Clinical trial NCT05125679
Conditions: Psoriasis
Sponsor: Janssen-Cilag Ltd.
Start date: 2021-11-23; Completion date: 2023-07-28
Enrollment: 15 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to evaluate the effect of guselkumab on coronary flow reserve (CFR), measured by transthoracic doppler-echocardiography, in participants with moderate-to-severe psoriasis and intermediate cardiovascular risk.

Detailed description:
Psoriasis is a common chronic inflammatory disease that affects 2 percent (%)-3% of the population and has an impact on physical and emotional health-related quality-of-life that is comparable to major illnesses such as cancer, heart disease and depression. Guselkumab is a fully human immunoglobulin G1 lambda monoclonal antibody that binds to the p19 protein subunit of human interleukin 23 (IL-23) with high specificity and affinity. Binding of guselkumab to the IL-23 p19 subunit blocks the binding of extracellular IL-23 to the cell surface IL-23 receptor, inhibiting IL-23 specific intracellular signaling and subsequent cytokine production. Guselkumab is indicated for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy. This study aims to investigate the efficacy of guselkumab in reducing surrogate parameters of vascular dysfunction and cardiovascular risk. This study will consist of two Screening Visits (Screening Visit S1 at a maximum of 2 weeks prior to Screening Visit S2, to occur at a minimum of 2 weeks and maximum of 4 weeks prior to Week 0), a Treatment Phase (up to 28 weeks), Final Efficacy Visit 4 weeks later (Week 32), and Final Safety Visit (Week 40). The efficacy assessments will be done locally at the sites and safety will be monitored by assessment of adverse events, clinical laboratory tests, physical examinations, vital signs, and concomitant medication review. The total duration of the study will be 40 weeks.

Arms: arm 1: Participants will receive guselkumab 100 milligrams (mg) by subcutaneous injection at Weeks 0, 4, 12, 20 and 28.
Interventions: intervention 1: Guselkumab
Intervention descriptions: intervention 1: Guselkumab will be administered by subcutaneous injection.

Protocol documents:
Prot_000.pdf: 
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
1
Status: Approved, Date: 13 May 2022
Janssen EMEA*
Clinical Protocol
Protocol Title
APhase 4,Interventional, Single-arm, Open-label Study Evaluating the Effect of
Guselkumab on Cardiovascular Risk Surrogate Markers in Participants With Moderate to
Severe Plaque Psoriasis
G-CARE
Short Title
Effect of Guselkumab on Cardiovascular Risk Surrogate Markers in Participants With
Moderate to Severe Plaque Psoriasis
Protocol CNTO1959PSO4015; Phase 4
Amendment 2
CNTO1959 (guselkumab)
*Janssen EMEA is a regional organization that operates through different legal entities in various
countries. The legal entity acting as the Sponsor for Janssen EMEA studies may vary, such as, but not
limited to Janssen-Cilag International NV; Janssen Pharmaceutica NV; or Janssen Scientific Affairs,
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.
EudraCT NUMBER:2020-004061-39
Status: 
Approved
Date: 
13 May 2022
Prepared by: Janssen-Cilag Limited
EDMS number: 
EDMS-RIM-160183, 4.0
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.
NCT05125679


CNTO1959 (guselkumab)
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Status: Approved, Date: 13 May 2022
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document 
Date
Amendment 2 
13 May 2022
Amendment 1 
12 May 2021
Original Protocol 
1 April 2021
Amendment 2 (13 May 2022)
Overall Rationale for the Amendment: To ensure exclusion criterion regarding low density lipoprotein
(LDL) cutoff value (above which statin therapy should be initiated) is in line with the guidelines for
management of dyslipidemia by the European Society of Cardiology.
Section Number 
and Name
Description of Change 
Brief Rationale
Section 5.2 
Exclusion Criteria. 
Updated the LDL cutoff-value from 160 mg/dL to 
>190 mg/dL in Exclusion Criterion 1.
To bring cutoff value in line with
the guidelines for management of
dyslipidemia by the European
Society of Cardiology.
Section 3 Objectives 
And Endpoints. 
Updated secondary endpoint from “Change from
baseline in coronary flow reserve (CFR) at Week
16 and Week 24 among participants with CFR in
the ranges of 2 to 2.49, 2.5 to 3, and 3.01 to 3.5 at
baseline” to “Change from baseline in CFR at
Week 16 and Week 32 among participants with
CFR in the ranges of 2 to 2.49, 2.5 to 3, and 3.01 to
3.5 at baseline”.
To ensure consistence with all other
endpoints throughout the protocol.
Throughout the 
protocol. 
Minor grammatical, formatting, or spelling changes
were made.
Minor errors were noted.
Amendment 1 (12 May 2021)
Overall Rationale for the Amendment:The protocol was amended to include tests and measurements to
screen study participants for metabolic syndrome. In addition, the method used for calculation of body
surface area (BSA) affected by psoriasis was updated, and the latest versions of the patient reported
outcomes (PRO) questionnaires were added to the protocol.
Section Number 
and Name
Description of Change 
Brief Rationale
Schedule of
Activities.
 Measurement of waistline
circumference was added as part of
physical examination at Screening
Visit S1.
 The lipid panel was changed to
include metabolic tests, and serum
glucose and serum insulin tests were
added to the panel.
To screen study participants for metabolic
syndrome.
Schedule of
Activities.
Foot note “g” pertaining to cardiology
assessments was updated.
To ensure participant comfort and compliance,
participants who have fasted for the lipid and
metabolic panel at Weeks 16 and 32 will be
permitted to have a non-caffeinated drink prior
to the cardiology assessments.
Section 8: Study
Assessments and
Procedures.
Text in the “Study Visits Weeks 16 and
32” section was updated.
To ensure participant comfort and compliance,
participants who have fasted for the lipid and
metabolic panel at Weeks 16 and 32 will be


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Section Number
and Name
Description of Change 
Brief Rationale
permitted to have a non-caffeinated drink prior
to the cardiology assessments.
Section 8.1.2:
Psoriasis
Assessments.
The section “Body Surface Area” was
updated, and a new reference was
added.
Text consistent with the updated “Rule of 9”
calculation for BSA measurement was added.
Section 8.2.1:
Physical
Examination.
Measurement of waistline
circumference was added to the list of
physical examinations.
To screen study participants for metabolic
syndrome.
Section 10.2
Appendix 2:
Clinical Laboratory
Tests.
The lipid panel was changed to include
metabolic tests, and serum glucose and
serum insulin tests were added to the
panel.
To screen study participants for metabolic
syndrome.
Section 10.7
Appendix 7.
A new “Appendix 7: Body Surface
Area” was added.
The new appendix is consistent with the
updated “Rule of 9” used for BSA
measurement.
Throughout the
protocol.
Minor grammatical, formatting, or
spelling changes were made.
Minor errors were noted.


CNTO1959 (guselkumab)
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TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................................... 2
TABLE OF CONTENTS ............................................................................................................................... 4
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)........................................................................................................... 12
2. 
INTRODUCTION................................................................................................................................ 16
2.1. 
Study Rationale.............................................................................................................................. 19
2.2. 
Background.................................................................................................................................... 19
2.3. 
Benefit-Risk Assessment............................................................................................................... 22
2.3.1. 
Risks for Study Participation....................................................................................................... 22
2.3.2. 
Benefits for Study Participation .................................................................................................. 24
2.3.3. 
Benefit-Risk Assessment for Study Participation ....................................................................... 25
3. 
OBJECTIVES AND ENDPOINTS ..................................................................................................... 26
4. 
STUDY DESIGN ................................................................................................................................ 27
4.1. 
Overall Design................................................................................................................................ 27
4.2. 
Scientific Rationale for Study Design............................................................................................. 28
4.2.1. 
Study-Specific Ethical Design Considerations ........................................................................... 30
4.3. 
Justification for Dose...................................................................................................................... 30
4.4. 
End of Study Definition................................................................................................................... 30
5. 
STUDY POPULATION ...................................................................................................................... 31
5.1. 
Inclusion Criteria............................................................................................................................ 31
5.2. 
Exclusion Criteria........................................................................................................................... 35
5.3. 
Lifestyle Considerations................................................................................................................. 39
5.4. 
Screen Failures.............................................................................................................................. 40
6. 
STUDY INTERVENTION................................................................................................................... 41
6.1. 
Guselkumab Administration ........................................................................................................... 41
6.1.1. 
Combination Product .................................................................................................................. 41
6.2. 
Preparation/Handling/Storage/Accountability ................................................................................ 42
6.3. 
Measures to Minimize Bias: Randomization and Blinding............................................................. 42
6.4. 
Study Intervention Compliance...................................................................................................... 43
6.5. 
Concomitant Therapy..................................................................................................................... 43
6.5.1. 
Concomitant Medications for Treatment of Psoriasis................................................................. 44
6.5.1.1. 
Topical Therapy....................................................................................................................... 44
6.5.1.2. 
Phototherapy or Systemic Therapy for Psoriasis .................................................................... 44
6.5.2. 
Concomitant Medications for Conditions Other than Psoriasis .................................................. 44
6.5.3. 
Concomitant Medications of Special Interest ............................................................................. 44
6.6. 
Dose Modification........................................................................................................................... 46
6.7. 
Intervention After the End of the Study.......................................................................................... 46
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL............................................................................................... 46
7.1. 
Discontinuation of Guselkumab ..................................................................................................... 46
7.2. 
Participant Discontinuation/Withdrawal From the Study................................................................ 47
7.3. 
Lost to Follow-up............................................................................................................................ 49
8. 
STUDY ASSESSMENTS AND PROCEDURES ............................................................................... 49
8.1. 
Efficacy Assessments .................................................................................................................... 53


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8.1.1. 
Cardiovascular Evaluations ........................................................................................................ 53
8.1.2. 
Psoriasis Assessments............................................................................................................... 54
8.1.3. 
Patient-Reported Outcomes....................................................................................................... 55
8.1.4. 
Other Efficacy Evaluations.......................................................................................................... 56
8.1.4.1. 
Biomarker Analysis.................................................................................................................. 56
8.2. 
Safety Assessments....................................................................................................................... 57
8.2.1. 
Physical Examinations................................................................................................................ 57
8.2.2. 
Vital Signs................................................................................................................................... 57
8.2.3. 
Electrocardiograms..................................................................................................................... 57
8.2.4. 
Clinical Safety Laboratory Assessments .................................................................................... 58
8.2.5. 
Early Detection of Active Tuberculosis....................................................................................... 58
8.2.6. 
Pregnancy Testing...................................................................................................................... 59
8.3. 
Adverse Events and Serious Adverse Events ............................................................................... 59
8.3.1. 
Time Period and Frequency for Collecting Adverse Event and Serious Adverse Event
Information.................................................................................................................................. 59
8.3.2. 
Follow-up of Adverse Events and Serious Adverse Events ....................................................... 60
8.3.3. 
Regulatory Reporting Requirements for Serious Adverse Events ............................................. 60
8.3.4. 
Pregnancy................................................................................................................................... 60
8.3.5. 
Disease-Related Events and Disease-Related Outcomes not Qualifying as Adverse
Events or Serious Adverse Events............................................................................................. 61
8.3.6. 
Adverse Events of Special Interest............................................................................................. 61
8.4. 
Treatment of Overdose .................................................................................................................. 61
8.5. 
Pharmacokinetics........................................................................................................................... 61
8.6. 
Pharmacodynamics........................................................................................................................ 61
8.7. 
Biomarkers..................................................................................................................................... 61
8.8. 
Medical Resource Utilization and Health Economics .................................................................... 62
9. 
STATISTICAL CONSIDERATIONS.................................................................................................. 62
9.1. 
Statistical Hypotheses.................................................................................................................... 62
9.2. 
Sample Size Determination ........................................................................................................... 62
9.3. 
Populations for Analyses................................................................................................................ 63
9.4. 
Statistical Analyses ........................................................................................................................ 63
9.4.1. 
Primary Endpoint ........................................................................................................................ 63
9.4.2. 
Secondary Endpoints.................................................................................................................. 63
9.4.3. 
Exploratory Endpoints................................................................................................................. 63
9.4.4. 
Safety Analyses.......................................................................................................................... 63
9.4.5. 
Other Analyses ........................................................................................................................... 64
9.5. 
Interim Analysis.............................................................................................................................. 64
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ............................ 65
10.1. 
Appendix 1: Abbreviations ............................................................................................................. 65
10.2. 
Appendix 2: Clinical Laboratory Tests ........................................................................................... 67
10.3. 
Appendix 3: Hepatitis B Virus (HBV) Screening with HBV DNA.................................................... 69
10.4. 
Appendix 4: QuantiFERON®-TB GOLD TESTING ....................................................................... 70
10.5. 
Appendix 5: Investigator Global Assessment ................................................................................ 73
10.6. 
Appendix 6: Psoriasis Area and Severity Index............................................................................. 74
10.7. 
Appendix 7: Body Surface Area..................................................................................................... 75
10.8. 
Appendix 8: Dermatology Life Quality Index.................................................................................. 76
10.9. 
Appendix 9: Pittsburgh Sleep Quality Index................................................................................... 78
10.10. Appendix 10: Alcohol Consumption Screening AUDIT Questionnaire in Adults ........................... 84
10.11. Appendix 11: Hospital Anxiety and Depression Scale................................................................... 86
10.12. Appendix 12: Regulatory, Ethical, and Study Oversight Considerations....................................... 87
10.13. Appendix 13: Adverse Events: Definitions and Procedures for Recording, Evaluating,
Follow-up, and Reporting............................................................................................................... 98
10.14. Appendix 14: Contraceptive and Barrier Guidance and Collection of Pregnancy
Information ................................................................................................................................... 103
10.15. Appendix 15: Guidance on Study Conduct During a Pandemic.................................................. 106


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11. REFERENCES................................................................................................................................. 112
INVESTIGATOR AGREEMENT............................................................................................................... 115


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LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1: 
Concomitant Medication of Special Interest ............................................................................. 45
FIGURES
Figure 1: Schematic Overview of the Study............................................................................................. 11






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EFFICACY EVALUATIONS
The following key assessments will be carried out as detailed in the Schedule of Activities. Efficacy
assessments will be done locally at the sites. Results of the GLS and CFR assessments, along with other
cardiology data, will be reviewed by a cardiology core lab for blinded analysis of endpoints.
 
Carotid-femoral Pulse Wave Velocity
 
Global Longitudinal Strain for left ventricular function
 
Coronary Flow Reserve
SAFETY EVALUATIONS
The safety and tolerability of guselkumab will be monitored by collecting information on adverse events,
clinical laboratory tests, physical examinations, vital signs, and concomitant medication review through
Week 40.
STATISTICAL METHODS
The sample size calculation is based on the assumption that participants will show an average
improvement of 20% in CFR at Week 32. To detect a CFR mean change of 0.3 from baseline with 80%
power, and assuming a standard deviation of0.8 and a 5% dropout rate, 50 participants are expected to be
enrolled in the study. Sample size may be increased if the dropout rate is higher than expected, in
accordance with the sample size assumptions stated above.
INTERIM ANALYSIS
An interim analysis will be performed after a sufficient proportion ofthe participants (to be defined
during the study) have accrued Week 16 CFR measurements. The scope of the interim analysis will be
developed and documented in a statistical analysis plan. Other interim analyses may be planned based on
specific questions from the medical field. The data from these interim analyses will allow for assessment
of coverage and follow-up of participant types and treatment modalities to investigate specific research
questions.


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1.2. 
Schema
Figure 1: 
Schematic Overview of the Study










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2. 
INTRODUCTION
Psoriasis is a common chronic inflammatory disease that affects 2% 3% of the population and has
an impact on physical and emotional health-related quality-of-life that is comparable to major
illnesses such as cancer, heart disease and depression.50 It is also increasingly viewed as a systemic
inflammatory syndrome due to its association with serious comorbidities including:
 
cardiovascular disease (CVD); including risk factors such as obesity, diabetes, hypertension,
dyslipidemia,
 
inflammatory bowel disease (IBD),
 
mood disorders,
 
kidney disease and
 
malignancy.55,61
Psoriasis and Cardiovascular Comorbidities
Cardiovascular disease is of particular concern since it is a leading cause of death in people with
psoriasis, who have an increased risk over healthy individuals; the absolute and excess risk of
death is highest for cardiovascular disease (61.9 deaths/1000 and 3.5 deaths/1000 person years,
respectively).11  It is now considered likely that psoriasis confers an independent risk ofmyocardial
infarction (MI),23 which is relatively higher in young patients with severe psoriasis, whose risk of
cardiovascular death increases from 5.5% to 8.2% compared with a control population (relative
risk 57%).41
Research has revealed atherosclerosis to be a complex inflammatory and immune-mediated
longitudinal process, occurring on a continuum over decades. In its earlier stages, coronary
microvascular dysfunction, wherein the coronary microvasculature becomes increasingly less able
to control delivery of blood to the myocardium by adjusting blood flow to meet demand, is a
reversible event.39 It is also associated with increased vascular smooth muscle tone, arterial
stiffening, and thickening of vascular walls, which culminates in irreversible structural changes in
the large pericardial vessels that are associated with adverse clinical outcomes such as myocardial
ischaemia.17,20,53,57
The microvascular endothelium is capable of rapid and sensitive response to blood flow, physical
stress, and a vast range of mediators including hormones, metabolites and neurotransmitters.17,20,26
Classical vascular dysfunction and remodeling follows the disturbed blood flow model, which is
based on dynamic endothelial responses that attempt to normalize altered shear stress and preserve
constant coronary blood flow.26,57 Chronic abnormalities in blood flow, such as uncontrolled
hypertension, lead to adverse remodeling and thickening of medial walls and intima.17,26,58
Endothelial shear stress also causes expression of inflammatory mediators and cellular adhesion
molecules, which can amplify into a chronic inflammatory situation.58


CNTO1959 (guselkumab)
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More recent research has also shown that chronic systemic inflammation can also cause such
coronary microvascular dysfunction, as is seen in diseases with elevated levels of pro-
inflammatory cytokines such as psoriasis.20 Emerging evidence shows overlap of the
pathophysiological processes underlying psoriasis and atherogenesis. The interleukin (IL)-23/IL-
17 axis is a key factor in psoriasis development and persistence, with IL-23 driving a downstream
Th17 immune response involving an array of pro-inflammatory cytokines such as IL-17, IL-22
and Tumor necrosis factor (TNF).13,23,31,41,43,45 There is also evidence for involvement of IL-23 in
atherogenesis,37,40,55 and high plasma levels of IL-23 have been associated with increased mortality
during follow-up of patients with carotid plaques,11 leading to its proposal as a novel target for
treating atherosclerosis.40
As with shear stress-mediated remodeling, this inflammation-induced microvascular dysfunction
is associated with increased incidence of major adverse cardiovascular events (MACE).57 It is
therefore likely that better clinical outcomes will be seen if the early stages of endothelial
dysfunction and atheroma development can be limited, before irreversible structural changes
occur. Accordingly, it has been proposed that patients with psoriasis should be candidates for early
cardiovascular risk factor modification.47
The European Academy of Dermatology and Venereology (EADV) states that dermatologists are
in a position for early CVD detection or referral of those at risk due to unhealthy  lifestyle
behavior.46 In accord with the increased cardiovascular risk in these patients, European and North
American psoriasis guidelines state that adults with severe psoriasis of any type should undergo a
cardiovascular risk assessment at presentation and provide recommendations for continued
monitoring, management, and patient education.19,33,43,44,46,55 However, despite such
recommendations, cardiovascular comorbidities in patients with psoriasis remain consistently
underdiagnosed and undertreated.12,23,37 Furthermore, given that psoriasis confers an independent
risk for CVD, there is a need to evaluate the interactions between psoriasis therapies and markers
of inflammation and cardiovascular health.29
Measurement of vascular dysfunction is challenging, as no technique can visualize the human
coronary microvasculature in vivo. Therefore, indirect measurements must be used, many of which
are invasive.17
Coronary Flow Reserve and Measurement of Cardiovascular Dysfunction
The concept of coronary flow reserve (CFR) was first introduced by Gould et al in 1974. It
describes the ability of coronary blood flow to increase substantially when demanded by metabolic
requirements, which may be up to 4- or 5-times resting values during normal exercise and even
more by administration of pharmacological substances.19 CFR assessment is conducted via
transthoracic ultrasound of the coronary vasculature and provides an integrated measure of flow
through both the large epicardial arteries and the coronary microcirculation.17 This is a key factor
to its relevance in G-CARE, because effective diagnosis and management of atherosclerosis is
now thought to depend on interaction of both macro- and microvessels in the coronary
circulation.57 A normal CFR implies maximal dilation of resistance vessels, ie, an inability to
further increase myocardial blood flow.47 Causes of altered CFR include obstructive coronary


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atherosclerosis (primary cause) and other diseases involving the microcirculation, sometimes
occurring with angiographically normal arteries, in conditions such as psoriasis, diabetes and
systemic sclerosis.47
It is essential that during measurement of coronary blood flow, maximal flow is stimulated and
that both basal and maximal flow  measurements are accurately assessed.19 Pharmacological
stimulation of maximal flow may be done with agents that act directly on, or bypass, the
endothelium. Endothelium-dependent agents, such as acetylcholine, stimulate vasodilation in the
presence of a healthy endothelium. Endothelium-independent agents, such as dipyridamole, can
bypass the endothelium and directly stimulate relaxation of vascular smooth muscle cells,20 which
may be advantageous in the case of an unhealthy endothelium and can also counteract the
autoregulatory mechanisms controlling coronary vasodilation.39 The hyperemic action of
adenosine, a commonly used agent in CFR assessment that is often thought of as endothelium-
independent, may in fact partly depend on an intact healthy endothelium.20,39 Use of adenosine
may thus identify endothelial dysfunction and early microvascular wall pathology, as both are
contributors to reduced myocardial perfusion reserve. 20
Other studies have used alternative methods of measuring cardiovascular impact. The Vascular
Inflammation in Psoriasis (VIP) study series have investigated the effects of adalimumab,
secukinumab, apremilast, and ustekinumab on aortic inflammation, with mixed results in
completed studies to date: VIP and VIP-S showed a neutral effect of adalimumab and
secukinumab, respectively, on aortic inflammation at Week 12 using 18-FDG positron emission
tomography/computed tomography (PET/CT),29,43 whereas in the VIP-U study, ustekinumab
improved aortic inflammation versus placebo at 12 weeks.30
The Evaluation of Cardiovascular Risk Markers in Psoriasis Patients Treated with Secukinumab
(CARIMA) study used the flow-mediated dilation (FMD) technique to assess the impact of
secukinumab on endothelial dysfunction.60 FMD is another non-invasive method of assessing
microvascular dysfunction, via external vascular ultrasound assessment of the brachial artery
during reactive hyperaemia.56 Hence, FMD records peripheral arterial function and often cannot
be translated to coronary vessels due to different mechanisms of microvascular activation or
regulation between the two beds,49 which certainly exist in terms of cellular anatomy and
vasodilatory function.26 Despite numerous studies often correlating FMD with presence of
coronary artery disease, it has been demonstrated that pathologic FMD does not always identify
individuals with coronary microvascular dysfunction that has otherwise been assessed by CFR,
notably in a similar CVD phenotype to that proposed for G-CARE.25 Conversely, functional
remodeling of the coronary microvasculature is a key cause of CFR reduction in patients with
inflammatory disease and reflective of pathologies such as impaired vasodilation, enhanced
vasoconstriction and structural remodeling, as well as MACE risk.20,57 Thus, CFR is capable of
detecting coronary microvascular dysfunction in the absence of detectable obstructive
atherosclerosis, which may be missed by FMD.20,25,57 Indeed, these patients are now proposed to
present a prevalent phenotype of CVD with unique prognostic and therapeutic implications.57


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Therefore, CFR has been chosen over other methods as a primary outcome measure in G-CARE,
because it detects the sensitive early changes in the cardiac microvasculature in patients with
chronic inflammatory diseases, before onset of irreversible structural changes.
For the most comprehensive nonclinical and clinical information regarding guselkumab, refer to
the latest version of the Investigator’s Brochure (IB) for guselkumab.
The term “study intervention” throughout the protocol, refers to guselkumab  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.
The term “participant” throughout the protocol refers to the common term “subject”, describing
patients with psoriasis participating in this study.
2.1. 
Study Rationale
Guselkumab is an  IL-23 inhibitor which  has been approved for the treatment of adults with
moderate-to-severe plaque psoriasis and active psoriatic arthritis. Guselkumab has also
demonstrated superiority  to inhibitors of TNF-α, IL-17, and IL-12/23 in terms of long-term
efficacy and safety.13,33,41,50 However, there may be potential benefits for guselkumab beyond
those related to skin clearance. The promising results of IL-12/23 inhibition in the Vascular
Inflammation in Psoriasis-Ustekinumab (VIP-U) study,28 combined with the role of IL-23 in the
early stages of atherogenesis,24 suggest a potential benefit of IL-23 inhibition on vascular
inflammation. However, additional research is necessary to further determine the effects of IL-23
inhibition on surrogate markers ofcardiovascular outcomes and therefore improve understanding
of a major serious comorbidity in patients with plaque psoriasis.
This study aims to investigate the effect of guselkumab on surrogate markers of cardiovascular
risk, primarily CFR, in participants with moderate-to-severe plaque psoriasis.
2.2. 
Background
Nonclinical Studies
Refer to the IB19 for guselkumab for information about nonclinical studies.
Clinical Studies
Psoriasis
In guselkumab Phase 3 studies in moderate-to-severe plaque psoriasis, the key efficacy findings
are summarized below:
 
In 2 large placebo- and active-controlled studies (CNTO1959PSO3001 [VOYAGE-1] and
CNTO1959PSO3002 [VOYAGE-2]),


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The proportion of participants who demonstrated improvements in psoriasis as assessed
by all 4 Psoriasis Area and Severity Index (PASI) (PASI 100, PASI 90, PASI 75, and
PASI 50) and investigator global assessment (IGA) responses was higher among those
receiving guselkumab 100 mg subcutaneously (SC) at Weeks 0, 4, and q8w compared
with the placebo and adalimumab groups. Responses were observed up to Week 252.
 
In participants with baseline physician’s global assessment of psoriasis on the hands
and/or feet (hf-PGA) scores ≥2, guselkumab treatment led to a significantly higher
(p<0.001) proportion of participants with hf-PGA scores of clear (0) or almost clear (1)
at Week 16 and Week 48, compared with the adalimumab group.
 
Most participants experienced clinically meaningful improvements in psoriasis
symptoms (erythema, induration, and scaling) and involved body regions (head, trunk,
upper extremities, and lower extremities) as measured by PASI 75 response. Following
sustained treatment, the proportions of participants achieving PASI 90 response within 5
months after initiation, and PASI 100 response within 7 months were maintained through
5 years.
 
In a plaque psoriasis study (CNTO1959PSO3003: NAVIGATE), participants with an
inadequate response to ustekinumab benefitted from switching to guselkumab, and
approximately twice as many participants receiving guselkumab achieved clinical responses
compared with participants receivingustekinumab, with significant improvement in PASI and
IGA scores as early as 4 weeks after switching.
 
In a plaque psoriasis study in Japan (CNTO1959PSO3004), in general, clinical responses
obtained at Week 16 in the guselkumab 50 mg and 100 mg groups either continued to improve
or were maintained after Week 16 through Week 52 for all endpoints. In addition, the body
surface area (BSA) involvement which was assessed over time from baseline through Week
52, demonstrated improvement with guselkumab treatment (50 and 100 mg) in all treatment
groups (including placebo-crossover participants).
 
Efficacy of guselkumab in the treatment of generalized pustular psoriasis (GPP) and
erythrodermic psoriasis (EP) has been demonstrated (CNTO1959PSO3005). A majority of
participants with GPP (77.8%) and EP (90.9%) achieved treatment success with guselkumab
at Week 16, with maintenance of effect of guselkumab through Week 52.
 
In participants with moderate-to-severe plaque psoriasis (CNTO1959PSO3006: ORION),
guselkumab treatment using a novel self-injection device gave rise to significantly higher
proportions of participants achieving an IGA score of 0 or 1 (80.6% versus 0.0%, p<0.001)
and a PASI 90 response (75.8% versus 0.0%, p<0.001), compared with placebo. In addition,
significantly higher proportions of participants receiving guselkumab achieved an IGA score
of 0 (56.5% vs 0.0%, p<0.001) and a PASI 100 response (50.0% vs 0.0%, p<0.001) at
Week 16, compared with placebo.
 
In participants with moderate-to-severe plaque psoriasis (CNTO1959PSO3008) who had not
received any prior systemic therapy, the study  comparing guselkumab with the
active-comparator (fumaric acid esters) met its primary and major secondary endpoints, with
significantly higher proportions of participants treated with guselkumab achieving PASI 90
(81.7% vs 13.6%, p<0.0001) and PASI 75 ( 90.0% vs 27.1%, p<0.0001) response at Week 24
compared with the active-comparator.


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Psoriatic Arthritis
There are 3 Phase 3 studies evaluating the efficacy of guselkumab in participants with active
psoriatic 
arthritis 
(PsA) who 
have 
inadequate 
response 
to 
standard 
therapies
(CNTO1959PSA3001- DISCOVER-1), in biologic naïve population with inadequate response to
non-biologic therapies (CNTO1959PSA3002-DISCOVER-2), and in participants who have had
an inadequate response to anti-tumor necrosis factor alpha (anti-TNFα) (CNTO1959PSA3003-
COSMOS). In the DISCOVER-1 study, the primary endpoint was met: American College of
Rheumatology  (ACR) 20 at Week 24 was achieved by significantly greater proportions of
participants in the guselkumab every 4 weeks group (76 [59%] of 128 [95% CI 50 68]) and every
8 weeks group (66 [52%] of 127 [43 61]) than in the placebo group, with significant percentage
differences versus placebo for the every 4 weeks group and the every 8 weeks group (both
p<0.0001). In the DISCOVER-2 study, significantly greater proportions of participants in the
guselkumab every 4 weeks group (156 [64%] of 245 [95% CI 57 70]) and every 8 weeks group
(159 [64%] of 248 [58 70]) than in the placebo group achieved an ACR 20 response at Week 24;
both p<0.0001). In the COSMOS (CNTO1959PSA3003) study, treatment with guselkumab 100
mg at Week 0 and Week 4, and then every 8 weeks in this study demonstrated the superiority of
guselkumab over placebo with respect to the primary endpoint of ACR 20 response. At Week 24,
a significantly higher proportion of participants in the guselkumab group achieved ACR 20
response compared with the placebo group (44.4% [n 84] versus 19.8% [n 19] p<0.001).
Superiority of guselkumab was also established in terms of all 4 key secondary endpoints at Week
24, based on a predefined hierarchical testing procedure: HAQ-DI, ACR 50 response, SF36 PCS,
and PASI 100.
Palmoplantar Pustulosis
In a Phase 3 study (CNTO1959PPP3001) evaluating the efficacy of guselkumab for the treatment
of palmoplantar pustulosis, the study achieved the primary endpoint, with both guselkumab dose
groups showing superior efficacy to the placebo group at Week 16 as measured by change from
baseline in the Palmoplantar Psoriatic Area and Severity Index (PPPASI) total score (p 0.017 for
guselkumab 200 mg versus placebo and p<0.001 for guselkumab 100 mg versus placebo). The
proportion of PPPASI-50 responders in the guselkumab 100 mg and the guselkumab 200 mg
groups continued to increase through Week 52 and reached a maximum of 83.3% and 84.6%.
Safety
The safety of guselkumab was analyzed in participants from placebo- and active-controlled
Phase 3 studies for up to 156 weeks of treatment (CNTO1959PSO3001, CNTO1959PSO3002,
CNTO1959PSO3003, CNTO1959PSO3005, CNTO1959PSO3006, CNTO1959PSO3008 and
CNTO1959PPP3001).
 
