention group and overall:
!
Participants randomized
!
Participants who received study intervention
!
Participants who completed the study
!
Participants who enrolled in LTE
!
Participants who discontinued study intervention
∀
Reasons for discontinuation of study intervention, including those due to COVID-19 
related events
!
Participants who terminated study prematurely, including those due to COVID-19 related 
events
∀
Reasons for termination of study


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The above categories will include summaries through Week 28 and through Week 60 for the main 
study, and from Week 52 through Week 112 for participants in the LTE period excluding the 
summary of participants randomized.
A listing of participants will be provided for the following categories:
!
Participants who discontinued study intervention
!
Participants who terminated study prematurely
!
Participants who were unblinded during the study period
!
Participants who were randomized yet did not receive study intervention
5.3.
Primary Endpoint Analysis
The primary endpoint is the proportion of participants achieving GC-free remission at Week 28
(ie, meeting remission definition and not on GC for GCA at Week 28).
5.3.1.
Definition of Endpoint
GC-free remission response at Week 28 is defined as:
1.
No signs or symptoms of active GCA at Week 28
AND
2.
Absence of GCA flare from first dose of the study agent through Week 28,
AND
3.
Adherence to the protocol specified 26-week GC taper
Definition of GCA Flare: GCA flare is defined as the recurrence of signs and symptoms of active 
GCA, with or without elevation of inflammatory markers, and with the necessity for an increase 
in GC dose for GCA.
Having CRP/ESR elevations in isolation without clinical signs and symptoms attributable to GCA,
does not qualify as flare, unless the investigator decided to increase the GC dose.
Definition of GC Taper Adherence. The protocol specified 26-Week open-label GC tapering 
schedule is provided in Section 10.8 of the protocol. Adherence to this schedule is required. 
Participants will remain on the GC dose they were on at baseline for one week (Week 0). The taper 
is starting at Week 1 and continues down to GC-free in Week 26, as per the schedule. Participant 
should adhere to the tapering schedule through Week 26 unless they require use of rescue GC 
therapy for GCA disease flare.
A participant will be considered as not adherent to the protocol-defined 26-week GC taper, if the 
compliance of GC intake (any oral GC intake) is greater than 120% cumulative prednisone (or 
equivalent) dose, between first and last planned dose of GC taper. Patients not adhering to the GC


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taper will be considered as non-responders in the primary analysis. Participants receiving less than 
the planned amount of prednisone (or equivalent) will not be considered as non-responders. 
Compliance of GC intake will be calculated as follows:
Compliance (%) = (actual GC dose taken/total GC dose supposed to be taken) x100.
If a participant receives GC other than prednisone or prednisolone, the amount of GC dosage 
equivalent to prednisone recorded on Concomitant Therapy page in the eCRFs will be converted 
to a prednisone-equivalent dose using the following table.
GC
Conversion factor from alternative GC to 
prednisone equivalent dose (mg)
Cortisone acetate
0.2
Hydrocortisone
0.25
Deflazacort
0.67
Prednisone
1
Prednisolone
1
Triamcinolone
1.25
Methylprednisolone
1.25
Dexamethasone
6.67
Betamethasone
6.67
The following rules will be used to assess a GC-free remission at Week 28:
A participant will not be considered to be in GC-free remission at Week 28, if a participant meets 
one of the following criteria; otherwise the participant will be considered as a GC-free remission 
at Week 28:
!
If an investigator answers the question “What is the participant’s disease status at the time of 
the visit?” at Week 28 as “Participant has stable active disease, not requiring increase in GC 
dose.” on the Clinical Assessment of GCA – Signs and Symptoms eCRF page.
!
If an investigator answers the question “What is the participant’s disease status at the time of 
the visit?” from first dose of the study agent through Week 28, inclusive as “GCA Flare or 
has experienced a GCA flare since last visit.” on the Clinical Assessment of GCA – Signs and 
Symptoms eCRF page including both scheduled and flare visits.
!
The participant cannot adhere to the protocol specified 26-week GC taper.
5.3.2.
Estimand
Primary Trial Objective: To evaluate the efficacy of guselkumab compared to placebo, in 
combination with a 26-week glucocorticoid (GC) taper regimen, in adult participants with 
new-onset or relapsing giant cell arteritis (GCA).


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Clinical Question of Interest: For a patient with new-onset or relapsing GCA, what would the 
expected effect of being assigned guselkumab together with the protocol allowed background 
26-week GC-taper medication on the likelihood of experiencing a treatment response at Week 28?
5.3.2.1.
Primary Estimand
The primary estimand, based on the above primary objective, is defined by the following 
5 components which assess the treatment effects not only based on the variable measurements, but 
also based on intercurrent events:
!
Study intervention:
∀
Guselkumab in addition to 26-week GC-taper (including participants who received 
400 mg IV induction doses followed by 200 mg SC dosing from Week 12 onwards and 
participants that received 200 mg SC dosing only)
∀
Placebo in addition to 26-week GC-taper
!
Population: adult participants 50 years or older with active new-onset or relapsing GCA
(defined by American College of Rheumatology criteria).
!
Variable: Binary response variable, where a responder is defined as a participant achieving 
GC-free remission at Week 28. A participant with an intercurrent event in categories 1-3 
defined below will be considered as a non-responder.
!
Summary Measure (Population-level summary): difference in the proportions of GC-free 
remission at Week 28 between the guselkumab group and the placebo group.
!
Intercurrent Events: 
Intercurrent Events (ICEs)
Strategy for Addressing Intercurrent Events and Its 
Description
1. Discontinuation (DC) of 
study intervention due to 
lack of efficacy or an AE of 
worsening of GCA.
2. Initiation of a 
protocol-prohibited 
medication during the study 
that could improve GCA.
3. Initiation of GC rescue 
therapy.
Composite Strategy: A participant with this intercurrent 
event is considered as a non-responder after this event. The 
occurrence of this intercurrent event is captured in the 
variable definition.
4. Discontinuation of study 
intervention other than ICEs 
#1
Treatment Policy: Use observed data regardless of 
whether or not this intercurrent event had occurred
Note: For participants experiencing multiple ICEs, an ICE in categories 2 or 3 will override an ICE in 
category 4.


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5.3.2.2.
Supplementary Estimand
5.3.2.2.1.
Supplementary Estimand 1 (Hypothetical Strategy Estimand)
In this supplementary estimand, the only component that changes from the definition of the 
primary estimand is that the hypothetical strategy will be used for addressing ICEs 1-4.
Hypothetical strategy: assess the treatment effect as if the intercurrent event would not have 
occurred. Under the hypothetical strategy, data collected after ICEs 1-4 will not be used in analysis
and will be imputed using a MAR multiple imputation method.
5.3.2.2.2.
Supplementary Estimand 2 (Treatment Policy Estimand)
Treatment policy estimand has the same components as the primary estimand, except for the 
strategies used for the intercurrent events 1-4:
Treatment policy strategy: assess the treatment effect regardless of whether or not intercurrent 
events had occurred. Under the treatment policy strategy, the observed data after the intercurrent 
event will be used in analysis.
5.3.3.
Analysis Methods for the Primary Estimand
The primary endpoint will be compared between the guselkumab group and the placebo group at 
Week 28 based on the primary estimand (Section 5.3.2.1) and the data from all participants in FAS
(Section 4) will include data from all randomized participants who received at least one 
administration of study intervention based on their assigned intervention group, regardless of the 
actual intervention received.
The primary endpoint will be analyzed using the primary estimand. Participants with ICEs 1-3 
before Week 28 will be considered as GC-free remission non-responders at Week 28. Participants 
with ICE 4, observed data after this ICE will be utilized in the analysis. For participants 
experiencing multiple ICEs, an ICEs 2 or 3 will override an ICE in category 4. 
After accounting for the ICEs for the primary estimand, the remaining missing data of the primary 
endpoint at Week 28 will be considered as a non-responder. 
In this primary analysis, the proportion of participants who achieve GC-free remission at Week 28 
will be summarized for each intervention group. To address the primary objective, 
Cochran-Mantel-Haenszel chi-square statistic stratified by baseline disease status (new-onset and 
relapsing GCA), and the baseline GC dose (≤30 mg/day or >30 mg/day) at a 2-sided significance 
level of 0.10 will be used. Difference in response rates between the guselkumab group and the 
placebo group at Week 28 adjusted for baseline disease status (new-onset and relapsing GCA), 
and the baseline GC dose (≤30 mg/day or >30 mg/day) using Mantel-Haenszel weight and the 
corresponding 90% CI will be presented. Baseline disease status (new-onset and relapsing GCA), 
and the baseline GC dose (≤30 mg/day or >30 mg/day) entered into IWRS are to be used. Similar 
analyses using the observed baseline disease status (new-onset and relapsing GCA), and the 
observed baseline GC dose (≤30 mg/day or >30 mg/day) will be performed as sensitivity analyses. 


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5.3.4.
Supplementary Estimand Analyses
5.3.4.1. Supplementary Analysis 1 (Supplementary Estimand 1, Hypothetical 
Strategy Estimand)
The primary endpoint will be analyzed using the Hypothetical Estimand for ICEs 1-4 (see 
Section 5.3.2.2.1). Under this estimand, data after an ICE will be set as missing and missing data 
will be imputed using multiple imputations by fully conditional specification (FCS).
More specifically, the missing GC-free remission response status at Week 28 will be imputed using 
the FCS logistic regression including intervention group, the baseline disease status (new-onset 
and relapsing GCA), the baseline GC dose (≤30 mg/day or >30 mg/day), and remission response 
status as defined in Section 5.5.1.3 starting from Week 4 in the model with seed = 1231 and 
500 imputations.
The proportion difference of GC-free remission at Week 28 adjusted for the baseline disease status 
(new-onset and relapsing GCA), and the baseline GC dose (≤30 mg/day or >30 mg/day) using
Mantel-Haenszel weight between the guselkumab group and the placebo group and its 90% CI 
combining multiple datasets will be provided. Each imputed dataset will be analyzed by CMH test 
stratified by baseline disease status (new-onset and relapsing GCA), and the baseline GC dose 
(≤30 mg/day or >30 mg/day). 
The values of the general association test statistics from the CMH test for each imputed dataset
will be transformed using the Wilson-Hilferty transformation to create a more normal distributed 
statistic:
 =
(	)(/)/
(/)(/)
.
The resulting transformed values will be combined using SAS PROC MIANALYZE and obtain 
overall p-value for the CMH test.
5.3.4.2. Supplementary Analysis 2 (Supplementary Estimand 2, Treatment Policy 
Estimand)
The primary endpoint will be analyzed utilizing the Treatment Policy (de Facto) Estimand. For 
participants who experience an intercurrent event through Week 28, the analysis will be performed 
using observed data regardless of intercurrent events. Missing data will not be imputed. The 
Cochran-Mantel-Haenszel chi-square statistic stratified by baseline disease status (new-onset and 
relapsing GCA), and the baseline GC dose (≤30 mg/day or >30 mg/day) at a 2-sided significance 
level of 0.10 will be used. Difference in response rates between the 2 study intervention groups at 
Week 28 adjusted for baseline disease status (new-onset and relapsing GCA), and the baseline GC
dose (≤30 mg/day or >30 mg/day) using Mantel-Haenszel weight and the corresponding 90% CI 
will be presented.


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5.3.4.3. Supplementary Analysis 3 (Supplementary Estimand 2, Treatment Policy 
Estimand [Sensitivity Analysis])
The primary endpoint will be analyzed utilizing the Treatment Policy Estimand. For participants 
who experience an intercurrent event through Week 28, the analysis will be performed using 
observed data regardless of intercurrent events. 
The same missing data handling rules and analysis methods specified in Section 5.3.4.1 for 
Supplementary Analysis 1 (Hypothetical Strategy Estimand) will be applied.
5.3.4.4. Supplementary Analysis 4 (Supplementary Estimand 2, Treatment Policy 
Estimand)
A generalized linear model with logit link for binary repeated measurement data will be performed 
on the primary endpoint after applying the Treatment Policy to ICEs. The model will include the 
intervention group, baseline disease status (new-onset and relapsing GCA), and the baseline GC
dose (≤30 mg/day or >30 mg/day), visit, and intervention and visit interaction in the model. The 
derived odds ratio on GC-free remission at Week 28 and its 2-sided 90% CI will be provided. In 
addition, the proportion difference of GC-free remission response at Week 28 between the 
guselkumab and the placebo group and its 2-sided 90% CI will also be provided. Missing data will 
not be imputed and will be handled by the model under missing at random assumption.
5.3.5.
Per Protocol Analysis
The primary analyses for primary endpoint will also be performed on per protocol analysis set 
(Section 4). The same data handling rules specified in Section 5.3.2 and Section 5.3.3 will be 
applied.
5.4.
Secondary Endpoints Analysis
5.4.1.
Secondary Endpoints
Objective: To evaluate the efficacy of guselkumab with a comparison to placebo, in combination
with a 26-week GC taper regimen, in adult participants with new-onset or relapsing GCA for 
the following secondary endpoints:
1.
The proportion of participants achieving GC-free remission from Week 28 through Week 52 
by visit
2.
The proportion of participants achieving GC-free remission and normalization of ESR at 
Week 28 and from Week 28 through Week 52 by visit
3.
The proportion of participants achieving GC-free remission and normalization of CRP at 
Week 28 and from Week 28 through Week 52 by visit
4.
The proportion of participants achieving GC-free remission and normalization of both ESR 
and CRP at Week 28 and from Week 28 through Week 52 by visit
5.
The cumulative GC dose through Week 28 and through Week 52


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6.
The time to first GCA disease flare or discontinuation of study intervention due to AE of 
worsening of GCA through Week 28 and through Week 52
7.
The number of GCA disease flares or discontinuation of study intervention due to AE of 
worsening of GCA through Week 28and through Week 52
5.4.1.1.
Definition of Endpoints
5.4.1.1.1.
GC-free Remission at Each Timepoint from Week 28 through Week 52
1.
No signs or symptoms of active GCA at timepoint Week X
AND
2.
Absence of GCA flare from first dose of the study agent through Week X
AND
3.
Adherence to the protocol specified 26-week GC taper
5.4.1.1.2.
GC-free Remission and Normalization of ESR at Week 28 and from 
Week 28 through Week 52 by Visit
1.
No signs or symptoms of active GCA at timepoint Week X
AND
2.
Absence of GCA flare from first dose of the study agent through Week X, inclusive,
AND
3.
Adherence to the protocol specified 26-week GC taper
AND
4.
Normalization of ESR is defined as ESR <30 mm/hr at Week X.
5.4.1.1.3.
GC-free Remission and Normalization of CRP at Week 28 and from 
Week 28 through Week 52 by Visit
1.
No signs or symptoms of active GCA at timepoint Week X
AND
2.
Absence of GCA flare from first dose of the study agent through Week X, inclusive,
AND
3.
Adherence to the protocol specified 26-week GC taper,
AND
4.
Normalization of CRP is defined as CRP <10 mg/L or <1 mg/dL.


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5.4.1.1.4.
Cumulative GC Dose
The total cumulative GC dose administered will include GCA taper, GC rescue therapy as well as 
for all other indications (any oral GC) from first dose of the study agent to Week 28 or Week 52. 
5.4.1.1.5.
Time to First GCA Disease Flare or Discontinuation of Study 
Intervention due to AE of Worsening of GCA
Time to occurrence of GCA disease flare is defined as the time from first dose of the study agent 
to the occurrence of the first observation of GCA disease flare or discontinuation due to AE of 
worsening of GCA.
The definition of GCA disease flare is defined in Section 5.3.1.
5.4.1.1.6.
Number of GCA Disease Flares or Discontinuation of Study 
Intervention due to AE of Worsening of GCA
The number of GCA disease flares or discontinuation of study intervention due to AE of worsening 
of GCA is the total number of flares or discontinuation of study intervention due to AE of 
worsening of GCA participants experience from first dose of the study agent through Week 28 or 
through Week 52.
The definition of GCA disease flare is defined in Section 5.3.1.
5.4.1.2.
Estimands
The study intervention and population are the same as the primary estimand. The following table 
provides the list of variables, summary measure (population-level summary) and intercurrent event 
for secondary endpoints.
Table 2:
List of Secondary Endpoints and Estimands
Estimands
Variable
Summary Measure 
(Population-level 
summary)
Intercurrent Events
Sec 1
Binary response variable, where a 
responder is defined as a participant 
achieving GC-free remission from
Week 28 through Week 52 by visit
Difference in the 
proportions of achieving 
GC-free remission between 
the guselkumab groups and 
the placebo group
Using the same analysis 
strategies as the primary 
estimand.
Sec 2
Binary responder variable, where a 
responder is defined as a participant 
achieving GC-free remission and 
normalization of ESR at Week 28 and 
from Week 28 through Week 52 by 
visit
Difference in the 
proportions of achieving 
GC-free remission and 
normalization of ESR 
between the guselkumab 
group and the placebo 
group 
1.
The analysis strategies 
for the Week 28 
endpoint will be the 
same as those for the
primary estimand. 
2.
The analysis strategies
for summary over time 
by visit from Week 28 
through Week 52 are
the same as those in #1 
in this table.