Serious adverse events (SAEs) were relatively infrequent among guselkumab-treated
participants, with most SAEs consisting of infection-related events; rates of SAEs did not
increase with longer duration of guselkumab exposure.


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 
Serious infections with guselkumab were infrequent, with most being single events without a
clear pattern. No events of tuberculosis (TB) or opportunistic infection were reported with
guselkumab treatment.
 
The incidences of malignancies, MACE, and suicidal ideation and behavior through 3 years
of treatment with guselkumab were low and did not increase with increased duration of
exposure. These results demonstrate that with additional guselkumab exposure through
approximately 3 years, the rates of infections, serious infections, malignancies, and MACE
remained stable, suggesting that there is no increased risk of these events with prolonged
guselkumab exposure.
 
The analyses of pooled data support the conclusion that guselkumab is well tolerated through
3 years of treatment, and the safety profile remains consistent when compared with Week 48
data, at the approved dose regimen of 100 mg, administered SC at Weeks 0, 4, and then q8w,
in adult participants with moderate-to-severe plaque psoriasis.
A review of the cumulative safety data and risk-benefit analysis did not identify any change to the
risk-benefit profile of guselkumab.
2.3. 
Benefit-Risk Assessment
More detailed information about the known and expected benefits and risks of guselkumab may
be found in the IB.
2.3.1. 
Risks for Study Participation
Potential Risks of 
Clinical Significance 
Summary of Data/
Rationale for Risk  
Mitigation Strategy
Potential Risks Due to Guselkumab
Serious infections and 
reactivation of latent 
infections 
Available animal and 
human data suggest that 
blockade of IL-23 may be 
associated with an increased 
infection risk. 
 Participants with a history of, or ongoing,
chronic or recurrent infectious disease,
including human immunodeficiency virus
(HIV), Hepatitis B or C virus (HBV, HCV),
will be excluded from the study. Similarly,
participants with evidence of active or
untreated latent tuberculosis (TB) will be
excluded from the study (Section 5.2).
 Participants who have received a live viral or
bacterial vaccination within 12 weeks of Week
0 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 guselkumab (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
(Section 8.2.5).
 Discontinuation of a participant’s guselkumab
must be strongly considered if the participant
develops a serious infection, including but not


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limited to sepsis or pneumonia. In addition, any
serious infection should be discussed with the
medical monitor or designee, and guselkumab
should be withheld until the clinical assessment
is complete (Sections 5.2, 7.1).
Hypersensitivity reactions,
including serious
hypersensitivity reactions.
Serious hypersensitivity
reactions including
anaphylaxis have been
reported in post-marketing
experience with guselkumab
in psoriasis patients.
 Participants with known allergy,
hypersensitivity, or intolerance to guselkumab
or its excipients will be excluded from the
study.
 Sites are instructed that before any
administration of guselkumab, appropriately
trained personnel and medications (eg,
injectable epinephrine) must be available to
treat hypersensitivity reactions, including
anaphylaxis. In addition, all participants must
be observed carefully for signs and symptoms
of a hypersensitivity reaction (eg, urticaria,
pruritis, angioedema, wheezing, dyspnea, or
hypotension).
 Any participant who develops a serious
hypersensitivity reaction such as anaphylaxis
must discontinue guselkumab (Section 7.1).
Malignancy  
The preponderance of
preclinical data suggests
that blockade of endogenous
IL-23 would not be
detrimental and may in fact
be beneficial in tumor
immunosurveillance and
host protection; however, a
risk of malignancy cannot
be excluded.
 Those participants who currently have a
malignancy or have a history of malignancy
within 5 years prior to screening (with
exceptions noted in Section 5.2) will be
excluded from the study.
 During the conduct of the study, participants
will undergo regular clinical monitoring
including routine safety labs to assess for any
changes in health status that may indicate a
possible malignancy.
 Participants who develop a malignancy during
the study (with the exception of no more than 2
localized basal cell skin cancers that are treated
with no evidence of recurrence or residual
disease) will be discontinued from guselkumab
(Section 7.1).
Liver injury  
A 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, 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.
 Participants with marked liver enzyme
elevations or symptoms or signs of liver
dysfunction (eg, jaundice), should undergo a
thorough investigation for possible causes of
liver injury (Section 5.1).


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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, participants who
have previously or are currently receiving allergy
immunotherapy, IL-12/23, IL-17, or IL-23
inhibitors, B or T-cell modulators or systemic
immunosuppressants will be excluded from the
study (Section 5.2).
Potential Risks due to Study Procedure (Adenosine Injection)
Potential Risks of 
Clinical Significance 
Indications for Stopping
Adenosine Infusion
and/or Administering
Aminophylline 
Mitigation Strategy
 Vascular related: Flushing 
 Thoracic related: dyspnea 
(shortness of breath), chest 
discomfort 
 Nervous system 
related: Headache, dizziness, 
light- 
headedness, paresthesia 
 Gastrointestinal 
related: Nausea 
 Cardiac related: bradycardia, 
sinus pause, skipped beats, 
atrial extrasystoles, Atrio- 
Ventricular block, 
ventricular excitability 
disorders such as ventricular 
extrasystoles, non-sustained 
ventricular tachycardia 
Stopping Adenosine and/or 
further medical intervention 
is at the discretion of the 
cardiology investigator and 
should be considered in case 
of: 
 Severe hypotension: 
Systolic pressure <80 mm 
Hg or 20 mmHg fall which 
persists 
 ST depression: >3 mm 
beyond baseline ECG 
without angina or >2 mm 
with angina 
 Persistent 2nd or 3rd degree 
heart block  
 Severe chest discomfort,
dizziness, dyspnea,
headache, nausea, syncope
or dysrhythmia
The half-life of adenosine is less than 10
seconds. Thus, the adverse effects are generally
rapidly self-limiting. Treatment of any prolonged
adverse effect should be individualized and
directed toward the specific effect.
 Stop infusion –most effects resolve within 30-
60 seconds post infusion
 If symptoms persist, administer aminophylline,
125 mg, IV by slow infusion (1 minute)
on cardiology investigator’s direction. Dosage
may be repeated in five minutes if there is no
response to the first dose.
Note:Adverse events (AEs) should be reported if
medical intervention beyond stopping adenosine
infusion is necessary. Please refer Appendix 13
for further information.
2.3.2. 
Benefits for Study Participation
Guselkumab was first approved for the treatment of moderate-to-severe plaque psoriasis by the
United States Food and Drug Administration on 13 July 2017 and has since been approved in
several other countries worldwide (including the EU, Canada, and Japan). Since 14 July 2020,
guselkumab has been approved for the treatment of active psoriatic arthritis
It has been shown that serum levels of IL-12 and IL-23 are augmented in patients with CVD.35
IL-12 and IL-23 are present in atherosclerotic plaques, thereby affecting the pro-inflammatory
status in these patients.24 Taken together, this evidence suggest that targeting IL-12/23 could
represent a valid therapeutic option for psoriatic disease, with benefits on cutaneous involvement
and on cardiovascular comorbidities.


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2.3.3. 
Benefit-Risk Assessment for Study Participation
Considering the measures taken to minimize risk to participants ofthis study, the potential risks
identified in association with guselkumab  are justified by the anticipated benefits that may be
afforded to participants with moderate-to-severe plaque psoriasis with intermediate cardiovascular
risk.
Guselkumab has undergone extensive nonclinical and clinical development as summarized in the
latest version of the IB. The collective efficacy and safety results of the Phase 1, Phase 2, and
Phase 3 clinical studies in healthy volunteers and participants with plaque psoriasis and active
psoriatic arthritis established a favorable benefit-risk profile for guselkumab in the treatment of
plaque psoriasis and active psoriatic arthritis and regulatory approval for these indications.
Potential risks of guselkumab, including those of serious infection and malignancy, 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 summary, the collective preclinical and clinical evidence for the anti-IL-23 mechanism of
action, and the benefit-risk profile of guselkumab established to date in psoriasis and other immune
mediated diseases provide a strong scientific and clinical rationale for investigating the efficacy of
guselkumab in reducing vascular inflammation.




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Refer to Section 8, Study Assessments and Procedures for evaluations related to the endpoints.
HYPOTHESIS
The primary hypothesis of this study is that guselkumab (administered as 100 mg at Weeks 0, 4,
12, 20 and 28) is effective in reducing surrogate markers of cardiovascular risk as assessed by the
change from baseline in CFR at Week 32.
4. 
STUDY DESIGN
4.1. 
Overall Design
This is an interventional, single-arm, open-label, oligocentric study  to evaluate the effect of
guselkumab on cardiovascular risk surrogate markers in adult men and women diagnosed with
moderate-to-severe plaque psoriasis (with or without PsA) for at least 6 months prior to study
entry. Participants will be assessed for eligibility at 2 screening visits; at Screening Visit S1,
dermatology, medical history, and laboratory parameters will be assessed. Participants fulfilling
eligibility criteria at Screening Visit S1 will be referred to the cardiology department and will
undergo cardiologic assessments (cfPWV, GLS  and CFR [via transthoracic doppler
echocardiography]) at Screening Visit S2, and again at Week 0. Only participants with CFR ≥2
and ≤3.5 at both these time-points will be enrolled in the study. The CFR measurement at Week 0
will be considered as the baseline value.
Approximately 50 participants are planned to be enrolled, and will receive guselkumab (100 mg)
SC at Weeks 0, 4, 12, 20 and 28. Approximately 20 of the enrolled participants should be active
nicotine users. The number of nicotine users for enrollment in the study is capped at 20. Once this
number is reached, only non-users may be enrolled to fulfil the sample size. Enrollment of nicotine
users versus non-users will be stratified on a site-by-site basis. All participants will be instructed
to abstain from caffeinated and nicotine-containing products at least 12 hours prior to any
scheduled cardiology assessments.
The first dose of the guselkumab  will always be administered at the site and by a health care
professional (HCP). Subsequent doses can be self-administered under the supervision of site-staff
after the participant has been adequately trained in the procedure.
Key efficacy evaluations will be carried out at the time-points detailed in  the Schedule of
Activities, and will include cardiology assessments (cfPWV, GLS and CFR), and skin assessments
(IGA, PASI and BSA). Efficacy assessments will be done locally at the sites. The CFR assessments
for eligibility will be immediately evaluated on-site at Screening Visit S2 and Week 0. All the CFR
and GLS assessments in the study will be reviewed by a cardiology core lab for blinded analysis
of endpoints. Quality-of-life and lifestyle changes during the study will be measured using the
Dermatology Life Quality Index (DLQI), Pittsburg Sleep Quality Index (PSQI) and Alcohol Use
Disorders Identification Test (AUDIT) questionnaires, and mood and anxiety will be assessed
using the Hospital Anxiety and Depression Scale (HADS, if available).


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Safety evaluations will include monitoring of vital signs, 12-lead electrocardiogram (ECG) at
Screening Visit S1, monitoring of tuberculosis status, pregnancy testing at each visit, and recording
of AEs throughout the study. Biomarker assessments will include the evaluation of relevant
markers in serum, plasma, and urine for all participants.
For participants completing the study, the total duration will be 40 weeks, including 28 weeks of
treatment and a Final Efficacy Visit 4 weeks later (Week 32). The Final Safety Visit will occur
12 weeks after the last dose of the guselkumab  (Week 40). Participants who discontinue
guselkumab prior to Week 28 will be considered to have completed the study if they complete all
the assessments of the Final Efficacy Visit at the time of discontinuation (or soon after), and the
Final Safety Visit scheduled 12 weeks after the last guselkumab dose. For participants who opt to
receive commercially available guselkumab from their healthcare provider after Week 28, the visit
at which the first dose of guselkumab is received outside the study (Week 36) will be considered
as the Final Safety Visit.
An interim analysis will be conducted after a sufficient proportion ofthe participants (to be defined
during the study) have accrued Week 16 CFR measurements. The scope of the interim analysis
will be developed and documented in a statistical analysis plan.
The GLS and CFR assessments throughout the study will be conducted per the echocardiology
protocol provided by the cardiology core lab. The results from GLS, CFR and other cardiology
assessments will be securely transmitted to the cardiology core lab for blinded independent review
of endpoints, per guidelines laid down in the process document of the core lab. Further details
regarding materials to be forwarded to the core lab can be found in the core lab Standard Operating
Procedures and process documents.
A diagram of the study design is provided in Section 1.2, Schema.
4.2. 
Scientific Rationale for Study Design
Eligibility Criteria for Inclusion in the Study
The eligibility criteria for inclusion in the study are aligned with those in pivotal clinical trials
evaluating the efficacy of guselkumab for the treatment of moderate-to-severe plaque psoriasis.
Participants with renal disease and coagulopathies are excluded as there is strong evidence that
they have independent effects on epithelial dysfunction and thereby the primary endpoint. In
addition, participants with a history or currently suffering from certain cardiovascular conditions
are excluded to reduce the risk of cardiovascular AEs during the study (please refer Section 5.2,
Exclusion Criteria).
Rationale for Study Duration
Previous studies investigating the effects of adalimumab and phototherapy,43 and secukinumab
(VIP-S),28 on psoriasis and surrogate cardiovascular risk markers by evaluating the primary
endpoint after 12 weeks of intervention, failed to demonstrate a significant change in vascular
inflammation. A study using flow mediated dilatation of the brachial artery also failed to
demonstrate a significant improvement at 12 weeks versus placebo (primary endpoint) but clearly


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showed a dose and time dependent effect with a statistically significant effect at 52 weeks of
secukinumab treatment.60 Ustekinumab, an IL-12/23 blocker has demonstrated a significant
improvement of vascular inflammation after 12 weeks.28 In all studies the effect on skin
improvement was in line with previous results in clinical trials.
These observations hint towards the assumption that cardiovascular inflammation of peripheral
arteries assessed by surrogate markers improve slower than the skin parameters (eg, PASI, IGA).
Therefore, the rationale for G-CARE is to assess the primary endpoint at Week 32 and assess a
secondary endpoint at Week 16 for a detailed investigation of the timeline of effects of guselkumab
on the coronary system. Further, these results will be correlated with  the timeline of skin
improvement. These results will help to better understand the effect of long-term treatment and the
effects on cardiovascular endpoints like myocardial infarction, stroke, and cardiovascular death.
Biomarker Collection
Biomarker samples will be collected to evaluate the mechanism of action of guselkumab and help
to explain interindividual variability in clinical outcomes or may help to identify population
subgroups that respond differently to an intervention. Markers of cardiovascular risk and psoriasis
will be analyzed in the study, along with the effect of guselkumab treatment on these markers over
40 weeks of treatment.
Guselkumab has been shown to selectively inhibit IL-23 in psoriasis and produce substantial
clinical responses.32  The association between IL-23 and disease progression in patients with
carotid atherosclerosis has been previously shown, with a potential involvement ofIL-17-related
mechanisms.11 Interleukin-6 and high-sensitivity C-reactive protein  (hsCRP) levels will be
analyzed in the study, as they are related to the prevention ofCV events and death, independent of
lowering serum lipids.51,52
Olink high-throughput proteomic assays will be utilized to better define serum inflammatory and
cardiovascular risk proteins in psoriasis.15 Additional proteomic research assays (eg, Somascan)
may also be applied. Psoriasis pathogenesis via SAA production and its role in maintaining a
cutaneous inflammatory environment will be investigated.18
Malondialdehyde in combination with oxidative lipid damage [8-Isoprostane (GC-MS)],
concentration of antioxidants (Vitamin C and Vitamin E) and nucleotide damage markers
(8-Oxo-7,8-dihydro2’-desoxyguanosine) will provide a clearer picture of oxidative stress at
baseline and during treatment,22,34 Vitamin D, which has been shown to play a role in metabolic
syndrome and improve psoriatic skin lesions,27 will be investigated.
Cytokines (TNF-α, IL-6, IL-17A and F, IL-22, IL-23) have been shown to be involved in  the
pathogenesis of psoriasis, but little is known about their potential role in microvascular
inflammation. Adipocytokines (leptin and adiponectin) are increasingly recognized as important
regulators of inflammation, and a dysregulation of their levels and/or functions has been shown in
psoriasis.21


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HbA1c levels will be analyzed because inflammation-induced insulin resistance and endothelial
dysfunction provide a pathogenetic link between psoriasis and atherosclerosis.14
N-terminal pro b-type natriuretic peptide (NT-proBNP) is a biomarker of CV disease in both
normo- and hyperlipidemic groups, and is elevated in patients with psoriasis. NT-proBNP levels
in the current study population will be useful to investigate the risk of cardiovascular disease
associated with psoriasis.48,54
Biomarker samples may be used to help address emerging issues and to enable the development
of safer, more effective, and ultimately individualized therapies.
4.2.1. 
Study-Specific Ethical Design Considerations
Potential participants will be fully informed of the risks and requirements of the study and, during
the study, participants will be given any new information that may affect their decision to continue
participation. They will be told that their consent to participate in the study is voluntary and may
be withdrawn at any time with no reason given and without penalty or loss of benefits to which
they would otherwise be entitled. Only participants who are fully able to understand the risks,
benefits, and potential AEs of the study, and provide their consent voluntarily will be enrolled.
The total blood volume to be collected (approximately 185 mL) is considered to be an acceptable
amount of blood over this time period for the population in this study.
4.3. 
Justification for Dose
Participants will receive guselkumab at Weeks 0, 4, 12, 20 and 28. This dosing regimen is approved
for use in patients with moderate-to-severe plaque psoriasis based on the data from global Phase 3
studies (CNTO1959PSO3001 and CNTO1959PSO3002).
4.4. 
End of Study Definition
End of Study Definition
The end of study is considered as the last visit for the last participant in the study at Week 40. 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 study if he or she has completed
assessments at Week 40 of the study.
Participants who prematurely discontinue guselkumab  for any reason before Week 28 will be
considered to have completed the studyonce all assessments scheduled for the Final Efficacy Visit
are performed at the time of discontinuation, or as soon as possible. For these participants, the last
study visit will be the Final Safety Visit 12 weeks after last guselkumab administration.


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5. 
STUDY POPULATION
Eligibility of the participants will be assessed at 2 screening visits:
 
At Screening Visit S1, participants will be assessed by the dermatology investigator based on
dermatology, medical history, and laboratory parameters.
 
Screening Visit S2 will occur a maximum of 2 weeks after Screening Visit S1, where
eligibility based on the CFR performed by the cardiology investigator will be assessed.
 
A minimum of 2 weeks, and a maximum of 4 weeks after Screening Visit S2, the Week 0 visit
will occur, and the cardiology assessments will be repeated by the cardiology investigator.
Participants fulfilling all the eligibility criteria at Screening Visit S1, Screening Visit S2 and
Week 0 will be enrolled, and will receive the first dose of guselkumab.
Refer to Section  5.4, Screen Failures for conditions under which the repeat of any screening
procedures are allowed. Please refer to Schedule of Activities for details on the assessments at
each study time-point.
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.
For a discussion of the statistical considerations of participant selection, refer to Section 9.2,
Sample Size Determination.
5.1. 
Inclusion Criteria
Inclusion criteria will be assessed by the dermatologist, unless otherwise indicated below. Each
potential participant must satisfy all the following criteria to be enrolled in the study:
Participant population-related inclusion criteria
The participant
1. 
Is male or female (according to their reproductive organs and functions assigned by
chromosomal complement), 18 years of age (or the legal age of consent in the jurisdiction
in which the study is taking place) and above.
2. 
Has a diagnosis of moderate-to-severe plaque psoriasis (with or without PsA) for at least
6 months prior to the first dose of guselkumab at Week 0. Moderate-to-severe plaque
psoriasis is defined as PASI ≥12, IGA ≥3 and involved BSA ≥10% at Screening Visit S1.
Participants with a predominantly non-plaque form of psoriasis (eg, erythrodermic,
guttate, or pustular) will not be eligible for inclusion in the study.
3. 
Has intermediate cardiovascular risk defined by CFR ≥2 to ≤3.5 (Criterion to be assessed
by cardiologist at Screening Visit S2 and Week 0).


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4. 
Is a candidate for systemic treatment for psoriasis (either naïve or history of previous
treatment).
5. 
Does not have any abnormalities in  physical examination, medical history, clinical
laboratory tests, vital signs, and 12-lead ECG  performed at screening that are not
consistent with the underlying illness in the study population. This determination must be
recorded in the participant’s source documents and initialed by the investigator. The
12-lead ECG must be assessed by the dermatologist at Screening Visit S1.
6. 
Must sign an informed consent form (ICF) indicating that he or she understands the
purpose of, and procedures required for, the study and is willing to participate in the study.
Reproduction-related inclusion criteria
7. 
A woman of childbearing potential must have a negative highly sensitive serum (-human
chorionic gonadotropin [-hCG]) at Screening Visit S1.
8. 
A woman must be
a. not of childbearing potential
b. of childbearing potential and practicing a highly effective method of
contraception (failure rate of <1% per year when used consistently and correctly)
and must agree to remain on a highly effective method while receiving
guselkumab and until 12 weeks after the last dose the end of relevant systemic
exposure. Examples of highly effective methods of contraception are described
in  Appendix 14, Contraceptive and Barrier Guidance and Collection of
Pregnancy Information.
9. 
A woman using oral contraceptives must use an additional contraceptive method (as
detailed in Appendix 14, Contraceptive and Barrier Guidance and Collection of
Pregnancy Information).
10. 
A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted
reproduction during the study and for a period of 12 weeks after receiving the last
administration of guselkumab.
11. 
A male participant must wear a condom when engaging in any activity that allows for
passage of ejaculate to another person. Male participants should also be advised of the
benefit for a female partner to use a highly effective method of contraception as condom
may break or leak.
12. 
Amale participant must agree not to donate sperm for the purpose of reproduction during
the study and for a minimum 12 weeks after receiving the last dose of guselkumab.


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Infectious disease-related inclusion criteria
The participant
13. 
Is considered eligible according to the following TB screening criteria:
a. Has no history of latent or active TB before screening. An exception is made for
participants who have a history of latent TB and are currently receiving treatment
for latent TB, will initiate treatment for latent TB before the first administration
of guselkumab, or have documentation of having completed appropriate
treatment for latent TB within 3 years before the first administration of study
agent. It is the responsibility of the investigator to verify the adequacy of
previous anti-tuberculosis treatment and provide appropriate documentation.
b. Has no signs or symptoms suggestive of active TB upon medical history and/or
physical examination.
c. Has had no recent close contact with a person with active TB or, if there has
been such contact, will be referred to a physician specializing in TB to undergo
additional evaluation and, if warranted, receive appropriate treatment for latent
TB before the first administration of study agent.
Within 2 months before the first administration of guselkumab, has a negative
QuantiFERON-TB  Gold test result, or has a newly identified positive
QuantiFERON-TB Gold test result in which active TB has been ruled out and
for which appropriate treatment for latent TB has been initiated before the first
administration of guselkumab. A participant whose first QuantiFERON-TB
Gold test result is indeterminate should have the test repeated. In the event that
the second QuantiFERON-TB Gold test result is also indeterminate, the
participant may be enrolled without treatment for latent TB, if active TB is ruled
out, his/her chest radiograph shows no abnormality suggestive of TB (active or
old, inactive TB), and the participant has no additional risk factors for TB as
determined by the investigator. 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.
The QuantiFERON-TB  Gold test is 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.
14. 
Has a chest radiograph (posterior-anterior view), taken within 3 months before the first
administration of study agent and read by a qualified radiologist, with no evidence of
current, active TB or old, inactive TB.
15. 
Agrees not to receive a live virus or live bacterial vaccination during the study, or within
12 weeks after the last administration of guselkumab.


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16. 
Agree not to receive a BCG vaccination during the study, and within 12 months after the
last administration of guselkumab.
Clinical laboratory-related inclusion criteria
The participant
17. 
Has screening laboratory test results within the following parameters, if one or more of
the laboratory parameters is out of range, a single re-test of laboratory values is permitted:
 Hemoglobin  
≥10 g/dL  
(SI: ≥100 g/L)
 White blood cells 
≥3.5 x 103/µL 
(SI: ≥3.5 GI/L)
 Neutrophils 
≥1.5 x 103/µL 
(SI: ≥1.5 GI/L)
 Platelets 
≥100 x 103/µL 
(SI: ≥100 GI/L)
 Serum creatinine 
≤1.5 mg/dL 
(SI: ≤135 μmol/L)
Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline
phosphatase levels must be ≤2 × upper limit of normal (ULN) for the laboratory
conducting the test.
Other inclusion criteria
The participant must
18. 
Agree to reduce risk of sun burn, and avoid use of tanning booths or other ultraviolet
(UV) light sources during study.
19. 
Be willing to refrain from the use of complementary therapies for plaque psoriasis
including ayurvedic medicine, traditional Taiwanese, Korean, or Chinese medications
and acupuncture within 2 weeks before the first guselkumab administration and through
Week 40.
20. 
Be willing to refrain from using or consuming any caffeinated and nicotine-containing
products including but not limited to smoking, vaping, chewing tobacco, nicotine gum
and patches 12 hours before the cardiology assessments.
21. 
Be willing and able to adhere to the Schedule of Activities, comply with protocol
requirements, and the prohibitions and restrictions specified in this protocol.
22. 
It is recommended that participants are up to date on age-appropriate vaccinations prior
to screening as per routine local medical guidelines. For study participants who received
locally approved COVID-19 vaccines recently prior to study entry, follow applicable
local labelling, guidelines, and standards of care for participants receiving
immune-targeted therapy when determining an appropriate interval between vaccination
and study enrolment (please refer Section 6.5, Concomitant Therapy).


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5.2. 
Exclusion Criteria
Any potential participant who meets any of the following criteria will be excluded from
participating in the study:
Participant population-related exclusion criteria
1. 
Changed per Amendment 2.
1.1 
Has low-density lipoprotein (LDL) >190 mg/dL.
2. 
Has uncontrolled hypertension that needs immediate medication  (criterion to be
assessed by the dermatologist at Screening Visit S1 and by the cardiologist at Screening
Phase 2).
3. 
Has any clinically significant evidence of cardiac functional or valvular abnormalities,
other than intermediate cardiovascular risk defined by CFR ≥2 and ≤3.5, including but
not limited to: coronary stenosis, history of any MI or transient ischemic attacks, stroke,
cerebrovascular disease, peripheral atherosclerosis, congestive heart failure, chronic
pulmonary disease, fast atrial fibrillation, supraventricular arrhythmia, valvular
abnormalities, ventricular wall movement abnormalities observed during the CFR
assessment (Criterion to be assessed by the dermatologist at Screening Visit S1, and to
be confirmed by the cardiologist at Screening Visit S2).
4. 
Has any contraindications to adenosine infusion, including but not limited to asthma
with ongoing wheezing, hypersensitivity to adenosine, known or suspected
bronchoconstrictive or bronchospastic lung disease (history of acute respiratory distress
syndrome, emphysema), greater than first degree heart block without a pacemaker or
sick sinus syndrome, systolic blood pressure <90 mmHg and severe sinus bradycardia
(heart rate <40 bpm), or other contraindications listed in the SmPC  (Criterion to be
assessed by the dermatologist at Screening Visit S1 and confirmed by the cardiologist
at Screening Visit S2).
5. 
Unable or unwilling to abstain from caffeine- or nicotine-containing products including
but not limited to smoking, vaping, chewing tobacco, nicotine gum and patches for 12
hours prior to the cardiology assessments.
6. 
Has diabetes or has HbA1c >6.5.
7. 
Has a predominantly non-plaque form of psoriasis (eg, erythrodermic, guttate, or
pustular).
8. 
Has a history of liver or renal insufficiency (estimated creatinine clearance below 60
mL/min); significant cardiac, vascular, pulmonary, gastrointestinal, endocrine,
neurologic, hematologic, rheumatologic (except PsA), psychiatric, metabolic


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disturbances or coagulopathies. Participants with AS, RA, SLE, BD, Sjögren’s
syndrome, etc. will not be permitted.
9. 
Has a history of malignancy within 5 years before screening (exceptions are squamous
and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy,
which is considered cured with minimal risk of recurrence).
10. 
Has a diagnosed severe chronic mental disorder, including but not limited to major
depression, anxiety disorder, and schizophrenia.
11. 
Has known allergies, hypersensitivity, or intolerance to guselkumab  or its excipients
(refer to the IB).19
12. 
Has known intolerance or hypersensitivity to any biologic medication, or known
allergies or clinically significant reactions to murine, chimeric, or human proteins,
mAbs, or antibody fragments.
13. 
Has a history of 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 nonremitting cystitis), fungal
infection (mucocutaneous candidiasis), or open, draining, or infected skin wounds or
ulcers.
14. 
Has contraindications to the use of guselkumab per local prescribing information.
Concomitant or previous medical therapies-related exclusion criteria
15. 
Has taken any prohibited therapies before the planned first dose of guselkumab  (as
noted in Section 6.5, Concomitant Therapy and Table 1).
16. 
Has had major surgery, (eg, requiring general anesthesia) within  8 weeks before
screening, or will not have fully recovered from surgery, or has surgery planned during
the time the participant is expected to participate in the study, or within 16 weeks after
the last dose of guselkumab.
Note: Participants with planned surgical procedures to be conducted under local
anesthesia may participate.
17. 
Is currently undergoing or has previously undergone allergy immunotherapy for a
history of anaphylactic reactions.
18. 
Has received any anti-TNFα biologic within 3 months or 5 half-lives of the first
administration of guselkumab, whichever is longer.
19. 
Has previously received IL-23 inhibitors (guselkumab, tildrakizumab or risankizumab).