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Estimands
Variable
Summary Measure 
(Population-level 
summary)
Intercurrent Events
Sec 3
Binary response variable, where a 
responder is defined as a participant 
achieving GC-free remission and 
normalization of CRP at Week 28 and
from Week 28 through Week 52 by 
visit
Difference in the 
proportions of achieving 
GC-free remission and 
normalization of CSR 
between the guselkumab 
group and the placebo 
group 
1.
The analysis strategies 
for the Week 28 
endpoint will be the 
same as those for the 
primary estimand.
2.
The analysis strategies 
for summary over time 
are the same as those 
in #1 in this table.
Sec 4
Binary response variable, where a 
responder is defined as a participant 
achieving GC-free remission and 
normalization of both ESR and CRP 
at Week 28 and from Week 28 
through Week 52 by visit
Difference in the 
proportion of achieving 
GC-free remission and 
normalization of both ESR 
and CRP between the 
guselkumab group and the 
placebo group
1.
The analysis strategies 
for the Week 28 
endpoint will be the 
same as those for the 
primary estimand.
2.
The analysis strategies 
for summary over time 
by visit from Week 28 
through Week 52 are 
the same as those in #1 
in this table.
Sec 5
Cumulative GC dose through Week 
28 and through Week 52
Descriptive statistics for 
the guselkumab group and 
the placebo group
Treatment Policy strategy 
will be used regardless of 
ICEs.
Sec 6
Time to first GCA disease flare or 
discontinuation of study intervention 
due to AE of worsening of GCA
through Week 28 and through 
Week 52
Hazard ratio of the 
guselkumab group vs. the 
placebo group
Treatment Policy strategy
will be used regardless of 
the ICEs.
Sec 7
Number of GCA disease flares or 
discontinuation of study intervention 
due to AE of worsening of GCA 
through Week 28and through 
Week 52
Descriptive statistics for 
the guselkumab group and 
the placebo group
Treatment Policy strategy 
will be used regardless of 
the ICEs.
5.4.1.3.
Analysis Methods
Unless otherwise specified, the analysis population will be the FAS defined in Section 4. The 
endpoints will be summarized by intervention group.
Simple descriptive statistics, such as n, mean, SD, median, IQ range, minimum and maximum for 
continuous variables and counts and percentages for discrete variables will be used to summarize 
most data, if appropriate.


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5.4.1.3.1.
Binary Endpoints (Secondary Endpoints 1 - 4)
Analyses for binary secondary endpoints (proportion of responders) at Week 28 will be the same 
as the primary endpoint.
For secondary binary endpoints at Week 28, Cochran-Mantel-Haenszel chi-square statistic 
stratified by baseline disease status (new-onset and relapsing GCA), and the baseline GC dose 
(≤30 mg/day or >30 mg/day) at a 2-sided significance level of 0.10 will be used to compare 
between the guselkumab and the placebo groups. Difference in response rates between the 
2 intervention groups at Week 28 adjusted for baseline disease status (new-onset and relapsing 
GCA), and the baseline GC dose (≤30 mg/day or >30 mg/day) using Mantel-Haenszel weight and 
the corresponding 90% CI will be presented.
For the summary over time by visit, after accounting for the ICEs for the primary estimand, any 
missing data for an endpoint will be imputed as not achieving the associated binary endpoints at 
Week X.
5.4.1.3.2.
Continuous Endpoint (Secondary Endpoints 5, 7)
Analyses for continuous endpoints will be based upon the Treatment Policy estimand. If a 
participant experiences an intercurrent event, the intercurrent event does not affect the outcome, 
and the data collected at and after the event will be used for analysis. Missing data will not be 
imputed.
The total cumulative glucocorticoid dose will be compared between the guselkumab and the 
placebo groups using van Elteren test stratified by baseline disease status (new-onset and relapsing 
GCA) and baseline GC dose (≤30 mg/day or >30 mg/day) at Week 28.
5.4.1.3.3.
Time to First Event Endpoint
For time to first event data, the hazard ratio will be estimated using the Cox proportional hazards 
model, adjusting for the baseline disease status (new-onset or relapsing GCA), and the baseline 
GC dose (≤30 mg/day or >30 mg/day), and its associated 90% confidence interval will be 
presented. The proportional hazards assumption will be verified with appropriate methods 
(e.g. log-minus-log plots) as part of the analysis. The reported p-value for time to first flare analysis 
will be derived from a log-rank test. The survival curves will be estimated using Kaplan-Meier 
estimates.
Efficacy data through Week 28 and through Week 52 will be summarized and displayed by the 
following intervention groups:
1.
Placebo
2.
Guselkumab


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5.5.
Exploratory Endpoints Analysis for the Main Study
Objective: To evaluate the efficacy of guselkumab with a compared to placebo, in combination
with a 26-week GC taper regimen, in adult participants with new-onset or relapsing GCA for 
the following exploratory endpoints:
Other Efficacy Endpoints
!
Summary of signs, symptoms, and elevated CRP and/or ESR due to GCA disease flares
!
Proportion of participants who experience at least one GCA disease flare or discontinuation 
of study intervention due to AE of worsening of GCA through week 28 and from Week 28 
through Week 52 by visit
!
Proportion of participants in sustained remission through Week 52 following remission at
Week 8
!
Proportion of participants in sustained remission through Week 52 following remission at
Week 12
!
Proportion of participants in sustained remission through Week 52 following remission at
Week 16
!
Proportion of participants in sustained remission from Week 28 through Week 52 by visit
following remission at Week 8
!
Proportion of participants in sustained remission from Week 28 through Week 52 by visit 
following remission at Week 12
!
Proportion of participants in sustained remission from Week 28 through Week 52 by visit 
following remission at Week 16
!
Cumulative GC dose through Week 28 and through Week 52 by baseline disease status
(new-onset or relapsing GCA)
!
Cumulative GC dose through Week 28 and through Week 52 by baseline GC dose 
(≤30 mg/day or >30 mg/day)
!
Change from baseline in ESR through Week 28 and from Week 28 through Week 52 by visit
!
Proportion of participants with normalization of ESR through Week 28 and from Week 28 
through Week 52 by visit
!
Change from baseline in CRP through Week 28 and from Week 28 through Week 52 by visit
!
Proportion of participants with normalization of CRP through Week 28 and from Week 28 
through Week 52 by visit
Sustained remission through Week 52 is defined as: No signs and symptoms of GCA through
Week 52, and completion of the protocol defined GC taper, and not having required GC rescue
therapy at any time by Week 52.


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Efficacy data through Week 28 and through Week 52 will be summarized and displayed by the 
following intervention groups:
1.
Placebo
2.
Guselkumab 
Clinical Outcome Assessments (COAs)
In this study, patient-reported outcome measures include patient’s global assessment of their GCA 
disease activity (PGA), pain severity assessment, SF-36 health survey, Functional Assessment of 
Chronic Illness Therapy-Fatigue (FACIT-fatigue) and a clinician-reported outcome, the 
Physician's Global Assessment of Disease Activity (PhGA). The following analyses will be 
performed by treatment group. This section outlines the definitions and analyses for the following 
PRO and ClinRO endpoints.
Other efficacy endpoints related to COAs include:
Patient-reported Outcomes 
!
Change from baseline in PGA at Week 28 and at Week 52.
!
Change from baseline in Pain Severity Assessment at Week 28 and at Week 52.
!
Change from baseline SF-36 PCS (physical component summary) score and MCS (mental 
component summary) score at Week 28 and at Week 52.
!
Change from baseline in SF-36 individual domains at Week 28 and at Week 52.
!
Change from baseline in FACIT-fatigue scale score (raw score) at Week 28 and Week 52.
!
Proportions of participants with FACIT-fatigue scale score ≥40 (mean=40, SD=10) at 
Week 0, 28, and 52. 
!
Proportions of participants with ≥ 4-points improvement in FACIT-fatigue scale score (raw 
score) at Week 28 and 52.
Physician-reported Outcomes
!
Change from baseline in PhGA at Week 28 and Week 52.
COAs data at Week 28 and Week 52 will be summarized and displayed by the following 
intervention groups:
1.
Placebo
2.
Guselkumab


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5.5.1.
Definition of Endpoints
5.5.1.1.
Sustained Remission through Week 52 Following Induction of 
Remission at Week 8
1.
Remission at Week 8
AND
2.
No signs or symptoms of active GCA from Week 8 through Week 52, inclusive
AND
3.
Adherence to the protocol specified 26-week GC taper
AND
4.
Absence of GCA flare from first dose through Week 52
Similar definitions for sustained remission through Week 52 following induction of remission at 
Week 12 and following induction of remission at Week 16.
5.5.1.2.
Sustained Remission from Week 28 through Week 52 by Visit
Following Induction of Remission at Week 8
1.
Remission at Week 8
AND
2.
No signs or symptoms of active GCA from Week 8 through Week X, inclusive
AND
3.
Adherence to the protocol specified 26-week GC taper
AND
4.
Absence of GCA flare from first dose through Week X
Similar definitions for sustained remission through Week X following induction of remission at 
Week 12 and following induction of remission at Week 16.
5.5.1.3.
Normalization of CRP and ESR
The normalization of CRP is defined as CRP<10 mg/L or <1 mg/dL and the normalization of ESR
is defined as ESR<30 mm/hr.
5.5.1.4.
Patient’s Global Assessment of Disease Activity (PGA)
The patient’s global assessment of their GCA disease activity is recorded on a 10-cm VAS with 
verbal anchors on how their GCA feels today are “very poor” on the far-left side of the scale and 
“very well” on the far right of the scale. For this endpoint, a positive change from baseline reflects 
an improvement, and a negative change from baseline reflects a worsening.


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The baseline measurement for the PGA is defined as the closest measurement taken prior to the 
initiation of the Week 0 administration.
5.5.1.5.
Pain Severity Assessment
Participants will be asked to rate the severity of their average pain now on 10-cm VAS with 
anchors ranging from 0, “no pain” to 10, “worst pain imaginable”. For this endpoint, a negative 
change from baseline reflects an improvement, and a positive change from baseline reflects a 
worsening.
The baseline measurement for the pain assessment is defined as the closest measurement taken 
prior to the initiation of the Week 0 administration.
5.5.1.6.
SF-36
The Medical Outcome Study health measure entitled the 36-item Short-Form Version 2 acute 
(SF-36v2 acute) health survey questionnaire was developed as part of the Rand Health Insurance
Experiment and consists of 8 multi-item scales.
!
Limitations in physical functioning due to health problems.
!
Limitations in usual role activities due to physical health problems.
!
Bodily pain.
!
General mental health (psychological distress and well-being).
!
Limitations in usual role activities due to personal or emotional problems.
!
Limitations in social functioning due to physical or mental health problems.
!
Vitality (energy and fatigue).
!
General health perception.
These scales will be scored following two approaches: Based on transformed raw scores that range 
from 0 to 100 with higher scores indicating better health, and standardized scores using a T-score 
transformation to compare to the US general population normative values (mean=50, SD=10) or 
other populations of interest. 
Another algorithm yields 2 summary scores, the Physical Component Score (PCS) and Mental 
Component Score (MCS). These summary scores are also scaled with higher scores indicating 
better health. The concepts measured by the SF-36 are not specific to any age, disease, or 
intervention group, allowing comparison of relative burden of different diseases and the relative 
benefit of different treatments).
Change from baseline in SF-36 score measures the change in health-related quality of life, where
a positive change indicates an improvement, and a negative change indicates a worsening.


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Missing data will be handled following the Full Missing Score Estimation (Full MSE) method, 
which assumes that the missing item responses in a given scale are the same as the response to the 
scale’s answered item. The final item response values are assigned accordingly. This approach 
should not be used in the Physical Functioning (PF) domain scale, but the PF can be estimated 
using item response theory (IRT), which is performed by the QualityMetric Health Outcomes™ 
Scoring Software 5.0.
5.5.1.7.
FACIT-fatigue
The FACIT-fatigue version 4.0 is a 13-item questionnaire formatted for self-administration that 
assesses patient-reported fatigue and its impact upon daily activities and function over the past 
7 days. Participants will be asked to answer each question using a 5-point Likert-type scale (0=Not
at all; 1=A little bit; 2=Somewhat; 3=Quite a bit; and 4=Very much). Questions 1-6 and 9-13 are 
scored in reverse order. If 7 or more questions are answered, then the score can be calculated and 
is adjusted by the number of available questions. The interpretation of FACIT-fatigue scores is 
such that a higher score indicates less fatigue, with a range of possible scores of 0-52, with 0 being 
the worst possible score and 52 the best.
Change from baseline in FACIT-fatigue scores measures the change in fatigue where a positive 
change indicates an improvement, and a negative change indicates a worsening.
Missing data will be handled by calculating a total score that is prorated from the score of the 
answered items as long as more than 50% of the items (i.e., at least 7 of 13) were answered.
5.5.1.8.
Physician’s Global Assessment of Disease Activity (PhGA)
The physician’s global assessment independent of participants’ assessment of the patients GCA
activity is recorded on a 10-cm visual analog scale (VAS) with verbal anchors “No GCA” on the
far-left side of the scale and “Very severe GCA” on the far right of the scale. For this endpoint, a 
negative change from baseline reflects an improvement, and a positive change from baseline 
reflects a worsening.
The baseline measurement for the PhGA is defined as the closest measurement taken prior to the 
initiation of the Week 0 administration.
5.5.1.9.
Analysis Methods
Unless otherwise specified, the analysis population will be the FAS defined in Section 4. 
The endpoints will be summarized by intervention group as specified in Section 5.6.
Analyses for binary endpoints (proportion of responders) over time will be the same as the analyses 
for the above secondary endpoints 1-4 in Table 2 based upon the primary estimand only.


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Unless otherwise specified, the analyses for continuous endpoints at Week 28 and Week 52 will 
be based on the following strategies to handle ICEs and missing data:
!
ICEs in categories 1-3 in the primary estimand (definitions in Section 5.3.2) will be handled 
with the Composite Strategy. Participants experiencing ICEs 1-3 will have a zero change (or 
zero improvement) from baseline assigned from that point onward.
!
ICE in category 4 in the primary estimand will be handled by the Treatment Policy strategy. 
The analysis will be performed using observed data regardless of intercurrent events. For 
participants experiencing multiple ICEs, an ICE in categories 2 or 3 of the primary estimand 
will override an ICE in category 4.
!
Missing data will not be imputed after applying the rules for intercurrent events.
Simple descriptive statistics, such as n, mean, SD, median, IQ range, minimum and maximum for 
these continuous variables.
5.6.
Exploratory Endpoints Analysis for the LTE Period
!
Proportion of participants achieving GC-free remission from Week 52 (LTE Week 0) through 
Week 104 (LTE Week 52) by visit
!
Time to first GCA disease flare discontinuation of study intervention due to AE of worsening 
of GCA from Week 52 (LTE Week 0) through Week 104 (LTE Week 52)
!
The number of GCA disease flares or discontinuation of study intervention due to AE of 
worsening of GCA from Week 52 (LTE Week 0) through Week 104 (LTE Week 60) by visit
!
Change from baseline in ESR from Week 52 (LTE Week 0) through Week 104 (LTE 
Week 52) by visit
!
Proportion of participants with normalization of ESR from Week 52 (LTE Week 0) through 
Week 104 (LTE Week 52) by visit
!
Change from baseline in CRP from Week 52 (LTE Week 0) through Week 104 (LTE 
Week 52) by visit
!
Proportion of participants with normalization of CRP from Week 52 (LTE Week 0) through 
Week 104 (LTE Week 52) by visit
Patient-reported Outcomes by visit at Weeks 52, 76, and 104
!
Change from baseline in PGA.
!
Change from baseline in Pain Severity Assessment.
!
Change from baseline SF-36 PCS (physical component summary) score and MCS (mental 
component summary) score.
!
Change from baseline in SF-36 individual domains.
!
Change from baseline in FACIT-fatigue scale score (raw score).
!
Proportions of participants with FACIT-fatigue scale score ≥40 (mean= 40, SD=10).