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20. 
Has received any therapeutic agent directly targeted to IL-12/23 or IL-17 within
6 months of the first administration of guselkumab (including but not limited to
ustekinumab, tildrakizumab [MK3222], secukinumab [AIN457], ixekizumab
[LY2439821], or brodalumab [AMG 827]).
21. 
Has received natalizumab, belimumab, or agents that modulate B-cells or T-cells (eg,
rituximab, alemtuzumab, abatacept, or visilizumab) within 12 months of the first
administration of guselkumab.
22. 
Has received any systemic immunosuppressants (eg, methotrexate [MTX],
azathioprine, cyclosporine, 6-thioguanine, mercaptopurine, mycophenolate mofetil,
tacrolimus) or anakinra within 4 weeks of the first administration of guselkumab.
23. 
Has received phototherapy or any systemic medications/treatments that could affect
psoriasis or IGA evaluations (including, but not limited to, oral or injectable
corticosteroids, retinoids, 1,25-dihydroxy vitamin D3 (calcitriol), psoralens,
sulfasalazine, hydroxyurea, fumaric acid derivatives, herbal treatments, or traditional
Taiwanese, Korean, or Chinese medicines) within 4 weeks of the first administration of
guselkumab. Oral vitamin D supplements (ergocalciferol and/or cholecalciferol) are
permitted.
24. 
Is currently receiving lithium, antimalarials, or intramuscular (IM) gold, or have
received lithium, antimalarials, or IM gold within 4 weeks of the first administration of
guselkumab.
25. 
Has received an experimental antibody or biologic therapy within the previous
6 months, or received any other experimental therapy or new investigational agent
within 30 days or 5 half-lives (whichever is longer) of any guselkumab administration
or is currently enrolled in another study using an investigational agent or procedure.
26. 
Has received, or is expected to receive, any live virus or bacterial vaccination within
3 months before the first administration of guselkumab.
27. 
Has had a BCG vaccination within 12 months of screening.
Infections or predisposition to infections-related exclusion criteria
28. 
Has a transplanted organ (with exception of a corneal transplant >3 months before the
first administration of guselkumab).
29. 
Has a history of an infected joint prosthesis, or has received antibiotics for a suspected
infection of a joint prosthesis, if that prosthesis has not been removed or replaced.


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30. 
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
screening.
31. 
Has or has had herpes zoster within the 2 months before screening.
32. 
Has current drug-induced psoriasis (eg, a new onset of psoriasis or an exacerbation of
psoriasis from beta-blockers, calcium channel blockers, or lithium).
33. 
Has a history of active granulomatous infection, including histoplasmosis or
coccidioidomycosis, before screening. Refer to Inclusion Criterion 13 for information
regarding eligibility with a history of latent TB.
34. 
Has a chest radiograph within 3 months before the first dose of guselkumab that shows
an abnormality suggestive of a malignancy or current active infection, including TB.
35. 
Has ever had a nontuberculous mycobacterial infection or opportunistic infection (eg,
cytomegalovirus, pneumocystosis, aspergillosis).
36. 
Is infected with human immunodeficiency virus (HIV, positive serology for HIV
antibody).
37. 
Tests positive for hepatitis B virus (HBV) infection or is seropositive for antibodies to
hepatitis C virus (HCV) at screening.
38. 
During the 4 weeks prior to Week 0, have had ANY of (a) confirmed SARS-CoV-2
(COVID-19) infection (test positive), OR (b) suspected SARS-CoV-2 infection
(clinical features without documented test results), OR (c) close contact with a person
with known or suspected SARS-CoV-2 infection
 
Exception: if recommended by local guidelines and as part of standard of care
in the respective country, participants may be included with a documented
negative result for a validated SARS-CoV-2 test (direct detection methods)
(1) 
obtained at least 2 weeks after conditions (a), (b), (c) above (timed from
resolution of key clinical features if present, eg, fever, cough, dyspnea)
AND
(ii) with absence of ALL conditions (a), (b), (c) above during the period
between the negative test result and the Week 0 study visit
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.


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Precaution: for those who may carry a higher risk for severe COVID-19 illness, follow
guidance from local health authorities when weighing the potential benefits and risks
of enrolling in the study, and during participation in the study.
Other exclusion criteria
39. 
Pregnant, or breastfeeding, or planning to become pregnant while enrolled in this study
or within 5 months after the last dose of guselkumab.
40. 
Plans to father a child while enrolled in this study or within 12 weeks after the last dose
of guselkumab.
41. 
Any condition for which, in the opinion of the investigator, participation would not be
in the best interest of the participant (eg, compromise the well-being) or that could
prevent, limit, or confound the protocol-specified assessments (Criterion to be assessed
by both dermatologist and cardiologist during Screening Visits 1 and 2).
42. 
Is known to have had a substance abuse (drug or alcohol) problem within the previous
12 months.
43. 
Lives in an institution on court or authority order.
44. 
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 both
Screening Visit S1 and Screening Visit S2. 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 guselkumab is given such that he or she no longer meets all eligibility criteria, then
the participant should be excluded from participation in the study. Section 5.4, Screen Failures,
describes options for retesting. The required source documentation to support meeting the
enrollment criteria are noted in  Appendix 12, Regulatory, Ethical, and Study Oversight
Considerations.
5.3. 
Lifestyle Considerations
Potential participants must be willing and able to adhere to the following lifestyle restrictions
during the course of the study to be eligible for participation:
1. 
Refer to Section 6.5, Concomitant Therapy  for details regarding prohibited and
restricted therapy during the study.
2. 
Agree to follow all requirements that must be met during the study as noted in the
Inclusion and Exclusion Criteria (eg, contraceptive requirements).


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3. 
This study will enroll both nicotine users and non-users. Those using tobacco products
and/or nicotine products including, but not limited to cigarettes (including e-cigarettes
or the equivalent of e-cigarettes), cigars, chewing tobacco, patch, gum, etc, will be
considered nicotine users. To be considered a nicotine non-user, the participant must
have refrained from using the above tobacco/nicotine products for at least 3 months
before Screening Visit S1. Participants will be instructed to abstain from
nicotine-containing products for at least 12 hours before the scheduled cardiology
assessments. A urine nicotine test will be conducted before measurement of CFR to
confirm tobacco/nicotine use.
4. 
Caffeine is a potent antagonist of adenosine. All eligible participants must abstain from
consuming coffee, tea, cola drinks, energy drinks, other caffeinated beverages, food, or
using any substances containing caffeine for at least 12 hours prior to the scheduled
cardiology assessments during the study.
5. 
Agree to use sun protective measures (such as a hat, sunglasses, protective clothing,
sunscreen), limit prolonged exposure to natural sunlight, and avoid artificial sunlight
(tanning beds or phototherapy) from Screening Visit S1 until the last dose of
guselkumab.
6. 
Participants will be instructed not to make significant changes in their exercise routines,
diet, and their nicotine consumption, drinking, or sleeping habits during the study,
outside the requirements ofthe study eligibility criteria.
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 enrolled into
the study, the date of Screening Visit S1 and age at initial informed consent will be used.
Screening Visit S2 must occur no later than 2 weeks after Screening Visit S1, and the Week 0 visit
must occur a minimum of 2 weeks and a maximum of 4 weeks after Screening Visit S2.
Exceptional and limited retesting of abnormal screening values that lead to exclusion are allowed
only once within the 2-week period. Eligibility may be reassessed at a single unscheduled visit
during the screening period, or at Screening Visit S2 along with the scheduled cardiology
assessments. If the CFR measurement is unsuccessful during Screening Visit S2, ie, if the acoustic


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window of the coronary artery cannot be properly found, 2 attempts to measure a CFR can be made
on different days within the 2-week screening period.
In general, if a participant is a screening failure but, in the future, meets all the eligibility criteria,
the participant may be re-screened after a new informed consent has been obtained. Participants
who are re-screened will be assigned a new participant number and will restart a new Screening
Visit. Re-screening will be permitted once.
6. 
STUDY INTERVENTION
6.1. 
GuselkumabAdministration
Guselkumab administration must be captured in the source documents and the case report form
(CRF). Guselkumab will be manufactured and provided under the responsibility of the Sponsor.
Refer to the IB for a list of excipients.
Participants enrolled in the study will receive guselkumab 100 mg at Weeks 0, 4, 12, 20 and 28.
The first dose of guselkumab  will always be administered at the site and by a health care
professional (HCP). Subsequent doses can be self-administered at the site under supervision by
site-staff after the participant has been adequately trained in the procedure.
Study intervention administration must be captured in the source documents and the CRF.
For a definition of guselkumab overdose, refer to Section 8.4, Treatment of Overdose.
Guselkumab 100 mg will be provided in a single-use prefilled syringe (PFS) assembled with the
UltraSafe PLUSTM Passive Needle Guard (PFS-U). Malfunctions of the syringe must be detected,
documented, and reported by the investigator throughout the study.
6.1.1. 
Combination Product
 
The Sponsor-manufactured combination product (or those manufactured for the Sponsor by a
third party) provided for use in this study is guselkumab 100 mg provided in a single use PFS
assembled with the UltraSafe PLUSTM Passive Needle Guard (PFS-U).
 
Instructions for use of the PFS and PFS-U will be provided.
 
All deficiencies (including failure, malfunction, improper or inadequate design, manufacturer
error, use error, and inadequate labeling) of the PFS and PFS-U shall be documented and
reported by the investigator throughout the study. For studies in combination product, these
deficiencies will be reported as product quality complaints (PQC) (see Appendix 13: 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.


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6.2. 
Preparation/Handling/Storage/Accountability
Preparation/Handling/Storage
Guselkumab must be stored according to the labeled storage conditions, at 2°C to 8°C (36ºF to
46ºF) and protected from exposure to light. Vigorous shaking of the product should be avoided.
The sterile product does not contain preservatives and is designed for single use only. Protection
from light is not required during administration.
Refer to the pharmacy manual/study-site investigational product and procedures manual for
additional guidance on guselkumab preparation, handling, and storage.
Accountability
The investigator is responsible for ensuring that all the guselkumab doses received at the site are
inventoried and accounted for throughout the study. Guselkumab administered to the participant
must be documented on the intervention accountability form. Guselkumab  will be stored and
disposed of according to the Sponsor’s instructions. Study-site personnel must not combine
contents of the guselkumab containers.
Guselkumab 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 guselkumab must be available for verification by the Sponsor’s
study-site monitor during on-site monitoring visits. The return to the Sponsor of unused
guselkumab, or used returned guselkumab for destruction, will be documented on the intervention
return form. When the study-site is an authorized destruction unit and guselkumab supplies are
destroyed on-site, this must also be documented on the intervention return form.
Guselkumab should be dispensed under the supervision of the investigator or a qualified member
of the study-site personnel, or by a hospital/clinic pharmacist. Guselkumab will be supplied only
to participants participating in the study. Guselkumab may not be relabeled or reassigned for use
by other participants. The investigator agrees neither to dispense guselkumab 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 guselkumab are provided in the pharmacy manual/study-site
investigational product and procedures manual.
6.3. 
Measures to Minimize Bias: Randomization and Blinding
Intervention Allocation
Procedures for Randomization and Stratification
Randomization will not be used in this study.
Blinding
As this is an open-label study, blinding procedures are not applicable.


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The GLS and CFR assessments throughout the study will be conducted per the echocardiology
protocol provided by the cardiology core lab. The results from GLS and CFR assessments will be
securely transmitted to the cardiology core lab for blinded review of endpoints, per guidelines laid
down in the process document of the core lab. The received images and examinations will be
loaded and copied to the ultrasound software at the core lab. Both the computer and the software
used for analysis will have restricted access and will be password protected, with only responsible
physicians and biomedical technicians having access to the password.
6.4. 
Study Intervention Compliance
When participants are dosed at the site, they will receive guselkumab directly from the investigator
or designee, under medical supervision. The date of each dose administered in the clinic will be
recorded in the source documents and recorded in the CRF. The dose of guselkumab and study
participant identification will be confirmed at the time of dosing by a member of the study-site
personnel other than the person administering the guselkumab.
Compliance will be assessed during the site visits and documented in the source documents and
CRF. Deviation(s) from the prescribed dosage regimen should be recorded in the CRF. A record
of the number of guselkumab doses dispensed to and taken by each participant must be maintained
and reconciled with study intervention and compliance records. Guselkumab start and stop dates,
including dates for delays will also be recorded in the CRF.
6.5. 
Concomitant Therapy
Concomitant therapies must be recorded throughout the study beginning with start of the first dose
of guselkumab up to 12 weeks after the last dose of guselkumab. Concomitant therapies should
also be recorded beyond Week 40 only in conjunction with SAEs that meet the criteria outlined in
Serious Adverse Events in Section 8.3.1, Time Period and Frequency for Collecting Adverse Event
and Serious Adverse Event Information.
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 CRF. 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 preexisting therapy should not be made for the explicit purpose of
entering a participant into the study.
When considering the use of locally approved COVID-19 vaccines in study participants, follow
applicable local labelling, guidelines, and standards of care for participants receiving
immune-targeted therapy. For study participants receiving a locally approved COVID-19 vaccine,
it is recommended where possible that the vaccine and study intervention be administered on
different days, separated by as large an interval as is practical within the protocol.


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6.5.1. 
Concomitant Medications for Treatment of Psoriasis
6.5.1.1. 
Topical Therapy
Use of topical psoriasis treatment (eg, corticosteroids, tar, anthralin, calcipotriene, tazarotene,
methoxsalen, pimecrolimus, tacrolimus) is permitted at the investigator’s discretion from
Screening Visit S1 up to Week 4. The treatment should only cover a maximum of 20% body
surface area, ie, for the scalp, the intertriginous regions, palms/soles. However, Class IV topical
corticosteroids (alone or in combination) and phototherapy are prohibited until end of the study.
Shampoos (containing tar or salicylic acid only) and topical moisturizers are allowed throughout
the study, but participants should not use these topical agents (shampoos, moisturizers) on the day
of a study visit. Nonmedicated shampoos may be used on the day of the study visit. Traditional
Taiwanese, Korean, or Chinese medicines are prohibited during the study.
6.5.1.2. 
Phototherapy or Systemic Therapy for Psoriasis
The use of phototherapy or systemic antipsoriatic medications is not permitted at any time during
the study. These medications include those targeted for reducing TNF (including but not limited
to infliximab or etanercept), drugs targeted for reducing IL-12/23, IL-17, or IL-23 (including but
not limited to ustekinumab, tildrakizumab [MK3222], risankizumab, secukinumab [AIN457],
ixekizumab [LY2439821], or brodalumab [AMG827]), alpha-4 integrin antagonists (including but
not limited to natalizumab), steroids, any conventional systemic therapy that could affect psoriasis
or the IGA evaluation (including but not limited to MTX, cyclosporine, acitretin), herbal
treatments, or traditional Taiwanese, Korean, or Chinese medicines, and any other biological agent
or other systemic medication that could affect psoriasis or the IGA evaluation.
6.5.2. 
Concomitant Medications for Conditions Other than Psoriasis
Every effort should be made to keep participants on stable concomitant medications. If the
medication is temporarily discontinued because of abnormal laboratory values, side-effects,
concurrent illness, or the performance of a procedure, the change and reason for it should be clearly
documented in the participant’s medical record. The use of stable doses of nonsteroidal anti-
inflammatory drugs is allowed. However, disease-modifying agents such as MTX, sulfasalazine,
or IM gold are prohibited during the study. Antimalarial agents, except for chloroquine, may be
used after Week 40. The use of corticosteroids for indications other than psoriasis should be limited
to situations for which, in the opinion of the treating physician, there are no adequate alternatives.
They should be used on a short-term basis, preferably for ≤2 weeks. Longer-term use of
corticosteroids should be discussed with the Medical Monitor or designee and may require
discontinuation of study drug. Inhaled, otic, ocular, nasal, or other routes of mucosal delivery of
corticosteroids are allowed throughout the study.
6.5.3. 
Concomitant Medications of Special Interest
Every effort should be made to keep participants on stable concomitant medications. If the
medication is temporarily discontinued because of abnormal laboratory values, side-effects,
concurrent illness, or the performance of a procedure, the change and reason for it should be clearly






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continued to completion. Participants who have an indeterminate result should have the
test repeated. Guselkumab must be discontinued for participants with persistently
indeterminate QuantiFERON-TB Gold test results .
 
Discontinues treatment for latent TB prematurely or is noncompliant with the therapy.
 
The participant is unable to adhere to the study visit schedule or comply with protocol
requirements.
 
The participant develops an allergic reaction such as bronchospasm with wheezing and/or
dyspnea requiring ventilatory support, or symptomatic hypotension that occurs following a
guselkumab administration.
 
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 guselkumab. These
may be accompanied by other events including pruritus, facial, hand, or lip edema, dysphagia,
urticaria, sore throat, and/or headache.
 
 Participants who develop a serious or opportunistic infection. Discussion of such participants
with the Medical Monitor or designee should also be considered.
 
The participant receives a concomitant medication that is prohibited by the protocol.
 
The study is terminated by the Sponsor.
If a participant permanently discontinues guselkumab before Week 28, the Final Efficacy Visit
should occur at the time of discontinuation or as soon as possible, and all assessments scheduled
for the Final Efficacy Visit should be performed. The participant should also return for a Final
Safety Visit, 12 weeks after the last guselkumab dose.
If the reason for withdrawal from the study is withdrawal of consent, then no additional
assessments are allowed. If a participant discontinues study treatment and starts another biologic
treatment, an interval of at least 12 weeks between the last guselkumab administration and the start
of the new treatment is recommended. The number of dropouts in the study are expected to be
low; however, additional participants will be entered to maintain the sample size and ensure that
the protocol-specified number of participants complete the study.
7.2. 
Participant Discontinuation/Withdrawal From the Study
Reasons for participant discontinuation/withdrawal from the study may include:
 
Adverse event, eg, Major Adverse Cardiac Event (myocardial infarction, non-fatal stroke, or
cardiovascular death)
 
Lost to follow-up
 
The investigator decides to withdraw the participant from the study
 
Protocol violation
 
Study termination by the Sponsor
 
Pregnancy


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 
Lack of efficacy
 
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. For each participant discontinuing the study,
the investigator should attempt to obtain a CFR reading. 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 (eg, consult with family members, contacting the participant’s other physicians,
medical records, database searches) 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. Withdrawal of consent should be an infrequent occurrence in clinical studies, 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  upon confirmation from the study Sponsor. These may include (as local
regulations permit):
 
Less frequent clinical visits
 
Telemedicine
 
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
Details regarding these contacts must be properly documented in source records including
responses by participants.


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7.3. 
Lost to Follow-up
To reduce the chances of a participant being deemed lost to follow-up, attempts should be made
to obtain contact information from each participant, eg, home, work, and mobile telephone
numbers and email addresses for both the participant as well as appropriate family members.
A participant will be considered lost to follow-up if he or she repeatedly fails to return for
scheduled visits and is unable to be contacted by the study-site. A participant cannot be deemed
lost to follow-up until all reasonable efforts made by the study-site personnel to contact the
participant are deemed futile. The following actions must be taken if a participant fails to return to
the study-site for a required study visit:
 
The study-site personnel must attempt to contact the participant to reschedule the missed visit
as soon as possible, to counsel the participant on the importance of maintaining the assigned
visit schedule, to ascertain whether the participant wishes to or should continue in the study.
 
Before a participant is deemed lost to follow-up, the investigator or designee must make every
reasonable effort to regain contact with the participant (where possible, 3 telephone calls, e-
mails, fax, and, if necessary, a certified letter to the participant’s last known mailing address,
or local equivalent methods). These contact attempts should be documented in the
participant’s medical records.
 
Should the participant continue to be unreachable, they will be considered to have withdrawn
from the study.
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 Schedule of Activities summarizes the frequency and timing of efficacy, biomarker, and safety
measurements applicable to this study. Participants will provide informed consent before
undergoing any study-related procedures or assessments.
Multiple assessments are scheduled for the same time-point. As a rule, all PRO assessments should
be conducted/completed before any tests, procedures, or other consultations to prevent influencing
participant perceptions. The PRO assessments should be completed in the order DLQI, PSQI,
HADS (if available) and AUDIT.
The current study will integrate dermatological and cardiological aspects of the systemic disease
psoriasis.
Screening Visit S1
At Screening Visit S1, participants presenting with moderate-to-severe plaque psoriasis at
dermatology departments/sites will be assessed for eligibility by the dermatology investigator
following informed consent. Demography and medical history  will be recorded, and the


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participants’ TB, HIV and pregnancy status will be checked. Participants will undergo physical
examinations, 12-lead ECG, dermatologic examinations and PASI, BSA, and IGA assessments.
The dermatology site will navigate the participants through the study, and will own the study
documentation for the participants.
Screening laboratory samples will be obtained from eligible participants. Once the laboratory test
results are available and the inclusion and exclusion criteria related to laboratory parameters are
reviewed, the participant will be referred to the participating cardiology department for
assessments related to Screening Visit S2. The participant may undergo Screening visit S2 while
the QuantiFERON-TB Gold results are pending, however, the result must be reviewed and
confirmed prior to enrolment at Week 0. All the other Screening Visit S1 laboratory parameters
must be available and reviewed prior to the participant being referred for Screening Visit S2.


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Screening Visit S2
Screening Visit S2 will occur no more than 2 weeks after Screening Visit S1. At the dermatology
site, all participants will undergo a urine nicotine test to determine nicotine status (user/non-user)
of the participant, and a urine pregnancy test (if applicable). The nicotine status (user/non-user)
must be recorded in the eCRF. A positive pregnancy tests will lead to exclusion of the participant.
The participants will then proceed with the cardiologic assessments performed by the cardiology
investigator. A cardiologic anamnesis will be performed including cardiologic family history, vital
signs and review of the relevant eligibility criteria.
Once eligibility is confirmed, the participant will undergo the cfPWV, GLS and CFR assessments.
The preferred order of the cardiology assessments is cfPWV, GLS and CFR. If the participant is
ineligible based on CFR results, the subsequent assessments can be deferred or avoided.
If the cardiology investigator is unsuccessful in obtaining a CFR measurement, eg, if the acoustic
window of the coronary artery cannot be found, 2 additional attempts to measure the CFR can be
made on different days.
Study Visit Week 0
The Week 0 visit will occur a minimum of 2 weeks and a maximum of 4 weeks after Screening
Visit S2. At this visit, the eligibility criteria will be reviewed, and the participant will complete the
PRO questionnaires prior to other assessments. A physical examination including PASI, BSA, and
IGA will be performed by the dermatology investigator. The PASI and IGA values will be
documented but not be considered as inclusion criteria. The participants will provide serum,
plasma, and urine samples, and cardiology assessments (cfPWV, GLS and CFR)will be performed
by the cardiologist following a urine nicotine test to determine nicotine use by the participant, and
a negative urine pregnancy test (if applicable). Only participants with CFR ≥2 and ≤3.5 at both
Screening Visit S2 and Week 0 will be enrolled in the study. The CFR measurement at Week 0
will be considered as the baseline value. Participants will then  receive the guselkumab SC
injection, and may receive training for self-administration of subsequent doses in the study, if
applicable.
Study Visits Weeks 4, 12, 20 and 28
At these visits, participants will undergo PASI, BSA and IGA assessments as assessed by the
dermatology investigator. Safety assessments including urine pregnancy test (where applicable)
will be performed per the Schedule of Activities, and adverse events and concomitant therapy will
be recorded. Guselkumab will be administered only after completion of all the assessments for that
time-point.


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Study Visits Weeks 16 and 32
At Week 16 and 32, the participant will complete the PRO questionnaires (DLQI first, followed
by other PROs) prior to other assessments and procedures. The dermatological investigator will
review the safety assessments and concomitant medication, and enquire about nicotine use in the
12 hours prior to the visit. The physical examination will include vital signs and PASI, BSA, and
IGA assessments performed by the dermatology investigator. Serum, plasma, and urine samples
will be drawn. After a urine nicotine test to determine nicotine use, and a negative urine pregnancy
test (if applicable), the participant will proceed to the cardiology department, where the cfPWV,
GLS, CFR and other assessments will be performed in arbitrary sequence by the cardiology
investigator. Participants who have been fasting for the lipid and metabolic panel are permitted to
have a non-caffeinated drink prior to the cardiology assessments.
If CFR measurement is unsuccessful at any time-point during the study, eg, if the acoustic window
of the coronary artery cannot be properly found, 2 attempts to measure the CFR can be made on
different days. At Weeks 16 and 32, the visit window can be extended by 7 additional days
(CFR visit window
-7/+14 days). If all 3 attempts to obtain CFR at Week 16 are unsuccessful,
the participant may still proceed the study with all the scheduled procedures. Actual dates of
assessments will be recorded in the source documentation and CRF.
Week 40 (Final Safety Visit)
This visit will occur 12 weeks after the last dose of guselkumab at the dermatology department.
Participants will undergo physical examination and recording of vital signs. Pregnancy tests will
be conducted, if applicable. Blood and urine sample will be provided for clinical laboratory tests.
Concomitant therapy received and adverse events since the last visit will be recorded in the CRF.
For guidance on study conduct during a pandemic, please refer to Appendix 15.
Sample Collection and Handling
The actual dates of sample collection must be recorded in the CRF or laboratory requisition form.
Refer to the Schedule of Activities 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.
The total blood volume for the study is approximately 185 mL. Repeat or unscheduled samples
may be taken for safety reasons or for technical issues with the samples.
Study-Specific Materials
The investigator will be provided with the following supplies:


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 
IB
 
Pharmacy manual/study-site and procedures manual
 
Laboratory manual and laboratory supplies
 
Paper PRO questionnaires and PRO completion guidelines
 
IWRS Manual
 
eDC Manual
 
Sample ICF and related participant materials
 
Instructions for Use (IFU) for guselkumab
8.1. 
Efficacy Assessments
Every effort should be made to ensure that the cardiology physician or designee who performed
the cardiology efficacy assessments (cfPWV, GLS and CFR) for a participant at Week 0 should
also perform the evaluations for the participant at Week 16 and Week 32. Every effort must be
made to perform the assessments at the same lab, on the same machine, using the same software
for all the visits. Assessments should be processed per the guidelines from the core lab. All CFR
and GLS assessments must be recorded. The results from GLS and CFR assessments will be
securely transmitted to the cardiology core lab for blinded independent review of endpoints, per
guidelines laid down in the process document of the core lab. To determine eligibility, the CFR
results obtained at the study site will be used. The use of contrast media for assessments is not
permitted. Sites staff will be trained by the Sponsor or designee to perform the CV assessments to
ensure standardization of the procedures.
The following assessments will be carried out as detailed in the Schedule of Activities. The
efficacy assessments will be performed locally at the sites.
8.1.1. 
Cardiovascular Evaluations
Carotid-femoral Pulse Wave Velocity
The measurement of cfPWV is accepted as the most simple, non-invasive, robust, and reproducible
method to determine arterial stiffness.38 Carotid-femoral (cf) PWV is a direct measurement, and it
corresponds to the widely accepted propagative model of the arterial system. Measured along the
aortic and aorto-iliac pathway, it is the most clinically relevant since the aorta and its first branches
are what the left ventricle ‘sees’ and are thus responsible for most of the pathophysiological effects
of arterial stiffness. cfPWV is usually measured using the foot-to-foot velocity method from
various waveforms. These are obtained transcutaneously at the right common carotid artery and
the right femoral artery (ie, ‘carotid-femoral’ PWV), and the time delay (∆t or transit time)
measured between the feet of the 2  waveforms. A variety of different waveforms can be used
including pressure, distension, and Doppler. The distance (D) covered by the waves is usually
assimilated to the surface distance between the 2 recording sites. cfPWV is calculated as
cfPWV D (meters)/ ∆t (seconds).


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Global Longitudinal Strain for Left Ventricular Function
In the G-CARE study, speckle tracking echocardiography (STE) will be employed for the
detection of left-ventricular (LV) myocardial strain. Two-dimensional STE is based on the
temporal and spatial tracking of naturally occurring intramyocardial reflectors of ultrasound
(speckles) within the 2D echocardiographic images of the LV walls, and measures LV regional
and global deformations as a marker of contractility and elasticity. The GLS and global
longitudinal strain rate will be calculated at systole and diastole. The ratio of the arterial stiffness
measured with cfPWV (described below) and the myocardial performance represented by GLS
will be calculated as an index reflecting the arterial-ventricular interaction. In addition, the
estimated LV peak twisting and untwisting at the time of mitral valve opening will be measured,
and the percentage difference between LV twist and untwisting at the mitral valve opening will be
calculated.42
The strain-pressure curves recorded from the GLS measurement may be used to calculate the
myocardial work index at selected sites.
Coronary Flow Reserve
Coronary flow reserve will be measured non-invasively using transthoracic doppler
echocardiography,36 using a high-resolution ultrasound system with a suitable transducer and the
respective software. The acoustic window will be around the midclavicular line in the fourth and
fifth intercostal spaces in the left lateral decubitus position. Long-axis views of the left ventricle
will be obtained, and the ultrasound beam will then be angled laterally and superiorly to image the
anterior interventricular groove. The coronary blood flow in the distal portion of the left anterior
descending artery(LAD)will be examined with the help of color Doppler flow mapping. A sample
volume will be positioned on the color signal in the LAD, and Doppler spectral tracings of flow
velocity will be recorded. First, the baseline spectral Doppler signals in the distal portion of the
LAD will be recorded. Then 140 µg/kg/min adenosine, a coronary vasodilator, will be
administered for 5 minutes. Doppler signals will be recorded continuously at baseline and during
the period of adenosine infusion. Measurements of hyperemic coronary flow velocity will be done
continuously during the adenosine infusion, and the CFR measurement will be recorded based on
the guidelines provided by the cardiology core lab.
Cardiac parameters, along with strain and coronary parameters will be assessed by the cardiology
core lab as defined in the process document of the core lab.
8.1.2. 
Psoriasis Assessments
Investigator’s Global Assessment
The IGA documents the investigator’s assessment of the participant’s psoriasis at a given time-
point (Appendix 5). Overall lesions are graded for induration, erythema, and scaling. The
participant’s psoriasis is assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4).


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Psoriasis Area and Severity Index
The PASI is a system used for assessing and grading the severity of psoriatic lesions and their
response to therapy(Appendix 6). In the PASI system, the body is divided into 4 regions: the head,
trunk, upper extremities, and lower extremities. Each of these areas is assessed separately for
erythema, induration, and scaling, which are each rated on a scale of 0 to 4. The PASI produces a
numeric score that can range from 0 to 72. A PASI 75 response is defined as ≥75% improvement
in PASI score from baseline; PASI 90 and PASI 100 are similarly defined. A higher score indicates
more severe disease.
The Sponsor will provide PASI training on assessment of PASI scores. Documentation of this
training will be maintained in the site’s training files. Previous PASI training by the Sponsor within
the last 3 years with adequate documentation (eg, training certification) will be considered
adequate for this study; however, repeat training prior to start of the study is encouraged.
Body Surface Area
The BSA score is the arithmetic mean of the affected skin surface. The most commonly used
method to estimate the BSA of psoriatic lesions is the “rule of nines”, which was originally
developed for estimating the surface area of burns. It is defined as 9% coverage for the head and
neck, 9% for each arm, 9% for the anterior and posterior legs, and 9% for each of 4 trunk quadrants,
and 1% for the groin. The area of the palm can be used as a unit of measure which represents
approximately 1% of the BSA. The number of patient hand areas affected can then be calculated.
The formula for the calculation of BSA is provided in Appendix 7.
8.1.3. 
Patient-Reported Outcomes
Patient-reported outcomes will be assessed using paper PROs at the study sites.
Dermatology Life Quality Index
The DLQI is a dermatology-specific quality-of-life instrument designed to assess the impact of the
disease on a participant’s quality-of-life (Appendix 8). It is a 10 item PRO questionnaire that, in
addition to evaluating overall quality-of-life, can be used to assess 6 different aspects that may
affect quality-of-life: symptoms and feelings, daily activities, leisure, work or school performance,
personal relationships, and treatment. The DLQI produces a numeric score that can range from 0
to 30. A higher score indicates more severe disease.
Pittsburg Sleep Quality Index
The PSQI is an effective instrument used to measure the quality and patterns of sleep in the older
adult (Appendix 9). It differentiates “poor” from “good” sleep by measuring 7 domains: subjective
sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of
sleep medication, and daytime dysfunction over the last month. The participant self-rates each of
these 7 areas of sleep. Scoring of the answers is based on a 0 to 3 scale, whereby 3 reflects the
negative extreme on the Likert Scale. A global sum of “5” or greater indicates a “poor” sleeper.


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Alcohol Use Disorders Identification Test
The AUDIT is a 10-item screening tool developed by the World Health Organization (WHO) to
assess alcohol consumption, drinking behaviors, and alcohol-related problems (Appendix 10).
Both a clinician-administered version (page 1) and a self-report version of the AUDIT (page 2) are
provided. Participants should be encouraged to answer the questions in terms of standard drinks.
A chart illustrating the approximate number of standard drinks in different alcohol beverages is
included. A score of 8 or more is considered to indicate hazardous or harmful alcohol use. The
AUDIT has been validated across genders and in a wide range of racial/ethnic groups and is well
suited for use in primary care settings.
The Hospital Anxiety and Depression Scale (if available)
The Hospital Anxiety and Depression Scale measures anxiety and depression which commonly
coexist in a general medical population of patients (Appendix 11).62  The HADS focuses on
non-physical symptoms so that it can be used to diagnose depression in people with significant
physical ill-health. The questionnaire comprises 7 questions for anxiety and 7 questions for
depression, and takes 2-5 minutes to complete. Although the anxiety and depression questions are
interspersed within the questionnaire, they are scored separately, and cut-off scores are available
for quantification. The HADS questionnaire has been validated in many languages, countries and
settings, including general practice and community settings.
8.1.4. 
Other Efficacy Evaluations
8.1.4.1. 
Biomarker Analysis
High levels of inflammatory markers are associated with atherosclerosis, coronary artery disease
and are predictors of cardiovascular events. The following biomarkers will be analyzed at the time-
points detailed in the Schedule of Activities:
Serum Samples:
 
Inflammatory markers: hsCRP, IL-6, IL-17A/F, IL-22, IL-23, SAA1, SAA2
 
Lipid biomarkers: LDL cholesterol, HDL cholesterol, total cholesterol, triglycerides
 
Metabolic biomarkers: HbA1c
 
Markers of cardiovascular injury: NT-proBNP
 
Olink cardiovascular and inflammatory panels
Plasma Samples:
 
Oxidative stress markers:
 
Concentration of oxidative lipid damage (8-Isoprostane) and malondialdehyde (HPLC,
GC-MS)
 
Concentration of antioxidants (Vitamins C and E)
 
Adipokines- leptin and adiponectin


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Urine samples:
 
DNA damage markers (8-Oxo-7,8-dihydro2'-desoxyguanosine)
8.2. 
Safety Assessments
Adverse events will be reported and followed by the investigator as specified in Section 8.3,
Adverse Events and Serious Adverse Events and Appendix 13, Adverse Events: Definitions and
Procedures for Recording, Evaluating, Follow-Up, and Reporting.
Any clinically relevant changes occurring during the study must be recorded on the Adverse Event
section of the CRF.
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 Schedule of Activities.
8.2.1. 
Physical Examinations
Physical examinations, including skin and recording of height, weight and waistline circumference
will be performed by the investigator or designated physician as specified in the Schedule of
Activities. Any abnormalities or changes in severity noted during the review of body systems
should be documented in the source document.
8.2.2. 
Vital Signs
Temperature (axillary, tympanic or forehead), pulse/heart rate, blood pressure will be assessed by
the dermatologist. Blood pressure and pulse/heart rate measurements will be assessed with a
completely automated device. Manual techniques will be used only if an automated device is not
available. 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).
Vital signs measured during the CV procedures at the cardiology department may be recorded and
used for data analysis.
8.2.3. 
Electrocardiograms
Standard 12-lead electrograms will be taken at Screening Visit S1 at the dermatology department.
During the collection of the 12-lead ECG, participants should be in a quiet setting without
distractions (eg, television, cell phones). Participants should rest in a supine position for at least
5 minutes before ECG collection and should refrain from talking or moving arms or legs. If blood
sampling or vital sign measurement is scheduled for the same time-point as ECG recording, the
procedures should be performed in the following order: ECG, vital signs, blood draw.


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8.2.4. 
Clinical Safety Laboratory Assessments
Blood samples for serum chemistry and hematology will be collected as noted in Appendix 2,
Clinical Laboratory Tests. The investigator must review the laboratory results, document this
review, and record any clinically relevant changes occurring during the study in the adverse event
section of the CRF. The laboratory reports must be filed with the source documents.
8.2.5. 
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
Schedule of Activities) or by telephone contact approximately every 8 to 12 weeks. The following
series of questions is suggested for use during the evaluation:
 
“Have you had a new cough of >14 days’ duration or a change in a chronic cough?”
 
“Have you had any of the following symptoms:
 
Persistent fever?
 
Unintentional weight loss?
 
Night sweats?”
 
“Have you had close contact with an individual with active TB?” (If there is uncertainty as to
whether a contact should be considered “close,” a physician specializing in TB should be
consulted.)
If the evaluation raises suspicion that a participant may have TB reactivation or new TB infection,
an immediate and thorough investigation should be undertaken, including, where possible,
consultation with a physician specializing in TB.
Investigators should be aware that TB reactivation in immunocompromised participants may
present as disseminated disease or with extrapulmonary features. Participants with evidence of
active TB should be referred for appropriate treatment.
Participants who experience close contact with an individual with active TB during the conduct of
the study must have a repeat chest radiograph, a repeat QuantiFERON-TB Gold test, and, if
possible, referral to a physician specializing in TB to determine the participant’s risk of developing
active TB and whether treatment for latent TB is warranted.
Guselkumab administration should be interrupted during the study. A positive QuantiFERON-TB
Gold test result should be considered detection of latent TB. If the QuantiFERON-TB Gold test
result is indeterminate, the test should be repeated as outlined in Section 8.2.5. Participants who
discontinue treatment for latent TB prematurely or who are noncompliant with therapy must
immediately discontinue further administration of guselkumab and be encouraged to return for all
subsequent scheduled study visits according to the Schedule of Activities.


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8.2.6. 
Pregnancy Testing
Serum pregnancy tests will be performed at Screening Visit S1. Further urine pregnancy tests may
be performed, as determined necessary by the investigator, or required by local regulation, to
establish the absence of pregnancy at all the study visits as detailed in the Schedule of Activities.
8.3. 
Adverse Events and Serious Adverse Events
Timely, accurate, and complete reporting and analysis of safety information from clinical studies
are crucial for the protection of participants, investigators, and the Sponsor, and are mandated by
regulatory agencies worldwide. The Sponsor has established Standard Operating Procedures in
conformity with regulatory requirements worldwide to ensure appropriate reporting of safety
information; all clinical studies conducted by the Sponsor or its affiliates will be conducted in
accordance with those procedures.
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, surrogate,
or the participant's legally acceptable representative) for the duration of the study.
The usual pharmacodynamic actions and expected effects of adenosine administration during CFR
assessment are not considered as AEs.
As guselkumab is classified as a combination product, malfunctions or deficiencies of the device
constituent will be reported as PQC.
For further details on AEs and SAEs (Definitions and Classifications; Attribution Definitions;
Severity Criteria; Special Reporting Situations; Procedures) as well as PQCs, refer to
Appendix 13, Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow-Up,
and Reporting.
8.3.1. 
Time Period and Frequency for Collecting Adverse Event and Serious
Adverse Event Information
All Adverse Events
All AEs and special reporting situations, whether serious or non-serious, will be reported from the
time a signed and dated ICF is obtained until completion of the participant's last study-related
procedure, which may include contact for follow-up of safety. Serious adverse events, including
those spontaneously reported to the investigator within 12 weeks after the last dose of guselkumab,
must be reported using the Serious Adverse Event Form. The Sponsor will evaluate any safety
information that is spontaneously reported by an investigator beyond the time frame specified in
the protocol.
Serious Adverse Events
All SAEs occurring during the study must be reported to the appropriate Sponsor contact person
by study-site personnel within 24 hours of their knowledge of the event.


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Information regarding SAEs will be transmitted to the Sponsor using the Serious Adverse Event
Form and Safety Report Form of the CRF, which must be completed and reviewed 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 by facsimile (fax) via a secure
transmission system.
Any possible Hy’s law case (AST or ALT ≥3x ULN together with bilirubin ≥2X 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, even before all other possible causes of liver injury
have been excluded. The INR criterion is not applicable to participants receiving anticoagulants.
8.3.2. 
Follow-up of Adverse Events and Serious Adverse Events
Adverse events, including pregnancy, will be followed by the investigator as specified in
Appendix 13, Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow-up,
and Reporting.
8.3.3. 
Regulatory Reporting Requirements for Serious Adverse Events
The Sponsor assumes responsibility for appropriate reporting of AEs to the regulatory authorities.
The Sponsor will also report to the investigator (and the head of the investigational institute where
required) all suspected unexpected serious adverse reactions (SUSARs). The investigator (or
Sponsor where required) must report SUSARs to the appropriate Independent Ethics
Committee/Institutional Review Board (IEC/IRB) that approved the protocol unless otherwise
required and documented by the IEC/IRB.
All AEs will be recorded in the CRF and will be reported to the Sponsor as described under All
Adverse Events in Section 8.3.1, Time Period and Frequency for Collecting Adverse Event and
Serious Adverse Event Information.
8.3.4. 
Pregnancy
All initial reports of pregnancy in female participants or partners of male participants must be
reported to the Sponsor by the study-site personnel within 24 hours of their knowledge of the event
using the appropriate pregnancy notification form. Abnormal pregnancy outcomes (eg,
spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are
considered SAEs and must be reported using the Serious Adverse Event Form. Any participant
who becomes pregnant during the study must discontinue further doses of guselkumab.
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the
infant will be required.


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8.3.5. 
Disease-Related Events and Disease-Related Outcomes not
Qualifying as Adverse Events or Serious Adverse Events
All events that meet the definition of a serious adverse event will be reported as SAEs, regardless
of whether they are protocol-specific assessments.
The cause of death of a participant in a study ≤24 hours of the last dose of guselkumab, regardless
of causality or association with guselkumab, is considered a SAE.
8.3.6. 
Adverse Events of Special Interest
Any newly identified malignancy or case of active TB occurring after the participant's first
guselkumab administration must be reported within 24 hours by the investigator according to the
procedures in  Section 8.3 and Section 8.3.1. 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 a SAE.
8.4. 
Treatment of Overdose
No clinical studies in humans have been conducted to assess a toxic threshold for guselkumab.
The highest single SC dose of guselkumab investigated in humans was 300 mg. The maximum IV
dose (10 mg/kg) in humans was 987 mg.
In the event of an overdose (any dose greater than that prescribed for the study), the investigator
or treating physician should:
 
Contact the Medical Monitor immediately.
 
Closely monitor the participant for AE/SAE and appropriate symptomatic treatment instituted
immediately.
Decisions regarding dose interruptions or modifications will be made by the investigator in
consultation with the Medical Monitor based on the clinical evaluation of the participant.
8.5. 
Pharmacokinetics
Pharmacokinetics will not be evaluated for this study.
8.6. 
Pharmacodynamics
Pharmacodynamics will be assessed as described in the endpoints.
8.7. 
Biomarkers
Biomarker sample collections will be conducted at the time-points presented in the Schedule of
Activities to measure serum markers. Data collected from these samples will be used for
exploratory research that will include the following objectives:
 
To understand the molecular effects of guselkumab.
 
To understand psoriasis.


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 
To understand why people may respond differently to guselkumab.
 
To develop tests related to guselkumab or psoriasis.
Instructions for the collection and shipment of these samples can be found in the appropriate
Laboratory Manual.
8.8. 
Medical Resource Utilization and Health Economics
Health Economics/Medical Resource Utilization and Health Economics parameters are not
evaluated in this study.
9. 
STATISTICAL CONSIDERATIONS
Statistical analysis will be done by the Sponsor or under the authority of the Sponsor. A general
description of the statistical methods to be used to analyze the efficacy and safety data is outlined
below. Specific details will be provided in the Statistical Analysis Plan.
Descriptive statistics, such as mean, standard deviation (SD), median, inter quartile range,
minimum, and maximum for continuous variables, and counts and percentages for discrete
variables will be used to summarize most data. In addition, graphical data displays (eg, line plots)
and participant listings may also be used to summarize/present the data.
In general, for continuous or ordinal efficacy endpoints, a Mixed-Effect Model Repeated Measures
(MMRM) model will be used. Covariates such as BMI, smoking status, presence, or absence of
PsA, age, gender, left ventricular mass index and hypertension diagnosis will be incorporated into
these models. For binary efficacy endpoints, 95% confidence intervals for binomial proportions
will be provided using exact methods, such as Clopper-Pearson or Chan-Zhang.
In general, all statistical tests will be performed at a 2-sided significance level of α 0.05.
9.1. 
Statistical Hypotheses
The primary hypothesis of this study is that guselkumab is effective in reducing surrogate markers
ofcardiovascular risk as assessed by the change from baseline in CFR at Week 32.
9.2. 
Sample Size Determination
The sample size calculation is based on the assumption that participants will show an average
increase of 20% in CFR at Week 32. To detect a CFR mean change of 0.3 from baseline with 80%
power, and assuming a SD of 0.8 and a 5% dropout rate, 50 participants are expected to be enrolled
in the study.42




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0 results will be presented in pre- versus post-intervention cross-tabulations (with classes for
below, within, and above normal ranges). Frequency tabulations of the laboratory abnormalities
will be made. A listing of participants with any laboratory results outside the reference ranges will
be provided. A listing of participants with any markedly abnormal laboratory results will also be
provided.
Electrocardiogram
All clinically relevant abnormalities in ECG waveform that are changes from the Screening Visit
S2 readings will be reported (eg, changes in T-wave morphology or the occurrence of U-waves).
The effects on ECG variables may be evaluated by means of descriptive statistics and frequency
tabulations.
Vital Signs
Vital signs including temperature, pulse/heart rate, and blood pressure (systolic and diastolic) will
be summarized over time, using descriptive statistics and/or graphically. The percentage of
participants with values beyond clinically important limits will be summarized.
9.4.5. 
Other Analyses
Biomarker Analyses
Changes in serum biomarkers over time will be summarized. Associations between Week 0 levels
and changes from Week 0 in select markers and clinical response will be explored. Biomarker
analyses will be summarized in separate technical reports.
9.5. 
Interim Analysis
An interim analysis will be performed after a sufficient proportion ofthe participants (to be defined
during the study) have accrued Week 16 CFR data. The scope of the interim analysis will be
developed and documented in a statistical analysis plan. Other interim analyses may be planned
based on specific questions from the medical field. The data from these interim analyses will allow
for assessment of coverage and follow-up of participant types and treatment modalities to
investigate specific research questions.


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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Abbreviations
AE 
Adverse events
ALT  
Alanine aminotransferase
AST  
Aspartate aminotransferase
AUDIT  
Alcohol use disorders identification test
BCG  
Bacillus Calmette-Guérin
BMI 
Body mass index
BSA 
Body surface area
cfPWV  
Carotid-femoral pulse wave velocity
CFR  
Coronary flow reserve
CI 
Confidence interval
COVID-19 
Coronavirus disease 2019
CRF  
Case report form(s) (paper or electronic as appropriate for this study)
CVD  
Cardiovascular disease
DLQI 
Dermatology life quality index
DMC  
Data monitoring committee
DNA  
Deoxyribonucleic acid
EADV  
European Academy of Dermatology and Venereology
ECG  
Electrocardiogram
eDC  
Electronic data capture
EU  
European Union
FMD  
Flow-mediated dilation
FSH  
Follicle stimulating hormone
GC-MS  
Gas chromatography-mass spectrometry
GCP  
Good clinical practice
GLS  
Global longitudinal strain
GPP  
Generalized pustular psoriasis
HADS  
Hospital anxiety and depression scale
HBsAg 
Hepatitis B surface antigen
HBV  
Hepatitis B virus
HCP  
Health care professional
HCV  
Hepatitis C virus
HDL 
High-density lipoproteins
hf-PGA  
Physician’s global assessment of psoriasis on the hands and/or feet
HIV  
human immunodeficiency virus
HPLC  
High performance liquid chromatography
HRT  
Hormonal replacement therapy
hsCRP  
high-sensitivity C-reactive protein
IB  
Investigator’s brochure
IBD  
Inflammatory bowel disease
ICF  
Informed consent form
ICH  
International Conference on Harmonisation
ICMJE 
International Committee of Medical Journal Editors
IEC  
Independent ethics committee
IFU  
Instructions for use
IL 
Interleukin
INR  
International normalized ratio
IRB  
Institutional review board
IWRS  
Interactive web response system
LAD  
Left anterior descending artery
LC-MS  
Liquid chromatography–mass spectrometry
LDL 
Low-density lipoprotein
LV  
Left ventricular
MACE  
Major adverse cardiovascular events
MedDRA  
Medical Dictionary for Regulatory Activities


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MI 
Myocardial infarction
MMRM  
Mixed-effect model repeated measure
MTX  
Methotrexate
NT-proBNP  
N-terminal pro b-type natriuretic peptide
PASI 
Psoriasis area and severity index
PFS  
Prefilled syringe
PPP  
Palmoplantar pustulosis
PPPASI 
Palmoplantar pustulosis area and severity index
PQC  
Product quality complaint
PRO  
Patient-reported outcome(s) (paper or electronic as appropriate for this study)
PsA  
Psoriatic arthritis
PSQI 
Pittsburg sleep quality index
SAE 
Serious adverse events
SC 
Subcutaneous
SD 
Standard deviation
SoA  
Schedule of activities
STE 
Speckle tracking echocardiography
SUSAR  
Suspected unexpected serious adverse reaction
TB  
Tuberculosis
TC 
Total cholesterol
TG 
Triglycerides
TNF  
Tumor necrosis factor
ULN  
Upper limit of normal
VIP  
Vascular inflammation in psoriasis
WBC  
White blood cell
WHO  
World health organization
Definitions of Terms
Electronic source
system
Contains data traditionally maintained in a hospital or clinic record to document medical
care or data recorded in a CRF as determined by the protocol. Data in this system may be
considered source documentation




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Routine
Urinalysis
Dipstick  
Specific gravity  
pH  
Glucose 
Protein  
Blood 
Ketones 
Bilirubin
Urobilinogen  
Nitrite 
Leukocyte esterase 
Sediment (if dipstick result is abnormal)
Red blood cells
White blood cells
Epithelial cells
Crystals
Casts
Bacteria
DNA damage markers
(8-Oxo-7,8-dihydro2'-
desoxyguanosine) Concentration of
oxidative lipid damage [8-Isoprostane]
and Malondialdehyde in plasma
Concentration of antioxidants (Vitamins
C, E).
If dipstick result is abnormal, flow cytometry will be used to measure sediment. In
case of discordance between the dipstick results and the flow cytometric results, the
sediment will be examined microscopically.
Dipstick and flow cytometric analysis of the urine samples will be performed in
parallel, ie, in the same sample at the same time.
Specific gravity, pH, glucose, protein, blood, ketones, bilirubin, and urobilinogen will
be determined using a dipstick. Red blood cells, WBCs, epithelial cells, crystals, casts,
and bacteria will be measured using flow cytometry. If there is discordance between
the dipstick results and the flow cytometric results, the sediment will be examined
microscopically.
Other
Screening Tests
 
Serum and Urine Pregnancy Testing for women of childbearing potential only
 
Nicotine Dipstick
 
TB QuantiFERON Test
 
Serology (HIV antibody, hepatitis B surface antigen [HBsAg], and HCV
antibody)




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10.4. Appendix 4: QuantiFERON®-TB GOLD TESTING
The QuantiFERON®-TB Gold test is one of the interferon-(IFN-) based blood assays for TB
screening (Cellestis, 2009). It utilizes the recently identified M. tuberculosis-specific antigens
ESAT-6 and CFP-10 in the standard format, as well as TB7.7 (p4) in the In-Tube format, to detect
in vitro cell-mediated immune responses in infected individuals. The QuantiFERON®-TB Gold
assay measures the amount of IFN- produced by sensitized T-cells when stimulated with the
synthetic M. tuberculosis-specific antigens. In M. tuberculosis-infected persons, sensitized
T lymphocytes will secrete IFN- in response to stimulation with the M. tuberculosis-specific
antigens and, thus, the QuantiFERON®-TB Gold test should be positive. Because the antigens used
in the test are specific to M. tuberculosis and not found in BCG, the test is not confounded by BCG
vaccination, unlike the tuberculin skin test. However, there is some cross-reactivity with the 3
Mycobacterium species, M. kansasii, M. marinum, and M. szulgai. Thus, a positive test could be
the result of infection with one of these 3 species of Mycobacterium, in the absence of M.
tuberculosis infection.
In a study of the QuantiFERON®-TB Gold test (standard format) in participants with active TB,
sensitivity has been shown to be approximately 89% (Mori et al, 2004). Specificity of the test in
healthy BCG-vaccinated individuals has been demonstrated to be more than 98%. In contrast, the
sensitivity and specificity of the tuberculin skin test was noted to be only about 66% and 35% in a
study of Japanese patients with active TB and healthy BCG-vaccinated young adults, respectively.
However, sensitivity and specificity of the tuberculin skin test depend on the population being
studied, and the tuberculin skin test performs best in healthy young adults who have not been BCG-
vaccinated.
Data from a limited number of published studies examining the performance of the
QuantiFERON®-TB Gold assay in immunosuppressed populations suggest that the sensitivity of
the QuantiFERON®-TB Gold test is better than the tuberculin skin test even in immunosuppressed
patients (Ferrara et al, 2005; Kobashi et al, 2007; Matulis et al, 2008). The ability of IFN--based
tests to detect latent infection has been more difficult to study due to the lack of a gold standard
diagnostic test; however, several TB outbreak studies have demonstrated that the tests correlated
better than the tuberculin skin test with the degree of exposure that contacts had to the index TB
case (Brock et al, 2004; Ewer et al, 2003). In addition, TB contact tracing studies have shown that
patients who had a positive QuantiFERON®-TB Gold test result and were not treated for latent TB
infection were much more likely to develop active TB during longitudinal follow-up than those
who had a positive tuberculin skin test and a negative QuantiFERON®-TB Gold test result
(Higuchi et al, 2007; Diel et al, 2008).
Although the performance of the new IFN--based blood tests for active or latent M. tuberculosis
infection have not been well validated in the immunosuppressed population, experts believe these
new tests will be at least as, if not more, sensitive, and definitely more specific, than the tuberculin
skin test (Barnes, 2004; personal communication, April, 2008 TB Advisory Board).


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Performing the QuantiFERON®-TB Gold Test
The QuantiFERON®-TB Gold test In-Tube format will be provided for this study. The In-Tube
format contains 1 additional M. tuberculosis-specific antigen, TB7.7 (p4), which is thought to
increase the specificity of the test.
To perform the test using the In-Tube format, blood is drawn through standard venipuncture into
supplied tubes that already contain the M. tuberculosis-specific antigens. Approximately 3 tubes
will be needed per participant, each requiring 1 mL of blood. One tube contains the M.
tuberculosis-specific antigens, while the remaining tubes contain positive and negative control
reagents. Thorough mixing of the blood with the antigens is necessary prior to incubation. The
blood is then incubated for 16 to 24 hours at 37C, after which tubes are centrifuged for
approximately 15 minutes at 2000 to 3000 g. Following centrifugation, plasma is harvested from
each tube, frozen, and shipped on dry ice to the central laboratory. The central laboratory will
perform an ELISA to quantify the amount of IFN-present in the plasma using spectrophotometry
and computer software analysis.
The central laboratory will analyze and report results for each participant, and sites will be
informed of the results. Participants who have an indeterminate result should have the test
repeated.
Adherence to Local Guidelines
Local country guidelines for immunocompromised patients should be consulted for acceptable
anti-tuberculosis treatment regimens for latent TB. If no local country guidelines for
immunocompromised patients exist, US guidelines must be followed.
In countries in which the QuantiFERON®-TB Gold test is not considered approved/registered, a
tuberculin skin test is additionally required.


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References
1. 
Barnes PF. Diagnosing latent tuberculosis infection: Turning glitter to gold [editorial]. Amer J Respir Crit Care
Med. 2004;170:5-6.
2. 
Brock I, Weldingh K, Lillebaek T, et al. Comparison of tuberculin skin test and new specific blood test in
tuberculosis contacts. Am J Respir Crit Care Med. 2004;170:65-69.
3. 
Cellestis. QuantiFERON-TB Gold clinicians guide and QuantiFERON-TB Gold In-Tube Method package
insert. Downloaded from www.cellestis.com, February 2009.
4. 
Diel R, Loddenkemper R, Meywald-Walter K, Niemann S, Nienhaus A. Predictive value of a whole blood
IFN-assay for the development of active tuberculosis disease after recent infection with mycobacterium
tuberculosis. Am J Respir Crit Care Med. 2008;177:1164-1170.
5. 
Ewer K, Deeks J, Alvarez L, et al. Comparison of T-cell-based assay with tuberculin skin test for diagnosis of
Mycobacterium tuberculosis infection in a school tuberculosis outbreak. Lancet. 2003;361:1168-73.
6. 
Ferrara G, Losi M, Meacci M, et al. Routine hospital use of a new commercial whole blood interferon-assay
for the diagnosis of tuberculosis infection. Am J Respir Crit Care Med. 2005; 172:631-635.
7. 
Higuchi K, Nobuyuki H, Mori T, Sekiya Y. Use of QuantiFERON-TB Gold to investigate tuberculosis
contacts in a high school. Respirology. 2007;12:88-92.
8. 
Kobashi Y, Mouri K, Obase Y, et al. Clinical evaluation of QuantiFERON-TB-2G test for
immunocompromised patients. Eur Respir J. 2007; 30:945-950.
9. 
Matulis G, Jüni P, Villiger PM, Gadola SD. Detection of latent tuberculosis in immunosuppressed patients with
autoimmune diseases: performance of a Mycobacterium tuberculosis antigen-specific interferon assay.
Rheum Dis. 2008;67:84-90.
10. Mori T, Sakatani M, Yamagishi F, et al. Specific detection of tuberculosis infection: An interferon--based
assay using new antigens. Am J Respir Crit Care Med. 2004;170:59-64.


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10.5. Appendix 5: Investigator Global Assessment
CCI


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10.6. Appendix 6: Psoriasis Area and Severity Index
The PASI is a system used for assessing and grading the severity of psoriatic lesions and their
response to therapy. The PASI produces a numeric score that can range from 0 to 72. The severity
of the disease is calculated as follows.
In the PASI system, the body is divided into 4 regions: the head (h), trunk (t), upper extremities
(u), and lower extremities (l), which account for 10%, 30%, 20%, and 40% of the total BSA,
respectively. Each of these areas is assessed separately for erythema, induration and scaling, which
are each rated on a scale of 0 to 4.
The scoring system for the signs of the disease (erythema, induration, and scaling) is: 0
none, 1
 slight, 2  moderate, 3  severe, and 4  very severe.
The scale for estimating the area of involvement for psoriatic lesions is outlined below.
0  no involvement
1  1% to 9% involvement
2  10% to 29% involvement
3  30% to 49% involvement
4  50% to 69% involvement
5  70% to 89% involvement
6  90% to 100% involvement
To help with the area assessments, the following conventions should be noted:
a. 
The neck is considered part of the head
b. The axillae and groin are part of the trunk
c. 
The buttocks are part of the lower extremities
The PASI formula is:
PASI  0.1 (Eh + Ih + Sh) Ah + 0.3 (Et + It + St) At + 0.2 (Eu + Iu + Su) Au + 0.4 (El + Il + Sl)
Al
Where E  erythema, I  induration, S  scaling, and A  area


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10.7. Appendix 7: Body Surface Area


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10.8. Appendix 8: Dermatology Life Quality Index
CCI


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AY Finlay, GK Khan, April 1992 www.dermatology.org.uk, this must not be copied without the permission of the authors.
CCI










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Form Administration Instructions, References, and Scoring
Form Administration Instructions
The range of values for questions 5 through 10 are all 0 to 3.
Questions 1 through 9 are not allowed to be missing except as noted below. If these questions are
missing, then any scores calculated using missing questions are also missing. Thus it is important to
make sure that all questions 1 through 9 have been answered.
In the event that a range is given for an answer (for example, ‘30 to 60’ is written as the answer to Q2,
minutes to fall asleep), split the difference and enter 45.
Reference
Buysse DJ, Reynolds CF, Monk TH, Berman SR, Kupfer DJ: The Pittsburgh Sleep Quality Index: A new
instrument for psychiatric practice and research. Psychiatry Research 28:193-213, 1989.
Scores –reportable in publications
On May 20, 2005, on the instruction of Dr. Daniel J. Buysse, the scoring of the PSQI was changed to set
the score for Q5J to 0 if either the comment or the value was missing. This may reduce the DISTB score
by 1 point and the PSQI Total Score by 1 point.
PSQIDURAT 
DURATION OF SLEEP
IF Q4 >7, THEN set value to 0
IF Q4 < 7 and >6, THEN set value to 1
IF Q4 < 6 and >5, THEN set value to 2
IF Q4 < 5, THEN set value to 3
Minimum Score = 0 (better); Maximum Score = 3 (worse)
PSQIDISTB  
SLEEP DISTURBANCE
IF Q5b + Q5c + Q5d + Q5e + Q5f + Q5g + Q5h + Q5i + Q5j (IF Q5JCOM is null
or Q5j is null, set the value of Q5j to 0) = 0, THEN set value to 0
IF Q5b + Q5c + Q5d + Q5e + Q5f + Q5g + Q5h + Q5i + Q5j (IF Q5JCOM is null
or Q5j is null, set the value of Q5j to 0) >1 and < 9, THEN set value to 1
IF Q5b + Q5c + Q5d + Q5e + Q5f + Q5g + Q5h + Q5i + Q5j (IF Q5JCOM is null
or Q5j is null, set the value of Q5j to 0) > 9 and < 18, THEN set value to 2
IF Q5b + Q5c + Q5d + Q5e + Q5f + Q5g + Q5h + Q5i + Q5j (IF Q5JCOM is null
or Q5j is null, set the value of Q5j to 0) > 18, THEN set value to 3
Minimum Score = 0 (better); Maximum Score = 3 (worse)
PSQILATEN 
SLEEP LATENCY
First, recode Q2 into Q2new thusly:
IF Q2 >0 and < 15, THEN set value of Q2new to 0
IF Q2 > 15 and < 30, THEN set value of Q2new to 1
IF Q2 > 30 and < 60, THEN set value of Q2new to 2
IF Q2 > 60, THEN set value of Q2new to 3
Next
IF Q5a + Q2new = 0, THEN set value to 0
IF Q5a + Q2new >1 and < 2, THEN set value to 1
IF Q5a + Q2new >3 and < 4, THEN set value to 2
IF Q5a + Q2new >5 and < 6, THEN set value to 3


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Minimum Score = 0 (better); Maximum Score = 3 (worse)
PSQIDAYDYS 
DAY DYSFUNCTION DUE TO SLEEPINESS
IF Q8 + Q9 = 0, THEN set value to 0
IF Q8 + Q9 >1 and < 2, THEN set value to 1
IF Q8 + Q9 >3 and < 4, THEN set value to 2
IF Q8 + Q9 >5 and < 6, THEN set value to 3
Minimum Score = 0 (better); Maximum Score = 3 (worse)
PSQIHSE  
SLEEP EFFICIENCY
Diffsec = Difference in seconds between day and time of day Q1 and day Q3
Diffhour = Absolute value of diffsec / 3600
      newtib =IF diffhour > 24, then newtib = diffhour –24
     IF diffhour < 24, THEN newtib = diffhour
(NOTE, THE ABOVE JUST CALCULATES THE HOURS BETWEEN GNT (Q1)
AND GMT (Q3))
tmphse = (Q4 / newtib) * 100
IF tmphse >85, THEN set value to 0
IF tmphse < 85 and >75, THEN set value to 1
IF tmphse < 75 and >65, THEN set value to 2
IF tmphse < 65, THEN set value to 3
Minimum Score = 0 (better); Maximum Score = 3 (worse)
PSQISLPQUAL  
OVERALL SLEEP QUALITY
Q6
Minimum Score = 0 (better); Maximum Score = 3 (worse)
PSQIMEDS 
NEED MEDS TO SLEEP
Q7
Minimum Score = 0 (better); Maximum Score = 3 (worse)
PSQI 
TOTAL
DURAT + DISTB + LATEN + DAYDYS + HSE + SLPQUAL + MEDS
Minimum Score = 0 (better); Maximum Score = 21 (worse)
Interpretation: TOTAL < 5 associated with good sleep quality
TOTAL > 5 associated with poor sleep quality


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10.10. Appendix 10: Alcohol Consumption Screening AUDIT Questionnaire in
Adults


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10.12. Appendix 12: Regulatory, Ethical, and Study Oversight Considerations
REGULATORY AND ETHICAL CONSIDERATIONS
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the
protocol, current ICH guidelines on Good Clinical Practice (GCP), and applicable regulatory and
country-specific requirements.
Good Clinical Practice is an international ethical and scientific quality standard for designing,
conducting, recording, and reporting studies that involve the participation of human participants.
Compliance with this standard provides public assurance that the rights, safety, and well-being of
study participants are protected, consistent with the principles that originated in the Declaration of
Helsinki, and that the study data are credible.
Protocol Amendments
Neither the investigator nor the Sponsor will modify this protocol without a formal amendment by
the Sponsor. All protocol amendments must be issued by the Sponsor, and signed and dated by the
investigator. Protocol amendments must not be implemented without prior IEC/IRB approval, or
when the relevant competent authority has raised any grounds for non-acceptance, except when
necessary to eliminate immediate hazards to the participants, in which case the amendment must
be promptly submitted to the IEC/IRB and relevant competent authority. Documentation of
amendment approval by the investigator and IEC/IRB must be provided to the Sponsor. When the
change(s) involve only logistic or administrative aspects of the study, the IEC/IRB (where
required) only needs to be notified.
During the course of the study, in situations where a departure from the protocol is unavoidable,
the investigator or other physician in attendance will contact the appropriate Sponsor
representative listed in the Contact Information page(s), which will be provided as a separate
document. Except in emergency situations, this contact should be made before implementing any
departure from the protocol. In all cases, contact with the Sponsor must be made as soon as possible
to discuss the situation and agree on an appropriate course of action. The data recorded in the CRF
and source documents will reflect any departure from the protocol, and the source documents will
describe this departure and the circumstances requiring it.
In case of restrictions and limitations arising from a pandemic, study procedures and assessments
may be executed as detailed in Appendix 15.
Regulatory Approval/Notification
This protocol and any amendment(s) must be submitted to the appropriate regulatory authorities
in each respective country, if applicable. A study may not be initiated until all local regulatory
requirements are met.