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!
Proportions of participants with ≥ 4-points improvement in FACIT-fatigue scale score (raw 
score).
Physician-reported Outcomes
!
Change from baseline in PhGA.
5.6.1.
Definition of Endpoints
5.6.1.1.
GC-free Remission at Each Timepoint from Week 52 through 
Week 104
1.
No signs or symptoms of active GCA at timepoint Week X
AND
2.
Absence of GCA flare from first dose of the study agent from Week 52 through Week X
5.6.2.
Analysis Methods
The analysis population will be participants who enter into the Long-Term Extension. The 
endpoints will be summarized by intervention group.
The Treatment Policy strategy will be applied to the binary exploratory secondary endpoints 
(proportion of responders). For participants who experience an intercurrent event from Week 52 
through Week 104, the analysis will be performed using observed data regardless of intercurrent 
events. Missing data will not be imputed. 
The survival curves will be estimated using Kaplan-Meier estimates for time to first GCA disease 
flare or discontinuation of study intervention due to AE of worsening of GCA from Week 52 
through Week 104.
Simple descriptive statistics, such as n, mean, SD, median, IQ range, minimum and maximum for 
the continuous variables over time. The remaining missing data will not be imputed.
The efficacy data during the LTE period will be summarized and displayed by the following 
intervention groups:
1.
Placebo
2.
Guselkumab 
5.7.
Safety Analyses
All safety analyses for the main study will be based on the safety analysis set based on actual 
intervention received, unless otherwise specified. Safety analyses for the long-term extension will 
include participants who complete the Week 52 visits and are assessed to be in GC-free remission 
with at least one SC injection at Week 52 or later. 


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For all continuous safety variables, descriptive statistics by intervention group will include the N, 
mean, standard deviation, median, minimum, and maximum. Categorical variables will be 
summarized by intervention group using frequency counts and percentages.
Depending on the safety data, the cumulative safety data will be analyzed through different study 
periods which include but are not limited to through Week 28 and through Week 60 for the main 
study. The safety analyses through Week 60 for the main study will include safety data through
Week 60 for participants not entering the LTE and safety data through Week 52 for participants 
continuing onto the LTE. Safety analyses from Week 52 (LTE Week 0) through Week 112 (LTE 
Week 60) will be performed for participants in the LTE period.
5.7.1.
Extent of Exposure
The number and percentage of participants who receive study intervention will be summarized. 
The cumulative dose and number of administrations of study intervention received will be 
summarized by treatment group for the safety analysis.
Study agent lots received by treatment, including matching placebo for active treatment will be 
summarized.
In addition, the average exposure (number of administrations) and average duration of follow-up 
(weeks) will also be summarized by treatment group in the safety tables through different study 
time periods.
For IV and SC study intervention:
Descriptive statistics will be presented for the following parameters:
!
Number of administrations
!
Cumulative total dose
Compliance to randomized intervention versus actual intervention will be presented in a summary 
table.
5.7.2.
Adverse Events
The verbatim terms used in the CRF by investigators to identify adverse events will be coded using 
the Medical Dictionary for Regulatory Activities (MedDRA). Any AE occurring at or after the 
initial administration of study intervention is considered to be treatment emergent. If the event 
occurs on the day of the initial administration of study intervention, and either event time or time 
of administration are missing, then the event will be assumed to be treatment emergent. If the event 
date is recorded as partial or completely missing, then the event will be considered to be treatment 
emergent unless it is known to be prior to the first administration of study intervention based on 
partial onset date or resolution date. All reported treatment-emergent adverse events will be 
included in the analysis. For each adverse event, the number and percentage of participants who 
experience at least 1 occurrence of the given event will be summarized by intervention group.


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Safety data will be summarized and displayed by the following intervention groups:
!
through Week 28
1.
Placebo
2.
Guselkumab
In addition, overall AEs will be also summarized and displayed by the following intervention 
groups:
a.
Placebo IV: participants receiving placebo during the study.
b.
Placebo SC: participants receiving placebo during the study.
c.
Guselkumab ─ Receiving 400 mg IV Induction Doses: participants receiving at least 
one administration of guselkumab 400 mg IV at Week 0, 4 and 8
d.
Guselkumab ─ Receiving 200 mg SC Induction Doses: participants receiving at least 
one administration of guselkumab 200 mg SC at Week 0, 4, and 8.
!
through Week 60
1.
Placebo
2.
Guselkumab
!
during the LTE period
1.
Placebo
2.
Guselkumab
The following summary tables will be provided for treatment-emergent adverse events:
!
AEs
!
AEs with a frequency threshold of 5% or more
!
Serious AEs (SAEs)
!
AEs leading to discontinuation of study intervention
!
AEs by severity
!
AEs by relationship to each study agent within a study intervention
!
AEs temporally associated with an IV infusion
!
Injection-site reactions 
In addition to the summary tables, listings will be provided for participants who:
!
Had SAEs
!
Had AEs leading to discontinuation of study intervention
!
Had AEs of severity
!
Had temporally associated with infusion


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!
Had VTEs
!
Had arterial thromboembolic AEs
!
Had anaphylactic reactions and serum sickness reactions 
!
Had suicidal ideation or suicidal behavior
!
Had COVID-19 related AEs
!
Had died
5.7.3.
Additional Safety Assessments
5.7.3.1.
Clinical Laboratory Tests
Clinical laboratory tests will be displayed for the participants included in the safety analysis set.
Descriptive statistics and graphical displays will be presented for selected chemistry and
hematology laboratory tests at scheduled time points.
Change from baseline through Week 28 and through Week 60 for the main study, and from 
Week 52 (LTE Week 0) through Week 112 (LTE Week 60) will be summarized for chemistry and 
hematology tests and displayed by intervention group. A box plot of change from baseline through 
Week 28 and through Week 60 for the main study, and from Week 52 (LTE Week 0) through 
Week 112 (LTE Week 60) will be provided.
!
Hematology assessments will include but are not limited to the following: hemoglobin, 
hematocrit, lymphocytes, neutrophils, platelet count, total and differential White Blood Cell 
(WBC) count.
!
Blood chemistry assessments will include but are not limited to the following: chemistry 
panel (total and direct bilirubin, ALT, AST, alkaline phosphatase, albumin, total protein, 
calcium, phosphate, sodium, potassium, chloride, blood urea nitrogen/urea, and creatinine).
The National Cancer Institute’s Common Terminology Criteria for Adverse Events will be used 
in the summary of laboratory data (Grade 0-4). The proportion of participants with post-baseline 
values by maximum toxicity grade for clinical laboratory tests will be summarized by study 
intervention group. Shift tables will be provided summarizing the shift in laboratory values from 
baseline to the end of the reporting period with respect to NCI-CTCAE grades. Participants with 
toxicity grades ≥ 2 will be listed.
For ALT and AST, highest postbaseline elevated liver function tests will be summarized by 
intervention group. In addition to the summary table, listings will be provided for participants with 
highest postbaseline elevated liver function tests ALT ≥3, ≥5, ≥8xULN, AST ≥3, ≥5, ≥8xULN, 
and participants meeting combined criteria (total bilirubin ≥2xULN, and either AST or ALT ≥3x 
ULN), respectively.