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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
 
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)


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 
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 research and for the corresponding ICF must
be obtained from the IEC/IRB. Approval for the protocol can be obtained independent of this
optional research component.
During the study the investigator (or Sponsor where required) will send the following documents
and updates to the IEC/IRB for their review and approval, where appropriate:
 
Protocol amendments (excluding the ones that are purely administrative, with no
consequences for participants, data or study conduct)
 
Revision(s) to ICF and any other written materials to be provided to participants
 
If applicable, new or revised participant recruiting materials approved by the Sponsor
 
Revisions to compensation for study-related injuries or payment to participants for
participation in the study, if applicable
 
New edition(s) of the IB and amendments/addenda
 
Summaries of the status of the study at intervals stipulated in guidelines of the IEC/IRB (at
least annually)
 
Reports of 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


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 
Development Safety Update Report and Line Listings, where applicable
 
Any other documents required by the IEC/IRB
For all protocol amendments (excluding the ones that are purely administrative, with no
consequences for participants, data or study conduct), the amendment and applicable ICF revisions
must be submitted promptly to the IEC/IRB for review and approval before implementation of the
change(s).
At least once a year, the IEC/IRB will be asked to review and reapprove this study, where required.
At the end of the study, the investigator (or Sponsor where required) will notify the IEC/IRB about
the study completion (if applicable, the notification will be submitted through the head of
investigational institution).
Other Ethical Considerations
For study-specific ethical design considerations, refer to Section 4.2.1.
FINANCIAL DISCLOSURE
Investigators and subinvestigators will provide the Sponsor with sufficient, accurate financial
information in accordance with local regulations to allow the Sponsor to submit complete and
accurate financial certification or disclosure statements to the appropriate regulatory authorities.
Investigators are responsible for providing information on financial interests during the course of
the study and for 1 year after completion of the study.
Refer to Required Prestudy Documentation (above) and contracts for details on financial
disclosure.
INFORMED CONSENT PROCESS
Each participant must give written consent according to local requirements after the nature of the
study has been fully explained. The ICF(s) must be signed before performance of any study-related
activity. The ICF(s) that is/are used must be approved by both the Sponsor and by the reviewing
IEC/IRB and be in a language that the participant can read and understand. The informed consent
should be in accordance with principles that originated in the Declaration of Helsinki, current ICH
and GCP guidelines, applicable regulatory requirements, and Sponsor policy.
Before enrollment in the study, the investigator or an authorized member of the study-site
personnel must explain to potential participants the aims, methods, reasonably anticipated benefits,
and potential hazards of the study, and any discomfort participation in the study may entail.
Participants will be informed that their participation is voluntary and that they may withdraw
consent to participate at any time. They will be informed that choosing not to participate will not
affect the care the participant will receive for the treatment of his or her disease. Participants will
be told that alternative treatments are available if they refuse to take part and that such refusal will
not prejudice future treatment. Finally, they will be told that the investigator will maintain a


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participant identification register for the purposes of long-term follow-up if needed and that their
records may be accessed by health authorities and authorized Sponsor personnel without violating
the confidentiality of the participant, to the extent permitted by the applicable law(s) or regulations.
By signing the ICF the participant is authorizing such access. It also denotes that the participant
agrees to allow his or her study physician to recontact the participant for the purpose of obtaining
consent for additional safety evaluations, and subsequent disease-related treatments, if needed.
The participant will be given sufficient time to read the ICF and the opportunity to ask questions.
After this explanation and before entry into the study, consent should be appropriately recorded by
means of the participant's personally dated signature. After having obtained the consent, a copy of
the ICF must be given to the participant.
Participants who are re-screened are 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.
If the participant is unable to read or write, an impartial witness should be present for the entire
informed consent process (which includes reading and explaining all written information) and
should personally date and sign the ICF after the oral consent of the participant is obtained.
DATA PROTECTION
Privacy of Personal Data
The collection and processing of personal data from participants enrolled in this study will be
limited to those data that are necessary to fulfill the objectives of the study.
These data must be collected and processed with adequate precautions to ensure confidentiality
and compliance with applicable data privacy protection laws and regulations. Appropriate
technical and organizational measures to protect the personal data against unauthorized disclosures
or access, accidental or unlawful destruction, or accidental loss or alteration must be put in place.
Sponsor personnel whose responsibilities require access to personal data agree to keep the identity
of participants confidential.
The informed consent obtained from the participant includes explicit consent for the processing of
personal data and for the investigator/institution to allow direct access to his or her original medical
records (source data/documents) for study-related monitoring, audit, IEC/IRB review, and
regulatory inspection. This consent also addresses the transfer of the data to other entities and to
other countries.
The participant has the right to request through the investigator access to his or her personal data
and the right to request rectification of any data that are not correct or complete. Reasonable steps


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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.
The Sponsor cannot make decisions as to the significance of any findings resulting from
exploratory research. Therefore, exploratory research data will not be returned to participants or
investigators, unless required by law or local regulations. Privacy and confidentiality of data
generated in the future on stored samples will be protected by the same standards applicable to all
other clinical data.
LONG-TERM RETENTION OF SAMPLES FOR ADDITIONAL FUTURE RESEARCH
Samples collected in this study may be stored for up to 15 years (or according to local regulations)
for additional research. Samples will only be used to understand guselkumab, to understand plaque
psoriasis, to understand differential intervention responders, and to develop tests/assays related to
guselkumab and plaque psoriasis. 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.
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 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 per protocol. Recruitment
performance or specific expertise related to the nature and the key assessment parameters of the
study will be used to determine a coordinating investigator for the study. Results of
pharmacogenomic or exploratory biomarker analyses performed after the Clinical Study Report
has been issued will be reported in a separate report and will not require a revision of the Clinical
Study Report.


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


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Guidelines for CRF completion will be provided and reviewed with study-site personnel before
the start of the study. The Sponsor will review 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
Case report forms are prepared and provided by the Sponsor for each participant in electronic
format. All data relating to the study must be recorded in 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.
The study data will be transcribed by study-site personnel from the source documents onto an
electronic CRF, if applicable. Study-specific data will be transmitted in a secure manner to the
Sponsor.
If necessary, queries will be generated in the 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.
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 recorded directly into the CRF and will be considered source data :
 Race
 Blood pressure and pulse/heart rate


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 Height and weight
 Details of physical examination
The minimum source documentation requirements for Section 5.1, Inclusion Criteria and
Section 5.2, Exclusion Criteria that specify a need for documented medical history are as follows:
 Referral letter from treating physician or
 Complete history of medical notes at the site
 Discharge summaries
Inclusion and exclusion criteria not requiring documented medical history must be verified at a
minimum by participant interview or other protocol-required assessment (eg, physical
examination, laboratory assessment) and documented in the source documents.
An eSource system may be utilized, which contains data traditionally maintained in a hospital or
clinic record to document medical care (eg, electronic source documents) as well as the clinical
study-specific data fields as determined by the protocol. This data is electronically extracted for
use by the Sponsor. If eSource is utilized, references made to the 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 (risk-based, 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 will 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 ofverifying
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 and facilitate remote source data verification, where applicable.
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.


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If it becomes necessary for the Sponsor or the appropriate regulatory authority to review any
documentation relating to this study, the investigator/institution must permit access to such reports.
STUDY AND SITE START AND CLOSURE
First Act of Recruitment
The first site open is considered the first act of recruitment and it becomes the study start date.
Study Termination
The Sponsor reserves the right to close the study-site or terminate the study at any time for any
reason at the sole discretion of the Sponsor. Study sites will be closed upon study completion. A
study-site is considered closed when all required documents and study supplies have been collected
and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable cause and
sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study-site by the Sponsor or investigator may include but are not
limited to:
 Failure of the investigator to comply with the protocol, the requirements of the IEC/IRB or
local health authorities, the Sponsor's procedures, or GCP guidelines
 Inadequate recruitment of participants by the investigator
 Discontinuation of further study intervention development
 The study outcomes do not pass the criteria for futility analysis


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10.13. Appendix 13: Adverse Events: Definitions and Procedures for Recording,
Evaluating, Follow-up, and Reporting
ADVERSE EVENT DEFINITIONS AND CLASSIFICATIONS
Adverse Event
An adverse event is any untoward medical occurrence in a clinical study participant administered
a medicinal (investigational or non-investigational) product. An adverse event does not necessarily
have a causal relationship with the intervention. An adverse event can therefore be any unfavorable
and unintended sign (including an abnormal finding), symptom, or disease temporally associated
with the use of a medicinal (investigational or non-investigational) product, whether or not related
to that medicinal (investigational or non-investigational) product. (Definition per International
Conference on Harmonisation [ICH])
This includes any occurrence that is new in onset or aggravated in severity or frequency from the
baseline condition, or abnormal results of diagnostic procedures, including laboratory test
abnormalities.
Note: The Sponsor collects AEs starting with the signing of the ICF (refer to All Adverse Events
under Section 8.3.1, Time Period and Frequency for Collecting Adverse Events and Serious
Adverse Events Information, for time of last adverse event recording).
For combination products with a device constituent, AEs include those resulting from insufficient
or inadequate instructions for use, deployment, implantation, installation, or operation, or any
malfunction of the device. It includes any adverse event resulting from use error or from intentional
misuse of the investigational device.
Serious Adverse Event
A serious adverse event based on ICH and EU Guidelines on Pharmacovigilance for Medicinal
Products for Human Use is any untoward medical occurrence that at any dose:
 
Results in death
 
Is life-threatening
(The participant was at risk of death at the time of the event. It does not refer to an event that
hypothetically might have caused death if it were more severe)
 
Requires inpatient hospitalization or prolongation of existing hospitalization
 
Results in persistent or significant disability/incapacity
 
Is a congenital anomaly/birth defect
 
Is a suspected transmission of any infectious agent via a medicinal product
 
Is Medically Important*
*Medical and scientific judgment should be exercised in deciding whether expedited reporting is
also appropriate in other situations, such as important medical events that may not be immediately
life-threatening or result in death or hospitalization but may jeopardize the participant or may


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require intervention to prevent one of the other outcomes listed in the definition above. These
should usually be considered serious.
If a serious and unexpected adverse event occurs for which there is evidence suggesting a causal
relationship between the study intervention and the event (eg, death from anaphylaxis), the event
must be reported as a serious and unexpected suspected adverse reaction even if it is a component
of the study endpoint (eg, all-cause mortality).
For combination products with a device constituent, 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.
Unlisted (Unexpected) Adverse Event/Reference Safety Information
An adverse event is considered unlisted if the nature or severity is not consistent with the applicable
product reference safety information. For guselkumab, the expectedness of an adverse event will
be determined by whether or not it is listed in the IB.
ATTRIBUTION DEFINITIONS
Assessment of Causality
The causal relationship to study treatment is determined by the investigator. The following
selection should be used to assess all AEs.
Related
There is a reasonable causal relationship between study treatment administration and the AE.
Not Related
There is not a reasonable causal relationship between study treatment administration and the AE.
The term "reasonable causal relationship" means there is evidence to support a causal relationship.
SEVERITY CRITERIA
An assessment of severity grade will be made using the following general categorical descriptors:
Mild: Awareness of symptoms that are easily tolerated, causing minimal discomfort and not
interfering with everyday activities.
Moderate: Sufficient discomfort is present to cause interference with normal activity.
Severe: Extreme distress, causing significant impairment of functioning or incapacitation.
Prevents normal everyday activities.


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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 in an interventional studythat may require
expedited reporting or safety evaluation include, but are not limited to:
 
Overdose of a Sponsor study intervention
 
Suspected abuse/misuse of a Sponsor study intervention
 
Accidental or occupational exposure to a Sponsor study intervention
 
Any failure of expected pharmacologic action (ie, lack of effect) of a Sponsor study
intervention
 
Unexpected therapeutic or clinical benefit from use of a Sponsor study intervention
 
Suspected transmission of any infectious agent via administration of a Johnson & Johnson
medicinal product
 
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 CRF, where possible. Any special reporting
situation that meets the criteria of a serious adverse event should be recorded on the serious adverse
event page of the CRF.
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 CRF. 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 CRF 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


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 
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
Serious Adverse Events
All SAEs that have not resolved by the end of the study, or that have not resolved upon
discontinuation of the participant's participation in the study, must be followed until any of the
following occurs:
 
The event resolves
 
The event stabilizes
 
The event returns to baseline, if a baseline value/status is available
 
The event can be attributed to agents other than the study intervention or to factors unrelated
to study conduct
 
It becomes unlikely that any additional information can be obtained (participant or health care
practitioner refusal to provide additional information, lost to follow-up after demonstration of
due diligence with follow-up efforts)
Suspected transmission of an infectious agent by a medicinal product will be reported as a serious
adverse event. Any event requiring hospitalization (or prolongation of hospitalization) that occurs
during the course of a participant's participation in a study must be reported as a serious adverse
event, except hospitalizations for the following:
 
Hospitalizations not intended to treat an acute illness or adverse event (eg, social reasons such
as pending placement in long-term care facility).
 
Surgery or procedure planned before entry into the study (must be documented in the 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 serious adverse event.
 
For convenience the investigator may choose to hospitalize the participant for the duration of
the intervention period.
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
serious adverse event.
CONTACTING SPONSOR REGARDING SAFETY
The names (and corresponding telephone numbers) of the individuals who should be contacted
regarding safety issues or questions regarding the study are listed in the Contact Information
page(s), which will be provided as a separate document.


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PRODUCT QUALITY COMPLAINT HANDLING
A product quality complaint (PQC) is defined as any suspicion of a product defect related to
manufacturing, labeling, or packaging, ie, any dissatisfaction relative to the identity, quality,
durability, or reliability of a product, including its labeling or package integrity. A PQC may have
an impact on the safety and efficacy of the product. Timely, accurate, and complete reporting and
analysis of PQC information from studies are crucial for the protection of participants,
investigators, and the Sponsor, and are mandated by regulatory agencies worldwide. The Sponsor
has established procedures in conformity with regulatory requirements worldwide to ensure
appropriate reporting of PQC information; all studies conducted by the Sponsor or its affiliates
will be conducted in accordance with those procedures.
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.
If the defect is combined with a serious adverse event, the study-site personnel must report the
PQC to the Sponsor according to the serious adverse event reporting timelines (refer to
Section 8.3.1, Time Period and Frequency for Collecting Adverse Event and Serious Adverse
Event Information). A sample of the suspected product should be maintained for further
investigation if requested by the Sponsor.
Contacting Sponsor Regarding Product Quality
The names (and corresponding telephone numbers) of the individuals who should be contacted
regarding product quality issues are listed in the Contact Information page(s), which will be
provided as a separate document.


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10.14. Appendix 14: Contraceptive and Barrier Guidance and Collection of
Pregnancy Information
Participants must follow contraceptive measures as outlined in Section 5.1, Inclusion Criteria.
Pregnancy information will be collected and reported as noted in Section 8.3.4, Pregnancy and
Appendix 13, Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow-up,
and Reporting.
Definitions
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming postmenopausal unless
permanently sterile (see below).
Woman Not of Childbearing Potential
 
premenarchal
A premenarchal state is one in which menarche has not yet occurred.
 
postmenopausal
A postmenopausal state is defined as no menses for 12 months without an alternative medical
cause. A high follicle stimulating hormone (FSH) level (>40 IU/L or mIU/mL) in the
postmenopausal range may be used to confirm a postmenopausal state in women not using
hormonal contraception or hormonal replacement therapy (HRT), however in the absence of
12 months 
of 
amenorrhea, 
a 
single 
FSH 
measurement 
is 
insufficient.
If there is a question about menopausal status in women on HRT, the woman will be required
to use one of the non-estrogen-containing hormonal highly effective contraceptive methods if
she wishes to continue HRT during the study.
 
permanently sterile
Permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal
occlusion/ligation procedures, and bilateral oophorectomy.
Note: If the childbearing potential changes after start of the study (eg, a premenarchal woman
experiences menarche) or the risk of pregnancy changes (eg, a woman who is not heterosexually
active becomes active), a woman must begin a highly effective method of contraception, as
described throughout the inclusion criteria.
If reproductive status is questionable, additional evaluation should be considered.
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 STUDYINCLUDE:
USER-INDEPENDENT
Highly Effective Methods That Are User-Independent Failure rate of <1% per year when used
consistently and correctly
 Implantable progestogen-only hormone contraception associated with inhibition of ovulationb
 Intrauterine device (IUD)
 Intrauterine hormone-releasing system (IUS)
 Bilateral tubal occlusion
 Vasectomized partner
(Vasectomized partner is a highly effective contraceptive method provided that the partner is the
sole sexual partner of the woman of childbearing potential and the absence of sperm has been
confirmed. If not, additional highly effective method of contraception should be used.
Spermatogenesis cycle is approximately 74days.)
USER DEPENDENT
Highly Effective Methods That Are User Dependent Failure rate of <1% per year when used
consistently and correctly.
 4
 Progestogen-only hormone contraception associated with inhibition of ovulationb
 oral
 injectable
 Sexual abstinence
(Sexual abstinence is considered a highly effective method only if defined as refraining from
heterosexual intercourse during the entire period of risk associated with the study intervention.
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study
and the preferred and usual lifestyle of the participant.)
NOT ALLOWED AS SOLE METHOD OF CONTRACEPTION DURING THE STUDY (not
considered to be highly effective - failure rate of 1% per year)
 Progestogen-only oral hormonal contraception where inhibition of ovulation is not the primary
mode of action.
 Male or female condom with or without spermicidec
 Cap, diaphragm, or sponge with spermicide
 A combination of male condom with either cap, diaphragm, or sponge with spermicide (double-
barrier methods)c
 Periodic abstinence (calendar, symptothermal, post-ovulation methods)
 Withdrawal (coitus-interruptus)
 Spermicides alone
 Lactational amenorrhea method (LAM)
a) Typical use failure rates may differ from those when used consistently and correctly. Use should be
consistent with local regulations regarding the use of contraceptive methods for participants in
clinical studies.
b) Hormonal contraception may be susceptible to interaction with the study intervention, which may
reduce the efficacy of the contraceptive method. In addition, consider if the hormonal contraception
may interact with the study intervention.
c) Male condom and female condom should not be used together (due to risk of failure with friction).


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Pregnancy During the Study
A female 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.
Because the effect of the study intervention on sperm is unknown, pregnancies in partners of male
participants included in the study will be reported. A male study participant is not required to
discontinue study intervention if their partner becomes pregnant during the study.
Pregnancy Testing
A woman of childbearing potential must have a negative serum pregnancy test at screening and a
negative urine pregnancy test at all dosing visits prior to administration of study intervention.
Additional serum or urine pregnancy tests may be performed, as determined necessary by the
investigator or required by local regulation, to establish the absence of pregnancy at any time
during the participation in the study.


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10.15. Appendix 15: Guidance on Study Conduct During aPandemic
It is recognized that a pandemic situation (eg, Coronavirus Disease 2019 [COVID-19], or other)
may have an impact on the conduct of this clinical study due to, for example: self-
isolation/quarantine by participants and/or study-site personnel; travel restrictions and/or limited
access to public places, including hospitals; and study-site personnel being reassigned to critical
tasks.
In alignment with health authority guidance, the Sponsor is providing options for study-related
participant management in the event of disruption to the conduct of the study. These
recommendations do not supersede any local or government requirements or the clinical judgment
of the investigator to protect the health and well-being of participants and site-staff. If, at any time,
a participant’s safety is considered to be at risk, study intervention will be discontinued, and
follow-up will be conducted.
GENERAL GUIDANCE
Scheduled visits that cannot be conducted in person at a study-site will be performed
remotely/virtually to the extent possible or may be delayed until such time that on-site visits can
be resumed. At each contact, participants will be interviewed to collect safety data. Participants
will also be questioned regarding their general health status.
Every effort should be made to adhere to protocol-specified assessments for participants on study
intervention, including follow-up. Modifications to protocol-required assessments may be
permitted after consultation between the participant and investigator, and with the agreement of
the Sponsor. Missed assessments/visits will be captured in the clinical trial management system
for protocol deviations. Discontinuations of study interventions and withdrawal from the study
should be documented with the appropriate prefix (eg, “COVID-19-related” or other in accordance
with Sponsor recommendations) in the case report form.
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 a pandemic infection, the investigator should contact the
Sponsor’s responsible medical officer to discuss plans for study intervention and follow-up.
Modifications made to the study conduct as a result of the pandemic should be summarized in the
Clinical Study Report.


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GUIDANCE SPECIFIC TO THIS PROTOCOL:
These emergency provisions are meant to ensure the safety of participants on study while site
capabilities are compromised by pandemic restrictions. As restrictions are lifted, sites should revert
to original protocol conduct as soon as feasible.
Enrollment of new participants may be halted at the Sponsor’s discretion and restarted once the
situation permits. The investigator’s assessment of the risks versus benefit, depending on the
situation at their particular site and the ability to monitor the safety of participants must be
considered when restarting enrollment at a specific site.
The following provisions are being implemented by the Sponsor with respect to the following
protocol mandated procedures to mitigate the impact of a pandemic:
1. Study intervention
2. Management of discontinuations and withdrawals due to a pandemic
3. Options for efficacy and other assessments
4. Options for safety assessments
5. Handling of missed assessments, visits or doses
6. Management of participants with COVID-19 infection
7. Statistical considerations
1. 
Study Intervention
a. Study Intervention Administration: Home-or Self-administration
Study intervention should be continued if, in the assessment of the investigator, it does not result
in risk to the participant. Remote medical consultation and alternatives to study medication
dispensing, administration, and clinical safety laboratory assessments (including home health
nursing) will allow continued study participation for participants in this study. In cases where site
visits are not possible under the restrictions and limitations due to a pandemic, participants who
have adequate experience and have been trained how to self-inject may self-administer
subcutaneous (SC) study intervention outside a study-site (eg, at home) up to the time when
pandemic-related restrictions are lifted, and site visits can be resumed. Participants must self-
administer the study intervention in compliance with the Instructions for Use (IFU) document at
the times instructed by the investigator. Site-staff will contact the participants by phone prior to,
and 30 minutes after the administration of the study intervention for evaluation of AEs. The
study-intervention must be self-administered only on completion of the phone contact with the
site-staff.
Study-site personnel will instruct participants on how to store study intervention for at-home use,
and disposal of used syringes. For each administration of study intervention, the time and date of
injection, whether study intervention was self-administered, and if so, whether SC administration
was complete will be recorded in the study participant drug administration card.


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b. Preparation/Handling/Storage/Accountability
In case site visits are not possible due to the restrictions arising from a pandemic, any participant
who will be self-administering study intervention outside of a study-site will receive detailed
instructions on how to store study intervention, disposal of used syringes, and handling of unused
study material. Participants will also receive a sharps container to dispose of used syringes and
will be instructed to return the sharps container and all unused cartons with syringes.
Participants will maintain a record of the time and date of study intervention administrations in the
study participant drug administration cards which will be shipped in advance to the participants.
Study-site personnel will utilize the study participant drug administration card to ensure
compliance and document at-home study intervention administrations in the CRF.
c. Notes on Shipment of Study Intervention to Participants
If it is necessary to ship the study intervention directly to study participants, shipment by the
study-site itself is preferred under this exception due to a pandemic. Shipment should be made in
a manner that allows tracking of both transport and delivery. The participant should acknowledge
receipt of the shipment to the site (eg, by returning a dated and signed receipt form).
In case adequate shipment by the study-site is not possible (for example, owing to capacity
limitations, logistics, or special transport conditions for the study intervention), direct transport by
the Sponsor may be accepted in justified exceptional cases, provided that the Sponsor appoints a
suitably qualified service provider as trustee. Both the transport and handover conditions for study
intervention should be part of the contractual arrangements, so that pharmaceutical drug safety of
study intervention as well as protection of the privacy and personal data of participants are
adequately safeguarded. The study intervention must be delivered directly to the participant or a
person authorized by the participant, and must not be given to neighbors or deposited at a storage
location. Written confirmation of dose and dose regimens by the investigator should also be
obtained prior to shipment.
The personnel of the service provider in charge of the transport should be trained and instructed
accordingly. As personal data are transferred to the service provider, this requires a contract of
assignment with the Sponsor or legal representative.
For direct shipment of study intervention to participants, instructions on storage and return of used
and unused study intervention should be provided to participants. When shipped by study sites,
the receipt, consumption and return of study intervention must be documented in a form that allows
the study-site to meet its documentation requirements (ie, drug accountability), as defined in ICH
GCP 4.6.3.
d. Discontinuation of Study Intervention
If at any time the safety of a participant is considered to be at risk, study intervention will be
temporarily or permanently discontinued, while every effort should be made to maintain follow-up
on study.


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The benefit of continuing study treatment should be considered by the investigator for each
individual participant, considering the potential impact of reduced direct clinical supervision on a
participant’s safety. A temporary interruption of study intervention might be considered based on
investigator´s discretion and documented.
Discontinuations of study interventions due to pandemic-related reasons should be documented
with a prefix (eg, “COVID-19-related” or in accordance with Sponsor recommendations) in the
CRF.
2. 
Management of Discontinuations and Withdrawals due to a Pandemic
Withdrawal from the study due to pandemic-related reasons should be documented with a prefix
(eg, “COVID-19-related” or in accordance with Sponsor recommendations) in the CRF. Study
intervention assigned to the withdrawn participant may not be assigned to another participant. If
the sample size is not achieved due to pandemic-related reasons or other emergency situations,
enrollment of additional participants will be considered by the Sponsor.
3. 
Options for Efficacyand Other Assessments
To safely maintain participants on study treatment while site capabilities are compromised by
pandemic or other emergency restrictions, participants may have tele-health visits (conducted via
phone or video conversation per local regulation) until such time that on-site visits can be resumed.
Normal study procedures should be followed for the applicable visit as closely as possible,
however it is recognized that remote visits may be limited to the collection of the following data:
 
Concomitant therapy checks
 
PROs
Patient-reported outcomes (PRO) questionnaires in paper format may be shipped to participants
along with instructions for completion. The PROs must be completed on the day of the scheduled
visit prior to administration of the study intervention and any tests, procedures or consultations
and sent to the investigator by appropriate means per Sponsor instructions.
Actual dates of assessments will be recorded by the participants and transcribed to the CRF. Missed
assessments/visits will be captured in the clinical trial management system for protocol deviations.
If assessments are not possible as outlined in the Schedule of Activities, missed assessments should
be documented as a deviation related to the pandemic and be made up as soon as possible.
4. 
Options for Safety Assessments
All efforts should be done to perform the following safety assessments, when applicable:
 
Vital signs
 
Weight
 
Early Detection of Active Tuberculosis (per protocol Section 8.2.5)


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 
Urine pregnancy testing
 
Safety assessments related to study intervention administration, including injection-site
reactions evaluation
 
Clinical Safety Laboratory Assessments (including through home collection of samples or at
certified local laboratory, where possible)
At each contact/remote visit, participants will be interviewed to collect safety data per the list
above. At drug administration time-points, site-staff will contact the participants by phone prior
to, and 30 minutes after the administration of the study intervention  (when done at home) for
evaluation of AEs including injection-site reactions.
In cases where participants receive SC injections outside the study-site during the treatment period,
participants are requested to contact their treating physician as soon as they experience any
untoward medical occurrence. The treating physician should consider reporting any AEs.
Home testing may be employed for urine pregnancy tests. The urine pregnancy test will be shipped
in advance to the participants. For women of childbearing potential, a negative pregnancy test must
be recorded on the study participant drug administration card before self-administering the study
intervention.
Clinical laboratory safety monitoring may be performed using home collection of samples or at a
certified local laboratory rather than at the central laboratory. A copy of the external laboratory
report should be reviewed by the investigator and retained, along with reference ranges, for source
documentation and captured in the CRF.
5. 
Handling of Missed Assessments/Visits/Doses
Relevant study data elements impacted by a pandemic or other emergency situations should be
documented (eg, “COVID-19-related” or in accordance with Sponsor recommendations) in CRFs
and/or other study systems, as directed by Sponsor guidance; these may include
missed/delayed/modified study visits/assessments/dosing, and instances where temporary
measures such as those above are implemented.
6. 
Management of Participants Infected With SARS-CoV-2
If a participant develops SARS-CoV-2 infection or related disease, the investigator should contact
the Sponsor to discuss plans for study intervention and follow-up. An interruption of study
treatment should be considered by the investigator, depending on symptoms and concomitant
medication used for the treatment of COVID-19. Treatment must be interrupted if prohibited
medication is used. Standard adverse event and serious adverse event reporting requirements
apply.
When a participant for whom study treatment has been interrupted recovers from suspected or
confirmed SARS-CoV-2 infection or related disease and all toxicities improve to Grade ≤1, the
investigator should discuss with the Sponsor about resuming study treatment.