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5.7.3.2.
Vital Signs and Physical Examination Findings
Continuous vital sign parameters including temperature, respiratory rate, weight, pulse, blood 
pressure (systolic and diastolic), and Body Mass Index (BMI) will be summarized at each 
assessment time point. Body Mass Index will be calculated as weight (kg)/(height (m))2, at each 
time point that body weight is measured. The height measurement collected at screening will be 
used in the calculation. Change from baseline will be summarized through Week 28 and from 
Week 28 through Week 60 for the main study, and from Week 52 through Week 112 for 
participants in the LTE period. Descriptive statistics (mean, standard deviation, median, minimum 
and maximum) will be presented.
Incidence of treatment-emergent clinically important abnormal vital signs during intervention, as 
defined in Table 3, will be summarized for participants who had a baseline assessment and at 
least 1 postbaseline assessment for that vital sign. A listing of participants with treatment-emergent 
clinically important abnormality in vital signs will be presented.
Table 3:
Clinically Important Abnormal Limits for Vital Signs
Vital Sign
Criteria
Pulse
>115 bpm and with >30 bpm increase from baseline
<50 bpm and with >20 bpm decrease from baseline
Systolic blood pressure
>150 mm Hg and with >40 mm Hg increase from baseline
<90 mm Hg and with >30 mm Hg decrease from baseline
Diastolic blood pressure
>95 mm Hg and with >30 mm Hg increase from baseline
<50 mm Hg and with >20 mm Hg decrease from baseline
Interarm blood pressure 
interarm blood pressure absolute difference ≥15 mmHg in systolic blood 
pressure at 3 consecutive visits
Temperature
>38.4oC and with ≥1oC increase from baseline 
Weight
increase 10% from baseline
decrease 10% from baseline
Respiratory rate
>20 breaths per minute
5.7.3.3.
Columbia-Suicide Severity Rating Scale
The C-SSRS will be used as a screening tool to prospectively evaluate suicidal ideation and 
behavior among study participants. The C-SSRS measures 5 possible levels of suicidal ideation 
and 4 possible suicidal behaviors, as well as non-suicidal self-injurious behavior. The assessment 
is a fully-structured, participant self-report C-SSRS questionnaire, including standardized 
questions, follow-up prompts, error handling routines, and scoring conventions. Two versions of 
the C-SSRS will be used in this study, the Lifetime version and the Since Last Contact version. 
The Lifetime version will be conducted during the screening visit and the Since Last Contact
version will be conducted at all other visits.


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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. Participants will be interviewed by the investigator or trained study site 
personnel in a private, quiet place.
The following are C-SSRS categories and have binary responses (yes/no). A “yes” response to any 
C-SSRS category will be assigned a score as below:
Suicidal Ideation (1-5)
1 = Wish to be Dead
2 = Non-specific Active Suicidal Thoughts
3 = Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act
4 = Active Suicidal Ideation with Some Intent to Act, without Specific Plan
5 = Active Suicidal Ideation with Specific Plan and Intent
Suicidal Behavior (6-10)
6 = Preparatory Acts or Behavior
7 = Aborted Attempt
8 = Interrupted Attempt
9 = Actual Attempt (non-fatal)
10 = Completed Suicide
If no events qualify for a score of 1 to 10, a score of 0 will be assigned (0=“Negative result 
[no suicidal ideation or behavior]”). Higher scores indicate greater severity.
The summary for suicidal ideation and behavior will be based on the safety analysis set. Suicidal 
ideation and behavior will be summarized based on the most severe/maximum post baseline 
C-SSRS outcome or AE of suicidal ideation, suicidal behavior excluding completed suicide, or 
completed suicide through Week 28 or through Week 60 for the main study, and from Week 52 
through Week 112 for participants in the LTE period. The baseline is defined as the most 
severe/maximum C-SSRS score at either screening or Week 0.
The maximum score assigned for each participant will also be summarized into one of three broad 
categories: No suicidal ideation or behavior, suicidal ideation, suicidal behavior. A shift table for 
change in C-SSRS categories of no suicidal ideation or behavior, suicidal ideation, and suicidal 
behavior from baseline through Week 28 and through 60 for the main study, and from Week 52 


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through Week 112 for participants in the LTE period will be presented, where the baseline category 
is based on C-SSRS score and the post baseline is based on C-SSRS or AE data.
5.8.
Other Analyses
5.8.1.
Pharmacokinetics
Pharmacokinetics (PK) samples for measuring serum guselkumab concentrations will be collected 
from all participants at the specified visits as shown in the Schedule of Activities. All PK 
evaluations will be performed on the PK analysis set for the main study, defined as participants 
who have received at least 1 administration of guselkumab and have at least one post-dose sample 
collection. The PK analyses for LTE period will include all participants who participate LTE 
period. 
Descriptive statistics (N, mean, SD, median, range, coefficient of variation (%CV) and IQ range) 
will be used to summarize guselkumab serum concentrations at each sampling time point. PK data 
may be displayed graphically, such as median +/- IQ range PK concentrations over time. The 
following analyses will be performed as appropriate:
!
Summary of serum guselkumab concentrations at each visit 
!
Summary of serum guselkumab concentrations at each visit by baseline body weight quartiles
!
Summary of participants with serum guselkumab concentrations below the lowest level of 
quantification x minimum required dilution (LLOQxMRD) at each visit
!
Plot of median +/- IQ range serum guselkumab concentrations over time
If sufficient data are available, then population PK analysis using serum guselkumab 
concentration-time data will be performed using nonlinear mixed-effects modeling to estimate 
total systemic clearance and volume of distribution. Details will be given in a population PK 
analysis plan and the results of the analysis will be presented in a separate report.
The relationship between serum guselkumab concentrations (quartiles) at Week 28 and the 
proportion of participants achieving GC-free remission at Week 28 and Week 52 will be 
performed. The relationship between serum guselkumab concentrations and key secondary 
endpoints (e.g. GC-free remission through Week 52, time to first flare, and cumulative GC dose 
through Week 28 and Week 52) may also performed. In addition, summary of change from 
baseline in CRP concentration (mg/L), ESR at Week 28 by serum guselkumab concentration 
quartiles at Week 28 will be perform when appropriate. 
5.8.1.1.
Data Handling Guidelines
Unless otherwise specified, the following data handling guideline will apply to PK analyses:
!
All serum concentration summaries for a particular timepoint will include data obtained from 
treated participants at the timepoint of interest without imputing any missing data
!
A concentration not quantifiable (below LLOQ) will be treated as 0 in the summary statistics 
and shown as the lower limit of quantification (<LLOQ) in the data listings


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!
The data from a participant who meets one of the following dosing deviation criteria will be 
excluded from the by-visit data analyses and from that point onwards:
∀
Discontinue guselkumab administrations
∀
Skipped a guselkumab administration
∀
Received incomplete/incorrect dose
∀
Received incorrect study agent
∀
Received additional dose
Of note, serum guselkumab concentrations prior to the first of such events will be included in the 
summaries. In addition, if a participant has an administration outside of dosing window, the 
concentration data collected at and after that will be excluded from the by-visit data analyses. 
Additional exclusions for PK data to be implemented based on TV-GDL-00362. All participants 
and samples excluded from analysis will be documented in the Clinical Study Report. 
5.8.2.
Immunogenicity
Blood samples will be collected to examine the formation of antibodies to guselkumab at the 
specified visits as shown in the Schedule of Activities of the protocol.
“Sample ADA status” and sample titer as well as the cumulative “subject ADA status” and peak 
titer through the visit will be coded and provided by the bioanalytical group. 
5.8.2.1.
Participant ADA Classifications
Participants evaluable for immunogenicity are defined as having at least one post-dose ADA time 
point collected for antibodies to guselkumab detection.
1.
Participants with treatment-emergent antibodies to guselkumab include participants with 
treatment-induced antibodies to guselkumab and treatment-boosted antibodies to guselkumab.
2.
Participants with treatment-induced antibodies to guselkumab have antibodies to 
guselkumab negative sample prior to guselkumab administration and at least one antibody to 
guselkumab positive sample after guselkumab.
3.
Participants with treatment-boosted
antibodies to guselkumab have antibodies to 
guselkumab positive sample prior to guselkumab administration and at least one antibody to 
guselkumab positive sample after guselkumab with a 2-fold increase in titer over baseline.
If titer remains the same after intervention or if ADA titer reduces or ADA disappears, the 
participant is classified as “treatment-emergent ADA negative”. Participants that are unevaluable 
for treatment-emergent ADA following intervention will be classified as “participants with 
baseline samples only”, ie, no appropriate sample is available after intervention.


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5.8.2.2.
Immunogenicity Analyses
The summary and evaluation of antibodies to guselkumab will be based on the observed data; 
therefore, no imputation of missing data will be performed. Note: participant status is through each 
visit, thus, participant status and peak titers may change as the study progresses over time. 
Therefore, the ‘subject ADA status’ at a visit represents the cumulative ADA status through that 
visit. For example, if a study has a lock at Week 28, datasets through Week 28 will have participant 
level status (eg, negative) but at Week 40, they may have developed ADA and the participant status 
becomes “treatment-emergent ADA positive” from the primary to the final DBL. Peak titers can 
also change (increase) if a higher titer occurs after an initial DBL.
The summary of participants with baseline positive samples is taken from the sample status at 
baseline. There is no participant level status at baseline.
The data analysis of antibodies to guselkumab includes the following when appropriate:
1.
Incidence of antibody (evaluable, treatment-emergent ADA positive, treatment-emergent 
ADA negative) status and neutralizing antibodies (NAb) to gueslkumab will be summarized.
2.
Descriptive statistics (N, mean, SD, median, range, and IQ range) and incidence (N, %) of the 
relationship between treatment-emergent antibodies to guselkumab status (positive or 
negative) and PK concentration will be assessed.
3.
Participants in response (N, %) for treatment-emergent antibodies to guselkumab status 
(positive or negative) and efficacy endpoints may be assessed:
∀
Participants evaluable for immunogenicity
∀
Efficacy endpoints repeated for different levels of response (eg, GC-free remission)
o
Number of participants (N)
o
Participants in response (N, %)
4.
Incidence (N, %) between treatment-emergent antibodies to guselkumab status (positive or 
negative) and infusion-related reactions may be assessed:
∀
Participants evaluable for immunogenicity
∀
Participants with infusion-related reaction
∀
Participants with severe infusion-related reaction
∀
Participants with serious infusion-related reaction
∀
Participants with infusion-related reaction leading to discontinuation
∀
Guselkumab infusions with infusion-related reactions (out of total number of guselkumab 
infusions)
∀
Placebo infusions with infusion-related reactions (out of total number of placebo 
infusions).


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5.
Incidence (N, %) between treatment-emergent antibodies to guselkumab status (positive or 
negative) and injection site reactions may be assessed:
∀
Participants evaluable for immunogenicity
∀
Participants with injection site reaction
∀
Participants with severe injection site reaction
∀
Participants with serious injection site reaction
∀
Participants with injection site reaction leading to discontinuation
∀
Guselkumab injections with injection site reactions (out of total number of guselkumab 
injections)
∀
Placebo injections with injection site reactions (out of total number of placebo injections).
In addition, listings of participants with baseline positive ADA samples, participants who are 
classified as positive for treatment-emergent antibodies to guselkumab and participants who 
discontinue the study by antibodies to guselkumab status as well as graphical representation of 
median serum concentration by antibody status may be presented.
5.8.3.
Pharmacokinetic/Pharmacodynamic Relationships
Exploratory PK-PD analyses, including graphical exploration of PK-PD data, may be performed.
For binary PD/efficacy endpoints, percent responders within each quartile of PK concentration 
may be presented, if data permits.
If deemed feasible and necessary, exposure-response analyses may be performed. The analysis 
methods may be summarized in a separate analysis plan. Results of such analyses may be presented 
in a separate technical report.
5.8.4.
Biomarkers
Biomarker analyses will be used to examine the biologic response to treatment and to identify 
biomarkers which are relevant to guselkumab treatment, GCs, and GCA. These biomarker analyses 
are exploratory and will include characterization of the molecular effects of guselkumab treatment, 
assessment of GCA pathogenesis, and determination if these markers can predict response to 
guselkumab. Exploratory changes in serum analytes and RNA levels in whole blood may be 
summarized by intervention group, in separate technical reports. Additionally, single cells from 
PBMC and leukocyte subset counts and frequencies in PBMCs over time may be assessed from 
PBMC collections and summarized in separate technical reports. Associations between baseline 
levels and changes from baseline in select markers and clinical response on primary and major 
secondary endpoints in Section 9.4.2 and Section 9.4.3 of the protocol will be explored and 
summarized in separate technical reports. Planned biomarker analyses may be deferred if emerging 
study data show no likelihood of providing useful scientific information. Any biomarker samples 
received by the contract vendor or sponsor after the cutoff date will not be analyzed, and therefore, 
excluded from the biomarker analysis.


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5.8.5.
Pharmacogenomic Analyses
Genetic (DNA) analyses will be conducted only in participants who sign the consent form to 
participate in the pharmacogenomic substudy. DNA samples will be used for research related to 
Guselkumab, GCs, or GCA. Pharmacogenomic research may consist of the analysis of one or more 
candidate genes or of the analysis of genetic markers throughout the genome (as appropriate) in 
relation to Guselkumab, GCs or GCA clinical endpoints. These analyses are considered 
exploratory and will be summarized in a separate technical report.
5.8.6.
Exploratory FDG-PET/CT Imaging Analyses
FDG-PET/CT scans will be qualitatively assessed for FDG uptake in 9 arterial territories (carotid
arteries, subclavian arteries, brachiocephalic artery, ascending aorta, aortic arch, descending 
thoracic aorta, and the abdominal aorta). The degree of arterial uptake will be visually assessed 
relative to liver uptake as: 0 = no uptake; 1 = less than liver; 2 = same as liver; 3 = greater than 
liver. To assess the qualitative inflammatory burden by arterial FDG uptake across multiple arterial 
regions, a summary score (hereafter termed PET Vascular Activity Score [PETVAS]) will be 
created by adding the qualitative scores in specific arterial territories.
A separate analysis plan for FDG-PET/CT imaging analyses will describe how the data will be 
analyzed including a detailed description of the data summarization methods and modeling 
approach. These analyses are considered exploratory and will be summarized in a separate 
technical report.
5.8.7.
Digital Health - Actigraphy Analyses
A separate digital biomarker analysis plan will describe how actigraphy data will be analyzed
including a detailed description of the data summarization methods and modeling approach. 
Results of the actigraphy analysis will be presented in a separate digital biomarker technical report.
5.8.8.
Definition of Subgroups
To evaluate the consistency of the primary efficacy endpoint (proportion of participants who 
achieve GC-free remission at Week 28), subgroup analyses may be performed when the number 
of participants in the subset permits (at least 5 participants for each intervention group within a 
subset).


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The subgroups for subgroup analysis may include, but are not limited to, the following:
1.
Demographic subgroups
Subgroup
Variant
Definition
Region
1
!
North America
!
Europe
!
Asian
Sex
1
!
Male
!
Female
Race
1
!
White 
!
Black or African American 
!
Asian
!
Other
Age Group
1
!
≥50 to ≤64
!
≥65
Body Weight Group
1
!
≤70 kg 
!
>70 kg
BMI
1
!
normal <25 kg/m2
!
overweight 25-<30 kg/m2
!
obese ≥30 kg/m2
2.
Disease Characteristics subgroups
Subgroup
Variant
Definition
Age at diagnosis
1
!
≤Median 
!
> Median
GCA disease duration
1
!
≤Median 
!
> Median
Baseline GC dose
1
!
≤30 mg/day
!
>30 mg/day
Baseline disease status
1
!
New-onset GCA
!
Relapsing GCA
Baseline ESR
1
!
≥30 mm/hr
!
<30 mm/hr
Baseline CRP
1
!
≥10 mg/L
!
<10 mg/L
Participant was in 
remission (No signs or 
symptoms of GCA) at 
baseline
1
!
Yes
!
No
3.
Prior medication subgroups
Subgroup
Variant
Definition
IV glucocorticoids
1
!
Yes/No
Tocilizumab
1
!
Yes/No
Other biologic therapy
1
!
Yes/No
Methotrexate
1
!
Yes/No
Other non-biologic 
immunosuppressant (other 
than methotrexate)
1
!
Yes/No
4.
Baseline medication subgroups
Subgroup
Variant
Definition
Methotrexate
1
!
Yes/No


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5.9.
Interim Analyses
No formal interim analysis is planned. However, a Data Monitoring Committee (DMC) will 
monitor the safety for this study.
5.9.1.
Data Monitoring Committee (DMC) or Other Review Board
An independent DMC will monitor data on an ongoing basis to ensure the continuing safety of the 
participants enrolled in the study. The committee will meet periodically to review interim safety 
data. After the review, the DMC will make recommendations regarding the continuation of the 
study. If there is any safety concern, the GMS Therapeutic Area Head should call Safety
Management Team (SMT) to discuss concerns of safety within the clinical study.
The DMC will consist of one external and one internal clinical physician with relevant therapeutic 
expertise (rheumatology), the internal GMS Therapeutic Area Safety Head, and one internal 
statistician. An additional internal statistical modeling expert would be involved in Week 28 IA 
and is optional in participating in the other DMC safety reviews. No DMC member is directly 
involved with the study conduct.
The major function of the DMC is to monitor the safety of the study agent and to provide 
recommendations for placing the study on hold or stopping the study in the event of serious safety 
concerns. The content of the safety summaries, the DMC roles and responsibilities and the general 
procedures (including communication plan) and their possible recommendations on study conduct 
will be defined and documented in the DMC Charter prior to the first DMC review.
In addition, during the study, the sponsor's study responsible physician (or designee) will regularly
review blinded safety data from the sites and notify the DMC and appropriate sponsor personnel
of any issues.