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Consenting and re-consenting of participants will be performed as applicable for the measures
taken (including remote consenting by phone or video consultation) and according to local
guidance for informed consent applicable during the COVID-19 pandemic.
7. 
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 detailed
in the protocol.
The Sponsor will evaluate the totality of impact of the restrictions and limitations arising from a
pandemic on collection of key study data and additional data analyses will be outlined in the
Statistical Analysis Plan(s).
In line with the protocol Section 8.9.2. the sample size may be further revised to compensate for
major protocol deviations during a pandemic which could potentially impact the primary endpoint.
The new sample size will also account for any future dropouts.
Note: In case of emergency situations where the recommendations specified in this protocol
are insufficient, the investigator or site-staff are instructed to follow local guidelines and
recommendations, or contact the Sponsor for guidance.


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11. 
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42. Makavos G, Ikonomidis I, Andreadou I, et al. Effects of interleukin 17A inhibition on myocardial deformation
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opportunities. J Clin Invest. 2004 Jun;113(12):1664-1675.
46. Pathirana D, Ormerod AD, Saiag P, et al. European S3-guidelines on the systemic treatment of psoriasis
vulgaris. J Eur Acad Dermatol Venereol. 2009 Oct;23 Suppl 2:1-70.
47. Petretta M, Acampa W, Zampella E, et al. Imaging techniques for assessment of coronary flow reserve.
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48. Pietrzak A, Bartosinska J, Blaszczyk R, et al. Increased serum level of N-terminal Pro-B-type natriuretic
peptide as a possible biomarker of cardiovascular risk in psoriatic patients. J Eur Acad Dermatol Venereol.
2015;29(5):1010-1014. doi:10.1111/jdv.12528
49. Pries AR, Habazettl H, Ambrosio G, et al. A review of methods for assessment of coronary microvascular
disease in both clinical and experimental settings. Cardiovasc Res. 2008 Nov 1;80(2):165-174.


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50. Rapp SR, Feldman SR, Exum ML, et al. Psoriasis causes as much disability as other major medical diseases. J
Am Acad Dermatol. 1999 Sep;41(3 Pt 1):401-407.
51. Ridker PM, MacFadyen JG, Everett BM, et al. Relationship of C-reactive protein reduction to cardiovascular
event reduction following treatment with canakinumab: a secondary analysis from the CANTOS randomised
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rates of atherosclerotic events and all-cause mortality: analyses from the Canakinumab Anti-Inflammatory
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coronary computed tomography angiography. Circ Cardiovasc Imaging. 2015 Jul;8(7):e003316.
54. Shahidi-Dadras M, Niknezhad N, Niknejad N, et al. Can serum level of N-terminal pro B-type natriuretic
peptide be used in patients with psoriasis as a predictor of cardiovascular disease?. Dermatol Ther.
2019;32(3):e12865. doi:10.1111/dth.12865
55. Smith CH, Anstey AV, Barker JN, et al. British Association of Dermatologists' guidelines for biologic
interventions for psoriasis 2009. Br J Dermatol. 2009 Nov;161(5):987-1019.
56. Raitakari OT, Celermajer DS. Flow-mediated dilatation. Br J Clin Pharmacol. 2000 Nov;50(5):397-404.
57. Taqueti VR, Di Carli MF. Coronary microvascular disease pathogenic mechanisms and therapeutic options:
JACC State-of-the-Art Review. J Am Coll Cardiol. 2018 Nov 27;72(21):2625-2641.
58. Terui T, Kobayashi S, Okubo Y, Murakami M, Hirose K, Kubo H. Efficacy and Safety of Guselkumab, an
Anti–interleukin 23 Monoclonal Antibody, for Palmoplantar Pustulosis: A Randomized Clinical Trial. JAMA
Dermatol. 2018;154(3):309–316. doi:10.1001/jamadermatol.2017.5937
59. Thondapu V, Bourantas CV, Foin N, Jang IK, Serruys PW, Barlis P. Biomechanical stress in coronary
atherosclerosis: emerging insights from computational modelling. Eur Heart J. 2017 Jan 7;38(2):81-92.
60. von Stebut E, Reich K, Thaçi D, et al. Impact of Secukinumab on endothelial dysfunction and other
cardiovascular disease parameters in psoriasis patients over 52 weeks. J Invest Dermatol. 2019
May;139(5):1054-1062.
61. World Health Organisation global report on psoriasis
https://apps.who.int/iris/bitstream/handle/10665/204417/9789241565189 eng.pdf.psoriasis;jsessionid=352D8
A96C9AC34EA9CBA35F2B39195E4?sequence=1 Accessed October 2019.
62. Zigmond AS, Snaith RP. The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand 1983;67:361–370.


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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 Pharmaceutica NV
Signature: 
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
 
15-May-2022
08:27:43
(GMT)
Document Approval
PPD

SAP_001.pdf: 
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 21 July 2023
Janssen Research & Development
Statistical Analysis Plan
A Phase 4, Interventional, Single-arm, Open-label Study Evaluating the Effect of
Guselkumab on Cardiovascular Risk Surrogate Markers in Participants with Moderate to
Severe Plaque Psoriasis
Protocol CNTO1959PSO4015; Phase 4
CNTO1959  (guselkumab)
Status:
Approved
Date:
21 July 2023
Prepared by:
ClinChoice
Document No.: EDMS-RIM-1094465, 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.
NCT05125679


CNTO1959  (guselkumab)
Statistical Analysis Plan CNTO1959PSO4015
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Status: Approved, Date: 21 July 2023
TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
VERSION HISTORY..................................................................................................................................... 4
1.
INTRODUCTION.................................................................................................................................. 5
1.1.
Objectives and Endpoints ................................................................................................................ 5
1.2.
Study Design.................................................................................................................................... 6
2.
STATISTICAL HYPOTHESES............................................................................................................ 7
3.
SAMPLE SIZE DETERMINATION...................................................................................................... 7
4.
POPULATIONS (ANALYSIS SETS) FOR ANALYSIS....................................................................... 8
5.
STATISTICAL ANALYSES................................................................................................................. 8
5.1.
General Considerations ................................................................................................................... 8
5.1.1.
Visit Windows ............................................................................................................................... 9
5.2.
Participant Dispositions.................................................................................................................. 11
5.3.
Primary Endpoint Analysis ............................................................................................................. 12
5.3.1.
Definition of Endpoint.................................................................................................................. 12
5.3.1.1.
Coronary flow reserve (CFR)................................................................................................... 12
5.3.2.
Estimand..................................................................................................................................... 13
5.3.3.
Analysis Methods........................................................................................................................ 14
5.3.3.1.
Main Estimator (Analysis) for the Primary Estimand............................................................... 14
5.4.
Secondary Endpoint(s) Analysis .................................................................................................... 14
5.4.1.
Key Confirmatory Secondary Endpoint(s) .................................................................................. 14
5.4.1.1.
Definition of Endpoint(s) .......................................................................................................... 14
5.4.1.1.1.
Global Longitudinal Strain (GLS) for Left Ventricular Function............................................ 15
5.4.1.1.2.
Carotid-femoral Pulse Wave Velocity (cf-PWV)................................................................... 15
5.4.1.2
Estimand..................................................................................................................................... 15
5.4.1.3
Analysis Methods........................................................................................................................ 16
5.5.
Tertiary/Exploratory Endpoint(s) Analysis:..................................................................................... 17
5.5.1.
Psoriasis Area and Severity Index.............................................................................................. 17
5.5.2.
Body Surface Area...................................................................................................................... 18
5.5.3.
Dermatology Life Quality Index .................................................................................................. 19
5.5.4.
Investigator’s Global Assessment .............................................................................................. 19
5.5.5.
Pittsburg Sleep Quality Index ..................................................................................................... 20
5.5.6.
Alcohol Use Disorders Identification Test................................................................................... 22
5.5.7.
The Hospital Anxiety and Depression Scale .............................................................................. 23
5.6.
Other Safety Analyses ................................................................................................................... 23
5.6.1.
Extent of Exposure ..................................................................................................................... 23
5.6.2.
Adverse Events........................................................................................................................... 24
5.6.2.1.
Imputation Rules for Missing Adverse Event Date/Time of Onset .......................................... 25
5.6.2.1.1.
Treatment-emergent AEs..................................................................................................... 25
5.6.2.1.2.
Imputation Rules .................................................................................................................. 25
5.6.3.
Additional Safety Assessments (if applicable)............................................................................ 27
5.6.3.1.
Clinical Laboratory Tests......................................................................................................... 27
5.6.3.2.
Vital Signs and Physical Examination Findings....................................................................... 28
5.6.3.3.
Electrocardiogram ................................................................................................................... 28
5.6.3.4.
Other Safety Parameters......................................................................................................... 28
5.7.
Other Analyses............................................................................................................................... 29
5.7.1.
Pharmacokinetics ....................................................................................................................... 29
5.7.2.
Immunogenicity........................................................................................................................... 29
5.7.3.
Pharmacodynamics .................................................................................................................... 29
5.7.4.
Pharmacokinetic/Pharmacodynamic Relationships ................................................................... 29


CNTO1959  (guselkumab)
Statistical Analysis Plan CNTO1959PSO4015
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Status: Approved, Date: 21 July 2023
5.7.5.
Biomarkers.................................................................................................................................. 29
5.7.6.
Health Economics....................................................................................................................... 29
5.7.7.
Other Variables and/or Parameters............................................................................................ 29
5.7.8.
Definition of Subgroups .............................................................................................................. 29
5.8.
Interim Analyses............................................................................................................................. 29
5.8.1.
Data Monitoring Committee (DMC) or Other Review Board ...................................................... 29
6.
SUPPORTING DOCUMENTATION .................................................................................................. 30
6.1.
Appendix 1 List of Abbreviations.................................................................................................... 30
6.2.
Appendix 2 Changes to Protocol-Planned Analyses ..................................................................... 31
6.3.
Appendix 3 Demographics and Baseline Characteristics.............................................................. 33
6.4.
Appendix 4 Protocol Deviations ..................................................................................................... 34
6.5.
Appendix 5 Prior and Concomitant Medications............................................................................ 35
6.6.
Appendix 6 Medical History ........................................................................................................... 36
6.7.
Appendix 7 Intervention Compliance ............................................................................................. 37
6.8.
Appendix 8 Adverse Events of Special Interest............................................................................. 38
6.9.
Appendix 9 Medications of Special Interest................................................................................... 39
6.10.
Appendix 10 Laboratory Toxicity Grading...................................................................................... 40
6.11.
Appendix 11 Potential Risks due to Study Procedure (Adenosine Injection). ............................... 46
7.
REFERENCES................................................................................................................................... 47


CNTO1959  (guselkumab)
Statistical Analysis Plan CNTO1959PSO4015
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Status: Approved, Date: 21 July 2023
VERSION HISTORY
Table 1 – SAP Version History Summary
SAP Version
Approval Date
Change
Rationale
1.0
21 Jul 2023
Not Applicable
Initial release


CNTO1959  (guselkumab)
Statistical Analysis Plan CNTO1959PSO4015
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Status: Approved, Date: 21 July 2023
1.
INTRODUCTION
This statistical analysis plan (SAP) contains the definitions of analysis sets, key derived variables,
and statistical methods to evaluate the safety and efficacy of guselkumab in adult participants with
moderate to severe plaque psoriasis Protocol CNTO1959PSO4015. Analysis results titles, mock-
ups, and programming instructions for all statistical outputs (tables, figures, and listings) will be
provided in a separate document entitled Data Presentation Specifications (DPS).
This current SAP covers the analyses to be performed following the Sponsor decision to 
prematurely terminate the study on 31 MAY 2023 due to slow enrollment.
1.1.
Objectives and Endpoints
Objectives
Endpoints
Primary
To evaluate the effect of guselkumab on Coronary
flow reserve (CFR) measured by transthoracic 
doppler-echocardiography, 
in 
participants 
with 
moderate-to-severe 
psoriasis 
and 
intermediate 
cardiovascular risk*
Change from baselineϯ in Coronary Flow
Reverse (CFR) at Week 32
Secondary
To evaluate the short-term effect of guselkumab on 
CFR 
measured 
by 
transthoracic 
doppler
echocardiography, in participants with moderate-to-
severe psoriasis and intermediate cardiovascular risk.
Change from baseline in CFR at Week 16.
To evaluate the effect of guselkumab on Global 
Longitudinal Strain (GLS) as a surrogate marker of
left
ventricular function in participants with 
moderate-to-severe 
psoriasis 
and 
intermediate 
cardiovascular risk.
Change from baseline in GLS at Week 32.
Change from baseline in GLS at Week 16.
To evaluate the effect of guselkumab on carotid 
femoral pulse wave velocity (cfPWV) as a surrogate 
marker of arterial stiffness in participants with 
Change from baseline in carotid-femoral
pulse wave velocity (cfPWV) at Week 32.
Change from baseline in cfPWV at Week 16.
To evaluate the effect of guselkumab on CFR among 
participants in the different CFR categories.
Change from baseline in CFR at Week 16
and Week 32 among participants with CFR
in the ranges of 2 to 2.74, and 2.75 to 3.5 at
baseline.


CNTO1959  (guselkumab)
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Status: Approved, Date: 21 July 2023
To evaluate the effect of guselkumab on surrogate 
CV risk markers among nicotine users and non-users 
in the participant population

Change from baseline in CFR at Week 16 
and Week 32 among nicotine users and non-
users.

Change from baseline in GLS at Week 16 
and Week 32 among nicotine users and non-
users.

Change from baseline in cfPWV at Week 16 
and Week 32 in nicotine users and non-
users.
* Intermediate cardiovascular risk defined by CFR ≥2 and ≤3.5 at Screening Visit S2.
ϯ cfPWV, GLS and CFR measurements at Week 0 will be considered as the baseline value. CFR 
must not be <2 or >3.5 at both Screening Visit S2 and Week 0.
The G-CARE study will also investigate the following exploratory objectives:

To evaluate the correlation between skin improvement and cardiovascular risk surrogate 
markers in participants with moderate-to-severe psoriasis and intermediate cardiovascular 
risk.

To evaluate the effect of guselkumab on disease-related quality-of-life in participants with 
moderate-to-severe psoriasis and intermediate cardiovascular risk.

To evaluate the effect of guselkumab on quality of sleep, alcohol intake patterns and 
depression and anxiety in participants with moderate-to-severe psoriasis and intermediate 
cardiovascular risk.

To evaluate the effect of guselkumab on biomarkers in participants with moderate-to-severe 
psoriasis and intermediate cardiovascular risk.
1.2.
Study Design
This is an interventional, single-arm, open-label, oligocentric study to evaluate the effect of
guselkumab on cardiovascular risk surrogate markers in adult men and women diagnosed with
moderate-to-severe plaque psoriasis (with or without psoriatic arthritis [PsA]) for at least 6 months 
prior to study entry. Participants will be assessed for eligibility at 2 screening visits; at Screening 
Visit S1, dermatology, medical history, and laboratory parameters will be assessed. Participants 
fulfilling eligibility criteria at Screening Visit S1 will be referred to the cardiology department and 
will undergo cardiologic assessments (cfPWV, GLS and CFR [via transthoracic doppler
echocardiography]) at Screening Visit S2, and again at Week 0. Only participants with CFR ≥2
and ≤3.5 at both these time-points will be enrolled in the study. The CFR measurement at Week 0
will be considered as the baseline value.
An overview of the intervention study is presented in Figure 1 below:


CNTO1959  (guselkumab)
Statistical Analysis Plan CNTO1959PSO4015
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 21 July 2023
Figure 1:
Schematic Overview of Study Design
The study is prematurely discontinued on 31st of May 2023,
o
All data collected will be analyzed and therefore, all data will need to go through data
cleaning process.
o
Before the 31st of May 2023, per protocol visits can be scheduled, this allows sites to
decide for continued patient treatment, either on commercial guselkumab or any other
treatment
o
After the 31st of May 2023 only the Final Efficacy visits, and Final Safety visits are to be
scheduled.
o
There are instances where the sponsor recommends not to do the per-protocol visits prior
to 31st of May in case this results in too much patient burden in terms of assessments e.g.,
2 cardiovascular assessments in a short timeframe.
2.
STATISTICAL HYPOTHESES
The primary hypothesis of this study is that guselkumab (administered as 100 mg at Weeks 0, 4, 
12, 20 and 28) is effective in reducing surrogate markers of cardiovascular risk as assessed by the 
change from baseline of CFR measurement at Week 32 (i.e., change from baseline of CFR 
measurement at Week 32 is positive).
3.
SAMPLE SIZE DETERMINATION
The initial sample size calculation was based on the assumption that participants will show an 
average increase of 20% in CFR at Week 32. To detect a CFR, mean change of 0.3 from baseline 
with 80% power, and assuming a standard deviation of 0.8 and a 5% dropout rate, 50 participants 
are expected to be enrolled in the study. Sample size may be increased if the dropout rate is higher 
than expected, in accordance with the sample size assumptions stated above.
After the decision to prematurely terminate the study, this sample size calculation was no longer 
relevant.


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4.
POPULATIONS (ANALYSIS SETS) FOR ANALYSIS
Analysis Set
Description
Screened
All participants who signed the informed
consent form (ICF).
Full Analysis Set (FAS)
The FAS includes all participants who 
received at least 1 dose of guselkumab.
Safety Analysis Set 
The safety analysis set includes all 
participants who received at least 1 dose of
adenosine and guselkumab.
5.
STATISTICAL ANALYSES
5.1.
General Considerations
Descriptive statistics (eg, mean, median, standard deviation (SD), minimum, and maximum) will 
be used to summarize continuous variables. Counts and percentages will be used to summarize 
categorical variables. Graphic data displays may also be used to summarize the data. In addition, 
graphical data displays (eg, line plots) and participant listings may also be used to summarize the 
data.
The summarized data will be presented by Nicotine-user, non-Nicotine user and total group.
Baseline Value: For all endpoints the last non-missing measurement prior to or on the day of the 
first administration of the study treatment (guselkumab) will be the Baseline value in the study 
(i.e., at ‘Week 0, Baseline’ analysis visit, following assignment of the actual visits using visit 
windows, as indicated in Table 2).
Level of Significance: In general, all tests will be performed at a 2-sided significance level of 
0.05, unless otherwise specified. All interval estimations will be reported using 2-sided 95%CI.
Nominal p-values will be presented.
Change from Baseline:
For the continuous variables pertaining to the cardiology outcomes, skin related outcomes, or paper 
PRO outcomes the determination of change from baseline will be determined only when both,
baseline and the measurement for the particular visit is available.
ℎ	 
 		    = 			 
ℎ	   −		 	 
 ℎ	 		
The number of patients with missing change from baseline values will be also presented in the 
statistical outputs.
For continuous or ordinal efficacy endpoints, a Mixed-effect Model for Repeated Measures
(MMRM) will be used. Covariates such as Nicotine use, body mass index (BMI), presence, or 
absence of PsA, age, gender, and visit will be incorporated into these models. 
For binary efficacy endpoints, 95% confidence interval [CI] for binomial proportions will be 
provided using exact methods, such as Clopper-Pearson or Chan-Zhang.


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5.1.1.
Visit Windows
Baseline will be defined as the last non-missing measurement prior to or on the day of the first 
dose of study treatment (guselkumab).
Study day will be calculated as follows:

Days prior to first dose: Study Day = date – treatment first dose date.

Days on or after first dose: Study Day = date – treatment first dose date + 1.
First dose refers to guselkumab.
As participants do not always adhere to the protocol visit schedule, the following rules are applied 
to assign actual visits to analysis visits. Listed below are the visit windows and the target days for 
each visit. The reference day is Study Day 1. If a participant has 2 or more actual visits in 1 visit 
window, the visit closest to the target day will be used as the protocol visit for that visit window.
The other additional visit(s) will not be used in the summaries or analyses but they can be used for 
determination of clinically important endpoints. If 2 actual visits are equidistant from the target 
day within a visit window, the later visit is used.
The Time Interval (label on output), Time Interval (Day) and the Target Time Point (Day) are 
indicated in Table 2. If an assessment is not scheduled for every visit, windows will be combined 
so that the interval between targeted study days is split evenly and consistently between visits. 
Table 2:
Visit Windows
Scheduled 
Visit 
Number
Time 
Interval
(label on 
output)
Planned 
Time Point
Target Time Point 
(Interval for tests) 
Time Interval 
(Day) *
Target Time 
Point (Day) *
S1
Screening 
Visit S1
Screening
Visit S1
(Dermatology)
(Maximum of 
2 weeks prior 
to Screening 
Visit S2)
-42 – -28
(Only for 
pregnancy test)
-42 – -28
-
-42 – -14
(Only for clinical 
laboratory tests and 
vital signs [blood 
pressure, 
pulse/heart rate and
temperature])
-42 – -14 (Prior to 
Screening
Visit S2)
-
-56 – -1
(Only for 
QuantiFERON-TB 
Gold test) 
(Within 2 months 
before
Week 0)
-56 – -1
-
-84 – -1
-84 – -1
-


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Scheduled 
Visit 
Number
Time 
Interval
(label on 
output)
Planned 
Time Point
Target Time Point 
(Interval for tests) 
Time Interval 
(Day) *
Target Time 
Point (Day) *
(Only for Chest 
radiograph) 
(Within 3 months 
before
Week 0)
-42 – -14
-42 – -14
-
S2
Screening 
Visit S2
Screening
Visit S2
(Cardiology)
(Minimum of
2 weeks and
maximum of 4 
weeks prior to 
Week 0)
-27 – -14
(Only for 
pregnancy test, 
urine nicotine test, 
cfPWV, GLS and 
CFR)
-27 – -14
-
1
Week 0, 
Baseline
Treatment 
Phase: 
Week 0
1 (Pre-dose)
≤1 (Pre-dose based 
on the time of the 
assessment if 
applicable) a
1
-13 – 1 (Pre-dose 
based on the time 
of the assessment if 
applicable) a
(For cfPWV, GLS 
and CFR)
1
2
Week 4
Treatment 
Phase: 
Week 4 (±7 
days)
22 – 36 (Pre-dose)
2 – 57 (Pre-dose 
based on the time 
of the assessment if 
applicable)
29
3
Week 12
Treatment 
Phase: 
Week 12 (±7 
days)
78 – 92 (Pre-dose)
58– 99 (Pre-dose 
based on the time 
of the assessment if 
applicable)
85
4
Week 16
Treatment 
Phase: 
Week 16 
(-7 to +7 or 
+14 days) b
106 – 120 (Pre-
dose)
100 – 125
113
106 – 127 (Pre-
dose) 
(Only for CFR)
100 – 129
113
5
Week 20
Treatment 
Phase: 
Week 20 (±7 
days)
134 – 148 (Pre-
dose)
126 – 169 (Pre-
dose based on the 
time of the 
assessment if 
applicable)
141
130 – 169 (Pre-
dose based on the 
time of the 
141


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Scheduled 
Visit 
Number
Time 
Interval
(label on 
output)
Planned 
Time Point
Target Time Point 
(Interval for tests) 
Time Interval 
(Day) *
Target Time 
Point (Day) *
assessment if 
applicable)
(Only for CFR)
6
Week 28
Treatment 
Phase: 
Week 28 (±7 
days)
190 – 204 (Pre-
dose)
170 – 210 (Pre-
dose based on the 
time of the 
assessment if 
applicable)
197
7
Final 
Efficacy 
Visit 
(Week 32)
Final Efficacy 
Visit: 
Week 32 
(-7 to +7 or 
+14 days) b
218 – 232
211 - 252 c
225
218 – 239
(Only for CFR)
211 - 256 c
225
8
Final 
Safety 
Visit 
(Week 40)
Final Safety 
Visit: 
12 Weeks (±7 
days) after the 
last dose of 
guselkumab 
within the 
treatment 
phase
77 – 91 **
(after the last dose 
of guselkumab
within the 
treatment phase)
253 – 287 d e
or
77 – 91 ** (after the 
last dose of 
guselkumab within 
the treatment 
phase) e
281
or 
85 **
* Relative to the day of first administration of the study treatment (guselkumab).
** Relative to the day of last administration of the study treatment (guselkumab) within the treatment 
phase.
a Baseline
b If CFR measurement is unsuccessful, 2 attempts to measure a CFR can be made on different days. In 
such cases, at Weeks 16 and 32 the visit window for the CFR parameter can be extended by 7 additional 
days (CFR visit window = -7 / +14 days).
c For participants, who do have a Week 28 assessment, 4 weeks after the last dose of the guselkumab 
within the treatment phase. For participants who permanently discontinue guselkumab before Week 28, 
the date of discontinuation. Following the premature termination of the study 4 to 8 weeks after the last 
dose of guselkumab within the treatment phase.
d Only for participants, who do have a Week 28 assessment.
e For participants who receive guselkumab after the treatment phase, the date of the first dose of 
guselkumab outside of the treatment phase.
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 Nicotine-user, non-Nicotine user groups and overall:

Participants enrolled (e.g., Participants who fulfilled eligibility criteria at Screening Visit S1
and with CFR ≥2 and ≤3.5 both at Screening Visit S2, and at Week 0.).


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
Participants who received study intervention (guselkumab).

Participants who completed the study.

Participants who discontinued study intervention (guselkumab).
o
Reasons for discontinuation of study intervention (guselkumab).

Participants who terminated study prematurely along with primary reasons.
Listings of participants will be provided for the following categories:

Participants who discontinued study intervention (guselkumab).

Participants who terminated study prematurely

Participants who were enrolled yet did not receive study intervention (guselkumab).
5.3.
Primary Endpoint Analysis
The efficacy analysis of the primary endpoint will be based on the FAS. 
5.3.1.
Definition of Endpoint
5.3.1.1. Coronary flow reserve (CFR)
Coronary flow reserve will be measured non-invasively using transthoracic doppler 
echocardiography, using a high-resolution ultrasound system with a suitable transducer and the 
respective software. The acoustic window will be around the midclavicular line in the fourth and 
fifth intercostal spaces in the left lateral decubitus position. Long-axis views of the left ventricle 
will be obtained, and the ultrasound beam will then be angled laterally and superiorly to image the 
anterior interventricular groove. The coronary blood flow in the distal portion of the left anterior 
descending artery (LAD) will be examined with the help of color Doppler flow mapping. A sample 
volume will be positioned on the color signal in the LAD, and Doppler spectral tracings of flow 
velocity will be recorded. First, the baseline spectral Doppler signals in the distal portion of the 
LAD will be recorded. Then 140 μg/kg/min adenosine, a coronary vasodilator, will be 
administered for 5 minutes. Doppler signals will be recorded continuously at baseline and during 
the period of adenosine infusion. Measurements of hyperemic coronary flow velocity will be done 
continuously during the adenosine infusion, and the CFR measurement will be recorded based on 
the guidelines provided by the cardiology core lab.
Cardiac parameters, along with strain and coronary parameters will be assessed by the cardiology 
core lab as defined in the process document of the core lab.
The primary endpoint for the study is the change from baseline in CFR at Final Efficacy Visit
(Week 32) based on FAS.
Data Handling of Primary Efficacy Endpoint


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For most of the secondary efficacy analyses (eg, over time summaries), after the treatment failures 
are applied, no imputation will be performed for missing data (eg, lost to follow-up, missed study 
visit) and the values will remain as missing and as observed data will be used for the analysis.
5.3.2.
Estimand
Primary Trial Objective: To evaluate the effect of guselkumab on CFR measured by 
transthoracic doppler-echocardiography, in participants with moderate-to-severe psoriasis and 
intermediate cardiovascular risk. Intermediate cardiovascular risk is defined by CFR ≥2 and ≤3.5 
at Screening Visit S2.
Estimand Scientific Question of Interest: What level of change from baseline of CFR considered 
to have benefited from guselkumab for the pre-specified duration (32 weeks).
Study intervention: 

Guselkumab (100 mg SC [Subcutaneous] injections at Week 0, 4, 12, 20 and 28)
Population: Participants with moderate to severe plaque psoriasis (with or without PsA) for at 
least 6 months prior to study entry. The target population consists of men or women aged 18 years 
and above with moderate to severe plaque psoriasis of at least 6 months’ duration, defined as 
psoriasis area and severity index (PASI) ≥12, and involved body surface area (BSA) ≥ 10% at 
Screening Visit S1 and CFR with ≥ 2 to ≤ 3.5 at Screening Visit S2. Participants should not be 
with CFR of <2 or >3.5 at both Screening Visit S2 and Week 0.
Variable: Change from baseline in the CFR measurement at Final Efficacy Visit (Week 32). The 
CFR measurement at Week 0, Baseline will be considered as baseline value. Participants who had 
adequate primary endpoint measurements will be assessed at Final Efficacy Visit (Week 32) 
considering as observed for the analysis.
Summary measure (Population-level summary): Least squares means (LSmeans), together with 
the 95% CI and p-values based on the MMRM.
Intercurrent events and their corresponding strategies:
Intercurrent Events
Strategy for Addressing Intercurrent Events and Its 
Description
Usage of disallowed cardiac 
medication* (as listed in Table 1 of the
protocol) during the treatment phase
Composite Strategy: A participant with this 
intercurrent event will be excluded from the analysis.
* List of concomitant medications from ADaM datasets will be shared with the clinical team after the receipt 
of SDTM data by the programming team for each data cut. The clinical team will review the list and flag 
the appropriate disallowed medications. This list will be used for the intercurrent events.