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6.
SUPPORTING DOCUMENTATION
6.1.
Appendix 1 List of Abbreviations
ADA
anti-drug antibody
AE
adverse event
ALT/SGPT
alanine aminotransferase
AST/SGOT
aspartate aminotransferase
ATC
anatomic and therapeutic class
BMI
body mass index
CI
confidence interval
CRF
case report form
CSR
Clinical Study Report
CTCAE
Common Terminology Criteria for Adverse Events
CV
coefficient of variation
DMC
Data Monitoring Committee
DPS
Data Presentation Specifications
eCRF
electronic case report form
FAS
full analysis set
GCA
giant cell arteritis
GMS
Global Medical Safety
hr
hour
IQ
interquartile
IWRS
interactive web response system
LLOQ
lower limit of quantification
MedDRA
Medical Dictionary for Regulatory Activities
MRD
minimum required dilution
NAb
neutralizing antibodies
PD
pharmacodynamic(s)
PK
pharmacokinetic(s)
PP
per protocol
SAE
serious adverse event
SAP
Statistical Analysis Plan
SD
standard deviation
SMT
Safety Management Team
SoA
Schedule of Activities
TEAE
treatment-emergent adverse event
US NCI
VTE
United States National Cancer Institute
Venous Thromboembolic adverse events
WHO
World Health Organization
WHO-DD
World Health Organization Drug Dictionary


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6.2.
Appendix 2 Demographics and Baseline Characteristics
The number of participants in full analysis set will be summarized and listed by intervention group, 
and overall. In addition, the distribution of participants by region, country, and site ID will be 
presented unless otherwise noted.
Table 4 presents a list of the demographic variables that will be summarized by intervention group, 
and overall for the full analysis set.
Table 4:
Demographic 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)
Body Mass Index (BMI) (kg/m2)
Categorical Variables
Age 50−64 years, and ≥65 years)
Frequency distribution with the 
number and percentage of 
participants in each category.
Sex (male, female)
Racea (American Indian or Alaska Native, Asian, Black or African 
American, Native Hawaiian or other Pacific Islander, White, Not reported, 
Unknown, Multiple)
Ethnicity (Hispanic or Latino, Not Hispanic or Latino, Not reported, 
Unknown)
BMI (normal <25 kg/m2, overweight ≥25-<30 kg/m2, obese ≥30 kg/m2)
a
If multiple race categories are indicated, the Race is recorded as 'Multiple'
Table 5 presents a list of the screening or baseline disease characteristics that will be summarized 
by intervention group and overall for the Full Analysis Set.
Table 5:
Screening or Baseline Disease Characteristics
Continuous Variables:
Categories
Summary Type
GCA disease duration (weeks)
Descriptive statistics (N, 
mean, standard deviation 
[SD], median and range 
[minimum and maximum], 
and IQ range).
Age at diagnosis (years)
Total criteria score
GC dose at baseline (mg/day)
Descriptive statistics (N, 
mean, standard deviation 
[SD], median and range 
[minimum and maximum], 
and IQ range).
Baseline erythrocyte sedimentation rate (ESR)
Baseline C-reactive protein (CRP)
Physician’s Global Assessment of Disease Activity 
(PhGA)
Patient’s Global Assessment of Disease Activity 
(PGA)
Pain assessment
FACIT-fatigue scale score (raw score)


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Continuous Variables:
Categories
Summary Type
Categorical Variables
Frequency distribution with 
the number and percentage 
of participants in each 
category.
GCA diagnosis at screening
Disease type
! New-onset
! Relapsing
Baseline GC use
! ≤30 mg/day
! >30 mg/day
Remission status at baseline
Participant was in remission 
(No signs or symptoms of 
GCA)
GCA disease assessment at baseline
! Symptoms of GCA
! Signs of GCA
Acute-phase reactants and renders at screening
! ESR ≥ 30 mm/hr
! CRP ≥ 10 mg/L
Acute-phase reactants and renders at baseline
! ESR ≥ 30 mm/hr
! CRP ≥ 10 mg/L


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6.3.
Appendix 3 Protocol Deviations
In general, the following list of major protocol deviations may have the potential to impact 
participants’ rights, safety or well-being, or the integrity and/or result of the clinical study. 
Participants with major protocol deviations will be identified prior to database lock and the 
participants with major protocol deviations will be summarized by category.
!
Developed withdrawal criteria but not withdrawn
!
Entered but did not satisfy criteria
!
Received a disallowed concomitant treatment
!
Received wrong treatment or incorrect dose
!
Other
∀
due to COVID-19
In addition to the summary tables, the following listings will be provided:
!
List of participants with major protocol deviations 


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6.4.
Appendix 4 Prior and Concomitant Medications
Prior and Concomitant medications will be coded using the World Health Organization Drug 
Dictionary (WHO-DD). Prior medications are defined as any therapy used before the day of first 
dose (partial or complete) of study intervention. Concomitant medications are defined as any 
therapy used on or after the same day as the first dose of study intervention, including those that 
started before and continue on after the first dose of study intervention.
Summaries of concomitant medications with non-rescue therapies for GCA will be presented by 
ATC term and intervention group for non-rescue therapy. 


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6.5.
Appendix 5 Medical History of Interest
Medical history of interest will be summarized by intervention group.


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6.6.
Appendix 6 Laboratory Toxicity Grading
The grading scale use for lab assessments is based on the latest version of ‘Common Terminology 
Criteria for Adverse Events (CTCAE).
Pre-baseline measurements will use the same grading ranges as applied to baseline measurements. 
In case a test has two sets of ranges – one for baseline normal and one for baseline abnormal, the 
one for baseline normal will be applied for all measurements taken pre-baseline and on baseline.
Text in gray italic in the table is present in the grading scale but is not applied by Janssen when 
grading lab data.


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6.7.
Appendix 7 COVID-19 Related Summaries
Participant disposition as related to COVID-19 will be summarized by intervention group. This 
includes the following COVID-19 related disposition events:
!
Termination of study due to COVID-19
!
Discontinuation of stud agent due to COVID-19
!
Death related to COVID-19
Participants discontinuing treatment or terminating study participation due to COVID-19 and/or
reason(s) will be listed.
Protocol deviations (major and minor) as related to COVID-19 will be summarized and listed.
Adverse events related to COVID-19 will be identified and coded using the MedDRA coding 
guidance for COVID-19, and summary tables will be provided for COVID-19 related TEAEs. The 
following will be listed by participant:
!
TEAEs related to COVID-19
!
Serious TEAEs related to COVID-19


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6.8.
Appendix 8 Protocol-prohibited Concomitant Medications/Therapies
The prohibited medications/therapies for GCA disease include the below concomitant 
medications/therapies with the answer “Yes” to the question “Is this a prohibited medication?” on 
eCRFs Concomitant Therapy page: 
!
Immunomodulatory biologic agent
!
Other biologic therapy
!
Methotrexate
!
Other non-biologic immunomodulator
!
Investigational agent 
!
Other
In addition to the above, the below glucocorticoid will also be considered as protocol-prohibited
concomitant medications.
!
Any oral glucocorticoid for indications other than GCA
!
Any intramuscular, intra-articular, intrabursal, epidural, intra-lesional, or IV GCs