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5.3.3.
Analysis Methods
5.3.3.1.
Main Estimator (Analysis) for the Primary Estimand
A MMRM will be used to determine the change from baseline in Cardiovascular measurement at 
Week 32 or Week 16 in the open label phase to compare the participant groups of nicotine users 
vs non-nicotine users, will be analyzed using a MMRM based on observed case data. The models 
will include baseline CFR measurement at Week 0, Baseline before first administration of 
guselkumab as a covariate, and Nicotine use, BMI, presence or absence of PsA, age, gender, and 
visit.
The estimates for the primary estimand of the treatment effect of guselkumab will be provided by 
the difference of change from baseline at Week 32 in the LSmeans. The 95% CI for the differences 
in LSmeans and p-values will be calculated based on the MMRM. The within-subject covariance 
between visits will be estimated via an unstructured variance-covariance matrix. In case of 
convergence problems, alternative variance-covariance structures will be tried in the following 
order, with the first structure that converges being used in the analysis: heterogeneous Toeplitz, 
standard Toeplitz, and autoregressive order 1 (AR[1]) with separate subject random effect.
5.4.
Secondary Endpoint(s) Analysis
5.4.1.
Key Confirmatory Secondary Endpoint(s)
The key secondary endpoints include the following at Week 16 and Week 32:

Change from baseline in CFR at Week 16

Change from baseline in absolute GLS at Week 16 and Week 32.

Change from baseline in carotid-femoral pulse wave velocity (cfPWV) at Week 16.

Change from baseline in cfPWV at Week 32.

Change from baseline in CFR at Week 16 and Week 32 among participants with CFR in 
the ranges of 2 to >2.75 and ≤ 2.75 to 3.5 at baseline.

Change from baseline in CFR at Week 16 and Week 32 among nicotine users and non-
users.

Change from baseline in absolute GLS at Week 16 and Week 32 among nicotine users 
and non-users.

Change from baseline in cfPWV at Week 16 and Week 32 in nicotine users and non-
users.

Rate of Adverse Events (AEs) among participants treated with guselkumab at Week 16 
and Week 32.
5.4.1.1. Definition of Endpoint(s)
Refer to Section 5.3.1 for Definition of CFR Endpoint 
The secondary endpoint for the study is the change from baseline in CFR at Week 16 or GLS/cf-
PWV at Week 16 and Week 32 are based on FAS.


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5.4.1.1.1.
Global Longitudinal Strain (GLS) for Left Ventricular Function
In the G-CARE study, speckle tracking echocardiography (STE) will be employed for the 
detection of left-ventricular (LV) myocardial strain. Two-dimensional STE is based on the 
temporal and spatial tracking of naturally occurring intramyocardial reflectors of ultrasound 
(speckles) within the 2D echocardiographic images of the LV walls, and measures LV regional 
and global deformations as a marker of contractility and elasticity. The GLS and global 
longitudinal strain rate will be calculated at systole and diastole. The ratio of the arterial stiffness 
measured with cfPWV (described below) and the myocardial performance represented by GLS 
will be calculated as an index reflecting the arterial-ventricular interaction. In addition, the 
estimated LV peak twisting and untwisting at the time of mitral valve opening will be measured, 
and the percentage difference between LV twist and untwisting at the mitral valve opening will 
be calculated.
The strain-pressure curves recorded from the GLS measurement may be used to calculate the 
myocardial work index at selected sites.
5.4.1.1.2.
Carotid-femoral Pulse Wave Velocity (cf-PWV)
The measurement of cfPWV is accepted as the most simple, non-invasive, robust, and 
reproducible method to determine arterial stiffness.28 Carotid-femoral (cf) PWV is a direct 
measurement, and it corresponds to the widely accepted propagative model of the arterial 
system. Measured along the aortic and aorto-iliac pathway, it is the most clinically relevant since 
the aorta and its first branches are what the left ventricle ‘sees’ and are thus responsible for most 
of the pathophysiological effects of arterial stiffness. cfPWV is usually measured using the foot-
to-foot velocity method from various waveforms. These are obtained transcutaneously at the 
right common carotid artery and the right femoral artery (ie, ‘carotid-femoral’ PWV), and the 
time delay (Δt or transit time) measured between the feet of the 2 waveforms. A variety of 
different waveforms can be used including pressure, distension, and Doppler. The distance (D) 
covered by the waves is usually assimilated to the surface distance between the 2 recording sites. 
cfPWV is calculated as cfPWV=D (meters)/ Δt (seconds). Average of triplicate cfPWV 
measurements will be derived and used for the analysis at each of the treatment time point.
Data Handling Rules for Efficacy Analyses
The secondary efficacy analyses (eg, over time summaries), after the treatment failures are applied, 
no imputation will be performed for missing data (eg, lost to follow-up, missed study visit) and 
the values will remain as missing and as observed data will be used for the analysis.
5.4.1.2
Estimand
Secondary Trial Objective: To evaluate the effect of guselkumab on CFR/GLS/cf-PWV
measured by transthoracic doppler-echocardiography, in participants with moderate-to-severe 
psoriasis and intermediate cardiovascular risk. Intermediate cardiovascular risk is defined by CFR 
≥2 and ≤3.5 at Screening Visit S2.
Estimand Scientific Question of Interest: What level of change from baseline of CFR/GLS/cf-
PWV considered to have benefited from guselkumab for the pre-specified duration (16 weeks).


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Study intervention: 

Guselkumab (100 mg SC [Subcutaneous] injections at Week 0, 4, 12, 20 and 28)
Population: Participants with moderate to severe plaque psoriasis (with or without PsA) for at 
least 6 months prior to study entry. The target population consists of men or women aged 18 years 
and above with moderate to severe plaque psoriasis of at least 6 months’ duration, defined as PASI
≥12, and involved BSA ≥ 10% at Screening Visit S1 and CFR with ≥ 2 to ≤ 3.5 at Screening Visit 
S2. Participants should not be with CFR of <2 or >3.5 at both Screening Visit S2 and Week 0.
Variable: Change from baseline in the CFR measurement at Week 16. The CFR measurement at 
Week 0, Baseline will be considered as baseline value. Similarly, for other secondary endpoints 
of GLS/cf-PWV at Week 16 and Week 32. Participants who had adequate secondary endpoint 
measurements will be assessed at Week 16 as per Table 2 and Final Efficacy Visit (Week 32)
considering as observed for the analysis.
Secondary Estimand:
Summary measure (Population-level summary): LSmeans, together with the 95% CI and p-
values based on the MMRM.
Intercurrent events and their corresponding strategies:
Intercurrent Events
Strategy for Addressing Intercurrent Events and Its 
Description
Usage of disallowed cardiac medication 
(as listed in Table 1 of the protocol) 
during the treatment phase
Composite Strategy: A participant with this 
intercurrent event will be excluded from the analysis.
5.4.1.3
Analysis Methods
Main Estimator (Analysis) for the Primary Estimand
A MMRM will be used to determine the change from baseline in Cardiovascular measurement at 
Week 16 or Week 32 in the open label phase to compare the participant groups of nicotine users 
vs non-nicotine users, will be analyzed using a MMRM based on observed case data. The models 
will include baseline CFR/GLS/cf-PWV measurement at Week 0, Baseline before first 
administration of guselkumab as a covariate, and Nicotine use, BMI, presence, or absence of 
PsA, age, gender, and visit.
The estimates for the primary estimand of the treatment effect of guselkumab will be provided by 
the difference of change from baseline at Week 32 in the LSmeans. The 95% CI for the differences 
in LSmeans and p-values will be calculated based on the MMRM. The within-subject covariance 
between visits will be estimated via an unstructured variance-covariance matrix. In case of 
convergence problems, alternative variance-covariance structures will be tried in the following 
order, with the first structure that converges being used in the analysis: heterogeneous Toeplitz, 
standard Toeplitz, and AR(1) with separate subject random effect.


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5.5.
Tertiary/Exploratory Endpoint(s) Analysis:
As the study was prematurely terminated all exploratory endpoints will be presented by listing 
only with change from baseline where applicable.
5.5.1.
Psoriasis Area and Severity Index
The psoriasis area and severity index (PASI) is a system used for assessing and grading the 
severity of psoriatic lesions and their response to therapy. In the PASI system, the body is 
divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these 
areas is assessed separately for the percentage of the area involved, which translates to a numeric 
score that ranges from 0 (indicates no involvement) to 6 (90%-100% involvement), and for 
erythema, induration, and scaling, which are each rated on a scale of 0 to 4. The PASI produces a 
numeric score that can range from 0 (no psoriasis) to 72. A higher score indicates more severe 
disease. 
The Scoring system of PASI:
The scoring system for the signs of the disease (erythema, induration, and scaling) is: 
0 = none, 
1 = slight, 
2 = moderate, 
3 = severe, and 
4 = very severe.
The scale for estimating the area of involvement for psoriatic lesions is outlined below.
0 = no involvement
1 = 1% to 9% involvement
2 = 10% to 29% involvement
3 = 30% to 49% involvement
4 = 50% to 69% involvement
5 = 70% to 89% involvement
6 = 90% to 100% involvement
To help with the area assessments, the following conventions should be noted:
a.
The neck is considered part of the head.
b. The axillae and groin are part of the trunk.
c.
The buttocks are part of the lower extremities,
The PASI formula is:
 = 0.1(Eh + Ih + Sh) ∗Ah + 0.3 (Et + It + St) ∗ + 0.2 (- +  + ) ∗ + 0.4 ∗(- +  + ) ∗
Where E = erythema, I = induration, S = scaling, and A = area.


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Listing of PASI will be presented with change from baseline at each of the scheduled timepoints.
5.5.2.
Body Surface Area 
The body surface area (BSA) score arithmetic mean of the affected skin surface. The most 
commonly used
method to estimate the BSA of psoriatic lesions is the “rule of nines”, which was originally
developed for estimating the surface area of burns. It is defined as 9% coverage for the head and
neck, 9% for each arm, 9% for the anterior and posterior legs, and 9% for each of 4 trunk 
quadrants, and 1% for the groin. The area of the palm can be used as a unit of measure which 
represents approximately 1% of the BSA. The number of patient hand areas affected can then be 
calculated is a system used for assessing and grading the severity of psoriatic lesions and their 
response to therapy.  The formula of BSA calculation is provided below:
Listing of BSA will be presented with change from baseline at each of the scheduled timepoints.


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5.5.3.
Dermatology Life Quality Index
The dermatology life quality index (DLQI) is a dermatology-specific quality-of-life instrument 
designed to assess the impact of the disease on a participant’s quality-of-life It is a 10 item PRO 
questionnaire that, in addition to evaluating total quality-of-life, can be used to assess 6 different 
aspects that may affect quality-of-life: symptoms and feelings, daily activities, leisure, work or 
school performance, personal relationships, and treatment. The DLQI produces a numeric score 
that can range from 0 to 30. A higher score indicates more severe disease.
Listing of DLQI will be presented with change from baseline at each of the scheduled timepoints.
5.5.4.
Investigator’s Global Assessment
The investigator’s global assessment (IGA) documents the investigator’s assessment of the 
participant’s psoriasis at a given timepoint. Total lesions are graded for induration, erythema, and 
scaling. The participant’s psoriasis is assessed as cleared (0), minimal (1), mild (2), moderate (3), 
or severe (4). The IGA mod 2011 scale is static, i.e., it referred exclusively to the participant’s 
disease at the time of the assessment and did not compare with any of the participant’s previous 
disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = 
moderate and 4 = severe.
Induration (I) (averaged over all lesions; use the National Psoriasis Foundation Reference card 
for measurement)
0 = no evidence of plaque elevation
1 = minimal plaque elevation, = 0.25 mm
2 = mild plaque elevation, = 0.5 mm
3 = moderate plaque elevation, = 0.75 mm
4 = severe plaque elevation, > 1 mm
Erythema (E) (averaged over all lesions)
0 = no evidence of erythema, hyperpigmentation may be present
1 = faint erythema
2 = light red coloration
3 = moderate red coloration
4 = bright red coloration
Scaling (S) (averaged over all lesions)
0 = no evidence of scaling
1 = minimal; occasional fine scale over less than 5% of the lesion
2 = mild; fine scale dominates
3 = moderate; coarse scale predominates
4 = severe; thick, scale predominates
/ 		 = (  + - + ) / 3


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Average will be calculated in the device but not displayed. Numeric result will be included in 
data transfer.
Investigator’s Global Assessment based upon above Total Average
0 = Cleared, except for residual discoloration
1 = Minimal - majority of lesions have individual scores for I + E + S / 3 that averages 1
2 = Mild- majority of lesions have individual scores for I + E + S / 3 that averages 2
3 = Moderate - majority of lesions have individual scores for I + E + S / 3 that averages 3
4 = Severe - majority of lesions have individual scores for I + E + S / 3 that averages 4
Note: Scores should be rounded to the nearest whole number. 
If total ≤ 1.49, score = 1; 
if total ≥1.50, score = 2.
Listing of IGA will be presented with change from baseline at each of the timepoints scheduled.
5.5.5.
Pittsburg Sleep Quality Index
The pittsburg sleep quality index (PSQI) is an effective instrument used to measure the quality 
and patterns of sleep in the older adult. It differentiates “poor” from “good” sleep by measuring 7 
domains: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep 
disturbances, use of sleep medication, and daytime dysfunction over the last month. The 
participant self-rates each of these 7 areas of sleep. Scoring of the answers is based on a 0 to 3 
scale, whereby 3 reflects the negative extreme on the Likert Scale. A global sum of “5” or 
greater indicates a “poor” sleeper.
The range of values for questions 5 through 10 are all 0 to 3. Questions 1 through 9 are not 
allowed to be missing except as noted below. If these questions are missing, then any scores 
calculated using missing questions are also missing. Thus, it is important to make sure that all 
questions 1 through 9 have been answered. In the event that a range is given for an answer (for 
example, ‘30 to 60’ is written as the answer to Q2, minutes to fall asleep), split the difference 
and enter 45.
On May 20, 2005, on the instruction of Dr. Daniel J. Buysse, the scoring of the PSQI was 
changed to set the score for Q5J to 0 if either the comment or the value was missing. This may 
reduce the DISTB score by 1 point and the PSQI Total Score by 1 point.
PSQIDURAT DURATION OF SLEEP
PSQIDURAT
DURATION OF SLEEP
IF Q4 ≥7, THEN set value to 0
IF Q4 < 7 and ≥6, THEN set value to 1
IF Q4 < 6 and ≥5, THEN set value to 2
IF Q4 < 5, THEN set value to 3


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Minimum Score = 0 (better); Maximum Score = 3 (worse)
Minimum Score = 0 (better); Maximum Score = 3 (worse)
PSQILATEN
SLEEP LATENCY
First, recode Q2 into Q2new thusly:
IF Q2 ≥0 and ≤15, THEN set value of Q2new to 0
IF Q2 > 15 and ≤ 30, THEN set value of Q2new to 1
IF Q2 > 30 and ≤60, THEN set value of Q2new to 2
IF Q2 > 60, THEN set value of Q2new to 3
Next
IF Q5a + Q2new = 0, THEN set value to 0
IF Q5a + Q2new ≥1 and ≤ 2, THEN set value to 1
IF Q5a + Q2new ≥3 and ≤ 4, THEN set value to 2
IF Q5a + Q2new ≥5 and ≤ 6, THEN set value to 3
Minimum Score = 0 (better); Maximum Score = 3 (worse)
PSQIDAYDYS
DAY DYSFUNCTION DUE TO SLEEPINESS
IF Q8 + Q9 = 0, THEN set value to 0
IF Q8 + Q9 ≥1 and ≤2, THEN set value to 1
IF Q8 + Q9 ≥3 and ≤ 4, THEN set value to 2
IF Q8 + Q9 ≥5 and ≤6, THEN set value to 3
Minimum Score = 0 (better); Maximum Score = 3 (worse)
PSQIHSE
SLEEP EFFICIENCY
Diffsec = Difference in seconds between day and time of day Q1 and day Q3
PSQIDISTB
SLEEP DISTURBANCE
IF Q5b + Q5c + Q5d + Q5e + Q5f + Q5g + Q5h + Q5i + Q5j 
(IF Q5JCOM is null or Q5j is null, set the value of Q5j to 0) = 0, 
THEN set value to 0
IF Q5b + Q5c + Q5d + Q5e + Q5f + Q5g + Q5h + Q5i + Q5j (IF 
Q5JCOM is null or Q5j is null, set the value of Q5j to 0) > 1 and < 9, 
THEN set value to 1
IF Q5b + Q5c + Q5d + Q5e + Q5f + Q5g + Q5h + Q5i + Q5j (IF 
Q5JCOM is null or Q5j is null, set the value of Q5j to 0) > 9 and < 18, 
THEN set value to 2
IF Q5b + Q5c + Q5d + Q5e + Q5f + Q5g + Q5h + Q5i + Q5j (IF 
Q5JCOM is null or Q5j is null, set the value of Q5j to 0) > 18, 
THEN set value to 3


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Diffhour = Absolute value of diffsec / 3600
newtib =IF diffhour > 24, then newtib = diffhour – 24
IF diffhour ≤24, THEN newtib = diffhour
(NOTE, THE ABOVE JUST CALCULATES THE HOURS BETWEEN 
GNT (Q1) AND GMT (Q3))
tmphse = (Q4 / newtib) * 100
IF tmphse ≥85, THEN set value to 0
IF tmphse < 85 and ≥75, THEN set value to 1
IF tmphse < 75 and ≥65, THEN set value to 2
IF tmphse < 65, THEN set value to 3
Minimum Score = 0 (better); Maximum Score = 3 (worse)
PSQISLPQUAL
TOTALSLEEP QUALITY
Q6
Minimum Score = 0 (better); Maximum Score = 3 (worse)
PSQIMEDS
NEED MEDS TO SLEEP
Q7
Minimum Score = 0 (better); Maximum Score = 3 (worse)
PSQI
TOTAL
DURAT + DISTB + LATEN + DAYDYS + HSE + SLPQUAL + MEDS
Minimum Score = 0 (better); Maximum Score = 21 (worse)
Interpretation: TOTAL ≤5 associated with good sleep quality
TOTAL > 5 associated with poor sleep quality
Listing of PSQI will be presented with change from baseline at each of the timepoints.
5.5.6.
Alcohol Use Disorders Identification Test
The alcohol use disorders identification test (AUDIT) is a 10-item screening tool developed by the 
World Health Organization (WHO) to assess alcohol consumption, drinking behaviors, and 
alcohol-related problems. Both a clinician-administered version and a self-report version of the 
AUDIT are provided. Participants should be encouraged to answer the questions in terms of 
standard drinks. A chart illustrating the approximate number of standard drinks in different alcohol 
beverages is included. A score of 8 or more is considered to indicate hazardous or harmful alcohol 
use. The AUDIT has been validated across genders and in a wide range of racial/ethnic groups and 
is well suited for use in primary care settings.
Score of AUDIT:
Scores for each question range from 0 to 4, with the first response for each question (e.g., never) 
scoring 0, the second (e.g., less than monthly) scoring 1, the third (e.g., monthly) scoring 2, the 
fourth (e.g., weekly) scoring 3, and the last response (e.g., daily or almost daily) scoring 4. For 
questions 9 and 10m which only have three responses, the scoring is 0, 2 and 4 (from left to 
right).


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A score of 8 or more is associated with harmful or hazardous drinking, a score of 13 or more in 
women, and 15 or more in men, is likely to indicate alcohol dependence.
Listing of AUDIT will be presented with change from baseline at each of the timepoints.
5.5.7.
The Hospital Anxiety and Depression Scale
The hospital anxiety and depression scale (HADS) measures anxiety and depression which 
commonly coexist in a general medical population of participants.1 The HADS focuses on non-
physical symptoms so that it can be used to diagnose depression in people with significant physical 
ill-health. The questionnaire comprises 7 questions for anxiety and 7 questions for depression and 
takes 2-5 minutes to complete. Although the anxiety and depression questions are interspersed 
within the questionnaire, they are scored separately, and cut-off scores are available for 
quantification. The HADS questionnaire has been validated in many languages, countries and 
settings, including general practice and community settings.
Listing of HADS will be presented with change from baseline at each of the timepoints.
5.6.
Other Safety Analyses
All safety analyses will be based on the safety analysis set based on actual intervention received, 
unless otherwise specified.
Missing safety data will generally not be imputed. Safety assessment values of the form of “<x” / 
“≤ x” (ie, below the lower limit of quantification) or “> x” / “≥ x” (ie, above the upper limit of 
quantification) will be imputed as “x” in the calculation of summary statistics but displayed as “< 
x” / “≤ x” or “>x” / “≥ x” in the listings.
For all continuous safety variables, descriptive statistics by Nicotine use, non-Nicotine use and 
Total group will include the N, mean, standard deviation, median, minimum, and maximum. 
Categorical variables will be summarized by Nicotine use, non-Nicotine use and Total group using 
frequency counts and percentages.
5.6.1.
Extent of Exposure
The number and percentage of participants who receive study intervention (guselkumab) will be 
summarized. The number and percentage of participants will also be summarized by visit of week.
Descriptive statistics for duration of study intervention (N, mean, SD, median, and range 
(minimum, maximum)) will be summarized. Participant-years of intervention are calculated as 
days of intervention/365.25. Participant-years will be presented by Nicotine use, non-Nicotine use 
and Total group.
Duration of intervention will be summarized in the following duration categories: 

<4 weeks, 

4-<12 weeks, 


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
12-<16 weeks, 

16-<20 weeks, 

20-<28 weeks within a study intervention
Cumulative duration of intervention >= 4 weeks, >=12 weeks, >= 16 weeks, >=20 weeks, >=28 
weeks will be summarized.
Study intervention duration is defined as (date of last dose of study intervention – date of first dose 
of study intervention) +1.
Total dosing days of intervention is defined as the total number of days that study intervention was 
administered to the participant (excluding days off study intervention).
The number (%) of participants with a dose not administered will be summarized by Nicotine use, 
non-Nicotine use and Total group and visit of week. Reasons for doses not administered will also 
be summarized by visit of week.
The number (%) of participants with a study intervention modification prior to injection will be 
summarized by Nicotine use, non-Nicotine use and Total group and week of visit. A similar 
summary will be presented for study intervention modification during the injection.
Descriptive statistics will be presented for the following parameters:

Number of injections

Cumulative total dose

Mean daily dose
The mean daily dose of study intervention is calculated as (sum of total daily dose during the 
intervention phase)/total dosing days of intervention.
Study intervention compliance will be summarized descriptively. See Appendix 7 for further 
details.
5.6.2. Adverse Events
The verbatim terms used in the case report form (CRF) by investigators to identify adverse events 
(AEs) will be coded using the latest version of Medical Dictionary for Regulatory Activities 
(MedDRA) (System Organ Class and Preferred Term).  
Any AE occurring at or after administration of adenosine or the initial administration of study 
intervention (guselkumab) through the day of last dose within the study phase plus 12 weeks or 
the date of the Final Safety visit, whichever is the latest, is considered to be treatment emergent 
adverse event (TEAE). 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 TEAE. If the event date is recorded as partial or completely missing, then the event 


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will be considered to be TEAE unless it is known to be prior to the first administration of study 
intervention based on partial onset date or resolution date. All reported TEAEs 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 Nicotine use, non-Nicotine use and Total 
group.
Any usual pharmacodynamic actions and expected effects of adenosine administration (refer to 
Appendix 6.11) of CFR assessment are not considered as AEs
Summary tables will be provided for TEAEs.
The incidence of other TEAEs of special interest will be summarized. See Appendix 8 for list of 
adverse events in each category.
Listing of all serious adverse events (SAEs) will be provided along with abnormalities of 
laboratory, vital signs, and other physical observations.
Deaths will be displayed by actual intervention received. Frequencies for the following parameters 
will be included in the summary table:

Number of participants who died

Cause of death

Relationship to study intervention (yes/no)
A listing of participants who died will be provided.
5.6.2.1.
Imputation Rules for Missing Adverse Event Date/Time of Onset
5.6.2.1.1.
Treatment-emergent AEs
AEs with completely missing onset dates will be considered as treatment-emergent (avoiding 
under reporting of treatment-emergent AEs). AEs with partially missing onset dates will also be 
included as treatment-emergent when the month (if it exists) and the year occur on or later than 
the month and year of the initial study treatment date.
5.6.2.1.2. Imputation Rules
The date value is split into day, month, and year parts as outlined below:
Day
Month
Year
Partial AE Start Date
Not used 
(missing and will be imputed) 
MON
YYYY
Treatment Start Date (TRTSDT)
Not used
TRTM
TRTY
Completely missing start dates will not be imputed. Partial AE start dates are imputed with 
reference to the treatment start date (TRTSDT) as outlined in the matrix of start year (YYYY) vs 
start month (MON) below. 


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The Italic bold font indicates the imputed values.
MON MISSING
MON < TRTM
MON = TRTM
MON > TRTM
YYYY 
MISSING
Do not impute
Do not impute
Do not impute
Do not impute
YYYY < 
TRTY
(D) = 31DECYYYY
Before Treatment 
Start 
(C) = 
01MONYYYY
Before 
Treatment Start 
(C) = 
01MONYYYY
Before 
Treatment Start
(C) = 
01MONYYYY
Before 
Treatment Start
YYYY = 
TRTY
(B) = min(TRTSDT, 
AE resolution)
Uncertain
(C) = 
01MONYYYY
Before 
Treatment Start
(B) = 
min(TRTSDT, 
AE resolution)
Uncertain
(A) = 
01MONYYYY
After Treatment 
Start
YYYY > 
TRTY
(E) = 01JANYYYY
After Treatment 
Start
(A) = 
01MONYYYY
After Treatment 
Start
(A) = 
01MONYYYY
After Treatment 
Start
(A) = 
01MONYYYY
After Treatment 
Start
The following table is the legend to the matrix above.
Relationship
Before Treatment Start 
Partial date indicates AE start date prior to Treatment Start 
Date 
After Treatment Start 
Partial date indicates AE start date after Treatment Start Date
Uncertain
Partial date insufficient to determine the sequence of AE start 
date and Treatment Start Date
Imputation Calculation
(A) After Treatment Start 
01MONYYYY 
(The closest date to the treatment start date for imputation)  
(B) Uncertain
min(TRTSDT, AE resolution)
(AE happed just after the treatment start)  
(C) Before Treatment Start
01MONYYYY
(Start-month point will be used for imputation)  
(D) Before Treatment Start
31DECYYYY
(End-year point will be used for imputation)  
(E) After Treatment Start
01JANYYYY
(The closest date to the treatment start date for imputation)  
Note: Imputation rules for concomitant medications follow the same approach as for AEs. In the 
case where prior or concomitant medication start/end dates are partial but is required in the 
calculation of time to first dose (see prior medication under section 6.5) temporary imputed 
variable(s) will be set earliest/latest possible date for medication start/end dates respectively.


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The imputed dates will be used in the calculation of time to first dose but displayed as those were
recorded in the listings.
5.6.3.
Additional Safety Assessments (if applicable)
5.6.3.1.
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 all chemistry, hematology, and 
urinalysis (pH and specific gravity) laboratory tests at scheduled time points. Week 0 is the 
Baseline visit for the Clinical Laboratory tests.
Hematology: Platelet Count, Reb blood cell count, Hemoglobin, Hematocrit, RBC Indices: MCV, 
MCH, %Reticulocytes, White Blood Cell (WBC) count with Differential: 
Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils.
Chemistry:  Sodium, Potassium, Chloride, Bicarbonate, Blood urea nitrogen (BUN), Creatinine, 
Aspartate 
aminotransferase 
(AST)/Serum 
glutamic-oxaloacetic, 
Alanine 
aminotransferase (ALT)/ Serum glutamic-oxaloacetic, Gamma- glutamyltransferase
(GGT), Bilirubin, Alkaline phosphatase (AP), Creatinine phosphokinase (CP), Lactic 
acid dehydrogenase (LDH), Uric acid, Calcium, Phosphate, Albumin, Total protein, 
Cholesterol, HbA1C, hsCRP, Lipid and Metabolic Panel: Triglycerides, Magnesium, 
Low-density lipoproteins (LDL), High-density lipoproteins (HDL), Very-Low-
density lipoproteins (VLDL) (calculated), Non-HDL (calculated), Serum glucose, 
Serum insulin
Urinalysis: Specific gravity, pH, Glucose, Protein, Blood, Ketones, Bilirubin, Urobilinogen, 
Nitrite, Leukocytes esterase, Red Blood Cells, White Blood Cells, Epithelial cells, 
Crystals, Casts, Bacteria, (8-Oxo-7,8-dihyd’o2'-desoxyguanosine) Concentration of 
oxidative lipid damage [8-Isoprostane] and Malondialdehyde in plasma 
Concentration of antioxidants (Vitamins C, E).
Screening: Serum and Urine Pregnancy Testing for women of childbearing potential only, 
Nicotine Dipstick, TB QuantiFERON Test, Serology (HIV antibody, hepatitis B 
surface antigen [HBsAg], and HCV antibody)
Change from baseline to week of visit will be summarized for chemistry, hematology, and 
urinalysis (pH, and specific gravity) tests and displayed by week of visit. 
Abnormality criteria normal ranges will be applied to baseline and postbaseline values as per the 
lab reference ranges which will be obtained as an external document.
Postbaseline abnormalities will be compared with their corresponding baseline result:

For abnormalities based on normal range and/or criteria: If the postbaseline value is above the 
upper limit and the baseline value is below the upper limit (eg, Normal or Low), then the 


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postbaseline abnormality will be considered TE. The same applies to the postbaseline value 
being below the lower limit with the baseline value being above the lower limit (eg, Normal 
or High).

For abnormalities based on observed values: If the postbaseline value is observed as abnormal 
and baseline value is normal (eg., Normal to Abnormal), then the postbaseline abnormality 
will be considered TE. If the postbaseline value is normal and the baseline value is abnormal 
(eg., Abnormal to Normal) then the postbaseline abnormality will not be considered TE.

If the baseline value is missing, a postbaseline abnormality will always be considered as TE.
Number and percentage of participants with treatment-emergent clinically important laboratory 
values and markedly abnormal treatment emergent values will be presented based on the standard
reference ranges provided by the Central Laboratory. A listing of clinically important laboratory 
values will be provided.
All abnormal laboratory values (out of standard reference range values) will be shared with the 
clinical team to obtain the flagging for markedly abnormal treatment emergent values.
The clinically important laboratory findings to be reported are described below during any post-
baseline visits and not necessarily at the same visits:

AST (U/L): 3 x ULN

ALT (U/L): 3 x ULN

Bilirubin > 2 x ULN or INR > 1.5 x ULN
Descriptive statistics and change from baseline analyses of clinical laboratory results will be 
presented.
5.6.3.2.
Vital Signs and Physical Examination Findings
Continuous vital sign parameters including temperature (axillary, tympanic or forehead), height,
weight, waist circumference, pulse/heart rate, blood pressure (systolic and diastolic), and BMI will 
be summarized at each assessment time point. BMI will be calculated as weight (kg)/(height (m))2, 
at each time point that body weight is measured. The height measurement collected at Screening
Visit S1 will be used in the calculation. Change from baseline will be summarized for the visit of 
week. Descriptive statistics (mean, standard deviation, median, minimum, and maximum) will be 
presented. Week 0 is the Baseline visit for the Vital Signs and Physical Examination Findings (for 
Waist Circumference).
5.6.3.3.
Electrocardiogram
Electrocardiogram (ECG) is collected only at Screening Visit S1. Listings will be produced for all 
ECG data including unscheduled visit data.
5.6.3.4.
Other Safety Parameters
Not Applicable


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5.7.
Other Analyses
5.7.1.
Pharmacokinetics
Pharmacokinetics analysis will not be evaluated for this study.
5.7.2.
Immunogenicity
Not Applicable.
5.7.3.
Pharmacodynamics
All Primary and Secondary endpoints in Section 5.3 and Section 5.4 are analyzed for the 
Pharmacodynamics endpoint.
5.7.4.
Pharmacokinetic/Pharmacodynamic Relationships
Not Applicable.
5.7.5.
Biomarkers
Not Applicable.
5.7.6.
Health Economics
Not Applicable.
5.7.7.
Other Variables and/or Parameters
Coronary Flow Reserve (CFR) screening and screening failure analysis in this study include but 
not limited to:
1.
Baseline characteristics of CRF Screening failure vs Included Participants.
2.
Screening Visit S2 vs Week 0 analysis for:
a.
Coronary Flow Reserve (CFR).
b. Global Longitudinal Strain (GLS).
c.
carotid-femoral Pulse Wave Velocity (cfPWV).
5.7.8.
Definition of Subgroups
The study will be conducted with a subgroup of nicotine users vs. non-nicotine users.
5.8.
Interim Analyses
No Interim Analyses will be performed for the study since it terminated prematurely.
5.8.1.
Data Monitoring Committee (DMC) or Other Review Board
No DMC will be performed for the study.


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6.
SUPPORTING DOCUMENTATION
6.1.
Appendix 1 List of Abbreviations
AE
adverse event
AR[1]
First order auto-regression correlation
ATC
anatomic and therapeutic class
AUDIT
Alcohol use disorders identification Test
BMI
body mass index
BSA
body surface area
cfPWV
carotid-femoral pulse wave velocity
CFR
Coronary Flow Reserve
CI
confidence interval
COVID-19
Coronavirus Disease 2019
CV
Cardiovascular
DBL
Database Lock
DLQI
Dermatology Life Quality Index
DPS
Data Presentation Specifications.
ECG
Electrocardiogram
FAS
Full Analysis Set
GLS
Global longitudinal strain
HADS
Hospital anxiety and depression scale
HLT
High level term
IA
Interim Analysis
ICF
Informed Consent Form
IGA
Investigator’s Global Assessment
IQ
Interquartile
LOCF
last observation carried forward
LSmeans
Least Square Means
MACE
Major Adverse Cardiovascular Events
MCAR
Missing Completely at Random
MedDRA
Medical Dictionary for Regulatory Activities
MMRM
Mixed-effect model for repeated measures
NRI
Non-responder imputation
PASI
Psoriasis area and severity index
PSQI
Pittsburg sleep quality index
PRO
Patient Reported Outcomes
PsA
Psoriatic Arthritis
SAE
serious adverse event
SAP
Statistical Analysis Plan
SC
Subcutaneous
SD
standard deviation
SMQs
standardized MedDRA queries
TEAE
treatment-emergent adverse event
TRTSDT
Treatment Start Date
ULN
upper limit of normal
WHO
World Health Organization
WHO-DD
World Health Organization Drug Dictionary


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6.2.
Appendix 2 Changes to Protocol-Planned Analyses
The Safety Analysis Set is different in the Protocol.
Safety analysis set defined in the protocol as “All enrolled participants who receive at least 1 dose 
of guselkumab.” Whereas in SAP we have modified the definition as “The safety analysis set 
includes all participants who received at least 1 dose of adenosine and guselkumab”.
The Safety Analysis Set will likely contain more participants than the FAS. It would not be 
appropriate to define the safety analysis set as participants receiving at least one dose of 
guselkumab. It is necessary to also capture possible safety related information starting with the 
first assessment of the Coronary Flow Reserve at visit S2, because it involves use of intravenous 
Adenosine.
All enrolled participants who receive at least 1 dose of guselkumab, while it is “The full analysis 
set (FAS) includes all participants who received at least 1 dose of guselkumab." in the current 
SAP.
In Protocol the primary and secondary efficacy endpoints are performed at Week 32 for CFR, GLS 
and cfPWV, while in SAP it is appropriately defined to be completed at Final Efficacy Visit (Week 
32) as per Table 2. The primary and secondary efficacy endpoints will be analyzed at Final 
Efficacy Visit (Week 32) with the definition applied as per Table 2 for the last dose after premature 
termination of the study.
In the protocol The Final Efficacy Visit (Week 32) should occur 4 weeks after the last dose of the 
guselkumab within the study. Whereas in SAP, following the premature termination of the study 
4 to 8 weeks after the last dose of guselkumab within the treatment phase will be used. 
In the protocol for participants who prematurely discontinues guselkumab before Week 28, the 
Final Efficacy Visit (Week 32) should take place at the time of discontinuation, or as soon as 
possible, and all assessments scheduled for the Final Efficacy Visit (Week 32) should be 
performed, whereas in the SAP for participants who permanently discontinue guselkumab before 
Week 28, the date of discontinuation will be used. 
In the protocol for a Final Safety Visit (Week 40), the participants opting to receive commercially 
available guselkumab after Week 28, the first dose of guselkumab outside the study (Week 36) 
should be considered as the Final Safety Visit (Week 40). Whereas in the SAP for Final Safety 
Visit (Week 40) for participants who receive guselkumab after the treatment phase, the date of the first 
dose of guselkumab outside of the treatment phase will be used.
The secondary endpoint 'Change from baseline in CFR at Week 16 and Week 32 among 
participants with CFR in the ranges of 2 to 2.49, 2.5 to 3, and 3.01 to 3.5 at baseline' in the protocol, 
however a different range of 2 to 2.74 and 2.75 to 3.5 will be used for the final analysis. For the 
final analysis the study had a low number of participants after premature termination of the study. 
The ranges were updated accordingly.


CNTO1959  (guselkumab)
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Status: Approved, Date: 21 July 2023
Since the study was terminated prematurely the exploratory objectives and endpoints are removed 
from the corresponding SAP section.
No interim analysis will be performed per the protocol since the study prematurely terminated.
Biomarker analysis will not be performed due to the low number of participants after premature 
termination of the study. 


CNTO1959  (guselkumab)
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CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 21 July 2023
6.3.
Appendix 3 Demographics and Baseline Characteristics
The number of participants in each analysis set will be summarized and listed by Nicotine user, 
Non-nicotine user and overall. In addition, the distribution of participants by country, and site ID
will be presented unless otherwise noted.
Table 3 presents a list of the demographic variables that will be summarized by Nicotine user, 
Non-nicotine user and total for the FAS.
Similarly, baseline characteristics, including Years of Plaque Type Psoriasis Diagnosis, IGA 
Score, PASI Score, PsA and Cardiologic Family History, Psoriatic arthritis present, Prior 
nonbiologic systemic therapy, Prior biologic systemic therapy, Dyslipidemia/hyperlipidemia, 
hypertension, and Nicotine use status ([Never, Former, and Current]). will be summarized by 
Nicotine user, non-nicotine user and total for the FAS.  Years of Psoriasis Plaque Type Diagnosis 
is defined as Year of baseline assessment – Year of first onset of plaque type psoriasis, as collected 
in the CRF.
Table 3:
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)
BMI (kg/m2)
Waist circumference (cm)
BSA (%)
Baseline PASI
Time since plaque type psoriasis diagnosis in years
Categorical Variables
Frequency distribution with the 
number and percentage of 
participants in each category.
Age ([<45 years and >= 45 years])
Sex (male, female, undifferentiated)
Race (White, Black, Asian, Other)
BMI ([underweight <18.5 kg/m2, normal 18.5-<25 kg/m2, overweight 25-
<30 kg/m2, obese >=30 kg/m2])
Psoriatic arthritis present
PsA family history
Cardiologic family history
Dyslipidemia/hyperlipidemia
Baseline IGA score (0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 
4 = severe.)
Hypertension
Nicotine use status ([Never, Former, Current])
Prior nonbiologic systemic therapy
Prior biologic systemic therapy
A listing of prior topical therapy and phototherapy or systemic therapy for Psoriasis will be 
provided.


CNTO1959  (guselkumab)
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CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 21 July 2023
6.4.
Appendix 4 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. Details and 
definitions will be defined in the major protocol deviations criteria form (TV-FRM-04718).

Missed Assessment/Visit

Not Meeting the Inclusion or Meeting the Exclusion criteria

Intake of Prohibited Concomitant Medication
Eligibility criteria deviations are deviations from Section 5.1 and 5.2 of the Protocol inclusion and 
exclusion criteria.
Post-entry deviations are deviations from the protocol that occurred after the patient was assigned 
to the study.
All major protocol deviation criteria will be listed by coded term and verbatim term. 
Major PDs will be listed for patients with at least one corona virus disease 2019 (COVID-19) 
related PD, without any COVID-19 related PD being recorded and regardless of COVID-19 related 
PDs.
Additionally, listings for patients with major protocol deviations will be provided.


CNTO1959  (guselkumab)
Statistical Analysis Plan CNTO1959PSO4015
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 21 July 2023
6.5.
Appendix 5 Prior and Concomitant Medications
Prior and Concomitant medications will be coded using the World Health Organization Drug 
Dictionary (WHO-DD).
Prior medications are defined as any therapy used before the day of first dose (partial or complete) 
of study intervention. If the stop date is missing or partial and it cannot be determined whether the 
participant stopped the medication before the start of study intervention (guselkumab), the 
medication will be considered as concomitant.
Concomitant medications are defined as any therapy used on or after 12 weeks after last dose of 
guselkumab or 8 weeks if the patient switches to commercial guselkumab or any other drug, the 
same day as the first dose of study injection, including those that started before and continue on 
after the first dose of study intervention. If the start or stop date is missing or partial and cannot be 
determined, the medication will be considered as concomitant.
Summaries of concomitant medications will be presented by Anatomical Therapeutic Chemical 
(ATC) level terms (Level 2 and Level 4) and standardized medication name. The proportion of 
participants who receive each concomitant medication will be summarized as well as the 
proportion of participants who receive at least 1 concomitant medication. The proportion of 
participants receiving a medication will be summarized for Nicotine and Non-nicotine users and 
across the study (total). If participants receive a medication more than once within the treatment 
phase, they will be counted only once. 
In addition, concomitant medications of special interest will be presented with at least ≥ 80% of 
the total column.  These include [special interest categories] and standardized medication name. 
See Appendix 9 for list of medications in each category.
Prior medications will be summarized by ATC term.
The concomitant medication data listing will be displayed on the Safety analysis set.
Percentages will be calculated relative to the number of participants in the Safety analysis set.


CNTO1959  (guselkumab)
Statistical Analysis Plan CNTO1959PSO4015
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 21 July 2023
6.6.
Appendix 6 Medical History
Investigators should document all significant medical conditions that the participant has 
experienced in the past. Any medical condition present at the time informed consent is given is to 
be regarded as concomitant. A condition first occurring or detected on or after the day of the 
Baseline visit and/or worsening of a concomitant condition on or after the day of the baseline visit 
is to be documented as an AE on the CRF.
All conditions will be coded using latest version of MedDRA.

A summary of medical history will be provided.

A listing of medical history will be provided.


CNTO1959  (guselkumab)
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CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 21 July 2023
6.7.
Appendix 7 Intervention Compliance
All guselkumab discontinuations, and the primary reasons for the discontinuation will be recorded 
in the Electronic case report form (eCRF).
Compliance to guselkumab will be summarized up to Week 28 only.
Compliance will be summarized descriptively. 
The number and percentage of participants who have at least 80% compliance through the time of 
visit will be summarized.
Compliance will be calculated as follows:
Compliance (%) = 100 x Completed injections/total possible injections
Compliance will be summarized by Nicotine use, non-Nicotine use and Total group, descriptive 
statistics will be provided with N, mean, SD, median, and range (minimum, maximum).
In addition, the number (%) of participants in each compliance categories will be presented. 


CNTO1959  (guselkumab)
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CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 21 July 2023
6.8.
Appendix 8 Adverse Events of Special Interest
Adverse events of special interest are categorized preferred terms. Adverse events of special 
interest will be programmatically derived from a predefined list of preferred terms (as mentioned 
in section 8.3.6 of the study protocol) from an external data from the clinical team.


CNTO1959  (guselkumab)
Statistical Analysis Plan CNTO1959PSO4015
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 21 July 2023
6.9.
Appendix 9 Medications of Special Interest
A listing of concomitant medications (excel file) will be provided by the ClinChoice programming 
team with treatment start date, study day, and duration to the sponsor clinical team to identify the
disallowed medication and medication of special interest in the study. During the study the 
spreadsheet will be updated for every data cut and the list with flagging will be updated
accordingly. 


CNTO1959  (guselkumab)
Statistical Analysis Plan CNTO1959PSO4015
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 21 July 2023
6.10.
Appendix 10 Laboratory Toxicity Grading
The grading scale use for lab assessments is based on ‘Common Terminology Criteria for Adverse 
Events (CTCAE) v5.0’.
If a laboratory value falls within the grading as specified below but also within the local laboratory 
normal limits, the value is considered to be normal and will be reset to grade 0.
Pre-baseline measurements will use the same grading ranges as applied to baseline 
measurements. In case a test has two sets of ranges – one for baseline normal and one for 
baseline abnormal, the one for baseline normal will be applied for all measurements taken pre-
baseline and on baseline.


CNTO1959  (guselkumab)
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CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 21 July 2023
CTCAE Term
Grade 1
Grade 2
Grade 3
Grade 4
Janssen 
implementation notes
Blood and lymphatic system disorders
Anemia
Hemoglobin (Hgb) 
<LLN - 10.0 g/dL; 
<LLN - 6.2 mmol/L;
<LLN - 100 g/L
Hemoglobin (Hgb)  
<10.0 - 8.0 g/dL;
<6.2 - 4.9 mmol/L;
<100 - 80g/L
Hemoglobin (Hgb)  <8.0 
g/dL;
<4.9 mmol/L;
<80 g/L; 
transfusion indicated
Life-threatening 
consequences; 
urgent intervention 
indicated
Clinical signs and 
symptoms are not taken 
into consideration for 
grading.
Leukocytosis
-
-
>100,000/mm3;
>100 x 10e9 /L
Clinical manifestations 
of leucostasis; 
urgent intervention 
indicated
Clinical signs and 
symptoms are not taken 
into consideration for 
grading;
Added ranges in SI unit 
(x 10e9 /L)
Investigations
Alanine aminotransferase 
increased
>ULN - 3.0 x ULN if 
baseline was normal;
1.5 - 3.0 x baseline if 
baseline was abnormal
>3.0 - 5.0 x ULN if 
baseline was normal;
>3.0 - 5.0 x baseline if 
baseline was abnormal
>5.0 - 20.0 x ULN if 
baseline was normal;
>5.0 - 20.0 x baseline if 
baseline was abnormal
>20.0 x ULN if baseline 
was normal;
>20.0 x baseline if 
baseline was abnormal
Ranges defined for 
“abnormal baseline” are 
applied only if baseline > 
ULN. If baseline < LLN, 
then ranges for “normal 
baseline” are applied.
Alkaline phosphatase 
increased
>ULN - 2.5 x ULN if 
baseline was normal;
2.0 - 2.5 x baseline if 
baseline was abnormal
>2.5 - 5.0 x ULN if 
baseline was normal;
>2.5 - 5.0 x baseline if 
baseline was abnormal
>5.0 - 20.0 x ULN if 
baseline was normal;
>5.0 - 20.0 x baseline if 
baseline was abnormal
>20.0 x ULN if baseline 
was normal;
>20.0 x baseline if 
baseline was abnormal
Ranges defined for 
“abnormal baseline” are 
applied only if baseline > 
ULN. If baseline < LLN, 
then ranges for “normal 
baseline” are applied.
Aspartate 
aminotransferase 
increased
>ULN - 3.0 x ULN if 
baseline was normal;
1.5 - 3.0 x baseline if 
baseline was abnormal
>3.0 - 5.0 x ULN if 
baseline was normal;
>3.0 - 5.0 x baseline if 
baseline was abnormal
>5.0 - 20.0 x ULN if 
baseline was normal;
>5.0 - 20.0 x baseline if 
baseline was abnormal
>20.0 x ULN if baseline 
was normal;
>20.0 x baseline if 
baseline was abnormal
Ranges defined for 
“abnormal baseline” are 
applied only if baseline > 
ULN. If baseline < LLN, 
then ranges for “normal 
baseline” are applied.
Blood bilirubin increased
>ULN - 1.5 x ULN if 
baseline was normal;
> 1.0 - 1.5 x baseline if 
baseline was abnormal
>1.5 - 3.0 x ULN if 
baseline was normal;
>1.5 - 3.0 x baseline if 
baseline was abnormal
>3.0 - 10.0 x ULN if 
baseline was normal;
>3.0 - 10.0 x baseline if 
baseline was abnormal
>10.0 x ULN if baseline 
was normal;
>10.0 x baseline if 
baseline was abnormal
Ranges defined for 
“abnormal baseline” are 
applied only if baseline > 
ULN. If baseline < LLN, 
then ranges for “normal 
baseline” are applied.


CNTO1959  (guselkumab)
Statistical Analysis Plan CNTO1959PSO4015
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 21 July 2023
CTCAE Term
Grade 1
Grade 2
Grade 3
Grade 4
Janssen 
implementation notes
Cholesterol high
>ULN - 300 mg/dL;
>ULN - 7.75 mmol/L
>300 - 400 mg/dL;
>7.75 - 10.34 mmol/L
>400 - 500 mg/dL;
>10.34 - 12.92 mmol/L
>500 mg/dL;
>12.92 mmol/L
CPK increased
>ULN - 2.5 x ULN
>2.5 x ULN - 5 x ULN
>5 x ULN - 10 x ULN
>10 x ULN
Creatinine increased
Creatine Kinase
>ULN - 1.5 x ULN
Creatine Kinase
>1.5 - 3.0 x baseline;
>1.5 - 3.0 x ULN
Creatine Kinase
>3.0 x baseline;
>3.0 - 6.0 x ULN
Creatine Kinase
>6.0 x ULN
GGT increased
>ULN - 2.5 x ULN if 
baseline was normal;
2.0 - 2.5 x baseline if 
baseline was abnormal
>2.5 - 5.0 x ULN if 
baseline was normal;
>2.5 - 5.0 x baseline if 
baseline was abnormal
>5.0 - 20.0 x ULN if 
baseline was normal;
>5.0 - 20.0 x baseline if 
baseline was abnormal
>20.0 x ULN if baseline 
was normal;
>20.0 x baseline if 
baseline was abnormal
Ranges defined for 
“abnormal baseline” are 
applied only if baseline > 
ULN. If baseline < LLN, 
then ranges for “normal 
baseline” are applied.
Hemoglobin increased
Increase in >0 - 2 g/dL;
Increase in >0 - 20 g/L
Increase in >2 - 4 g/dL;
Increase in >20 - 40 g/L
Increase in >4 g/dL;
Increase in >40 g/L
-
The increase indicates 
the level of increase 
above normal (above 
ULN). Applied as, e.g.,
grade 1 (g/dL): >ULN –
ULN+2 g/dL;
Added ranges in SI unit 
(g/L).
INR increased
>1.2 - 1.5;
>1 - 1.5 x baseline if on 
anticoagulation;
monitoring only 
indicated
>1.5 - 2.5;
>1.5 - 2.5 x baseline if 
on anticoagulation;
dose adjustment 
indicated
>2.5;
>2.5 x baseline if on 
anticoagulation;
bleeding
-
Concomitant therapy or 
clinical signs and 
symptoms are not taken 
into consideration for 
grading.
Lymphocyte count 
decreased
<LLN - 800/mm3;
<LLN - 0.8 x 10e9/L
<800 - 500/mm3;
<0.8 - 0.5 x 10e9 /L
<500 - 200/mm3;
<0.5 - 0.2 x 10e9 /L
<200/mm3;
<0.2 x 10e9 /L
Lymphocyte count 
increased
-
>4000/mm3 -
20,000/mm3;
>4 - 20 x 10e9 /L
>20,000/mm3;
>20 x 10e9 /L
-
Added ranges in SI unit 
(x 10e9 /L).
Neutrophil count 
decreased
<LLN - 1500/mm3;
<LLN - 1.5 x 10e9 /L
<1500 - 1000/mm3;
<1.5 - 1.0 x 10e9 /L
<1000 - 500/mm3;
<1.0 - 0.5 x 10e9 /L
<500/mm3;
<0.5 x 10e9 /L
Both Neutrophils and 
segmented neutrophils 
are graded using these 
criteria.
Platelet count decreased
<LLN - 75,000/mm3;
<LLN - 75.0 x 10e9 /L
<75,000 - 50,000/mm3;
<75.0 - 50.0 x 10e9 /L
<50,000 - 25,000/mm3;
<50.0 - 25.0 x 10e9 /L
<25,000/mm3;
<25.0 x 10e9 /L
White blood cell 
decreased
<LLN - 3000/mm3; 
<LLN - 3.0 x 10e9 /L
<3000 - 2000/mm3; <3.0 
- 2.0 x 10e9 /L
<2000 - 1000/mm3; <2.0 
- 1.0 x 10e9 /L
<1000/mm3; 
<1.0 x 10e9 /L


CNTO1959  (guselkumab)
Statistical Analysis Plan CNTO1959PSO4015
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 21 July 2023
CTCAE Term
Grade 1
Grade 2
Grade 3
Grade 4
Janssen 
implementation notes
Metabolism and nutrition disorders
Acidosis
pH <normal, but >=7.3
-
pH <7.3
Life-threatening 
consequences
pH <normal is 
implemented as pH 
<LLN.
Clinical signs and 
symptoms are not taken 
into consideration for 
grading.
Alkalosis
pH >normal, but <=7.5
-
pH >7.5
Life-threatening 
consequences
pH >normal is 
implemented as pH 
>ULN.
Clinical signs and 
symptoms are not taken 
into consideration for 
grading.
Hyperkalemia
Potassium >ULN - 5.5 
mmol/L
Potassium >5.5 - 6.0 
mmol/L;
intervention initiated
Potassium >6.0 - 7.0 
mmol/L;
hospitalization indicated
Potassium >7.0 mmol/L;
life-threatening 
consequences
Clinical signs and 
symptoms are not taken 
into consideration for 
grading.
Hypermagnesemia
Magnesium
>ULN - 3.0 mg/dL;
>ULN - 1.23 mmol/L
-
Magnesium
>3.0 - 8.0 mg/dL;
>1.23 - 3.30 mmol/L
Magnesium
>8.0 mg/dL;
>3.30 mmol/L;
life-threatening 
consequences
Clinical signs and 
symptoms are not taken 
into consideration for 
grading.
Hypernatremia
Sodium >ULN - 150 
mmol/L
Sodium >150 - 155 
mmol/L;
intervention initiated
Sodium >155 - 160 
mmol/L;
hospitalization indicated
Sodium >160 mmol/L;
life-threatening 
consequences
Clinical signs and 
symptoms are not taken 
into consideration for 
grading.
Hypertriglyceridemia
Triglycerides
150 mg/dL - 300 mg/dL;
1.71 mmol/L - 3.42 
mmol/L
Triglycerides
>300 mg/dL - 500 
mg/dL;
>3.42 mmol/L - 5.7 
mmol/L
Triglycerides
>500 mg/dL - 1000 
mg/dL;
>5.7 mmol/L - 11.4 
mmol/L
Triglycerides
>1000 mg/dL;
>11.4 mmol/L;
life-threatening 
consequences
Clinical signs and 
symptoms are not taken 
into consideration for 
grading.
Hypoalbuminemia
Albumin
<LLN - 3 g/dL;
<LLN - 30 g/L
Albumin
<3 - 2 g/dL;
<30 - 20 g/L
Albumin
<2 g/dL;
<20 g/L
Life-threatening 
consequences;
urgent intervention 
indicated
Clinical signs and 
symptoms are not taken 
into consideration for 
grading.


CNTO1959  (guselkumab)
Statistical Analysis Plan CNTO1959PSO4015
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 21 July 2023
CTCAE Term
Grade 1
Grade 2
Grade 3
Grade 4
Janssen 
implementation notes
Hypocalcemia
Corrected serum calcium 
of <LLN - 8.0 mg/dL; 
<LLN - 2.0 mmol/L;
Ionized calcium <LLN -
1.0 mmol/L
Corrected serum calcium 
of <8.0 - 7.0 mg/dL; <2.0 
- 1.75 mmol/L;
Ionized calcium <1.0 -
0.9 mmol/L;
symptomatic
Corrected serum calcium 
of <7.0 - 6.0 mg/dL; 
<1.75 - 1.5 mmol/L;
Ionized calcium <0.9 -
0.8 mmol/L;
hospitalization indicated
Corrected serum calcium 
of <6.0 mg/dL; <1.5 
mmol/L;
Ionized calcium <0.8 
mmol/L;
life-threatening 
consequences
Clinical signs and 
symptoms are not taken 
into consideration for 
grading.
Hypoglycemia
Glucose
<LLN - 55 mg/dL;
<LLN - 3.0 mmol/L
Glucose
<55 - 40 mg/dL;
<3.0 - 2.2 mmol/L
Glucose
<40 - 30 mg/dL;
<2.2 - 1.7 mmol/L
Glucose
<30 mg/dL;
<1.7 mmol/L;
life-threatening 
consequences;
seizures
Clinical signs and 
symptoms are not taken 
into consideration for 
grading. Urine glucose is 
not graded.
Hypokalemia
Potassium <LLN - 3.0 
mmol/L
Symptomatic with
Potassium <LLN - 3.0 
mmol/L;
intervention indicated
Potassium <3.0 - 2.5 
mmol/L;
hospitalization indicated
Potassium <2.5 mmol/L;
life-threatening 
consequences
“Symptomatic” ranges 
are applied for grade 2, 
grade 1 not assigned, i.e.,
worst case applied.
Clinical signs and 
symptoms are not taken 
into consideration for 
grading of grade 3 and 4. 
Hypomagnesemia
Magnesium
<LLN - 1.2 mg/dL;
<LLN - 0.5 mmol/L
Magnesium
<1.2 - 0.9 mg/dL;
<0.5 - 0.4 mmol/L
Magnesium
<0.9 - 0.7 mg/dL;
<0.4 - 0.3 mmol/L
Magnesium
<0.7 mg/dL;
<0.3 mmol/L;
life-threatening 
consequences
Clinical signs and 
symptoms are not taken 
into consideration for 
grading.
Hyponatremia
Sodium <LLN - 130 
mmol/L
Sodium 125-129 mmol/L 
and asymptomatic
Sodium 125-129 mmol/L 
symptomatic;
120-124 mmol/L 
regardless of symptoms
Sodium <130-120 
mmol/L
Sodium <120 mmol/L;
life-threatening 
consequences
Clinical signs and 
symptoms are not taken 
into consideration for 
grading.
Worst case (“<130-120 
mmol/L” for grade 3 
added by Janssen) is 
applied across grade 2/3 
ranges: 120-129 mol/L 


CNTO1959  (guselkumab)
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Status: Approved, Date: 21 July 2023
CTCAE Term
Grade 1
Grade 2
Grade 3
Grade 4
Janssen 
implementation notes
assigned to grade 3, 
grade 2 not used.
Renal and urinary disorders
Proteinuria
1+ proteinuria;
urinary protein ≥ULN -
<1.0 g/24 hrs;
urinary protein ≥ULN -
<1000 mg/day
Adult:
2+ and 3+ proteinuria;
urinary protein 1.0 - <3.5 
g/24 hrs; 
urinary protein 1000 -
<3500 mg/day
Pediatric:
Urine P/C 
(Protein/Creatinine) ratio 
0.5 - 1.9;
Urine P/C 
(Protein/Creatinine) 56.5 
– 214.7 g/mol
Adult:
4+ proteinuria;
urinary protein >=3.5 
g/24 hrs;
urinary protein >=3500 
mg/day;
Pediatric:
Urine P/C 
(Protein/Creatinine) ratio 
>1.9;
Urine P/C 
(Protein/Creatinine)  
>214.7 g/mol
-
In case both 24-h urine 
collection and dipstick 
are collected, then worst 
case is taken, as opposed 
to having 24-h urine 
collection take 
precedence over dipstick.
Added ranges in SI unit 
for urinary protein 
(mg/day) and for urine 
P/C (g/mol).
Pediatric grading is 
applied to age range [0-
18]. Adult grading is 
applied for ages [>18].
* Grade 0 is assigned to a lab assessment when the lab test is described in the table, but the lab value is not assigned a grade 1 or higher.


CNTO1959  (guselkumab)
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Status: Approved, Date: 21 July 2023
6.11.
Appendix 11 Potential Risks due to Study Procedure (Adenosine Injection).
Potential Risks due to Study Procedure (Adenosine Injection)
Potential Risks of Clinical Significance
Indications for Stopping
Adenosine Infusion
and/or Administering
Aminophylline
Mitigation Strategy
Vascular related: Flushing
Stopping Adenosine and/or
further medical intervention
is at the discretion of the
cardiology investigator and
should be considered in case
of:
The half-life of adenosine is less than 10
seconds. Thus, the adverse effects are 
generally rapidly self-limiting. Treatment 
of any Prolonged adverse effect should be 
individualized and directed toward the 
specific effect.
Thoracic related: dyspnea (shortness of breath), 
chest discomfort

Severe hypotension: Systolic pressure 
<80 mm Hg or 20 mmHg fall which 
persists
Stop infusion –most effects resolve within 
30- 60 seconds post infusion
Nervous system related: Headache, dizziness, 
lightheadedness, paresthesia

ST depression: >3 mm beyond baseline 
ECG without angina or >2 mm with 
angina
If symptoms persist, administer 
aminophylline, 125 mg, IV by slow 
infusion (1 minute) on cardiology 
investigator’s direction. Dosage may be 
repeated in five minutes if there is no
response to the first dose.
Gastrointestinal related: Nausea

Persistent 2nd or 3rd degree heart 
block
Note: Adverse events (AEs) should be 
reported if medical intervention beyond 
stopping adenosine infusion is necessary. 
Please refer Appendix 13 of protocol 
for further information.
Cardiac related: bradycardia, sinus pause, skipped 
beats, atrial extrasystoles, Atrio- Ventricular block, 
ventricular excitability disorders such as ventricular 
extrasystoles, non-sustained ventricular tachycardia
Severe chest discomfort, dizziness, 
dyspnea, headache, nausea, syncope or 
dysrhythmia


CNTO1959  (guselkumab)
Statistical Analysis Plan CNTO1959PSO4015
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
47
Status: Approved, Date: 21 July 2023
7.
REFERENCES
1.
Zigmond AS, Snaith RP. The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand 1983;67:361–
370.